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Single-cell transcriptomics reveals T-cell heterogeneity and immunomodulatory role of CD4+T native cells in Candida albicans infection

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BIOCELL 2024年第9期48卷 1355-1368页

作者： Jia, Keran Zhang, Yanhao Jiang, Mengyu Cui, Mengge wang, Jia Zhang, Jiajia Zhao, Huihai Li, Mengyan wang, Hua Zou, Quanming Zeng, Hao Army Med Univ Coll Pharm Natl Engn Res Ctr Immunol Prod Dept Microbiol & Biochem Pharm Chongqing 400038 Peoples R China Bethune Int Peace Hosp 980th Hosp PLA Joint Logist Support Force Dept Clin Lab Shijiazhuang 050082 Peoples R China

Objective: Candida albicans is a common fungal pathogen that triggers complex host defense mechanisms, including coordinated innate and adaptive immune responses, to neutralize invading fungi effectively. Exploring the immune microenvironment has the potential to inform the development of therapeutic strategies for fungal infections. Methods: The study analyzed individual immune cell pro f iles in peripheral blood mononuclear cells from Candida albicans-infected mice and healthy control mice using single-cell transcriptomics, fl uorescence quantitative PCR, and Western blotting. We investigated intergroup differences in the dynamics of immune cell subpopulation in fi ltration, pathway enrichment, and differentiation during Candida albicans infection. Results: Our fi ndings indicate that in f iltration of CD4 + naive cells, regulatory T (Treg) cells, and Microtubules-associated (MT)-associated cells increased after infection, along with impaired T cell activity. Notably, CD4 ' T cells and plasma cells were enhanced after infection, suggesting that antibody production is dependent on T cells. In addition, we screened 6 hub genes, transcription factor forkhead box protein 3(Foxp3), cytotoxic T-lymphocyte associated protein 4 (CTLA4), Interleukin 2 Receptor Subunit Beta (Il2rb), Cd28, C-C Motif Chemokine Ligand 5 (Ccl5), and Cd27 for alterations associated with CD4 ' T cell differentiation. Conclusions: These results provide a comprehensive immunological landscape of the mechanisms of Candida albicans infection and greatly advance our understanding of adaptive immunity in fungal infections.

关键词： Candida albicans Single-cell transcriptomics Immune microenvironment Fungal infections Hub gene NEUTROPHILS IMMUNITY

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Clinical efficacy of Gamma Knife® combined with transarterial chemoembolization and immunotherapy in the treatment of primary liver cancer

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1601-1608页

作者： Guo-Feng wang Chang-Xin Shu Xiao-Dong Cai Hong-Bo wang Jian-Hong Xu Yu-Qing Jia Department of General Surgery Yangzhou Friendship Hospital Affiliated to Medical College of Yangzhou UniversityYangzhou 225000Jiangsu ProvinceChina

BACKGROUND This study was designed to investigate the clinical efficacy and safety of Gamma Knife®combined with transarterial chemoembolization(TACE)and immunotherapy in the treatment of primary liver *** To investigate the clinical efficacy and safety of Gamma Knife®combined with TACE and immune-targeted therapy in the treatment of primary liver *** Clinical data from 51 patients with primary liver cancer admitted to our hospital between May 2018 and October 2022 were retrospectively *** patients underwent Gamma Knife®treatment combined with TACE and *** clinical efficacy,changes in liver function,overall survival(OS),and progression-free survival(PFS)of patients with different treatment responses were evaluated,and adverse reactions were *** The last follow-up for this study was conducted on October 31,*** evaluation of the 51 patients with primary liver cancer revealed a partial response(PR)in 27 patients,accounting for 52.94%(27/51);stable disease(SD)in 16 patients,accounting for 31.37%(16/51);and progressive disease(PD)in 8 patients,accounting for 15.69%(8/51).The objective response rate was 52.94%,and the disease control rate was 84.31%.Alanine aminotransferase,aspartate aminotransferase,lactate dehydrogenase,and alpha-fetoprotein isoform levels decreased after treatment compared with pretreatment(all P=0.000).The median OS was 26 months[95%confidence interval(95%CI):19.946-32.054]in the PR group and 19 months(95%CI:14.156-23.125)in the SD+PD group,with a statistically significant difference(P=0.015).The median PFS was 20 months(95%CI:18.441-34.559)in the PR group and 12 months(95%CI:8.745-13.425)in the SD+PD group,with a statistically significant difference(P=0.002).Common adverse reactions during treatment included nausea and vomiting(39.22%),thrombocytopenia(27.45%),and leukopenia(25.49%),with no treatment-related deaths *** Gamma Knife®combined with TACE and immune-targeted th

