The gut-brain axis has been a subject of significant interest in recent years. Understanding the link between the gut and brain axis is crucial for the treatment of disorders. Here, the intricate components and unique relationship between gut microbiota-derived metabolites and the brain are explained in detail. Additionally, the association between gut microbiota-derived metabolites and the integrity of the blood-brain barrier and brain health is emphasized. Meanwhile, gut microbiota-derived metabolites with their recent applications, challenges and opportunities their pathways on different disease treatment are focus discussed. The prospective strategy of gut microbiota-derived metabolites potential applies to the brain disease treatments, such as Parkinson's disease and Alzheimer's disease, is proposed. This review provides a broad perspective on gut microbiota-derived metabolites characteristics facilitate understand the connection between gut and brain and pave the way for the development of a new medication delivery system for gut microbiota-derived metabolites. The brain and gut microbiota have a close relationship, with gut microbes significantly influencing the brain. Additionally, the gut and the brain share many similarities and characteristics, including the presence of numerous neurons and glial cells that provide support and nourishment to neurons. Within the human body, the gut is responsible for producing more than forty neurotransmitters, including fifty percent of the body's dopamine and ninety-five percent of its serotonin As the most significant micro-ecological system in the human body, gut bacteria play a crucial role in the material and energy metabolism of the body, significantly impacting human health. These bacteria live attached to the gut of animals and aid in carrying out a wide range of physiological and biochemical processes Metabolites produced in the gut are closely linked to brain activity, and communication between the gut and brain occurs through the "gut-brain axis"While gut-derived γ-aminobutyric acid (GABA) can enter the brain through the corresponding transporters on the blood-brain barrier As a result, this review aims to summarize the intricate relationship between gut microbial metabolites and the brain. The types of gut microbial metabolites, gut-brain signaling pathways, the effects of metabolites on brain cells, and brain diseases and treatment measures related to metabolites are all thoroughly explained. The review also highlights the crucial role of gut microbial metabolites in brain diseases and their treatment, providing viable treatment strategies for non-invasive brain diseases and paving the way for the continuous development of related fields.There is a growing body of evidence supporting the important role of gut microbe-driven metabolites in the development and progression of brain diseases. Short-chain fatty acids (SCFAs) such as acetate, propionate and butyrate, produced by gut microbes, have been shown to regulate the blood-brain barrier, affect neuroplasticity, and modulate the maturation of microglia. The metabolites produced by the microbiota, including short-chain fatty acids, trimethylamine, and amino acid metabolites, among others, take many different forms, which are further classified and elaborated upon below. Figure Fatty acids are carboxylic acids with aliphatic tails of varying lengths, and SCFAs are generally defined as carboxylic acids with aliphatic tails of fewer than 6 carbons Furthermore, SCFAs can affect the physiological structure of the brain by regulating gut permeability through modulating tight junction proteins that are also components of the blood-brain barrier. Thus, there is evidence that SCFAs may also affect the integrity of the blood-brain barrier. Studies on sterile mice have shown that SCFAs can indeed regulate the permeability of the blood-brain barrier, thereby influencing the extent to which beneficial or harmful molecules from the circulation reach brain tissue. For example, during the body's development, SCFAs can strengthen the blood-brain barrier and reduce its permeability to harmful factors such as inflammatory molecules, thus protecting the brain from damage. Alterations in the gut microbiota composition of sterile mice affected the maturation of microglia in the brain, resulting in impaired innate immunity. However, oral administration of SCFAs restored morphological changes in microglia.Additionally, SCFAs can also impact the body's behavior and mood. For instance, sodium butyrate as a histone deacetylase inhibitor, can induce temporary acetylation of histones in the frontal cortex and hippocampus of mice after injection into depression model mice. Furthermore, there was also a dynamic change in the expression of brain-derived neurotrophic factor (BDNF), a gene involved in the behavioral and pharmacological model of depression. After long-term administration of sodium butyrate, the depressive behavior of mice significantly reduced In addition, it has been found that changes in propionic acid level are related to the symptoms of Parkinson's patients. After taking the treatment drugs, the serum concentration of propionic acid recovered, indicating that SCFAs may affect the symptoms of Parkinson's patients through the bloodstream Furthermore, the role of SCFAs in cardiovascular diseases cannot be ignored. Bartolomaeus and his team found that propionate can significantly reduce myocardial hypertrophy, fibrosis, vascular dysfunction, and hypertension by studying the role of propionate in a hypertensive mouse model Finally, SCFAs also affect the tumor growth in the digestive tract system by inhibiting HDACs preventing the occurrence of colorectal cancer and related inflammation SCFAs play a crucial role in the brain, and their levels have been found to be altered in various neurological disorders, including Parkinson's disease and Alzheimer's disease. Moreover, it has been suggested that SCFAs may also contribute to the pathogenesis of these diseases. These findings highlight the potential importance of SCFAs in the development and progression of brain diseases, and offer a new perspective for future therapeutic interventions.Trimethylamine is a precursor of trimethylamine-N-oxide (TMAO), which is produced by the metabolism of nutritional precursors such as choline, phosphatidylcholine and L-carnitine by gut microorganisms. The conversion of trimethylamine to TMAO occurs in the host liver FMO3 (flavin-containing monooxygenase 3) Figure . TMAO isA long-term study conducted by Yoriko and his team measured TMAO levels in the blood of 760 healthy women who had drawn blood twice at 10-year intervals. Among them, patients with coronary heart disease patients n=380) had no difference in TMAO levels compared to the control group (n=380) at the first blood draw, but higher plasma TMAO levels were found at the second blood draw 0 had no The concentration of TMAO in the cerebrospinal fluid of patients with Alzheimer's disease has been found to significantly increase The presence of tryptophan is essential for protein synthesis in the human body and it plays a crucial role in the microbe-gut-brain axis. As the solo precursor of the neurotransmitter serotonin, tryptophan is involved in various human activities. Its metabolic pathways primarily include the kynurenine pathway and 5-HT pathway, and it can also be directly converted into various of compounds. Depending on its metabolic pathway, tryptophan can produce different metabolites that impact the occurrence of depression Gut bacteria containing glutamate racemase, such as corynebacterium Glutamicum, have the ability to convert L-glutamic acid into D-glutamic acid, which can affect N-methyl-D-aspartate (NMDA) glutamate receptors and cognitive function in patients with Alzheimer's disease. NMDA glutamate receptor enhancers have been found to improve the cognitive function of patients with Alzheimer's disease and dementia 3 deficiency is often associated with brown skin disease, accompanied by dementia, delirium and other symptoms Robert summarized and discussed the important role of vitamins in the gut microbiota. Although the human body obtains most of its vitamins from daily diets, the gut microbiota is also an important source of vitamins, such as vitamin C, vitamin K, and B vitamins Retinoic acid (RA) is a product of vitamin A metabolism by gut epithelial cells, which regulates the development of protective and pathogenic immune responses in the gut in a concentration-dependent manner. However, gut microbiota such as Clostridium can reduce the level of retinol in the gut by inhibiting the expression of retinol dehydrogenase 7. By comparing the levels of vitamin A-related metabolites in the gut and liver of sterile mice and normal mice, it was found that the content of vitamin A active metabolites in the gut and the storage of vitamin A in the liver Dietary polysaccharides are the main source of energy for mammalian gut microbiota. However, most polysaccharides cannot be directly digested and absorbed after entering the digestive tract. Herbivores get 70% of their energy from these polysaccharides due to the role of gut microbes in breaking down the polysaccharide polymers Plant polysaccharides are believed to have various pharmacological activities, such as regulating immune function, anti-tumor, anti-aging effects. They also affect the gut environment after entering the gut. For example, they increase the production of acidic substances in the gut through fermentation, which reduces the gut pH value and affect the composition of the microbiota and the balance of microbial metabolites. This can indirectly increase the number of bacteria producing butyrate and the level of butyrate 2S, NO and CO, which are generally associated with cardiovascular disease Apart from the gut microbiota metabolites discussed above, other metabolites in the body play an important role in physiological and pathological activities. Polyphenols, urolithins, and some gas molecules are some examples. Polyphenols can promote memory, learning and cognitive abilities by protecting neurons and inhibiting neuroinflammation. They protect the brain both directly and indirectly. The direct effect is their ability to cross the blood-brain barrier Tannins can be metabolized by gut microorganisms to produce urolithin A, B, and C. Urolithin A has been shown to inhibit osteoporosis by enhancing the autophagy ability of bone marrow macrophages and has the opposite effect of TMAO Various neurological, neurodegenerative, and neuropsychiatric illnesses have been linked to changes in the composition of the gut microbiota. Microbes in the gut transform and metabolize chemicals from food and the host to produce various metabolites with both local and systemic effects. These metabolites have the potential to affect the normal function of the body, particularly the brain. This chapter provides a comprehensive analysis of the metabolic pathways that lead to the brain via "gut-brain axis". The "gut-brain axis" is a complex system that involves the blood, immune system, and vagus nerve, and facilitates communication between the brain and the metabolites produced by the gut microbiota. The following sections provide detailed descriptions of these routes of gut microbe-driven metabolites to the brain  are monolayer cells that line the interior of blood vessels, and their nutritional and biochemical functions play a crucial role in cardiovascular function. Endothelial cell dysfunction is now recognized as a hallmark of most cardiovascular diseases, including microangiopathy associated with neurodegenerative diseases in diabetic patients. TMAO activates the mitogen-activated protein kinase (MAPK) pathway and induces EC dysfunction in vascular smooth muscle cells through NF-κB signaling, leading to upregulation of inflammatory signals and increased leukocyte adhesion to ECs. This aggravates endothelial dysfunction, reducing the ability of ECs to self-repair and increasing monocyte self-adhesion. These effects have been demonstrated in vitroMicroglia is resident immune cell in the brain, which