Periodontitis,a prevalent microbe-driven disease,is characterized by the progressive destruction of tooth-supporting tissues.Porphyromonas gingivalis(P.gingivalis),a keystone pathogen in chronic periodonti-tis,evades ...Periodontitis,a prevalent microbe-driven disease,is characterized by the progressive destruction of tooth-supporting tissues.Porphyromonas gingivalis(P.gingivalis),a keystone pathogen in chronic periodonti-tis,evades clearance by periodontal immune cells,leading to microbial dysbiosis and alveolar bone re-sorption.Effective treatment requires the elimination of periodontopathogens and restoration of alveolar bone.Macrophages serve as the primary defense against periodontal pathogens.Cell stiffness,an intrin-sic mechanical property of macrophage,is closely linked to their motility,deformability,and phagocytic function,presenting a potential target for enhancing macrophage antibacterial activities.Black phospho-rus nanosheets(BPNS),a novel two-dimensional material that degrades into nontoxic phosphate in phys-iological environments,offer distinct advantages in bone regeneration.In this study,BPNS was functional-ized with spermidine(Spd),a natural polyamine with immunomodulatory effects,to improve periodon-tal infection control.In addition to preserving BPNS's osteogenic activity,BPNS@Spd further enhanced macrophage antibacterial function by targeting cell stiffness.Reduced cell stiffness enhanced macrophage deformability and membrane fluidity,facilitating more efficient phagocytosis and clearance of P.gingi-valis.Mechanistically,BPNS@Spd modulated macrophage stiffness and function by decreasing membrane cholesterol content,in which autophagy-mediated cholesterol efflux plays a critical role.This work under-scores the potential of modulating membrane cholesterol and cell stiffness to boost macrophage-mediated bacterial clearance,offering an innovative immunomodulatory approach for managing microbe-driven in-flammatory diseases beyond periodontitis.展开更多
Glacial lake outburst floods(GLOFs)are increasingly frequent under warming and degradation,exerting profound impacts on regional ecosystems,geomorphology,and human systems.Ice-dammed lakes account for nearly 70%of GLO...Glacial lake outburst floods(GLOFs)are increasingly frequent under warming and degradation,exerting profound impacts on regional ecosystems,geomorphology,and human systems.Ice-dammed lakes account for nearly 70%of GLOFs worldwide,yet their dynamics remain poorly understood in remote regions such as the interior Tibetan Plateau.Here,we present the first systematic assessment of the evolution and drainage of ice-dammed lakes across the region using multi-source satellite imagery.Between 1973 and 2024,the number of ice-dammed lakes increased from 256 to 323,while the total area declined from 22.66±0.93 km^(2)to 20.43±1.6 km^(2)due to repeated drainage and diminished reservoir capacity.Newly formed lakes tended to shift toward higher elevations.A total of 775 previously unreported GLOFs were detected based on abrupt lake area loss.Bayesian regression reveals a sharp rise in GLOF frequency,from an average of 11 GLOFs per year during 1990-1994 to 42.6 GLOFs per year during 2020-2024.Meanwhile,GLOF timing has shifted earlier by 9.07±3.71 days,and pre-drainage lake areas declined by 0.02±0.01 km^(2)compared to 1990.These findings highlight the evolving behavior of ice-dammed lakes in response to climate change and glacial recession,with important implications for regional cryospheric research and disaster mitigation.展开更多
目的:本文报道1例无托槽隐形矫治器联合种植支抗和舌刺矫治成年骨性Ⅱ类高角伴前牙开[牙合]的病例。诊治经过:成年女性,骨性Ⅱ类高角型,磨牙中性关系,前牙开[牙合],采用无托槽隐形矫治器进行矫治,上下磨牙区植入支抗钉进行磨牙压低,上...目的:本文报道1例无托槽隐形矫治器联合种植支抗和舌刺矫治成年骨性Ⅱ类高角伴前牙开[牙合]的病例。诊治经过:成年女性,骨性Ⅱ类高角型,磨牙中性关系,前牙开[牙合],采用无托槽隐形矫治器进行矫治,上下磨牙区植入支抗钉进行磨牙压低,上下前牙粘接舌刺纠正吐舌习惯。结果:经过26个月的正畸治疗,患者开改善,尖牙磨牙中性,上下中线一致,牙根平行度好,上齿槽座点-鼻根点-下齿槽座点夹角(A point-nasion-B point angle,ANB)减小,下颌平面角减小,侧貌改善,随访半年保持效果良好。结论:无托槽隐形矫治器联合种植支抗可在骨性Ⅱ类高角伴前牙开的正畸治疗中进行有效的垂直向控制,联合舌刺可同时改善吐舌习惯。展开更多
