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 ...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).展开更多
A novel small molecule depressant(M-DEP)was used to separate chalcopyrite and molybdenite via flotation.The results showed that M-DEP had an excellent selective depression on molybdenite,while had little effect on the...A novel small molecule depressant(M-DEP)was used to separate chalcopyrite and molybdenite via flotation.The results showed that M-DEP had an excellent selective depression on molybdenite,while had little effect on the flotation of chalcopyrite.The adsorption capacity of M-DEP on the surface of molybdenite was greater than that on chalcopyrite surface.The adsorption of M-DEP reduced the floatability of molybdenite and had less effect on the floatability of chalcopyrite,which was due to its different adsorption modes on the surface of the two minerals.Furthermore,the interaction between chalcopyrite and M-DEP was mainly chemical interaction,and almost all of the adsorbed M-DEP molecules were removed and replaced by sodium butyl xanthate(SBX).By contrast,hydrophobic interaction was the main way in which M-DEP was adsorbed on the molybdenite surface with little chemical interaction,which was less interfered by SBX addition.Therefore,M-DEP had a super selective depression on molybdenite.The study provided a novel depressant and approach for the deep separation of chalcopyrite and molybdenite via flotation.展开更多
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 ...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.展开更多
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...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.展开更多
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 ...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.展开更多
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 ch...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.展开更多
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 random...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.展开更多
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 De...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.展开更多
With the fast-pacing of globalization,cross-cultural communications are becoming increasingly frequent. Translation of the literary works,or novels is one of the most popular models of cultural exchange. While the tra...With the fast-pacing of globalization,cross-cultural communications are becoming increasingly frequent. Translation of the literary works,or novels is one of the most popular models of cultural exchange. While the translation of novel titles comes with first importance as successful translation of the titles facilitates a bird's eye view of the whole context. However,the translation of novel titles is no easy without consideration of cultural differences which directly influence people's thoughts and understanding. Therefore,translating novel titles requires an overall analysis of such cultural elements as religion,cultural images,way of thinking,and historical allusions.展开更多
Naipaul's novels are real and acute, which reflect many countries and social realities, especially terrible lives and depressed emotions, including human interests, opinions, ideas, consciousnesses, self-acceptance, ...Naipaul's novels are real and acute, which reflect many countries and social realities, especially terrible lives and depressed emotions, including human interests, opinions, ideas, consciousnesses, self-acceptance, idea crisis, looking for identity, spiritual trouble, contradiction between religion and life, cultural conflict in colonized countries and post-colonized areas. Such novels are from actual realities, life facts, street matters with miscellaneous, vicissitudinous, and integrative skills and abilities.展开更多
There is a great discovery that most respondents prefer to use movies to assist their learning of English novels and they are more competent in the course according to a survey. Through watching movies, learners could...There is a great discovery that most respondents prefer to use movies to assist their learning of English novels and they are more competent in the course according to a survey. Through watching movies, learners could better understand and appreciate the basic elements of a novel including plot, character, setting, narrative point of view, theme and style. Thus this approach is recommended to teachers and learners of British and American novels.展开更多
With his keen insight,William Golding becomes very conscious of the darkness of the human heart and the necessity that we become aware of this darkness if we are to save ourselves. All his novels,therefore,attempt to ...With his keen insight,William Golding becomes very conscious of the darkness of the human heart and the necessity that we become aware of this darkness if we are to save ourselves. All his novels,therefore,attempt to deal with the essential human condition. All Golding's novels,products of his peculiar literary temperament and habit,are reactive experiments. Each of them represents a response to a specific book by an early writer.展开更多
Though novel reading is a common experience to everybody,little has been researched to help average readers to understand a novel.In practice,there are two ways for them to understand a novel:one is to use literary cr...Though novel reading is a common experience to everybody,little has been researched to help average readers to understand a novel.In practice,there are two ways for them to understand a novel:one is to use literary criticism theories and the other is to refer to professional critics'criticism directly.However,the trouble is that the two methods are either time-consuming or far from convincing.In this paper,an experimental reading method is discussed to help average readers enhance reading experience.It aims at reaching the goal of reading without criticism,which,through making clear the aim of reading,putting main focus on the story only,will help readers to have a better understanding of reading.展开更多
Within the structure of globalisation,the field of world culture faces challenges that are manifested in the decline of national culture and the crisis of homogeneity of world culture.In this case,world culture should...Within the structure of globalisation,the field of world culture faces challenges that are manifested in the decline of national culture and the crisis of homogeneity of world culture.In this case,world culture should be promoted as a viable path to prosperity and development if it is done on the basis of adhering to the higher consciousness of national culture,developing intercultural dialogue,with the intention forming a situation of mutual learning and promoting the fusion of horizons.The Chinese Culture,Qilu genetic code and native writing embody Mo Yan’s conscious adherence to national culture,his thorough knowledge of “Seeking Roots” and “Vanguard”,the fusion of national and international characteristics and the integration of his hometown and other countries.These show his enthusiasm and courage in launching intercultural dialogue and reaching towards the fusion of horizons.How to face cultural challenges under this changing world pattern?The successful experience of Mo Yan’s novels provides us with vivid examples.展开更多
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 re...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.展开更多
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 t...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.展开更多
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...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.展开更多
基金supported by a Visiting Scholar Fellowship at Max Planck Institute for the History of Science, Berlin
文摘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).
