An efficient method for constructing a random insertional mutant library for forward genetics in Nannochloropsis oceanica

Insertional mutation,phenotypic evaluation,and mutated gene cloning are widely used to clone genes from scratch.Exogenous genes can be integrated into the genome during non-homologous end joining(NHEJ)of the double-strand breaks of DNA,causing insertional mutation.The random insertional mutant library constructed using this method has become a method of forward genetics for gene cloning.However,the establishment of a random insertional mutant library requires a high transformation efficiency of exogenous genes.Many microalgal species show a low transformation efficiency,making constructing random insertional mutant libraries difficult.In this study,we established a highly efficient transformation method for constructing a random insertional mutant library of Nannochloropsis oceanica,and tentatively tried to isolate its genes to prove the feasibility of the method.A gene that may control the growth rate and cell size was identified.This method will facilitate the genetic studies of N.oceanica,which should also be a reference for other microalgal species.

Interaction between diet and genetics in patients with inflammatory bowel disease

In this editorial,we comment on the article by Marangoni et al,published in the recent issue of the World Journal of Gastroenterology 2023;29:5618-5629,about“Diet as an epigenetic factor in inflammatory bowel disease”.The authors emphasized the role of diet,especially the interaction with genetics,in promoting the inflam-matory process in inflammatory bowel disease(IBD)patients,focusing on DNA methylation,histone modifications,and the influence of microRNAs.In this editorial,we explore the interaction between genetics,gut microbiota,and diet,in an only way.Furthermore,we provided dietary recommendations for patients with IBD.The Western diet,characterized by a low fiber content and deficiency the micronutrients,impacts short-chain fatty acids production and may be related to the pathogenesis of IBD.On the other hand,the consumption of the Mediter-ranean diet and dietary fibers are associated with reduced risk of IBD flares,particularly in Crohn’s disease(CD)patients.According to the dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases(IOIBD),the regular consumption of fruits and vegetables while reducing the consumption of saturated,trans,dairy fat,additives,processed foods rich in maltodextrins,and artificial sweeteners containing sucralose or saccharine is recommended to CD patients.For patients with ulcerative colitis,the IOIBD recommends the increased intake of natural sources of omega-3 fatty acids and follows the same restrictive recommendations aimed at CD patients,with the possible inclusion of red meats.In conclusion,IBD is a complex and hetero-geneous disease,and future studies are needed to elucidate the influence of epigenetics on diet and microbiota in IBD patients.

A Theory of Bio-Quantum Genetics

The physical mechanism of heredity or inheritance of genes is a quantum mechanical and/or quantum computational process. A theory of bio-quantum genetics is established in this paper. Principle of Bio-quantum Genetics is suggested. I propose and define the soft-genes of genetics controlling the processes of heredity or inheritance of genes. This research deals with the quantum mechanisms of Mendel plant heredity and family inheritance as examples of bio-quantum genetics, deepening our understanding of heredity or inheritance. I believe that more contributions will be made to promote researches of bio-quantum genetics or quantum biology at large.

The Practice and Exploration of Applying EBM to Bilingual Teaching of Medical Genetics at OSBCM

In the process of teaching medical genetics of undergraduate clinical medicine, the practice and exploration of applying EBM to the bilingual teaching of OSBCM medical genetics are carried out. Using CBL and PBL as the carrier can make up for the shortcomings of a single teaching mode, synthesize the advantages of multiple teaching modes. It starts from integrating the basic theoretical knowledge of medicine and clinical practice knowledge, improving students’ bilingual level of medical genetics, cultivating students’ literature retrieval ability, and promoting early clinical, multi-clinical and repeated clinical consciousness for medical students. Therefore, it is more conducive to cultivate students’ ability to learn independently, accurately analyze and solve problems, improve medical students’ clinical thinking ability and scientific research awareness, improve medical students’ ability of international communication, and lay a solid foundation for improving medical students’ future post competence, innovative spirit and lifelong learning ability.

