Premenstrual syndrome (PMS) is a group of psychological, physical, and behavioral symptoms that recur with the menstrual cycle, usually occurring a few days before menstruation and ceasing with the onset of menstruation. Premenstrual dysphoric disorder (PMDD) is a severe form of PMS that has been included in a subcategory of depression in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) according to the latest diagnostic criteria. Patients usually present with mild to moderate emotional and physical symptoms that affect their routine work, social activities, and family lives. The pathogenesis of PMDD remains unclear, and some researchers believe that it is related to fluctuations in ovarian hormone levels. However, the details of the interrelationships and regulating effects between ovarian hormones, symptoms, and the brain need to be more comprehensively determined. Recent studies have revealed some novel findings on PMS and PMDD based on brain morphology, function, and metabolism. Additionally, multiple studies have suggested that PMS and PMDD are closely related to brain structural and functional variations in certain core temporal lobe regions, such as the amygdala and hippocampus. We summarized neuroimaging studies of PMS and PMDD related to the temporal lobe by retrospectively reviewing relevant literature over the past decade. This review contributes to further clarifying the significant role of the temporal lobe in PMS and PMDD and understanding the neurochemical links between hormones, symptoms, and the brain. Estrogen and progesterone have far-reaching effects on females throughout their lifespan . Many feIn the past three decades, the application of modern science and technology to investigate PMS and PMDD has lagged significantly behind that of other diseases. Today, while neuroimaging research is starting to be applied to these disorders, the neuropathological mechanisms are unclear . Even soMini-Review.It is well-known that the medial temporal lobe (MTL) includes the amygdala, hippocampal region, and entorhinal cortex and is responsible for memory and emotion processing . ExtensiThe amygdala is located deep in the MTL and plays an essential role in the limbic system and central emotional circuitry . Its funMore recent evidence has shown that the hippocampus is a rich-club hub and the most sensitive region to menstrual cycle changes . In healHow do sex hormones act on the hippocampus? These actions are mainly due to the neurotrophic influence of estradiol  and the Another key question is why the amygdala and hippocampal region are the most susceptible regions in PMS and PMDD. In brief, the amygdala and hippocampus are potential targets of sex hormone effects . There iIn addition to the MTL, other temporal lobe regions are also relevant in PMS and PMDD. Fractional amplitude of low-frequency fluctuation (fALFF) values in the left inferior temporal cortex and left hippocampus were higher in PMS females than in healthy individuals . RegionaAdditionally, other evidence suggests that the fusiform gyrus also changes with the menstrual cycle in healthy women. An fMRI study reported abnormal functional activity in the amygdala, fusiform gyrus, inferior temporal gyrus, and middle temporal gyrus . ProgestRegions with different properties and locations in the brain form neural circuits through various forms of complex connections. When a particular node is abnormal, other brain regions within the circuit are likely to be disrupted, thereby affecting the overall function of the circuit. In fact, the amygdala and hippocampus occupy core positions in several pivotal neural circuits, such as the hippocampus-amygdala, hippocampus-entorhinal cortex, hippocampus-prefrontal circuit, amygdala-prefrontal cortex, and amygdala-thalamus circuits .Of note, significant variations in several circuits assessed with neuroimaging have also been found in PMS and PMDD. Taking the hippocampus-amygdala circuit as an example, functional activity in this circuit basically coincides with fluctuating levels of ovarian gonadal hormones across menstrual cycle phases in healthy females . Namely,Besides neural circuits, brain regions also constitute neural networks—the execution and maintenance of normal function in bodies rely on homeostasis within and coordination between these networks , 65. PreOverall, insight into the susceptibility and plasticity of network dynamics and topology is necessary to comprehensively explore the neuropathological mechanisms underlying PMS and PMDD , 66. HowIn general, harmonious covariations between the metabolism, structure, and function of the brain and ovarian gonadal hormone levels during the menstrual cycle exist in healthy females. In contrast, the diverse array of inappropriate manifestations and remodeling of metabolism, structure, and function have occurred in multiple regions in PMS and PMDD women. However, there was a high level of heterogeneity in the current results due to differences in MRI scanning equipment and sequence parameters, analysis methods, and the menstrual phase in which women were scanned. Nevertheless, the existing neuroimaging findings showed high consistency regarding the involvement of temporal lobe regions, such as the amygdala and hippocampus, which confirms the prominent role of the temporal lobe in PMS and PMDD. Furthermore, genetics and environmental factors, abnormal immune responses, and changes in circadian rhythms trigger increased sensitivity to sex hormones, which in turn affect other neurotransmitters and hormonal systems , thereby influencing the temporal lobe and further affecting mental health and behavior –72. TherAll authors contributed to the article and approved the submitted version.This work was supported by the Health Commission of Wuhan scientific research project (WX19D62 to LL).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. 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Hepatic ischemia-reperfusion injury (HIRI) is an additional injury to ischemic tissue after hepatic revascularization, and its pathological mechanism is complex. HIRI is not only involved in the molecular targets that mediate cell death, such as ion channel activation, abnormal protease activation and mitochondrial dysfunction, but also related to the down-regulation of endogenous protective signals. As a by-product of normal aerobic metabolism, reactive oxygen species (ROS) act as a multi effect physiological signal factor at low concentration. However, liver ischemia-reperfusion will lead to excessive ROS accumulation, destroy redox homeostasis, lead to oxidative stress, cause cell death through a variety of mechanisms, and drive the further damage of ischemic liver. Recent studies have found that the antioxidant treatment of nano selenium can reduce the excessive production of ROS and play a potential protective role in reducing HIRI. This paper reviews the molecular mechanism of the antioxidant effect of nano selenium for the prevention and treatment of HIRI, in order to provide further experimental basis for the clinical prevention and treatment of HIRI. Hepatic ischemia-reperfusion injury (HIRI) refers to the recovery of hepatic perfusion blood flow after a period of ischemic liver injury, which leads to the further aggravation of the original liver injury. Its occurrence is an important reason for postoperative liver function injury, liver failure and even death. At present, it is considered that the role of calcium overload is closely related to the destruction of the structure and function of neutrophils. HIRI can be divided into two stages: ischemia and reperfusion. In the ischemic stage, ATP concentration in cells decreases, leading to Na/K pump failure, cell edema and increased cytoplasmic calcium concentration, which will lead to cell damage. At the early stage of reperfusion , Kupffer cells release proinflammatory mediators  and reactive oxygen species (ROS); In the late stage of reperfusion , neutrophil mediated inflammatory reaction occurs. Complement factors, chemokines and Cytokines recruit neutrophils into the liver and destroy the liver cells by releasing ROS or proteases.Among them, a crucial role in HIRI is played by oxidative stress. Excessive ROS can lead to calcium overload, apoptosis, up regulation of cytokines and changes of DNA and protein , which cBecause the molecular mechanism involved in ischemia-reperfusion injury is very complex and the correlation between various pathways is very close, this leads to the limited effect of a single intervention factor on liver ischemia-reperfusion injury, and can not comprehensively and fully avoid the occurrence of liver ischemia-reperfusion injury. Drugs for HIRI treatment should meet multiple treatment indexes at the same time, so as to give better play to the curative effect of drug treatment. It has been reported that nano selenium can play an antioxidant role by directly scavenging reactive oxygen species, enhancing the antioxidant capacity of enzymatic antioxidant system and inhibiting cell apoptosis. Because nano selenium can play an important role in preventing and protecting HIRI caused by oxidative stress, this paper reviews the progress of nano selenium in regulating oxidative stress in HIRI, in order to provide reference for clinical prevention of HIRI.2-), and hydrogen peroxide (H2O2). It is worth noting that ROS, as a second messenger, can be used as a physiological signal factor in the normal process of cell growth, migration and death when it exists in low concentration  and reactive nitrogen (RNS), so that the degree of oxidation exceeds the removal of oxidants, and the balance between the oxidation system and the antioxidant system is broken, resulting in tissue damage, which is Oxidative Stress. ROS mainly refers to hydroxyl radicals (•OH), superoxide anions  signaling pathway in myeloid differentiation factor 88 dependent pathway, and then stimulates IL-1β, IL-18 expression  - 1β, The maturation and secretion of IL-18 and the leakage of cell contents lead to a pro-inflammatory form of programmed cell death called focal death . In recepression . The latpression . Becausepression . At the pression . By intrpression ,  plays an important role as one of the essential trace elements. It mainly exists in organic selenium in the body, including selenase, selenium ribonucleic acid, selenoprotein and other forms . It is aIn vitro, the ability of nano selenium with different particle sizes to directly scavenge free radicals is significantly different. The smaller the particle, the better the scavenging effect. Tong Chunyi et al. (2SeO3; The maximum clearance concentration of nano selenium is about 1/3 of vitamin C and 1/5 of Na2SeO3; The semi clearance concentration of nano selenium is also lower than that of the other two antioxidants. It shows that nano selenium has good antioxidant effect, and has great advantages in dose. It is an efficient antioxidant.Nano selenium can directly remove ROS. The nano selenium spherical particles modified by CS with different molecular weight have good scavenging ability to DPPH, ABTS and other free radicals; In a certain range, the inhibition intensity of ROS in skin and intestinal cells depends on the concentration of selenium in nano materials. The higher the concentration, the greater the inhibition intensity of ROS . Huang ei et al.  detectedin vivo. As a first line of defense against ROS, SOD converts superoxide free radicals into H2O2 and water; CAT