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IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation

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Oncology Research 2024年第4期32卷 625-641页

作者： wen GE YA LI YUTING RUAN NINGXIA WU PEI MA TONGPENG XU YONGQIAN SHU YINGWEI WANG wen QIU CHENHUI ZHAO Department of Immunology Nanjing Medical UniversityNanjing210000China Key Laboratory of Immunological Environment and Disease Nanjing Medical UniversityNanjing210000China Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210000China Jiangsu Key Laboratory of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing210000China

The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.

关键词： NSCLC cell migration and invasion IL-17 p300 STAT3 MMP19 Acetylation and phosphorylation

The Multi-parameter Test of Gravitational Wave Dispersion with Principal Component Analysis

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Research in Astronomy and Astrophysics 2024年第5期24卷 140-150页

作者： Zhi-Chu Ma Rui Niu wen Zhao CAS Key Laboratory for Research in Galaxies and Cosmology Department of AstronomyUniversity of Science and Technology of ChinaHefei 230026China School of Astronomy and Space Sciences University of Science and Technology of ChinaHefei 230026China

In this work, we consider a conventional test of gravitational wave(GW) propagation which is based on the phenomenological parameterized dispersion relation to describe potential departures from General Relativity(GR)along the propagation of GWs. But different from tests conventionally performed previously, we vary multiple deformation coefficients simultaneously and employ the principal component analysis(PCA) method to remedy the strong degeneracy among deformation coefficients and obtain informative posteriors. The dominant PCA components can be better measured and constrained, and thus are expected to be more sensitive to potential departures from the waveform model. Using this method we analyze ten selected events and get the result that the combined posteriors of the dominant PCA parameters are consistent with GR within 99.7% credible intervals. The standard deviation of the first dominant PCA parameter is three times smaller than that of the original dispersion parameter of the leading order. However, the multi-parameter test with PCA is more sensitive to not only potential deviations from GR but also systematic errors of waveform models. The difference in results obtained by using different waveform templates hints that the demands of waveform accuracy are higher to perform the multiparameter test with PCA. Whereas, it cannot be strictly proven that the deviation is indeed and only induced by systematic errors. It requires more thorough research in the future to exclude other possible reasons in parameter estimation and data processing.

关键词： gravitational waves-gravitation-black hole physics

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Novel MIP gene mutation causes autosomal-dominant congenital cataract

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 454-465页

作者： Jing-Lan Ni Hua-Ming wen Xiao-Sheng Huang Qian-wen Li Jia-Min Cai Bao-Jian Fan Jun Zhao The Second Clinical Medical College Jinan UniversityShenzhen 518020Guangdong ProvinceChina Department of Ophthalmology Dongguan Chang’an HospitalDongguan 523843Guangdong ProvinceChina Shenzhen Eye Hospital Affiliated to Jinan University Shenzhen Eye InstituteShenzhen 518040Guangdong ProvinceChina Department of Oral&Maxillofacial Surgery Shenzhen Stomatology Hospital Affiliated to Shenzhen UniversityShenzhen 518040Guangdong ProvinceChina Department of Neurosurgery Massachusetts General Hospital and Harvard Medical SchoolBoston 02114MassachusettsUSA Department of Ophthalmology Shenzhen People’s Hospital(the Second Clinical Medical CollegeJinan Universitythe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020Guangdong ProvinceChina

●AIM:To identify disease-causative mutations in families with congenital cataract.●METHODS:Two Chinese families with autosomaldominant congenital cataract(ADCC)were recruited and underwent comprehensive eye examinations.Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family.Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis.The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis.Major intrinsic protein(MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos.Zebrafish embryonic lens phenotypes were screened using confocal microscopy.●RESULTS:A novel heterozygous mutation(c.85G>A;p.G29R)in the MIP gene was identified in the proband of one family.A known heterozygous mutation(c.97C>T;p.R33C;rs864309693)in MIP was found in the proband of another family.In-silico prediction indicated that the novel mutation might affect the MIP protein function.Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP.●CONCLUSION:Two missense mutations in the MIP gene in Chinese cataract families are identified,and one of which is novel.These findings expand the genetic spectrum of MIP mutations associated with cataracts.The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation.

