The era of open science is upon us,and journals are finally beginning to mandate that analyses be fully reproducible.This entails providing both the methods and underlying data used,which will be critical for overcomi...The era of open science is upon us,and journals are finally beginning to mandate that analyses be fully reproducible.This entails providing both the methods and underlying data used,which will be critical for overcoming current biases in our knowledge of even the most basic distribution of species across the tree of life[1].These efforts are key for achieving FAIR(Findability,Accessibility,Interoperability,and Reuse)goals of transparent and interoperable scientific progress;[2].However,some ways that scientists share data are functionally more open than others,and even when data are said to be available upon request,the vast majority(83%)of queries are unfulfilled[3].Those data that are effectively unreachable,including those lacking sufficient meta-data,are declared“dark data”[4].Although a repository allowing straightforward direct data uploads(e.g,Dryad)might be sufficient to directly replicate a single study,these data are effectively inaccessible to downstream analyses without,in many cases,paper-by-paper approaches to searching for,downloading,and processing data due to lacking standards;some of these necessary papers are even at the risk of disappearing[5].In a world of increasingly large-scale analyses across space and time[6]using a variety of data types,dark data increasingly hinders us from understanding and preserving the natural world.展开更多
The mechanical properties of biological soft tissues play a critical role in the study of biomechanics and the development of protective measures against human injury.Various testing techniques at different scales hav...The mechanical properties of biological soft tissues play a critical role in the study of biomechanics and the development of protective measures against human injury.Various testing techniques at different scales have been employed to characterize the mechanical behavior of soft tissues,which is essential for developing accurate tissue simulants and numerical models.This review comprehensively explores the mechanical properties of soft tissues,examining experimental methods,mechanical models,numerical simulations,and the progress in materials that mimic the mechanical performance of soft tissues.Finally,it reviews the damage and protection of human tissues under kinetic impacts,anticipating the future construction of soft tissue surrogate targets.The aim is to provide a systematic theoretical foundation and the latest advancements in the field,addressing the design,preparation,and quantitative modeling of biomimetic materials,thereby promoting the in-depth development of soft tissue mechanics and its applications.展开更多
Dear Colleagues,It is my distinct honor to serve as the Honorary Chief Editor of AMEM,an international open-access journal,dedicated to serve as a platform for international exchange,and the translation of research ou...Dear Colleagues,It is my distinct honor to serve as the Honorary Chief Editor of AMEM,an international open-access journal,dedicated to serve as a platform for international exchange,and the translation of research outcomes in the field of life sciences.AMEM strives to establish itself as a high-level international academic exchange platform that brings together scientific wisdom from around the world and offers a prestigious journal for presenting research findings,and disseminating state of the art knowledge in the vibrant fields of life sciences.展开更多
Background: Biological maturation refers to the progressive process through which individuals transition toward an adult state during growth and development. To address the challenges posed by differences in biologica...Background: Biological maturation refers to the progressive process through which individuals transition toward an adult state during growth and development. To address the challenges posed by differences in biological maturity and the limitations of existing testing methods, particularly in adolescent sports contexts, there is a pressing need for a non-invasive method that is convenient, accurate, and broadly applicable to monitor the biological maturity of adolescent athletes comprehensively. In response to this need, a maturity assessment method based on the smartphone application Maturo has been developed. This study evaluates the accuracy and validity of the Maturo software, an automated tool for estimating biological age and related maturation metrics.Methods: A sample of 103 actively training teenage athletes aged 9-17 years. The sample included 76 males(age = 11.74 ± 1.55 years, mean ±SD) and 27 females(age = 13.95 ± 1.40 years), all without medical conditions that might impact growth or development.Results: Compared to traditional expert evaluations, the intraclass correlation coefficients(ICCs) and Pearson correlation coefficients demonstrated reliable positive correlations and significant agreement between the Maturo software and expert methods across multiple metrics, such as biological age(ICC = 0.965, R = 0.97), corrected biological age(ICC = 0.973, R = 0.99), predicted adult height(ICC = 0.991, R = 0.99), and percentage of adult height achieved(ICC = 0.955, R = 0.97). The Bland-Altman plots provided additional evidence of the validity of the Maturo software estimations, showing low systematic error in most measures. The linear regression analysis produced excellent adjusted R2values: 0.95for biological age and 0.99 for anticipated adult height. The Maturo approach demonstrated a high level of dependability in classifying teenagers into groups based on their maturity status and timing. The κ coefficients of 0.93 for maturity status and 0.82 for maturity timing indicate a nearly perfect agreement with the expert technique.Conclusion: While the Maturo software's non-invasive nature, cost-effectiveness, and ease of use could make it a potential tool for regular monitoring of growth and maturation in young athletes, its promising results in assessing maturation should be interpreted with caution due to limitations such as sample size and demographic constraints. Further longitude research with larger and more diverse populations is needed to validate these preliminary findings and strengthen the evidence for its broader applicability.展开更多
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
