摘要：The visual system remains highly malleable even after its maturity or impairment.Our visual function can be enhanced through many ways,such as transcranial electrical stimulation(tES)and visual perceptual learning(VPL).TES can change visual function rapidly,but its modulation effect is short-lived and unstable.By contrast,VPL can lead to a substantial and long-lasting improvement in visual function,but extensive training is typically required.Theoretically,visual function could be further improved in a shorter time frame by combining tES and VPL than by solely using tES or VPL.Vision enhancement by combining these two methods concurrently is both theoretically and practically significant.In this review,we firstly introduced the basic concept and possible mechanisms of VPL and tES;then we reviewed the current research progress of visual enhancement using the combination of two methods in both general and clinical population;finally,we discussed the limitations and future directions in this field.Our review provides a guide for future research and application of vision enhancement and resto-ration by combining VPL and tES.

摘要：Cancer is a fetal and complex disease.Individual differences of the same cancer type or the same patient at different stages of cancer development may require distinct treatments.Pathological differences are reflected in tis-sues,cells and gene levels etc.The interactions between the cancer cells and nearby microenvironments can also influence the cancer progression and metastasis.It is a huge challenge to understand all of these mechanistically and quantitatively.Researchers applied pattern recogni-tion algorithms such as machine learning or data mining to predict cancer types or classifications.With the rapidly growing and available computing powers,researchers begin to integrate huge data sets,multi-dimensional data types and information.The cells are controlled by the gene expressions determined by the promoter sequences and transcription regulators.For example,the changes in the gene expression through these underlying mechanisms can modify cell progressing in the cell-cycle.Such molec-ular activities can be governed by the gene regulations through the underlying gene regulatory networks,which are essential for cancer study when the information and gene regulations are clear and available.In this review,we briefly introduce several machine learning methods of cancer prediction and classification which include Artificial Neural Networks(ANNs),Decision Trees(DTs),Support Vector Machine(SVM)and naive Bayes.Then we describe a few typical models for building up gene regu-latory networks such as Correlation,Regression and Bayes methods based on available data.These methods can help on cancer diagnosis such as susceptibility,recurrence,survival etc.At last,we summarize and compare the modeling methods to analyze the development and pro-gression of cancer through gene regulatory networks.These models can provide possible physical strategies to analyze cancer progression in a systematic and quantita-tive way.

摘要：Bone has long been considered as a silent organ that provides a reservoir of calcium and phosphorus,traditionally.Recently,further study of bone has revealed additional functions as an endocrine organ connecting systemic organs of the whole body.Communication between bone and other organs participates in most physiological and pathological events and is responsible for the maintenance of homeostasis.Here,we present an overview of the crosstalk between bone and other organs.Furthermore,we describe the factors mediating the cross-talk and review the mechanisms in the development of potential associated diseases.These connections shed new light on the pathogenesis of systemic diseases and provide novel potential targets for the treatment of systemic diseases.

摘要：At least 78 million people worldwide are affected by autism,a neurodevelopmental disorder characterized by deficits in social interactions,and repetitive behaviors and/or interests.Autism typically manifests in early child-hood,and affects social communications and behaviors throughout the lifespan of the individual.Under the umbrella of autism spectrum disorder,it is a highly het-erogeneous disorder,with some individuals profoundly affected and needing care every day,while others can live highly independent lives,with some adjustments.The past 60 years has seen a major influx of interest in autism,and significant advances in many areas.However,a large gap remains between current scientific knowledge and the help and support that people with autism and their families need.To address these concerns,the Lancet commissioned a report on the"future of care and clinical research in autism".The Commission calls for government coordina-tion between health-care,education and social sectors,as well as active participation from people with autism and their families.The Commission proposes personalized,evidence-based assessments and intervention,that is accessible and affordable to all,and call for increased appreciation of neurodiversity and prioritization of research that can improve the lives of people with autism and their families.How to support each and every autistic individual and their families is highly challenging.The 64-page Lancet Commission Report,published on December 2021,was written jointly by 32 authors from 6 continents and 13 disciplines,including clinicians,other health-care pro-viders,researchers,advocates,autistic individuals and their parents.