can control innate immune function, and is crucial to the growth and development of the brain Gut microbes play a critical role in maintaining the overall human health, including the health of the brain. Recent research has demonstrated that these microbes produce a range of metabolites that can impact brain function and may have therapeutic potential in treating brain diseases  in brain tumor cells while leaving healthy cells unaffected, making it an appealing candidate for use in brain tumor therapy Another gut microbe-produced metabolite that has shown promise in brain tumor applications is indole-3-acetate (IAA). IAA is produced by several types of gut bacteria and has been demonstrated to inhibit the growth and proliferation of brain tumor cells. IAA achieves this by blocking the activity of a protein that is necessary for the survival and growth of cancer cells. Like butyrate, IAA can selectively target cancer cells while leaving healthy cells unaffected Gut microbes-mediated metabolites have the potential to be a valuable tool in the treatment of brain tumors. The ability of these metabolites to selectively target cancer cells while sparing healthy cells makes them an attractive alternative to traditional chemotherapy and radiation therapy. Further research is necessary to fully comprehend the mechanisms by which these metabolites work, as well as their potential side effects and optimal dosages. Nonetheless, the promising results observed in preclinical studies suggest that gut microbes-mediated metabolites could play a critical role in the future of brain tumor therapy.Parkinson's disease and Alzheimer's disease are common and incurable diseases among the elderly in China, with no drugs available effectively solve the problem of disease progression. Therefore, more effective treatment strategies are urgently needed. In recent years, several studies have focused on the decline of the immune system and the imbalance of the gut microbiota in the elderly, and the role of the gut microbiota in age-related neurodegenerative diseases has received increasing attention Vogt and his team compared the gut microbes 25 patients with Alzheimer's disease and 25 healthy individuals and found that the diversity of gut microbes in Alzheimer's patients was reduced, with a decrease in the number of general Firmicutes and an increase in the number of Proteobacteria and Bacteroidetes.There is ample evidence that healthy eating habits, including high intake of plant foods, reduced intake of saturated fat, and probiotic supplementation, can delay the occurrence of neurocognitive disorders and ultimately reduce the risk of Alzheimer's disease. Fermented milk products containing probiotics can regulate brain function and have a positive effect on cognitive function and metabolic status in Alzheimer's patients Parkinson's disease is a neurodegenerative disease often accompanied by gastrointestinal tract symptoms, and increasing evidence shows that there is a two-way connection between gut microbiota and its metabolites and Parkinson's disease. Gut microbiota contributes to the maturation and activation of microglia, and one of the pathogenesis of Parkinson's disease is microglia-induced neuroinflammation. Therefore, gut microbiota imbalance is likely to induce Parkinson's disease In 2019, a Chinese hospital performed fecal microbiota transplantation by transplanting gut microorganisms from a healthy 26-year-old donor to an elderly patient with Parkinson's disease who had constipation symptoms. The treatment resulted in a significant improvement in the patient's lower limb tremor and constipation symptoms. This marks the first time that fecal microbiota transplantation has been used as a biological therapy for Parkinson's disease. However, the improvement in the patient's lower limb tremor was observed for only one week Epilepsy is a neurological disorder characterized by abnormal discharge of neurons leading to increased excitability. Clinical reports have shown that there is a relationship between stress and epilepsy. Self-reported stress in patients with epilepsy triggers or worsens seizures. Patients with epilepsy have higher levels of stress hormones compared to healthy individuals, and higher levels after seizures, indicating a two-way relationship between stress and disease. Gut microbiota can contribute to the occurrence of epilepsy by producing neurotransmitters that regulate neural networks and by activating the immune system to mediate the pro-excitation of peripheral inflammation Of course, the role of probiotics in the clinical treatment of epilepsy cannot be ignored. Gómez-Eguílaz and his team administered mixed probiotics treatment to patients with resistant epilepsy. During the four-month treatment, the number of seizures and quality of life of patients were evaluated. It was found that the number of seizures in some patients was greatly reduced, and their quality of life was also significantly improved, proving that probiotics treatment may be used as a complementary therapy for epilepsy treatment 4 T cells in the spleen of mice increased, and almost completely recovered to normal levels The mammalian gastrointestinal tract is a complex ecosystem, consisting of numerous gut microbiota and the host immune system, which complement each other. Specific microbiota in the gut can promote the maturation of the host immune system. Mazmanian and his team studied the effect of colonizing Bifidobacterium fragile in the gut of sterile mice on the immune system of mice. The results showed that CDCancer has always been a major challenge for humanity to overcome. Current treatment methods cannot cure most cancers, and a key feature of cancer is its immune function deficiency. Cancer cells can create an immunosuppressive microenvironment, allowing them to grow and escape immune destruction. In recent years, new evidence has shown that immunotherapy can offer hope in the treatment of cancer, particularly immune checkpoint blockade, which reactivates the immune function of immune cells by blocking immune checkpoints to restore their anti-tumor activity. Gut microorganisms can not only regulate the body's own immune function, but also work with immune checkpoint inhibitors to reduce adverse reactions For example, Marie's study on the use of antibodies against CTLA-4, a major regulator of T-cell activation, for cancer immunotherapy found that its anti-tumor effect may depend on the different types of Bacteroides in the body Furthermore, the presence of gut microorganisms can help mitigate complications during cancer immunotherapy. For example, Lactobacillus reuteri has been shown to completely eliminate colitis induced by immune checkpoint inhibitors Studies have shown that FMT of young donor microbiota into elderly mice can improve age-related central nervous system inflammation and slow down the loss of key functional proteins in the eyes Studies have shown that supplementation of prebiotics can reduce the body's stress immune response, improve symptoms such as depression and anxiety, increase the expression of brain-derived neurotrophic factor, and improve cognitive status. Additionally, prebiotics supplementation can increase the level of SCFAs in the body, improve the social behavior and sleep pattern of autistic patients, and reduce the anxiety score of patients with irritable bowel syndrome in vivoPropionic acid, a gut metabolite of Clostridium difficile, has been linked to autism due to increased levels found in the gut. Researchers have induced autism in rats using propionic acid and used probiotics (Bifidobacterium and Lactobacillus) to treat them. Afaf El-Ansary and colleagues found that probiotic treatment reduced glutamate excitotoxicity by increasing GABA and Mg2+ consumption and decreasing glutamate levels There is a significant relationship between gut microbiota and multiple sclerosis (MS). Borody and his team observed the conditions of three patients with multiple sclerosis with different complications after treatment with FMT. The patients' gut and neurological symptoms were improved, and they speculated that FMT eliminated occult gut pathogens that caused MS It is well known that the most common adverse symptom of radiation therapy for cancer is gastrointestinal dysfunction, which can cause further damage to the body and terminate treatment However, when it comes to treating diseases mediated by these metabolites, the process can be slightly more complex, as the efficacy of drug treatment is influenced by the gastrointestinal tract and the blood-brain barrier. The blood-brain barrier is the central nervous system's most important protective mechanism, allowing certain small molecules to enter the brain while preventing harmful substances from entering. However, it also limits drug delivery and increases the difficulty of treating brain diseases For instance, Liu and her colleagues developed a method for delivering mesoporous silica nanospheres loaded with Bifidobacteria to the intestine through nasal administration. This approach overcomes the harsh acidic and bile salt conditions in the gastrointestinal tract that can destroy the beneficial bacteria. The study confirmed that this approach can inhibit intestinal inflammation, reduce brain Aβ load, and improve symptoms in patients with Alzheimer's disease (AD) Gut microbes-mediated metabolites have emerged as a potential new frontier in the treatment of brain diseases. The gut-brain axis, a complex communication network between the gut and the brain, has been found to play a crucial role in the regulation of brain function and the development of brain diseases. This has led to a growing interest in the therapeutic potential of gut microbes-mediated metabolites in the treatment of brain diseases.Gut microbes-mediated metabolites have shown promising results in the treatment of neurological diseases such as Parkinson's disease and Alzheimer's disease. For example, butyrate, a short-chain fatty acid produced by gut bacteria, has been shown to improve motor function and reduce neuroinflammation in animal models of Parkinson's disease. Similarly, the metabolite indole-3-propionic acid (IPA) has been found to protect against neuronal damage in Alzheimer's disease. In addition to neurological diseases, gut microbes-mediated metabolites have also shown potential in the treatment of psychiatric disorders such as depression and anxiety. Studies have found that certain gut microbes can produce metabolites that act on the central nervous system and regulate mood and behavior. For example, the metabolite kynurenine has been found to play a role in the development of depression, while butyrate has been shown to improve anxiety-like behavior in animal models.While the potential of gut microbes-mediated metabolites in the treatment of brain diseases is promising, there are still many challenges to be addressed. One of the major challenges is understanding the complex interactions between gut microbes, their metabolites, and the brain. Another challenge is developing effective delivery methods for these metabolites, as they must be able to cross the blood-brain barrier to exert their therapeutic effects. However, recent advancements in neuroscience and microbiome research have provided new opportunities for developing targeted and effective treatments for brain diseases.In summary, the microbial metabolism substance of the gut, which serves as the primary material foundation of the gut-brain axis, offers a path forward for understanding brain illnesses formation and developing treatments for them. The future of gut microbes-mediated metabolites in the treatment of brain diseases is bright. The potential of these metabolites to regulate brain function and ameliorate the symptoms of neurological and psychiatric disorders is a promising area of research. Continuing effort and advances in the fields of materials science and engineering, chemistry, biology, and computer science are expected to lead to success in precise manipulation of the human gut microbiota-derived metabolites and translating into clinical applications in the near future.


