The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even...The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.展开更多
Precision medicine has become a cornerstone in modern therapeutic strategies, with nucleic acid aptamers emerging aspivotal tools due to their unique properties. These oligonucleotide fragments, selected through the S...Precision medicine has become a cornerstone in modern therapeutic strategies, with nucleic acid aptamers emerging aspivotal tools due to their unique properties. These oligonucleotide fragments, selected through the Systematic Evolution ofLigands by Exponential Enrichment process, exhibit high affinity and specificity toward their targets, such as DNA, RNA,proteins, and other biomolecules. Nucleic acid aptamers offer significant advantages over traditional therapeutic agents,including superior biological stability, minimal immunogenicity, and the capacity for universal chemical modifications thatenhance their in vivo performance and targeting precision. In the realm of osseous tissue repair and regeneration, a complexphysiological process essential for maintaining skeletal integrity, aptamers have shown remarkable potential in influencingmolecular pathways crucial for bone regeneration, promoting osteogenic differentiation and supporting osteoblast survival. Byengineering aptamers to regulate inflammatory responses and facilitate the proliferation and differentiation of fibroblasts,these oligonucleotides can be integrated into advanced drug delivery systems, significantly improving bone repair efficacywhile minimizing adverse effects. Aptamer-mediated strategies, including the use of siRNA and miRNA mimics or inhibitors,have shown efficacy in enhancing bone mass and microstructure. These approaches hold transformative potential for treatinga range of orthopedic conditions like osteoporosis, osteosarcoma, and osteoarthritis. This review synthesizes the molecularmechanisms and biological roles of aptamers in orthopedic diseases, emphasizing their potential to drive innovative andeffective therapeutic interventions.展开更多
The weak adsorption energy of oxygen-containing intermediates on Co center leads to a considerable performance dis-parity between Co-N-C and costly Pt benchmark in catalyzing oxygen reduction reaction(ORR).In this wor...The weak adsorption energy of oxygen-containing intermediates on Co center leads to a considerable performance dis-parity between Co-N-C and costly Pt benchmark in catalyzing oxygen reduction reaction(ORR).In this work,we strategi-cally engineer the active site structure of Co-N-C via B substitution,which is accomplished by the pyrolysis of ammonium borate.During this process,the in-situ generated NH_(3)gas plays a critical role in creating surface defects and boron atoms substituting nitrogen atoms in the carbon structure.The well-designed CoB_(1)N_(3)active site endows Co with higher charge density and stronger adsorption energy toward oxygen species,potentially accelerating ORR kinetics.As expected,the resulting Co-B/N-C catalyst exhibited superior ORR performance over Co-N-C counterpart,with 40 mV,and fivefold en-hancement in half-wave potential and turnover frequency(TOF).More importantly,the excellent ORR performance could be translated into membrane electrode assembly(MEA)in a fuel cell test,delivering an impressive peak power density of 824 mW·cm^(-2),which is currently the best among Co-based catalysts under the same conditions.This work not only demon-strates an effective method for designing advanced catalysts,but also affords a highly promising non-precious metal ORR electrocatalyst for fuel cell applications.展开更多
Tuojiang River Basin is a first-class tributary of the upper reaches of the Yangtze River—which is the longest river in China.As phytoplankton are sensitive indicators of trophic changes inwater bodies,characterizing...Tuojiang River Basin is a first-class tributary of the upper reaches of the Yangtze River—which is the longest river in China.As phytoplankton are sensitive indicators of trophic changes inwater bodies,characterizing phytoplankton communities and their growth influencing factors in polluted urban rivers can provide new ideas for pollution control.Here,we used direct microscopic count and environmental DNA(eDNA)metabarcoding methods to investigate phytoplankton community structure in Tuojiang River Basin(Chengdu,Sichuan Province,China).The association between phytoplankton community structure and water environmental factors was evaluated by Mantel analysis.Additional environmental monitoring data were used to pinpoint major factors that influenced phytoplankton growth based on structural equation modeling.At the phylum level,the dominant phytoplankton taxa identified by the conventional microscopic method mainly belonged to Bacillariophyta,Chlorophyta,and Cyanophyta,in contrast with Chlorophyta,Dinophyceae,and Bacillariophyta identified by eDNA metabarcoding.Inα-diversity analysis,eDNA metabarcoding detected greater species diversity and achieved higher precision than the microscopic method.Phytoplankton growth was largely limited by phosphorus based on the nitrogen-to-phosphorus ratios>16:1 in all water samples.Redundancy analysis and structural equation modeling also confirmed that the nitrogen-to-phosphorus ratio was the principal factor influencing phytoplankton growth.The results could be useful for implementing comprehensive management of the river basin environment.It is recommended to control the discharge of point-and surface-source pollutants and the concentration of dissolved oxygen in areas with excessive nutrients(e.g.,Jianyang-Ziyang).Algae monitoring techniques and removal strategies should be improved in 201 Hospital,Hongrihe Bridge and Colmar Town areas.展开更多
Manipulating catalyst structures to control product selectivity while maintaining high activity presents a considerable challenge in CO_(2)hydrogenation.Combining density functional theory calculations and microkineti...Manipulating catalyst structures to control product selectivity while maintaining high activity presents a considerable challenge in CO_(2)hydrogenation.Combining density functional theory calculations and microkinetic analysis,we proposed that graphene-supported isolated Pt atoms(Pt1/graphene)and Pt_(2)dimers(Pt_(2)/graphene)exhibited distinct selectivity in CO_(2)hydrogenation.Pt_(1)/graphene facilitated the conversion of CO_(2)into formic acid,whereas Pt_(2)/graphene favored methanol generation.The variation in product selectivity arose from the synergistic interaction of Pt_(2)dimers,which facilitated the migration of H atoms between two Pt atoms and promoted the transformation from*COOH intermediates to*C(OH)_(2)intermediates,altering the reaction pathways compared to isolated Pt atoms.Additionally,an analysis of the catalytic activities of three Pt_(1)/graphene and three Pt_(2)/graphene structures revealed that the turnover frequencies for formic acid generation on Pt_(1ii)/graphene and methanol generation on Pt_(2i)/graphene were as high as 744.48 h-1and 789.48 h^(-1),respectively.These values rivaled or even surpassed those previously reported in the literature under identical conditions.This study provides valuable insights into optimizing catalyst structures to achieve desired products in CO_(2)hydrogenation.展开更多
