Journal of Zhejiang University SCIENCE B最新文献

{"title":"Improving the thermal stability of <i>trans</i>-epoxysuccinate hydrolase.","authors":"Wenna Bao, Jinfeng Yao, Haifeng Pan, Ronglin Zhu, Xinying Li, Hongxiu Liao","doi":"10.1631/jzus.B2500069","DOIUrl":"10.1631/jzus.B2500069","url":null,"abstract":"<p><p>This study used molecular dynamics simulations, B-factor analysis, and saturation mutagenesis screening to enhance the thermal stability of the <i>trans</i>-epoxysuccinate hydrolase (TESH) derived from <i>Pseudomonas koreensis</i>. Eleven mutants that influence this characteristic were selected, yielding four mutants with improved activity. Among them, mutants A142C and S178Q exhibited lower Michaelis constant (<i>K</i>_m) values, and their <i>k</i>_cat/<i>K</i>_m ratios (<i>k</i>_cat, catalytic constant) were 3.7 and 0.9 times higher than those of the wild type, respectively. The values of half-life at 50 ℃ (T 1/ 2 50) of the two mutants were increased by 107% and 59%, respectively, compared to the wild type. Molecular docking and molecular dynamics simulations indicated that the two mutants showed stronger substrate interaction, lower binding energy, and reduced root mean square deviation compared to the wild type, along with decreased electrostatic potential energy and increased hydrophobicity near their mutation sites. The study of protein thermal stability engineering and associated mechanisms provides a valuable reference and holds practical significance for the industrial production of <i>meso</i>-tartaric acid.</p>","PeriodicalId":17797,"journal":{"name":"Journal of Zhejiang University SCIENCE B","volume":"27 1","pages":"89-100"},"PeriodicalIF":5.7,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12848554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146064442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of <i>try</i> and <i>amy</i> in feeding, digestion, growth, and development of the Japanese medaka (<i>Oryzias latipes</i>): insight from a comparative gene knockout study.","authors":"Xiaodan Jia, Shulin Tang, Hexiong Feng, Dimei Xu, Chenyuan Zhu, Ke Lu, Xufang Liang","doi":"10.1631/jzus.B2400246","DOIUrl":"10.1631/jzus.B2400246","url":null,"abstract":"<p><p>Digestive enzymes of fish are critical to food digestion at the larval stage, but convincing evidence proving the function and necessity of the associated digestive enzymes remains lacking. In this study, we generated the trypsin (<i>try</i>) gene and amylase (<i>amy</i>) gene in the Japanese medaka (<i>Oryzias latipes</i>) using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) for the first time. <i>try</i> deletion significantly decreased the expression of <i>try</i> anddigestive capacity in <i>try</i>^-/- medaka larvae; after 8.5 h of digestion, incompletely digested brine shrimp was observed in the digestive tract at 4 and 15 d post-hatching (dph) of <i>try</i>^-/- medaka larvae. Furthermore, the height of intestinal villi and total body length decreased significantly within 15-dph <i>try</i>^-/- medaka larvae. However, <i>amy</i> deletion did not influence the digestion of medaka larvae at 4 dph. Only a small amount of incompletely digested brine shrimp was observed in 15-dph <i>amy</i>^-/- medaka larvae. Further analysis of the growth, nitrogen metabolism, and intestinal microbes of <i>try</i>^-/- adult medaka showed that the body length and weight of adult medaka decreased significantly, while the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the blood significantly increased. Pathological observation of the liver and intestinal tissues showed that <i>try</i> knockout resulted in vacuolar degeneration of liver cells, thinning of the intestinal wall, sparse arrangement of villi, and lower villi height. High-throughput 16S ribosomal RNA (rRNA) sequencing revealed that <i>try</i> knockout reduced the diversity of intestinal microbes. These findings demonstrated that <i>try</i> was indispensable for medaka larvae because it continuously affects their growth, nitrogen metabolism, and intestinal development.