Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesio...Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesions remain unclear.Long non-coding RNAs(lnc RNAs)have been shown to influence the occurrence and development of these lesions.We previously identified lnc_011797 as a biomarker of white matter lesions by high-throughput sequencing.To investigate the mechanism by which lnc_011797 regulates white matter lesions,we established subjected human umbilical vein endothelial cells to oxygenglucose deprivation to simulate conditions associated with white matter lesions.The cells were transfected with lnc_011797 overexpression or knockdown lentiviruses.Our findings indicate that lnc_011797 promoted ferroptosis in these cells,leading to the formation of white matter lesions.Furthermore,lnc_011797 functioned as a competitive endogenous RNA(ce RNA)for mi R-193b-3p,thereby regulating the expression of WNK1 and its downstream ferroptosis-related proteins.To validate the role of lnc_011797 in vivo,we established a mouse model of white matter lesions through bilateral common carotid artery stenosis.The results from this model confirmed that lnc_011797 regulates ferroptosis via WNK1 and promotes the development of white matter lesions.These findings clarify the mechanism by which lnc RNAs regulate white matter lesions,providing a new target for the diagnosis and treatment of white matter lesions.展开更多
Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms o...Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.展开更多
Band inversion induced by spin–orbit coupling in topological semimetals typically generates light charge carriers with high Fermi velocities,which are highly desirable for low-dissipation and coherent quantum transpo...Band inversion induced by spin–orbit coupling in topological semimetals typically generates light charge carriers with high Fermi velocities,which are highly desirable for low-dissipation and coherent quantum transport in topological devices.The presence of these carriers in real materials strongly depends on the Fermi-level position.2M-WSe_(2),with its topological and van der Waals nature,serves as an ideal platform for studying quantum transport in two-dimensional systems,despite the fact that interlayer coupling suppresses the formation of light carriers.In this study,we solvothermally intercalate 1,3-diaminopropane molecules into the interlayer space of 2M-WSe_(2);these molecules effectively adapt to the electronic structure by eliminating interlayer coupling.Simultaneously,slight electron doping via charge transfer results in a small Fermi pocket with an extremely light effective mass,0.04–0.06 me,as revealed by quantum oscillation measurements.This study demonstrates that molecular intercalation is an effective approach for engineering van der Waals topological materials to achieve specific quantum transport properties.展开更多
Traditional strategies for designing hyperhalogens,superatoms with exceptional electron-withdrawing capacity,rely on complex superhalogen assembly,posing significant experimental challenges.Here,we introduce a non-inv...Traditional strategies for designing hyperhalogens,superatoms with exceptional electron-withdrawing capacity,rely on complex superhalogen assembly,posing significant experimental challenges.Here,we introduce a non-invasive dual external field(DEF) approach combining solvent effects and an oriented external electric field(OEEF) to construct hyperhalogens,as demonstrated by density functional theory(DFT) calculations.Our DEF strategy proves versatile,successfully designing hyperhalogens not only in simplified Ag_n^(-) model systems but also in the experimentally synthesized Ag_(25) nanocluster.Using the 3D Ag_(19)^(-) structure as a model,we further reveal the DEF's pivotal role in O_(2) activation,where solvent-OEEF synergy induces tunable O-O bond elongation and charge transfer,proportional to field strength.Our findings establish a field-driven paradigm for hyperhalogen design that preserves native cluster composition,providing a theoretical foundation for tailoring high-performance catalysts through precise activesite modulation.展开更多
The Jellium closed-shell model,a cornerstone of cluster science,has long guided the design of superatoms by dictating electron-counting rules.However,its reliance on precise control of cluster composition and electron...The Jellium closed-shell model,a cornerstone of cluster science,has long guided the design of superatoms by dictating electron-counting rules.However,its reliance on precise control of cluster composition and electron shell occupancy presents significant experimental challenges.Here,we introduce a ligation strategy that circumvents these limitations by demonstrating that the adiabatic electron affinity(AEA) of aluminum-based clusters,whether with filled or partially filled electron shells,can be dramatically enhanced through the attachment of organic Lewis acid ligands.It was evidenced that the AEA of PAl12can be significantly increased by 2.17 e V after the ligation of two ligands,indicating a remarkable improvement in its electron-accepting ability.This approach yields superhalogen species,offering a versatile and practical means to tune the electronic properties of clusters while preserving their superatomic states,independent of shell occupancy.Remarkably,this ligand-induced modulation is not confined to naked clusters but also extends to nano-confined systems,hinting at its broader applicability.Given the indispensable role of ligands in cluster synthesis,this strategy holds promise for advancing the field of condensed-phase superatom synthesis,potentially complementing traditional electron-counting rules in a broader range of applications.展开更多
This study investigates the effect of BaHfO_(3)(BHO)addition on the optical properties of YBa_2Cu_(3)O_(7-δ)(YBCO)superconducting thin films using spectroscopic ellipsometry.Through Raman spectroscopy and SEM analysi...This study investigates the effect of BaHfO_(3)(BHO)addition on the optical properties of YBa_2Cu_(3)O_(7-δ)(YBCO)superconducting thin films using spectroscopic ellipsometry.Through Raman spectroscopy and SEM analysis,optimal 10-min Ar ion etching effectively removes surface a-axis-oriented grains and Ba–Cu–O impurities,enhancing surface quality.Optical conductivity analysis reveals a doping-dependent evolution:10%BHO doping maximizes free carrier density and interband transition efficiency,attributed to optimized Cu–O bond contraction and reduced lattice distortions.Higher doping induces defect clustering,carrier scattering,and redshifted transitions due to lattice expansion.Dielectric function and loss function analyses confirm enhanced plasmonic behavior and flux pinning at 10%doping,while excessive doping degrades electronic transitions.These results highlight the critical role of controlled BHO addition and surface treatment in tailoring the optical and superconducting properties of YBCO,offering insights into the interplay among doping,carrier dynamics,and electronic structure in high-temperature superconductors(HTS).展开更多
