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Electrobiocorrosion by microbes without outer-surface cytochromes

mLife 2024年第1期3卷 110-118页

作者： Dawn E.Holmes Trevor L.Woodard Jessica A.Smith Florin Musat Derek R.Lovley Department of Microbiology University of Massachusetts AmherstAmherstMassachusettsUSA Department of Physical and Biological Science Western New England UniversitySpringfieldMassachusettsUSA Department of Biomolecular Sciences Central Connecticut State UniversityNew BritainConnecticutUSA Department of biology Section for MicrobiologyAarhus UniversityAarhusDenmark Department of molecular biology and Biotechnology Facuity of Biology and GeologyBabes-Bolyai UniversityCluj-NapocaRomania

Anaerobic microbial corrosion of iron-containing metals causes extensive economic damage.Some microbes are capable of direct metal-to-microbe electron transfer(electrobiocorrosion),but the prevalence of electrobiocorrosion among diverse methanogens and acetogens is poorly understood because of a lack of tools for their genetic manipulation.Previous studies have suggested that respiration with 316L stainless steel as the electron donor is indicative of electrobiocorrosion,because,unlike pure Fe^(0),316L stainless steel does not abiotically generate H2 as an intermediary electron carrier.Here,we report that all of the methanogens(Methanosarcina vacuolata,Methanothrix soehngenii,and Methanobacterium strain IM1)and acetogens(Sporomusa ovata and Clostridium ljungdahli)evaluated respired with pure Fe^(0)as the electron donor,but only M.vacuolata,Mx.soehngeni,and S.ovata were capable of stainless steel electrobiocorrosion.The electrobiocorrosive methanogens re-quired acetate as an additional energy source in order to produce methane from stainless steel.Cocultures of S.ovata and Mx.soehngeni demonstrated how acetogens can provide acetate to methanogens during corrosion.Not only was Meth-anobacterium strain IM1 not capable of electrobiocorrosion,but it also did not accept electrons from Geobacter metal-lireducens,an effective electron-donating partner for direct interspecies electron transfer to all methanogens that can directly accept electrons from Fe^(0).The finding that M.vacuolata,Mx.soehngeni,and S.ovata are capable of electrobiocorrosion,despite a lack of the outer-surface c-type cytochromes previously found to be important in other electrobiocorrosive microbes,demonstrates that there are multiple microbial strategies for making electrical contact with Fe^(0).

关键词： acetogen corrosion Fe^(0) methanogen stainless steel

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Anoctamin 4 defines glucose-inhibited neurons in the ventromedial hypothalamus

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Neural Regeneration Research 2024年第6期19卷 1177-1178页

作者： Longlong Tu Yanlin He Yong Xu Children's Nutrition Research Center Department of Pediatrics Baylor College of Medicine Department of molecular and Cellular biology Section of Endocrinology Diabetes and Metabolism Department of Medicine Baylor College of Medicine Brain Glycemic and Metabolism Control Department Pennington Biomedical Research Center Louisiana State University

Glucose is the primary fuel source of the brain,and therefore glucose levels need to be tightly regulated and maintained within a small physiological range.Certainly,the body necessitates a stable supply of energy mainly provided by glucose for various bodily functions.High or low blood glucose levels would impair the physiological functions of various organs of the body.Prolonged high blood glucose(i.e.,

关键词： HYPOGLYCEMIA

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Stereoselective recognition of morphine enantiomers by μ-opioid receptor

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National Science Review 2024年第3期11卷 183-191页

作者： Yibo Wang Van A.Ngo Xiaohui Wang Laboratory of Chemical biology Changchun Institute of Applied ChemistryChinese Academy of Sciences Advanced Computing for Life Sciences and Engineering Group Science Engagement Section National Center for Computational Sciences Oak Ridge National Lab School of Applied Chemistry and Engineering University of Science and Technology of China Beijing National Laboratory for molecular Sciences

Stereospecific recognition of chiral molecules plays a crucial role in biological systems. The μ-opioid receptor（MOR） exhibits binding affinity towards（-）-morphine, a well-established gold standard in pain management, while it shows minimal binding affinity for the（+）-morphine enantiomer, resulting in a lack of analgesic activity. Understanding how MOR stereoselectively recognizes morphine enantiomers has remained a puzzle in neuroscience and pharmacology for over half-a-century due to the lack of direct observation techniques. To unravel this mystery, we constructed the binding and unbinding processes of morphine enantiomers with MOR via molecular dynamics simulations to investigate the thermodynamics and kinetics governing MOR's stereoselective recognition of morphine enantiomers. Our findings reveal that the binding of（-）-morphine stabilizes MOR in its activated state, exhibiting a deep energy well and a prolonged residence time. In contrast,（+）-morphine fails to sustain the activation state of MOR.Furthermore, the results suggest that specific residues, namely D1142.50and D1473.32, are deprotonated in the active state of MOR bound to（-）-morphine. This work highlights that the selectivity in molecular recognition goes beyond binding affinities, extending into the realm of residence time.