</p>","PeriodicalId":17797,"journal":{"name":"Journal of Zhejiang University SCIENCE B","volume":"27 3","pages":"280-294"},"PeriodicalIF":5.7,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world data and evidence: pioneering frontiers in precision oncology.","authors":"Jingxin Jiang, Weiwei Pan, Liyang Sun, Liwei Pang, Hailang Chen, Jian Huang, Wuzhen Chen","doi":"10.1631/jzus.B2400285","DOIUrl":"10.1631/jzus.B2400285","url":null,"abstract":"<p><p>Real-world studies (RWSs) have emerged as a transformative force in oncology research, complementing traditional randomized controlled trials (RCTs) by providing comprehensive insights into cancer care within routine clinical settings. This review examines the evolving landscape of RWSs in oncology, focusing on their implementation, methodological considerations, and impact on precision medicine. We systematically analyze how RWSs leverage diverse data sources, including electronic health records (EHRs), insurance claims, and patient registries, to generate evidence that bridges the gap between controlled clinical trials and real-world clinical practice. The review underscores the key contributions of RWSs, including capturing therapeutic outcomes in traditionally underrepresented populations, expanding drug indications, and evaluating long-term safety and effectiveness in routine clinical settings. While acknowledging significant challenges, including data quality variability and privacy concerns, we discuss how emerging technologies like artificial intelligence are helping to address these limitations. The integration of RWSs with traditional clinical research is revolutionizing the paradigm of precision oncology and enabling more personalized treatment approaches based on real-world evidence.</p>","PeriodicalId":17797,"journal":{"name":"Journal of Zhejiang University SCIENCE B","volume":"27 1","pages":"44-57"},"PeriodicalIF":5.7,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12848558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146064447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative combination of gas‒liquid-phase plasma mutagenesis and high-throughput screening to enhance eicosapentaenoic acid production by <i>Schizochytrium</i> sp.","authors":"Chao Yu, Jialin Zhu, Jinyong Wu, Xiangsong Chen, Shuhuan Lu, Xiangyu Li, Sa Zhao, Weiwei Zhu, Min Shu, Mianbin Wu, Jianming Yao","doi":"10.1631/jzus.B2400427","DOIUrl":"10.1631/jzus.B2400427","url":null,"abstract":"<p><p>Dietary consumption of eicosapentaenoic acid (EPA) offers diverse health benefits, such as the regulation of blood triglycerides and the prevention of cardiovascular diseases. EPA is naturally synthesized by <i>Schizochytrium</i> sp.; however, its low production level limits its potential for industrial application. The goal of this study was to increase EPA productivity in <i>Schizochytrium</i> sp. by gas‒liquid-phase plasma (GLPP) mutagenesis combined with a high-throughput screening method. First, a diverse array of mutants was generated through GLPP mutagenesis. Next, the mutants with elevated EPA productivity were identified through near-infrared spectroscopy (NIRS). Notably, the M7-25 mutant demonstrated the highest and most consistent EPA production. After the culture medium was optimized, the EPA titer increased from 0.45 to 1.70 g/L. Finally, a cofermentation strategy using ammonia and glucose feeding was employed, and the EPA titer reached 2.08 g/L in a 7-L fermenter. This study reports the highest EPA titer achieved in <i>Schizochytrium</i> sp. via mutagenesis to date, highlighting its great market potential for industrial production.</p>","PeriodicalId":17797,"journal":{"name":"Journal of Zhejiang University SCIENCE B","volume":"27 3","pages":"250-263"},"PeriodicalIF":5.7,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shuyu capsule improves estrous cycle-dependent depression-like behavior in premenstrual dysphoric disorder (PMDD) mice by increasing GABAergic neuronal activation and downregulating GABA_AR δ subunit expression in the dorsal periaqueductal gray (dPAG) region.","authors":"Jialing Xu, Kun Liu, Yaru Cui, Hao Zhang, Xinyu Wang, Minghui Hu, Zifa Li, Peng Gao, Wei Liu, Mingqi Qiao, Wenqiang Cui, Xiwen Geng, Sheng Wei","doi":"10.1631/jzus.B2400410","DOIUrl":"10.1631/jzus.B2400410","url":null,"abstract":"<p><p>Premenstrual dysphoric disorder (PMDD), a subtype of premenstrual syndrome (PMS), involves physical and emotional symptoms that impact patients' daily lives and productivity. A reliable, side-effect-free clinical intervention is needed. Shuyu capsule is an effective traditional Chinese medicine preparation for PMDD used in the clinics, but its therapeutic mechanism remains unclear. Previous research has suggested that the γ-aminobutyric acidergic (GABAergic) system in the periaqueductal gray (PAG) may play a role in treating PMDD with traditional Chinese medicine, but there is a lack of functional verification. This study aims to reveal the potential mechanism of the Shuyu capsule in treating PMDD. The study employed an experimental design using female C57BL/6J