Functional analysis of the novel mitochondrial tRNA^(Trp)and tRNA^(Ser(AGY))variants associated with type 2 diabetes mellitus

BACKGROUND Mutations in mitochondrial tRNA(mt-tRNA)genes that result in mitochondrial dysfunction play important roles in type 2 diabetes mellitus(T2DM).We previously reported a large Chinese pedigree with maternally inherited T2DM that harbors novel mt-tRNA^(Trp)A5514G and tRNA^(Ser(AGY))C12237T variants,however,the effects of these mt-tRNA variants on T2DM progression are largely unknown.AIM To assess the potential pathogenicity of T2DM-associated m.A5514G and m.C12237T variants at genetic,molecular,and biochemical levels.METHODS Cytoplasmic hybrid(cybrid)cells carrying both m.A5514G and m.C12237T variants,and healthy control cells without these mitochondrial DNA(mtDNA)variants were generated using trans-mitochondrial technology.Mitochondrial features,including mt-tRNA steady-state level,levels of adenosine triphosphate(ATP),mitochondrial membrane potential(MMP),reactive oxygen species(ROS),mtDNA copy number,nicotinamide adenine dinucleotide(NAD+)/NADH ratio,enzymatic activities of respiratory chain complexes(RCCs),8-hydroxy-deoxyguanine(8-OhdG),malondialdehyde(MDA),and superoxide dismutase(SOD)were examined in cell lines with and without these mt-tRNA variants.RESULTS Compared with control cells,the m.A5514G variant caused an approximately 35%reduction in the steady-state level of mt-tRNA^(Trp)(P<0.0001);however,the m.C12237T variant did not affect the mt-tRNA^(Ser(AGY))steady-state level(P=0.5849).Biochemical analysis revealed that cells with both m.A5514G and m.C12237T variants exhibited more severe mitochondrial dysfunctions and elevated oxidative stress than control cells:ATP,MMP,NAD+/NADH ratio,enzyme activities of RCCs and SOD levels were markedly decreased in mutant cells(P<0.05 for all measures).By contrast,the levels of ROS,8-OhdG and MDA were significantly increased(P<0.05 for all measures),but mtDNA copy number was not affected by m.A5514G and m.C12237T variants(P=0.5942).CONCLUSION The m.A5514G variant impaired mt-tRNA^(Trp)metabolism,which subsequently caused mitochondrial dysfunction.The m.C12237T variant did not alter the steady-state level of mt-tRNA^(Ser(AGY)),indicating that it may be a modifier of the m.A5514G variant.The m.A5514G variant may exacerbate the pathogenesis and progression of T2DM in this Chinese pedigree.

Fatty acid binding protein 5 is a novel therapeutic target for hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive subtype of liver cancer and is one of the most common cancers with high mortality worldwide.Reprogrammed lipid metabolism plays crucial roles in HCC cancer cell survival,growth,and evolution.Emerging evidence suggests the importance of fatty acid binding proteins(FABPs)in contribution to cancer progression and metastasis;however,how these FABPs are dysregulated in cancer cells,especially in HCC,and the roles of FABPs in cancer progression have not been well defined.AIM To understand the genetic alterations and expression of FABPs and their associated cancer hallmarks and oncogenes in contributing to cancer malignancies.METHODS We used The Cancer Genome Atlas datasets of pan cancer and liver hepatocellular carcinoma(LIHC)as well as patient cohorts with other cancer types in this study.We investigated genetic alterations of FABPs in various cancer types.mRNA expression was used to determine if FABPs are abnormally expressed in tumor tissues compared to non-tumor controls and to investigate whether their expression correlates with patient clinical outcome,enriched cancer hallmarks and oncogenes previously reported for patients with HCC.We determined the protein levels of FABP5 and its correlated genes in two HCC cell lines and assessed the potential of FABP5 inhibition in treating HCC cells.RESULTS We discovered that a gene cluster including five FABP family members(FABP4,FABP5,FABP8,FABP9 and FABP12)is frequently co-amplified in cancer.Amplification,in fact,is the most common genetic alteration for FABPs,leading to overexpression of FABPs.FABP5 showed the greatest differential mRNA expression comparing tumor with non-tumor tissues.High FABP5 expression correlates well with worse patient outcomes(P<0.05).FABP5 expression highly correlates with enrichment of G2M checkpoint(r=0.33,P=1.1e-10),TP53 signaling pathway(r=0.22,P=1.7e-5)and many genes in the gene sets such as CDK1(r=0.56,P=0),CDK4(r=0.49,P=0),and TP53(r=0.22,P=1.6e-5).Furthermore,FABP5 also correlates well with two co-expressed oncogenes PLK1 and BIRC5 in pan cancer especially in LIHC patients(r=0.58,P=0;r=0.58,P=0;respectively).FABP5high Huh7 cells also expressed higher protein levels of p53,BIRC5,CDK1,CDK2,and CDK4 than FABP5low HepG2 cells.FABP5 inhibition more potently inhibited the tumor cell growth in Huh7 cells than in HepG2 cells.CONCLUSION We discovered that FABP5 gene is frequently amplified in cancer,especially in HCC,leading to its significant elevated expression in HCC.Its high expression correlates well with worse patient outcome,enriched cancer hallmarks and oncogenes in HCC.FABP5 inhibition impaired the cell viability of FABP5high Huh7 cells.All these support that FABP5 is a novel therapeutic target for treating FABP5high HCC.

Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen:Novel viral biomarkers for chronic hepatitis B management

The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.

Analyzing the Adaptation of Rebecca from the Novel to the Film in Light of the Black-and-White

Classical Chinese aesthetics is based on Chinese philosophy.The characteristic of classical Chinese aesthetics regards“artistic conception”as one of the basic aesthetic categories.Chinese art speaks highly of the charm of the black-and-white.During the adaptation,there is the same beauty in the black-and-white photography and the“color without color”of Chinese paintings.The“artistic conception”is similar between them from the aesthetic perspective.Therefore,the unique“artistic conception”of the novel should be mastered,if the adapter aims to retain the“soul”of it.In other words,film adaptation not only considers“similarity in form”,but also draws much attention to“similarity in spirit”.The latter is the essence of film adaptation.

Prevention and Nursing of Adverse Reactions of Novel Coronavirus Inactivated Vaccine (Vero Cells)

Objective:To discuss and analyze the causes of adverse reactions caused by the inactivated novel coronavirus vaccine(Vero cells),and to propose methods of prevention and care.Methods:A questionnaire was used to randomly select 229 adults who were vaccinated with the inactivated novel coronavirus vaccine(Vero cells)at Xi’an People’s Hospital(Xi’an Fourth Hospital).The adverse reactions were statistically analyzed.Results:Among the 229 adults vaccinated with the inactivated novel coronavirus vaccine(Vero cells),30 experienced vaccination reactions.The main reaction was local induration at the inoculation site,and dizziness was the primary systemic symptom.Conclusion:To reduce the incidence of adverse reactions to the inactivated novel coronavirus vaccine(Vero cells),it is necessary to effectively evaluate the health status of adults before vaccination,select the correct vaccination site,and strictly implement the rules of 3-inspections,7-checks,and 1-verification.Standardizing the operation process and providing thorough health education after vaccination can effectively reduce the occurrence of adverse reactions.

The Application of Newmark’s Metaphor Theory in Novel Translation--A Case Study of“the Jade King:History of a Chinese Muslim Family”

This paper examines the metaphorical part of“The Jade King:History of a Chinese Muslim Family”,Hoda’s novel,under the guidance of Newmark’s theory of metaphor.Newmark proposes six categories of metaphors,namely Dead Metaphor,ClichéMetaphor,Stock or Standard Metaphor,Adapted Metaphor,Recent Metaphor,Original Metaphor;and seven strategies of metaphor translation,including reproducing the same image in the target language,replacing the image in the source language with a standard target language image,translation of metaphor by simile,translation of metaphor(or simile)by simile plus sense,conversion of metaphor to sense,deletion and same metaphor combined with sense.They can provide a strong theoretical support for analyzing the expressions of metaphors in novels and their translation methods.By deeply analyzing the expressions of metaphor and its translation methods in novels,it not only helps to understand the metaphorical meaning and cultural connotation of the original works,but also helps to explore the cultural differences and challenges faced by English and Chinese bilingualism in the process of metaphor translation,thereby significantly improving the translation level and promoting the development of translation research.

AI绘画软件的创作特征研究——以绘画软件Novel AI生成的动漫人物形象为例

近年来,随着扩散模型、Lora模型、Controlnet等技术应用于绘画领域,现今的AI绘画软件已经能够生成完整的动漫人物,具备了较高的可控性和精确性。文章通过分析AI绘画软件“Novel AI”生成的动漫人物形象,总结了这一AI软件表现出的绘画创作特征,并在此基础上评估了现今人工智能技术对于动漫创作产生的影响。

Clinical and genetic characteristics of retinoblastoma patients in a single center with four novel RB1 variants

