Pathological mineralizations in breast lesions are closely associated with disease progression and serves as a critical diagnostic indicator.However,systematic understanding remains lacking regarding the phase categor...Pathological mineralizations in breast lesions are closely associated with disease progression and serves as a critical diagnostic indicator.However,systematic understanding remains lacking regarding the phase categories,distribution patterns,and proportional occurrences of mineral phases across different breast lesion types.The diagnostic implications of specific phases,such as calcium oxalate,for distinguishing benign and malignant lesions remain controversial.This study employed polarizing microscopy,environmental scanning electron microscopy(SEM)with energy dispersive spectroscopy(EDS),transmission electron microscopy(TEM),Fourier transform infrared spectroscopy(FTIR),and Raman spectroscopy to analyze the phase composition of 61 mineralized samples from three lesion types:Invasive carcinoma,carcinoma in situ and benign lesions.Results demonstrate that breast lesion mineralizations predominantly comprise calcium phosphates,including hydroxyapatite(HA),amorphous calcium phosphate(ACP),and whitlockite,occasionally accompanied by calcium oxalate(monohydrate or dihydrate).Distinct distribution patterns and proportional occurrences of minerals were observed among the three types of lesion mineralizations.HA,as the predominant phase,was ubiquitously present across all three lesion categories.ACP,a mineralization precursor phase,emerged during early mineralization stages across all lesion types.Notably,whitlockite exclusively occurred in benign lesions and carcinoma in situ,with higher prevalence in benign cases,suggesting a progressive decline in Mg^(2+)concentration within the lesion microenvironment as malignancy advances.Calcium oxalate coexisted with HA in mineralized regions across all lesion types,and its presence in invasive carcinoma specimens warrants heightened clinical attention.展开更多
Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize ...Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize the bone regeneration.However,how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood.Here,by employing single-cell transcriptional profiling combined with lineage-specific tracing models,we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.Importantly,our data demonstrated that the Sonic hedgehog(Shh)signaling was responsible for the transition process initiation,which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers.Collectively,these findings depict an injuryspecific niche signal-mediated Plp1-lineage cells transition towards Gli1+MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.展开更多
Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen,particularly the Porphyromonas gingivalis(P.gingivalis),by inducing ...Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen,particularly the Porphyromonas gingivalis(P.gingivalis),by inducing apoptosis.However,it remains obscure whether accumulated apoptotic cells in P.gingivalis-accelerated plaque formation are associated with impaired macrophage clearance.展开更多
As is known to all, nitrogen not only plays an important role in the industrial development of human society but also plays an important part in the proteins that constitute the essence of life[1]. In 1910, the Haber-...As is known to all, nitrogen not only plays an important role in the industrial development of human society but also plays an important part in the proteins that constitute the essence of life[1]. In 1910, the Haber-Bosch process was first used to synthesize ammonia.展开更多
Integrated sensing and communication(ISAC) is considered an effective technique to solve spectrum congestion in the future. In this paper, we consider a hybrid reconfigurable intelligent surface(RIS)-assisted downlink...Integrated sensing and communication(ISAC) is considered an effective technique to solve spectrum congestion in the future. In this paper, we consider a hybrid reconfigurable intelligent surface(RIS)-assisted downlink ISAC system that simultaneously serves multiple single-antenna communication users and senses multiple targets. Hybrid RIS differs from fully passive RIS in that it is composed of both active and passive elements, with the active elements having the effect of amplifying the signal in addition to phase-shifting. We maximize the achievable sum rate of communication users by collaboratively improving the beamforming matrix at the dual function base station(DFBS) and the phase-shifting matrix of the hybrid RIS, subject to the transmit power constraint at the DFBS, the signal-to-interference-plus-noise-ratio(SINR) constraint of the radar echo signal and the RIS constraint are satisfied at the same time. The builtin RIS-assisted ISAC design problem model is significantly non-convex due to the fractional objective function of this optimization problem and the coupling of the optimization variables in the objective function and constraints. As a result, we provide an effective alternating optimization approach based on fractional programming(FP) with block coordinate descent(BCD)to solve the optimization variables. Results from simulations show that the hybrid RIS-assisted ISAC system outperforms the other benchmark solutions.展开更多