Objectives:B-cell lymphoma 6(BCL6)is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma(DLBCL),making it a promising therapeutic target.This study ai...Objectives:B-cell lymphoma 6(BCL6)is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma(DLBCL),making it a promising therapeutic target.This study aims to identify a novel small molecule,synthesized via proteolysis-targeting chimeras(PROTACs),capable of degrading BCL6,thereby inhibiting DLBCL growth and providing a foundation for future preclinical studies.Methods:The expression of BCL6 in DLBCL was analyzed using The Cancer Genome Atlas(TCGA)database and the Human Protein Atlas.Western blotting assays confirmed BCL6 expression in tumor cell lines,leading to the identification of the small molecule compound DZ-865B.To evaluate DZ-865B’s in vitro efficacy,multiple assays were performed,including protein immunoblotting,immunofluorescence,reverse transcription quantitative PCR,EDU proliferation,and soft agar cloning assays.Results:TCGA analysis revealed significant overexpression of BCL6 in DLBCL(p<0.05),corroborated by immunohistological staining and western blotting.DZ-865B induced BCL6 degradation in DLBCL cell lines(OCI-LY-1 and SU-DHL-4)in a concentration-and time-dependent manner,and induced the degradation of nuclear BCL6 through the ubiquitin-proteasome pathway.Notably,DZ-865B did not alter BCL6 mRNA levels but modulated downstream gene expression,leading to the activation of apoptosis pathway proteins and inhibition of DNA synthesis,effectively suppressing DLBCL cell growth.Conclusion:This study demonstrates that the small molecule DZ-865B targets and degrades BCL6 in DLBCL cells,promoting apoptosis and inhibiting cellular proliferation.These findings highlight DZ-865B as a potential therapeutic agent for diffuse large B-cell lymphoma.展开更多
The transition of perovskite solar cells(PSCs)from laboratory-scale devices to large-area commercial modules is fundamentally challenged by the poor uniformity and repeatability of conventional solution-based surface ...The transition of perovskite solar cells(PSCs)from laboratory-scale devices to large-area commercial modules is fundamentally challenged by the poor uniformity and repeatability of conventional solution-based surface passivation.To overcome this critical bottleneck,we introduce a vacuumevaporated passivation strategy using the thermally evaporable molecule bathophenanthroline(BPhen).This solvent-free approach yields highly uniform passivation layers,effectively suppressing surface defects and enhancing charge extraction through synergistic π-π stacking with the C60 electron transport layer.Our fully vacuum-evaporated PSCs achieve a remarkable power conversion efficiency(PCE)of 20.13%for champion cells and 18.42%for 5 cm×5 cm mini-modules.These results not only demonstrate the superiority of evaporated passivation for fabricating large-area devices but also establish a scalable and robust engineering pathway toward the commercial production of highperformance perovskite photovoltaics.展开更多
针对线控转向(steer by wire, SBW)系统主动转向时面临的系统参数不确定性、轮胎回正力矩阻碍、转向电机电磁特性耦合等非线性干扰问题,提出一种自适应抗扰转角控制策略。采用径向基函数神经网络和鲁棒滑模理论设计外环转角控制器,自适...针对线控转向(steer by wire, SBW)系统主动转向时面临的系统参数不确定性、轮胎回正力矩阻碍、转向电机电磁特性耦合等非线性干扰问题,提出一种自适应抗扰转角控制策略。采用径向基函数神经网络和鲁棒滑模理论设计外环转角控制器,自适应补偿SBW系统参数不确定性和轮胎回正力矩阻碍。在内环电流控制器中引入线性自抗扰控制应对转向执行电机电磁特性耦合问题,提高SBW系统动态响应性能。仿真和硬件在环试验结果表明,设计的控制策略能够帮助SBW在多种工况中维持转角稳态跟随误差在1.5°内。展开更多
Since the Beijing 2022 Winter Olympics was the first Winter Olympics in history held in continental winter monsoon climate conditions across complex terrain areas,there is a deficiency of relevant research,operational...Since the Beijing 2022 Winter Olympics was the first Winter Olympics in history held in continental winter monsoon climate conditions across complex terrain areas,there is a deficiency of relevant research,operational techniques,and experience.This made providing meteorological services for this event particularly challenging.The China Meteorological Administration(CMA)Earth System Modeling and Prediction Centre,achieved breakthroughs in research on short-and medium-term deterministic and ensemble numerical predictions.Several key technologies crucial for precise winter weather services during the Winter Olympics were developed.A comprehensive framework,known as the Operational System for High-Precision Weather Forecasting for the Winter Olympics,was established.Some of these advancements represent the highest level of capabilities currently available in China.The meteorological service provided to the Beijing 2022 Games also exceeded previous Winter Olympic Games in both variety and quality.This included achievements such as the“100-meter level,minute level”downscaled spatiotemporal resolution and forecasts spanning 1 to 15 days.Around 30 new technologies and over 60 kinds of products that align with the requirements of the Winter Olympics Organizing Committee were developed,and many of these techniques have since been integrated into the CMA’s operational national forecasting systems.These accomplishments were facilitated by a dedicated weather forecasting and research initiative,in conjunction with the preexisting real-time operational forecasting systems of the CMA.This program represents one of the five subprograms of the WMO’s high-impact weather forecasting demonstration project(SMART2022),and continues to play an important role in their Regional Association(RA)II Research Development Project(Hangzhou RDP).Therefore,the research accomplishments and meteorological service experiences from this program will be carried forward into forthcoming highimpact weather forecasting activities.This article provides an overview and assessment of this program and the operational national forecasting systems.展开更多
Objective: To investigate the current situation of the demand for geriatric care services of community residents in Beijing and analyze the influencing factors to provide a reference basis for meeting the demand for d...Objective: To investigate the current situation of the demand for geriatric care services of community residents in Beijing and analyze the influencing factors to provide a reference basis for meeting the demand for diversified and professional geriatric care services. Methods: A self-made questionnaire was used to randomly survey 1558 elderly individuals at community health service centers in 8 urban districts where elderly care centers were planned to be built. The influencing factors of the different characteristics of elderly care service needs from three aspects were analyzed using a dichotomous logistic regression model: predisposing, enabling, and, need factors. Results: 69.7% of the elderly required home care services, 22.8% wanted to get care services at elderly care centers, 15.9% wanted to get care services at nursing homes, 12.3% required community care services, and 7.4% didn’t know where to access care services. 68.5% of the elderly required care services for disabilities/semi-disabilities, 58.0% for dementia, 54.7% for common diseases, 34.9% for rehabilitation training, 33.0% for plumbing care, and 7.5% for hospice care. At the same time, there were urban- rural differences in the demand for elderly care services, with suburban elderly having a higher demand for care services than those living in urban areas (P < 0.05). The elderly’s demand for care services was mainly related to age, place of residence, and gender in the causative factors, mode of residence and physical condition among able factors, and mode of care services and care needs among need factors (P < 0.05). Conclusion: The demand for elderly care services was differentiated by factors including place of residence, age, and gender. It is crucial to accurately match the demand for elderly care services, innovate the mode of elderly care services, and improve the service quality to improve the elderly health service system.展开更多
