Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecul...Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecular mechanisms involved in these types of scars and developing effective treatments requires the use of controlled ex-perimental models,especially animals,to overcome the limitations of clinical studies.The aim of this sistematic review is to critically analyze the animal models used in the last five years(2020-2025)for the study of pathological scars,highlighting their advantages,limitations and applicability in the development of new therapeutic strat-egies.Murine,rabbit and porcine models,as well as alternative models,offer varied perspectives on the formation and treatment of HTS and KS,with an emphasis on histological and molecular correlations with human pathology.By synthesizing recent data,the paper highlights the essential role of preclinical research in optimizing an-tifibrotic treatments and in advancing the translation of data into the clinical sphere.Overall,animal models remain essential for bridging mechanistic insights with clinical translation,supporting the development of more effective and personalized anti-scar therapies.展开更多
Background:An increasing number of studies have shown that ferroptosis is related to the initiation and development of small cell lung cancer(SCLC).The systematic review aimed to summarize the characteristics of ferro...Background:An increasing number of studies have shown that ferroptosis is related to the initiation and development of small cell lung cancer(SCLC).The systematic review aimed to summarize the characteristics of ferroptosis from its pathogenetic role to translational therapeutic implications in SCLC.Methods:This systematic review,registered in PROSPERO(CRD420251090058),followed PRISMA 2020 guidelines.Comprehensive research of PubMed,Scopus,and Web of Science was performed for studies published between January 2010 and July 2025 investigating ferroptosis mechanisms,genetic or pharmacological modulation,or molecular profiling in SCLC.Two reviewers independently performed data extraction and quality assessment.Results:Nineteen preclinical studies met the inclusion criteria.Key regulators included solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),ferroptosis suppressor protein 1(FSP1),and acyl-CoA synthetase long chain family member 4(ACSL4).The molecular subtypes of SCLC,achaete-scute homolog 1(ASCL1),neuronal differentiation 1(NEUROD1),POU class 2 homeobox 3(POU2F3),and Yes1 associated transcriptional regulator(YAP1)exhibit differential ferroptosis gene expressions,influencing therapeutic responsiveness.Non-neuroendocrine subtypes are more ferroptosis-prone,whereas neuroendocrine variants display enhanced antioxidant defenses.Ferroptosis induction also promotes immune activation through stimulator of interferon genes(STING)-mediated CD8+T-cell recruitment.Conclusions:Ferroptosis constitutes a promising therapeutic axis in SCLC.Integrating ferroptosis biomarkers into molecular stratification frameworks could refine patient selection and support precision oncology strategies,warranting further translational and clinical validation.展开更多
Hepatocellular carcinoma(HCC)recurrence after liver transplantation(LT)presents a significant challenge,with recurrence rates ranging from 8%to 20%globally.Current biomarkers,such as alpha-fetoprotein(AFP)and des-gamm...Hepatocellular carcinoma(HCC)recurrence after liver transplantation(LT)presents a significant challenge,with recurrence rates ranging from 8%to 20%globally.Current biomarkers,such as alpha-fetoprotein(AFP)and des-gamma-carboxy prothrombin(DCP),lack specificity,limiting their utility in risk strati-fication.YKL-40,a glycoprotein involved in extracellular matrix remodeling,hepatic stellate cell activation,and immune modulation,has emerged as a promising biomarker for post-LT surveillance.Elevated serum levels of YKL-40 are associated with advanced liver disease,tumor progression,and poorer post-LT outcomes,highlighting its potential to address gaps in early detection and personalized management of HCC recurrence.This manuscript synthesizes clinical and mechanistic evidence to evaluate YKL-40’s predictive utility in post-LT care.While preliminary findings demonstrate its specificity for liver-related pathologies,challenges remain,including assay standardization,lack of pro-spective validation,and the need to distinguish between malignant and non-malignant causes of elevated levels.Integrating YKL-40 into multi-biomarker panels with AFP and DCP could enhance predictive accuracy and enable tailored therapeutic strategies.Future research should focus on multicenter studies to validate YKL-40’s clinical utility,address confounding factors like graft rejection and systemic inflammation,and explore its role in predictive models driven by emerging technologies such as artificial intelligence.YKL-40 holds transformative potential in reshaping post-LT care through precision medicine,providing a pathway for better outcomes and improved management of high-risk LT recipients.展开更多
A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity.However,regulatory mechanisms at the translational level under cardiac stress remain poorly und...A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity.However,regulatory mechanisms at the translational level under cardiac stress remain poorly understood.Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction(TAC)and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy(DCM).The results showed that the heart weight to body weight ratio was significantly elevated,and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC.Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle.RNAseq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling,metabolic processes,and signaling cascades associated with pathological cardiomyocyte growth.When combined with ribosome profiling analysis,we revealed that translation efficiency(TE)of 1,495 genes was enhanced,while the TE of 933 genes was inhibited following TAC.In DCM patients,1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level.Although the majority of the genes were not shared between mouse and human,we identified 93 genes,including Nos3,Kcnj8,Adcy4,Itpr1,Fasn,Scd1,etc.,with highly conserved translational regulations.These genes were remarkably associated with myocardial function,signal transduction,and energy metabolism,particularly related to cGMP-PKG signaling and fatty acid metabolism.Motif analysis revealed enriched regulatory elements in the 5′untranslated regions(5′UTRs)of transcripts with differential TE,which exhibited strong cross-species sequence conservation.Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.展开更多
