As an important food and feed crop, cultivated rye (Secale cereale L.) exhibits excellent resistance to biotic and abiotic stresses, making it a valuable genetic resource for wheat improvement. However, the functions of phytochromes in rye remain poorly characterized. Here, we cloned and characterized PhyB from the Weining rye variety (ScPhyB). The predicted protein contains conserved phytochrome domains-PAS, GAF, PHY, and HATPase-and phylogenetic analysis revealed that ScPhyB is most closely related to wheat TaPhyB, with both belonging to the monocot clade. Promoter analysis identified multiple cis-acting elements related to hormone response, meristem expression, low temperature responsiveness, light response, and MYB binding. Heterologous expression of ScPhyB in Arabidopsis enhanced photomorphogenesis under white light (WL), red light (R), and blue light (B). Furthermore, ScPhyB attenuated shade avoidance responses to 70 % and 90 % of wildtype seedlings measured by hypocotyl length by perceiving high and low R/FR red to far-red (R/FR) light ratio, respectively. ScPhyB also modulated plant architecture and delayed flowering (6-7d) by repressing FT expression. Yeast two-hybrid (Y2H) assays and split-luciferase (LUC) assay confirmed that ScPhyB interacts with both ScPIF3 and ScCOP1, indicating functional conservation within the PIF signaling pathway and the COP1-SPA1 complex. Our findings provide insight into the role of ScPhyB in light signaling and suggest its potential utility for improving crop traits.
{"title":"The rye photoreceptor ScphyB integrates light signals to control development and architecture in Arabidopsis thaliana.","authors":"Mengdan Ning, Yankun Li, Luhao Yang, Yongtao Li, Yirong Yu, Yu Zhang, Yanpei Zhang, Tao Mu, Maciren Ni, Qiang Qin, Shaowei Li, Junxi Wu, Jianping Yang, Yong Shi","doi":"10.1016/j.gene.2026.150009","DOIUrl":"https://doi.org/10.1016/j.gene.2026.150009","url":null,"abstract":"<p><p>As an important food and feed crop, cultivated rye (Secale cereale L.) exhibits excellent resistance to biotic and abiotic stresses, making it a valuable genetic resource for wheat improvement. However, the functions of phytochromes in rye remain poorly characterized. Here, we cloned and characterized PhyB from the Weining rye variety (ScPhyB). The predicted protein contains conserved phytochrome domains-PAS, GAF, PHY, and HATPase-and phylogenetic analysis revealed that ScPhyB is most closely related to wheat TaPhyB, with both belonging to the monocot clade. Promoter analysis identified multiple cis-acting elements related to hormone response, meristem expression, low temperature responsiveness, light response, and MYB binding. Heterologous expression of ScPhyB in Arabidopsis enhanced photomorphogenesis under white light (WL), red light (R), and blue light (B). Furthermore, ScPhyB attenuated shade avoidance responses to 70 % and 90 % of wildtype seedlings measured by hypocotyl length by perceiving high and low R/FR red to far-red (R/FR) light ratio, respectively. ScPhyB also modulated plant architecture and delayed flowering (6-7d) by repressing FT expression. Yeast two-hybrid (Y2H) assays and split-luciferase (LUC) assay confirmed that ScPhyB interacts with both ScPIF3 and ScCOP1, indicating functional conservation within the PIF signaling pathway and the COP1-SPA1 complex. Our findings provide insight into the role of ScPhyB in light signaling and suggest its potential utility for improving crop traits.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"150009"},"PeriodicalIF":2.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1016/j.gene.2026.150012
Liyan Qiu , Caisheng Xu , Renhua Lu , Shaobin Lin , Fang Yang
WNT7B-related pulmonary hypoplasia, diaphragmatic anomalies, anophthalmia/microphthalmia, and cardiac defects (PDAC) syndrome is rarely reported. To date, only two each nonsense and missense variants of WNT7B were identified in five pedigrees affected with a PDAC spectrum from two independent studies. Additionally, the gene-disease association between WNT7B and PDAC syndrome is not yet clarified in OMIM database. Here, the whole exome sequencing was used to identify biallelic novel loss-of-function (LoF) variants c.324C > G (p.Tyr108*) and c.668_669dup (p.Val224Argfs*6) of WNT7B in a fetus affected with a typical PDAC spectrum, including pulmonary hypoplasia/agenesis, bilateral microphthalmia, and absence of pulmonary arteries and veins, from a Chinese family. Subsequent functional analysis revealed that the two LoF variants decreased the RNA and protein expression levels of WNT7B, and significantly impaired the canonical WNT-β-Catenin signaling pathway, which is essential for regulation of human lung development. We broaden the variant spectrum of WNT7B, and provide genetic and experimental evidence to confirm the association between WNT7B pathogenic variants and PDAC spectrum.