further catalyzes H2O2 to produce water and oxygen (Both enzymatic and non-enzymatic antioxidant systems can clear ROS. Non-enzymatic antioxidant system is mainly divided into water-soluble antioxidants and fat soluble antioxidants; Enzymatic antioxidant system includes various antioxidant enzymes, such as SOD, CAT, GPX and TRX. SOD and cat are very important antioxidant enzymes d oxygen .in vivo. Loeschner et al. (2Se, and then incorporated into the active sites of various selenoproteins such as GPX and TRX, so as to significantly improve the activity of selenoproteins and prevent oxidative damage to the body. The intake of nano selenium particles first leads to the reduction of human ROS level. Before apoptosis, it stimulates the transcription of various downstream antioxidant enzyme genes by activating nuclear transcription factor Nrf2, promotes the human body to clear ROS and protects the intestine from oxidative stress (Nano selenium can enhance the antioxidant capacity of enzymatic antioxidant system r et al.  found the stress .Nano selenium can play an antioxidant role by inhibiting apoptosis. By upregulating the expression of anti-apoptotic protein Bcl-2 and down-regulating the expression of apoptotic protein Bax, nanoselenium regulates mitochondrial membrane permeability and inhibits the release of pro-apoptotic proteins into the cell, including cytochrome C, thereby inhibiting the occurrence of apoptosis . In addiAlthough the good antioxidant effect of selenium nanoparticles has attracted the attention of researchers, due to the specific intracellular function of an appropriate amount of ROS, while ordinary antioxidants will affect healthy tissues that have not suffered oxidative damage while providing intervention treatment. At the same time, researchers also found that some receptors, proteins or enzymes are abnormally high expressed in specific damaged cells, but not expressed or low expressed in normal tissues and organs. It is possible to use these expression differences to guide drugs to target cells, so as to improve effects and reduce side effects. Therefore, based on the above view, targeted antioxidants show great potential. For example, mitoxantrone methanesulfonate can combine with lipophilic triphenylphosphine to produce active antioxidant ubiquitin in mitochondria and prevent the production of mtROS in ischemia-reperfusion model .In the application field of nano selenium, functional modified nano selenium is also a research hotspot in recent years. The nanoparticles modified by targeted polypeptide surface can bind to the receptor overexpressed by targeted cells, so as to achieve the purpose of specific drug function. In addition, the surface modified nanoparticles can also improve the absorption and efficacy of drugs by corresponding target cells. At present, many scientific research teams have conducted in-depth research on the functionalization of nano selenium and prepared a variety of functionalized nano selenium. For example, the study of Chen et al.  demonstrIn conclusion, ROS mediated oxidative stress plays an important role in HIRI. Reducing the large amount of ROS produced during HIRI is of great significance to reduce HIRI. Nano selenium, as an antioxidant with high efficiency and low toxicity, shows a good application prospect in anti HIRI. Compared with other forms of selenium, nano selenium can not only act as a separate antioxidant drug, but also play an antioxidant role by directly scavenging reactive oxygen species, enhancing the antioxidant capacity of enzymatic antioxidant system and inhibiting cell apoptosis; It can also further improve the antioxidant capacity and targeting through functional modification, and play an important role in preventing and protecting HIRI caused by oxidative stress. With the continuous improvement of scientific and technological level and the deepening of research, a nano selenium drug with strong antioxidant capacity, good targeting and high stability may appear in the future, which can be used in the treatment of clinical HIRI.


In the field of advanced melanoma, there is an urgent need to investigate novel approaches targeting specific components of the cancer–immunity cycle beyond immune checkpoint inhibitors. The authors reviewed the basic understanding of the role of neutrophils in cancer biology, and the latest clinical evidence supporting the correlation between cancer-associated neutrophils and the prognosis and response to the immunotherapy of advanced melanoma. Finally, they propose that granulocyte and monocyte apheresis, an emerging non-pharmacological treatment in current dermatology, could become an investigative treatment targeting melanoma-associated neutrophils which could be potentially used in combination with the usual immune checkpoint inhibitors. The introduction of immunotherapy with immune checkpoint inhibitors has transformed the treatment scenario of advanced and metastatic melanoma with the achievement of sustained response and long-term survival rates that were unthinkable with classical oncologic therapies ,2. MelanHowever, patients with advanced or metastatic melanoma (as well as those with other solid neoplasms) may not respond to this systemic treatment in up to 50% of cases and can benefit from limited therapeutic alternatives . EffectiThe authors have reviewed the current knowledge of the role of neutrophils in cancer biology, with a focus on melanoma, and the recent correlation of cancer-associated neutrophils with the prognosis and response to immunotherapy in advanced melanoma. Finally, they propose granulocyte and monocyte absorptive apheresis, an emerging non-pharmacological treatment in dermatology, as a future investigative treatment targeting melanoma-associated neutrophils that could be potentially used in combination with the usual immune checkpoint inhibitors.While it is established that neutrophils are the key players of the innate immune system, orchestrating infective and inflammatory responses, the study of their role in tumors is relatively recent . TraditiThe developmental stages of neutrophils succeed one another during granulopoiesis, which takes place in the bone marrow: hematopoietic stem cells yield multipotent progenitors, followed by common myeloid progenitors, granulocyte and monocyte progenitors, pro-neutrophils or committed progenitors, neutrophil precursors, immature neutrophils, and mature cells . BaselinIn the TME of melanoma, as in that of other tumors, the most represented immune cell population is that of neutrophils. Despite their abundancy, the molecular interactions in which they are involved have only been partially explored. It is known that cancer secretes the potent pro-inflammatory cytokines, TGF-beta, IL-6 and IL-8, that are able to recruit neutrophils, and drive a switch from an anti-tumor phenotype to a tumor-promoting and immunosuppressive profile ,13.The mobilization of neutrophils from the bone marrow is regulated by activating the CXCR2 chemokine receptor . IL-8 isThe apparently linear model of ontogenesis described above does not reflect the actual complexity of neutrophil states and subsets that have been described in the literature. In cancer biology, neutrophil heterogeneity underlies the differential roles of these cells and impacts the feasibility of therapeutic strategies targeting all or only individual neutrophil subsets. Neutrophil heterogeneity and function have been related to general host factors: infection, including severe COVID-19 , chronicNeutrophils have also been credited with protective functions related to an anti-tumorigenic phenotype . This apMoreover, cells of the innate immune system can become trained after host exposure to agonists with anti-tumor effects, such as beta-glucans , adding Finally, though our current knowledge is informative of associations between neutrophil states and tumors, mechanistic evidence on their causative role in tumor promotion is still incomplete. Moreover, an in-depth understanding of neutrophil heterogeneity in cancer will be required to devise targeted strategies aimed at specific neutrophil subtypes relevant to cancer.A substantial fraction of subjects with advanced melanoma is not responsive to immune checkpoint inhibitors, and, in the era of precision medicine, the identification of predictive biomarkers is a current unmet need. Ideal biomarkers are expected to specifically inform on the response and tolerability to treatment while being easily measurable in the clinical setting. Candidate tumor markers related to the mechanism of action of PD-1 inhibitors, such as PD-L1 tissue expression, immune cell infiltrate and tumor mutation burden are not reliable predictors of a response to immunotherapy in melanoma ,28. ConsSerum lactate dehydrogenase is an established prognostic factor in metastatic melanoma and its role as a predictive marker has been recently investigated in a meta-analysis .Elevation in peripheral blood neutrophils, measured as an absolute count and as a neutrophil-to-lymphocyte ratio (NLR), has been assessed as a potential biomarker in melanoma. A 2018 study by Capone et al. showed significantly lower progression-free survival (PFS) and overall survival (OS) with an NLR ≥ 5 than with a low NLR  in melanoma patients receiving nivolumab. An improved response to treatment was also observed in the low NLR group . AnotherThese studies suggest that markers of general immune function and systemic inflammatory response such as the NLR are related to survival in subjects treated with PD-1 inhibitors. Moreover, measurement of the NLR in the serum is straightforward and economic, enabling repeatable dynamic sampling. Further investigation is required to establish their predictive role to aid in the patient selection of subjects that would maximally respond to immunotherapy and, conversely, to spare those who would not benefit from treatment from the risk of toxicity. Finally, the immune mechanism underlying the relation between a high NLR and worse clinical outcome in melanoma is still unknown.Granulocyte and monocyte apheresis (GMA) is an extracorporeal adsorptive apheresis technique which has been proposed in dermatology as an innovative alternative treatment option for disorders mediated by active neutrophils . A growiThe effects of GMA are due to a selective depletion of activated cells of the myeloid lineage . The molThe principal advantage supporting the use of GMA is its excellent safety. Adverse events reported in the literature were related to obtaining a venous access and maintaining an adequate flow, risk of coagulation, increased venous pressure and difficulty in venous return, and none was considered serious ,43. The Past studies provided preliminary evidence on the effect of GMA in the setting of advanced cancer associated with increased granulocytes. In a 1995 trial, seventeen subjects with recurrent metastatic tumors underwent fifteen sessions of GMA, showing a partial response in four cases and no significant side effects . These rIn melanoma, an increased presence of cancer-associated neutrophils has been related to an unfavorable prognosis and poor treatment outcomes .This informative association constitutes the basis for expanding our knowledge on the role of neutrophils in cancer immunology and for discovering neutrophil-targeted immunotherapies . Specifi