摘要：Neural networks are groups of interconnected neurons,which collectively give rise to emergent neural activities and functions that cannot be explained by the activity of single neurons.How neural networks are assembled is poorly understood.While all aspects of neuronal development are essential for the assembly of a functional neural network,we know little about high-level principles that govern neural network assembly beyond the basic steps of neuronal development.In this review,I use vertebrate spinal motor columns,Drosophila larval motor circuit,and the lamination in the vertebrate inner retina to highlight the spatial codes,temporal codes,and cell adhe-sion codes for neural network assembly.Nevertheless,these examples only show preliminary connections between neural network development and their functions.Much needs to be done to understand the molecular mechanisms that underlie the assembly of functional neural networks.

摘要：Alzheimer's disease and related dementias(AD/ADRD)affects more than 50 million people worldwide but there is no clear therapeutic option affordable for the general patient population.Recently,drug repositioning studies featuring collaborations between academic in-stitutes,medical centers,and hospitals are generating novel therapeutics candidates against these devastating diseases and filling in an important area for healthcare that is poorly represented by pharmaceutical companies.Such drug repositioning studies converge expertise from bioinformat-ics,chemical informatics,medical informatics,artificial in-telligence,high throughput and high-content screening and systems biology.They also take advantage of multi-scale,multi-modality datasets,ranging from transcriptomic and proteomic data,electronical medical records,and medical imaging to social media information of patient behaviors and emotions and epidemiology profiles of disease pop-ulations,in order to gain comprehensive understanding of disease mechanisms and drug effects.We proposed a recursive drug repositioning paradigm involving the itera-tion of three processing steps of modeling,prediction,and validation to identify known drugs and bioactive com-pounds for AD/ADRD.This recursive paradigm has the po-tential of quickly obtaining a panel of robust novel drug candidates for AD/ADRD and gaining in-depth under-standing of disease mechanisms from those repositioned drug candidates,subsequently improving the success rate of predicting novel hits.

摘要：With the presence of Coronavirus Disease 2019(COVID-19)asymptomatic infections detected,their pro-portion,transmission potential,and other aspects such as immunity and related emerging challenges have attracted people's attention.We have found that based on high-quality research,asymptomatic infections account for at least one-third of the total cases,whereas based on sys-tematic review and meta-analysis,the proportion is about one-fifth.Evaluating the true transmission potential of asymptomatic cases is difficult but critical,since it may affect national policies in response to COVID-19.We have summarized the current evidence and found,compared with symptomatic cases,the transmission capacity of asymptomatic individuals is weaker,even though they have similar viral load and relatively short virus shedding duration.As the outbreak progresses,asymptomatic in-fections have also been found to develop long COVID-19.In addition,the role of asymptomatic infection in COVID-19 remains to be further revealed as the severe acute respi-ratory syndrome coronavirus 2(SARS-CoV-2)variants continue to emerge.Nevertheless,as asymptomatic in-fections transmit the SARS-CoV-2 virus silently,they still pose a substantial threat to public health.Therefore,it is essential to conduct screening to obtain more knowledge about the asymptomatic infections and to detect them as soon as possible;meanwhile,management of them is also a key point in the fight against COVID-19 community transmission.The different management of asymptomatic infections in various countries are compared and the expe-rience in China is displayed in detail.

摘要：Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused hundreds of millions of in-fections and millions of deaths over past two years.Currently,many countries have still not been able to take the pandemic under control.In this review,we systemat-ically summarized what we have done to mitigate the COVID-19 pandemic,from the perspectives of virus trans-mission,public health control measures,to the develop-ment and vaccination of COVID-19 vaccines.As a virus most likely coming from bats,the SARS-CoV-2 may trans-mit among people via airborne,faecal-oral,vertical or foodborne routes.Our meta-analysis suggested that the Ro of COVID-19 was 2.9(95％CI:2.7-3.1),and the estimates in Africa and Europe could be higher.The median Rt could decrease by 23-96％following the nonpharmacological interventions,including lockdown,isolation,social dis-tance,and face mask,etc.Comprehensive intervention and lockdown were the most effective measures to control the pandemic.According to the pooled R0 in our meta-analysis,there should be at least 93.3％(95％CI:89.9-96.2％)people being vaccinated around the world.Limited amount of vaccines and the inequity issues in vaccine allocation call for more international cooperation to achieve the anti-epidemic goals and vaccination fairness.

