This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to...This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to both screening and diagnosis.For the clinical adaptation of AI,several challenges remain for its effective translation.The establishment of high-quality clinical databases,such as the National Clinical Database and Japan Endoscopy Database in Japan,which covers almost all cases of esophageal cancer,is essential for validating multimodal AI models.This requires rigorous external validation using diverse datasets,including those from different endoscope manufacturers and image qualities.Furthermore,endoscopists’skills significantly affect diagnostic accuracy,suggesting that AI should serve as a supportive tool rather than a replacement.Addressing these challenges,along with country-specific legal and ethical considerations,will facilitate the successful integration of multimodal AI into the management of esophageal cancer,particularly in endoscopic diagnosis,and contribute to improved patient outcomes.Although this review focused on Japan as a case study,the challenges and solutions described are broadly applicable to other high-incidence regions.展开更多
The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evi...The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.展开更多
Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated...Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).展开更多
The neuromuscular junction and its proregenerative niche:The mammalian peripheral nervous system,unlike the central nervous system,has preserved throughout evolution the ability to regenerate and fully restore functio...The neuromuscular junction and its proregenerative niche:The mammalian peripheral nervous system,unlike the central nervous system,has preserved throughout evolution the ability to regenerate and fully restore function.Key factors for effective nerve regeneration include a supportive neuronal environment and a coordinated tissue response(Brosius Lutz and Barres,2014).展开更多
Myelination,the continuous ensheathment of neuronal axons,is a lifelong process in the nervous system that is essential for the precise,temporospatial conduction of action potentials between neurons.Myelin also provid...Myelination,the continuous ensheathment of neuronal axons,is a lifelong process in the nervous system that is essential for the precise,temporospatial conduction of action potentials between neurons.Myelin also provides intercellular metabolic support to axons.Even minor disruptions in the integrity of myelin can impair neural performance and increase susceptibility to neurological diseases.In fact,myelin degeneration is a well-known neuropathological condition that is associated with normal aging and several neurodegenerative diseases,including multiple sclerosis and Alzheimer’s disease.In the central nervous system,compact myelin sheaths are formed by fully mature oligodendrocytes.However,the entire oligodendrocyte lineage is susceptible to changes in the biological microenvironment and other risk factors that arise as the brain ages.In addition to their well-known role in action potential propagation,oligodendrocytes also provide intercellular metabolic support to axons by transferring energy metabolites and delivering exosomes.Therefore,myelin degeneration in the aging central nervous system is a significant contributor to the development of neurodegenerative diseases.Interventions that mitigate age-related myelin degeneration can improve neurological function in aging individuals.In this review,we investigate the changes in myelin that are associated with aging and their underlying mechanisms.We also discuss recent advances in understanding how myelin degeneration in the aging brain contributes to neurodegenerative diseases and explore the factors that can prevent,slow down,or even reverse age-related myelin degeneration.Future research will enhance our understanding of how reducing age-related myelin degeneration can be used as a therapeutic target for delaying or preventing neurodegenerative diseases.展开更多
Extreme cold weather seriously harms human thermoregulatory system,necessitating high-performance insulating garments to maintain body temperature.However,as the core insulating layer,advanced fibrous materials always...Extreme cold weather seriously harms human thermoregulatory system,necessitating high-performance insulating garments to maintain body temperature.However,as the core insulating layer,advanced fibrous materials always struggle to balance mechanical properties and thermal insulation,resulting in their inability to meet the demands for both washing resistance and personal protection.Herein,inspired by the natural spring-like structures of cucumber tendrils,a superelastic and washable micro/nanofibrous sponge(MNFS)based on biomimetic helical fibers is directly prepared utilizing multiple-jet electrospinning technology for high-performance thermal insulation.By regulating the conductivity of polyvinylidene fluoride solution,multiple-jet ejection and multiple-stage whipping of jets are achieved,and further control of phase separation rates enables the rapid solidification of jets to form spring-like helical fibers,which are directly entangled to assemble MNFS.The resulting MNFS exhibits superelasticity that can withstand large tensile strain(200%),1000 cyclic tensile or compression deformations,and retain good resilience even in liquid nitrogen(-196℃).Furthermore,the MNFS shows efficient thermal insulation with low thermal conductivity(24.85 mW m^(-1)K^(-1)),close to the value of dry air,and remains structural stability even after cyclic washing.This work offers new possibilities for advanced fibrous sponges in transportation,environmental,and energy applications.展开更多
Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival a...Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.展开更多
Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for sign...Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.展开更多