Glacial lake outburst floods(GLOFs) are a major concern in the Himalaya and on the Tibetan Plateau(TP),where several disasters occurring over the past century have caused significant loss of life and damage to infrast...Glacial lake outburst floods(GLOFs) are a major concern in the Himalaya and on the Tibetan Plateau(TP),where several disasters occurring over the past century have caused significant loss of life and damage to infrastructure. This study responds directly to the needs of local authorities to provide guidance on the most dangerous glacial lakes across TP where local monitoring and other risk reduction strategies can subsequently be targeted. Specifically, the study aims to establish a first comprehensive prioritisation ranking of lake danger for TP, considering both the likelihood and possible magnitude of any outburst event(hazard), and the exposure of downstream communities. A composite inventory of 1,291 glacial lakes(>0.1 km^2) was derived from recent remote sensing studies, and a fully automated and object assessment scheme was implemented using customised GIS tools. Based on four core determinates of GLOF hazard(lake size, watershed area, topographic potential for ice/rock avalanching, and dam steepness), the scheme accurately distinguishes the high to very high hazard level of 19 out of 20 lakes that have previously generated GLOFs. Notably, 16% of all glacial lakes threaten human settlements, with a hotspot of GLOF danger identified in the central Himalayan counties of Jilong, Nyalam, and Dingri, where the potential trans-boundary threat to communities located downstream in Nepal is also recognised. The results provide an important and object scientific basis for decision-making, and the methodological approach is ideally suited for replication across other mountainous regions where such first-order studies are lacking.展开更多
Irregular defects generated by trauma or surgery in orthopaedics practice were usually difficult to be fitted by the preformed traditional bone graft substitute.Therefore,the injectable hydrogels have attracted an inc...Irregular defects generated by trauma or surgery in orthopaedics practice were usually difficult to be fitted by the preformed traditional bone graft substitute.Therefore,the injectable hydrogels have attracted an increasing interest for bone repair because of their fittability and mini-invasivity.However,the uncontrollable spreading or mechanical failures during its manipulation remain a problem to be solved.Moreover,in order to achieve vascularized bone regeneration,alternatives of osteogenic and angiogenic growth factors should be adopted to avoid the problem of immunogenicity and high cost.In this study,a novel injectable self-healing hydrogel system(GMO hydrogel)loaded with KP and QK peptides had been developed for enhancing vascularized regeneration of small irregular bone defect.The dynamic imine bonds between gelatin methacryloyl and oxidized dextran provided the GMO hydrogel with self-healing and shear-thinning abilities,which led to an excellent injectability and fittability.By photopolymerization of the enclosed GelMA,GMO hydrogel was further strengthened and thus more suitable for bone regeneration.Besides,the osteogenic peptide KP and angiogenic peptide QK were tethered to GMO hydrogel by Schiff base reaction,leading to desired releasing profiles.In vitro,this composite hydrogel could significantly improve the osteogenic differentiation of BMSCs and angiogenesis ability of HUVECs.In vivo,KP and QK in the GMO hydrogel demonstrated a significant synergistic effect in promoting new bone formation in rat calvaria.Overall,the KP and QK loaded GMO hydrogel was injectable and self-healing,which can be served as an efficient approach for vascularized bone regeneration via a minimally invasive approach.展开更多
