SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study...SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study,the role of SIL1 in APP processing was explored both in vitro and in vivo.In the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695.In the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates.Western blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant parameters.Results indicated that SIL1 expression decreased in APP23/PS45 mice.Overexpression of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in vitro.Conversely,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 cells.Furthermore,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice.Importantly,Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice.These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.展开更多
[Objectives]To establish a thin-layer chromatography(TLC)method for the determination of rubiadin-1-methyl ether in Yao Medicine Chuanlianzhu(Damnacanthus giganteus).[Methods]A silica gel G thin-layer plate was adopte...[Objectives]To establish a thin-layer chromatography(TLC)method for the determination of rubiadin-1-methyl ether in Yao Medicine Chuanlianzhu(Damnacanthus giganteus).[Methods]A silica gel G thin-layer plate was adopted for TLC.Petroleum ether(60-90℃)-chloroform-methanol-water(7:15:3:1)was used as the developing solvent and inspected under ultraviolet lamp(365 nm).The content was determined by Inertsil ODS-3 C 18 column(4.60 mm×250 mm,5μm),mobile phase:acetonitrile-0.2%phosphoric acid gradient elution,detection wavelength 277 nm,flow rate 1.0 mL/min,column temperature 30℃,injection volume 10μL.[Results]The spots of 10 Chuanlianzhu samples from different origins showed the same color at the same position as the control,and the spots were clear and specific.The injection volume of rubiadin-1-methyl ether showed a good linear relationship in the range of 2.90-145μg(R=0.9996).The average recovery rate of rubiadin-1-methyl ether in the low,medium and high dose groups of Yao Medicine Chuanlianzhu was 98.72%,and RSD=1.78%.[Conclusions]This method can effectively identify Yao Medicine Chuanlianzhu medicinal materials and accurately determine the content of rubiadin-1-methyl ether in the medicinal materials.It provides a scientific basis for the development and utilization of Yao Medicine Chuanlianzhu medicinal resources.展开更多
奥灰岩溶裂隙含水层是影响华北型煤矿深部开采的重要水害,在水-岩相互作用下奥灰含水层易导致煤层底板突水。为进一步认识奥灰岩溶突水问题,文章以新集矿区深部1煤层开采为例,利用矿区近些年最新积累的奥灰钻孔资料,选取断层强度指数、...奥灰岩溶裂隙含水层是影响华北型煤矿深部开采的重要水害,在水-岩相互作用下奥灰含水层易导致煤层底板突水。为进一步认识奥灰岩溶突水问题,文章以新集矿区深部1煤层开采为例,利用矿区近些年最新积累的奥灰钻孔资料,选取断层强度指数、断层交叉点与尖灭点、含水层水压、富水性、隔水层等效厚度、脆塑比7个因素作为奥灰岩溶突水的主控因素,并结合层次分析法(analytic hierarchy process,AHP)确定各主控因素影响权重。运用地理信息系统(geographic information system,GIS)空间分析功能建立各主控因素专题图,通过对专题栅格图归一化处理,将各主控因素按照权重进行空间复合叠加,最终获得1煤层底板奥灰岩溶突水危险性评价分区结果。将评价结果与突水系数法计算结果对比分析可知,基于GIS的煤层底板突水危险性评价方法更符合矿区实际地质情况,可以为矿区深部煤层开采与水害防治工作提供参考依据。展开更多
为利用干酪乳杆菌制备发酵菠萝果汁饮品,本研究对干酪乳杆菌LK-1(Lactobacillus casei LK-1,L. casei LK-1)的生长曲线、产酸、耐酸和耐糖等特性进行研究分析,并以活菌数和总酸为指标,通过单因素实验及响应面法考察L. casei LK-1发酵菠...为利用干酪乳杆菌制备发酵菠萝果汁饮品,本研究对干酪乳杆菌LK-1(Lactobacillus casei LK-1,L. casei LK-1)的生长曲线、产酸、耐酸和耐糖等特性进行研究分析,并以活菌数和总酸为指标,通过单因素实验及响应面法考察L. casei LK-1发酵菠萝果汁的最佳条件。结果表明,L. casei LK-1在pH5~7和0%~10%质量分数葡萄糖环境下,具备良好的生长繁殖能力;在酸性(pH3)和高糖(40%质量分数葡萄糖)环境中培养3 h,其存活率分别为76%和71%;在MRS培养基中培养48 h,产酸量为5.35 g/kg,产酸能力良好,适用于果汁的发酵。L. casei LK-1发酵菠萝果汁的最佳条件为:初始pH6.8,发酵温度37℃,接种量1%(v/v),发酵时间30 h,此条件下制备的发酵菠萝果汁饮品活菌数为8.99±0.04 lg CFU/mL,总酸含量为7.16±0.26 g/kg,且色泽鲜亮,酸甜适口,风味较好,为L. casei LK-1在发酵食品中的进一步应用提供了理论和技术依据。展开更多
