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Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis

Signal Transduction and Targeted Therapy 2024年第2期9卷 738-750页

作者： yun Zhang Lijun Du Chenxi Wang Zhangsheng Jiang Qingchi Duan yiping Li Zhijun xie Zhixing He yi Sun Lin Huang Liwei Lu Chengping wen Key Laboratory of Chinese medicine rheumatology of Zhejiang Province Research Institute of Chinese Medical Clinical Foundation and ImmunologyCollege of Basic Medical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China Department of General Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Cancer Center of Zhejiang University Hangzhou 310029China Department of Pathology and Shenzhen Institute of Research and Innovation The University of Hong KongHong KongChina Chongqing International Institute for Immunology Chongqing 400038China

Systemic lupus erythematosus(SLE),a severe autoimmune disorder,is characterized by systemic inflammatory response,autoantibody accumulation and damage to *** dysregulation of double-negative(DN)T cells is considered as a crucial commander during ***,a significant type of protein post-translational modification(PTM),has been well-proved to regulate T cell-mediated immune ***,the function of neddylation in SLE is still ***,we reported that neddylation inactivation with MLN4924,a specific inhibitor of NEDD8-activating enzyme E1(NAE1),or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus *** investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells,contributing to the apoptosis of the accumulated DN T cells in lupus *** double knockout(KO)lupus-prone mice(Ube2m-/-Bim-/-lpr)were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus *** findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus ***,we also found that in SLE patients,the proportion of DN T cells was raised and their apoptosis was ***,compared to healthy groups,SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation ***,the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE ***,our findings provide the direct evidence about the function of neddylation during lupus,suggesting a promising therapeutic approach for this disease.

关键词： inactivation double finding

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Intelligent diagnostic model for pterygium by combining attention mechanism and MobileNetV2

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1184-1192页

作者： Mao-Nian Wu Kai He yi-Bei yu Bo Zheng Shao-Jun Zhu xiang-Qian Hong wen-Qun xi Zhe Zhang School of Information Engineering Huzhou UniversityHuzhou 313000Zhejiang ProvinceChina Zhejiang Province Key Laboratory of Smart Management and Application of Modern Agricultural Resources Huzhou UniversityHuzhou 313000Zhejiang ProvinceChina School of Mathematical Information Shaoxing UniversityShaoxing 312000Zhejiang ProvinceChina Shenzhen Eye Institute Shenzhen Eye HospitalJinan UniversityShenzhen 518040Guangdong ProvinceChina

AIM:To evaluate the application of an intelligent diagnostic model for ***:For intelligent diagnosis of pterygium,the attention mechanisms—SENet,ECANet,CBAM,and Self-Attention—were fused with the lightweight MobileNetV2 model structure to construct a tri-classification *** study used 1220 images of three types of anterior ocular segments of the pterygium provided by the Eye Hospital of Nanjing Medical *** classification models—VGG16,ResNet50,MobileNetV2,and EfficientNetB7—were trained on the same dataset for *** evaluate model performance in terms of accuracy,Kappa value,test time,sensitivity,specificity,the area under curve(AUC),and visual heat map,470 test images of the anterior segment of the pterygium were ***:The accuracy of the MobileNetV2+Self-Attention model with 281 MB in model size was 92.77%,and the Kappa value of the model was 88.92%.The testing time using the model was 9ms/image in the server and 138ms/image in the local *** sensitivity,specificity,and AUC for the diagnosis of pterygium using normal anterior segment images were 99.47%,100%,and 100%,respectively;using anterior segment images in the observation period were 88.30%,95.32%,and 96.70%,respectively;and using the anterior segment images in the surgery period were 88.18%,94.44%,and 97.30%,***:The developed model is lightweight and can be used not only for detection but also for assessing the severity of pterygium.

关键词： deep learning attention mechanism pterygium intelligent diagnosis

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Timing of Continuous Renal Replacement Therapy Initiation in Sepsis-Associated Acute Kidney Injury: A Comprehensive Review and Future Directions

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Journal of Clinical and Nursing Research 2024年第8期8卷 21-30页

作者： Zhengshuang Liu Chuanren Zhuang xuehuan wen Cangnan Hospital of Traditional Chinese Medicine Wenzhou 325800Zhejiang ProvinceChina The Affiliated Cangnan Hospital Wenzhou Medical UniversityWenzhou 325800Zhejiang ProvinceChina

This review examines the application of continuous renal replacement therapy(CRRT)in patients with sepsis-associated acute kidney injury(S-AKI),with a particular focus on the timing of CRRT *** review addresses the controversy surrounding initiation timing and proposes future research *** a systematic review of recent literature on CRRT for S-AKI,working principles,therapeutic mechanisms,initiation timing of CRRT,and related meta-analyses were *** studies indicate that the optimal timing for CRRT initiation in S-AKI patients remains inconclusive,with ongoing debate regarding whether early initiation significantly improves patient survival and renal *** lack of consensus reflects the heterogeneity of the S-AKI patient population and the limitations of existing research *** studies should focus on advancing the application of precision medicine in S-AKI and developing individualized treatment strategies by integrating multidimensional information to optimize CRRT utilization and improve patient outcomes.