关键词： congenital cataract major intrinsic protein missense mutation zebrafish model

Palladium Complexes with N,O-Bidentate Ligands Based on N-Oxide Units from Cyclic Secondary Amines:Synthesis and Catalytic Application in Mizoroki-Heck Reaction

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Chinese Journal of Chemistry 2024年第3期42卷 294-300页

作者： Xuefeng Jia Yanyan wen Changhui He Xianqiang Huang Key Laboratory of Magnetic Molecules and Magnetic Information Materials of Ministry of Education School of Chemistry and Materials ScienceShanxi Normal UniversityTaiyuanShanxi030032 China Shandong Provincial Key Laboratory of Chemical Energy Storage and Novel Cell Technology School of Chemistry & Chemical EngineeringLiaocheng UniversityLiaochengShandong252059 China

Palladium-catalyzed Mizoroki-Heck reaction is a powerful and efficient method for construction of Csp2–Csp2 bonds.Herein,four palladium complexes(I—IV)with N,O-bidentate ligands(L1—L4)based on N-oxide units from cyclic secondary amines were easily synthesized and successfully applied in Mizoroki-Heck reaction of aryl bromides with electron-deficient olefins.X-ray diffraction analyses indicated the palladium(II)atom of II took the distorted square planar geometry and was four-coordinated by nitrogen and oxygen atoms from two ligands(L2).Two free chloride ions were presented as counter anions in complex II.But the palladium(II)center of IV was coordinated by nitrogen and oxygen atoms from one ligand(L4)as well as two chlorine atoms,which exhibited the nearly square-planar geometry.The study on catalytic properties of palladium complexes revealed that complex II exhibited high activity superior to the other complexes.The coupling reactions of a series of aryl bromides and olefin derivatives proceeded in the presence of 2—5 mol%palladium complex II,giving the desired products in good to excellent yields.The advantages of this method such as good compatibility of functional groups,high yields,and short reaction times made it more attractive for constructing Csp2–Csp2 bonds in the synthesis of functional molecules and materials.

关键词： Palladium complexes N,O-Bidentate ligands N-Oxide units Mizoroki-Heck reaction Aryl bromide Electron-deficient olefins C—C coupling Homogeneous catalysis Substituent effects

Postoperative pneumocranium after endoscopic transnasal optic canal decompression

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 973-975页

作者： Sheng-Jian Lu Bo Yu wen-Can Wu The Eye Hospital School of Ophthalmology&OptometryWenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina

Dear Editor,We present the first time,a case of a patient developed cerebrospinal fluid(CSF)leak and pneumocranium following optic canal decompression(OCD).INTRODUCTION Indirect traumatic optic neuropathy(ITON)impairs visual functions and quality of life.Endoscopic transnasal optic canal decompression(ETOCD)is one of the standard treatment strategies for the ITON.During the ETOCD,the optic nerve sheath are usually incised for sufficient decompression of optic nerve after removal of optic canal,which is associated with complications like CSF leakage,ophthalmic artery injury,and optic nerve injury[1].Generally,the mild CSF leak is common and can heal spontaneously using conventional treatment,the severe CSF leak requires surgical repair[2].

关键词： decompression nasal traumatic

Icariin plus curcumol enhances autophagy through the mTOR pathway and promotes cathepsin B-mediated pyroptosis of prostate cancer cells

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Asian Pacific Journal of Tropical Biomedicine 2024年第2期14卷 55-64页

作者： Xu-Yun Wang wen-Jing Xu Bo-Nan Li Tian-Song Sun wen Sheng Department of Andrology Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing100010China Department of Dermatology The First Affiliated Hospital of Hunan University of Chinese MedicineChangsha410021China School of Integrated Chinese and Western Medicine Hunan University of Chinese MedicineChangsha410208China Andrology Laboratory Hunan University of Chinese MedicineChangsha410208China School of Rehabilitation Medicine and Health Care Hunan University of MedicineHuaihua418000China School of Traditional Chinese Medicine Hunan University of MedicineHuaihua418000China

Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and proliferation.Autophagy expression was analyzed using monodansylcadaverine staining.Immunofluorescence and Western blot analyses were used to evaluate protein expressions related to autophagy,pyroptosis,and the mTOR pathway.Cellular damage was examined using the lactate dehydrogenase assay.Moreover,cathepsin B and NLRP3 were detected by co-immunoprecipitation.Results:Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of autophagy.The levels of LC3-Ⅱ/LC3-Ⅰand beclin-1 were increased,while the levels of p62 and mTOR were decreased after treatment with icariin plus curcumol.These changes were reversed upon overexpression of mTOR.Furthermore,3-methyladenine resulted in a decrease in inflammatory cytokines,pyroptosis-related protein levels,and lactate dehydrogenase concentration,compared to the icariin plus curcumol group.Inhibiting cathepsin B reversed the regulatory effects of icariin plus curcumol.Conclusions:Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin B.These findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.