Background:The Vietnamese swine represents a promising animal model due to its anatomical,physiological,and pathophysiological similarities to humans.Notably,the arrangement of lobes and ducts in the mammary glands is...Background:The Vietnamese swine represents a promising animal model due to its anatomical,physiological,and pathophysiological similarities to humans.Notably,the arrangement of lobes and ducts in the mammary glands is highly comparable to that of humans and is histologically indistinguishable.Leveraging these advantages through the chemical induction of carcinogenesis in this model offers a robust approach to mimic human exposure to carcinogenic compounds.Methods:This study elaborates on a protocol for developing a representative model of MNU-induced invasive breast carcinoma in three Vietnamese swine,validated histologically and immunologically.It evaluates not only the tissue similarity with humans,but also the development of chemically induced mammary tumors in an immunologically competent animal.Moreover,this study addresses the existing gap in histological knowledge regarding mammary tissue in the porcine model.Results:Our findings suggest that this model encompasses the full spectrum of cancer.It incorporates the key elements of a tumor microenvironment that enable tumor growth and propagation,such as immune cells,blood vessels,fibroblasts,extracellular matrix,fatty acids,and signaling molecules.Conclusions:This model offers significant potential to advance the understanding of cancer pathogenesis and facilitate the development of innovative therapeutic strategies by closely replicating human tumor biology.展开更多
Multiple myeloma is a complex and challenging blood cancer,particularly in cases where the disease has relapsed or become resistant to treatment.These situations often have a significant impact on both patient surviva...Multiple myeloma is a complex and challenging blood cancer,particularly in cases where the disease has relapsed or become resistant to treatment.These situations often have a significant impact on both patient survival and quality of life.Over recent years,advances in precision medicine and translational medicine have brought about a shift in treatment strategies,moving toward more personalized and targeted approaches.This review highlights the latest developments in the management of refractory and relapsed multiple myeloma,focusing on the current state of precision diagnosis and treatment,the role of translational medicine,and potential future directions in research.By reviewing key studies and clinical trial data,we aim to offer fresh perspectives and strategies that could improve clinical outcomes.展开更多
An article recently published in the World Journal of Diabetes,provides valuable insights into using immune biomarkers to identify renal damage in pediatric patients with newly diagnosed type 1 diabetes(T1D).Although ...An article recently published in the World Journal of Diabetes,provides valuable insights into using immune biomarkers to identify renal damage in pediatric patients with newly diagnosed type 1 diabetes(T1D).Although these findings are promising,clinical translation of these immune markers into routine diagnostics and preventive care remains challenging.In this letter,we propose building on the authors’work by exploring the integration of immune biomarkers into a more comprehensive dynamic risk stratification model for early renal injury.Com-bining immune system indicators with metabolic and genetic factors could enhance the predictive accuracy and support more personalized interventions.Longitudinal studies are needed to evaluate temporal changes in immune biomarkers and their association with long-term renal outcomes in children with T1Ds.Immunomodulatory therapies targeting early immune dysfunction can prevent or slow the progression of diabetic nephropathy.By incorporating these aspects,we hope to translate immune biomarkers from research into practical clinical tools,ultimately improving patient outcomes and reducing the burden of kidney-related complications in pediatric diabetes.展开更多
Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix,with oral-derived stem cells playing a significant role in this process.Various post-translational modifications(P...Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix,with oral-derived stem cells playing a significant role in this process.Various post-translational modifications(PTMs),such as phosphorylation,acetylation,methylation,and glycosylation,regulate osteogenic differentiation(OD).These modifications influence the expression of osteogenic genes by modulating the activity of key transcription factors like runt-related transcription factor 2 and osterix.While the molecular mechanisms behind OD are increasingly understood,many questions remain,particularly regarding how PTMs control the specificity and efficiency of stem cell differentiation.Recent research into these modifications has underscored the potential of stem cell therapy for bone regeneration and treating bone-related diseases.This review summarizes the role of PTMs in the OD of oral-derived stem cells,discusses their clinical applications,and suggests future research directions.展开更多