Plant height(PH),primary lateral branch length(PBL),and branch number(BN)are architectural components impacting peanut pod yield,biomass production,and adaptivity to mechanical harvesting.In this study,a recombinant i...Plant height(PH),primary lateral branch length(PBL),and branch number(BN)are architectural components impacting peanut pod yield,biomass production,and adaptivity to mechanical harvesting.In this study,a recombinant inbred population consisting of 181 individual lines was used to determine genetic controls of PH,PBL,and BN across three environments.Phenotypic data collected from the population demonstrated continuous distributions and transgressive segregation patterns.Broad-sense heritability of PH,PBL,and BN was found to be 0.87,0.88,and 0.92,respectively.Unconditional individual environmental analysis revealed 35 additive QTLs with phenotypic variation explained(PVE)ranging from 4.57 to 21.68%.A two-round meta-analysis resulted in 24consensus and 19 unique QTLs.Five unique QTLs exhibited pleiotropic effects and their genetic bases(pleiotropy or tight linkage)were evaluated.A joint analysis was performed to estimate the QTL by environment interaction(QEI)effects on PH,PBL,and BN,collectively explaining phenotypic variations of 10.80,11.02,and 7.89%,respectively.We identified 3 major and stable QTL regions(uq9-3,uq10-2,and uq16-1)on chromosomes 9,10,and 16,spanning1.43-1.53 Mb genomic regions.Candidate genes involved in phytohormones biosynthesis,signaling,and cell wall development were proposed to regulate these morphological traits.These results provide valuable information for further genetic studies and the development of molecular markers applicable to peanut architecture improvement.展开更多
As the penetration rate of distributed energy increases,the transient power angle stability problem of the virtual synchronous generator(VSG)has gradually become prominent.In view of the situation that the grid impeda...As the penetration rate of distributed energy increases,the transient power angle stability problem of the virtual synchronous generator(VSG)has gradually become prominent.In view of the situation that the grid impedance ratio(R/X)is high and affects the transient power angle stability of VSG,this paper proposes a VSG transient power angle stability control strategy based on the combination of frequency difference feedback and virtual impedance.To improve the transient power angle stability of the VSG,a virtual impedance is adopted in the voltage loop to adjust the impedance ratio R/X;and the PI control feedback of the VSG frequency difference is introduced in the reactive powervoltage link of theVSGto enhance the damping effect.Thesecond-orderVSGdynamic nonlinearmodel considering the reactive power-voltage loop is established and the influence of different proportional integral(PI)control parameters on the system balance stability is analyzed.Moreover,the impact of the impedance ratio R/X on the transient power angle stability is presented using the equal area criterion.In the simulations,during the voltage dips with the reduction of R/X from 1.6 to 0.8,Δδ_(1)is reduced from 0.194 rad to 0.072 rad,Δf_(1)is reduced from 0.170 to 0.093 Hz,which shows better transient power angle stability.Simulation results verify that compared with traditional VSG,the proposedmethod can effectively improve the transient power angle stability of the system.展开更多
In the face of constantly changing environments,the central nervous system(CNS)rapidly and accurately calculates the body's needs,regulates feeding behavior,and maintains energy homeostasis.The arcuate nucleus of ...In the face of constantly changing environments,the central nervous system(CNS)rapidly and accurately calculates the body's needs,regulates feeding behavior,and maintains energy homeostasis.The arcuate nucleus of the hypothalamus(ARC)plays a key role in this process,serv-ing as a critical brain region for detecting nutrition-related hormones and regulating appetite and energy homeostasis.Agouti-related protein(AgRP)/neuropeptide Y(NPY)neu-rons in the ARC are core elements that interact with other brain regions through a complex appetite-regulating network to comprehensively control energy homeostasis.In this review,we explore the discovery and research progress of AgRP neurons in regulating feeding and energy metabolism.In addition,recent advances in terms of feeding behavior and energy homeostasis,along with the redundant neural mecha-nisms involved in energy metabolism,are discussed.Finally,the challenges and opportunities in the field of neural regula-tion of feeding and energy metabolism are briefly discussed.展开更多
Enhancing neurological recovery and improving the prognosis of spinal cord injury have gained research attention recently.Spinal cord injury is associated with a complex molecular and cellular microenvironment.This co...Enhancing neurological recovery and improving the prognosis of spinal cord injury have gained research attention recently.Spinal cord injury is associated with a complex molecular and cellular microenvironment.This complexity has prompted researchers to elucidate the underlying pathophysiological mechanisms and changes and to identify effective treatment strategies.Traditional approaches for spinal cord injury repair include surgery,oral or intravenous medications,and administration of neurotrophic factors;however,the efficacy of these approaches remains inconclusive,and serious adverse reactions continue to be a concern.With advancements in tissue engineering and regenerative medicine,emerging strategies for spinal cord injury repair now involve nanoparticle-based nanodelivery systems,scaffolds,and functional recovery techniques that incorporate biomaterials,bioengineering,stem cell,and growth factors as well as three-dimensional bioprinting.Ideal biomaterial scaffolds should not only provide structural support for neuron migration,adhesion,proliferation,and differentiation but also mimic the mechanical properties of natural spinal cord tissue.Additionally,these scaffolds should facilitate axon growth and neurogenesis by offering adjustable topography and a range of physical and biochemical cues.The three-dimensionally interconnected porous structure and appropriate physicochemical properties enabled by three-dimensional biomimetic printing technology can maximize the potential of biomaterials used for treating spinal cord injury.Therefore,correct selection and application of scaffolds,coupled with successful clinical translation,represent promising clinical objectives to enhance the treatment efficacy for and prognosis of spinal cord injury.This review elucidates the key mechanisms underlying the occurrence of spinal cord injury and regeneration post-injury,including neuroinflammation,oxidative stress,axon regeneration,and angiogenesis.This review also briefly discusses the critical role of nanodelivery systems used for repair and regeneration of injured spinal cord,highlighting the influence of nanoparticles and the factors that affect delivery efficiency.Finally,this review highlights tissue engineering strategies and the application of biomaterial scaffolds for the treatment of spinal cord injury.It discusses various types of scaffolds,their integrations with stem cells or growth factors,and approaches for optimization of scaffold design.展开更多