Macrophages represent the most functionally versatile cells in the animal body. In addition to recognizing and destroying pathogens, macrophages remove senescent and exhausted cells, promote wound healing, and govern tissue and metabolic homeostasis. In addition, many specialized populations of tissue-resident macrophages exhibit highly specialized functions essential for the function of specific organs. Sometimes, however, macrophages cease to perform their protective function and their seemingly incomprehensible response to certain stimuli leads to pathology. In this study, we address the question of the origin of the functional versatility of macrophages. To this end, we have searched for the evolutionary origin of macrophages themselves and for the emergence of their characteristic properties. We hypothesize that many of the characteristic features of proinflammatory macrophages evolved in the unicellular ancestors of animals, and that the functional repertoire of macrophage-like amoebocytes further expanded with the evolution of multicellularity and the increasing complexity of tissues and organ systems. We suggest that the entire repertoire of macrophage functions evolved by repurposing and diversification of basic functions that evolved early in the evolution of metazoans under conditions barely comparable to that in tissues of multicellular organisms. We believe that by applying this perspective, we may find an explanation for the otherwise counterintuitive behavior of macrophages in many human pathologies. The human body is made up of more than two hundred types of cells . Unlike via cytokine signaling    . We thenHolozoa)  to formuDictyostelium discoideum; Amoebozoa)   to exploPorifera; Holozoa), which represent multicellular animals without yet fully differentiated tissues and organs  as a representative of a simple animal with fully developed tissues and organs at a level of complexity comparable to that of mammals , components of the complement cascade , or formyl peptides . Unlike  the ECM .To effectively distinguish various pathogens from the body’s own cells, macrophages must sense and recognize specific pathogen-associated antigens on the surface of the foreign cells. These molecules are recognized by immune-cell-specific receptors called pattern recognition receptors (PRRs) . MammaliThe underlying mechanism enabling these changes is the modification of cellular metabolism. Strikingly, pro-inflammatory macrophages adopt aerobic glycolysis as the predominant method of ATP production, driven by the stabilization of the transcription factor HIF1α . While oIn addition to pathogenic activation, macrophages are activated by signals produced by damaged, metabolically stressed cells and tissues, known as DAMPs (danger-associated molecular patterns), leading to M2 macrophage polarization . While tM2 macrophages differ significantly from their M1 counterparts in cellular metabolism, which determines their different function. While the amino acid arginine serves as a substrate for iNOS in M1 macrophages, as it is essential for the production of ROS , M2 macrM2 macrophages are also responsible for maintaining tissue homeostasis under physiological conditions by detecting and removing apoptotic and damaged cells through efferocytosis. The term “efferocytosis” was introduced by M2 macrophages can be divided into different polarization subtypes, such as M2a, M2b, M2c, and M2d, based the on the specific cocktail of chemokines, cytokines, and growth factors they polarize with and subsequently produce . In addiOverall, macrophages are truly unique cells of the animal body that can play many roles in different tissues and body contexts by combining several specific properties. In particular, macrophages are exceptional at sensing chemotactic signals, exhibiting controlled active motility, recognizing molecular patterns associated with pathogen or tissue damage, and adopting metabolic and functional polarization accordingly. These properties predispose them to deal with stressful situations in the body .Acanthamoeba and macrophages share the principal mechanisms used for chemotaxis towards bacteria, motility, interaction with bacteria, phagocytosis, the killing of bacteria in the phagolysosome, and production of antimicrobial peptides  outside the phagolysosomes, thereby limiting the ability of engulfed bacterial to use metalloenzymes required to escape the phagolysosome . The slug conforms to all the parameters of a multicellular organism. The originally amoeboid vegetative cells differentiate into four distinct cell types that coordinate their behavior and give rise to a fruiting body that produces resistant spores . These surface receptors show substantial homology to many mammalian PRRs, such as scavenger receptors (LIMP-2), toll-like receptors , leucine-rich repeats receptors (LrrA), and C-type lectin receptors. Activation of these receptors triggers intracellular signaling cascades initiating phagocytosis, phagosome maturation and bacterial killing, and stress-related cascades and detoxification response  or Fc receptors analogously initiates increased motility, phagocytosis, and production of pro-inflammatory factors , which is analogous to the mammalian toll-like receptors  may have looked like . Among tagellata . HoweverChoanoflagellata are able to switch to amoeboid cells under certain circumstances , which represent a phylum of basal multicellular organisms with incomplete tissues and organ systems  have taken over the original nutritional function of amoebocytes, thus providing macrophages with the opportunity to acquire additional diverse functions.D. melanogaster, a simple animal with clearly defined tissues and organs.Considering macrophage functions have diversified in animal evolution with the increasing complexity of the body, it is important to pay close attention to the macrophage-like plasmatocytes in Drosophila is a simple, genetically tractable model organism, often used to model human diseases. Over a century of genetic and molecular biological research has led to many fundamental discoveries and a knowledge base that is unparalleled by any other invertebrate model used for biological research  or eiger (TNFα)  .In addition to their protective functions, plasmatocytes also have many macrophage-like properties essential for tissue homeostasis. They are responsible for clearing apoptotic, senescent, and damaged cells through efferocytosis and express various genes required for the remodeling of the ECM . These aDrosophila embryo, plasmatocytes are attracted to the site of the wound by oxygen peroxide produced by the injured cells. Plasmatocytes infiltrating the wounded tissue clear the damaged cells and provide ECM components and growth factors necessary for tissue regeneration , a master regulator of metabolic reprogramming in mammalian M1 macrophages. The transcriptional program directed by HIF1α is required for the infection-induced increase in glycolytic flux, glucose consumption, and accelerated conversion of pyruvate to lactate in Drosophila plasmatocytes. This metabolic reprogramming, which closely resembles aerobic glycolysis in mammalian M1 macrophages, is essential for increased bactericidal activity of plasmatocytes and resistance of flies to bacterial infection , which reduces insulin signaling in the fat body. In turn, the fat body produces lipoproteins and carbohydrates that replenish activated immune cells  and systemic attenuation of insulin signaling via JAK/STAT signaling  and are responsible for the immune protection of neurons and elimination of toxic and harmful substances, and for the maintenance, neuronal pruning, and proper functioning of synapses in CNS  and draper (drpr)  . Glial cneration . Moreoveess drpr . In addiess drpr .Drosophila. It has been documented that fruit flies display enhanced survival of streptococcal infection if re-encountered by an otherwise lethal dose of the same bacteria and that this protective mechanism lies in the action of phagocytes and the Toll signaling pathway  has been identified as a specific surface receptor for highly pro-inflammatory macrophages, such as those found in the synovial tissue of arthritic patients, in atherosclerotic plaques, or in pulmonary fibrosis  abundantly expressed by macrophages and neutrophils . Activatathogens . Howeverathogens . Therefoathogens .In both cases, inadequate activation of receptors, initially designed to detect bacterial secondary metabolites and tracking bacteria in the environment, causes pathology in a complex multicellular organism, where their activation can occur even under sterile conditions .Dictyostelium produce cAMP as a potent aggregation chemoattractant  macrophages. This indicates that the bactericidal macrophage polarization represents an ancestral polarization type and the protective function of macrophages evolved from hunting microbes for nutritional reasons .Inspired by the currently revised theory of the origin of animal multicellularity , we beliGiven that the last common ancestor of animals likely switched between free-living and colonial life stages during its life cycle in response to extrinsic cues , it is pPorifera) suggests that, together with the increasing complexity of body plans, there is a need for polarization of macrophage-like archaeocytes into both phenotypes within a single organism, with the polarization phenotype depending on context rather than life stage (We can hypothesize that the divergence of macrophage functions in emerging multicellular organisms was driven by the differentiation of specialized cell types for obtaining nutrition, the growing need for harmonizing force, and the recognition of cellular identity. The diversification of the functional repertoire of macrophages in primitive multicellular organisms (fe stage . We may Upon the evolution of complex multicellular organisms, macrophages expanded their functions, reaching their full potential, participating in development, organogenesis, immune protection, self-recognition, tissue and metabolic homeostasis maintenance, and many tissue- and context-specific tasks . It is lDictyostelium, carried out in the laboratory of Erika Pearce, one of the leading scientists working on macrophage immuno-metabolism (Dictyostelium and sponges in the macrophages of higher animals and humans.We present a perspective of evolutionary biology, combined with knowledge from modern biomedical research. Both approaches can be mutually inspiring in future research on the biology of macrophage-like cells. One critical feature which contributes to the functional versatility of macrophages is their ability to adopt distinct metabolic polarization phenotypes, which are determined by epigenetic modifications and activation of specific signaling cascades. Therefore, investigating polarization phenotypes of unicellular and facultative multicellular relatives of true animals would be of interest. A seminal study addressing this was performed on tabolism . This woIn addition, we believe that understanding the role of ancestral macrophage-like cells may help to understand the biology of mammalian macrophages and possibly discover new functions. Given the ancestral origin of macrophage functions, some difficult-to-understand pathological behaviors of macrophages can be explained by the activation of ancient vestigial functions that may appear counterintuitive in a specific context in a complex multicellular body. We believe that this perspective may shed new light on the function and pathogenesis of macrophages in animals and humans.