Frequent typhoons can significantly change the temperature,nutrient availability,and phytoplankton biomass in marginal seas.The oceanic response to typhoons is usually influenced by the features of the typhoon,among w...Frequent typhoons can significantly change the temperature,nutrient availability,and phytoplankton biomass in marginal seas.The oceanic response to typhoons is usually influenced by the features of the typhoon,among which the translational speed is critically important.By using a high resolution coupled physical-biological model,we investigated the response of the Yellow and East China seas(YECS)to two typhoons at different translational speeds,Muifa in August 2011 and Bolaven in August 2012.The model well reproduced the spatial and temporal variations of temperature,chlorophyll-a concentration over the YECS.Results show that typhoons with slower translational speeds uplift more deep water,leading to a more significant oceanic response.Divergence and convergence caused nutrient fluxes in opposite directions in the surface and bottom layers.Moreover,the nutrient flux in the bottom layer was greater than that in the surface layer.These phenomena are closely related to the spatial distribution of nutrients.Further studies show that the degree of ocean response to typhoons is highly correlated with the initial conditions of physical and biological elements of the upper ocean before the typhoon,as well as with ocean structure.Pretyphoon initial conditions of oceanic physical and ecological elements,mixed layer depth,and potential energy anomalies can all alter the degree of typhoon-induced oceanic response.This study emphasizes the important roles of the translational speed of typhoons and the initial oceanic conditions in the oceanic response to typhoons.展开更多
The Good Wife is an American TV series that focuses on women’s independence,politics,and law.The drama has been remade in China,Japan,and South Korea.This research aims to use Nida’s Functional Equivalence Theory to...The Good Wife is an American TV series that focuses on women’s independence,politics,and law.The drama has been remade in China,Japan,and South Korea.This research aims to use Nida’s Functional Equivalence Theory to analyze the methods of its English-to-Chinese subtitle translation by considering social,cultural,and historic backgrounds between China and America.After data collection and case analysis,the study found that:(1)Five major translation methods are adopted in the subtitle translation of The Good Wife.They are free translation,variation,literal translation,addition,and omission.Among them,free translation is the most frequently used,while omission is used least.(2)The subtitle translation of films and TV series is limited by time and space restrictions,social-cultural differences,and other factors.When translating,translators should try to use humorous words,euphemism,intonation,and other ways,and combine different methods such as literal translation,free translation,variation,addition,omission,and other methods to seek equivalence both in the meaning and function of subtitles under the guidance of Functional Equivalence Theory.展开更多
The lysosomal enzyme β-glucocerebrosidase(GCase) belongs to the family of glycosidases and hydrolyses the glycosphingolipid glucosylceramide(GluCer) into glucose and ceramide. The enzyme is of central importance for ...The lysosomal enzyme β-glucocerebrosidase(GCase) belongs to the family of glycosidases and hydrolyses the glycosphingolipid glucosylceramide(GluCer) into glucose and ceramide. The enzyme is of central importance for two pathologies:(1) the lysosomal storage disorder Gaucher's disease(GD) and(2) the neurodegenerative disorder Parkinson's disease(PD).展开更多
In this study,tropical cyclone(TC)translation speed was introduced as a new similarity factor within the generalized initial value(GIV)framework,enhancing the disaster preassessment capability of the dynamical statist...In this study,tropical cyclone(TC)translation speed was introduced as a new similarity factor within the generalized initial value(GIV)framework,enhancing the disaster preassessment capability of the dynamical statistical analog ensemble forecast model for landfalling TC disasters(DSAEF_LTD model).Three TC translation speed indicators most relevant to TC precipitation were incorporated:the maximum speed on Day 1(the first day of TC-induced precipitation and wind occurring on land)and the average and minimum speeds over All Days(all days of TC-induced precipitation and wind occurring on land),all classified using the Kmeans clustering algorithm.Simulation experiments showed that integrating TC translation speed enhanced the model's performance.The model provided a better optimal common scheme,with the TSS UM(sum of threat scores for severe and above and extremely severe and above disasters)increasing by 2.66%(from 0.5117 to 0.5253)compared with the original model.More importantly,its preassessment ability improved significantly,with the average TSS UM for independent samples increasing by 6.43%(from 0.6488 to0.6905).The modified model demonstrated greater accuracy in capturing disaster severity and distribution of TCs with significant speed characteristics or with regular tracks.This improvement stemmed from reduced false alarms due to the selection of analogs that are more similar to the target TC.The enhanced preassessment ability can be attributed to the key role of TC translation speed,which significantly influences TC precipitation patterns and improves TC precipitation forecasting.Since precipitation is one of the most crucial disaster-causing factors,better TC precipitation forecasting leads to improved disaster preassessment outcomes.These findings emphasize the promising potential of the DSAEF_LTD model for future TC disaster research and management,contributing to the achievement of the Sustainable Development Goals set by the United Nations 2030 Agenda by strengthening coastal resilience.展开更多