The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly f...The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area.However,only a small percentage of these neurons survive,and many do not reach the damaged area,possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex.A second major obstacle to stem cell therapy is the strong inflammatory reaction induced by cerebral ischemia,whereby the associated phagocytic activity of brain macrophages removes both therapeutic cells and/or cell-based drug carriers.To address these issues,neurogenesis was electrically stimulated in the subventricular zone,followed by isolation of proliferating cells,including newly formed neurons,which were subsequently mixed with a nutritional hydrogel.This mixture was then transferred to the stroke cavity of day 14 post-stroke mice.We found that the performance of the treated animals improved in behavioral tests,including novel object,open field,hole board,grooming,and“time-to-feel”adhesive tape tests.Furthermore,immunostaining revealed that the stem cell marker nestin,the neuroepithelial marker Mash1,and the immature neuronal marker doublecortin-positive cells survived in the transplanted area for 2 weeks,possibly due to reduced phagocytic activity and supportive angiogenesis.These results clearly indicate that the transplantation of committed subventricular zone stem cells combined with a protective nutritional gel directly into the infarct cavity after the peak of stroke-induced neuroinflammation represents a feasible approach to improve neurorestoration after cerebral ischemia.展开更多
The rapid growth of biomedical data,particularly multi-omics data including genomes,transcriptomics,proteomics,metabolomics,and epigenomics,medical research and clinical decision-making confront both new opportunities...The rapid growth of biomedical data,particularly multi-omics data including genomes,transcriptomics,proteomics,metabolomics,and epigenomics,medical research and clinical decision-making confront both new opportunities and obstacles.The huge and diversified nature of these datasets cannot always be managed using traditional data analysis methods.As a consequence,deep learning has emerged as a strong tool for analysing numerous omics data due to its ability to handle complex and non-linear relationships.This paper explores the fundamental concepts of deep learning and how they are used in multi-omics medical data mining.We demonstrate how autoencoders,variational autoencoders,multimodal models,attention mechanisms,transformers,and graph neural networks enable pattern analysis and recognition across all omics data.Deep learning has been found to be effective in illness classification,biomarker identification,gene network learning,and therapeutic efficacy prediction.We also consider critical problems like as data quality,model explainability,whether findings can be repeated,and computational power requirements.We now consider future elements of combining omics with clinical and imaging data,explainable AI,federated learning,and real-time diagnostics.Overall,this study emphasises the need of collaborating across disciplines to advance deep learning-based multi-omics research for precision medicine and comprehending complicated disorders.展开更多
Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the ...Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies. Astrocytes, the largest group of nonneuronal cells in the central nervous system, play several crucial roles in maintaining ionic and energy metabolic homeostasis in neurons, regulating neurotransmitter levels, and modulating synaptic plasticity. This article briefly reviews the critical role of astrocytes in maintaining balance within the central nervous system. Building on previous research, we discuss how astrocyte dysfunction contributes to the onset and progression of epilepsy through four key aspects: the imbalance between excitatory and inhibitory neuronal signaling, dysregulation of metabolic homeostasis in the neuronal microenvironment, neuroinflammation, and the formation of abnormal neural circuits. We summarize relevant basic research conducted over the past 5 years that has focused on modulating astrocytes as a therapeutic approach for epilepsy. We categorize the therapeutic targets proposed by these studies into four areas: restoration of the excitation–inhibition balance, reestablishment of metabolic homeostasis, modulation of immune and inflammatory responses, and reconstruction of abnormal neural circuits. These targets correspond to the pathophysiological mechanisms by which astrocytes contribute to epilepsy. Additionally, we need to consider the potential challenges and limitations of translating these identified therapeutic targets into clinical treatments. These limitations arise from interspecies differences between humans and animal models, as well as the complex comorbidities associated with epilepsy in humans. We also highlight valuable future research directions worth exploring in the treatment of epilepsy and the regulation of astrocytes, such as gene therapy and imaging strategies. The findings presented in this review may help open new therapeutic avenues for patients with drugresistant epilepsy and for those suffering from other central nervous system disorders associated with astrocytic dysfunction.展开更多
Nanoparticles are increasingly being recognized for their potential utility in biological applications including nanomedicine.Here,we have synthesized zinc oxide(ZnO)nanorods using zinc acetate and hexamethylenetetram...Nanoparticles are increasingly being recognized for their potential utility in biological applications including nanomedicine.Here,we have synthesized zinc oxide(ZnO)nanorods using zinc acetate and hexamethylenetetramine as precursors followed by characterizing using X-ray diffraction,fourier transform infrared spectroscopy,scanning electron microscopy and transmission electron microscopy.The growth of synthesized zinc oxide nanorods was found to be very close to its hexagonal nature,which is confirmed by X-ray diffraction.The nanorod was grown perpendicular to the long-axis and grew along the[001]direction,which is the nature of ZnO growth.The morphology of synthesized ZnO nanorods from the individual crystalline nucleus was confirmed by scanning and transmission electron microscopy.The length of the nanorod was estimated to be around 21 nm in diameter and 50 nm in length.Our toxicology studies showed that synthesized ZnO nanorods exposure on hela cells has no significant induction of oxidative stress or cell death even in higher concentration(10μg/ml).The results suggest that ZnO nanorods might be a safer nanomaterial for biological applications.展开更多
