Although therapeutic methods have been developed, gastric cancer (GC) still leads to high rates of mortality and morbidity and is the fourth leading cause of cancer-associated death and the fifth most common cancer worldwide. To understand the factors associated with the prognostic prediction of GC and to discover efficient therapeutic targets, previous studies on tumour pathogenesis have mainly focused on the cancer cells themselves; in recent years, a large number of studies have shown that cancer invasion and metastasis are the results of coevolution between cancer cells and the microenvironment. It seems that studies on the tumour microenvironment could help in prognostic prediction and identify potential targets for treating GC. In this review, we mainly introduce the research progress for prognostic prediction and the immune microenvironment in GC in recent years, focusing on cancer-associated fibroblasts (CAFs), tumour-associated macrophages (TAMs), and tumour-infiltrating lymphocytes (TILs) in GC, and discuss the possibility of new therapeutic targets for GC. According to GLOBOCAN 2020, gastric cancer (GC) ranking fifth for incidence and fourth for mortality globally . The inc.Immunotherapy has gradually appeared in the treatment of GC in recent years. Various types of immunotherapeutic approaches have been developed, such as vaccine therapy , chimeri.In recent years, many studies have shown that cancer invasion and metastasis are caused by interactions between cancer cells and the immune microenvironment –14. The In this article, we reviewed the main components of stromal cells in the TME framework, including tumour-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and tumour-infiltrating lymphocytes (TILs), which are involved in the regulation of the immune microenvironment (Cancer-associated fibroblasts (CAFs), also called stromal cells, work as an essential component of the tumour microenvironment and perform diverse functions, including extracellular matrix deposition and tissue remodelling, cross-talk signalling, and interacting with cancer cells and infiltrating immune cells , 78.Recent studies have shown that morphological analysis of the tumour-stromal ratio (TSR) at the periphery of tumour invasion can further evaluate the clinical significance of the TME and help in the discovery of new tumour prognostic indicators. As a new prognostic indicator, there is a significant positive correlation between high TSR, oesophageal cancer, breast cancer, and cervical cancer , 23, 24.TSR is an important prognostic index, but it is still necessary to further analyse whether TSR parameters can represent the overall characteristics of the TME. According to the TME theory, it can be hypothesized that the more frequent the interaction is between the tumour and the interstitium, the greater the intensity of the action, the more significant the proliferation of various cellular components in the interstitium, and the greater the TSR value at the histological level. Previous studies have supported this conjecture that tumour cells can activate nearby tumour stroma, thereby promoting the evolution of the TME; activated tumour stroma components receive tumour-related signals and change both in quantity and morphology and then promote the occurrence and development of tumours , 27. TheIn addition, some studies have shown that when the proportion of stromal cells in some tumours is increased, the prognosis is often worse . The canTumour-infiltrating lymphocytes (TILs) play an essential role in modulating the occurrence and development of tumours . In a phUnder the recruiting influence of tumour signals, the appearance of mononuclear immune TILs infiltrating the tumour tissue can reflect the strength of the body’s antitumour immune response. Analysing the characteristics of TILs helps in clinical practice . StudiesIn addition, according to the latest consensus of the International TIL Working Group, the study of TILs in cancer nests is of little significance, and TILs in the tumour stroma need to be analysed. According to the consensus, it is appropriate to use the percentage of stromal TILs (psTILs) to study the degree of TIL infiltration in the interstitium rather than the number of TILs or the TIL density in the interstitium . CurrentSome studies have explored the value of the percentage of stromal tumour-infiltrating lymphocytes (psTIL) as an indicator in GC, focusing on analysing the main clinicopathological characteristics of psTILs and the prognostic significance in GC patients. In theory, the specific cellular components of TILs have multiple subtypes, which can be divided into different cell types according to different antigens on the cell surface, leading to the complexity and changes in TIL research and significant differences in the interpretation of the results , 38, 43.In the process of tumour development, cancer cells interact with TILs and coevolve together. TILs exert their immune function to kill cancer cells; in contrast, upon induction by cancer cells, TILs may develop into different numbers or proportions of subtypes. When the antitumour-related subtypes decrease and the proportion of tumour-promoting subtypes increase, TILs become associated with a cancer-promoting effect . In GC rIn the process of GC occurrence and development, the tumour microenvironment undergoes dynamic and complex changes, including tumour-related inflammation and angiogenesis . A key mIn addition, studies have shown that the prognostic significance of TAMs for different tumour patients is also varied , 54, 56.The relationship between the total number of TAMs and the prognosis of GC patients has different conclusions. Studies have shown that the number of infiltrating macrophages in GC tissues is significantly higher than that in adjacent tissues, suggesting that as GC develops, macrophages are recruited and interact closely with cancer cells . Zhang eTo solve the shortcomings regarding the number of TAMs, future research should propose a definition for the TAM distribution types, that is, according to the potential functions of TAMs in different locations, provide a comprehensive comparison, and analysis of different types of macrophages, and explore classifications that may be able to reflect, at least to a certain extent, whether TAMs participate in the evolution of GC-interstitial interactions . It has In addition to the widely studied T cells and macrophages, other immune cells infiltrate the tumour immune microenvironment in GC.Natural killer cells (NK cells) are natural immune cells with the ability to kill tumour cells . StatistMast cells may promote tumour progression in the GC microenvironment. Mast cells can synthesize and release various growth factors and proteases(VEGF-A and MMP-9), thus promoting blood vessels and lymphatic generation . StudiesImmunosuppression is a significant feature of advanced GC and is closely related to GC progression. Previous studies have suggested that IL-35 is secreted by regulatory T cells, while recent studies have found that IL-35 can also be produced by B cells in mice and GC patients, and the expression of IL-35 in B cells is significantly upregulated in patients with advanced GC . In addiGC is a malignant tumor with high morbidity and mortality. At present, immunotherapy is applied for tumor treatment, but in GC, there are few clinical trials showing that immunotherapy can benefit patients. Patients with PD-L1 combined positive score (CPS) ≥5 who received nivolumab (PD-L1 inhibitor) plus chemotherapy improved OS compared with chemotherapy alone . HoweverThe tumor immune microenvironment plays an important role in tumor progression and prognosis in patients with gastric cancer, and is also related to the response to immunotherapy. This article mainly reviews cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and tumor-infiltrating lymphocytes (TILs) in GC. Under the recruitment of tumor-related signals, various immune cell components in the immune microenvironment interact closely with cancer cells, and then evolve with each other to jointly promote the development of tumors. Cancer-associated fibroblasts (CAFs) can interact with tumor cells and immune cells. For example, CAFs can promote the invasive ability of cancer cells, and CAFs can also attract immune cell infiltration, including T cells and macrophages, by secreting cytokines and chemokines. Tumour-stromal ratio (TSR) may be regarded as one of the routine parameters of clinicopathological analysis. Tumor infiltrating lymphocytes (TIL) and tumor associated macrophages (TAM) are particularly important, but TIL and TAM is a double-edged sword in the immune microenvironment of gastric cancer, and plays a bidirectional regulatory role in the occurrence and development of gastric cancer. Therefore, the absolute cell number of TILs and TAMs couldn’t work as prognostic indicators. Increasing evidences suggested that psTILs are an independent prognostic factor of GC, and TAM distribution type can be used as an important prognostic indicator for GC patients. Among them, TILs may interact with TAMs, for example, the CD4 T cell-secreted IL4 may be involved in the M1-M2 transition , therebyMM and JS are the co-first authors of this paper. Other authors contributed to this writing and editing of this manuscript. All authors contributed to the article and approved the submitted version.This study was funded by the CSCO-ROCHE Research Fund (No. Y-2019 Roche-015), Beijing Xisike Clinical Oncology Research Foundation (Y-HS2019-43), Wu Jieping Medical Foundation , CAMS Innovation Fund for Medical Sciences (2020-I2M-C &T-B-027) and Beijing Bethune Charitable Foundation (WCJZL202106).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Subacute ruminal acidosis (SARA) is a common metabolic disease in ruminants. In the early stage of SARA, ruminants do not exhibit obvious clinical symptoms. However, SARA often leads to local inflammatory diseases such as laminitis, mastitis, endometritis and hepatitis. The mechanism by which SARA leads to inflammatory diseases is largely unknown. The gut microbiota is the totality of bacteria, viruses and fungi inhabiting the gastrointestinal tract. Studies have found that the gut microbiota is not only crucial to gastrointestinal health but also involved in a variety of disease processes, including metabolic diseases, autoimmune diseases, tumors and inflammatory diseases. Studies have shown that intestinal bacteria and their metabolites can migrate to extraintestinal distal organs, such as the lung, liver and brain, through endogenous pathways, leading to related diseases. Combined with the literature, we believe that the dysbiosis of the rumen microbiota, the destruction of the rumen barrier and the dysbiosis of liver function in the pathogenesis of SARA lead to the entry of rumen bacteria and/or metabolites into the body through blood or lymphatic circulation and place the body in the “chronic low-grade” inflammatory state. Meanwhile, rumen bacteria and/or their metabolites can also migrate to the mammary gland, uterus and other organs, leading to the occurrence of related inflammatory diseases. The aim of this review is to describe the mechanism by which SARA causes inflammatory diseases to obtain a more comprehensive and profound understanding of SARA and its related inflammatory diseases. Meanwhile, it is also of great significance for the joint prevention and control of diseases. Subacute ruminal acidosis (SARA) is a common nutritional metabolic disease in ruminants, especially in high-yield dairy cows. In recent years, to improve the milk production performance of dairy cows, farmers have used a large number of high-grain diets as feed, which has induced a series of metabolic diseases, especially SARA. SARA will reduce milk yield and decrease the fat content of the milk of dairy cows . MeanwhiCurrent