Optical coherence tomography (OCT) is one of the newest and most important optical non-invasive methods for the investigation and testing of various materials  that are at least partly transparent to infrared light. This method is ideal for eye diagnostics, especially of the anterior segment or the retina. That is why commercially available OCT devices have revolutionized the clinical practice of ophthalmology. However, OCT may also be a very interesting technology for biometrics, including the biometrics of the human eye.Data acquisition with the use of OCT devices is constantly being improved and becoming more and more popular, as exemplified by, for instance, OCTA  solutions, which allow observation of the retinal vessels. OCT is also applicable in other fields beyond ophthalmology and allows a successful examination of other materials and their structures. OCT can, among others, be used for the measurement of material thickness, testing of thin silicon wafers, structural analysis of polymer composites, as well as to examine the structure of the artwork.OCT solutions are the subject of further research related to data processing. Various challenges include improving image quality, increasing segmentation accuracy, and automatic classification of selected diseases. Data processing requires the use of advanced IT methods, including deep neural networks and other machine learning algorithms.This Special Issue of the Sensors Journal deals with the research of OCT technologies and techniques in biometric applications. The authors of the articles come from various research centers around the world: Korea, Poland, Great Britain, Germany, Norway, Australia and the United States. Five articles focus on issues related to retinal analysis. The research was carried out using databases obtained using various OCT devices: Heidelberg Spectralis HRA+OCT, Avanti RTVue XR Optovue, or ENVISU C Bioptigen. One article in this Special Issue concerns the analysis of a fingerprint, which was imaged using a special device.A key element of OCT image analysis is the initial segmentation and, in the case of retinal B-scans, layer segmentation. Segmentation techniques can be based on graph theory and dynamic programming, while newer solutions use deep neural networks in the encoder-decoder architecture. An example of such a network is the popular U-Net solution. In the article , the autSolutions based on neural networks in the aspect of the human eye retina are also presented in the article  in whichDeep neural networks are also suitable for effective segmentation of the preretinal space . In thisOptical coherence tomography angiography (OCTA) allows the observation of blood flow and imaging of retinal blood vessels, including micro vascularization. In conventional OCTA analysis, decorrelation of multiple A-scans is performed, which is a time-consuming computational operation. The authors of  proposedOphthalmic OCT devices offer various scanning modes. The simplest and fastest mode is the acquisition of a single B-scan, but in the case of diagnostics of some lesions, better imaging can be obtained by three-dimensional radial scanning or three-dimensional linear scanning consisting of a fixed number of parallel B-scans. Article  proposesAs mentioned in the Introduction, OCT imaging also has interesting advantages in applications other than ophthalmic diagnostics. Article  presentsMachine learning techniques using deep neural networks are currently intensively used to analyze OCT images. The authors of the Special Issue showed the effectiveness of various networks such as U-Net, Mask R-CNN, DarkNet53, ReLayNet or LFU-Net. It can be seen that the effectiveness of individual neural networks depends on the specificity of the task. Improving the effectiveness of classification and segmentation using deep learning (DL) requires the development of large datasets with appropriate ground truth.In the case of ophthalmology diagnostics, biometric retinal examination using OCT devices is becoming a standard. OCT devices are still characterized by a relatively high cost, and for this reason, their popularity is currently not very high in other solutions, e.g., fingerprint recognition. However, it should be noted that biometric fingerprint analysis with the use of OCT has several advantages that are unattainable for standard solutions.


In the context of China’s 14th Five-Year Plan and 2035 visionary goals of national economic and social development, to achieve the national dual carbon goals, an innovation-driven green development strategy must be implemented, and the relationship between environmental regulation and green innovation efficiency must be clarified. Based on the DEA-SBM model, in this study, we measured the green innovation efficiency of 30 provinces and cities in China from 2011 to 2020 by introducing environmental regulation as the core explanatory variable, and two threshold variables, environmental protection input and fiscal decentralization, to empirically analyze the threshold effect of environmental regulation on green innovation efficiency. We found that: (1) The green innovation efficiency of 30 provinces and municipalities in China is spatially distributed as strong in the east and weak in the west. (2) A double-threshold effect exists with environmental protection input as the threshold variable. Environmental regulation showed an inverted N-shaped relationship of first inhibiting, then promoting, and finally inhibiting green innovation efficiency. (3) A double-threshold effect exists with fiscal decentralization as the threshold variable. Environmental regulation showed an inverted N-shaped relationship of inhibiting, promoting, and then inhibiting green innovation efficiency. The study results provide theoretical guidance and practical reference for China to achieve the dual carbon goal. With the strengthening global economy, environmental pollution has become increasingly serious. In the 2030 Agenda for Sustainable Development, the United Nations set up future development goals for economic and environmental issues through which countries can continue to adjust their development models and accelerate green transformation. At present, both green innovation and green low-carbon transition have become widespread hot topics in China. At the 75th UN General Debate in September 2020, President Xi Jinping proposed that “China will adopt stronger policies and measures to strive to achieve peak carbon by 2030 and carbon neutrality by 2060”, which means that China will reach the goal of carbon neutrality in half the time compared with western countries. Thus, achieving the dual carbon targets is required for China to achieve high-quality green development and for the government to vigorously promote regional green innovation and green transformation. During the 14th Five-Year Plan period, China should promote the innovation of green technologies, such as pollution and carbon reduction, under the vision of carbon neutrality and carbon peaking to achieve green development. To achieve carbon neutrality, abandon development models that damage the ecological environment, break the old dynamics of regional development, and build a beautiful country, and the whole country should, in the context of strengthening environmental regulation, take a development path that prioritizes the ecological environment and green low-carbon innovation, insist on innovation as the first force driving development, implement the development concept of “green mountains and clear water are equal to mountains of gold and silver”, continuously optimize the ecological innovation environment, improve the regional innovation environment, and enhance the efficiency of regional green innovation.Within this context, most researchers have explored the relationship between environmental regulation and green innovation efficiency at the micro level, such as in the construction industry  and heavTherefore, we focused on the core question of how to improve green innovation efficiency through environmental regulation and explored the threshold effect of environmental regulation on green innovation efficiency in 30 provinces and cities in China during 2011–2020. We followed a main logical line of model construction, empirical testing, then result analysis. We used the DEA-SBM to measure the green innovation efficiency of 30 provinces in China, introduced environmental regulation as the core explanatory variable, and environmental protection input and fiscal decentralization as the threshold variables to construct a panel threshold model. We then empirically analyzed the threshold effect of environmental regulation on green innovation efficiency. In summary, we extracted common patterns by analyzing the threshold effects; our study provides theoretical references for achieving the dual carbon goal.The academic research on environmental regulation and green innovation efficiency has mainly focused on the Porter hypothesis. Environmental regulation can be divided into formal and informal environmental regulation. Formal environmental regulation refers to the institutional arrangement in which the government uses policies and regulations, economic instruments, and market mechanisms to regulate the behavior of the public to protect the environment . InformaThree views on the influence of environmental protection input and green innovation efficiency have been expressed. One is the opposing theory based on the traditional hypothesis, in which neoclassical economic theory states that environmental protection input will increase the economic burden and increase the cost of innovation, which is not conducive to the improvement in green innovation efficiency . The secThe relationship between fiscal decentralization and green innovation efficiency has received extensive academic attention. Fiscal decentralization  is a metBy summarizing the existing literature, we found that the domestic discussion on green innovation efficiency from different perspectives has been thorough, with scholars considering the factors influencing green innovation efficiency ,18, spatIn summary, although many empirical results on green innovation efficiency have been published, few studies have linked environmental regulation to green innovation efficiency at the provincial level. Therefore, the marginal contribution of this is a discussion of the threshold effect of environmental regulation on green innovation efficiency from dual perspectives: environmental protection input and fiscal decentralization. This study complements the literature on how environmental regulation affects green innovation efficiency at the provincial level, and we provide policy recommendations for exploring the impact of different thresholds on green innovation efficiency from the perspectives of environmental protection input and fiscal decentralization, thereby promoting sustainable development, high-quality development, and the achievement of the dual carbon goal.Considering the influence of two factors, fiscal decentralization and environmental protection input, environmental regulation may have a nonlinear relationship with green innovation efficiency in different environments. Therefore, we constructed a panel threshold model based on Hansen’s (1999)  panel daTaking environmental protection input and fiscal decentralization as threshold variables, respectively, we explored the nonlinear relationship between environmental regulation and green innovation efficiency and constructed a double-threshold model with the following expressions:The DEA method is widely used in efficiency measurement, but the traditional DEA model ignores unexpected outputs and does not consider the input–output slack at the same time. The DEA-SBM unexpected output model proposed by Tone (2001) , which cIn this study, we took each province as a production decision unit, and we assumed each had M inputs, In this study, we defined green innovation efficiency from two perspectives: green innovation input and green innovation output, where input considers three main aspects: human, capital, and energy; output considers two main aspects: economic and environmental benefit. The definition of green innovation efficiency variables is detailed in In prior studies, scholars did not have a relatively unified standard for measuring environmental regulation. At present, environmental regulation is measured mainly from two perspectives, the first of which is the effect of environmental regulation. Liu and He (2021)  used sin1.Fiscal Decentralization (FD)The fiscal decentralization indicator reflects autonomous local finance. Researchers have measured fiscal decentralization mainly from three perspectives: fiscal revenue, fiscal freedom, and fiscal expenditure. We referred to Zhang et al. (2022)  to measu2.Environmental Protection Inputs (IPC)Various measures are available for environmental protection input in China, such as greening coverage, the amount of high investment in urban public transportation, subsidies and investment in industry, and the amount of completed investment in environmental pollution control . As our Based on prior studies and to avoid estimation bias caused by omitted variables, we included four indicators: regional economic development level, energy consumption intensity, education level, and regional openness as control variables in the analysis model. These specifically included (i) regional economic development level (GDP), expressed as regional GDP per capita; (ii) energy consumption intensity (EI), expressed as the ratio of total energy consumption to regional GDP in each