Organoids possess immense potential for unraveling the intricate functions of human tissues and facilitating preclinical disease treatment.Their applications span from high-throughput drug screening to the modeling of...Organoids possess immense potential for unraveling the intricate functions of human tissues and facilitating preclinical disease treatment.Their applications span from high-throughput drug screening to the modeling of complex diseases,with some even achieving clinical translation.Changes in the overall size,shape,boundary,and other morphological features of organoids provide a noninvasive method for assessing organoid drug sensitivity.However,the precise segmentation of organoids in bright-field microscopy images is made difficult by the complexity of the organoid morphology and interference,including overlapping organoids,bubbles,dust particles,and cell fragments.This paper introduces the precision organoid segmentation technique(POST),which is a deep-learning algorithm for segmenting challenging organoids under simple bright-field imaging conditions.Unlike existing methods,POST accurately segments each organoid and eliminates various artifacts encountered during organoid culturing and imaging.Furthermore,it is sensitive to and aligns with measurements of organoid activity in drug sensitivity experiments.POST is expected to be a valuable tool for drug screening using organoids owing to its capability of automatically and rapidly eliminating interfering substances and thereby streamlining the organoid analysis and drug screening process.展开更多
Nasopharyngeal carcinoma(NPC)is a malignant tumor prevalent in southern China and Southeast Asia,where its early detection is crucial for improving patient prognosis and reducing mortality rates.However,existing scree...Nasopharyngeal carcinoma(NPC)is a malignant tumor prevalent in southern China and Southeast Asia,where its early detection is crucial for improving patient prognosis and reducing mortality rates.However,existing screening methods suffer from limitations in accuracy and accessibility,hindering their application in large-scale population screening.In this work,a surface-enhanced Raman spectroscopy(SERS)-based method was established to explore the profiles of different stratified components in saliva from NPC and healthy subjects after fractionation processing.The study findings indicate that all fractionated samples exhibit diseaseassociated molecular signaling differences,where small-molecule(molecular weight cut-offvalue is 10 kDa)demonstrating superior classification capabilities with sensitivity of 90.5%and speci-ficity of 75.6%,area under receiver operating characteristic(ROC)curve of 0:925±0:031.The primary objective of this study was to qualitatively explore patterns in saliva composition across groups.The proposed SERS detection strategy for fractionated saliva offers novel insights for enhancing the sensitivity and reliability of noninvasive NPC screening,laying the foundation for translational application in large-scale clinical settings.展开更多
The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of ...The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of pre-conceptional and early pregnancy screening initiatives for severe thalassemia prevention in a diverse population of 28,043 women.Using next-generation sequencing(NGS),we identify 4,226(15.07%)thalassemia carriers across 29 ethnic groups and categorize them into high-(0.75%),low-(25.86%),and unknown-risk(69.19%)groups based on their spouses'screening results.Post-screening follow-up reveals 59 fetuses with severe thalassemia exclusively in high-risk couples,underscoring the efficacy of risk classification.Among 25,053 live births over 6 months of age,two severe thalassemia infants were born to unknown-risk couples,which was attributed to incomplete screening and late NGS-based testing for a rare variant.Notably,64 rare variants are identified in 287 individuals,highlighting the genetic heterogeneity of thalassemia.We also observe that migrant flow significantly impacts carrier rates,with 93.90%of migrants to Chenzhou originating from high-prevalence regions in southern China.Our study demonstrates that NGS-based screening during pre-conception and early pregnancy is effective for severe thalassemia prevention,emphasizing the need for continuous screening efforts in areas with high and underestimated prevalence.展开更多
This review highlights advances in inner ear organoids(IEOs)as a novel platform for drug screening and disease modeling,particularly for hearing loss.IEOs,derived from embryonic stem cells,induced pluripotent stem cel...This review highlights advances in inner ear organoids(IEOs)as a novel platform for drug screening and disease modeling,particularly for hearing loss.IEOs,derived from embryonic stem cells,induced pluripotent stem cells,or tissue-specific progenitors,provide a physiologically relevant alternative to traditional animal models.Significant progress has been made in utilizing various cell sources,extracellular matrix materials such as Matrigel and hydrogels,and methods for controlling microenvironments through biochemical and biophysical signals.Applications of IEOs in drug screening,disease modeling,and personalized medicine enable exploration of hearing loss mechanisms and therapeutic testing.However,challenges remain,including the incomplete maturation of cochlear cells and difficulty replicating in vivo environments.Future research should focus on optimizing IEO generation,incorporating microfluidic technologies,and advancing high-throughput screening to enhance drug discovery and clinical translation.展开更多
At Beijing Tongren Hospital,an AI-powered retinal screening system can screen for 10 chronic illnesses from just two photos in two minutes.Using one fundus image from each eye,it scans for early signs of diabetic reti...At Beijing Tongren Hospital,an AI-powered retinal screening system can screen for 10 chronic illnesses from just two photos in two minutes.Using one fundus image from each eye,it scans for early signs of diabetic retinopathy,hypertension,atherosclerosis and other conditions,with a reported accuracy of about 90 percent.展开更多
Autism spectrum disorder(AsD)is a highly heterogeneous neurodevelopmental disorder.Early diagnosis and intervention are crucial for improving outcomes.Traditional single-modality diagnostic methods are subjective,limi...Autism spectrum disorder(AsD)is a highly heterogeneous neurodevelopmental disorder.Early diagnosis and intervention are crucial for improving outcomes.Traditional single-modality diagnostic methods are subjective,limited,and struggle to reveal the underlying pathological mechanisms.In contrast,multimodal data analysis integrates behavioral,physiological,and neuroimaging information with advanced machine-learning and deeplearning algorithms to overcome these limitations.In this review,we surveyed the recent pediatric AsD literature,highlighting artificial intelligence-driven diagnostic techniques,multimodal data fusion strategies,and emerging trends in ASD assessment.We surveyed studies that integrated two or more modalities and summarized the fusion levels,learning paradigms,tasks,datasets,and metrics.Multimodal approaches outperform singlemodality baselines in classification,severity estimation,and subtyping by leveraging complementary information and reducing modality-specific biases.Multimodal approaches significantly enhance diagnostic accuracy and comprehensiveness,enabling early screening of AsD,symptom subtyping,severity assessment,and personalized interventions.Advances in multimodal fusion techniques have promoted progress in precision medicine for the treatment of ASD.展开更多
Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonst...Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonstrated that supernatant(SPX)improved kidney function in adriamycin(ADR)-induced nephropathy mice model.Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor(C3aR)pathway.Peptidomic analysis identified 304 peptides from SPX,with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3.Three peptides(PMGFPFDR,FNDPK,AAQFFNR)exhibiting docking scores below-8.0 were synthesized to verify complement inhibition and anti-fibrotic activities.The synthetic peptide AAQFFNR demonstrated complement inhibitory activity,with an inhibitory complement hemolytic 50%(ICH_(50))value of 24.54μmol·L^(-1),and exhibited superior protective effects in ADR-induced HK-2 cells.Surface plasmon resonance(SPR)assay revealed direct interaction between AAQFFNR and complement C3 with K_(d)value of 16.8μmol·L^(-1).The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice.This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through in silico and in vivo validation approaches.展开更多
Diabetic retinopathy(DR)is a leading cause of vision loss among working-age populations,with early screening significantly reducing the risk of blindness.However,resource-limited regions often face challenges in DR sc...Diabetic retinopathy(DR)is a leading cause of vision loss among working-age populations,with early screening significantly reducing the risk of blindness.However,resource-limited regions often face challenges in DR screening due to a shortage of ophthalmologists.This study reports the implementation and outcomes of the Chinese local standard DB52/T 1726-2023,Regulations for the application of diabetic retinopathy screening artificial intelligence,in Cambodian healthcare institutions.A pilot DR screening program with independent operational capability is established by providing a non-mydriatic fundus camera and deploying a localized diabetic retinopathy artificial intelligence(DR-AI)screening platform at the Cambodia-Kingdom Friendship Hospital in Phnom Penh,along with comprehensive training.From January to August 2025,a total of 565 patients with type 2 diabetes were screened,yielding a DR detection rate of 26.0%(147 cases).Research findings demonstrate that applying mature Chinese DR-AI screening standards and technological solutions through international collaboration in regions with a scarcity of ophthalmic professionals is both feasible and effective.This project serves as a reference for promoting DR-AI in resource-constrained countries and regions,highlighting its significant potential to leverage AI in addressing the global burden of chronic diseases and advancing the modernization of health systems.展开更多
The equilibrium dynamics and nonlinear rheology of unentangled polymer blends remain inadequately understood,especially regarding the influence of short-chain matrix length N_(S) on the structure and rheological behav...The equilibrium dynamics and nonlinear rheology of unentangled polymer blends remain inadequately understood,especially regarding the influence of short-chain matrix length N_(S) on the structure and rheological behavior of dispersed long chains.Using molecular dynamics simulations based on the Kremer-Grest model,we systematically explore the N_(S)-dependence of static conformations,equilibrium dynamics,and nonlinear shear responses in unentangled long-chain/short-chain polymer blends.Our results demonstrate a decoupling between the static and dynamic sensitivity to N_(S):while the static chain size,R_g,follows Flory theory with slight swelling at small N_(S) due to incomplete excluded volume screening,the diffusion coefficient,D,and the relaxation time,τ_(0),exhibit a strong,non-monotonic N_(S)-dependence,transitioning from monomeric friction dominance at small N_(S) to collective segmental rearrangement at large N_(S).Additionally,we observe partial decoupling between the viscous and normal stress responses:while the zero-shear viscosity,η,is strongly N_(S)-dependent,the first and second normal stress coefficients,Ψ_(1) and Ψ_(2),collapse onto universal curves when scaled by the dimensionless shear rate,γτ_(0),suggesting a common mechanism of orientation and stretching.Under shear,long chains compress in the vorticity direction λ_(z)~Wi^(-0.2),which reduces collision frequency and contributes to shear thinning,while the scaling of weaker orientation resistance m_(G)~Wi^(0.35)reflects hydrodynamic screening by the short-chain matrix.These findings highlight the limitations of single-chain models and emphasize the necessity of considering N_(S)-dependent matrix dynamics and flow-induced structural changes in understanding the rheology of unentangled polymer blends.展开更多
The definition of environmental pollution is becoming increasingly diverse,with accelerating change and exposure to complex mixtures that defy traditional detection-based monitoring approaches.We discuss the current t...The definition of environmental pollution is becoming increasingly diverse,with accelerating change and exposure to complex mixtures that defy traditional detection-based monitoring approaches.We discuss the current trends in environmental analytical chemistry whereby,rather than targeted quantification,an integrated pollutant assessment,which upholds chemical discovery,interpretability,and real-world relevance,is desired.We initially explain the conceptual change between preset sets of analytes to the chemical space exploration made possible by exploring the chemical space using high-resolution mass spectrometry,multidimensional separations,and rapid/direct analysis technologies.We next mention how the new classes of contaminants and transformation products,as well as the complexity of mixtures,reveal the long-standing gaps in sensitivity,selectivity,and confidence of the identification,especially in the non-targeted workflows.In response to such limitations,we now mention changes that combine chemical measurement with biological and data-informed aspects,such as effect-based assays,exposure-oriented metrics,chemometrics,and machine learning feature prioritization and structure annotation.We also look at the transformation of higher orders of analytical products into clean-up programs and decision programs,which should focus on continuous and in-place sensing,tiered monitoring designs,and risk-based prioritization plans that more closely reflect the changing realities of the environment.Lastly,we determine future research requirements in harmonization,open data infrastructure,and reproducibility,and the development of autonomous and intelligent analytical systems that can perform adaptive monitoring and provide insights quickly.All these changing frontiers transform environmental analysis into a detection instrument into an actionable environmental intelligence that can be used to proactively manage and protect the ecosystems and human health.展开更多