In multi-domain neural machine translation tasks,the disparity in data distribution between domains poses significant challenges in distinguishing domain features and sharing parameters across domains.This paper propo...In multi-domain neural machine translation tasks,the disparity in data distribution between domains poses significant challenges in distinguishing domain features and sharing parameters across domains.This paper proposes a Transformer-based multi-domain-aware mixture of experts model.To address the problem of domain feature differentiation,a mixture of experts(MoE)is introduced into attention to enhance the domain perception ability of the model,thereby improving the domain feature differentiation.To address the trade-off between domain feature distinction and cross-domain parameter sharing,we propose a domain-aware mixture of experts(DMoE).A domain-aware gating mechanism is introduced within the MoE module,simultaneously activating all domain experts to effectively blend domain feature distinction and cross-domain parameter sharing.A loss balancing function is then added to dynamically adjust the impact of the loss function on the expert distribution,enabling fine-tuning of the expert activation distribution to achieve a balance between domains.Experimental results on multiple Chinese-to-English and English-to-French datasets demonstrate that our proposed method significantly outperforms baseline models in both BLEU,chrF,and COMET metrics,validating its effectiveness in multi-domain neural machine translation.Further analysis of the probability distribution of expert activations shows that our method achieves remarkable results in both domain differentiation and cross-domain parameter sharing.展开更多
LargeLanguageModels(LLMs)are increasingly appliedinthe fieldof code translation.However,existing evaluation methodologies suffer from two major limitations:(1)the high overlap between test data and pretraining corpora...LargeLanguageModels(LLMs)are increasingly appliedinthe fieldof code translation.However,existing evaluation methodologies suffer from two major limitations:(1)the high overlap between test data and pretraining corpora,which introduces significant bias in performance evaluation;and(2)mainstream metrics focus primarily on surface-level accuracy,failing to uncover the underlying factors that constrain model capabilities.To address these issues,this paper presents TCode(Translation-Oriented Code Evaluation benchmark)—a complexity-controllable,contamination-free benchmark dataset for code translation—alongside a dedicated static feature sensitivity evaluation framework.The dataset is carefully designed to control complexity along multiple dimensions—including syntactic nesting and expression intricacy—enabling both broad coverage and fine-grained differentiation of sample difficulty.This design supports precise evaluation of model capabilities across a wide spectrum of translation challenges.The proposed evaluation framework introduces a correlation-driven analysis mechanism based on static program features,enabling predictive modeling of translation success from two perspectives:Code Form Complexity(e.g.,code length and character density)and Semantic Modeling Complexity(e.g.,syntactic depth,control-flow nesting,and type system complexity).Empirical evaluations across representative LLMs—including Qwen2.5-72B and Llama3.3-70B—demonstrate that even state-of-the-art models achieve over 80% compilation success on simple samples,but their accuracy drops sharply below 40% on complex cases.Further correlation analysis indicates that Semantic Modeling Complexity alone is correlated with up to 60% of the variance in translation success,with static program features exhibiting nonlinear threshold effects that highlight clear capability boundaries.This study departs fromthe traditional accuracy-centric evaluation paradigm and,for the first time,systematically characterizes the capabilities of large languagemodels in translation tasks through the lens of programstatic features.The findings provide actionable insights for model refinement and training strategy development.展开更多
“By successfully integrating artificial intelligence(AI)into research workflows,researchers could substantially increase scientific productivity”[1].In biofabrication,AI is dr iving a paradigm shift from empiricism ...“By successfully integrating artificial intelligence(AI)into research workflows,researchers could substantially increase scientific productivity”[1].In biofabrication,AI is dr iving a paradigm shift from empiricism toward intelligen t,data centric manufacturing[2].By integrating computation,automation,and biology,AI gives rise to self-evolving,adaptive systems that learn from data,predict complex behaviors,and autonomously optimize fabrication outcomes.Such systems translate experimental insights into patient-specific and clinically relevant solutions,bridging laboratory research and regenerative therapies[3].This emerging frontier is rapidly advancing from concept to application.This Special Column highlights how AI-driven advanc es in materials,design,and manufacturing are reshaping biof abrication for regenerative medicine and clinical translation.展开更多
GLOBAL GOVERNANCE AS AN INSTRUMENT FOR TRANSFORMING CHAOS INTO ORDERLY MULTIPOLARITY The current global geopolitical situation,marked by instability,the erosion of the post-WWII international order and the weakening o...GLOBAL GOVERNANCE AS AN INSTRUMENT FOR TRANSFORMING CHAOS INTO ORDERLY MULTIPOLARITY The current global geopolitical situation,marked by instability,the erosion of the post-WWII international order and the weakening of US unipolar dominance,requires joint efforts by major international actors and the wider international community to establish a functional international order for the twenty-first century.展开更多
基金Ministry of Research,Innovation and Digitization,CCCDI-UEFISCDI,Grant/Award Number:PN-IV-P7-7.1-PED-2024-1578,within PNCDI Ⅳ.