Glacier-related slope failures,including ice avalanches,ice-rock avalanches,glacier collapses,and rock avalanches on glaciers,are generally characterized by large collapse volumes,solid-liquid phase transition,and hig...Glacier-related slope failures,including ice avalanches,ice-rock avalanches,glacier collapses,and rock avalanches on glaciers,are generally characterized by large collapse volumes,solid-liquid phase transition,and high mobility[1].They are one of the major types of geo-hazards in high mountain areas.Glacier-related slope failures have cascading effects since they often evolve into glacial lake outburst floods(GLOFs),debris flows,and dammed lakes,which significantly prolong and amplify the impacts of the hazard.Tragic slope failures have cumulatively claimed more than tens of thousands of lives.For example,the 1962 and 1970 Huascaran events in the Peruvian Andes caused approximately 20,000 deaths[2],and the 2021 Chamoli ice-rock avalanche in the Indian Himalayas left more than 200 people dead or missing[3].展开更多
Lake-effect snowfall(LES)occurs when cold air moves across open lakes.LES is expected to occur more frequently over the TP,due to the intensified lake expansion caused by intensified global warming.Thus,there is an ur...Lake-effect snowfall(LES)occurs when cold air moves across open lakes.LES is expected to occur more frequently over the TP,due to the intensified lake expansion caused by intensified global warming.Thus,there is an urgent need to comprehensively assess the LES over the TP.Here,we revealed that the LES is triggered by westerly southward shift leading to the drop in air temperature and is positively correlated with lake area,wind speed and longitude across 12 large lakes(>300 km^(2))based on satellite observations and reanalysis data.Using a sensitivity model simulation,we determined that large lakes in the southern TP contributed to more than 50%of the snowfall in the downwind area in 2013.Projections indicate that the westerly-triggered LES will increase under the future RCP4.5 climate warming scenario,highlighting the importance of developing adaptive policies to address the growing risks associated with future LES.展开更多
基金supported by the National Key Re-search and Development Program of China(No.2023YFB3809904)the National Natural Science Foundation of China(Nos.82373255 and 82001005)+2 种基金the Natural Science Foundation of Guangdong Province,China(Nos.2024A1515012918 and 2023A1515030015)the Special Funds for the Cultivation of Guangdong College Stu-dents’Scientific and Technological Innovation(“Climbing Program”Special Funds.pdjh2024b018)the National Undergraduate Train-ing Program for Innovation and Entrepreneurship(No.20240543).
文摘Periodontitis,a prevalent microbe-driven disease,is characterized by the progressive destruction of tooth-supporting tissues.Porphyromonas gingivalis(P.gingivalis),a keystone pathogen in chronic periodonti-tis,evades clearance by periodontal immune cells,leading to microbial dysbiosis and alveolar bone re-sorption.Effective treatment requires the elimination of periodontopathogens and restoration of alveolar bone.Macrophages serve as the primary defense against periodontal pathogens.Cell stiffness,an intrin-sic mechanical property of macrophage,is closely linked to their motility,deformability,and phagocytic function,presenting a potential target for enhancing macrophage antibacterial activities.Black phospho-rus nanosheets(BPNS),a novel two-dimensional material that degrades into nontoxic phosphate in phys-iological environments,offer distinct advantages in bone regeneration.In this study,BPNS was functional-ized with spermidine(Spd),a natural polyamine with immunomodulatory effects,to improve periodon-tal infection control.In addition to preserving BPNS's osteogenic activity,BPNS@Spd further enhanced macrophage antibacterial function by targeting cell stiffness.Reduced cell stiffness enhanced macrophage deformability and membrane fluidity,facilitating more efficient phagocytosis and clearance of P.gingi-valis.Mechanistically,BPNS@Spd modulated macrophage stiffness and function by decreasing membrane cholesterol content,in which autophagy-mediated cholesterol efflux plays a critical role.This work under-scores the potential of modulating membrane cholesterol and cell stiffness to boost macrophage-mediated bacterial clearance,offering an innovative immunomodulatory approach for managing microbe-driven in-flammatory diseases beyond periodontitis.