关键词： Sepsis Sepsis-related acute kidney injury Continuous renal replacement therapy(CRRT) Timing of initiation

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The AaBBx21–AaHy5 module mediates light-regulated artemisinin biosynthesis in Artemisia annua L.

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Journal of Integrative Plant Biology 2024年第8期66卷 1735-1751页

作者： Weizhi He Hang Liu Zhangkuanyu Wu Qing Miao xinyi Hu xin yan Hangyu wen yaojie Zhang xueqing Fu Li Ren Kexuan Tang Ling Li Frontiers Science Center for Transformative Molecules Joint International ResearchLaboratory of Metabolic and Developmental SciencesKey Laboratory of Urban Agriculture(South)Ministry of AgriculturePlant Biotechnology Research CenterFudan-SJTU-Nottingham Plant Biotechnology R&D CenterSchool of Agriculture and BiologyShanghai Jiao Tong UniversityShanghai 200240China Institute for Agri-Food Standards and Testing Technology Shanghai Academy of Agricultural SciencesShanghai 201403China

The sesquiterpene lactone artemisinin is an important anti-malarial component produced by the glandular secretory trichomes of sweet wormwood(Artemisia annua L.).Light was previously shown to promote artemisinin production,but the underlying regulatory mechanism remains *** this study,we demonstrate that ELONGATED HyPOCOTyL5(Hy5),a central transcription factor in the light signaling pathway,cannot promote artemisinin biosynthesis on its own,as the binding of AaHy5 to the promoters of artemisinin biosynthetic genes failed to activate their *** analysis and yeast two-hybrid screening revealed the B-box transcription factor AaBBx21 as a potential interactor with ***21 showed a trichome-specific expression ***,the AaBBx21–AaHy5 complex cooperatively activated transcription from the promoters of the downstream genes AaGSW1,AaMyB108,and AaORA,encoding positive regulators of artemisinin ***,AaHy5 and AaBBx21 physically interacted with the *** E3 ubiquitin ligase CONSTITUTIVELy PHOTOMORPHOGENIC 1(COP1).In the dark,AaCOP1 decreased the accumulation of AaHy5 and AaBBx21 and repressed the activation of genes downstream of the AaHy5–AaBBx21 complex,explaining the enhanced production of artemisinin upon light *** study provides insights into the central regulatory mechanism by which light governs terpenoid biosynthesis in the plant kingdom.

关键词： AaBBx21 AaHy5 AaCOP1 Artemisia annua L. artemisinin biosynthesis light

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Zyx promotes invasion and metastasis of gastric cancer cells via WNK1/SNAI1axis

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Genes & Diseases 2024年第2期11卷 564-567页

作者： yi Jiang Dongfang xiang xianmei wen Mingmin He yan Qin xiaoxue yao Zexuan yan xiuli Geng yong Ren xiongwei Cai youhong Cui yan Wang Institute of Pathology and Southwest Cancer Center Southwest HospitalArmy Medical University (Third Military Medical University)Chongqing 400038China Department of Pathology General Hospital of Central Theater Command of PLAWuhanHubei 430070China Department of Obstetrics and Gynecology Southwest HospitalArmy Medical University (Third Military Medical University)Chongqing 400038China Department of Pharmacy The Hospital of 83rd Group of PLAXinxiangHenan 453000China Department of Gynecology Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical UniversityChongqing 400013China

Gastric cancer(GC)is the third most common cause of cancer death globally and a large portion of patients are diagnosed at advanced stages with cancer invasion and metastasis1,***,the mechanisms underlying the invasion and metastasis of GC remain to be *** plays critical roles in cell mobility via cytoskeleton regulation in various cell types.3 In this study,we further reported that Zyx promoted migration,invasion,and metastasis of GC ***,Zyx promoted WNK1 activation and SNAl1 up-regulation,inducing epithelial-mesenchymal transition(EMT)to enhance the mobility of GC *** of WNK1 impaired the mobility of GC ***,Zyx/WNK1 could be potential therapeutic targets for GC treatment.