Cancer poses a significant threat due to its aggressive nature,potential for widespread metastasis,and inherent heterogeneity,which often leads to resistance to chemotherapy.Lung cancer ranks among the most prevalent ...Cancer poses a significant threat due to its aggressive nature,potential for widespread metastasis,and inherent heterogeneity,which often leads to resistance to chemotherapy.Lung cancer ranks among the most prevalent forms of cancer worldwide,affecting individuals of all genders.Timely and accurate lung cancer detection is critical for improving cancer patients’treatment outcomes and survival rates.Screening examinations for lung cancer detection,however,frequently fall short of detecting small polyps and cancers.To address these limitations,computer-aided techniques for lung cancer detection prove to be invaluable resources for both healthcare practitioners and patients alike.This research implements an enhanced EfficientNetB1 deep learning model for accurate detection and classification using histopathological images.The proposed technique accurately classifies the histopathological images into three distinct classes:(1)no cancer(benign),(2)adenocarcinomas,and(3)squamous cell carcinomas.We evaluated the performance of the proposed technique using the histopathological(LC25000)lung dataset.The preprocessing steps,such as image resizing and augmentation,are followed by loading a pretrained model and applying transfer learning.The dataset is then split into training and validation sets,with fine-tuning and retraining performed on the training dataset.The model’s performance is evaluated on the validation dataset,and the results of lung cancer detection and classification into three classes are obtained.The study’s findings show that an enhanced model achieves exceptional classification accuracy of 99.8%.展开更多
Aluminum alloy thin-walled structures are widely used in the automotive industry due to their advantages related to light weight and crashworthiness.They can be produced at room temperature by the electrohydraulic for...Aluminum alloy thin-walled structures are widely used in the automotive industry due to their advantages related to light weight and crashworthiness.They can be produced at room temperature by the electrohydraulic forming process.In the present study,the influence of the related parameters on the forming quality of a 6063 aluminum alloy sinusoidal corrugation tube has been assessed.In particular,the orthogonal experimental design(OED)and central composite design(CCD)methods have been used.Through the range analysis and variance analysis of the experimental data,the influence degree of wire diameter(WD)and discharge energy(DE)on the forming quality was determined.Multiple regression analysis was performed using the response surface methodology.A prediction model for the attaching-die state coefficient was established accordingly.The following optimal arrangement of parameters was obtained(WD=0.759 mm,DE=2.926 kJ).The attaching-die state coefficient reached the peak value of 0.001.Better optimized wire diameter and discharge energy for a better attaching-die state could be screened by CCD compared with OED.The response surface method in CCD was more suitable for the design and optimization of the considered process parameters.展开更多
BAY-069是目前体外活性最强的支链氨基酸转氨酶1(BCAT1)抑制剂,但其报道的合成路线存在原料成本较高、总收率极低和中间体结构表征不充分等缺点。本研究基于已有合成路线,重点对其合成工艺中的Ullmann偶联反应进行了系统优化。以1-硝基...BAY-069是目前体外活性最强的支链氨基酸转氨酶1(BCAT1)抑制剂,但其报道的合成路线存在原料成本较高、总收率极低和中间体结构表征不充分等缺点。本研究基于已有合成路线,重点对其合成工艺中的Ullmann偶联反应进行了系统优化。以1-硝基萘(1)为起始原料,经过7步反应和手性色谱柱手性拆分合成目标化合物BAY-069。所有中间体和目标化合物均经1 H NMR,13 C NMR和HR-MS表征。以Ullmann偶联反应为主要优化步骤的路线,其优化后的总收率为11.0%(3b→(±)-BAY-069),是原总收率1.6%(3a→(±)-BAY-069)的6.9倍。展开更多
基金National Natural Science Foundation of China(82230043,82293642)。
文摘SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study,the role of SIL1 in APP processing was explored both in vitro and in vivo.In the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695.In the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates.Western blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant parameters.Results indicated that SIL1 expression decreased in APP23/PS45 mice.Overexpression of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in vitro.Conversely,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 cells.Furthermore,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice.Importantly,Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice.These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.