Numerous pathological states of the nervous system involve alterations in neuronal excitability and synaptic dysfunction,which depend on the function of ion channels.Due to their critical involvement in health and dis...Numerous pathological states of the nervous system involve alterations in neuronal excitability and synaptic dysfunction,which depend on the function of ion channels.Due to their critical involvement in health and disease,the search for new compounds that modulate these proteins is still relevant.Traditional medicine has long been a rich source of neuroactive compounds.For example,the indigenous Mapuche people have used the leaves and bark of the Drimys winteri tree for centuries to treat various diseases.Consequently,several studies have investigated the biological effects of compounds in Drimys winteri,highlighting sesquiterpenes such asα-humulene,drimenin,polygodial,andα-,β-,γ-eudesmol.However,there is currently no literature review focusing on the ability of these sesquiterpenes to modulate ion channels.This review summarizes the current knowledge about neuroactive compounds found in Drimys winteri,with special emphasis on their direct actions on neuronal ion channels.Several Drimys winteri sesquiterpenes modulate a diverse array of neuronal ion channels,including transient receptor potential channels,gamma-aminobutyric acid A receptors,nicotinic acetylcholine receptors,and voltage-dependent Ca^(2+)and Na^(+)channels.Interestingly,the modulation of these molecular targets by Drimys winteri sesquiterpenes correlates with their therapeutic actions.The promiscuous pharmacological profile of Drimys winteri sesquiterpenes suggests they modulate multiple protein targets in vivo,making them potentially useful for treating complex,multifactorial diseases.Further studies at the molecular level may aid in developing multitargeted drugs with enhanced therapeutic effects.展开更多
Ufmylation is an ubiquitin-like post-translational modification characterized by the covalent binding of mature UFM1 to target proteins.Although the consequences of ufmylation on target proteins are not fully understo...Ufmylation is an ubiquitin-like post-translational modification characterized by the covalent binding of mature UFM1 to target proteins.Although the consequences of ufmylation on target proteins are not fully understood,its importance is evident from the disorders resulting from its dysfunction.Numerous case reports have established a link between biallelic loss-of-function and/or hypomorphic variants in ufmylation-related genes and a spectrum of pediatric neurodevelopmental disorders.展开更多
Higher prevalence of sporadic Alzheimer’s disease in women:Alzheimer’s disease(AD)is a progressive neurodegenerative disorder caused by the accumulation of amyloid-β(Aβ)plaques and Tau neurofibrillary tangles in t...Higher prevalence of sporadic Alzheimer’s disease in women:Alzheimer’s disease(AD)is a progressive neurodegenerative disorder caused by the accumulation of amyloid-β(Aβ)plaques and Tau neurofibrillary tangles in the affected brain regions.The clearance of these pathological protein aggregates by microglia can trigger excessive neuroinflammation,which contributes to brain atrophy.AD exhibits clinical heterogeneity and is characterized by highly complex,multifactorial etiology(Lopez-Lee et al.,2024).展开更多
Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules form...Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules formation mechanism is conserved across species,from yeast to mammals,and they play a critical role in minimizing cellular damage during stress.Composed of heterogeneous ribonucleoprotein complexes,stress granules are enriched not only in mRNAs but also in noncoding RNAs and various proteins,including translation initiation factors and RNA-binding proteins.Genetic mutations affecting stress granule assembly and disassembly can lead to abnormal stress granule accumulation,contributing to the progression of several diseases.Recent research indicates that stress granule dynamics are pivotal in determining their physiological and pathological functions,with acute stress granule formation offering protection and chronic stress granule accumulation being detrimental.This review focuses on the multifaceted roles of stress granules under diverse physiological conditions,such as regulation of mRNA transport,mRNA translation,apoptosis,germ cell development,phase separation processes that govern stress granule formation,and their emerging implications in pathophysiological scenarios,such as viral infections,cancer,neurodevelopmental disorders,neurodegeneration,and neuronal trauma.展开更多
Alzheimer s disease is a neurodegenerative disorder that leads to progressive memory loss,cognitive decline,and behavioral changes.Des pite ongoing research,its exa ct causes and effective treatments remain elusive.Tr...Alzheimer s disease is a neurodegenerative disorder that leads to progressive memory loss,cognitive decline,and behavioral changes.Des pite ongoing research,its exa ct causes and effective treatments remain elusive.Traditional approaches have focused on symptom management,but breakthroughs in bioinformatics and high-thro ughput drug screening are offering new pathways to potential therapies.This review highlights our recent effo rts to identify novel drug candidates for Alzheimer's disease by leve raging computational methods and la rge-scale biological datasets.Our work introduces two key innovations in Alzheimer's disease research:addressing sex-specific diffe rences and leve raging drug repurposing for accelerated treatment discove ry.By combining sex-stratified preclinical data with machine learning and in vivo validation,we improve translational relevance and support precision medicine.Using the TgF344-AD rat model,which mimics human Alzheimer's disease spatial memory deficits and pathology,we explored the efficacy of various US Food and Drug Administrationapproved and investigational drugs.These included ibudilast,timapiprant,RG2833,diazoxide/dibenzoylmethane(combined),and BT-11,which targeted key Alzheimer's disease-related molecular pathways such as amyloid-beta plaques,Ta u tangles,and neuroinflammation.These drugs,at various stages of development,offer hope for not only managing symptoms but also addressing the underlying mechanisms of Alzheimer's disease.This review underscores the need for a multifaceted approach to Alzheimer's disease treatment,combining symptom relief with disease modification.展开更多
Reproductive diapause is an insect survival strategy in which reproduction temporarily halts in response to adverse environmental changes.This process is characterized by arrested ovarian development and lipid accumul...Reproductive diapause is an insect survival strategy in which reproduction temporarily halts in response to adverse environmental changes.This process is characterized by arrested ovarian development and lipid accumulation in females.A reduction in juvenile hormone(JH)biosynthesis is known to initiate reproductive diapause,but its regulatory mechanism remains unclear.Seven up(Svp),a transcription factor from the nuclear receptor family,plays a crucial role in various developmental processes in insects.In this study,using the cabbage beetle Colaphellus bowringi as a model,we observed higher expression of Svp in the heads of female adults under reproductive photoperiodic conditions(short-day[SD])compared to diapause conditions(long-day[LD]).RNA interference-mediated knockdown of Svp in SD females induced typical diapause phenotypes,including ovarian arrest and lipid accumulation.The application of methoprene(ME),a JH receptor agonist,reversed these diapause phenotypes and restored reproduction,indicating that Svp’s regulation of reproductive diapause is dependent on JH signaling.Additionally,Svp knockdown led to the downregulation of JH pathway genes and a reduction in JH titers.Further evidence suggested that Svp regulates the expression of JHAMT1,a critical gene in JH biosynthesis,which determines diapause entry in C.bowringi.These findings suggest that diapause-inducing photoperiods suppress Svp expression,blocking JH production and triggering diapause.This work reveals a critical transcription factor that regulates reproductive diapause initiation through modulating JH production,providing a potential target for controlling pests capable of entering reproductive diapause.展开更多
