摘要：With the evolution of nanomedicine,the past de-cades witnessed diversified nanomaterials as marvelous anti-tumor tools ushering in a new era of tumor diagnosis and treatment.Among them,two-dimensional layered nano-material as an emerging class of nanomaterials has one dimension less than 100 nm,showing a high specific area and the thinnest sheet-like structure(Liu S,Pan X,Liu H.Twodi-mensional nanomaterials for photothermal therapy.Angew Chem Int Ed 2020;59:5890-900).The discovery of graphene drove the exploration of various new two-dimensional layered nanomaterials for tumor diagnosis and treatment including graphene-based nanomaterials,black phosphorus(BP),transition metal dichalcogenides(TMDs),layered double hydroxides(LDHs),and bismuth oxyhalides(BiOX,X=F,CL Br,I)(Ma H,Xue MQ.Recent advances in the photothermal applications of two-dimensional nanomaterial:photothermal therapy and beyond.J Mater Chem 2021;9:17569).On the one hand,they exhibit strong near-infrared(NIR)absorption and the capacity of optimizing corresponding properties by adjusting the crystal structure.On the other hand,they own unique strengths such as fantastic physicochemical proper-ties(graphene-based nanomaterials),high loading capacity(BP),distinct phase-dependent optical properties(TMDs),a specific chemical response to the tumor microenvironment(LDHs),and large X-ray attenuation coefficient(BiOX).Herein,we briefly introduce three typical two-dimensional layered nanomaterials,their prospects and future research priorities in tumor diagnosis and treatment are concluded.

摘要：Our oral cavity houses various types of microbes including bacteria,protozoa,fungi and viruses,harboring over 700 bacterial species.Oral dysbiosis refers to the imbalance between symbionts and pathobionts in the oral cavity,posing potential threats to host cardiovascular health.Importantly,oral dysbiosis promotes cardiovas-cular pathophysiology through different mechanisms.Although overgrowth of certain pathogenic bacteria have been indicated in some cardiometabolic diseases,it is still premature to consider oral microbiome as a suitable pre-dictor for non-invasive diagnostic purpose.However,tar-geting oral microbiome might still provide preventive and therapeutic insights on cardiovascular diseases.Further extensive efforts are needed to deepen our understanding on oral-cardiovascular connection in the context of diag-nostic and therapeutic perspectives.

摘要：Gastric cancer(GC)is one of the commonest cancers with high morbidity and mortality in the world.How to realize precise diagnosis and therapy of GC owns great clinical requirement.In recent years,artificial intel-ligence(AI)has been actively explored to apply to early diagnosis and treatment and prognosis of gastric carci-noma.Herein,we review recent advance of AI in early screening,diagnosis,therapy and prognosis of stomach carcinoma.Especially AI combined with breath screening early GC system improved 97.4％of early GC diagnosis ratio,AI model on stomach cancer diagnosis system of saliva biomarkers obtained an overall accuracy of 97.18％,speci-ficity of 97.44％,and sensitivity of 96.88％.We also discuss concept,issues,approaches and challenges of AI applied in stomach cancer.This review provides a comprehensive view and roadmap for readers working in this field,with the aim of pushing application of AI in theranostics of stomach cancer to increase the early discovery ratio and curative ratio of GC patients.

摘要：Proteins function as integral actors in essential life processes,rendering the realm of protein research a fundamental domain that possesses the potential to propel advancements in pharmaceuticals and disease investiga-tion.Within the context of protein research,an imperious demand arises to uncover protein functionalities and untan-gle intricate mechanistic underpinnings.Due to the exorbi-tant costs and limited throughput inherent in experimental investigations,computational models offer a promising alter-native to accelerate protein function annotation.In recent years,protein pre-training models have exhibited note-worthy advancement across multiple prediction tasks.This advancement highlights a notable prospect for effectively tackling the intricate downstream task associated with protein function prediction.In this review,we elucidate the historical evolution and research paradigms of computational methods for predicting protein function.Subsequently,we summarize the progress in protein and molecule represen-tation as well as feature extraction techniques.Furthermore,we assess the performance of machine learning-based algorithms across various objectives in protein function prediction,thereby offering a comprehensive perspective on the progress within this field.

