A female sable antelope with a history of gradual loss of body condition was found dead by the owner. Macroscopic examination revealed an enlarged spleen and liver that were covered in white-to-cream-coloured nodules. The uterus also showed a few small, white-to-cream-coloured nodules, with similar nodules present in other parts of the body. Microscopic analysis of sections of the uterus revealed tumour cells with an appearance that was similar those seen in sections of the other tissues. Critically, tumour cells were seen in the lymphatics within the lungs. The tumour cells in the uterus showed positive staining for cytokeratin as did the tumour cells in the sections of other tissues, confirming they were of epithelial origin. In addition, electron microscopy of the uterus and liver showed tumour cells arranged in groups with junctions present between the cells. This confirmed that the tumour cells seen in the liver were the same as those seen in the uterus and were of epithelial origin. Thus, a diagnosis was made of uterine adenocarcinoma with widespread metastasis. This is the first report of uterine adenocarcinoma in a sable antelope.Hippotragus niger) with a six-week history of gradual loss of body condition was found dead by the owner and presented for autopsy. Macroscopic examination revealed an enlarged spleen and liver with the hepatic and splenic parenchyma showing extensive infiltration with firm, white to cream-coloured nodules. The uterus showed a few small, firm, well-demarcated, white-to-cream-coloured nodules in the uterine body. Similar nodules were present in the mediastinum, parietal pleura, heart, and marrow cavity of the femur. Histological analysis of the uterus revealed densely cellular neoplastic proliferations, forming nests, tubules, and acini within an abundant fibrovascular stroma. The samples from the other tissues revealed neoplastic cells with a similar appearance to those seen in the uterus, also forming nests and acini in a fibrovascular stroma. Importantly, multiple neoplastic cells were also seen in the peribronchiolar lymphatic vessels. The neoplastic cells in the uterine sections showed positive immunohistochemical labelling for cytokeratin, as did the neoplastic cells in the sections of liver and parietal pleura, confirming they were of epithelial origin. In addition, transmission electron microscopy of the uterus and liver showed neoplastic cells arranged in groups surrounded by basement membranes and interspersed with collagen fibres. Junctions were present between the cells, and junctional complexes could be seen at some cell surfaces. This confirmed that the neoplastic cells seen in the liver sample were the same as those seen in the uterine sample and were of epithelial origin. Thus, a diagnosis was made of uterine adenocarcinoma with widespread metastasis. This is the first report of uterine adenocarcinoma in a sable antelope.A nine-year-old intact female sable antelope ( Cervus nippon) [Cervus elaphus nelsoni) [Uterine cancer is uncommon in domestic animals ,2 in con nippon) , and elknelsoni) , it has nelsoni) . In addinelsoni) . Furthernelsoni) . In addinelsoni) ,13,14, anelsoni) .Tragelaphus eurycerus isaaci) [Oryx dammah) [There are only two reports of uterine tumours in antelopes to date, including uterine leiomyomas in three captive eastern bongos ( isaaci)  and a ut dammah) . The lat dammah) . The preHippotragus niger) that was part of a herd with wireworm (Haemonchus contortus) infestation and had a six-week history of gradual loss of body condition was found dead by the owner. The sable antelope originated from a private game farm where the animals are kept in an extensive system consisting of large camps (20 ha) with natural vegetation and receiving some supplementary feeding during the dry winter months. She was born on the farm and had given birth uneventfully to six calves on a yearly basis since reaching reproductive maturity in 2008 until her death in 2014.In this report, a nine-year-old intact female sable antelope (Strongyloids-type ova (scoring 2+).The relatively fresh carcass of the sable antelope was presented for post-mortem examination. External examination found no abnormal lesions present on the skin; however, the body condition was poor (scored as 2/5). Macroscopic examination of the abdomen revealed an enlarged spleen and liver with multifocal-to-coalescing, firm, white-to-cream coloured-nodules a. The cuTM Polymer-HRP IHC Detection System  was used according to the manufacturer’s instructions. Sections were further incubated with a DAB chromogen  for 1–2 min, followed by routine counterstaining in Mayer’s haematoxylin, washing in running tap water, dehydration in alcohol and xylene, and coverslipping. All sections were examined by light microscopy by a veterinary pathologist. Standard transmission electron microscopy (TEM) was performed on selected tissue samples (uterus and liver). Briefly, the formalin-fixed samples were post-fixed in 1% osmium tetroxide in Millonig’s buffer, dehydrated through a graded ethanol series, infiltrated with a propylene oxide/epoxy resin mixture and embedded in absolute resin. Ultra-thin resin sections were stained with uranyl acetate and lead citrate and examined in a Philips CM 10 transmission electron microscope operated at 80 kV.Tissue samples from the uterus, heart, lung, pleura, mediastinum, spleen, liver, lymph node, and bone marrow were fixed in 10% buffered formalin, embedded in paraffin wax, and sectioned for histopathological evaluation. Sections (4 μm) were stained with haematoxylin and eosin (HE). Immunohistochemistry (IHC) was performed on selected sections to evaluate the expression of cytokeratin using a monoclonal mouse anti-human pan-cytokeratin antibody . After dewaxing, sections were treated with 3% hydrogen peroxide in methanol for 15 min, then enzymatic epitope retrieval using a protease solution  followed by incubation with the primary cytokeratin antibody at 1:400 dilution for one hour. Thereafter, the BioGenex Super SensitiveHistological analysis of all the affected organs were performed, and all the samples revealed similar changes that were characterised by densely cellular proliferations of neoplastic cells forming sheets, nests, and occasionally tubules and acini. The epithelial appearance in some areas came as a surprise since at necropsy, the most affected organ was the spleen, and at the time, the neoplasm was suspected to be lymphoid in origin. The uterine lesions that were originally interpreted as involuted caruncles revealed similar neoplastic cells that appeared to originate from the uterine glandular epithelium and displayed the same pattern as the other neoplastic foci a. In theThe mitotic rate was extremely high ranging from 15 mitoses per high power field in the primary tumour to almost 50 mitoses per high power field in some of the metastatic foci. Small areas of necrosis were occasionally interspersed between the neoplastic cells. Given the histopathological similarity of the neoplastic foci present in the different tissues to those seen in the uterus, it was suspected that the primary tumour was a uterine adenocarcinoma with widespread metastasis.Due to the scant cytoplasm and a mild degree of autolysis resulting in occasional cell distortion in some areas of the tissues, IHC and TEM were elected to confirm the epithelial nature of the neoplastic cells. In the uterine sections, the majority of the neoplastic cells showed strong cytokeratin-specific positive cytoplasmic labelling a as did TEM of the uterus and liver showed neoplastic cells with a similar appearance . The uterus showed neoplastic cells arranged in groups surrounded by basement membranes and interspersed with collagen fibres, adjacent to normal appearing endometrial glands. Intermediate filaments and lipid droplets were sometimes seen in the cytoplasm, attachments were present between the cells, and junctional complexes could be discerned at some cell surfaces a–c. The Hippotragus niger) is a gramivorous and folivorous savanna woodland species that is found in East and Southern Africa [The sable antelope  ,34 and uStudies on uterine adenocarcinoma in humans have shown it is a multifactorial disease, with many underlying factors playing a role in its development, including exposure to excess oestrogen and/or a relative lack of progesterone , and certain dietary factors, such as consumption of foods high in animal fats and sugars (as opposed to diets high in vegetables and fruits) . In humaThis is the first report of a uterine adenocarcinoma in a sable antelope and adds to the knowledge of the range of tumour types that can be developed by this species. In addition, the present case is an additional contribution to the very few histopathological reports of this tumour type in domestic and wild animals. Given the invasive nature of uterine adenocarcinomas and as such patients frequently have spread to the lungs and other organs at the time of presentation, metastatic uterine carcinoma should be added to the differential diagnosis of sable antelopes showing a generalised poor condition. It is hoped that further investigations of sable antelopes in wildlife reserves or zoological facilities will add to a better knowledge and understanding of the tumour types and pathologies developed by this species to aid in diagnosis and therapeutic options.


