Intergeneric chromosome-specific painting reveals differential chromosomal transmission from Tripidium arundinaceum in sugarcane progeny

Sugarcane has recently attracted increasing attention for its potential as a source of sugar and bioethanol,so increasing its yield is essential to ensure the sugar security and bioenergy production.Intergeneric hybridization is a highly efficient method to produce new genetic variants of crop plants,particularly those species with high ploidy such as sugarcane(Saccharum spp.).Tripidium arundinaceum exhibits many desirable agronomic traits,and has been widely studied to produce hybrids with improved stress tolerance and other characteristics in sugarcane breeding.However,the genetic relationship between T.arundinaceum and Saccharum species,and the individual T.arundinaceum chromosomal compositions in sugarcane hybrids are still elusive.Here we used whole-genome single-nucleotide polymorphisms(SNPs)to ascertain the phylogenetic relationships between these species and found that T.arundinaceum is more closely related to Saccharum than Sorghum,in contrast to the previous narrow genetic analyses using chloroplast DNA.Additionally,oligonucleotide(oligo)-based chromosome-specific painting derived from Saccharum officinarum was able to distinctly identify the chromosomes of T.arundinaceum.We developed the oligo-genomic in situ hybridization(GISH)system for the first time,to unveil the novel chromosome translocations and the transmission of individual T.arundinaceum chromosomes in sugarcane progeny.Notably,we discovered that the chromosomal transmission of T.arundinaceum exhibited several different inheritance modes,including n,2n,and over 2n in the BC1 progenies.Such inheritance patterns may have resulted from first division restitution(FDR)or FDR+nondisjunction of a chromosome with the sister chromatids in the second meiosis division/second division restitution(FDR+NSC/SDR)model during meiosis.These results will be of substantial benefit for the further selection of T.arundinaceum chromosomes for sugarcane genetic improvement.

STING-mediated IL-6 Inhibits OATP1B1 Expression via the TCF4 Signaling Pathway in Cholestasis

Background and Aims Organic anion-transporting polypeptides(OATPs)play a crucial role in the transport of bile acids and bilirubin.In our previous study,interleukin 6(IL-6)reduced OATP1B3 levels in cholestatic disease.However,it remains unclear whether IL-6 inhibits OATP1B1 expression in cholestatic diseases.This study aimed to investigate whether IL-6 can inhibit OATP1B1 expression and explore the underlying mechanisms.Methods The effect of stimulator of interferon genes(STING)signaling on inflammatory factors was investigated in a cholestatic mouse model using RT-qPCR and enzyme-linked immunosorbent assay.To assess the impact of inflammatory factors on OATP1B1 expression in hepatocellular carcinoma,we analyzed OATP1B1 expression by RT-qPCR and Western Blot after treating PLC/PRF/5 cells with TNF-α,IL-1β,and IL-6.To elucidate the mechanism by which IL-6 inhibits OATP1B1 expression,we examined the expression of the OATP1B1 regulator TCF4 in PLC/PRF/5 and HepG2 cells using RT-qPCR and Western Blot.The interaction mechanism betweenβ-catenin/TCF4 and OATP1B1 was investigated by knocking downβ-catenin/TCF4 through siRNA transfection.Results The STING inhibitor decreased inflammatory factor levels in the cholestatic mouse model,with IL-6 exhibiting the most potent inhibitory effect on OATP1B1.IL-6 downregulatedβ-catenin/TCF4,leading to decreased OATP1B1 expression.Knocking-downβ-catenin/TCF4 counteracted theβ-catenin/TCF4-mediated repression of OATP1B1.Conclusions STING-mediated IL-6 up-regulation may inhibit OATP1B1,leading to reduced transport of bile acids and bilirubin by OATP1B1.This may contribute to altered pharmacokinetics in patients with diseases associated with increased IL-6 production.

肠道菌群与高尿酸血症及痛风的相关性研究

高尿酸血症以及痛风的发病率持续升高,已经成为一个重大的公共卫生问题。肠道菌群的结构改变或失调可引起机体代谢紊乱,肠道微生态尤其与代谢性疾病的发生发展关系密切。目前研究发现高尿酸血症、痛风患者存在肠道菌群失调,降尿酸治疗后肠道菌群可发生相应改变,并且益生菌制剂具有降尿酸作用。本文概述高尿酸血症及痛风患者的肠道菌群特点,从高嘌呤及高果糖饮食对肠道菌群的影响、肠道参与嘌呤和尿酸的代谢、代谢性内毒素血症以及痛风相关炎症因子等方面探讨肠道菌群与高尿酸血症及痛风的关系,并展望肠道菌群可能成为未来诊治高尿酸血症以及痛风的一种新方法。

An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease

Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.However,to date,there is no appropriate guidance on CKD in individuals with MAFLD.Furthermore,there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Methods and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.Conclusions:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.

In-depth analysis of de novo lipogenesis in non-alcoholic fatty liver disease:Mechanism and pharmacological interventions

Non-alcoholic fatty liver disease(NAFLD)is characterized by the abnormal buildup of lipids in the liver tissue.Non-alcoholic fatty liver(NAFL)may progress to non-alcoholic steatohepatitis.Triglycerides in the liver can originate from various sources,including de novo lipogenesis(DNL).Research indicates that DNL significantly escalates in NAFLD,worsening steatosis.However,the precise regulatory mechanism of DNL in the development of this disease is not fully understood.Therefore,the targeted reduction of DNL could be a crucial therapeutic strategy.Currently,numerous pharmaceutical agents targeting DNL have been developed,attracting significant attention.This review examines the mechanism of DNL upregulation in NAFLD,assessing its potential as a therapeutic target for hepatic steatosis.Furthermore,we thoroughly examine hepatocellular lipotoxicity and provide an extensive review of the application and limitations of relevant therapeutic drugs,with a focus on key enzymes involved in DNL.The implementation of these pharmacological strategies is expected to significantly improve the management and overall outcomes for patients with NAFLD.