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How variable progenitor clones construct a largely invariant neocortex

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National Science Review 2024年第1期11卷 129-144页

作者： Zhongfu Shen Jiajun Yang Qiangqiang Zhang Kuiyu Wang Xiaohui Lv Xiaolin Hu Jian Ma Song-Hai Shi New Cornerstone Science Laboratory IDG/McG overn Institute for Brain Research Tsinghua-Peking Center for Life Sciences Beijing Frontier Research Center for Biological Structure School of Life Sciences Tsinghua University Department of Computer Sciences Tsinghua University College of life Sciences Nankai University Chinese Institute for Brain research

The neocortex contains a vast collection of diverse neurons organized into distinct layers. While nearly all neocortical neurons are generated by radial glial progenitors(RGPs), it remains largely unclear how a complex yet organized neocortex is constructed reliably and robustly. Here, we show that the division behavior and neuronal output of RGPs are highly constrained with patterned variabilities to support the reliable and robust construction of the mouse neocortex. The neurogenic process of RGPs can be well-approximated by a consistent Poisson-like process unfolding over time, producing deep to superficial layer neurons progressively. The exact neuronal outputs regarding layer occupation are variable; yet, this variability is constrained systematically to support all layer formation, largely reflecting the variable intermediate progenitor generation and RGP neurogenic entry and exit timing differences. Together, these results define the fundamental features of neocortical neurogenesis with a balanced reliability and variability for the construction of the complex neocortex.

关键词： neocortex radial glial progenitor intermediate progenitor neurogenesis clonal variability layer formation

Mechanism of action of cordycepin in the treatment of hepatocellular carcinoma via regulation of the Hippo signaling pathway

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Food Science and Human Wellness 2024年第2期13卷 1040-1054页

作者： Xiaomin Li Qing Liu Songyu Xie Xiaoping Wu Junsheng Fu College of life Sciences Mycological Research CenterFujian Agriculture and Forestry UniversityFuzhou 350002China

Hepatocellular carcinoma(HCC)is one of the common most malignant *** study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of *** results of in vitro and in vivo studies revealed that cordycepin inhibited proliferation and migration in HepG-2 cells and inhibited the growth of HepG-2 xenograft-bearing nude mice by inducing *** sequencing analysis revealed a total of 403 differential genes,which revealed that cordycepin may play an anti-HCC role by regulating Hippo signaling *** regulatory effects of cordycepin on the Hippo signaling pathway was further investigated using a YAP1 *** results demonstrated that cordycepin upregulated the expression of MST1 and LAST1,and subsequently inhibited YAP1,which activated the Hippo signaling *** in turn downregulated the expression of GBP3 and ETV5,and subsequently inhibited cell proliferation and ***,YAP1 regulated the expression of Bax and Bcl-2,regulated the mitochondrial apoptotic pathway,and induced apoptosis by upregulating the expression of the caspase-3 *** summary,this study reveals that cordycepin exerts its anti-hepatocarcinoma effect through regulating Hippo signaling pathway,and GBP3 and ETV5 may be potential therapeutic targets for hepatocarcinoma.

关键词： Cordycepin Hepatocellular carcinoma Hippo signaling pathway GBP3 ETV5

A phase separation-fortified bi-specific adaptor for conditional tumor killing

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Science China(life Sciences) 2024年第7期67卷 1385-1397页

作者： Yuyan Liu Yuting Zhu Weifan Xu Pilong Li State Key Laboratory of Membrane Biology Frontier Research Center for Biological StructureTsinghua University-Peking University Joint Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China

A common approach in therapeutic protein development involves employing synthetic ligands with multivalency,enabling sophisticated control of signal *** the emerging concept of liquid-liquid phase separation(LLPS)and its ability to organize cell surface receptors into functional compartments,we herein have designed modular ligands with phase-separation modalities to engineer programmable interreceptor communications and precise control of signal pathways,thus inducing the rapid,potent,and specific apoptosis of tumor *** their simplicity,these“triggers”,named phase-separated Tumor Killers(hereafter referred to as psTK),are sufficient to yield interreceptor clustering of death receptors(represented by DR5)and tumor-associated receptors,with notable features:LLPSmediated robust high-order organization,well-choreographed conditional activation,and broad-spectrum capacity to potently induce apoptosis in tumor *** development of novel therapeutic proteins with phase-separation modalities showcases the power of spatially reorganizing signal *** approach facilitates the diversification of cell fate and holds promising potential for targeted therapies against challenging tumors.

