To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-en...To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-environment contact,as well as the implementation of new M72/AS01_(E)vaccine.Motivated by this,a coupled age-structured tuberculosis(TB)model is proposed.Its well-posedness requirement is verified using the integrated semigroup theory.Furthermore,this study presents a comprehensive analysis of threshold dynamics associated with the proposed model.Specifically,the global stability of the disease-free and positive steady states is demonstrated by employing Lyapunov functionals.Lastly,the effects of the vaccination with M72/AS01_(E)and contaminated environments on TB control are numerically simulated.Experimental results indicate that high concentrations of Mycobacterium tuberculosis in contaminated environments may somewhat impede TB control efforts,but that large-scale deployment of new vaccine could significantly reduce the prevalence of TB.展开更多
Background Methane(CH_(4))emissions from ruminants significantly contribute to greenhouse gas effects and energy loss in livestock production.Methyl-coenzyme M reductase(MCR)is the key enzyme in methanogenesis,making ...Background Methane(CH_(4))emissions from ruminants significantly contribute to greenhouse gas effects and energy loss in livestock production.Methyl-coenzyme M reductase(MCR)is the key enzyme in methanogenesis,making it a promising target for CH_(4) mitigation.This study aimed to identify and validate plant-derived inhibitors by using molecular docking to screen compounds with strong binding affinity to the F430 active site of MCR and assessing their efficacy in reducing CH_(4) emissions.Results Molecular docking analysis identified salvianolic acid C(SAC)as a potent inhibitor of MCR,showing a strong binding affinity to the F430 active site(binding energy:-8.2 kcal/mol).Enzymatic inhibition assays confirmed its inhibitory effect,with a half-maximal inhibitory concentration(IC50)of 692.3μmol/L.In vitro rumen fermentation experiments demonstrated that SAC supplementation(1.5 mg/g DM)significantly reduced CH_(4)production(P<0.01)without negatively affecting major fermentation parameters.Microbial community analysis using 16S rRNA sequencing and metagenomics revealed that SAC selectively altered the rumen microbiota,increasing the relative abundance of Bacteroidota while significantly reducing Methanobrevibacter(P=0.04).Moreover,metagenomic analysis showed the downregulation of key methanogenesis-related genes(mcrA and rnfC),suggesting a dual mechanism involving direct enzymatic inhibition and microbial community modulation.Conclusions These findings indicate that SAC effectively reduces CH_(4)production by inhibiting MCR activity and reshaping the rumen microbial community.As a plant-derived compound with strong inhibitory effects on methanogenesis,SAC presents a promising and sustainable alternative to synthetic CH_(4) inhibitors,offering potential applications for mitigating CH_(4)emissions in livestock production.展开更多
The mitochondrial 3243A>G mutation(m.3243A>G)is associated with diverse clinical phenotypes.To elucidate the underlying mechanisms and explore intervention strategies in m.3243A>G patients,urine-derived stem ...The mitochondrial 3243A>G mutation(m.3243A>G)is associated with diverse clinical phenotypes.To elucidate the underlying mechanisms and explore intervention strategies in m.3243A>G patients,urine-derived stem cells(USCs)and a mitochondrial leucyl-tRNA synthetase gene(lars-2)deficient Caenorhabditis elegans(C.elegans)model are used to assess mitochondrial homeostasis and neuromuscular dysfunction.Patient-derived USCs with high levels of m.3243A>G heteroplasmy exhibit impaired mitochondrial function,disrupted mitochondrial dynamics,and inhibited mitophagy,which are reversed by MitoQ through suppression of OMA1 zinc metallopeptidase(OMA1)-induced mitochondrial phosphatase and tensin(PTEN)induced kinase 1(PINK1)degradation.Furthermore,lars-2 knockdown in C.elegans induces mitochondrial stress and mimics the loss of neural and muscle functions observed in patients with the m.3243A>G mutation.MitoQ treatment partially improves neurobehavioral function by promoting the PINK1 pathway.These findings suggest that MitoQ has therapeutic potential in the context of the m.3243A>G mutation.展开更多
“好房子”承载着千家万户对美好生活的向往,2025年被首次写入政府工作报告,住房城乡建设部及各地行业主管部门相继对“好房子”建设提出了一系列要求,并持续推动政策落地,建设“好房子”由此成为房地产领域产业转型发展的新赛道。在此...“好房子”承载着千家万户对美好生活的向往,2025年被首次写入政府工作报告,住房城乡建设部及各地行业主管部门相继对“好房子”建设提出了一系列要求,并持续推动政策落地,建设“好房子”由此成为房地产领域产业转型发展的新赛道。在此背景下,由贝壳集团旗下贝好家推出的C2M(Customer to Manufacturer,从消费者到制造者)全链解决方案,经过一段时间的探索和落地实践,已取得不错的实践成效和市场反馈。展开更多
In the article titled“Inhibiting SHP2 reduces glycolysis,promotes microglial M1 polarization,and alleviates secondary inflammation following spinal cord injury in a mouse model,”published in Neural Regeneration Rese...In the article titled“Inhibiting SHP2 reduces glycolysis,promotes microglial M1 polarization,and alleviates secondary inflammation following spinal cord injury in a mouse model,”published in Neural Regeneration Research(Ding et al.,2025),the title was incorrectly presented due to an error during the language polishing process.展开更多