Brain vascular dysfunction in Alzheimer s disease(AD) pathogenesis has become increasingly clea r.Accumulating evidence shows that damaged vascular,including large or small vessels and even neurovascular unit,may acce...Brain vascular dysfunction in Alzheimer s disease(AD) pathogenesis has become increasingly clea r.Accumulating evidence shows that damaged vascular,including large or small vessels and even neurovascular unit,may accelerate the neuropathological process of AD via disrupting brain hypoperfusion,aberrant angiogenesis,and neuroinflammatory response,etc.Thus,vascular dysfunction makes a substantially contribution to the cognitive decline of AD patients.展开更多
Wound healing in diabetic ulcers remains a significant clinical challenge,primarily due to bacterial infection and impaired angiogenesis.Periplaneta americana extract(PAE)has been widely used to treat diabetic wounds,...Wound healing in diabetic ulcers remains a significant clinical challenge,primarily due to bacterial infection and impaired angiogenesis.Periplaneta americana extract(PAE)has been widely used to treat diabetic wounds,yet its underlying mechanisms are not fully understood.This study aimed to elucidate these mechanisms by analyzing long non-coding RNA(lncRNA)expressions in the wound tissues from diabetic anal fistula patients treated with or without PAE,using high-throughput sequencing.Peripheral blood monocytes from patients were differentiated into M0 macrophages with human macrophage colony-stimulating factor(hMCSF)and subsequently polarized into M1 macrophages with lipopolysaccharide.The results indicated that LINC01133 and SLAMF9 were downregulated in wound tissues of patients treated with PAE.Furthermore,PAE suppressed M1 macrophage polarization and enhanced human umbilical vein endothelial cell(HUVEC)proliferation,migration,and angiogenesis.These effects were diminished when LINC01133 or SLAMF9 were overexpressed.Mechanistically,LINC01133 was shown to upregulate SLAMF9 through interaction with ELAVL1.Overexpression of SLAMF9 reversed the effects of LINC01133 silencing on macrophage polarization and HUVEC functions.In conclusion,PAE facilitates the healing of infected diabetic ulcers by downregulating the LINC01133/SLAMF9 pathway.展开更多
This study investigated the spatial distribution and genesis of iron(Fe),manganese(Mn),arsenic(As),nitrate nitrogen(NO_(3)-N),and ammonia nitrogen(NH_(3)-N)in groundwater across representative regions of Beijing Plain...This study investigated the spatial distribution and genesis of iron(Fe),manganese(Mn),arsenic(As),nitrate nitrogen(NO_(3)-N),and ammonia nitrogen(NH_(3)-N)in groundwater across representative regions of Beijing Plain(Yongding River alluvial fans-plains).An integrated methodology incorporating hydrochemical analysis,isotopic fingerprinting,sediment geochemistry,mineralogical and micromorphology analysis was systematically implemented.Analytical results demonstrated that groundwater As and NH_(3)-N concentrations remained below the Class Ⅲ water criteria of China's standard for groundwater quality.Groundwater NO_(3)-N,Fe,and Mn concentrations exceeded their Class Ⅲ standards in 7.69%,11.54%,and 19.23% of samples,respectively.Comprehensive assessments demonstrated that human health risks from groundwater hazard substances remained within acceptable thresholds.Mineralogical analysis results indicated that Fe/Mn-bearing minerals distributed in sediments were the primary geogenic sources of groundwater Fe/Mn.Furthermore,isotopic evidences coupled with hydrochemical fingerprints demonstrated that shallow groundwater NO_(3)-N concentrations were influenced by anthropogenic nitrogen inputs.Hydrogeochemical processes induced spatially heterogeneous distributions of As,Fe,Mn,NO_(3)-N,and NH_(3)-N concentrations in groundwater.In the northwestern piedmont area,groundwater Mn enrichment was mainly influenced by the underlying coal seams.The central alluvial fan area exhibited co-enrichment of NO_(3)-N and Fe primarily attributed to the combined effects of the geogenic Fe-bearing minerals dissolution under nitrifying conditions,manure and sewage inputs,and further intensified by the evaporation-concentration effects.In the southeastern alluvial plain,the co-enrichment of Fe and/or Mn concurrent with As/NH_(3)-N concentration fluctuation was governed by nitrate reduction,iron/manganese reduction,and iron/manganese-sulfate reduction processes.In addition,pH-dependent mineral dissolution-precipitation and adsorption-desorption further modulated the mobilization of As,Fe,and Mn in the alluvial plain area.These findings are crucial for groundwater protection and can also provide a scientific basis for ensuring drinking water security in Beijing.展开更多
