Ischemic stroke,which is characterized by hypoxia and ischemia,triggers a cascade of injury responses,including neurotoxicity,inflammation,oxidative stress,disruption of the blood-brain barrier,and neuronal death.In t...Ischemic stroke,which is characterized by hypoxia and ischemia,triggers a cascade of injury responses,including neurotoxicity,inflammation,oxidative stress,disruption of the blood-brain barrier,and neuronal death.In this context,tryptophan metabolites and enzymes,which are synthesized through the kynurenine and 5-hydroxytryptamine pathways,play dual roles.The delicate balance between neurotoxic and neuroprotective substances is a crucial factor influencing the progression of ischemic stroke.Neuroprotective metabolites,such as kynurenic acid,exert their effects through various mechanisms,including competitive blockade of N-methyl-D-aspartate receptors,modulation ofα7 nicotinic acetylcholine receptors,and scavenging of reactive oxygen species.In contrast,neurotoxic substances such as quinolinic acid can hinder the development of vascular glucose transporter proteins,induce neurotoxicity mediated by reactive oxygen species,and disrupt mitochondrial function.Additionally,the enzymes involved in tryptophan metabolism play major roles in these processes.Indoleamine 2,3-dioxygenase in the kynurenine pathway and tryptophan hydroxylase in the 5-hydroxytryptamine pathway influence neuroinflammation and brain homeostasis.Consequently,the metabolites generated through tryptophan metabolism have substantial effects on the development and progression of ischemic stroke.Stroke treatment aims to restore the balance of various metabolite levels;however,precise regulation of tryptophan metabolism within the central nervous system remains a major challenge for the treatment of ischemic stroke.Therefore,this review aimed to elucidate the complex interactions between tryptophan metabolites and enzymes in ischemic stroke and develop targeted therapies that can restore the delicate balance between neurotoxicity and neuroprotection.展开更多
To develop a new magnesium alloy with excellent formability at room temperature, the effect of Y, Ce, and Gd addition on texture and stretch formability of Mg-1.5Zn alloys was carried out. The result shows that Y, Ce,...To develop a new magnesium alloy with excellent formability at room temperature, the effect of Y, Ce, and Gd addition on texture and stretch formability of Mg-1.5Zn alloys was carried out. The result shows that Y, Ce, and Gd addition in Mg-1.5Zn alloys can effectively weaken and modify the basal plane texture, characterized by TD-split texture in which the position of basal is titled from normal direction （ND） toward transverse direction （TD）. When Mg-1.5Zn alloy with Gd addition appears low texture intensity and TD-split texture, where the position of basal poles is tilted by about 4-35° from ND toward to TD, the largest Erichsen value of 7.0 and the elongation rate reaches 29.1% in TD direction. However, Y and Ce addition in Mg-1.5Zn alloys promote a large number of second phase particles, which cancel the contribution of the unique basal texture to stretch formability and ductility.展开更多
The amount of rainfall varies unevenly in different regions of the Qinghai-Tibet Plateau,with some regions becoming wetter and others drier.Precipitation has an important impact on the process of surface energy balanc...The amount of rainfall varies unevenly in different regions of the Qinghai-Tibet Plateau,with some regions becoming wetter and others drier.Precipitation has an important impact on the process of surface energy balance and the energy-water transfer within soils.To clarify the thermal-moisture dynamics and thermal stability of the active layer in permafrost regions under wet/dry conditions,the verified water-vapour-heat coupling model was used.Changes in the surface energy balance,energy-water transfer within the soil,and thickness of the active layer were quantitatively analyzed.The results demonstrate that rainfall changes significantly affect the Bowen ratio,which in turn affects surface energy exchange.Under wet/dry conditions,there is a positive correlation between rainfall and liquid water flux under the hydraulic gradient;water vapour migration is the main form under the temperature gradient,which indicates that the influence of water vapour migration on thermalmoisture dynamics of the active layer cannot be neglected.Concurrently,regardless of wet or dry conditions,disturbance of the heat transport by conduction caused by rainfall is stronger than that of convection by liquid water.In addition,when rainfall decreases by 1.5 times(212 mm)and increases by 1.5 times(477 mm),the thickness of the active layer increases by 0.12 m and decreases by 0.21 m,respectively.The results show that dry conditions are not conducive to the preservation of frozen soil;however,wet conditions are conducive to the preservation of frozen soil,although there is a threshold value.When this threshold value is exceeded,rainfall is unfavourable for the development of frozen soil.展开更多
