AIM: To evaluate the expression of uncoupling protein 2(UCP2) in a retinal pigment epithelium cell line(ARPE-19), under oxidative stress(OS).METHODS: ARPE-19 cells were divided into groups treated with various concent...AIM: To evaluate the expression of uncoupling protein 2(UCP2) in a retinal pigment epithelium cell line(ARPE-19), under oxidative stress(OS).METHODS: ARPE-19 cells were divided into groups treated with various concentrations of hydrogen peroxide(H2 O2;0, 150, 300, 500, 700, and 900 μmol/L) for 24 h, to induce oxidative damage and cell viability was assessed by MTT assay. UCP2 mRNA expression in cells treated with H2 O2 was investigated by reverse transcription-polymerase chain reaction(RT-PCR). UCP2 protein expression was assessed by Western blotting and ROS levels analyzed by flow cytometry(FCM). Further, UCP2-siRNA treated cultures were exposed to H2 O2(0, 75, 150, and 300 μmol/L) for 2 h and cell viability determined by MTT assay.RESULTS: Cells treated with higher concentrations of H2 O2 appeared shrunken;their adhesion to adjacent cells was disrupted, and the number of dead cells increased. The results of cell viability assays demonstrated that the numbers of cells were decreased in a dose-dependent manner following treatment with H2 O2. Compared with untreated controls, cell viability was significantly reduced after treatment with >300 μmol/L H2 O2(P<0.05). Cell metabolic activity was decreased with increased concentrations of H2 O2 as detected by MTT assay. Levels of OS were further decreased in cells treated with UCP2-siRNA compared with those treated with H2 O2 alone(P<0.05). The results of RT-PCR and Western blotting demonstrated that UCP2 expression was reduced in H2 O2-treated groups compared with controls(P<0.05). FCM analysis showed that cell reactive oxygen species(ROS) levels were increased in H2 O2-treated groups and further upregulated by UCP2-si RNA treatment(P<0.05).CONCLUSION: Expression levels of UCP2 are decreased in ARPE-19 cells treated with H2 O2. ROS levels are further increased in cells treated with UCP2-siRNA relative to those treated with H2 O2 alone. UCP2 may have a protective role in ARPE-19 cells during oxidative injury.展开更多
目的系统评价临床常用精神类药物对阿尔茨海默病(AD)激越症状的疗效、安全性及认知功能的影响,基于累积排序概率曲线下面积(SUCRA)进行多维度概率排名,为临床决策提供参考。方法系统检索PubMed、the Cochrane Library、Web of Science和...目的系统评价临床常用精神类药物对阿尔茨海默病(AD)激越症状的疗效、安全性及认知功能的影响,基于累积排序概率曲线下面积(SUCRA)进行多维度概率排名,为临床决策提供参考。方法系统检索PubMed、the Cochrane Library、Web of Science和Embase数据库,纳入抗精神病药与安慰剂治疗AD的随机对照研究,采用平均值(MD)及其95%置信区间(95%CI)量化疗效差异,并基于SUCRA进行不同药物治疗效果的优劣排序。结果共检索3615篇文献,最终纳入11篇文献,涉及12项研究(涵盖8种干预措施与安慰剂对照)。网状meta分析结果显示,与安慰剂相比,依匹哌唑可显著降低Cohen-Mansfield激越问卷(CMAI)评分(MD=-3.88,95%CI:-5.89~-1.88)和神经精神问卷(NPI)评分(MD=-4.60,95%CI:-7.54~-1.66),其疗效在CMAI(SUCRA=85.2%)评分改善与NPI(SUCRA=89.2%)评分改善方面的累积概率排名均为首位,但其不良事件风险显著升高(RR=1.11,95%CI:1.02~1.21)。米氮平在认知功能改善方面具有优势(SMD=5.10,95%CI:0.69~9.51,SUCRA=96.1%),但激越症状控制效果有限。结论依匹哌唑是改善AD激越症状方面具有统计学优势的药物,但需警惕不良反应风险;米氮平对认知功能的获益有潜在治疗价值,但核心激越症状控制效能不足。展开更多