definitions of SARA are based on the pH of rumen fluid. Due to the different methods of rumen fluid collection, the pH of rumen fluid that defines SARA is usually between 5.5 and 6.0. Garrett et al. suggested that a pH of 5.5 be used as the threshold of SARA when rumen fluid samples were collected by rumenocentesis . MoreoveRuminal pH is mainly affected by the concentration of organic acids, such as volatile fatty acids (VFAs) and lactic acids, in the rumen. Under a normal fermentation condition, the concentration of VFA in the rumen increases gradually with the utilization of carbohydrates by the microbiota, and the rumen pH gradually decreases. The acidic rumen environment promotes the removal of VFA absorption through the rumen epithelium . In addiAfter feeding, rumen microbes ferment the carbohydrate intake of dairy cows to produce VFA and lactate, which reduces the rumen pH. Part of the temporarily increased VFA is absorbed by the rumen wall and part is neutralized by secreted saliva to keep the rumen pH within a certain range. When dairy cows eat a large amount of concentrate feed for a long time, on the one hand, excessive carbohydrates will produce excessive VFA under the fermentation of rumen microbiota; on the other hand, a low proportion of neutral detergent fiber (NDF) cannot stimulate ruminants and does not produce enough saliva to neutralize the large accumulation of VFA in the rumen, resulting in rumen pH drops below the physiological threshold ,10 Figu. In addiOnce dairy cows ingest too many carbohydrates, the VFA generated in the rumen and lactic acid energy substances cannot be timely absorbed by the rumen wall, and the amount of saliva secretion is reduced, resulting in a pH lower than 5.6–5.8 in the rumen, and SARA occurs. The peripartum period refers to the period from 3 weeks prepartum to 3 weeks postpartum and is an important period affecting the health of the cow, milk production and the occurrence of many diseases . In receThe liver is the final barrier preventing gastrointestinal bacteria and their products, such as Lipopolysaccharide (LPS) and histamine, from entering systemic circulation . SystemiMastitis, the inflammation of the mammary gland, is the most frequent disease of dairy cows. The occurrence of the disease causes a decline in the milk yield and milk quality of dairy cows and brings huge economic losses to dairy farming. A large number of studies have shown a link between SARA and mastitis ,27. A reStaphylococcus aureus-induced endometritis [Endometritis, inflammation in the inner lining of the uterus, is the major uterine disease of dairy cattle. Under normal conditions, the uterus is exposed to bacteria during calving. A healthy immune system can resist pathogenic colonization. Recent studies have shown that the gut microbiota plays a critical role in the regulation of the host’s immune system . It playmetritis . These rChronic laminitis is the most important clinical sign in dairy herds suffering from SARA, and once the prevalence of chronic laminitis is above 10%, it indicates the occurrence of SARA in the dairy herd . AcidosiLow-grade inflammation (LGI), also known as subclinical inflammation or low-grade chronic inflammation, is a chronic and low-grade inflammatory pathological state. LGI refers to inflammation below the level of infectious and autoimmune inflammation, without local and systemic symptoms such as redness, swelling, heat and pain, and exhibits a subclinical pathological state that is easily ignored . LGI is Inflammation acts as both a friend and foe. Inflammation is beneficial as an acute, transient reaction to harmful conditions, facilitating the defense, repair, turnover and adaptation of many tissues. However, IGL is likely to be detrimental for many tissues and for normal functions. A large body of studies has demonstrated a significant link between a mild proinflammatory state and many diseases. IGL contributes to the development of many diseases, such as metabolic syndrome (MetS), nonalcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM) and osteoarthritis ,56,57,58In recent years, many possible triggers of LGI have been proposed. Among these factors, the gut microbiota has been reported to play a central role in IGL. The role of gut-microbiota-mediated intestinal inflammation has long been appreciated . HoweverRumen microbiota disorder causes the rumen bacteria and their harmful metabolites to be released into the blood, damages liver function and induces a systemic chronic inflammatory response. Then, these harmful substances enter the body through the circulation of the blood and lymph circulation, enter various tissues and organs, increase the risk of metabolic diseases, reduce the defensive capabilities of the tissues and organs and increase the risk of infectious diseases. Bacteroidetes and Firmicutes were the most abundant phyla in the rumen. Meanwhile, the abundances of Firmicutes and Actinobacteria increased, and the abundances of Cyanobacteria and Verrucomicrobia in the rumen decreased in SARA cows. At the genus level, the abundances of Rickettsiales, Acholeplasmatales, Victivallaceae, Sutterella and Shuttleworthia decreased, and the abundance of Succinivibrio in the rumen increased in SARA cows [Ruminococcus, Candidatus, Saccharimonas, Lachnospiraceae, Eubacterium coprostanoligenes, Pseudobutyrivibrio and Saccharofermentans increased, and those of Prevotella, Rikenellaceae, Prevotellaceae, Succiniclasticum and Bacteroidales decreased during a grain-based SARA challenge. Mao et al. [Prevotella, Treponema, Anaeroplasma, Papillibacter and Acinetobacter decreased, and those of Ruminococcus, Atopobium, unclassified Clostridiales and Bifidobacterium increased in SARA cows.The rumen is the largest and most important digestive organ of ruminants. The rumen is similar to an anaerobic biological fermentation tank, which contains a large number of microorganisms, including bacteria, fungi, protozoa, archaea and viruses. These microbiotas have been functionally connected to digestion and absorption, metabolism, immune homeostasis and the neuroendocrine regulation of the host. An increasing number of studies have demonstrated that the rumen microbiota is closely related to the production performance of dairy cows ,64. DistARA cows . Chen etARA cows  identifio et al.  identifiRuminal metabolism is closely related to alterations in the rumen microbiota. Previous studies showed that alterations in rumen metabolite activity were observed in dairy cattle and goats with SARA. Mao et al.  reportedA large body of studies have confirmed that gut microbiota dysbiosis can cause intestinal tissue damage and enhanced permeability, resulting in a “leaky gut” ,74. MeanThe liver is an important organ for human health and is required for metabolic activities, nutrient storage, detoxification and immunological activities. Harmful intestinal bacteria and metabolites pass through the intestine and need to be detoxified and filtered by the liver before they can reach other tissues or organs. Under normal circumstances, intestinal bacteria, bacterial metabolites and other harmful substances enter the liver through the blood and can be taken up and cleared by Kupffer cells in the liver . MeanwhiCombined with the literature, we found that liver dysfunction occurred in the pathogenesis of SARA . TsuchiyUnder normal physiological conditions, the rumen and blood contain a small amount of LPS, which is not harmful to animal health. However, the occurrence of SARA will lead to a decrease in the pH value in the rumen, which results in the death of a large number of Gram-negative bacteria and the release of a large amount of LPS. Plaizier et al.  reportedAllisonella histaminiformans is the major producer of histamine in the rumen, and histidine is the only energy source for this bacterium [Histamine is an important mediator of type I allergies, which can cause vasodilation and increase vascular permeability. Meanwhile, it is also an important inflammatory mediator and has the ability to cause immune injury to humans and animals. Histamine is synthesized by decarboxylation of histidine via L-histidine decarboxylase . Allisonacterium . It is gacterium ,91. Undeacterium  found thacterium . They foacterium . Furtheracterium . When caacterium .In addition to LPS and histamine, other metabolites in the rumen can also enter the blood and cause or promote the occurrence of some diseases. γ-D-Glutamyl-meso-diaminopimelic acid (iE-DAP), which constitutes the peptidoglycan (PGN) layer of bacteria, increased significantly in the rumen fluid and blood of dairy cows suffering from SARA . StudiesBacterial translocation is the process by which gut bacteria cross the intestinal mucosal barrier into the mesenteric lymph nodes and portal system and then into systemic circulation and organs . Just asStenotrophomonas was enriched in the rumen and appeared in the mammary gland. Meanwhile, we found that Stenotrophomonas could cause mastitis in mice by gavage. The results indicate that the massively proliferating Stenotrophomonas in the rumen may translocate to the mammary gland through a certain pathway, leading to the occurrence of mastitis [As mentioned above, the occurrence of SARA is also accompanied by bacterial translocation. Jeon et al.  showed tmastitis . WhetherS. aureus-induced mastitis (data have not been published). In addition, SARA cows treated with LPS through intramammary infusion had higher acute phase proteins and modulated the blood metabolome differently than LPS-treated cows without SARA [Rumen microorganisms are necessary “organs” for normal physiological homeostasis and affect the immune system’s response to pathogens. Studies have shown that disruption of the homogeneous gastrointestinal microbiota may thus facilitate the development of pathogen-induced diseases. Accumulating studies have demonstrated that the gut microbiota is involved in the maturation of the immune system. It stimulates innate immunity in the early years of life, leading to the maturation of gut-associated lymphoid tissue and acquired immunity through the stimulation of local and systemic immune responses . The comout SARA . These sDisturbances of the rumen microbiota and metabolites are closely related to the occurrence of SARA and related diseases. Therefore, targeted regulation of the rumen microbiota may be an important approach to prevent and treat SARA and related diseases. Evidence showed that thiamine supplementation inhibited gut injury, increased the relative abundance of beneficial bacteria and reduced intestinal dysbacteriosis in SARA cows induced by a high-concentrate diet . Others In addition, rumen transplantation is commonly used in the treatment of digestive disorders, including left-sided abomasal displacement . RecentlSARA is an important metabolic disorder in dairy cows that affects animal welfare and the economy of milk production. It often leads to local inflammatory diseases such as laminitis, mastitis, endometritis and hepatitis. Clarifying the mechanism of SARA-mediated inflammatory diseases is of great significance for the joint prevention and control of these diseases. This review concludes that the rumen microbiota and its metabolites play a critical role in SARA-mediated inflammatory diseases. It is a bridge of SARA and its related inflammatory diseases. Dysbiosis of the rumen microbiota, destruction of the rumen barrier and dysbiosis of liver function in the pathogenesis of SARA will lead to the entry of rumen bacteria and/or metabolites into the body and place the body in the chronic low-grade inflammatory state. Meanwhile, rumen bacteria and/or their metabolites can also migrate to the mammary gland, uterus and other organs, leading to the occurrence of related inflammatory diseases. The rumen microbiota can be used as a target for the treatment of SARA and its related diseases.