Background:Fulminant myocarditis(FM)is associated with high mortality and an unfavorable long-term prognosis.However,noninvasive,rapid diagnostic and monitoring methods for FM are lacking.Case summary:This report deta...Background:Fulminant myocarditis(FM)is associated with high mortality and an unfavorable long-term prognosis.However,noninvasive,rapid diagnostic and monitoring methods for FM are lacking.Case summary:This report details the case of a patient diagnosed with FM through a comprehensive assessment involving typical clinical symptoms,laboratory analyses,echocardiographic evidence,and cardiac magnetic resonance(CMR)findings.Before the patient underwent CMR,optical pumped magnetometer magnetocardiography(OPM-MCG)revealed abnormalities characteristic of substantial myocardial injury.After invasive coronary angiography,the patient’s coronary arteries were determined not to exhibit significant stenosis.Additionally,a myocardial bridge was observed in the middle segment of the anterior descending branch of the left coronary artery.Over a 7-month follow-up,the patient’s symptoms showed marked improvement,and the OPM-MCG eventually normalized,aligning with the findings indicated by the CMR.Conclusion:OPM-MCG is a valuable tool for therapy monitoring in FMs,offering a safe,non-invasive,and highly effective test for ancillary diagnostics and long-term prognostic follow-up.Additionally,MCG may potentially assist in clinical decision-making regarding the need for further interventions in patients with myocardial bridge.展开更多
African swine fever virus(ASFV)is the etiological agent of African swine fever(ASF),an often lethal disease in domestic and wild pigs.ASF represents a major threat to the swine industry worldwide.Currently,no commerci...African swine fever virus(ASFV)is the etiological agent of African swine fever(ASF),an often lethal disease in domestic and wild pigs.ASF represents a major threat to the swine industry worldwide.Currently,no commercial vaccine is available because of the complexity of ASFV or biosecurity concerns.Live attenuated viruses that are naturally isolated or genetically manipulated have demonstrated reliable protection against homologous ASFV strain challenge.In the present study,a mutant ASFV strain with the deletion of ASFV MGF-110-9L(ASFV-D9L)was generated from a highly virulent ASFV CN/GS/2018 parental strain,a genotypeⅡASFV.Relative to the parental ASFV isolate,deletion of the MGF-110-9L gene significantly decreased the ability of ASFV-D9L to replicate in vitro in primary swine macrophage cell cultures.The majority of animals inoculated intramuscularly with a low dose of ASFV-D9L(10 HAD50)remained clinically normal during the 21-day observational period.Three of five ASFV-D9L-infected animals displayed low viremia titers and low virus shedding and developed a strong virus-specific antibody response,indicating partial attenuation of the ASFV-D9L strain in pigs.The findings imply the potential usefulness of the ASFV-D9L strain for further development of ASF control measures.展开更多
AIM To evaluate the clinical and prognostic significance of preoperative and postoperative cytokeratin 19(CK19) and carcinoembryonic antigen(CEA) m RNA levels in peripheral blood of patients with gastric cardia cancer...AIM To evaluate the clinical and prognostic significance of preoperative and postoperative cytokeratin 19(CK19) and carcinoembryonic antigen(CEA) m RNA levels in peripheral blood of patients with gastric cardia cancer(GCC).METHODS We detected the preoperative and postoperative mR NA levels of CK19 and CEA in peripheral blood of 129 GCC patients by using reverse transcription-polymerase chain reaction and evaluated their clinical and prognostic significance by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard analysis. A new prognostic model which stratified patients into three different risk groups was established based on the independent prognostic factors.RESULTS Elevated preoperative and postoperative CK19 and CEA mR NA levels in peripheral blood of GCC patients were associated with lymph node metastasis. Univariate analysis showed that tumor size, histological grade, depth of tumor invasion, lymph node metastasis, preoperative CK19 m RNA, and preoperative and postoperative CEA m RNA levels were correlated with the prognosis of GCC patients. The multivariate analysis showed that lymph node status(P = 0.018), preoperative CK19(P = 0.035) and CEA(P = 0.011) m RNA levels were independent prognostic factors for overall survival(OS). The 5-year OS rates for the low-, intermediate-, and high-risk groups were 48.3%, 22.6%, and 4.6%, respectively(P < 0.001).CONCLUSION Elevated preoperative CK19 and CEA mR NA levels may be regarded as promising biomarkers for predicting lymph node metastasis and poor prognosis in patients with GCC. This new prognostic model may help us identify the subpopulations of GCC patients with the highest risk.展开更多
The health status of distribution equipment and networks is not considered directly in existing distribution network planning methods.In order to effectively consider the health status and deal with the risk associate...The health status of distribution equipment and networks is not considered directly in existing distribution network planning methods.In order to effectively consider the health status and deal with the risk associated with load and renewable generation uncertainties,this paper presents a new optimal expansion planning approach for distribution network(EPADN)incorporating equipment’s health index(HI)and non-network solutions(NNSs).HI and relevant risk are used to help develop the optimal equipment replacement strategy and temporary NNSs are considered as promising options for handling the uncertainties of load growth,reliability requirements of power supply and output of distributed energy resources(DERs)at a lower cost than network alternatives.An EPADN model using network solutions(NSs)and NNSs is proposed.The planning objectives of the proposed model are safety,reliability,economy,and‘greenness’that are also the meaning of distribution network HI.A method integrating an improved niche genetic algorithm(INGA)and a spanning tree algorithm(STA)is fitted to solve the model presented here for real sized networks with a manageable computational cost.Simulation results of an actual 22-node distribution network in China,illustrate the effectiveness of the proposed approach.展开更多