wnt7b相关的肺发育不全、膈异常、眼无/小眼和心脏缺陷(PDAC)综合征很少报道。迄今为止,只有两个无义和错义的WNT7B变体被鉴定在5个家谱受影响的PDAC从两个独立的研究。此外,在OMIM数据库中,WNT7B与PDAC综合征之间的基因-疾病关联尚未明确。本研究利用全外显子组测序技术,鉴定了来自一个中国家庭的WNT7B双等位基因新型功能缺失(LoF)变异c.324C > G (p.Tyr108*)和c.668_669dup (p.Val224Argfs*6),这些变异具有典型的PDAC谱系,包括肺发育不全/发育不全、双侧小眼和肺动脉静脉缺失。随后的功能分析显示,这两个LoF变异降低了WNT7B的RNA和蛋白表达水平,并显著损害了典型的WNT-β-Catenin信号通路,该信号通路是调节人类肺发育所必需的。我们拓宽了WNT7B的变异谱,并提供了遗传和实验证据来证实WNT7B致病变异与PDAC谱之间的关联。
{"title":"Identification and functional analysis of biallelic loss-of-function variants of WNT7B in a Chinese family affected with PDAC syndrome","authors":"Liyan Qiu , Caisheng Xu , Renhua Lu , Shaobin Lin , Fang Yang","doi":"10.1016/j.gene.2026.150012","DOIUrl":"10.1016/j.gene.2026.150012","url":null,"abstract":"<div><div><em>WNT7B</em>-related pulmonary hypoplasia, diaphragmatic anomalies, anophthalmia/microphthalmia, and cardiac defects (PDAC) syndrome is rarely reported. To date, only two each nonsense and missense variants of <em>WNT7B</em> were identified in five pedigrees affected with a PDAC spectrum from two independent studies. Additionally, the gene-disease association between <em>WNT7B</em> and PDAC syndrome is not yet clarified in OMIM database. Here, the whole exome sequencing was used to identify biallelic novel loss-of-function (LoF) variants c.324C > G (p.Tyr108*) and c.668_669dup (p.Val224Argfs*6) of <em>WNT7B</em> in a fetus affected with a typical PDAC spectrum, including pulmonary hypoplasia/agenesis, bilateral microphthalmia, and absence of pulmonary arteries and veins, from a Chinese family. Subsequent functional analysis revealed that the two LoF variants decreased the RNA and protein expression levels of <em>WNT7B</em>, and significantly impaired the canonical WNT-β-Catenin signaling pathway, which is essential for regulation of human lung development. We broaden the variant spectrum of <em>WNT7B</em>, and provide genetic and experimental evidence to confirm the association between <em>WNT7B</em> pathogenic variants and PDAC spectrum.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"985 ","pages":"Article 150012"},"PeriodicalIF":2.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Next-generation sequencing (NGS) is a high-throughput technology capable of determining the sequence of nucleotides in the genome. Over the past few years, the advent of NGS-based methods has provided timely and economical approaches for diagnosing and screening genetic conditions throughout an individual's lifespan, and prenatal period. Prenatal screening for congenital abnormalities has opened the door to reducing the incidence of genetic disorders. Early detection of genetic diseases using NGS-based methods enables better management of these conditions, thereby improving the quality of life for patients. NGS has also played a pivotal role in pharmacogenetics and drug delivery, facilitating a more personalized approach to medicine. NGS-based methods are increasingly being utilized in genome editing to provide essential information that enhances the precision and effectiveness of editing techniques. This review presents information on how various NGS-based methods function from a technical perspective. Furthermore, we will explore the applications and benefits of these methods in the fields of diagnosis, screening, pharmacogenetics, and genome editing.