The zoonotic SARS-CoV-2 virus was present before the onset of the pandemic. It undergoes evolution, adaptation, and selection to develop variants that gain high transmission rates and virulence, resulting in the pandemic. Structurally, the spike protein of the virus is required for binding to ACE2 receptors of the host cells. The gene coding for the spike is known to have a high propensity of mutations, as a result generating numerous variants. The variants can be generated by random point mutations or recombination during replication. However, SARS-CoV-2 can also produce hybrid variants on co-infection of the host by two distinct lineages of the virus. The genomic sequences of the two variants undergo recombination to produce the hybrid variants. Additionally, these sub-variants also contain numerous mutations from both the parent variants, as well as some novel mutations unique to the hybrids. The hybrid variants  can be identified through numerous techniques, such as peak PCR, NAAT, and hybrid capture SARS-CoV-2 NGS (next generation sequencing) assay, etc., but the most accurate approach is genome sequencing. There are numerous immunological diagnostic assays, such as ELISA, chemiluminescence immunoassay, flow-cytometry-based approaches, electrochemiluminescence immunoassays, neutralization assays, etc., that are also designed and developed to provide an understanding of the hybrid variants, their pathogenesis, and other reactions. The objective of our study is to comprehensively analyze the variants of SARS-CoV-2, especially the hybrid variants. We have also discussed the techniques available for the identification of hybrids, as well as the immunological assays and studies for analyzing the hybrid variants. Rhinolophus) in China and pangolins .,34.16,34The variant-specific antibodies serve as a reliable biomarker of the previous infection by the virus as well as the stage of infection. A study discovered that 40% of positive cases reported measurable levels of IgM and IgG during the first 7 days of infection, whereas cross-antibody levels are observed after 15 days. The ELISA test can be used for the rapid detection and quantification of IgA, IgM, and IgG against the receptor-binding domain of the variants of SARS-CoV-2. These receptor-binding domains are the target sites for neutralizing antibodies . This apIt has been observed that the new emerging variants and subvariants possess the ability to evade the immune response by escaping neutralizing antibodies. The neutralizing antibodies are generated in a host on vaccination or past incidence of infection. They have the ability to inhibit the interaction between the viral spike protein and the host Angiotensin Converting Enzyme 2 (ACE-2) receptor. The activity of neutralizing antibodies can be estimated to detect a person’s current status of protection against specific variants of SARS-CoV-2. These neutralization assays employ techniques, such as live virus plaque reduction and ACE-2 binding inhibition assays, to study the impact of neutralizing antibodies on hybrid variants . The altELISA, CLIA, electro-chemiluminescent assays, and flow cytometer-based assays can potentially be used as sensitive and specific diagnostic assays for hybrid variants, whereas neutralization assays may be used to understand the pathogenesis and identify prospective therapeutics and vaccines for hybrid variants. Thus, the immunological assays can not only be utilized for accurate diagnosis of the hybrid variants but also propose effective and specific prophylactic approaches (therapeutics) and preventive measures (vaccinations). These approaches will potentially be accepted and performed in the near future. The advantages and limitations of the discussed methods are mentioned in There are numerous novel assays submitted to the FDA for emergency-use authorization; however, studies reveal that they lack standardization and inaccurately detect the binding antibodies instead of antigen-specific antibodies . AnotherThere are several challenges associated with the immunological assays for hybrid variants. Although the neutralization assays are recognized as the gold standard for the analysis of neutralizing antibodies, the assays require exclusive facilities with biosafety level 3 certification. Neutralization assays in addition to ELISA tests essentially require skilled technicians to perform the tests. Another major limitation of immunological assays is that different immunoglobins are detected at different time intervals in the host. IgM is detected at an average of 5 days post-onset of symptoms, whereas IgG is detected after about 14 days. A major concern associated with immunological or serological assays is the production of false negative outputs due to the cross-reactivity of antibodies . This crCOVID-19 is a complex infection majorly attributed to the high propensity of mutations in its spike proteins that confer alterations in the attributes and transmission rates, as well as virulence. The virus undergoes frequent random point mutations or recombination during replication which results in the development of new variants. Further, two distinct lineages of SARS-CoV-2 can also recombine to form hybrid variants that can be monitored to track conversion into a variant of concern. There are numerous methods to identify the hybrid variants; however, the most accurate approach is genome sequencing. Numerous immunological diagnostic tests are also designed to identify and examine the variants of SARS-CoV-2.Mutations and recombinations in the viral genome can render the currently available drugs and vaccines ineffective. Therefore, the understanding of various aspects of hybrid variants such as the mechanism of development, mutations involved, pathogenicity, transmission rate, resistance to therapies and vaccines, etc., is essential to design more efficient drugs and vaccines for the control of the infection. The hybrid variants require to be constantly monitored and comprehensively analyzed, as they can become converted to a variant of concern. The invention of novel techniques to detect or diagnose the variants, in addition to immunological studies and assays to understand them, are the need of the hour to control the transmission of these variants. These approaches further facilitate improvement in our understanding of viral mechanisms and evolution, which can benefit easy mitigation and control of future outbreaks of viral infections. The immunological assays described have the potential to be used for efficient and accurate diagnosis of the hybrid variants in the near future.


Near-death experiences (NDEs) including out-of-body experiences (OBEs) have been fascinating phenomena of perception both for affected persons and for communities in science and medicine. Modern progress in the recording of changing brain functions during the time between clinical death and brain death opened the perspective to address and understand the generation of NDEs in brain states of altered consciousness. Changes of consciousness can experimentally be induced in well-controlled clinical or laboratory settings. Reports of the persons having experienced the changes can inform about the similarity of the experiences with those from original NDEs. Thus, we collected neuro-functional models of NDEs including OBEs with experimental backgrounds of drug consumption, epilepsy, brain stimulation, and ischemic stress, and included so far largely unappreciated data from fighter pilot tests under gravitational stress generating cephalic nervous system ischemia. Since we found a large overlap of NDE themes or topics from original NDE reports with those from neuro-functional NDE models, we can state that, collectively, the models offer scientifically appropriate causal explanations for the occurrence of NDEs. The generation of OBEs, one of the NDE themes, can be localized in the temporo-parietal junction (TPJ) of the brain, a multimodal association area. The evaluated literature suggests that NDEs may emerge as hallucination-like phenomena from a brain in altered states of consciousness (ASCs). The focus of our present review is the etiology of personal experiences which have fascinated, for a long time, both scientific, medical and esoteric communities, the near-death experiences (NDEs). Although reports about NDEs are known from many cultural backgrounds and for many centuries  this terphenomenal consciousness . In the broad context of neuropsychology, ASCs are approached as deviations from the states of wakefulness and/or awareness which are the two main conditions allowing consciousness to be generated. Wakefulness refers to that daily state in the circadian rhythm of sleeping and waking when a person can interact with the world and engage in coherent activities ; awareneiousness . Furtherxecution  and selfxecution . Phenomexecution . Oppositxecution . ASCs arxecution .Three definitions and a set of components regarded as necessary elements of NDEs shall be presented. They somehow reflect the historical course of scientific thinking about NDEs. The first NDE definition was proposed by any conscious perceptual experience which takes place during a ‘near encounter,’ an event in which a person could very easily die or be killed  but none the less survives, and continues physical life.”“…conscious perceptual experience,” although the persons were unconscious and often clinically dead during the time of their experience. Later, Greyson, a dedicated psychiatrist in the field of NDE research, introduced the term “transcendental,” giving a perspective with relation to the paranormal  a relation with death, (2) a sense of transcendence, (3) ineffability, (4) positive transformative effects (related to meaning and purpose to life), and a (5) severity of illness that leads to loss of consciousness (LOC), together with the (6) absence of features of other coma-related experiences  or elsewhere).”via the knowledge of the neurophysiological bases of the generation of wakefulness and awareness and of changes in these basic attributes of consciousness  being involved in the generation of NDEs. Further, it is fact that many topics or themes in NDE narratives can be found in reports characterizing experiences induced by modified brain functions which not necessarily imply LOC . We will name these experiences NDE-like. The relationship between NDEs, NDE-like phenomena and consciousness has been discussed in the context of various states and conditions of consciousness . Here, wThe content of an NDE report is the narrative describing the subjective experience of a person having survived life-threatening conditions. The reports have usually been collected by family members or health professionals, hours, days, weeks, or more up to several years after the NDE experiencer (NDEr) had returned to consciousness from an unconscious phase which could have lasted minutes, hours, days, weeks or several months or years as a result of a life-threatening event. Thus, these reports and the studies based on the reports are naturally retrospective, uncontrolled, unblinded, and possibly heavily biased by the health, religion, culture, social relations, lifestyle, etc., of the NDEr at the time of reporting, and the interview style  of the person asking for the report . More reIn general, about 9–20% of the people having survived life-threatening conditions such as clinical death reported NDEs . ContentLists of major themes occurring in NDE reports have been derived from standardized questionnaires used in interviews of large numbers of potential NDErs e.g., . Such ap(1)identifying potential NDErs,(2)separating NDE-related from other stories of a potential NDEr,(3)viaranking themes according to their prevalence and relative frequency of occurrence in order to evaluate possible psychological and neurological relationships (4)testing for differences in experiences between age/sex/social/cultural/etc., groups,(5)comparing themes from NDE reports with themes having been reported after awakening from unconsciousness caused by non-life-threatening events  in order to identify relevant mimics and scientific alternatives for studying the causation of NDE themes,(6)relating themes to likely neural substrates known to be involved in generating certain perceptual experiences.More recently, qualitative and quantitative text analyses have also been used to characterize the content-related structure and/or the frequency of occurrence of certain words in NDE reports. Sequences of themes such as OBEs, experiencing a tunnel, seeing a bright light, and feeling of peace have been found , time-boThe focus of our present analysis will be on the aspect (3) in combination with (5) and (6) of the above list, which we will develop in combining rather unvalued old data from NDE-like contexts with more recent evidence about brain activity under physiological stress such as near death. In this context, we rely on the widely accepted and used NDE scale of Although the perceptions/feelings of the great majority of NDEs have been described as positive or neutral  in the analysis of frontal cortical EEG signals . The digMore recently, This recorded sequence of changes in neuronal activity—non-spreading depression, spreading depolarization, negative ultraslow potential–is a characteristic response of brain areas to the loss of energy supply not only after cardiac arrest but also after ischemia of other geneses, e.g., traumatic brain injury or hemorrhage . Again, via gamma-waves in a well-coordinated way between sensory, motor, and association areas of the brain. Such a gamma-wave occurrence is typical for perception and associative use of memory content in a conscious person  antagonist ketamine and DMT, an endogenous agonist of sigma-1 receptors, are known to inhibit spreading depolarization  reported an altered sense of time and past visual images reminding of some reported experiences from NDErs. More recently, A reduction of the blood flow to the brain generates cerebral hypoxia or, in more dramatic cases, anoxia causing LOC and the occurrence of NDE phenomena . A studyCerebral hypoxia could also induce feelings of happiness and euphoria and of having minds clearer than normal, and intellects keener than before . Such obOur glimpse on several generally known and well-studied classes of modifications of brain function revealed common effects of the modifications on the perception of the affected persons. The reported perceptual experiences were often similar to if not identical with those of NDE reports and, together, covered the NDE themes of the During aerial combats, fighter pilots are exposed to high head-to-foot acceleration  to the brain as mentioned before.–the generation of OBEs compared to other NDE themes appears as a response to increased ischemic stress.Major perceptions and experiences reported after G-LOC episodes are shared with NDEs. They include tunnel vision and bright lights, floating sensations, automatic movement, autoscopy, OBEs, not wanting to be disturbed, pleasurable sensations, psychological alterations of euphoria and dissociation, the inclusion of friends and family, the inclusion of prior memories and thoughts, and a strong urge to understand the experience. According to via the use of drugs and anesthetics, recordings during epileptic seizures, electrical brain stimulation and modifications of blood flow to the brain including G-LOC tests—have all been successful to generate perceptual experiences that mimic NDEs. Further, lucid dreaming and hallucinations of various genesis can reproduce NDE themes  and emotional memory e.g.,  can be ePositioned at the transition from the temporal to the parietal and occipital cortices, the TPJ;  plays anvia EEG recordings started recently  of the brain, all these modifications of brain functioning have been shown to generate subjective perceptions closely covering those of NDEs including OBEs. Therefore, neuro-functional models of NDE including OBE generation offer scientifically appropriate causal explanations for the occurrence of NDEs, possibly as hallucinations of a brain in ASCs. Such alterations are very likely expressions of physiological changes in a brain under ischemic stress as has been shown mainly after cardiac arrest in persons attested to be clinically dead. Neuro-functional NDE models may be used in further studies under well-controlled clinical/laboratory settings to gain more insight into NDE-specific questions such as the generation of specific NDE themes by local cortical activity, or which actual state of consciousness may allow NDE memory content to be saved. In general, the study of NDE models will contribute to the understanding of how brain activity can generate and represent subjective experiences at all. NDEs actually seem to be promising gates to the study of brain functions, especially in situations in which states of altered consciousness may be traced back to defined measures or sets of measures of brain activity.The original contributions presented in this study are included in the article/RR initiated the project, supplied the relevant literature, and wrote the first draft. GE contributed ideas and literature, deepened the scientific background, and wrote the final manuscript together with RR. Both authors contributed to the article and approved the submitted version.