摘要：Natural killer(NK)cells possess innate abilities to effectively eliminate cancer cells.However,because of difficulties of proliferation and easy to be induced dysfunc-tion in the setting of cancer post NK cell therapy,the curative effect of NK cell infusion has been constrained and not been widely applicable in clinical practice.The rapid development of biotechnology has promoted the development of NK cell therapy for cancer treatment.In this review,we will provide a comprehensive analysis of the current status and future prospects of NK cell therapy for cancer,focusing on the biological characteristics of NK cells,as well as strategies to enhance their targeting capabilities and overcome tumor immune suppression within the microenvironment.

摘要：Introduction The pursuit of optimal health and longevity is a long-standing human aspiration [1, 2]. Advances in public health policies and population medicine have significantly extended life expectancy, which has tripled from 20-30 years a century and a half ago.

摘要：Boron neutron capture therapy(BNCT)is a potential radiation therapy modality for cancer,and tumor-targeted stable boron-10(10B)delivery agents are an important component of BNCT.Currently,two low-molecular-weight boron-containing compounds,sodium mercaptoundecahydro-closo-dodecaborate(BSH)and boronophenylalanine(BPA),are mainly used in BNCT.Although both have suboptimal tu-mor selectivity,they have shown some therapeutic benefit in patients with high-grade glioma and several other tumors.To improve the efficacy of BNCT,great efforts have been devoted for the development of new boron delivery agents with better uptake and favorable pharmacokinetic profiles.This article reviews the application and research progress of boron nano-materials as boron carriers in boron neutron capture therapy and hopes to stimulate people's interest in nanomaterial-based delivery agents by summarizing various kinds of boron nanomaterial patents disclosed in the past decade.

摘要：Iron oxide(IO)nanoparticles(NPs)have gained significant attention in the field of biomedicine,particularly in drug targeting and cancer therapy.Their potential in magnetic drug targeting(MDT)and ferroptosis-based cancer therapy is highly promising.IO NPs serve as an effective drug delivery system(DDS),utilizing external magnetic fields(EMFs)to target cancer cells while minimizing damage to healthy organs.Additionally,IO NPs can generate reactive oxygen species(ROS)and induce ferroptosis,resulting in cytotoxic effects on cancer cells.This article explores how IO NPs can potentially revolutionize cancer research,focusing on their applications in MDT and ferroptosis-based therapy.

摘要：Systemic lupus erythematosus(SLE)is a complex autoimmune disease.Current SLE therapies include immunosuppressants,antimalarial drugs,non-steroidal anti-inflammatory drugs(NSAIDs),and corticosteroids,but these treatments can cause substantial toxicities to organs and may not be effective for all patients.In recent years,significant progress has been made in the treatment of SLE using immunotherapy,including Benlysta and Saphnelo.These advances in immunotherapy hold promise for SLE patients,providing new therapeutic options that may offer better clinical benefit and effectiveness.Simul-taneously,several new biological therapies focusing on cytokines,peptides,targeted antibodies,and cell-based approaches are under clinical evaluation and have shown immense potential for the treatment of SLE.However,the complexity of SLE immunopathogenesis and disease het-erogeneity present significant challenges in the develop-ment of effective immunological therapies.This review aims to discuss past experiences and understanding of diverse immunological targeting therapies for SLE and highlight future perspectives for the development of novel immunological therapies.

摘要：The complexity of the tumor microenvironment(TME)severely hinders the therapeutic effects of various cancer treatment modalities.The TME differs from normal tissues owing to the presence of hypoxia,lowpH,and immune-suppressive characteristics.Modulation of the TME to reverse tumor growth equilibrium is considered an effective way to treat tumors.Recently,polymeric nanomedicines have been widely used in cancer therapy,because their synthesis can be controlled and they are highly modifiable,and have demon-strated great potential to remodel the TME.In this review,we outline the application of various stimuli responsive polymeric nanomedicines to modulate the TME,aiming to provide in-sights for the design of the next generation of polymeric nanomedicines and promote the development of polymeric nanomedicines for cancer therapy.