AIM:To assess the clinical and genetic characteristics of children diagnosed with retinoblastoma(RB)at Gazi University Faculty of Medicine’s Department of Pediatric Oncology.METHODS:All cases diagnosed with RB and received treatment and follow-up in the Ophthalmology and Pediatric Oncology Department,October 2016 to May 2021 were evaluated retrospectively.The RB1 gene was analyzed by next-generation sequencing(NGS)technique in DNAs obtained from peripheral blood samples of the patients.RESULTS:This study included 53 cases with 67 RBaffected eyes during the study period.The mean age was 24.6(median:18.5,range:3–151)mo.There were 15(22.3%)Group D eyes and 39(58.2%)Group E eyes.The RB1 gene was sequenced by the NGS method in 19 patients.Heterozygous RB1:NM_000321.3:c.54_76del(p.Glu19AlafsTer4)variant was detected in a 15-month-old female with bilateral RB.Heterozygous RB1:NM_000321.3:c.1814+3A>T variant was detected in a 5.5-month-old male with bilateral RB.The intronic RB1:NM_000321.3:c.1332+4A>G variant was detected in patient 14,a 13-month-old male with unilateral RB.The RB1:NM_000321.3:c.575_576del(p.Lys192SerfsTer10)variant was found in an 18-month-old female with an allele frequency of 37%.These variants have not been reported in the literature and mutation databases.CONCLUSION:Four novel variants are described and one of them is found in two different patients.This data is crucial for assessing prognosis.It serves as a guide for estimating the long-term risk of secondary malignancy as well as the short-term risk of developing additional malignancies in the same eye and the other eye.

Identification and functional analyses of a novel FOXL2 pathogenic variant causing blepharophimosis, ptosis, and epicanthus inversus syndrome

AIM: To discover the molecular pathogenic basis of the blepharophimosis, ptosis, and epicanthus inversus syndrome(BPES), and to predict the clinical subtype according to in vitro experiments, which is significant to the prognosis.METHODS: A 3-year-old sporadic female patient with typical clinical manifestations of BPES was enrolled. The coding region of forkhead box L2(FOXL2) gene was sequenced, and the functional assays were performed in vitro by Western blotting, subcellular localization experiment, luciferase reporter assay, and quantitative realtime polymerase chain reaction.RESULTS: A novel FOXL2 point pathogenic variant(c.274G>T) was detected, resulting in a truncated protein(p.E92*). Functional studies demonstrated that the FOXL2 pathogenic variant induced the subcellular mislocalization and the abnormal transcriptional activity on promoters of the steroidogenic acute regulatory protein(StAR or STARD1) gene and the odd-skipped related 2 transcription factor(OSR2) gene.CONCLUSION: A novel pathogenic variant is identified to expand the spectrum of the known FOXL2 mutations. The in vitro experiments provide reference data and more insights to the molecular pathogenesis of BPES. The predicted high risk of ovarian insufficiency makes it significant for the patient enrolled to have further follow-up and therapy concerning female endocrinology.

A novel Ti-5.55Al-6.70Zr-1.50V-0.70Mo-3.41Nb-0.21Si alloy designed using cluster-plus-glue-atom model for laser additive manufacturing

A novel Ti-5.55Al-6.70Zr-1.50V-0.70Mo-3.41Nb-0.21Si alloy was designed using the cluster formula approach(cluster-plus-glue-atom model)and prepared by laser melting deposition(LMD).Its composition formula 12[Al-Ti_(12)](AlTi_(2))+5[Al_(0.8)Si_(0.2)-Ti_(12)Zr_(2)](V_(0.8)Mo_(0.2)Nb_(1)Ti)features an enhancedβ-Ti via co-alloying of Zr,V,Mo,Nb and Si.The experimental results show that the cluster formula ofαandβphases in the novel alloy are respectivelyα-[Al-Ti_(11.5)Zr_(0.5)](Al_(1)Ti_(2))andβ-[Al_(0.8)Si_(0.2)-Ti_(13.2)Zr_(0.8)](V_(1)Mo_(0.4)Nb_(1.6)),both containing Zr elements.The fitted composition via the α andβphase cluster formulas has little difference with the actual alloy composition,suggesting that the validity of cluster-plus-glue-atom model in the alloy composition design.After hot isostatic pressing(HIP),both the Ti-6Al-4V and the novel alloy by LMD are characterized by prior-βcolumnar grains,while the typical<100>texture disappears.Compared with Ti-6Al-4V,Ti-5.55Al-6.70Zr-1.50V-0.70Mo-3.41Nb-0.21Si alloy exhibits a combination of higher strength(1,056 MPa)and higher ductility(14%)at room temperature and higher strength(580 MPa)at 550℃ after HIP,and can potentially serves as LMD materials.