Background Frailty is common and significantly impacts prognosis in heart failure(HF). The Vulnerable Elders Survey-13(VES-13), widely used in oncogeriatrics and public health, remains unexplored as a frailty screenin...Background Frailty is common and significantly impacts prognosis in heart failure(HF). The Vulnerable Elders Survey-13(VES-13), widely used in oncogeriatrics and public health, remains unexplored as a frailty screening tool in HF outpatients. In this study, we prospectively evaluated VES-13 against a multimodal screening assessment in detecting frailty and predicting individual risk of adverse prognosis.Methods Frailty was assessed at the initial visit using both a multimodal approach, incorporating Barthel Index, Older American Resources and Services scale, Pfeiffer Test, abbreviated Geriatric Depression Scale, age > 85 years, lacking support systems,and VES-13. Patients scoring ≥ 3 on VES-13 or meeting at least one multimodal criterion were classified as frail. Endpoints included all-cause mortality, a composite of death or HF hospitalization, and recurrent HF hospitalizations.Results A total of 301 patients were evaluated. VES-13 identified 40.2% as frail and the multimodal assessment 33.2%. In Cox regression analyses, frailty identified by VES-13 showed greater prognostic significance than the multimodal assessment for allcause mortality(HR = 3.70 [2.15–6.33], P < 0.001 vs. 2.40 [1.46–4.0], P = 0.001) and the composite endpoint(HR = 3.13 [2.02–4.84], P< 0.001 vs. 1.96 [1.28–2.99], P = 0.002). Recurrent HF hospitalizations were four times more frequent in VES-13 frail patients while two times in those identified as frail by the multimodal assessment. Additionally, stratifying patients by VES-13 tertiles provided robust risk differentiation.Conclusions VES-13, a simple frailty tool, outperformed a comprehensive multimodal assessment and could be easily integrated into routine HF care, highlighting its clinical utility in identifying patients at risk for poor outcomes.展开更多
With the increasing demand for understanding skin physiology and advancing regenerative medicine,in vitro three-dimensional(3D)functional skin tissue models have become vital tools in dermatological research.These mod...With the increasing demand for understanding skin physiology and advancing regenerative medicine,in vitro three-dimensional(3D)functional skin tissue models have become vital tools in dermatological research.These models effectively mimic the complex structure and functions of human skin.This review comprehensively discusses the latest advancements in construction techniques,material selection,and applications of 3D skin models.It highlights the advantages and challenges associated with cutting-edge technologies such as layer-by-layer cell coating,3D bioprinting,bio-spray technology,and photolithographic microfabrication in creating highly realistic skin models.Moreover,it examines the wide-ranging applications of 3D skin models,includingelucidation of skin disease mechanisms,investigation of skin barrier functions,studies on skin aging and repair,hair regeneration,efficacy screening of therapeutic agents,cosmetic safety assessment,and personalized medicine.Finally,this review anticipates future trends in developing 3D skin models with greater structural and functional complexity,enhanced multifunctionality,and improved clinical translation.展开更多
Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual pat...Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.展开更多
The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cereb...The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.展开更多
The combustion and detonation processes of energetic materials exhibit remarkable complexity and ultra-fast transient characteristics.While reactive molecular dynamics has been extensively employed to investigate the ...The combustion and detonation processes of energetic materials exhibit remarkable complexity and ultra-fast transient characteristics.While reactive molecular dynamics has been extensively employed to investigate the reaction dynamics of energetic materials,its utility is often constrained to capturing only fundamental reaction events and species information,thereby limiting mechanistic investigations of complex reaction pathways.To elucidate the topological features of energetic material reaction networks and identify critical reaction pathways with high fidelity,this study presents ReacNetwork-an advanced large-scale reaction network analysis methodology that synergistically integrates complex network theory with molecular simulation techniques.Specifically,we have developed a multi-dimensional feature screening protocol based on node centrality metrics and K-shell decomposition algorithms.Takingα-Hexahydro-1,3,5-trinitro-1,3,5-triazine(α-RDX)as the subject,we successfully constructed a comprehensive high-temperature thermal decomposition reaction network consisting of 1,134 distinct chemical species and 3,626 elementary reactions.Through systematic application of community detection algorithms and global topological feature extraction techniques,we achieved effective dimensionality reduction and successfully identified the dominant reaction pathway within theα-RDX thermal decomposition network.The computational results not only validate the well-established initial reaction mechanism dominated by N-NO2 homolytic bond cleavage,but also provide unprecedented visualization ofα-RDX framework ring-opening dynamics and subsequent radical chain propagation networks.展开更多