文摘Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecular mechanisms involved in these types of scars and developing effective treatments requires the use of controlled ex-perimental models,especially animals,to overcome the limitations of clinical studies.The aim of this sistematic review is to critically analyze the animal models used in the last five years(2020-2025)for the study of pathological scars,highlighting their advantages,limitations and applicability in the development of new therapeutic strat-egies.Murine,rabbit and porcine models,as well as alternative models,offer varied perspectives on the formation and treatment of HTS and KS,with an emphasis on histological and molecular correlations with human pathology.By synthesizing recent data,the paper highlights the essential role of preclinical research in optimizing an-tifibrotic treatments and in advancing the translation of data into the clinical sphere.Overall,animal models remain essential for bridging mechanistic insights with clinical translation,supporting the development of more effective and personalized anti-scar therapies.
基金supported by Regione Autonoma della Sardegna,pursuant to Regional Law 07 August 2007,n.7“Promotion of Scientific Research and Technological Innovation in Sardinia—UGOV Project RAS_CRP2023 CARRULilt Nazionale—5 per mille Program for the year 2022,LILT 2023 scientific-health research call,Number:LILT—Protocol number 2024U0001294 of 29.03.2024。
文摘Background:An increasing number of studies have shown that ferroptosis is related to the initiation and development of small cell lung cancer(SCLC).The systematic review aimed to summarize the characteristics of ferroptosis from its pathogenetic role to translational therapeutic implications in SCLC.Methods:This systematic review,registered in PROSPERO(CRD420251090058),followed PRISMA 2020 guidelines.Comprehensive research of PubMed,Scopus,and Web of Science was performed for studies published between January 2010 and July 2025 investigating ferroptosis mechanisms,genetic or pharmacological modulation,or molecular profiling in SCLC.Two reviewers independently performed data extraction and quality assessment.Results:Nineteen preclinical studies met the inclusion criteria.Key regulators included solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),ferroptosis suppressor protein 1(FSP1),and acyl-CoA synthetase long chain family member 4(ACSL4).The molecular subtypes of SCLC,achaete-scute homolog 1(ASCL1),neuronal differentiation 1(NEUROD1),POU class 2 homeobox 3(POU2F3),and Yes1 associated transcriptional regulator(YAP1)exhibit differential ferroptosis gene expressions,influencing therapeutic responsiveness.Non-neuroendocrine subtypes are more ferroptosis-prone,whereas neuroendocrine variants display enhanced antioxidant defenses.Ferroptosis induction also promotes immune activation through stimulator of interferon genes(STING)-mediated CD8+T-cell recruitment.Conclusions:Ferroptosis constitutes a promising therapeutic axis in SCLC.Integrating ferroptosis biomarkers into molecular stratification frameworks could refine patient selection and support precision oncology strategies,warranting further translational and clinical validation.
文摘Hepatocellular carcinoma(HCC)recurrence after liver transplantation(LT)presents a significant challenge,with recurrence rates ranging from 8%to 20%globally.Current biomarkers,such as alpha-fetoprotein(AFP)and des-gamma-carboxy prothrombin(DCP),lack specificity,limiting their utility in risk strati-fication.YKL-40,a glycoprotein involved in extracellular matrix remodeling,hepatic stellate cell activation,and immune modulation,has emerged as a promising biomarker for post-LT surveillance.Elevated serum levels of YKL-40 are associated with advanced liver disease,tumor progression,and poorer post-LT outcomes,highlighting its potential to address gaps in early detection and personalized management of HCC recurrence.This manuscript synthesizes clinical and mechanistic evidence to evaluate YKL-40’s predictive utility in post-LT care.While preliminary findings demonstrate its specificity for liver-related pathologies,challenges remain,including assay standardization,lack of pro-spective validation,and the need to distinguish between malignant and non-malignant causes of elevated levels.Integrating YKL-40 into multi-biomarker panels with AFP and DCP could enhance predictive accuracy and enable tailored therapeutic strategies.Future research should focus on multicenter studies to validate YKL-40’s clinical utility,address confounding factors like graft rejection and systemic inflammation,and explore its role in predictive models driven by emerging technologies such as artificial intelligence.YKL-40 holds transformative potential in reshaping post-LT care through precision medicine,providing a pathway for better outcomes and improved management of high-risk LT recipients.