To overcome the limitations of traditional single-crystal X-ray diffraction(SCXRD)for microcrystalline materials and the peak-overlapping issue of powder X-ray diffraction(PXRD),this study employed cryogenic continuou...To overcome the limitations of traditional single-crystal X-ray diffraction(SCXRD)for microcrystalline materials and the peak-overlapping issue of powder X-ray diffraction(PXRD),this study employed cryogenic continuous rotation electron diffraction(cryo-cRED)with a low-dose strategy to determine the crystal structure of CL30,a novel silicogermanate framework.It is confirmed that CL30 crystallizes in the C2/m space group and has layered topology composed of discontinuous zigzag chains connected by double four-membered ring(d4r)units,with fluoride anions(F^(-))occluded in the d4r units.In CL30,charge balance involves organic structure-directing agent(OSDA)cations,occluded F^(-),and terminal oxygen sites whose protonation state cannot be established from the present three dimensional(3D)ED data.F^(-)encapsulated in the d4r units contributes to charge compensation as the counter-anion to OSDA cations,rather than only balancing the framework charge.Although the refinement indices(R_(1)=0.29,wR_(2)=0.71)exceeded typical small-molecule crystallography standards,the structural model remained highly reliable,as supported by geometric restraints and validation.In electron diffraction,elevated R_(1) values are commonly attributed to the intrinsic factors of the technique,such as dynamic scattering,detector noise from scintillator-based detectors,and TEM stage instability(large spheres of confusion).This study introduces a new structural prototype to the silicogermanate family and establishes a feasible workflow for determining the structures of radiation-sensitive microcrystalline porous materials.展开更多
This study systematically analyzed the spatiotemporal evolution characteristics of geomagnetic anomalies before and after the 2013 Sichuan Lushan M7.0 earthquake and the Gansu Minxian M6.6 earthquake by constructing a...This study systematically analyzed the spatiotemporal evolution characteristics of geomagnetic anomalies before and after the 2013 Sichuan Lushan M7.0 earthquake and the Gansu Minxian M6.6 earthquake by constructing a geomagnetic diurnal variation model based on Taylor polynomial fitting,combined with midnight mean values of the geomagnetic F component from China,s geomagnetic observatory network.The results reveal distinct differences in anomaly patterns,namely per-sistent positive anomalies were observed in the epicentral region of the Lushan earthquake,while significant negative anomalies characterized the Minxian earthquake zone.This differential response reveals the modulating effect of the electrical structure of the seismogenic medium on space electromagnetic disturbances,namely positive anomalies may correspond to the stage of stable stress accumulation in intact rock,while the expansion of negative anomalies may reflect an amplification of electromagnetic disturbances induced by fracture expansion.Further analysis demonstrates that both anomalies exhibit a three-stage evolutionary pattern,namely pre-seismic accumulation,co-seismic release,and post-seismic adjustment.The phase transitions in these anomalies are closely correlated with regional tectonic stress accumulation and destabilization processes.These findings not only provide new evidence for the physical interpretation of seismomagnetic precursors but also establish a theoretical foundation for developing earthquake prediction methods based on the dynamic evolution of geomagnetic anomalies.展开更多
Scour around bridge pier foundations is a complex phenomenon that can threaten structural stability.Accurate prediction of scour depth around compound piers remains challenging for bridge engineers.This study investig...Scour around bridge pier foundations is a complex phenomenon that can threaten structural stability.Accurate prediction of scour depth around compound piers remains challenging for bridge engineers.This study investigated the effect of foundation elevation on scour around compound piers and developed reliable scour depth prediction models for economical foundation design.Experiments were conducted under clear-water conditions using two circular piers:(1)a uniform pier(with a diameter of D)and(2)a compound pier consisting of a uniform pier resting on a circular foundation(with a foundation diameter(D_(f))of 2D)positioned at various elevations(Z)relative to the channel bed.Results showed that foundation elevation significantly affected scour depth.Foundations at or below the bed(Z/D≥0)reduced scour,while those projecting into the flow field(Z/D<0)increased scour.The optimal foundation elevation was found to be 0.1D below the bed level,yielding a 57%reduction in scour depth compared to the uniform pier due to its shielding effect against downflow and horseshoe vortices.In addition,regression,artificial neural network(ANN),and M5 model tree models were developed using experimental data from this and previous studies.The M5 model outperformed the traditional HEC-18 equation,regression,and ANN models,with a coefficient of determination greater than 0.85.Sensitivity analysis indicated that flow depth,foundation elevation,and diameter significantly influenced scour depth prediction,whereas sediment size had a lesser impact.展开更多