The rational design of high-performance CO_(2)adsorbents remains a critical challenge in addressing global carbon emissions,with metal-organic frameworks(MOFs)emerging as promising candidates due to their tunable pore...The rational design of high-performance CO_(2)adsorbents remains a critical challenge in addressing global carbon emissions,with metal-organic frameworks(MOFs)emerging as promising candidates due to their tunable pore environments.However,the lack of systematic guidelines for functional group selection has hindered their practical implementation in carbon capture applications.Here,this gap was addressed by developing a comprehensive design framework through high-throughput computational screening.Through construction of a topology-directed database of 4797,integrating 10 metal centers with 144 functionalized ligands(18 ligands modified by–NH_(2),–NO_(2),–CH_(3),–CF_(3),–SH_(2),–SO_(2),–OH,and–OLi)across 36 topologies,the fundamental structure–property relationships governing CO_(2)capture performance was established.Multi-metric evaluation reveals that–NO_(2),–SO_(2),and–OLi dramatically enhance CO_(2)selectivity over CH_4/N_(2)via selectivity(S_(ads)),working capacity(ΔN),adsorbent performance score(APS),sorbent selection parameter(S_(sp)),and renewability R.Specially,ΔN rises from 2.34(pristine)to 5.91–7.94 mmol g^(-1)and S_(ads)surges from 24.94/40.36 to 121.11/176.87(–NO_(2)),149.94/215.54(–SO_(2)),and 58.64/267.44(–OLi).Besides,the critical trade-off between adsorption strength and renewability demonstrates that enhanced performance comes at the cost of reduced renewability,where stronger CO_(2)affinity(isosteric heat of-29.15,-29.96,and-30.09 for–NO_(2),–SO_(2),and–OLi)compromises renewability(R reduced by -50%).To resolve this trade-off,a novel energy efficiency(η)metric was introduced,which holistically evaluates both adsorption performance(S_(ads),ΔN,APS,S_(sp),and R)and energy inputs(desorption heat,pressure-swing energy,net loss).This leads to the identification of–SO_(2)as the optimal functional group that balances exceptional CO_(2)capture(η=6.17/12.78 for CO_(2)over CH_4/N_(2)),surpassing the second higher of 4.74/8.80 in–CF_(3)and 0.99/2.18 in non-functionalized counterparts.Adopting high-throughput computational screening methods,this work provides both fundamental insights into host–vip interactions in functionalized MOFs and a practical framework for designing next-generation adsorbents,bridging the gap between materials discovery and process engineering considerations in carbon capture technologies.展开更多
Investigating the mechanisms underlying central nervous system disorders is a major scientific issue in the 21st century.However,the inaccessibility and complexity of the human brain have always represented a challeng...Investigating the mechanisms underlying central nervous system disorders is a major scientific issue in the 21st century.However,the inaccessibility and complexity of the human brain have always represented a challenge in understanding the pathophysiology of the central nervous system.Brain organoids are self-assembled threedimensional aggregates derived from pluripotent stem cells with cell types and structures similar to the embryonic human brain,giving them potential for investigating the atypical cellular,molecular,and genetic characteristics characteristic of central nervous system disorders.Brain organoids also provide a platform for drug screening and serve as a potential source for transplantation therapy for brain injuries.However,the broad application of brain organoids is hampered by several limitations,such as the lack of high-fidelity cell types,insufficient maturation,and considerable heterogeneity,undermining their reliability in specific applications.This review summarizes brain organoid evolution,discusses recent technological and methodological innovations,and reviews their applications in drug screening,transplantation therapy,and disease modeling,as well as clinical research progress.Additionally,we emphasize the limitations of current brain organoid research and explore the potential for advancing the technology to enhance its applicability.展开更多
Brain organoids are artificial neural tissues derived in vitro,containing a variety of cell types,as well as structural and/or functional brain regions.They can partially mimic brain physiological activities and disea...Brain organoids are artificial neural tissues derived in vitro,containing a variety of cell types,as well as structural and/or functional brain regions.They can partially mimic brain physiological activities and diseased processes.Owing to their operability and sample accessibility,brain organoids serve as a bridge between in vitro monolayer cell culture models and in vivo animal models.An increasing number of induction protocols for brain organoids have been developed over the preceding decade.A key future research direction will focus on ensuring the complexity and quality of brain organoids.The integration of powerful technologies,such as the CRISP R/Cas9 genome editing and lineage tra cing systems,shall precipitate practical and broad applications of brain organoids.In this review,we discuss the generation and application of brain organoids,as well as their integration with genome editing technologies,in the study of neural development,disease modeling,and mechanistic investigations.The innovative combination of these two technologies may offer a fresh perspective for exploring the fundamental aspects of the human nervous system and related diseases.展开更多
Emerging and powerful genome editing tools,particularly CRISPR/Cas9,are facilitating functional genomics research and accelerating crop improvement(Jiang et al.2021;Cao et al.2023;Chen C et al.2023;Liu et al.2023a).Ho...Emerging and powerful genome editing tools,particularly CRISPR/Cas9,are facilitating functional genomics research and accelerating crop improvement(Jiang et al.2021;Cao et al.2023;Chen C et al.2023;Liu et al.2023a).However,the detection and screening of transgenic lines remain major bottlenecks,being time-consuming,labor-intensive,and inefficient during transformation and subsequent mutation identification.A simple and efficient visual marker system plays a critical role in addressing these challenges.Recent studies demonstrated that the GmW1 and RUBY reporter systems were used to obtain visual transgenic soybean(Glycine max) plants(Chen L et al.2023;Chen et al.2024).展开更多
基金supported by the National Key R&D Program of China(No.2022YFC2504403)the National Natural Science Foundation of China(No.62172202)+1 种基金the Experiment Project of China Manned Space Program(No.HYZHXM01019)the Fundamental Research Funds for the Central Universities from Southeast University(No.3207032101C3)。
文摘Organoids possess immense potential for unraveling the intricate functions of human tissues and facilitating preclinical disease treatment.Their applications span from high-throughput drug screening to the modeling of complex diseases,with some even achieving clinical translation.Changes in the overall size,shape,boundary,and other morphological features of organoids provide a noninvasive method for assessing organoid drug sensitivity.However,the precise segmentation of organoids in bright-field microscopy images is made difficult by the complexity of the organoid morphology and interference,including overlapping organoids,bubbles,dust particles,and cell fragments.This paper introduces the precision organoid segmentation technique(POST),which is a deep-learning algorithm for segmenting challenging organoids under simple bright-field imaging conditions.Unlike existing methods,POST accurately segments each organoid and eliminates various artifacts encountered during organoid culturing and imaging.Furthermore,it is sensitive to and aligns with measurements of organoid activity in drug sensitivity experiments.POST is expected to be a valuable tool for drug screening using organoids owing to its capability of automatically and rapidly eliminating interfering substances and thereby streamlining the organoid analysis and drug screening process.
