Over the past few decades,the Sonic Hedgehog protein has become a pivotal player in many biological processes,including tumourigenesis,embryonic development,and protective mechanisms after cerebral damage.The Sonic He...Over the past few decades,the Sonic Hedgehog protein has become a pivotal player in many biological processes,including tumourigenesis,embryonic development,and protective mechanisms after cerebral damage.The Sonic Hedgehog signaling pathway is crucial in the central nervous system,with implications in a diverse range of diseases,including Parkinson's disease,Alzheimer's disease,spinal cord injury,traumatic brain injury,depression,Sonic Hedgehog medulloblastoma,and stroke.In this comprehensive review,we examined Sonic Hedgehog from the perspective of canonical and non-canonical pathways,elucidating their complex connections to the central nervous system.Subsequently,we summarize the latest advancements in drug therapies that offer novel strategies for treating neurological diseases by modulating the Sonic Hedgehog protein.Finally,we summarize and extend the technologies and tools for studying the Sonic Hedgehog signaling field,with the aim of providing new research ideas and methods.展开更多
The sulfation and decomposition process has proven effective in selectively extracting lithium from lepidolite.It is essential to clarify the thermochemical behavior and kinetic parameters of decomposition reactions.A...The sulfation and decomposition process has proven effective in selectively extracting lithium from lepidolite.It is essential to clarify the thermochemical behavior and kinetic parameters of decomposition reactions.Accordingly,comprehensive kinetic study by employing thermalgravimetric analysis at various heating rates was presented in this paper.Two main weight loss regions were observed during heating.The initial region corresponded to the dehydration of crystal water,whereas the subsequent region with overlapping peaks involved complex decomposition reactions.The overlapping peaks were separated into two individual reaction peaks and the activation energy of each peak was calculated using isoconversional kinetics methods.The activation energy of peak 1 exhibited a continual increase as the reaction conversion progressed,while that of peak 2 steadily decreased.The optimal kinetic models,identified as belonging to the random nucleation and subsequent growth category,provided valuable insights into the mechanism of the decomposition reactions.Furthermore,the adjustment factor was introduced to reconstruct the kinetic mechanism models,and the reconstructed models described the kinetic mechanism model more accurately for the decomposition reactions.This study enhanced the understanding of the thermochemical behavior and kinetic parameters of the lepidolite sulfation product decomposition reactions,further providing theoretical basis for promoting the selective extraction of lithium.展开更多
A M_(S)6.4 earthquake occurred on 21 May 2021 in Yangbi county,Dali prefecture,Yunnan,China,at 21:48 Beijing Time(13:48 UTC).Earthquakes with an M3.0 or higher occurred before and after the main shock.Seismic data ana...A M_(S)6.4 earthquake occurred on 21 May 2021 in Yangbi county,Dali prefecture,Yunnan,China,at 21:48 Beijing Time(13:48 UTC).Earthquakes with an M3.0 or higher occurred before and after the main shock.Seismic data analysis is essential for the in-depth investigation of the 2021 Yangbi M_(S)6.4 earthquake sequence and the seismotectonics of northwestern Yunnan.Institute of Geophysics,China Earthquake Administration(CEA),has compiled a dataset of seismological observations from 157 broadband stations located within 500 km of the epicenter,and has made this dataset available to the earthquake science research community.The dataset(total file size:329 GB)consists of event waveforms with a sampling frequency of 100 sps collected from 18 to 28 May 2021,20-Hz and 100-Hz continuous waveforms collected from 12 to 31 May 2021,and seismic instrument response files.To promote data sharing,the dataset also includes the seismic event waveforms from 20 to 22 May 2021 recorded at 50 stations of the ongoing Binchuan Active Source Geophysical Observation Project,for which the data protection period has not expired.Sample waveforms of the main shock are included in the appendix of this article and can be downloaded from the Earthquake Science website.The event and continuous waveforms are available from the Earthquake Science Data Center website(www.esdc.ac.cn)on application.展开更多
The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
