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Immune checkpoint inhibitors:breakthroughs in cancer treatment

Cancer Biology & Medicine 2024年第6期21卷 451-472页

作者： Xueqing Kong Jinyi Zhang Shuwei Chen Xianyang Wang Qing Xi Han Shen Rongxin Zhang Laboratory of Immunology and Inflammation School of Life Sciences and BiopharmaceuticsGuangdong Pharmaceutical UniversityGuangzhou 510006China Department of Biology School of Life Sciences and BiopharmaceuticsGuangdong Pharmaceutical UniversityGuangzhou 510006China

Over the past two decades,immunotherapies have increasingly been considered as first-line treatments for most *** such treatment is immune checkpoint blockade(ICB),which has demonstrated promising results against various solid tumors in clinical *** antibodies(mAbs)are currently available as immune checkpoint inhibitors(ICIs).These ICIs target specific immune checkpoints,including cytotoxic T-lymphocyte-associated antigen-4(CTLA-4)and programmed cell death protein 1(PD-1).Clinical trial results strongly support the feasibility of this immunotherapeutic ***,a substantial proportion of patients with cancer develop resistance or tolerance to treatment,owing to tumor immune evasion mechanisms that counteract the host immune ***,substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1,anti-programmed cell death ligand 1(anti-PD-L1),and anti-CTLA-4 ***,several immune checkpoint molecular targets have been identified,such as T cell immunoreceptor with Ig and ITIM domains(TIGIT),mucin domain containing-3(TIM-3),lymphocyte activation gene-3(LAG-3),V-domain immunoglobulin suppressor of T cell activation(VISTA),B and T lymphocyte attenuator(BTLA),and signal-regulatory proteinα(SIRPα).Functional m Abs targeting these molecules are under ***-4,PD-1/PD-L1,and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of *** review discusses these structures,as well as clinical progress in m Abs targeting these immune checkpoint molecules and their potential applications.

关键词： Immunotherapy cancer ICIs PD-1 CTLA-4

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The pathogenesis of Parkinson’s disease and crosstalk with other diseases

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BIOCELL 2024年第8期48卷 1155-1179页

作者： TINGTING LIU DINGYOU GUO JIANSHE WEI Institute for Brain sciences Research School of Life SciencesHenan UniversityKaifeng475004China

In China,Parkinson’s disease(PD)is the second most prevalent central nervous system(CNS)degenerative illness affecting middle-aged and older *** disorders including resting tremor,bradykinesia,myotonia,postural instability,and gait instability are the predominant clinical *** two main types of PD are sporadic and familial,with sporadic PD being the more prevalent of the *** environment,genetics,mitochondrial dysfunction,oxidative stress,inflammation,protein aggregation and misfolding,loss of trophic factors,cell death,and gut microbiota may all have a role in the etiology of *** is inversely connected with other cancers and positively correlated with COVID-19,diabetes mellitus(DM),melanoma,and ischemic heart disease(IHD)*** disease progression,managing motor and non-motor symptoms,and avoiding and controlling dysfunction in the middle and later phases of the disease are the key areas of research and development for its ***,the development and progression of PD can be slowed down by using conventional pharmacology,natural items,and innovative *** article reviews the pathogenesis of PD,its correlations with other non-genetic diseases,and the research progress of drugs and technologies for alleviating PD.

关键词： Parkinson’s disease Mitochondrial dysfunction Oxidative stress Inflammation Cancer Therapies

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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

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A zebrafish tufm mutant model for the COXPD4 syndrome of aberrant mitochondrial function

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Journal of Genetics and Genomics 2024年第9期51卷 922-933页

作者： Ting Li Tursunjan Aziz Guangyuan Li Lin Zhang Jihua Yao Shunji Jia school of life sciences Fudan UniversityShanghai 200438China State Key Laboratory of Membrane Biology Tsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Mitochondrial dysfunction is a critical factor leading to a wide range of clinically heterogeneous and often severe disorders due to its central role in generating cellular *** in the TUFM gene are known to cause combined oxidative phosphorylation deficiency 4(COXPD4),a rare mitochondrial disorder characterized by a comprehensive quantitative deficiency in mitochondrial respiratory chain(MRC)*** development of a reliable animal model for COXPD4 is crucial for elucidating the roles and mechanisms of TUFM in disease pathogenesis and benefiting its medical *** this study,we construct a zebrafish tufm−/−mutant that closely resembles the COXPD4 syndrome,exhibiting compromised mitochondrial protein translation,dysfunctional mitochondria with oxidative phosphorylation defects,and significant metabolic suppression of the tricarboxylic acid *** this COXPD4 zebrafish model,we comprehensively validate the clinical relevance of TUFM mutations and identify probucol as a promising therapeutic approach for managing *** data offer valuable insights for understanding mitochondrial diseases and developing effective treatments.

