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Rational design of a single-component mRNA vaccine against orthopoxvirus and SARS-CoV-2

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Science China(Life Sciences) 2024年第6期67卷 1311-1313页

作者： Yilong Yang Xiaofan Zhao Yu Li Xiaodong Zai Xinyi Wang Yue Zhang Xiaolin Wang Peng Lv Jun Zhang Lihua Hou Junjie Xu Wei Chen Laboratory of Advanced biotechnology Beijing Institute of BiotechnologyAcademy of Military Medical SciencesBeijing 100071China

Dear Editor,In the era of COVID-19,the prevalence of viruses from other families poses new threats to humans.Despite the eradication of smallpox in 1980,the global outbreak of monkeypox in 2022(Lum et al.,2022;Nuzzo et al.,2022)alerted that the re-emerging orthopoxvirus(OPXV)remained a persistent threat to global health.OPXV includes a number of viruses with a broad host range,including variola virus(VARV),monkeypox virus(MPXV),vaccinia virus(VACV).

关键词： al. vaccine Rational

Cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance

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Genes & Diseases 2024年第1期11卷 189-204页

作者： Ebrahim H.Maleki Ahmad Reza Bahrami Maryam M.Matin Department of Biology Faculty of ScienceFerdowsi University of Mashhad*** MashhadIran Jagiellonian Centre for Experimental Therapeutics(JCET) Jagiellonian University31-007 KrakowPoland Doctoral School of Exact and Natural Sciences Jagiellonian University30-348 KrakowPoland Industrial biotechnology research Group Institute of BiotechnologyFerdowsi University of Mashhad*** MashhadIran Novel Diagnostics and Therapeutics research Group Institute of BiotechnologyFerdowsi University of Mashhad***MashhadIran Stem Cell and Regenerative Medicine research Group Iranian Academic Center for EducationCulture and Research(ACECR)Khorasan Razavi Branch917751376 MashhadIran

Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology,as it represents a major obstacle to effective cancer treatment.Since tumor cells are highly diverse at genetic,epigenetic,and phenotypic levels,intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects,and recurrence of the tumor.Based on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment;herein,we aim to establish a comprehensive definition for adaptation of neoplastic cells against therapy.We discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy:"resistant"and"tolerant"popula-tions.Furthermore,this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer cells.Beyond understanding the mechanisms under-lying the quiescence,it provides an insightful perspective on cancer stem cells(CsCs)and their dual and intertwined functions based on their cell cycle state in response to treatment.More-over,CSCs,epithelial-mesenchymal transformed cells,circulating tumor cells(CTCs),and disseminated tumor cells(DTCs),which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in tumors.Overall,increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions,and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.

关键词： Cancer stem cells(CSCs) Carcinoma Cell cycle heterogeneity Quiescence Therapy resistance Therapy tolerance Tumor dormancy

Lactiplantibacillus plantarum FRT4 attenuates high-energy low-protein dietinduced fatty liver hemorrhage syndrome in laying hens through regulating gut-liver axis

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Journal of Animal Science and biotechnology 2024年第3期15卷 1292-1311页

作者： Daojie Li Hongying Cai Guohua Liu Yunsheng Han Kai Qiu Weiwei Liu Kun Meng Peilong Yang Key Laboratory of Feed biotechnology of Ministry of Agriculture and Rural Affairs Institute of Feed ResearchChinese Academy of Agricultural SciencesBeijing 100081China National Engineering research Center of Biological Feed Beijing 100081China

Background Fatty liver hemorrhage syndrome(FLHS)becomes one of the most major factors resulting in the laying hen death for caged egg production.This study aimed to investigate the therapeutic effects of Lactiplantibacillus plan-tarum(Lp.plantarum)FRT4 on FLHS model in laying hen with a focus on liver lipid metabolism,and gut microbiota.Results The FLHS model of laying hens was established by feeding a high-energy low-protein(HELP)diet,and the treatment groups were fed a HELP diet supplemented with differential proportions of Lp.plantarum FRT4.The results indicated that Lp.plantarum FRT4 increased laying rate,and reduced the liver lipid accumulation by regulating lipid metabolism(lipid synthesis and transport)and improving the gut microbiota composition.Moreover,Lp.plan-tarum FRT4 regulated the liver glycerophospholipid metabolism.Meanwhile,“gut-liver”axis analysis showed that there was a correlation between gut microbiota and lipid metabolites.Conclusions The results indicated that Lp.plantarum FRT4 improved the laying performance and alleviated FLHS in HELP diet-induced laying hens through regulating“gut-liver”axis.Our findings reveal that glycerophospholipid metabolism could be the underlying mechanism for the anti-FLHS effect of Lp.plantarum FRT4 and for future use of Lp.plantarum FRT4 as an excellent additive for the prevention and mitigation of FLHS in laying hens.