Magnesium(Mg)and its alloys have been identified as one of the most promising structural,energy and biomaterials owing to their exceptional combination of properties.These include low density,high specific strength,go...Magnesium(Mg)and its alloys have been identified as one of the most promising structural,energy and biomaterials owing to their exceptional combination of properties.These include low density,high specific strength,good damping,high castability,high capacity of hydrogen storage。展开更多
Background Clinical brain-computer interface(BCI)for mental disorders is an emerging interdisciplinary research field,posing new ethical concerns and challenges,yet lacking practical ethical governance guidelines for ...Background Clinical brain-computer interface(BCI)for mental disorders is an emerging interdisciplinary research field,posing new ethical concerns and challenges,yet lacking practical ethical governance guidelines for stakeholders and the entire community.Aims This study aims to establish a multidisciplinary consensus of principles for ethical governance of clinical BCI research for mental disorders and offer practical ethical guidance to stakeholders involved.Methods A systematic literature review,symposium and roundtable discussions,and a pre-Delphi(round 0)survey were conducted to form the questionnaire for the three-round modified Delphi study.Two rounds of surveys,followed by a third round of independent interviews of 25 experts from BCI-related research domains,were involved.We conducted quantitative analysis of responses and agreements among experts to reveal the consensus and differences regarding the ethical governance of mental BCI research from a multidisciplinary perspective.Results The Delphi panel emphasised important concerns of ethical review practices and ethical principles within the BCI context,identified qualified and highly influential institutions and personnel in conducting and advancing clinical BCI research,and recognised prioritised aspects in the risk-benefit evaluation.Experts expressed diverse opinions on specific ethical concerns,including concerns about invasive technology,its impact on humanity and potential social consequences.Agreement was reached that the practices of ethical governance of clinical BCI for mental disorders should focus on patient voluntariness,autonomy,long-term effects and related assessments of BCI interventions,as well as privacy protection,transparent reporting and ensuring that the research is conducted in qualified institutions with strong data security.Conclusions Ethical governance of clinical research on BCI for mental disorders should include interdisciplinary experts to balance various needs and incorporate the expertise of different stakeholders to avoid serious ethical issues.It requires scientifically grounded approaches,continuous monitoring and interdisciplinary collaboration to ensure evidence-based policies,comprehensive risk assessments and transparency,thereby promoting responsible innovations and protecting patient rights and well-being.展开更多
Periodontal disease is a risk factor for many systemic diseases such as Alzheimer’s disease and adverse pregnancy outcomes.Cleft palate(CP),the most common congenital craniofacial defect,has a multifaceted etiology i...Periodontal disease is a risk factor for many systemic diseases such as Alzheimer’s disease and adverse pregnancy outcomes.Cleft palate(CP),the most common congenital craniofacial defect,has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection.A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring.However,the precise relationship remains unclear.In this study,the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P.gingivalis injected intravenously and orally into pregnant mice.We investigated an obvious increasing CP(12.5%)in sonicated P.gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium.Then glycolysis and H4K12 lactylation(H4K12la)were detected to elevate in both mouse embryonic palatal mesenchyme(MEPM)cells and macrophages under P.gingivalis exposure which further promoted the transcription of metallopeptidase domain17(ADAM17),subsequently mediated the shedding of transforming growth factor-beta receptor 1(TGFBR1)in MEPM cells and mer tyrosine kinase(MerTK)in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate,eventually caused abnormalities in palate fusion and ossification.The abnormal efferocytosis also led to a predominance of M1 macrophages,which indirectly inhibited palatal osteogenesis via extracellular vesicles.Furthermore,pharmacological ADAM17 inhibition could ameliorate the abnormality of P.gingivalis-induced abnormal palate development.Therefore,our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.展开更多
基金supported by the Qingdao Medical Health Research Project,No.2023-WJZD212(to XX)。
文摘Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesions remain unclear.Long non-coding RNAs(lnc RNAs)have been shown to influence the occurrence and development of these lesions.We previously identified lnc_011797 as a biomarker of white matter lesions by high-throughput sequencing.To investigate the mechanism by which lnc_011797 regulates white matter lesions,we established subjected human umbilical vein endothelial cells to oxygenglucose deprivation to simulate conditions associated with white matter lesions.The cells were transfected with lnc_011797 overexpression or knockdown lentiviruses.Our findings indicate that lnc_011797 promoted ferroptosis in these cells,leading to the formation of white matter lesions.Furthermore,lnc_011797 functioned as a competitive endogenous RNA(ce RNA)for mi R-193b-3p,thereby regulating the expression of WNK1 and its downstream ferroptosis-related proteins.To validate the role of lnc_011797 in vivo,we established a mouse model of white matter lesions through bilateral common carotid artery stenosis.The results from this model confirmed that lnc_011797 regulates ferroptosis via WNK1 and promotes the development of white matter lesions.These findings clarify the mechanism by which lnc RNAs regulate white matter lesions,providing a new target for the diagnosis and treatment of white matter lesions.