基金financially supported by National Natural Science Foundation ofChina(No.12374405)Provincial Science Foundation for Distinguished Young Scholars of Fujian(No.2024J010024)+1 种基金Natural Science Foundation of Fujian Province of China(No.2023J011267)Major Research Projects for Young and Middle-aged Researchers of Fujian Provincial Health Commission(No.2021ZQNZD010).
文摘Nasopharyngeal carcinoma(NPC)is a malignant tumor prevalent in southern China and Southeast Asia,where its early detection is crucial for improving patient prognosis and reducing mortality rates.However,existing screening methods suffer from limitations in accuracy and accessibility,hindering their application in large-scale population screening.In this work,a surface-enhanced Raman spectroscopy(SERS)-based method was established to explore the profiles of different stratified components in saliva from NPC and healthy subjects after fractionation processing.The study findings indicate that all fractionated samples exhibit diseaseassociated molecular signaling differences,where small-molecule(molecular weight cut-offvalue is 10 kDa)demonstrating superior classification capabilities with sensitivity of 90.5%and speci-ficity of 75.6%,area under receiver operating characteristic(ROC)curve of 0:925±0:031.The primary objective of this study was to qualitatively explore patterns in saliva composition across groups.The proposed SERS detection strategy for fractionated saliva offers novel insights for enhancing the sensitivity and reliability of noninvasive NPC screening,laying the foundation for translational application in large-scale clinical settings.
基金supported by the National Natural Science Foundation of China(81760037)Yunling Scholar Project of Yunnan Province(YNWR-YLXZ-2019-0005)+1 种基金Hunan Provincial Innovation Platform and Talent Program(2018SK4004)Hunan Provincial Natural Science Foundation(2019JJ80048).
文摘The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of pre-conceptional and early pregnancy screening initiatives for severe thalassemia prevention in a diverse population of 28,043 women.Using next-generation sequencing(NGS),we identify 4,226(15.07%)thalassemia carriers across 29 ethnic groups and categorize them into high-(0.75%),low-(25.86%),and unknown-risk(69.19%)groups based on their spouses'screening results.Post-screening follow-up reveals 59 fetuses with severe thalassemia exclusively in high-risk couples,underscoring the efficacy of risk classification.Among 25,053 live births over 6 months of age,two severe thalassemia infants were born to unknown-risk couples,which was attributed to incomplete screening and late NGS-based testing for a rare variant.Notably,64 rare variants are identified in 287 individuals,highlighting the genetic heterogeneity of thalassemia.We also observe that migrant flow significantly impacts carrier rates,with 93.90%of migrants to Chenzhou originating from high-prevalence regions in southern China.Our study demonstrates that NGS-based screening during pre-conception and early pregnancy is effective for severe thalassemia prevention,emphasizing the need for continuous screening efforts in areas with high and underestimated prevalence.
基金supported by the National Natural Science Foundation of China(82222017 and 82271183)Hubei Province’s Key Research and Development Program(2022BCA046)the Start-up Research Fund of Southeast University(RF1028623028).
文摘This review highlights advances in inner ear organoids(IEOs)as a novel platform for drug screening and disease modeling,particularly for hearing loss.IEOs,derived from embryonic stem cells,induced pluripotent stem cells,or tissue-specific progenitors,provide a physiologically relevant alternative to traditional animal models.Significant progress has been made in utilizing various cell sources,extracellular matrix materials such as Matrigel and hydrogels,and methods for controlling microenvironments through biochemical and biophysical signals.Applications of IEOs in drug screening,disease modeling,and personalized medicine enable exploration of hearing loss mechanisms and therapeutic testing.However,challenges remain,including the incomplete maturation of cochlear cells and difficulty replicating in vivo environments.Future research should focus on optimizing IEO generation,incorporating microfluidic technologies,and advancing high-throughput screening to enhance drug discovery and clinical translation.
文摘At Beijing Tongren Hospital,an AI-powered retinal screening system can screen for 10 chronic illnesses from just two photos in two minutes.Using one fundus image from each eye,it scans for early signs of diabetic retinopathy,hypertension,atherosclerosis and other conditions,with a reported accuracy of about 90 percent.
基金supported by the National Key Research and Development Program of China(Research Grant Number:2023YFC3603600).
文摘Autism spectrum disorder(AsD)is a highly heterogeneous neurodevelopmental disorder.Early diagnosis and intervention are crucial for improving outcomes.Traditional single-modality diagnostic methods are subjective,limited,and struggle to reveal the underlying pathological mechanisms.In contrast,multimodal data analysis integrates behavioral,physiological,and neuroimaging information with advanced machine-learning and deeplearning algorithms to overcome these limitations.In this review,we surveyed the recent pediatric AsD literature,highlighting artificial intelligence-driven diagnostic techniques,multimodal data fusion strategies,and emerging trends in ASD assessment.We surveyed studies that integrated two or more modalities and summarized the fusion levels,learning paradigms,tasks,datasets,and metrics.Multimodal approaches outperform singlemodality baselines in classification,severity estimation,and subtyping by leveraging complementary information and reducing modality-specific biases.Multimodal approaches significantly enhance diagnostic accuracy and comprehensiveness,enabling early screening of AsD,symptom subtyping,severity assessment,and personalized interventions.Advances in multimodal fusion techniques have promoted progress in precision medicine for the treatment of ASD.
基金supported by the National Natural Science Foundation of China(No.82104353)China Postdoctoral Science Foundation funded project(No.2022M711680).
