目的:通过网状Meta分析评价中医外治疗法缓解化疗诱导外周神经病变(CIPN)症状的疗效。方法:检索PubMed、the Cochrane Library、EMbase、Web of Science、中国知网、万方数据库、维普数据库等中英文数据库中有关中医外治疗法缓解CIPN症...目的:通过网状Meta分析评价中医外治疗法缓解化疗诱导外周神经病变(CIPN)症状的疗效。方法:检索PubMed、the Cochrane Library、EMbase、Web of Science、中国知网、万方数据库、维普数据库等中英文数据库中有关中医外治疗法缓解CIPN症状的随机对照试验,检索时限为各数据库建库到2023年8月15日。由2名研究者独立筛选文献、提取数据及文献质量评价。应用Stata 17.0软件进行网状Meta分析。结果:共纳入32项随机对照试验,共计2492例CIPN病人,涉及穴位贴敷、中药熏洗+甲钴胺联合治疗、穴位针灸+甲钴胺联合治疗等多种中西医结合疗法。网状Meta分析结果显示:总有效率疗效较好的为中药熏洗+甲钴胺治疗和穴位针灸大类+甲钴胺治疗;生活质量指数较优的为中药熏洗、穴位针灸大类+甲钴胺治疗。结论:现有证据显示,6种中西医结合治疗有效率高于常规护理和两种单纯西医治疗,且中药熏洗+甲钴胺治疗、穴位针灸大类+甲钴胺治疗两类中西医结合治疗疗效较好。展开更多
The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of ...The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of reducing substances (e.g., ascorbic acid, glutathione, uric acid and tea polyphenols) in the systemic circulation. This may lead to toxicity, particularly in oral prodrugs that require more frequent and high-dose treatments. Fine-tuning the activation kinetics of these prodrugs is a promising prospect for more efficient on-target cancer therapies. In this study, disulfide, steric disulfide, and ester bonds were used to bridge cabazitaxel (CTX) to an intestinal lymph vessel-directed triglyceride (TG) module. Then, synthetic prodrugs were efficiently incorporated into self-nanoemulsifying drug delivery system (corn oil and Maisine CC were used as the oil phase and Cremophor EL as the surfactant). All three prodrugs had excellent gastric stability and intestinal permeability. The oral bioavailability of the disulfide bond-based prodrugs (CTX-(C)S-(C)S-TG and CTX-S-S-TG) was 11.5- and 19.1-fold higher than that of the CTX solution, respectively, demonstrating good oral delivery efficiency. However, the excessive reduction sensitivity of the disulfide bond resulted in lower plasma stability and safety of CTX-S-S-TG than that of CTX-(C)S-(C)S-TG. Moreover, introducing steric hindrance into disulfide bonds could also modulate drug release and cytotoxicity, significantly improving the anti-tumor activity even compared to that of intravenous CTX solution at half dosage while minimizing off-target adverse effects. Our findings provide insights into the design and fine-tuning of different disulfide bond-based linkers, which may help identify oral prodrugs with more potent therapeutic efficacy and safety for cancer therapy.展开更多
A monolithic column-based mass spectrometry(MS)analysis kit was prepared for whole blood analysis with MS.The kit is disposable and can be used for purification,storage,transportation and direct analysis of whole bloo...A monolithic column-based mass spectrometry(MS)analysis kit was prepared for whole blood analysis with MS.The kit is disposable and can be used for purification,storage,transportation and direct analysis of whole blood.The kit mainly consists of a capillary for quantitative microsampling,a cation exchange monolithic column for purification and storage,and a syringe for loading sample.This kit is very friendly to various users that one can easily siphon the blood in the kit followed by rapid clean-up.We established a quantitative method using the kit with a limit detection as low as 0.33 nmol/L,and achieved more than five orders of magnitude enhancement in sensitivity compared to direct nanoelectrospray ionization MS analysis.The column can avoid analyte exposure to environment,which helps the storage of the sample for laboratory analysis.The relative standard deviation of immediate blood analysis and storage blood analysis within 10 d was less than 10%.This method has been successfully applied to the quantitative analysis of procainamide hydrochloride in 2μL rat blood.These results indicate that this disposable kit does have the potential to achieve highly sensitive quantitative MS analysis in biological samples,which is expected to become a cost-effective and powerful tool for in vitro diagnostics.展开更多
As a powerful cell-based therapeutic approach,CAR-T therapy was originally designed for treating acquired immunodeficiency syndrome(AIDS)(Baker et al.,2023),but had been strikingly successful in curing hematologic mal...As a powerful cell-based therapeutic approach,CAR-T therapy was originally designed for treating acquired immunodeficiency syndrome(AIDS)(Baker et al.,2023),but had been strikingly successful in curing hematologic malignancies and multiple solid tumors.Numerous evidence has expanded the medical application of CAR-T therapy for the treatment of many other human diseases beyond cancer.In this article,we discuss the principle of CAR-T and enumerate the current application and limitation in oncology.Finally,we provide a comprehensive perspective of current advance and future directions of CAR-T in treating multiple non-tumoral diseases.展开更多