Organoids are three-dimensional stem cell-derived models that offer a more physiologically relevant representation of tumor biology compared to traditional two-dimensional cell cultures or animal models.Organoids pres...Organoids are three-dimensional stem cell-derived models that offer a more physiologically relevant representation of tumor biology compared to traditional two-dimensional cell cultures or animal models.Organoids preserve the complex tissue architecture and cellular diversity of human cancers,enabling more accurate predictions of tumor growth,metastasis,and drug responses.Integration with microfluidic platforms,such as organ-on-a-chip systems,further enhances the ability to model tumor-environment interactions in real-time.Organoids facilitate in-depth exploration of tumor heterogeneity,molecular mechanisms,and the development of personalized treatment strategies when coupled with multi-omics technologies.Organoids provide a platform for investigating tumor-immune cell interactions,which aid in the design and testing of immune-based therapies and vaccines.Taken together,these features position organoids as a transformative tool in advancing cancer research and precision medicine.展开更多
目的分析丙泊酚复合3种使用剂量瑞芬太尼靶控输注在经喉罩纤维支气管镜介入术中的麻醉质量。方法选取2019年2月-2021年12月该院择期行纤维支气管镜介入治疗的患者96例,采用随机数表法分为A组、B组和C组,各32例。3组均行喉罩全身麻醉,A组...目的分析丙泊酚复合3种使用剂量瑞芬太尼靶控输注在经喉罩纤维支气管镜介入术中的麻醉质量。方法选取2019年2月-2021年12月该院择期行纤维支气管镜介入治疗的患者96例,采用随机数表法分为A组、B组和C组,各32例。3组均行喉罩全身麻醉,A组、B组和C组瑞芬太尼剂量分别为0.2μg/(kg·min)(低剂量)、0.3μg/(kg·min)(中剂量)和0.4μg/(kg·min)(高剂量)。比较3组患者手术时间、麻醉质量(麻醉时间和手术医生麻醉满意度)、不同时间点心率(HR)、平均动脉压(MAP)、氧化应激因子[过氧化氢酶(CAT)、丙二醛(MDA)、超氧化物歧化酶(SOD)]水平、麻醉苏醒质量(苏醒时间、听指令睁眼时间和滞留苏醒室时间)、苏醒后不同时间点舒适度评分(BCS)和不良反应发生情况。结果B组和C组手术医生麻醉满意度评分均高于A组(P<0.05);B组和C组T_(2)、T_(3)时点HR和MAP均低于A组(P<0.05);B组和C组手术开始10 min血清CAT和SOD水平均高于A组,血清MDA水平均低于A组(P<0.05);3组患者苏醒时间、听指令睁眼时间和滞留苏醒室时间比较,差异均无统计学意义(P>0.05);B组和C组苏醒后10 min和1 h BCS均高于A组(P<0.05);B组不良反应发生率为0.00%,低于A组的18.75%和C组的18.75%,差异均有统计学意义(P<0.05)。结论经喉罩纤维支气管镜介入术全身麻醉中应用中剂量瑞芬太尼复合丙泊酚,能获得满意的麻醉质量,不良反应少,安全性高。展开更多
In natural language processing(NLP),managing multiple downstream tasks through fine-tuning pre-trained models often requires maintaining separate task-specific models,leading to practical inefficiencies.To address thi...In natural language processing(NLP),managing multiple downstream tasks through fine-tuning pre-trained models often requires maintaining separate task-specific models,leading to practical inefficiencies.To address this challenge,we introduce AdaptForever,a novel approach that enables continuous mastery of NLP tasks through the integration of elastic and mutual learning strategies with a stochastic expert mechanism.Our method freezes the pre-trained model weights while incorporating adapters enhanced with mutual learning capabilities,facilitating effective knowledge transfer from previous tasks to new ones.By combining Elastic Weight Consolidation(EWC)for knowledge preservation with specialized regularization terms,AdaptForever successfully maintains performance on earlier tasks while acquiring new capabilities.Experimental results demonstrate that AdaptForever achieves superior performance across a continuous sequence of NLP tasks compared to existing parameter-efficient methods,while effectively preventing catastrophic forgetting and enabling positive knowledge transfer between tasks.展开更多
Yunnan in southwest China is a geographically and ethnically complex region at the intersection of southern China and Southeast Asia,and a focal point for human migrations.To clarify its maternal genetic history,we ge...Yunnan in southwest China is a geographically and ethnically complex region at the intersection of southern China and Southeast Asia,and a focal point for human migrations.To clarify its maternal genetic history,we generated 152 complete mitogenomes from 17 Yunnan archaeological sites.Our results reveal distinct genetic histories segregated by geographical regions.Maternal lineages of ancient populations from northwestern and northern