The application of single-cell RNA sequencing(scRNA-seq)in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategie...The application of single-cell RNA sequencing(scRNA-seq)in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategies.With the expansion of capacity for high-throughput scRNA-seq,including clinical samples,the analysis of these huge volumes of data has become a daunting prospect for researchers entering this field.Here,we review the workflow for typical scRNA-seq data analysis,covering raw data processing and quality control,basic data analysis applicable for almost all scRNA-seq data sets,and advanced data analysis that should be tailored to specific scientific questions.While summarizing the current methods for each analysis step,we also provide an online repository of software and wrapped-up scripts to support the implementation.Recommendations and caveats are pointed out for some specific analysis tasks and approaches.We hope this resource will be helpful to researchers engaging with scRNA-seq,in particular for emerging clinical applications.展开更多
With people living longer,the societal impact of age-related cognitive decline is becoming more pronounced(Crimmins,2015).Thus,it is increasingly important to comprehend the cognitive shifts linked to aging-whether th...With people living longer,the societal impact of age-related cognitive decline is becoming more pronounced(Crimmins,2015).Thus,it is increasingly important to comprehend the cognitive shifts linked to aging-whether they are physiological or pathological.展开更多
BACKGROUND Emerging evidence implicates Candida albicans(C.albicans)in human oncogenesis.Notably,studies have supported its involvement in regulating outcomes in colorectal cancer(CRC).This study investigated the para...BACKGROUND Emerging evidence implicates Candida albicans(C.albicans)in human oncogenesis.Notably,studies have supported its involvement in regulating outcomes in colorectal cancer(CRC).This study investigated the paradoxical role of C.albicans in CRC,aiming to determine whether it promotes or suppresses tumor development,with a focus on the mechanistic basis linked to its metabolic profile.AIM To investigate the dual role of C.albicans in the development and progression of CRC through metabolite profiling and to establish a prognostic model that integrates the microbial and metabolic interactions in CRC,providing insights into potential therapeutic strategies and clinical outcomes.METHODSA prognostic model integrating C. albicans with CRC was developed, incorporating enrichment analysis, immuneinfiltration profiling, survival analysis, Mendelian randomization, single-cell sequencing, and spatial transcriptomics.The effects of the C. albicans metabolite mixture on CRC cells were subsequently validated in vitro. Theprimary metabolite composition was characterized using liquid chromatography-mass spectrometry.RESULTSA prognostic model based on five specific mRNA markers, EHD4, LIME1, GADD45B, TIMP1, and FDFT1, wasestablished. The C. albicans metabolite mixture significantly reduced CRC cell viability. Post-treatment analysisrevealed a significant decrease in gene expression in HT29 cells, while the expression levels of TIMP1, EHD4, andGADD45B were significantly elevated in HCT116 cells. Conversely, LIME1 expression and that of other CRC celllines showed reductions. In normal colonic epithelial cells (NCM460), GADD45B, TIMP1, and FDFT1 expressionlevels were significantly increased, while LIME1 and EHD4 levels were markedly reduced. Following metabolitetreatment, the invasive and migratory capabilities of NCM460, HT29, and HCT116 cells were reduced. Quantitativeanalysis of extracellular ATP post-treatment showed a significant elevation (P < 0.01). The C. albicans metabolitemixture had no effect on reactive oxygen species accumulation in CRC cells but led to a reduction in mitochondrialmembrane potential, increased intracellular lipid peroxidation, and induced apoptosis. Metabolomic profilingrevealed significant alterations, with 516 metabolites upregulated and 531 downregulated.CONCLUSIONThis study introduced a novel prognostic model for CRC risk assessment. The findings suggested that the C.albicans metabolite mixture exerted an inhibitory effect on CRC initiation.展开更多
Lipids serve as fundamental constituents of cell membranes and organelles.Recent studies have highlighted the significance of lipids as biomarkers in the diagnosis of breast cancer.Although liquid chromatography coupl...Lipids serve as fundamental constituents of cell membranes and organelles.Recent studies have highlighted the significance of lipids as biomarkers in the diagnosis of breast cancer.Although liquid chromatography coupled with tandem mass spectrometry(LC-MS/MS)is widely employed for lipid analysis in complex samples,it suffers from limitations such as complexity and time-consuming procedures.In this study,we have developed dopamine-modified TiO_(2)nanoparticles(TiO_(2)-DA)and applied the materials to assist the analysis of lipids by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS).The TiO_(2)-DA can provide large specific surface area and acidic environment,well suited for lipid analysis.The method was initially validated using standard lipid molecules.Good sensitivity,reproducibility and quantification performance was observed.Then,the method was applied to the analysis of 90 serum samples from 30 patients with breast cancer,30 patients with benign breast disease and 30 healthy controls.Five lipid molecules were identified as potential biomarkers for breast cancer.We constructed a classification model based on the MALDI-TOF MS signal of the 5 lipid molecules,and achieved high sensitivity,specificity and accuracy for the differentiation of breast cancer from benign breast disease and healthy control.We further collected another 60 serum samples from 20 healthy controls,20 patients with benign breast disease and 20 patients with breast cancer for MALDITOF MS analysis to verify the accuracy of the classification model.This advancement holds great promise for the development of diagnostic models for other lipid metabolism-related diseases.展开更多