Atherosclerosis is an important pathological basis of coronary heart disease, and the antisense non-coding RNA in the INK4 locus (ANRIL) is located in the genetically susceptible segment with the strongest correlation with it - the short arm 2 region 1 of chromosome 9 (Chr9p21). ANRIL can produce linear, circular and other transcripts through different transcriptional splicing methods, which can regulate the proliferation and apoptosis of related cells and closely related to the development of atherosclerotic plaques. Linear ANRIL can regulate proliferation of vascular smooth muscle cells (VSMCs) in plaques by chromatin modification, as well as affecting on proliferation and the apoptosis of macrophages at the transcriptional level; circular ANRIL can affect on proliferation and apoptosis of VSMCs by chromatin modification as well as interfering with rRNA maturation. In this review we describe the evolutionary characteristics of ANRIL, the formation and structure of transcripts, and the mechanism by which each transcript regulates the proliferation and apoptosis of vascular cells and then participates in atherosclerosis. In the early stage of atherosclerosis, long-term mechanical change in blood flow, high-fat and high-glucose environment, inflammatory infection damage, etc. The pathological factors of injury and pro-apoptotic factors increase, leading to the increase of endothelial cell injury and apoptosis, and the destruction of vascular endothelial integrity . SubsequNon-coding RNA (ncRNA) refers to RNAs that are not translated into proteins, mainly including microRNA (miRNAs), long non-coding RNA (lncRNA), and circular RNA (circRNA) ,6. They LncRNAs are a class of RNAs with transcripts longer than 200bp that do not encode proteins . LncRNAsThe antisense non-coding RNA  in the INK4 locus originated in placental mammals and acquired additional exons during evolution, and then part of the exons was gradually lost, and finally It is fully formed in apes . ANRIL iThis article reviews the research progress of ANRIL transcripts with different structures that affect the occurrence and development of atherosclerosis by regulating the proliferation and apoptosis of vascular cells.2Last few years the function of circular ANRIL has also been gradually explored, and with the progression of atherosclerosis, the expression level of circular ANRIL in plaque lesion tissue gradually decreases ,64. Prot3Cyclic ANRIL can also be used as a molecular scaffold for chromatin modification complexes, affecting target gene expression by regulating the covalent modification of histones, thereby affecting cell proliferation and apoptosis; or as a dynamic scaffold, binding, storing or transport transcription factors to specific subcellular locations such as mitochondria, affecting cell proliferation and metabolism ,70. Ther3.1Meseure et al. found by RNA co-immunoprecipitation method that linear ANRIL binds efficiently to polycomb family proteins such as CBX7 and SUZ12 . Polycom3.2trans-action, which can activate gene transcription by binding to target gene promoters such as cyclins, and affect the level of target gene transcription and expression. Cytologically, it is manifested as increased macrophage proliferation, enhanced metabolic activity, and decreased apoptosis [Linear ANRIL can affect the transcriptional expression levels of multiple genes and increase the risk of atherosclerosis by interfering with the transcription of target genes. Overexpression of linear ANRIL in macrophage cell lines can induce AEBP2, EZH2, Jumonji/Jmj Jarid2 C-domain family protein, MEL18 DNA-binding protein, YY1 transcriptional repressor proteins, Gli-Kruppel family proteins with transcription regulation functions, such as COREST/REST, and these proteins are enriched in Alu repeats with the most active transcription of genes in the chromosomal segment ,78. Alu poptosis . Holdt epoptosis . Also, lpoptosis .4More and more evidences show that ANRIL plays an important role in atherosclerotic cardiovascular disease, but what mechanism affects cell proliferation and apoptosis and participates in the occurrence and development of atherosclerosis still needs further research. With the continuous emergence of new technologies, studies have discovered the existence of more ANRIL transcripts, and there are more means to detect the transcriptional expression levels of target genes and protein molecules in different pathways, which provides an important guarantee for more effective mechanism exploration. However, due to the presence of many common exon fragments among different ANRIL transcripts, it is difficult to distinguish it, and the expression level of ANRIL in peripheral blood is low, and the degradation rate of linear ANRIL in vitro is high. These factors can become a serious obstacle to the process of studying the effect of ANRIL on the mechanism of the onset and development of atherosclerosis. Therefore, it is necessary to create a more stable system and a more accurate measurement method to further study the mechanism of action of ANRIL.Ilgiz Gareev, Valentin Kudriashov and Albert Sufianov conceptualized and designed the study. All authors participated in the acquisition, analysis and interpretation of the data. Sema Begliarzade, Tatiana Ilyasova and Yanchao Liang drafted the manuscript. Ozal Beylerli contributed to critical revisions of the manuscript. All authors agreed on the journal to which the article would be submitted, gave final approval for the version to be published, and agreed to be accountable for all aspects of the work.None.The authors declare that no conflicts of interest exist.


Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread across the globe since the end of 2019, posing significant challenges for global medical facilities and human health. Treatment of hospital wastewater is vitally important under this special circumstance. However, there is a shortage of studies on the sustainable wastewater treatment processes utilized by hospitals. Based on a review of the research trends regarding hospital wastewater treatment in the past three years of the COVID-19 outbreak, this review overviews the existing hospital wastewater treatment processes. It is clear that activated sludge processes (ASPs) and the use of membrane bioreactors (MBRs) are the major and effective treatment techniques applied to hospital wastewater. Advanced technology  has also achieved good results, but the use of such technology remains small scale for the moment and poses some side effects, including increased cost. More interestingly, this review reveals the increased use of constructed wetlands (CWs) as an eco-solution for hospital wastewater treatment and then focuses in slightly more detail on examining the roles and mechanisms of CWs’ components with respect to purifying hospital wastewater and compares their removal efficiency with other treatment processes. It is believed that a multi-stage CW system with various intensifications or CWs incorporated with other treatment processes constitute an effective, sustainable solution for hospital wastewater treatment in order to cope with the post-pandemic era. By the end of 2021, 1,044,000 medical facilities, including 36,000 hospitals, were established in China [During the evolution of wastewater treatment technology, the activated sludge process was the first to emerge. It was the treatment process most commonly employed in wastewater treatment plants (WWTPs) . The actIn the past three years since the outbreak of COVID-19, numerous studies and review articles have been published on hospital wastewater treatment-related topics. These articles reflect the current demand for hospital wastewater treatment and the urgency of the scenario. Ajala et al.  analyzedThrough reviewing the relevant literature and the extraction of the main ideas of these articles, we were able to identify the most important hospital wastewater issues, including the challenges and reasonable solutions, from an effective, eco-friendly, and sustainable basis. Based on the published literature and by bridging the knowledge gap, this review begins with the status of the hospital wastewater treatment profile and identifies the new challenges under the current situation. The focus then shifts to the various processes used and that have emerged for hospital wastewater treatment. Thereafter, the review clarifies the decontamination principle of each component of the CWs and their performance in terms of hospital wastewater treatment efficiency. The ecological value and engineering issues of CWs are discussed via comparison with other treatment processes. Accordingly, the multi-stage CW system can be identified as an efficient and sustainable treatment process for hospital wastewater treatment while coping with the post-pandemic era.To determine the research status and trends in hospital wastewater treatment over the past three years, we searched the Web of Science database using the following search terms: “hospital wastewater” OR “hospital wastewaters” OR “hospital effluent” OR “hospital sewage” OR “waste water from hospital”) AND , and the steps included the deletion of unrelated and similar keywords, followed by the drawing of a keyword network figure and its modification using Pajek (version 5.16). There are five clusters in the figure, each representing a different research direction . ClusterUndoubtedly, the monitoring of SARS-CoV-2 in hospital wastewater and the disinfection of treated effluent were the main focuses, without regard to the treatment processed employed, of research over the past three years.A multitude of causes including drug residues, waste iodine contrast agents, viral transmission, and the excessive growth of germs, especially during the epidemic era, contribute to the complex composition of hospital wastewater . HospitaIndeed, most countries and organizations have established legislation or guidelines for treating and discharging hospital wastewater. In China, the State Environmental Protection Administration issued the “Water Pollutant Discharge Standard for Medical Institutions” in 2006, which regulates the concentration or content of COD, BOD, phosphorus (P), halogen, and fecal coliform bacteria in hospital wastewater . In the The anti-COVID-19 drugs recommended for use during the epidemic are listed in It seems that the adherence to inadequate systems including tight legislations or guidelines with which to consider the lessons learned from the last three years of the pandemic may result in an increased discharge of hazardous substances from hospital wastewater, endangering both humans and the environment, especially in the ensuing post-pandemic era. These issues represent the real challenges for this kind of wastewater treatment.The information and summary of the traditional treatments, advanced technology, and CWs regarding hospital wastewater from the literature are listed in The ASP and MBRs have a long history of technological advancement ,35. The 2O2. In some studies, the removal rate of quinolones such as norfloxacin, ofloxacin, and ciprofloxacin by an MBR exceeded 90% [The combined process associated with the ASP can be used to eliminate pharmaceuticals and other contaminants, and such combinations include ASP followed by the use of a biofilter  or dosineded 90% ,37,38,39eded 90% ,20.As time passes, the filtration performance of the filter membrane will deteriorate, resulting in membrane fouling. At this point, the cleaning or replacement of the membrane is required ; otherwiThe literature on the treatment of hospital wastewater by advanced technology is shown in 2+ and H2O2), and the process is suited to the treatment of industrial wastewater and landfill leachate [Fenton oxidation is the oxidation of contaminants by hydroxyl radicals (•OH) generated by