province; (iii) education level (EDU), expressed as the educated level of employed persons in each province; and (iv) regional openness (OP), expressed as the ratio of the foreign direct investment amount to GDP in each province.According to data availability, we selected the panel data of 30 provinces in China  from 2011 to 2020 for the study. We obtained all data from the China Environmental Yearbook, the China Population and Employment Statistical Yearbook, the China Labor Statistical Yearbook, and the China Energy Statistical Yearbook. The descriptive statistics for each variable are shown in To avoid pseudo-regression and increase the smoothness of the panel data, we conducted the unit root test on the panel data of 30 provinces. In this study, we chose the Levin–Lin–Chu test for the unit root test. p-value of the single-threshold test for Model (2) with environmental protection input as the threshold variable was 0.000 (0.000 ≤ 0.000), which was significant at the 1% statistical level, indicating the existence of a single-threshold effect. Second, we proceeded with the double-threshold test. The results showed that the p-value of the double-threshold test was 0.000 (0.000 ≤ 0.000), which was significant at the 1% statistical level, indicating a double-threshold effect. Similarly, the p-value of the double threshold test for Model (3) with fiscal decentralization as the threshold variable was 0.000 (0.000 ≤ 0.000), indicating a double-threshold effect in Model (3). Furthermore, According to Models (2) and (3), we used STATA16 to explore the effect of environmental regulation on green innovation efficiency, with environmental protection input (IPC) and fiscal decentralization (FD) as the threshold variables, respectively. First, we estimated the threshold values and tested them for significance. As shown in The estimation results of the threshold values in The regression results of the panel threshold model are shown in To further prove the preceding conclusions and consider the possible time-lag effects of the threshold variables, environmental protection input and fiscal decentralization, on green innovation efficiency, we adopted an extended time window to conduct robustness tests by treating the threshold variables  with one and two lags, respectively. The robustness tests involved the following four models:Models (4) and (5) are based on the model with environmental protection input as the threshold variable, replacing the threshold variable with one period lagged and two periods lagged, respectively, where According to the test, in Models (4) to (7), all of which have double-threshold effects, as the intensity of the lagged threshold variables, environmental protection input and fiscal decentralization, changed from weak to strong, the effect of environmental regulation on green innovation efficiency presented an inverse N-shaped relationship of first inhibiting, then promoting, and finally inhibiting. This finding is consistent with the conclusion drawn in a previous study; that is, the threshold regression model in this study is robust .First, during 2011–2020, the average green innovation efficiency in the central and western regions irregularly fluctuated compared with the national average; in the eastern region, the average green innovation efficiency was higher than the national average. Thus, we found that development of regional green innovation was uneven, being strong in the east and weak in the west. This is roughly the same as the findings of Wang 2019) , which i , which Second, using environmental protection input as the threshold variable, we found that the effect on green innovation efficiency was significant at the 1% statistical level, which supported a double-threshold effect. The effect of environmental regulation on green innovation efficiency is an inverted N-shape: first inhibiting, then promoting, and finally inhibiting. In provinces with environmental protection investment below the first threshold, for example, Shanghai, Tianjin, and Jilin, and other provinces and cities that accelerated industrial transformation and upgrading during 2017–2019, environmental regulation played an inhibitory role in green innovation efficiency but did not pass the significance test, probably because regions below the first threshold, whose governments did not focus on the treatment of environmental pollution during 2017–2019, invested less in environmental protection. The relationship between the intensity of environmental regulation, green innovation efficiency, and environmental protection investment was not strong in this period. Regions between the two thresholds, such as Guangdong and Qinghai, responded to the call of China’s 12th and 13th Five-Year Plans during the sample period to strengthen the cooperation among resources, finance, trade, and tourism to maximize the benefits and increase the investment in environmental protection, which, in turn, stimulated local green innovation. In this case, environmental regulation played a main role in promoting the efficiency of green innovation. In regions where environmental protection investments exceeded the second threshold, such as Beijing, Jiangsu, Zhejiang, Fujian, and other economically developed eastern regions, local governments had sufficient funds to invest in environmental protection, but environmental regulations inhibited green innovation efficiency at this time, probably because as the demand for investment in environmental management increased, funding support for green innovation technologies was neglected or reduced due to the uneven distribution of funds. Our conclusion regarding this inverted N-shaped relationship is identical to that found by Shen (2022) [Third, when fiscal decentralization was used as the threshold variable, it had a significant effect on green innovation efficiency at the statistical levels of 10% and 1%. This indicated a double-threshold effect, where the effect of environmental regulation on green innovation efficiency showed an inverted N-shaped relationship of first inhibiting, then promoting, and finally inhibiting. For the green innovation efficiency for provinces with fiscal decentralization below the first threshold, such as Heilongjiang, Jilin, and Liaoning, environmental regulation had a significant inhibitory effect on green innovation efficiency, probably because of the persistent low regional GDP due to overcapacity, and the special decentralization system of “responsibility at the grassroots and purse at the top”, which is characteristic of Chinese fiscal decentralization. This results in a small degree of regional fiscal decentralization, and the local governments do not have enough funds to attract dynamic green innovation enterprises, which inhibits the development of green innovation. This is broadly similar to the conclusion of Dong (2022) , who argWe measured the green innovation efficiency in China through a DEA-SBM model, and we empirically analyzed the results based on the panel data of 30 provinces in China from 2011 to 2020 to explore the threshold effect of environmental protection input and fiscal decentralization in environmental regulation, affecting green innovation efficiency. The results are as follows:First, from 2011 to 2020, the green innovation efficiency of Chinese provinces was trending upward, and the level of green innovation efficiency in each region was spatially heterogeneous, being strong in the east and weak in the middle and west.Second, we found a nonlinear relationship between environmental regulation and green innovation efficiency for the 30 provinces and cities in China during 2011–2020. We identified a double-threshold effect with environmental inputs as the threshold variable, as well as an inverted N-shaped relationship between environmental regulations on green innovation efficiency.Third, we found a double-threshold effect with fiscal decentralization as the threshold variable, with an inverted N-shaped relationship between environmental regulations and green innovation efficiency.Based on the results of the empirical analysis, we developed the following policy implications from the perspective of improving ecological and environmental protection and enhancing the efficiency of regional green innovation:First, the following are required: improving local ecological and environmental protection measures, completing the local budget management system, and establishing a system of synergistic development between them. We should improve the local government’s budgetary expenditure management system and increase the scale and proportion of special funds for environmental protection according to local resources and advantages, as well as improve the reasonable supervision system. At present, the Chinese budget monitoring system is not sufficiently transparent and binding, so local governments may divert funds meant for ecological and environmental management to other projects to improve their performance. Additionally, we should establish an ecological and environmental management system with synergy among economic and ecological development, so that each local government can ensure the implementation of effective environmental protection measures according to its characteristics and stimulate the enthusiasm to engage in ecological and environmental management. While promoting Chinese economic development from the stage of high-speed growth to the stage of high-quality development, we should create appropriate defenses of the environmental ecosystem.Second, an incentive policy for differentiated green innovation should be formulated to guide the synergistic development of regional scientific and technological innovation and environmental protection, as well as to strengthen regional innovation capacity building and talent training. During the sample period in this study, the eastern region of China had the highest green innovation efficiency; thus, the eastern region should use its regional advantages to encourage the increase in independent innovation capacity and advocate for the environment to promote the green innovation efficiency while stabilizing the high-quality economic development. The central and western regions in China had lower green innovation efficiency, based on which they should use their rich resources and technological opportunities to increase the regional environmental protection efforts. Based on the economic development trend, they should break the original fixed pattern and expand incentive policies, such as by increasing policy preferences, introducing scientific and technological talent, orienting and training scientific and technological talent, and attracting high-tech environmental management technologies from other developed countries to provide personnel and policy guarantees for the development of regional green innovation projects and fully use the technology spillover effect to promote the achievement of the dual carbon goals.Third, the Chinese fiscal decentralization system should be improved, the construction of a modern fiscal system should be accelerated, and the reform of the fiscal and taxation system should be deepened. Additionally, the division of fiscal affairs and responsibilities between the central and local governments should be completed. Either too low or too high a degree of fiscal decentralization will inhibit green innovation efficiency. Therefore, the central government’s commitment to providing basic public services should be moderately increased, the central government’s direct involvement in grassroots finance should be reduced, and the local government’s fiscal freedom should be controlled within a reasonable range. Moreover, the local government should completely fulfill its responsibility for affairs within the central government’s authorization, take advantage of its knowledge of local resources and development, and manage their affairs according to local conditions to better focus on the goal of achieving green and low-carbon goals and promoting the efficiency of green innovation.Fourth, we should control the strength of environmental regulations and add fiscal and taxation policies and environmental protection investments to promote the efficiency of regional green innovation, ensure the sustainability of environmental regulations, and avoid too strict and too quick enforcement. Therefore, we must implement appropriate environmental regulation policies for regions with different economic development conditions; effectively increase the investment in human, capital, and energy; increase the policy support for the research and development of low-carbon and green innovation technologies; and increase the application and promotion of these technologies to help promote green development strategies, along with high-quality economic development.Due to the constraints of data availability and study length, this study has certain shortcomings that can be further explored in the future, mainly in the following aspects: First, the relationship between the intensity of environmental protection inputs, the intensity of fiscal decentralization, and the green innovation efficiency, such as regional and spatial distribution patterns, still needs to be further explored. Second, environmental regulation has mainly been measured from two aspects: intensity and effect. In this study, we only considered one aspect: the intensity of environmental regulation. In future studies, we can measure environmental regulation from different perspectives to further improve our understanding of the mechanism through which environmental regulation impacts green innovation efficiency.