Bacillus nattokinase is a potential low-cost thrombolytic drug without side-effects and has been introduced into the consumer market as a functional food or dietary supplement. This review firstly summarizes the biodiversity of sources and the fermentation process of nattokinase, and systematically elucidates the structure, catalytic mechanism and enzymatic properties of nattokinase. In view of the problems of low fermentation yield, insufficient activity and stability of nattokinase, this review discusses the heterologous expression of nattokinase in different microbial hosts and summarizes the protein and genetic engineering progress of nattokinase-producing strains. Finally, this review summarizes the clinical applications of nattokinase.Thrombosis has threatened human health in past decades.  The incidence of cardiovascular diseases has increased significantly worldwide and showed a trend of younger onset. Among cardiovascular diseases, cerebral infarction, ischemic stroke, and myocardial infarction are all related to thrombi formed by the coagulation of fibrin and platelets, and the current clinical application of thrombolytic agents including urokinase, tissue plasminogen activator (t-PA) and streptokinase all have serious side effects such as bleeding or gastric ulcer ,2. ThereBacillus subtilis, is a traditional food with a long history in Japan. Intake of natto and other related fermented soy products is inversely related to the incidence of cardiovascular diseases, hence long-term consumption of natto is considered to be one of the important reasons for the longevity of Japanese . S. SBacillThe catalytic mechanism of nattokinase has not yet been reported. Since the three-dimensional structure of nattokinase highly overlaps with that of other alkaline serine proteases in its family, its molecular mechanism is similar to that of the alkaline serine protease family. First, the ring nitrogen atom of the His64 residue in the catalytically active center receives the hydroxyl proton of Ser221, which enhances the nucleophilic ability of Ser221 and attacks the hydroxyl carbon of the peptide bond of the substrate to form a tetrahedral transition state intermediate. Asp32 stabilizes the protonation state of His64 through the negative charge of the carboxyl group. Next, His64 donates a proton to the newly formed amino group to release the first product (acylation reaction) while forming a covalent acyl-enzyme complex. As the water molecule nucleophilically attacks the covalent acyl–enzyme complex to form a tetrahedral intermediate, His64 transfers the proton back to Ser221, and the transition state disintegrates to release the first product, thereby completing the deacylation reaction ,41,42.The propeptide of nattokinase plays a key role in the correct folding of nattokinase. By comparing the thrombolytic activities of nattokinase holoenzyme (propeptide + mature peptide) and nattokinase mature peptide, Weng et al. found that only nattokinase expressing both propeptide and mature peptide has thrombolytic activity, inferring that the propeptide may be involved in the correct folding of nattokinase as an intramolecular chaperone . Based oThe protein structure of nattokinase has now been resolved. However, the molecular mechanism of thrombolysis induced by nattokinase and the role of propeptide in the correct folding of nattokinase still need to be elucidated.Obtaining nattokinase by strain fermentation is the main process for the industrial production of nattokinase. Therefore, it is of great significance to study the fermentation process of nattokinase to improve its fermentation yield. The traditional natto fermentation process involves wrapping steamed soybeans with boiled rice straw and fermenting at 40 °C for about one day. At present, the industrial fermentation modes for nattokinase are divided into solid fermentation and liquid fermentation, and the main goals of nattokinase fermentation technology research are to reduce the cost and improve the yield.Bacillus subtilis during the fermentation process could stimulate the biosynthesis of nattokinase ..43].Escherichia coli [Lactobacillus [Bacillus [Pichia pastoris [Escherichia coli is the most widely studied host for nattokinase expression. However, the expression of nattokinase in Escherichia coli results in mostly inactive inclusion bodies [Escherichia coli has been reported, the fibrinolytic activity of recombinant nattokinase is still lower than that of natural nattokinase synthesized by Bacillus. Therefore, how to realize the soluble expression of nattokinase encoding gene in Escherichia coli has become an urgent problem to be solved [Escherichia coli, Lactococcus lactis [Lactobacillus bulgaricus [Pichia pastoris were used as hosts to express soluble recombinant nattokinase with thrombolytic activity, showing the great potential of nattokinase in the food and pharmaceutical industries [The use of genetically engineered bacteria to express nattokinase has been proven to be an important way to increase the yield of nattokinase. At present, nattokinase has been expressed in hia coli , Lactobabacillus , BacilluBacillus  and Pichpastoris . Escherin bodies . Althouge solved . Compares lactis , Lactobalgaricus  and Pichdustries ,81,83.Bacillus can be greatly improved by optimizing the regulatory elements upstream of the open reading frame of nattokinase. For example, replacing the promoter and signal peptide upstream of the nattokinase encoding gene was confirmed to improve the expression efficiency and secretion rate of nattokinase during Bacillus fermentation, respectively. Cai et al. replaced the signal peptide upstream of the nattokinase-encoding gene, heterologously expressed in Bacillus licheniformis with nattokinase, and successfully improved the secretion efficiency of nattokinase [Bacillus subtilis WB800, and the activity of nattokinase reached 816.7 ± 30.0 FU/mL after fermentation in a 5 L fermenter [Bacillus subtilis 168 [Bacillus licheniformis DW2. This 5′-UTR effectively enhanced green fluorescent protein expression by approximately 50-fold and exhibited good adaptation to nattokinase [Bacillus. Wei et al. improved the fermentation yield of nattokinase by knocking out the protease that may hydrolyze nattokinase [Bacillus subtilis WB 800 strain lacking eight extracellular protease genes , which fermented nattokinase with a yield of 600 mg/L [At present, many studies have confirmed that the synthesis efficiency and fibrinolytic activity of nattokinase in tokinase . By simutokinase . Liu et ermenter . Cheng eilis 168 . In additokinase . Knockoutokinase . Nguyen 600 mg/L .Escherichia coli expression system has relatively high expression levels and is easy to purify, but the expression products are mostly inactive or extremely low-activity inclusion bodies, which require renaturation of inclusion bodies to obtain functional enzymes; Bacillus subtilis had the best expression activity, but the existence of impurity proteins in the fermentation broth increased the difficulty of purification; the Pichia pastoris expression system can obtain high-purity nattokinase, but the enzyme activity is low and the expression amount is relatively small. How to further improve the recombinant expression efficiency of nattokinase through site-directed mutagenesis of nattokinase, co-expression of nattokinase propeptide, optimization of regulatory elements, selection of protease-deficient host cells, and optimization of the purification process of recombinant nattokinase will be the focuses of future research.Different expression systems have their own advantages and disadvantages due to their own characteristics. The The traditional antithrombotic drugs have a poor thrombolytic effect, bleeding tendency, and single-mode of administration, while the high thrombolytic activity, low side effects, and oral administration of nattokinase make it a potential thrombolytic alternative drug. Fujita et al. first discovered the thrombolytic effect of nattokinase in acetic acid-induced arterial thrombosis rats. They found that the thrombolytic activity of nattokinase was much higher than that of urokinase . As nattIn addition to its use in the treatment of thrombotic diseases, nattokinase has also been shown to prevent thrombosis. Compared with traditional drugs such as aspirin, nattokinase can not only effectively prevent the formation of blood clots, but also avoid side effects such as bleeding tendency and gastric ulcers . Kamiya The mechanism of nattokinase blood absorption after oral administration is still not fully resolved. First, intraduodenal administration of nattokinase at a dose of 80 mg/kg was able to induce fibrinolysis in rat plasma, implying that this dose was too high . Second,Hypertension can directly increase the probability of stroke and myocardial infarction, and it is considered to be one of the most important risk factors for cardiovascular diseases. Antihypertensive drugs such as angiotensin-converting enzyme inhibitors, thiazide diuretics, and angiotensin II receptor blockers must be used in consideration of many factors, including adverse reactions, contraindications, and special populations . NattokiOral