Soil salinity severely limits crop yields and quality.Plants have evolved several strategies to mitigate the adverse effects of salinity,including redistribution and compartmentalization of toxic ions using ion-specif...Soil salinity severely limits crop yields and quality.Plants have evolved several strategies to mitigate the adverse effects of salinity,including redistribution and compartmentalization of toxic ions using ion-specific transporters.However,the mechanisms underlying the regulation of these ion transporters have not been fully elucidated.Loss-of-function mutants of OsHKT2;1,which is involved in sodium uptake,exhibit strong salt stress-resistant phenotypes.In this study,OsHKT2;1 was identified as a transcriptional target of the type-B response regulator OsRR22.Loss-of-function osrr22 mutants showed resilience to salt stress,and OsRR22-overexpression plants were sensitive to salt stress.OsRR22 was found to activate the expression of OsHKT2;1 by directly binding to the promoter region of OsHKT2;1 via a consensus cis-element of type-B response regulators.Moreover,rice DELLA protein OsSLR1 directly interacted with OsRR22 and functioned as a transcriptional co-activator.This study has uncovered a novel transcriptional regulatory mechanism by which a type-B response regulator controls sodium transport under salinity stress.展开更多
The safety valve is an important component to ensure the safe operation of lithium-ion batteries(LIBs).However,the effect of safety valve type on the thermal runaway(TR)and gas venting behavior of LIBs,as well as the ...The safety valve is an important component to ensure the safe operation of lithium-ion batteries(LIBs).However,the effect of safety valve type on the thermal runaway(TR)and gas venting behavior of LIBs,as well as the TR hazard severity of LIBs,are not known.In this paper,the TR and gas venting behavior of three 100 A h lithium iron phosphate(LFP)batteries with different safety valves are investigated under overheating.Compared to previous studies,the main contribution of this work is in studying and evaluating the effect of gas venting behavior and TR hazard severity of LFP batteries with three safety valve types.Two significant results are obtained:(Ⅰ)the safety valve type dominates over gas venting pressure of battery during safety venting,the maximum gas venting pressure of LFP batteries with a round safety valve is 3320 Pa,which is one order of magnitude higher than other batteries with oval or cavity safety valve;(Ⅱ)the LFP battery with oval safety valve has the lowest TR hazard as shown by the TR hazard assessment model based on gray-fuzzy analytic hierarchy process.This study reveals the effect of safety valve type on TR and gas venting,providing a clear direction for the safety valve design.展开更多
基金supported by National Natural Science Foundation of China(No.82173766,82104109)Natural Science Foundation of Liaoning Province(2022-BS158)+1 种基金Liaoning Province Applied Basic Research Program(No.2022JH2/101300097)National Key R&D Program of China(No.2022YFE0111600).
文摘The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of reducing substances (e.g., ascorbic acid, glutathione, uric acid and tea polyphenols) in the systemic circulation. This may lead to toxicity, particularly in oral prodrugs that require more frequent and high-dose treatments. Fine-tuning the activation kinetics of these prodrugs is a promising prospect for more efficient on-target cancer therapies. In this study, disulfide, steric disulfide, and ester bonds were used to bridge cabazitaxel (CTX) to an intestinal lymph vessel-directed triglyceride (TG) module. Then, synthetic prodrugs were efficiently incorporated into self-nanoemulsifying drug delivery system (corn oil and Maisine CC were used as the oil phase and Cremophor EL as the surfactant). All three prodrugs had excellent gastric stability and intestinal permeability. The oral bioavailability of the disulfide bond-based prodrugs (CTX-(C)S-(C)S-TG and CTX-S-S-TG) was 11.5- and 19.1-fold higher than that of the CTX solution, respectively, demonstrating good oral delivery efficiency. However, the excessive reduction sensitivity of the disulfide bond resulted in lower plasma stability and safety of CTX-S-S-TG than that of CTX-(C)S-(C)S-TG. Moreover, introducing steric hindrance into disulfide bonds could also modulate drug release and cytotoxicity, significantly improving the anti-tumor activity even compared to that of intravenous CTX solution at half dosage while minimizing off-target adverse effects. Our findings provide insights into the design and fine-tuning of different disulfide bond-based linkers, which may help identify oral prodrugs with more potent therapeutic efficacy and safety for cancer therapy.