Teleost peripheral blood contains a remarkably high proportion of B cells,accounting for 15%-50%of circulating lymphocytes.However,their immune responses to bacterial infection are yet to be elucidated.In the present ...Teleost peripheral blood contains a remarkably high proportion of B cells,accounting for 15%-50%of circulating lymphocytes.However,their immune responses to bacterial infection are yet to be elucidated.In the present study,10×Genomics single-cell RNA sequencing(scRNA-seq)was employed to characterize the transcriptomic landscape of peripheral blood IgM^(+)B cells in grass carp(Ctenopharyngodon idella)following challenge with Aeromonas hydrophila,a major aquatic pathogen.Six transcriptionally distinct IgM^(+)B cell subpopulations were identified,including(im)mature B cells,innate B cells,proliferating B cells,IgD^(high)B cells,and two infection-induced subsets denoted as infectionⅠandⅡB cells.Bacterial infection altered the cellular heterogeneity of IgM^(+)B cells,triggered metabolic reprogramming in(im)mature and innate B cell subpopulations,and enhanced the immunological activation of circulating B cells.Notably,infectionⅠB cells demonstrated robust induction of interferonφ1(IFNφ1),a type I IFN,following A.hydrophila exposure.This induction was further validated through in vitro bacterial stimulation,indicating that teleost B cells actively contribute to innate antibacterial responses through IFN signaling.Additionally,the IgD^(high)B cell subpopulation remained consistently present in peripheral blood across both infected and uninfected states,pointing to a constitutive and likely mature phenotype.These findings significantly advance our understanding of the heterogeneity of peripheral blood IgM^(+)B cells and provide new insights into IgM^(+)B cell-mediated immune responses in teleost fish.展开更多
Developing nonprecious electrocatalysts with bifunctional performances for oxygen reduction(ORR)and evolution reactions(OER)remains a crucial challenge in rechargeable Zn-air batteries(RZABs).In this study,we report t...Developing nonprecious electrocatalysts with bifunctional performances for oxygen reduction(ORR)and evolution reactions(OER)remains a crucial challenge in rechargeable Zn-air batteries(RZABs).In this study,we report the synthesis of a three-dimensional(3D)porous N,P-doped carbon-wrapped cobalt phosphide composite(Co2P@3DNPC)via direct calcination of a novel organic/inorganic porous coordi-nation polymer by an in-situ phosphating strategy.DFT calculations demonstrate the intricate interac-tions occurring during the PEI-directed grinding self-assembly process among Co^(2+),phytic acid(PA),and polyethylenimine(PEI).Specifically,Co^(2+)ions initially adsorb onto PEI molecules before integrating with PA to form a 3D coordination polymer matrix.As-fabricated Co2P@3DNPC composite exhibits impressive ORR/OER bifunctional performances,with a half-wave potential of 0.78 V and an overpotential of 1.71 V,respectively.Its bifunctional activities enable a power density of 148.5 mW cm^(-2)in rechargeable ZABs,with remarkable stability(>480 h)during a discharge-charge cycle.The interconnected porous structure and embedded Co2P nanoparticles optimize the electrode-electrolyte interfacial contact,boosting energy density and cycle life of as-assembled ZABs.This innovative approach paves the way for efficient,cost-effective production of bifunctional electrocatalysts for RZABs.展开更多
Membrane fusion is essential for many cellular physiological functions,which is modulated by highly precise molecular mechanism involving multiple energy barriers.Nanoparticles(NPs),which exhibit immense potential in ...Membrane fusion is essential for many cellular physiological functions,which is modulated by highly precise molecular mechanism involving multiple energy barriers.Nanoparticles(NPs),which exhibit immense potential in the field of biomedical applications,can act as fusogen proteins to initiate and regulate membrane fusion.However,the underlying mechanisms of NP-induced membrane fusion and the molecular details involved remain largely elusive.Here,using coarse-grained molecular dynamics simulations,we systematically investigate the NP-induced membrane fusion behaviors and the influences of NP properties(size,hydrophobicity and hydrophilicity).Our results show that the vesicle-bilayer fusion induced by a hydrophobic NP is an intricately state-wise process,involving the approach and local deformation of the vesicle and bilayer bridging by the NP,the flip-flop of lipids from proximal leaflets and the formation of a fusion stalk,as well as further lipid interactions between distal leaflets and complete fusion.Moreover,we find that NP properties have distinct effects on membrane fusion and thus the optimal NP conditions for facilitating membrane fusion are obtained.Our work provides a mechanistic understanding of NP-induced membrane fusion and offers useful insights for efficient and controlled regulation of membrane fusion.展开更多
The period of infancy is important for the formation of social behaviors due to the rapid postnatal development of the brain functions underlying emotions and social skills.Ilustration of the neural circuits involved ...The period of infancy is important for the formation of social behaviors due to the rapid postnatal development of the brain functions underlying emotions and social skills.Ilustration of the neural circuits involved in the developmental process of infant social behaviors could foster new therapies for some social impairments occurring in the infant period.展开更多
The development of maize(Zea mays)kernels is a complex physiological process regulated by numerous genes in a spatially and temporally coordinated manner.However,many regulatory genes involved in this process remain u...The development of maize(Zea mays)kernels is a complex physiological process regulated by numerous genes in a spatially and temporally coordinated manner.However,many regulatory genes involved in this process remain unidentified.In this study,we identified ZmZFP2,a gene encoding a C4HC3-type RING zinc finger protein,which regulates kernel size and weight.This discovery was based on suppression subtractive hybridization from maize endosperm in our previous research.We further investigated the role of ZmZFP2 in regulating kernel development.The zmzfp2-ems mutant exhibited significantly reduced kernel size and weight,accompanied by fewer endosperm cells and altered starch and protein accumulation.CRISPR/Cas9-mediated knockouts and overexpression lines confirmed that ZmZFP2 positively regulates kernel size and weight,with overexpression leading to increased kernel size and weight.Transcriptome analysis revealed that ZmZFP2 regulates genes involved in zeatin biosynthesis,starch metabolism,and protein processing,further supporting its role in kernel development.Additionally,ZmZFP2 was shown to interact with the transcription factor ZmEREB98,implicating it in the gene regulatory network during grain filling.Together,these findings demonstrate that ZmZFP2 is a key regulator of maize kernel size and weight,functioning through its E3 ubiquitin ligase activity and interactions with various metabolic pathways.This study provides novel insights into the genetic regulation of kernel development and presents potential strategies for improving maize yield and quality.展开更多