关键词： Gamma Knife® Transarterial chemoembolization Immunotherapy Primary liver cancer Liver function

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Establishing cell suitability for high-level production of licorice triterpenoids in yeast

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ACTA PHARMACEUTICA SINICA B 2024年第9期14卷 4134-4148页

作者： Sun, Wentao Wan, Shengtong Liu, Chuyan wang, Ruwen Zhang, Haocheng Qin, Lei wang, Runming Lv, Bo Li, Chun Tsinghua Univ Dept Chem Engn Beijing 100084 Peoples R China Tsinghua Univ Key Lab Ind Biocatalysis Minist Educ Beijing 100084 Peoples R China Tsinghua Univ Ctr Synthet & Syst Biol Beijing 100084 Peoples R China Beijing Inst Technol Inst Biochem Engn Sch Chem & Chem Engn Key Lab Med Mol Sci & Pharmaceut Engn Beijing 100081 Peoples R China Univ Chicago Chicago IL 60637 USA Tsinghua Univ Inst Biopharmaceut & Hlth Engn Tsinghua Shenzhen Int Grad Sch Shenzhen 518055 Peoples R China

Yeast has been an indispensable host for synthesizing complex plant-derived natural compounds, yet the yields remained largely constrained. This limitation mainly arises from overlooking the importance of cell and pathway suitability during the optimization of enzymes and pathways. Herein, beyond conventional enzyme engineering, we dissected metabolic suitability with a framework for simultaneously augmenting cofactors and carbon flux to enhance the biosynthesis of het erogenous triterpenoids. We further developed phospholipid microenvironment engineering strategies, dramatically improving yeast's suitability for the high performance of endoplasmic reticulum (ER)-localized, rate- limiting plant P450s. Combining metabolic and microenvironment suitability by manipulating only three genes, NHMGR (NADH-dependent HMG-CoA reductase), SIP4 (a DNA-binding transcription factor)and GPP1 (Glycerol-1-phosphate phosphohydrolase 1), we enabled the high-level production of 4.92 g/L rare licorice triterpenoids derived from consecutive oxidation of b-amyrin by two P45 0 enzymes after fermentation optimization. This production holds substantial commercial value, highlighting the critical role of establishing cell suitability in enhancing triterpenoid biosynthesis and offering a versatile framework applicable to various plant natural product biosynthetic pathways.

关键词： Cell suitability Phospholipid microenvironment Cytochrome P450 Triterpenoids Saccharomyces cerevisiae SACCHAROMYCES-CEREVISIAE ENGINEERING COFACTOR BIOSYNTHESIS METABOLISM PHOSPHATIDYLINOSITOL GENOMICS

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Two-Dimensional van der Waals Superconductor Heterostructures:Josephson Junctions and Beyond

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Precision Chemistry 2024年第7期2卷 273-281页

作者： Chao wang Zhenjia Zhou Libo Gao National Laboratory of Solid State Microstructures Jiangsu Key Laboratory for NanotechnologySchool of Physics Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China

The past few years have witnessed prominent progress in two-dimensional(2D)van der Waals *** assembled in an artificial manner,these atomically thin layers possess distinctive electronic,magnetic,and other properties,which have provided a versatile platform for both fundamental exploration and practical applications in condensed matter physics and materials *** various potential combinations,a particular set of van der Waals superconductor(SC)heterostructures,which is realized by stacking fabrication based on two-dimensional SCs,is currently attracting intense *** example,the Josephson junction,a specific structure in which a nonsuperconducting barrier is inserted between two proximity-coupled SCs,shows phenomena and outstanding properties with atomic-scale *** this Perspective,we first review this emerging research area of van der Waals SC heterostructures,especially progress on the 2D van der Waals Josephson junctions,from the aspects of preparation,performance,and application,and also propose our vision for the future direction and potential innovation opportunities.