As the world journeys towards the endemic phase that follows a pandemic, public health authorities are reviewing the efficacy of COVID-19 pandemic responses. The responses by Aboriginal and Torres Strait Islander communities in Australia have been heralded across the globe as an exemplary demonstration of how self-determination can achieve optimal health outcomes for Indigenous peoples. Despite this success, the impacts of pandemic stressors and public health responses on immediate and long-term mental health and wellbeing require examination. In December 2021, Aboriginal and Torres Strait Islander mental health and wellbeing leaders and allies (N = 50) attended a virtual roundtable to determine the key issues facing Aboriginal and Torres Strait Islander peoples and communities, and the actions required to address these issues. Roundtable attendees critically reviewed how the rapidly evolving pandemic context has impacted Aboriginal and Torres Strait Islander mental health and social and emotional wellbeing (SEWB). This paper presents an overview of this national collaborative consultation process, and a summary of the key issues and actions identified. These results build on evidence from other roundtables held in Australia during 2020, and the emerging consensus across the globe that Indigenous self-determination remains essential to Indigenous SEWB, especially during and following a pandemic. As the world starts to journey towards the endemic phase following the COVID-19 pandemic, health authorities across the globe are reviewing the efficacy of responses to the pandemic ,3,4,5. DIn December 2021, Aboriginal and Torres Strait Islander leaders and allies from across Australia came together for a virtual roundtable to determine the key issues facing Aboriginal and Torres Strait Islander mental health and SEWB, and the actions required to address these issues. This paper presents an overview of the collaborative consultation process, and a summary of the key issues and actions outlined in the roundtable final report . The finCOVID-19 was first reported in December 2019 and was initially known as the Novel Coronavirus (nCoV-2019). The follow year on 25 January 2020, Australia recorded its first case, and by March 2020, the World Health Organisation announced COVID-19 as pandemic . At thesRoadmap to Recovery report, which was presented to the Australian government. Importantly, this chapter outlined four recommendations to ensure the health of Aboriginal and Torres Strait Islander peoples [Aboriginal and Torres Strait Islander leaders were also driving strategic responses to the pandemic, with wide-reaching public health policy implications. For example, to ensure pandemic preparedness, an Aboriginal and Torres Strait islander COVID-19 Advisory Group was convened between the National Aboriginal Community Controlled Health Organisation (NACCHO) and the Australian Government. This group developed a national pandemic management plan, advising on health issues related to the COVID-19 pandemic response [ peoples . Importa peoples .The above efforts proved effective in protecting Aboriginal and Torres Strait Islander peoples from exposure, infection, and transmission of COVID-19 in early stages of the pandemic. Historically, Indigenous peoples have been disproportionally negatively impacted by pandemics, due to a range of complex factors  linked to historical and ongoing experiences of colonisation . Despitehttps://timhwb.org.au/ accessed on 29 November 2022) at the University of Western Australia (UWA) in April 2020 to explore the mental health and SEWB needs of Aboriginal and Torres Strait Islander peoples as perceived at the early stages of the pandemic. This initial roundtable was made up of 30 Aboriginal and Torres Strait Islander academics, SEWB experts, Elders, health professionals, and representatives from ACCHOs, and non-Indigenous allies. Using a yarning and consensus methodology [Recognising that pandemics incur significant mental health challenges and economic burden, a first virtual roundtable was called by the Transforming Indigenous Mental Health and Wellbeing team  entered strict lockdowns that would last several months. Other states  had virtually no community transmission of COVID-19, and experienced only a few strict snap lockdowns, keeping international and domestic border shut up until March 2022 . There wSince the first roundtable, there are now emerging empirical data relating to the mental health impacts of the pandemic. Although limited, evidence points towards a negative impact of the pandemic on immediate mental health and wellbeing in the general Australian population. For example, in August 2021, Australia’s national mental health support call centre recorded the busiest days in its 57-year existence , pointinAs a result of the social determinants of health ,38,39, AThere have also been important changes to policy relating to Aboriginal and Torres Strait Islander health and SEWB during the pandemic. Most noticeably, in July 2020, the National Agreement on Closing the Gap was formalised. This landmark National Agreement has been described as marking “a new chapter in the national effort to close the gap between Indigenous and non-Indigenous Australians” ( p. 1) anTo reconsider the impacts of the pandemic on Aboriginal and Torres Strait Islander mental health and SEWB in this significantly evolved context, a second Aboriginal and Torres Strait Islander roundtable was convened to discuss the ongoing impacts of the pandemic . This roThe first roundtable (April 2020) sessions responded to the immediate threat of the pandemic. In contrast, the second roundtable (December 2021) was convened two years into the pandemic and took a more critical review into how the rapidly evolving pandemic context had impacted mental health and SEWB for Aboriginal and Torres Strait Islander peoples. The second roundtable also provided a timely reflection on the extent to which the Australian Commonwealth Government would implement the recommendations outlined in the first roundtable report, and deliver on other commitments, such as those outlined in the 2020 National Agreement on Closing the Gap .At the time the second roundtable was held (December 2021), there was a national average of about 1500 new COVID-19 cases reported each day, with the majority being from Victoria and New South Wales. This number was growing following the emerging Omicron variant in the Eastern states. In contrast, other states such as Western Australia and the Northern Territory, had no community transmission of COVID-19 and still had stringent border restrictions. There had been just over 2000 deaths from COVID-19, with the majority of these being from Victoria and New South Wales. The vaccination rollout was well underway, with 92.9% of people (aged 16 years and older) having received at least one dose of vaccination. However, only 73.9% of Aboriginal and Torres Strait Islander peoples had received their first dose, with significant variability in vaccination rates between communities and regions.The roundtable was made up of a working party (N = 50) of Aboriginal and Torres Strait Islander mental health experts, community leaders, academics, service providers, representatives from the Aboriginal Community Controlled Sector, and non-Indigenous colleagues. There was also international Indigenous representation from Aotearoa  and Turtle Island (US and Canada). The group participated in the roundtable during a single 3 h meeting which was held online (via Zoom), as detailed further below.Like the first roundtable, the second roundtable meeting followed a collaborative process aligned with Aboriginal and Torres Strait Islander ways of knowing, being, and doing . As suchThe roundtable meeting occurred as a semi-structured discussion, led by two Aboriginal facilitators. The meeting began with ceremony: an acknowledgment of Country (due to being on Zoom) from a senior Aboriginal group member, and attendees then introduced themselves, including their name, connection to Country (where relevant), and affiliation. The purpose of these introductions was to build trust amongst the group through connecting participants to each other in a culturally relevant way, and to create a culturally safe space. These introductions are also custom to yarning. Yarning is the way that Aboriginal and Torres Strait Islander people refer to having a conversation. Yarning is a method which privileges Indigenous ontologies and is considered a culturally safe way of engaging with Aboriginal and Torres Strait Islander peoples ,45.Following these introductions, international Indigenous representatives from Turtle Island and Aotearoa provided a brief overview of the pandemic in their respective countries. These overviews allowed the group to place the Aboriginal and Torres Strait Islander response to the pandemic within the international context. These overviews were then followed by three brief presentations by Aboriginal members from the group. These members were purposefully selected, as they each lived in different Australian states/territories, and provided different perspectives and experiences of the pandemic. For example, one presenter was an Aboriginal psychologist working in New South Wales, another presenter was an Aboriginal CEO of an ACCHO in the Northern Territory, and the third presenter was an Aboriginal health and SEWB expert working in the Australian Capital Territory. In response to these presentations, the group engaged in unstructured topic yarning altogether, guided by the Aboriginal facilitators. This unstructured yarning did not follow any particular instructions and occurred spontaneously following the presentations.Topic yarning was then employed by the facilitators to generate more focused and semi-structured discussions around (1) the impact of the pandemic on Aboriginal and Torres Strait Islander wellbeing, mental health, and the social determinants of health, and (2) what is needed to address the biggest uncertainties that communities face in the transition to living with COVID-19. The group was randomly divided into in five small breakout rooms (~8 people in each group) on Zoom to facilitate the yarning. A representative was nominated by each group to share the main messages from their discussion with the wider group. In these discussions, Aboriginal and Torres Strait Islander voices and frontline experiences were prioritised. The facilitators ensured that the discussions remained on-topic, productive, and in line with a strengths-based approach ,47. A stA smaller working group (N = 4) was convened to synthesise key findings from the Roundtable. This group was comprised of two Aboriginal project leads, who were supported by two non-Indigenous team members from the Transforming Indigenous Mental Health and Wellbeing project. The two Aboriginal members were academics who contributed to the roundtable and provided cultural oversight during the synthesis and writing of the report. One non-Indigenous working group member attended the roundtable to take notes and did not contribute to the roundtable discussions. The other non-Indigenous working group member did not attend the roundtable.The working group collaborated online during a 6-month period to develop and refine the key issues discussed during the yarn at the roundtable, and actions required to address these issues  were sometimes at odds with the actions required to ensure social and emotional wellbeing . What should be the cultural mechanisms of decision making in these complex situations, and who should be responsible for making these decisions?To address a lack of cultural safety, two key actions were identified in the roundtable report . First, In instances where ACCHOs are unable or not suitable to deliver services, Aboriginal and Torres Strait Islander peoples should be provided with culturally safe services. To ensure cultural safety, all mainstream organisations whose work impacts Aboriginal and Torres Strait Islander people should implement the Cultural Respect Framework . This woThere was consensus during the Roundtable that mental health and SEWB challenges were not adequately addressed during the pandemic due to a lack of appropriate consultation with and resourcing to ACCHOs . As mentTo address the above, the roundtable called for needs-based funding and support for ACCHOs in order to address the disproportionate need and burden of disease experienced by Aboriginal and Torres Strait Islander peoples and communities and for this to be supported by policy that upholds the right to self-determination . This coIn the context of COVID-19, the Roadmap to Recovery report  estimateThe mental health impacts of COVID-19 must be understood in the context of pre-existing social inequities for Aboriginal and Torres Strait Islander peoples. That is, akin to how people with a higher burden of chronic disease  are more likely to have a severe reaction to a virus infection, people with a high burden of psychological distress and cumulative complex trauma  are more likely to be negatively impacted by pandemics ,68. A reThe