Current experimental and computational methods have limitations in accurately and efficiently classifying ion channels within vast protein spaces.Here we have developed a deep learning algorithm,GPT2 Ion Channel Class...Current experimental and computational methods have limitations in accurately and efficiently classifying ion channels within vast protein spaces.Here we have developed a deep learning algorithm,GPT2 Ion Channel Classifier(GPT2-ICC),which effectively distinguishing ion channels from a test set containing approximately 239 times more non-ion-channel proteins.GPT2-ICC integrates representation learning with a large language model(LLM)-based classifier,enabling highly accurate identification of potential ion channels.Several potential ion channels were predicated from the unannotated human proteome,further demonstrating GPT2-ICC’s generalization ability.This study marks a significant advancement in artificial-intelligence-driven ion channel research,highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data.Moreover,it provides a valuable computational tool for uncovering previously uncharacterized ion channels.展开更多
Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play p...Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.展开更多
Quantitative detection of trace small-sized nanoplastics(<100 nm)remains a significant challenge in surface-enhanced Raman scattering(SERS).To tackle this issue,we developed a hydrophobic CuO@Ag nanowire substrate ...Quantitative detection of trace small-sized nanoplastics(<100 nm)remains a significant challenge in surface-enhanced Raman scattering(SERS).To tackle this issue,we developed a hydrophobic CuO@Ag nanowire substrate and introduced a multiplex-feature analysis strategy based on the coffee ring effect.This substrate not only offers high Raman enhancement but also exhibits a high probability of detection(POD),enabling rapid and accurate identification of 50 nm polystyrene nanoplastics over a broad concentration range(1–10−10 wt%).Importantly,experimental results reveal a strong correlation between the coffee ring formation and the concentration of nanoplastic dispersion.By incorporating Raman signal intensity,coffee ring diameter,and POD as combined features,we established a machine learning-based mapping between nanoplastic concentration and coffee ring characteristics,allowing precise predictions of dispersion concentration.The mean squared error of these predictions is remarkably low,ranging from 0.21 to 0.54,representing a 19 fold improvement in accuracy compared to traditional linear regression-based methods.This strategy effectively integrates SERS with wettability modification techniques,ensuring high sensitivity and fingerprinting capabilities,while addressing the limitations of Raman signal intensity in accurately reflecting concentration changes at ultra-low levels,providing a new idea for precise SERS measurements of nanoplastics.展开更多
Influenza,a highly contagious respiratory infectious disease caused by an influenza virus,is a threat to public health worldwide.Avian influenza viruses(AIVs)have the potential to cause the next pandemic by crossing t...Influenza,a highly contagious respiratory infectious disease caused by an influenza virus,is a threat to public health worldwide.Avian influenza viruses(AIVs)have the potential to cause the next pandemic by crossing the species barrier through mutation of viral genome.Here,we investigated the pathogenicity of AIVs obtained from South Korea and Mongolia during 2018–2019 by measuring viral titers in the lungs and extrapulmonary organs of mouse models.In addition,we assessed the pathogenicity of AIVs in ferret models.Moreover,we compared the ability of viruses to replicate in mammalian cells,as well as the receptor-binding preferences of AIV isolates.Genetic analyses were finally performed to identify the genetic relationships and amino acid substitutions between viral proteins during mammalian adaptation.Of the 24 AIV isolates tested,A/Mallard/South Korea/KNU2019-34/2019(KNU19-34;H1N1)caused severe bodyweight loss and high mortality in mice.The virus replicated in the lungs,kidneys,and heart.Importantly,KNU19-34-infected ferrets showed high viral loads in both nasal washes and lungs.KNU19-34 replicated rapidly in A549 and bound preferentially to human likeα2,6-linked sialic acids rather than to avian-likeα2,3-linked sialic acids,similar to the pandemic A/California/04/2009(H1N1)strain.Gene segments of KNU19-34 were distributed in Egypt and Asia lineages from 2015 to 2018,and the virus had several amino acid substitutions compared to H1N1 AIV isolates that were non-pathogenic in mice.Collectively,the data suggest that KNU19-34 has zoonotic potential and the possibility of new mutations responsible for mammalian adaptation.展开更多
基金Supported by Japan Society for the Promotion of Science,No.24K11935.
文摘This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to both screening and diagnosis.For the clinical adaptation of AI,several challenges remain for its effective translation.The establishment of high-quality clinical databases,such as the National Clinical Database and Japan Endoscopy Database in Japan,which covers almost all cases of esophageal cancer,is essential for validating multimodal AI models.This requires rigorous external validation using diverse datasets,including those from different endoscope manufacturers and image qualities.Furthermore,endoscopists’skills significantly affect diagnostic accuracy,suggesting that AI should serve as a supportive tool rather than a replacement.Addressing these challenges,along with country-specific legal and ethical considerations,will facilitate the successful integration of multimodal AI into the management of esophageal cancer,particularly in endoscopic diagnosis,and contribute to improved patient outcomes.Although this review focused on Japan as a case study,the challenges and solutions described are broadly applicable to other high-incidence regions.
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC).
文摘The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.
文摘Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).
基金supported by the University of Padua(to MR)by the project“RIPANE”of the Italian Ministry of Defense(to CM)by Cariparo Foundation(to CM)。
文摘The neuromuscular junction and its proregenerative niche:The mammalian peripheral nervous system,unlike the central nervous system,has preserved throughout evolution the ability to regenerate and fully restore function.Key factors for effective nerve regeneration include a supportive neuronal environment and a coordinated tissue response(Brosius Lutz and Barres,2014).
