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Novel lactylation-related signature to predict prognosis for pancreatic adenocarcinoma

World Journal of Gastroenterology 2024年第19期30卷 2575-2602页

作者： Tian Peng Fang Sun jia-Chun Yang Mei-Hong Cai Man-Xiu Huai jia-xing Pan Fei-Yu Zhang Lei-Ming Xu Department of Gastroenterology Xinhua Hospital Affiliated to Shanghai Jiao Tong UniversityShanghai 200092China

BACKGROUND Lactate,previously considered a metabolic byproduct,is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment.Further investigations confirmed that lactate is a primary regulator,introducing recently described post-translational modifications of histone and non-histone proteins,termed lysine lactylation.Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation.However,our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited.AIM To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer.METHODS RNA-seq and clinical data of pancreatic adenocarcinoma(PDAC)were obtained from the GTEx(Genotype-Tissue Expression)and TCGA(The Cancer Genome Atlas)databases via Xena Explorer,and GSE62452 datasets from GEO.Data on lactylation-related genes were obtained from publicly available sources.Differential expressed genes(DEGs)were acquired by using R package“DESeq2”in R.Univariate COX regression analysis,LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model.Further analyses,including functional enrichment,ESTIMATE,and CIBERSORT,were performed to analyze immune status and treatment responses in patients with pancreatic cancer.PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention;two PDAC cell lines with the most pronounced lactylation were selected.Subsequently,RT-PCR was employed to assess the expression of LRGs genes;SLC16A1,which showed the highest expression,was selected for further investigation.SLC16A1-mediated lactylation was analyzed by immunofluorescence,lactate production analysis,colony formation,transwell,and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells.In vivo validation was performed using an established tumor model.RESULTS In this study,we successfully identified 10 differentially e

关键词： Pancreatic adenocarcinoma Lactylation Prognosis Immunotherapy Tumor microenvironment

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LncRNA HCP5-encoded protein contributes to adriamycin resistance through ERK/mTOR pathway-mediated autophagy in breast cancer cells

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Genes & Diseases 2024年第4期11卷 69-72页

作者： jia-Ni xing Yi-Ni Shang Zheng-Ling Yu Shun-Heng Zhou Wang-Yang Chen Li-Hong Wang Department of Pathophysiology Medical College of Southeast UniversityNanjingJiangsu 210009China Department of Biomedical Engineering Nanjing University of Aeronautics and AstronauticsNanjingJiangsu 211106China School of Medicine Taizhou UniversityTaizhouZhejiang 318000China jiangsu Provincial Key Laboratory of Critical Care Medicine NanjingJiangsu 210009China

Adriamycin(ADR),also known as doxorubicin,is an anthracycline anticancer drug and a chemotherapeutic drug commonly used in breast cancer treatments.1 However,breast cancer patients can gradually become tolerant to chemotherapy.Therefore,improving the curative effect of ADR remains an urgent problem to be solved.Autophagy is a complex catabolic process;normal living cells break down damaged organelles or aggregated molecules and absorb energy to maintain homeostasis through autophagy.

关键词： breast cancer homeostasis

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Comparison of inebilizumab or rituximab in addition to glucocorticoid therapy for neuromyelitis optica spectrum disorders

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1073-1078页

作者： Chu-Yuan Lou Yong Wang jia-Yuan xing Teng Ma Lei Tao Xiao-Tang Wang Run-Sheng Wang Neuroophthalmic Center Xi’an People’s Hospital(Xi’an Fourth Hospital)Xi’an 710004Shaanxi ProvinceChina

AIM:To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders(NMOSD).METHODS:A total of 33 patients with NMOSD treated with inebilizumab(Group INB,n=15)or rituximab(Group RTX,n=18)in addition to high-dose glucocorticoids were included.Both groups underwent hormone shock therapy during the acute phase.Subsequently,Group INB received inebilizumab injections during the remission phase,while Group RTX received rituximab injections.A comparison of aquaporins 4(AQP4)titer values,peripheral blood B lymphocyte counts,and visual function recovery was conducted before and 8wk after treatment.Additionally,adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes.RESULTS:Following inebilizumab treatment,there was a significantly improvement in the visual acuity of NMOSD patients(P0.05).Furthermore,inebilizumab exhibited higher safety levels than that of rituximab injections.CONCLUSION:The combination of inebilizumab and high-dose glucocorticoids proves to be effective.In comparison to rituximab injections,inebilizumab displays better tolerance and safety.Moreover,it demonstrates a partial effect in preventing optic nerve atrophy.Thus,it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.