In 2018,a catastrophic high-altitude landslide occurred at Baige,located within the tectonic suture zone of the Upper Jinsha River.The failure mechanism of this event remains poorly understood.This study aims to eluci...In 2018,a catastrophic high-altitude landslide occurred at Baige,located within the tectonic suture zone of the Upper Jinsha River.The failure mechanism of this event remains poorly understood.This study aims to elucidate the deformation characteristics and failure mechanism of the Baige landslide by employing a comprehensive methodology,including field geological surveys,analysis of historical remote sensing imagery,high-density electrical resistivity surveys,and advanced displacement monitoring.Additionally,the physical modeling experiments were conducted to replicate the unique failure modes.The findings propose a novel perspective on the failure mechanism of the Baige landslide,which involves two critical stages:first,the brittle shear zone bypasses and fails at the lower locked segment,and second,the failure of the upper locked segment,combined with the shear zone's impact on the lower locked segment,triggers overall slope instability.Physical modeling experiments revealed a transition from initial acceleration to a rapid acceleration phase,particularly marked by a significant increase in velocity following the failure of the upper locked segment.The intensity of acoustic emission signals was found to correlate with the failure of the locked segments and the state of particle collisions post-failure.It offers new insights into the failure mechanisms of tectonic mélange belt large-scale landslides in suture zones,contributing to the broader field of landslide research.展开更多
文摘To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-environment contact,as well as the implementation of new M72/AS01_(E)vaccine.Motivated by this,a coupled age-structured tuberculosis(TB)model is proposed.Its well-posedness requirement is verified using the integrated semigroup theory.Furthermore,this study presents a comprehensive analysis of threshold dynamics associated with the proposed model.Specifically,the global stability of the disease-free and positive steady states is demonstrated by employing Lyapunov functionals.Lastly,the effects of the vaccination with M72/AS01_(E)and contaminated environments on TB control are numerically simulated.Experimental results indicate that high concentrations of Mycobacterium tuberculosis in contaminated environments may somewhat impede TB control efforts,but that large-scale deployment of new vaccine could significantly reduce the prevalence of TB.
基金funded by the Integrated Demonstration of Scalable and Efficient Healthy Breeding for Cattle and Sheep(Grant No.2022YFD1301100)Instant Intelligent Diagnosis and Risk Warning Methods for Nutritional and Metabolic-Type Periparturient Cow Paralysis(Grant No.2024-YWF-ZYSQ-10)。
文摘Background Methane(CH_(4))emissions from ruminants significantly contribute to greenhouse gas effects and energy loss in livestock production.Methyl-coenzyme M reductase(MCR)is the key enzyme in methanogenesis,making it a promising target for CH_(4) mitigation.This study aimed to identify and validate plant-derived inhibitors by using molecular docking to screen compounds with strong binding affinity to the F430 active site of MCR and assessing their efficacy in reducing CH_(4) emissions.Results Molecular docking analysis identified salvianolic acid C(SAC)as a potent inhibitor of MCR,showing a strong binding affinity to the F430 active site(binding energy:-8.2 kcal/mol).Enzymatic inhibition assays confirmed its inhibitory effect,with a half-maximal inhibitory concentration(IC50)of 692.3μmol/L.In vitro rumen fermentation experiments demonstrated that SAC supplementation(1.5 mg/g DM)significantly reduced CH_(4)production(P<0.01)without negatively affecting major fermentation parameters.Microbial community analysis using 16S rRNA sequencing and metagenomics revealed that SAC selectively altered the rumen microbiota,increasing the relative abundance of Bacteroidota while significantly reducing Methanobrevibacter(P=0.04).Moreover,metagenomic analysis showed the downregulation of key methanogenesis-related genes(mcrA and rnfC),suggesting a dual mechanism involving direct enzymatic inhibition and microbial community modulation.Conclusions These findings indicate that SAC effectively reduces CH_(4)production by inhibiting MCR activity and reshaping the rumen microbial community.As a plant-derived compound with strong inhibitory effects on methanogenesis,SAC presents a promising and sustainable alternative to synthetic CH_(4) inhibitors,offering potential applications for mitigating CH_(4)emissions in livestock production.