Objectives:Drug resistance is the major determinant of chemotherapy failure,leading to relapse and tumor progression,demonstrating the urgent need for novel antineoplastic drugs.This study aimed to evaluate the antica...Objectives:Drug resistance is the major determinant of chemotherapy failure,leading to relapse and tumor progression,demonstrating the urgent need for novel antineoplastic drugs.This study aimed to evaluate the anticancer potential of two novel pyrazole derivatives,P3C.1 and P3C.2,and to elucidate their mechanism of action in cancer cells.Methods:The cytotoxicity of the compounds was evaluated across 27 different cancer cell lines via a nuclear staining assay.Subsequent flow cytometric and biochemical analyses were performed to assess reactive oxygen species(ROS)generation,apoptosis induction,mitochondrial integrity,and cell cycle progression.Additional studies included transcriptome analyses and immunoassays to characterize the molecular mechanisms underlying drug activity.Results:Two novel pyrazole derivatives,P3C.1 and P3C.2,were identified with potent cytotoxicity on a variety of cancer cell lines.Among the adherent cell lines tested,the triple-negative breast cancer(TNBC)cell line MDA-MB-231 exhibited the highest sensitivity to both compounds and was therefore selected for further experimentation.In vitro assays demonstrated that both compounds induced ROS generation,mitochondrial membrane depolarization,cell cycle arrest and apoptosis.Whole-transcriptome sequencing of P3C.1 and P3C.2-treated MDA-MB-231 and two lymphoblastic leukemia cell lines revealed four genes in common associated with cell signaling and membrane dynamics.Connectivity Map(CMAP)database comparisons of shared genes for each cancer subtype revealed a strong similarity between the two compounds with tubulin inhibitors,and subsequent assays confirmed that these compounds act as microtubule-disrupting agents.Moreover,protein phosphorylation analysis indicated that both compounds induced hyperphosphorylation of JNK,and ERK1/2,along with hypophosphorylation of p38 kinases.Conclusions:P3C.1 and P3C.2 emerged as promising anti-breast cancer agents with dual mechanisms of action involving microtubule disruption and altered kinase signaling,leading to induction of apoptosis.展开更多
Targeted protein degradation(TPD)is an innovative strategy for selectively eliminating pathogenic proteins,enabling precise degradation of once-undruggable targets in cancer therapy.However,current TPD molecules are o...Targeted protein degradation(TPD)is an innovative strategy for selectively eliminating pathogenic proteins,enabling precise degradation of once-undruggable targets in cancer therapy.However,current TPD molecules are often limited by poor tumor targeting and the need for high doses.To overcome these limitations,assembly/disassembly-based TPD systems have been proposed to effectively degrade proteins of interest and enhance therapeutic efficacy.Herein,we summarize the recent advances in such TPD systems and categorize the strategies employed,including nanosphere morphology of assembled TPD systems,nanofiber morphology of assembled TPD systems,carrier-mediated TPD release systems,and stimulus-induced free TPD molecule formation nanosystems.Finally,we outline future directions and identify the remaining challenges in assembly/disassembly-based TPD systems.展开更多
The immune system is a complex protective network that is tightly controlled to protect and defend the host.Inflammation is a precisely regulated response that is crucial for host defense,while dysregulation can lead ...The immune system is a complex protective network that is tightly controlled to protect and defend the host.Inflammation is a precisely regulated response that is crucial for host defense,while dysregulation can lead to tissue damage and systemic diseases.Defining the mechanisms that initiate,amplify,and resolve inflammation is crucial for understanding our complex immune system.The inflammasome,a multiprotein complex that functions as a sensor,plays a key role in regulating this inflammatory response.Inflammasomes act as molecular platforms that integrate upstream danger signals,catalyze the activation of caspase-1,and drive the maturation and secretion of proinflammatory cytokines such as IL-1βand IL-18.These inflammatory cytokines are released through pyroptosis,a lytic form of programmed cell death that eliminates infected or damaged cells while simultaneously propagating inflammation through the release of cytokines or chemokines[1].展开更多
The addition of sarcomeres in series(sarcomerogenesis)in skeletal muscle has increasingly fascinated exercise scientists in recent years due to its potential to positively impact performance.1,2 In their new review ar...The addition of sarcomeres in series(sarcomerogenesis)in skeletal muscle has increasingly fascinated exercise scientists in recent years due to its potential to positively impact performance.1,2 In their new review article,Triggering sarcomerogenesis:Examining key stimuli and the role attributed to eccentric training—Historical,systematic,and meta-analytic review,Blazevich et al.3 provide a commendable overview of the history behind this area of research from the 1600s to present.展开更多
The generation of human induced pluripotent stem cell-derived motor neurons overcomes limited access to human tissues and offers an unprecedented approach to modeling motor neuron diseases such as dystonia and amyotro...The generation of human induced pluripotent stem cell-derived motor neurons overcomes limited access to human tissues and offers an unprecedented approach to modeling motor neuron diseases such as dystonia and amyotrophic lateral sclerosis.Motor neurons generated through different strategies may exhibit substantial differences in purity,maturation,characterization,and even neuronal identity,leading to variable outcomes in disease modeling and drug screening.However,very few comparative studies have been conducted to determine the similarities and differences among motor neurons prepared via different protocols.In this study,we prepared human induced pluripotent stem cell-derived motor neurons via lentiviral delivery of transcription factors and chemical induction and performed a systematic comparative analysis.We found that motor neurons generated by both approaches showed typical motor neuron morphology and robustly expressed motor neuron-specific markers,such as nuclear homeobox transcription factor 9 and choline acetyltransferase.The chemical induction protocol utilizes a combination of small molecules to induce motor neuron differentiation,offering a significantly faster maturation time of 35 days compared to 46 days with lentiviral delivery of transcription factors.Additionally,while lentiviral delivery of transcription factors are suitable for downstream biochemical analysis,chemical induction are more applicable for therapeutic approaches as they avoid the use of lentiviruses.Both approaches produce motor neurons with high purity(>95%)and yield.No significant differences were found between chemical induction and lentiviral delivery of transcription factors in terms of motor neuron markers and maturation markers.These robust methodologies offer researchers powerful tools for investigating motor neuron diseases and potential therapeutic strategies.展开更多