EXPERIMENT is one of the necessary conditions for scientific progress.For cognitive science,neuroscience,biomedical science and other human-related disciplines,experiments involving human subjects can confirm or dispr...EXPERIMENT is one of the necessary conditions for scientific progress.For cognitive science,neuroscience,biomedical science and other human-related disciplines,experiments involving human subjects can confirm or disprove scientific hypotheses in a controlled and systematic manner,while establishing causal relationships between studied variables.These experiments also provide both qualitative and quantitative analysis capable of statistically identifying significant patterns.Thus,solid experiments directly support testable and replicable scientific conclusions.However,limited by the budget as well as the available candidate group,current experiment design selects random subjective in an arbitrary scale,bringing a question that how they can stand for the whole studied population.展开更多
BACKGROUND Acute variceal bleeding(AVB)represents a life-threatening complication in hepatocellular carcinoma(HCC)patients undergoing systemic therapy,mainly including immune checkpoint inhibitors(ICIs)and antivascula...BACKGROUND Acute variceal bleeding(AVB)represents a life-threatening complication in hepatocellular carcinoma(HCC)patients undergoing systemic therapy,mainly including immune checkpoint inhibitors(ICIs)and antivascular drugs used alone or in combination.The pathogenesis of AVB in this population may involve tumor-related factors,treatment-induced effects,or progression of underlying portal hypertension.Identifying high-risk factors for AVB is crucial for the management of this patient population.AIM To develop and validate a risk prediction model for AVB occurrence in cirrhotic HCC patients receiving ICI-based systemic therapy.METHODS This retrospective study analyzed 286 HCC patients(2021-2022)receiving ICIs(mono-/combination therapy),randomly split into training(n=184)and validation(n=102)cohorts.In the training cohort,bleeding vs nonbleeding groups were compared for general information,etiological data,laboratory indicators,tumor staging,systemic treatment drugs,variceal bleeding history,and endoscopic treatment history.Risk factors for AVB were identified and used to establish a logistic regression model for predicting bleeding,which was further validated in the validation cohort.RESULTS The bleeding group had significantly higher proportions of patients with platelet count≥100×10^(9)/L,alphafetoprotein≥400 ng/mL,tumor diameter≥5 cm,portal vein tumor thrombosis,ascites,bleeding history,prior endoscopic treatment,albumin-bilirubin grade level 2-3,fibrosis-4 index(FIB-4)≥4.57,and prognostic nutritional index<45 compared to the non-bleeding group.Multivariate analysis identified tumor diameter≥5 cm,portal vein thrombosis,bleeding history,and elevated FIB-4 as independent risk factors for bleeding(P<0.05).A predictive model based on these factors showed good discrimination,with area under the receiver operating characteristic curve values of 0.861(training)and 0.816(validation).CONCLUSION A history of pre-ICI bleeding significantly increases recurrent bleeding risk,necessitating close monitoring.The FIB-4 fibrosis model,combined with tumor features,can also serve as a predictive factor for bleeding.展开更多
Dear Editor,As the Internet of things(IoT)and autonomous driving continue to evolve,positioning technology faces increasing demands for higher accuracy and reliability.Traditional positioning methods often struggle in...Dear Editor,As the Internet of things(IoT)and autonomous driving continue to evolve,positioning technology faces increasing demands for higher accuracy and reliability.Traditional positioning methods often struggle in complex signal environments with multipath interference and non-line-of-sight(NLOS)conditions.Reconfigurable intelligent surfaces(RIS),an innovative technology that can flexibly control signal propagation,offer new possibilities for positioning systems.展开更多
N6-methyladenosine(m^(6)A)modification of mRNA is a critical post-transcriptional regulatory mechanism that modulates mRNA metabolism and neuronal function.The m^(6)A reader YTHDF1 has been shown to enhance the transl...N6-methyladenosine(m^(6)A)modification of mRNA is a critical post-transcriptional regulatory mechanism that modulates mRNA metabolism and neuronal function.The m^(6)A reader YTHDF1 has been shown to enhance the translational efficiency of m^(6)A-modified mRNAs in the brain and is essential for learning and memory.However,its role in the mature retina remains unclear.Herein,we report a novel role of Ythdf1 in the maintenance of retinal function using a genetic knockout model.Loss of Ythdf1 resulted in impaired scotopic electroretinogram(ERG)responses and progressive retinal degeneration.Detailed analyses of rod photoreceptors confirmed substantial degenerative changes in the absence of ciliary defects.Single-cell RNA sequencing revealed comprehensive molecular alterations across all retinal cell types in Ythdf1-deficient retinas.Integrative analysis of methylated RNA immunoprecipitation(MeRIP)sequencing and RIP sequencing identified Tulp1 and Dhx38,two inheritable retinal degeneration disease-associated gene homologs,as direct targets of YTHDF1 in the retina.Specifically,YTHDF1 recognized and bound m^(6)A-modified Tulp1 and Dhx38 mRNA at the coding sequence(CDS),enhancing their translational efficiency without altering mRNA levels.Collectively,these findings highlight the essential role of YTHDF1 in preserving visual function and reveal a novel regulatory mechanism of m^(6)A reader proteins in retinal degeneration,identifying potential therapeutic targets for severe retinopathies.展开更多