Fenton reagents , and the incorporation/combination of other treatment processes into/with CWs . Lutterbeck et al.  treated spective . Khan etspective ,93 combiacetamol . To alleeuticals ,94. Aeraeuticals . Auvineneuticals  developeAside from the enhanced treatment performance of integrated CWs, a CW is a low-carbon technology . Chen etCW systems are usually constructed outdoors, while multi-stage CWs are usually employed to secure the treatment efficiency. Some engineering issues should be considered in order to correctly use a CW system, as this will enable the maximization of its treatment performance. These include the incorporation of seasonal variety, especially in winters with particularly low temperatures; substrate clogging; wetland plant harvesting; etc. When winter arrives, the low temperature will affect the nitrification and denitrification processes in the wetland, which will, in turn, affect the removal rate of nitrogen from the effluent. In winter, when plants are in a dormant phase, they release less oxygen . AdsorptThe hospital wastewater entering CWs should be pre-treated to avoid substrate clogging . In addiThe global COVID-19 pandemic remains critical in some countries after almost three years. More than 600 million people across the globe have been diagnosed with COVID-19, and more than 6 million have died as a result . SARS-CoAt present, there are no indications that SARS-CoV-2 present in wastewater is contagious. From February 18 to 2 June 2020, Wu et al.  studied The detection of SARS-CoV-2 in wastewater can enable us to infer the presence and severity of an epidemic in a particular hospital or community . RegularEach hospital wastewater treatment process has its own merits, but combinatory processes frequently achieve higher levels of treatment effectiveness. Suggestions for the future directions of studies on hospital wastewater treatment from a macro and micro perspective are as follows:Macro perspective:Hospitals generating enormous volumes of wastewater may develop their own wastewater treatment facility/plants, rather than having said wastewater jointly treated with domestic wastewater. This is in consideration of the specific features of hospital wastewater.The existing literature on the treatment of hospital wastewater by CWs is promising but minimal. Herein, the use of a CW system, specifically, a multi-stage CW, is recommended. Its use is required to assess the treatment capacity of CWs of various sizes for hospital wastewater. The combination of CWs with landscape ecology so as to take full advantage of the landscape value of CWs is highly suggested.The creation of an integrated treatment system consisting of an MBR combined with advanced treatment processes followed by the use of enhanced CWs would increase efficiency and thus lead to better hospital wastewater purification.Micro perspective:The chemical structures of the pollutants in hospital wastewater should be examined in great detail. The specific drugs and chemicals used in the pandemic period and post-pandemic era should be carefully considered to help establish hospital wastewater treatment strategies.Concerns such as the role of microorganisms in CWs with respect to eliminating pollutants in hospital wastewater; any link between microorganisms and pollutants; and influencing mechanisms and interactions between microbes and plants should be investigated and comprehensively addressed. In addition, the pathways of the viruses surviving and spreading throughout hospitals and wastewater systems and wiser and more effective strategies for the inactivation and disinfection of these viruses should be jointly investigated.After examining the characteristics of hospital wastewater and the challenges faced in the pandemic period and post-pandemic era, this paper initially reviewed the application of traditional and advanced treatment processes applied to hospital wastewater. It is reasonable to believe that both the ASP and MBRs offer generally positive performance and should be utilized as key processes for large-scale hospital wastewater treatment. Advanced technologies and processes  can render hospital wastewater harmless on a small scale, but technical and monetary issues have not been resolved; thus, it is difficult to apply such techniques and technologies to large-scale projects. As a sustainable and eco-friendly treatment approach, in this review, it is shown that CWs have excellent absorption capabilities and can eliminate the majority of pollutants, including viruses, in hospital wastewater contaminants. CWs can be used as a wastewater-sanitizing, post-processing phase after the ASP or coupled with an MBR and some advanced techniques. Certainly, the development a multi-stage CW system is recommended for hospital wastewater treatment, for which various intensifications have been developed so far. The unique ecological and landscape-related value of CWs cannot be obtained through any other treatment technology. Thus, it is reasonable to recommend that an integrated treatment system containing multi-stage CWs is an effective, sustainable solution for hospital wastewater treatment in order to cope with the post-pandemic era. Following the SARS-CoV-2 outbreak and the emergence of the post-pandemic era, treatment technology should integrate the merits of each treatment process, which must be continually optimized and whose essential characteristics must be extracted, thereby leading to the development of an efficient and sustainable treatment approach.


Endophytes, which are widely found in host plants and have no harmful effects, are a vital biological resource. Plant endophytes promote plant growth and enhance plants’ resistance to diseases, pests, and environmental stresses. In addition, they enhance the synthesis of important secondary metabolites in plants and improve the potential applicability of plants in agriculture, medicine, food, and horticulture. In this review, we summarize the recent progress in understanding the interaction between endophytes and plants and summarize the construction of synthetic microbial communities (SynComs) and metaomics analysis of the interaction between endophytes and plants. The application and development prospects of endophytes in agriculture, medicine, and other industries are also discussed to provide a reference for further study of the interaction between endophytes and plants and further development and utilization of endophytes. Endophytes are diverse and valuable resources in nature with the potential for human exploitation. In the early stage of endophyte discovery, the soil microbiota was the main seed bank for bioactive compounds ,2. In reSecondary metabolites (SMs) are the products formed by interactions with the environment during plant growth and development. SMs mainly include alkaloids, flavonoids, terpenoids, peptides, phenols, sterols, and additional minor molecular organic compounds ,9. As esTo date, several reviews on plant SMs have been published ,16,17, bEndophytes play a significant role in promoting the growth of host plants, and conversely, plant bodies are also crucial for the adaptation of endophytes to complex environments . An esseEndophytes interact with plants over extended periods of time. In nature, the ocean is the cradle of life, with algae and bacteria being the main remaining members from the early ocean. They produce oxygen during metabolism to support life and promote the switch from aquatic to terrestrial life ,27. Two A major problem facing humanity in the 21st century is the lack of plant resources , a challPlant genes are fundamental to cellular processes and defense mechanisms in general. However, long ago, plants actively evolved genetic modules to support symbiosis and benefit from the presence of microorganisms. This represented an essential genetic shift in plants from aquatic to terrestrial life and formed a strong basis for active genetic innovation in plants. Despite the risk of invasion by pathogens, these modules are still retained in plants and support the interaction between plants and endophytes . CurrentChanges in genetic material are important for plant evolution and the core factor affecting endophyte–plant interactions. The interactions of early microbes depended only on the shallow surface area or on free space in the plant body ,41, and Plants actively seek the help of microbes to survive stressful situations. Over the past decade, there has been a paradigm shift in plant science, with the discovery of microbial functions and community composition increasingly being seen as drivers for improving the functioning of plant hosts. The endophytic microbiome can expand the plant genome and metabolic capacity to provide or promote a range of functions that help plants maintain basic life activities, including nutrient acquisition, immune regulation, and biological stress tolerance. Although endophytic microbial communities have been proposed as the next platform for the Green Revolution, basic research on the mechanisms of microbial community assembly and activity is still in its infancy . FortunaFew topics in plant biology have aroused as much interest and controversy as endophyte–plant microecosystems. However, although the phenomenon of endophyte–plant microecosystems is now widely accepted, there are still various questions about how and why endophytes develop, how they maintain balance, and how they affect the growth processes of plants . NumerouTo date, many unique metabolic substances have been discovered in plant–endophyte microecosystems. These substances provide a reference for successfully revealing the types of interactions in endophyte–plant microecosystems. For example, microorganisms can stimulate plant growth by metabolizing tryptophan and other small molecules in plant secretions and producing plant hormones, including coenzymes, gibberellic acid (GA), cytokinin (CTK), and plant hormone analogues . CoenzymEndophyte action is a popular research topic in research on plant secondary metabolite formation and its influencing factors. Previous studies have suggested that the synthesis of diverse secondary metabolites in plants is related to the influence of various environmental factors, such as temperature, light, and microorganisms. Endophytes, as important environmental factors, play an important role in the formation and accumulation of secondary metabolites in plants. There have been many studies on the mechanisms by which endophytes promote the synthesis of secondary metabolites in plants, but there is no unified view within the scientific community. At present, there are four main hypothesized mechanisms: endophytes promote the accumulation of photosynthetic material in plants ,56,57,58Endophytes promote the accumulation of photosynthesis-related substances, increase plant nutrient intake, and induce the synthesis of secondary metabolites. More than 90% of plant dry matter comes from the carbon fixation reaction of photosynthesis, and the organic matter assimilated by photosynthesis is the material basis for the formation of plant metabolites. Therefore, improving the efficiency of the utilization of light energy by plants is an important way to improve crop yield . As reliCsAPX, CsTCS1, CsPAL, CsC4H, CsF3H, and CsDFR showed the same trend as their corresponding quality parameters, indicating that AMF could promote the synthesis of secondary metabolites by upregulating the expression of related genes, thus affecting tea quality [Euphorbia officinalis was increased by 19.35% after treatment with an elicitor from the endophytic fungus Fusarium oxysporum, while the levels of isoflavin and diphenol were 5.81 times and 3.56 times those in the control, respectively. The activity of 1-deoxy-D-xylosulfos-5-phosphate synthetase (the key enzyme for the biosynthesis of