Health benefits of Grifola frondosa polysaccharide on intestinal microbiota in type 2 diabetic mice

Grifola frondosa polysaccharide(GFP)as the natural compounds have been reported to exert diverse bioactivities.The aim of this study was to investigate the regulatory effects of GFP on intestinal microbiota in type 2 diabetic mice.The changes of microbiota in faeces of the diabetic mice upon high fat diet were determined and the V3 region of the 16S rRNA was sequenced by Illumina MiSeq high-throughput sequencing platform.Eighty operational taxonomic unit were identified to be shared by all samples,and the quality and richness of sequencing were assessed via rarefaction and rank abundance curves.The diversity of gut flora was slightly improved in diabetic mice after GFP treatment.The composition and relative abundance of gut microbiota at phylum and genus levels were altered by GFP.The abundance of Robinsoniella,Flavonifractor,Anaerotruncus,and Desulfvibrio were found to concentrate on diabetic mice through LEfSe analysis.Furthermore,Alloprevotella and Burkholderia had strong relevancy with other gut flora.Based on the findings,GFP might be a desired candidate on ameliorating the intestinal unbalance in diabetes.

Targeting autophagy overcomes cancer-intrinsic resistance to CAR-T immunotherapy in B-cell malignancies

Background:Chimeric antigen receptor T(CAR-T)therapy has substantially revolutionized the clinical outcomes of patients with hematologic malignan-cies,but the cancer-intrinsic mechanisms underlying resistance to CAR-T cells remain yet to be fully understood.This study aims to explore the molecular deter-minants of cancer cell sensitivity to CAR-T cell-mediated killing and to provide a better understanding of the underlying mechanisms and potential modulation to improve clinical efficacy.Methods:The human whole-genome CRISPR/Cas9-based knockout screening was conducted to identify key genes that enable cancer cells to evade CD19 CAR-T-cell-mediated killing.The in vitro cytotoxicity assays and evaluation of tumor tissue and bone marrow specimens were further conducted to confirm the role of the key genes in cancer cell susceptibility to CAR-T cells.In addition,the specific mechanisms influencing CAR-T cell-mediated cancer clearance were elucidated in mouse and cellular models.Results:The CRISPR/Cas9-based knockout screening showed that the enrich-ment of autophagy-related genes(ATG3,BECN1,and RB1CC1)provided protec-tion of cancer cells from CD19 CAR-T cell-mediated cytotoxicity.These findings were further validated by in vitro cytotoxicity assays in cells with genetic and pharmacological inhibition of autophagy.Notably,higher expression of the three autophagy-related proteins in tumor samples was correlated with poorer respon-siveness and worse survival in patients with relapsed/refractory B-cell lymphoma after CD19 CAR-T therapy.Bulk RNA sequencing analysis of bone marrow samples from B-cell leukemia patients also suggested the clinical relevance of autophagy to the therapeutic response and relapse after CD19 CAR-T cell ther-apy.Pharmacological inhibition of autophagy and knockout of RB1CC1 could dramatically sensitize tumor cells to CD19 CAR-T cell-mediated killing in mouse models of both B-cell leukemia and lymphoma.Moreover,our study revealed that cancer-intrinsic autophagy mediates evasion of CAR-T cells via the TNF-α-TNFR1 axis-mediated apoptosis and STAT1/IRF1-induced chemokine signaling activation.Conclusions:These findings confirm that autophagy signaling in B-cell malig-nancies is essential for the effective cytotoxic function of CAR-T cells and thereby pave the way for the development of autophagy-targeting strategies to improve the clinical efficacy of CAR-T cell immunotherapy.

Global seaweed farming and processing in the past 20 years

Seaweed has emerged as one of the most promising resources due to its remarkable adaptability, short development period, and resource sustainability. It is an effective breakthrough to alleviate future resource crises. Algal resources have reached a high stage of growth in the past years due to the increased output and demand for seaweed worldwide. Several aspects global seaweed farming production and processing over the last 20 years are reviewed, such as the latest situation and approaches of seaweed farming. Research progress and production trend of various seaweed application are discussed. Besides, the challenges faced by seaweed farming and processing are also analyzed, and the related countermeasures are proposed, which can provide advice for seaweed farming and processing. The primary products, extraction and application, or waste utilization of seaweed would bring greater benefits with the continuous development and improvement of applications in various fields.

Correction:Global seaweed farming and processing in the past 20 years

https://fppn.biomedcentral.com/articles/10.1186/s43014-022-00103-2.In the original publication of this article(Zhang et al.,2022),the author affiliations 1 and 2 need to be exchanged.