关键词： two-dimensional van der Waals heterostructures superconductor Josephson junctions transition metal dichalcogenides

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The amplification effect of PGA and the large-scale liquefaction-triggered mudflow during the December 18,2023 M 6.2 Jishishan Earthquake in Gansu Province,China

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Earthquake Research Advances 2024年第2期4卷 11-13页

作者： Lanmin wang Shiyang Xu Key Laboratory of Loess Earthquake Engineering of China Earthquake Administration&Gansu Province Lanzhou730000GansuChina Key Laboratory of Earthquake Engineering and Engineering Vibration of China Earthquake Administration Institute of Engineering MechanicsChina Earthquake Administration Harbin150080HeilongjiangChina

At 23:59 on December 18, 2023, a strong earthquake (M 6.2) struck Jishishan County in Gansu province, China, which is situated in the transition zone between Qinghai-Xizang Plateau and the Loess *** focal depth is 10 km, and the epicenter (35.70°N and 102.79°E) is about 100 km southwest away from Lanzhou, the capital city of Gansu province. As of December 31, 2023, the earthquake has caused 151 people dead and 979 people wounded in Gansu and Qinghai.

关键词： Gansu southwest situated

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Graphdiyne oxide substrate-enhanced peroxidase-mimicking performance of Ru nanoparticles with physiological pH preference

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Nano Research 2024年第3期17卷 1123-1131页

作者： Cong Xu Wenjie Ma Haozhi wang Leihou Shao Weiqi Li Ping Yu Lanqun Mao Beijing National Laboratory for Molecular Science Key Laboratory of Analytical Chemistry for Living BiosystemsInstitute of ChemistryChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Marine Resource Utilization in South China Sea School of Materials Science and EngineeringHainan UniversityHaikou 570228China College of Chemistry Beijing Normal UniversityBeijing 100875China

Modulating electronic structure of metal nanoparticles via metal–support interaction has attracted intense interest in the field of catalytic ***,the roles of supporting substrates in regulating catalytic properties of nanozymes remain *** this study,we find that the use of graphdiyne oxide(GDYO)as the substrate for self-terminating growth of Ru nanoparticles(Ru@GDYO)endows the peroxidase-like activity of Ru nanoparticles with intrinsic physiological pH preference and natural horseradish peroxidase(HRP)comparable *** nanoparticles electrolessly deposited onto GDYO possess a partially oxidized electronic structure owing to limited charge transfer between Ru and GDYO,contributing to the intrinsic physiological pH preference of the peroxidase-mimicking *** importantly,the substrate GDYO plays an influential factor in enhancing catalytic activity,that is,the activity of Ru@GDYO is much higher than that of Ru nanoparticles deposited on other carbon substrates including graphene oxides and *** demonstrate the application of Ru@GDYO nanozyme in neutral solutions,we employ Ru@GDYO with nicotinamide adenine dinucleotide(NAD+)-dependent dehydrogenases in physiological conditions to realize a sustainable cascade reaction by means of forming continuous NAD^(+)/dihydronicotiamide adenine dinucleotide(NADH)*** finding represents a promising perspective on designing high-performance peroxidase-mimicking nanozymes with broader applicability,raising fundamental understanding of structure–activity relationship,and investigating new applications of nanozymes in biological systems.

关键词： nanozyme graphdiyne reactive oxygen species electroless deposition metal–support interaction

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Nanostructured AlFeO_(3) thin films as a novel photoanode for photoelectrochemical water splitting

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Nano Research 2024年第3期17卷 1075-1085页

作者： Xin Sun Min wang Qi Geng Shuailin Chen Xiaojun Lv Xunlei Ding Meicheng Li State Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources School of New EnergyNorth China Electric Power UniversityBeijing 102206China School of Mathematics and Physics North China Electric Power UniversityBeijing 102206China