This study focuses on the vulnerability of soil carbon storage and the ecological restoration processes in karst regions.Given that land-use changes significantly influence the stability and functionality of soil carb...This study focuses on the vulnerability of soil carbon storage and the ecological restoration processes in karst regions.Given that land-use changes significantly influence the stability and functionality of soil carbon pools,this study investigated the vertical and temporal dynamics of soil organic carbon(SOC)and its labile fractions under five land-use types in a fragile karst region of Guizhou,China.Soil samples from five depths(0–100 cm)were collected in 2019 and 2020 from agricultural land,abandoned land,shrubland,and middle-aged and over-mature Pinus massoniana forests.Analyses showed that SOC,readily oxidizable organic carbon(ROOC),and watersoluble organic carbon(WSOC)decreased significantly with depth(P<0.001).Mean SOC was 10.51 g·kg^(-1),with the highest topsoil content in agricultural land(13.24–15.14 g·kg^(-1)).Shrubland exhibited the highest surface carbon sequestration efficiency,indicated by a Carbon Management Index(CMI)of 149.37 in the 0–20 cm layer and higher carbon pool activity(L=1.31 at 0–40 cm).Redundancy analysis identified total potassium,total phosphorus,and ROOC as key factors governing CMI variability(97.75%variance explained).The results advocate for stratified land management promoting shrubland for surface carbon sequestration and adopting reduced tillage in agriculture to enhance carbon retention in karst ecosystems.展开更多
This study investigates the genetic variability and environmental adaptability of Acacia hybrid clones across three distinct ecological regions,providing insights into growth characteristics and stem quality for futur...This study investigates the genetic variability and environmental adaptability of Acacia hybrid clones across three distinct ecological regions,providing insights into growth characteristics and stem quality for future breeding strategies.42 natural hybrid clones were evaluated over a five-year period in three clonal trials in northern,central and southern Vietnam for height(HT),diameter at breast height(DBH),volume(VOL),trunk straightness(STR),branch size(BRA)and survival.Significant clonal differences were found in all traits across all three regions.From age 2-5,the clone repeatability(H_(C)^(2))for growth traits improved from 0.19 to 0.59,indicating substantial genetic control.Genotypic coefficients of variation(CVG)for volume ranged from 21%to 34%,suggesting significant potential for genetic improvement.Site-to-site genotypic correlations ranged from 0.53 to 0.78,pointing to the existence of genotype-environment interactions.Clones derived from Acacia mangium material demonstrated enhanced growth,while the hybrid clones exhibited superior stem quality,particularly in terms of straightness.The findings emphasize the importance of selecting clones that are adapted to specific environmental conditions,with both growth and quality traits considered in breeding programs.展开更多
The Earth's environment is undergoing significant transformation due to mining,pollution,and climate change.Although mining is essential for economic development,it contributes significantly to the release of pote...The Earth's environment is undergoing significant transformation due to mining,pollution,and climate change.Although mining is essential for economic development,it contributes significantly to the release of potentially harmful elements(PHEs)that threaten human health and destabilize microbial communities.Anthropogenic climate change,driven by greenhouse gas emissions,alters water availability and soil composition,further affecting ecosystem balance and microbial diversity.This review aggregates findings from studies covering the last two decades to assess how mining pollution and climate change impact microbial diversity,their adaptation mechanisms,and the associated health risks.It reveals that environmental stressors favour resistant microbial taxa while eliminating sensitive species,thereby reshaping microbial ecosystems.Microorganisms demonstrate genetic,biochemical,and physiological adaptations that enable them to survive in polluted or changing environments,often resulting in a higher prevalence of pathogenic and antibiotic-resistant strains.These variations in microbial dynamics contribute to health challenges such as respiratory infections,foodborne illnesses,and increased exposure in children and immune-compromised individuals.The review highlights the linkages between environmental degradation,microbial ecology,and human health,underscoring the need for integrative policies and interventions to mitigate long-term risks,support microbial ecosystem stability,promote sustainable health and agricultural outcomes.展开更多
文摘The era of open science is upon us,and journals are finally beginning to mandate that analyses be fully reproducible.This entails providing both the methods and underlying data used,which will be critical for overcoming current biases in our knowledge of even the most basic distribution of species across the tree of life[1].These efforts are key for achieving FAIR(Findability,Accessibility,Interoperability,and Reuse)goals of transparent and interoperable scientific progress;[2].However,some ways that scientists share data are functionally more open than others,and even when data are said to be available upon request,the vast majority(83%)of queries are unfulfilled[3].Those data that are effectively unreachable,including those lacking sufficient meta-data,are declared“dark data”[4].Although a repository allowing straightforward direct data uploads(e.g,Dryad)might be sufficient to directly replicate a single study,these data are effectively inaccessible to downstream analyses without,in many cases,paper-by-paper approaches to searching for,downloading,and processing data due to lacking standards;some of these necessary papers are even at the risk of disappearing[5].In a world of increasingly large-scale analyses across space and time[6]using a variety of data types,dark data increasingly hinders us from understanding and preserving the natural world.