基金supported by the National Natural Science Foundation of China(Grant Nos.424B2002,U23A2011)National Key R&D Program of China(Grant No.2024YFF0808603)Second Tibetan Plateau Scientific Expedition and Research(STEP)Program(Grant Nos.2024QZKK0500,2024QZKK0400).
文摘Glacial lake outburst floods(GLOFs)are increasingly frequent under warming and degradation,exerting profound impacts on regional ecosystems,geomorphology,and human systems.Ice-dammed lakes account for nearly 70%of GLOFs worldwide,yet their dynamics remain poorly understood in remote regions such as the interior Tibetan Plateau.Here,we present the first systematic assessment of the evolution and drainage of ice-dammed lakes across the region using multi-source satellite imagery.Between 1973 and 2024,the number of ice-dammed lakes increased from 256 to 323,while the total area declined from 22.66±0.93 km^(2)to 20.43±1.6 km^(2)due to repeated drainage and diminished reservoir capacity.Newly formed lakes tended to shift toward higher elevations.A total of 775 previously unreported GLOFs were detected based on abrupt lake area loss.Bayesian regression reveals a sharp rise in GLOF frequency,from an average of 11 GLOFs per year during 1990-1994 to 42.6 GLOFs per year during 2020-2024.Meanwhile,GLOF timing has shifted earlier by 9.07±3.71 days,and pre-drainage lake areas declined by 0.02±0.01 km^(2)compared to 1990.These findings highlight the evolving behavior of ice-dammed lakes in response to climate change and glacial recession,with important implications for regional cryospheric research and disaster mitigation.
文摘目的:本文报道1例无托槽隐形矫治器联合种植支抗和舌刺矫治成年骨性Ⅱ类高角伴前牙开[牙合]的病例。诊治经过:成年女性,骨性Ⅱ类高角型,磨牙中性关系,前牙开[牙合],采用无托槽隐形矫治器进行矫治,上下磨牙区植入支抗钉进行磨牙压低,上下前牙粘接舌刺纠正吐舌习惯。结果:经过26个月的正畸治疗,患者开改善,尖牙磨牙中性,上下中线一致,牙根平行度好,上齿槽座点-鼻根点-下齿槽座点夹角(A point-nasion-B point angle,ANB)减小,下颌平面角减小,侧貌改善,随访半年保持效果良好。结论:无托槽隐形矫治器联合种植支抗可在骨性Ⅱ类高角伴前牙开的正畸治疗中进行有效的垂直向控制,联合舌刺可同时改善吐舌习惯。
基金supported by the Swiss National Science Foundation (IZLCZ2_169979/1)counterpart grant of the National Natural Science Foundation of China (21661132003)+1 种基金support of the Strategic Priority Research Program (A) of the Chinese Academy of Sciences (XDA20060201)collaboration within the Dragon 4 project funded by the European Space Agency (4000121469/17/I-NB)
文摘Glacial lake outburst floods(GLOFs) are a major concern in the Himalaya and on the Tibetan Plateau(TP),where several disasters occurring over the past century have caused significant loss of life and damage to infrastructure. This study responds directly to the needs of local authorities to provide guidance on the most dangerous glacial lakes across TP where local monitoring and other risk reduction strategies can subsequently be targeted. Specifically, the study aims to establish a first comprehensive prioritisation ranking of lake danger for TP, considering both the likelihood and possible magnitude of any outburst event(hazard), and the exposure of downstream communities. A composite inventory of 1,291 glacial lakes(>0.1 km^2) was derived from recent remote sensing studies, and a fully automated and object assessment scheme was implemented using customised GIS tools. Based on four core determinates of GLOF hazard(lake size, watershed area, topographic potential for ice/rock avalanching, and dam steepness), the scheme accurately distinguishes the high to very high hazard level of 19 out of 20 lakes that have previously generated GLOFs. Notably, 16% of all glacial lakes threaten human settlements, with a hotspot of GLOF danger identified in the central Himalayan counties of Jilong, Nyalam, and Dingri, where the potential trans-boundary threat to communities located downstream in Nepal is also recognised. The results provide an important and object scientific basis for decision-making, and the methodological approach is ideally suited for replication across other mountainous regions where such first-order studies are lacking.