关键词： Icariin Curcumol Autophagy mTOR Cathepsin B Pyroptosis Prostate cancer

Use of curcumin and its nanopreparations in the treatment of inflammatory bowel disease

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World Journal of Gastroenterology 2024年第3期30卷 280-282页

作者： Zi-wen Meng Bing Chang Li-Xuan Sang Department of Gastroenterology Shengjing Hospital of China Medical UniversityShenyang 110022Liaoning ProvinceChina Department of Gastroenterology the First Affiliated Hospital of China Medical UniversityShenyang 110001Liaoning ProvinceChina

Inflammatory bowel disease(IBD)is a nonspecific inflammatory disease of the intestine that includes Crohn’s disease and ulcerative colitis.Because IBD is difficult to heal and easily relapses,it could worsen patient quality of life and increase economic burdens.Curcumin(CUR)is a bioactive component derived from the rhizome of turmeric(Curcuma longa).Many basic and clinical studies have shown that CUR can efficiently treat IBD by decreasing the activity of proinflammatory cytokines by communicating with transcription factors and signaling molecules.However,due to the limitations of being almost insoluble in aqueous solutions and having low oral bioavailability,it is important to select appropriate pharmaceutical preparations.

关键词： Curcumin Inflammatory bowel disease Bioavailability Nanotherapeutics

Applications of single-cell RNA sequencing in spermatogenesis and molecular evolution

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Zoological Research 2024年第3期45卷 575-585页

作者： wen-Bo Chen Meng-Fei Zhang Fan Yang Jin-Lian Hua College of Veterinary Medicine Shaanxi Centre of Stem Cells Engineering&TechnologyNorthwest A&F UniversityYanglingShaanxi 712100China Key Laboratory of Livestock Biology Northwest A&F UniversityYanglingShaanxi 712100China

Spermatogenic cell heterogeneity is determined by the complex process of spermatogenesis differentiation.However,effectively revealing the regulatory mechanisms underlying mammalian spermatogenic cell development and differentiation via traditional methods is difficult.Advances in technology have led to the emergence of many single-cell transcriptome sequencing protocols,which have partially addressed these challenges.In this review,we detail the principles of 10x Genomics technology and summarize the methods for downstream analysis of single-cell transcriptome sequencing data.Furthermore,we explore the role of single-cell transcriptome sequencing in revealing the heterogeneity of testicular ecological niche cells,delineating the establishment and disruption of testicular immune homeostasis during human spermatogenesis,investigating abnormal spermatogenesis in humans,and,ultimately,elucidating the molecular evolution of mammalian spermatogenesis.

关键词： Single-cell RNA sequencing(scRNA-seq) Spermatogenesis Molecular evolution Sertoli cell

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Ferromagnetism and insulating behavior with a logarithmic temperature dependence of resistivity in Pb_(10-x)Cux(PO_(4))_(6)O

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Science China(Physics,Mechanics & Astronomy) 2024年第1期67卷 106-111页

作者： Yuhang Zhang Cong Liu Xiyu Zhu Hai-Hu wen Center for Superconducting Physics and Materials National Laboratory of Solid State Microstructures and Department of PhysicsNational Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China

Recent claim of discovering above-room-temperature superconductivity(Tc≈400 K)at ambient pressure in copper doped apatite Pb10(PO_(4))_(6)O has stimulated world-wide enthusiasm and impulse of motion.A lot of follow-up works have been carried out with controversial conclusions.To check whether superconductivity is really present or absent in the material,we need samples which should have a rather pure phase of Pb_(10-x)Cux(PO_(4))_(6)O.Here we report the characterization results from the Pb_(10-x)Cux(PO_(4))_(6)O with a fraction of about 97 wt.%inferred from the fitting to the X-ray diffraction pattern,if assuming Cu2S as the only impurity.The resistivity measurements show that it is a semiconductor characterized roughly by a ln(1/T)temperature dependence in wide temperature region without trace of superconductivity.Magnetization measurements show that it has a general ferromagnetic signal with a weak superparamagnetic background.Many grains of the sample show clear interactions with a Nb Fe B magnet.The detected Cu concentration is much lower than the expected nominal one.Our results show the absence of metallicity and superconductivity in Pb_(10-x)Cux(PO_(4))_(6)O at ambient pressure,and suggest the presence of strong correlation effect.

关键词： superconductivity Pb10(PO4)6O ferromagnetic correlation effect

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