{"title":"Next-generation sequencing as an applicable method: from technical basis to use in medical diagnosis.","authors":"Arman Moradi, Mina Mousavi, Majid Maleki, Seyedeh Zoha Tabatabaei, Mahshid Malakootian","doi":"10.1016/j.gene.2026.150002","DOIUrl":"https://doi.org/10.1016/j.gene.2026.150002","url":null,"abstract":"<p><p>Next-generation sequencing (NGS) is a high-throughput technology capable of determining the sequence of nucleotides in the genome. Over the past few years, the advent of NGS-based methods has provided timely and economical approaches for diagnosing and screening genetic conditions throughout an individual's lifespan, and prenatal period. Prenatal screening for congenital abnormalities has opened the door to reducing the incidence of genetic disorders. Early detection of genetic diseases using NGS-based methods enables better management of these conditions, thereby improving the quality of life for patients. NGS has also played a pivotal role in pharmacogenetics and drug delivery, facilitating a more personalized approach to medicine. NGS-based methods are increasingly being utilized in genome editing to provide essential information that enhances the precision and effectiveness of editing techniques. This review presents information on how various NGS-based methods function from a technical perspective. Furthermore, we will explore the applications and benefits of these methods in the fields of diagnosis, screening, pharmacogenetics, and genome editing.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"150002"},"PeriodicalIF":2.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-08DOI: 10.1016/j.gene.2026.150003
Md. Ruhul Quddus , M. Akhlasur Rahman , Mehfuz Hasan , Md. Golam Rasul , Md. Abdul Mannan , Md. Jamil Hasan
Salinity, exacerbated by climate change, is a major threat to rice production. Seedling biomass under salt stress is one of the key indicators of salinity tolerance. This is the first study that involved 276 diverse hybrid rice parental lines to analyze GWAS on critical trait seedling biomass under 12 dS/m salt stress. Genetic diversity analysis using UPGMA clustering separated the genotypes into three major and three small distinct groups. Path analysis among 25 traits revealed that root biomass was important determinant for maintaining seedling biomass under salt stress. Genome-wide association analysis (GWAS) for seedling biomass traits under salt stress detected seven significant SNP markers on chromosomes 2, 4, 6, 7, 10, and 11. We report three novel candidate genes associated with seedling biomass maintenance under salt stress: LOC_Os02g55630.1 (chloroplast activity), LOC_Os07g04240.1 (mitochondrial function), and the uncharacterized LOC_Os04g06520.1. In conclusion, a robust root system is vital for seedling biomass retention under salt stress, and identified genetic markers will be useful for the development of salt-resilient hybrid and inbred rice.
{"title":"Genetic diversity and genome-wide association mapping for salt stress tolerance in diverse parental lines of hybrid rice","authors":"Md. Ruhul Quddus , M. Akhlasur Rahman , Mehfuz Hasan , Md. Golam Rasul , Md. Abdul Mannan , Md. Jamil Hasan","doi":"10.1016/j.gene.2026.150003","DOIUrl":"10.1016/j.gene.2026.150003","url":null,"abstract":"<div><div>Salinity, exacerbated by climate change, is a major threat to rice production. Seedling biomass under salt stress is one of the key indicators of salinity tolerance. This is the first study that involved 276 diverse hybrid rice parental lines to analyze GWAS on critical trait seedling biomass under 12 dS/m salt stress. Genetic diversity analysis using UPGMA clustering separated the genotypes into three major and three small distinct groups. Path analysis among 25 traits revealed that root biomass was important determinant for maintaining seedling biomass under salt stress. Genome-wide association analysis (GWAS) for seedling biomass traits under salt stress detected seven significant SNP markers on chromosomes 2, 4, 6, 7, 10, and 11. We report three novel candidate genes associated with seedling biomass maintenance under salt stress: <em>LOC_Os02g55630.1</em> (chloroplast activity), <em>LOC_Os07g04240.1</em> (mitochondrial function), and the uncharacterized <em>LOC_Os04g06520.1</em>. In conclusion, a robust root system is vital for seedling biomass retention under salt stress, and identified genetic markers will be useful for the development of salt-resilient hybrid and inbred rice.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"984 ","pages":"Article 150003"},"PeriodicalIF":2.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-05DOI: 10.1016/j.gene.2026.149999
Ahmet Efe Köseoğlu , Nadir Gül , Tuğçe Duran , Cenk Öztürk , Nezih Hekim
Malaria remains a major global health threat, with Plasmodium species, especially P. falciparum, increasingly resistant to drugs and vaccines. Novel strategies are needed to address antigenic diversity and the parasite’s intracellular immune evasion. This study aimed to identify conserved and immunogenic B-cell epitopes in P. falciparum and human erythrocytes to design a bispecific antibody model, COMED hook, capable of blocking erythrocyte invasion. Surface and secretory proteins of P. falciparum and erythrocytes were retrieved from public databases. B-cell epitopes were predicted and filtered based on antigenicity, allergenicity, and toxicity. Conservancy was assessed via BLAST. Selected epitopes were structurally modeled, docked to B-cell receptors, and used for antibody design via DiffAb. A total of 123 antigenic P. falciparum B-cell epitopes were identified, with 58 conserved across species. Additionally, 92 non-conserved human erythrocyte B-cell epitopes were discovered, of which 12 were selected as host-targeting domains. Two highly conserved Plasmodium epitopes (KHVETWTQRVQNM, LHSNFYIKRF) were predicted to have favorable Fab binding. Designed antibodies likewise exhibited computationally suggested sequence and docking profiles compatible with COMED hook construction. Overall, this study presents an in silico computational design framework for a bispecific antibody model targeting both Plasmodium and host erythrocytes, generating testable predictions for future work. The predicted interactions and the proposed COMED hook concept will require experimental validation to assess biological feasibility.