关键词： Fatty liver hemorrhage syndrome Gut microbiota Lactiplantibacillus plantarum FRT4 Laying hens Lipid metabolism

Multi-omics:Powerful accelerator for uncovering plant specialized metabolic pathways:The case of leonurine

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Molecular Plant 2024年第1期17卷 13-15页

作者： Priyanka Gupta Anuj Sharma Dinesh A.Nagegowda Molecular Plant Biology and biotechnology Lab CSIR-Central Institute of Medicinal and Aromatic PlantsResearch CentreBengaluru 560065India Academy of Scientific and Innovative research Ghaziabad 201002India

As sessile organisms,plants employ a unique adaptive strategy to survive harsh terrestrial environments and defend against or interact with coevolving animals and microorganisms.This strategy involves expanding their metabolic systems,resulting in the production of plant specialized metabolites(PSMs)or natural products.Chemically,PSMs constitute a highly diverse group of compounds based on their common core structure,comprising terpenoids,phenylpropanoids,benzenoids,alkaloids and nitrogen-containing compounds,glucosinolates,indoles and sulfur-containing indole compounds,phenolics,and fatty acid derivatives(Garagounis et al.,2021).

关键词： expanding alkaloids sulfur

Fine mapping and cloning of the sterility gene Bra2Ms in nonheading Chinese cabbage(Brassica rapa ssp.chinensis)

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Journal of Integrative Agriculture 2024年第4期23卷 1195-1204页

作者： Liping Song Xia Li Liguang Tang Chuying Yu Bincai Wang Changbin Gao Yanfeng Xie Xueli Zhang Junliang Wang Chufa Lin Aihua Wang Wuhan Vegetable research institute Wuhan Academy of Agricultural SciencesWuhan 430345China biotechnology and Genetic Resources institute Yunnan Academy of Agricultural SciencesKunming 650000China

The application of a male-sterile line is an ideal approach for hybrid seed production in non-heading Chinese cabbage(Brassica rapa ssp.chinensis).However,the molecular mechanisms underlying male sterility in B.rapa are still largely unclear.We previously obtained the natural male sterile line WS24-3 of non-heading Chinese cabbage and located the male sterile locus,Bra2Ms,on the A2 chromosome.Cytological observations revealed that the male sterility of WS24-3 resulted from disruption of the meiosis process during pollen formation.Fine mapping of Bra2Ms delimited the locus within a physical distance of about 129 kb on the A2 chromosome of B.rapa.The Bra039753 gene encodes a plant homeodomain(PHD)-finger protein and is considered a potential candidate gene for Bra2Ms.Bra039753 was significantly downregulated in sterile line WS24-3 compared to the fertile line at the meiotic anther stage.Sequence analysis of Bra039753 identified a 369 bp fragment insertion in the first exon in male sterile plants,which led to an amino acid insertion in the Bra039753 protein.In addition,the 369 bp fragment insertion was found to cosegregate with the male sterility trait.This study identified a novel locus related to male sterility in non-heading Chinese cabbage,and the molecular marker obtained in this study will be beneficial for the marker-assisted selection of excellent sterile lines in non-heading Chinese cabbage and other Brassica crops.

关键词： non-heading Chinese cabbage male sterility Bra2Ms fine mapping PHD-finger protein

RSPO2 as Wnt signaling enabler: Important roles in cancer development and therapeutic opportunities

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Genes & Diseases 2024年第2期11卷 788-806页

作者： Ankit Srivastava Deeksha Rikhari Sameer Srivastava Department of biotechnology Motilal Nehru National Institute of TechnologyAllahabadUttar Pradesh 211004India

R-spondins are secretory proteins localized in the endoplasmic reticulum and Golgi bodies and are processed through the secretory pathway.Among the R-spondin family,RSPO2 has emanated as a novel regulator of Wnt signaling,which has now been acknowledged in numerous in vitro and in vivo studies.Cancer is an abnormal growth of cells that proliferates and spreads uncontrollably due to the accumulation of genetic and epigenetic factors that constitutively activate Wnt signaling in various types of cancer.Colorectal cancer (CRC) begins when cells in the colon and rectum follow an indefinite pattern of division due to aberrant Wnt activation as one of the key hallmarks.Decades-long progress in research on R-spondins has demonstrated their oncogenic function in distinct cancer types,particularly CRC.As a critical regulator of the Wnt pathway,it modulates several phenotypes of cells,such as cell proliferation,invasion,migration,and cancer stem cell properties.Recently,RSPO mutations,gene rearrangements,fusions,copy number alterations,and altered gene expression have also been identified in a variety of cancers,including CRC.In this review,we addressed the recent updates regarding the recurrently altered R-spondins with special emphasis on the RSPO2 gene and its involvement in potentiating Wnt signaling in CRC.In addition to the compelling physiological and biological roles in cellular fate and regulation,we propose that RSPO2 would be valuable as a potential biomarker for prognostic,diagnostic,and therapeutic use in CRC.