A Study on the Loss of Tourist Attractions in Central China Hubei Province During the Anti-Japanese War

This paper takes the Wudang Mountains and Wuhan Battle Memorial Hall as examples to investigate and analyze the losses of Wuhan during the Anti-Japanese War.The paper concludes with two inspirations:to make full use of the intangible cultural heritage spots to carry out patriotism education for primary and middle school students;and to effectively transform the cultural resources of the tourist spots in Hubei Province into cultural industries,in order to achieve the sustainable development of intangible cultural resources of Hubei Province tourist attractions.

Research on the Winter Study Movement in Shanxi Anti-Japanese Base Area from the Perspective of Mass

Playing a major role on social education in Shanxi anti-Japanese base area,the winter study movement is a popular education movement implemented by the Communist Party of China,which takes into consideration the base area’s reality and makes full use of the leisure time in winter of rural area.With a wide coverage of education in culture,politics,daily life,anti-Japanese war as well as other aspects.The winter study movement provides efficient education to rural peasants,achieving great effects on mobilization on the masses of the people.This paper focuses on the original archives of the grassroots,conveying comprehensive analysis on the institutional arrangement,organizational mechanism and specific implementation of the winter study movement,thus to provide an overall understanding of the winter study movement in Shanxi anti-Japanese base area from the perspective of mass mobilization.

The Grass-Roots Governance of the National Government in Tianjin Recovery Area After the Triumph of the Anti-Japanese War

The national government wants to penetrate into the grass-roots unit after the triumph of the Anti-Japanese War in the recovery area.Through the reorganization of the Baojia system,the government expects to achieve local autonomy and then solve the people’s livelihood issues.The new Baojia system provides a platform for people to achieve their own demands,which presents the vision of civil rights to a certain extent.However,because of the complexity of the postwar social environment,the Baojia system cannot completely represent the will of the people,and finally becomes a militarized organization that was used as a tool to carry out the government decree.

Novel combined endoscopic and laparoscopic surgery for advanced T2 gastric cancer:Two case reports

BACKGROUND The standard treatment for advanced T2 gastric cancer(GC)is laparoscopic or surgical gastrectomy(either partial or total)and D2 lymphadenectomy.A novel combined endoscopic and laparoscopic surgery(NCELS)has recently been proposed as a better option for T2 GC.Here we describe two case studies demonstrating the efficacy and safety of NCELS.CASE SUMMARY Two T2 GC cases were both resected by endoscopic submucosal dissection and full-thickness resection and laparoscopic lymph nodes dissection.This method has the advantage of being more precise and minimally invasive compared to current methods.The treatment of these 2 patients was safe and effective with no complications.These cases were followed up for nearly 4 years without recurrence or metastasis.CONCLUSION This novel method provides a minimally invasive treatment option for T2 GC,and its potential indications,effectiveness and safety needs to be further evaluated in controlled studies.

Under the Pagoda Mountain:Japanese POW Reformation During the Anti-Japanese War

As a typical Lenin-style political party,what should be concerned most is the CPC’s (Communist Party of China) capacity in fighting against and clearing enemies.This study provides a distinct perspective to observe and recognize CPC’s ability of turning hostility into friendship.Japanese prisoners of war (POW) had been poisoned by ultra-nationalism and militarism for years,and thus were extremely difficult to be reformed.However,under the correct ideological guidance of Mao and the unremitting efforts of the CPC’s political officers and cadres,a great number of them acknowledged the CPC’s political ideology and joined the CPC’s team.

新质人才培养:数智时代教育的新使命

大力培养新质人才是深入实施人才强国战略、加快建设世界重要人才中心和创新高地的行动要义。新质人才所具有的创变思维使其具有了创新恒常性,复合思维使其具有了生态营造性,技术思维使其具有了技术具身性,这就使得他们符合新质生产力的需要,助力中国式现代化不断开拓发展新赛道。新质人才具有成长心态与高意识学习特质、人机共生思维与AI渗透技能、开拓精神与“破界”能力、创想能力与实践智慧、人文精神与科技合伦行动力、人类共同体思维与跨文化行动力等特质。新质人才的培育需要建构一体化的培养范式,包括:细化融通培养机制,以素养导向的AI教育培育新质后备人才的基础教育;依托智能学科平台,以“AI+X”微专业塑造新质中坚人才的高等教育;建立数字孪生平台,以产教融合认证发展新质技能人才的职业教育。未来的新质人才应当是具有创新潜质的AI原民,新质人才培养思路应推广到新生代(AI原民)人才的培养,致力培植好人才成长的沃土,让新质人才不断涌现。

