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Stress granules: friend or foe in neurodegenerative disorders?

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Neural Regeneration Research 2024年第2期19卷 403-404页

作者： Shanshan Xu Nico P.Dantuma Department of cell and molecular biology(CMB) Karolinska InstitutetSolnavägen 9S-17165 StockholmSweden

Neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis,despite the diversity in clinical symptoms,share a striking feature at the cellular level:the accumulation of insoluble aggregates of misfolded proteins that are sequestered in intraneuronal inclusion *** mutations in disease-associated proteins that render them aggregation-prone,the decline of protein homeostasis(***)with aging is also believed to be a contributing factor to the accumulation of protein aggregates.

关键词： degenerative homeostasis clinical

Potential of molecular chaperones for treating Alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2343-2344页

作者： Gefei Chen Jan Johansson Department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden Department of cell and molecular biology Uppsala UniversityUppsalaSweden

Alzheimer’s disease(AD)is the most prevalent form of dementia,i.e.,progressive memory loss and profound cognitive dysfunction,resulting in a considerable societal *** the neuropathological level,the brains of AD patients exhibit amyloid-β(Aβ)plaques,neurofibrillary tangles,and neuroinflammation(Sala Frigerio and De Strooper,2016).

关键词： Alzheimer inflammation Aβ

Pandemic punch:SARS-CoV-2 hits pancreas

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1779-1780页

作者： Ninel Azoitei Sandra Heller Alexander Kleger Institute of molecular Oncology and Stem cell biology Ulm UniversityUlmGermany division of Interdisciplinary Pancreatology Clinic of Internal Medicine IUniversity Hospital UlmUlmGermany

The COVID-19 pandemic has profoundly impacted global health systems,revealing the extensive repercussions of SARS-CoV-2 beyond respiratory ***,traditionally considered a respiratory virus,SARS-CoV-2’s showcased the ability to target multiple organ systems including pancreas,an organ crucial for regulating blood sugar levels and aiding digestion.

关键词： pancreas respiratory traditionally

Heat Shock Factor A1s are required for phytochrome-interacting factor 4-mediated thermomorphogenesis in Arabidopsis

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Journal of Integrative Plant biology 2024年第1期66卷 20-35页

作者： Bingjie Li Shimeng Jiang Liang Gao Wenhui Wang Haozheng Luo Yining Dong Zhihua Gao Shuzhi Zheng Xinye Liu Wenqiang Tang Key Laboratory of molecular and cellular biology of Ministry of Education Hebei Research Center of the Basic Discipline of Cell BiologyHebei Collaboration Innovation Center for Cell SignalingHebei Key Laboratory of Molecular and Cellular BiologyCollege of Life SciencesHebei Normal UniversityShijiazhuang 050024China School of Information Technology Hebei University of Economics and BusinessShijiazhuang 050061China

Thermomorphogenesis and the heat shock(HS)response are distinct thermal responses in plants that are regulated by PHYTOCHROME-INTERACTING FACTOR 4(PIF4)and HEAT SHOCK FACTOR A1s(HSFA1s),*** is known about whether these responses are interconnected and whether they are activated by similar *** analysis of transcriptome dynamics in response to warm temperature(28℃)treatment revealed that 30 min of exposure activated the expression of a subset of HSFA1 target genes in Arabidopsis ***,a loss-of-function HSFA1 quadruple mutant(hsfa1-cq)was insensitive to warm temperature-induced hypocotyl *** hsfa1-cq plants grown at 28℃,the protein and transcript levels of PIF4 were greatly reduced,and the circadian rhythm of many thermomorphogenesis-related genes(including PIF4)was ***,the nuclear localization of HSFA1s and the binding of HSFA1d to the PIF4 promoter increased following warm temperature exposure,whereas PIF4 overexpression in hsfa1-cq partially rescued the altered warm temperature-induced hypocotyl growth of the *** together,these results suggest that HSFA1s are required for PIF4 accumulation at a warm temperature,and they establish a central role for HSFA1s in regulating both thermomorphogenesis and HS responses in Arabidopsis.