Hybrid lipid-nanoparticle complexes have shown attractive characteristics as drug carriers due to their integrated advantages from liposomes and nanoparticles.Here we developed a kind of lipid-small molecule hybrid na...Hybrid lipid-nanoparticle complexes have shown attractive characteristics as drug carriers due to their integrated advantages from liposomes and nanoparticles.Here we developed a kind of lipid-small molecule hybrid nanoparticles(LPHNPs) for imaging and treatment in an ortho topic glioma model.LPHNPs were prepared by engineering the co-assembly of lipids and an amphiphilic pheophorbide a-quinolinium conjugate(PQC),a mitochondria-targeting small molecule.Compared with the pure nanofiber self-assembled by PQC,LPHNPs not only preserve the comparable antiproliferative potency,but also possess a spherical nanostructure that allows the PQC molecules to be administrated through intravenous injection.Also,this co-assembly remarkably improved the drug-loading capacity and formulation stability against the physical encapsulation using conventional liposomes.By integrating the advantages from liposome and PQC molecule,LPHNPs have minimal system toxicity,enhanced potency of photodynamic therapy(PDT) and visualization capacities of drug biodistribution and tumor imaging.The hybrid nanoparticle demonstrates excellent curative effects to significantly prolong the survival of mice with the orthotopic glioma.The unique co-assembly of lipid and small molecule provides new potential for constructing new liposome-derived nanoformulations and improving cancer treatment.展开更多
Regulation of aluminum distribution in zeolite framework is an effective method for improving its catalytic performance for propane aromatization.Herein,we found that recrystallization and post-realuminization of ZSM-...Regulation of aluminum distribution in zeolite framework is an effective method for improving its catalytic performance for propane aromatization.Herein,we found that recrystallization and post-realuminization of ZSM-5 cannot only create hollow structures to enhance the diffusion ability,but also adjust the content and position of paired aluminum species in its framework.Various characterizations results confirmed that increase of paired aluminum content and inducement of more aluminum atoms sited in the intersection cavity are beneficial to the formation of aromatic products in propane aromatization.As a result,the hollow-structured ZSM-5 zeolite with more paired aluminum(H-200-hollow)showed higher propane conversion and aromatics selectivity than other samples at the same conditions.The catalytic performance of H-200-hollow can be further improved by ion-exchanging with a small amount of Ga(III)species.The propane conversion and aromatics selectivity of Ga-200-hollow reached as high as 95%and 70%,respectively,at 540℃ and 1 atm.展开更多
CRISPR-Cas tools for mammalian genome editing typically rely on single Cas9 or Cas12a proteins.While type I CRISPR systems in Class I may offer greater specificity and versatility,they are not well-developed for genom...CRISPR-Cas tools for mammalian genome editing typically rely on single Cas9 or Cas12a proteins.While type I CRISPR systems in Class I may offer greater specificity and versatility,they are not well-developed for genome editing.Here,we present an alternative type I-C CRISPR system from Desulfovibrio vulgaris(Dvu)for efficient and precise genome editing in mammalian cells and animals.We optimized the Dvu type I-C editing complex to generate precise deletions at multiple loci in various cell lines and pig primary fibroblast cells using a paired PAM-in crRNA strategy.These edited pig cells can serve as donors for generating transgenic cloned piglets.The Dvu type I-C editor also enabled precise large fragment replacements with homology-directed repair.Additionally,we adapted the Dvu-Cascade effector for cytosine and adenine base editing,developing Dvu-CBE and Dvu-ABE systems.These systems efficiently induced C-to-T and A-to-G substitutions in human genes without double-strand breaks.Off-target analysis confirmed the high specificity of the Dvu type I-C editor.Our findings demonstrate the Dvu type I-C editor′s potential for diverse mammalian genome editing applications,including deletions,fragment replacement,and base editing,with high efficiency and specificity for biomedicine and agriculture.展开更多
Head and neck squamous cell carcinoma(HNSCC) is one of the most common human cancers;however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map(cMap) bas...Head and neck squamous cell carcinoma(HNSCC) is one of the most common human cancers;however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map(cMap) based on bioinformatics, queried out 35 compounds with therapeutic potential, and screened out parbendazole as a most promising compound, which had an excellent inhibitory effect on the proliferation of HNSCC cell lines. In addition, tubulin was identified as a primary target of parbendazole, and the direct binding between them was further verified. Parbendazole was further proved as an effective tubulin polymerization inhibitor, which can block the cell cycle, cause apoptosis and prevent cell migration, and it exhibited reasonable therapeutic effect and low toxicity in the in vivo and in vitro anti-tumor evaluation. Our study repositioned an anthelmintic parbendazole to treat HNSCC, which revealed a therapeutic utility and provided a new treatment option for human cancers.展开更多