基金funded by the NIH Office of Research Infrastructure Programs(P40 OD010440)supported by the National Natural Science Foundation of China(82471893 and 82070913)+2 种基金Key discipline project of Hongkou District Health Commission(HKLCFC202403)Tongji Hospital Start-up Funding for Scientific Research(RCQD2301)Research fund from Shanghai Fourth People's Hospital(sykyqd01801,SYXKZT-2021-1001).
文摘The mitochondrial 3243A>G mutation(m.3243A>G)is associated with diverse clinical phenotypes.To elucidate the underlying mechanisms and explore intervention strategies in m.3243A>G patients,urine-derived stem cells(USCs)and a mitochondrial leucyl-tRNA synthetase gene(lars-2)deficient Caenorhabditis elegans(C.elegans)model are used to assess mitochondrial homeostasis and neuromuscular dysfunction.Patient-derived USCs with high levels of m.3243A>G heteroplasmy exhibit impaired mitochondrial function,disrupted mitochondrial dynamics,and inhibited mitophagy,which are reversed by MitoQ through suppression of OMA1 zinc metallopeptidase(OMA1)-induced mitochondrial phosphatase and tensin(PTEN)induced kinase 1(PINK1)degradation.Furthermore,lars-2 knockdown in C.elegans induces mitochondrial stress and mimics the loss of neural and muscle functions observed in patients with the m.3243A>G mutation.MitoQ treatment partially improves neurobehavioral function by promoting the PINK1 pathway.These findings suggest that MitoQ has therapeutic potential in the context of the m.3243A>G mutation.
文摘“好房子”承载着千家万户对美好生活的向往,2025年被首次写入政府工作报告,住房城乡建设部及各地行业主管部门相继对“好房子”建设提出了一系列要求,并持续推动政策落地,建设“好房子”由此成为房地产领域产业转型发展的新赛道。在此背景下,由贝壳集团旗下贝好家推出的C2M(Customer to Manufacturer,从消费者到制造者)全链解决方案,经过一段时间的探索和落地实践,已取得不错的实践成效和市场反馈。
文摘In the article titled“Inhibiting SHP2 reduces glycolysis,promotes microglial M1 polarization,and alleviates secondary inflammation following spinal cord injury in a mouse model,”published in Neural Regeneration Research(Ding et al.,2025),the title was incorrectly presented due to an error during the language polishing process.
基金supported by the National Natural Science Foundation of China (Grant No.12374021)Beijing Natural Science Foundation (Grant No.1252031)。
文摘To overcome the limitations of traditional single-crystal X-ray diffraction(SCXRD)for microcrystalline materials and the peak-overlapping issue of powder X-ray diffraction(PXRD),this study employed cryogenic continuous rotation electron diffraction(cryo-cRED)with a low-dose strategy to determine the crystal structure of CL30,a novel silicogermanate framework.It is confirmed that CL30 crystallizes in the C2/m space group and has layered topology composed of discontinuous zigzag chains connected by double four-membered ring(d4r)units,with fluoride anions(F^(-))occluded in the d4r units.In CL30,charge balance involves organic structure-directing agent(OSDA)cations,occluded F^(-),and terminal oxygen sites whose protonation state cannot be established from the present three dimensional(3D)ED data.F^(-)encapsulated in the d4r units contributes to charge compensation as the counter-anion to OSDA cations,rather than only balancing the framework charge.Although the refinement indices(R_(1)=0.29,wR_(2)=0.71)exceeded typical small-molecule crystallography standards,the structural model remained highly reliable,as supported by geometric restraints and validation.In electron diffraction,elevated R_(1) values are commonly attributed to the intrinsic factors of the technique,such as dynamic scattering,detector noise from scintillator-based detectors,and TEM stage instability(large spheres of confusion).This study introduces a new structural prototype to the silicogermanate family and establishes a feasible workflow for determining the structures of radiation-sensitive microcrystalline porous materials.