and Vgat-Cre mice to assess the effects of Shuyu capsules on PMDD, with a focus on the GABAergic system in the dorsal PAG (dPAG). Assessments were conducted using the forced swimming test (FST) to gauge depression-like behaviors and western blot (WB) and immunofluorescence (IF) to measure the numbers of active GABAergic neurons and the γ-aminobutyric acid type A receptor (GABA_AR) δ subunit (GABRD) expression. Chemogenetic techniques and adeno-associated virus were specifically used to activate GABAergic neurons and knock down the expression of subunits, respectively, providing insights into the neurobiological mechanisms underpinning the therapeutic effects of Shuyu capsules in treating PMDD. After being stressed by FST, the immobility duration of PMDD mice in the late dioestrus (LD) phase decreased after the Shuyu capsule intervention, implying that it can improve the estrous cycle-dependent depression-like phenotype in PMDD mice. Additionally, the application of Shuyu capsule can downregulate the expression of GABRD and reverse the downtrend of activated GABAergic neurons in the dPAG of PMDD model mice. We also found that single-target manipulation was enough to improve the depression-like behavior of PMDD model mice. Transgenic mice with <i>GABRD</i> knockout were established, and their behaviors were tested, revealing changes in their exploratory behaviors, indicating that the GABRD may be closely related to anxiety disorders. Shuyu capsule plays an anti-PMDD role by activating GABAergic neurons and downregulating the expression of GABRD in the dPAG. This provides a theoretical basis for the clinical treatment of PMDD with traditional Chinese medicine and promotes the development of drugs for treating PMDD.</p>","PeriodicalId":17797,"journal":{"name":"Journal of Zhejiang University SCIENCE B","volume":"27 1","pages":"73-88"},"PeriodicalIF":4.9,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12848557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146064036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depleting CBR1 increases chemosensitivity by reducing stemness and quiescence traits in non-small cell lung cancer.","authors":"Weiwen Li, Jialu Zhao, Weihong Lan, Xiaofei Ye, Kejing Ying","doi":"10.1631/jzus.B2400509","DOIUrl":"10.1631/jzus.B2400509","url":null,"abstract":"<p><p>Carbonyl reductase 1 (CBR1), a member of the short-chain dehydrogenase/reductase (SDR) superfamily, is implicated in tumor progression and treatment resistance. However, its role in non-small cell lung cancer (NSCLC) remains unclear. This study examined CBR1 expression in NSCLC tissues and cell lines, using gene interference and pharmacological inhibition to assess its impact on stemness, chemosensitivity, and quiescence, and to explore underlying mechanisms. Our findings indicate that CBR1 expression is elevated in NSCLC tissues and cell lines, and further increases in the presence of cisplatin (CDDP). Gene interference reducing CBR1 expression significantly decreased the percentage of cluster of differentiation 133 (CD133)-positive cells and the expression of octamer-binding transcription factor 4 (OCT4) and SRY (sex determining region Y)-box 2 (SOX2), while enhancing CDDP chemosensitivity. The CBR1-specific inhibitor hydroxy-PP-Me (PP-Me) markedly increased CDDP cytotoxicity and reduced stemness. Additionally, CBR1 inhibition via short hairpin RNA (shRNA) CBR1 (sh-CBR1) or PP-Me disrupted NSCLC cell quiescence, as shown by a decrease in G0 phase cells and p27 expression, alongside an increase in cyclin D1 and phospho-retinoblastoma (pRb) expression. Furthermore, SET domain-containing protein 4 (SETD4), which mediates stemness, chemosensitivity, and quiescence in NSCLC cells, was downregulated by sh-CBR1 or PP-Me treatment. The overexpression of SETD4 counteracted the enhanced chemosensitivity resulting from CBR1 inhibition. In A549 xenografts, combined PP-Me and CDDP therapy significantly inhibited tumor growth compared to either treatment alone. In conclusion, CBR1 inhibition enhances CDDP chemosensitivity by suppressing stemness and quiescence in NSCLC.