isofluoromycin) was not significantly improved, while the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (the key enzyme for phenol) was 1.67 times higher than that in the control [B. polymyxis and ginseng significantly increased the levels of 12 kinds of ginsenoside monomers, especially the levels of the rare ginsenosides CK and protopanaxadiol, which increased by 1.38- and 7.78-fold, respectively [Endophytes regulate genes related to the synthesis of secondary metabolites by plant cells through their signal transduction pathways. Endophytes also change the rate and intensity of the expression of these genes and induce the production and accumulation of corresponding secondary metabolites in plants . The res quality . Other r control . In addiectively ,81.Phomopsis sp., an endophytic fungus isolated from orchids in northern Ecuador, secretes the volatile organic compounds junienes, which are found only in higher plants [Bacillus pumilus showed increased levels of total flavonoids, total polysaccharides, and glycyrrhizic acid. After inoculation with B. pumilus, the expression levels of HMGR, SQS, and β-AS, the key enzymes of glycyrrhizin synthesis, were significantly increased. These results indicated that B. pumilus could promote the growth of Ural hay by modifying the accumulation of antioxidants and increasing the glycyrrhizin content by changing the expression of key enzymes [Lysinibacillus fusiformis, Bacillus megaterium, B. lichenifera, B. pumilus, Brevibacterium halotolerans, Achromobacter xylosoxidans and Pseudomonas putida, were isolated from the roots of the halophyte Prosopis strombulifera in the Khewra salt region of Pakistan. The plant hormone abscisic acid (ABA) was widely present in these isolates [Kocuria turfanensis 2M4 from the rhizosphere of salt-tolerant plants. This strain exhibited IAA production, phosphorus solubilization, and ferrophilia. In conclusion, the same or similar secondary metabolites were produced when endophytes interacted with plants, which suggested that compounds and even genetic material might be transferred between them during symbiosis.Transfer of compounds or genetic material occurs between endophytes and hosts . Phomopsr plants . The roo enzymes . In addiisolates . ResearcSphingomonas melonis, an endophytic bacterium found in rice, confers resistance to disease-prone phenotypes by producing anthranilic acid. When Burkholderia plantarii infects rice, S. melonis secretes the small extracellular signaling molecule ammonia acetic acid to coordinate the host response and then interferes with the regulation of the RpoS transcriptional cascade that is dependent on the virulence factor biosynthesis pathway of B. plantarii. This prevents B. plantarii infection and promotes the accumulation of plant secondary metabolites [Huperzia serrata. These endophytes enhanced the production of ursolic acid. Denise [Endophytes can synthesize compounds that the host cannot synthesize, or can only synthesize small amounts, changing the method of metabolite synthesis in the host and affecting metabolite levels. abolites . By compabolites . In addiabolites  screenedabolites  screened. Denise  used an Microorganisms rarely exist alone, and there is a positive correlation between species diversity and community productivity in nature. The ubiquity of these microbial communities in nature highlights the possible advantages of endophytic strains in coculture . HoweverSaccharomyces cerevisiae was genetically modified through genetic hybridization, and two nonmating strains, R and Y, with different metabolic abilities were obtained. R synthesized lysine but needed adenine for growth, and Y synthesized adenine but needed lysine for growth [SynComs were first reported in the early 21st century. r growth . A stablr growth ,111,112.r growth . Subsequr growth ,115,116.r growth . TherefoEndophytes promote the synthesis of plant secondary metabolites in various complex ways, and traditional research methods have been insufficient for studying secondary metabolites through these relationships . StudiesTo date, the application of multiomic technology in studies on secondary metabolism to determine the interactions between plants and endophytes is becoming more widespread ,131. In However, the current metaomic research methods still have some shortcomings and inadequacies. Metaomic analysis of plant samples, while potentially capable of representing all the diversity in gene sequence and function, has not been able to elucidate all the genes and functions of a single microorganism, and this has presented great difficulties in exploring the functions of plant endophytes. Fortunately, modern methods such as single-cell genome sequencing (SCGS) have been slowly developed . TherefoEndophytes are ideal resources for facilitating the formation and accumulation of secondary metabolites in plants. Earth is a large biological resource bank, with approximately 270,000 plant species, and the number of endophytes that can be isolated exceeds one million based on the calculation that there are approximately four distinct endophytes in each plant . The stuEndophytes are an important part of the plant microecosystem. They have a special symbiotic and metabolic relationship with host plants and are a potential resource pool for the synthesis and accumulation of plant secondary metabolites. At present, research on endophytic bacteria in plants is still in its infancy, and only some plant groups have been studied. The existing research is more focused on endophytes as a resource, and their various novel structures and bioactive secondary metabolites have been discussed. As a result, most research on the substances in host plants has been confined to those that are the same or similar to active substances in endophytes. Thus, the construction of a systemic database of endophytes and plants is not possible due to the lack of information and the need for an endophyte resource platform. Endophytes play an important role in the development of plant secondary metabolites and in promoting the synthesis and accumulation of plant secondary metabolites. Many bioactive plant secondary metabolites are transformed by endophytes to induce plant synthesis and accumulation. However, the structure, dynamics, and functions of plant endophytic colonies, the factors influencing the interaction between plant secondary metabolites and endophytic colonies, the spatial patterns and signal transduction pathways, and the specific mechanism and molecular basis of the regulation of the biosynthesis of plant secondary metabolites by endophytes still need to be further explored. In addition, the fundamental genetic control of endophytes in plants and how they are affected by changes in other microbiota and environmental conditions also require attention.In fact, although researchers have found valuable active substances in the study of some endophytes promoting plant secondary metabolites, many problems have yet to be addressed in related research and practical applications. Most plant endophytes have not been effectively isolated, and the molecular mechanisms and effects of plant endophytes are not clear. In addition, endophytes cannot be used in practice for biocontrol, and it is not clear what kind of community they need in different growth stages and when they act on plants. Therefore, further exploration of the interaction between endophytes and plants is urgently needed to understand the origin and mechanism of action of endophytes in plants.Interdisciplinary research in plant physiology, molecular biology, genetics, microbiology, and many other disciplines has been formed in many studies. With the help of analytical tools such as single-cell genomics and specialized plant metabolomics, we can focus on identifying gene clusters of secondary metabolite biosynthetic pathways within plants through whole-genome sequences to investigate the resources of novel endophytes with sustainable secondary metabolite synthesis and to reveal the molecular signals and transcription factors that regulate the expression of secondary metabolic biosynthesis-related gene clusters. These data can be used to explore the microbial communities coevolving with plants as they grow and develop and to provide a new theoretical basis and research perspective for revealing the regulation of plant growth and development by endophytes through secondary metabolites and the industrialization of synthetic communities. In the future, in-depth research on plant endophytes and their applications in various fields will bring more benefits to humans and will have broad prospects for development and application.


Concerns regarding the capability of the International Olympic Committee to address doping in sport catalyzed the formation of the World Anti-Doping Agency (WADA) in 1999. In its establishment phase, WADA sought geopolitical legitimacy and support from governments (including non-Western states) for financing and acceptance. Africa was not considered during WADA's creation, relegating African states to a passive role in the global anti-doping program, and yet is still subject to the strict compliance requirements for WADA's global policy. African countries face challenges establishing anti-doping support structures and implementing the universal policy, including competing macro-level policy demands that favor addressing legacies of colonialism and human capacity development. To develop robust anti-doping support structures, African nations must spearhead anti-doping initiatives by leveraging existing infrastructure and encouraging collaborations between NADOs such that capacity can be built for policy implementation. On November 5, 1998, the members of the Monitoring Group of the Council of Europe's Anti-Doping Convention held an extraordinary meeting in Strasbourg, France, to prepare proposals for the 1999 World Conference on Doping in Sport and recount recent events in the doping sphere. This included discussions on the Festina affair in France where large quantities of the endurance-enhancing drug erythropoietin were uncovered by custom agents on route to a professional cycling team, the case of Chinese swimmers' attempted effort to bring human growth hormone into Australia during the World Swimming Championships, and deficient doping control procedures in Italian football . While SThe failure to adequately incorporate Africa in the activities preceding the formation of WADA was myopic and arguably led to decisions that undermined WADA's legitimacy in Africa. Executive decisions to create WADA were made predominantly from a western-centric standpoint , yet comThough the organization and governance of modern sport might seem foreign, the nature of activities engaged in are not any different from those of the pre-colonial generation. Performance and winning competitions were of utmost importance in both instances. Yet, ill-will had no place and credit was given for the exhibition of fairness . To gainHowever, WADA has sought other strategies to gain acceptance in Africa. WADA's need for geopolitical legitimacy during its formation phases, instigated the establishment of a regional office in Cape Town, South Africa . The offThese efforts to support anti-doping programs in Africa by WADA are seemingly instrumental in gaining geopolitical legitimacy. Furthermore, African governments support the world anti-doping program, as shown by 52 African countries that have ratified the International Convention against Doping in Sport . To dateThe developmental processes experienced by African states, which are associated with colonialism and the subjugation of African states by European imperialists, have created circumstances where sport policy and programs, in general, and anti-doping policy can be fringe. Colonialism is regarded as a