关键词： neuromyelitis optica spectrum disorders inebilizumab rituximab glucocorticoids

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A Comprehensive Study of the Association between LEPR Gene rs1137101 Variant and Risk of Digestive System Cancers

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Biomedical and Environmental Sciences 2024年第5期37卷 445-456页

作者： HU Wei Qiong ZHOU Wei Guang ZHOU Guang Wei LIAO jia Xi SHI jia xing XIE FengYang LI Shou Heng WANG Yong FENG Xian Hong GU Xiu Li CHEN Bi Feng Department of Biological Science and Technology School of ChemistryChemical Engineering and Life SciencesWuhan University of TechnologyWuhan 430070HubeiChina Institute of WUT-AMU Wuhan University of TechnologyWuhan 430070HubeiChina Department of Clinical Laboratory Wuhan Xinzhou District People’s HospitalWuhan 430499HubeiChina Department of Reproductive Genetics Wuhan Huake Reproductive HospitalWuhan 430013HubeiChina

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case–control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk.Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reactionrestriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis.Results After Bonferroni correction,the case–control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population.Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

关键词： LEPR gene rs1137101 Digestive system cancers Genetic susceptibility Meta-analysis

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Underestimated benefits of NO_(x) control in reducing SNA and O_(3) based on missing heterogeneous HONO sources

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Frontiers of Environmental Science & Engineering 2024年第3期18卷 57-67页

作者： Shuping Zhang Haotian Zheng Jun Liu Yao Shi Tianzeng Chen Chaoyang Xue Fenfen Zhang Yueqi jiang Xiangping Zhang Shovan Kumar Sahu Biwu Chu jia xing State Key Joint Laboratory of Environment Simulation and Pollution Control School of EnvironmentTsinghua UniversityBeijing 100084China China Academy of Civil Aviation Science and Technology Beijing 100028China State Key Joint Laboratory of Environment Simulation and Pollution Control Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Yellow River Institute of Hydraulic Research Zhengzhou 450003China Centre for Climate Research Singapore Meteorological Service SingaporeSingapore 537054Singapore

Substantial NO_(x) emission mitigation is crucial for the synergistic reduction of particulate matter and ozone(O_(3))pollution in China.The traditional air quality model does not consider heterogeneous HONO chemistry,leading to uncertainties in estimating the benefits of NO_(x) control.Previous studies have shown that the parameterization of heterogeneous HONO formation increases both the simulated value of sulfate–nitrate–ammonium(SNA)and that of O_(3),thus adding the heterogeneous reactions of HONO into air quality models inevitably leads to changes in the estimated benefits of NO_(x) abatement.Here we investigated the changes in SNA and O_(3)concentrations from NO_(x) emission reduction before and after adding heterogeneous HONO reactions in the Community Multi-Scale Air Quality(CMAQ)model.Including heterogeneous HONO reactions in the simulation improved the benefits of NO_(x) reduction in terms of SNA control in winter.With 80%NO_(x) reduction,the reduction in SNA increased from 36.9%without considering heterogeneous HONO reactions to 42.8%with heterogeneous HONO chemistry.The reduction in the maximum daily 8h average(MDA8)O_(3)in summer caused by NO_(x) reduction increased slightly from 4.7%to 5.2%after adding heterogeneous HONO reactions.The results in this study highlight the enhanced effectiveness of NO_(x) controls for the reduction of SNA and O_(3)after considering heterogeneous HONO formation in a complex chemical ambient,demonstrating the importance of NO_(x) controls in reducing PM2.5 and O_(3)pollution in China.

关键词： Heterogeneous HONO NO_(x) reduction PM_(2.5) O_(3)

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Transfer learning and neural networks in predicting quadrupole deformation

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Chinese Physics C 2024年第6期48卷 162-168页

作者：原林李佳星张鸿飞 School of Science Xi'an Polytechnic UniversityXi'an 710048China Engineering Research Center of Flexible Radiation Protection Technology Universities of Shaanxi ProvinceXi'an 710048China Xi'an Key Laboratory of Nuclear Protection Textile Equipment Technology Xi'an 710048China School of Physics Xi'an Jiaotong UniversityXi'an 710049China School of Nuclear Science and Technology Lanzhou UniversityLanzhou 730000China