Cognitive function represents a complex neurophysiological capacity of the human brain, encompassing a higher level of neural processing and integration. It is widely acknowledged that the cerebrum plays a commanding role in the regulation of cognitive functions. However, the specific role of the cerebellum in cognitive processes has become a subject of considerable scholarly intrigue. In 1998, Schmahmann first proposed the concept of “cognitive affective syndrome (CCAS),” linking cerebellar damage to cognitive and emotional impairments. Since then, a substantial body of literature has emerged, exploring the role of the cerebellum in cognitive neurological function. The cerebellum’s adjacency to the cerebral cortex, brainstem, and spinal cord suggests that the cerebral-cerebellar network loops play a crucial role in the cerebellum’s participation in cognitive neurological functions. In this review, we comprehensively examine the recent literature on the involvement of the cerebellum in cognitive functions from three perspectives: the cytological basis of the cerebellum and its anatomical functions, the cerebellum and cognitive functions, and Crossed cerebellar diaschisis. Our aim is to shed light on the role and mechanisms of the cerebellum in cognitive neurobrain networks. Cognitive function represents a complex neurophysiological capacity of the human brain, encompassing a higher level of neural processing and integration. According to a systematic analysis conducted by From an evolutionary standpoint, studies have indicated a relatively consistent ratio between the number of neurons in the cerebral cortex and the cerebellum, with an average of 3.6 across the 19 species analyzed. When significant evolutionary changes occur in the number of neurons in the cerebral cortex, there is a corresponding adjustment in the number of neurons in the cerebellum, suggesting a self-organizing mechanism. The cortico-ponto-cerebellar projection emerges as a plausible mechanism for facilitating the numerical congruence between neurons in the cerebral and cerebellar cortices . FurtherCerebellar damage frequently gives rise to a diverse range of cognitive dysfunctions. In light of this, our hypothesis posits that the cerebellum exerts influence on specific cerebral regions via the cerebro-cerebellar loop, thereby contributing to cognitive dysfunction. Several research methods, including neuropsychology, electroencephalography (EEG), and functional magnetic resonance imaging (fMRI), have effectively delineated the specific brain regions accountable for cognitive functions, as well as the interconnections between these regions, thereby establishing the brain network. In their study, Contemporary research has revealed the involvement of the cerebellum in a multitude of functions, encompassing motor, cognitive, emotional, and social domains . The cerRecent research has presented compelling evidence regarding the impact of cerebellar lesions on the cerebrum. However, a comprehensive exploration is still needed to unveil the precise influence of the cerebellum on the cerebrum and the specific cognitive functions that are affected. Previous investigations have primarily focused on examining the cognitive functions associated with individual brain regions while neglecting the crucial interplay among these regions within neural networks. Thus, the objective of the present study is to address this gap by investigating the neural networks that connect the cerebellum and the cerebrum.From a cytological perspective, the cerebellum is comprised of two main types of cells: cerebellar cortical neurons and deep cerebellar neurons. Deep neurons are primarily involved in basic muscle coordination, whereas neurons in the cerebellar cortex are responsible for regulating, connecting, and maintaining higher cognitive functions, such as memory. Mossy fibers serve as excitatory afferent fibers within the cerebellum. They transmit information from the spinal cord, pontine nucleus, and reticular nucleus of the brainstem to the granule cells in the granular layer. The granular layer also contains Golgi cells, which secrete GABA transmitters to inhibit the activity of granule cells. Climbing fibers, another type of excitatory afferent fiber, form direct synapses with the dendrites of Purkinje cells. They play a critical role in learning and working memory in humans. The molecular layer of the cerebellum houses two types of inhibitory interneurons: astrocytes and basket cells. These interneurons have axons that form synapses with Purkinje cell dendrites, thereby regulating the activity of Purkinje cells. Purkinje cell axon terminals predominantly terminate within the cerebellar nuclei, representing the sole efferent fibers originating from the cerebellar cortex. The cerebellar function relies significantly on the orchestrated activity of granule cells and Purkinje cells . GranuleFrom an anatomical perspective, the cerebellum consists of the left and right hemispheres, along with the cerebellar vermis situated in the middle. It can be further divided into three lobes based on distinctive grooves and fissures: the anterior lobe, the posterior lobe, and the flocculonodular lobe. Alternatively, Schmahmann’s classification categorizes the cerebellum into 10 lobes, with lobes I through V comprising the anterior cerebellar lobe, lobes VI through IX forming the posterior cerebellar lobe, and lobes X constituting the flocculonodular lobe. Additionally, a particular study has revealed that lobule VII, which encompasses approximately 48% of the human cerebellar cortex and is located in the posterior lobe, exhibits an increase in size in correlation with higher cognitive abilities . By emplCerebellar lesions can occur in various locations, leading to distinct clinical manifestations in patients with cerebellar injury . SeveralIn addition to having distinct anterior and posterior lobe functions, the cerebellum also exhibits some lateralization in the cognitive processes of its left and right hemispheres. The Addenbrooke’s Cognitive Test ACE III and the Pathway Test TMT were used to assess cognitive function in 31 patients with localized cerebellar lesions and 31 healthy volunteers. It was discovered that patients with left-sided cerebellar lesions were impaired in the attention and visuospatial domains, while patients with right-sided cerebellar damage had deficits in general cognitive function . The resThe anatomical structure plays a crucial role in determining its function to a significant extent. The left and right hemispheres of the brain exhibit distinct functions, while demonstrating interconnections with the cerebellum, thereby forming cerebrum-cerebellum networks. Consequently, it can be ascertained that the left and right hemispheres of the cerebellum exhibit discrepant functions. Additionally, the cerebellar structure comprises anterior and posterior lobes, which are further subdivided into 10 lobules. Presently, research has solely elucidated the functions of select lobules within this complex. Nevertheless, with the extensive application and advancement of neuropsychology, neurophysiology, and fMRI, we anticipate the revelation of additional insights into the functionality of the cerebellar lobules.A large number of studies have shown that the cerebellum is involved in cognitive functions such as visuospatial, attention, execution, working memory, and language. Below we will discuss in detail which neural functions the cerebellum is involved in and the neural regulation mechanism of the Cerebro-cerebellar networks.The capacity to assess and incorporate spatial data is referred to as the visuospatial function. As a result, defective spatial analysis or integration results in impaired spatial perception and behavior, which is what is meant by visuospatial dysfunction. Visuospatial dysfunction clinically usually includes impairments in visuospatial perception, visuospatial construction, and visuospatial memory .Cortical and subcortical regions are responsible for maintaining the function of visuospatial processing. Visual information normally travels from the retina through the thalamus to the occipital cortex , from there it travels by ventral and dorsal fibers to the frontal cortex . MolinarRecent research has unequivocally established the role of the cerebellum in visuospatial function, particularly in relation to the frontoparietal lobe. However, there is still insufficient evidence to pinpoint the exact cerebellar lobule that is involved. Consequently, exploring this aspect in greater detail could be pursued as a promising avenue for future investigations within this field.According to cognitive neuroscience, the higher cognitive function of attention plays a crucial role in effectively allocating the brain’s processing resources to relevant stimuli . Posner The cerebellum has been identified as a critical component in the functioning of visual attention, as demonstrated by studies conducted by In their study, The aforementioned studies provide evidence supporting the involvement of the cerebellum in the attentional network. Nevertheless, the precise connectivity between the cerebellum and the dorsal and ventral attentional networks remains unclear. It is hypothesized that the cerebro-pontocerebellar-cerebellar loop may play a crucial role in this regard, and its exploration can be facilitated through the use of diffusion tensor imaging. By employing such methods, a more comprehensive understanding of the anatomical connections between these networks can be achieved.Executive Functions (EF) is a conceptual framework that encompasses a diverse array of sub-cognitive neural functions, including but not limited to working memory, inhibitory control, cognitive flexibility, planning, reasoning, and decision-making .The involvement of the cerebellum in the regulation of EF remains a topic of ongoing debate and lacks consensus among researchers. Multiple studies have consistently identified the frontal lobe as a crucial node within the executive control network, alongside the cerebellum. Nevertheless, the specific circuits and connections through which the cerebellum participates in the activation of the executive control network remain unclear. Considering this, there is a growing hypothesis that the pontine brain and thalamus may serve as crucial intermediaries in facilitating communication between the cerebellum and other components of the executive control network. Further research is warranted to explore these potential pathways and shed light on the intricate interactions between the cerebellum, pontine brain, thalamus, and the executive control network.Working memory plays a crucial role in various cognitive neuropsychological activities, including reading, comprehension, and learning. The term “working memory” was coined by Miller in 1960, and since then, both Miller and Baddeley have made significant contributions to its development. In 1974, Baddeley proposed the concept of working memory and has continued to refine it over the years. In his 2005 research, Baddeley likened working memory to a storage system, wherein information is initially perceived by the sensory system, temporarily stored in the limited-capacity short-term memory, and eventually transferred to long-term memory for permanent storage. The frontoparietal lobe, which serves as the primary cerebral cortex for the maintenance of working memory and as the source of top-down signals, has been extensively studied in relation to the regulatory mechanisms of working memory neural networks. It exerts influence on how working memory is processed in other cerebral cortex and subcortical regions . Zhao etWhen a participant is exposed to an external stimulus, fMRI is commonly utilized to identify neural activity and the activation of functional regions in the relevant areas of the cerebral cortex. In a study conducted by To explore the relationship between the cerebellum and working memory, Seese conducted a comprehensive literature search using specific search phrases in MEDLINE and PubMed. The search focused on articles published between October 1, 2019, and January 8, 2020, encompassing systematic reviews, meta-analyses, thematic