关键词： phase separation therapeutic proteins receptor-ligand interactions DR5 tumor apoptosis

Di-and tri-methylation of histone H3K36 play distinct roles in DNA double-strand break repair

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Science China(life Sciences) 2024年第6期67卷 1089-1105页

作者： Runfa Chen Meng-Jie Zhao Yu-Min Li Ao-Hui Liu Ru-Xin Wang Yu-Chao Mei Xuefeng Chen Hai-Ning Du Hubei Key Laboratory of Cell Homeostasis College of Life SciencesTaiKang Center for Life and Medical SciencesFrontier Science Center for Immunology and MetabolismHubei Clinical Research Center of Emergency and ResuscitationEmergency Center of Zhongnan HospitalWuhan UniversityWuhan 430072China Hubei Key Laboratory of Cell Homeostasis College of Life SciencesTaiKang Center for Life and Medical SciencesFrontier Science Center for Immunology and MetabolismWuhan UniversityWuhan 430072China

Histone H3 Lys36(H3K36)methylation and its associated modifiers are crucial for DNA double-strand break(DSB)repair,but the mechanism governing whether and how different H3K36 methylation forms impact repair pathways is ***,we unveil the distinct roles of H3K36 dimethylation(H3K36me2)and H3K36 trimethylation(H3K36me3)in DSB repair via non-homologous end joining(NHEJ)or homologous recombination(HR).Yeast cells lacking H3K36me2 or H3K36me3 exhibit reduced NHEJ or HR efficiency.y Ku70 and Rfa1 bind H3K36me2-or H3K36me3-modified peptides and chromatin,*** these interactions impairs y Ku70 and Rfa1 recruitment to damaged H3K36me2-or H3K36me3-rich loci,increasing DNA damage sensitivity and decreasing repair ***,H3K36me2-enriched intergenic regions and H3K36me3-enriched gene bodies independently recruit y Ku70 or Rfa1 under DSB ***,human KU70 and RPA1,the homologs of y Ku70 and Rfa1,exclusively associate with H3K36me2 and H3K36me3 in a conserved *** findings provide valuable insights into how H3K36me2 and H3K36me3 regulate distinct DSB repair pathways,highlighting H3K36 methylation as a critical element in the choice of DSB repair pathway.

关键词： histone H3K36 methylation Ku70 RPA non-homologous end joining homologous recombination

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Distinguishing the observational signatures of hot spots orbiting Reissner-Nordström spacetime

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Chinese Physics C 2024年第7期48卷 221-230页

作者：吴天枢陈一千 center for theoretical Physics College of PhysicsSichuan UniversityChengdu 610064China

This paper investigates observable signatures of hot spots orbiting Reissner-Nordström(RN)black holes and naked *** an RN black hole,we find two discernible lensing image tracks in time integrated images,capturing a complete orbit of hot spots and a image shadow within the critical curve where photons with a small impact parameter fall into the event ***,in RN singularities,additional image tracks can be found within the critical curve,originating from photons reflected by the infinitely high effective potential ***,we find incomplete and converging tracks from the time integrated images of hot spot orbiting RN singularities that have no photon *** presence of these additional image tracks significantly influences temporal magnitudes at their local maxima,enabling us to differentiate between RN black holes and RN naked singularities.

关键词： astrometry gravitational lensing black hole physics D0I:10.1088/1674-1137/ad3c2d

Anthrax lethal toxin and tumor necrosis factor-a synergize on intestinal epithelia to induce mouse death

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Protein & Cell 2024年第2期15卷 135-148页

作者： Xinhe Gao Teng Teng Yifei Liu Tingting Ai Rui Zhao Yilong Fu Peipei Zhang Jiahuai Han Yingying Zhang State Key Laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China research Unit of Cellular Stress of CAMS Xiang'an Hospital of Xiamen UniversityCancer Research Center of Xiamen UniversitySchool of MedicineFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China Laboratory Animal center Faculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China

Bacillus anthracis lethal toxin(LT)is a determinant of lethal *** function in myeloid cells is required for bacterial dissemination,and LT itself can directly trigger dysfunction of the cardiovascular *** interplay between LT and the host responses is important in the pathogenesis,but our knowledge on this interplay remains *** necrosis factor-a(TNF-a)is a pleiotropic pro-inflammatory cytokine induced by bacterial *** LT accumulates and cytokines,predominantly TNF,amass during *** infection,co-treatment of TNF+LT in mice was used to mimic in vivo conditions for LT to function in inflamed *** marrow transplantation and genetically engineered mice showed unexpectedly that the death of intestinal epithelial cells(IECs)rather than that of hematopoietic cells led to LT+TNF-induced *** of p38a mitogen-activated protein kinase(MAPK)signaling by LT in IECs promoted TNF-induced apoptosis and necroptosis of IECs,leading to intestinal damage and mouse ***,p38a inhibition by LT enhanced TNF-mediated cell death in human colon epithelial HT-29 *** intestinal damage is one of the leading causes of lethality in anthrax patients,the IEC damage caused by LT+TNF would most likely be a mechanism underneath this clinical manifestation and could be a target for interventions.