摘要：Microbubbles have been the earliest and most widely used ultrasound contrast agents by virtue of their unique features:such as non-toxicity,intravenous inject-ability,ability to cross the pulmonary capillary bed,and significant enhancement of echo signals for the duration of the examination,resulting in essential preclinical and clinical applications.The use of microbubbles functional-ized with targeting ligands to bind to specific targets in the bloodstream has further enabled ultrasound molecular imaging.Nevertheless,it is very challenging to utilize targeted microbubbles for molecular imaging of extra-vascular targets due to their size.A series of acoustic nanomaterials have been developed for breaking free from this constraint.Especially,biogenic gas vesicles,gas-filled protein nanostructures from microorganisms,were engineered as the first biomolecular ultrasound contrast agents,opening the door for more direct visual-ization of cellular and molecular function by ultrasound imaging.The ordered protein shell structure and unique gas filling mechanism of biogenic gas vesicles endow them with excellent stability and attractive acoustic responses.What's more,their genetic encodability enables them to act as acoustic reporter genes.This article reviews the upgrading progresses of ultrasound contrast agents from microbubbles to biogenic gas vesicles,and the opportu-nities and challenges for the commercial and clinical translation of the nascent field of biomolecular ultrasound.

摘要：Single-nucleotide variants account for about half of known pathogenic genetic variants in human.Genome editing strategies by reversing pathogenic point mutations with minimum side effects have great therapeutic potential and are now being actively pursued.The emerge of precise and efficient genome editing strategies such as base editing and prime editing provide powerful tools for nucleotide conversion without inducing double-stranded DNA breaks(DSBs),which have shown great potential for curing genetic disorders.A diverse toolkit of base editors has been devel-oped to improve the editing efficiency and accuracy in different context of application.Here,we summarized the evolving of base editors(BEs),their limitations and future perspective of base editing-based therapeutic strategies.

摘要：The central circadian clock in the brain controls the time-of-the-day variations in acute meal responses,with a low glycemic response but a high satiety/thermo-genic response to meals consumed at waking compared to other time points.Consistently,studies show that consuming a significant proportion of calories,particularly carbohydrates,in breakfast is beneficial for the chronic management of obesity and its associated metabolic syndrome,compared to consuming identical meals at dinner.Conversely,breakfast skipping or/and late dinner can have unfavorable metabolic outcomes.It remains controversial how meal frequency affects metabolic health.In contrast,irregular meals,especially irregular breakfasts,show consistent adverse metabolic consequences.Time-restricted feeding(TRF),with all calories consumed within less than 12-h per day,can improve metabolism and extend lifespan.A major component of TRF in humans is caloric restriction,which contributes significantly to the beneficial effects of TRF in humans.By comparison,TRF effects in rodents can be independent of caloric restriction and show day/night phase specificity.TRF could alleviate metabolic abnormalities due to circadian disruption,but its effects appear independent of the circadian clock in rodents.Understanding neuroendocrine mechanisms underlying clock-mediated metabolic regulation will shed light on the metabolic effects of temporal meal patterns.

摘要：Macrophage polarization is an essential process involved in immune regulation.In response to different microenvironmental stimulation,macrophages polarize into cells with different phenotypes and functions,most typically M1(pro-inflammatory)and M2(anti-inflammatory)macro-phages.Iron-based nanoparticles have been widely explored and reported to regulate macrophage polarization for various biomedical applications.However,the influence factors and modulation mechanisms behind are complicated and not clear.In this review,we systemically summarized different iron-based nanoparticles that regulate macrophage polari-zation and function and discussed the influence factors and mechanisms underlying the modulation process.This review aims to deepen the understanding of the modulation of macrophage polarization by iron-based nanoparticles and expects to provide evidence and guidance for subsequent design and application of iron-based nanoparticles with specific macrophage modulation functions.

摘要：Artificial Intelligence(AI)is an emerging technology which aims to make intelligent machines,especially intelligent computer programs.It can be utilized to enable human intelligence on machines,but the ability of AI does not have to confine itself to biologically observable methods.It can identify hidden relationships,correlations,and trends that may not be apparent in traditional viewpoints.As a result,AI-enabled technologies have achieved significant achieve-ments for medical care including diagnosis,treatment,drug discovery,and healthcare management[1].

摘要：The biomedical literature is a vast and invalu-able resource for biomedical research.Integrating knowl-edge from the literature with biomedical data can help biological studies and the clinical decision-making process.Efforts have been made to gather information from the biomedical literature and create biomedical knowledge bases,such as KEGG and Reactome.However,manual curation remains the primary method to retrieve accurate biomedical entities and relationships.Manual curation becomes increasingly challenging and costly as the volume of biomedical publications quickly grows.Fortunately,recent advancements in Artificial Intelligence(AI)tech-nologies offer the potential to automate the process of curating,updating,and integrating knowledge from the literature.Herein,we highlight the AI capabilities to aid in mining knowledge and building the knowledge base from the biomedical literature.