administration of nattokinase relieves symptoms of hypertension mainly by effectively reducing systolic and diastolic blood pressure. Oral administration of nattokinase can reduce blood pressure in spontaneously hypertensive rats, and the intact nattokinase and its hydrolyzed fragments can be absorbed from the intestinal tract . Human eIn addition to the research of nattokinase in the fields of thrombosis and hypertension treatment, nattokinase can also be used as a drug or adjuvant to treat diseases such as cancer , AlzheimAD is a neurodegenerative disease characterized by the presence of amyloid plaques in the form of fibrillar proteins in the brain, and nattokinase has a strong ability to hydrolyze amyloid . In an aDiseases such as retinopathy of prematurity, diabetic retinopathy, and retinal vein occlusion all cause irreversible visual impairment and blindness through the formation of pathological neovascularization. Nattokinase attenuated neovascularization in the retinas of mice with oxygen retinopathy but activated the Nrf2/HO-1 pathway to ameliorate ischemic retinopathy . In addiIn addition to its antithrombotic function, nattokinase has been reported to lower blood pressure, arteriosclerosis, coronary heart disease (such as angina pectoris), stroke and peripheral vascular disease. However, the molecular mechanism of nattokinase in the treatment of these diseases remains to be explored, and the dosage and toxicity of administration are still unclear. The solution of these problems can establish a theoretical basis and technical support for us to better use nattokinase.Bacillus nattokinase is a potential thrombolytic drug with a powerful thrombolytic effect, diverse mechanisms, and safety, and is becoming a focus of cardiovascular drug research. Although current research on the pharmacodynamics and pharmacology of nattokinase has been completed, there are still many problems in the application of nattokinase in the fields of medicine and functional food. First of all, the product quality evaluation of nattokinase still needs to be improved; the current quality evaluation of nattokinase products mainly relies on the determination of enzyme activity, which is not comprehensive. The activity evaluation of nattokinase combined with its stability evaluation under different temperatures, pH, and other influencing factors will be more conducive to the development of nattokinase health foods and thrombolytic drugs. Secondly, the physicochemical properties of nattokinase are still insufficient for industrial production and application: as a macromolecular compound, commercially available nattokinase has relatively insufficient activity and is very sensitive to acid, high temperature, and oxides. Therefore, it is easy for the activity of nattokinase to be lost during production, preservation, and oral administration, which limits its clinical application. Effective means to solve the stability defects of nattokinase include but are not limited to the following: (1) screen nattokinase strains with strong activity and stability, and explore fermentation processes to improve the secretion efficiency of nattokinase; (2) stabilize nattokinase by physical embedding, nanoparticle binding, temperature, and pH control, and adjustment of coexisting substances; (3) use modern genetic engineering technology and mutation breeding technology to improve the activity and stability of nattokinase. The combination of drugs is a common method for the clinical treatment of diseases. Although reports on the combination of nattokinase with other drugs are lacking, research on the combination of nattokinase with other cardiovascular disease drugs may provide a new approach to the treatment of cardiovascular disease.


In particular, the smart bioactive surfaces on the implants, which can not only mimics the in vivo three-dimensional microenvironment but also promote wound healing and tissue repair through the in vivo physiological environment, can endowed the implant with the multi-functional ability to actively adapt to and regulate the interfacial physiological responses, resulting in better promotion of wound healing and tissue repair.Biomaterials and implantable/interventional medical devices play an irreplaceable role in saving human life and promoting human health. Their surface properties and functions largely determine their clinic performances after the implantation. The introduction of the bioactive factors on the surfaces to design the surface biological function and construct the surface microenvironment, so as to further endow the surfaces with the ability to advances in smart bioactive surfaces for wounding healing and tissue repair, which can be potentially used in the clinic biomaterials and implants. We have collected two review articles and two original research articles, which highlight several emerging trends of smart bioactive surfaces for wounding healing and tissue repair.The Research Topic mainly focuses on the most recent Xia et al., reviewed the application of chitosan-based materials in surgical or postoperative hemostasis. In this review, the physiological hemostasis, the physicochemical properties of chitosan and its role in hemostasis were firstly discussed in brief. Subsequently, the recent advances in the chitosan-based hemostatic materials, including hydrogels, dressing, sponge and nanocomposites, were mainly summarized in detail. The methods to increase the water absorption, porosity, and compressive strength of the chitosan-based hemostatic material are also discussed for each kind of chitosan-based hemostatic materials. Finally, the authors emphasized that, although chitosan-based hemostatic materials have shown good effects in vitro and in vivo animal experiments, they have not been widely in clinic. Due to the advantages of higher hemostatic efficiency and lower price of chitosan-based hemostatic materials than the existing hemostatic materials such as gelatin sponge, they will have important roles in clinical practice, which is worth further strengthening exploration.Gong et al., the hydrogel-based delivery system applied in the local anti-osteoporotic bone defects was summarized. The hydrogels for adjuvants loading, including nature-based, synthetic, and composite hydrogels, were firstly reviewed, followed by discussing the anti-osteoporosis adjuvants-loaded hydrogel for preventing osteoblast and promoting osteogenesis. The hormone analogs and osteo immunomodulators loaded in the hydrogels for osteoporosis treatment was also discussed briefly. Finally, the authors pointed out that the detection of the ideal hydrogel-adjuvant system for the treatment of the local anti-osteoporotic bone defects had the potential to ease the transition from basic research to clinical application, and it required the joint efforts of clinicians and researchers.Hydrogels are the attractive candidates as fillers for bone injuries with irregular shapes and as carriers for local therapeutic treatments, such as osteoporosis. In the review article by Zhang et al., the biomechanical and clinical properties of the novel internal fixation Interlocking Hip Screw (IHS) and conventional inverted triangle cannulated screws (ITCS) for treatment of Pauwels III femoral neck fractures were comparatively studied. Twenty synthetic femurs were osteotomized to simulate 70° Pauwels Ⅲ femoral neck fractures and randomly divided into two groups: Group IHS and Group ITCS. The biomechanical and the clinical properties, such as demographic data, operating duration, intraoperative blood loss, number of fluoroscopies, length of hospital stay, fracture healing time, Harris Hip Score (HHS), the score of Visual Analogue Scale (VAS) and complications such as non-union, avascular necrosis, and femoral neck shortening were comparatively explored. The results indicated that IHS provided better biomechanical and clinical performances due to its unique biological and biomechanical mechanisms, compared with ITCS. Thus, the author believed that IHS was a feasible alternative to ITCS for the fixation of Pauwels Ⅲ femoral neck fractures.In the article by Wang et al., prepared a kind of nanoparticles called W18O49@EP to release reactive oxygen species (ROS) during the combined tumor radiotherapy (RT) and photodynamic therapy (PDT). It was found that the ROS release by the nanoparticles during near infrared light (NIR) irradiation can enhance the effect of PDT treatment without inducing hypoxia. Hence, this strategy can greatly improve the anti-tumor effect, which could provide an effective approach for clinical anti-tumor studies.Insufficient oxygen supply and hypoxia caused by tumor lead to a poor therapeutic effect and poor prognosis. In order to overcome this issue, Overall, this Research Topic covers recent advances in smart bioactive surfaces for wound healing and tissue repair. The editors hope that the current Research Topic will contribute to the research and development in the field of surface modification of biomaterials and implantable/interventional medical devices for wounding healing and tissue repair, inspiring future exploration to expand the biomedical applications of smart bioactive biomaterials.