BACKGROUND The peritumoral region possesses attributes that promote cancer growth and progression.However,the potential prognostic biomarkers in this region remain relatively underexplored in radiomics.AIM To investig...BACKGROUND The peritumoral region possesses attributes that promote cancer growth and progression.However,the potential prognostic biomarkers in this region remain relatively underexplored in radiomics.AIM To investigate the prognostic value and importance of peritumoral radiomics in locally advanced rectal cancer(LARC).METHODS This retrospective study included 409 patients with biopsy-confirmed LARC treated with neoadjuvant chemoradiotherapy and surgically.Patients were divided into training(n=273)and validation(n=136)sets.Based on intratumoral and peritumoral radiomic features extracted from pretreatment axial high-resolution small-field-of-view T2-weighted images,multivariate Cox models for progression-free survival(PFS)prediction were developed with or without clinicoradiological features and evaluated with Harrell’s concordance index(C-index),calibration curve,and decision curve analyses.Risk stratification,Kaplan-Meier analysis,and permutation feature importance analysis were performed.RESULTS The comprehensive integrated clinical-radiological-omics model(ModelICRO)integrating seven peritumoral,three intratumoral,and four clinicoradiological features achieved the highest C-indices(0.836 and 0.801 in the training and validation sets,respectively).This model showed robust calibration and better clinical net benefits,effectively distinguished high-risk from low-risk patients(PFS:97.2%vs 67.6%and 95.4%vs 64.8%in the training and validation sets,respectively;both P<0.001).Three most influential predictors in the comprehensive ModelICRO were,in order,a peritumoral,an intratumoral,and a clinicoradiological feature.Notably,the peritumoral model outperformed the intratumoral model(C-index:0.754 vs 0.670;P=0.015);peritumoral features significantly enhanced the performance of models based on clinicoradiological or intratumoral features or their combinations.CONCLUSION Peritumoral radiomics holds greater prognostic value than intratumoral radiomics for predicting PFS in LARC.The comprehensive model may serve as a reliable tool for better stratification and management postoperatively.展开更多
Layered manganese dioxide(δ-MnO_(2))is a promising cathode material for aqueous zinc-ion batteries(AZIBs)due to its high theoretical capacity,high operating voltage,and low cost.However,its practical application face...Layered manganese dioxide(δ-MnO_(2))is a promising cathode material for aqueous zinc-ion batteries(AZIBs)due to its high theoretical capacity,high operating voltage,and low cost.However,its practical application faces challenges,such as low electronic conductivity,sluggish diffusion kinetics,and severe dissolution of Mn^(2+).In this study,we developed a δ-MnO_(2) coated with a 2-methylimidazole(δ-MnO_(2)@2-ML)hybrid cathode.Density functional theory(DFT)calculations indicate that 2-ML can be integrated into δ-MnO_(2) through both pre-intercalation and surface coating,with thermodynamically favorable outcomes.This modification expands the interlayer spacing of δ-MnO_(2) and generates Mn-N bonds on the surface,enhancing Zn^(2+)accommodation and diffusion kinetics as well as stabilizing surface Mn sites.The experimentally prepared δ-MnO_(2)@2-ML cathode,as predicted by DFT,features both 2-ML pre-intercalation and surface coating,providing more zinc-ion insertion sites and improved structural stability.Furthermore,X-ray diffraction shows the expanded interlayer spacing,which effectively buffers local electrostatic interactions,leading to an enhanced Zn^(2+)diffusion rate.Consequently,the optimized cathode(δ-MnO_(2)@2-ML)presents improved electrochemical performance and stability,and the fabricated AZIBs exhibit a high specific capacity(309.5mAh/g at 0.1 A/g),superior multiplicative performance(137.6mAh/g at 1 A/g),and impressive capacity retention(80%after 1350 cycles at 1 A/g).These results surpass the performance of most manganese-based and vanadium-based cathode materials reported to date.This dual-modulation strategy,combining interlayer engineering and interface optimization,offers a straightforward and scalable approach,potentially advancing the commercial viability of low-cost,high-performance AZIBs.展开更多
An organoid is a three-dimensional(3D)cell culture model that can reproduce the distinct structure and inherent functionality of certain organs.Nevertheless,a major limitation of organoids is the absence of a complex ...An organoid is a three-dimensional(3D)cell culture model that can reproduce the distinct structure and inherent functionality of certain organs.Nevertheless,a major limitation of organoids is the absence of a complex vascular network,thus restricting the supply of oxygen and essential nutrients.Coupled with their inherent size constraints and metabolite accumulation,it is challenging for organoids to replicate the natural intricacies of organs,thereby limiting their applicability.To overcome the challenges associated with this technology,we developed a culture platform to cultivate tumors or organ-derived organoids up to the centimeter scale.Initially,a customized organoid-on-a-chip including a microvascular network at the micron scale was designed using 3D printing.Further,by integrating an infusion device,the chip ensures an adequate supply of nutrients and fluid immersion while mimicking blood flow dynamics.Our method overcomes the issue of the limited size of organoids due to insufficient nutrient access,making it possible to produce large-scale tumor and normal tissue models in vitro,while providing insights into drug efficacy and toxicology evaluation as well as standardized organoid production.展开更多
