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Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients

World Journal of Diabetes 2024年第2期15卷 275-286页

作者： Ping Shi Yang tian Feng xu Lu-Na Liu Wan-Hong Wu Ying-Zhou Shi An-Qi Dai Hang-Yu Fang Kun-Xia Li Chao xu Department of Endocrinology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021Shandong ProvinceChina Department of Pediatric Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityYantai 264099Shandong ProvinceChina

BACKGROUND Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)plays a crucial role in regulating insulin signaling and glucose *** in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14(MODY14).Currently,only two mutations[c.1655T>A(***552*)and c.281G>A p.(Asp94Asn)]have been identified in association with this *** the limited understanding of MODY14,it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 *** To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 *** Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the *** exome sequencing was performed on the patients as well as their family *** pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics *** addition,the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional ***,the impact of these variants on APPL1 protein expression and the insulin pathway were assessed,and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further *** A total of five novel mutations were identified,including four missense mutations(Asp632Tyr,Arg633His,Arg532Gln,and Ile642Met)and one intronic mutation(1153-16A>T).Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all *** Asp632Tyr and Arg633His variants also had pathogenicity based on *** addition,multiple alignment of amino acid sequences showed that the Arg532Gln,Asp632Tyr,and Arg633His variants were conserved across different ***,in in vitro functional experiments,both the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations

关键词： Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1 Maturity-onset diabetes of the young Bioinformatics analysis Gene mutation Domain

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Association between Exposure of Rare Earth Elements and Outcomes of In Vitro Fertilization-Embryo Transfer in Beijing

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Biomedical and Environmental Sciences 2024年第8期37卷 876-886页

作者： Yutong Wang Jing Li Shirong xu Shengli Lin Zhenchen Hou Linlin Wang Yali Huang Yue Sun Wei Guo Lailai Yan Ying Wang Chan tian State Key Laboratory of Female Fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China Department of Medical Genetics Peking UniversityBeijing 100191China National Clinical Research Center for Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China Key Laboratory of Assisted Reproduction(Peking University) Ministry of EducationBeijing 100191China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology Beijing 100191China Central Laboratory of School of Public Health Peking UniversityBeijing 100191China School of Basic Medical Sciences Peking UniversityBeijing 100191China

Objective The study aimed to investigate the impact of rare earth elements(REEs)exposure on pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)by analyzing samples from *** A total of 141 couples were *** and follicular fluid from the wives and semen plasma from the husbands,were analyzed for REEs using inductively coupled plasma mass spectrometry(ICP-MS).Spearman's correlation coefficients and the Mann–Whitney U test were used to assess correlations and compare REE concentrations among three types of samples,*** models were utilized to estimate the individual REE effect on IVF-ET outcomes,while BKMR and WQS models explored the mixture of REE interaction effects on IVF-ET *** Higher La concentration in semen(median 0.089 ng/mL,P=0.03)was associated with a lower fertilization ***,this effect was not observed after artificial selection intervention through intracytoplasmic sperm injection(ICSI)(P=0.27).In semen,the REEs mixture did not exhibit any significant association with clinical *** Our study revealed a potential association between high La exposure in semen and a decline in fertilization rate,but not clinical pregnancy *** is the first to report REEs concentrations in follicular fluid with La,Ce,Pr,and Nd found at significantly lower concentrations than in serum,suggesting that these four REEs may not accumulate in the female reproductive ***,at the current exposure levels,mixed REEs exposure did not exhibit reproductive toxicity.

关键词： Rare earth elements In vitro fertilization Pregnancy outcomes Mixture exposure analysis

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Molecular characterization and structure basis of a malonyltransferase with both substrate promiscuity and catalytic regiospecificity from Cistanche tubulosa

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2333-2348页

作者： Xiao Liu Yuyu Liu Xiping xu Wenqian Huang Yaru Yan Yingxia Wang Weisheng tian Ting Mo Xiaoxue Cui Jun Li She-Po Shi Pengfei Tu Modern Research Center for Traditional Chinese Medicine Beijing Research Institute of Chinese MedicineBeijing University of Chinese MedicineBeijing 100029China Modern Research Center for Traditional Chinese Medicine School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing 100029China