摘要：The kidneys are susceptible to a range of insults that can cause damage to them.Early diagnosis,timely prevention,and proper treatment are crucial for improving the outcome of kidney injury.However,the complexity of renal structure and function makes it difficult to reach the demand of early detection and comprehensive evaluation of kidney injury.No successful drug therapy caused by the elaborate pathogenesis mechanism network of kidney injury calls for a systematical interpretation in mechanism researches.Recent advances in renal imaging and omics studies have provided novel views and deeper insights into kidney injury,but also raise challenges in reaching a comprehensive cellular and molecular atlas of kidney injury.Progresses in imaging and omics of kidney injury are being made in various directions,with the initiative of construction a high-resolution structural atlas of kid-ney,dynamic and non-invasive evaluation of renal func-tion,and systematic establishment of spatially resolved molecular atlas by transcriptomics and metabolomics.With the limitations of a single modality,novel multi-modal integration technologies of imaging and omics are being attempted to achieve a systematic description of nephropathy mechanisms.Further extensive efforts in renal multimodal imaging and omics studies are extremely required to deepen our understanding on kidney injury in the context of diagnostic,mechanistic and therapeutic perspectives.

摘要：Considering the main factor that causes or trig-gers depression in humans is stress.Several stress factors are applied to form depression-like symptoms in rodents.Depression tests are used to analyze the nature and patterns of depression.Well-founded modeling and versatile evalu-ation of tests are necessary to investigate a hypothesis that is related to depression.It is impossible to model or test all aspects of depression in humans by using experimental animals.As a result,the aims of the study should be determined specifically in depression models.The correct interpretation of the tests that are suitable for these aims is indispensable for the reliability of the data.To achieve this goal,the biological basis of the depression-related behaviors of animals should be well known.In this review,model and test concepts related to depression are discussed and behavioral patterns of rodents are explained with several examples.

摘要：Pluripotent stem cells(PSCs),characterized by self-renewal and capacity of differentiating into three germ layers,are the programmable building blocks of life.PSC-derived cells and multicellular systems,particularly organoids,exhibit great potential for regenerative medicine.However,this field is still in its infancy,partly due to limited strategies to robustly and precisely control stem cell behaviors,which are tightly regulated by inner gene regu-latory networks in response to stimuli from the extracellular environment.Synthetic receptors and genetic circuits are powerful tools to customize the cellular sense-and-response process,suggesting their underlying roles in precise control of cell fate decision and function reconstruction.Herein,we review the progress and challenges needed to be overcome in the fields of PSC-based cell therapy and multicellular system generation,respectively.Furthermore,we summa-rize several well-established synthetic biology tools and their applications in PSC engineering.Finally,we highlight the challenges and perspectives of harnessing synthetic biology to PSC engineering for regenerative medicine.

摘要：From the approval of COVID-19 mRNA vaccines to the 2023 Nobel Prize awarded for nucleoside base modifi-cations,RNA therapeutics have entered the spotlight and are transforming drug development.While the term"RNA therapeutics"has been used in various contexts,this review focuses on treatments that utilize RNA as a component or target RNA for therapeutic effects.We summarize the latest advances in RNA-targeting tools and RNA-based technolo-gies,including but not limited to mRNA,antisense oligos,siRNAs,small molecules and RNA editors.We focus on the mechanisms of current FDA-approved therapeutics but also provide a discussion on the upcoming workforces.The clinical utility of RNA-based therapeutics is enabled not only by the advances in RNA technologies but in conjunction with the significant improvements in chemical modifications and delivery platforms,which are also briefly discussed in the review.We summarize the latest RNA therapeutics based on their mechanisms and therapeutic effects,which include expressing proteins for vaccination and protein replace-ment therapies,degrading deleterious RNA,modulating transcription and translation efficiency,targeting noncoding RNAs,binding and modulating protein activity and editing RNA sequences and modifications.This review emphasizes the concept of an RNA therapeutic toolbox,pinpointing the readers to all the tools available for their desired research and clinical goals.As the field advances,the catalog of RNA therapeutic tools continues to grow,further allowing re-searchers to combine appropriate RNA technologies with suitable chemical modifications and delivery platforms to develop therapeutics tailored to their specific clinical challenges.