关键词： WNK1 invasion metastasis

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A novel small-animal locomotor activity recording device for biological clock research

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Animal Models and Experimental Medicine 2024年第1期7卷 71-76页

作者： yi-Long Wu Ming Zhong Jun yin Wei-Jie Ou yu-Bin Zhuang Nan-wen Zhang Su Lin yue-yong Zhu Endoscopy Center The First Affiliated HospitalFujian Medical UniversityFuzhouChina Department of Endocrinology The First Affiliated HospitalFujian Medical UniversityFuzhouChina Chuangke Workshop Technology Co. LtdShenzhenChina Department of Digestive Nutrition Fujian Children's HospitalFuzhouChina Experimental Animal Center Fujian Medical UniversityFuzhouChina Department of Pharmacology Fujian Medical UniversityFuzhouChina Department of Hepatology Hepatology Research InstituteClinical Research Center for Liver and Intestinal Diseases of Fujian ProvinceThe First Affiliated HospitalFujian Medical UniversityFuzhouChina

The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian *** study demonstrated how to construct a simple and intelligent running-wheel recording *** running wheel was attached to the cage's base,whereas the Hall sensor was attached to the cage's ***,the RJ25 adaptor relayed the running signal to the main control ***,the main control board was connected to the USB port of the computer with the USB *** were collected using the online-accessible,self-created software *** Magturning,generated data were saved and exported in real ***,the device was validated by collecting data on the locomotor activities of mice under dif-ferent light *** conclusion,this new device can record circadian activity of *** device is appropriate for interdisciplinary investigations related to biological clock research.

关键词： biological clock circadian rhythm intelligent equipment locomotor activity running wheel

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Metabolomic reveals the inhibition mechanism of proline on hexanal production in chicken meat

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Food Science and Human Wellness 2024年

作者： Huanxian Cui yuxi Jin yanke Wang xiaoya yuan Li Liu Jie wen Guiping Zhao State Key Laboratory of Animal Nutrition， Institute of Animal Science， Chinese Academy of Agricultural Sciences

Hexanal contributes significantly to meat flavor. The aim of this study was to identify the metabolic pathways of hexanal formation in chicken meat. We found 32 metabolites associated with hexanal content in chicken meat， mainly including fatty acids (linoleic acid， etc.， positive correlation) and some amino acids (L-proline， etc.， negative correlation). A comparative analysis of the expression of these 32 metabolites between two groups of chickens with high- and low hexanal content revealed that L-proline and phenylacetaldehyde were downregulated， while ADP-ribose and 4-methylphenol were upregulated in the high-hexanal content chickens. It was also found that the increase of ADP-ribose induced the conversion of L-proline to other amino acids， such as arginine， through a process likely involving the pyrimidine metabolism pathway， leading to a reduction in proline content， which in turn abolished the inhibitory effect of proline on hexanal and enhanced the formation of hexanal. These findings confirm the effect of linoleic acid on hexanal content， and also reveal a negative regulatory effect of proline on the production of hexanal and its elimination mechanism in chicken meat.

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Potential preservative mechanisms of cardiac rehabilitation pathways on endothelial function in coronary heart disease

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Science China Life Sciences 2024年

作者： wen-Tao Sun Jian-yong Du Jia Wang yi-Long Wang Er-Dan Dong Research Center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital)School of Health and Life SciencesUniversity of Health and Rehabilitation Sciences Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalThe Institute of Cardiovascular SciencesPeking UniversityState Key Laboratory of Vascular Homeostasis and RemodelingPeking University

Cardiac rehabilitation, a comprehensive exercise-based lifestyle and medical management, is effective in decreasing morbidity and improving life quality in patients with coronary heart disease. Endothelial function, an irreplaceable indicator in coronary heart disease progression, is measured by various methods in traditional cardiac rehabilitation pathways, including medicinal treatment, aerobic training, and smoking cessation. Nevertheless, studies on the effect of some emerging cardiac rehabilitation programs on endothelial function are limited. This article briefly reviewed the endothelium-beneficial effects of different cardiac rehabilitation pathways, including exercise training, lifestyle modification and psychological intervention in patients with coronary heart disease, and related experimental models, and summarized both uncovered and potential cellular and molecular mechanisms of the beneficial roles of various cardiac rehabilitation pathways on endothelial function. In exercise training and some lifestyle interventions, the enhanced bioavailability of nitric oxide, increased circulating endothelial progenitor cells(EPCs), and decreased oxidative stress are major contributors to preventing endothelial dysfunction in coronary heart disease. Moreover, the preservation of endothelial-dependent hyperpolarizing factors and inflammatory suppression play roles. On the one hand, to develop more endothelium-protective rehabilitation methods in coronary heart disease, adequately designed and sized randomized multicenter clinical trials should be advanced using standardized cardiac rehabilitation programs and existing assessment methods. On the other hand, additional studies using suitable experimental models are warranted to elucidate the relationship between some new interventions and endothelial protection in both macro-and microvasculature.