Enzymatic malonylation of natural glycosides provides a promising alternative method for drug-like malonylated glycosides ***,the catalytic potential and structural basis of plant malonyltransferase are far from being fully *** work identified a new malonyltransferase CtMaT1 from Cistanche *** displayed unprecedented mono-and/or di-malonylation activity toward diverse glucosides with different aglycons.A“one-pot”system by CtMaT1 and a malonyl-CoA synthetase was established to biosynthesize nine new malonylated *** investigations revealed that CtMaT1 possesses an adequately spacious acyl-acceptor pocket capable of accommodating diverse ***,it recognizes malonyl-CoA through strong electrotactic and hydrogen ***/MM calculation revealed the H167-mediated SN2 reaction mechanism of CtMaT1,while dynamic simulations detected the formation of stable hydrogen bonds between the glucose-6-OH group and H167,resulting in its high malonylation *** energy profiles of two isomeric glycosides highlighted lower reaction energy barriers towards glucoside substrates,emphasizing CtMaT1's preference for ***,a mutant CtMaT1H36A with notably increased di-malonylation activity was *** underlying molecular mechanism was illuminated through MM/GBSA binding free energy *** study significantly advances the understanding of plant acyltransferases from both functional and protein structural perspectives,while also providing a versatile tool for enzymatic malonylation applications in pharmacology.

关键词： Plant acyltransferase Malonyltransferase Malonylated glycosides Enzymatic catalysis Enzyme promiscuity

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Peritoneal fluid indocyanine green test for diagnosis of gut leakage in anastomotic leakage rats and colorectal surgery patients

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1825-1834页

作者： Yu Huang tian-Yang Li Jie-Feng Weng Hui Liu Yu-Jie xu Shuai Zhang Wei-Li Gu Department of Surgery Guangzhou First People's HospitalGuangzhou 510180Guangdong ProvinceChina

BACKGROUND Application of indocyanine green(ICG)fluorescence has led to new developments in gastrointestinal ***,little is known about the use of ICG for the diagnosis of postoperative gut leakage(GL).In addition,there is a lack of rapid and intuitive methods to definitively diagnose postoperative *** To investigate the effect of ICG in the diagnosis of anastomotic leakage in a surgical rat GL model and evaluate its diagnostic value in colorectal surgery *** Sixteen rats were divided into two groups:GL group(n=8)and sham group(n=8).Approximately 0.5 mL of ICG(2.5 mg/mL)was intravenously injected *** peritoneal fluid was collected for the fluorescence test at 24 and 48 *** patients with rectal cancer who had undergone laparoscopic rectal cancer resection plus enterostomies were injected with 10 mL of ICG(2.5 mg/mL)on postoperative day *** ostomy fluids were collected 24 h after ICG injection to identify the possibility of the ICG excreting from the peripheral veins to the enterostomy *** who had undergone colectomy or rectal cancer resection were enrolled in the diagnostic *** peritoneal fluids from drainage were collected 24 h after ICG *** ICG fluorescence test was conducted using OptoMedic endoscopy along with a near-infrared fluorescent imaging *** The peritoneal fluids from the GL group showed ICG-dependent green fluorescence in contrast to the sham *** samples of ostomy fluids showed green fluorescence,indicating the possibility of ICG excreting from the peripheral veins to the enterostomy stoma in *** peritoneal fluid ICG test exhibited a sensitivity of 100%and a specificity of 83.3%for the diagnosis of *** positive predictive value was 71.4%,while the negative predictive value was 100%.The likelihood ratios were 6.0 for a positive test result and 0 for a negative *** The postoperative ICG test in a drainage tube is a valuable and simple t

关键词： Gut leakage Indocyanine green Anastomotic leakage model Diagnostic test Diagnostic technique

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Respiratory protein-driven selectivity during the Permian-Triassic mass extinction

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The Innovation 2024年第3期5卷 122-128页

作者： Haijun Song Yuyang Wu xu Dai Jacopo Dal Corso Fengyu Wang Yan Feng Daoliang Chu Li tian Huyue Song William JFoster State Key Laboratory of Biogeology and Environmental Geology School of Earth SciencesChina University of GeosciencesWuhan 430074China Biogéosciences UMR 6282CNRSUniversitéde Bourgogne21000 DijonFrance Universitat Hamburg Institute for Geology20148 HamburgGermany

Extinction selectivity determines the direction of macroevolution,especially during mass extinction;however,its driving mechanisms remain poorly *** investigating the physiological selectivity of marine animals during the Permian-Triassic mass extinction,we found that marine clades with lower O2-carrying capacity hemerythrin proteins and those relying on O2 diffusion experienced significantly greater extinction intensity and body-size reduction than those with higher O2-carrying capacity hemoglobin or hemocyanin *** findings suggest that animals with high O2-carrying capacity obtained the necessary O2 even under hypoxia and compensated for the increased energy requirements caused by ocean acidification,which enabled their survival during the Permian-Triassic mass ***,high O2-carrying capacity may have been crucial for the transition from the Paleozoic to the Modern Evolutionary Fauna.