关键词： lethal toxin TNF p38a intestinal epithelial cell cell death

PABP-driven secondary condensed phase within RSV inclusion bodies activates viral mRNAs for ribosomal recruitment

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Virologica Sinica 2024年第2期39卷 235-250页

作者： Qiang Zhang Hanzhe Ye Cong Liu Haiwu Zhou Mingbin He Xiaodong Liang Yu Zhou Kun Wang Yali Qin Zhifei Li Mingzhou Chen State Key Laboratory of Virology and Modern Virology research center College of Life SciencesWuhan UniversityWuhan430072China Taikang center for life and Medical Sciences Wuhan UniversityWuhan430072China Hubei Jiangxia Laboratory Wuhan430200China

Inclusion bodies(IBs)of respiratory syncytial virus(RSV)are formed by liquid-liquid phase separation(LLPS)and contain internal structures termed“IB-associated granules”(IBAGs),where anti-termination factor M2-1 and viral mRNAs are ***,the mechanism of IBAG formation and the physiological function of IBAGs are ***,we found that the internal structures of RSV IBs are actual M2-1-free viral messenger ribonucleoprotein(mRNP)condensates formed by secondary ***,the RSV nucleoprotein(N)and M2-1 interact with and recruit PABP to IBs,promoting PABP to bind viral mRNAs transcribed in IBs by RNArecognition motif and drive secondary phase ***,PABP-eIF4G1 interaction regulates viral mRNP condensate composition,thereby recruiting specific translation initiation factors(eIF4G1,eIF4E,eIF4A,eIF4B and eIF4H)into the secondary condensed phase to activate viral mRNAs for ribosomal *** study proposes a novel LLPS-regulated translation mechanism during viral infection and a novel antiviral strategy via targeting on secondary condensed phase.

关键词： Respiratory syncytial virus(RSV) Inclusion bodies(IBs) Biomolecular condensates Liquid-liquid phase separation(LLPS) Secondary condensed phase mRNA activation

Long way up:rethink diseases in light of phase separation and phase transition

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Protein & Cell 2024年第7期15卷 475-492页

作者： Mingrui Ding Weifan Xu Gaofeng Pei Pilong Li State Key Laboratory of Membrane Biology&Frontier research center for Biological Structure School of Life SciencesTsinghua UniversityBeijing 100084China Tsinghua-Peking center for life Sciences Beijing 100084China NuPhase Therapeutics Beijing 100083China

Biomolecular condensation, driven by multivalency, serves as a fundamental mechanism within cells, facilitating the formation of distinct compartments, including membraneless organelles that play essential roles in various cellular processes. Perturbations in the delicate equilibrium of condensation, whether resulting in gain or loss of phase separation, have robustly been associated with cellular dysfunction and physiological disorders. As ongoing research endeavors wholeheartedly embrace this newly acknowledged principle, a transformative shift is occurring in our comprehension of disease. Consequently, significant strides have been made in unraveling the profound relevance and potential causal connections between abnormal phase separation and various diseases. This comprehensive review presents compelling recent evidence that highlight the intricate associations between aberrant phase separation and neurodegenerative diseases, cancers, and infectious diseases. Additionally, we provide a succinct summary of current efforts and propose innovative solutions for the development of potential therapeutics to combat the pathological consequences attributed to aberrant phase separation.

关键词： multivalency compartments aberant phase separation therapeutics gain or loss of phase separation diseases

Observational appearances of hairy black holes in the framework of gravitational decoupling

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Communications in theoretical Physics 2024年第8期76卷 103-117页

作者： Yizhi Liang Xin Lyu Jun Tao center for theoretical Physics College of PhysicsSichuan UniversityChengdu 610065China

We investigate the observational appearance of static and spherically symmetric hairy black holes in the framework of gravitational decoupling with the weak energy condition(WEC). Two types of thin illumination conditions are studied: spherical accretion and disk accretion. As the hairy parameter increases, the size of the photon sphere and photon rings in both models decreases, and the overall luminosity attenuation becomes more pronounced. In spherical accretion, the luminosity of infalling accretion is significantly lower than that of stationary accretion. In disk accretion the luminosity of the black hole is contributed by direct emission, the lensing ring and the photon ring. Employing four types of astrophysical disk luminosity model,we investigate the appearance of halos and note that their luminosities do not superimpose when the source is on or beyond the innermost stable circular orbit.

关键词： hairy black hole shadow gravitational decoupling accretion disk