roundtable report  specificIn some cases, public health restrictions put in place to slow the spread of the virus amplified pre-existing disadvantages and inequities. For example, in some communities, families of up to 15 people were reportedly forced to share a single standard household when stay-at-home orders were introduced, with restrictions also placed on their ability to visit Country and engage in wellbeing practices ,72. ThisTo address the above, the roundtable report called for governments to target the social and cultural determinants of health . The socAboriginal and Torres Strait Islander peoples have also drawn attention to the importance of cultural determinants of health ,79,80,81Finally, the roundtable  highlighDespite the above, data regarding the mental health impacts of the pandemic have been delayed . Often, Although there have been many stories of success for Aboriginal and Torres Strait Islander peoples during the pandemic ,15,61, tThe roundtable report calls for Indigenous data sovereignty as part of a global movement regarding the human right of Indigenous peoples to govern the creation, collection, ownership and application of their data ,84. ThesIn Australia, Aboriginal and Torres Strait Islander-led initiatives have enabled an effective public health response to the COVID-19 pandemic. Despite this success during the first waves, it is imperative that governments also consider the longer-term impacts of the pandemic on mental health and SEWB that will be disproportionately felt by certain populations due to new and pre-existing inequities within the social determinants of health. Aboriginal and Torres Strait Islander peoples are one population that is vulnerable to the health and mental health impacts of pandemics for these reasons.This paper builds on the Close the Gap Priority Reforms  and recoThe results in this paper are specific to Aboriginal and Torres Strait Islander peoples. There is great diversity amongst Indigenous populations globally, and it would be important to consider how the pandemic has impacted the wellbeing of other Indigenous peoples, and any effective strategies which have mitigated these impacts. Our roundtable did have international Indigenous representation from Aotearoa  and Turtle Island (US and Canada), who further reinforced the importance of self-determination.This paper highlights the continuing need for governments to focus on addressing the four Priority Reforms as outlined in the National Agreement on Closing the Gap . These i


With the acceleration of the pace of life and work, the incidence rate of invasive breast cancer is getting higher and higher, and early diagnosis is very important. This study screened and analyzed the published literature on ultrasound-guided biopsy of invasive breast cancer and obtained the accuracy and practicality of preoperative biopsy.  The four databases were screened for the literature. There was no requirement for the start date of retrieval, and the deadline was July 2, 2022. Two researchers screened the literature, respectively, and included the literature on preoperative ultrasound-guided biopsy and intraoperative and postoperative pathological diagnosis of invasive breast cancer. The diagnostic data included in the literature were extracted and meta-analyzed with RevMan 5.4 software, and the bias risk map, forest map, and summary receiver operating characteristic curves (SROC) were drawn.  The included 19 studies involved about 18668 patients with invasive breast cancer. The degree of bias of the included literature is low. The distribution range of true positive, false positive, true negative, and false negative in the forest map is large, which may be related to the large difference in the number of patients in each study. Most studies in the SROC curve are at the upper left, indicating that the accuracy of ultrasound-guided axillary biopsy is very high.  For invasive breast cancer, preoperative ultrasound-guided biopsy can accurately predict staging and grading of breast cancer, which has important reference value for surgery and follow-up treatment. Invasive breast cancer is a kind of malignant tumor , and no At present, no clear therapeutic factors for breast cancer have been found. It is generally believed that pathogenic factors are family history and genetics , endogenWe searched the database PubMed, Embase, Cochrane Library, and Web of Science with Mesh terms and keywords . The MesThe retrieved literature was screened according to the inclusion and exclusion criteria. Inclusion criteria were as follows: (1) complete literature can be obtained; (2) the literature mainly describes the diagnosis and treatment of patients with invasive breast cancer; (3) there are preoperative biopsy reports and intraoperative and postoperative pathological diagnosis reports of patients with invasive breast cancer in the literature; (4) preoperative biopsy was axillary lymph node puncture biopsy guided by ultrasound; (5) node puncture biopsy includes ultrasound-guided fine needle aspiration (US-FNA), ultrasound-guided core needle biopsy (US–CNB), and other puncture biopsies; (6) the literature has no language restrictions and no publication time restrictions.Exclusion criteria were as follows: (1) duplicate literature; (2) review literature; (3) meta-analysis literature; (4) literature on metastasis of primary cancers such as pancreatic cancer, thyroid cancer, liver cancer, gastric cancer, or cervical cancer on the breast and armpit; (5) literature unrelated to preoperative biopsy, such as cryosurgery, chemoradiotherapy, and biopsy technology; (6) unclear description or results and incomplete patient data records.Two researchers screened the literature and independently extracted the data from the selected literature using structured data collection tables. We extracted the basic data of patients with invasive breast cancer included in the literature and the basic situation of the literature. The extracted variables include true positive, false positive, true negative, and false negative; that is, the results of intraoperative and postoperative pathological diagnosis are compared with the results of preoperative ultrasound-guided axillary lymph node biopsy, and the former shall prevail to obtain the true and false diagnosis results of the latter. The progress information of postoperative patients was extracted, the information of postoperative complications was extracted, and relevant information was extracted from patients with long-term follow-up records.The Review Manager 5.4 (RevMan 5.4) software of the Cochrane Collaboration Network was used to evaluate the bias risk of the included literature. The specific evaluation contents included the generation of random sequences, allocation concealment, blinding of subjects, blinding of result evaluators, data integrity, and selective reporting. If the opinions assessed by the two researchers were not the same, a third researcher was required to participate in the assessment. RevMan 5.4 software was used to compare the preoperative biopsy results with the intraoperative and postoperative pathological results of all patients with invasive breast cancer included in the literature, and the forest map was made and analyzed. The specificity was studied using 95% confidence interval and calculated using the Mantel– Haenszel random-effect model. Funnel charts were made for all the included literature to visually and clearly reflect the bias.Four databases were searched, and a total of 647 documents were obtained. Among them, there are 135 PubMed, 155 Embase, 30 Cochrane Library, and 327 web of science. Among them, 137 literature reviews were repeated. After reading the title and abstract, combined with the conditions of inclusion and exclusion of documents, 411 documents were eliminated. After intensive reading of the articles, 80 articles were eliminated, and 19 articles were finally included in meta-analysis. The flowchart of literature screening is shown in The authors, countries, languages, the number of patients with invasive breast cancer, and types of preoperative ultrasound-guided biopsy of 19 literature reviews were extracted and listed. As shown in RevMan 5.4 software was used to analyze the bias of 20 included literature reviews. The literature reviews were analyzed from four aspects: patient selection, index test, reference standard, and flow and timing (see The forest map was drawn with RevMan 5.4 software, and false positive, false negative, true positive, and true negative of 19 studies were counted (see Using RevMan 5.4 software to draw the SROC curve, it is found that most studies are distributed in the upper left, some of which are close to 1, and only two studies are distributed in the lower left see .Invasive breast cancer metastasis to axillary lymph nodes can help determine the stage of invasive breast cancer. Through imaging examination of other parts of the body, if no metastasis is found, it is determined to be in the early stage of breast cancer. Lymph node metastasis in breast cancer is usually stage 2 or more. After the tumor focus of breast cancer metastasizes to ipsilateral axillary lymph nodes, it can still be pushed locally, indicating that it has entered stage 2 breast cancer. Stage 3 of breast cancer will present after tumor foci have metastasized to the ipsilateral axillary lymph nodes. Metastasis develops to supraclavicular lymph node metastasis, and the patient also has distant organ metastasis, which indicates that it is stage 4 of breast cancer. Ultrasound-guided axillary lymph node biopsy can make a more accurate judgment on the staging of breast cancer, so as to guide the treatment method and the surgical resection scope. At present, there are many new biopsy technologies, such as nuclear magnetic resonance-guided biopsy, and ultrasound-guided biopsy is the most widely used and longest used biopsy technology. There is an urgent need to summarize and analyze the accuracy and applicability of this technology to provide guidance for clinical biopsy of breast cancer.In this study, 19 literature reviews were selected to compare the preoperative ultrasound-guided axillary biopsy of invasive breast cancer with the intraoperative and postoperative pathological results, and we found out the number of false positive, false negative, true positive, and true negative and drew the forest map and SROC curve. The results showed that most of the studies had high sensitivity and specificity, most of the studies were on the upper left of the SROC curve, and some of these studies are close to 1, indicating that preoperative ultrasound biopsy has high diagnostic accuracy and can effectively predict the metastasis of breast cancer.In recent years, there have been many new techniques for preoperative biopsy of breast cancer. The application of imaging in the diagnosis of breast cancer is becoming more and more mature, especially the application of ultrasound technology. Chung et al.  comparedIt can be seen that ultrasound technology itself can accurately and clearly diagnose breast cancer, while biopsy guided by gold standard ultrasound and histopathological analysis can make an accurate diagnosis of malignant invasive breast cancer. Ji et al.  evaluateX-ray interventional biopsy have appeared, which can compare various imaging biopsies and draw clinically meaningful conclusions. Preoperative biopsies of different types of invasive breast cancer can be studied to find the differences, such as the location of invaded axillary lymph nodes, so as to conduct in-depth research on invasive breast cancer [In this study, the preoperative ultrasound-guided biopsy of invasive breast cancer was meta-analyzed and compared with the final diagnostic results. There are some limitations in this study that need to be supplemented by subsequent research. The literature searched is still small, so we should search other databases such as clinical trials and national libraries of various countries. It is necessary to use the full-text search function to retrieve the literature related to preoperative ultrasound biopsy. There may be some literature related to relevant content, but it is not the subject content of the literature. This kind of literature should also be carefully read and screened, and there may be some gains. Ultrasound-guided biopsy is the most widely used. In recent years, MRI-guided biopsy and t cancer , 55.For invasive breast cancer, preoperative ultrasound-guided axillary lymph node biopsy can accurately predict the grading and staging of breast cancer, with an accuracy of more than 95%, which can provide a reference for surgery. The histopathological examination of the tumor during and after the operation was highly consistent with the preoperative biopsy, which confirmed that the accuracy of ultrasound-guided biopsy was very high. At present, ultrasound-guided biopsy of breast cancer is the most widely used technology, and other imaging methods cannot compete with it. Preoperative ultrasound-guided biopsy plays a key role in the operation and treatment of breast cancer or even a decisive role.