基金supported by the National Key R&D Program of China,Nos.2021YFA1101703/2021YFA1101700(to YD).
文摘Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.
基金supported by the National Key Research and Development Program of China (Grant No.2023YFA1406301)the National Natural Science Foundation of China (Grant Nos.52250308 and 52525205)。
文摘Band inversion induced by spin–orbit coupling in topological semimetals typically generates light charge carriers with high Fermi velocities,which are highly desirable for low-dissipation and coherent quantum transport in topological devices.The presence of these carriers in real materials strongly depends on the Fermi-level position.2M-WSe_(2),with its topological and van der Waals nature,serves as an ideal platform for studying quantum transport in two-dimensional systems,despite the fact that interlayer coupling suppresses the formation of light carriers.In this study,we solvothermally intercalate 1,3-diaminopropane molecules into the interlayer space of 2M-WSe_(2);these molecules effectively adapt to the electronic structure by eliminating interlayer coupling.Simultaneously,slight electron doping via charge transfer results in a small Fermi pocket with an extremely light effective mass,0.04–0.06 me,as revealed by quantum oscillation measurements.This study demonstrates that molecular intercalation is an effective approach for engineering van der Waals topological materials to achieve specific quantum transport properties.
基金supported by the National Natural Science Foundation of China (NSFC,Nos.12474274,92161101)the Innovation Project of Jinan Science and Technology Bureau(No.2021GXRC032)the Natural Science Foundation of Shandong Province (No.ZR2024MA091)。
文摘Traditional strategies for designing hyperhalogens,superatoms with exceptional electron-withdrawing capacity,rely on complex superhalogen assembly,posing significant experimental challenges.Here,we introduce a non-invasive dual external field(DEF) approach combining solvent effects and an oriented external electric field(OEEF) to construct hyperhalogens,as demonstrated by density functional theory(DFT) calculations.Our DEF strategy proves versatile,successfully designing hyperhalogens not only in simplified Ag_n^(-) model systems but also in the experimentally synthesized Ag_(25) nanocluster.Using the 3D Ag_(19)^(-) structure as a model,we further reveal the DEF's pivotal role in O_(2) activation,where solvent-OEEF synergy induces tunable O-O bond elongation and charge transfer,proportional to field strength.Our findings establish a field-driven paradigm for hyperhalogen design that preserves native cluster composition,providing a theoretical foundation for tailoring high-performance catalysts through precise activesite modulation.
基金supported by the National Natural Science Foundation of China (NSFC,Nos.12474274,92161101)the Innovation Project of Jinan Science and Technology Bureau (No.2021GXRC032)the Natural Science Foundation of Shandong Province (No.ZR2024MA091)。
文摘The Jellium closed-shell model,a cornerstone of cluster science,has long guided the design of superatoms by dictating electron-counting rules.However,its reliance on precise control of cluster composition and electron shell occupancy presents significant experimental challenges.Here,we introduce a ligation strategy that circumvents these limitations by demonstrating that the adiabatic electron affinity(AEA) of aluminum-based clusters,whether with filled or partially filled electron shells,can be dramatically enhanced through the attachment of organic Lewis acid ligands.It was evidenced that the AEA of PAl12can be significantly increased by 2.17 e V after the ligation of two ligands,indicating a remarkable improvement in its electron-accepting ability.This approach yields superhalogen species,offering a versatile and practical means to tune the electronic properties of clusters while preserving their superatomic states,independent of shell occupancy.Remarkably,this ligand-induced modulation is not confined to naked clusters but also extends to nano-confined systems,hinting at its broader applicability.Given the indispensable role of ligands in cluster synthesis,this strategy holds promise for advancing the field of condensed-phase superatom synthesis,potentially complementing traditional electron-counting rules in a broader range of applications.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.52172271,12374378,52307026,and 52477022)the National Key Research and Development Program of China(Grant No.2022YFE03150200)Shanghai Science and Technology Innovation Program(Grant No.23511101600)。
文摘This study investigates the effect of BaHfO_(3)(BHO)addition on the optical properties of YBa_2Cu_(3)O_(7-δ)(YBCO)superconducting thin films using spectroscopic ellipsometry.Through Raman spectroscopy and SEM analysis,optimal 10-min Ar ion etching effectively removes surface a-axis-oriented grains and Ba–Cu–O impurities,enhancing surface quality.Optical conductivity analysis reveals a doping-dependent evolution:10%BHO doping maximizes free carrier density and interband transition efficiency,attributed to optimized Cu–O bond contraction and reduced lattice distortions.Higher doping induces defect clustering,carrier scattering,and redshifted transitions due to lattice expansion.Dielectric function and loss function analyses confirm enhanced plasmonic behavior and flux pinning at 10%doping,while excessive doping degrades electronic transitions.These results highlight the critical role of controlled BHO addition and surface treatment in tailoring the optical and superconducting properties of YBCO,offering insights into the interplay among doping,carrier dynamics,and electronic structure in high-temperature superconductors(HTS).