基金financially supported by the National Natural Science Foundation of China(No.22104112)the startup foundation of Wuhan University(No.600460076).
文摘A monolithic column-based mass spectrometry(MS)analysis kit was prepared for whole blood analysis with MS.The kit is disposable and can be used for purification,storage,transportation and direct analysis of whole blood.The kit mainly consists of a capillary for quantitative microsampling,a cation exchange monolithic column for purification and storage,and a syringe for loading sample.This kit is very friendly to various users that one can easily siphon the blood in the kit followed by rapid clean-up.We established a quantitative method using the kit with a limit detection as low as 0.33 nmol/L,and achieved more than five orders of magnitude enhancement in sensitivity compared to direct nanoelectrospray ionization MS analysis.The column can avoid analyte exposure to environment,which helps the storage of the sample for laboratory analysis.The relative standard deviation of immediate blood analysis and storage blood analysis within 10 d was less than 10%.This method has been successfully applied to the quantitative analysis of procainamide hydrochloride in 2μL rat blood.These results indicate that this disposable kit does have the potential to achieve highly sensitive quantitative MS analysis in biological samples,which is expected to become a cost-effective and powerful tool for in vitro diagnostics.
基金supported by the National Key Research and Development Program of China(Grant no.2019YFA0111400,2022YFE0200100)the National Natural Science Foundation of China(Grant no.32271165,82070144,82270155)the Interdisciplinary Project of Central Universities(Grant no.2022-2-ZD-02).
文摘As a powerful cell-based therapeutic approach,CAR-T therapy was originally designed for treating acquired immunodeficiency syndrome(AIDS)(Baker et al.,2023),but had been strikingly successful in curing hematologic malignancies and multiple solid tumors.Numerous evidence has expanded the medical application of CAR-T therapy for the treatment of many other human diseases beyond cancer.In this article,we discuss the principle of CAR-T and enumerate the current application and limitation in oncology.Finally,we provide a comprehensive perspective of current advance and future directions of CAR-T in treating multiple non-tumoral diseases.
基金supported by the National Natural Science Foundation of China (32001448,32272027)。
文摘Soil salinity severely limits crop yields and quality.Plants have evolved several strategies to mitigate the adverse effects of salinity,including redistribution and compartmentalization of toxic ions using ion-specific transporters.However,the mechanisms underlying the regulation of these ion transporters have not been fully elucidated.Loss-of-function mutants of OsHKT2;1,which is involved in sodium uptake,exhibit strong salt stress-resistant phenotypes.In this study,OsHKT2;1 was identified as a transcriptional target of the type-B response regulator OsRR22.Loss-of-function osrr22 mutants showed resilience to salt stress,and OsRR22-overexpression plants were sensitive to salt stress.OsRR22 was found to activate the expression of OsHKT2;1 by directly binding to the promoter region of OsHKT2;1 via a consensus cis-element of type-B response regulators.Moreover,rice DELLA protein OsSLR1 directly interacted with OsRR22 and functioned as a transcriptional co-activator.This study has uncovered a novel transcriptional regulatory mechanism by which a type-B response regulator controls sodium transport under salinity stress.
基金supported by the National Key R&D Program of China(No.2021YFB2402001)the Postgraduate Innovation and Entrepreneurship Practice Project of Anhui Province(No.2022cxcysj013)+2 种基金the China Postdoctoral Science Foundation(No.2022T150615)the Fundamental Research Funds for the Central Universities(No.WK5290000002)supported by Youth Innovation Promotion Association CAS(No.Y201768)。
文摘The safety valve is an important component to ensure the safe operation of lithium-ion batteries(LIBs).However,the effect of safety valve type on the thermal runaway(TR)and gas venting behavior of LIBs,as well as the TR hazard severity of LIBs,are not known.In this paper,the TR and gas venting behavior of three 100 A h lithium iron phosphate(LFP)batteries with different safety valves are investigated under overheating.Compared to previous studies,the main contribution of this work is in studying and evaluating the effect of gas venting behavior and TR hazard severity of LFP batteries with three safety valve types.Two significant results are obtained:(Ⅰ)the safety valve type dominates over gas venting pressure of battery during safety venting,the maximum gas venting pressure of LFP batteries with a round safety valve is 3320 Pa,which is one order of magnitude higher than other batteries with oval or cavity safety valve;(Ⅱ)the LFP battery with oval safety valve has the lowest TR hazard as shown by the TR hazard assessment model based on gray-fuzzy analytic hierarchy process.This study reveals the effect of safety valve type on TR and gas venting,providing a clear direction for the safety valve design.