Recognizing the future leaders of Evolutionary and Genomic Microbiology is fundamental to safeguarding tomorrow's driving force in innovation. This Research Topic will showcase the high-quality work of internationally recognized researchers in the early stages of their careers. We aimed to highlight research by leading scientists of the future across the entire breadth of Evolutionary and Genomic Microbiology, and present advances in theory, experiment and methodology with applications to compelling problems.Wang et al. leading a group in the Beijing Institute of Biotechnology in China investigated changes in chromosomal structure of Klebsiella Pneumoniae under Simulated Microgravity (SMG). The authors, asked whether phenotypic changes induced by SMG in the subpopulations of K. pneumoniae are driven by genome higher-order structural changes. By the combination of genome-wide chromosome conformation capture (Hi-C), RNA-seq and whole-genome methylation (WGS) analyses, they found that the along with the global chromosome interactions change, the compacting extent of M1, M2 subpopulations were much looser under SMG and even with an increase in active, open chromosome regions. In addition, transcriptome data showed that the function of most differentially expressed genes (DEGs) were mainly associated with membrane fractions. Additionally, WGS analysis revealed that methylation levels were lower in M1 and M2. Finally, they discovered that most upregulated DEGs were enriched in the boundary regions of the variable chromosomal interaction domains (CIDs), in which genes regulating biofilm formation were mainly located. These results suggest that K. pneumoniae may regulate gene expression patterns through DNA methylation and changes in genome structure, thus resulting in new phenotypes in response to altered gravity.Among the chromosomal structures and genomic differentiation articles,Stanojković et al. from the University in Prague, Czechia explored the genomic differentiation and gene flow within the genus Laspinema (cyanobacteria). In this regard, the authors used phylogenomics and a population genomic approach to investigate the extent of local genomic diversity and the mechanisms underlying sympatric speciation of Laspinema thermale. They found two highly genetically diverse cryptic lineages of Laspinema with recombination occurring more frequently within than between them. That suggests the existence of a barrier to gene flow, which further maintains divergence.In contrast, the group of Han et al. evaluated the epidemiological characteristics and molecular evolution mechanisms of carbapenem-resistant hypervirulent Klebsiella pneumoniae (hvKP). In particular, the authors summarize the evolutionary mechanisms of resistance and plasmid-borne virulence as well as the prevalence of CR-hvKP. Alternatively, Guillén-Chable et al. from the Universidad Nacional Autónoma de México, Mexico, described the presence and possible differences in the microbial resistome of four sites from the Yucatan coast through the evaluation of the composition and abundance of Antibiotic Resistance Genes (ARGs) using a high-throughput analysis of metatranscriptomic sequences. They found ARGs, which participate in the resistance to tetracycline, macrolide, rifamycin, fluoroquinolone, phenicol, aminoglycoside, cephalosporin, and other antibiotics. This study contributes to generating information about the current state of antibiotic resistance on the Yucatan coasts and probably, to other coastal sites.As a consequence of the antibiotic resistances identified in the bacterial world as one of the greatest human and clinical challenges associated with different pathogenic organisms, from the Inner Mongolia Medical University, in China, de novo assembly of complex data like metatranscriptomic and metagenomic data are currently of a high demand. The group headed by Prjibelski, St. Petersburg State University, Russia describes “MetaGT: A pipeline for de novo assembly of metatranscriptomes with the aid of metagenomic data.” This pipeline is based on the idea of simultaneous usage of both metatranscriptomic and metagenomic sequencing data obtained from the same sample. MetaGT assembles metatranscriptomic contigs and fills in missing regions based on their alignments to metagenome assembly. It was demonstrated that metagenomic data greatly improve completeness of assembled transcripts compared to sequences assembled solely from metatranscriptomic data. As a result, presented approach allows to overcome known complexities and obtain complete RNA sequences, as well as estimate their abundances.User-friendly pipelines for Xu et al. in the Chinese Academy of Agricultural Sciences, China, evaluated a potential biocontrol mechanism for two strains of Lysobacter enzymogenes. For this, the complete genomes of two strains of L. enzymogenes were obtained and characterized. One of them, CX03, has been shown to exhibit a broad spectrum of antagonistic activity against a variety of bacteria, while CX06 exhibits antagonistic activity against various fungi and oomycetes. Annotation of functional genes showed that strains CX03 and CX06 have many genes or gene clusters associated with the biosynthesis of various secondary metabolites, which may be responsible for different antagonistic activity against various plant pathogens.Using comparative genomics, Begmatov et al., leading a group in the Research Center of Biotechnology of the Russian Academy of Sciences, Russia, assembled a near-complete genome of a member of MBNT15 from a boreal peatland metagenome and used genomic data to analyze the metabolic pathways of this bacterium and its ecological role. Comparative genome analysis of the MBNT15 phylum revealed that the vast majority of its members are capable of aerobic respiration and dissimilatory iron reduction and some species also can reduce sulfur and nitrogen compounds, but not sulfate. Based on phylogenetic and genomic analyses, the novel bacterium is proposed to be classified as Candidatus Deferrimicrobium borealis, within a candidate phylum Deferrimicrobiota.In contrast, the Genome analysis of the candidate phylum MBNT15 bacterium from a boreal peatland predicted its respiratory versatility and dissimilatory iron metabolism. In this work, Prakash and Kumar from the Indian Institute of Technology Guwahati in India, achieved a transcriptional analysis of CRISPR I-B arrays of Leptospira interrogans serovar Lai and its processing by Cas6. The authors predicted in silico database seven CRISPR arrays in L. interrogans serovar Lai positioned between the two independent cas-operons. Here, we present the redefined repeat-spacer boundaries of the CRISPR subtype I-B locus of serovar Lai. Using the reverse transcription-PCR (RT-PCR), the authors account that the seven CRISPR are transcriptionally active in serovar Lai.Finally, in the Research Topic, We believe that the field of Evolutionary and Genomic Microbiology is of great importance and its scope of interest is expanding. This is evidenced by the variety of topics and the quality of the manuscripts included in this Research Topic. We also appreciate the interest and reception from the scientific community and hope that this Research Topic will interest researchers in the fields of genomics, microbiology, antimicrobial resistance, biomedicine and bioinformatics, among others.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Colorectal cancer (CRC) is a worldwide disease threatening people's lives. Surgery and chemotherapy are still the main methods for CRC treatment. However, the side effects and chemotherapeutic drug resistance restrict the application of chemotherapy. Trametes Robiniophila Murr, also known as Huaier, is a traditional Chinese medicine that has been used for more than 1,600 years. Huaier extracts have promising anti-cancer effects on hepatoma, breast cancer, and gastric cancer. Nowadays, the tumor inhibition of Huaier on CRC has attracted more and more attention. This review mainly provides the possible anti-tumor mechanisms of Huaier for CRC treatment in apoptosis and inhibiting proliferation of tumor cells, preventing epithelial-mesenchymal transformation (EMT), weakening proliferation and differentiation of CRC stem cells, decreasing the vessel density in tumor tissues, and enhancing the immune system and chemotherapeutic efficacy. Huaier extract may be a good candidate for CRC treatment, especially when combined with other chemotherapeutic agents. Colorectal cancer (CRC) is a common malignant tumor in the digestive tract, and its incidence is increasing. The mortality of CRC is on the rise and ranks third among all malignancies  that serTrametes Robiniophila Murr, also known as Huaier, has a history of more than 1,600 years as traditional Chinese medicine. Huaier granules are common clinical pharmaceutical agents. Huaier is a medicinal fungus that grows on acacia, locust tree, sandalwood and many other trees, and it contains various organic components and more than 10 minerals. The main ingredient of Huaier is the fungal matter, which includes polysaccharides, proteins, ketones, and alkaloids, and the active ingredient is polysaccharide-protein . Huaier et al. found that Huaier extract can improve the severity of inflammatory bowel disease-related tumors, induce apoptosis of related tumor cells, and inhibit tumor cell proliferation in CRC mouse model. In addition, the apoptosis-associated protein levels, including p53 and Bcl-2, show significant differences when treated with Huaier in CRC cell lines  refers to the biological process by which epithelial cells are transformed into cells with interstitial phenotypes through specific procedures . EMT is CRC stem cells have a stronger ability to proliferate, infiltrate, and metastasize than CRC cells . Inhibitet al. found that Huaier polysaccharide (TP-1) can reduce the expression of hypoxia-inducible factor and VEGF in tumor tissues in mice bearing hepatocellular carcinoma SMMC-7721 tumors model  The active ingredient of Huaier for tumor treatment has not been determined. (2) Although increasing studies have focused on the direct effects of Huaier on cancer cells, few studies have explored its molecular and immunomodulatory mechanisms. (3) Whether the inhibitory effect of Huaier granules on the invasion and migration of CRC is related to the influence of intestinal flora needs further study. (4) More basic and clinical studies should be performed to provide a more convincing basis for applying Huaier in the treatment of CRC.In conclusion, Huaier extracts may inhibit the progression of CRC in various ways, include inducing apoptosis and inhibition of tumor cell proliferation, blocking epithelial mesenchymal transition (EMT), attenuating proliferation and differentiation of CRC stem cells, reducing vascular density in tumor tissue, and enhancing the immune system. Therefore, Huaier may be an excellent candidate to enhance the sensitivity of chemotherapy while enhancing the immune system and decreasing side effects. The genes, signaling pathways, and related molecular mechanisms involved in the interaction between Huaier extracts and CRC are the focuses of future research.BL drafted the review. QC generated the graph and guided the construction of the manuscript. ZL edited the review. All authors contributed to the article and approved the submitted version.This study was supported by Science and Technology Department of Jilin Province (20200201325JC).The authors declare that this study received funding from Qidong Gaitianli Pharmaceutical Co., LTD. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