After entering Beijing in January 1949, the Communist Party immediately sent cadres to local factories in order to mobilize female industrial workers into a women＇s movement and to establish the idea of ＂revolutiona...After entering Beijing in January 1949, the Communist Party immediately sent cadres to local factories in order to mobilize female industrial workers into a women＇s movement and to establish the idea of ＂revolutionary citizenship.＂ The Party wished to nurture this idea in both the local political arena and in women＇s lives inside and outside the factories. This article demonstrates that a host of factors defined revolutionary citizenship, including party directives, choices in revolutionary strategy, cadres＇ interpretations of directives and their own initiatives, and workers＇ reactions to mobilization. It was in this complex mix of mobilization, women＇s strategies to protect and advance their own interests, and the politics of group representation in the revolution, that female workers came to understand the meaning and impact of revolutionary citizenship and the shape of labor-state relations in the emerging socialist China.展开更多
Nanotheranostics with comprehensive diagnostic and therapeutic capabilities show exciting cancer treatment potentials.Here,we develop an excipient-free drug delivery system for cancer diagnosis as well as therapy,in w...Nanotheranostics with comprehensive diagnostic and therapeutic capabilities show exciting cancer treatment potentials.Here,we develop an excipient-free drug delivery system for cancer diagnosis as well as therapy,in which a near infra-red photosensitizer and a chemotherapeutic drug can be self-delivered without any carriers.The building block of the drug delivery system was synthesized by covalently conjugating four anticancer drugs(7-ethyl-10-hydroxy-camptothecin,SN-38)with a photosensitizer(porphyrin)via hydrolyzable ester linkage,which endows the drug delivery system with 100%active pharmaceutical ingredients,excellent imaging,and therapeutic functionalities.The conjugates can readily self-assemble into nanosheets(PS NSs)and remain stable for at least 20 days in aqueous solution.In PS NSs,fluorescence resonance energy transfer(FRET)dominates the fluorescence of SN-38 and enables to monitor the drug release fluorescentiy.The PS NSs also show excellent anticancer activity in vitro,due to the increased cell uptake with the synergistic effect of photodynamic therapy and chemotherapy.展开更多
The authors regret that a mistake occurred during the presentation of Fig.5A,in which the result of 0.1μmol/L CA-4 group appeared incorrectly when merging different imaging pictures into one.This correction does not ...The authors regret that a mistake occurred during the presentation of Fig.5A,in which the result of 0.1μmol/L CA-4 group appeared incorrectly when merging different imaging pictures into one.This correction does not significantly impact the findings and conclusions of the paper.The authors would like to assure readers that the corrected image does not alter the validity of the research.The original data of these figures have been provided to the Editorial Office,and the corresponding author can be contacted for original data access.The authors would like to apologize for any inconvenience caused and thank the anonymous reader for finding this mistake.The corrected Fig.5 appears below.展开更多
This special issue grows out of a shared research interest in the state-building process during the formative years of the People＇s Republic of China （roughly defined, 1949-66） and its profound political, social, e...This special issue grows out of a shared research interest in the state-building process during the formative years of the People＇s Republic of China （roughly defined, 1949-66） and its profound political, social, economic, and cultural consequences. Five articles in this issue demonstrate that the Communist Party of China made a great effort to mobilize different political constituents, social classes, professional groups, and cultural communities to consolidate its rule and advance its revolutionary agendas. Governing a deeply diverse and discontented society, the Party created a system of control and mobilization based on the combined mechanisms of political indoctrination, bureaucratic intervention, neighborhood surveillance, and social voluntarism. Communist rule in the 1950s and early 1960s created new cultural forms, business practices, and a new framework under which the party-state＇s political agenda and bureaucratic apparatus interacted with individual lives.展开更多
The city of Suzhou never ceases to intrigue historians. Located at the heart of the fabled lower-Yangtze River Delta, it is best known as the home of the most erudite scholars, sophisticated connoisseurs, shrewd merch...The city of Suzhou never ceases to intrigue historians. Located at the heart of the fabled lower-Yangtze River Delta, it is best known as the home of the most erudite scholars, sophisticated connoisseurs, shrewd merchants, and talented women writers imperial China had ever seen.展开更多
基金supported by Shanghai Shenkang Center Demonstration Research Ward Construction,No.SHDC2022CRW010(to MF)Shanghai Shenkang Center Medical Enterprise Integration and Innovation Collaborative Special Project,No.SHDC2022CRT018(to MF)+4 种基金Shanghai Health System Key Supported Discipline-Rehabilitation Medicine,No.2023ZDFC0301(to JT)Science and Technology Development Project of Shanghai University of Traditional Chinese Medicine,No.23KFL009(to JT)Shanghai Postdoctoral Excellence Program,No.2022515(to CY)Yangfan Special Project of Shanghai Science and Technology Innovation Action Plan,No.23YF1447600(to CY)China Postdoctoral Science Foundation,No.2023M732338(to CY).