Bone defect repair remains a great challenge in the field of orthopedics.Human body essential trace element such as copper is essential for bone regeneration,but how to use it in bone defects and the underlying its me...Bone defect repair remains a great challenge in the field of orthopedics.Human body essential trace element such as copper is essential for bone regeneration,but how to use it in bone defects and the underlying its mechanisms of promoting bone formation need to be further explored.In this study,by doping copper into mesoporous bioactive glass nanoparticles(Cu-MBGNs),we unveil a previously unidentified role of copper in facilitating osteoblast mitophagy and mitochondrial dynamics,which enhance amorphous calcium phosphate(ACP)release and subsequent biomineralization,ultimately accelerating the process of bone regeneration.Specifically,by constructing conditional knockout mice lacking the autophagy gene Atg5 in osteogenic lineage cells,we first confirmed the role of Cu-MBGNs-promoted bone formation via mediating osteoblast autophagy pathway.Then,the in vitro studies revealed that Cu-MBGNs strengthened mitophagy by inducing ROS production and recruiting PINK1/Parkin,thereby facilitating the efficient release of ACP from mitochondria into matrix vesicles for bio-mineralization during bone regeneration.Moreover,we found that Cu-MBGNs promoted mitochondrion fission via activating dynamin related protein 1(Drp1)to reinforce mitophagy pathway.Together,this study highlights the potential of Cu-MBGNs-mediated mitophagy and biomineralization for augmenting bone regeneration,of-fering a promising avenue for the development of advanced bioactive materials in orthopedic applications.展开更多
基金financially supported by the National Natural Science Foundation of China(41772033,41272048).
文摘Pathological mineralizations in breast lesions are closely associated with disease progression and serves as a critical diagnostic indicator.However,systematic understanding remains lacking regarding the phase categories,distribution patterns,and proportional occurrences of mineral phases across different breast lesion types.The diagnostic implications of specific phases,such as calcium oxalate,for distinguishing benign and malignant lesions remain controversial.This study employed polarizing microscopy,environmental scanning electron microscopy(SEM)with energy dispersive spectroscopy(EDS),transmission electron microscopy(TEM),Fourier transform infrared spectroscopy(FTIR),and Raman spectroscopy to analyze the phase composition of 61 mineralized samples from three lesion types:Invasive carcinoma,carcinoma in situ and benign lesions.Results demonstrate that breast lesion mineralizations predominantly comprise calcium phosphates,including hydroxyapatite(HA),amorphous calcium phosphate(ACP),and whitlockite,occasionally accompanied by calcium oxalate(monohydrate or dihydrate).Distinct distribution patterns and proportional occurrences of minerals were observed among the three types of lesion mineralizations.HA,as the predominant phase,was ubiquitously present across all three lesion categories.ACP,a mineralization precursor phase,emerged during early mineralization stages across all lesion types.Notably,whitlockite exclusively occurred in benign lesions and carcinoma in situ,with higher prevalence in benign cases,suggesting a progressive decline in Mg^(2+)concentration within the lesion microenvironment as malignancy advances.Calcium oxalate coexisted with HA in mineralized regions across all lesion types,and its presence in invasive carcinoma specimens warrants heightened clinical attention.
基金supported by the National Natural Science Foundation of China(grants 81970910 and 82370931)Jiangsu Province Capability Improvement Project through Science,Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit(YJXYYJSDW4)Jiangsu Provincial Medical Innovation Center(CXZX202227).
文摘Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize the bone regeneration.However,how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood.Here,by employing single-cell transcriptional profiling combined with lineage-specific tracing models,we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.Importantly,our data demonstrated that the Sonic hedgehog(Shh)signaling was responsible for the transition process initiation,which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers.Collectively,these findings depict an injuryspecific niche signal-mediated Plp1-lineage cells transition towards Gli1+MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.
基金supported by the National Natural Science Foundation of China(grants82001012,81970910,and 81771092)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(grants 19KJA360003)China Postdoctoral Science Foundation(2021M691640)。
文摘Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen,particularly the Porphyromonas gingivalis(P.gingivalis),by inducing apoptosis.However,it remains obscure whether accumulated apoptotic cells in P.gingivalis-accelerated plaque formation are associated with impaired macrophage clearance.