基金supported by grants from National Natural Science Foundation of China(No.82370392)Shenzhen Medical Research Fund(No.B2302026)+4 种基金Science,Technology and Innovation Commission of Shenzhen Municipality(No.RCJC20210706091947009)National Key R&D Program of China(No.2022YFA1104500)CAMS Innovation Fund for Medical Sciences(No.2023-I2M-1-003 and 2022-I2M-2-001)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2019PT320026)National High Level Hospital Clinical Research Funding(No.2022-GSP-GG-7)。
文摘A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity.However,regulatory mechanisms at the translational level under cardiac stress remain poorly understood.Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction(TAC)and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy(DCM).The results showed that the heart weight to body weight ratio was significantly elevated,and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC.Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle.RNAseq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling,metabolic processes,and signaling cascades associated with pathological cardiomyocyte growth.When combined with ribosome profiling analysis,we revealed that translation efficiency(TE)of 1,495 genes was enhanced,while the TE of 933 genes was inhibited following TAC.In DCM patients,1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level.Although the majority of the genes were not shared between mouse and human,we identified 93 genes,including Nos3,Kcnj8,Adcy4,Itpr1,Fasn,Scd1,etc.,with highly conserved translational regulations.These genes were remarkably associated with myocardial function,signal transduction,and energy metabolism,particularly related to cGMP-PKG signaling and fatty acid metabolism.Motif analysis revealed enriched regulatory elements in the 5′untranslated regions(5′UTRs)of transcripts with differential TE,which exhibited strong cross-species sequence conservation.Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
基金C.E.Vera-Tizatl(CVU:708156)thank the National Council for Science and Technology(CONACYT,Mexico)for the scholarship granted。
文摘Background:The Vietnamese swine represents a promising animal model due to its anatomical,physiological,and pathophysiological similarities to humans.Notably,the arrangement of lobes and ducts in the mammary glands is highly comparable to that of humans and is histologically indistinguishable.Leveraging these advantages through the chemical induction of carcinogenesis in this model offers a robust approach to mimic human exposure to carcinogenic compounds.Methods:This study elaborates on a protocol for developing a representative model of MNU-induced invasive breast carcinoma in three Vietnamese swine,validated histologically and immunologically.It evaluates not only the tissue similarity with humans,but also the development of chemically induced mammary tumors in an immunologically competent animal.Moreover,this study addresses the existing gap in histological knowledge regarding mammary tissue in the porcine model.Results:Our findings suggest that this model encompasses the full spectrum of cancer.It incorporates the key elements of a tumor microenvironment that enable tumor growth and propagation,such as immune cells,blood vessels,fibroblasts,extracellular matrix,fatty acids,and signaling molecules.Conclusions:This model offers significant potential to advance the understanding of cancer pathogenesis and facilitate the development of innovative therapeutic strategies by closely replicating human tumor biology.
基金supported by grants from the 925th Science Foundation(Grant Nos.2023-3 and 2024-2/3).
文摘Multiple myeloma is a complex and challenging blood cancer,particularly in cases where the disease has relapsed or become resistant to treatment.These situations often have a significant impact on both patient survival and quality of life.Over recent years,advances in precision medicine and translational medicine have brought about a shift in treatment strategies,moving toward more personalized and targeted approaches.This review highlights the latest developments in the management of refractory and relapsed multiple myeloma,focusing on the current state of precision diagnosis and treatment,the role of translational medicine,and potential future directions in research.By reviewing key studies and clinical trial data,we aim to offer fresh perspectives and strategies that could improve clinical outcomes.
文摘An article recently published in the World Journal of Diabetes,provides valuable insights into using immune biomarkers to identify renal damage in pediatric patients with newly diagnosed type 1 diabetes(T1D).Although these findings are promising,clinical translation of these immune markers into routine diagnostics and preventive care remains challenging.In this letter,we propose building on the authors’work by exploring the integration of immune biomarkers into a more comprehensive dynamic risk stratification model for early renal injury.Com-bining immune system indicators with metabolic and genetic factors could enhance the predictive accuracy and support more personalized interventions.Longitudinal studies are needed to evaluate temporal changes in immune biomarkers and their association with long-term renal outcomes in children with T1Ds.Immunomodulatory therapies targeting early immune dysfunction can prevent or slow the progression of diabetic nephropathy.By incorporating these aspects,we hope to translate immune biomarkers from research into practical clinical tools,ultimately improving patient outcomes and reducing the burden of kidney-related complications in pediatric diabetes.