Neoadjuvant chemotherapy (NAC) is increasingly widely used in breast cancer treatment, and accurate evaluation of its response provides essential information for treatment and prognosis. Thus, the imaging tools used to quantify the disease response are critical in evaluating and managing patients treated with NAC. We discussed the recent progress, advantages, and disadvantages of common imaging methods in assessing the efficacy of NAC for breast cancer. The World Health Organization International Agency for Research on Cancer (IARC) released the world’s latest cancer burden data in 2020. New breast cancer cases reached 2.26 million in 2020, replacing lung cancer as the world’s most extensive cancer. In 2020, the number of new breast cancer cases in China was about 420,000, and the death toll reached 120,000 , National Comprehensive Cancer Network (NCCN), Chinese Society of Clinical Oncology (CSCO), and other guidelines have recommended the selection of an intention-to-treat population. “Based on the actual clinical needs, and guided by the therapeutic purpose” is an important clinical practice NAC candidate selection principle . Figure On the entry of the candidates into the NAC process, the NAC efficacy needs to be evaluated. The current methods used to assess the efficacy of NAC in breast cancer include clinical manifestations, laboratory examinations , imagingAs the gold standard for evaluating tumor response after chemotherapy, through pathological examination, changes, degeneration, necrosis, and tumor cell disappearance after chemotherapy, can be observed directly with high diagnostic accuracy. In particular, patients who achieved pCR after NAC have a better prognosis. A study  revealedImaging, as one of the most important methods to evaluate the efficacy, has the advantage of being non-invasive and can be used throughout the whole process of breast cancer treatment, including a pre-treatment baseline image to determine the scope of the lesion, treatment efficacy evaluation during NAC, and post-treatment residual lesion evaluation. Imaging examination can not only objectively be used to evaluate the efficacy of NAC, but also provides an important basis for clinicians to choose an appropriate surgical approach and determine patients’ prognosis. At present, the commonly used clinical imaging evaluation methods include mammography, ultrasound, magnetic resonance imaging (MRI), and positron emission tomography CT (PET-CT). Nevertheless, there is no unified guideline for the imaging evaluation of NAC response, and in recent times, the efficacy evaluation is mainly based on changes in tumor size, changes in the degree of ultrasound or MRI enhancement, and the form of tumor regression. Currently, the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1  remains There are different imaging methods suitable for evaluating NAC efficacy in different stages of breast cancer, and each imaging method also has its own area of emphasis for evaluating efficacy in breast cancer of different molecular types. It is crucial for clinicians to familiarize themselves with the progress, advantages, and disadvantages of these imaging methods in evaluating NAC efficacy. Currently, several studies, reviews, and meta-analyses exist on imaging assessment of NAC. To this end, this article reviews the value and recent progress of imaging in evaluating NAC efficacy for breast cancer based on the study of a large number of relevant literature.Mammography evaluation shows signs of tumor lesion calcification disappearance and burr shortening or disappearance after breast cancer NAC. However, the above features have low accuracy in evaluating the efficacy of NAC. The evaluation of efficacy after NAC by mammography is mainly based on changes in tumor size and density. Two retrospective studies , 14 showAlthough mammography can describe malignant calcification well, microcalcification is not reliable evidence of the persistence of residual tumors. A previous study  shows thIn conclusion, mammography has certain limitations in assessing the efficacy of NAC in breast cancer: 1) it is unable to accurately determine the changes of multicenter breast cancer lesions; 2) it has X-ray radiation and cannot be used to examine frequently; 3) it is not suitable for the identification of tumor residue, fibrosis, and scar tissue after NAC; and 4) residual microcalcification after NAC is often overestimated. Therefore, The American College of Radiology recommended mammography, ultrasound, and MRI as the highest grade (grade 9) at baseline (pre-NAC), while MRI was still recommended at grade 9 during and after treatment; however, ultrasound and mammography were reduced to grade 8 and grade 7, respectively .CESM, an examination combined with contrast agents based on conventional mammography, is a new mammary gland imaging technique used to obtain low energy and subtraction images after post-processing them through rapid high and low energy dual exposure, after intravenous injection of contrast agents. It can show abnormal vascular proliferation in tumor tissues, thus significantly reducing the false positive and false negative rates and improves the sensitivity and accuracy of detection , 21.MRI is currently the most recommended imaging for efficacy assessment during NAC. One study  comparedThe results of previous studies suggest that CESM can be used to assess the efficacy of NAC and has good application in predicting pCR early after NAC. Due to the shorter examination time of CESM, better patient tolerance, and lower price, CESM has a broader prospect in the evaluation of the pathological response of breast cancer to NAC. However, the technique requires multiple breast images in different positions after contrast injection; hence, its use is limited in patients with contrast agent allergies. In addition, more extensive studies are necessary to better understand the efficacy evaluation of NAC for different molecular subtypes of breast cancer, exploration of tumor regression patterns, assessment of efficacy after NAC for tumors containing calcified foci, and assessment of CESM radiomics.Ultrasound is a safe, fast, reproducible, and economical imaging evaluation method. Conventional ultrasound can describe the size, morphology, and boundary of tumors. Ultrasound imaging technology can further evaluate the tumor volume, internal blood vessels, and other subtle structures, as well as the softness and hardness of the tumor . The ChiTwo-dimensional ultrasound can reflect the size, morphology, boundary, and other information of breast lesions and show the structure and morphology of lymph nodes well . HoweverTumor vascular distribution is an alternative indicator of tumor burden. In addition to evaluating tumor size and morphology, color Doppler ultrasound can also be used to evaluate tumor vascular distribution through a variety of parameters that compare tumor changes before and after chemotherapy, to assess the response to chemotherapy . A studyCEUS, a purely blood pool imaging technique, detects micro-vessels to show the neovascularization of breast tumors and the perfusion pattern of blood flow, to obtain contrast-enhanced images. It shows the morphology and distribution of lesions and blood vessels clearly . CEUS caChanges in tumor blood vessels after NAC precede morphological changes, so the difference in blood perfusion is critical for NAC efficacy evaluation . EspeciaIn summary, CEUS, as a cutting-edge research field, has good clinical application in assessing the efficacy of NAC for breast cancer patients who cannot undergo dynamic contrast-enhanced MRI (DCE-MRI) or require multiple evaluations; it can measure the maximum diameter of lesions after NAC more accurately than conventional ultrasound and is in good agreement with histopathological results. However, large sample multi-center studies are needed to further explore more sensitive indicators of NAC response. The limitation of CEUS in clinical practice is the poor visualization of multiple lesions and large lesions beyond the imaging range.ABVS uses the advantages of multi-plane remodeling to create a three-dimensional ultrasound imaging of the breast tissue. It can better reflect the growth mode of breast tumors and the relationship with the surrounding tissues through automatic, full-volume, and coronal scanning of the breast . Since iA Chinese study  first exThe tumor tissue changes complicatedly during the treatment, including cell degeneration, necrosis, liquefaction, slow proliferation rate, tissue fibrosis, and focal tissue hardness. Pathological biopsy after NAC showed that patients with ineffective (or effective) treatment had higher (or lower) cancer cell density, resulting in changes in the elastic coefficient before and after NAC. Therefore, ultrasound elastography can be used to evaluate the efficacy of NAC . In receStudies in other countries , 44 founOne study showed breast thickness and lesion depth as important factors affecting the quality of elastography images . In addiQUS utilizes changes in the acoustic properties of tissues to reflect changes in their microstructure. It works by scanning the breast tumors using a clinical ultrasound system; then, the ultrasound radio frequency (RF) data within the tumor regions of interest were retained and displayed as a frequency spectrum using a fast Fourier transform (FFT). The analysis of the power spectrum leads to various features like spectral slope (SS), spectral intercept (SI) at 0 MHz, mid-band fit (MBF), average scatterer diameter (ASD), average acoustic concentration (AAC), attenuation coefficient estimate (ACE), and spacing among scatterers (SAS) . Its parOPTI-MUS is a new imaging technology that combines conventional ultrasound and diffused optical tomography through specific technological means. Diffused optical tomography uses the diffuse scattering effect of tissue on the multi-wavelength laser to complete the three-dimensional imaging of tissue physiological information. Measuring the total hemoglobin (HBT), deoxyhemoglobin (HBO2), and other parameters in each section of the tumor region indirectly reflects the tumor angiogenesis activity to evaluate the efficacy of NAC at the molecular level . OPTI-MUThere are various diagnostic modalities to assess the efficacy of breast cancer after NAC. Although many studies have tried to determine the best imaging method in evaluating the efficacy of NAC, no consensus has been reached. To date, MRI is the most used accurate imaging method to assess the extent of tumor residual after NAC . MoreoveMRI has high soft-tissue resolution and can effectively distinguish residual tumors from post-chemotherapy fibrotic or necrotic tissue. The therapeutic effect can be judged mainly by morphology and by measuring the change in the maximum diameter of the lesion. Therefore, to some extent, MRI can reflect the actual size of the mass. The length and diameter measurements were also based on RECIST 1.1 efficacy assessment criteria, and tumor responses were classified as either responsive (CR and PR) or non-responsive (SD and PD). The presence or absence of residual lesions after NAC of breast cancer, accurate size measurement, and accurate pCR prediction directly affect the adjustment of treatment plan and the choice of surgical approach in clinical practice. Compared with mammography, ultrasound, or clinical palpation, lesion size measured by MRI has a higher correlation with pathological examination. A prospective ultrasound trial  enrolledPost-NAC MRI shows two main types of tumor shrinkage: concentric and nested or dendritic shrinkage . It can trans), rate