关键词： stereoselective recognition thermodynamics and kinetics residence time morphine enantiomers μ-opioid receptor

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DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

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Genes & Diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli Shan Zhou Xingfang Yu Kanaga Sabapathy Yong Li Department of Medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA Division of Cellular&molecular Research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense mutant.However,there are currently no approved targeted therapies or immunotherapies against mutant p53.Here,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in vitro.We then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic effects.Our results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type p53.In cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular cytotoxicity.We made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 alleles.In vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in mice.The administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 antibody.These results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

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The transcriptional control of LcIDL1–LcHSL2 complex by LcARF5 integrates auxin and ethylene signaling for litchi fruitlet abscission

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Journal of Integrative Plant biology 2024年第6期66卷 1206-1226页

作者： Xingshuai Ma Zidi He Ye Yuan Zhijian Liang Hang Zhang Vilde Olsson Lalun Zhuoyi Liu Yanqing Zhang Zhiqiang Huang Yulian Huang Jianguo Li Minglei Zhao State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources Guangdong Laboratory for Lingnan Modern Agriculture Key Laboratory of Biology and Genetic Improvement of Horticultural Crops(South China) Ministry of Agriculture and Rural Affairs Guangdong Litchi Engineering Research Center College of Horticulture South China Agricultural University Dongguan Botanical Garden section for Genetics and Evolutionary biology Department of Biosciences University of Oslo College of Agriculture Guangxi University

At the physiological level, the interplay between auxin and ethylene has long been recognized as crucial for the regulation of organ abscission in plants. However, the underlying molecular mechanisms remain unknown. Here, we identified transcription factors involved in indoleacetic acid(IAA) and ethylene(ET)signaling that directly regulate the expression of INFLORESCENCE DEFICIENT IN ABSCISSION(IDA)and its receptor HAESA(HAE), which are key components initiating abscission. Specifically, litchi IDAlike 1(LcIDL1) interacts with the receptor HAESA-like2(LcHSL2). Through in vitro and in vivo experiments,we determined that the auxin response factor LcARF5 directly binds and activates both LcIDL1 and LcHSL2. Furthermore, we found that the ETHYLENE INSENSITIVE 3-like transcription factor LcEIL3 directly binds and activates LcIDL1. The expression of IDA and HSL2 homologs was enhanced in Lc ARF5and Lc EIL3 transgenic Arabidopsis plants, but reduced in ein3 eil1 mutants. Consistently, the expressions of LcIDL1 and LcHSL2 were significantly decreased in Lc ARF5-and LcEIL3-silenced fruitlet abscission zones(FAZ), which correlated with a lower rate of fruitlet abscission. Depletion of auxin led to an increase in 1-aminocyclopropane-1-carboxylic acid(the precursor of ethylene) levels in the litchi FAZ, followed by abscission activation. Throughout this process, LcRF5 and LcEIL3 were induced in the FAZ. Collectively, our findings suggest that the molecular interactions between litchi AUXIN RESPONSE FACTOR 5(LcARF5)–LcIDL1/LcHSL2 and LcEIL3–LcIDL1 signaling modules play a role in regulating fruitlet abscission in litchi and provide a long-sought mechanistic explanation for how the interplay between auxin and ethylene is translated into the molecular events that initiate abscission.

关键词： auxin ethylene fruit abscission IDA–HAE/HSL2 litchi

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Circulating tumor DNA and its role in detection, prognosis and therapeutics of hepatocellular carcinoma

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Chinese Journal of Cancer Research 2024年第2期36卷 195-214页

作者： Sana Rashid Yingchuan Sun Umair Ali Khan Saddozai Sikandar Hayyat Muhammad Usman Munir Muhammad Usman Akbar Muhammad Babar Khawar Zhiguang Ren Xinying Ji Malik Ihsan Ullah Khan Institute of molecular biology and Biotechnology University of LahoreLahore 54590Pakistan Department of Internal Oncology(section Ⅰ) Xuchang Municipal Central HospitalXuchang 461000China Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225001China Australian Institute for Bioengineering&Nanotechnology the University of QueenslandBrisbane 4072Australia Gomal Center of Biochemistry and Biotechnology Gomal UniversityDera Ismail Khan 29111Pakistan Applied molecular biology and Biomedicine Lab Department of ZoologyUniversity of NarowalNarowal Punjab 51600Pakistan Kaifeng Municipal Key Laboratory for Infection and Biosafety Henan International Joint Laboratory of Nuclear Protein RegulationSchool of Basic Medical SciencesHenan UniversityKaifeng 475004China Faculty of Basic Medical Subjects Shu-Qing Medical College of ZhengzhouZhengzhou 450064China Department of Medicine Huaxian County People's HospitalHuaxian 456400China

Hepatocellular carcinoma(HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers;the most prominent is circulating tumor DNA(ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction(PCR) [emulsion PCR(ePCR), digital PCR(dPCR), and bead, emulsion, amplification, magnetic(BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection,treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations(either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1;2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF;3) DNA methylation(RASSF1A, SEPT9, KMT2C and CCNA2);4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1;and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results.Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.