关键词： CRC Gene fusion R-Spondins RSPO2 Therapeutics Wnt signaling

Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells

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Oncology research 2024年第1期32卷 101-125页

作者： ROGHAYEH GHORBANI MAHMOUD GHARBAVI ALI SHARAFI ELHAM RISMANI HAMED REZAEEJAM YOUSEF MORTAZAVI BEHROOZ JOHARI Department of Medical biotechnology School of MedicineZanjan University of Medical SciencesZanjanIran Nanotechnology research Center Ahvaz Jundishapur University of Medical SciencesAhvazIran Zanjan Pharmaceutical biotechnology research Center Zanjan University of Medical SciencesZanjanIran Department of Pharmaceutical biotechnology School of PharmacyZanjan University of Medical SciencesZanjanIran Molecular Medicine Department Biotechnology Research CenterPasteur Institute of IranPasteur AvenueTehranIran Department of Radiology Technology School of Allied Medical SciencesZanjan University of Medical SciencesZanjanIran

In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells.Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays.ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure.The physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis tests.Subsequently,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell line.The results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,respectively.The results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles.The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL.The ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic pH.The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the control.The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells.This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

关键词： Chemoradiotherapy Combination therapy Decoy oligodeoxynucleotides Myc transcription factor Selenium nanoparticle Prostate cancer

Ferroptosis mediators vary in metabolic syndrome,type-2 diabetes,and hypercholesterolemia:A meta-analysis report

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Genes & Diseases 2024年第3期11卷 109-112页

作者： Indra Kundu Ashlesha Pande Tannishtha Das Susan Idicula-Thomas Biomedical Informatics Centre Indian Council of Medical Research-National Institute for Research in Reproductive and Child HealthMumbaiMaharashtra 400012India Department of biotechnology St.Xavier's CollegeKolkataWest Bengal 700016India

Metabolic syndrome(MetS)is a complex disorder characterized by the coexistence of phenotypes such as obesity,hypertension,hyperglycemia,high triglyceride level,and low level of high-density lipoprotein cholesterol.Inflammation majorly driven by oxidative stress has an overarching role in obesity and IR-mediated mechanisms leading to Mets.Besides these factors.

关键词： obesity cholesterol diabetes

Emerging roles of microRNAs as diagnostics and potential therapeutic interest in type 2 diabetes mellitus

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World Journal of Clinical Cases 2024年第3期12卷 525-537页

作者： Dharmsheel Shrivastav Desh Deepak Singh Amity institute of biotechnology Amity University RajasthanJaipur 303002India

BACKGROUND Type 2 diabetes mellitus(T2DM)is a metabolic disease of impaired glucose utilization.Uncontrolled high sugar levels lead to advanced glycation end products(AGEs),which affects several metabolic pathways by its receptor of advanced glycation end products(RAGE)and causes diabetic complication.MiRNAs are small RNA molecules which regulate genes linked to diabetes and affect AGEs pathogenesis,and target tissues,influencing health and disease processes.AIM To explore miRNA roles in T2DM's metabolic pathways for potential therapeutic and diagnostic advancements in diabetes complications.METHODS We systematically searched the electronic database PubMed using keywords.We included free,full-length research articles that evaluate the role of miRNAs in T2DM and its complications,focusing on genetic and molecular disease mechanisms.After assessing the full-length papers of the shortlisted articles,we included 12 research articles.RESULTS Several types of miRNAs are linked in metabolic pathways which are affected by AGE/RAGE axis in T2DM and its complications.miR-96-5p,miR-7-5p,miR-132,has_circ_0071106,miR-143,miR-21,miR-145-5p,and more are associated with various aspects of T2DM,including disease risk,diagnostic markers,complications,and gene regulation.CONCLUSION Targeting the AGE/RAGE axis,with a focus on miRNA regulation,holds promise for managing T2DM and its complications.MiRNAs have therapeutic potential as they can influence the metabolic pathways affected by AGEs and RAGE,potentially reducing inflammation,oxidative stress,and vascular complications.Additionally,miRNAs may serve as early diagnostic biomarkers for T2DM.Further research in this area may lead to innovative therapeutic strategies for diabetes and its associated complications.

关键词： Type 2 diabetes mellitus MicroRNAs Advanced glycation end products Receptor for advanced glycation end products