Constructing silicon(Si)-based composite electrodes that possess high energy density,long cycle life,and fast charging capability simultaneously is critical for the development of high performance lithium-ion batterie...Constructing silicon(Si)-based composite electrodes that possess high energy density,long cycle life,and fast charging capability simultaneously is critical for the development of high performance lithium-ion batteries for mitigating range anxiety and slow charging issues in new energy vehicles.Herein,a thick silicon/carbon composite electrode with vertically aligned channels in the thickness direction(VC-SC)is constructed by employing a bubble formation method.Both experimental characterizations and theoretical simulations confirm that the obtained vertical channel structure can effectively address the problem of sluggish ion transport caused by high tortuosity in conventional thick electrodes,conspicuously enhance reaction kinetics,reduce polarization and side reactions,mitigate stress,increase the utilization of active materials,and promote cycling stability of the thick electrode.Consequently,when paired with LiNi_(0.6)Co_(0.2)Mn_(0.2)O_(2)(NCM622),the VC-SC||NCM622 pouch type full cell(~6.0 mAh cm^(-2))exhibits significantly improved rate performance and capacity retention compared with the SC||NCM622 full cell with the conventional silicon/carbon composite electrode without channels(SC)as the anode.The assembled VC-SC||NCM622 pouch full cell with a high energy density of 490.3 Wh kg^(-1)also reveals a remarkable fast charging capability at a high current density of 2.0 mA cm^(-2),with a capacity retention of 72.0%after 500 cycles.展开更多
基金supported by the National Natural Science Foundation of China,No.82474468the Science and Technology Innovation Program of Hunan Province,No.2024RC3200+3 种基金the Health Commission Talent Project of Hunan Province,No.20240304118the Scientific Research Project of Hunan Department of Education,No.23A0281the Open Fund for Chinese Medicine Powder and Innovative Drugs in the Cultivation Base of the Provincial-Ministry Jointly Established State Key Laboratory of Chinese Medicine,No.23PTKF1013the Training Plan of Outstanding Innovative Youth of Changsha,No.kq2009018(all to PM)。
文摘Over the past few decades,the Sonic Hedgehog protein has become a pivotal player in many biological processes,including tumourigenesis,embryonic development,and protective mechanisms after cerebral damage.The Sonic Hedgehog signaling pathway is crucial in the central nervous system,with implications in a diverse range of diseases,including Parkinson's disease,Alzheimer's disease,spinal cord injury,traumatic brain injury,depression,Sonic Hedgehog medulloblastoma,and stroke.In this comprehensive review,we examined Sonic Hedgehog from the perspective of canonical and non-canonical pathways,elucidating their complex connections to the central nervous system.Subsequently,we summarize the latest advancements in drug therapies that offer novel strategies for treating neurological diseases by modulating the Sonic Hedgehog protein.Finally,we summarize and extend the technologies and tools for studying the Sonic Hedgehog signaling field,with the aim of providing new research ideas and methods.
基金financially supported by the National Natural Science Foundation of China(Nos.52034002 and U2202254)the Fundamental Research Funds for the Central Universities,China(No.FRF-TT-19-001)。
文摘The sulfation and decomposition process has proven effective in selectively extracting lithium from lepidolite.It is essential to clarify the thermochemical behavior and kinetic parameters of decomposition reactions.Accordingly,comprehensive kinetic study by employing thermalgravimetric analysis at various heating rates was presented in this paper.Two main weight loss regions were observed during heating.The initial region corresponded to the dehydration of crystal water,whereas the subsequent region with overlapping peaks involved complex decomposition reactions.The overlapping peaks were separated into two individual reaction peaks and the activation energy of each peak was calculated using isoconversional kinetics methods.The activation energy of peak 1 exhibited a continual increase as the reaction conversion progressed,while that of peak 2 steadily decreased.The optimal kinetic models,identified as belonging to the random nucleation and subsequent growth category,provided valuable insights into the mechanism of the decomposition reactions.Furthermore,the adjustment factor was introduced to reconstruct the kinetic mechanism models,and the reconstructed models described the kinetic mechanism model more accurately for the decomposition reactions.This study enhanced the understanding of the thermochemical behavior and kinetic parameters of the lepidolite sulfation product decomposition reactions,further providing theoretical basis for promoting the selective extraction of lithium.