基金supported by grants from Guangdong Basic and Applied Basic Research Foundation,No.2021A1515110801(to SW)the National Natural Science Foundation of China,No.82301511(to SW)+1 种基金“Double First-Class”Construction Project of NPU,Nos.0515023GH0202320(to JC),0515023SH0201320(to JC)973 Program,No.2011CB504100(to JC).
文摘Myelination,the continuous ensheathment of neuronal axons,is a lifelong process in the nervous system that is essential for the precise,temporospatial conduction of action potentials between neurons.Myelin also provides intercellular metabolic support to axons.Even minor disruptions in the integrity of myelin can impair neural performance and increase susceptibility to neurological diseases.In fact,myelin degeneration is a well-known neuropathological condition that is associated with normal aging and several neurodegenerative diseases,including multiple sclerosis and Alzheimer’s disease.In the central nervous system,compact myelin sheaths are formed by fully mature oligodendrocytes.However,the entire oligodendrocyte lineage is susceptible to changes in the biological microenvironment and other risk factors that arise as the brain ages.In addition to their well-known role in action potential propagation,oligodendrocytes also provide intercellular metabolic support to axons by transferring energy metabolites and delivering exosomes.Therefore,myelin degeneration in the aging central nervous system is a significant contributor to the development of neurodegenerative diseases.Interventions that mitigate age-related myelin degeneration can improve neurological function in aging individuals.In this review,we investigate the changes in myelin that are associated with aging and their underlying mechanisms.We also discuss recent advances in understanding how myelin degeneration in the aging brain contributes to neurodegenerative diseases and explore the factors that can prevent,slow down,or even reverse age-related myelin degeneration.Future research will enhance our understanding of how reducing age-related myelin degeneration can be used as a therapeutic target for delaying or preventing neurodegenerative diseases.
基金supported by Young Elite Scientists Sponsorship Program by China Association for Science and Technology(No.2022QNRC001)the National Natural Science Foundation of China(No.52273053)the Chenguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(No.21CGA41)。
文摘Extreme cold weather seriously harms human thermoregulatory system,necessitating high-performance insulating garments to maintain body temperature.However,as the core insulating layer,advanced fibrous materials always struggle to balance mechanical properties and thermal insulation,resulting in their inability to meet the demands for both washing resistance and personal protection.Herein,inspired by the natural spring-like structures of cucumber tendrils,a superelastic and washable micro/nanofibrous sponge(MNFS)based on biomimetic helical fibers is directly prepared utilizing multiple-jet electrospinning technology for high-performance thermal insulation.By regulating the conductivity of polyvinylidene fluoride solution,multiple-jet ejection and multiple-stage whipping of jets are achieved,and further control of phase separation rates enables the rapid solidification of jets to form spring-like helical fibers,which are directly entangled to assemble MNFS.The resulting MNFS exhibits superelasticity that can withstand large tensile strain(200%),1000 cyclic tensile or compression deformations,and retain good resilience even in liquid nitrogen(-196℃).Furthermore,the MNFS shows efficient thermal insulation with low thermal conductivity(24.85 mW m^(-1)K^(-1)),close to the value of dry air,and remains structural stability even after cyclic washing.This work offers new possibilities for advanced fibrous sponges in transportation,environmental,and energy applications.
基金supported by the National Research Foundation of Korea,Nos.2021R1A2C2006110,2021M3E5D9021364,2019R1A5A2026045(to BGK)the Korea Initiative for Fostering University of Research and Innovation(KIURI)Program of the NRF funded by the MSIT(to HK),No.NRF2021M3H1A104892211(to HSK)。
文摘Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.
基金supported by the National Natural Science Foundation of China(NSFC/RGC/JRF N_HKU735/21)Research Grant Council of Hong Kong,China(17102120,17108821,17103922,C1024-22GF,C7074-21G)+1 种基金Health and Medical Research Fund(HMRF 09200966)(to CSWL)FRQS Postdoctoral Fellowship(to AHKF).
文摘Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.
基金supported by European Union Funding Programme,PNRR,No. 760058(to DMH)the UEFISCDI Project,No. PN-III-P4-IDPCE-2020-059(to APW)
文摘The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area.However,only a small percentage of these neurons survive,and many do not reach the damaged area,possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex.A second major obstacle to stem cell therapy is the strong inflammatory reaction induced by cerebral ischemia,whereby the associated phagocytic activity of brain macrophages removes both therapeutic cells and/or cell-based drug carriers.To address these issues,neurogenesis was electrically stimulated in the subventricular zone,followed by isolation of proliferating cells,including newly formed neurons,which were subsequently mixed with a nutritional hydrogel.This mixture was then transferred to the stroke cavity of day 14 post-stroke mice.We found that the performance of the treated animals improved in behavioral tests,including novel object,open field,hole board,grooming,and“time-to-feel”adhesive tape tests.Furthermore,immunostaining revealed that the stem cell marker nestin,the neuroepithelial marker Mash1,and the immature neuronal marker doublecortin-positive cells survived in the transplanted area for 2 weeks,possibly due to reduced phagocytic activity and supportive angiogenesis.These results clearly indicate that the transplantation of committed subventricular zone stem cells combined with a protective nutritional gel directly into the infarct cavity after the peak of stroke-induced neuroinflammation represents a feasible approach to improve neurorestoration after cerebral ischemia.