constant (Kep), and extracellular space volume ratio (Ve), can be used for early prediction of breast cancer response to NAC  may be underestimated due to poor imaging , the pseudo-diffusion coefficient due to microcirculatory diffusion (D*), and the perfusion fraction (f), which may have a good potential for predicting NAC effects. Several studies have confirmed the potential value of the IVIM model in monitoring chemotherapy response in a variety of malignancies, such as liver cancer , head anIVIM model has the possibility of increasing ADC value to predict NAC efficacy. However, few studies exist on the application of IVIM model in the efficacy evaluation and prediction of NAC in breast cancer, and further research and confirmation are still needed. IVIM parameters are affected by many factors including respiration collection method, fitting method, and tumor heterogeneity –93, resuDTI is considered an extension of DWI, which characterizes water motion by measuring it in six or more directions. DTI quantifies two parameters: mean diffusion coefficient (MD) and fractional anisotropy (FA). MD is an estimate of mean anisotropy, and FA reflects the degree of anisotropy . AlthougDKI is a new MRI method to depict the diffusion of non-Gaussian water molecules in tissues. DWI is based on the assumption of the homogeneity of the microenvironment, and considers that the diffusion distribution of water molecules obeys Gaussian distribution . In fact1H-MRS is used to assess the therapeutic effect of total choline (tCho) in malignant tumors by measuring the changes in its concentration. After effective treatment with NAC, tumor cells are damaged and their density decreases, thus the tCho peak on the MRS spectrum subsequently reduces.The levels of choline (Cho) and its metabolites reflect the level of cellular metabolism, which is mainly involved in cell membrane transport and diffusion functions. As an active metabolite, the concentration of free Cho in normal tissues is low, and the increase in Cho level reflects an increase in cell membrane synthesis or cell proliferation. Cho peaks are significantly elevated in malignant regions, so Cho complexes are usually considered as markers of malignancy . 1H-MRS 1H-MRS helped in assessing the response of breast cancer to NAC. However, they used qualitative observations rather than the quantitative determination of tCho concentration to monitor tumor changes. Subsequently, several studies  the low choline detection rate currently observed; 2) as the lesions shrink, less tumor tissue can be measured, especially since small lesions less than 1 cm are difficult to quantify in tCho; and 3) the relatively low sensitivity of 1H-MRS compared to MRI , which serves the purpose of early monitoring and assessment of NAC by comparing SUVmax changes before and after chemotherapy. A study added its contribution to the early screening of chemotherapy non-responders, based on a 45% decrease in SUV after the first cycle as a threshold, and a treatment non-responsive NPV of approximately 90% . StudiesPET-CT is helpful for tumor diagnosis and prognosis assessment. It has high accuracy and can be used in the early evaluation of NAC efficacy in breast cancer. Still, the specificity of PET-CT in the efficacy assessment of NAC is low; NAC is a continuous process that requires multiple tests, and the cost of PET-CT and the use of radionuclides limits its clinical application. Therefore, PET-CT has no absolute advantages over MRI. Consequently, it is not used much in clinical practice to evaluate the efficacy of NAC.The concept of radiomics was first proposed by one American scholar  in 2010 MRI radiomics is the most commonly used technique. A recent study involving four centers  showed tIn summary, various imaging methods are used to evaluate the efficacy of NAC for breast cancer in clinical practice. The value of some of the new imaging techniques has not been thoroughly studied; thus, it is not suitable for clinical application at present. With the emergence and development of new imaging techniques, we believe that certain models may exhibit high sensitivity and specificity for specific tumor subtypes. Thus, imaging evaluation is likely to become increasingly individualized. The value of mammography, ultrasound, MRI, and PET-CT in evaluating NAC in breast cancer was discussed in this paper. Additional details on the references included in this paper can be found in XK and QZ equally contributed to the manuscript. XK and QZ reviewed the literature, and wrote the manuscript. XW, TZ, JD, SS and JN contributed to developing the manuscript,and drafting and revising the text, tables, and figure. CT, MT, MW, JZ and YX revised the manuscript. ZHL and ZL designed and revised the manuscript.This study was supported by grants from the National Nature Science Foundation of China (No.82060481); the Outstanding Youth Science Foundation of Yunnan Basic Research Project (202101AW070001); the Yunnan Applied Basic Research Projects (No.202001AT070046); the Yunnan Province technology innovation talent training object project (No. 202105AD160014); and the Graduate Innovation Fund project of Kunming Medical University (No. 2021S252).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This article analyzes the significance of linear and quadratic convection on the dynamics of micropolar fluid due to a stretching surface in the presence of magnetic force and a rotational frame. Modern technological implementations have attracted researchers to inquire about non-Newtonian fluids, so the effect of linear and nonlinear convection conditions is accounted for in the dynamics of non-Newtonian fluid. The highly nonlinear governing equations are converted into a system of dimensionless ODEs by using suitable similarity transformations. The bvp4c technique is applied in MATLAB software to obtain a numerical solution. This investigation examines the behavior of various parameters with and without quadratic convection on the micro-rotation, velocity, and temperature profiles via graphical consequences. The velocity profile decreases with a higher input by magnetic and rotating parameters, and fluid velocity is more elevated in the nonlinear convection case. However, the temperature profile shows increasing behavior for these parameters and quadratic convection increases the velocity profile but has an opposite tendency for the temperature distribution. The micro-rotation distribution is augmented for higher magnetic inputs in linear convection but reduces against thermal buoyancy. The mixing and flowing of fluids are generated through density variation caused by differences in temperature within the fluid, known as natural convection. The fluid density near the heated surface is lower than that of the cold fluid. Gravity raises the hot fluid upward, causing the buoyant force to manifest. The convective flux problems of working liquid have various engineering implementations, such as food preservation, cryogenic devices, solar collectors, energy storage, and nuclear reactor technology. Nonlinear convection exists in the buoyancy force because of temperature fluctuations substantially affecting flux characteristics. Awan et al.  analyzedThe fluids class showing microscopic change induced by micro-rotation and the local formation of fluid molecules are known as microfluids. The notion of this type of fluid was firstly offered by Eringen et al. . In receThe study of magnetohydrodynamics (MHD) in liquid flux gains importance in handling flux characteristics. Essentially, MHD is concerned with the magnetic properties of electrically conductive liquid. The effects of MHD on fluid flow have been observed in several real-world instances in chemistry, physics, and industry such as stream meters, crystal growth, pumps, power plants, controlled thermonuclear reactors, wire drawing, MHD generators, and oil recovery techniques. Experimental and theoretical analysis of magnetohydrodynamic pumps is explored by Jang et al. . Ali et Recently, analyzing energy and fluid transport problems in a rotational frame has been widely studied in various mathematics models and turned into a fascinating phenomenon. It is due to their tremendous applications in the food industry, cosmic liquid dynamics, viscometry, and computer stockpiling devices. Since rotational flux is critical, researchers attempt to comprehend the underlying science. The foremost endeavor of this pathway was developed by Wang . Dessie (i)incorporate the micropolar fluid as host fluid,(ii)analyze with and without quadratic convection on the dynamic of micropolar fluid, and(iii)consider the significant effects of magnetohydrodynamics subject to a rotating frame of reference.This analysis investigates the significance of linear and nonlinear convection on the dynamics of micropolar fluid and heat transfer across a horizontal expanding surface. The current study has the following novelties:Since the authors pointed out that none of the cited studies above are focused on the elaborated problem, the bvp4c technique is applied, and differentiated outcomes for micro-rotation, velocity, temperature, skin friction, and Nusselt number are obtained.(1)To explore the significance of material, magnetic, and rotating parameters on the dynamic of microplar fluid: the case of linear and quadratic convection.(2)To observe the influence of Lorentz and Coriolis forces on micro-rotation profile: the case of linear and quadratic convection.(3)To observe the variations in skin friction coefficients and Nusselt number against growing values of rotating, magnetic, thermal buoyancy, and material parameters in the case of linear and quadratic convection.This analysis gives scientific answers to the following research questions:x-axis to stretch the sheet at a velocity of z-direction, and under the small magnetic field Reynolds number assumption, the induced magnetic field is negligible. Further, Ohmic dissipation and Hall current impacts are neglected because the applied magnetic field is not very strong , where The above first-order differential equations with seven initial conditions are solved via the shooting technique. The numerical computation has been performed for various physical emerging parameters for the appropriate computational domain  instead of [0,Case 1: with linear convection  parameter, rotating (K), thermal buoyancy  parameters in quadratic convection case.The fluid particles’ temperature increases with higher inputs of rotating and magnetic parameters in linear convection case but is reduced against growing strength of rotating (x direction, the skin friction coefficient decreases with the amplified value of magnetic, rotating, and material parameters in the linear convection case. Along the y direction, the skin friction coefficient is raised by enlargement in magnetic and material parameters without quadratic convection case. However, it decreases for thermal buoyancy and rotating parameters in the quadratic convection case.Along the The magnitude of the Nusselt number is reduced with a higher contribution of rotating and magnetic parameters in the linear convection case. However, it increases against material and thermal buoyancy in the nonlinear convection case.The linear and quadratic convection flux of non-Newtonian fluid in 3D on extending surfaces in the presence of magnetohydrodynamics is investigated in this study. Fluid velocity, micro-rotation, temperature distribution, skin friction factor, and Nusselt number are conducted using the technique of bvp4c. A few significant consequences are summarized as follows:


For the successful application of brain-computer interface (BCI) systems, accurate recognition of electroencephalography (EEG) signals is one of the core issues. To solve the differences in individual EEG signals and the problem of less EEG data in classification and recognition, an attention mechanism-based multi-scale convolution network was designed; the transfer learning data alignment algorithm was then introduced to explore the application of transfer learning for analyzing motor imagery EEG signals. The data set 2a of BCI Competition IV was used to verify the designed dual channel attention module migration alignment with convolution neural network (MS-AFM). Experimental results showed that the classification recognition rate improved with the addition of the alignment algorithm and adaptive adjustment in transfer learning; the average classification recognition rate of nine subjects was 86.03%. Brain-computer interface (BCI) systems are used to establish a connection between a brain and a computer; the computers are controlled by monitoring the activities of electroencephalography (EEG) signals. With the rapid development and promotion of BCI technology, the research on BCI technology has become the focus of attention in the field of brain science and biomedicine. BCI systems based on motor imagery are a popular research topic, and these have considerable application potential in games and nerve rehabilitation, among other fields ,2,3,4. BDeep learning, a branch of machine learning, simulates the operation of the human brain by establishing complex interconnected neural structures, and building a general model that can deal with various data. Deep learning is an end-to-end method that does not rely on manual design feature extraction methods; it can learn a large number of necessary parameters and detect valuable information . CompareWith the development of deep learning, the end-to-end deep learning method is used to process the EEG signals of motor imagery, and different network structures are designed to adapt to the classification of EEG signals of motor imagery, which meets the requirements of extracting effective features and has higher robustness. An et al.  applied To overcome the differences in EEG data between subjects and the limitation of adjusting algorithms to deal with different data sets, multi-scale convolutional neural networks have been proposed for motion imagination, and these have shown good results. Dai et al.  proposedThe size of the data and the quality of the data limit the effect of deep learning, and EEG signals due to its complex acquisition process, and higher acquisition conditions, resulting in less practical training data. In recent years, some scholars have proposed various isomorphism and heterogeneous transfer learning methods to solve the problem of fewer EEG signals. Zhang et al.  proposedTo solve the differences among individual EEG signals and the problem of less EEG data, as well as to explore a more universal deep learning method, in this study, a multi-scale convolution network is proposed based on an attention mechanism; further, a transfer learning data alignment algorithm is added to explore the application of transfer learning in the analysis of motor imagery EEG signals. The data set 2a of BCI Competition IV is used to verify the proposed network . Experimental results show that adding the alignment algorithm and adaptive adjustment in transfer learning improves the classification recognition rate, and the average classification recognition rate for nine subjects reaches 86.03%.In machine learning, one of the main assumptions is that training data and test data belong to the same feature space and obey the same probability distribution. If this distribution changes, most statistical models need to use newly collected training data to retrain from scratch. In many real-world applications, it is expensive or challenging to obtain the required training data and reconstruct the model, that is, the need and workload of collecting training data again should be reduced. To achieve this, transfer of knowledge or learning between task domains is necessary. During EEG signal processing, due to the individual differences between subjects, these hypotheses of machine learning cannot be fully met. Typically, this problem is addressed by calibrating the session for a long time to collect high-quality and large amounts of EEG data sets; however, this depends on subjects’ cooperation and the quality of signal acquisition, greatly limiting the practical application of BCI ,22,23. Tith trial, and the reference matrix Let us assume that there are Then, the average covariance matrix of all calibrated tests is given as follows:The average covariance matrix of all subjects before and after data alignment is equal, which shows that the distribution of the covariance matrix from different subjects is more similar. The aligned data can be directly used for transfer learning.To classify motor imagery EEG signals, we propose a multi-scale convolution network based on an attention mechanism. The proposed multi-scale convolutional neural network based on attention mechanism is a parallel three-way cascade network; it comprises four modules, namely, a channel weight calculation module, a multi-scale convolution module, a convolutional block attention module (CBAM) attention mechanism module, and a classification module. The network structure is referred to as multi-scale attention convolutional neural network MACNN, . TypicalIn the field of image processing, during the actual image processing, for the same image, convolution kernels with different sizes have different receptive fields as well as performance. Therefore, by using convolution kernels with different sizes for images with different scales, better results can be achieved. Similarly, during the processing of motor imagery EEG signals, differences in the physiological structures of subjects, as well as the non-linearity and non-stationarity of potential spontaneous activity signals in motor imagery, there are considerable differences among EEG signals collected by different subjects and those collected by the same subject at different time periods. Therefore, a single convolution scale network has a better classification effect on the data of specific subjects, while the data classification results of other subjects are limited. The proposed multi-branch cascade multi-scale convolution network is used to extract the characteristics of different scales to adapt to the differences between signals of different subjects or the same subject.The multi-scale convolution network module includes a combination of inception and residuals of three parallel branches; the inception module is inspired by the Inception module in the classical GoogLeNet. The inception part of a single branch of the network has four parallel branches, three convolution branches, and one pooling branch. After each convolution, batch normalization (BN) layer and activation layer  operations are carried out; the size of the three convolution cores is To prevent degradation of the network, a residual module is added after the multi-scale convolution of each branch, which also increases the network depth. Similarly, there are BN layer and ReLU operations after each convolution. The calculation results of the residual part and convolution part are combined, that is, output characteristics of the shallow layer are transmitted to the deep layer, which prevents network degradation.In deep learning, the attention mechanism is used to focus on critical points among varied feature information; it ignores unimportant feature information. A CBAM is a lightweight general module. It focuses on the relationship between channels and spatial dimensions and automatically learns the importance of channels and spatial features; also, it can be integrated into any CNN architecture. Compared with the SE module which only focuses on the relationship between channels (squeeze-and-excitation), the CBAM module shows better results. Therefore, in this study, the CBAM module is added to the proposed network structure; the features calculated by the multi-scale convolution network module are further refined by giving as input to the CBAM attention mechanism module.The overall structure and submodule structure of the CBAM attention mechanism module are shown in https://keras.io/, accessed on 29 September 2020) for algorithm implementation; NVIDIA Titan Xp128 G GPU is used for network model training and testing in the Linux system.This experiment uses Python 3.9 and the deep learning keras framework , it is provided by the Department of Medical Informatics, Institute of Biomedical Engineering, Graz University of Technology . The dataset comprises EEG data of nine subjects. The experimental paradigm employed visual cues; subjects completed four motor imagery tasks, namely, motor imagery of the left hand, right hand, feet, and tongue. Each subject recorded data for two sessions on separate days; each session consisted of six sets of trials with 48 motor imagery sessions (12 motor imagery sessions per category), with a short rest after each session; thus, there were 288 motor imagery trials in one session and 576 motor imagery sessions in two sessions.The data set used is BCI Competition IV data set 2a , direct model transfer (TL), model transfer with target data fine-tuning (TL + FT), data alignment processing model transfer (EA + TL), and data alignment processing model transfer with target data fine-tuning (EA + TL + FT), and the results are shown in For the four classification data of motor imagery, in order to observe the classification performance of the proposed method on the four-class data of each subject, the confusion matrix of a motor imagery classification and recognition experiment of nine subjects is shown in In this study, an attention mechanism-based multi-scale convolutional network is designed, and the transfer learning data alignment algorithm is introduced to analyze motor imagery EEG signals for improving the classification of motor imagery EEG signals. Experimental results showed that the average recognition rate of the proposed algorithm dual channel attention module migration alignment with convolution neural network (MS-AFM) reaches 80.76%, and the average classification result after the introduction of the transfer learning data alignment method is 86.03%, which is a significant improvement. In the experiment, five modes were compared: no sample transfer, direct sample transfer, sample transfer plus a small amount of target data fine-tuning, data alignment processing and sample transfer, data alignment processing and sample transfer, and a small amount of target data fine-tuning. The results show that the data alignment plus transfer learning Processing and fine-tuning with a small amount of target data have the highest classification accuracy, with an average recognition result of 86.0% for nine subjects, which is 5.3%, 9.4%, 3.4%, and 6.7% higher than the other four modalities, respectively. Furthermore, for the classification of motor imagery EEG signals, the direct sample transfer method without data alignment may reduce the classification accuracy, the sample transfer learning alignment method makes the EEG data distribution similar, and the sample isomorphic transfer learning can increase deep learning. The training set data to improve the classification accuracy of motor imagery EEG signals. At the same time, the EA method used in this paper is computationally simple and unsupervised, and can be used in more preprocessing situations.