基金Supported by State Administration of Traditional Chinese Medicine High-level Key Discipline Construction Project of Traditional Chinese Medicine-Ethnic Minority Pharmacy (Zhuang Pharmacy) (zyyzdxk-2023165)General Scientific Research Program of Guangxi University of Chinese Medicine in 2020 (2020MS063)+4 种基金Key R&D Project of Guangxi Science and Technology Department (Guike AB21196057)Young Talent Cultivation Program of Guangxi International Zhuang Medicine Hospital (2022001)Funding Project of High-level Talent Cultivation and Innovation Team of Guangxi University of Chinese Medicine (2022A008)Guangxi Traditional Chinese Medicine Interdisciplinary Innovation Team Project (GZKJ2309)State Administration of Traditional Chinese Medicine"Twelfth Five-Year Plan"Key Discipline of Traditional Chinese Medicine (Ethnic Pharmacy)Zhuang Pharmacy.
文摘[Objectives]To establish a thin-layer chromatography(TLC)method for the determination of rubiadin-1-methyl ether in Yao Medicine Chuanlianzhu(Damnacanthus giganteus).[Methods]A silica gel G thin-layer plate was adopted for TLC.Petroleum ether(60-90℃)-chloroform-methanol-water(7:15:3:1)was used as the developing solvent and inspected under ultraviolet lamp(365 nm).The content was determined by Inertsil ODS-3 C 18 column(4.60 mm×250 mm,5μm),mobile phase:acetonitrile-0.2%phosphoric acid gradient elution,detection wavelength 277 nm,flow rate 1.0 mL/min,column temperature 30℃,injection volume 10μL.[Results]The spots of 10 Chuanlianzhu samples from different origins showed the same color at the same position as the control,and the spots were clear and specific.The injection volume of rubiadin-1-methyl ether showed a good linear relationship in the range of 2.90-145μg(R=0.9996).The average recovery rate of rubiadin-1-methyl ether in the low,medium and high dose groups of Yao Medicine Chuanlianzhu was 98.72%,and RSD=1.78%.[Conclusions]This method can effectively identify Yao Medicine Chuanlianzhu medicinal materials and accurately determine the content of rubiadin-1-methyl ether in the medicinal materials.It provides a scientific basis for the development and utilization of Yao Medicine Chuanlianzhu medicinal resources.