Yunnan exhibit closer affinities with past and present-day populations from northern East Asia and Xizang,providing important genetic evidence for the migration and interaction of populations along the Tibetan-Yi corridor since the Neolithic.Between 5500 and 1800 years ago,central Yunnan populations maintained their internal genetic relationships,including a 7000-year-old basal lineage of the rare and widely dispersed haplogroup M61.At the Xingyi site,changes in mitochondrial DNA haplogroups occurred between the Late Neolithic and Bronze Age,with haplogroups shifting from those predominant in the Yellow River region to those predominant in coastal southern China.These results highlight the high diversity of Yunnan populations during the Neolithic to Bronze Age.展开更多
Sodium-ion batteries stand out as potential candidates for large-scale energy storage systems due to the abundant resource of sodium.However,similar to lithium-ion batteries,there also exist challenges related to ther...Sodium-ion batteries stand out as potential candidates for large-scale energy storage systems due to the abundant resource of sodium.However,similar to lithium-ion batteries,there also exist challenges related to thermal safety in practical applications.The cathode,anode,and electrolyte of sodium-ion batteries can significantly influence the occurrence of thermal runaway events.Comprehensive understandings on the thermal behaviors of these components and their interactions are critically pivotal for unraveling the thermal runaway mechanisms of sodium-ion batteries and ensuring their safe operations.This review,pivoting on the origins and solutions for thermal runaway of sodium-ion batteries,summarizes and discusses the recent progress on thermal stability characteristics of the cathode,anode,and electrolyte.Some strategies are suggested to potentially enhance safety performance.The review aims to offer valuable insights for a more profound exploration of the thermal runaway mechanisms and inform the design of safe sodium-ion batteries.展开更多
Numerous bird species have adapted to rapid urbanization,navigating challenges introduced by novel stressors.While prior research has explored how urban exploiters adjust their physiology relative to their rural count...Numerous bird species have adapted to rapid urbanization,navigating challenges introduced by novel stressors.While prior research has explored how urban exploiters adjust their physiology relative to their rural counterparts during breeding season,the modulation of multiple physiological markers outside of reproduction,and the maintenance of sex-specific differences,remain less understood.Using an urban exploiter,the Eurasian tree sparrow(ETS;Passer montanus),we investigated how both sexes of urban and rural populations modulate twenty-two physiological markers of nutrition,body condition,oxidative stress,and antioxidative responses during pre-breeding stage.Our results showed that urban ETSs displayed distinct glucolipid metabolism compared to rural ETSs,characterized by higher levels of free fatty acids,β-hydroxybutyric acid,high-density lipoprotein(HDL),and total cholesterol,alongside lower levels of triglycerides,glucose(Glu),and fat content(FC).No significant differences were observed in other physiological markers.Additionally,both sexes of urban ETSs exhibited similar profiles across these markers,unlike rural populations where females showed higher Glu and total protein levels and lower HDL and FC levels than males.Our findings suggest that birds adjust their nutritional physiological markers in response to urbanization,likely due to dietary differences between urban and rural environments.Furthermore,sex differences in physiological markers of nutrition,body condition,oxidative stress,and antioxidant responses appear to diminish in urban settings.展开更多