基金supported by the National Natural Science Foundation of China(82260716)the Key Research and Development Program of Ningxia(2023BEG02010).
文摘Objectives:B-cell lymphoma 6(BCL6)is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma(DLBCL),making it a promising therapeutic target.This study aims to identify a novel small molecule,synthesized via proteolysis-targeting chimeras(PROTACs),capable of degrading BCL6,thereby inhibiting DLBCL growth and providing a foundation for future preclinical studies.Methods:The expression of BCL6 in DLBCL was analyzed using The Cancer Genome Atlas(TCGA)database and the Human Protein Atlas.Western blotting assays confirmed BCL6 expression in tumor cell lines,leading to the identification of the small molecule compound DZ-865B.To evaluate DZ-865B’s in vitro efficacy,multiple assays were performed,including protein immunoblotting,immunofluorescence,reverse transcription quantitative PCR,EDU proliferation,and soft agar cloning assays.Results:TCGA analysis revealed significant overexpression of BCL6 in DLBCL(p<0.05),corroborated by immunohistological staining and western blotting.DZ-865B induced BCL6 degradation in DLBCL cell lines(OCI-LY-1 and SU-DHL-4)in a concentration-and time-dependent manner,and induced the degradation of nuclear BCL6 through the ubiquitin-proteasome pathway.Notably,DZ-865B did not alter BCL6 mRNA levels but modulated downstream gene expression,leading to the activation of apoptosis pathway proteins and inhibition of DNA synthesis,effectively suppressing DLBCL cell growth.Conclusion:This study demonstrates that the small molecule DZ-865B targets and degrades BCL6 in DLBCL cells,promoting apoptosis and inhibiting cellular proliferation.These findings highlight DZ-865B as a potential therapeutic agent for diffuse large B-cell lymphoma.
基金financial support from the National Key Research and Development Program of China(No.2024YFE0103600)the National Natural Science Foundation of China(No.52273189)+5 种基金the Natural Science Foundation of Jiangsu Province(Nos.BG2024016,BZ2023052,BE2022026-2,BK20240756)the Natural Science Foundation of Anhui Province(No.202423h08050004)the China Postdoctoral Science Foundation(Nos.2024T170622,2023M742526,GZB20240518)the Jiangsu Funding Program for Excellent Postdoctoral Talent(No.2024ZB061)the Suzhou science and technology plan project(Nos.ST202212,ST202312)supported by the Suzhou Key Laboratory of Functional Nano&Soft Materials。
文摘The transition of perovskite solar cells(PSCs)from laboratory-scale devices to large-area commercial modules is fundamentally challenged by the poor uniformity and repeatability of conventional solution-based surface passivation.To overcome this critical bottleneck,we introduce a vacuumevaporated passivation strategy using the thermally evaporable molecule bathophenanthroline(BPhen).This solvent-free approach yields highly uniform passivation layers,effectively suppressing surface defects and enhancing charge extraction through synergistic π-π stacking with the C60 electron transport layer.Our fully vacuum-evaporated PSCs achieve a remarkable power conversion efficiency(PCE)of 20.13%for champion cells and 18.42%for 5 cm×5 cm mini-modules.These results not only demonstrate the superiority of evaporated passivation for fabricating large-area devices but also establish a scalable and robust engineering pathway toward the commercial production of highperformance perovskite photovoltaics.
文摘针对线控转向(steer by wire, SBW)系统主动转向时面临的系统参数不确定性、轮胎回正力矩阻碍、转向电机电磁特性耦合等非线性干扰问题,提出一种自适应抗扰转角控制策略。采用径向基函数神经网络和鲁棒滑模理论设计外环转角控制器,自适应补偿SBW系统参数不确定性和轮胎回正力矩阻碍。在内环电流控制器中引入线性自抗扰控制应对转向执行电机电磁特性耦合问题,提高SBW系统动态响应性能。仿真和硬件在环试验结果表明,设计的控制策略能够帮助SBW在多种工况中维持转角稳态跟随误差在1.5°内。
基金This work was jointly supported by the National Natural Science Foundation of China(Grant Nos.41975137,42175012,and 41475097)the National Key Research and Development Program(Grant No.2018YFF0300103).
文摘Since the Beijing 2022 Winter Olympics was the first Winter Olympics in history held in continental winter monsoon climate conditions across complex terrain areas,there is a deficiency of relevant research,operational techniques,and experience.This made providing meteorological services for this event particularly challenging.The China Meteorological Administration(CMA)Earth System Modeling and Prediction Centre,achieved breakthroughs in research on short-and medium-term deterministic and ensemble numerical predictions.Several key technologies crucial for precise winter weather services during the Winter Olympics were developed.A comprehensive framework,known as the Operational System for High-Precision Weather Forecasting for the Winter Olympics,was established.Some of these advancements represent the highest level of capabilities currently available in China.The meteorological service provided to the Beijing 2022 Games also exceeded previous Winter Olympic Games in both variety and quality.This included achievements such as the“100-meter level,minute level”downscaled spatiotemporal resolution and forecasts spanning 1 to 15 days.Around 30 new technologies and over 60 kinds of products that align with the requirements of the Winter Olympics Organizing Committee were developed,and many of these techniques have since been integrated into the CMA’s operational national forecasting systems.These accomplishments were facilitated by a dedicated weather forecasting and research initiative,in conjunction with the preexisting real-time operational forecasting systems of the CMA.This program represents one of the five subprograms of the WMO’s high-impact weather forecasting demonstration project(SMART2022),and continues to play an important role in their Regional Association(RA)II Research Development Project(Hangzhou RDP).Therefore,the research accomplishments and meteorological service experiences from this program will be carried forward into forthcoming highimpact weather forecasting activities.This article provides an overview and assessment of this program and the operational national forecasting systems.
