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METTL5 promotes cell proliferation,invasion,and migration by up-regulating Toll-like receptor 8 expression in colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2006-2017页

作者： Ling-Shang Kong Ran Tao Yi-Fan Li Wen-Bin Wang xue zhao Department of General Surgery The Second Affiliated Hospital of Anhui Medical UniversityHefei 230001Anhui ProvinceChina Department of Vascular Surgery The Second Affiliated Hospital of Anhui Medical UniversityHefei 230002Anhui ProvinceChina Department of General Surgery The First Affiliated Hospital of Anhui Medical UniversityHefei 230001Anhui ProvinceChina Anhui Public Health Clinical Center Hefei 230012Anhui ProvinceChina Department of Scientific Research Anhui Public Health Clinical CenterHefei 230012Anhui ProvinceChina Department of Scientific Research The First Affiliated Hospital of Anhui Medical UniversityHefei 230001Anhui ProvinceChina

BACKGROUND N6-methyladenosine(m6A)modification represents the predominant alteration found in eukaryotic messenger RNA and plays a crucial role in the progression of various tumors.However,despite its significance,the comprehensive investigation of METTL5,a key m6A methyltransferase,in colorectal cancer(CRC)remains limited.AIM To investigate the role of METTL5 in CRC.METHODS We assessed METTL5 expression levels in clinical samples obtained from CRC patients as well as in CRC cell lines.To elucidate the downstream targets of METTL5,we performed RNA-sequencing analysis coupled with correlation analysis,leading us to identify Toll-like receptor 8(TLR8)as a potential downstream target.In vitro functional assessments of METTL5 and TLR8 were conducted using CCK-8 assays,scratch assays,as well as assays measuring cell migration and invasion.RESULTS Our findings reveal a pronounced upregulation of METTL5 expression in both CRC cells and tissues,which correlated significantly with an unfavorable prognosis.In vitro experiments unequivocally demonstrated the oncogenic role of METTL5,as evidenced by its promotion of CRC cell proliferation,invasion,and migration.Notably,we identified TLR8 as a downstream target of METTL5,and subsequent down-regulation of TLR8 led to a significant inhibition of CRC cell proliferation,invasion,and tumor growth.CONCLUSION The heightened expression of METTL5 in CRC is strongly associated with clinicopathological features and a poor prognosis,thereby underscoring its potential utility as a critical marker for facilitating early diagnosis and prognostication in CRC.

关键词： METTL5 Toll-like receptor 8 Colorectal cancer

Comprehensive integration of single-cell transcriptomic data illuminates the regulatory network architecture of plant cell fate specification

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Plant Diversity 2024年第3期46卷 372-385页

作者： Shanni Cao xue zhao Zhuojin Li Ranran Yu Yuqi Li Xinkai Zhou Wenhao Yan Dijun Chen Chao He State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing 210023China National Key Laboratory of Crop Genetic Improvement Hubei Hongshan LaboratoryHuazhong Agricultural UniversityWuhan 430070China

Plant morphogenesis relies on precise gene expression programs at the proper time and position which is orchestrated by transcription factors(TFs)in intricate regulatory networks in a cell-type specific manner.Here we introduced a comprehensive single-cell transcriptomic atlas of Arabidopsis seedlings.This atlas is the result of meticulous integration of 63 previously published scRNA-seq datasets,addressing batch effects and conserving biological variance.This integration spans a broad spectrum of tissues,including both below-and above-ground parts.Utilizing a rigorous approach for cell type annotation,we identified 47 distinct cell types or states,largely expanding our current view of plant cell compositions.We systematically constructed cell-type specific gene regulatory networks and uncovered key regulators that act in a coordinated manner to control cell-type specific gene expression.Taken together,our study not only offers extensive plant cell atlas exploration that serves as a valuable resource,but also provides molecular insights into gene-regulatory programs that varies from different cell types.