{"title":"Computational epitope discovery and in silico design of a bispecific antibody model (COMED hook) to block Plasmodium invasion into erythrocytes","authors":"Ahmet Efe Köseoğlu , Nadir Gül , Tuğçe Duran , Cenk Öztürk , Nezih Hekim","doi":"10.1016/j.gene.2026.149999","DOIUrl":"10.1016/j.gene.2026.149999","url":null,"abstract":"<div><div>Malaria remains a major global health threat, with <em>Plasmodium</em> species, especially <em>P. falciparum</em>, increasingly resistant to drugs and vaccines. Novel strategies are needed to address antigenic diversity and the parasite’s intracellular immune evasion. This study aimed to identify conserved and immunogenic B-cell epitopes in <em>P. falciparum</em> and human erythrocytes to design a bispecific antibody model, COMED hook, capable of blocking erythrocyte invasion. Surface and secretory proteins of <em>P. falciparum</em> and erythrocytes were retrieved from public databases. B-cell epitopes were predicted and filtered based on antigenicity, allergenicity, and toxicity. Conservancy was assessed via BLAST. Selected epitopes were structurally modeled, docked to B-cell receptors, and used for antibody design via DiffAb. A total of 123 antigenic <em>P. falciparum</em> B-cell epitopes were identified, with 58 conserved across species. Additionally, 92 non-conserved human erythrocyte B-cell epitopes were discovered, of which 12 were selected as host-targeting domains. Two highly conserved <em>Plasmodium</em> epitopes (KHVETWTQRVQNM, LHSNFYIKRF) were predicted to have favorable Fab binding. Designed antibodies likewise exhibited computationally suggested sequence and docking profiles compatible with COMED hook construction. Overall, this study presents an <em>in silico</em> computational design framework for a bispecific antibody model targeting both <em>Plasmodium</em> and host erythrocytes, generating testable predictions for future work. The predicted interactions and the proposed COMED hook concept will require experimental validation to assess biological feasibility.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"984 ","pages":"Article 149999"},"PeriodicalIF":2.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Parkinson's disease (PD) is a progressive degenerative neuronal disorder that involves the selective loss of dopaminergic neurons in the substantia nigra, resulting in severe motor and non-motor impairments. Key pathological hallmarks include the accumulation of misfolded α-synuclein and mitochondrial dysfunction. Emerging evidence indicates that innate immune signalling, particularly the cGAS-STING pathway, contributes to PD pathogenesis. It acts as a cytosolic DNA sensor; cGAS can recognise genomic instability or mitochondrial damage by generating an IFN-I response through STING activation. Persistent stimulation of the cGAS-STING pathway in microglia promotes chronic neuroinflammation and contributes to dopaminergic neuronal loss. Mitochondrial dysfunction, impaired DNA repair, and α-Synuclein aggregation may converge to sustain pathway activation, establishing a self-reinforcing cycle of inflammation and neurodegeneration. Understanding the interaction of cGAS-STING signalling, mitochondrial integrity, and protein aggregation offers important mechanistic insights into PD pathology. It suggests meaningful targets for disease-modifying therapeutic approaches for PD that address neuroinflammation and neuronal survival.
