Journal of Advanced Research最新文献

{"title":"Sequential allogeneic HSCT after CAR-T therapy for relapsed/refractory acute lymphoblastic leukemia patients: A long-term follow-up result","authors":"Tingting Yang, Yetian Dong, Jimin Shi, Mingming Zhang, Delin Kong, Jingjing Feng, Shan Fu, Pingnan Xiao, Ruimin Hong, Huijun Xu, Yi Luo, Yanmin Zhao, Jian Yu, Xiaoyu Lai, Lizhen Liu, Huarui Fu, Yishan Ye, Dawei Cui, Jiazhen Cui, Simao Huang, Yongxian Hu","doi":"10.1016/j.jare.2025.02.006","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.006","url":null,"abstract":"<h3>Introduction</h3>CAR-T cell therapy has revolutionized the therapeutic landscape for relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), and bridging with allogeneic hematopoietic stem cell transplantation (allo-HSCT) has the potential to lower relapse rates. Nevertheless, the majority of existing studies have exclusively focused on short-term outcomes, resulting in a lack of comprehensive understanding of the long-term sustainability of overall prognosis.<h3>Objectives</h3>Our study aimed to provide real-world, long-term follow-up data for patients who underwent sequential therapy.<h3>Methods</h3>Patients with R/R B-ALL who achieved MRD^-CR following CAR-T therapy and subsequently underwent allo-HSCT between January 2016 and May 2024 were enrolled. The primary outcomes included overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM) and cumulative incidence of relapse (CIR). Acute and chronic graft-versus-host disease (GVHD) and graft-versus-host disease-free survival (GRFS) were also investigated.<h3>Results</h3>The median age at transplant of 32.1 years. Of these patients, 88.2 % underwent haploidentical-HSCT, and 11.8 % received either unrelated matched or related matched HSCT. The cumulative incidences of grades I-IV and grade II-IV aGVHD at day 100 were 31.4 % and 15.7 %, respectively. The cumulative incidence of cGVHD at 4 y ears was 48.3 %. With a median follow-up time of 43.2 months, OS, LFS, and GRFS at 4 years were 68.9 %, 61.4 %, and 39.5 %, respectively. Fifteen cases (29.4 %) experienced relapse, predominantly antigen-positive relapse (n = 11). NRM and CIR at 4 years were 10.6 % and 28.0 %, respectively. In the multivariate analyses, patients over 45 years of age and with poor-risk had significantly dismal OS (<em>P</em> = 0.018; <em>P</em> = 0.038) and LFS (<em>P</em> = 0.01; <em>P</em> = 0.03).<h3>Conclusion</h3>Our study exhibits favorable long-term outcomes consistent with those reported in clinical trials, with sustained, durable responses observed at the 4-year follow-up. However, these benefits are less pronounced in older patients and those with poor-risk disease characteristics.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"7 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetate prevents pistil dysfunction in rice under heat stress by inducing methyl jasmonate and quercetin synthesis","authors":"Hubo Li, Yongqiang Xu, Jie Lin, Baohua Feng, Aike Zhu, Xia Zhao, Danying Wang, Yuxiang Zeng, Haining Yang, Shimei Wang, Guanfu Fu","doi":"10.1016/j.jare.2025.02.015","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.015","url":null,"abstract":"<h3>Introduction</h3>Acetic acid (HAC) is a crucial signal molecule in plant stress responses; however, its role in conferring heat tolerance to rice remains unclear.<h3>Objectives</h3>This study aims to investigate the effect of HAC in protecting pistil function under heat stress and its potential role in facilitating pollen germination and tube growth via HAC-induced synthesis of methyl jasmonate (MeJA) and quercetin (QR).<h3>Methods</h3>Physiological analysis, including pollen germination, pollen tube growth into the ovule, reactive oxygen species (ROS), as well as the levels of HAC, acetyl coenzyme A (acetyl-CoA), MeJA, and QR in the pistils of heat stress-treated early indica rice cultivars Zhongzao39 (ZZ39) and Zhongjiazao17 (ZJZ17), were conducted. RNA sequencing (RNA-seq) was performed to identify differentially expressed genes involved in this process. Effect of exogenous acetate (NaAC), MeJA, and QR on spikelet fertility were also investigated.