关键词： Arabidopsis Single cell transcriptome Gene regulatory network Data integration Plant cell atlas

Application of multidisciplinary in situ simulation training in the treatment of acute ischemic stroke: a quality improvement project

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World Journal of Emergency Medicine 2024年第1期15卷 41-46页

作者： Ganying Huang Huijie Yang Huan Yao Xinxin Fan Wenqin Xia Yuansheng Xu Xiaoling Shen xue zhao Fourth School of Clinical Medicine Zhejiang Chinese Medical UniversityHangzhou 310053China Emergency Medicine Departent Hangzhou First People's HospitalHangzhou 310006China

BACKGROUND:Ischemic stroke refers to a disorder in the blood supply to a local area of brain tissue for various reasons and is characterized by high morbidity,mortality,and disability.Early reperfusion of brain tissue at risk of injury is crucial for the treatment of acute ischemic stroke.The purpose of this study was to evaluate comfort levels in managing acute stroke patients with hypoxemia who required endotracheal intubation after multidisciplinary in situ simulation training and to shorten the door-to-image time.METHODS:This quality improvement project utilized a comprehensive multidisciplinary in situ simulation exercise.A total of 53 participants completed the two-day in situ simulation training.The main outcome was the self-reported comfort levels of participants in managing acute stroke patients with hypoxemia requiring endotracheal intubation before and after simulation training.A 5-point Likert scale was used to measure participant comfort.A paired-sample t-test was used to compare the mean self-reported comfort scores of participants,as well as the endotracheal intubation time and door-to-image time on the fi rst and second days of in situ simulation training.The door-to-image time before and after the training was also recorded.RESULTS:The findings indicated that in situ simulation training could enhance participant comfort when managing acute stroke patients with hypoxemia who required endotracheal intubation and shorten door-to-image time.For the emergency management of hypoxemia or tracheal intubation,the mean post-training self-reported comfort score was signifi cantly higher than the mean pre-training comfort score(hypoxemia:4.53±0.64 vs.3.62±0.69,t=-11.046,P<0.001;tracheal intubation:3.98±0.72 vs.3.43±0.72,t=-6.940,P<0.001).We also observed a decrease in the tracheal intubation and door-to-image time and a decreasing trend in the door-to-image time,which continued after the training.CONCLUSION:Our study demonstrates that the implementation of in situ simulation training in a clinical environmen

关键词： Ischemic stroke Endotracheal intubation Door-to-image time In situ simulation Multidisciplinary approach

Timing effect of high temperature exposure on the plasticity of internode and plant architecture in maize

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Journal of Integrative Agriculture 2024年第2期23卷 551-565页

作者： Binbin Li Xianmin Chen Tao Deng xue zhao Fang Li Bingchao Zhang Xin Wang Si Shen Shunli Zhou College of Agronomy and Biotechnology China Agricultural UniversityBeijing 100193China China Tobacco Hunan Industrial Corporation Changsha 410019China Innovation Center of Agricultural Technology for Lowland Plain of Hebei Wuqiao 061802China

The occurrence of high temperature(HT)in crop production is becoming more frequent and unpredictable with global warming,severely threatening food security.The state of an organ’s growth and development is largely determined by the temperature conditions it is exposed to over time.Maize is the main cereal crop,and its stem growth and plant architecture are closely related to lodging resistance,and especially sensitive to temperature.However,systematic research on the timing effect of HT on the sequentially developing internode and stem is currently lacking.To identify the timing effect of HT on the morphology and plasticity of the stem in maize,two hybrids(Zhengdan 958(ZD958),Xianyu 335(XY335))characterized by distinct morphological traits in the stem were exposed to a 7-day HT treatment from the V6 to V17 stages(Vn presents the vegetative stage with n leaves fully expanded)in 2019-2020.The results demonstrated that exposure to HT during V6-V12 accelerated the rapid elongation of stems.For instance,HT occurring at V7 and V12 specifically promoted the lengths and weights of the 3rd-5th and 9th-11th internodes,respectively.Meanwhile,HT slowed the growth of internodes adjacent to the promoted internodes.Interestingly,compared with control,the plant height was significantly increased soon after HT treatment,but the promotion effect became narrower at the subsequent flowering stage,demonstrating a self-adjusting mechanism in the maize plant in response to HT.Importantly,HT altered the plant architectures,including a rising of the ear position and increase in the ear position coefficient.XY335 exhibited greater sensitivity in stem development than ZD958 under HT treatment.These findings improve our systematic understanding of the plasticity of internode and plant architecture in response to the timing of HT exposure.