文摘Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonstrated that supernatant(SPX)improved kidney function in adriamycin(ADR)-induced nephropathy mice model.Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor(C3aR)pathway.Peptidomic analysis identified 304 peptides from SPX,with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3.Three peptides(PMGFPFDR,FNDPK,AAQFFNR)exhibiting docking scores below-8.0 were synthesized to verify complement inhibition and anti-fibrotic activities.The synthetic peptide AAQFFNR demonstrated complement inhibitory activity,with an inhibitory complement hemolytic 50%(ICH_(50))value of 24.54μmol·L^(-1),and exhibited superior protective effects in ADR-induced HK-2 cells.Surface plasmon resonance(SPR)assay revealed direct interaction between AAQFFNR and complement C3 with K_(d)value of 16.8μmol·L^(-1).The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice.This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through in silico and in vivo validation approaches.
基金funded by the Chronic Disease Management Research Project of National Health Commission Capacity Building and Continuing Education Center 2025(GWJJMB202510024146)the Post-Subsidy Project for Standard Development of Guizhou Provincial Market Supervision and Administration Bureau 2025(DB52/T1726-2023)the Guizhou Provincial Health Commission Science and Technology Fund Project(gzwkj2024-076,gzwkj2026-146).
文摘Diabetic retinopathy(DR)is a leading cause of vision loss among working-age populations,with early screening significantly reducing the risk of blindness.However,resource-limited regions often face challenges in DR screening due to a shortage of ophthalmologists.This study reports the implementation and outcomes of the Chinese local standard DB52/T 1726-2023,Regulations for the application of diabetic retinopathy screening artificial intelligence,in Cambodian healthcare institutions.A pilot DR screening program with independent operational capability is established by providing a non-mydriatic fundus camera and deploying a localized diabetic retinopathy artificial intelligence(DR-AI)screening platform at the Cambodia-Kingdom Friendship Hospital in Phnom Penh,along with comprehensive training.From January to August 2025,a total of 565 patients with type 2 diabetes were screened,yielding a DR detection rate of 26.0%(147 cases).Research findings demonstrate that applying mature Chinese DR-AI screening standards and technological solutions through international collaboration in regions with a scarcity of ophthalmic professionals is both feasible and effective.This project serves as a reference for promoting DR-AI in resource-constrained countries and regions,highlighting its significant potential to leverage AI in addressing the global burden of chronic diseases and advancing the modernization of health systems.
基金financially supported by the National Natural Science Foundation of China(Nos.22341304,22303100 and 12205270)the National Key R&D Program of China(Nos.2023YFA1008800 and 2020YFA0713601)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDC0180303)。
文摘The equilibrium dynamics and nonlinear rheology of unentangled polymer blends remain inadequately understood,especially regarding the influence of short-chain matrix length N_(S) on the structure and rheological behavior of dispersed long chains.Using molecular dynamics simulations based on the Kremer-Grest model,we systematically explore the N_(S)-dependence of static conformations,equilibrium dynamics,and nonlinear shear responses in unentangled long-chain/short-chain polymer blends.Our results demonstrate a decoupling between the static and dynamic sensitivity to N_(S):while the static chain size,R_g,follows Flory theory with slight swelling at small N_(S) due to incomplete excluded volume screening,the diffusion coefficient,D,and the relaxation time,τ_(0),exhibit a strong,non-monotonic N_(S)-dependence,transitioning from monomeric friction dominance at small N_(S) to collective segmental rearrangement at large N_(S).Additionally,we observe partial decoupling between the viscous and normal stress responses:while the zero-shear viscosity,η,is strongly N_(S)-dependent,the first and second normal stress coefficients,Ψ_(1) and Ψ_(2),collapse onto universal curves when scaled by the dimensionless shear rate,γτ_(0),suggesting a common mechanism of orientation and stretching.Under shear,long chains compress in the vorticity direction λ_(z)~Wi^(-0.2),which reduces collision frequency and contributes to shear thinning,while the scaling of weaker orientation resistance m_(G)~Wi^(0.35)reflects hydrodynamic screening by the short-chain matrix.These findings highlight the limitations of single-chain models and emphasize the necessity of considering N_(S)-dependent matrix dynamics and flow-induced structural changes in understanding the rheology of unentangled polymer blends.
文摘The definition of environmental pollution is becoming increasingly diverse,with accelerating change and exposure to complex mixtures that defy traditional detection-based monitoring approaches.We discuss the current trends in environmental analytical chemistry whereby,rather than targeted quantification,an integrated pollutant assessment,which upholds chemical discovery,interpretability,and real-world relevance,is desired.We initially explain the conceptual change between preset sets of analytes to the chemical space exploration made possible by exploring the chemical space using high-resolution mass spectrometry,multidimensional separations,and rapid/direct analysis technologies.We next mention how the new classes of contaminants and transformation products,as well as the complexity of mixtures,reveal the long-standing gaps in sensitivity,selectivity,and confidence of the identification,especially in the non-targeted workflows.In response to such limitations,we now mention changes that combine chemical measurement with biological and data-informed aspects,such as effect-based assays,exposure-oriented metrics,chemometrics,and machine learning feature prioritization and structure annotation.We also look at the transformation of higher orders of analytical products into clean-up programs and decision programs,which should focus on continuous and in-place sensing,tiered monitoring designs,and risk-based prioritization plans that more closely reflect the changing realities of the environment.Lastly,we determine future research requirements in harmonization,open data infrastructure,and reproducibility,and the development of autonomous and intelligent analytical systems that can perform adaptive monitoring and provide insights quickly.All these changing frontiers transform environmental analysis into a detection instrument into an actionable environmental intelligence that can be used to proactively manage and protect the ecosystems and human health.