文摘Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix,with oral-derived stem cells playing a significant role in this process.Various post-translational modifications(PTMs),such as phosphorylation,acetylation,methylation,and glycosylation,regulate osteogenic differentiation(OD).These modifications influence the expression of osteogenic genes by modulating the activity of key transcription factors like runt-related transcription factor 2 and osterix.While the molecular mechanisms behind OD are increasingly understood,many questions remain,particularly regarding how PTMs control the specificity and efficiency of stem cell differentiation.Recent research into these modifications has underscored the potential of stem cell therapy for bone regeneration and treating bone-related diseases.This review summarizes the role of PTMs in the OD of oral-derived stem cells,discusses their clinical applications,and suggests future research directions.
基金Supported by the National Natural Science Foundation of China(Nos.42006018,42276009,42376199)the Open Fund Project of the Key Laboratory of Ocean Observation and Information of Hainan Province(No.HKLOOI-OF-2023-03)the Tianjin Natural Science Foundation(Nos.21JCYBJC00500,21JCQNJC00590)。
文摘Frequent typhoons can significantly change the temperature,nutrient availability,and phytoplankton biomass in marginal seas.The oceanic response to typhoons is usually influenced by the features of the typhoon,among which the translational speed is critically important.By using a high resolution coupled physical-biological model,we investigated the response of the Yellow and East China seas(YECS)to two typhoons at different translational speeds,Muifa in August 2011 and Bolaven in August 2012.The model well reproduced the spatial and temporal variations of temperature,chlorophyll-a concentration over the YECS.Results show that typhoons with slower translational speeds uplift more deep water,leading to a more significant oceanic response.Divergence and convergence caused nutrient fluxes in opposite directions in the surface and bottom layers.Moreover,the nutrient flux in the bottom layer was greater than that in the surface layer.These phenomena are closely related to the spatial distribution of nutrients.Further studies show that the degree of ocean response to typhoons is highly correlated with the initial conditions of physical and biological elements of the upper ocean before the typhoon,as well as with ocean structure.Pretyphoon initial conditions of oceanic physical and ecological elements,mixed layer depth,and potential energy anomalies can all alter the degree of typhoon-induced oceanic response.This study emphasizes the important roles of the translational speed of typhoons and the initial oceanic conditions in the oceanic response to typhoons.
文摘The Good Wife is an American TV series that focuses on women’s independence,politics,and law.The drama has been remade in China,Japan,and South Korea.This research aims to use Nida’s Functional Equivalence Theory to analyze the methods of its English-to-Chinese subtitle translation by considering social,cultural,and historic backgrounds between China and America.After data collection and case analysis,the study found that:(1)Five major translation methods are adopted in the subtitle translation of The Good Wife.They are free translation,variation,literal translation,addition,and omission.Among them,free translation is the most frequently used,while omission is used least.(2)The subtitle translation of films and TV series is limited by time and space restrictions,social-cultural differences,and other factors.When translating,translators should try to use humorous words,euphemism,intonation,and other ways,and combine different methods such as literal translation,free translation,variation,addition,omission,and other methods to seek equivalence both in the meaning and function of subtitles under the guidance of Functional Equivalence Theory.
基金supported by the Michael J Fox Foundation (to PA and FZ)。
文摘The lysosomal enzyme β-glucocerebrosidase(GCase) belongs to the family of glycosidases and hydrolyses the glycosphingolipid glucosylceramide(GluCer) into glucose and ceramide. The enzyme is of central importance for two pathologies:(1) the lysosomal storage disorder Gaucher's disease(GD) and(2) the neurodegenerative disorder Parkinson's disease(PD).
基金supported by the Key Laboratory of South China Sea Meteorological Disaster Prevention and Mitigation of Hainan Province(No.SCSF202307)the Basic Research Fund of CAMS(No.2023Z016)+1 种基金the National Natural Scientific Foundation of China(No.42275037)the Jiangsu Collaborative Innovation Center for Climate Change。
文摘In this study,tropical cyclone(TC)translation speed was introduced as a new similarity factor within the generalized initial value(GIV)framework,enhancing the disaster preassessment capability of the dynamical statistical analog ensemble forecast model for landfalling TC disasters(DSAEF_LTD model).Three TC translation speed indicators most relevant to TC precipitation were incorporated:the maximum speed on Day 1(the first day of TC-induced precipitation and wind occurring on land)and the average and minimum speeds over All Days(all days of TC-induced precipitation and wind occurring on land),all classified using the Kmeans clustering algorithm.Simulation experiments showed that integrating TC translation speed enhanced the model's performance.The model provided a better optimal common scheme,with the TSS UM(sum of threat scores for severe and above and extremely severe and above disasters)increasing by 2.66%(from 0.5117 to 0.5253)compared with the original model.More importantly,its preassessment ability improved significantly,with the average TSS UM for independent samples increasing by 6.43%(from 0.6488 to0.6905).The modified model demonstrated greater accuracy in capturing disaster severity and distribution of TCs with significant speed characteristics or with regular tracks.This improvement stemmed from reduced false alarms due to the selection of analogs that are more similar to the target TC.The enhanced preassessment ability can be attributed to the key role of TC translation speed,which significantly influences TC precipitation patterns and improves TC precipitation forecasting.Since precipitation is one of the most crucial disaster-causing factors,better TC precipitation forecasting leads to improved disaster preassessment outcomes.These findings emphasize the promising potential of the DSAEF_LTD model for future TC disaster research and management,contributing to the achievement of the Sustainable Development Goals set by the United Nations 2030 Agenda by strengthening coastal resilience.