基金supported by a Collaborative Project of the National Natural Science Foundation of China on Technical Maintenance and Data Preprocessing of the GPS Observation Array for the Qiaojia Earthquake(No.0120603)the National Natural Science Foundation of China(No.41274079).
文摘This study systematically analyzed the spatiotemporal evolution characteristics of geomagnetic anomalies before and after the 2013 Sichuan Lushan M7.0 earthquake and the Gansu Minxian M6.6 earthquake by constructing a geomagnetic diurnal variation model based on Taylor polynomial fitting,combined with midnight mean values of the geomagnetic F component from China,s geomagnetic observatory network.The results reveal distinct differences in anomaly patterns,namely per-sistent positive anomalies were observed in the epicentral region of the Lushan earthquake,while significant negative anomalies characterized the Minxian earthquake zone.This differential response reveals the modulating effect of the electrical structure of the seismogenic medium on space electromagnetic disturbances,namely positive anomalies may correspond to the stage of stable stress accumulation in intact rock,while the expansion of negative anomalies may reflect an amplification of electromagnetic disturbances induced by fracture expansion.Further analysis demonstrates that both anomalies exhibit a three-stage evolutionary pattern,namely pre-seismic accumulation,co-seismic release,and post-seismic adjustment.The phase transitions in these anomalies are closely correlated with regional tectonic stress accumulation and destabilization processes.These findings not only provide new evidence for the physical interpretation of seismomagnetic precursors but also establish a theoretical foundation for developing earthquake prediction methods based on the dynamic evolution of geomagnetic anomalies.
文摘Scour around bridge pier foundations is a complex phenomenon that can threaten structural stability.Accurate prediction of scour depth around compound piers remains challenging for bridge engineers.This study investigated the effect of foundation elevation on scour around compound piers and developed reliable scour depth prediction models for economical foundation design.Experiments were conducted under clear-water conditions using two circular piers:(1)a uniform pier(with a diameter of D)and(2)a compound pier consisting of a uniform pier resting on a circular foundation(with a foundation diameter(D_(f))of 2D)positioned at various elevations(Z)relative to the channel bed.Results showed that foundation elevation significantly affected scour depth.Foundations at or below the bed(Z/D≥0)reduced scour,while those projecting into the flow field(Z/D<0)increased scour.The optimal foundation elevation was found to be 0.1D below the bed level,yielding a 57%reduction in scour depth compared to the uniform pier due to its shielding effect against downflow and horseshoe vortices.In addition,regression,artificial neural network(ANN),and M5 model tree models were developed using experimental data from this and previous studies.The M5 model outperformed the traditional HEC-18 equation,regression,and ANN models,with a coefficient of determination greater than 0.85.Sensitivity analysis indicated that flow depth,foundation elevation,and diameter significantly influenced scour depth prediction,whereas sediment size had a lesser impact.
基金supported by the National Major Scientific Instruments and Equipment Development Projects of China(No.41827808)the Major Program of the National Natural Science Foundation of China(No.42090055)Supported by Science and Technology Projects of Xizang Autonomous Region,China(No.XZ202402ZD0001)。
文摘In 2018,a catastrophic high-altitude landslide occurred at Baige,located within the tectonic suture zone of the Upper Jinsha River.The failure mechanism of this event remains poorly understood.This study aims to elucidate the deformation characteristics and failure mechanism of the Baige landslide by employing a comprehensive methodology,including field geological surveys,analysis of historical remote sensing imagery,high-density electrical resistivity surveys,and advanced displacement monitoring.Additionally,the physical modeling experiments were conducted to replicate the unique failure modes.The findings propose a novel perspective on the failure mechanism of the Baige landslide,which involves two critical stages:first,the brittle shear zone bypasses and fails at the lower locked segment,and second,the failure of the upper locked segment,combined with the shear zone's impact on the lower locked segment,triggers overall slope instability.Physical modeling experiments revealed a transition from initial acceleration to a rapid acceleration phase,particularly marked by a significant increase in velocity following the failure of the upper locked segment.The intensity of acoustic emission signals was found to correlate with the failure of the locked segments and the state of particle collisions post-failure.It offers new insights into the failure mechanisms of tectonic mélange belt large-scale landslides in suture zones,contributing to the broader field of landslide research.