关键词： maize high temperature internode growth plasticity plant architecture

Short-term effects of cupping and scraping therapy for chronic nonspecific low-back pain:A prospective,multicenter randomized trial

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Journal of Integrative Medicine 2024年第1期22卷 39-45页

作者： Jun-yan He Xiao-yu Tu Zi-fei Yin Hui Mu Ming-jun Luo Xing-yu Chen Wei-bin Cai xue zhao Can Peng Fan-fu Fang Can Lü Bai Li School of Traditional Chinese Medicine Naval Medical UniversityShanghai 200433China Department of Rehabilitation Medicine and Physiotherapy the First Affiliated Hospital of Naval Medical UniversityShanghai 200433China Department of Rehabilitation Medicine and Training PLA 458 HospitalGuangzhou 510602Guangdong ProvinceChina No.3 Ward of Acupuncture Rehabilitation Department Guangdong Second Traditional Chinese Medicine HospitalGuangzhou 510095Guangdong ProvinceChina

Background As one of the most common musculoskeletal ailments,chronic nonspecific low-back pain(CNLBP)causes persistent disability and substantial medical expenses.Epidemiological evidence shows that the incidence rate of CNLBP in young and middle-aged people who are demanded rapidly recovery and social contribution is rising.Recent guidelines indicate a reduced role for medicines in the management of CNLBP.Objective The present study investigates the short-term effects of cupping and scraping therapy using a medicated balm,compared to nonsteroidal anti-inflammatory drug(NSAID)with a capsaicin plaster,in the treatment of CNLBP.Design,setting,participants and interventions We designed a prospective multicenter randomized clinical trial enrolling patients from January 1,2022 to December 31,2022.A total of 156 patients with CNLBP were randomized into two parallel groups.Diclofenac sodium-sustained release tablets were administered orally to participants in the control group for one week while a capsaicin plaster was applied externally.Patients in the test group were treated with cupping and scraping using a medical device and medicated balm.Main outcome measures Primary outcome was pain recorded using the visual analogue scale(VAS).Two secondary outcomes were recorded using the Japanese Orthopedic Association low-back pain scale(JOA)and the traditional Chinese medicine(TCM)syndrome integral scale(TCMS)as assessment tools.Results Between baseline and postintervention,all changes in outcome metric scales were statistically significant(P<0.001).Compared to the control group,patients in the test group had a significantly greater treatment effect in all outcome variables,as indicated by lower VAS and TCMS scores and higher JOA scores,after the one-week intervention period(P<0.001).Further,according to the findings of multivariate linear regression analysis,the participants’pain(VAS score)was related to their marital status,age,smoking habits and body mass index.No adverse reactions were reported for any participants in t

关键词： Chronic nonspecific low-back pain Traditional Chinese medicine Cupping and scraping therapy

The complex roles of m6A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

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Neural Regeneration Research 2025年第6期 1582-1598页

作者： Yanxi Li Jing xue Yuejia Ma Ke Ye xue zhao Fangliang Ge Feifei Zheng Lulu Liu Xu Gao Dayong Wang Qing Xia Department of Biochemistry and Molecular Biology College of Basic Medical Sciences Harbin Medical University College of Basic Medical Sciences Harbin Medical University Basic Medical Institute Heilongjiang Academy of Medical Sciences Key Laboratory of Heilongjiang Province for Genetically Modified Animals Harbin Medical University Translational Medicine Research and Cooperation Center of Northern China Heilongjiang Academy of Medical Sciences Dongzhimen Hospital Beijing University of Chinese Medicine