基金supported by the NationalNatural Science Foundation of China(U2004163)Key Research and Development Program of Henan Province(No.251111211200).
文摘In multi-domain neural machine translation tasks,the disparity in data distribution between domains poses significant challenges in distinguishing domain features and sharing parameters across domains.This paper proposes a Transformer-based multi-domain-aware mixture of experts model.To address the problem of domain feature differentiation,a mixture of experts(MoE)is introduced into attention to enhance the domain perception ability of the model,thereby improving the domain feature differentiation.To address the trade-off between domain feature distinction and cross-domain parameter sharing,we propose a domain-aware mixture of experts(DMoE).A domain-aware gating mechanism is introduced within the MoE module,simultaneously activating all domain experts to effectively blend domain feature distinction and cross-domain parameter sharing.A loss balancing function is then added to dynamically adjust the impact of the loss function on the expert distribution,enabling fine-tuning of the expert activation distribution to achieve a balance between domains.Experimental results on multiple Chinese-to-English and English-to-French datasets demonstrate that our proposed method significantly outperforms baseline models in both BLEU,chrF,and COMET metrics,validating its effectiveness in multi-domain neural machine translation.Further analysis of the probability distribution of expert activations shows that our method achieves remarkable results in both domain differentiation and cross-domain parameter sharing.
文摘LargeLanguageModels(LLMs)are increasingly appliedinthe fieldof code translation.However,existing evaluation methodologies suffer from two major limitations:(1)the high overlap between test data and pretraining corpora,which introduces significant bias in performance evaluation;and(2)mainstream metrics focus primarily on surface-level accuracy,failing to uncover the underlying factors that constrain model capabilities.To address these issues,this paper presents TCode(Translation-Oriented Code Evaluation benchmark)—a complexity-controllable,contamination-free benchmark dataset for code translation—alongside a dedicated static feature sensitivity evaluation framework.The dataset is carefully designed to control complexity along multiple dimensions—including syntactic nesting and expression intricacy—enabling both broad coverage and fine-grained differentiation of sample difficulty.This design supports precise evaluation of model capabilities across a wide spectrum of translation challenges.The proposed evaluation framework introduces a correlation-driven analysis mechanism based on static program features,enabling predictive modeling of translation success from two perspectives:Code Form Complexity(e.g.,code length and character density)and Semantic Modeling Complexity(e.g.,syntactic depth,control-flow nesting,and type system complexity).Empirical evaluations across representative LLMs—including Qwen2.5-72B and Llama3.3-70B—demonstrate that even state-of-the-art models achieve over 80% compilation success on simple samples,but their accuracy drops sharply below 40% on complex cases.Further correlation analysis indicates that Semantic Modeling Complexity alone is correlated with up to 60% of the variance in translation success,with static program features exhibiting nonlinear threshold effects that highlight clear capability boundaries.This study departs fromthe traditional accuracy-centric evaluation paradigm and,for the first time,systematically characterizes the capabilities of large languagemodels in translation tasks through the lens of programstatic features.The findings provide actionable insights for model refinement and training strategy development.
文摘“By successfully integrating artificial intelligence(AI)into research workflows,researchers could substantially increase scientific productivity”[1].In biofabrication,AI is dr iving a paradigm shift from empiricism toward intelligen t,data centric manufacturing[2].By integrating computation,automation,and biology,AI gives rise to self-evolving,adaptive systems that learn from data,predict complex behaviors,and autonomously optimize fabrication outcomes.Such systems translate experimental insights into patient-specific and clinically relevant solutions,bridging laboratory research and regenerative therapies[3].This emerging frontier is rapidly advancing from concept to application.This Special Column highlights how AI-driven advanc es in materials,design,and manufacturing are reshaping biof abrication for regenerative medicine and clinical translation.
文摘GLOBAL GOVERNANCE AS AN INSTRUMENT FOR TRANSFORMING CHAOS INTO ORDERLY MULTIPOLARITY The current global geopolitical situation,marked by instability,the erosion of the post-WWII international order and the weakening of US unipolar dominance,requires joint efforts by major international actors and the wider international community to establish a functional international order for the twenty-first century.