After the excavation of deep mining tunnels and underground caverns,the stability of surrounding rock controlled by structural planes is prone to structural damage and even engineering disasters due to three-dimension...After the excavation of deep mining tunnels and underground caverns,the stability of surrounding rock controlled by structural planes is prone to structural damage and even engineering disasters due to three-dimensional stress redistribution and multi-directional dynamic construction interference.However,the shear mechanical behavior,fracture evolution mechanism and precursor characteristics of rockmass under true triaxial stress and multi-directional coupling disturbance are not unclear.Therefore,this study carried out true triaxial shear tests on limestone intermittent structural planes under uni-,bi-and tri-directional coupling disturbances to analyze its mechanical behavior,fracture evolution mechanism and precursor characteristics.The results show that as the disturbance direction increase,the shear strength of limestone generally decreases,while the roughness of structural planes and the degree of anisotropy generally exhibit an increasing trend.The proportion of shear cracks on the structural plane increases with the increase of shear stress.The disturbance strain rate before failure shows a U-shaped trend.Near to disturbance failure,there were more high-energy and high-amplitude acoustic emission events near the structural plane,and b-value drops rapidly below 1,while lgN/b ratio increased to above 3.These findings provide experimental recognition and theoretical support for assessing the stability of rockmass under blasting excavation.展开更多
The Li-CO_(2)battery has been highly rated as an intriguing technique for balancing the carbon cycle for years,but it is still significantly challenged by the obstacles such as limited reversibility,sluggish kinetics,...The Li-CO_(2)battery has been highly rated as an intriguing technique for balancing the carbon cycle for years,but it is still significantly challenged by the obstacles such as limited reversibility,sluggish kinetics,and poor energy efficiency.Hence,the design and development of advance catalysts that can enhance the kinetics and reversibility of the CO_(2)electrochemical cycling reactions are considered the imperative tasks.Transition metal-based catalysts are widely considered appealing owing to their unfilled dorbitals,rich and adjustable valences,as well as processibility.In this review,the working mechanism and the key issues of the CO_(2)electrochemical cycling reaction are discussed first.Then the strategies for composition and structure design of different type of transition metal-based catalysts are highlighted,including their benefits,limitations,and the ways to implement these strategies.Finally,based on the pioneering research,the perspectives on the challenges and key points for the future development of cathode catalyst are proposed.展开更多
In November 1984,China launched its first expedition to the Southern Ocean and the Antarctic continent,culminating in the establishment of its first year-round research station—Great Wall Station—on the Antarctic Pe...In November 1984,China launched its first expedition to the Southern Ocean and the Antarctic continent,culminating in the establishment of its first year-round research station—Great Wall Station—on the Antarctic Peninsula in February 1985.Forty years later,in February 2024,China’s fifth research station,Qinling Station,commenced operations on Inexpress-ible Island near Terra Nova Bay.展开更多
The prevalence of Class Ⅲ malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can serio...The prevalence of Class Ⅲ malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore,early orthodontic treatment for Class Ⅲ malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class Ⅲ malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class Ⅲ malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class Ⅲ malocclusion through early orthodontic treatment.展开更多
OBJECTIVE:To assess the acute organ toxicity of Strychnos nux-vomica with zebrafish model visually.METHODS:To assess acute toxicity,we initially determined the lethal concentration after Strychnos nux-vomica treatment...OBJECTIVE:To assess the acute organ toxicity of Strychnos nux-vomica with zebrafish model visually.METHODS:To assess acute toxicity,we initially determined the lethal concentration after Strychnos nux-vomica treatment for 24 h.Zebrafish was treated with five concentrations Strychnos nux-≦vo LC10 for 24 h,and the effects ofmica on morphology,function of heart,central nervous system,liver,kidney and organ-specific cell death were assessed.Next,we assessed the reversibility of toxic effect.RESULTS:Strychnos nux-vomica has an effect on the different organs of zebrafish,including heart,central nervous system,liver,and kidney,and cadiotoxicity induced by Strychnos nux-vomica was reversible to some extent.CONCLUSION:Zebrafish model is suitable for confirming the toxic target organs for Chinese traditional medicine.展开更多
基金supported by the National Natural Science Foundation of China,No.81921006(to GHL)。
文摘The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.
基金Key research and development projects of Sichuan Science and Technology Plan Project(2024YFFK0135)Fujian Provincial Natural Science Foundation of China(2024J011450).
文摘Precision medicine has become a cornerstone in modern therapeutic strategies, with nucleic acid aptamers emerging aspivotal tools due to their unique properties. These oligonucleotide fragments, selected through the Systematic Evolution ofLigands by Exponential Enrichment process, exhibit high affinity and specificity toward their targets, such as DNA, RNA,proteins, and other biomolecules. Nucleic acid aptamers offer significant advantages over traditional therapeutic agents,including superior biological stability, minimal immunogenicity, and the capacity for universal chemical modifications thatenhance their in vivo performance and targeting precision. In the realm of osseous tissue repair and regeneration, a complexphysiological process essential for maintaining skeletal integrity, aptamers have shown remarkable potential in influencingmolecular pathways crucial for bone regeneration, promoting osteogenic differentiation and supporting osteoblast survival. Byengineering aptamers to regulate inflammatory responses and facilitate the proliferation and differentiation of fibroblasts,these oligonucleotides can be integrated into advanced drug delivery systems, significantly improving bone repair efficacywhile minimizing adverse effects. Aptamer-mediated strategies, including the use of siRNA and miRNA mimics or inhibitors,have shown efficacy in enhancing bone mass and microstructure. These approaches hold transformative potential for treatinga range of orthopedic conditions like osteoporosis, osteosarcoma, and osteoarthritis. This review synthesizes the molecularmechanisms and biological roles of aptamers in orthopedic diseases, emphasizing their potential to drive innovative andeffective therapeutic interventions.
