The big data challenge-and how polypharmacology supports the translation from pre-clinical research into clinical use against neurodegenerative diseases and beyond

Introductory comments:The identification and validation of disease-modifying proteins are fundamental aspects in drug development.However,the m ultifactority of n eurodegen era tive diseases poses a real challenge for targeted therapies.Furthermore,the behavior of individually(over-)expressed to rget proteins in vitro is likely to differ from their actual functional behavior when embedded in cascades and pathways in vivo.

RNPS1 stabilizes NAT10 protein to facilitate translation in cancer via tRNA ac^(4)C modification

Existing studies have underscored the pivotal role of N-acetyltransferase 10(NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma(HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1(RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6(ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac^(4)C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel t RNA-ac^(4)C modification sites, thereby providing a potent sequencing tool for tRNAac^(4)C research. Our findings expand the repertoire of tRNA ac^(4)C modifications and identify a role of tRNA ac^(4)C in the regulation of mRNA translation in HNSCC.

Effective extraction of polyribosomes from astrocytes enables future discoveries on translation regulation

Translation regulation is an important layer of gene expression:Generation of genome-wide expression datasets at multi-omics levels in spatial,temporal,and cell-type resolution is essential for deciphering brain complexity.Regulation of gene expression is a highly dynamic process aiming at the production of precise levels of gene products to guarantee optimal cellular function,in response to physiological cues.Speedy advances in next-generation sequencing enabled the understanding of epigenomic and transcriptomic dynamic landscapes of different brain regions along development,aging,and disease progression.However,the correlation of the“transcriptome”with protein levels is poor because numerous mRNAs are subjected to manipulation of their translation efficiency,to warrant a favorable result under certain conditions.Hence,it is widely accepted that regulation at the translation level is a vital layer of gene expression.Quantification of actively translated mRNA populations(i.e.,“translatome”)is a more reliable predictor of the“proteome”(Wang et al.,2020).

FPR1 Antagonist (BOC-MLF) Inhibits Amniotic Epithelial-mesenchymal Transition

Objective:Premature rupture of membranes(PROM)is a common pregnancy disorder that is closely associated with structural weakening of fetal membranes.Studies have found that formyl peptide receptor 1(FPR1)activates inflammatory pathways and amniotic epithelial-mesenchymal transition(EMT),stimulates collagen degradation,and leads to membrane weakening and membrane rupture.The purpose of this study was to investigate the anti-inflammatory and EMT inhibitory effects of FPR1 antagonist(BOC-MLF)to provide a basis for clinical prevention of PROM.Methods:The relationship between PROM,FPR1,and EMT was analyzed in human fetal membrane tissue and plasma samples using Western blotting,PCR,Masson staining,and ELISA assays.Lipopolysaccharide(LPS)was used to establish a fetal membrane inflammation model in pregnant rats,and BOC-MLF was used to treat the LPS rat model.We detected interleukin(IL)-6 in blood from the rat hearts to determine whether the inflammatory model was successful and whether the anti-inflammatory treatment was effective.We used electron microscopy to analyze the structure and collagen expression of rat fetal membrane.Results:Western blotting,PCR and Masson staining indicated that the expression of FPR1 was significantly increased,the expression of collagen was decreased,and EMT appeared in PROM.The rat model indicated that LPS caused the collapse of fetal membrane epithelial cells,increased intercellular gaps,and decreased collagen.BOC-MLF promoted an increase in fetal membrane collagen,inhibited EMT,and reduced the weakening of fetal membranes.Conclusion:The expression of FPR1 in the fetal membrane of PROM was significantly increased,and EMT of the amniotic membrane was obvious.BOC-MLF can treat inflammation and inhibit amniotic EMT.

语料库翻译研究背景下的“translationese”与“翻译共性”刍议

近年来,在基于语料库的翻译研究背景下,翻译语言特征描写中的两个关键词——“translationese”与“翻译共性”备受关注,两者之间既有区别,亦有交织重叠的地方。在国内翻译研究领域,“translationese”的译名和定义也不尽一致。本研究梳理了语料库研究方法背景下两者的概念和研究模式的发展,进而探讨了translationese的连续性特征以及它与翻译共性假设的关系问题,提出以“特征译语”为译名以突出其特点,并阐明了本研究在理论与实践方面的意义。