关键词： Hepatocellular carcinoma circulating tumor DNA biomarkers single nucleotide variations diagnosis prognosis

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Fetal lung growth predicts the risk for early-life respiratory infections and childhood asthma

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World Journal of Pediatrics 2024年第5期20卷 481-495页

作者： Dimitra E.Zazara Olympia Giannou Steven Schepanski Mirja Pagenkemper Anastasios D.Giannou Maike Pincus Ioannis Belios Stefan Bonn Ania C.Muntau Kurt Hecher Anke Diemert Petra Clara Arck Division for Experimental Feto-Maternal Medicine Department of Obstetrics and Fetal MedicineUniversity Medical Center Hamburg-Eppendorf(UKE)Martinistraße 5220251HamburgGermany University Children’s Hospital UKEHamburgGermany Computer Engineering and Informatics Department Polytechnic SchoolUniversity of PatrasPatrasGreece Institute of Developmental Neurophysiology Center for Molecular Neurobiology Hamburg(ZMNH)UKEHamburgGermany Department of Obstetrics and Fetal Medicine UKEHamburgGermany Department of General Visceral and Thoracic SurgeryUKEHamburgGermany section of molecular Immunology and Gastroenterology I.Department of MedicineUKEHamburgGermany Pediatrics and Pediatric Pneumology Practice BerlinGermany Institute of Medical Systems biology ZMNHUKEHamburgGermany Hamburg Center for Translational Immunology UKEHamburgGermany

Background Early-life respiratory infections and asthma are major health burdens during childhood.Markers predicting an increased risk for early-life respiratory diseases are sparse.Here,we identified the predictive value of ultrasound-monitored fetal lung growth for the risk of early-life respiratory infections and asthma.Methods Fetal lung size was serially assessed at standardized time points by transabdominal ultrasound in pregnant women participating in a pregnancy cohort.Correlations between fetal lung growth and respiratory infections in infancy or early-onset asthma at five years were examined.Machine-learning models relying on extreme gradient boosting regressor or classifier algorithms were developed to predict respiratory infection or asthma risk based on fetal lung growth.For model development and validation,study participants were randomly divided into a training and a testing group,respectively,by the employed algorithm.Results Enhanced fetal lung growth throughout pregnancy predicted a lower early-life respiratory infection risk.Male sex was associated with a higher risk for respiratory infections in infancy.Fetal lung growth could also predict the risk of asthma at five years of age.We designed three machine-learning models to predict the risk and number of infections in infancy as well as the risk of early-onset asthma.The models’R2 values were 0.92,0.90 and 0.93,respectively,underscoring a high accuracy and agreement between the actual and predicted values.Influential variables included known risk factors and novel predictors,such as ultrasound-monitored fetal lung growth.Conclusion Sonographic monitoring of fetal lung growth allows to predict the risk for early-life respiratory infections and asthma.

关键词： Asthma Child risk Early-life respiratory infections Prenatal lung development Sexual dimorphism

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Role of pituitary adenylate cyclase-activating polypeptide in peripheral nerve regeneration:a cellular and molecular perspective

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Neural Regeneration Research 2024年第7期19卷 1429-1430页

作者： Grazia Maugeri Velia D’Agata section of Anatomy Histology and Movement SciencesDepartment of Biomedical and Biotechnological SciencesUniversity of CataniaCataniaItaly

Neuro regeneration is a very complex phenomenon characterized by the generation of new neurons and synapses,involving connections between adjacent cells and axonal projections.Neuroregeneration supplies additional lon... 详细信息

关键词： replace functional regeneration

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The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

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Cancer biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center Research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and beyond.Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of cancer.Looking back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed.The quantity and quality of these samples will be compatible with omics analyses.All biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

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A simplified noncryogenic strategy to transport mesenchymal stem cells: Potential applications in cell therapy and regenerative medicine

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Genes & Diseases 2024年第3期11卷 26-29页

作者： Xiangyu Dong Yannian Gou Meichun Guo Jiamin Zhong Aohua Li Ailing Hao Wei Zeng Rex C.Haydon Hue H.Luu Russell R.Reid Tongchuan He Yan Xu Jiaming Fan Ministry of Education Key Laboratory of Diagnostic Medicine And Department of Clinical BiochemistryCollege of Laboratory MedicineChongqing Medical UniversityChongqing 400016China molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Laboratory of Craniofacial Suture biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Institute of Sports Medicine Beijing Key Laboratory of Sports InjuriesPeking University Third HospitalBejing 100191China

With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport strategies.Except for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods.

关键词： transport methods simplified

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