基金the National Key Research and Development Program of China(2022YFB4004100)National Natural Science Foundation of China(22272161,22179126)+1 种基金the Jilin Province Science and Technology Development Program(YDZJ202202CXJD011,20240101019JC)Jilin Province major science and technology project(222648GX0105103875)for financial supports.
文摘The weak adsorption energy of oxygen-containing intermediates on Co center leads to a considerable performance dis-parity between Co-N-C and costly Pt benchmark in catalyzing oxygen reduction reaction(ORR).In this work,we strategi-cally engineer the active site structure of Co-N-C via B substitution,which is accomplished by the pyrolysis of ammonium borate.During this process,the in-situ generated NH_(3)gas plays a critical role in creating surface defects and boron atoms substituting nitrogen atoms in the carbon structure.The well-designed CoB_(1)N_(3)active site endows Co with higher charge density and stronger adsorption energy toward oxygen species,potentially accelerating ORR kinetics.As expected,the resulting Co-B/N-C catalyst exhibited superior ORR performance over Co-N-C counterpart,with 40 mV,and fivefold en-hancement in half-wave potential and turnover frequency(TOF).More importantly,the excellent ORR performance could be translated into membrane electrode assembly(MEA)in a fuel cell test,delivering an impressive peak power density of 824 mW·cm^(-2),which is currently the best among Co-based catalysts under the same conditions.This work not only demon-strates an effective method for designing advanced catalysts,but also affords a highly promising non-precious metal ORR electrocatalyst for fuel cell applications.
基金supported by the National Natural Science Foundation of China (No.72091511)the Science Fund for Distinguished Young Scholars of Hebei Province (No.E2022402064).
文摘Tuojiang River Basin is a first-class tributary of the upper reaches of the Yangtze River—which is the longest river in China.As phytoplankton are sensitive indicators of trophic changes inwater bodies,characterizing phytoplankton communities and their growth influencing factors in polluted urban rivers can provide new ideas for pollution control.Here,we used direct microscopic count and environmental DNA(eDNA)metabarcoding methods to investigate phytoplankton community structure in Tuojiang River Basin(Chengdu,Sichuan Province,China).The association between phytoplankton community structure and water environmental factors was evaluated by Mantel analysis.Additional environmental monitoring data were used to pinpoint major factors that influenced phytoplankton growth based on structural equation modeling.At the phylum level,the dominant phytoplankton taxa identified by the conventional microscopic method mainly belonged to Bacillariophyta,Chlorophyta,and Cyanophyta,in contrast with Chlorophyta,Dinophyceae,and Bacillariophyta identified by eDNA metabarcoding.Inα-diversity analysis,eDNA metabarcoding detected greater species diversity and achieved higher precision than the microscopic method.Phytoplankton growth was largely limited by phosphorus based on the nitrogen-to-phosphorus ratios>16:1 in all water samples.Redundancy analysis and structural equation modeling also confirmed that the nitrogen-to-phosphorus ratio was the principal factor influencing phytoplankton growth.The results could be useful for implementing comprehensive management of the river basin environment.It is recommended to control the discharge of point-and surface-source pollutants and the concentration of dissolved oxygen in areas with excessive nutrients(e.g.,Jianyang-Ziyang).Algae monitoring techniques and removal strategies should be improved in 201 Hospital,Hongrihe Bridge and Colmar Town areas.
基金supported by the National Key Research and Development Program(No.2022YFA1505800)the National Natural Science Foundation of China(No.22373092)+5 种基金CAS Project for Young Scientists in Basic Research(No.YSBR-051)China Association for Science and Technology(No.YESS20200031)the Start-up Funding of Central South University(No.502045005)Industry-University-Research Cooperation Projects with Zhejiang NHU Co.,Ltd.Ningbo Fengcheng Advanced Energy Materials Research Institutesupported by USTC Tang Scholarship。
文摘Manipulating catalyst structures to control product selectivity while maintaining high activity presents a considerable challenge in CO_(2)hydrogenation.Combining density functional theory calculations and microkinetic analysis,we proposed that graphene-supported isolated Pt atoms(Pt1/graphene)and Pt_(2)dimers(Pt_(2)/graphene)exhibited distinct selectivity in CO_(2)hydrogenation.Pt_(1)/graphene facilitated the conversion of CO_(2)into formic acid,whereas Pt_(2)/graphene favored methanol generation.The variation in product selectivity arose from the synergistic interaction of Pt_(2)dimers,which facilitated the migration of H atoms between two Pt atoms and promoted the transformation from*COOH intermediates to*C(OH)_(2)intermediates,altering the reaction pathways compared to isolated Pt atoms.Additionally,an analysis of the catalytic activities of three Pt_(1)/graphene and three Pt_(2)/graphene structures revealed that the turnover frequencies for formic acid generation on Pt_(1ii)/graphene and methanol generation on Pt_(2i)/graphene were as high as 744.48 h-1and 789.48 h^(-1),respectively.These values rivaled or even surpassed those previously reported in the literature under identical conditions.This study provides valuable insights into optimizing catalyst structures to achieve desired products in CO_(2)hydrogenation.