基金the National Natural Science Foundation of China(32071341,82001005,81600824,52003302)Natural Science Foundation of Guangdong Province(2018A030310278,2019A1515011935,2017A030308004)+2 种基金Science and Technology Program of Guangzhou(201804010459,201804020011)the fellowship of China Postdoctoral Science Foundation(2021M691464)National Key R&D Program of China(2016YFC0905203).
文摘Irregular defects generated by trauma or surgery in orthopaedics practice were usually difficult to be fitted by the preformed traditional bone graft substitute.Therefore,the injectable hydrogels have attracted an increasing interest for bone repair because of their fittability and mini-invasivity.However,the uncontrollable spreading or mechanical failures during its manipulation remain a problem to be solved.Moreover,in order to achieve vascularized bone regeneration,alternatives of osteogenic and angiogenic growth factors should be adopted to avoid the problem of immunogenicity and high cost.In this study,a novel injectable self-healing hydrogel system(GMO hydrogel)loaded with KP and QK peptides had been developed for enhancing vascularized regeneration of small irregular bone defect.The dynamic imine bonds between gelatin methacryloyl and oxidized dextran provided the GMO hydrogel with self-healing and shear-thinning abilities,which led to an excellent injectability and fittability.By photopolymerization of the enclosed GelMA,GMO hydrogel was further strengthened and thus more suitable for bone regeneration.Besides,the osteogenic peptide KP and angiogenic peptide QK were tethered to GMO hydrogel by Schiff base reaction,leading to desired releasing profiles.In vitro,this composite hydrogel could significantly improve the osteogenic differentiation of BMSCs and angiogenesis ability of HUVECs.In vivo,KP and QK in the GMO hydrogel demonstrated a significant synergistic effect in promoting new bone formation in rat calvaria.Overall,the KP and QK loaded GMO hydrogel was injectable and self-healing,which can be served as an efficient approach for vascularized bone regeneration via a minimally invasive approach.
基金the Second Tibetan Plateau Scientific Expedition and Research Program(STEP)(2019QZKK0208)International Partnership Program of the Chinese Academy of Sciences(131C11KYSB20200029)Lhasa Earth System MultiDimension Observatory Network(LEMON)。
文摘Glacier-related slope failures,including ice avalanches,ice-rock avalanches,glacier collapses,and rock avalanches on glaciers,are generally characterized by large collapse volumes,solid-liquid phase transition,and high mobility[1].They are one of the major types of geo-hazards in high mountain areas.Glacier-related slope failures have cascading effects since they often evolve into glacial lake outburst floods(GLOFs),debris flows,and dammed lakes,which significantly prolong and amplify the impacts of the hazard.Tragic slope failures have cumulatively claimed more than tens of thousands of lives.For example,the 1962 and 1970 Huascaran events in the Peruvian Andes caused approximately 20,000 deaths[2],and the 2021 Chamoli ice-rock avalanche in the Indian Himalayas left more than 200 people dead or missing[3].
基金supported by the Youth Innovation Promotion Association of Chinese Academy of Sciences(CAS2022067)the Basic Science Center for Tibetan Plateau Earth System(41988101)。
文摘Lake-effect snowfall(LES)occurs when cold air moves across open lakes.LES is expected to occur more frequently over the TP,due to the intensified lake expansion caused by intensified global warming.Thus,there is an urgent need to comprehensively assess the LES over the TP.Here,we revealed that the LES is triggered by westerly southward shift leading to the drop in air temperature and is positively correlated with lake area,wind speed and longitude across 12 large lakes(>300 km^(2))based on satellite observations and reanalysis data.Using a sensitivity model simulation,we determined that large lakes in the southern TP contributed to more than 50%of the snowfall in the downwind area in 2013.Projections indicate that the westerly-triggered LES will increase under the future RCP4.5 climate warming scenario,highlighting the importance of developing adaptive policies to address the growing risks associated with future LES.