VX-509 attenuates the stemness characteristics of colorectal cancer stem-like cells by regulating the epithelial-mesenchymal transition through Nodal/Smad2/3 signaling

BACKGROUND Colorectal cancer stem cells(CCSCs)are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer(CRC)patients.CCSCs are generally accepted to be important sources of CRC and are responsible for the progression,metastasis,and therapeutic resistance of CRC.Therefore,targeting this specific subpopulation has been recognized as a promising strategy for overcoming CRC.AIM To investigate the effect of VX-509 on CCSCs and elucidate the underlying mechanism.METHODS CCSCs were enriched from CRC cell lines by in conditioned serum-free medium.Western blot,Aldefluor,transwell and tumorigenesis assays were performed to verify the phenotypic characteristics of the CCSCs.The anticancer efficacy of VX-509 was assessed in HCT116 CCSCs and HT29 CCSCs by performing cell viability analysis,colony formation,sphere formation,flow cytometry,and western blotting assessments in vitro and tumor growth,immunohistochemistry and immunofluorescence assessments in vivo.RESULTS Compared with parental cells,sphere cells derived from HCT116 and HT29 cells presented increased expression of stem cell transcription factors and stem cell markers and were more potent at promoting migration and tumori-genesis,demonstrating that the CRC sphere cells displayed CSC features.VX-509 inhibited the tumor malignant biological behavior of CRC-stem-like cells,as indicated by their proliferation,migration and clonality in vitro,and suppressed the tumor of CCSC-derived xenograft tumors in vivo.Besides,VX-509 suppressed the CSC character-istics of CRC-stem-like cells and inhibited the progression of epithelial-mesenchymal transition(EMT)signaling in vitro.Nodal was identified as the regulatory factor of VX-509 on CRC stem-like cells through analyses of differen-tially expressed genes and CSC-related database information.VX-509 markedly downregulated the expression of Nodal and its downstream phosphorylated Smad2/3 to inhibit EMT progression.Moreover,VX-509 reversed the dedifferentiation of CCSCs and inhibited the progression of EMT induced by Nodal overexpression.CONCLUSION VX-509 prevents the EMT process in CCSCs by inhibiting the transcription and protein expression of Nodal,and inhibits the dedifferentiated self-renewal of CCSCs.

LncRNA MEG3 Inhibits the Epithelial-mesenchymal Transition of Bladder Cancer Cells through the Snail/E-cadherin Axis

Objective This study aimed to investigate the role of the long noncoding RNA(lncRNA)maternally expressed gene 3(MEG3)in the epithelial-mesenchymal transition(EMT)of bladder cancer cells and the potential mechanisms.Methods Cell invasion,migration,and wound healing assays were conducted to assess the effects of MEG3 on the invasive and migratory capabilities of bladder cancer cells.The expression levels of E-cadherin were measured using Western blotting,RT-qPCR,and dual luciferase reporter assays.RNA immunoprecipitation and pull-down assays were performed to investigate the interactions between MEG3 and its downstream targets.Results MEG3 suppressed the invasion and migration of bladder cancer cells and modulated the transcription of E-cadherin.The binding of MEG3 to the zinc finger region of the transcription factor Snail prevented its ability to transcriptionally repress E-cadherin.Additionally,MEG3 suppressed the phosphorylation of extracellular regulated protein kinase(ERK),c-Jun N-terminal kinase(JNK),and P38,thereby decreasing the expression of Snail and stimulating the expression of E-cadherin.Conclusion MEG3 plays a vital role in suppressing the EMT in bladder cancer cells,indicating its potential as a promising therapeutic target for the treatment of bladder cancer.

CALD1 facilitates epithelial-mesenchymal transition progression in gastric cancer cells by modulating the PI3K-Akt pathway