OA is a major contributor to pain, loss of function, and reduced quality of life. Over the last decade, considerable research efforts have focused on cell-based therapies, including several stem cell-derived approaches to reverse the cartilage alterations associated with OA. Although several tissue sources for deriving cell-based therapies have been identified, none of the resident stem cell populations have adequately fulfilled the promise of curing OA. Indeed, many cell products do not contain true stem cells. As well, issues with aggressive marketing efforts, combined with a lack of evidence regarding efficacy, lead the several national regulatory bodies to discontinue the use of stem cell therapy for OA until more robust evidence becomes available. A review of the evidence is timely to address the status of cell-based cartilage regeneration. The promise of stem cell therapy is not new and has been used successfully to treat non-arthritic diseases, such as hematopoietic and muscle disorders. These fields of regenerative therapy have the advantage of a considerable foundation of knowledge in the area of stem cell repair mechanisms, the role of the stem cell niche, and niche-supporting cells. This foundation is lacking in the field of cartilage repair. So, where should we look for the ideal stem cell to regenerate cartilage? It has recently been discovered that cartilage itself may contain a population of SC-like progenitors. Other potential tissues include stem cell-rich dental pulp and the adolescent growth plate, the latter of which contains chondrocyte progenitors essential for producing the cartilage scaffold needed for bone growth. In this article, we review the progress on stem cell therapies for arthritic disorders, focusing on the various stem cell populations previously used for cartilage regeneration, successful cases of stem cell therapies in muscle and hemopoietic disorders, some of the reasons why these other fields have been successful , and finally, novel potential sources of stem cells for regenerating damaged cartilage  Osteoarthritis (OA) is a major health concern, affecting more than 50% of adults over the age of 65 . OA contOA is a total joint disease, but the end result is the complete loss of articular cartilage. The presence of early cartilage defects is a strong risk factor for OA progression . In the Surgical strategies to halt the progression from cartilage defect to the development of OA have been limited and prone to failure . Marrow-The development of OA in the joint represents a failure of the endogenous articular repair system to maintain healthy osteochondral units . Specifivia the articular space in order to initiate repair. This repair pathway was supported by experiments in a canine model showing that synovium-derived MSCs are able to adhere to the areas of cartilage injury  of these progenitor cells in cartilage repair and homeostasis unclear at this time -determined bone marrow lesions is five-fold greater than non-bone marrow lesion . In addition, not all clinical studies characterized the stem cells being injected, for example, using the ISCT minimal criteria for MSCs  contribute to establishing the myogenic cell identity, to the subsequent differentiation and formation of muscle fibers during muscle regeneration in postnatal life . Moleculin vitro, and the development of specific cell differentiation protocols  originating from neural crest mesenchyme in the dental pulp, can be extracted with minimal donor site morbidity . The den factors . Like bo factors . Preclin factors . Lo Monaed media . Mata etlignment . Fernandlignment . Overallproliferative zone of the growth plate  suggest that tissue-embedded stem cell populations are more efficient at repairing damaged tissue compared to MSCs   . In 2018atility) . Within ytometry . As wellal bones . The autl tissue . We are in vivo, Murphy et al. evaluated the response of SSCs to microfracture in both the distal femur of mice that had undergone the destabilization of the medial meniscus (a well-described model of OA), as well as human fetal phalangeal bone (In line with enhancing the endogenous stem cell population toward repairing cartilage defects eal bone . Followieal bone . The addRecently, research has emerged evaluating the differentiation of iPSCs toward chondrocytes for the purpose of treating OA . iPSCs wCurrent strategies to regenerate cartilage in the OA joint are limited to surgical interventions that may fail or yield fibrocartilaginous tissue with insufficient biomechanical properties for joint load distribution. Furthermore, such surgical treatments are less ideal for larger, non-focal areas of cartilage loss, as seen in the later stages of OA. Regenerative medicine thus remains an attractive option for OA treatment. Although stem cell therapy holds promise for cartilage regeneration in OA, safe and reliable strategies to either optimize endogenous stem cells toward cartilage repair, to apply exogenous stem cells into damaged joints, or both simultaneously, have yet to emerge. The research study has emphasized the importance of the stem cell source niche, which proffers the characteristics that stem cells bring to the table with respect to their regenerative capacity. Despite this, however, there remains a lack of standardization across clinical studies regarding stem cell tissue source and phenotypic characterization. A well-characterized cell product that can be reproducibly isolated or manufactured, and that can reliably produce healthy cartilage in the avascular cartilage microenvironment—that is, standardization of stem cells used for treatment and evidence-based outcome measures—will be an essential factor for moving the field of cartilage regeneration forward. The effective means of contending with the catabolic microenvironment of the OA joint and maintaining cellular chondrogenic functional capacity in a region primed toward cartilage destruction will also be an important challenge to overcome. The lessons from other areas of regenerative medicine can be applied to the field of cartilage regeneration. Hematopoietic therapies benefit from a deep understanding of the impact of the microenvironment on stem cell activity, not only the stem cells, but also the intricate role played by other support cells within the hematopoietic niche. A well-established international infrastructure responsible for thoroughly characterizing, standardizing, and distributing hematopoietic stem cells represents a major advantage. The field of muscle regeneration also takes the advantage of decades of data describing the mechanism of regeneration as well as the impact on the microenvironment on the satellite cells, additionally benefiting from a strong understanding of molecular pathways by which satellite cells develop, replicate, and respond to external function-altering stimuli. As compared to these other areas of regenerative medicine, our current understanding of the optimal cartilage-producing stem cell, its niche, the identity and role of niche-supporting cells, and the molecular mechanisms governing functional potential remains limited. Further research is needed to address these fundamental factors .Even though stem cell therapy will likely 1 day become a valuable tool for cartilage regeneration, OA remains a whole-joint disease . Articul


The main objective of this study is to examine the impact of reinforcements on the strength of natural fiber composites. Recent advancements in natural fiber composites have minimized the usage of man-made fibers, especially in the field of structural applications such as aircraft stiffeners and rotor blades. However, large variations in the strength and modulus of natural fiber degrade the properties of the composites and lower the safety level of the structures under dynamic load. Without compromising the safety of the composite structure, it is significant to enrich the strength and modulus of natural fiber reinforcement for real-time applications. The strength and durability of natural fiber can be enriched by reinforcing natural fiber. The reinforcement effect on natural fiber in their woven, braided, and knit forms enhances their structural properties. It improves the properties of natural fiber composites related to reinforcement with short and random-orientation fibers. The article also reviews the effect of the hybridization of natural fiber with cellulosic fiber, synthetic fiber, and intra-ply hybridization on its mechanical properties, dynamic mechanical properties, and free vibration characteristics, which are important for predicting the life and performance of natural fiber composites for weight-sensitive applications under dynamic load. This century has already perceived notable achievements in green technology, especially in the domain of materials science, with the evolution of high-performance materials made from natural resources for various structural, manufacturing, bio-medical, aerospace, and automotive applications ,2. Due tIn the last two decades, natural fiber has found extensive usage in aerospace, naval, and structural fields . The maiThe large variation in strength and modulus makes NFCs incompatible under dynamic load and minimizes the safety level of the component. To overcome this drawback, NFCs are reinforced with NFRs in the polymer matrix to improve the structural applications’ strength, modulus, and safety.Most researchers have developed NFCs with random orientation and short natural fibers as reinforcements in the polymer matrix, creating non-uniform stress distribution due to fiber discontinuity, which further leads to early failure of composites. The modulus of natural fibers can be enriched by reinforcing them with natural fibers in plain, braided, and knitted arrangements. It is observed that the Young’s modulus of NFCs reinforced with NFRs in distinctive patterns in weavings such as basket, plain, stain, twill, etc. have increased promisingly. Similarly, braided NRCs enriched the Young’s modulus of jute-fiber reinforcement by 30% compared to conventional weaving ,13. SapuReinforcing the NFC with synthetic fiber enhances its mechanical properties and load-carrying capacities and can be used for different structural applications . DamodarIn this paper, a systematic review of NFC enhancement by modifying the Young’s modulus of natural fiber reinforcement is reported. A critical review was done on various processes such as weaving, braiding, and knitting concerning mechanical, dynamic mechanical, and free vibration properties. Further hybridization effects of natural fiber with synthetic fiber in the context of mechanical, dynamic mechanical, and dynamic properties were reviewed. In addition, the fabrication and advantages of intra-ply woven NFC made with two different yarn fibers are also discussed.Many researchers have investigated the mechanical, dynamic mechanical, and tribological properties of randomly oriented