关键词： HSFA1 PIF4 thermomorphogenesis

SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer

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Genes & Diseases 2024年第2期11卷 978-992页

作者： Ming-Yan Shi Yarong Wang Ying Shi Ruofei Tian Xiaohong Chen Hai Zhang Ke Wang Zhinan Chen Ruo Chen National Translational Science Center for molecular Medicine & Department of cell biology Fourth Military Medical UniversityXi'anShaanxi 710032China

Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor ***147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism ***,the relationship between the PTMs of CD147 and apoptosis has not been *** our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent ***1 was identified as the methyltransferase catalyzing CD147 to generate ***-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)***,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell *** vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell *** together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.

关键词： CD147 di-methylation cell apoptosis FOSB Non-small cell lung cancer SETDB1

Emerging role of cellular senescence in normal lung development and perinatal lung injury

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 10-16页

作者： Phyllis A.Dennery Hongwei Yao Department of molecular biology Cell Biology&BiochemistryDivision of Biology and MedicineBrown UniversityProvidenceRI 02912USA Department of Pediatrics Warren Alpert Medical School of Brown UniversityProvidenceRI 02903USA

cellular senescence is a status of irreversible growth arrest,which can be triggered by the p53/p21cip1 and p16INK4/Rb pathways via intrinsic and external *** cells are typically enlarged and flattened,and characterized by numerous molecular *** latter consists of increased surfaceome,increased resid-ual lysosomal activity at pH 6.0(manifested by increased activity of senescence-associated beta-galactosidase[SA-𝛽-gal]),senescence-associated mitochondrial dysfunction,cytoplasmic chromatin fragment,nuclear lamin b1 exclusion,telomere-associated foci,and the senescence-associated secretory *** features vary depending on the stressor leading to senescence and the type of *** senescence plays pivotal roles in organismal aging and in the pathogenesis of aging-related ***,senescence can also both promote and inhibit wound healing *** recently report that senescence as a programmed pro-cess contributes to normal lung *** senescence is also observed in Down Syndrome,as well as in premature infants with bronchopulmonary dysplasia and in a hyperoxia-induced rodent model of this ***,this senescence results in neonatal lung *** this review,we briefly discuss the molecular features of *** then focus on the emerging role of senescence in normal lung development and in the pathogenesis of bronchopulmonary dysplasia as well as putative signaling pathways driving ***,we discuss potential therapeutic approaches targeting senescent cells to prevent perinatal lung diseases.

关键词： Senescence Normal lung development Bronchopulmonary dysplasia Down syndrome Senolytics

Pyruvate kinase M in germ cells is essential for sperm motility and male fertility but not spermatogenesis

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Asian Journal of Andrology 2024年第2期26卷 212-219页

作者： Gao-Qing Qian Xiao-Chen Wang Xi Zhang Bin Shen Qiang Liu State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical UniversityNanjing 211166China Shanghai Key Laboratory of Reproductive Medicine Department of HistoembryologyGenetics and Developmental BiologyShanghai Jiao Tong University School of MedicineShanghai 200025China State Key Laboratory of molecular biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China

Male germ cells employ specific metabolic pathways throughout their developmental *** a previous study,we discovered heightened expression of pyruvate kinase M(PKM),a pivotal glycolytic enzyme,in spermatogonia and *** gain deeper insights into PKM's roles in spermatogenesis,sperm function,and male fertility,we engineered a conditional-knockout mouse model(Pkm-vkO mice)to selectively disrupt the Pkm gene within germ *** maintaining regular testicular histology and sperm morphology,the male Pkm-vko mice were infertility,characterized by significant impairments in sperm motility and adenosine triphosphate(ATP)*** addition,Pkm-null spermatozoa exhibited similar deficits in protein tyrosine phosphorylation linked to capacitation,as well as compromised performance in in vitro fertilization *** conclude,PKM's presence is not obligatory for the entirety of spermatogenesis in male germ cells;however,it emerges as a critical factor influencing sperm motility and overall male fertility.