文摘A M_(S)6.4 earthquake occurred on 21 May 2021 in Yangbi county,Dali prefecture,Yunnan,China,at 21:48 Beijing Time(13:48 UTC).Earthquakes with an M3.0 or higher occurred before and after the main shock.Seismic data analysis is essential for the in-depth investigation of the 2021 Yangbi M_(S)6.4 earthquake sequence and the seismotectonics of northwestern Yunnan.Institute of Geophysics,China Earthquake Administration(CEA),has compiled a dataset of seismological observations from 157 broadband stations located within 500 km of the epicenter,and has made this dataset available to the earthquake science research community.The dataset(total file size:329 GB)consists of event waveforms with a sampling frequency of 100 sps collected from 18 to 28 May 2021,20-Hz and 100-Hz continuous waveforms collected from 12 to 31 May 2021,and seismic instrument response files.To promote data sharing,the dataset also includes the seismic event waveforms from 20 to 22 May 2021 recorded at 50 stations of the ongoing Binchuan Active Source Geophysical Observation Project,for which the data protection period has not expired.Sample waveforms of the main shock are included in the appendix of this article and can be downloaded from the Earthquake Science website.The event and continuous waveforms are available from the Earthquake Science Data Center website(www.esdc.ac.cn)on application.
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
文摘BACKGROUND The peritumoral region possesses attributes that promote cancer growth and progression.However,the potential prognostic biomarkers in this region remain relatively underexplored in radiomics.AIM To investigate the prognostic value and importance of peritumoral radiomics in locally advanced rectal cancer(LARC).METHODS This retrospective study included 409 patients with biopsy-confirmed LARC treated with neoadjuvant chemoradiotherapy and surgically.Patients were divided into training(n=273)and validation(n=136)sets.Based on intratumoral and peritumoral radiomic features extracted from pretreatment axial high-resolution small-field-of-view T2-weighted images,multivariate Cox models for progression-free survival(PFS)prediction were developed with or without clinicoradiological features and evaluated with Harrell’s concordance index(C-index),calibration curve,and decision curve analyses.Risk stratification,Kaplan-Meier analysis,and permutation feature importance analysis were performed.RESULTS The comprehensive integrated clinical-radiological-omics model(ModelICRO)integrating seven peritumoral,three intratumoral,and four clinicoradiological features achieved the highest C-indices(0.836 and 0.801 in the training and validation sets,respectively).This model showed robust calibration and better clinical net benefits,effectively distinguished high-risk from low-risk patients(PFS:97.2%vs 67.6%and 95.4%vs 64.8%in the training and validation sets,respectively;both P<0.001).Three most influential predictors in the comprehensive ModelICRO were,in order,a peritumoral,an intratumoral,and a clinicoradiological feature.Notably,the peritumoral model outperformed the intratumoral model(C-index:0.754 vs 0.670;P=0.015);peritumoral features significantly enhanced the performance of models based on clinicoradiological or intratumoral features or their combinations.CONCLUSION Peritumoral radiomics holds greater prognostic value than intratumoral radiomics for predicting PFS in LARC.The comprehensive model may serve as a reliable tool for better stratification and management postoperatively.
基金supported by the the National Natural Science Foundation of China(52203303)the Shenzhen Science and Technology Program(SGDX20211123151002003 and GJHZ20220913142812025)+1 种基金the International Partnership Program of the Chinese Academy of Sciences(321GJHZ2023189FN)the SIAT International Joint Lab(E5G108).