文摘The rapid growth of biomedical data,particularly multi-omics data including genomes,transcriptomics,proteomics,metabolomics,and epigenomics,medical research and clinical decision-making confront both new opportunities and obstacles.The huge and diversified nature of these datasets cannot always be managed using traditional data analysis methods.As a consequence,deep learning has emerged as a strong tool for analysing numerous omics data due to its ability to handle complex and non-linear relationships.This paper explores the fundamental concepts of deep learning and how they are used in multi-omics medical data mining.We demonstrate how autoencoders,variational autoencoders,multimodal models,attention mechanisms,transformers,and graph neural networks enable pattern analysis and recognition across all omics data.Deep learning has been found to be effective in illness classification,biomarker identification,gene network learning,and therapeutic efficacy prediction.We also consider critical problems like as data quality,model explainability,whether findings can be repeated,and computational power requirements.We now consider future elements of combining omics with clinical and imaging data,explainable AI,federated learning,and real-time diagnostics.Overall,this study emphasises the need of collaborating across disciplines to advance deep learning-based multi-omics research for precision medicine and comprehending complicated disorders.
基金supported by the National Key Research and Development Program of China,No. 2023YFF0714200 (to CW)the National Natural Science Foundation of China,Nos. 82472038 and 82202224 (both to CW)+3 种基金the Shanghai Rising-Star Program,No. 23QA1407700 (to CW)the Construction Project of Shanghai Key Laboratory of Molecular Imaging,No. 18DZ2260400 (to CW)the National Science Foundation for Distinguished Young Scholars,No. 82025019 (to CL)the Greater Bay Area Institute of Precision Medicine (Guangzhou)(to CW)。
文摘Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies. Astrocytes, the largest group of nonneuronal cells in the central nervous system, play several crucial roles in maintaining ionic and energy metabolic homeostasis in neurons, regulating neurotransmitter levels, and modulating synaptic plasticity. This article briefly reviews the critical role of astrocytes in maintaining balance within the central nervous system. Building on previous research, we discuss how astrocyte dysfunction contributes to the onset and progression of epilepsy through four key aspects: the imbalance between excitatory and inhibitory neuronal signaling, dysregulation of metabolic homeostasis in the neuronal microenvironment, neuroinflammation, and the formation of abnormal neural circuits. We summarize relevant basic research conducted over the past 5 years that has focused on modulating astrocytes as a therapeutic approach for epilepsy. We categorize the therapeutic targets proposed by these studies into four areas: restoration of the excitation–inhibition balance, reestablishment of metabolic homeostasis, modulation of immune and inflammatory responses, and reconstruction of abnormal neural circuits. These targets correspond to the pathophysiological mechanisms by which astrocytes contribute to epilepsy. Additionally, we need to consider the potential challenges and limitations of translating these identified therapeutic targets into clinical treatments. These limitations arise from interspecies differences between humans and animal models, as well as the complex comorbidities associated with epilepsy in humans. We also highlight valuable future research directions worth exploring in the treatment of epilepsy and the regulation of astrocytes, such as gene therapy and imaging strategies. The findings presented in this review may help open new therapeutic avenues for patients with drugresistant epilepsy and for those suffering from other central nervous system disorders associated with astrocytic dysfunction.
基金supported by NASA funding NNX08BA47ANCC-1-02038+1 种基金NIH-1P20MD001822-1NSF(RISE)HRD-0734846
文摘Nanoparticles are increasingly being recognized for their potential utility in biological applications including nanomedicine.Here,we have synthesized zinc oxide(ZnO)nanorods using zinc acetate and hexamethylenetetramine as precursors followed by characterizing using X-ray diffraction,fourier transform infrared spectroscopy,scanning electron microscopy and transmission electron microscopy.The growth of synthesized zinc oxide nanorods was found to be very close to its hexagonal nature,which is confirmed by X-ray diffraction.The nanorod was grown perpendicular to the long-axis and grew along the[001]direction,which is the nature of ZnO growth.The morphology of synthesized ZnO nanorods from the individual crystalline nucleus was confirmed by scanning and transmission electron microscopy.The length of the nanorod was estimated to be around 21 nm in diameter and 50 nm in length.Our toxicology studies showed that synthesized ZnO nanorods exposure on hela cells has no significant induction of oxidative stress or cell death even in higher concentration(10μg/ml).The results suggest that ZnO nanorods might be a safer nanomaterial for biological applications.