关键词： glycolysis male fertility pyruvate kinase M sperm motility spermatogenesis

c-myb is involved in CML progression and is a therapeutic target in the zebrafish CML model

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Animal Models and Experimental Medicine 2024年第2期7卷 136-144页

作者： Yin Ye Xiaojun Yang Feifei Li Wei Liu Wenqing Zhang Zhibin Huang division of cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhouChina

Background:Despite the success of tyrosine kinase inhibitors in chronic myeloid leukemia(CML)therapy,CML still faces the challenges of drug resistance and progression to blast ***-five percent of patients have imatinib resistance and treatment difficulties due to heterogeneity after progression,but little is known about the mechanism.A key transcription factor in hematopoiesis,MYB,has been reported to increase abnormally in several types of aggressive blood disorders including ***:This study used a zebrafish model to explore the relationship between BCR/ABL1 and c-myb in CML progression.A CML zebrafish model was crossed with a c-myb hyperactivity transgenic ***:It was found that both exogenous BCR/ABL1 and c-myb could up-regulate the expression of neutrophil-related *** seriously,neutrophil accumulation was observed when BCR/ABL1 was combined with c-myb *** studies showed that c-myb may be one of the downstream targets of BCR/ABL1 and the effect of BCR/ABL1 on neutrophils was c-myb *** advantage of this inheritable in vivo model,it was shown that a combination of imatinib and flavopiridol,a cyclin-dependent kinase inhibitor targeting MYB,could more effectively alleviate the aggressive phenotype of the double transgene ***:In summary,this study suggests that c-myb acts downstream of BCR/ABL1 and is involved in CML progression and is therefore a risk factor and a valuable target for the treatment of CML *** model used in the study could be helpful in high-throughput drug screening in CML transformation.

关键词： chronic myeloid leukemia c-myb flavopiridol zebrafish model

AtVQ25 promotes salicylic acid-related leaf senescence by fine-tuning the self-repression of AtWRKY53

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Journal of Integrative Plant biology 2024年第6期66卷 1126-1147页

作者： Qi Tan Mingming Zhao Jingwei Gao Ke Li Mengwei Zhang Yunjia Li Zeting Liu Yujia Song Xiaoyue Lu Zhengge Zhu Rongcheng Lin Pengcheng Yin Chunjiang Zhou Geng Wang Ministry of Education Key Laboratory of molecular and cellular biology Hebei Research Center of the Basic Discipline of Cell BiologyHebei Collaboration Innovation Center for Cell Signaling and Environmental AdaptationHebei Key Laboratory of Molecular and Cellular BiologyCollege of Life SciencesHebei Normal UniversityShijiazhuang 050024China College of Chemical Engineering Shijiazhuang UniversityShijiazhuang 050035China Institute of Botany Chinese Academy of SciencesBeijing 100093China

Most mechanistic details of chronologically ordered regulation of leaf senescence are *** networks centered on AtWRKY53 are crucial for orchestrating and integrating various senescence-related ***,AtWRKY53binds to its own promoter and represses transcription of AtWRKY53,but the biological significance and mechanism underlying this selfrepression remain *** this study,we identified the VQ motif-containing protein AtVQ25as a cooperator of *** expression level of AtVQ25 peaked at mature stage and was specifically repressed after the onset of leaf ***25-overexpressing plants and atvq25 mutants displayed precocious and delayed leaf senescence,***,we identified AtWRKY53 as an interacting partner of *** determined that interaction between AtVQ25 and AtWRKY53 prevented AtWRKY53from binding to W-box elements on the AtWRKY53promoter and thus counteracted the selfrepression of *** addition,our RNA-sequencing data revealed that the AtVQ25-AtWRKY53 module is related to the salicylic acid(SA)*** leaf senescence and SA-induced leaf senescence in AtVQ25-overexpressing lines were inhibited by an SA pathway mutant,atsid2,and Nah G transgenic plants;AtVQ25-overexpressing/atwrky53 plants were also insensitive to SA-induced leaf ***,we demonstrated that AtVQ25 directly attenuates the self-repression of AtWRKY53 during the onset of leaf senescence,which is substantially helpful for understanding the timing of leaf senescence onset modulated by AtWRKY53.

关键词： AtWRKY53 leaf senescence salicylic acid transcriptional regulation VQ motif-containing proteins