文摘Layered manganese dioxide(δ-MnO_(2))is a promising cathode material for aqueous zinc-ion batteries(AZIBs)due to its high theoretical capacity,high operating voltage,and low cost.However,its practical application faces challenges,such as low electronic conductivity,sluggish diffusion kinetics,and severe dissolution of Mn^(2+).In this study,we developed a δ-MnO_(2) coated with a 2-methylimidazole(δ-MnO_(2)@2-ML)hybrid cathode.Density functional theory(DFT)calculations indicate that 2-ML can be integrated into δ-MnO_(2) through both pre-intercalation and surface coating,with thermodynamically favorable outcomes.This modification expands the interlayer spacing of δ-MnO_(2) and generates Mn-N bonds on the surface,enhancing Zn^(2+)accommodation and diffusion kinetics as well as stabilizing surface Mn sites.The experimentally prepared δ-MnO_(2)@2-ML cathode,as predicted by DFT,features both 2-ML pre-intercalation and surface coating,providing more zinc-ion insertion sites and improved structural stability.Furthermore,X-ray diffraction shows the expanded interlayer spacing,which effectively buffers local electrostatic interactions,leading to an enhanced Zn^(2+)diffusion rate.Consequently,the optimized cathode(δ-MnO_(2)@2-ML)presents improved electrochemical performance and stability,and the fabricated AZIBs exhibit a high specific capacity(309.5mAh/g at 0.1 A/g),superior multiplicative performance(137.6mAh/g at 1 A/g),and impressive capacity retention(80%after 1350 cycles at 1 A/g).These results surpass the performance of most manganese-based and vanadium-based cathode materials reported to date.This dual-modulation strategy,combining interlayer engineering and interface optimization,offers a straightforward and scalable approach,potentially advancing the commercial viability of low-cost,high-performance AZIBs.
基金supported by the National Key Research and Development Program of China(No.2024YFA1300128)the National Natural Science Foundation of China(No.82372663)+2 种基金the Key Research and Development Program of Yunnan Province(No.202302AA310024)the Key Research and Development Program of Jiangxi Province(No.20232BBG70024)the Natural Science Foundation of Shandong Province(No.ZR2023LSW008).
文摘An organoid is a three-dimensional(3D)cell culture model that can reproduce the distinct structure and inherent functionality of certain organs.Nevertheless,a major limitation of organoids is the absence of a complex vascular network,thus restricting the supply of oxygen and essential nutrients.Coupled with their inherent size constraints and metabolite accumulation,it is challenging for organoids to replicate the natural intricacies of organs,thereby limiting their applicability.To overcome the challenges associated with this technology,we developed a culture platform to cultivate tumors or organ-derived organoids up to the centimeter scale.Initially,a customized organoid-on-a-chip including a microvascular network at the micron scale was designed using 3D printing.Further,by integrating an infusion device,the chip ensures an adequate supply of nutrients and fluid immersion while mimicking blood flow dynamics.Our method overcomes the issue of the limited size of organoids due to insufficient nutrient access,making it possible to produce large-scale tumor and normal tissue models in vitro,while providing insights into drug efficacy and toxicology evaluation as well as standardized organoid production.
基金National Key R&D Program of China,Grant/Award Number:2023YFB2503900National Natural Science Foundation of China,Grant/Award Number:12172143Shenzhen Science and Technology Program,Grant/Award Numbers:JCYJ20220818100418040,JCYJ20220530160816038。
文摘Constructing silicon(Si)-based composite electrodes that possess high energy density,long cycle life,and fast charging capability simultaneously is critical for the development of high performance lithium-ion batteries for mitigating range anxiety and slow charging issues in new energy vehicles.Herein,a thick silicon/carbon composite electrode with vertically aligned channels in the thickness direction(VC-SC)is constructed by employing a bubble formation method.Both experimental characterizations and theoretical simulations confirm that the obtained vertical channel structure can effectively address the problem of sluggish ion transport caused by high tortuosity in conventional thick electrodes,conspicuously enhance reaction kinetics,reduce polarization and side reactions,mitigate stress,increase the utilization of active materials,and promote cycling stability of the thick electrode.Consequently,when paired with LiNi_(0.6)Co_(0.2)Mn_(0.2)O_(2)(NCM622),the VC-SC||NCM622 pouch type full cell(~6.0 mAh cm^(-2))exhibits significantly improved rate performance and capacity retention compared with the SC||NCM622 full cell with the conventional silicon/carbon composite electrode without channels(SC)as the anode.The assembled VC-SC||NCM622 pouch full cell with a high energy density of 490.3 Wh kg^(-1)also reveals a remarkable fast charging capability at a high current density of 2.0 mA cm^(-2),with a capacity retention of 72.0%after 500 cycles.