基金supported by the National Natural Science Foundation of China(Grant No.U2241273)the Beijing Municipal Natural Science Foundation(Grant No.Z240017)+3 种基金the 111 project(Grant No.B13003)the Fundamental Research Funds for the Central Universitiesthe China Scholarship Councilthe Academic Excellence Foundation of BUAA for PhD Students.
文摘The mechanical properties of biological soft tissues play a critical role in the study of biomechanics and the development of protective measures against human injury.Various testing techniques at different scales have been employed to characterize the mechanical behavior of soft tissues,which is essential for developing accurate tissue simulants and numerical models.This review comprehensively explores the mechanical properties of soft tissues,examining experimental methods,mechanical models,numerical simulations,and the progress in materials that mimic the mechanical performance of soft tissues.Finally,it reviews the damage and protection of human tissues under kinetic impacts,anticipating the future construction of soft tissue surrogate targets.The aim is to provide a systematic theoretical foundation and the latest advancements in the field,addressing the design,preparation,and quantitative modeling of biomimetic materials,thereby promoting the in-depth development of soft tissue mechanics and its applications.
文摘Dear Colleagues,It is my distinct honor to serve as the Honorary Chief Editor of AMEM,an international open-access journal,dedicated to serve as a platform for international exchange,and the translation of research outcomes in the field of life sciences.AMEM strives to establish itself as a high-level international academic exchange platform that brings together scientific wisdom from around the world and offers a prestigious journal for presenting research findings,and disseminating state of the art knowledge in the vibrant fields of life sciences.
文摘Background: Biological maturation refers to the progressive process through which individuals transition toward an adult state during growth and development. To address the challenges posed by differences in biological maturity and the limitations of existing testing methods, particularly in adolescent sports contexts, there is a pressing need for a non-invasive method that is convenient, accurate, and broadly applicable to monitor the biological maturity of adolescent athletes comprehensively. In response to this need, a maturity assessment method based on the smartphone application Maturo has been developed. This study evaluates the accuracy and validity of the Maturo software, an automated tool for estimating biological age and related maturation metrics.Methods: A sample of 103 actively training teenage athletes aged 9-17 years. The sample included 76 males(age = 11.74 ± 1.55 years, mean ±SD) and 27 females(age = 13.95 ± 1.40 years), all without medical conditions that might impact growth or development.Results: Compared to traditional expert evaluations, the intraclass correlation coefficients(ICCs) and Pearson correlation coefficients demonstrated reliable positive correlations and significant agreement between the Maturo software and expert methods across multiple metrics, such as biological age(ICC = 0.965, R = 0.97), corrected biological age(ICC = 0.973, R = 0.99), predicted adult height(ICC = 0.991, R = 0.99), and percentage of adult height achieved(ICC = 0.955, R = 0.97). The Bland-Altman plots provided additional evidence of the validity of the Maturo software estimations, showing low systematic error in most measures. The linear regression analysis produced excellent adjusted R2values: 0.95for biological age and 0.99 for anticipated adult height. The Maturo approach demonstrated a high level of dependability in classifying teenagers into groups based on their maturity status and timing. The κ coefficients of 0.93 for maturity status and 0.82 for maturity timing indicate a nearly perfect agreement with the expert technique.Conclusion: While the Maturo software's non-invasive nature, cost-effectiveness, and ease of use could make it a potential tool for regular monitoring of growth and maturation in young athletes, its promising results in assessing maturation should be interpreted with caution due to limitations such as sample size and demographic constraints. Further longitude research with larger and more diverse populations is needed to validate these preliminary findings and strengthen the evidence for its broader applicability.
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supported by ANID-FONDECYT 1200908(to JF),ANID-FONDECYT 1211082 and 1250856(to GEY)by the Millennium Nucleus for the Study of Pain NCN19_038(Mi Nu SPain)(to GEY)funded by the ANID scholarship 21201176。
文摘Numerous pathological states of the nervous system involve alterations in neuronal excitability and synaptic dysfunction,which depend on the function of ion channels.Due to their critical involvement in health and disease,the search for new compounds that modulate these proteins is still relevant.Traditional medicine has long been a rich source of neuroactive compounds.For example,the indigenous Mapuche people have used the leaves and bark of the Drimys winteri tree for centuries to treat various diseases.Consequently,several studies have investigated the biological effects of compounds in Drimys winteri,highlighting sesquiterpenes such asα-humulene,drimenin,polygodial,andα-,β-,γ-eudesmol.However,there is currently no literature review focusing on the ability of these sesquiterpenes to modulate ion channels.This review summarizes the current knowledge about neuroactive compounds found in Drimys winteri,with special emphasis on their direct actions on neuronal ion channels.Several Drimys winteri sesquiterpenes modulate a diverse array of neuronal ion channels,including transient receptor potential channels,gamma-aminobutyric acid A receptors,nicotinic acetylcholine receptors,and voltage-dependent Ca^(2+)and Na^(+)channels.Interestingly,the modulation of these molecular targets by Drimys winteri sesquiterpenes correlates with their therapeutic actions.The promiscuous pharmacological profile of Drimys winteri sesquiterpenes suggests they modulate multiple protein targets in vivo,making them potentially useful for treating complex,multifactorial diseases.Further studies at the molecular level may aid in developing multitargeted drugs with enhanced therapeutic effects.
文摘Ufmylation is an ubiquitin-like post-translational modification characterized by the covalent binding of mature UFM1 to target proteins.Although the consequences of ufmylation on target proteins are not fully understood,its importance is evident from the disorders resulting from its dysfunction.Numerous case reports have established a link between biallelic loss-of-function and/or hypomorphic variants in ufmylation-related genes and a spectrum of pediatric neurodevelopmental disorders.