摘要：Bile acids are recognized as important signaling molecules that enable fine-tuned inter-communication from the liver,through the intestine,to virtually any organ,thus encouraging their pleiotropic physiological effects.Aging is a complex natural process defined as a progressive decline in cellular and organismal functions.A causal link between bile acids and the aging process is emerging.However,there are gaps in our understanding of the molecular mechanisms and precise targets responsible for the alteration of bile acid pro-files and their role in the aging process.Intestinal barrier dysfunction leads to endotoxemia,systemic inflammation,insulin resistance,diabetes,lipid accumulation,obesity and fatty liver diseases,and health decline and death.In fact,in-testinal barrier dysfunction is suggested to be an evolution-arily conserved hallmark of aging.Bile acids may modulate the aging process by regulating intestinal barrier integrity.

摘要：Metabolic dysfunction-associated fatty liver dis-ease(MAFLD)has reached epidemic proportions globally in parallel to the rising prevalence of obesity.Despite its signif-icant burden,there is no approved pharmacotherapy specif-ically tailored for this disease.Many potential drug candidates for MAFLD have encountered setbacks in clinical trials,due to safety concerns or/and insufficient therapeutic efficacy.Nonetheless,several investigational drugs that mimic the actions of endogenous metabolic hormones,including thyroid hormone receptor β(THRβ)agonists,fibroblast growth factor 21(FGF21)analogues,and glucagon-like peptide-1 receptor agonists(GLP-1RAs),showed promising therapeutic efficacy and excellent safety profiles.Among them,resmetirom,a liver-targeted THRβ-selective agonist,has met the primary outcomes in alleviation of metabolic dysfunction-associated steatohepatitis(MASH),the advanced form of MAFLD,and liver fibrosis in phase-3 clinical trials.These hormone-based pharmacotherapies not only exhibit varied degrees of thera-peutic efficacy in mitigating hepatic steatosis,inflammation and fibrosis,but also improve metabolic profiles.Further-more,these three hormonal agonists/analogues act in a complementary manner to exert their pharmacological effects,suggesting their combined therapies may yield synergistic therapeutic benefits.Further in-depth studies on the intricate interplay among these metabolic hormones are imperative for the development of more efficacious combination therapies,enabling precision management of MAFLD and its associated comorbidities.

摘要：To the editor:Since the onset of COVID-19,several new treatments have been studied,but only a few have received approval for clinical use.However,a challenge we still face is that in real-world medical practice,the patient population may differ from those in clinical trials.For instance,pro-longed viral elimination has become an issue in immuno-compromised patients[1,2].

摘要：As a key sensor of double-stranded DNA(dsDNA),cyclic GMP-AMP synthase(cGAS)detects cytosolic dsDNA and initiates the synthesis of 2'3'cyclic GMP-AMP(cGAMP)that activates the stimulator of interferon genes(STING).This finally promotes the production of type Ⅰ interferons(IFN-Ⅰ)that is crucial for bridging innate and adaptive im-munity.Recent evidence show that several antitumor ther-apies,including radiotherapy(RT),chemotherapy,targeted therapies and immunotherapies,activate the cGAS-STING pathway to provoke the antitumor immunity.In the last decade,the development of STING agonists has been a major focus in both basic research and the pharmaceutical in-dustry.However,up to now,none of STING agonists have been approved for clinical use.Considering the broad expression of STING in whole body and the direct lethal effect of STING agonists on immune cells in the draining lymph node(dLN),research on the optimal way to activate STING in tumor microenvironment(TME)appears to be a promising direction.Moreover,besides enhancing IFN-Ⅰsignaling,the cGAS-STING pathway also plays roles in senescence,autophagy,apoptosis,mitotic arrest,and DNA repair,contributing to tumor development and metastasis.In this review,we summarize the recent advances on cGAS-STING pathway's response to antitumor therapies and the strategies involving this pathway for tumor treatment.