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Insight into structural degradation of NCMs under extreme fast charging process

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Rare Metals 2024年第1期43卷 41-50页

作者： yu Tang xing-yu Wang Jin-Can Ren Bo-wen Chen Zhi-yong Huang Wei Wang ya-Lan Huang Bing-Hao Zhang Si Lan Zhang-Long He Qi Liu Hao He Department of Physics City University of Hong KongHong Kong 999077China Shenzhen Research Institute City University of Hong KongShenzhen 518057China College of Materials Science and Engineering Changsha University of Science&TechnologyChangsha 410114China

Lithium-ion batteries(LIBs)with extreme fast charging(xFC)capability are considered an effective way to alleviate range anxiety for electric vehicle(EV)*** to the high ionic and electronic conductivity of LiNi_(x)Co_(y)Mn_zO_(2)(x+y+z=1,NCM)cathodes,the inevitable Li plating of graphite in NCM|graphite cell is usually identified as a key bottleneck for xFC ***,the capacity decay mechanism of cathode materials under xFC has not been fully *** this work,three typical NCM cathode materials with different Ni fractions were chosen and their electrochemical performances under xFC associated with structural evolution were investigated.A faster capacity decay of NCMs under xFC conditions is observed,especially for Ni-rich ***-situ x-ray diffraction(xRD)reveals that the multiple caxis parameters appear at the high-voltage regions in Nirich NCMs,which is probably triggered by the larger obstruction of Li(de)***,NCMs with moderate Ni fraction also present a similar trend under xFC *** phenomenon is more detrimental to the structural and morphological stability,resulting in a faster capacity decay than that under low current *** work provides new insight into the degradation mechanism of NCMs under xFC conditions,which can promote the development of NCM cathode materials with xFC capability.

关键词： Lithium-ion batteries Ni fraction Extreme fast charging Structural evolution

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Modulation doping of p-type Cu_(12)Sb_(4)S_(13)toward improving thermoelectric performance

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Journal of Materials Science & Technology 2024年第4期171卷 71-79页

作者： Khak Ho Lim Mingquan Li yu Zhang yue Wu Qimin Zhou Qingyue Wang xuan yang Pingwei Liu wen-Jun Wang Ka Wai Wong Ka Ming Ng yu Liu Andreu Cabot Institute of Zhejiang University-Quzhou Quzhou 324000China College of Chemical and Biological Engineering Zhejiang UniversityHangzhou 310007China School of Chemistry and Chemical Engineering Hefei University of TechnologyHefei 230009China Materials Research Institute The Pennsylvania State UniversityUniversity ParkPA 16802USA Ostia Technologies Limited United Kingdom Department of Chemical and Biological Engineering The Hong Kong University of Science and TechnologyClear Water BayHong KongChina ICREA Pg.Lluis Companys 23Barcelona 08010Spain Catalonia Energy Research Institute-IREC Sant Adria del BesosBarcelona 08930Spain

The commercial viability of thermoelectric(TE)devices relies heavily on two factors:cost reduction and efficiency *** this study,we first produce p-type Cu_(12)Sb_(4)S_(16-x)(x=0,3,4)using a low-temperature bottom-up approach and demonstrate Cu_(12)Sb_(4)S_(13)to show the best TE performance among the three tested ***,the TE energy conversion efficiency of Cu_(12)Sb_(4)S_(13)is further enhanced by optimizing its electronic band structure through the incorporation of small amounts of *** an optimal Te content of 5 mol%,more than a twofold increase in the TE figure of merit(zT)is *** gain insight into the mechanism of improvement on the transport properties of the mate-rial,we compare the interphase transport mechanism by incorporating nanodomains of different metals(Ag and Cu)into the Cu_(12)Sb_(4)S_(13)*** improved electrical conductivity obtained with Cu_(12)Sb_(4)S_(13)-Te nanocomposites is attributed to a charge flooding of the Cu_(12)Sb_(4)S_(13)*** contrast,excessive down-ward band-bending at the interphases of Ag/Cu metal-semiconductor drastically reduces the electrical ***,a weighted mobility(μw)analysis shows a dominant thermal activation of carri-ers in Cu_(12)Sb_(4)S_(13)-Te *** this material,a strong decrease in lattice thermal conductivity is also found,which is associated with a phonon-carrier scattering *** work shows the impor-tance of proper band-engineering in TE nanocomposites to decouple electrical and thermal transport to enhance TE performance,and the efficacy ofμw for electrical and thermal transport analysis.

关键词： Modulation doping Thermoelectric Interphase transport Charge flooding Phonon-carrier scattering

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