<h3>Results</h3>Compared with ZJZ17, severe inhibition of spikelet fertility, pollen germination, and pollen tube growth was observed in ZZ39, due to the ROS burst and an irregular distribution across the stigma, style, and ovule. RNA-seq and physiological data indicate that HAC may activate acetyl-CoA to enhance heat tolerance by inducing the synthesis of MeJA and QR. Exogenous NaAC enhanced spikelet fertility under heat stress, accompanied by elevated antioxidant enzyme activities, improved energy status, and increased levels of acetyl-CoA, MeJA, and QR in the pistils. Additionally, NaAC, MeJA, and QR, either alone or in combination, effectively augmented spikelet fertility under heat stress, while the combination of MeJA and QR inhibitors significantly reduced fertility.<h3>Conclusion</h3>Acetate activates acetyl-CoA to induce the synthesis of both MeJA and QR, thereby alleviating heat-induced pistil dysfunction by maintaining ROS homeostasis and enhancing the pollen germination, pollen tube growth and spikelet fertility. Our results offer a promising strategy to enhance the heat tolerance of crops.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"50 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory roles of extracellular vesicles in pregnancy complications","authors":"Qian Sun, Hua Chang, Huan Wang, Lufeng Zheng, Yang Weng, Donghan Zheng, Dongming Zheng","doi":"10.1016/j.jare.2025.02.010","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.010","url":null,"abstract":"<h3>Background</h3>Extracellular vesicles (EVs) are heterogeneous membranous structures released by various cell types, including large vesicles, microvesicles (MVs), and exosomes. These vesicles play crucial roles in intercellular communication within interstitial fluids and are involved in numerous physiological and pathological processes.<h3>Aim of Review</h3>This review aims to examine the regulatory roles of EVs in pregnancy complications, focusing on their involvement in gestational diabetes mellitus (GDM), preeclampsia (PE), and preterm birth (PTB).<h3>Key Scientific Concepts of Review</h3>Placenta- and embryo-derived EVs have gained significant attention for their biological roles due to their effects on inflammation, immune response and immunomodulation. Recent research highlights the importance of EVs in embryonic development and gestation. During pregnancy, several EVs functioned in complex endocrine regulation and pregnancy complications that can affect both the mother and fetus, with long-term cardiovascular and metabolic risks. This review discusses the current evidence on how EVs modulate pregnancy outcomes and explores their biological roles in the pathology of GDM, PE, and PTB. In spite of the current difficulties in relating these findings to the pathogenesis of pregnancy complications and the insufficient evidence for clinical practice, the potential impact of specific proteins and miRNAs transported by EVs is noteworthy on the emergence of pregnancy complications. Future research should continue to explore the complex interactions mediated by EVs to develop novel diagnostic and therapeutic strategies for pregnancy-related disorders.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"26 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthetic tunable promoters for flexible control of multi-gene expression in mammalian cells","authors":"Zong-Heng Fu, Si Cheng, Jia-Wei Li, Nan Zhang, Yi Wu, Guang-Rong Zhao","doi":"10.1016/j.jare.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.008","url":null,"abstract":"<h3>Introduction</h3>Synthetic biology revolutionizes our ability to decode and recode genetic systems. The capability to reconstruct and flexibly manipulate multi-gene systems is critical for understanding cellular behaviors and has significant applications in therapeutics.<h3>Objectives</h3>This study aims to construct a diverse library of synthetic tunable promoters (STPs) to enable flexible control of multi-gene expression in mammalian cells.