Novel Deletion in Exon 7 of Betaine Aldehyde Dehydrogenase 2(BADH2)

The fragrance of rice is one of the premium characteristics that breeders want to include in rice varieties due to the higher market value. Nucleotide deletions in exons 2(7 bp) and 7(8 bp) of Betaine Aldehyde Dehydrogenase 2(BADH2) are associated with fragrance in rice. In this study, a new 13 bp deletion in exon 7 of the BADH2 gene was discovered in the Nang Thom Cho Dao(NTCD) variety, and the mutation has been closely related to the genetic background of indica subspecies through the Bayesian phylogenetic approach and haplotype network analysis of the 3 000 Rice Genomes Project. In addition, a set of functional markers(EX07-13F, EX07-13RN, and EX07-13RM) identified the 13 bp deletion only within NTCD(no amplified band) compared with both non-aromatic and other aromatic rice varieties(110 bp band). The deletion of 13 bases instead of 8 bases in exon 7 of BADH2 caused a premature stop codon, which down-regulated the expression of the BADH2 transcript while associated with up-regulation of OsP5CS and the high amount of 2-acetyl-1-pyrroline. It is potential to use the deletion in exon 7 of the BADH2 gene as a novel marker for adulteration and breeding of fragrant rice varieties, particularly for NTCD.

Chinese Sources for AfterWards:From Premodern Poetry,Paintings,and Medical Texts to Modern Novels,Film,and Documentaries

This paper focuses on Chinese sources suggested for a narrative medicine(NM)program,called AfterWards.Dr Lauren Small established AfterWards in 2014 and has been coordinating it since out of the Pediatrics Department at Johns Hopkins Medicine.In early 2019,she started giving a series of lectures and workshops about AfterWards to Chinese medical educators and clinicians in Beijing and Shanghai.She created an AfterWards Facilitator’s Guide based on Western-language sources for workshop participants.She also started to organize with Jiang Yuhong(Peking Union Medical College)a workshop for Chinese colleagues to be held at Johns Hopkins Medicine in October 2019.They invited the author to participate.The idea was hatched then to develop Chinese source materials following the AfterWards structure for an updated Facilitator’s Guide that Dr Small had initially written.A typical one-hour AfterWards session consists of a specific five-part structure:a literary text or artwork,an associated theme,discussion topics,a writing exercise,and shared reflection.While the content of the program always changes from session to session,the basic structure remains the same.This paper summarizes the types of Chinese sources and their related narrative-medicine themes that were originally selected for inclusion in the updated AfterWards Facilitator’s Guide intended for Chinese colleagues.These sources about coping with sick family members,aging,and illness ranged from the textual(classical Chinese poems on aging and diagnostic forms for training students)and visual(premodern Chinese paintings and murals of medical encounters)to the fictive(novels)and performative(contemporary Asian-American film in English and Chinese-language film and documentaries).

Characterization and distribution of novel alleles of the vernalization gene Vrn-A1 in Chinese wheat(Triticum aestivum L.) cultivars

The ability of wheat to adapt to a wide range of environmental conditions is determined mostly by allelic diversity among genes regulating vernalization requirement.Vrn-1 is a major regulator of this requirement.In this study,two novel alleles of Vrn-A1 were discovered in Chinese cultivars:vrn-A1n was identified in two landraces,Jiunong 2 and Ganchun 16,and Vrn-A1o was detected in Duanhongmangmai.Both novel alleles showed a linked duplication in the promoter region.The common copy of these two alleles was identical to the recessive allele vrn-A1.Compared with the recessive allele vrn-A1,the other copy of vrn-A1n contained a 54-bp deletion in the promoter region and the distinct copy of Vrn-A1o contained an11-bp deletion in the promoter region.In segregating populations in the greenhouse under nonvernalizing(20–25°C)and long-day(16 h light)conditions,plants with the novel vrn-A1n allele did not head earlier than those with the recessive vrn-A1 allele.However,plants that were either homozygous or heterozygous for the novel Vrn-A1o allele headed earlier than those with the recessive vrn-A1 allele.To identify the novel allele with the small-sized product and facilitate screening,a DNA marker for the novel dominant allele Vrn-A1o was designed.Analysis of the novel-allele distribution showed that two cultivars carrying the vrn-A1n allele were dispersed in the northwestern spring wheat zone,and 12 cultivars carrying the dominant Vrn-A1o allele were widely distributed in the northwestern spring wheat zone,Xinjiang winter and spring wheat zone,Yellow and Huai River valley winter wheat zone,and QinghaiTibetan Plateau spring and winter wheat zone.Our study identifies useful germplasm and a DNA marker for wheat breeding.