关键词： Tufm Mitochondria COXPD4 Disease model Zebrafish

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Perspective on new cell-free DNA technologies for early cancer detection

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Cancer Biology & Medicine 2024年第2期21卷 139-143页

作者： Jie Li Xun Lan Department of Basic Medical sciences School of MedicineTsinghua UniversityBeijing 100084China MOE Key Laboratory of Bioinformatics Tsinghua UniversityBeijing 100084China Tsinghua-Peking joint Center for life sciences Tsinghua UniversityBeijing 100084China

High cancer heterogeneity and aggressiveness are major factors contributing to the poor prognosis of patients with advanced cancer~(1-5).Early detection of cancer can significantly improve the prognosis of patients with early-stage cancer after standard *** traditional cancer detection technologies,such as endoscopy for gastrointestinal cancer,mammography for breast cancer。

关键词： prognosis cancer patients

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A repertoire of intronic lariat RNAs reveals tissue-specific regulation and target mimicry potential in plants

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Science China(life sciences) 2024年第6期67卷 1280-1291页

作者： Yong Zhang Xiaotuo Zhang Qi Tang Lei Li Ting Jiang Yixiao Fang Hong Zhang Jixian Zhai Guodong Ren Binglian Zheng State Key Laboratory of Genetic Engineering Institute of Plant BiologySchool of Life SciencesFudan UniversityShanghai 200438China Department of Biology School of Life SciencesSouthern University of Science and TechnologyShenzhen 518055China

Lariat RNA is concomitantly produced by excised intron during RNA splicing,which is usually debranched by DBR1,an RNA debranching ***,increasing evidence showed that some lariat RNA could escape *** is known about how and why these lariat RNAs could be *** comparing the atlas of lariat RNAs between the non-dividing cell(mature pollen)and three actively dividing tissues(young shoot apex,young seeds,and young roots),we identified hundreds to thousands of lariat RNA naturally retained in each tissue,and the incidence of lariat RNA retention is much less in shoot apex while much more in *** lariat RNAs derived from the same intron or different lariat RNAs from the same pre-m RNA could be retained in one tissue while degraded in the other *** deciphering lariat RNA sequences,we identified an AG-rich(RAAAAVAAAR)motif and a UC-rich(UCUCUYUCUC)motif for pollen-specific and the other three tissues-retained lariat RNAs,*** of the pollen-specific AG-rich motif indeed enhanced lariat RNA retention in ***,hundreds of lariat RNAs harbored mi RNA binding sites,and dual-luciferase reporter assay showed that these natural lariat RNAs had the potential to protect expression of mi RNA target ***,our results uncover that selective retention of lariat RNA is an actively regulatory process,and provide new insights into understanding how lariat RNA metabolism may impact mi RNA activity.

关键词： intron turnover lariat RNA miRNA RNA splicing DBR1

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Environmental concentration of ammonia nitrogen induced marked changes in proteome of clam Ruditapes philippinarum in dose-and time-dependent manner

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Journal of Oceanology and Limnology 2024年第5期42卷 1634-1650页

作者： Ming CONG Zhaoshun LI Wenwen TIAN Yuanmei LI Jiasen LÜ school of Ocean Yantai UniversityYantai 264005China school of life sciences Yantai UniversityYantai 264005China

Previous studies have revealed that ammonia nitrogen has several adverse effects on clam Ruditapes ***,knowledge is lacking regarding the related proteins involved in the toxicological responses,which is vital to elucidate the underlying mechanism of ammonia *** this study,clams *** were exposed to ammonia nitrogen for 21 d at two environmentally relevant *** tandem mass tags approach(TMT)was applied to assay the differentially expressed proteins(DEPs)in clam gill tissues on the 3 rd and 21 st ***,a total of 7263 proteins were *** analyses revealed that clam protein profiles changed in dose-and time dependent manner after ammonia nitrogen *** inferred that the clams may face heavy challenges after ammonia exposure,such as unbalanced gender ratio,lysosomal disease,energy lack,neurological disorders,altered glutamine metabolism,increased lipid synthesis,and impaired *** profiles of enzyme activities of glutaminase and glutamine synthase provided direct evidence to verify the related inference from proteome *** of the inferred toxic effects merit further *** study identified important proteins related to ammonia nitrogen toxicity in the clam and indicated the severe stress of marine ammonia pollution on the healthy development of mollusc aquaculture.