文摘Objective: To investigate the current situation of the demand for geriatric care services of community residents in Beijing and analyze the influencing factors to provide a reference basis for meeting the demand for diversified and professional geriatric care services. Methods: A self-made questionnaire was used to randomly survey 1558 elderly individuals at community health service centers in 8 urban districts where elderly care centers were planned to be built. The influencing factors of the different characteristics of elderly care service needs from three aspects were analyzed using a dichotomous logistic regression model: predisposing, enabling, and, need factors. Results: 69.7% of the elderly required home care services, 22.8% wanted to get care services at elderly care centers, 15.9% wanted to get care services at nursing homes, 12.3% required community care services, and 7.4% didn’t know where to access care services. 68.5% of the elderly required care services for disabilities/semi-disabilities, 58.0% for dementia, 54.7% for common diseases, 34.9% for rehabilitation training, 33.0% for plumbing care, and 7.5% for hospice care. At the same time, there were urban- rural differences in the demand for elderly care services, with suburban elderly having a higher demand for care services than those living in urban areas (P < 0.05). The elderly’s demand for care services was mainly related to age, place of residence, and gender in the causative factors, mode of residence and physical condition among able factors, and mode of care services and care needs among need factors (P < 0.05). Conclusion: The demand for elderly care services was differentiated by factors including place of residence, age, and gender. It is crucial to accurately match the demand for elderly care services, innovate the mode of elderly care services, and improve the service quality to improve the elderly health service system.
基金supported by the Natural Science Foundation of Shandong Province,China(ZR2022MC045)the National Natural Science Foundation of China(32001584,32201876)+2 种基金the Major Science and Technology Program of Xinjiang Uygur Autonomous Region,China(2022A02008-3)the Breeding Project from Department of Science&Technology of Shandong Province,China(2022LZGC007)the Agricultural Scientific and the Technological Innovation Project of Shandong Academy of Agricultural Sciences,China(CXGC2023A06,CXGC2023A39 and CXGC2023A46),and the Major Scientific and Technological Achievements Cultivation Program of Shandong Academy of Agricultural Sciences,China(CXGC2025E02)。
文摘Plant height(PH),primary lateral branch length(PBL),and branch number(BN)are architectural components impacting peanut pod yield,biomass production,and adaptivity to mechanical harvesting.In this study,a recombinant inbred population consisting of 181 individual lines was used to determine genetic controls of PH,PBL,and BN across three environments.Phenotypic data collected from the population demonstrated continuous distributions and transgressive segregation patterns.Broad-sense heritability of PH,PBL,and BN was found to be 0.87,0.88,and 0.92,respectively.Unconditional individual environmental analysis revealed 35 additive QTLs with phenotypic variation explained(PVE)ranging from 4.57 to 21.68%.A two-round meta-analysis resulted in 24consensus and 19 unique QTLs.Five unique QTLs exhibited pleiotropic effects and their genetic bases(pleiotropy or tight linkage)were evaluated.A joint analysis was performed to estimate the QTL by environment interaction(QEI)effects on PH,PBL,and BN,collectively explaining phenotypic variations of 10.80,11.02,and 7.89%,respectively.We identified 3 major and stable QTL regions(uq9-3,uq10-2,and uq16-1)on chromosomes 9,10,and 16,spanning1.43-1.53 Mb genomic regions.Candidate genes involved in phytohormones biosynthesis,signaling,and cell wall development were proposed to regulate these morphological traits.These results provide valuable information for further genetic studies and the development of molecular markers applicable to peanut architecture improvement.
基金supported by theMajor Science and Technology Projects of China Southern Power Grid(Grant number CGYKJXM20210328).
文摘As the penetration rate of distributed energy increases,the transient power angle stability problem of the virtual synchronous generator(VSG)has gradually become prominent.In view of the situation that the grid impedance ratio(R/X)is high and affects the transient power angle stability of VSG,this paper proposes a VSG transient power angle stability control strategy based on the combination of frequency difference feedback and virtual impedance.To improve the transient power angle stability of the VSG,a virtual impedance is adopted in the voltage loop to adjust the impedance ratio R/X;and the PI control feedback of the VSG frequency difference is introduced in the reactive powervoltage link of theVSGto enhance the damping effect.Thesecond-orderVSGdynamic nonlinearmodel considering the reactive power-voltage loop is established and the influence of different proportional integral(PI)control parameters on the system balance stability is analyzed.Moreover,the impact of the impedance ratio R/X on the transient power angle stability is presented using the equal area criterion.In the simulations,during the voltage dips with the reduction of R/X from 1.6 to 0.8,Δδ_(1)is reduced from 0.194 rad to 0.072 rad,Δf_(1)is reduced from 0.170 to 0.093 Hz,which shows better transient power angle stability.Simulation results verify that compared with traditional VSG,the proposedmethod can effectively improve the transient power angle stability of the system.
基金supported by Grants from the Research Funds of the Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYPY20220018)the National Natural Science Foundation of China(31822026,32271063,31500860,and 32100821)the National Science and Technology Innovation 2030 Major Project of China(2021ZD0203900).
文摘In the face of constantly changing environments,the central nervous system(CNS)rapidly and accurately calculates the body's needs,regulates feeding behavior,and maintains energy homeostasis.The arcuate nucleus of the hypothalamus(ARC)plays a key role in this process,serv-ing as a critical brain region for detecting nutrition-related hormones and regulating appetite and energy homeostasis.Agouti-related protein(AgRP)/neuropeptide Y(NPY)neu-rons in the ARC are core elements that interact with other brain regions through a complex appetite-regulating network to comprehensively control energy homeostasis.In this review,we explore the discovery and research progress of AgRP neurons in regulating feeding and energy metabolism.In addition,recent advances in terms of feeding behavior and energy homeostasis,along with the redundant neural mecha-nisms involved in energy metabolism,are discussed.Finally,the challenges and opportunities in the field of neural regula-tion of feeding and energy metabolism are briefly discussed.