<h3>Methods</h3>We designed and constructed synthetic tunable promoters (STPs) that incorporate both a universal activation site (UAS) and a specific activation site (SAS), enabling multi-level expression control via the CRISPR activation (CRISPRa) system. To evaluate promoter activity, we utilized Massively Parallel Reporter Assays (MPRA) to assess the basal strengths of the STPs and their activation responses. Next, we constructed a three-gene reporter system to assess the capacity of the synthetic promoters for achieving multilevel control of single-gene expression within multi-gene systems.<h3>Results</h3>The promoter library contains 24,960 unique non-redundant promoters with distinct sequence characteristics. MPRA revealed a wide range of promoter activities, showing different basal strengths and distinct activation levels when activated by the CRISPRa system. When regulated by targeting the SAS, the STPs exhibited orthogonality, allowing multilevel control of single-gene expression within multi-gene systems without cross-interference. Furthermore, the combinatorial activation of STPs in a multi-gene system enlarged the scope of expression levels achievable, providing fine-tuned control over gene expression.<h3>Conclusion</h3>We provide a diverse collection of synthetic tunable promoters, offering a valuable toolkit for the construction and manipulation of multi-gene systems in mammalian cells, with applications in gene therapy and biotechnology.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"31 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long non-coding RNAs: Emerging regulators of invasion and metastasis in pancreatic cancer","authors":"Mengmeng Shi, Rui Zhang, Hao Lyu, Shuai Xiao, Dong Guo, Qi Zhang, Xing-Zhen Chen, Jingfeng Tang, Cefan Zhou","doi":"10.1016/j.jare.2025.02.001","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.001","url":null,"abstract":"<h3>Background</h3>The invasion and metastasis of pancreatic cancer (PC) are key factors contributing to disease progression and poor prognosis. This process is primarily driven by EMT, which has been the focus of recent studies highlighting the role of long non-coding RNAs (lncRNAs) as crucial regulators of EMT. However, the mechanisms by which lncRNAs influence invasive metastasis are multifaceted, extending beyond EMT regulation alone.<h3>Aim of review</h3>This review primarily aims to characterize lncRNAs affecting invasion and metastasis in pancreatic cancer. We summarize the regulatory roles of lncRNAs across multiple molecular pathways and highlight their translational potential, considering the implications for clinical applications in diagnostics and therapeutics.<h3>Key scientific concepts of review</h3>The review focuses on three principal scientific themes. First, we primarily summarize lncRNAs orchestrate various signaling pathways, such as TGF-β/Smad, Wnt/β-catenin, and Notch, to regulate molecular changes associated with EMT, thereby enhancing cellular motility and invasivenes. Second, we summarize the effects of lncRNAs on autophagy and ferroptosis and discuss the role of exosomal lncRNAs in the tumor microenvironment to regulate the behavior of neighboring cells and promote cancer cell invasion. Third, we emphasize the effects of RNA modifications (such as m⁶A and m⁵C methylation) on stabilizing lncRNAs and enhancing their capacity to mediate invasive metastasis in PC. Lastly, we discuss the translational potential of these findings, emphasizing the inherent challenges in using lncRNAs as clinical biomarkers and therapeutic targets, while proposing prospective research strategies.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"29 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neonatal sevoflurane exposures inhibits DHHC5-mediated palmitoylation of TfR1 in oligodendrocytes, leading to hypomyelination and neurological impairments","authors":"Huiqing Liu, Binxiao Su, Zhihao Zhang, Sansan Jia, Jiajia Wang, Fang Zhou, Yang Liu, Qiuxia Cao, Jun Tang, Zhimin Ou, Ming-Ming Zhang, Ying Chen, Hailong Dong, Haixing Zhong","doi":"10.1016/j.jare.2025.02.009","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.009","url":null,"abstract":"<h3>Introduction</h3>Neonatal anesthesia-related neurological impairments are of significant concern, closely linked to oligodendrocyte dysfunction. However, there is a notable temporal discrepancy between the sustained development of oligodendrocytes (myelination) and the short-term vulnerability to anesthesia exposures.