文摘Ischemic stroke,which is characterized by hypoxia and ischemia,triggers a cascade of injury responses,including neurotoxicity,inflammation,oxidative stress,disruption of the blood-brain barrier,and neuronal death.In this context,tryptophan metabolites and enzymes,which are synthesized through the kynurenine and 5-hydroxytryptamine pathways,play dual roles.The delicate balance between neurotoxic and neuroprotective substances is a crucial factor influencing the progression of ischemic stroke.Neuroprotective metabolites,such as kynurenic acid,exert their effects through various mechanisms,including competitive blockade of N-methyl-D-aspartate receptors,modulation ofα7 nicotinic acetylcholine receptors,and scavenging of reactive oxygen species.In contrast,neurotoxic substances such as quinolinic acid can hinder the development of vascular glucose transporter proteins,induce neurotoxicity mediated by reactive oxygen species,and disrupt mitochondrial function.Additionally,the enzymes involved in tryptophan metabolism play major roles in these processes.Indoleamine 2,3-dioxygenase in the kynurenine pathway and tryptophan hydroxylase in the 5-hydroxytryptamine pathway influence neuroinflammation and brain homeostasis.Consequently,the metabolites generated through tryptophan metabolism have substantial effects on the development and progression of ischemic stroke.Stroke treatment aims to restore the balance of various metabolite levels;however,precise regulation of tryptophan metabolism within the central nervous system remains a major challenge for the treatment of ischemic stroke.Therefore,this review aimed to elucidate the complex interactions between tryptophan metabolites and enzymes in ischemic stroke and develop targeted therapies that can restore the delicate balance between neurotoxicity and neuroprotection.
基金supported by the Ministry of Science and Technology ‘‘Twelfth Five-Year’’ Plan for Science & Technology Support(No.2011BAE22B00)
文摘To develop a new magnesium alloy with excellent formability at room temperature, the effect of Y, Ce, and Gd addition on texture and stretch formability of Mg-1.5Zn alloys was carried out. The result shows that Y, Ce, and Gd addition in Mg-1.5Zn alloys can effectively weaken and modify the basal plane texture, characterized by TD-split texture in which the position of basal is titled from normal direction （ND） toward transverse direction （TD）. When Mg-1.5Zn alloy with Gd addition appears low texture intensity and TD-split texture, where the position of basal poles is tilted by about 4-35° from ND toward to TD, the largest Erichsen value of 7.0 and the elongation rate reaches 29.1% in TD direction. However, Y and Ce addition in Mg-1.5Zn alloys promote a large number of second phase particles, which cancel the contribution of the unique basal texture to stretch formability and ductility.
基金funded by the National Natural Science Foundation of China(No.42261028,No.41961010,No.41801033)the"Light of West China"Program for the Organization Department of the Central Committee of the CPC,etc.(Zhang Mingli)+2 种基金the Chinese Academy of Sciences"Light of West China"Program for Western Young ScholarsIndustrial support program of higher education of Gansu province(2020C-40)Basic Research Innovation Group of Gansu province(20JR5RA478)
文摘The amount of rainfall varies unevenly in different regions of the Qinghai-Tibet Plateau,with some regions becoming wetter and others drier.Precipitation has an important impact on the process of surface energy balance and the energy-water transfer within soils.To clarify the thermal-moisture dynamics and thermal stability of the active layer in permafrost regions under wet/dry conditions,the verified water-vapour-heat coupling model was used.Changes in the surface energy balance,energy-water transfer within the soil,and thickness of the active layer were quantitatively analyzed.The results demonstrate that rainfall changes significantly affect the Bowen ratio,which in turn affects surface energy exchange.Under wet/dry conditions,there is a positive correlation between rainfall and liquid water flux under the hydraulic gradient;water vapour migration is the main form under the temperature gradient,which indicates that the influence of water vapour migration on thermalmoisture dynamics of the active layer cannot be neglected.Concurrently,regardless of wet or dry conditions,disturbance of the heat transport by conduction caused by rainfall is stronger than that of convection by liquid water.In addition,when rainfall decreases by 1.5 times(212 mm)and increases by 1.5 times(477 mm),the thickness of the active layer increases by 0.12 m and decreases by 0.21 m,respectively.The results show that dry conditions are not conducive to the preservation of frozen soil;however,wet conditions are conducive to the preservation of frozen soil,although there is a threshold value.When this threshold value is exceeded,rainfall is unfavourable for the development of frozen soil.