关键词： extinction selectivity finding

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OsWRKY78 regulates panicle exsertion via gibberellin signaling pathway in rice

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Journal of Integrative Plant Biology 2024年第4期66卷 771-786页

作者： Enyang Mei Mingliang He Min xu Jiaqi Tang Jiali Liu Yingxiang Liu Zhipeng Hong Xiufeng Li Zhenyu Wang Qingjie Guan Xiaojie tian Qingyun Bu State Key Laboratory of Black Soils Conservation and Utilization Key Laboratory of Soybean Molecular Design BreedingNortheast Institute of Geography and AgroecologyChinese Academy of SciencesHarbin 150081China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Saline-alkali Vegetation Ecology Restoration Northeast Forestry UniversityMinistry of EducationHarbin 150040China College of Life Science Northeast Forestry UniversityHarbin 150040China

Panicle exsertion is one of the crucial agronomic traits in rice(Oryza sativa).Shortening of panicle exsertion often leads to panicle enclosure and severely reduces seed ***(GA)plays important roles in regulating panicle ***,the underlying mechanism and the relative regulatory network remain ***,we characterized the oswrky78 mutant showing severe panicle enclosure,and found that the defect of oswrky78 is caused by decreased bioactive GA *** analysis demonstrates that OsWRKY78 can directly activate GA biosynthesis and indirectly suppress GA ***,we found OsWRKY78 can interact with and be phosphorylated by mitogen-activated protein kinase(MAPK)kinase OsMAPK6,and this phosphorylation can enhance OsWRKY78 stability and is necessary for its biological *** together,these results not only reveal the critical function of OsWRKY78,but also reveal its mechanism via mediating crosstalk between MAPK and the GA signaling pathway in regulating panicle exsertion.

关键词： gibberellin MAPK cascades OsWRKY78 panicle exsertion rice

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Surface engineering of Li-and Mn-rich layered oxides for superior Li-ion battery

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Tungsten 2024年第1期6卷 259-268页

作者： Lu-Xiang Ma tian-Dong Chen Chun-Xi Hai Sheng-De Dong Xin He Qi xu Hang Feng AXin Ji-Tao Chen Yuan Zhou College of Materials and Chemistry and Chemical Engineering Chengdu University of TechnologyChendu 610000China Qinghai Building and Materials Research Co. LtdXining 810000China Beijing National Laboratory for Molecular Sciences College of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China

The Li-and Mn-rich layered oxides(R-LNCM)are considered as promising cathode materials for high-energy density lithium-ion batteries(LIBs).However,the interface side reaction aggravates the voltage and capacity fading between cathode material and electrolyte at high voltage,which severely hinders the practical application of LIB ***,lithium polyacrylate(LiPAA)as the binder and coating agent is applied to suppress the voltage and capacity fading of R-LNCM *** flexible LiPAA layers with high elasticity are capable of impeding cathode cracks on the particle surface via mechanical stress ***,superior voltage and capacity fading suppression on R-LNCM electrode is finally *** a result,LiPAA-R-LNCM cathode exhibits a remarkable specific capacity of 186 mA·h·g^(-1)with~73%retention at 1℃after ***,the corresponding average discharge potential is maintained to~3.1 V with only~0.4 V falling.

关键词： LiPAA interphase layer Interface side reaction Cathode cracks Capacity and voltage fading suppression Liand Mn-rich cathode

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Polarization-dependent photoinduced metal–insulator transitions in manganites

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Science Bulletin 2024年第2期69卷 183-189页

作者： Lina Deng Weiye Zhang Hanxuan Lin Lifen Xiang Ying xu Yadi Wang Qiang Li Yinyan Zhu Xiaodong Zhou Wenbin Wang Lifeng Yin Hangwen Guo Chuanshan tian Jian Shen State Key Laboratory of Surface Physics Institute for Nanoelectronic Devices and Quantum Computingand Department of PhysicsFudan UniversityShanghai 200433China Shanghai Research Center for Quantum Sciences Shanghai 201315China Zhangjiang Fudan International Innovation Center Fudan UniversityShanghai 201210China Collaborative Innovation Center of Advanced Microstructures Nanjing 210093China Shanghai Branch CAS Center for Excellence and Synergetic Innovation Center in Quantum Information and Quantum PhysicsShanghai 201315China