<h3>Objectives</h3>Given the significant rise in iron demand by oligodendrocytes during neonatal period, our objective was to clarify the potential roles and underlying mechanisms of iron homeostasis, particularly focusing on transferrin receptor 1 (TfR1), in governing the transient susceptibility to anesthesia.<h3>Methods</h3>Sevoflurane (3 %, 2 h/day) was administered to wildtype or Pdgfrα-Cre^ERT mice from postnatal day (P)6 to P8. Subsequently, behavioral tests, genetic modulation, co-immunoprecipitation assays, Acyl-resin assisted capture assay and single-cell RNA sequencing were employed on P8 and/or P32.<h3>Results</h3>Following neonatal exposure to sevoflurane, the observed cognitive impairments and hypomyelination at P32 were attributed to iron accumulation and ferroptosis, particularly within oligodendrocytes of the corpus callosum (CC). This ferroptosis was mediated by enhanced endocytosis of transiently expressed TfR1, rather than its overexpression, due to inhibited palmitoylation. Among the 21 palmitoyltransferases, only Asp-His-His-Cys5 (DHHC5) was down-regulated in oligodendrocytes, reducing palmitoylation of TfR1 at the C98 cysteine site. Furthermore, specific overexpression of DHHC5 in oligodendrocytes significantly restored TfR1 endocytosis, hypomyelination, and ferroptosis, thereby preventing neuronal ferroptosis across multiple brain regions by decreasing iron transport, ultimately mitigating neurological impairments.<h3>Conclusion</h3>We discovered that decreased DHHC5 in oligodendrocytes promotes TfR1 associated ferroptosis, resulting in hypomyelination and initiating neuronal ferroptosis, thereby impairing cognition following neonatal sevoflurane exposures. The transiently expressed TfR1 may mediate the critical period for neonatal anesthesia vulnerability. These findings highlight the pivotal role of TfR1-associated ferroptosis in neonatal anesthesia-associated neurotoxicity and oligodendrocyte-neuron interaction, while providing new perspect to understand temporary neurotoxicity of anesthesia. DHHC5 may represent promising therapeutic target to enhance the safety of neonatal anesthesia and iron-related oligodendrocytes disorders.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"20 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PA2G4 in health and disease: An underestimated multifunctional regulator","authors":"Wenlong Jia, Gaocheng Wang, Sheng Sun, Xiaoping Chen, Shuai Xiang, Bixiang Zhang, Zhao Huang","doi":"10.1016/j.jare.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.002","url":null,"abstract":"<h3>Background</h3>Proliferation-associated protein 2G4 (PA2G4), also known as ErbB3-binding protein 1 (EBP1), is an evolutionarily conserved, ubiquitously expressed, multifunctional factor in health and disease. In recent decades, its role as a sophisticated regulator in a broad range of biological processes has drawn widespread attention from researchers.<h3>Aim of review</h3>We introduce the molecular structure, functional modules, and post-translational modifications of PA2G4. We further elaborate on its role and function in immune microenvironment modulation, cell growth, neural homeostasis and embryonic development. In particular, we summarize its relevance to tumorigenesis and cancer progression and describe its molecular mechanisms in regulating the hallmarks of cancers. This review aims to provide a comprehensive blueprint of PA2G4 functions and to inspire further basic and translational studies.<h3>Key scientific concepts of review</h3>Owing to its versatile domains and motifs, PA2G4 regulates a variety of molecular processes, including transcription, translation, proteostasis and epigenetic modulation, suggesting its critical roles in maintaining homeostasis. There are two isoforms of the PA2G4 protein: PA2G4-p42 and PA2G4-p48. While both isoforms regulate cellular activities, they often exert distinct or even contradictory effects. Dysfunction and aberrant expression of PA2G4 isoforms lead to the occurrence and progression of various diseases, indicating their role as predictive markers or therapeutic targets.