文摘Background Frailty is common and significantly impacts prognosis in heart failure(HF). The Vulnerable Elders Survey-13(VES-13), widely used in oncogeriatrics and public health, remains unexplored as a frailty screening tool in HF outpatients. In this study, we prospectively evaluated VES-13 against a multimodal screening assessment in detecting frailty and predicting individual risk of adverse prognosis.Methods Frailty was assessed at the initial visit using both a multimodal approach, incorporating Barthel Index, Older American Resources and Services scale, Pfeiffer Test, abbreviated Geriatric Depression Scale, age > 85 years, lacking support systems,and VES-13. Patients scoring ≥ 3 on VES-13 or meeting at least one multimodal criterion were classified as frail. Endpoints included all-cause mortality, a composite of death or HF hospitalization, and recurrent HF hospitalizations.Results A total of 301 patients were evaluated. VES-13 identified 40.2% as frail and the multimodal assessment 33.2%. In Cox regression analyses, frailty identified by VES-13 showed greater prognostic significance than the multimodal assessment for allcause mortality(HR = 3.70 [2.15–6.33], P < 0.001 vs. 2.40 [1.46–4.0], P = 0.001) and the composite endpoint(HR = 3.13 [2.02–4.84], P< 0.001 vs. 1.96 [1.28–2.99], P = 0.002). Recurrent HF hospitalizations were four times more frequent in VES-13 frail patients while two times in those identified as frail by the multimodal assessment. Additionally, stratifying patients by VES-13 tertiles provided robust risk differentiation.Conclusions VES-13, a simple frailty tool, outperformed a comprehensive multimodal assessment and could be easily integrated into routine HF care, highlighting its clinical utility in identifying patients at risk for poor outcomes.
文摘With the increasing demand for understanding skin physiology and advancing regenerative medicine,in vitro three-dimensional(3D)functional skin tissue models have become vital tools in dermatological research.These models effectively mimic the complex structure and functions of human skin.This review comprehensively discusses the latest advancements in construction techniques,material selection,and applications of 3D skin models.It highlights the advantages and challenges associated with cutting-edge technologies such as layer-by-layer cell coating,3D bioprinting,bio-spray technology,and photolithographic microfabrication in creating highly realistic skin models.Moreover,it examines the wide-ranging applications of 3D skin models,includingelucidation of skin disease mechanisms,investigation of skin barrier functions,studies on skin aging and repair,hair regeneration,efficacy screening of therapeutic agents,cosmetic safety assessment,and personalized medicine.Finally,this review anticipates future trends in developing 3D skin models with greater structural and functional complexity,enhanced multifunctionality,and improved clinical translation.
基金supported by the Natural Science Foundation of Guangdong Province(No.2021B1515120053)Guangdong Basic and Applied Basic Research Foundation(Grant No.2024A1515140166).
文摘Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.
基金supported by the Grant PID2021-126715OB-IOO financed by MCIN/AEI/10.13039/501100011033 and"ERDFA way of making Europe"by the Grant PI22CⅢ/00055 funded by Instituto de Salud CarlosⅢ(ISCⅢ)+6 种基金the UFIECPY 398/19(PEJ2018-004965) grant to RGS funded by AEI(Spain)the UFIECPY-396/19(PEJ2018-004961)grant financed by MCIN (Spain)FI23CⅢ/00003 grant funded by ISCⅢ-PFIS Spain) to PMMthe UFIECPY 328/22 (PEJ-2021-TL/BMD-21001) grant to LM financed by CAM (Spain)the grant by CAPES (Coordination for the Improvement of Higher Education Personnel)through the PDSE program (Programa de Doutorado Sanduiche no Exterior)to VSCG financed by MEC (Brazil)
文摘The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.
基金support from the National Natural Science Foundation of China(Grant No.22275018).
文摘The combustion and detonation processes of energetic materials exhibit remarkable complexity and ultra-fast transient characteristics.While reactive molecular dynamics has been extensively employed to investigate the reaction dynamics of energetic materials,its utility is often constrained to capturing only fundamental reaction events and species information,thereby limiting mechanistic investigations of complex reaction pathways.To elucidate the topological features of energetic material reaction networks and identify critical reaction pathways with high fidelity,this study presents ReacNetwork-an advanced large-scale reaction network analysis methodology that synergistically integrates complex network theory with molecular simulation techniques.Specifically,we have developed a multi-dimensional feature screening protocol based on node centrality metrics and K-shell decomposition algorithms.Takingα-Hexahydro-1,3,5-trinitro-1,3,5-triazine(α-RDX)as the subject,we successfully constructed a comprehensive high-temperature thermal decomposition reaction network consisting of 1,134 distinct chemical species and 3,626 elementary reactions.Through systematic application of community detection algorithms and global topological feature extraction techniques,we achieved effective dimensionality reduction and successfully identified the dominant reaction pathway within theα-RDX thermal decomposition network.The computational results not only validate the well-established initial reaction mechanism dominated by N-NO2 homolytic bond cleavage,but also provide unprecedented visualization ofα-RDX framework ring-opening dynamics and subsequent radical chain propagation networks.