基金supported by the National Natural Science Foundation of China(32373162,31972824)Major Science and Technology Project of Hubei Province(2023BBA001),HZAU-AGIS Cooperation Fund(SZYJY2023006)China Agriculture Research System of MOF and MARA(CARS-46)。
文摘Teleost peripheral blood contains a remarkably high proportion of B cells,accounting for 15%-50%of circulating lymphocytes.However,their immune responses to bacterial infection are yet to be elucidated.In the present study,10×Genomics single-cell RNA sequencing(scRNA-seq)was employed to characterize the transcriptomic landscape of peripheral blood IgM^(+)B cells in grass carp(Ctenopharyngodon idella)following challenge with Aeromonas hydrophila,a major aquatic pathogen.Six transcriptionally distinct IgM^(+)B cell subpopulations were identified,including(im)mature B cells,innate B cells,proliferating B cells,IgD^(high)B cells,and two infection-induced subsets denoted as infectionⅠandⅡB cells.Bacterial infection altered the cellular heterogeneity of IgM^(+)B cells,triggered metabolic reprogramming in(im)mature and innate B cell subpopulations,and enhanced the immunological activation of circulating B cells.Notably,infectionⅠB cells demonstrated robust induction of interferonφ1(IFNφ1),a type I IFN,following A.hydrophila exposure.This induction was further validated through in vitro bacterial stimulation,indicating that teleost B cells actively contribute to innate antibacterial responses through IFN signaling.Additionally,the IgD^(high)B cell subpopulation remained consistently present in peripheral blood across both infected and uninfected states,pointing to a constitutive and likely mature phenotype.These findings significantly advance our understanding of the heterogeneity of peripheral blood IgM^(+)B cells and provide new insights into IgM^(+)B cell-mediated immune responses in teleost fish.
基金supported by the Research Project of the Hubei Provincial Department of Education(Grant No.Q20232503)the Hubei Provincial Natural Science Foundation and Huangshi of China(No.2022CFD039)+8 种基金the National Natural Science Foundation of China(Nos.22075072 and 52301272)the Program for Innovative Teams of Outstanding Young and Middle-aged Researchers in the Higher Education Institutions of Hubei Province(No.T2021010)the Natural Science Foundation of Hubei Province(No.2023AFB1010)the Natural Science Foundation of Zhejiang Province(No.LQ23E020002)the Wenzhou Key Scientific and Technological Innovation Research Project(No.ZG2023053)the Wenzhou Natural Science Foundation(No.G20220019)the Cooperation between industry and education project of Ministry of Education(No.220601318235513)the Wenzhou Science and Technology Association Serves Scientific and Technological Innovation Projects(KJFW0201)The State Key Laboratory funding of Disaster Prevention&Mitigation of Explosion&Impact(No.LGD-SKL-202203).
文摘Developing nonprecious electrocatalysts with bifunctional performances for oxygen reduction(ORR)and evolution reactions(OER)remains a crucial challenge in rechargeable Zn-air batteries(RZABs).In this study,we report the synthesis of a three-dimensional(3D)porous N,P-doped carbon-wrapped cobalt phosphide composite(Co2P@3DNPC)via direct calcination of a novel organic/inorganic porous coordi-nation polymer by an in-situ phosphating strategy.DFT calculations demonstrate the intricate interac-tions occurring during the PEI-directed grinding self-assembly process among Co^(2+),phytic acid(PA),and polyethylenimine(PEI).Specifically,Co^(2+)ions initially adsorb onto PEI molecules before integrating with PA to form a 3D coordination polymer matrix.As-fabricated Co2P@3DNPC composite exhibits impressive ORR/OER bifunctional performances,with a half-wave potential of 0.78 V and an overpotential of 1.71 V,respectively.Its bifunctional activities enable a power density of 148.5 mW cm^(-2)in rechargeable ZABs,with remarkable stability(>480 h)during a discharge-charge cycle.The interconnected porous structure and embedded Co2P nanoparticles optimize the electrode-electrolyte interfacial contact,boosting energy density and cycle life of as-assembled ZABs.This innovative approach paves the way for efficient,cost-effective production of bifunctional electrocatalysts for RZABs.
基金supported by the National Natural Science Foundation of China (Nos.22303060,12274307,32230063,12347102 and 22203059)Natural Science Foundation of Jiangsu Province (Nos.BK20230470 and BK20210100)+2 种基金the Natural Science Foundation of Guangdong Province of China (No.2023A1515011610)the Program of Jiangsu Provincial Key Lab of Thin Films (No.KJS2131)the open research fund of State Key Laboratory of Surface Physics of Fudan University (No.KF2023_03)
文摘Membrane fusion is essential for many cellular physiological functions,which is modulated by highly precise molecular mechanism involving multiple energy barriers.Nanoparticles(NPs),which exhibit immense potential in the field of biomedical applications,can act as fusogen proteins to initiate and regulate membrane fusion.However,the underlying mechanisms of NP-induced membrane fusion and the molecular details involved remain largely elusive.Here,using coarse-grained molecular dynamics simulations,we systematically investigate the NP-induced membrane fusion behaviors and the influences of NP properties(size,hydrophobicity and hydrophilicity).Our results show that the vesicle-bilayer fusion induced by a hydrophobic NP is an intricately state-wise process,involving the approach and local deformation of the vesicle and bilayer bridging by the NP,the flip-flop of lipids from proximal leaflets and the formation of a fusion stalk,as well as further lipid interactions between distal leaflets and complete fusion.Moreover,we find that NP properties have distinct effects on membrane fusion and thus the optimal NP conditions for facilitating membrane fusion are obtained.Our work provides a mechanistic understanding of NP-induced membrane fusion and offers useful insights for efficient and controlled regulation of membrane fusion.