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"59 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactation duration and the risk of type 2 diabetes mellitus in parous women: A perspective on socioeconomic status disparity","authors":"Qian Yi, Weidi Sun, Leying Hou, Jiajun Hao, He Bai, Shuting Li, Jing Wu, Changzheng Yuan, Xue Li, Sheyu Li, Peige Song","doi":"10.1016/j.jare.2025.02.007","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.007","url":null,"abstract":"Background &amp; Aims: Whether and how socioeconomic status (SES) influences the associations between type 2 diabetes mellitus (T2DM) and lactation remains unknown. We aimed to evaluate the associations between lactation duration and T2DM from a perspective of SES disparity.Methods: A total of 263,859 parous women without diabetes at baseline (2004–2008) in the China Kadoorie Biobank were included. Lactation duration was counted for the first-child, per-child and lifetime. The latent class analysis (LCA) of education level, household income, occupation, and residence was conducted to derive SES as low, intermediate, and high. T2DM cases were identified through linkage with disease registry system and health insurance data during follow-up (2008–2015). Multivariable Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95 % confidence intervals for T2DM. Population attributable fraction evaluated the cases tied to insufficient lactation by SES.Results: In a median 9.2-year follow-up, 8204 cases were identified. Women who breastfed their first child for 12–24 and &gt; 24 months respectively, had a reduced risk of diabetes (HR: 0.84 [0.75–0.94] and 0.81 [0.70–0.95]). Similar results were found for per-child (0.84 [0.72–0.98] and 0.71 [0.59, 0.85]), and lifetime lactation for &gt; 36 months (0.66 [0.56, 0.77]). For dose–response associations, every 5-month increase in lactation duration (first-child, per-child, lifetime) was linked to a 7 %, 10 %, and 4 % lower T2DM risk. These associations were significant among low SES women but not for intermediate or high SES women. For low SES women, 36.42 % of diabetes cases were attributable to per-child lactation duration of &lt; 24 months, and 5.76 %, 25.37 %, 47.29 %. 19.04 % of cases would be prevented if women lactated for 0, 0–6, 6–12, and 12–24 months extended their lactation duration to at least 2 years.Conclusion: Longer lactation duration is associated with a decreased risk of T2DM among women, especially those with low SES. The promotion of extended breastfeeding could potentially prevent a significant proportion of diabetes events.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"12 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA CRCMSL interferes in phospholipid unsaturation to suppress colorectal cancer progression via reducing membrane fluidity","authors":"Muhong Jiang, Lijun Xu, Wandie Lin, Weiwei Liu, Yujie Zhang, Hui Wang, Liang Zhao","doi":"10.1016/j.jare.2025.02.003","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.003","url":null,"abstract":"<h3>Introduction</h3>Reprogrammed metabolism is an important basis of colorectal cancer (CRC) progression; however, its mechanisms remain unclear. This study illustrated a novel mechanism for long noncoding RNA (lncRNA) CRCMSL in CRC, which was identified as a CRC suppressor in our previous study.<h3>Objective</h3>To investigate whether CRCMSL suppresses colorectal cancer by interfering in lipid metabolism.<h3>Methods</h3>Potential functions of CRCMSL were predicted by GSEA, which led to lipidomics. Ferroptosis process in CRC were evaluated by protein markers, probe-reported lipid peroxidation signals and transmission electron microscopy. Order and fluidity of phospholipid bilayers were detected by Laurdan generalized polarization (GP) assays and fluorescence recovery after photobleaching (FRAP) assays, respectively. RNA pull-down and RIP assays were performed to explore the target of CRCMSL. qPCR, western blot and enzyme activity detections were used to explore the effects of CRCMSL on the target. Orthotopic and subcutaneous xenografts in nude mice were used to validate efficacy of CRC in vivo.