Accurately determining the quadrupole deformation parameters of atomic nuclei is crucial for understanding their structural and dynamic properties.This study introduces an innovative approach that combines transfer learning techniques with neural networks to predict the quadrupole deformation parameters of even-even nuclei.With the application of this innovative technique,the quadrupole deformation parameters of 2331 even-even nuclei are successfully predicted within the nuclear region defined by proton numbers 8≤Z≤134 and neutron numbers N≥8.Additionally,we discuss the impact of nuclear quadrupole deformation parameters on the capture cross-sections in heavy-ion fusion reactions,reconstructing the capture cross-sections for the reactions48Ca+244Pu and48Ca+248Cm.This research offers new insights into the application of neural networks in nuclear physics and highlights the potential of merging advanced machine learning techniques with both theoretical and experimental data,particularly in fields where experimental data are limited.

关键词： nuclear deformation neural networks transfer learning heavy-ion fusion reactions

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SERPINE2 promotes liver cancer metastasis by inhibiting c-Cbl-mediated EGFR ubiquitination and degradation

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Cancer Communications 2024年第3期44卷 384-407页

作者： Shiyu Zhang xing jia Haojiang Dai xingxin Zhu Wenfeng Song Suchen Bian Hao Wu Shinuo Chen Yangbo Tang Junran Chen Cheng Jin Mengqiao Zhou Haiyang Xie Shusen Zheng Penghong Song Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP.R.China National Health Commission Key Laboratory of Combined Multi-organ Transplantation HangzhouZhejiangP.R.China Key Laboratory of the Diagnosis and Treatment of Organ Transplantation Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic CancerChinese Academy of Medical SciencesHangzhouZhejiangP.R.China Key Laboratory of Organ Transplantation Research Center for Diagnosis and Treatment of Hepatobiliary DiseasesHangzhouZhejiangP.R.China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP.R.China

Background:Liver cancer is a malignancy with high morbidity and mortality rates.Serpin family E member 2(SERPINE2)has been reported to play a key role in the metastasis of many tumors.In this study,we aimed to investigate the potential mechanism of SERPINE2 in liver cancer metastasis.Methods:The Cancer Genome Atlas database(TCGA),including DNA methy-lation and transcriptome sequencing data,was utilized to identify the crucial oncogene associated with DNA methylation and cancer progression in liver can-cer.Data from the TCGA and RNA sequencing for 94 pairs of liver cancer tissues were used to explore the correlation between SERPINE2 expression and clin-ical parameters of patients.DNA methylation sequencing was used to detect the DNA methylation levels in liver cancer tissues and cells.RNA sequencing,cytokine assays,immunoprecipitation(IP)and mass spectrometry(MS)assays,protein stability assays,and ubiquitination assays were performed to explore the regulatory mechanism of SERPINE2 in liver cancer metastasis.Patient-derived xenografts and tumor organoid models were established to determine the role of SERPINE2 in the treatment of liver cancer using sorafenib.Results:Based on the public database screening,SERPINE2 was identified as a tumor promoter regulated by DNA methylation.SERPINE2 expression was significantly higher in liver cancer tissues and was associated with the dismal prognosis in patients with liver cancer.SERPINE2 promoted liver cancer metas-tasis by enhancing cell pseudopodia formation,cell adhesion,cancer-associated fibroblast activation,extracellular matrix remodeling,and angiogenesis.IP/MS assays confirmed that SERPINE2 activated epidermal growth factor receptor(EGFR)and its downstream signaling pathways by interacting with EGFR.Mechanistically,SERPINE2 inhibited EGFR ubiquitination and maintained its protein stability by competing with the E3 ubiquitin ligase,c-Cbl.Additionally,EGFR was activated in liver cancer cells after sorafenib treatment,and SER-PINE2 knockdown-induced EGFR downregulation sig

关键词： liver cancer metastasis DNA methylation SERPINE2 EGFR c-Cbl ubiquitination

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A probe into the acid deposition mitigation path in China over the last four decades and beyond

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National Science Review 2024年第4期11卷 84-92页

作者： Qian Yu Xiaodong Ge Haotian Zheng jia xing Lei Duan Dongwei Lv Dian Ding Zhaoxin Dong Yisheng Sun Posch Maximilian Danni Xie Yu Zhao Bin Zhao Shuxiao Wang Jan Mulder Thorj?rn Larssen Jiming Hao State Key Laboratory of Environmental Simulation and Pollution Control School of EnvironmentTsinghua University State Key Laboratory of Pollution Control &Resource Reuse and School of the Environment Nanjing University State Environmental Protection Key Laboratory of Sources and Control of Air Pollution Complex School of EnvironmentTsinghua University International Institute for Applied System Analysis(IIASA) School of Land Engineering Chang'an University Faculty of Environmental Sciences and Natural Resource Management Norwegian University of Life Sciences Norwegian Institute for Water Research