基金supported by Temasek Life Sciences Laboratory core funding(3160)(to CTO).
文摘Higher prevalence of sporadic Alzheimer’s disease in women:Alzheimer’s disease(AD)is a progressive neurodegenerative disorder caused by the accumulation of amyloid-β(Aβ)plaques and Tau neurofibrillary tangles in the affected brain regions.The clearance of these pathological protein aggregates by microglia can trigger excessive neuroinflammation,which contributes to brain atrophy.AD exhibits clinical heterogeneity and is characterized by highly complex,multifactorial etiology(Lopez-Lee et al.,2024).
基金supported by a grant from the Merkin Peripheral Neuropathy and Nerve Regeneration Center(to PKS)the Rutgers University Startup Fund(to PKS).
文摘Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules formation mechanism is conserved across species,from yeast to mammals,and they play a critical role in minimizing cellular damage during stress.Composed of heterogeneous ribonucleoprotein complexes,stress granules are enriched not only in mRNAs but also in noncoding RNAs and various proteins,including translation initiation factors and RNA-binding proteins.Genetic mutations affecting stress granule assembly and disassembly can lead to abnormal stress granule accumulation,contributing to the progression of several diseases.Recent research indicates that stress granule dynamics are pivotal in determining their physiological and pathological functions,with acute stress granule formation offering protection and chronic stress granule accumulation being detrimental.This review focuses on the multifaceted roles of stress granules under diverse physiological conditions,such as regulation of mRNA transport,mRNA translation,apoptosis,germ cell development,phase separation processes that govern stress granule formation,and their emerging implications in pathophysiological scenarios,such as viral infections,cancer,neurodevelopmental disorders,neurodegeneration,and neuronal trauma.
基金National Institutes of Health,No.R01AG057555(to PI,L.Xie,co-l,MEFP,PAS,PR)。
文摘Alzheimer s disease is a neurodegenerative disorder that leads to progressive memory loss,cognitive decline,and behavioral changes.Des pite ongoing research,its exa ct causes and effective treatments remain elusive.Traditional approaches have focused on symptom management,but breakthroughs in bioinformatics and high-thro ughput drug screening are offering new pathways to potential therapies.This review highlights our recent effo rts to identify novel drug candidates for Alzheimer's disease by leve raging computational methods and la rge-scale biological datasets.Our work introduces two key innovations in Alzheimer's disease research:addressing sex-specific diffe rences and leve raging drug repurposing for accelerated treatment discove ry.By combining sex-stratified preclinical data with machine learning and in vivo validation,we improve translational relevance and support precision medicine.Using the TgF344-AD rat model,which mimics human Alzheimer's disease spatial memory deficits and pathology,we explored the efficacy of various US Food and Drug Administrationapproved and investigational drugs.These included ibudilast,timapiprant,RG2833,diazoxide/dibenzoylmethane(combined),and BT-11,which targeted key Alzheimer's disease-related molecular pathways such as amyloid-beta plaques,Ta u tangles,and neuroinflammation.These drugs,at various stages of development,offer hope for not only managing symptoms but also addressing the underlying mechanisms of Alzheimer's disease.This review underscores the need for a multifaceted approach to Alzheimer's disease treatment,combining symptom relief with disease modification.
基金funded by the National Natural Science Foundation of China,China(grant no.32472543).
文摘Reproductive diapause is an insect survival strategy in which reproduction temporarily halts in response to adverse environmental changes.This process is characterized by arrested ovarian development and lipid accumulation in females.A reduction in juvenile hormone(JH)biosynthesis is known to initiate reproductive diapause,but its regulatory mechanism remains unclear.Seven up(Svp),a transcription factor from the nuclear receptor family,plays a crucial role in various developmental processes in insects.In this study,using the cabbage beetle Colaphellus bowringi as a model,we observed higher expression of Svp in the heads of female adults under reproductive photoperiodic conditions(short-day[SD])compared to diapause conditions(long-day[LD]).RNA interference-mediated knockdown of Svp in SD females induced typical diapause phenotypes,including ovarian arrest and lipid accumulation.The application of methoprene(ME),a JH receptor agonist,reversed these diapause phenotypes and restored reproduction,indicating that Svp’s regulation of reproductive diapause is dependent on JH signaling.Additionally,Svp knockdown led to the downregulation of JH pathway genes and a reduction in JH titers.Further evidence suggested that Svp regulates the expression of JHAMT1,a critical gene in JH biosynthesis,which determines diapause entry in C.bowringi.These findings suggest that diapause-inducing photoperiods suppress Svp expression,blocking JH production and triggering diapause.This work reveals a critical transcription factor that regulates reproductive diapause initiation through modulating JH production,providing a potential target for controlling pests capable of entering reproductive diapause.