{"title":"cGAS-STING activation in Parkinson's Disease: From mechanisms to Disease-Modifying therapeutic strategies.","authors":"Jemimol Solomon, Snehashis Mandal, Khadga Raj Aran","doi":"10.1016/j.gene.2026.150000","DOIUrl":"https://doi.org/10.1016/j.gene.2026.150000","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive degenerative neuronal disorder that involves the selective loss of dopaminergic neurons in the substantia nigra, resulting in severe motor and non-motor impairments. Key pathological hallmarks include the accumulation of misfolded α-synuclein and mitochondrial dysfunction. Emerging evidence indicates that innate immune signalling, particularly the cGAS-STING pathway, contributes to PD pathogenesis. It acts as a cytosolic DNA sensor; cGAS can recognise genomic instability or mitochondrial damage by generating an IFN-I response through STING activation. Persistent stimulation of the cGAS-STING pathway in microglia promotes chronic neuroinflammation and contributes to dopaminergic neuronal loss. Mitochondrial dysfunction, impaired DNA repair, and α-Synuclein aggregation may converge to sustain pathway activation, establishing a self-reinforcing cycle of inflammation and neurodegeneration. Understanding the interaction of cGAS-STING signalling, mitochondrial integrity, and protein aggregation offers important mechanistic insights into PD pathology. It suggests meaningful targets for disease-modifying therapeutic approaches for PD that address neuroinflammation and neuronal survival.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"150000"},"PeriodicalIF":2.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-05DOI: 10.1016/j.gene.2026.150001
Monica Gagliardi , Radha Procopio , Alessia Felicetti , Andrea Quattrone , Gennarina Arabia , Maurizio Morelli , Antonio Gambardella , Grazia Annesi , Aldo Quattrone
Background
Pathogenic variants in the LRRK2 gene are among the most common genetic causes of autosomal dominant Parkinson’s disease (PD). A recent study provided strong genetic and functional evidence supporting the pathogenicity of the rare missense variant p.L1795F (c.5385G > T), identified exclusively in individuals of European ancestry. However, its prevalence in Southern European populations remains unknown.
Objective
The aim of the study was to evaluate the frequency of the p.L1795F variant in a cohort of PD patients from Southern Italy.
Methods
We screened 300 unrelated PD patients using Sanger sequencing to detect the presence of the p.L1795F (c.5385G > T) variant in the LRRK2 gene.
Results
No carriers of the p.L1795F variant were identified in our Southern Italian cohort.
Conclusion
These findings suggest that the p.L1795F variant may have very low or undetectable frequency in the Southern Italian population. Our results highlight the importance of including underrepresented geographic regions in genetic screening efforts for PD to better understand the population-specific distribution of pathogenic variants.
{"title":"No evidence for the LRRK2 p.L1795F variant in a Southern Italian cohort with Parkinson’s disease","authors":"Monica Gagliardi , Radha Procopio , Alessia Felicetti , Andrea Quattrone , Gennarina Arabia , Maurizio Morelli , Antonio Gambardella , Grazia Annesi , Aldo Quattrone","doi":"10.1016/j.gene.2026.150001","DOIUrl":"10.1016/j.gene.2026.150001","url":null,"abstract":"<div><h3>Background</h3><div>Pathogenic variants in the <em>LRRK2</em> gene are among the most common genetic causes of autosomal dominant Parkinson’s disease (PD). A recent study provided strong genetic and functional evidence supporting the pathogenicity of the rare missense variant p.L1795F (c.5385G > T), identified exclusively in individuals of European ancestry. However, its prevalence in Southern European populations remains unknown.</div></div><div><h3>Objective</h3><div>The aim of the study was to evaluate the frequency of the p.L1795F variant in a cohort of PD patients from Southern Italy.</div></div><div><h3>Methods</h3><div>We screened 300 unrelated PD patients using Sanger sequencing to detect the presence of the p.L1795F (c.5385G > T) variant in the <em>LRRK2</em> gene.</div></div><div><h3>Results</h3><div>No carriers of the p.L1795F variant were identified in our Southern Italian cohort.</div></div><div><h3>Conclusion</h3><div>These findings suggest that the p.L1795F variant may have very low or undetectable frequency in the Southern Italian population. Our results highlight the importance of including underrepresented geographic regions in genetic screening efforts for PD to better understand the population-specific distribution of pathogenic variants.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"984 ","pages":"Article 150001"},"PeriodicalIF":2.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-31DOI: 10.1016/j.gene.2025.149991
Fanfan Wang , Jian Liu , Yanyan Fang , Yang Li , Xueni Cheng , Shengfeng Liu
Background
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia and multi-organ damage. While existing therapies alleviate symptoms, they are accompanied by significant adverse effects. Fibroblast-like synoviocytes (FLS) drive RA progression through inflammation-coagulation interactions, necessitating safer multitarget drugs. Jianpi Wenyang Tongluo Prescription-Wuwei Wentong Chubi Capsule (WWT), a traditional Chinese medicine formula targeting the “cold-dampness obstruction syndrome” in RA, has demonstrated clinical efficacy, yet its mechanism remains unclear.
