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Probiotics intervention in colorectal cancer:From traditional approaches to novel strategies

Chinese Medical Journal 2024年第1期137卷 8-20页

作者： Suki Ha Xiang Zhang Jun Yu Institute of digestive disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina

The intestine harbors a large population of microorganisms that interact with epithelial cells to maintain host healthy physiological status.These intestinal microbiota engage in the fermentation of non-digestible nutrients and produce beneficial metabolites to regulate host homeostasis,metabolism,and immune response.The disruption of microbiota,known as dysbiosis,has been implicated in many intestinal diseases,including colorectal cancer(CRC).As the third most common cancer and the second leading cause of cancer-related death worldwide,CRC poses a significant health burden.There is an urgent need for novel interventions to reduce CRC incidence and improve clinical outcomes.Modulating the intestinal microbiota has emerged as a promising approach for CRC prevention and treatment.Current research efforts in CRC probiotics primarily focus on reducing the incidence of CRC,alleviating treatment-related side effects,and potentiating the efficacy of anticancer therapy,which is the key to successful translation to clinical practice.This paper aims to review the traditional probiotics and new interventions,such as next-generation probiotics and postbiotics,in the context of CRC.The underlying mechanisms of probiotic anti-cancer effects are also discussed,including the restoration of microbial composition,reinforcement of gut barrier integrity,induction of cancer cell apoptosis,inactivation of carcinogens,and modulation of host immune response.This paper further evaluates the novel strategy of probiotics as an adjuvant therapy in boosting the efficacy of chemotherapy and immunotherapy.Despite all the promising findings presented in studies,the evaluation of potential risks,optimization of delivery methods,and consideration of intra-patient variability of gut microbial baseline must be thoroughly interpreted before bench-to-bedside translation.

关键词： colorectal cancer probiotics gut microbiota dysbiosis adjuvant therapy immune modulation gut barrrier

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Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第2期21卷 144-162页

作者： Yang Song Harry CH Lau Xiang Zhang Jun Yu Institute of digestive disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina Department of Gastroenterology Zhongshan Hospital Xiamen UniversityXiamen 361004China

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

关键词： Bile acid gut microbiota hepatocellular carcinoma therapeutics microbiota modulation

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Multimodal Nature of the Single-cell Primate Brain Atlas:Morphology,Transcriptome,Electrophysiology,and Connectivity

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Neuroscience Bulletin 2024年第4期40卷 517-532页

作者： Yuhui Shen Mingting Shao Zhao-Zhe Hao Mengyao Huang Nana Xu Sheng Liu state key laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou510060China Guangdong Province key laboratory of Brain Function and disease Guangzhou510080China

Primates exhibit complex brain structures that augment cognitive function.The neocortex fulfills high-cognitive functions through billions of connected neurons.These neurons have distinct transcriptomic,morphological,and electrophysiological properties,and their connectivity principles vary.These features endow the primate brain atlas with a multimodal nature.The recent integration of next-generation sequencing with modified patch-clamp techniques is revolutionizing the way to census the primate neocortex,enabling a multimodal neuronal atlas to be established in great detail:(1)single-cell/single-nucleus RNA-seq technology establishes high-throughput transcriptomic references,covering all major transcriptomic cell types;(2)patch-seq links the morphological and electrophysiological features to the transcriptomic reference;(3)multicell patch-clamp delineates the principles of local connectivity.Here,we review the applications of these technologies in the primate neocortex and discuss the current advances and tentative gaps for a comprehensive understanding of the primate neocortex.