<h3>Results</h3>CRCMSL-knockdown upregulated lipid synthesis and remodeled fatty acyl chains in phospholipids, inspiring studies on ferroptosis and phospholipid bilayers. CRCMSL-mediated biological processes and behaviors were restored by stearoyl-CoA desaturase (SCD), a key enzyme for the synthesis of monounsaturated fatty acids (MUFAs), suggesting that CRCMSL promotes ferroptosis and reduces membrane fluidity by interfering in phospholipid unsaturation. The target of CRCMSL in fatty acid metabolism is acetyl-CoA carboxylase 1 (ACC1), a key enzyme for de novo fatty acid synthesis. CRCMSL promoted ACC1 phosphorylation to restrict its activity. Firsocostat, an ACC oral inhibitor ND630, is a potential drug for CRC treatment in combination with CRCMSL.<h3>Conclusion</h3>Our study illustrated a novel mechanism of CRCMSL-ACC1 axis-associated fatty acid metabolism in CRC progression, providing laboratory evidence for the development of targeted therapies for patients with advanced CRC.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"39 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A functional cascading of lignin modification via repression of caffeic acid O-methyltransferase for bioproduction and anti-oxidation in rice","authors":"Hua Yu, Guifen Zhang, Jingyuan Liu, Peng Liu, Hao Peng, Zhipeng Teng, Yong Li, Xifeng Ren, Chunxiang Fu, Jingfeng Tang, Mi Li, Yanting Wang, Lingqiang Wang, Liangcai Peng","doi":"10.1016/j.jare.2025.01.048","DOIUrl":"https://doi.org/10.1016/j.jare.2025.01.048","url":null,"abstract":"<h3>Introduction</h3>Crop straws provide substantial biomass resources that are transformable for sustainable biofuels and valuable bioproducts. However, the natural lignocellulose recalcitrance results in an expensive biomass process and secondary waste liberation. As lignin is a major recalcitrant factor, genetic engineering of lignin biosynthesis is increasingly being implemented in bioenergy crops, but much remains unclear about the desired lignocellulose alteration and resulting function.<h3>Objectives</h3>This study attempted to explore the mechanisms of lignin modification responsible for efficient lignocellulose conversion <em>in vitro</em> and an effective plant anti-oxidation response <em>in vivo</em>.<h3>Methods</h3>We initially selected specific rice mutants by performing modern CRISPR/cas9 editing with caffeic acid <em>O</em>-methyltransferase involved in the synthetic pathways of monolignols (G, S) and ferulic acid (FA), and then explored lignocellulose conversion and plant cadmium (Cd) accumulation using advanced chemical, biochemical and thermal-chemical analyses.<h3>Results</h3>Notable lignin modification was achieved from the predominately synergistic down-regulation of S-monomer synthesis in three mutants. This consequently upgraded lignocellulose porosity by up to 1.8 folds to account for significantly enhanced biomass saccharification and bioethanol production by 20 %-26 % relative to the wild-type. The modified lignin also favors the dissection of diverse lignin nanoparticles with dimensions reduced by 1.5–1.9 folds, applicable for thermal-chemical conversion into the carbon quantum dots with increased yields by 15 % and 31 %. The proportions of G-monomers and FA were significantly increased in the mutants, and the lignin extractions were further assayed with higher activities for two standard antioxidants (DPPH and ABTS) <em>in vitro</em> compared to the wild-type, revealing a distinctively enhanced plant antioxidative capacity in the mutants. Water culture showed that young mutant seedlings accumulated more Cd than wild-type did (<em>p</em> &lt; 0.01, n = 3), suggesting effective heavy metal phytoremediation in the mutants.<h3>Conclusion</h3>A hypothetical model of characteristic lignin modification for specific S-monomer reduction, accountable for improved lignocellulose recalcitrance, was proposed. It provides a powerful strategy for achieving high-yield biofuels and value-added bioproducts or enhancing plant antioxidative capacity for heavy metal phytoremediation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"10 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}