基金supported by NIH grant 1R16GM149379 to Renato J.Aguilerasupported by the core facilities of the BBRC,funded by the Research Centers in Minority Institutions grant 5U54MD007592 from the National Institute on Minority Health and Health Disparities to Robert A.Kirkensupported Denisse A.Gutierrez,Ana P.Betancourt,Elisa Robles-Escajeda and Armando Varela-Ramirez。
文摘Objectives:Drug resistance is the major determinant of chemotherapy failure,leading to relapse and tumor progression,demonstrating the urgent need for novel antineoplastic drugs.This study aimed to evaluate the anticancer potential of two novel pyrazole derivatives,P3C.1 and P3C.2,and to elucidate their mechanism of action in cancer cells.Methods:The cytotoxicity of the compounds was evaluated across 27 different cancer cell lines via a nuclear staining assay.Subsequent flow cytometric and biochemical analyses were performed to assess reactive oxygen species(ROS)generation,apoptosis induction,mitochondrial integrity,and cell cycle progression.Additional studies included transcriptome analyses and immunoassays to characterize the molecular mechanisms underlying drug activity.Results:Two novel pyrazole derivatives,P3C.1 and P3C.2,were identified with potent cytotoxicity on a variety of cancer cell lines.Among the adherent cell lines tested,the triple-negative breast cancer(TNBC)cell line MDA-MB-231 exhibited the highest sensitivity to both compounds and was therefore selected for further experimentation.In vitro assays demonstrated that both compounds induced ROS generation,mitochondrial membrane depolarization,cell cycle arrest and apoptosis.Whole-transcriptome sequencing of P3C.1 and P3C.2-treated MDA-MB-231 and two lymphoblastic leukemia cell lines revealed four genes in common associated with cell signaling and membrane dynamics.Connectivity Map(CMAP)database comparisons of shared genes for each cancer subtype revealed a strong similarity between the two compounds with tubulin inhibitors,and subsequent assays confirmed that these compounds act as microtubule-disrupting agents.Moreover,protein phosphorylation analysis indicated that both compounds induced hyperphosphorylation of JNK,and ERK1/2,along with hypophosphorylation of p38 kinases.Conclusions:P3C.1 and P3C.2 emerged as promising anti-breast cancer agents with dual mechanisms of action involving microtubule disruption and altered kinase signaling,leading to induction of apoptosis.
基金supported by NIGMS(SC1GM140907 to G.-Y.L.)the Prostate Cancer Research Racial Disparity Grant from the Prostate Cancer Research(PCR)in the United Kingdom(grant reference[5001],to G.-Y.L.)the AU Medical Center,Inc.with a Grant/Contract Number CAU-AU Partnership-Kavuri-Liou and by NIMHDsupported Research Capacity Core at CAU(U54MD007590)。
基金supported by National Natural Science Foundation of China(Grant 22407024)the Star-up Research Fund of Southeast University(RF1028624094)(X.W.)+7 种基金the China Postdoctoral Science Foundation(Grant 2025M772911)Natural Science Foundation of Jiangsu Province(Grants BK20251303)(X.L.)Postdoctoral Fellowship Program of CPSF(Grant GZC20251914)(X.L.)Jiangsu Funding Program for Excellent Postdoctoral Talent(Grant 2025ZB052)(X.L.)National Natural Science Foundation of China(Grant 22234002)(G.L.)National Key Research and Development Program of China(Grant 2023YFF0724100)(G.L.)Natural Science Foundation of Jiangsu Province(Grant BK20232007)(G.L.)Jiangsu ShuangChuang Team(Grant JSSCTD202409)(G.L.and X.W.).
文摘Targeted protein degradation(TPD)is an innovative strategy for selectively eliminating pathogenic proteins,enabling precise degradation of once-undruggable targets in cancer therapy.However,current TPD molecules are often limited by poor tumor targeting and the need for high doses.To overcome these limitations,assembly/disassembly-based TPD systems have been proposed to effectively degrade proteins of interest and enhance therapeutic efficacy.Herein,we summarize the recent advances in such TPD systems and categorize the strategies employed,including nanosphere morphology of assembled TPD systems,nanofiber morphology of assembled TPD systems,carrier-mediated TPD release systems,and stimulus-induced free TPD molecule formation nanosystems.Finally,we outline future directions and identify the remaining challenges in assembly/disassembly-based TPD systems.
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(2022R1C1C1007544,2024M3A9H5043152 to S.L.)a grant from the Korea Drug Development Fund funded by the Ministry of Science and ICT+7 种基金the Ministry of Trade,Industry,and Energythe Ministry of Health and Welfare(RS-2025--02222987 to S.L.)a grant from the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea,under the Korea Health Technology R&D Project(RS-2022--KH128422(HV22C015600)to S.L.)the Institute for Basic Science(IBS),Republic of Korea(IBS-R801--D9-A09,IBS-R801-D1-2025-a02 to S.L.)supported by the Circle Foundation(Republic of Korea)through the selection of the UNIST Pandemic Treatment Research Center as the 2023 Circle Foundation Innovative Science Technology Center(2023 TCF Innovative Science Project-01 to S.L.)Additionally,this study received funding from the Republic of Korea’s National Institute of Health(Project No.#2025ER160200,#2025ER240100 to S.L.)Additional support was provided by research funds from the Ulsan National Institute of Science&Technology(UNIST)(1.220112.01,1.220107.01 to S.L.)a grant from Yuhan Corporation(S.L.).
文摘The immune system is a complex protective network that is tightly controlled to protect and defend the host.Inflammation is a precisely regulated response that is crucial for host defense,while dysregulation can lead to tissue damage and systemic diseases.Defining the mechanisms that initiate,amplify,and resolve inflammation is crucial for understanding our complex immune system.The inflammasome,a multiprotein complex that functions as a sensor,plays a key role in regulating this inflammatory response.Inflammasomes act as molecular platforms that integrate upstream danger signals,catalyze the activation of caspase-1,and drive the maturation and secretion of proinflammatory cytokines such as IL-1βand IL-18.These inflammatory cytokines are released through pyroptosis,a lytic form of programmed cell death that eliminates infected or damaged cells while simultaneously propagating inflammation through the release of cytokines or chemokines[1].
文摘The addition of sarcomeres in series(sarcomerogenesis)in skeletal muscle has increasingly fascinated exercise scientists in recent years due to its potential to positively impact performance.1,2 In their new review article,Triggering sarcomerogenesis:Examining key stimuli and the role attributed to eccentric training—Historical,systematic,and meta-analytic review,Blazevich et al.3 provide a commendable overview of the history behind this area of research from the 1600s to present.
基金National Institute of Health(NIH)National Institute of Neurological Disorders and Stroke(NINDS),Nos.NS112910,NS133252(to BD)Department of Defense(DoD)Peer Reviewed Medical Research Program(PRMRP)Discovery Award,No.W81XWH2010186(to BD).