Sirtuin家族调控骨关节炎软骨细胞的作用机制研究进展

骨关节炎(osteoarthritis,OA)是常见的慢性退行性疾病,以关节软骨的进行性破坏为主要病理特征。研究证实软骨组织中软骨细胞功能障碍是OA进展的关键因素,包括能量代谢、生物钟、自噬和凋亡的异常激活及衰老软骨细胞的增加等生物过程。沉默信息调节因子(sirtuin,SIRT)是依赖于烟酰胺烟嘌呤二核苷酸的去乙酰化酶家族,通过参与并调节软骨细胞功能过程中的蛋白质去乙酰化,从而延缓OA进展。依据文献报道,本文将围绕SIRT家族成员对OA软骨细胞功能的调控作用机制进行概述,旨在对SIRT家族在OA软骨细胞的作用机制有进一步认识和为今后靶向治疗OA提供思路。

Population genetics of marmosets in Asian primate research centers and loci associated with epileptic risk revealed by whole-genome sequencing

The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independently reported in two Asian primate research centers.Nevertheless,the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated.Here,we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing.We identified 14558184 single nucleotide polymorphisms(SNPs)from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples.Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers.In addition,SNP and copy number variation(CNV)analyses suggested that the WW domain-containing oxidoreductase(WWOX)and Tyrosine-protein phosphatase nonreceptor type 21(PTPN21)genes may be associated with epilepsy in marmosets.Notably,KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets.This study provides valuable population genomic resources for marmosets in two Asian primate centers.Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers,while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.

沉默信息调节因子Sirtuins在牙周炎中的作用

背景:牙周炎是以牙菌斑生物膜为主要致病物质的炎症性、破坏性疾病,发生于牙龈、牙周膜、牙槽骨和牙骨质。细菌复合体的抗原及其分泌的毒素、酶等直接导致牙周组织的破坏,并引发宿主的免疫反应,使机体组织受到间接损害。沉默信息调节因子(Sirtuins,SIRTs)在抗衰老、抗氧化应激、调节炎症、介导细胞自噬等方面发挥重要作用,与牙周炎的发生和发展也有着密切的关系。目的:针对Sirtuins在牙周炎中的研究概况做一综述。方法:由第一作者应用计算机在PubMed、Web of Science、中国知网和万方数据库检索涉及Sirtuins在牙周炎中的相关研究,以“Sirtuins,Sirtuin1-7,periodontitis”为英文检索词,“沉默信息调节因子,沉默信息调节因子1-7,牙周炎”为中文检索词,经过筛选后纳入57篇文献进行综述分析。结果与结论:①SIRT1、SIRT2、SIRT3、SIRT6参与调控了牙周炎的发生与发展;②SIRT1:抑制SIRT1表达可能是牙周炎治疗靶点;SIRT1的过表达对牙周炎症有抑制作用,保护牙周组织;SIRT1的激活剂可减轻牙周组织的炎症,并可改善牙周炎引起的全身组织病变;③SIRT2:参与烟酰胺磷酸核糖转移酶介导的牙周炎症,SIRT2在牙周疾病的治疗和转归中发挥一定的作用;④SIRT3:可改善年龄相关的牙周病;天麻素可通过SIRT3的上调促进牙周膜干细胞成骨分化;SIRT3的激活剂通过调节细胞自噬水平,降低牙周炎对牙周和肾脏组织的破坏程度;⑤SIRT6:可抑制牙周组织炎症反应,抑制成牙骨质细胞的分化和矿化;SIRT6对根尖周炎的预后有利;⑥SIRT4、SIRT5、SIRT7与牙周炎的关系鲜有报道。

Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis

BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.

Genetic pathways in cerebral palsy:a review of the implications for precision diagnosis and understanding disease mechanisms

Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal brain.These disturbances severely impact the child’s daily life and impose a substantial economic burden on the family.Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity.This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development.It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa ctors.Des pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still elusive.However,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development.Moreove r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular autophagy.Furthermore,exploring targeted genotypes holds potential for precision treatment.In conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy.These breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical management.The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies.By elucidating the underlying cellular mechanisms,we can develop to rgeted interventions to optimize outcomes.A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.

姜黄素对热应激条件下蛋鸡性腺机能和Sirtuins基因家族表达的影响

为探究姜黄素对热应激条件下蛋鸡性腺生理机能及Sirtuins基因家族表达量的影响,试验选用42只健康、体重相近的30周龄罗曼粉蛋鸡(公母各半),随机分为常温组(CK组)、高温组(HC组)和高温处理组(HT组),每组公鸡和母鸡各7只。常温组和高温组饲喂基础饲粮,高温处理组在基础饲粮中添加200mg/kg姜黄素。常温组保持温度在(25±3)℃,高温组和高温处理组在常温组的基础上采用循环高温,保持每天10:00~16:00温度(32±3)℃,各组湿度维持在65%~80%,热应激处理3周。结果显示,与常温组相比,高温条件对鸡的性腺产生不良影响,其产蛋率或采精量明显下降,差异显著(P<0.05);Sirtuins家族各基因在卵巢中表达量明显减少(P<0.05),而Sirt4、Sirt5和Sirt7在睾丸中表达量也显著降低(P<0.05)。添加姜黄素后,产蛋率或采精量均显著上升(P<0.05),卵巢中Sirt1、Sirt2、Sirt3、Sirt5基因和睾丸中Sirt4和Sirt5的表达量均显著上升(P<0.05)。研究结果表明,添加姜黄素能有效缓解热应激对鸡性腺机能和Sirtuins基因家族表达量的影响。