基金supported by The National Natural Science Foundation of China(22471289 and 22478430)Shandong Natural Science Foundation(ZR2022ME105 and ZR2023ME004)+4 种基金Qingdao Natural Science Foundation(23-2-1-232-zyyd-jch)Geological body description and key technologies of reservoir engineering of CCUS oil displacement(2021ZZ01-03)Science and Technology Major Project on New Oil and Gas Exploration and Development:Research on Comprehensive Control Technology for CO_(2)-Enhanced Miscible and Immiscible Displacement(2024ZD1406601)State Key Laboratory of Enhanced Oil Recovery of Open Fund Funded Project(2024-KFKT-19)the Fundamental Research Funds for the Central Universities(24CX06042A and 24CX06070A)。
文摘The rational design of high-performance CO_(2)adsorbents remains a critical challenge in addressing global carbon emissions,with metal-organic frameworks(MOFs)emerging as promising candidates due to their tunable pore environments.However,the lack of systematic guidelines for functional group selection has hindered their practical implementation in carbon capture applications.Here,this gap was addressed by developing a comprehensive design framework through high-throughput computational screening.Through construction of a topology-directed database of 4797,integrating 10 metal centers with 144 functionalized ligands(18 ligands modified by–NH_(2),–NO_(2),–CH_(3),–CF_(3),–SH_(2),–SO_(2),–OH,and–OLi)across 36 topologies,the fundamental structure–property relationships governing CO_(2)capture performance was established.Multi-metric evaluation reveals that–NO_(2),–SO_(2),and–OLi dramatically enhance CO_(2)selectivity over CH_4/N_(2)via selectivity(S_(ads)),working capacity(ΔN),adsorbent performance score(APS),sorbent selection parameter(S_(sp)),and renewability R.Specially,ΔN rises from 2.34(pristine)to 5.91–7.94 mmol g^(-1)and S_(ads)surges from 24.94/40.36 to 121.11/176.87(–NO_(2)),149.94/215.54(–SO_(2)),and 58.64/267.44(–OLi).Besides,the critical trade-off between adsorption strength and renewability demonstrates that enhanced performance comes at the cost of reduced renewability,where stronger CO_(2)affinity(isosteric heat of-29.15,-29.96,and-30.09 for–NO_(2),–SO_(2),and–OLi)compromises renewability(R reduced by -50%).To resolve this trade-off,a novel energy efficiency(η)metric was introduced,which holistically evaluates both adsorption performance(S_(ads),ΔN,APS,S_(sp),and R)and energy inputs(desorption heat,pressure-swing energy,net loss).This leads to the identification of–SO_(2)as the optimal functional group that balances exceptional CO_(2)capture(η=6.17/12.78 for CO_(2)over CH_4/N_(2)),surpassing the second higher of 4.74/8.80 in–CF_(3)and 0.99/2.18 in non-functionalized counterparts.Adopting high-throughput computational screening methods,this work provides both fundamental insights into host–vip interactions in functionalized MOFs and a practical framework for designing next-generation adsorbents,bridging the gap between materials discovery and process engineering considerations in carbon capture technologies.
基金supported by Guizhou Provincial Higher Education Science and Technological Innovation Team,No.[2023]072 (to LX)Graduate Education and Teaching Innovation Program of Zunyi Medical University,No.ZYK262 (to QW)the Guizhou Graduate Research Fund,No.2024YJSKYJJ333 (to QW)
文摘Investigating the mechanisms underlying central nervous system disorders is a major scientific issue in the 21st century.However,the inaccessibility and complexity of the human brain have always represented a challenge in understanding the pathophysiology of the central nervous system.Brain organoids are self-assembled threedimensional aggregates derived from pluripotent stem cells with cell types and structures similar to the embryonic human brain,giving them potential for investigating the atypical cellular,molecular,and genetic characteristics characteristic of central nervous system disorders.Brain organoids also provide a platform for drug screening and serve as a potential source for transplantation therapy for brain injuries.However,the broad application of brain organoids is hampered by several limitations,such as the lack of high-fidelity cell types,insufficient maturation,and considerable heterogeneity,undermining their reliability in specific applications.This review summarizes brain organoid evolution,discusses recent technological and methodological innovations,and reviews their applications in drug screening,transplantation therapy,and disease modeling,as well as clinical research progress.Additionally,we emphasize the limitations of current brain organoid research and explore the potential for advancing the technology to enhance its applicability.
基金Special Projectfor Clinical Research of Shanghai Municipal Health Commission,No.202140403Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai,No.PWZxq2022-05+2 种基金Natural Science Foundation of Ningxia Hui Autonomous Region,No.2024AAC05084Ningxia Hui Autonomous Region Key Research and Development Program,No.2021BEG03084National Natural Science Foundation of China,Nos.32370895,32070862。
文摘Brain organoids are artificial neural tissues derived in vitro,containing a variety of cell types,as well as structural and/or functional brain regions.They can partially mimic brain physiological activities and diseased processes.Owing to their operability and sample accessibility,brain organoids serve as a bridge between in vitro monolayer cell culture models and in vivo animal models.An increasing number of induction protocols for brain organoids have been developed over the preceding decade.A key future research direction will focus on ensuring the complexity and quality of brain organoids.The integration of powerful technologies,such as the CRISP R/Cas9 genome editing and lineage tra cing systems,shall precipitate practical and broad applications of brain organoids.In this review,we discuss the generation and application of brain organoids,as well as their integration with genome editing technologies,in the study of neural development,disease modeling,and mechanistic investigations.The innovative combination of these two technologies may offer a fresh perspective for exploring the fundamental aspects of the human nervous system and related diseases.
基金supported by the Jilin Science and Technology Development Program,China (20240602032RC)the Jilin Agricultural Science and Technology Innovation Project,China (CXGC2024ZD001)+1 种基金the Jilin Agricultural Science and Technology Innovation Project,China (CXGC2024ZY012)the Jilin Province Development and Reform Commission-Project for Improving the Independent Innovation Capacity of Major Grain Crops,China (2024C002)。
文摘Emerging and powerful genome editing tools,particularly CRISPR/Cas9,are facilitating functional genomics research and accelerating crop improvement(Jiang et al.2021;Cao et al.2023;Chen C et al.2023;Liu et al.2023a).However,the detection and screening of transgenic lines remain major bottlenecks,being time-consuming,labor-intensive,and inefficient during transformation and subsequent mutation identification.A simple and efficient visual marker system plays a critical role in addressing these challenges.Recent studies demonstrated that the GmW1 and RUBY reporter systems were used to obtain visual transgenic soybean(Glycine max) plants(Chen L et al.2023;Chen et al.2024).