reviews, original research reports, and case reports. The study primarily targeted children as the study population, with a specific emphasis on acquired cerebellar diseases, cerebellar malformations, and genetic/developmental disorders of the cerebellum. This meticulous search aimed to facilitate a pooled analysis of existing research on the cerebellum and its involvement in working memory. Notably, working memory impairment emerged as a prevalent symptom in childhood cerebellar diseases, indicating the crucial role of the cerebellum in working memory function . In a prBased on the findings of these studies, it is proposed that the frontoparietal lobe, LOC, and cerebellum serve as primary brain regions involved in the regulation of the working memory network. Across different age groups, the cerebellum consistently demonstrates significant involvement in modulating working memory functions. Additionally, the close association between the cerebellar lobule VIIb/VIIIa and the frontoparietal brain network underscores their interconnected roles in working memory processes.Language processing involves the collaborative contribution of both cortical and subcortical regions. Traditionally, language function was believed to primarily rely on the frontal cortex (Broca’s area) and the superior temporal cortex (Wernicke’s area) within the cerebral cortex . HoweverTani and Sakai proposed the idea that cerebellar lesions could disrupt speech, based on a case study of a male patient with neurogenic stuttering caused by cerebellar infarction. Interestingly, the patient did not exhibit stammering after thalamic hemorrhage and frontal infarction but developed stuttering following cerebellar infarction . The neuReading is a fundamental aspect of language, and assessing reading ability typically involves employing various methods such as orthographic, phonological, and semantic tasks. The current body of research highlights the intricate involvement of the cerebellum in both motor and language functions. However, it remains uncertain whether the language function of the cerebellum represents an independent cognitive function or is closely intertwined with motor processes. It is important to note that motor abilities form the foundation of language, and extensive evidence from studies on individuals with cerebellar damage demonstrates impairments in both language and motor function. These findings from human research contribute valuable insights to our understanding of the role of the cerebellum in language function. Furthermore, it has been observed that bilateral damage to the cerebellum can result in language dysfunction. The disruption of the cerebral-cerebellar language network is considered to be the primary underlying cause of cerebellar language impairments. This highlights the critical role of the interaction between the cerebellum and cerebral regions in supporting language processing and suggests that disturbances in this network can significantly impact language function.15O2 and 15O2 combined with PET. This innovative approach allowed for the observation and measurement of reduced blood flow and metabolism in the contralateral cerebellum following a unilateral supratentorial cerebral lesion. Crossed cerebellar diaschisis (CCD) is characterized by a decrease in blood flow and metabolism in the contralateral cerebellum due to a unilateral supratentorial cerebral lesion. This phenomenon, as described by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and 11C-Pittsburgh Compound B positron emission tomography imaging techniques to identify CCD in patients diagnosed with AD. The advancement of imaging technology has facilitated a growing body of research dedicated to the study of CCD. In their study, As far back as, Tien and Ashdown (1992) reported the presence of cerebellar atrophy in a substantial number of patients diagnosed with CCD. These patients often exhibited notable contralateral supratentorial hemisphere atrophy as well . Gupta eThe cerebrum and cerebellum are interconnected and work together as cooperative assemblies, rather than being separate entities. Cerebro-cerebellar neural network loops serve as the anatomical basis for the involvement of the cerebellum in higher cognitive functions. Current research has demonstrated that cerebellar damage often results in cognitive impairments in domains such as visuospatial abilities, attention, EF, working memory, and language. These deficits are likely attributed to disruptions in the intact cerebro-cerebellar neural network pathways associated with cognition. However, the precise role of the cerebellum in the construction of cognitive neurobrain networks remains unclear. The current body of research on cerebellar involvement in cognitive functions has some limitations. Firstly, many studies have small sample sizes, which may be due to the rarity of isolated cerebellar lesions and the predominance of single-center studies. Additionally, the research methods employed are relatively homogeneous, primarily relying on imaging techniques, which can be costly. These limitations highlight the need for larger-scale studies involving diverse populations and the exploration of alternative research approaches to deepen our understanding of the cerebellum’s role in cognitive processes. Although imaging methods are more intuitive to study the anatomy of brain networks, the study of specific brain networks is not sufficiently detailed in the temporal dimension. Event-related potentials (ERPs) are electrophysiological responses recorded from the scalp using EEG in response to specific stimuli or cognitive processes. The advantages of using ERP as a research tool are numerous. Firstly, ERPs are non-invasive, making them safe and well-tolerated by participants. Additionally, they offer high temporal resolution, allowing for precise measurement of the timing of cognitive processes in the brain. ERPs are also relatively low-cost compared to other neuroimaging techniques, making them accessible for research in various settings. Moreover, ERPs have demonstrated good reliability and are sensitive to individual differences, enabling the investigation of inter-individual variations in cognitive processing. Lastly, ERP studies can be conducted in multicenter settings, facilitating larger-scale investigations and increasing the generalizability of findings. Overall, ERPs provide a valuable and versatile tool for studying cognitive neural processing in the brain. ERPs have the potential to serve as valuable biomarkers in the medical profession, as they can provide detailed information about brain function that may not be captured by traditional clinical tools . HoweverPZ, LD, YO, QL, LC, HQ, JW, JZ, and XY performed the literature searches and contributed to draft versions of the manuscript. PZ and LD wrote and revised the final version of the manuscript. XY made important suggestions and Guidance on the writing and revision of the manuscript. All authors contributed to the article and approved the submitted version.


In the summer of 2019–2020, multiple states of Australia experienced catastrophic bushfires, with koalas being the main wildlife species rescued. Many suffered burns which affected all parts of their body, but particularly their footpads. It can be more difficult to assess the severity of burns in animals than in humans due to the variation in their foot morphology , and because fur covers the majority of their body. Here, we describe the clinical and microscopic findings of burns in koalas, following biopsies obtained from animals that were euthanised on welfare grounds after rescue from bushfire. We also describe microscopic findings in the lungs of koalas due to smoke inhalation. These findings will assist veterinarians involved with triaging koalas affected by burns and help predict if they are candidates for rehabilitation or if their prognosis is too poor.In the wake of increasingly frequent bushfires emerging as a threat to wildlife worldwide, koalas have notably been the most rescued species in Australia. However, our understanding of burns and their severity in koalas is limited; hence, this study investigated the histopathological features and depth of burns in koala skin, as well as the presence of smoke-induced respiratory tract damage. In four bushfire-affected koalas that had been euthanised on welfare grounds, skin burns in various body regions were scored based on clinical appearance as superficial, partial thickness, or full thickness. Histological sections of affected regions of skin were assessed as Grades I–IV and showed that furred regions on the ear margins and dorsum were histologically more severe, at Grade III, compared with the clinical score. There was a similar finding for footpad burns, which were the most common body region affected. In the respiratory tract, pulmonary oedema and congestion were evident in all koalas. Overall, the results highlight that cutaneous burn lesions on furred and palmar/plantar surfaces can have higher severity based on the burn depth than is clinically apparent. Therefore, there is a need to consider this when developing treatment plans and establishing prognosis for burnt koalas at triage, as well as that a high likelihood of pulmonary oedema exists. Phascolarctos cinereus) accounted for 75% of rescued animals [In the summer of 2019–2020, multiple states of Australia experienced catastrophic bushfires affecting over 3 billion native vertebrate animals [ animals ,5, as hu animals  and may In dogs and cats, a clinical scoring system of 1–3  is used , based oFire victims also often have smoke inhalation damage in both the upper and lower airways, primarily causing pulmonary oedema. This may result in signs of respiratory distress, such as tachypnoea, dyspnoea, open-mouth breathing, or frothy nasal discharge . ProteinIn koalas, previous reports of burns in bushfire-rescued animals highlight smoke inhalation and burns to the footpads ,9,10, whUltimately, only skin histology can accurately assess the degree of the burn by characterising the pathological changes in the epidermis, dermis and hypodermis as reported in experimental animal models , but thiOn 24 January 2021, a bushfire in Cherry Gardens in the Mount Lofty Ranges, South Australia, burnt through 2700 ha of scrub and grassland. Four wild koalas that were euthanised on welfare grounds were received the following week and stored frozen for necropsy examination. Due to claw abnormalities being noted, prior to necropsy, radiographs were taken of the fore and hind digits of three of the koalas. Age was estimated according to the tooth wear class (TWC) method on the basis of dental wear of the fourth upper premolar . Body coAt necropsy, burn depth was scored as superficial, partial thickness or full thickness based on clinical appearance. This scoring system aligned with that used in burn severity assessment in Kangaroo Island koalas, as reported in Dunstan et al. (2021), based on the system used in dogs and cats . SamplesHistologically, cutaneous burn lesions were scored as Grade I , Grade IIa , Grade IIb , Grade III  and Grade IV  .Of the four bushfire-affected koalas examined, three were female and one was male. A summary of the tooth wear class, estimated age, body condition score and weight of koalas is shown in The footpads were the most consistently burnt part of the body of the examined koalas.For koala K21-047, the fur was singed all over the body, and the nostrils and pinna margins recorded as superficial-thickness burns a. BilateThe palmar surfaces were intact, with the claw of digit IV on the left having a blunted tip, and the claws of digits III and IV on the right having increased erythema on the concave surface. The left distal plantar surface of the footpad and digits I, IV and V were scored as having superficial-thickness burns. The entire right plantar surface, including all digits, was affected by superficial burns with partial-thickness burns on the lateral aspect. In the respiratory tract, serosanguinous froth and soot particles were present in the trachea, and congestion affected all lung lobes, particularly the right middle and caudal lobe margins.Koala K21-048 presented with