and short natural fibers as reinforcements in the polymer matrix. The main problem associated with short-form reinforcement in a high-density polymer matrix is that achieving uniform distribution is difficult. It affects the advantages of natural fiber composites seriously and makes them incompatible for structural applications. Almeida et al.  investigAnother problem associated with randomly distributed short natural fibers is that the polymer matrix is agglomerates as it affects the composites properties. A similar problem was reported by Joseph et al.  regardinArib et al.  studied Researchers also found that the random distribution of NFR affects the stiffness of composites due to poor stress transfer at the interface during loading. The dynamic behavior of banana–sisal hybrid short fiber-reinforced polyester composites was investigated by Idicula et al. . At 0.40Kumar et al.  comparedFrom the results of these reported studies, it is concluded that the properties of natural fibers with short form depend on the fiber aspect ratio, and improvements in properties are generally observed only up to a certain wt%. The main problem associated with short and randomly oriented fibers in composites is achieving uniform distribution in the polymer matrix . FurtherTo overcome the disadvantage of natural fiber with short and random orientation, researchers focused more on the reinforcement effect by incorporating WNFR to enhance the properties of NFCs for low and medium load applications. Because of its ease of processing, low fabrication cost, and improved characteristics, the idea of employing WNFR to produce NFCs was generally adopted. Due to stronger fiber–matrix bonding, the gap between warp and weft acts as a mechanical interlock among the polymer matrix, increasing resistance to failure under load. In addition, the chances of failure are less/delayed due to fiber pullout under dynamic loading conditions. In recent years, tremendous development in the textile sector has motivated researchers to explore the possibilities of improving natural fiber composite properties, making them suitable for many applications. Nowadays, natural fibers are used in continuous and woven forms, which further increases the inherent properties of NFCs. Several researchers analyzed the outcome of weaving patterns such as plain, twill, stain, and basket weaving patterns on the mechanical properties of NFCs. Results revealed that NFCs reinforced with NFR with varied weaving patterns exhibit improved mechanical properties. John et al.  and PothThe mechanical properties of natural fiber composites, such as impact, flexural, and tensile strength, are influenced by fiber percentage in the matrix, fiber strength, fiber–matrix adhesion, fiber orientation, concentration, and treatment type ,42. SteeIn an experimental investigation, Asim et al.  evaluateCarmisciano et al.  investigRajesh and Pitchaimani  analyzedThermal and dynamic mechanical characteristics of newly developed materials are significant parameters to be examined primarily for structural applications. At higher temperatures, the interactions between molecules in materials made out of conventional materials will be higher, which increases energy dissipation and lowers the stiffness. The fiber or yarn arrangement, reinforcement, amount of fiber in the matrix, and adhesion between the matrix in the space between two fiber yarns influence the dynamic characteristics of composite materials. Rajesh and Pitchaimani  investigThe impact of weaving patterns on the dynamic mechanical behavior of banana–epoxy composites was investigated by Venkateshwaran and Elayaperumal . The comThe materials used for structural applications must have superior damping properties, along with strength and stiffness. These properties are significantly influenced by the manufacturing process, type of reinforcement, and matrix. Researchers have fabricated composite laminates using a compression-molding process and compared them with a hand lay-up technique. Results revealed that composites fabricated using the compression-molding technique exhibited improved properties compared to those produced using the hand lay-up method. Kumar et al.  reportedFree vibration properties such as natural frequency and damping characteristics of fiber-reinforced composites have been analyzed by several researchers using experimental, analytical, and numerical methods. In free vibration analysis, the composite material’s natural frequency and corresponding damping factor were found using the fast Fourier transfer (FFT) algorithm. It changes a time-domain signal to a frequency response signal and provides an incessant peak for the corresponding natural frequency of the composite material. Chandradass et al.  experimeRecently, synthetic fibers have been replaced by natural fibers as reinforcements in the polymer matrix because of their better energy-dissipating behavior ,108. TheSimilarly, the effects of structure type, type of fibers, and physical properties such as density, thickness, and manufacturing process on the stiffness of the composite laminate influence the dynamic properties . Mishra According to Chandra et al. , fiber-rHybridization offers substantial improvement in the properties of composites, which has attracted the attention of researchers for structural applications. In general, a significant weight percentage of synthetic fibers such as carbon, glass, etc., are hybridized to enhance the inherent properties of natural fiber composites for the intended applications. For compressive applications, jute fibers are reinforced with glass fiber. However, the hybridization effect is not significant for tensile load applications. Thus, it reveals that the procedure requires applications regarding the hybridization of natural fiber with synthetic fiber to achieve the desired goals/applications. For example, Mansor et al.  carried The primary purpose of the hybridization of synthetic fiber/filler in the polymer matrix with natural fiber is to enrich the properties of composites, especially mechanical properties. It is determined by the filler dispersion in the polymer matrix, fiber distribution, fiber adherence to the matrix, fiber contact area, reinforcement high load-bearing behavior, fiber origin, surface treatment , and stacking sequence. Through experimental studies, most researchers reported that strength enhancement depends on fiber loading, treatment, aspect ratio, and contact area ,152,153.The hybridization of synthetic fiber with natural fiber helps to enrich the properties and to increase the resistance against water absorption and minimize environmental issues and cost. Though natural fibers have many advantages over man-made fibers, many hydroxyl groups present in cellulosic substances such as cellulose, hemi-cellulose, and lignin increase the interaction rate with moisture present in the environment, making them incompatible with hydrophobic applications. Researchers carried out a lot of experimentation on the hybridization of synthetic fiber with natural fiber. They established that the hybridization of synthetic fiber enhanced the mechanical properties of the composite. The improvement is due to the decrease in water absorption and enhancement in bonding. The major problems of natural fibers are moisture absorption due to the interaction of cellulosic substances available in the fiber cell wall. It can restrict the applications of natural fiber composites in various applications, especially outdoor applications, where the interaction of water particles is high. The water absorption of natural fiber composites is affected by the nature of the fiber, growing environment, volume fraction, and diffusivity. Water can enter through available micro-cracks in the matrix and microgaps between the fiber and matrix. Transportation of water particles can happen due to capillary action in the interface gap due to poor wetting. Therefore, composites exposed to the moisture environment can experience debonding and crack formation. In addition, those water molecules act as a plasticizer and reduce the load-carrying capacity, thus minimizing the mechanical properties of natural fiber composites. Henceforth, it is important to improve the resistance to water absorption behavior. Physical and chemical surface modification of natural fiber improves the compatibility of natural fiber with the polymer matrix. However, using a high concentration of harsh chemical treatment affects human health and the environment differently. Hence, to overcome the problem related to the moisture absorption and wettability of natural fibers, the hybridization of synthetic fiber and natural fiber is a better choice. It reduces the water molecule interaction and enhances the properties under various loading conditions for intended applications.Panthapulakkal and Sain  analyzedKureemun et al.  and RampThwe et al.  comparedResults showed that composites with carbon fiber as the outer skin layer exhibited enhanced dynamic properties and an increased glass transition temperature of 75 °C. Mochane et al.  found thNatural fiber composites with two or more types of natural fiber reinforced in the polymer matrix have better inherent properties and are more compatible than conventional materials for low/medium load applications and automobile applications such as home applications, outer car body, agricultural, interior parts, and packing applications. Edhirej et al.  found thThough hybridization addresses the drawbacks of single-fiber reinforcement, the incompatibility of hybrid reinforcement in the hydrophobic matrix is exacerbated by the presence of additional hydroxyl groups in the cellulose and hemicellulose in the fiber cell wall. As a result, the benefits of natural–natural fiber-reinforcing hybridization are diminished. As a consequence, increasing the interfacial bonding strength of hybrid reinforcement and matrix is essential. For example, when two stronger natural fibers are reinforced  in the hydrophobic matrix, it increases the interaction with water molecules present in the environment. The reason behind higher interaction with water molecules associated with stronger natural fibers is that the presence of more cellulose contributes to interaction with moisture. Thus, it reduces the interfacial adhesive bonding. Major parts of cellulose have a significant –OH-to-C ratio, which interacts with water molecules. Cellulose is semi-crystalline, and the crystalline region provides a barrier against water penetration, whereas the amorphous region of the cellulose allows the water molecules to pass through. Therefore, it affects the cellulosic chain and losses its stiffness. Hence, it minimizes the advantages of natural–natural fiber hybridization by increasing the incompatibility between fiber and matrix, generating more microvoids and delamination. King et al.  analyzed2O2 solution removed the hemicellulose and lignin from green coconut fiber. SEM results revealed that H2O2 removed a high amount of the waxy and fatty acid but did not alter the surface.Researchers modified the fiber surface using physical and chemical methods to improve the adhesive strength between fiber and matrix. In the chemical modification, alkali treatment is commonly used by researchers and has