</p>","PeriodicalId":17797,"journal":{"name":"Journal of Zhejiang University SCIENCE B","volume":"26 12","pages":"1216-1232"},"PeriodicalIF":4.9,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12768566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic insights into the diversity of rice cultivars developed in Heilongjiang Province, China.","authors":"Yuhan Zhou, Naixin Liu, Jiaqi Yang, Baicui Chen, Chengxin Li, Fanshan Bu, Sanling Wu, Ziqi Zhou, Qingtao Yu, Qingyao Shu","doi":"10.1631/jzus.B2400339","DOIUrl":"10.1631/jzus.B2400339","url":null,"abstract":"<p><p>Amid the rapid increase of the global population and the quest for sustainable agriculture, the need for enhanced rice breeding strategies has become increasingly pronounced, particularly in Heilongjiang, China's foremost rice-producing province, renowned for its premium temperate <i>japonica</i> rice. Here, we conducted an extensive genomic investigation of the elite rice cultivars developed in Heilongjiang Province. Using whole-genome re-sequencing of a total of 376 representative cultivars from Heilongjiang, of which 14 were developed by a single research group, we identified 4.9 million single nucleotide polymorphisms (SNPs) and 0.98 million insertions and deletions (InDels), offering a comprehensive perspective on genetic diversity and population structure. We classified the 376 rice cultivars into five subgroups based on their breeding years. Recently bred cultivars, assigned to subgroups HLJ-IV-1 and HLJ-IV-2, showed notable genetic differentiation. Through a selective sweep analysis, significant genomic variation in genes such as <i>OsACBP5</i>, <i>Os4CL5</i>, and <i>GFR1</i> was pinpointed, reflecting a concerted effort in selecting for broad-spectrum disease resistance and enhanced tillering capacity. Furthermore, to identify the strengths and areas for improvement within those series, we conducted an exhaustive analysis of aromatic compounds and their corresponding genes <i>OsODC</i> and <i>OsBadh2</i>, as well as the advantageous long-grain gene <i>OsGL3.1</i> haplotype within Hagengdao7. Additionally, strategies for reducing plant height through the introduction of the <i>sd1</i> gene have been elucidated. With a commitment to expediting the development of superior rice cultivars, our discoveries are poised to raise the sensory attributes and nutritional profile of rice, thereby bolstering the resilience and sustainability of global food systems.</p>","PeriodicalId":17797,"journal":{"name":"Journal of Zhejiang University SCIENCE B","volume":"27 3","pages":"264-279"},"PeriodicalIF":5.7,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel multi-component synergistic bioink that balances biocompatibility and mechanical strength for cartilage regeneration.","authors":"Zijun Ma, Wendan Jia, Xiaoyuan Wang, Rong Cheng, Lu Han, Meng Li, Xiaoning Yang, Shengbo Sang","doi":"10.1631/jzus.B2500343","DOIUrl":"10.1631/jzus.B2500343","url":null,"abstract":"<p><p>Hydrogels, owing to their porous network structure resembling the extracellular matrix (ECM), have become essential scaffold materials in the field of cartilage tissue engineering. Among them, gelatin methacrylate (GelMA) hydrogels are widely used in bioink development due to their excellent biocompatibility, biodegradability, and tunable photo-crosslinking properties. However, the high biocompatibility of pure GelMA often comes at the cost of mechanical strength, limiting its applicability in cartilage regeneration. To overcome this trade-off, this study developed composite bioinks based on GelMA, silk fibroin (SF), and polyethylene oxide (PEO) for fabricating porous hydrogel scaffolds, which were then systematically characterized in terms of morphology, porosity, hydrophilicity, mechanical strength, rheological behavior, printability, and cytocompatibility. In this design, PEO serves as a porogen to generate highly porous structures (porosity up to 88%), while SF compensates for the mechanical loss caused by PEO, enabling the scaffold to retain a compression strength of up to 29.10 kPa. Among the tested formulations, the 10% GelMA/1% SF/1.5% PEO (1%=0.01 g/mL) bioink exhibited excellent printability, mechanical integrity, and cytocompatibility, and it supported a robust deposition of collagen II and aggrecan by chondrocytes after printing. This work provides a versatile strategy for balancing the biocompatibility and mechanical robustness in bioinks, offering a promising platform for next-generation cartilage tissue engineering scaffolds.