摘要：Mammalian lung development starts from a spe-cific cluster of endodermal cells situated within the ventral foregut region.With the orchestrating of delicate choreog-raphy of transcription factors,signaling pathways,and cell-cell communications,the endodermal diverticulum extends into the surrounding mesenchyme,and builds the cellular and structural basis of the complex respiratory system.This review provides a comprehensive overview of the current molecular insights of mammalian lung devel-opment,with a particular focus on the early stage of lung cell fate differentiation and spatial patterning.Furthermore,we explore the implications of several congenital respiratory diseases and the relevance to early organogenesis.Finally,we summarize the unprecedented knowledge concerning lung cell compositions,regulatory networks as well as the promising prospect for gaining an unbiased understanding of lung development and lung malformations through state-of-the-art single-cell omics.

摘要：The protein,N-myc downstream-regulated gene 2(NDRG2),a tumor suppressor,is significantly decreased or absent in many types of cancer.There is a significant nega-tive correlation between the levels of NDRG2 and the development and progression of cancer tumor recurrence and tumor invasion,in different cancers.In contrast,the in vitro and in vivo overexpression of the NDRG2 protein decreases the proliferation,growth,adhesion and migration of many types of cancer cells.The in vitro overexpression of NDRG2 increases the efficacy of certain anticancer drugs in specific types of cancer cells.We hypothesize that the delivery of the mRNA of the NDRG2 protein,encapsulated by lipid nanoparticles,could represent a potential treatment of metastatic and drug-resistant cancers.This would be accomplished using a self-amplifying mRNA that encodes the NDRG2 protein and an RNA-dependent-RNA polymerase,obtained from an in vitrotranscribed(IVT)mRNA.The 1VT mRNA would be encapsulated in a lipid nanoformulation.The efficacy of the nanoformulation would be determined in cultured cancer cells and if the results are positive,nude mice transplanted with either drug-resistant or metastatic drug-resistant cancer cells,would be treated with the nano-formulation and monitored for efficacy and adverse effects.If the appropriate preclinical studies indicate this formula-tion is efficacious and safe,it is possible it could be evaluated in clinical trials.

摘要：Investigating the fine structure of mitochondria and their dynamic interactions with other organelles is crucial for unraveling the mechanisms underlying mitochondrial-related diseases.The development of super-resolution techniqpies has provided powerful visualization tools for mitochondrial research,which is significant for investigating mitochondrial cristae structure,the localization of mitochondrial-related protein complex,and the interactions between mitochondria and other organelles.In this perspective,we introduce several advanced super-resolution techniques and their applications in mitochondrial research,and discuss the potential roles these techniques may play in future studies of mitochondria.

摘要：Objectives:The majority of esophageal squamous dysplasia(ESD)patients progress slowly,while a subset of patients can undergo recurrence rapidly or progress to invasive cancer even after proper treatment.However,the molecular mechanisms underlying these clinical observations are still largely unknown. Methods:By sequencing the genomic data of 160 clinical samples from 49 tumor-free ESD patients and 88 esophageal squamous cell carcinoma(ESCC)patients,we demonstrated lower somatic mutation and copy number alteration(CNA)burden in ESD compared with ESCC. Results:Cross-species screening and functional assays identified ACSM5 as a novel driver gene for ESD progression.Furthermore,we revealed that miR-4292 promoted ESD progression and could serve as a non-invasive diagnostic marker for ESD. Conclusions:These findings largely expanded our under-standing of ESD genetics and tumorigenesis,which possessed promising significance for improving early diagnosis,reducing overtreatment,and identifying high-risk ESD patients.