基金Supported by the National Natural ScienceFoundation of China(No.81100665 No.81770929)
文摘AIM: To evaluate the expression of uncoupling protein 2(UCP2) in a retinal pigment epithelium cell line(ARPE-19), under oxidative stress(OS).METHODS: ARPE-19 cells were divided into groups treated with various concentrations of hydrogen peroxide(H2 O2;0, 150, 300, 500, 700, and 900 μmol/L) for 24 h, to induce oxidative damage and cell viability was assessed by MTT assay. UCP2 mRNA expression in cells treated with H2 O2 was investigated by reverse transcription-polymerase chain reaction(RT-PCR). UCP2 protein expression was assessed by Western blotting and ROS levels analyzed by flow cytometry(FCM). Further, UCP2-siRNA treated cultures were exposed to H2 O2(0, 75, 150, and 300 μmol/L) for 2 h and cell viability determined by MTT assay.RESULTS: Cells treated with higher concentrations of H2 O2 appeared shrunken;their adhesion to adjacent cells was disrupted, and the number of dead cells increased. The results of cell viability assays demonstrated that the numbers of cells were decreased in a dose-dependent manner following treatment with H2 O2. Compared with untreated controls, cell viability was significantly reduced after treatment with >300 μmol/L H2 O2(P<0.05). Cell metabolic activity was decreased with increased concentrations of H2 O2 as detected by MTT assay. Levels of OS were further decreased in cells treated with UCP2-siRNA compared with those treated with H2 O2 alone(P<0.05). The results of RT-PCR and Western blotting demonstrated that UCP2 expression was reduced in H2 O2-treated groups compared with controls(P<0.05). FCM analysis showed that cell reactive oxygen species(ROS) levels were increased in H2 O2-treated groups and further upregulated by UCP2-si RNA treatment(P<0.05).CONCLUSION: Expression levels of UCP2 are decreased in ARPE-19 cells treated with H2 O2. ROS levels are further increased in cells treated with UCP2-siRNA relative to those treated with H2 O2 alone. UCP2 may have a protective role in ARPE-19 cells during oxidative injury.
文摘目的系统评价临床常用精神类药物对阿尔茨海默病(AD)激越症状的疗效、安全性及认知功能的影响,基于累积排序概率曲线下面积(SUCRA)进行多维度概率排名,为临床决策提供参考。方法系统检索PubMed、the Cochrane Library、Web of Science和Embase数据库,纳入抗精神病药与安慰剂治疗AD的随机对照研究,采用平均值(MD)及其95%置信区间(95%CI)量化疗效差异,并基于SUCRA进行不同药物治疗效果的优劣排序。结果共检索3615篇文献,最终纳入11篇文献,涉及12项研究(涵盖8种干预措施与安慰剂对照)。网状meta分析结果显示,与安慰剂相比,依匹哌唑可显著降低Cohen-Mansfield激越问卷(CMAI)评分(MD=-3.88,95%CI:-5.89~-1.88)和神经精神问卷(NPI)评分(MD=-4.60,95%CI:-7.54~-1.66),其疗效在CMAI(SUCRA=85.2%)评分改善与NPI(SUCRA=89.2%)评分改善方面的累积概率排名均为首位,但其不良事件风险显著升高(RR=1.11,95%CI:1.02~1.21)。米氮平在认知功能改善方面具有优势(SMD=5.10,95%CI:0.69~9.51,SUCRA=96.1%),但激越症状控制效果有限。结论依匹哌唑是改善AD激越症状方面具有统计学优势的药物,但需警惕不良反应风险;米氮平对认知功能的获益有潜在治疗价值,但核心激越症状控制效能不足。
基金supported by the Chinese Academy of Medical Sciences(Grant No.2021RU002)Beijing Natural Science Foundation(Grant No.Z240013)+2 种基金National Natural Science Foundation of China(Grant Nos.82450111,82388102,82373416,and 92259303)Beijing Research Ward Excellence Program(Grant Nos.BRWEP2024W034080200 and BRWEP2024W034080204)Peking University People’s Hospital Research and Development Funds(Grant No.RZG2024-02).