BACKGROUND CALD1 has been discovered to be abnormally expressed in a variety of malignant tumors,including gastric cancer(GC),and is associated with tumor progression and immune infiltration;however,the roles and mechanisms of CALD1 in epithe-lial-mesenchymal transition(EMT)in GC are unknown.AIM To investigate the role and mechanism of CALD1 in GC progression,invasion,and migration.METHODS In this study,the relationship between CALD1 and GC,as well as the possible network regulatory mechanisms of CALD1,was investigated by bioinformatics and validated by experiments.CALD1-siRNA was synthesized and used to trans-fect GC cells.Cell activity was measured using the CCK-8 method,cell migration and invasive ability were measured using wound healing assay and Transwell assay,and the expression levels of relevant genes and proteins in each group of cells were measured using qRT-PCR and Western blot.A GC cell xenograft model RESULTS Bioinformatics results showed that CALD1 was highly expressed in GC tissues,and CALD1 was significantly higher in EMT-type GC tissues than in tissues of other types of GC.The prognosis of patients with high expression of CALD1 was worse than that of patients with low expression,and a prognostic model was constructed and evaluated.The experimental results were consistent with the results of the bioinformatics analysis.The expression level of CALD1 in GC cell lines was all higher than that in gastric epithelial cell line GES-1,with the strongest expression found in AGS and MKN45 cells.Cell activity was significantly reduced after CALD1-siRNA trans-fection of AGS and MKN45 cells.The ability of AGS and MKN45 cells to migrate and invade was reduced after CALD1-siRNA transfection,and the related mRNA and protein expression was altered.According to bioinfor-matics findings in GC samples,the CALD1 gene was significantly associated with the expression of members of the PI3K-AKT-mTOR signaling pathway as well as the EMT signaling pathway,and was closely related to the PI3K-Akt signaling pathway.Experimental validation revealed that upregulation of CALD1 increased the expression of PI3K,p-AKT,and p-mTOR,members of the PI3K-Akt pathway,while decreasing the expression of PTEN;PI3K-Akt inhibitor treatment decreased the expression of PI3K,p-AKT,and p-mTOR in cells overexpressing CALD1(still higher than that in the normal group),but increased the expression of PTEN(still lower than that in the normal group).CCK-8 results revealed that the effect of CALD1 on tumor cell activity was decreased by the addition of the inhibitor.Scratch and Transwell experiments showed that the effect of CALD1 on tumor cell migration and invasion was weakened by the addition of the PI3K-Akt inhibitor.The mRNA and protein levels of EMT-related genes in AGS and MKN45 cells were greatly altered by the overexpression of CALD1,whereas the effect of overex-pression of CALD1 was significantly weakened by the addition of the PI3K-Akt inhibitor.Animal experiments showed that tumour growth was slow after inhibition of CALD1,and the expression of some PI3K-Akt and EMT pathway proteins was altered.CONCLUSION Increased expression of CALD1 is a key factor in the progression,invasion,and metastasis of GC,which may be associated with regulating the PI3K-Akt pathway to promote EMT.

circPVT1 promotes silica-induced epithelial-mesenchymal transition by modulating the miR-497-5p/TCF3 axis

Epithelial-mesenchymal transition(EMT)is a vital pathological feature of silica-induced pulmonary fibrosis.However,whether circRNA is involved in the process remains unclear.The present study aimed to investigate the role of circPVT1 in the silica-induced EMT and the underlying mechanisms.We found that an elevated expression of circPVT1 promoted EMT and enhanced the migratory capacity of silica-treated epithelial cells.The isolation of cytoplasmic and nuclear separation assay showed that circPVT1 was predominantly expressed in the cytoplasm.RNA immunoprecipitation assay and RNA pull-down experiment indicated that cytoplasmic-localized circPVT1 was capable of binding to miR-497-5p.Furthermore,we found that miR-497-5p attenuated the silica-induced EMT process by targeting transcription factor 3(TCF3),an E-cadherin transcriptional repressor,in the silica-treated epithelial cells.Collectively,these results reveal a novel role of the circPVT1/miR-497-5p/TCF3 axis in the silica-induced EMT process in lung epithelial cells.Once validated,this finding may provide a potential theoretical basis for the development of interventions and treatments for pulmonary fibrosis.

Translation Strategies of Red Tourism Terms in the Central Plains-Taking Red Central Plains as an Example

In recent years,the Red Tourism in Central Plains has gradually become a new type of thematic tourism form,which is an important carrier to carry out patriotism and revolutionary traditional education and carry forward the national spirit.The translation of red tourism publicity is an important window for spreading Chinese culture,and the translation of professional terms is an important link in the red tourism publicity.How to spread the red culture of the Central Plains,glow the charm of the Central Plains culture,enhance the influence of the Central Plains culture,and spread the Central Plains culture to the world has become the mission of every child of the Central Plains.This paper adopts the case analysis method,combined with the specific and typical cases in“Red Central Plains”,and uses different translation strategies and methods to explore the difficulties and solutions of the translation of terms in the red tourism text.