基金suppor ted by the National Key Research and Development Program of China (2022YFC2702502)the National Natural Science Foundation of China (32170742, 31970646, and 32060152)+7 种基金the Start Fund for Specially Appointed Professor of Jiangsu ProvinceHainan Province Science and Technology Special Fund (ZDYF2021SHFZ051)the Natural Science Foundation of Hainan Province (820MS053)the Start Fund for High-level Talents of Nanjing Medical University (NMUR2020009)the Marshal Initiative Funding of Hainan Medical University (JBGS202103)the Hainan Province Clinical Medical Center (QWYH202175)the Bioinformatics for Major Diseases Science Innovation Group of Hainan Medical Universitythe Shenzhen Science and Technology Program (JCYJ20210324140407021)
文摘The application of single-cell RNA sequencing(scRNA-seq)in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategies.With the expansion of capacity for high-throughput scRNA-seq,including clinical samples,the analysis of these huge volumes of data has become a daunting prospect for researchers entering this field.Here,we review the workflow for typical scRNA-seq data analysis,covering raw data processing and quality control,basic data analysis applicable for almost all scRNA-seq data sets,and advanced data analysis that should be tailored to specific scientific questions.While summarizing the current methods for each analysis step,we also provide an online repository of software and wrapped-up scripts to support the implementation.Recommendations and caveats are pointed out for some specific analysis tasks and approaches.We hope this resource will be helpful to researchers engaging with scRNA-seq,in particular for emerging clinical applications.
基金Clévio Nóbrega’s laboratory is funded by the Cure CSB projectthe Viljem Julijan Association for Children with Rare Diseases(Slovenia)+1 种基金the Algarve Biomedical Center Research Institute(ABC-Ri)funded by CRESC Algarve 2020(Operation Code:ALG-01-0145-FEDER-072586)(to CN)。
文摘With people living longer,the societal impact of age-related cognitive decline is becoming more pronounced(Crimmins,2015).Thus,it is increasingly important to comprehend the cognitive shifts linked to aging-whether they are physiological or pathological.
基金Supported by Gansu Province Joint Fund General Program,No.24JRRA878Gansu Provincial Science and Technology Program Project,No.24JRRA1020+2 种基金Gansu Province Key Talent Program,No.2025RCXM006Teaching Research and Reform Program for Postgraduate Education at Gansu University of Traditional Chinese Medicine(GUSTCM),No.YBXM-202406Special Fund for Mentors of“Qihuang Talents”in the First-Level Discipline of Chinese Medicine,No.ZYXKBD-202415。
文摘BACKGROUND Emerging evidence implicates Candida albicans(C.albicans)in human oncogenesis.Notably,studies have supported its involvement in regulating outcomes in colorectal cancer(CRC).This study investigated the paradoxical role of C.albicans in CRC,aiming to determine whether it promotes or suppresses tumor development,with a focus on the mechanistic basis linked to its metabolic profile.AIM To investigate the dual role of C.albicans in the development and progression of CRC through metabolite profiling and to establish a prognostic model that integrates the microbial and metabolic interactions in CRC,providing insights into potential therapeutic strategies and clinical outcomes.METHODSA prognostic model integrating C. albicans with CRC was developed, incorporating enrichment analysis, immuneinfiltration profiling, survival analysis, Mendelian randomization, single-cell sequencing, and spatial transcriptomics.The effects of the C. albicans metabolite mixture on CRC cells were subsequently validated in vitro. Theprimary metabolite composition was characterized using liquid chromatography-mass spectrometry.RESULTSA prognostic model based on five specific mRNA markers, EHD4, LIME1, GADD45B, TIMP1, and FDFT1, wasestablished. The C. albicans metabolite mixture significantly reduced CRC cell viability. Post-treatment analysisrevealed a significant decrease in gene expression in HT29 cells, while the expression levels of TIMP1, EHD4, andGADD45B were significantly elevated in HCT116 cells. Conversely, LIME1 expression and that of other CRC celllines showed reductions. In normal colonic epithelial cells (NCM460), GADD45B, TIMP1, and FDFT1 expressionlevels were significantly increased, while LIME1 and EHD4 levels were markedly reduced. Following metabolitetreatment, the invasive and migratory capabilities of NCM460, HT29, and HCT116 cells were reduced. Quantitativeanalysis of extracellular ATP post-treatment showed a significant elevation (P < 0.01). The C. albicans metabolitemixture had no effect on reactive oxygen species accumulation in CRC cells but led to a reduction in mitochondrialmembrane potential, increased intracellular lipid peroxidation, and induced apoptosis. Metabolomic profilingrevealed significant alterations, with 516 metabolites upregulated and 531 downregulated.CONCLUSIONThis study introduced a novel prognostic model for CRC risk assessment. The findings suggested that the C.albicans metabolite mixture exerted an inhibitory effect on CRC initiation.
基金supported by National Natural Science Foundation of China(NSFC,Nos.22074022,22374031)the Ministry of Science and Technology of China,National Key R&D Program of China(No.2022YFC2704300).
文摘Lipids serve as fundamental constituents of cell membranes and organelles.Recent studies have highlighted the significance of lipids as biomarkers in the diagnosis of breast cancer.Although liquid chromatography coupled with tandem mass spectrometry(LC-MS/MS)is widely employed for lipid analysis in complex samples,it suffers from limitations such as complexity and time-consuming procedures.In this study,we have developed dopamine-modified TiO_(2)nanoparticles(TiO_(2)-DA)and applied the materials to assist the analysis of lipids by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS).The TiO_(2)-DA can provide large specific surface area and acidic environment,well suited for lipid analysis.The method was initially validated using standard lipid molecules.Good sensitivity,reproducibility and quantification performance was observed.Then,the method was applied to the analysis of 90 serum samples from 30 patients with breast cancer,30 patients with benign breast disease and 30 healthy controls.Five lipid molecules were identified as potential biomarkers for breast cancer.We constructed a classification model based on the MALDI-TOF MS signal of the 5 lipid molecules,and achieved high sensitivity,specificity and accuracy for the differentiation of breast cancer from benign breast disease and healthy control.We further collected another 60 serum samples from 20 healthy controls,20 patients with benign breast disease and 20 patients with breast cancer for MALDITOF MS analysis to verify the accuracy of the classification model.This advancement holds great promise for the development of diagnostic models for other lipid metabolism-related diseases.