soot particles around the nostrils and mouth and an erythematous nasal planum. Soot particles were also noted on the chest and rump. The claw of digit III on the right fore limb had a blunted tip. The distal region of digit I on the right hind showed sloughing of the superficial skin, whilst superficial burns covered the entire left plantar surface, including the digits, with regions of partial-thickness burns on the distal, proximal and lateral plantar surface a. The luKoala K21-050 was recorded with soot around the nostrils and mouth, and on the chest, upper fore limbs, dorsum of the trunk and rump. The central region of the right palmar surface, including that of digits III–V, was noted to have superficial-thickness burns. Similarly, the left palmar surface of digits III–V showed superficial burns, with proximal involvement of the palm. The claw of digit III showed a blunted tip, and the claw of digit IV was missing. The left plantar surface showed superficial burns on the lateral half with a small localised partial-thickness lesion centrally. The distal phalanx of digit V was fractured and displaced at the base of the claw. The entire right plantar surface showed superficial burns which extended to the plantar surface of digits II–V. The lung lobes were congested, particularly on the margins.Koala K21-057 presented with superficial burns to all four footpads. There were small regions of superficial burns on the palmar surface of left digits I and III–V, whilst the entire right palmar surface of digit IV was superficially burnt with small regions on digits III and V. The tip of the claw of digit V was blunted. The left plantar surface of digit V showed superficial-thickness burns, with a small region on digit IV. The right lateral plantar surface skin was sloughed and there were small regions of superficial-thickness plantar surface burns on digits II–V and the base of digit I. The lung lobes showed areas of congestion.Burn Grades I–III were observed in skin sampled from affected koalas in the selected sites , with trIn Grade IIb lesions, there was diffuse coagulative necrosis of all layers of the epidermis characterised by loss of cellular and nuclear detail and superficial dermal pallor and variable basophilia, with only deep adnexal structures remaining viable. Fibrin exudation was variable. Grade IIb lesions were the least commonly observed, being found on one footpad only.Grade III lesions were the most common, being seen in the footpads of three koalas and the pinna and dorsal skin over the left and right iliac crest regions in one koala (K21-047) b. Grade Radiologic examination of the digits of K21-047 showed mild acro-osteolysis of the distal phalanx of digits III and IV  of the rIn the lungs of all four koalas, diffuse alveolar congestion was observed with variable flooding of airways by translucent eosinophilic protein-rich oedema fluid, which was interpreted as alveolar injury and increased vascular permeability . LymphatOur study describes the characteristics of burn injuries to the skin of both the furred and unfurred body regions, and the respiratory tract, in euthanised koalas rescued from bushfire. The most common and severe areas of burn injury in koalas occurred in the plantar footpad skin of the hind limbs, likely due to their descent from trees to the scorched ground. Clinical assessment of burn depth often underestimated burn severity, particularly in the furred skin regions, according to the histopathologic assessment, which found that more severe damage of deeper cutaneous structures had occurred. This demonstrates the difficulty in assessing burns in animals, as reported by previous studies ,5. DamagThe clinical appearance of the burns of the four koalas varied from superficial to partial thickness, and microscopically, between Grade I and III. The most notable differences between clinical and histopathological scores occurred in the furred regions of koala K21-047. At necropsy, superficial burns on the ear margins were observed; however, the histopathological evaluation was Grade III. Similarly, for the dorsal skin over the left and right iliac crest regions of the same animal, the histopathological grading was Grade III, while the clinical assessment determined superficial- to partial-thickness burns. It is possible that the burn severity in these furred regions is difficult to visualise at clinical examination, and that the dense fur increases the heat convection, worsening the burn damage to deeper layers of the skin. Also, partial-thickness burns in dogs and cats can often create an exterior leathery eschar over several days. This makes it difficult to distinguish partial-thickness from full-thickness burns until this outer partial-thickness eschar separates , which cFor the plantar surfaces, the clinical assessment score of burn severity was lower than that established with histopathologic grading, which was Grade III or transitioning from Grade II in most cases. The lateral plantar surface was particularly prone to deep burns, which may reflect the weight-bearing stance of koalas, given their syndactyly of digits II and III . For K21The distal digits and claws were examined radiologically and histologically based on abnormalities of the claws noted at necropsy, such as blunted claw tips that appeared to be ‘melted’ and erythema. Anecdotally, claws are often lost in rehabilitating koalas in the weeks and months following footpad burns, and blunted or melted ends of claw tips have previously been observed (author obs.). Claw loss in burnt koalas mirrors that which occurs in other species, such as the loss of hooves in burnt livestock . In K21-Consistent findings from lung tissue were pulmonary oedema and congestion, possibly due to distal migration of upper airway material and the actions of systemic inflammatory mediators (mainly neutrophils) causing damage to the lower respiratory tract when hot air and smoke is inhaled ,5,17. KoPrevious studies in other animal species have shown that burn wounds to the skin covering less than 20% of the total body surface area (TBSA) can be regarded as local burns, and patients with more than 20% are more likely to develop life-threatening metabolic disturbances. Burns that encompass more than 50% are considered incompatible with survival . This meThis study identified that cutaneous burn lesions in koalas may be more severe than is apparent upon clinical examination, in both the furred regions of the body as well as the palmar and plantar surfaces (footpads). The plantar surfaces were most commonly affected, particularly on the lateral aspect, and this may extend to the distal phalanges, resulting in claw loss due to heat damage. A koala-specific chart for TBSA calculation for koalas that emphasises the importance of palmar/plantar surfaces is much needed, and if used in conjunction with assessment of burn depth, should improve veterinarians’ ability to predict prognosis for koalas. The likelihood of concurrent pulmonary oedema should also be considered alongside visible burn lesions in the assessment of koalas in the triage and rehabilitation phases.


Microbial nanotechnology, microorganisms-driven nanobiotechnology, is an emerging area of microbiotechnology that has leveraged biotechnological processes. Bioprospecting of microorganisms enables the production of a plethora of diverse nanoscale materials such as organic nanomaterials, metals, and their oxide nanomaterials, etc.  and a pathogenic bacterial load of Aeromonas hydrophila in the Nile tilapia fish, Oreochromis niloticus. Further authors recommended that the biogenic selenium nanoparticles may be ideal for use in the polluted water to minimize the side effects of pathogenic microbes and heavy metals; and thus, enhancing the productivity of the aquaculture industry.Impact of heavy metals and pathogenic bacteria can be minimized for the sustainable aquaculture industry with the advent of green nanotechnology. In this regard, Narware et al.). Narware et al. developed the facile methodology for the production of silver nanoparticles of size 48 nm with the aid of Trichoderma harzianum culture filtrate. The culture filtrate was enriched with bioactive molecules for providing the capping agent for the biosynthesis of robust silver nanoparticles. Silver nanoparticle validity was done using the advanced microscopy and spectroscopy techniques such as UV-Vis, FTIR, EDX, XRD, DLS, AFM, and SEM. Further, the given nanoparticles gave better anti-fungal results for in-vitro and in-vivo treatments to inhibit the pathogenic fungus namely Alternaria solani responsible for the late blight disease. The authors have demonstrated the anti-fungal effects of green silver nanoparticles more than the standard fungicide. Thus, this leads to an encouraging outcome in the near future to explore the fully biosynthesized green nanoparticles over the chemically synthesized fungicide.Fungal infection to the agricultural crops can lead to the severe loss to the agriculture productivity. Recently, the agricultural industry can be protected against the fungal infection with the aid of green nanotechnology (Altammar) discussed the critical survey for the production of metallic nanoparticles and their associated challenges in agri-food industries, medicine industry, defense industry, environment, electronics industry, and automotive industry. Ogunyemi et al. employed an innovative approach for developing the biogenic nanoparticles. Magnesium oxide (MgO) nanoparticles and manganese oxide (MnO2) nanoparticles and of sizes 12.5 and 9.8 nm, were biosynthesised using the lysate of Xanthomonas oryzae pv. oryzae (Xoo) bacteriophage X3 with the target application to plant protection from the bacterial pathogenic. Researchers investigated the minimize the ill-effect of bacterial leaf blight disease that causes yield loss of rice plants, the staple food of the region. The physicochemical characterization of bacteriophage mediated nanomaterials were characterized using sophisticated spectroscopy and microscopy methods. The authors have employed the chlorophyll fluorescence to determine the safety/toxicity of these nanoparticles to the plants. Thus, authors have successfully demonstrated the effective alternative biogenic production of MgO and MnO2 nanoparticles to circumvent the plant bacterial disease without any phytotoxic effect.Researcher . Researchers discussed the detailed production strategies with the potential applications of bioactive molecules. Further toxicological effects of zinc oxide nanoparticles on the environmental ecosystem were discussed. Furthermore, the potential applications of ZnO NP in different sections such as anti-bacterial, anti-fungal, anti-cancer, antioxidant activity, photocatalytic activity, drug delivery system, wound healing. The authors have discussed the production of intracellular and extracellular methods of nanoparticles production. The researchers have also highlighted the limitations as well as exact role of reproducibility of ZnO NP synthesis due to unavailability of stable microbes that further requires a rigorous screening method for the selection of robust microbes.Microbial nanotechnology is still in the infancy stage that has provided the vast opportunities for further explorations and innovations. The present Research topic demonstrated the impacts of microorganism driven nanotechnology for improving the processes of agri-food industries. And further microbial technology provides the green technologies for sustainable environment by detoxification and neutralization of the toxic waste materials. As per the above discussed research, it is clearly demonstrated that the role of green/microbial nanotechnology is expanding in diverse areas ranging from food to the environment. The results found at the laboratory scale is quite interesting. However, the massive scale production of these nanoparticles is the need of the hour. Thus, it may be concluded with the recently completed studies, that microbial nanotechnology will be a boon for the sustainable commodity production in near future.MV: Conceptualization, Writing—original draft, Writing—review and editing. PJ: Writing—review and editing. DS: Writing—review and editing.