摘要：Metabolic health is highly dependent on intestinal and hepatic handling of dietary and endogenous lipids and lipoproteins.Disorders of lipid and lipoprotein metabolism are commonly observed in patients with insulin resistant states such as obesity,metabolic syndrome,and type 2 diabetes.Ev-idence from both animal models and human studies indicates that a major underlying factor in metabolic or diabetic dysli-pidemia is the overproduction of hepatic and intestinal apoli-poprotein(apo)B-containing lipoprotein particles.These particles are catabolized down into highly proatherogenic remnants,which can be taken up into the arterial intima and promote plaque development.Several gut-derived peptides have been identified as key regulators of energy metabolism;one such peptide is the incretin hormone glucagon-like peptide(GLP)-1.Our laboratory has previously demonstrated that GLP-1 can signal both centrally and peripherally to reduce postprandial and fasting lipoprotein secretion.Moreover,we have demonstrated that GLP-1 receptor(GLP-1R)agonists can ameliorate diet-induced dyslipidemia.Recently,we published evidence for a novel vagal neuroendocrine signalling pathway by which native GLP-1 may exert its anti-lipemic effects.Furthermore,we demonstrated a novel role for other gut-derived peptides in regulating intestinal lipoprotein produc-tion.Overall,ample evidence supports a key role for GLP-1R on the portal vein afferent neurons and nodose ganglion in modulating intestinal fat absorption and lipoprotein produc-tion and identifies other gut-derived peptides as novel regula-tors of postprandial lipemia.Insights from these data may support identification of potential drug targets and the development of new therapeutics targeting treatment of dia-betic dyslipidemia.

摘要：Fibrosis resulting from pathological repair sec-ondary to recurrent or persistent tissue damage often leads to organ failure and mortality.Biliary fibrosis is a crucial but easily neglected pathological feature in hepatobiliary disorders,which may promote the development and pro-gression of benign and malignant biliary diseases through pathological healing mechanisms secondary to biliary tract injuries.Elucidating the etiology and pathogenesis of biliary fibrosis is beneficial to the prevention and treatment of biliary diseases.In this review,we emphasized the impor-tance of biliary fibrosis in cholangiopathies and summarized the clinical manifestations,epidemiology,and aberrant cellular composition involving the biliary ductules,chol-angiocytes,immune system,fibroblasts,and the micro-biome.We also focused on pivotal signaling pathways and offered insights into ongoing clinical trials and proposing a strategic approach for managing biliary fibrosis-related cholangiopathies.This review will offer a comprehensive perspective on biliary fibrosis and provide an important reference for future mechanism research and innovative therapy to prevent or reverse fibrosis.

摘要：COVID-19 posed a major challenge to the healthcare system and resources worldwide.The popularization of vaccines and the adoption of numerous prevention and control measures enabled the gradual end of the COVID-19 pandemic.However,successive occurrence of autoimmune diseases in patients with COVID-19 cannot be overlooked.Long COVID has been the major focus of research due to the long duration of different symptoms and the variety of systems involved.Autoimmunity may play a crucial role in the pathogenesis of long COVID.Here,we reviewed several autoimmune disorders occurring after COVID-19 infection and the pathogenesis of long COVID.

摘要：Lung transplantation is the only definitive ther-apy for end-stage pulmonary disease.Less than 20％of offered lungs are successfully transplanted due to a limited ischemic time window and poor donor lung quality man-ifested by pulmonary edema,hypoxia,or trauma.Therefore,poor donor organ recovery and utilization are significant barriers to wider implementation of the life-saving therapy of transplantation.While ischemia reperfusion injury(IRI)is often identified as the underlying molecular insult leading to immediate poor lung function in the post-operative period,this injury encompasses several pathways of cellular injury in addition to the recruitment of the innate immune system to the site of injury to propagate this inflammatory cascade.Pyroptosis is a central molecular inflammatory pathway that is the most significant contributor to injury in this early post-operative phase.Pyroptosis is another form of pro-grammed cell death and is often associated with IRI.The mitigation of pyroptosis in the early post-operative period following lung transplantation is a potential novel way to prevent poor allograft function and improve outcomes for all recipients.Here we detail the pyroptotic pathway,its importance in lung transplantation,and several therapeutic modalities that can mitigate this harmful inflammatory pathway.