Aim of the study
To investigate the therapeutic effects of WWT on adjuvant-induced arthritis (AA) rats with cold-dampness syndrome and explore its underlying mechanisms in regulating inflammation-coagulation balance and organ protection.
Materials and methods
AA rats with cold-dampness syndrome were established using Freund’s complete adjuvant (FCA) and a climate chamber, and treated with WWT (low/medium/high doses). Synovial pathology, organ function, inflammatory, and coagulation parameters were evaluated. Molecular docking, protein–protein interaction (PPI) networks, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were employed to identify key targets, with Western blot (WB) and immunofluorescence used to validate JAK2/STAT3 pathway activation. A coculture model of peripheral blood mononuclear cells (PBMCs) and FLS from RA patients was constructed for in vitro validation.
Results
In AA rats, WWT dose-dependently decreased pro-inflammatory cytokines (IL-6, IL-17) and pro-coagulant factors (PAF, FDP), while increasing anti-inflammatory cytokine IL-10 and anticoagulant factor PGI2 (P < 0.01). WWT reversed synovial mitochondrial vacuolation and protected liver and kidney function. Bioinformatics analysis and molecular docking revealed JAK2/STAT3 as the core target, with wogonin and icariin stably binding to JAK2 (ΔG = -8.2/-7.7 kcal/mol) and STAT3 (ΔG = -7.9/-9.9 kcal/mol). WWT rescued inflammation and hypercoagulation induced by the JAK2/STAT3 activator coumermycin A1. In vitro, WWT-containing serum inhibited the proliferation of cocultured RA-PBMCs and FLS and the secretion of pro-inflammatory and pro-coagulant factors by blocking JAK2/STAT3 and STAT3 nuclear translocation.
Conclusions
WWT alleviates RA progression by restoring inflammation-coagulation balance and protecting multi-organ function through inhibition of the JAK2/STAT3 pathway. This study integrates traditional Chinese medicine theory with molecular pathological mechanisms, providing a scientific basis for WWT as a multitarget therapeutic for RA.
背景:类风湿性关节炎(RA)是一种以滑膜增生和多器官损害为特征的慢性自身免疫性疾病。虽然现有的治疗方法减轻了症状,但它们伴随着显著的不良反应。纤维母细胞样滑膜细胞(FLS)通过炎症-凝血相互作用驱动RA进展,需要更安全的多靶点药物。健脾温阳通络方-武味温通除痹胶囊是一种治疗类风湿痹证的中药方剂,临床疗效较好,但其作用机制尚不清楚。研究目的:观察水灵汤对佐剂性关节炎(AA)大鼠寒湿证的治疗作用,并探讨其调节炎症-凝血平衡和器官保护的机制。材料和方法:采用弗氏完全佐剂(FCA)和气候室建立寒湿证AA大鼠,并给予低/中/高剂量WWT治疗。评估滑膜病理、器官功能、炎症和凝血参数。利用分子对接、蛋白-蛋白相互作用(PPI)网络和京都基因与基因组百科全书(KEGG)富集分析确定关键靶点,利用Western blot (WB)和免疫荧光验证JAK2/STAT3通路的激活。建立RA患者外周血单个核细胞(PBMCs)与FLS共培养模型进行体外验证。结果:在AA大鼠中,WWT剂量依赖性地降低了促炎因子(IL-6、IL-17)和促凝因子(PAF、FDP),同时增加了抗炎因子IL-10和抗凝因子PGI2 (P )。结论:WWT通过抑制JAK2/STAT3通路,恢复了炎症-凝平衡,保护了多器官功能,从而减轻了RA的进展。本研究将中医理论与分子病理机制相结合,为WWT多靶点治疗类风湿性关节炎提供科学依据。
{"title":"Revealing the dual mechanisms of Wuwei Wentong Chubi Capsule in alleviating rheumatoid arthritis: synergistic anti-inflammatory and anti-coagulant effects","authors":"Fanfan Wang , Jian Liu , Yanyan Fang , Yang Li , Xueni Cheng , Shengfeng Liu","doi":"10.1016/j.gene.2025.149991","DOIUrl":"10.1016/j.gene.2025.149991","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia and multi-organ damage. While existing therapies alleviate symptoms, they are accompanied by significant adverse effects. Fibroblast-like synoviocytes (FLS) drive RA progression through inflammation-coagulation interactions, necessitating safer multitarget drugs. Jianpi Wenyang Tongluo Prescription-Wuwei Wentong Chubi Capsule (WWT), a traditional Chinese medicine formula targeting the “cold-dampness obstruction syndrome” in RA, has demonstrated clinical efficacy, yet its mechanism remains unclear.