基金supported by Sponsored by Beijing Nova Program(20220484222)‘Deng Feng’Training Program(DFL20220603)Project of The Beijing Lab for Cardiovascular Precision Medicine(PXM2018_014226_000013).
文摘Background:Fulminant myocarditis(FM)is associated with high mortality and an unfavorable long-term prognosis.However,noninvasive,rapid diagnostic and monitoring methods for FM are lacking.Case summary:This report details the case of a patient diagnosed with FM through a comprehensive assessment involving typical clinical symptoms,laboratory analyses,echocardiographic evidence,and cardiac magnetic resonance(CMR)findings.Before the patient underwent CMR,optical pumped magnetometer magnetocardiography(OPM-MCG)revealed abnormalities characteristic of substantial myocardial injury.After invasive coronary angiography,the patient’s coronary arteries were determined not to exhibit significant stenosis.Additionally,a myocardial bridge was observed in the middle segment of the anterior descending branch of the left coronary artery.Over a 7-month follow-up,the patient’s symptoms showed marked improvement,and the OPM-MCG eventually normalized,aligning with the findings indicated by the CMR.Conclusion:OPM-MCG is a valuable tool for therapy monitoring in FMs,offering a safe,non-invasive,and highly effective test for ancillary diagnostics and long-term prognostic follow-up.Additionally,MCG may potentially assist in clinical decision-making regarding the need for further interventions in patients with myocardial bridge.
基金supported by grants from the National Key Research and Development Program(2018YFC0840402)National Natural Science Foundation of China(31941002)+2 种基金Special Fund for Basic Scientific Research of Chinese Academy of Agricultural Sciences (Y2019YJ07-01)Science and technology innovation engineering major scientific research program of Chinese Academy of Agricultural Sciences (CAASZDRW202006-03)State Key Laboratory of Veterinary Etiological Biology Major achievements cultivation project of Chinese Academy of Agricultural Sciences (SKLVEB2020CGPY02)。
文摘African swine fever virus(ASFV)is the etiological agent of African swine fever(ASF),an often lethal disease in domestic and wild pigs.ASF represents a major threat to the swine industry worldwide.Currently,no commercial vaccine is available because of the complexity of ASFV or biosecurity concerns.Live attenuated viruses that are naturally isolated or genetically manipulated have demonstrated reliable protection against homologous ASFV strain challenge.In the present study,a mutant ASFV strain with the deletion of ASFV MGF-110-9L(ASFV-D9L)was generated from a highly virulent ASFV CN/GS/2018 parental strain,a genotypeⅡASFV.Relative to the parental ASFV isolate,deletion of the MGF-110-9L gene significantly decreased the ability of ASFV-D9L to replicate in vitro in primary swine macrophage cell cultures.The majority of animals inoculated intramuscularly with a low dose of ASFV-D9L(10 HAD50)remained clinically normal during the 21-day observational period.Three of five ASFV-D9L-infected animals displayed low viremia titers and low virus shedding and developed a strong virus-specific antibody response,indicating partial attenuation of the ASFV-D9L strain in pigs.The findings imply the potential usefulness of the ASFV-D9L strain for further development of ASF control measures.
基金Supported by the National Key Clinical Specialist Construction Programs of China,No.2013-544Science and Technology Development Fund of Tianjin Education Commission for Higher Education,No.20130121Science Foundation of Tianjin Medical University,No.2016KYZM03
文摘AIM To evaluate the clinical and prognostic significance of preoperative and postoperative cytokeratin 19(CK19) and carcinoembryonic antigen(CEA) m RNA levels in peripheral blood of patients with gastric cardia cancer(GCC).METHODS We detected the preoperative and postoperative mR NA levels of CK19 and CEA in peripheral blood of 129 GCC patients by using reverse transcription-polymerase chain reaction and evaluated their clinical and prognostic significance by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard analysis. A new prognostic model which stratified patients into three different risk groups was established based on the independent prognostic factors.RESULTS Elevated preoperative and postoperative CK19 and CEA mR NA levels in peripheral blood of GCC patients were associated with lymph node metastasis. Univariate analysis showed that tumor size, histological grade, depth of tumor invasion, lymph node metastasis, preoperative CK19 m RNA, and preoperative and postoperative CEA m RNA levels were correlated with the prognosis of GCC patients. The multivariate analysis showed that lymph node status(P = 0.018), preoperative CK19(P = 0.035) and CEA(P = 0.011) m RNA levels were independent prognostic factors for overall survival(OS). The 5-year OS rates for the low-, intermediate-, and high-risk groups were 48.3%, 22.6%, and 4.6%, respectively(P < 0.001).CONCLUSION Elevated preoperative CK19 and CEA mR NA levels may be regarded as promising biomarkers for predicting lymph node metastasis and poor prognosis in patients with GCC. This new prognostic model may help us identify the subpopulations of GCC patients with the highest risk.
基金This work was supported in part by the Science and Technology Project of SGCC under Grant No.PD71-18-023.