</p>","PeriodicalId":17797,"journal":{"name":"Journal of Zhejiang University SCIENCE B","volume":"26 12","pages":"1156-1171"},"PeriodicalIF":4.9,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12768570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Future of PARP inhibitors in cancer treatment: overcoming resistance and enhancing efficacy with combination therapies.","authors":"Muhammad Shoaib, Zeeshan Ahmad Bhutta, Ahsan Javed, Muhammad Nabeel Amjad, Wenzhu Li, Kyung-Chul Choi, Wanxia Pu","doi":"10.1631/jzus.B2400146","DOIUrl":"10.1631/jzus.B2400146","url":null,"abstract":"<p><p>Poly(ADP-ribose) polymerase (PARP) is a family of proteins that play a crucial role in diverse cellular processes, including DNA repair, cell death, and changes in chromatin structure. PARP inhibitors (PARPi) have been recognized as notable agents in the realm of anticancer therapeutics owing to their capacity to specifically impact DNA repair pathways, thereby inducing targeted death of cancerous cells, particularly in cancers with homologous recombination deficiency (HRD). These inhibitors have been approved for the treatment of several cancers, such as ovarian, breast, and pancreatic cancers. Despite their promising therapeutic attributes, developing resistance to PARPi presents a formidable obstacle, curtailing their overall efficacy. This article presents a comprehensive description of the potential mechanisms related to PARPi resistance, an in-depth study of potential strategies to overcome resistance, and an assessment of the therapeutic potential of the PARPi in combination with alternative therapies.</p>","PeriodicalId":17797,"journal":{"name":"Journal of Zhejiang University SCIENCE B","volume":"27 1","pages":"23-43"},"PeriodicalIF":5.7,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12848556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146064457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential relationships between circulating gene expression of <i>ACE2</i>, <i>TLR4</i>, and <i>IL-17</i> and disease severity and outcome of hospitalized patients with COVID-19.","authors":"Marwa A Dahpy, Ragaa H Salama, Abdel-Raheim M A Meki, Ashraf Zein El-Abedeen, Maiada K Hashem, Ebtsam S Abdulkareem, Mohamed Mohany, Sinisa Djurasevic, Amal N Ibrahim, Nourhan M Hussein, Shima Gafar Mansor, Mohamed Ramadan Izzaldin, Marwa K Khairallah, Suzan Eid Elshishtawy Ibrahim, Alzahra Abdelbadea, Islam Khaled Ali Harby, Fatma Y A Abbas, Rasha M Ali, Marwa A Sabet, Salwa Seif ElDIN, Abdelraouf M S Abdelraouf, Amira A Kamel","doi":"10.1631/jzus.B2400345","DOIUrl":"10.1631/jzus.B2400345","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) is a form of progressive hypoxemia that can be brought on by a variety of cardiorespiratory or systemic disorders, such as coronavirus disease 2019 (COVID-19). The binding of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus spike protein to the cell membrane is mediated through its binding to angiotensin-converting enzyme 2 (ACE2) receptors, resulting in viral entry, replication, and induction of a signaling cascade inducing pro-inflammatory responses that are linked to a higher mortality rate and the progression of ARDS, leading to multi-organ failure in these patients. We aimed to analyze the relationships between circulating gene expression levels of <i>ACE2</i>, Toll-like receptor 4 (<i>TLR4</i>), and interleukin-17 (<i>IL-17</i>) and the clinical severity of COVID-19, as well as the associated pathogenic conditions, in hospitalized patients. Sixty COVID-19 patients (34 mild/moderate COVID-19 and 26 COVID-19 with severe ARDS manifestation) and 60 healthy controls were included. The patient group was also subdivided according to outcomes into 32 recoveries and 28 deaths. <i>ACE2</i>, <i>TLR4</i>, and <i>IL-17</i> levels were assessed by quantitative polymerase chain reaction (qPCR) in addition to all routine baseline laboratory investigations, including complete blood count (CBC) with differential analysis and the levels of C-reactive protein (CRP), ferritin, and d-dimer. ACE2, TLR4, and IL-17 serum expression levels were significantly higher in the COVID-19 group and subgroups and were correlated with different laboratory and clinical parameters. The serum expression levels of ACE2, TLR4, and IL-17 were accurate in differentiating between the patient groups and controls, with 86.7%, 91.7%, and 95.0% sensitivity and 96.7%, 98.3%, and 98.3% specificity, respectively, and correlated with more severe disease courses in COVID-19 patients. Higher levels are associated with overwhelmingly distressing outcomes. Our results allow us to conclude that increased circulating gene expression levels of <i>ACE2</i>, <i>TLR4</i>, and <i>IL-17</i> are important in assessing the severity of COVID-19. Consequently, targeting these biomarkers may offer additional therapeutic options for COVID-19 patients in the future.</p>","PeriodicalId":17797,"journal":{"name":"Journal of Zhejiang University SCIENCE B","volume":"27 2","pages":"181-193"},"PeriodicalIF":5.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}