The aim of the present study was to reveal the associations between skeletal and soft tissue features of the nasomaxillary complex and development and severity of obstructive sleep apnea (OSA) in adolescents. A total of 100 adolescents  were enrolled. All participants underwent full-night polysomnography and had an assessment of size and position of the tongue, tonsillar size, body mass index (BMI), and circumference of the waist, neck, and hip. The skeletal features of the nasomaxillary complex, including the zygomatic arch width, nasal cavity width, nasal base width, intercanine width, intermolar width, maxillary dental arch length, palatal vault angle, palatal depth, and SNA were measured on the three-dimensional images constructed with computed tomography data. Participants with an apnea and hypopnea index (AHI) of lower than 5 (AHI ≤ 5) were classified as control and participants while those with an AHI of greater than 5 were classified as OSA group. Each variable with a significant outcome in the independent T-test and age and sex factors were integrated into the multivariate linear regression and the dependent variable was AHI. There were significant differences in the BMI and hip circumference between two groups. The width of nasal base, palatal vault angle and SNA also showed significant differences between groups. The results from multivariate linear regression demonstrated that the BMI, width of the nasal base, and SNA showed significant contributions to the severity of OSA in adolescents. The features of the nasomaxillary complex seemed to have significant influences on development and severity of OSA. Obstructive sleep apnea (OSA) is characterized by repetitive complete or partial collapse of the upper airway during sleep, which causes a cessation or reduction in the airflow . A numbeAlthough obesity is the main risk factor, the facial profiles and soft tissue features of the upper airway have been regarded as other anatomical risk factors for OSA. Enlarged tonsils may have a role in the development of OSA, especially in pediatrics , 9. The Adolescence is a unique stage of life during individuals undergo biopsychological transitions from childhood to adulthood which is accompanied by an alteration in growth acceleration, pubertal development, sex and growth hormonal levels, and psychological maturation . The preThis was a cross-sectional study, which was conducted using the clinical and radiographic records and polysomnography (PSG) data of 100 adolescents  who had been referred to the Sleep Center of Ajou University Hospital, Suwon, Korea, owing to snoring and/or subjective sleep disturbance at night.The World Health Organization defines an adolescent as anyone between 10 and 19 years of age . To asseAll participants underwent a full overnight in-laboratory PSG . Total sleep time, sleep latency, sleep efficiency, rapid eye movement (REM) latency, apnea-hypopnea index (AHI), respiratory disturbance index (RDI), respiratory effort related arousal (RERA), and oxygen desaturation index (ODI) were assessed. Determination of apnea was conducted if both of the following were met: 1) There is a drop on the peak signal excursion by more than 90% of pre-event baseline using an oronasal thermal sensor; 2) The duration of the more than 90% drop in sensor signal is more than 10 seconds. The hypopnea was defined if all of the following were met: 1) The peak signal excursion drops by more than 30% of pre-event baseline using nasal pressure.; 2) The duration of the more than 30% drop in signal excursion is more than 10 seconds; 3) There is more than 3% oxygen desaturation from pre-event baseline or the event is associated with an arousal . Total aThe diagnostic criteria of PSG for adolescents were controversial, and the American Association of Sleep Medicine (AASM) suggested that adolescents could be scored using either pediatric or adult criteria . HoweverAll participants underwent an assessment of the size and position of the tongue, tonsillar size, height, weight, and circumference of the waist, neck, and hip. The modified Mallampati’s score was used to assess the size and position of the tongue  and tonsAll participants underwent the upper airway CT for screening for skeletal abnormality and soft tissue swelling. The three-dimensional images of the upper airway and nasomaxillary complex were constructed with CT data, using Mimics® software . The following parameters were measured: orbital width, which is defined as the distance between the orbitale (Or) from both sides; zygomatic arch width, indicating the transverse width between the points on the most lateral part of the zygomatic arch on the right and left (Z); nasal cavity width, defined as the transverse width between the points on the most lateral part of each nasal cavity (Nc); nasal base width, indicating the distance between the junction of the palatal cortical alveolar bone and the cortical nasal bone (Nf); SNA, defined as an angle made by the sella (S), nasion (N) and the A point (A) . IntercaSample size calculations were done based on a two-sided type I error of 5% and a power of 80%. The proportion between control and OSA group was based on previous report which demonstrated that prevalence of OSA in habitual snoring adolescents were about 21.2% . Power aAmong 100 participants, 79 were classified into the control group and 21 into the OSA group. No significant differences were observed in terms of age and sex distribution between the two groups. Among the anthropometric variables, BMI and hip circumference showed significant differences between the groups .The size and position of the tongue and tonsillar size seemed not to contribute significantly to the development of OSA. The variables related to orbital and zygomatic arch width seemed to have little association with the occurrence of OSA. Similarly, dental variables, including intercanine width, intermolar width, maxillary arch length, arch ratio, and palatal depth did not show significant relationships with the occurrence of OSA. On the other hand, the variables associated with the volume of the nasal cavity such as the width of the nasal base and palatal vault angle, and variables representing the anterior-posterior relationship of the cranium and maxilla such as the SNA showed significant differences .The total sleep time, sleep latency, sleep efficiency, REM latency, and RERA did not show significant differences. On the other hand, AHI, supine AHI, RDI, ODI, total arousal index, and relative snoring time showed significant differences between the two groups .The variable with a significant outcome in the independent T-test including BMI, hip circumference, width of the nasal base, palatal vault angle, and SNA and age and sex factors which were known as critical factors for incidence of OSA were integrated into the multivariate linear regression in order to identify whether these variables as a whole affected the severity of OSA. The outcome variable was AHI. The results from multivariate linear regression demonstrated that BMI, width of nasal base, and SNA contributed significantly to the AHI scores in adolescents .During the last decades, the significant therapeutic effects of many treatment modalities which tried to correct abnormal anatomical structures of the naxomaxillary complex on the increased volume of the upper airway and sleep quality have been proposed and therapeutic effects of some of those modalities are maximized during pubertal growth spurt –18. HoweThere are some risk factors for OSA need to be assessed differently for adults and children. For example, the contribution of adenotonsillar hypertrophy may be different in pediatric and adolescent OSA. The tonsillar size showed positive correlations with AHI in toddlers and preschoolers but not in adolescents . Our resThe modified Mallampati score has been regarded as a simple and valid method of assessing relationships between the tongue, soft palate, and oral cavity . This haThe results from multivariate linear regression showed that BMI, the width of the nasal base, and SNA seemed to have significant influences on the severity of OSA. The impacts of obesity on development and severity of OSA have been well-known , 51. MaxMany previous studies which attempt to reveal the associations between craniomaxillofacial features and severity of OSA have focused on the upper airway volume or cross-sectional area of pharynx , 54–56. There are several limitations to this study. Firstly, the present study simply defined the adolescents as individuals aged between 13–17 and did not consider the endocrinological factors. Secondly, because the present study was a hospital-based study, the participants were recruited from a tertiary medical center and not from the community. Thirdly, because only CT data were utilized in the study, limited information about soft tissue size measurement was provided. Finally, owing to the relatively small sample size, especially in the OSA group, the power of statistical significance is inevitably compromised. Furthermore, owing to the small number of female participants, this study could provide limited information about the sex contribution in the development of OSA in adolescents. Future studies with larger samples of participants recruited from the community and analysis about hormonal levels and soft tissue size measurement should be conducted to further elucidation of the risk factors for OSA in adolescents.Adolescence is different from childhood and adulthood, and the diagnosis and management of OSA in adolescents should differ from that in pediatrics or adults. A comprehensive understanding of the anatomical elements of the upper airway in terms of skeletal and pharyngeal growth rather than the quantification of anatomical abnormalities is essential for the proper management of OSA in adolescents.


The growth and stress responses developed by the plant in virtue of the action of PGPR are dictated by the changes in hormone levels and related signaling pathways. Each plant possesses its specific type of microbiota that is shaped by the composition of root exudates and the signal molecules produced by the plant and microbes. Plants convey signals through diverse and complex signaling pathways. The signaling pathways are also controlled by phytohormones wherein they regulate and coordinate various defense responses and developmental stages. On account of improved growth and stress tolerance provided by the PGPR to plants, there exist crosstalk of signaling events between phytohormones and other signaling molecules secreted by the plants and the PGPR. This review discusses some of the important aspects related to the ambiguities of signaling events occurring in plants, allowing the interaction of PGPR with plants and providing stress tolerance to the plant. Plant growth-promoting rhizobacteria (PGPR) are known to positively stimulate the growth of plants by providing important nutrients and stress tolerance . In addition to MAPKs, CDPKs have also shown an important role in plant growth and development under abiotic stresses by modulating abscisic acid (ABA) signaling and regulating reactive oxygen species (ROS) accumulation  pathways and calcium-dependent protein kinase (CDPK) pathways working inside the plant  and effector-triggered immunity (ETI). PTI is triggered by conserved microbial signatures called pathogen/microbe-associated molecular patterns (PAMP/MAMP), which are perceived by pattern recognition receptor (PRR) at the cell surface, leading to a basal level of the immune response. The second level of immunity, ETI, is developed against effector molecules injected by pathogens inside the plant to counteract the PTI. ETI is also called the R gene-dependent resistance or gene for gene resistance , Gibberellic acid (GA), zeatin, ET, and ABA  are important hormones regulating seed germination, apical dominance, senescence, and interaction of the plant with microbes  deaminase controlling excessive ethylene production . BacteriBesides signaling molecules produced by PGPR, the plant secretes low molecular weight, high molecular weight, volatile, and non-volatile compounds in the root exudates, which influences the interaction of various microbes in the rhizosphere. Studies have shown that signaling molecules such as coumarins, triterpenes, flavonoids, and benzoxazinoids allow the growth and inhibition of specific microbes in rhizospheric regions of plants . The SLs are involved in many of the important aspects of plant development earlier defined as ex-planta signaling molecules secreted by plants' roots inducing germination of parasitic plants. Later, they were found to help in establishing a symbiotic relationship between plants and arbuscular mycorrhizal fungi  also called Nod factors are signaling molecules, originally studied to be produced by Rhizobia with leguminous plants is with the help of recognition of LCOs/Nod factors (NFs) by Nod factor receptors (NFRs) of leguminous plants. Two NFR receptors, NFR1 and NFR5, bind Nod factors directly , which shows the dual functions, i.e., in symbiosis as well as in plant defense , containing oligosaccharide-binding LysM domain. It is presumed that binding of LCOs with LysM receptors activates the signaling pathway, leading to the oscillation of nuclear calcium concentration, leading to the formation of nodules, and promoting the symbiotic association. The symbiosis established by Oldroyd, . A studyOldroyd, . SeveralXanthomonas campestris. The induction of nodulation by Bel 2-5 effector is through the expression of cytokinin-related genes involved in nodule organogenesis and repressing ethylene and defense-related genes  to deliver virulence factors (T3 effector proteins), certain rhizobial strains also produce effector protein called nodulation outer protein L (NopL), affecting the nodule formation in symbiosis. NopL bypass the NFR for the formation of the nodule in the legume. NopL affects the process of nodule formation by interacting with plant signaling pathways. A study was performed to show that phosphorylation of NopL was inhibited by Ser/Thr kinase inhibitor and MAPKK inhibitor, suggesting NopL to be a substrate of MAPK  , late embryogenesis abundant (RAB18), and also the important players of MAPK signaling cascade MPK3 and MPK6, thus increasing the ROS scavenging activity  by the enzyme phosphoethanolamine-lipid-A transferase (EptA)  controls the Na+ import and overexpression of this transporter fails to impart salt tolerance, making plants more susceptible  was reported to improve salt and drought tolerance by reprogramming the biosynthesis of stress hormones, such as salicylic acid and abscisic acid, chlorophyll content, and expression of antioxidants  has been reported to act as a biocontrol agent apart from its beneficial role in imparting salt tolerance. This bacterium exerts its effect by modulating phytohormone signaling, producing secondary metabolites, osmoprotectants, and scavenging ROS  from University Grant Commission, Govt. of India, and DST-SERB start-up grant (File no. SRG/2021/001830-G) Govt. of India.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.