关键词： Neuron Brain atlas Patch-seq Connectivity Primate

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Albizzia chinensis(Osbeck)Merr extract YS ameliorates ethanol-induced acute gastric ulcer injury in rats by regulating NRF2 signaling pathway

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Animal Models and Experimental Medicine 2024年第3期7卷 275-282页

作者： Bo Tang Liangning Li Yuanzhi Yu Guibin Wang Shuanggang Ma Shishan Yu Jianjun Zhang Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina state key laboratory of digestive Health BeijingChina state key laboratory of Bioactive Substance and Function of Natural Medicines BeijingChina

Background:Around the world,there is a high incidence of gastric ulcers.YS,an extract from the Chinese herb Albizzia chinensis(Osbeck)Merr,has potential therapeutic applications for gastrointestinal diseases.Here we elucidated the protective effect and underlying mechanism of action of YS on gastric ulcer in rats injured by ethanol.Methods:The ethanol-i nduced gastric ulcer rat model was used to assess the protective effect of YS.A pathological examination of gastric tissue was performed by H&E staining.GES-1 cells damaged by hydrogen peroxide were used to simulate oxidative damage in gastric mucosal epithelial cells.Endogenous NRF2 was knocked down using small interfering RNA.Immunoprecipitation was used to detect ubiquitination of NRF2.Co-i mmunoprecipitation was used to detect the NRF2-Keap1 interaction.Results:YS(10 and 30 mg/kg,i.g.)significantly reduced the ulcer index,decreased MDA level,and increased SOD and GSH levels in gastric tissues damaged by ethanol.YS promoted NRF2 translocation from cytoplasm to nucleus and enhanced the NQO1 and HO-1 expression levels in injured rat gastric tissue.In addition,YS regulated NQO1 and HO-1 via NRF2 in H_(2)O_(2)-i nduced oxidative injured GES-1 cells.Further studies on the underlying mechanism indicated that YS reduced the interaction between NRF2 and Keap1 and decreased ubiquitylation of NRF2,thereby increasing its stability and expression of downstream factors.NRF2 knockdown abolished the effect of YS on MDA and SOD in GES-1 cells treated with H_(2)O_(2).Conclusion:YS reduced the NRF2-Keap1 interaction,promoting NRF2 translocation into the nucleus,which increasing the transcription and translation of NQO1 and HO-1 and improved the antioxidant capacity of rat stomach.

关键词： antioxidative ethanol gastric ulcer NRF2 YS

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M6PR interacts with the HA2 subunit of influenza A virus to facilitate the fusion of viral and endosomal membranes

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Science China(Life Sciences) 2024年第3期67卷 579-595页

作者： Yuzhen Hu Li Jiang Guangwen Wang Yangming Song Zhibo Shan Xuyuan Wang Guohua Deng Jianzhong Shi Guobin Tian Xianying Zeng Liling Liu Hualan Chen Chengjun Li state key laboratory for Animal disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membranes. In this study, we identified cation-dependent mannose-6-phosphate receptor(M6PR) as a crucial host factor for the replication of IAV. We found that siRNA knockdown of M6PR expression significantly reduced the growth titers of different subtypes of IAV, and that the inhibitory effect of M6PR siRNA treatment on IAV growth was overcome by the complement of exogenously expressed M6PR. When A549 cells were treated with siRNA targeting M6PR,the nuclear accumulation of viral nucleoprotein(NP) was dramatically inhibited at early timepoints post-infection, indicating that M6PR engages in the early stage of the IAV replication cycle. By investigating the role of M6PR in the individual entry and post-entry steps of IAV replication, we found that the downregulation of M6PR expression had no effect on attachment, internalization, early endosome trafficking,or late endosome acidification. However, we found that M6PR expression was critical for the fusion of viral envelope and late endosomal membranes. Of note, M6PR interacted with the hemagglutinin(HA) protein of IAV, and further studies showed that the lumenal domain of M6PR and the ectodomain of HA2 mediated the interaction and directly promoted the fusion of the viral and late endosomal membranes,thereby facilitating IAV replication. Together, our findings highlight the importance of the M6PR–HA interaction in the fusion of viral and late endosomal membranes during IAV replication.