文摘奥灰岩溶裂隙含水层是影响华北型煤矿深部开采的重要水害,在水-岩相互作用下奥灰含水层易导致煤层底板突水。为进一步认识奥灰岩溶突水问题,文章以新集矿区深部1煤层开采为例,利用矿区近些年最新积累的奥灰钻孔资料,选取断层强度指数、断层交叉点与尖灭点、含水层水压、富水性、隔水层等效厚度、脆塑比7个因素作为奥灰岩溶突水的主控因素,并结合层次分析法(analytic hierarchy process,AHP)确定各主控因素影响权重。运用地理信息系统(geographic information system,GIS)空间分析功能建立各主控因素专题图,通过对专题栅格图归一化处理,将各主控因素按照权重进行空间复合叠加,最终获得1煤层底板奥灰岩溶突水危险性评价分区结果。将评价结果与突水系数法计算结果对比分析可知,基于GIS的煤层底板突水危险性评价方法更符合矿区实际地质情况,可以为矿区深部煤层开采与水害防治工作提供参考依据。
文摘为利用干酪乳杆菌制备发酵菠萝果汁饮品,本研究对干酪乳杆菌LK-1(Lactobacillus casei LK-1,L. casei LK-1)的生长曲线、产酸、耐酸和耐糖等特性进行研究分析,并以活菌数和总酸为指标,通过单因素实验及响应面法考察L. casei LK-1发酵菠萝果汁的最佳条件。结果表明,L. casei LK-1在pH5~7和0%~10%质量分数葡萄糖环境下,具备良好的生长繁殖能力;在酸性(pH3)和高糖(40%质量分数葡萄糖)环境中培养3 h,其存活率分别为76%和71%;在MRS培养基中培养48 h,产酸量为5.35 g/kg,产酸能力良好,适用于果汁的发酵。L. casei LK-1发酵菠萝果汁的最佳条件为:初始pH6.8,发酵温度37℃,接种量1%(v/v),发酵时间30 h,此条件下制备的发酵菠萝果汁饮品活菌数为8.99±0.04 lg CFU/mL,总酸含量为7.16±0.26 g/kg,且色泽鲜亮,酸甜适口,风味较好,为L. casei LK-1在发酵食品中的进一步应用提供了理论和技术依据。
文摘Cancer poses a significant threat due to its aggressive nature,potential for widespread metastasis,and inherent heterogeneity,which often leads to resistance to chemotherapy.Lung cancer ranks among the most prevalent forms of cancer worldwide,affecting individuals of all genders.Timely and accurate lung cancer detection is critical for improving cancer patients’treatment outcomes and survival rates.Screening examinations for lung cancer detection,however,frequently fall short of detecting small polyps and cancers.To address these limitations,computer-aided techniques for lung cancer detection prove to be invaluable resources for both healthcare practitioners and patients alike.This research implements an enhanced EfficientNetB1 deep learning model for accurate detection and classification using histopathological images.The proposed technique accurately classifies the histopathological images into three distinct classes:(1)no cancer(benign),(2)adenocarcinomas,and(3)squamous cell carcinomas.We evaluated the performance of the proposed technique using the histopathological(LC25000)lung dataset.The preprocessing steps,such as image resizing and augmentation,are followed by loading a pretrained model and applying transfer learning.The dataset is then split into training and validation sets,with fine-tuning and retraining performed on the training dataset.The model’s performance is evaluated on the validation dataset,and the results of lung cancer detection and classification into three classes are obtained.The study’s findings show that an enhanced model achieves exceptional classification accuracy of 99.8%.
基金supported by National Natural Science Foundation of China(Grant Nos.51975202(Junjia Cui received the grant)and 52175315(Guangyao Li received the grant)).
文摘Aluminum alloy thin-walled structures are widely used in the automotive industry due to their advantages related to light weight and crashworthiness.They can be produced at room temperature by the electrohydraulic forming process.In the present study,the influence of the related parameters on the forming quality of a 6063 aluminum alloy sinusoidal corrugation tube has been assessed.In particular,the orthogonal experimental design(OED)and central composite design(CCD)methods have been used.Through the range analysis and variance analysis of the experimental data,the influence degree of wire diameter(WD)and discharge energy(DE)on the forming quality was determined.Multiple regression analysis was performed using the response surface methodology.A prediction model for the attaching-die state coefficient was established accordingly.The following optimal arrangement of parameters was obtained(WD=0.759 mm,DE=2.926 kJ).The attaching-die state coefficient reached the peak value of 0.001.Better optimized wire diameter and discharge energy for a better attaching-die state could be screened by CCD compared with OED.The response surface method in CCD was more suitable for the design and optimization of the considered process parameters.
文摘BAY-069是目前体外活性最强的支链氨基酸转氨酶1(BCAT1)抑制剂,但其报道的合成路线存在原料成本较高、总收率极低和中间体结构表征不充分等缺点。本研究基于已有合成路线,重点对其合成工艺中的Ullmann偶联反应进行了系统优化。以1-硝基萘(1)为起始原料,经过7步反应和手性色谱柱手性拆分合成目标化合物BAY-069。所有中间体和目标化合物均经1 H NMR,13 C NMR和HR-MS表征。以Ullmann偶联反应为主要优化步骤的路线,其优化后的总收率为11.0%(3b→(±)-BAY-069),是原总收率1.6%(3a→(±)-BAY-069)的6.9倍。