</div></div><div><h3>Aim of the study</h3><div>To investigate the therapeutic effects of WWT on adjuvant-induced arthritis (AA) rats with cold-dampness syndrome and explore its underlying mechanisms in regulating inflammation-coagulation balance and organ protection.</div></div><div><h3>Materials and methods</h3><div>AA rats with cold-dampness syndrome were established using Freund’s complete adjuvant (FCA) and a climate chamber, and treated with WWT (low/medium/high doses). Synovial pathology, organ function, inflammatory, and coagulation parameters were evaluated. Molecular docking, protein–protein interaction (PPI) networks, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were employed to identify key targets, with Western blot (WB) and immunofluorescence used to validate JAK2/STAT3 pathway activation. A coculture model of peripheral blood mononuclear cells (PBMCs) and FLS from RA patients was constructed for in vitro validation.</div></div><div><h3>Results</h3><div>In AA rats, WWT dose-dependently decreased pro-inflammatory cytokines (IL-6, IL-17) and pro-coagulant factors (PAF, FDP), while increasing anti-inflammatory cytokine IL-10 and anticoagulant factor PGI2 (P < 0.01). WWT reversed synovial mitochondrial vacuolation and protected liver and kidney function. Bioinformatics analysis and molecular docking revealed JAK2/STAT3 as the core target, with wogonin and icariin stably binding to JAK2 (ΔG = -8.2/-7.7 kcal/mol) and STAT3 (ΔG = -7.9/-9.9 kcal/mol). WWT rescued inflammation and hypercoagulation induced by the JAK2/STAT3 activator coumermycin A1. In vitro, WWT-containing serum inhibited the proliferation of cocultured RA-PBMCs and FLS and the secretion of pro-inflammatory and pro-coagulant factors by blocking JAK2/STAT3 and STAT3 nuclear translocation.</div></div><div><h3>Conclusions</h3><div>WWT alleviates RA progression by restoring inflammation-coagulation balance and protecting multi-organ function through inhibition of the JAK2/STAT3 pathway. This study integrates traditional Chinese medicine theory with molecular pathological mechanisms, providing a scientific basis for WWT as a multitarget therapeutic for RA.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"983 ","pages":"Article 149991"},"PeriodicalIF":2.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-30DOI: 10.1016/j.gene.2025.149988
Chenlu Tang, Xiaofeng Jin
Endometrial cancer (EC) is one of the three most common malignancies of the female reproductive system, with its global incidence and disease-related mortality continuing to rise. Cervical cancer (CC), also known as uterine cervical cancer, refers to cancer occurring in the cervix. Despite the development of various therapeutic strategies, patient prognosis and survival rates remain poor due to high rates of metastasis and recurrence. Ubiquitination denotes the process by which ubiquitin is covalently attached to target proteins, while deubiquitinases (DUBs) catalyze the reverse process. Accumulating evidence indicates that dysregulation of deubiquitination plays significant roles in the pathogenesis and progression of both EC and CC. This review systematically summarizes recent research advances in DUBs, outlining their intrinsic characteristics, classification, catalytic mechanisms, and modes of activity regulation. Furthermore, it explores the potential mechanisms by which DUB dysregulation contributes to endometrial and cervical carcinogenesis. Additionally, we present the successful application of DUB inhibitors in the treatment of malignancies and provide an analysis of the current research status regarding targeted therapies for EC and CC.