关键词： influenza A virus M6PR HA membrane fusion late endosome

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Magnitude and direction of temperature variability affect hospitalization for myocardial infarction and stroke:population-based evidence from Guangzhou,China

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Frontiers of Environmental Science & Engineering 2024年第3期18卷 1-11页

作者： Zhou Yang Murui Zheng Ze-Lin Yan Hui Liu Xiangyi Liu Jie-Qi Jin Jiagang Wu Chun-Quan Ou state key laboratory of Organ Failure Research Department of BiostatisticsGuangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public HealthSouthern Medical UniversityGuangzhou 510515China Guangzhou Center for disease Control and Prevention Guangzhou 510440China

Relationships between nonoptimal temperatures and cardiovascular disease(CVD)mortality have been well documented.However,evidence of the association between temperature variability(TV)and CVD morbidity is limited.This study aimed to quantify the risk and burden of CVD-related hospitalization associated with the magnitude and direction of TV.Data on meteorology and population-based hospitalizations for myocardial infarction(MI)and stroke were collected in Guangzhou,China,from 2013 to 2017.Hourly temperature variability(HTV)was measured as the standard deviation of hourly temperature records over specific exposure days.The direction(upward or downward)of HTV was defined as the average daily mean temperature change relative to that of the previous day during the exposure period.Quasi-Poisson regression was applied to assess the impact of HTV after adjusting for the daily mean temperature,and the hospitalization fractions attributable to HTV were calculated.A 1℃-increase in HTV was significantly associated with a 2.24%and 1.72%increase in hospitalizations for MI and hemorrhagic stroke(HS)at lag 0–1 d,respectively,and a 1.55%increase in hospitalizations for ischemic stroke(IS)at lag 0–3 d.During the study period,5.99%,4.64%,and 4.53%of MI,HS,and IS hospitalizations,respectively,were attributable to HTV.The upward TV exerts acute effects on CVD hospital admissions,whereas the impact of downward TV generally lags.These findings highlight the importance of the magnitude and direction of temperature fluctuations,in addition to the mean level,in assessing the adverse health impacts of temperature variations.

关键词： Hourly temperature variability Cardiovascular Hospitalization Direction China

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Cellular zinc metabolism and zinc signaling:from biological functions to diseases and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第2期9卷 401-441页

作者： Bonan Chen Peiyao Yu Wai Nok Chan Fuda Xie Yigan Zhang Li Liang Kam Tong Leung Kwok Wai Lo Jun Yu Gary M.K.Tse Wei Kang Ka Fai To Department of Anatomical and Cellular Pathology State Key Laboratory of Translational OncologyPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina state key laboratory of digestive disease Institute of Digestive DiseaseThe Chinese University of Hong KongHong KongChina CUHK-Shenzhen Research Institute The Chinese University of Hong KongShenzhenChina Department of Pathology Nanfang Hospital and Basic Medical CollegeSouthern Medical UniversityGuangdong Province Key Laboratory of Molecular Tumor PathologyGuangzhouChina Institute of Biomedical Research Taihe HospitalHubei University of MedicineShiyanChina Department of Pediatrics The Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

Zinc metabolism at the cellular level is critical for many biological processes in the body.A key observation is the disruption of cellular homeostasis,often coinciding with disease progression.As an essential factor in maintaining cellular equilibrium,cellular zinc has been increasingly spotlighted in the context of disease development.Extensive research suggests zinc’s involvement in promoting malignancy and invasion in cancer cells,despite its low tissue concentration.This has led to a growing body of literature investigating zinc’s cellular metabolism,particularly the functions of zinc transporters and storage mechanisms during cancer progression.Zinc transportation is under the control of two major transporter families:SLC30(ZnT)for the excretion of zinc and SLC39(ZIP)for the zinc intake.Additionally,the storage of this essential element is predominantly mediated by metallothioneins(MTs).This review consolidates knowledge on the critical functions of cellular zinc signaling and underscores potential molecular pathways linking zinc metabolism to disease progression,with a special focus on cancer.We also compile a summary of clinical trials involving zinc ions.Given the main localization of zinc transporters at the cell membrane,the potential for targeted therapies,including small molecules and monoclonal antibodies,offers promising avenues for future exploration.