The earth-abundant and robust aluminum ferrite,AlFeO_(3)(AFO),is mainly studied in the context of ***,we demonstrate that AFO can be used as a stable solar absorber in photoelectrochemical cells for solar water splitting,exhibiting attractive *** is the first report on the photoelectrochemical activity of *** thin-film photoelectrodes prepared by solution-processing methods are composed of vertically oriented thin nanosheets,featuring the rhombohedral symmetry(R3c)and n-type *** as-prepared AFO photoanodes generate a photocurrent density of+0.78 mA·cm^(-2) at 1.23 V *** hydrogen electrode(RHE)with the photocurrent _(onset) potential(U_(onset))close to the flat band potential of 0.5 V *** in the presence of hole ***,the U_(onset) of AFO for solar water splitting coincides with the flat band potential as well,which is rare in n-type inorganic *** also report other properties of AFO associated with photoelectrochemical *** films exhibit a band gap energy of 2.31 eV and positive band edges with low ***,the carrier lifetimes in AFO films are up to millisecond timescales under the mediation of defect *** on the photoelectrochemical behavior and optoelectronic properties,we believe that AFO has great potential for application in photoelectrochemical cells.

关键词： AlFeO_(3) photoanode nanosheets photoelectrochemistry onset potential

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Epidemiology and genetic characterization of tet(X4)-positive Klebsiella pneumoniae and Klebsiella quasipneumoniae isolated from raw meat in Chengdu City, China

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Biosafety and Health 2024年第2期6卷 116-124页

作者： Weishuai Zhai Yiqing wang Honghu Sun Bo Fu Qidi Zhang Congming Wu Jianzhong Shen Dejun Liu Yang wang National Key Laboratory of Veterinary Public Health and Safety College of Veterinary MedicineChina Agricultural UniversityBeijing 100193China Technology Innovation Center for Food Safety Surveillance and Detection Sanya InstituteChina Agricultural University Sanya 572025China Irradiation Preservation Key Laboratory of Sichuan ProvinceChengdu Institute of Food InspectionChengdu 611135China Collge of Veterlnary Medicine Qingdao Agricultural UniversityQingdao 266109China

The rapid spread of mobile tigecycline resistance presents a significant public health threat,particularly with the increasing prevalence of tet(X4)-positive Enterobacterales across various *** study aimed to inves-tigate the epidemic features and transmission dynamics of tet(X4)-positive Klebsiella pneumoniae(***-niae)through the analysis of 206 raw meats,including pork(n=182),beef(n=16),duck(n=5),and chicken(n=3).These samples were collected from schools,markets,and restaurants in Chengdu City,China.A total of 25 isolates were obtained from 13 administrative *** isolates exhibited resistance to tetracycline,tigecycline,ampicillin,chloramphenicol,and *** half of the isolates also demon-strated resistance to streptomycin(80%),sulfamethoxazole/trimethoprim(72%),ciprofloxacin(64%),and ampicillin/sulbactam(56%).Among these strains,14 distinct sequence types(STs)were identified,revealing evidence of inter-regional clonal spread,notably among 9 *** *** analysis revealed the presence of two *** ST5 closely resembling hypervirulent *** from ***,12 isolates were capable of transferring tigecycline resistance to Escherichia coli *** plasmid analysis showed that the tet(X4)-harboring plasmids in *** could be classified into four types,primarily belonging to the IncFIA(HI1)/HI1A/HI1B hybrid plasmid(n=16)and IncFII plasmid(n=7),which significantly contributed to the cross-species dissemination of tet(X4).In summary,this study highlights the prevalence of MDR tet(X4)-positive *** in Chengdu,driven predominantly by clonal expansion and plasmid-mediated horizontal gene *** findings emphasize the importance of contin-uous surveillance of tet(X4)-positive *** in raw meat and the implementation of effective measures to control their spread.