China currently has the highest acid deposition globally, yet research on its status, impacts, causes and controls is lacking. Here, we compiled data and calculated critical loads regarding acid deposition. The results showed that the abatement measures in China have achieved a sharp decline in the emissions of acidifying pollutants and a continuous recovery of precipitation p H, despite the drastic growth in the economy and energy consumption. However, the risk of ecological acidification and eutrophication showed no significant decrease. With similar emission reductions, the decline in areas at risk of acidification in China(7.0%) lags behind those in Europe(20%) or the USA(15%). This was because, unlike Europe and the USA, China's abatement strategies primarily target air quality improvement rather than mitigating ecological impacts. Given that the area with the risk of eutrophication induced by nitrogen deposition remained at 13%of the country even under the scenario of achieving the dual targets of air quality and carbon dioxide mitigation in 2035, we explored an enhanced ammonia abatement pathway. With a further 27% reduction in ammonia by 2035, China could largely eliminate the impacts of acid deposition. This research serves as a valuable reference for China's future acid deposition control and for other nations facing similar challenges.

关键词： acid deposition critical loads acidification eutrophication ammonia abatement

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突厥语族语言名词性领属结构的标注模式及领属标记的功能扩展

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语言研究 2024年第2期44卷 119-127页

作者：姚家兴江苏师范大学语言科学与艺术学院江苏东徐州221009

中国境内突厥语族语言名词性领属结构的典型标注模式为“Pr-领格+Pd-领属人称”的双重标注模式,当领有者为人称代词时更倾向选用“Pr-领格+Pd”“Pr+Pd-领属人称”“Pd-领属人称”的单标注模式,“Pr-领属物词尾”的标注模式体现出黏着... 详细信息

中国境内突厥语族语言名词性领属结构的典型标注模式为“Pr-领格+Pd-领属人称”的双重标注模式,当领有者为人称代词时更倾向选用“Pr-领格+Pd”“Pr+Pd-领属人称”“Pd-领属人称”的单标注模式,“Pr-领属物词尾”的标注模式体现出黏着语言的个性特点,并置模式“Pr+Pd”不具有普适性,一些濒危语言领属人称词尾呈现出“数一致关系弱化>人称一致关系弱化>标记数量减少”的渐变等级序列。除表达典型的领属义,突厥语族语言领属标记的非领有义特征也十分凸显,是非限定补足语从句和关系小句的重要组成部分。

关键词：突厥语族名词性领属结构标注模式领属标记扩展功能

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地方政府施政风格与经济高质量发展——基于僵尸企业的研究视角

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管理科学学报 2024年第1期27卷 75-95页

作者：游家兴魏珊珊厦门大学管理学院厦门361005 厦门大学财务管理与会计研究院厦门361005

在经济进入新常态、推动高质量发展的今天,政府应当扮演着什么样的角色?这是学术界迫切需要回答的重要问题,也是政策制定者、改革践行者最为关心的问题之一.本文区分了两种风格迥异的施政风格:浮夸型与稳健型,并通过政府工作报告的文本... 详细信息

在经济进入新常态、推动高质量发展的今天,政府应当扮演着什么样的角色?这是学术界迫切需要回答的重要问题,也是政策制定者、改革践行者最为关心的问题之一.本文区分了两种风格迥异的施政风格:浮夸型与稳健型,并通过政府工作报告的文本分析进行捕捉.在验证该量化方法合理性的基础上,以僵尸企业为研究切入点,以中国工业企业数据为样本,实证检验政府施政风格在其中所起的作用.研究发现:地方政府施政风格越浮夸,当地企业僵尸化的程度越高.进一步研究还发现,当僵尸企业在当地的社会重要性越高时或债务处置难度越大时,地方政府浮夸型施政风格与当地企业僵尸化程度之间的正向关系会表现得更加显著.僵尸企业的存在不仅扭曲了优胜劣汰的市场竞争机制,而且损害了市场资源配置的效率.因此,本文研究对于探索新常态下地方政府如何转化职能,加快实施僵尸企业的破产重组盘活,进而优化市场资源配置、促进经济高质量发展迈向新台阶具有积极的实践意义.

关键词：施政风格僵尸企业政府工作报告

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