基金supported by the National Key R&D Program of China(2017YFA0208300 and 2017YFA0700104)the National Natural Science Foundation of China(21671180 and 21406184)+2 种基金the Chengdu International Science and Technology Cooperation Fund(2020GH0200069HZ)the funding support from CAS Fujian Institute of Innovationfinancially supported by the DNL Cooperation Fund(DNL201918)。
文摘As is known to all, nitrogen not only plays an important role in the industrial development of human society but also plays an important part in the proteins that constitute the essence of life[1]. In 1910, the Haber-Bosch process was first used to synthesize ammonia.
文摘Integrated sensing and communication(ISAC) is considered an effective technique to solve spectrum congestion in the future. In this paper, we consider a hybrid reconfigurable intelligent surface(RIS)-assisted downlink ISAC system that simultaneously serves multiple single-antenna communication users and senses multiple targets. Hybrid RIS differs from fully passive RIS in that it is composed of both active and passive elements, with the active elements having the effect of amplifying the signal in addition to phase-shifting. We maximize the achievable sum rate of communication users by collaboratively improving the beamforming matrix at the dual function base station(DFBS) and the phase-shifting matrix of the hybrid RIS, subject to the transmit power constraint at the DFBS, the signal-to-interference-plus-noise-ratio(SINR) constraint of the radar echo signal and the RIS constraint are satisfied at the same time. The builtin RIS-assisted ISAC design problem model is significantly non-convex due to the fractional objective function of this optimization problem and the coupling of the optimization variables in the objective function and constraints. As a result, we provide an effective alternating optimization approach based on fractional programming(FP) with block coordinate descent(BCD)to solve the optimization variables. Results from simulations show that the hybrid RIS-assisted ISAC system outperforms the other benchmark solutions.
基金supported by the Science and Technology Innovation 2030-Major Projects,No.2022ZD021 1 600the National Natural Science Foundation of China,Nos.82271574 and82071204 (all to CX)。
文摘Brain vascular dysfunction in Alzheimer s disease(AD) pathogenesis has become increasingly clea r.Accumulating evidence shows that damaged vascular,including large or small vessels and even neurovascular unit,may accelerate the neuropathological process of AD via disrupting brain hypoperfusion,aberrant angiogenesis,and neuroinflammatory response,etc.Thus,vascular dysfunction makes a substantially contribution to the cognitive decline of AD patients.
基金supported by the Natural Science Foundation of Hunan Province(No.2021JJ30516).
文摘Wound healing in diabetic ulcers remains a significant clinical challenge,primarily due to bacterial infection and impaired angiogenesis.Periplaneta americana extract(PAE)has been widely used to treat diabetic wounds,yet its underlying mechanisms are not fully understood.This study aimed to elucidate these mechanisms by analyzing long non-coding RNA(lncRNA)expressions in the wound tissues from diabetic anal fistula patients treated with or without PAE,using high-throughput sequencing.Peripheral blood monocytes from patients were differentiated into M0 macrophages with human macrophage colony-stimulating factor(hMCSF)and subsequently polarized into M1 macrophages with lipopolysaccharide.The results indicated that LINC01133 and SLAMF9 were downregulated in wound tissues of patients treated with PAE.Furthermore,PAE suppressed M1 macrophage polarization and enhanced human umbilical vein endothelial cell(HUVEC)proliferation,migration,and angiogenesis.These effects were diminished when LINC01133 or SLAMF9 were overexpressed.Mechanistically,LINC01133 was shown to upregulate SLAMF9 through interaction with ELAVL1.Overexpression of SLAMF9 reversed the effects of LINC01133 silencing on macrophage polarization and HUVEC functions.In conclusion,PAE facilitates the healing of infected diabetic ulcers by downregulating the LINC01133/SLAMF9 pathway.