{"title":"Deubiquitinating enzymes in endometrial cancer and cervical cancer","authors":"Chenlu Tang, Xiaofeng Jin","doi":"10.1016/j.gene.2025.149988","DOIUrl":"10.1016/j.gene.2025.149988","url":null,"abstract":"<div><div>Endometrial cancer (EC) is one of the three most common malignancies of the female reproductive system, with its global incidence and disease-related mortality continuing to rise. Cervical cancer (CC), also known as uterine cervical cancer, refers to cancer occurring in the cervix. Despite the development of various therapeutic strategies, patient prognosis and survival rates remain poor due to high rates of metastasis and recurrence. Ubiquitination denotes the process by which ubiquitin is covalently attached to target proteins, while deubiquitinases (DUBs) catalyze the reverse process. Accumulating evidence indicates that dysregulation of deubiquitination plays significant roles in the pathogenesis and progression of both EC and CC. This review systematically summarizes recent research advances in DUBs, outlining their intrinsic characteristics, classification, catalytic mechanisms, and modes of activity regulation. Furthermore, it explores the potential mechanisms by which DUB dysregulation contributes to endometrial and cervical carcinogenesis. Additionally, we present the successful application of DUB inhibitors in the treatment of malignancies and provide an analysis of the current research status regarding targeted therapies for EC and CC.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"983 ","pages":"Article 149988"},"PeriodicalIF":2.4,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-30DOI: 10.1016/j.gene.2025.149990
Qiyue Ma , Ningna Wang , Kaikai Qiao , Kun Luo , Chenglong Zhao , Jiaxuan Yan , Shuli Fan , Junkang Rong , Qifeng Ma
Male reproductive development is fundamental to the life cycle of flowering plants, culminating in seed production. Aberrations in anther development frequently lead to male sterility, yet the underlying molecular mechanisms in upland cotton (Gossypium hirsutum) remain largely uncharacterized. The R2R3-MYB family of transcription factors are known key regulators of diverse developmental processes, including male fertility in several model species. Here, we identify and functionally characterize GhMYB35, an R2R3-MYB transcription factor that plays an essential role in cotton anther development. CRISPR/Cas9-mediated knockout of GhMYB35 resulted in complete male sterility, with mutants (ghmyb35) exhibiting indehiscent anthers, shorter filaments, and a total absence of viable pollen. Expression analyses reveal that GhMYB35 is predominantly expressed in anthers, with peak expression of its A- and D-subgenome homoeologs occurring at developmental stage 7. Subcellular localization results show that both GhMYB35_A and GhMYB35_D are nuclear-localized transcription factors. Furthermore, the total absence of GhMYB35 leads to pollen abortion and subsequent anther collapse without dehiscence. Collectively, our findings establish GhMYB35 as a critical regulator of anther maturation, thereby elucidating a key component of the molecular network governing male fertility in cotton.
{"title":"The R2R3-MYB transcription factor GhMYB35 governs anther development and pollen viability in upland cotton","authors":"Qiyue Ma , Ningna Wang , Kaikai Qiao , Kun Luo , Chenglong Zhao , Jiaxuan Yan , Shuli Fan , Junkang Rong , Qifeng Ma","doi":"10.1016/j.gene.2025.149990","DOIUrl":"10.1016/j.gene.2025.149990","url":null,"abstract":"<div><div>Male reproductive development is fundamental to the life cycle of flowering plants, culminating in seed production. Aberrations in anther development frequently lead to male sterility, yet the underlying molecular mechanisms in upland cotton (<em>Gossypium hirsutum</em>) remain largely uncharacterized. The R2R3-MYB family of transcription factors are known key regulators of diverse developmental processes, including male fertility in several model species. Here, we identify and functionally characterize <em>GhMYB35</em>, an R2R3-MYB transcription factor that plays an essential role in cotton anther development. CRISPR/Cas9-mediated knockout of <em>GhMYB35</em> resulted in complete male sterility, with mutants (<em>ghmyb35</em>) exhibiting indehiscent anthers, shorter filaments, and a total absence of viable pollen. Expression analyses reveal that <em>GhMYB35</em> is predominantly expressed in anthers, with peak expression of its A- and D-subgenome homoeologs occurring at developmental stage 7. Subcellular localization results show that both<!--> <em>GhMYB35_A</em> <!-->and<!--> <em>GhMYB35_D</em> <!-->are nuclear-localized transcription factors. Furthermore, the total absence of GhMYB35 leads to pollen abortion and subsequent anther collapse without dehiscence. Collectively, our findings establish <em>GhMYB35</em> as a critical regulator of anther maturation, thereby elucidating a key component of the molecular network governing male fertility in cotton.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"984 ","pages":"Article 149990"},"PeriodicalIF":2.4,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}