文摘The health status of distribution equipment and networks is not considered directly in existing distribution network planning methods.In order to effectively consider the health status and deal with the risk associated with load and renewable generation uncertainties,this paper presents a new optimal expansion planning approach for distribution network(EPADN)incorporating equipment’s health index(HI)and non-network solutions(NNSs).HI and relevant risk are used to help develop the optimal equipment replacement strategy and temporary NNSs are considered as promising options for handling the uncertainties of load growth,reliability requirements of power supply and output of distributed energy resources(DERs)at a lower cost than network alternatives.An EPADN model using network solutions(NSs)and NNSs is proposed.The planning objectives of the proposed model are safety,reliability,economy,and‘greenness’that are also the meaning of distribution network HI.A method integrating an improved niche genetic algorithm(INGA)and a spanning tree algorithm(STA)is fitted to solve the model presented here for real sized networks with a manageable computational cost.Simulation results of an actual 22-node distribution network in China,illustrate the effectiveness of the proposed approach.
基金support from NIH/NCI(R01CA199668,R01CA232845)NIH/NIDCR(1R01DE029237,USA)+1 种基金NIH/NICHD(R01HD086195,USA)UC Davis Comprehensive Cancer Centre Support Grant(CCSG,USA)awarded by the National Cancer Institute(NCI P30CA093373,USA)。
文摘Hybrid lipid-nanoparticle complexes have shown attractive characteristics as drug carriers due to their integrated advantages from liposomes and nanoparticles.Here we developed a kind of lipid-small molecule hybrid nanoparticles(LPHNPs) for imaging and treatment in an ortho topic glioma model.LPHNPs were prepared by engineering the co-assembly of lipids and an amphiphilic pheophorbide a-quinolinium conjugate(PQC),a mitochondria-targeting small molecule.Compared with the pure nanofiber self-assembled by PQC,LPHNPs not only preserve the comparable antiproliferative potency,but also possess a spherical nanostructure that allows the PQC molecules to be administrated through intravenous injection.Also,this co-assembly remarkably improved the drug-loading capacity and formulation stability against the physical encapsulation using conventional liposomes.By integrating the advantages from liposome and PQC molecule,LPHNPs have minimal system toxicity,enhanced potency of photodynamic therapy(PDT) and visualization capacities of drug biodistribution and tumor imaging.The hybrid nanoparticle demonstrates excellent curative effects to significantly prolong the survival of mice with the orthotopic glioma.The unique co-assembly of lipid and small molecule provides new potential for constructing new liposome-derived nanoformulations and improving cancer treatment.
基金supported by the National Key R&D Program of China(Grant No.2023YFB4103700)National Natural Science Foundation of China(Grant Nos.U1910203,21991090,21991092,22322208,22272195,U22A20431)+2 种基金Natural Science Foundation of Shanxi Province of China(Grant No.202203021224009)Innovation foundation of Institute of Coal Chemistry,Chinese Academy of Sciences(Grant No.SCJC-DT-2023-06)Youth Innovation Promotion Association CAS(Grant No.2021172).
文摘Regulation of aluminum distribution in zeolite framework is an effective method for improving its catalytic performance for propane aromatization.Herein,we found that recrystallization and post-realuminization of ZSM-5 cannot only create hollow structures to enhance the diffusion ability,but also adjust the content and position of paired aluminum species in its framework.Various characterizations results confirmed that increase of paired aluminum content and inducement of more aluminum atoms sited in the intersection cavity are beneficial to the formation of aromatic products in propane aromatization.As a result,the hollow-structured ZSM-5 zeolite with more paired aluminum(H-200-hollow)showed higher propane conversion and aromatics selectivity than other samples at the same conditions.The catalytic performance of H-200-hollow can be further improved by ion-exchanging with a small amount of Ga(III)species.The propane conversion and aromatics selectivity of Ga-200-hollow reached as high as 95%and 70%,respectively,at 540℃ and 1 atm.
基金funded by the National Key R&D Program of China(2021YFA0805900,2023YFF1000200,2023YFF1000900,and 2023YFC3402004)the China Postdoctoral Science Foundation(2021M703521).
文摘CRISPR-Cas tools for mammalian genome editing typically rely on single Cas9 or Cas12a proteins.While type I CRISPR systems in Class I may offer greater specificity and versatility,they are not well-developed for genome editing.Here,we present an alternative type I-C CRISPR system from Desulfovibrio vulgaris(Dvu)for efficient and precise genome editing in mammalian cells and animals.We optimized the Dvu type I-C editing complex to generate precise deletions at multiple loci in various cell lines and pig primary fibroblast cells using a paired PAM-in crRNA strategy.These edited pig cells can serve as donors for generating transgenic cloned piglets.The Dvu type I-C editor also enabled precise large fragment replacements with homology-directed repair.Additionally,we adapted the Dvu-Cascade effector for cytosine and adenine base editing,developing Dvu-CBE and Dvu-ABE systems.These systems efficiently induced C-to-T and A-to-G substitutions in human genes without double-strand breaks.Off-target analysis confirmed the high specificity of the Dvu type I-C editor.Our findings demonstrate the Dvu type I-C editor′s potential for diverse mammalian genome editing applications,including deletions,fragment replacement,and base editing,with high efficiency and specificity for biomedicine and agriculture.