关键词： tet(X4) Tigecycline K.pneumoniae Clonal spread Horizontal transfer

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Transformation of long-period stacking ordered structures in Mg-Gd-Y-Zn alloys upon synergistic characterization of first-principles calculation and experiment and its effects on mechanical properties

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Journal of Magnesium and Alloys 2024年第5期12卷 1867-1879页

作者： Mingyu Li Guangzong Zhang Siqi Yin Changfeng wang Ying Fu Chenyang Gu Renguo Guan School of Materials Science and Engineering Northeastern UniversityShenyang 110819China Key Laboratory of Near-Net Forming of Light Metals of Liaoning Province Dalian Jiaotong UniversityDalian 116028China Engineering Research Center of Continuous Extrusion Ministry of EducationDalian Jiaotong UniversityDalian 116028China Songshan Lake Materials Laboratory Dongguan 523808China

Based on experiments and first-principles calculations,the microstructures and mechanical properties of as-cast and solution treated Mg-10Gd-4Y-xZn-0.6Zr(x=0,1,2,wt.%)alloys are *** transformation process of long-period stacking ordered(LPSO)structure during solidification and heat treatment and its effect on the mechanical properties of experimental alloys are *** reveal that the stacking faults and 18R LPSO phases appear in the as-cast Mg-10Gd-4Y-1Zn-0.6Zr and Mg-10Gd-4Y-2Zn-0.6Zr alloys,*** solution treatment,the stacking faults and 18R LPSO phase transform into 14H LPSO *** Enthalpies of formation and reaction energy of 14H and 18R LPSO are calculated based on *** show that the alloying ability of 18R is stronger than that of *** reaction energies show that the 14H LPSO phase is more stable than the 18R *** elastic properties of the 14H and 18R LPSO phases are also evaluated by first-principles calculations,and the results are in good agreement with the experimental *** precipitation of LPSO phase improves the tensile strength,yield strength and elongation of the *** solution treatment,the Mg-10Gd-4Y-2Zn-0.6Zr alloy has the best mechanical properties,and its ultimate tensile strength and yield strength are 278.7 MPa and 196.4 MPa,*** elongation of Mg-10Gd-4Y-2Zn-0.6Zr reaches 15.1,which is higher than that of Mg-10Gd-4Y0.6Zr *** improving mechanism of elastic modulus by the LPSO phases and the influence on the alloy mechanical properties are also analyzed.

关键词： Mg-Gd-Y-Zn alloys Long-period stacking ordered First-principles calculations Enthalpies Mechanical properties

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Green Synthesized Liquid-like Dynamic Polymer Chains with Decreased Nonspecific Adhesivity for High-Purity Capture of Circulating Tumor Cells

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CCS Chemistry 2024年第2期6卷 507-517页

作者： Feng Wu Xiaofeng Chen Shuli wang Ruimin Zhou Chunyan wang Lejian Yu Jing Zheng Chaoyong Yang Xu Hou State Key Laboratory of Physical Chemistry of Solid Surfaces College of Chemistry and Chemical EngineeringXiamen UniversityXiamenFujian 361005 College of Physical Science and Technology Xiamen UniversityXiamenFujian 361005 College of Physics and New Energy Xuzhou University of TechnologyXuzhouJiangsu 221018 Fujian Engineering Research Center for Solid-State Lighting Department of Electronic ScienceSchool of Electronic Science and EngineeringXiamen UniversityXiamenFujian 361005 Institute of Artificial Intelligence Xiamen UniversityXiamenFujian 361005 Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) XiamenFujian 361102 State Key Laboratory of Bio-Fibers and Eco-Textiles Qingdao UniversityQingdaoShandong 266071

The capture of circulating tumor cells(CTCs)is of great significance in reducing cancer mortality and ***,the nonspecific binding of proteins and white blood cells(WBCs)weakens the targeting capabilities of the capture surfaces,which critically hampers the efficiency and purity of the captured ***,we propose a liquid-like interface design strategy that consists of liquid-like polymer chains and anti-EpCAM modification processes for high-purity and high-efficiency capture of *** dynamic flexible feature of the liquid-like chains endows the modified surfaces with excellent antiadhesion property for proteins and blood *** liquid-like surfaces can capture the target CTCs and show high cell viability due to the environmentfriendly surface modification *** liquid-like surface designs were introduced in the deterministic lateral displacement(DLD)-patterned microfluidic chip,the nonspecific adhesion rate of WBCs was reduced by more than fivefold compared to that in the DLD chip without liquid-like interface design,while maintaining comparable capture ***,this strategy provides a novel perspective on surface design for achieving high purity and efficient capture of CTCs.

关键词： green synthesis dynamic polymer chains liquid-like interface nonspecific adsorption capture of circulating tumor cells microfluidics

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