N6-methyladenosine（m6A）, the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m6A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m6A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m6A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m6A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m6A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m6A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m6A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m6A's role in neurodegenerative processes. The roles of m6A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m6A and its varying effects on distinc

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Testing Linearity in Functional Partially Linear Models

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Acta Mathematicae Applicatae Sinica 2024年第3期40卷 875-886页

作者： Fan-rong zhao Bao-xue ZHANG School of Mathematical Sciences Shanxi UniversityTaiyuan 030006China School of Statistics Capital University of Economics and BusinessBeijing 100070China

For the functional partially linear models including flexible nonparametric part and functional linear part,the estimators of the nonlinear function and the slope function have been studied in existing literature.How to test the correlation between response and explanatory variables,however,still seems to be missing.Therefore,a test procedure for testing the linearity in the functional partially linear models will be proposed in this paper.A test statistic is constructed based on the existing estimators of the nonlinear and the slope functions.Further,we prove that the approximately asymptotic distribution of the proposed statistic is a chi-squared distribution under some regularity conditions.Finally,some simulation studies and a real data application are presented to demonstrate the performance of the proposed test statistic.

关键词： asymptotic theory functional partially linear model Nadaraya-Watson estimate test statistic

Thymoquinone affects hypoxia-inducible factor-1αexpression in pancreatic cancer cells via HSP90 and PI3K/AKT/mTOR pathways

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World Journal of Gastroenterology 2024年第21期30卷 2793-2816页

作者： Zhan-xue zhao Shuai Li Lin-Xun Liu Department of General Surgery Qinghai Provincial People's HospitalXining 810007Qinghai ProvinceChina Department of Clinical Pharmacy The Affiliated Hospital of Qinghai UniversityXining 810001Qinghai ProvinceChina

BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory,anti-fibrosis and antioxidant pharmacological activities.Recent studies on hypoxia-inducible factor-1α(HIF-1α)and PC have shown that HIF-1αaffects the occurrence and development of PC in many aspects.In addition,TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α.Therefore,we speculate whether TQ affects HIF-1αexpression in PC cells and explore the mechanism.AIM To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1αexpression.METHODS Cell counting kit-8 assay,Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity,migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial(hTERTHPNE)cells.Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1αmRNA and protein in PC cells.The effects of TQ on the HIF-1αprotein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.RESULTS TQ significantly inhibited proliferative activity,migration,and invasion ability and promoted apoptosis of PANC-1 cells;however,no significant effects on hTERT-HPNE cells were observed.TQ significantly reduced the mRNA and protein expression levels of HIF-1αin PANC-1,AsPC-1,and BxPC-3 cells.TQ significantly inhibited the expression of the HIF-1αinitial expression pathway(PI3K/AKT/mTOR)related proteins,and promoted the ubiquitination degradation of the HIF-1αprotein in PANC-1 cells.TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1αprotein but affected the stability of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90,thus promoting its ubiquitination

关键词： Thymoquinone Pancreatic cancer Hypoxia-inducible factor-1α PI3K/AKT/mTOR HSP90

Underlying anti-hypertensive mechanism of the Mizuhopecten yessoensis derived peptide NCW in spontaneously hypertensive rats via widely targeted kidney metabolomics

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Food Science and Human Wellness 2024年第1期13卷 472-481页

作者： Wenjun xue Wenzhu zhao Sijia Wu Zhipeng Yu School of Food Science and Engineering Hainan UniversityHaikou 570228China College of Food Science and Engineering Bohai UniversityJinzhou 121013China Lab of Nutrition and Functional Food Jilin UniversityChangchun 130062China

The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.

关键词： ACE inhibitory peptide Kidney Mechanism Metabolomics Spontaneously hypertensive rats