基金supported by the Sichuan Science and Technology Program,No.2023YFS0164(to JC)the National Natural Science Foundation of China,No.82401629(to XL)+1 种基金the Natural Science Foundation of Sichuan Province,No.2024NSFSC1646(to XL)the China Postdoctoral Science Foundation,Nos.GZC20231811(to XL)and 2024T170601(to XL)。
文摘Enhancing neurological recovery and improving the prognosis of spinal cord injury have gained research attention recently.Spinal cord injury is associated with a complex molecular and cellular microenvironment.This complexity has prompted researchers to elucidate the underlying pathophysiological mechanisms and changes and to identify effective treatment strategies.Traditional approaches for spinal cord injury repair include surgery,oral or intravenous medications,and administration of neurotrophic factors;however,the efficacy of these approaches remains inconclusive,and serious adverse reactions continue to be a concern.With advancements in tissue engineering and regenerative medicine,emerging strategies for spinal cord injury repair now involve nanoparticle-based nanodelivery systems,scaffolds,and functional recovery techniques that incorporate biomaterials,bioengineering,stem cell,and growth factors as well as three-dimensional bioprinting.Ideal biomaterial scaffolds should not only provide structural support for neuron migration,adhesion,proliferation,and differentiation but also mimic the mechanical properties of natural spinal cord tissue.Additionally,these scaffolds should facilitate axon growth and neurogenesis by offering adjustable topography and a range of physical and biochemical cues.The three-dimensionally interconnected porous structure and appropriate physicochemical properties enabled by three-dimensional biomimetic printing technology can maximize the potential of biomaterials used for treating spinal cord injury.Therefore,correct selection and application of scaffolds,coupled with successful clinical translation,represent promising clinical objectives to enhance the treatment efficacy for and prognosis of spinal cord injury.This review elucidates the key mechanisms underlying the occurrence of spinal cord injury and regeneration post-injury,including neuroinflammation,oxidative stress,axon regeneration,and angiogenesis.This review also briefly discusses the critical role of nanodelivery systems used for repair and regeneration of injured spinal cord,highlighting the influence of nanoparticles and the factors that affect delivery efficiency.Finally,this review highlights tissue engineering strategies and the application of biomaterial scaffolds for the treatment of spinal cord injury.It discusses various types of scaffolds,their integrations with stem cells or growth factors,and approaches for optimization of scaffold design.
文摘Magnesium(Mg)and its alloys have been identified as one of the most promising structural,energy and biomaterials owing to their exceptional combination of properties.These include low density,high specific strength,good damping,high castability,high capacity of hydrogen storage。
基金funded by the Shanghai Philosophy and Social Science Planning Project (2021BZX008)the National Social Science Foundation of China (23BZX110)the National Office for Philosophy and Social Science (20&ZD045).
文摘Background Clinical brain-computer interface(BCI)for mental disorders is an emerging interdisciplinary research field,posing new ethical concerns and challenges,yet lacking practical ethical governance guidelines for stakeholders and the entire community.Aims This study aims to establish a multidisciplinary consensus of principles for ethical governance of clinical BCI research for mental disorders and offer practical ethical guidance to stakeholders involved.Methods A systematic literature review,symposium and roundtable discussions,and a pre-Delphi(round 0)survey were conducted to form the questionnaire for the three-round modified Delphi study.Two rounds of surveys,followed by a third round of independent interviews of 25 experts from BCI-related research domains,were involved.We conducted quantitative analysis of responses and agreements among experts to reveal the consensus and differences regarding the ethical governance of mental BCI research from a multidisciplinary perspective.Results The Delphi panel emphasised important concerns of ethical review practices and ethical principles within the BCI context,identified qualified and highly influential institutions and personnel in conducting and advancing clinical BCI research,and recognised prioritised aspects in the risk-benefit evaluation.Experts expressed diverse opinions on specific ethical concerns,including concerns about invasive technology,its impact on humanity and potential social consequences.Agreement was reached that the practices of ethical governance of clinical BCI for mental disorders should focus on patient voluntariness,autonomy,long-term effects and related assessments of BCI interventions,as well as privacy protection,transparent reporting and ensuring that the research is conducted in qualified institutions with strong data security.Conclusions Ethical governance of clinical research on BCI for mental disorders should include interdisciplinary experts to balance various needs and incorporate the expertise of different stakeholders to avoid serious ethical issues.It requires scientifically grounded approaches,continuous monitoring and interdisciplinary collaboration to ensure evidence-based policies,comprehensive risk assessments and transparency,thereby promoting responsible innovations and protecting patient rights and well-being.
基金funded by grants from the National Natural Science Foundation of China(grant numbers 82170912 and 82370910)the Beijing Stomatological Hospital,Capital Medical University Young Scientist Program(No.YSP202404).
文摘Periodontal disease is a risk factor for many systemic diseases such as Alzheimer’s disease and adverse pregnancy outcomes.Cleft palate(CP),the most common congenital craniofacial defect,has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection.A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring.However,the precise relationship remains unclear.In this study,the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P.gingivalis injected intravenously and orally into pregnant mice.We investigated an obvious increasing CP(12.5%)in sonicated P.gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium.Then glycolysis and H4K12 lactylation(H4K12la)were detected to elevate in both mouse embryonic palatal mesenchyme(MEPM)cells and macrophages under P.gingivalis exposure which further promoted the transcription of metallopeptidase domain17(ADAM17),subsequently mediated the shedding of transforming growth factor-beta receptor 1(TGFBR1)in MEPM cells and mer tyrosine kinase(MerTK)in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate,eventually caused abnormalities in palate fusion and ossification.The abnormal efferocytosis also led to a predominance of M1 macrophages,which indirectly inhibited palatal osteogenesis via extracellular vesicles.Furthermore,pharmacological ADAM17 inhibition could ameliorate the abnormality of P.gingivalis-induced abnormal palate development.Therefore,our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