文摘Organoids are three-dimensional stem cell-derived models that offer a more physiologically relevant representation of tumor biology compared to traditional two-dimensional cell cultures or animal models.Organoids preserve the complex tissue architecture and cellular diversity of human cancers,enabling more accurate predictions of tumor growth,metastasis,and drug responses.Integration with microfluidic platforms,such as organ-on-a-chip systems,further enhances the ability to model tumor-environment interactions in real-time.Organoids facilitate in-depth exploration of tumor heterogeneity,molecular mechanisms,and the development of personalized treatment strategies when coupled with multi-omics technologies.Organoids provide a platform for investigating tumor-immune cell interactions,which aid in the design and testing of immune-based therapies and vaccines.Taken together,these features position organoids as a transformative tool in advancing cancer research and precision medicine.
文摘目的分析丙泊酚复合3种使用剂量瑞芬太尼靶控输注在经喉罩纤维支气管镜介入术中的麻醉质量。方法选取2019年2月-2021年12月该院择期行纤维支气管镜介入治疗的患者96例,采用随机数表法分为A组、B组和C组,各32例。3组均行喉罩全身麻醉,A组、B组和C组瑞芬太尼剂量分别为0.2μg/(kg·min)(低剂量)、0.3μg/(kg·min)(中剂量)和0.4μg/(kg·min)(高剂量)。比较3组患者手术时间、麻醉质量(麻醉时间和手术医生麻醉满意度)、不同时间点心率(HR)、平均动脉压(MAP)、氧化应激因子[过氧化氢酶(CAT)、丙二醛(MDA)、超氧化物歧化酶(SOD)]水平、麻醉苏醒质量(苏醒时间、听指令睁眼时间和滞留苏醒室时间)、苏醒后不同时间点舒适度评分(BCS)和不良反应发生情况。结果B组和C组手术医生麻醉满意度评分均高于A组(P<0.05);B组和C组T_(2)、T_(3)时点HR和MAP均低于A组(P<0.05);B组和C组手术开始10 min血清CAT和SOD水平均高于A组,血清MDA水平均低于A组(P<0.05);3组患者苏醒时间、听指令睁眼时间和滞留苏醒室时间比较,差异均无统计学意义(P>0.05);B组和C组苏醒后10 min和1 h BCS均高于A组(P<0.05);B组不良反应发生率为0.00%,低于A组的18.75%和C组的18.75%,差异均有统计学意义(P<0.05)。结论经喉罩纤维支气管镜介入术全身麻醉中应用中剂量瑞芬太尼复合丙泊酚,能获得满意的麻醉质量,不良反应少,安全性高。
基金supported by the National Key R&D Program of China(No.2023YFB3308601)Sichuan Science and Technology Program(2024NSFJQ0035,2024NSFSC0004)the Talents by Sichuan provincial Party Committee Organization Department.
文摘In natural language processing(NLP),managing multiple downstream tasks through fine-tuning pre-trained models often requires maintaining separate task-specific models,leading to practical inefficiencies.To address this challenge,we introduce AdaptForever,a novel approach that enables continuous mastery of NLP tasks through the integration of elastic and mutual learning strategies with a stochastic expert mechanism.Our method freezes the pre-trained model weights while incorporating adapters enhanced with mutual learning capabilities,facilitating effective knowledge transfer from previous tasks to new ones.By combining Elastic Weight Consolidation(EWC)for knowledge preservation with specialized regularization terms,AdaptForever successfully maintains performance on earlier tasks while acquiring new capabilities.Experimental results demonstrate that AdaptForever achieves superior performance across a continuous sequence of NLP tasks compared to existing parameter-efficient methods,while effectively preventing catastrophic forgetting and enabling positive knowledge transfer between tasks.