基金supported by grants from the National Natural Science Foundation of China(32125018,32071005,and 32171079)Zhejiang Provincial Natural Science Foundation of China(LD24H090002 and LZ24C090001)+2 种基金the Fundamental Research Funds for the Central Universities(226-2024-00133)the Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZDCX20211102)the MOE Frontiers Science Center for Brain Science&Brain-Machine Integration of Zhejiang University.
文摘The period of infancy is important for the formation of social behaviors due to the rapid postnatal development of the brain functions underlying emotions and social skills.Ilustration of the neural circuits involved in the developmental process of infant social behaviors could foster new therapies for some social impairments occurring in the infant period.
基金supported by the National Natural Science Foundation of China(31971962,31771812,and 32272129 to Yuling Li)Zhongyuan Scholars in Henan Province(22400510003 to Yuling Li)+3 种基金the Major Public Welfare Projects of Henan Province(201300111100 to Yuling Li)Tackle Program of Agricultural Seed in Henan Province(2022010201 to Yuling Li)Technical System of Maize Industry in Henan Province(HARS62922-02-S to Yuling Li)Key Scientific Research Projects for Higher Education of Henan Province(19zx001 to Yuling Li).
文摘The development of maize(Zea mays)kernels is a complex physiological process regulated by numerous genes in a spatially and temporally coordinated manner.However,many regulatory genes involved in this process remain unidentified.In this study,we identified ZmZFP2,a gene encoding a C4HC3-type RING zinc finger protein,which regulates kernel size and weight.This discovery was based on suppression subtractive hybridization from maize endosperm in our previous research.We further investigated the role of ZmZFP2 in regulating kernel development.The zmzfp2-ems mutant exhibited significantly reduced kernel size and weight,accompanied by fewer endosperm cells and altered starch and protein accumulation.CRISPR/Cas9-mediated knockouts and overexpression lines confirmed that ZmZFP2 positively regulates kernel size and weight,with overexpression leading to increased kernel size and weight.Transcriptome analysis revealed that ZmZFP2 regulates genes involved in zeatin biosynthesis,starch metabolism,and protein processing,further supporting its role in kernel development.Additionally,ZmZFP2 was shown to interact with the transcription factor ZmEREB98,implicating it in the gene regulatory network during grain filling.Together,these findings demonstrate that ZmZFP2 is a key regulator of maize kernel size and weight,functioning through its E3 ubiquitin ligase activity and interactions with various metabolic pathways.This study provides novel insights into the genetic regulation of kernel development and presents potential strategies for improving maize yield and quality.
基金supported in part by National Natural Science Foundation of China(62476270,62076237)。
文摘EXPERIMENT is one of the necessary conditions for scientific progress.For cognitive science,neuroscience,biomedical science and other human-related disciplines,experiments involving human subjects can confirm or disprove scientific hypotheses in a controlled and systematic manner,while establishing causal relationships between studied variables.These experiments also provide both qualitative and quantitative analysis capable of statistically identifying significant patterns.Thus,solid experiments directly support testable and replicable scientific conclusions.However,limited by the budget as well as the available candidate group,current experiment design selects random subjective in an arbitrary scale,bringing a question that how they can stand for the whole studied population.
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-034AHebei Province 2025 Traditional Chinese Medicine Scientific Research Project Plan,No.T2025008.
文摘BACKGROUND Acute variceal bleeding(AVB)represents a life-threatening complication in hepatocellular carcinoma(HCC)patients undergoing systemic therapy,mainly including immune checkpoint inhibitors(ICIs)and antivascular drugs used alone or in combination.The pathogenesis of AVB in this population may involve tumor-related factors,treatment-induced effects,or progression of underlying portal hypertension.Identifying high-risk factors for AVB is crucial for the management of this patient population.AIM To develop and validate a risk prediction model for AVB occurrence in cirrhotic HCC patients receiving ICI-based systemic therapy.METHODS This retrospective study analyzed 286 HCC patients(2021-2022)receiving ICIs(mono-/combination therapy),randomly split into training(n=184)and validation(n=102)cohorts.In the training cohort,bleeding vs nonbleeding groups were compared for general information,etiological data,laboratory indicators,tumor staging,systemic treatment drugs,variceal bleeding history,and endoscopic treatment history.Risk factors for AVB were identified and used to establish a logistic regression model for predicting bleeding,which was further validated in the validation cohort.RESULTS The bleeding group had significantly higher proportions of patients with platelet count≥100×10^(9)/L,alphafetoprotein≥400 ng/mL,tumor diameter≥5 cm,portal vein tumor thrombosis,ascites,bleeding history,prior endoscopic treatment,albumin-bilirubin grade level 2-3,fibrosis-4 index(FIB-4)≥4.57,and prognostic nutritional index<45 compared to the non-bleeding group.Multivariate analysis identified tumor diameter≥5 cm,portal vein thrombosis,bleeding history,and elevated FIB-4 as independent risk factors for bleeding(P<0.05).A predictive model based on these factors showed good discrimination,with area under the receiver operating characteristic curve values of 0.861(training)and 0.816(validation).CONCLUSION A history of pre-ICI bleeding significantly increases recurrent bleeding risk,necessitating close monitoring.The FIB-4 fibrosis model,combined with tumor features,can also serve as a predictive factor for bleeding.
基金supported by the Open Fund Project of Key Laboratory of Ocean Observation Technology,MNR(2023klootA01).
文摘Dear Editor,As the Internet of things(IoT)and autonomous driving continue to evolve,positioning technology faces increasing demands for higher accuracy and reliability.Traditional positioning methods often struggle in complex signal environments with multipath interference and non-line-of-sight(NLOS)conditions.Reconfigurable intelligent surfaces(RIS),an innovative technology that can flexibly control signal propagation,offer new possibilities for positioning systems.