A Study of English Translation Strategies of Subtitles of the Domestic Animated Film Chang’an from the Perspective of Eco-translatology

This article conducts an analysis and exploration of the English subtitles translation of the domestic animated film Chang’an from the perspective of eco-translatology.Taking three-dimensional transformation as the entry point,it analyzes the adaptation and selection of subtitle translators in the translation process from the dimensions of language,culture,and communication in Chang’an,aiming to enrich the practical analysis of eco-translatology and provide valuable insights and references for the theoretical construction and practical application of eco-translatology.This article enriches the practical analysis of eco-translatology and also validates to a certain extent the applicability of“three-dimensional”transformation.

Translation Theory and Techniques in Optometry Literature: A Case Study of the “Optoform 80 Installation and Maintenance Manual”

Translation of specialized documents in optometry presents unique challenges,requiring a deep understanding of the professional context,terminology,and adherence to specific translation styles.This paper delves into the translation theory and techniques employed in the English-to-Chinese translation of the“Optoform 80 Installation and Maintenance Manual”,serving as a case study.Emphasizing Nida’s theory of functional equivalence,the paper explores the complexities of translating professional optometry literature,focusing on key points and common issues in translating installation and maintenance manuals for optometric devices.Special attention is given to the translation of professional terminology,employing methods such as addition,omission,conversion,and repetition.The translation process aims to meet specific requirements,ensuring accuracy and coherence while aligning with Chinese language conventions.The paper also analyzes translation methods and techniques concerning terminology,prepositions,conjunctions,and handling parallel elements based on practical insights from the Optoform 80 Manual.

A Comparative Study of Chinese Translations of Tagore’s Stray Birds From the Perspective of the“Three Beauties Theory”

For more than 60 years,Mr.Xu Yuanchong has been devoted to education.He has not only made remarkable achievements in translating from and into Chinese,English,French and other languages,but has also developed his own unique concept of translation.Since 1950,he has always adhered to the“Three Beauties Theory”,believing that translation should not only rely on the original text,but also realize the“beauty of meaning”,“beauty of sound”,and“beauty of form”.Based on Xu Yuanchong’s“Three Beauties Theory”,this paper takes Zheng Zhenduo’s and Feng Tang’s Chinese translations of Stray Birds as an example to explore in depth the specifics of poetry translation theory.The study summarizes the similarities and differences between these two translations in embodying the“three beauties”,providing insights into the Chinese translation techniques of philosophical prose poems.This endeavor seeks to offer valuable insights for the comparative study of Stray Birds translations。

A Descriptive Translation Study of Chinese Translation of French Musical Roméo et Juliette

This paper presents a Descriptive Translation Study(DTS)analysis of the Chinese translation of the French musical adaptation of Romeo and Juliet,titled Roméo et Juliette:de la Haineàl’Amour.Romeo and Juliet,a timeless play by Shakespeare,has captivated audiences since its premiere in 1597 and has been adapted into various forms,including stage productions,films,musicals,and operas.The focus of this study is to analyze the Chinese translation of the French musical adaptation from a DTS perspective.DTS is an approach that aims to understand the translation process and its reception in the target culture.By examining language choices,cultural references,and adaptation strategies,this study seeks to shed light on how the Chinese translation of the French musical functions within the target culture and influences the reception and interpretation of the source text.This analysis is expected to gain insights into the challenges and strategies employed in translating a musical adaptation of Romeo and Juliet into Chinese.The findings of this study will contribute to the field of translation studies and provide a deeper understanding of the complexities involved in the translation of musical works.

The Translation of Allusions in Political Discourse:An Intertextuality Perspective

drawn from ancient classics are the treasures of traditional Chinese culture.The allusions used in Xi Jinping:The Governance of China illustrate a distinctive feature of political discourse,and the publication of its English version provides a valuable opportunity for the study of allusions in translated political discourse.With the English translations of 241 allusions collected from two volumes of the book,we classified these allusions into three categories of history,culture,and literature based on their original sources.Then we analyzed the strategies used in translating the allusions,and provided typical examples to illustrate the use of such translation strategies for each category.Finally,we tried to account for the use of these strategies in light of the intertextuality theory.