practice by one people or political power of obtaining full or partial control over another people or political system (country), occupying the controlled state with settlers, and exploiting the controlled people and space economically . In Afrivia tourism and trade  in a country. For example, doping control and testing is a central tenet of the universal anti-doping program , however, it is expensive for nascent NADOs to implement adequately. Consequently, International Federations  continuously fund anti-doping testing initiatives for under-resourced NADOs in Africa to ensure the adequate testing of athletes.While 52 African countries ratified the UNESCO Convention against Doping in Sport, only 25 African nations have established independent NADOs within the last decade. Although this signifies a wider acceptance of the universalist anti-doping program and growth of anti-doping work in Africa, the delayed progress can be linked to the overall government objectives to address inequalities and broader social issues as legacies of colonialism, as aforementioned. Additionally, the absence of the experienced personnel needed to develop the necessary support structures to run such programs further hinders the efforts to establish strong anti-doping programs.There are limited opportunities to study sport and related areas in Africa. Consequently, most African countries have developed little human resource capacity in sport management. This lack of expertise presents challenges for anti-doping policy implementation, education programs, and management of sport in general. This means that sport has largely remained intellectually starved, with the running of sport left to people who lack relevant training, possibly government-appointed, and serve limited terms leading to high turnover and a loss of institutional knowledge . For exaFor African nations to develop robust anti-doping programs, they may need to spearhead anti-doping initiatives within the continent and encourage partnerships and collaborations between NADOs in Africa to build capacity. African nations may also need to pursue partnerships between NADOs/RADOs and corporations, as well as partnerships with other government departments and agencies to counter resource inadequacy. We, therefore, propose the following recommendations.First, in addition to WADA's efforts to assist and support African nations to establish vigorous anti-doping programs by establishing the RADOs and the WADA office in South Africa, there is a need for African countries to spearhead anti-doping efforts in the continent. A case in point is health research in Africa, where there has been a shift from international-led research and capacity building towards more Africa-led models . This moTo achieve this, greater demand for human capital in the region is needed. Some efforts in this regard are taking place, as shown by the NBA's movement into Africa  and partSecond, partnerships and collaborations between NADOs in Africa offer great opportunities for capacity building through information sharing and technical training based on mutual understanding and appreciation of socio-cultural factors. WADA's President, Witold Bańka has previously underscored the importance of collaboration in building anti-doping capacity across the continent of Africa . With thAfter the creation of WADA, African states looked up to established NADOs in Europe and Asia for technical support as they sought to operationalize their NADOs. Apart from South Africa, there was no country in Africa which had the technical knowhow of anti-doping. When the ADAK launched its program, it relied heavily on NADOs from England, China, and Norway to develop the technical competencies and educate its staff . As counThird, NADOs could leverage the existing infrastructure and collaborate with other government agencies to run anti-doping programs. Government agencies such as departments of Health, Education or Social Services are ideal partners in anti-doping education. The ADAK-KICD partnership mentioned earlier provides an exemplar case. Resources too can be acquired through collaboration. Partnerships between NADOs and corporations could plug the budgetary deficit experienced by most NADOs. These additional resources could be used for anti-doping programming such as capacity development of staff and athletes' education. In the former case, this could eventually lead to the increased attraction of sport management as a career choice. Regional and continental partnerships for anti-doping purposes should be pursued by the RADOs, and the WADA Regional Office with the help of WADA. Recently, WADA signed a sponsorship agreement with SuperSport (African-based broadcaster) that will provide direct funds and in-kind value to promote and coordinate the protection of clean sport in Africa . Though In this policy brief article, we have historically situated the challenges of implementing anti-doping policy and programs in Africa. These challenges have been associated with the peripheral role Africa played in the creation of WADA, and the colonial legacies that governments prioritize over sport, limiting financial resources and human capacity in sport. Though Africa continues to address inequalities and other social issues linked to colonialism, we have provided recommendations that may assist building robust anti-doping programs, and aid anti-doping policy implementation in the continent. The resource and capacity inefficiencies notwithstanding, African states are taking steps to implement anti-doping policy. As such, these countries should be supported in developing their NADOs.


Aguilar et al.). Physicochemical factors such as extreme changes in conductivity, temperature and nutrients were identified as factors accounting for viruses-to-prokaryotes (VPR) spatial and diel dynamics in Salar de Huasco high-altitude wetland  . Similar factors also determined the spatial variability of VPR in other contrasting environments of the Southern Hemisphere, such as marine  and Antarctic lakes . Also, the salinity gradients typically found in Salar de Huasco and associated with the main lake, ponds, springs, and streams were the natural laboratory selected to survey the diversity of lysis-resistant bacteria and archaea cells in sediments and microbial mats . Salinity is a significant factor that modulates cellular metabolisms. The study of halophilic fungi isolates  demonstrates the different molecular mechanisms for resistance in hypersaline systems. Salinity was also a determinant factor leading to the high complexity of microbial communities from semi-arid mangrove soils in Brazil .The Southern Hemisphere, with its geographical and landscape peculiarities, concentrates many hotspots of diverse and extreme environments where microbial life thrives. It includes “pristine” or less anthropogenically impacted environments, such as high-altitude and high-latitude ecosystems, which are highlighted in the content of the Research Topic , rather than determined by environmental conditions . Patagonia and the Antarctic Peninsula, still considered pristine, are a reservoir of undescribed microbial species, particularly fungal species . The polyextreme Deception Island in the Antarctic Peninsula where the microbial communities of volcanic glaciers are composed by both psychrophilic and thermophilic microorganisms such as Psychrobacter and Thermogemmatispora, respectively , has received particular attention.On the other hand, high-latitude ecosystems such as Patagonia and the Antarctic Peninsula are natural laboratories for investigating the processes determining microbial diversity, their dispersion, activities, and adaptation under changing conditions. In these extreme environments, the association between microorganisms and their hosts is key, as shown in the case of the Antarctic sponge core microbiome which was closely associated with the host species  and Spirochaeta .The Southern Ocean encompasses several biogeographical provinces and other spatial scale of variability associated with oceanic circulation and fronts, influencing the distribution of microbial populations, acting as “interconnectors” or “ecological boundaries” for microbial populations like Roldán et al.). Likewise, changing macronutrient stoichiometry by experimental amendments of phototrophic microbial mats in the Byers Península  showed shifts in the microbial communities and their contribution to biogeochemical processes after perturbations.Experimental approaches with complex communities are necessary to unravel ecological responses and interaction of microbial communities under global warming scenarios. For example, studying the tolerance and resistance of key functional microbial groups to temperature, such as the response of benthic methanotrophic Antarctic Lake communities . Macronutrients could explain the microbial changes associated with the wildfires in bulk soil and rhizosphere of a native Sclerophyll Forest in central Chile . Different natural perturbations affecting ecosystems, such as hurricanes, cyclones, heat waves, among other extreme events, were predicted to become more common due to climate change with potential significant consequences in nature, including microbial community dynamics. After a tropical cyclone in 2010, the ponds of Pozas Rojas were inundated and homogenized, and then isolated again after several years, representing a natural perturbed situation to study classical niche differentiation questions tested by Garcia-Ulloa et al. for microbial communities. Despite the homogenization effect, this research identified the importance of interspecific interactions compared to environmental control alone accounting for the microbial community establishment in the different ponds . Finally, several mechanisms involve the interaction between microorganisms and vegetation including the way in which the microbiome is acquired. Those mechanisms are relevant to understand host health as reported by Muster et al. for phosphate solubilization by lichens in native vs. invasive tree species in the Patagonian Forest, and by Guajardo-Leiva et al. showing differential sites origin for the acquisition of bacteria compared to fungi for rhizosphere establishment by Antarctic vascular plant.Functional redundancy could be significant for ecosystem function, especially under the harsh conditions of cold extreme environments. This was shown, for instance, by the monitoring of ammonia oxidation process in the surface sea waters of the West Antarctic Peninsula, where diverse and active nitrifying assemblages were reported to reach high abundances and rates during late-summer  and by measuring the specific activity rates of microbial processes and meta-omic techniques . Still, there is a need to expand and increase our knowledge of more microbial communities' traits in the Southern Hemisphere ecosystems, using integrative studies to improve and deepen our understanding of their adaptation to extreme and changing environmental conditions. Funding remains a major limitation to increase our baseline knowledge of the South, and in the frame of global change and the effect of anthropogenic perturbations, more than ever, scientific exchange and close collaborations are urgently needed to overcome the lack of funding. Furthermore, the representation of women in research is another major challenge to overcome. Although this is not an exclusive problem of the Southern Hemisphere, an even smaller proportion of women researchers has been found in low-income countries , abundance determinations and functional potential, for example, by profiling metabolic capabilities (VM, CL, YE, and PJ contributed to conception and design of the study. VM and CL wrote the first draft of the manuscript. YE and PJ wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.