关键词： ammonia nitrogen Ruditapes philippinarum proteomic analysis toxicity

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Eugenol targeting CrtM inhibits the biosynthesis of staphyloxanthin in Staphylococcus aureus

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Food Science and Human Wellness 2024年第3期13卷 1368-1377页

作者： Jiang Chang Bo Chen Zeqian Du Bowen Zhao Jiahui Li Ziyi Li Kannappan Arunachalam Ting Shi Dongqing Wei Chunlei Shi MOST-USDA joint Research Center for Food Safety School of Agriculture and BiologyState Key Laboratory of Microbial MetabolismShanghai Jiao Tong UniversityShanghai 200240China school of life sciences and Biotechnology Shanghai Jiao Tong UniversityShanghai 200240China

Staphylococcus aureus is a serious foodborne pathogen threatening food safety and public *** the emergence of methicillin-resistant Staphylococcus aureus(MRSA)increased the difficulty of *** *** is a crucial virulence factor of *** staphyloxanthin production could help the host immune system counteract the invading *** *** this study,we first screened for staphyloxanthin inhibitors using a virtual screening *** outcome of the virtual screening method resulted in the identification of eugenol(300μg/mL),which significantly inhibits the staphyloxanthin production in *** ATCC 29213,*** Newman,MRSA ATCC 43300 and MRSA ATCC BAA1717by 84.2%,63.5%,68.1%,and 79.5%,*** outcome of the growth curve assay,field-emission scanning electron,and confocal laser scanning microscopy analyses confirmed that eugenol at the test concentration did not affect the morphology and growth of ***,the survival rate of *** ATCC 29213 and MRSA ATCC 43300 under H_(2)O_(2) pressure decreased to 51.9%and 45.5%in the presence of eugenol,*** quantitative RT-PCR and molecular simulation studies revealed that eugenol targets staphyloxanthin biosynthesis by downregulating the transcription of the crtM gene and inhibiting the activity of the CrtM *** together,we first determined that eugenol was a prominent compound for staphyloxanthin inhibitor to combat *** especially MRSA infections.

关键词： Staphylococcus aureus Staphyloxanthin Eugenol Virtual screening 4 4’-Diapophytoene synthase(CrtM)

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Exploring lysosomal biology: current approaches and methods

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Biophysics Reports 2024年第2期10卷 111-120页

作者： Qiuyuan Yin Chonglin Yang State Key Laboratory of Conservation and Utilization of Bio-resources in Yunnan and Center for life sciences School of Life Sciences Yunnan University Southwest United Graduate school

Lysosomes are the degradation centers and signaling hubs in the cell. Lysosomes undergo adaptation to maintain cell homeostasis in response to a wide variety of cues. Dysfunction of lysosomes leads to aging and severe diseases including lysosomal storage diseases(LSDs), neurodegenerative disorders,and cancer. To understand the complexity of lysosome biology, many research approaches and tools have been developed to investigate lysosomal functions and regulatory mechanisms in diverse experimental systems. This review summarizes the current approaches and tools adopted for studying lysosomes, and aims to provide a methodological overview of lysosomal research and related fields.

关键词： Lysosome Method Cultured cell C. elegans Mice

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Females adopt sexual catalepsy to facilitate mating

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Current Zoology 2024年第2期70卷 174-181页

作者： Jihe Liu Keke Liu Yu Tang Weihua Wang Xiang Xu Jianhui Liang Yonghong Xiao Mark A.Elgar College of life sciences Jinggangshan UniversityJi'anJiangxi 343009China Pharmaceutical Center Tsinghua UniversityBeijing 100084China College of life sciences Hunan Normal UniversityChangshaHunan 410081China school of Pharmaceutical sciences Peking UniversityBeijing 100083China school of Biosciences University of MelbourneMelbourneVictoria 3010Australia school of life sciences and Technology Tongii UniversityShanghai 200092China

Theory predicts that males and females of dioecious species typically engage in an evolutionary sexual conflict over the frequency and choice of mating *** sexual cannibalism,a particularly dramatic illustration of this conflict,is widespread in certain animal taxa including ***,females of some funnel weaving spiders that are generally aggressive to conspecifics enter a cataleptic state after male courtship,ensuring the males can mate without risk of *** this study,we demonstrated that the physical posture and duration,metabo-lites,and central neurotransmitters of females of Aterigena aculeata in sexual catalepsy closely resemble females in thanatosis but are distinct from those in anesthesia,indicating that the courted females feign death to eliminate the risk of potentially aggressive responses and thereby allow preferred males to *** the taxonomically widespread thanatosis,which generally represents a deceptive visual signal that acts against the interest of the receivers,sexual catalepsy of females in the funnel weaving spiders may deliver a sexual-receptive signal to the courting males and thereby benefit both the signal senders and ***,sexual catalepsy in *** may not reflect a conflict butrather a confluence of interest betweenthe sexes.

关键词： female catalepsy funnel weaving spiders mate choice mating strategy sexual behavior.

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