文摘The generation of human induced pluripotent stem cell-derived motor neurons overcomes limited access to human tissues and offers an unprecedented approach to modeling motor neuron diseases such as dystonia and amyotrophic lateral sclerosis.Motor neurons generated through different strategies may exhibit substantial differences in purity,maturation,characterization,and even neuronal identity,leading to variable outcomes in disease modeling and drug screening.However,very few comparative studies have been conducted to determine the similarities and differences among motor neurons prepared via different protocols.In this study,we prepared human induced pluripotent stem cell-derived motor neurons via lentiviral delivery of transcription factors and chemical induction and performed a systematic comparative analysis.We found that motor neurons generated by both approaches showed typical motor neuron morphology and robustly expressed motor neuron-specific markers,such as nuclear homeobox transcription factor 9 and choline acetyltransferase.The chemical induction protocol utilizes a combination of small molecules to induce motor neuron differentiation,offering a significantly faster maturation time of 35 days compared to 46 days with lentiviral delivery of transcription factors.Additionally,while lentiviral delivery of transcription factors are suitable for downstream biochemical analysis,chemical induction are more applicable for therapeutic approaches as they avoid the use of lentiviruses.Both approaches produce motor neurons with high purity(>95%)and yield.No significant differences were found between chemical induction and lentiviral delivery of transcription factors in terms of motor neuron markers and maturation markers.These robust methodologies offer researchers powerful tools for investigating motor neuron diseases and potential therapeutic strategies.
基金the financial support from the National Natural Science Foundation of China(Projects No.32360379 and No.32360007)the Guizhou Provincial Department of Science and Technology Guizhou Provincial Basic Research Program of Natural Science(Project No.qjhe-MS[2025]211)+1 种基金the Guizhou Provincial Postgraduate Research Fund(Project No.2024YJSKYJJ230)the PhD Project of Guizhou Normal University(Project No.2019BS003)。
文摘This study focuses on the vulnerability of soil carbon storage and the ecological restoration processes in karst regions.Given that land-use changes significantly influence the stability and functionality of soil carbon pools,this study investigated the vertical and temporal dynamics of soil organic carbon(SOC)and its labile fractions under five land-use types in a fragile karst region of Guizhou,China.Soil samples from five depths(0–100 cm)were collected in 2019 and 2020 from agricultural land,abandoned land,shrubland,and middle-aged and over-mature Pinus massoniana forests.Analyses showed that SOC,readily oxidizable organic carbon(ROOC),and watersoluble organic carbon(WSOC)decreased significantly with depth(P<0.001).Mean SOC was 10.51 g·kg^(-1),with the highest topsoil content in agricultural land(13.24–15.14 g·kg^(-1)).Shrubland exhibited the highest surface carbon sequestration efficiency,indicated by a Carbon Management Index(CMI)of 149.37 in the 0–20 cm layer and higher carbon pool activity(L=1.31 at 0–40 cm).Redundancy analysis identified total potassium,total phosphorus,and ROOC as key factors governing CMI variability(97.75%variance explained).The results advocate for stratified land management promoting shrubland for surface carbon sequestration and adopting reduced tillage in agriculture to enhance carbon retention in karst ecosystems.
基金funded by the project:Breeding and selection of Acacia hybrids and Acacia auriculiformis for large-timber plantation establishment in major ecological zones(000.00.16.G06-230504-0003).
文摘This study investigates the genetic variability and environmental adaptability of Acacia hybrid clones across three distinct ecological regions,providing insights into growth characteristics and stem quality for future breeding strategies.42 natural hybrid clones were evaluated over a five-year period in three clonal trials in northern,central and southern Vietnam for height(HT),diameter at breast height(DBH),volume(VOL),trunk straightness(STR),branch size(BRA)and survival.Significant clonal differences were found in all traits across all three regions.From age 2-5,the clone repeatability(H_(C)^(2))for growth traits improved from 0.19 to 0.59,indicating substantial genetic control.Genotypic coefficients of variation(CVG)for volume ranged from 21%to 34%,suggesting significant potential for genetic improvement.Site-to-site genotypic correlations ranged from 0.53 to 0.78,pointing to the existence of genotype-environment interactions.Clones derived from Acacia mangium material demonstrated enhanced growth,while the hybrid clones exhibited superior stem quality,particularly in terms of straightness.The findings emphasize the importance of selecting clones that are adapted to specific environmental conditions,with both growth and quality traits considered in breeding programs.
基金the Copperbelt University Africa Centre of Excellence for Sustainable Mining(CBUACESM)at Copperbelt University in Kitwe,Zambia for funding this work。
文摘The Earth's environment is undergoing significant transformation due to mining,pollution,and climate change.Although mining is essential for economic development,it contributes significantly to the release of potentially harmful elements(PHEs)that threaten human health and destabilize microbial communities.Anthropogenic climate change,driven by greenhouse gas emissions,alters water availability and soil composition,further affecting ecosystem balance and microbial diversity.This review aggregates findings from studies covering the last two decades to assess how mining pollution and climate change impact microbial diversity,their adaptation mechanisms,and the associated health risks.It reveals that environmental stressors favour resistant microbial taxa while eliminating sensitive species,thereby reshaping microbial ecosystems.Microorganisms demonstrate genetic,biochemical,and physiological adaptations that enable them to survive in polluted or changing environments,often resulting in a higher prevalence of pathogenic and antibiotic-resistant strains.These variations in microbial dynamics contribute to health challenges such as respiratory infections,foodborne illnesses,and increased exposure in children and immune-compromised individuals.The review highlights the linkages between environmental degradation,microbial ecology,and human health,underscoring the need for integrative policies and interventions to mitigate long-term risks,support microbial ecosystem stability,promote sustainable health and agricultural outcomes.