Cardiothoracic surgical intensive care has developed in response to advances in cardiothoracic surgery. The invention of the cardiopulmonary bypass machine facilitated a motionless and bloodless surgical field and made operations of increasing complexity feasible. By the mid-1950s, the first successful procedures utilizing cardiopulmonary bypass took place. This was soon followed by the establishment of postoperative recovery units, the precursors to current cardiothoracic surgical intensive care units. These developments fostered the emergence of a new medical specialty: the discipline of critical care medicine. Together, surgeons and intensivists transformed the landscape of acute, in-hospital care. It is important to celebrate these achievements by remembering the individuals responsible for their conception. This article describes the early days of cardiothoracic surgery and cardiothoracic intensive care medicine. Cardiothoracic surgical intensive care has evolved in concert with advances in cardiac surgery. Although the first successful surgery on the heart is attributed to Dr. Daniel Hale Williams, who repaired a traumatic laceration to the right ventricle in 1893, cardiac surgery as we know it today began in the early 1950s with the development of the cardiopulmonary bypass machine . By the A motionless and bloodless surgical field was necessary to advance the discipline of cardiac surgery . After aIt was quickly recognized that significant perioperative complications were just as important to the patient’s well-being as the repair of cardiac pathology utilizing a heart–lung machine ,3,5. MorThe first intensive care unit dedicated to postoperative cardiac surgery patients opened on 2 October 1956 at Saint Mary’s Hospital, a Mayo Clinic affiliate, in Minnesota . It was Multidisciplinary involvement was key to the success of Mayo Clinic’s blossoming cardiac surgery program . This suCardiac surgery pioneers west of the Mississippi, Drs. John Osborn and Frank Gerbode, also described a need for specialized staff tending to postoperative open-heart surgery patients . In 1956The early days of cardiac surgery intensive care did not leave much of a written record in the scientific literature, however . Many adThe development of postoperative cardiothoracic surgical care could not have happened without other medical advancements. Fortunately, the cardiac surgical revolution coincided with another monumental transformation that allowed for the further growth of acute, in-hospital care. The widespread introduction of positive-pressure ventilation (PPV) during a polio epidemic changed medicine as a whole and was the impetus for the establishment of a new specialty: critical care medicine.Each year, 26 August marks Bjørn Ibsen Day, a medical hallmark quietly celebrated by far too few intensivists . It commRespiratory Care in 1965, the first book of its kind, describing the clinical knowledge and research specific to the critically ill, quickly heralded by professionals in the field as the “red bible”, given its red cover [The 1960s and 1970s marked the expansion of the technology and science of intensive care, including laboratory testing, invasive monitoring, mechanical ventilation, AC electrical defibrillation, transvenous pacing, cardiopulmonary resuscitation, and more . A team ed cover . This pued cover . These gCritical Care Medicine, in 1973 [The rate at which new technologies and techniques were emerging was perhaps outpacing the abilities of many physicians to keep up and comfortably care for patients who required the newer methods . Consequ in 1973 .Although anesthesiologists comprised the majority of intensive care specialists in most of Europe and Australia, this was not the case in the United States, where a mix of disciplines converged to practice critical care medicine. This heterogeneity created training and credentialing questions and resulted in stakeholders from surgery, anesthesiology, pediatrics, and internal medicine attempting to form a unified Board of Critical Care Medicine in the early 1980s . HoweverThe events surrounding the evolution of CCM had a great impact on the state of medicine, including cardiothoracic surgery and its postoperative care. Further innovations in cardiothoracic surgical techniques and improvements in patient outcomes would not have been possible without the advances in laboratory testing, diagnostic monitoring, mechanical ventilation, cardiopulmonary resuscitation, and many more. As with the innovations of Gibbon and Kirklin, it is important to treasure the ingenuity of the individuals responsible for the transformation of the care of critically ill patients.The management of cardiothoracic surgical intensive care units (CT-ICUs) remained mostly surgeon-driven for many decades. The model of care centered around attending surgeons rounding before or after scheduled operations with surgical trainees, consultants, trained nursing staff, and other technicians carrying out the dictated care plans ,18. In tstrategy and tactics, in which surgeons and attending intensivists established the plan for the day, and the ICU team would carry it out. The gradual inclusion of anesthesiologists into CT-ICUs set the stage for what followed next: a paradigm shift from a surgeon-centric to a collaborative care model.As a natural extension of intraoperative expertise and training, the trailblazing anesthesiologists entering CT-ICUs were often cardiovascular anesthesiologists by trade. The earliest participation of anesthesiologists occurred at MGH, with some anesthesiologists having postoperative involvement in patient care in the 1960s, surrounding the RICU innovations described previously . HoweverAt the turn of the 21st century, the approach to postoperative cardiothoracic care started to change once again. First, evidence of improved outcomes emerged, verifying the importance of intensivists’ participation in CT-CCM ,26,27,28The coronavirus pandemic, with its aftermath, is likely to open a new chapter in CT-CCM. As of 2022, the lesson on the importance of coalitions, collaborations, and unity could not be clearer. Given the stormy waters of the last few years, it is crucial to step back and re-evaluate the good and the bad and strive for further improvements and advancements. Learning about our history can be the first step in this process. The early days of cardiac surgery and its postoperative intensive care depended on groundbreaking innovations and the ingenuity of individuals and their teams. The memory of those accomplishments should be cherished and often revisited. Moreover, the recognition of the historical distinction of this field is critical when evaluating goals for the future. As recognized by our predecessors, our field needs specialized training to address unique challenges specific to intensive care of open-heart surgery, multidisciplinary involvement, scientific research, and the diplomatic acumen needed to convince stakeholders of the importance of necessary changes. Our future largely depends on understanding the lessons of the past.


Despite the challenges posed by the pandemic, several resourceful initiatives were implemented, across the educational landscape. As the lead organiser of the academic forum the expectation was to develop a format for on-line monthly academic teachings with streamlining further innovative ideas of change to best effect. The key objective of this QIP,is to use virtual platform to establish an educational forum that is efficient, safe, reliable, easy to use and replicableA zoom based online forum was convened using QI framework to identify gaps in the programme along with new ideas of change.The attendees experience new innovative practices within the programme format, in line with the original NWLD forum programme.A ‘think-group’ consisting of the previous NWLD forum lead, ID training programme director and higher trainee facilitators proposed ideas towards a varied educational topic bank, in line with the ID curriculumQualitative feedback from the forum members collected at baseline and regular intervals.As part of the implementation of these actions, conducted workshops evaluating the impact of COVID-19 on Educational, Psychological and Clinical landscapeThere were 18 virtual sessions,5 CPD hours per session, conducted monthly.9 sessions in the first PDSA cycle from June 2020 - Feb 2021, and 9 sessions in the second PDSA from March 2021-November 2021.Impact of COVID-19 workshops & Complex case management workshops conducted in the first and second PDSA cycle as part of the monthly academic programme.Participants for the academic regional teaching included Consultant Psychiatrist, higher trainees, Core trainees, Foundation doctor, specialty doctors, Medical Students and MDT professionals.New members regionally, nationally and internationally became part of the academic programme both as attendees and as speakers along with the Chair of the ID Faculty.The academic programme helped with educational and training needs. It helped in improving social participation for our members during COVID-19 pandemic.Qualitative feedback has been collated and analysed. The feedback contains a wealth of comprehensive information that has been used to enhance the programme and training needs for the trainees and trainers.The program is well-received and led to knowledge, skill, and attitude improvements.The depth analysis of the feedback has facilitated a targeted approach that has brought a meaningful improvement, in the quality of training and education.Audience participation and engagement remains a key area for improvement.


Brain injury is the main factor affecting the development and prognosis of the nervous system in premature infants. Early diagnosis and treatment are of great significance in reducing mortality and disability and improving the prognosis of premature infants. Craniocerebral ultrasound has become an important medical imaging method for evaluating the brain structure of premature infants due to its advantages of being non-invasive, cheap, simple, and bedside dynamic monitoring since it was applied to neonatal clinical practice. This article reviews the application of brain ultrasound to common brain injuries in premature infants. In recent years, with the continuous improvement of medical levels and the rapid development of neonatal intensive care technology, the rescue success rate of critically ill newborns such as premature infants and very low birth weight infants (VLBW) has been significantly improved. However, due to immature cerebrovascular development and poor cerebral blood flow self-regulation, these types of neonates are prone to cerebral hemodynamic disorders, thus, the incidence of brain injury is usually higher than in term infants , 2. The Brain ultrasound is a technique that uses specific sound waves to understand the structure and pathological changes of brain tissue . At presin vivo  Ultrasonic diagnosis of periventricular intraventricular hemorrhage: In 1978, Papile et al. . (2) UltPeriventricular leukomalacia is a disease closely related to motor function, audiovisual function, and cognitive function. It is the most serious case of brain injury in premature infants and one of the important causes of neonatal cerebral palsy . Li JinhAt present, according to different periods of periventricular leukomalacia ultrasound performance, it is generally divided into four levels . Grade INeonatal hypoxic-ischemic encephalopathy is hypoxic-ischemic brain damage caused by perinatal hypoxia and asphyxia. It is one of the most common brain injuries in premature infants and one of the leading causes of neonatal neurodevelopmental abnormalities and death . AccordiThe brain ultrasound diagnosis of hypoxic ischemic encephalopathy is based on the pathological process of the disease. In the early stages of the disease, the main pathological change is brain edema. Ultrasound showed diffuse and uneven echo enhancement in both cerebral hemispheres, with the most obvious enhancement in the periventricular white matter, even equal to the intensity of the choroid plexus. In the late stages of the disease, cystic or atrophic changes occur in the brain structure, and the ultrasound images can be clearly seen after 3–4 weeks. Cystic changes usually occur after extensive and severe brain edema. Ultrasound showed cysts of different sizes in the original echo-enhanced area. Atrophic changes are secondary to extensive brain injury. Ultrasound examination showed the extensive division of the brain, deep sulci, widened extra-frontal space, and atrophy of the gyrus .P < 0.05. The follow-up study of Guan (Pathological changes of neonatal hypoxic ischemic encephalopathy are a dynamic evolution process, mainly based on cerebral blood. Blood flow changes can be used for diagnosis. Color Doppler ultrasound can directly reflect the blood perfusion of lesions through the changes in the blood flow spectrum . By comp of Guan  and Liao of Guan  was simi of Guan , 39.In conclusion, craniocerebral ultrasound, as a non-invasive, cheap, simple, and bedside brain medical imaging method, can be used to screen and diagnose intracranial lesions in infants who have not yet closed the halo. Especially in the diagnosis of brain injury in premature infants, brain ultrasound shows good accuracy and specificity, which can clearly show the condition of brain injury and the hemodynamic changes of diseased tissues. Therefore, as an important screening project for brain injury in premature infants, it is conducive to the early detection of intracranial lesions in children and can provide an accurate basis for early clinical diagnosis and prognosis evaluation. In recent years, with the continuous improvement of brain ultrasound imaging, brain ultrasound has become the preferred diagnosis of brain disease in premature infants.The author confirms being the sole contributor of this work and has approved it for publication.