基金funded by grants from the National Key Research and Development Program of China(Grant Nos.:2022YFE0205600 and 2022YFC3400504)the National Natural Science Foundation of China(Grant Nos.:82373792 and 82273857)the Fundamental Research Funds for the Central Universities,China,and the East China Normal University Medicine and Health Joint Fund,China(Grant No.:2022JKXYD07001).
文摘Current experimental and computational methods have limitations in accurately and efficiently classifying ion channels within vast protein spaces.Here we have developed a deep learning algorithm,GPT2 Ion Channel Classifier(GPT2-ICC),which effectively distinguishing ion channels from a test set containing approximately 239 times more non-ion-channel proteins.GPT2-ICC integrates representation learning with a large language model(LLM)-based classifier,enabling highly accurate identification of potential ion channels.Several potential ion channels were predicated from the unannotated human proteome,further demonstrating GPT2-ICC’s generalization ability.This study marks a significant advancement in artificial-intelligence-driven ion channel research,highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data.Moreover,it provides a valuable computational tool for uncovering previously uncharacterized ion channels.
基金supported by the National Natural Science Foundation of China(No.82171599 and No.32270901)the National Key Research and Developmental Program of China(2022YFC2702601 and 2022YFA0806303)the Global Select Project(DJKLX-2022010)of the Institute of Health and Medicine,Hefei Comprehensive National Science Center.
文摘Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.
基金the National Natural Science Foundation of China(No.12174229 and 22375117)Natural Science Foundation of Shandong Province(No.ZR2022YQ02 and ZR2023MB149)Taishan Scholars Program of Shandong Province(No.tsqn202306152)for financial support.
文摘Quantitative detection of trace small-sized nanoplastics(<100 nm)remains a significant challenge in surface-enhanced Raman scattering(SERS).To tackle this issue,we developed a hydrophobic CuO@Ag nanowire substrate and introduced a multiplex-feature analysis strategy based on the coffee ring effect.This substrate not only offers high Raman enhancement but also exhibits a high probability of detection(POD),enabling rapid and accurate identification of 50 nm polystyrene nanoplastics over a broad concentration range(1–10−10 wt%).Importantly,experimental results reveal a strong correlation between the coffee ring formation and the concentration of nanoplastic dispersion.By incorporating Raman signal intensity,coffee ring diameter,and POD as combined features,we established a machine learning-based mapping between nanoplastic concentration and coffee ring characteristics,allowing precise predictions of dispersion concentration.The mean squared error of these predictions is remarkably low,ranging from 0.21 to 0.54,representing a 19 fold improvement in accuracy compared to traditional linear regression-based methods.This strategy effectively integrates SERS with wettability modification techniques,ensuring high sensitivity and fingerprinting capabilities,while addressing the limitations of Raman signal intensity in accurately reflecting concentration changes at ultra-low levels,providing a new idea for precise SERS measurements of nanoplastics.
基金funded by grants from the National Research Foundation of Korea(NRF)grant funded by the Korea government(2018M3A9H4055203 and 2023R1A2C2003679)from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(HV23C1857)from KRIBB Research Initiative Program(KGM9942421).
文摘Influenza,a highly contagious respiratory infectious disease caused by an influenza virus,is a threat to public health worldwide.Avian influenza viruses(AIVs)have the potential to cause the next pandemic by crossing the species barrier through mutation of viral genome.Here,we investigated the pathogenicity of AIVs obtained from South Korea and Mongolia during 2018–2019 by measuring viral titers in the lungs and extrapulmonary organs of mouse models.In addition,we assessed the pathogenicity of AIVs in ferret models.Moreover,we compared the ability of viruses to replicate in mammalian cells,as well as the receptor-binding preferences of AIV isolates.Genetic analyses were finally performed to identify the genetic relationships and amino acid substitutions between viral proteins during mammalian adaptation.Of the 24 AIV isolates tested,A/Mallard/South Korea/KNU2019-34/2019(KNU19-34;H1N1)caused severe bodyweight loss and high mortality in mice.The virus replicated in the lungs,kidneys,and heart.Importantly,KNU19-34-infected ferrets showed high viral loads in both nasal washes and lungs.KNU19-34 replicated rapidly in A549 and bound preferentially to human likeα2,6-linked sialic acids rather than to avian-likeα2,3-linked sialic acids,similar to the pandemic A/California/04/2009(H1N1)strain.Gene segments of KNU19-34 were distributed in Egypt and Asia lineages from 2015 to 2018,and the virus had several amino acid substitutions compared to H1N1 AIV isolates that were non-pathogenic in mice.Collectively,the data suggest that KNU19-34 has zoonotic potential and the possibility of new mutations responsible for mammalian adaptation.