基金supported by the National Natural Science Foundation of China(82371083,82471100,82121003,82271084)Program of Science and Technology International Cooperation Project of Qinghai province(China)(2022-HZ-814)。
文摘N6-methyladenosine(m^(6)A)modification of mRNA is a critical post-transcriptional regulatory mechanism that modulates mRNA metabolism and neuronal function.The m^(6)A reader YTHDF1 has been shown to enhance the translational efficiency of m^(6)A-modified mRNAs in the brain and is essential for learning and memory.However,its role in the mature retina remains unclear.Herein,we report a novel role of Ythdf1 in the maintenance of retinal function using a genetic knockout model.Loss of Ythdf1 resulted in impaired scotopic electroretinogram(ERG)responses and progressive retinal degeneration.Detailed analyses of rod photoreceptors confirmed substantial degenerative changes in the absence of ciliary defects.Single-cell RNA sequencing revealed comprehensive molecular alterations across all retinal cell types in Ythdf1-deficient retinas.Integrative analysis of methylated RNA immunoprecipitation(MeRIP)sequencing and RIP sequencing identified Tulp1 and Dhx38,two inheritable retinal degeneration disease-associated gene homologs,as direct targets of YTHDF1 in the retina.Specifically,YTHDF1 recognized and bound m^(6)A-modified Tulp1 and Dhx38 mRNA at the coding sequence(CDS),enhancing their translational efficiency without altering mRNA levels.Collectively,these findings highlight the essential role of YTHDF1 in preserving visual function and reveal a novel regulatory mechanism of m^(6)A reader proteins in retinal degeneration,identifying potential therapeutic targets for severe retinopathies.
基金support received from the National Natural Science Foundation of China(Nos.52274145,52469019,and 52109119)the Guangxi Natural Science Foundation(No.2025GXNSFAA069165)the Chinese Postdoctoral Science Fund Project(No.2022M723408).
文摘After the excavation of deep mining tunnels and underground caverns,the stability of surrounding rock controlled by structural planes is prone to structural damage and even engineering disasters due to three-dimensional stress redistribution and multi-directional dynamic construction interference.However,the shear mechanical behavior,fracture evolution mechanism and precursor characteristics of rockmass under true triaxial stress and multi-directional coupling disturbance are not unclear.Therefore,this study carried out true triaxial shear tests on limestone intermittent structural planes under uni-,bi-and tri-directional coupling disturbances to analyze its mechanical behavior,fracture evolution mechanism and precursor characteristics.The results show that as the disturbance direction increase,the shear strength of limestone generally decreases,while the roughness of structural planes and the degree of anisotropy generally exhibit an increasing trend.The proportion of shear cracks on the structural plane increases with the increase of shear stress.The disturbance strain rate before failure shows a U-shaped trend.Near to disturbance failure,there were more high-energy and high-amplitude acoustic emission events near the structural plane,and b-value drops rapidly below 1,while lgN/b ratio increased to above 3.These findings provide experimental recognition and theoretical support for assessing the stability of rockmass under blasting excavation.
基金financially supported by the National Natural Science Foundation of China(52201254,52234001,52074177)the National Key Research and Development Program(2022YFC3900905)+3 种基金the Natural Science Foundation of Shandong Province(ZR2020QE012,ZR2020MB090,ZR2023ME155,ZR2023ME085)the Scientific Research Foundation for New Talents in University of Jinan(XRC2406)the project of “20 Items of University”of Jinan(202228046)the Introducing Major Universities and Research Institutions to Jointly Build Innovative Carrier Project of Jining City(2023DYDS022)。
文摘The Li-CO_(2)battery has been highly rated as an intriguing technique for balancing the carbon cycle for years,but it is still significantly challenged by the obstacles such as limited reversibility,sluggish kinetics,and poor energy efficiency.Hence,the design and development of advance catalysts that can enhance the kinetics and reversibility of the CO_(2)electrochemical cycling reactions are considered the imperative tasks.Transition metal-based catalysts are widely considered appealing owing to their unfilled dorbitals,rich and adjustable valences,as well as processibility.In this review,the working mechanism and the key issues of the CO_(2)electrochemical cycling reaction are discussed first.Then the strategies for composition and structure design of different type of transition metal-based catalysts are highlighted,including their benefits,limitations,and the ways to implement these strategies.Finally,based on the pioneering research,the perspectives on the challenges and key points for the future development of cathode catalyst are proposed.
文摘In November 1984,China launched its first expedition to the Southern Ocean and the Antarctic continent,culminating in the establishment of its first year-round research station—Great Wall Station—on the Antarctic Peninsula in February 1985.Forty years later,in February 2024,China’s fifth research station,Qinling Station,commenced operations on Inexpress-ible Island near Terra Nova Bay.
文摘The prevalence of Class Ⅲ malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore,early orthodontic treatment for Class Ⅲ malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class Ⅲ malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class Ⅲ malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class Ⅲ malocclusion through early orthodontic treatment.
基金Supported by the Scientific Research And Postgraduate Education Joint Project(Key Technology Research and Application of Safety Evaluation for Toxic Chinese Medicinal Materials on the Basis of the Characteristics of Chemical Composition and Zebrafish,No.2050205)
文摘OBJECTIVE:To assess the acute organ toxicity of Strychnos nux-vomica with zebrafish model visually.METHODS:To assess acute toxicity,we initially determined the lethal concentration after Strychnos nux-vomica treatment for 24 h.Zebrafish was treated with five concentrations Strychnos nux-≦vo LC10 for 24 h,and the effects ofmica on morphology,function of heart,central nervous system,liver,kidney and organ-specific cell death were assessed.Next,we assessed the reversibility of toxic effect.RESULTS:Strychnos nux-vomica has an effect on the different organs of zebrafish,including heart,central nervous system,liver,and kidney,and cadiotoxicity induced by Strychnos nux-vomica was reversible to some extent.CONCLUSION:Zebrafish model is suitable for confirming the toxic target organs for Chinese traditional medicine.