The incidence of gastroesophageal junction adenocarcinoma has gradually increased. Proximal gastrectomy or total gastrectomy is recommended for early gastric cancer of the upper third of the stomach. Because total gastrectomy is often accompanied by body mass loss and nutrient absorption disorders, such as severe hypoproteinemia and anemia, Proximal gastrectomy is more frequently recommended by researchers for early upper gastric cancer (T1N0M0) and Siewert II gastroesophageal junction cancer less than 4 cm in length. Although some functions of the stomach are retained after proximal gastrectomy, the anatomical structure of the gastroesophageal junction can be destroyed, and the anti-reflux effect of the cardia is lost. In recent years, as various reconstruction methods for anti-reflux function have been developed, some functions of the stomach are retained, and serious reflux esophagitis is avoided after proximal gastrectomy. In this article, we summarized the indications, advantages, and disadvantages of various classic reconstruction methods and latest improved reconstruction method including esophageal and residual stomach anastomosis, tubular gastroesophageal anastomosis, muscle flap anastomosis, jejunal interposition, and double-tract reconstruction. Gastric cancer is one of the most common malignant tumors globally. In 2018, gastric cancer ranked fifth and third among malignant tumors in global incidence and mortality, respectively. China accounted for 44.1% and 49.9% of the global incidence and mortality of gastric cancer, respectivelyIn 1897, Mikulicz performed esophageal and residual stomach anastomosis for the first time  should be retained Table .Shiraishi et al.Tubular gastroesophageal anastomosis forms a structure similar to the gastric fundus at the top of the residual stomach, avoiding direct reflux to the lower end of the esophagus to a certain extent. Part of the gastric antrum is resected for the tubular stomach, thus reducing the secretion of gastrin and gastric acid, maintaining the anatomical structure of the stomach, and improving the quality of life of patients, but the incidence of reflux esophagitis remained higher Table .In 1998, Kamikawa designed the double-flap technique, also known as the Kamikawa method Figure A, to preTo overcome the shortcomings of complicated double-flap anastomosis, difficult surgical procedures, long operative times, and high rates of postoperative anastomotic stenosis, Peng et al. performed right open single-flap anastomosis after laparoscopic PG, finding that single-flap anastomosis had a simple procedureThe anastomotic stoma of the esophagus and stomach with a muscle flap is wrapped into a soft valve that acts as a one-way valve with good anti-reflux effects. The anastomotic stoma was wrapped with a seromuscular layer, resulting in a low incidence of anastomotic leak. However, muscle flap anastomosis has a complicated procedure, high requirements for suture technology, and a long operative time, thus increasing the incidence of anastomotic stenosis Table .Jejunal interposition aims to restore the connectivity between the esophagus and residual stomach by inserting a section of jejunum between the esophagus and residual stomach and build an anti-reflux barrier between the residual stomach and esophagus using the tolerance of the jejunum itself to acidic gastric juice and alkaline intestinal juice and the natural peristalsis of the intestine. In 1941, ZhenxinThis method has low requirements concerning the size of the residual stomach, and it is suitable for reconstruction after most PG procedures. However, because of the complicated operative procedure, long operative time, and high cost, the possibility of emptying obstruction and internal hernia increasesIn 1988, Aikou et al.Later, Aikou et al. improved the traditional double-tract reconstruction technique. Namely, after PG, esophagojejunostomy is performed behind the colon and residual stomach, and jejunostomy is performed at a distance of approximately 40 cm from the distal end of the anastomosis. The residual stomach is rotated 180° before anastomosis and restored to its normal position after anastomosis. The jejunum is “N”-shaped around the gastrojejunal anastomosis Figure A, allowiDouble-tract reconstruction is applicable to reconstruction of the digestive tract after most PGs. It has low requirements concerning the volume of the residual stomach, and it is applicable to patients who have undergone an excessive number of gastrectomies and who are not suitable for esophageal and residual stomach anastomosis. However, this surgery is relatively complicated and expensive, and it results in many anastomoses, which might increase the risk of anastomotic leak.Since the development of digestive tract reconstruction after PG, various improved methods have been introduced. Each reconstruction method is constantly changing and improving. Each reconstruction method has its own advantages and disadvantages. Although no uniform standard is available at present, in clinical practice, all surgeons have their own unique experience and thinking regarding the available reconstruction methods. Understanding the operating points and advantages and disadvantages of various digestive tract reconstruction can provide ideas for surgeons to make correct clinical decisions.


Apis mellifera) colonies and wild bees. Additionally, host–pathogen interactions that impact bee health are part of a multifactorial framework that involves dynamically balancing an array of threats and resources that interact at multiple levels of scales.Understanding the health status of bees is crucial in assessing the epidemiology of pathogens that cause diseases in honey bee , and black queen cell virus (BQCV) were found in both genotypes, environmental factors did not have a significant effect on the parasitism or infection intensity of colonies of either genotype. Therefore, it was concluded that the primary factor influencing the resistance of honey bee colonies to DWV, BQCV, and V. destructor is the genotype of the colony itself, independent of climate [A study conducted in Mexico investigated the effect of genotype and climate on the resistance of European and Africanized honey bee colonies to parasitic and viral diseases. Although  climate .V. destructor and Nosema. Additionally, the viruses ABPV, DWV, Kakugo virus (KV), and Varroa destructor virus-1 (VDV1), which are typically transmitted via the trophic activity of Varroa mites, were found to be present in nearly all of the apiaries investigated, with a prevalence of approximately 100% [A monitoring program was carried out on a total of 115 colonies located in the Marmara region of Turkey, revealing the significant prevalence of N. ceranae, which exhibited distinct seasonal patterns. Furthermore, a weak but significant correlation was observed between the abundance of DWV and N. ceranae and the geographical longitude of the apiaries, with higher values in locations situated close to the eastern coast [A study was conducted in the Emilia-Romagna region of northern Italy, utilizing 31 apiaries to monitor the health status of managed honeybees. The most abundant pathogens identified were DWV, CBPV, and rn coast .N. apis and N. ceranae in 474 honey bee colonies across the Azores during the years 2014–2015. Subsequent spatiotemporal analysis until 2020 revealed the rapid expansion of N. ceranae in all islands in the archipelago, with the exception of Flores and Santa Maria, where the apiaries remained unaffected by either Nosema species [Molecular analysis was performed to assess the presence of both N. ceranae exhibited the highest degree of prevalence among pathogenic agents in apiaries situated in Bulgaria. The absence of N. apis, which is indigenous to Europe, suggests that it has been eradicated from the aforementioned apiaries [The microsporidian apiaries .Crithidia acanthocephali, which was first identified in the digestive tract of Hemiptera, has the capacity to inhabit the gastrointestinal tract of honey bees. By means of artificial inoculation with this trypanosomatid, it has been observed that the flagella undergo a transformation, resulting in the formation of an adhesive pad that enables the parasite to fasten itself onto the gut wall by way of hemidesmosome-like junctions. Nevertheless, the effects of this species on bee welfare and its pathogenic mechanisms remain to be elucidated [ucidated .Bombus terrestris, and workers with wing deformities were detected. All tested specimens were found to be positive for replicative DWV, but adults showing deformities exhibited higher viral abundance compared to asymptomatic individuals. Additionally, viral infections were detected in the heads of these affected individuals. A sequence analysis of the DWV amplicons obtained indicated that they were characteristic of a strain that had been previously isolated in the United Kingdom [The occurrence of DWV was assessed in three commercial colonies of  Kingdom .V. destructor infestations in beehives, namely the sugar roll test and carbon dioxide (CO2) injection. The findings of the study revealed that the sugar roll technique was significantly more efficient and less hazardous compared to CO2 injection and afforded greater accuracy when diagnosing V. destructor infestations [A comparative investigation was conducted to evaluate the sensitivity and diagnostic accuracy of two field techniques for detecting stations .Lactiplantibacillus plantarum and four strains of Apilactobacillus kunkeei, which were isolated from the gastrointestinal tract of honey bees, against Paenibacillus larvae and Melissococccus plutonius. The outcomes of the study underscored the antimicrobial, biochemical, and cell surface attributes of these lactic acid bacteria, which are promising probiotics for beekeeping and as biocontrol agents against both foulbrood diseases [In vitro assays were carried out to examine the inhibitory activity of four strains of diseases .Origanum heracleoticum L. essential oil against V. destructor. The results of the study indicated the marked efficacy of the essential oil against the mite, suggesting a possible alternative for use in the control of varroosis [An in vitro study was conducted to evaluate the contact toxicity, fumigation effectiveness, and repellent property of arroosis .Ascosphaera apis, the causative agent of chalkbrood. The oils that exhibited the highest efficacy were Thymus herba-barona, Thymus capitatus, and Cinnamomum zeylanicum, which demonstrated minimum fungicidal concentration and minimum sporicidal concentration values ranging from 200 to 400 ppm. Future investigations conducted in apiaries will facilitate the evaluation of the impact of these essential oils on bees and their potential residues in hive products [Ten essential oils derived from indigenous Sardinian aromatic plants were subjected to in vitro testing for their efficacy against products .