基金support from the Project of Zhongyuan Critical Metals Laboratory(No.GJJSGFYQ202334)Natural Science Foundation of Henan Province(No.242300420002)+2 种基金National key research and development program(No.2020YFC1908804)National Natural Science Foundation of China(No.51804275)Modern Analysis and Gene Sequencing Centre in Zhengzhou University.
文摘A novel small molecule depressant(M-DEP)was used to separate chalcopyrite and molybdenite via flotation.The results showed that M-DEP had an excellent selective depression on molybdenite,while had little effect on the flotation of chalcopyrite.The adsorption capacity of M-DEP on the surface of molybdenite was greater than that on chalcopyrite surface.The adsorption of M-DEP reduced the floatability of molybdenite and had less effect on the floatability of chalcopyrite,which was due to its different adsorption modes on the surface of the two minerals.Furthermore,the interaction between chalcopyrite and M-DEP was mainly chemical interaction,and almost all of the adsorbed M-DEP molecules were removed and replaced by sodium butyl xanthate(SBX).By contrast,hydrophobic interaction was the main way in which M-DEP was adsorbed on the molybdenite surface with little chemical interaction,which was less interfered by SBX addition.Therefore,M-DEP had a super selective depression on molybdenite.The study provided a novel depressant and approach for the deep separation of chalcopyrite and molybdenite via flotation.
基金Supported by the Hangzhou Joint Fund of the Zhejiang Provincial Natural Science Foundation of China,No.LHZY24H020002Hangzhou Municipal Health Commission,No.ZD20220010Quzhou Bureau of Science and Technology,No.2022K51.
文摘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.
基金Tianjin Key Medical Discipline Construction Project,No.TJYXZDXK-034A.
文摘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.
文摘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.
基金The project name is“The Center for Teaching and Research of Ideology and Politics in English Courses of Sino-Foreign Cooperative Education Programs([2022]48)+English Course”.
文摘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.
文摘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.
文摘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.
文摘With the fast-pacing of globalization,cross-cultural communications are becoming increasingly frequent. Translation of the literary works,or novels is one of the most popular models of cultural exchange. While the translation of novel titles comes with first importance as successful translation of the titles facilitates a bird's eye view of the whole context. However,the translation of novel titles is no easy without consideration of cultural differences which directly influence people's thoughts and understanding. Therefore,translating novel titles requires an overall analysis of such cultural elements as religion,cultural images,way of thinking,and historical allusions.
文摘Naipaul's novels are real and acute, which reflect many countries and social realities, especially terrible lives and depressed emotions, including human interests, opinions, ideas, consciousnesses, self-acceptance, idea crisis, looking for identity, spiritual trouble, contradiction between religion and life, cultural conflict in colonized countries and post-colonized areas. Such novels are from actual realities, life facts, street matters with miscellaneous, vicissitudinous, and integrative skills and abilities.
文摘There is a great discovery that most respondents prefer to use movies to assist their learning of English novels and they are more competent in the course according to a survey. Through watching movies, learners could better understand and appreciate the basic elements of a novel including plot, character, setting, narrative point of view, theme and style. Thus this approach is recommended to teachers and learners of British and American novels.
文摘With his keen insight,William Golding becomes very conscious of the darkness of the human heart and the necessity that we become aware of this darkness if we are to save ourselves. All his novels,therefore,attempt to deal with the essential human condition. All Golding's novels,products of his peculiar literary temperament and habit,are reactive experiments. Each of them represents a response to a specific book by an early writer.
文摘Though novel reading is a common experience to everybody,little has been researched to help average readers to understand a novel.In practice,there are two ways for them to understand a novel:one is to use literary criticism theories and the other is to refer to professional critics'criticism directly.However,the trouble is that the two methods are either time-consuming or far from convincing.In this paper,an experimental reading method is discussed to help average readers enhance reading experience.It aims at reaching the goal of reading without criticism,which,through making clear the aim of reading,putting main focus on the story only,will help readers to have a better understanding of reading.
基金a phased achievement of the National Social Science Foundation project“Research on Mo Yan’s Novels and Overseas Acceptance from the Perspective of Postmodernism”(15BZ W041)Dalian Polytechnic University,2016J012a key research project in the field of basic research expenditure
文摘Within the structure of globalisation,the field of world culture faces challenges that are manifested in the decline of national culture and the crisis of homogeneity of world culture.In this case,world culture should be promoted as a viable path to prosperity and development if it is done on the basis of adhering to the higher consciousness of national culture,developing intercultural dialogue,with the intention forming a situation of mutual learning and promoting the fusion of horizons.The Chinese Culture,Qilu genetic code and native writing embody Mo Yan’s conscious adherence to national culture,his thorough knowledge of “Seeking Roots” and “Vanguard”,the fusion of national and international characteristics and the integration of his hometown and other countries.These show his enthusiasm and courage in launching intercultural dialogue and reaching towards the fusion of horizons.How to face cultural challenges under this changing world pattern?The successful experience of Mo Yan’s novels provides us with vivid examples.
文摘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.
基金Supported by Funds of Plastic Surgery Hospital of the Chinese Academy of Medical Sciences,Peking Union Medical College (No.YS202010)。
文摘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.
基金supported by the Natural Science Foundation of Shenyang,China(Grant No.22315605).
文摘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.