关键词： metabolism invasion involvement

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UniBind:a novel artificial intelligence-based prediction model for SARS-CoV-2 infectivity and variant evolution

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Signal Transduction and Targeted Therapy 2024年第1期9卷 14-15页

作者： Qihong Yan Jincun Zhao state key laboratory of Respiratory disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina

In a recent study published in Nature Medicine,Wang et al.developed an excellent framework called UniBind based on artificial intelligence(AI),which enables accurately predicting infectivity of SARS-CoV-2 variants and evolutionary trends of future viral variants.1 This computational method holds the possibility to not only serve as a valuable early-warning tool for monitoring potential pathogenic SARS-CoV-2 variants but also facilitate fundamental research on protein-protein interactions(PPIs).

关键词： artificial Bind prediction

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Micelle-directed self-assembly of single-crystal-like mesoporous stoichiometric oxides for high-performance lithium storage

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National Science Review 2024年第4期11卷 195-205页

作者： Yanhua Wan Changyao Wang Xingmiao Zhang Yang Yin Mengmeng Liu Bing Ma Linlin Duan Yuzhu Ma Wei Zhang Changlin Zheng Dongliang Chao Fei Wang Yongyao Xia Wei Li Department of Chemistry Laboratory of Advanced Materials Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials State Key Laboratory of Molecular Engineering of Polymers College of Chemistry and Materials ScienceFudan University state key laboratory of Surface Physics and Department of Physics Fudan University

Due to their uncontrollable assembly and crystallization process,the synthesis of mesoporous metal oxide single crystals remains a formidable challenge.Herein,we report the synthesis of single-crystal-like mesoporous Li2TiSiO5by using soft micelles as templates.The key lies in the atomic-scale self-assembly and step-crystallization processes,which ensure the formation of single-crystal-like mesoporous Li2TiSiO5microparticles via an oriented attachment growth mechanism under the confinement of an in-situ formed carbon matrix.The mesoporous Li2TiSiO5anode achieves a superior rate capability(148 mAh g-1at5.0 A g-1) and outstanding long-term cycling stability(138 mAh g-1after 3000 cycles at 2.0 A g-1) for lithium storage as a result of the ultrafast Li+diffusion caused by penetrating mesochannels and nanosized crystal frameworks（5-10 nm）.In comparison,bulk Li2TiSiO5exhibits poor rate capability and cycle performance due to micron-scale diffusion lengths.This method is very simple and reproducible,heralding a new way of designing and synthesizing mesoporous single crystals with controllable frameworks and chemical functionalities.

关键词： mesoporous materials micelles single-crystal-like Li2TiSiO5 lithium-ion batteries

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Conversion of a single-layer ANN to photonic SNN for pattern recognition

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Science China(Information Sciences) 2024年第1期67卷 261-270页

作者： Yanan HAN Shuiying XIANG Tianrui ZHANG Yahui ZHANG Xingxing GUO Yuechun SHI state key laboratory of Integrated Service Networks State Key Discipline Laboratory of Wide Bandgap Semiconductor TechnologyXidian University Yongjiang laboratory

This work presents a complete conversion scheme for photonic spiking neural networks(SNNs).We verified that the output of an artificial neural network(ANN) trained with the simulated optical activation function can be directly converted into the spike rate of a photonic spiking neuron model.To reveal the feasibility of hardware implementation,we considered the effects of different bit precisions of data and weight,noise level,and bias current mismatch on the converted results.The proposed scheme was evaluated using the Deterding vowel,IRIS,TIDIGITS,and MNIST datasets for pattern recognition,and achieved mean accuracies of 95.80%,98.67%,96.19%,and 92.33%,respectively.The proposed scheme can convert an ANN into a photonic SNN with almost no precision loss,and the performance was comparable to that of an ANN trained with the rectified linear unit function.The proposed scheme can enable the high-performance implementation of photonic SNNs.

关键词： photonic SNN conversion optical computing pattern recognition artificial neural network

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