Exploring the groundwater response to rainfall in a translational landslide using the master recession curve method and cross-correlation function

Rainfall is a common trigger for landslide reactivation,as it raises groundwater levels and reduces bedrock or soil shear resistance.This study focuses on the Kualiangzi landslide in the southern region of Sichuan Province,China.Real-time monitoring of groundwater levels and rainfall from July 2013 to September 2016 is analyzed.Groundwater table increments,considering groundwater drainage rate,were calculated using the water-table fluctuation and master recession curve method and the response time of the groundwater table to rainfall events was estimated using the cross-correlation function.Results reveal that groundwater level declines from tension troughs to landslide fronts in the rainy season,with a significant positive correlation between the groundwater level in the tension trough and landslide surface displacement.Evaluated spring elevations for groundwater discharge range from 410 m to 440 m,which is in agreement with the actual spring elevations(390-423 m).Lag times of groundwater response to rainfall decreases with cumulative rainfall of the rainy periods.In the middle part of the landslide,two responses between rainfall and groundwater levels indicate two water movement pathways:Vertical cracks or fractures resulting from the slow landslide movement,and matrix pore space in unconsolidated sediment.Variations in peak values of the cross-correlation function suggest early dominance of the uniform matrix flow and later dominance of preferential flow during the rainy period.

Beyond Gender Perspectives:A More Comprehensive Examination of Yang Yi’s Translation of Wuthering Heights

The renowned translator Yang Yi passed away in 2023.Many scholars argue that,influenced by their biological gender,female translators often employ translation methods in adherence to feminist translation or reflect characteristics typical of female translators.This study examines the translation of Wuthering Heights by Yang Yi,focusing on whether there is a definite influence of gender on translator behavior.While existing literature primarily analyzes Yang Yi’s work through a feminist lens,this research takes a broader approach.By considering the translator’s social background and translation practice,this paper challenges the assumption that her work strictly aligns with feminist translation theories.Instead,this study emphasizes the importance of considering diverse factors when interpreting translated works,moving beyond a singular gender-based standpoint.

A Case Study of Periodical Terminologies’Mis-translations in History of Chinese Journalism by Ko Kung-chen under Analysis-Synthesis Translation Mode

From the perspective of analysis-synthesis translation mode,this paper discusses the translator’s responsibility and the translator’s role in the translation of historiography,based on the case of Ko Kung-chen’s History of Chinese Journalism.Missionary J.S.Roberts believed that translation is the logical combination of two processes of analysis and synthesis.The analysis process is characterized by understanding,emphasizing accurate understanding and professional analysis of the source text,while the synthesis process focuses on the transformation of language and culture.The two processes are dependent,forming the whole process of translation altogether.As the indisputable subject of translation,the translator should assume his own subjective responsibility in the two processes.The translator should be responsible for the fact and professional academics in the analysis process,and language and culture and translation itself in the synthesis process,playing the role of a reviewer,disseminator and translator to ensure that the translation text would be correct,accurate and professional so as to realize the value of himself and translation.

Analysis on the Translation Methods of the Reported Speech in German Academic Papers-Taking the Translation of“Die Internationalisierung der deutschen Hochschulen”as an Example

Reporting is essential in language use,including the re-expression of other people’s or self’s words,opinions,psychological activities,etc.Grasping the translation methods of reported speech in German academic papers is very important to improve the accuracy of academic paper translation.This study takes the translation of“Internationalization of German Universities”(Die Internationalisierung der deutschen Hochschulen),an academic paper of higher education,as an example to explore the translation methods of reported speech in German academic papers.It is found that the use of word order conversion,part of speech conversion and split translation methods can make the translation more accurate and fluent.This paper helps to grasp the rules and characteristics of the translation of reported speech in German academic papers,and also provides a reference for improving the quality of German-Chinese translation.

Transcreation in Advertisement Slogans from the Perspective of Communicative Translation Theory

Through in-depth analysis of advertisement slogans,the present study probes into the unique contribution of trancreation in conveying brand messages and triggering emotional resonance of the audience.The study firstly outlines theoretical basis of transcreation from the perspective of Communicative Translation Theory,emphasizing its uniqueness in the traditional translation paradigm.Then the four key steps of transcreation,including in-depth understanding of the brand essence,sensitive response to cultural differences,flexible use of language skills,and incorporation of creative elements,are examined by means of case analysis in advertisement translation.Finally,the article sums up the positive impact of transcreation on cultural exchange,brand communication and translation field,particularly in the era of globalisation.