基金supported by the National Natural Science Foundation of China(41925009)National Key R&D Program of China(2022YFE0203800)+2 种基金the Ministry of Finance of the People’s Republic of China(YSBR-019)Science and Technology Innovation Team of Shaanxi Province(2024RS-CXTD-74)Xiaohong Wu was supported by the Key National Social Science Foundation of China(No.16ZDA144).
文摘Yunnan in southwest China is a geographically and ethnically complex region at the intersection of southern China and Southeast Asia,and a focal point for human migrations.To clarify its maternal genetic history,we generated 152 complete mitogenomes from 17 Yunnan archaeological sites.Our results reveal distinct genetic histories segregated by geographical regions.Maternal lineages of ancient populations from northwestern and northern Yunnan exhibit closer affinities with past and present-day populations from northern East Asia and Xizang,providing important genetic evidence for the migration and interaction of populations along the Tibetan-Yi corridor since the Neolithic.Between 5500 and 1800 years ago,central Yunnan populations maintained their internal genetic relationships,including a 7000-year-old basal lineage of the rare and widely dispersed haplogroup M61.At the Xingyi site,changes in mitochondrial DNA haplogroups occurred between the Late Neolithic and Bronze Age,with haplogroups shifting from those predominant in the Yellow River region to those predominant in coastal southern China.These results highlight the high diversity of Yunnan populations during the Neolithic to Bronze Age.
基金supported by the National Natural Science Foundation of China(Grant No.92372111 and 22179070)the Natural Science Foundation of Jiangsu Province(Grant No.BK20220073)the Fundamental Research Funds for the Central Universities(Grant No.RF1028623157)。
文摘Sodium-ion batteries stand out as potential candidates for large-scale energy storage systems due to the abundant resource of sodium.However,similar to lithium-ion batteries,there also exist challenges related to thermal safety in practical applications.The cathode,anode,and electrolyte of sodium-ion batteries can significantly influence the occurrence of thermal runaway events.Comprehensive understandings on the thermal behaviors of these components and their interactions are critically pivotal for unraveling the thermal runaway mechanisms of sodium-ion batteries and ensuring their safe operations.This review,pivoting on the origins and solutions for thermal runaway of sodium-ion batteries,summarizes and discusses the recent progress on thermal stability characteristics of the cathode,anode,and electrolyte.Some strategies are suggested to potentially enhance safety performance.The review aims to offer valuable insights for a more profound exploration of the thermal runaway mechanisms and inform the design of safe sodium-ion batteries.
基金supported by the National Natural Science Foundation of China(NSFC,31971413)to D.L.
文摘Numerous bird species have adapted to rapid urbanization,navigating challenges introduced by novel stressors.While prior research has explored how urban exploiters adjust their physiology relative to their rural counterparts during breeding season,the modulation of multiple physiological markers outside of reproduction,and the maintenance of sex-specific differences,remain less understood.Using an urban exploiter,the Eurasian tree sparrow(ETS;Passer montanus),we investigated how both sexes of urban and rural populations modulate twenty-two physiological markers of nutrition,body condition,oxidative stress,and antioxidative responses during pre-breeding stage.Our results showed that urban ETSs displayed distinct glucolipid metabolism compared to rural ETSs,characterized by higher levels of free fatty acids,β-hydroxybutyric acid,high-density lipoprotein(HDL),and total cholesterol,alongside lower levels of triglycerides,glucose(Glu),and fat content(FC).No significant differences were observed in other physiological markers.Additionally,both sexes of urban ETSs exhibited similar profiles across these markers,unlike rural populations where females showed higher Glu and total protein levels and lower HDL and FC levels than males.Our findings suggest that birds adjust their nutritional physiological markers in response to urbanization,likely due to dietary differences between urban and rural environments.Furthermore,sex differences in physiological markers of nutrition,body condition,oxidative stress,and antioxidant responses appear to diminish in urban settings.