基金supported by the Groundwater Environmental Background Value Investigation Research Project in the Beijing Plain area。
文摘This study investigated the spatial distribution and genesis of iron(Fe),manganese(Mn),arsenic(As),nitrate nitrogen(NO_(3)-N),and ammonia nitrogen(NH_(3)-N)in groundwater across representative regions of Beijing Plain(Yongding River alluvial fans-plains).An integrated methodology incorporating hydrochemical analysis,isotopic fingerprinting,sediment geochemistry,mineralogical and micromorphology analysis was systematically implemented.Analytical results demonstrated that groundwater As and NH_(3)-N concentrations remained below the Class Ⅲ water criteria of China's standard for groundwater quality.Groundwater NO_(3)-N,Fe,and Mn concentrations exceeded their Class Ⅲ standards in 7.69%,11.54%,and 19.23% of samples,respectively.Comprehensive assessments demonstrated that human health risks from groundwater hazard substances remained within acceptable thresholds.Mineralogical analysis results indicated that Fe/Mn-bearing minerals distributed in sediments were the primary geogenic sources of groundwater Fe/Mn.Furthermore,isotopic evidences coupled with hydrochemical fingerprints demonstrated that shallow groundwater NO_(3)-N concentrations were influenced by anthropogenic nitrogen inputs.Hydrogeochemical processes induced spatially heterogeneous distributions of As,Fe,Mn,NO_(3)-N,and NH_(3)-N concentrations in groundwater.In the northwestern piedmont area,groundwater Mn enrichment was mainly influenced by the underlying coal seams.The central alluvial fan area exhibited co-enrichment of NO_(3)-N and Fe primarily attributed to the combined effects of the geogenic Fe-bearing minerals dissolution under nitrifying conditions,manure and sewage inputs,and further intensified by the evaporation-concentration effects.In the southeastern alluvial plain,the co-enrichment of Fe and/or Mn concurrent with As/NH_(3)-N concentration fluctuation was governed by nitrate reduction,iron/manganese reduction,and iron/manganese-sulfate reduction processes.In addition,pH-dependent mineral dissolution-precipitation and adsorption-desorption further modulated the mobilization of As,Fe,and Mn in the alluvial plain area.These findings are crucial for groundwater protection and can also provide a scientific basis for ensuring drinking water security in Beijing.
基金supported by the National Natural Science Foundation of China(81771092,81970910 and 82370931)Jiangsu Province Capability Improvement Project through Science,Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit(YJXYYJSDW4)Jiangsu Provincial Medical Innovation Center(CXZX202227).
文摘Bone defect repair remains a great challenge in the field of orthopedics.Human body essential trace element such as copper is essential for bone regeneration,but how to use it in bone defects and the underlying its mechanisms of promoting bone formation need to be further explored.In this study,by doping copper into mesoporous bioactive glass nanoparticles(Cu-MBGNs),we unveil a previously unidentified role of copper in facilitating osteoblast mitophagy and mitochondrial dynamics,which enhance amorphous calcium phosphate(ACP)release and subsequent biomineralization,ultimately accelerating the process of bone regeneration.Specifically,by constructing conditional knockout mice lacking the autophagy gene Atg5 in osteogenic lineage cells,we first confirmed the role of Cu-MBGNs-promoted bone formation via mediating osteoblast autophagy pathway.Then,the in vitro studies revealed that Cu-MBGNs strengthened mitophagy by inducing ROS production and recruiting PINK1/Parkin,thereby facilitating the efficient release of ACP from mitochondria into matrix vesicles for bio-mineralization during bone regeneration.Moreover,we found that Cu-MBGNs promoted mitochondrion fission via activating dynamin related protein 1(Drp1)to reinforce mitophagy pathway.Together,this study highlights the potential of Cu-MBGNs-mediated mitophagy and biomineralization for augmenting bone regeneration,of-fering a promising avenue for the development of advanced bioactive materials in orthopedic applications.
文摘为了解西北印度洋公海中阿拉伯海外海的渔业资源开发状况、探究鸢乌贼(Symplectoteuthis oualaniensis)的渔场分布及其渔场环境要素对资源的影响,对阿拉伯海外海开展了2个航次的海上调查,获取每个调查站点的渔获量、水温等数据,利用广义可加模型(Generalized Additive Model,GAM)分析了多种海洋环境与时空要素对该海域鸢乌贼单位捕捞努力量渔获量(Catch per unit effort,CPUE)的影响。研究发现:1)鸢乌贼CPUE高值的集中区域主要有3个(60°E—61°E,16°N;62°E,16°N—18°N;61.50°E—63°E,17°N—17.75°N);2)最佳GAM模型的影响因素为经纬度、农历日、海表温度(Sea surface temperature,SST)、叶绿素a(Chl a)浓度和海表温度距平(Sea surface temperature anomaly,SSTA),其中方差解释率最高的前3位分别为经纬度、农历日和SSTA;3)农历日要素统计得到月黑夜总作业次数是月亮夜总作业次数的1.38倍,月黑夜的总渔获量比月亮夜的增加108.21%;4)GAM模型表明最适SST介于26.5~27.5℃,Chl a浓度介于0.30~0.50 mg·m^(−3),SSTA介于0~0.4℃。