been noticed to improve the adhesion between fiber and matrix by removing a substantial amount of hemicellulose and lignin from the fiber cell wall. Kabir et al.  used alkIn contrast, NaOCl/NaOH minimized the hemicellulose content from the fiber wall. NaOCl treatment did not affect it because it increased the hydrophilic nature of the fiber ,201. TheA higher contact area associated with filler material helps to establish better bonding between natural fiber reinforcement and polymer matrix, leading to improved mechanical properties by increasing the resistance against debonding and the initiation of cracks and the random propagation of them, and increasing the rigidity of the composites. However, reinforcement by fillers in polymer composites sometimes decreases the composites’ strength, stiffness, and modulus. This is due to the depression of the fillers in the polymer matrix, thus affecting the properties of the composites . In geneSimilarly, the tensile properties of madar fiber were enhanced by adding nanoclay to the polyester matrix . The decFiber yarn orientation influences the excellent properties of natural fiber composite. The relatively strong natural fiber yarn orientation in the loading direction exhibits a higher modulus and stiffness in natural fiber composites. In general, natural fiber composites are reinforced in a single-matrix system using natural fiber, synthetic fiber, or filler material to improve their properties. Many researchers investigated the hybridization of natural fiber with synthetic fiber and cellulosic fiber with natural fiber in a polymer matrix in an experimental investigation. They found that hybridization enhanced the mechanical properties of the natural fiber composites compared to natural fiber-reinforced composites alone in the matrix ,216. IntPark and Jang  fabricatIn contrast, the banana fiber in the loading direction enriched the energy-dissipating properties. However, the combination of jute and banana in the single-woven fabric enhanced both the modulus and the damping factor of the intra-ply hybrid composites. The review found that the selection of fiber and its orientation with the exemplary weaving architecture helped improve the properties of the natural fiber composite through intra and inter-ply hybridization.Inherent properties of composite material can be enhanced by reinforcing stiff fiber in the polymer matrix. In natural fiber composites, the stiffness of the natural fiber can be enhanced by replacing short natural fibers extracted from the natural source with continuous fiber yarn, which can be substituted into woven form. Though the woven form enhances the stiffness and modulus of the reinforcement, weaving architecture and interlacing between fiber yarn in the warp and weft directions influences the strength and modulus of the composite. Furthermore, to improve the properties of the composites, researchers have used advanced techniques such as braiding and knitting for natural fiber reinforcement. Compared to conventional yarn, braided yarn enhances the modulus value, enhancing the load-carrying behavior of the yarn. Reinforcement of those braided yarns increases the composites’ inherent properties compared to those reinforced using conventional twisted yarn . FurtherKnitted reinforcement is a special kind of reinforcement that helps overcome the delinquents associated with natural fiber reinforced in short form. It provides good stability and properties compared to unidirectional reinforcement. Woven-fabric reinforcement provides good stability and balances properties in the warp and weft directions due to the high crimp in the warp and weft directions’ tensile modulus of the composites ,231. A lThe influence of reinforcement on the strength improvement of natural fiber composites was thoroughly examined in this report. Short natural fiber reinforcement with random orientations provides poor resistance under loading due to high-stress concentration and rapid crack propagation. Thus, it increases the water-absorbing behavior and reduces the composites’ mechanical properties due to the significant surface contact of cellulosic natural fiber with moisture available in the environment.On the other hand, woven reinforcement enhances the tensile, flexural, and impact strength of natural fiber composite due to the presence of natural fiber in continuous yarn form. Thus, it increases the rigidity of the reinforcement and enriches the properties of the composite. However, it reduces the modulus value of the composites due to the high crimp in the fiber yarn in the warp and weft directions. In addition, various chemical and physical surface treatments were reviewed, and it was shown that they increase the interfacial bonding between fiber and matrix. Further, the hybridization of natural fiber with synthetic fiber, cellulosic fiber, and various fillers was reviewed.Furthermore, sophisticated weaving techniques such as braiding and knitting were reviewed, with the conclusion that braided composites significantly improve the characteristics of the composite material.Knitted composites, on the other hand, improve the energy dissipation capabilities of the composite materials, implying that braided fabric composites could be used in biological and structural applications.In future, natural fiber-reinforced composites should be further studied for their fatigue properties and biocompatible properties for possible considerations in biomedical fields such as orthopedic bone plates, total hip replacement, and prosthesis applications.


A timely and efficient seed germination is critical for plantlets’ establishment and robustness as well as plant development and plant performance in both natural ecosystems and agrosystems. Therefore, the go/no-go decision for a seed to germinate is tightly controlled by a variety of endogenous and environmental signals perceived and integrated during seed imbibition or accumulated during the later stages of seed development. In particular, the initial switch from a non-germinating to a germinating state includes the release of dormancy, an inhibitory process established during seed maturation. Nevertheless, this switch can be reversed and dormancy reactivated (dormancy cycling) as long as environmental conditions are uncertain for proper seedling growth. In this scheme, environmental factors, e.g., temperature or water availability, appear central to triggering or restricting germination, and ongoing global warming will dramatically affect germination efficiency, and thereby species spreading, growth and final yield. Ahead of this major challenge for sustainable agriculture, the development of efficient strategies to mitigate the effects of climate change on the phenology of seeds is urgent and crucial.To meet this challenge, it is essential to gain more understanding of the different levels of the regulation of seed germination and their spatiotemporal interplays, as well as their conservation in crops and non-model species. Indeed, recent major breakthroughs have significantly broadened our understanding of how germination is controlled. On the one hand, important advances on the molecular regulation of key actors have been achieved, as exemplified for DELAY OF GERMINATION-1 (DOG1), the most popular regulator of dormancy ,3. FinalThis Special Issue gathers together eight articles (four research and four review articles) that question various facets of the regulation of seed development, seed dormancy and germination, which eventually impact seed capacity to germinate.Hormonal metabolism and signaling are at the heart of the regulation of seed germination and, furthermore, control seed development, dormancy, vigor and longevity. Although these traits are regulated through complex interplays of many hormonal pathways, abscisic acid (ABA) and gibberellins (GA) remain the most important regulators and the balance between ABA and GA, the universal lever for the control of germination. In the present Issue, Sano and Marion-Poll  provide Arabidopsis thaliana Trx-y1 and y2, two y-type plastidial thioredoxins that exhibit antioxidant capacity. They report that trx-y1 and y2 mutations improve important seed traits, e.g., longevity or germination efficiency under water stress. Unexpectedly, no difference in seed reactive oxygen species (ROS) homeostasis is observed in mutant seeds and the authors propose that Trx-y participate in redox signaling rather than in ROS detoxification. Moreover, trx-y mutations impact the transcriptional regulation of abscisic acid (ABA) and gibberellin (GA) metabolisms. As redox-based signaling is central for seed dormancy release and germination [In the recent years, important efforts have been dedicated to the identification of new genes/proteins involved in specific aspects of seed capacity to germinate and the unravelling of their function. In this light, Née et al.  investigmination , furtherhira seeds exhibit a range of defects in relation to germination capacity. This study therefore establishes histone variant exchange as a new mechanism to regulate germination via the modification chromatin structure.The transitions from developing to dry mature and, eventually, to germinating seeds are accompanied by important changes in nuclear and chromatin organization, which reflect modifications in the global transcriptional activity, but also the necessary protection of genetic material during seed desiccation. The dynamics of DNA packaging are strongly dependent on the post-translational modifications (PTM) of histones and, possibly, the exchange between different histone variants. Consequences of histone PTM on seed dormancy and germination have been established but the dynamics and involvement of specific histone variants in this process are currently poorly documented. The study carried out by Layat et al.  providesThe specific functions of the different seed tissues, as well as their functional interactions, have been paid increasing attention and bridge seed development and seed germination processes over space and time . These iRecent studies have proven that mRNA metabolism is at the heart of the regulation of seed germination . Indeed,Although progresses in our understanding of the molecular mechanisms involved in germination control essentially come from the study of a handful of model plants and crops, the diversity of structure, germination behavior and responses to environmental signals of seeds among species requires broader studies, in particular towards wild and alternatively cultivated species. Indeed these plants represent unique opportunities to identify evolutionary-conserved regulatory networks and to investigate specific seed traits. In this Special Issue, a research paper by Pawłowski et al.  and a reThe studies compiled in this Special Issue further illustrate that the control of germination integrates diverse levels of regulation, including chromatin organization, gene transcription, mRNA translation and protein post-translational modification resulting in a fine-tuned regulation of the seed metabolism. A major challenge is now to gather these fragmented pieces of information into a holistic and dynamic model integrating the different seed tissues and the regulation by endogenous and environmental cues.