基金supported by grants from the National Natural Science Foundation of China (81673393 and 81874308)the Taishan Scholar Program at Shandong Province and the Shandong Natural Science Foundation (ZR2018ZC0233,China)。
文摘Head and neck squamous cell carcinoma(HNSCC) is one of the most common human cancers;however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map(cMap) based on bioinformatics, queried out 35 compounds with therapeutic potential, and screened out parbendazole as a most promising compound, which had an excellent inhibitory effect on the proliferation of HNSCC cell lines. In addition, tubulin was identified as a primary target of parbendazole, and the direct binding between them was further verified. Parbendazole was further proved as an effective tubulin polymerization inhibitor, which can block the cell cycle, cause apoptosis and prevent cell migration, and it exhibited reasonable therapeutic effect and low toxicity in the in vivo and in vitro anti-tumor evaluation. Our study repositioned an anthelmintic parbendazole to treat HNSCC, which revealed a therapeutic utility and provided a new treatment option for human cancers.
文摘After entering Beijing in January 1949, the Communist Party immediately sent cadres to local factories in order to mobilize female industrial workers into a women＇s movement and to establish the idea of ＂revolutionary citizenship.＂ The Party wished to nurture this idea in both the local political arena and in women＇s lives inside and outside the factories. This article demonstrates that a host of factors defined revolutionary citizenship, including party directives, choices in revolutionary strategy, cadres＇ interpretations of directives and their own initiatives, and workers＇ reactions to mobilization. It was in this complex mix of mobilization, women＇s strategies to protect and advance their own interests, and the politics of group representation in the revolution, that female workers came to understand the meaning and impact of revolutionary citizenship and the shape of labor-state relations in the emerging socialist China.
基金The authors gratefully acknowledge the support from Dr.Lis faculty startup funds at UC Davis and Dr.Xues National Natural Science Foundation of China(NSFC)(No.81803002).
文摘Nanotheranostics with comprehensive diagnostic and therapeutic capabilities show exciting cancer treatment potentials.Here,we develop an excipient-free drug delivery system for cancer diagnosis as well as therapy,in which a near infra-red photosensitizer and a chemotherapeutic drug can be self-delivered without any carriers.The building block of the drug delivery system was synthesized by covalently conjugating four anticancer drugs(7-ethyl-10-hydroxy-camptothecin,SN-38)with a photosensitizer(porphyrin)via hydrolyzable ester linkage,which endows the drug delivery system with 100%active pharmaceutical ingredients,excellent imaging,and therapeutic functionalities.The conjugates can readily self-assemble into nanosheets(PS NSs)and remain stable for at least 20 days in aqueous solution.In PS NSs,fluorescence resonance energy transfer(FRET)dominates the fluorescence of SN-38 and enables to monitor the drug release fluorescentiy.The PS NSs also show excellent anticancer activity in vitro,due to the increased cell uptake with the synergistic effect of photodynamic therapy and chemotherapy.
文摘The authors regret that a mistake occurred during the presentation of Fig.5A,in which the result of 0.1μmol/L CA-4 group appeared incorrectly when merging different imaging pictures into one.This correction does not significantly impact the findings and conclusions of the paper.The authors would like to assure readers that the corrected image does not alter the validity of the research.The original data of these figures have been provided to the Editorial Office,and the corresponding author can be contacted for original data access.The authors would like to apologize for any inconvenience caused and thank the anonymous reader for finding this mistake.The corrected Fig.5 appears below.
文摘This special issue grows out of a shared research interest in the state-building process during the formative years of the People＇s Republic of China （roughly defined, 1949-66） and its profound political, social, economic, and cultural consequences. Five articles in this issue demonstrate that the Communist Party of China made a great effort to mobilize different political constituents, social classes, professional groups, and cultural communities to consolidate its rule and advance its revolutionary agendas. Governing a deeply diverse and discontented society, the Party created a system of control and mobilization based on the combined mechanisms of political indoctrination, bureaucratic intervention, neighborhood surveillance, and social voluntarism. Communist rule in the 1950s and early 1960s created new cultural forms, business practices, and a new framework under which the party-state＇s political agenda and bureaucratic apparatus interacted with individual lives.
文摘The city of Suzhou never ceases to intrigue historians. Located at the heart of the fabled lower-Yangtze River Delta, it is best known as the home of the most erudite scholars, sophisticated connoisseurs, shrewd merchants, and talented women writers imperial China had ever seen.