Sirtuins家族和线粒体未折叠蛋白反应在疾病中的研究进展

线粒体未折叠蛋白反应(UPRmt)是一种适应性细胞内应激机制,通过促进编码线粒体伴侣蛋白和蛋白酶的基因转录来响应应激信号。随着研究的深入,UPRmt在疾病中的作用机制已逐渐明确。沉默信息调节因子(Sirtuins)是一类进化上高度保守的NAD+依赖性组蛋白去酰基酶,是多种生物过程中的关键信号通路。近年来Sirtuins在衰老和代谢中的多种调节功能相继报道,也有研究明确了UPRmt和Sirtuins家族之间存在着重要联系。该文总结了Sirtuins与UPRmt的最新研究成果,并归纳了两者在衰老、肿瘤以及代谢性疾病中的作用机制,阐明了Sirtuins与UPRmt在疾病中的研究进展。

Molecular phylogenetics and population demographic history of Amphioctopus fangsiao,inferred from mitochondrial and microsatellite DNA markers

Amphioctopus fangsiao(Cephalopoda:Octopodidae)is an important commercial species in the coastal waters of China.In recent years,however,the resource of A.fangsiao have declined because of habitat destruction and overfishing.To analyze the genetic variations of A.fangsiao caused by the fluctuation of resources,the population genetic structure of nine sampling locations collected from the Bohai Sea to the South China Sea were investigated,using mtDNA COI fragments and microsatellite DNA.The results of F-statistics,AMOVA,STRUCTURE and PCA analyses showed three phylogeographic clades(Clades A,B and C),revealing limited genetic exchange between north and south populations.These clades diverged in 2.23(Clades A and B)and 3.67(Clades A,B and C)million years ago,during the dramatic environmental fluctuations,such as sea level and temperature changes,have exerted great influence on the survival distribution pattern of global organisms.Our results for low genetic connectivity among A.fangsiao populations provide insights into the development of management strategies,that is,to manage this species as separate management unit.

Genetic screening of liver cancer:State of the art

Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver cancer.This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer.We discuss the genetic underpinnings of liver cancer,emphasizing the critical role of risk-associated genetic variants,somatic mutations,and epigenetic alterations.We also explore the intricate interplay between environmental factors and genetics,highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy,and advancements in high-throughput sequencing technologies.By synthesizing the latest research findings,we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer,shedding light on their potential to revolutionize early detection,risk assessment,and targeted therapies in the fight against this devastating disease.

Winter wheat yield improvement by genetic gain across different provinces in China

The replacement of winter wheat varieties has contributed significantly to yield improvement worldwide,with remarkable progress in China.Drawing on two sets of data,production yield from the National Bureau of Statistics of China and experimental yield from literature,this study aims to(1)illustrate the increasing patterns of production yield among different provinces from 1978 to 2018 in China,(2)explore the genetic gain in yield and yield relevant traits through the variety replacement based on experimental yield from 1937 to 2016 in China,and(3)compare the yield gap between experimental yield and production yield.The results show that both the production and experimental yields significantly increased along with the variety replacement.The national annual yield increase ratio for the production yield was 1.67%from 1978 to 2018,varying from 0.96%in Sichuan Province to 2.78%in Hebei Province;such ratio for the experimental yield was 1.13%from 1937 to 2016.The yield gap between experimental and production yields decreased from the 1970s to the 2010s.This study reveals significant increases in some yield components consequent to variety replacement,including thousand-grain weight,kernel number per spike,and grain number per square meter;however,no change is shown in spike number per square meter.The biomass and harvest index consistently and significantly increased,whereas the plant height decreased significantly.

去乙酰化酶Sirtuins家族与放射性肝病的关系

放射性肝病(RILD)或称放射性肝炎,是一种由辐射引起的亚急性肝损伤。去乙酰化酶家族Sirtuins(SIRTs)作为衰老相关研究的焦点具有DNA修复和染色质调节等分子功能,是基因组和表观基因组稳定性的枢纽。辐射诱导的肝脏DNA损伤和反应是RILD主要的生理病理过程,这与SIRTs表征的功能相似。本文简述了SIRTs蛋白家族的结构和功能,回顾了放射治疗的物理生理学基本概念及进展,主要从放射生物学角度分析了SIRTs与RILD二者的内在关系,指出SIRTs作为RILD防治靶点的可能性。

Genetic variants in C1GALT1 are associated with gastric cancer risk by influencing immune infiltration

Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.