In correlated oxides,collaborative manipulation on light intensity,wavelength,pulse duration and polarization has yielded many exotic discoveries,such as phase transitions and novel quantum *** view of potential optoelectronic applications,tailoring long-lived static properties by light-induced effects is highly *** far,the polarization state of light has rarely been reported as a control parameter for this ***,we report polarization-dependent metal-to-insulator transition(MIT)in phaseseparated manganite thin films,introducing a new degree of freedom to control static ***,we observed giant photoinduced resistance jumps with striking features:(1)a single resistance jump occurs upon a linearly polarized light incident with a chosen polarization angle,and a second resistance jump occurs when the polarization angle changes;(2)the amplitude of the second resistance jump depends sensitively on the actual change of the polarization *** transmittance measurements reveal that the origin of the above phenomena is closely related to the coexistence of anisotropic *** results represent a first step to utilize light polarization as an active knob to manipulate static phase transitions,pointing towards new pathways for nonvolatile optoelectronic devices and sensors.

关键词： Metal-insulator phase transitions Polarization of light Electronic phase separation Selective domain controllability

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Potassium alleviated high nitrogen-induced apple growth inhibition by regulating photosynthetic nitrogen allocation and enhancing nitrogen utilization capacity

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Horticultural Plant Journal 2024年第1期10卷 1-14页

作者： Xinxiang xu Guangyuan Liu Jingquan Liu Mengxue Lyu Fen Wang Yue Xing Hao Meng Min Li Yu Jiang Ge tian Zhanling Zhu Yuanmao Jiang Shunfeng Ge State Key Laboratory of Crop Biology College of Horticulture Science and EngineeringShandong Agricultural UniversityTai'anShandong 271018China Key Laboratory of Biochemistry and Molecular Biology in Universities of Shandong College of Biological and Agricultural EngineeringWeifang UniversityWeifangShandong 261061China

There is a close relationship between potassium(K)and nitrogen(N).However,the roles of K under high N conditions remain *** a hydroponics approach,we monitored the morphological,physiological,and molecular changes in M9T337 apple(Malus domestica)rootstocks under different nitrate(10 and 30 mmol·L^(-1)NO_(3)^(-))and K supply(0.5,6,10,and 20 mmol·L_(-1)K^(+))*** revealed that high nitrate inhibited the root growth of M9T337 rootstocks,downregulated the expressions of K transporter genes(MdPT5,MdHKT1,and MdATK1),and reduced the net NO3-and K+influx at the surface of roots,thereby resulting in an N/K imbalance in *** investigation showed that 10 mmol·L^(-1)K increased the activity of N metabolic enzymes(NR,GS,NiR,and GOGAT),upregulated the expressions of genes related to nitrate uptake and transport(MdNRT1.1,MdNRT1.2,MdNRT1.5,and MdNRT2.4),promoted15N transport from the roots to the shoots,optimized leaf N distribution,and improved photosynthetic N utilization efficiency under high nitrate *** results suggest that the negative effects of high nitrate may be related to the N/K imbalance and that reducing N/K in plants by increasing K supply level can effectively alleviate the inhibition of N assimilation by high nitrate stress.

关键词： Apple rootstock K level High nitrate stress N metabolism ^(15)N

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Ovarian function in patients with systemic lupus erythematosus:Pathogenesis,drug application and prospective therapies

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World Journal of Experimental Medicine 2024年第2期14卷 29-34页

作者： Min xu Li-Li tian Xiao-Liu Li Cheng Bao Hai-Wei Zhang Hong-Wei Chen Department of Rheumatology and Immunology Nanjing Drum Tower HospitalClinical College of Nanjing University of Chinese MedicineNanjing 210008Jiangsu ProvinceChina School of Life Science Nanjing Normal UniversityNanjing 210023Jiangsu ProvinceChina Department of Rheumatology and Immunology Nanjing Drum Tower HospitalNanjing 210008Jiangsu ProvinceChina Department of Rheumatology and Immunology Nanjing Pukou People’s HospitalNanjing 211800Jiangsu ProvinceChina Department of Rheumatology and Immunology Nanjing Drum Tower HospitalThe Affiliated Hospital of School of MedicineNanjing UniversityNanjing 210008Jiangsu ProvinceChina

Systemic lupus erythematosus(Sle)is a chronic autoimmune disease in which multiple organs are damaged that prevails in fertile ***,glucocorticoids and immunosuppressants are widely used to treat Sle ***,ovarian dysfunction occurs following the use of these drugs in women with ***,we summarize recent progress in terms of understanding ovarian injury,the effects of drug application and strategies to improve ovarian function in women with *** review could be helpful to precisely cure Sle in women desiring to have offspring.

关键词： Systemic lupus erythematosus Ovarian reserve Ovarian insufficiency Mesenchymal stem cells Fertility Autoimmune disease

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