Genetically modified pigs:Emerging animal models for hereditary hearing loss

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.

Conservation genomic investigation of an endangered conifer,Thuja sutchuenensis,reveals low genetic diversity but also low genetic load

Endangered species generally have small populations with low genetic diversity and a high genetic load.Thuja sutchuenensis is an endangered conifer endemic to southwestern China.It was once considered extinct in the wild,but in 1999 was rediscovered.However,little is known about its genetic load.We collected 67 individuals from five wild,isolated T.sutchuenensis populations,and used 636,151 SNPs to analyze the level of genetic diversity and genetic load in T.sutchuenensis to delineate the conservation units of T.sutchuenensis,based on whole transcriptome sequencing data,as well as target capture sequencing data.We found that populations of T.sutchuenensis could be divided into three groups.These groups had low levels genetic diversity and were moderately genetically differentiated.Our findings also indicate that T.sutchuenensis suffered two severe bottlenecks around the Last Glaciation Period and Last Glacial Maximum.Among Thuja species,T.sutchuenensis presented the lowest genetic load and hence might have purged deleterious mutations efficiently through purifying selection.However,distribution of fitness effects analysis indicated a high extinction risk for T.sutchuenensis.Multiple lines of evidence identified three management units for T.sutchuenensis.Although T.sutchuenensis possesses a low genetic load,low genetic diversity,suboptimal fitness,and anthropogenic pressures all present an extinction risk for this rare conifer.This might also hold true for many endangered plant species in the mountains all over the world.

Genetic variation of circHIBADH enhances prostate cancer risk through regulating HNRNPA1-related RNA splicing

The current study aimed to investigate associations of circRNAs and related genetic variants with the risk of prostate cancer(PCa)as well as to elucidate biological mechanisms underlying the associations.We first compared expression levels of circRNAs between 25 paired PCa and adjacent normal tissues to identify riskassociated circRNAs by using the MiOncoCirc database.We then used logistic regression models to evaluate associations between genetic variants in candidate circRNAs and PCa risk among 4662 prostate cancer patients and 3114 healthy controls,and identified circHIBADH rs11973492 T>C as a significant risk-associated variant(odds ratio=1.20,95%confidence interval:1.08-1.34,P=7.06×10^(-4))in a dominant genetic model,which altered the secondary structure of the corresponding RNA chain.In the in silico analysis,we found that circHIBADH sponged and silenced 21 RNA-binding proteins(RBPs)enriched in the RNA splicing pathway,among which HNRNPA1 was identified and validated as a hub RBP using an external RNA-sequencing data as well as the in-house(four tissue samples)and publicly available single-cell transcriptomes.Additionally,we demonstrated that HNRNPA1 influenced hallmarks including MYC target,DNA repair,and E2F target signaling pathways,thereby promoting carcinogenesis.In conclusion,genetic variants in circHIBADH may act as sponges and inhibitors of RNA splicing-associated RBPs including HNRNPA1,playing an oncogenic role in PCa.

Genetic algorithm assisted meta-atom design for high-performance metasurface optics

Metasurfaces,composed of planar arrays of intricately designed meta-atom structures,possess remarkable capabilities in controlling electromagnetic waves in various ways.A critical aspect of metasurface design involves selecting suitable meta-atoms to achieve target functionalities such as phase retardation,amplitude modulation,and polarization conversion.Conventional design processes often involve extensive parameter sweeping,a laborious and computationally intensive task heavily reliant on designer expertise and judgement.Here,we present an efficient genetic algorithm assisted meta-atom optimization method for high-performance metasurface optics,which is compatible to both single-and multiobjective device design tasks.We first employ the method for a single-objective design task and implement a high-efficiency Pancharatnam-Berry phase based metalens with an average focusing efficiency exceeding 80%in the visible spectrum.We then employ the method for a dual-objective metasurface design task and construct an efficient spin-multiplexed structural beam generator.The device is capable of generating zeroth-order and first-order Bessel beams respectively under right-handed and left-handed circular polarized illumination,with associated generation efficiencies surpassing 88%.Finally,we implement a wavelength and spin co-multiplexed four-channel metahologram capable of projecting two spin-multiplexed holographic images under each operational wavelength,with efficiencies over 50%.Our work offers a streamlined and easy-to-implement approach to meta-atom design and optimization,empowering designers to create diverse high-performance and multifunctional metasurface optics.