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Fei Li

Publications and source records attributed to Fei Li.

10 recordsLinked to original sources
PubMed2026

Generation and Phenotypic Characterization of a CRISPR/Cas9-Engineered Cracd-Deficient Mouse Model for Post-Myocardial Infarction Remodeling Studies.

Myocardial infarction (MI) remains a major cause of morbidity and mortality worldwide. This protocol describes a method for generating and characterizing a Cracd-deficient mouse line on the C57BL/6N background using CRISPR/Cas9 technology. Zygotes were co-injected with Cas9 mRNA, a gRNA construct, and a donor template designed to generate a 3153-bp genomic deletion. The edited allele was confirmed by PCR genotyping and Sanger sequencing. To assess the functional role of CRACD in post-MI remodeling, Cracd-deficient and wild-type (WT, C57BL/6N) mice underwent MI induced by permanent ligation of the left anterior descending coronary artery. On postoperative day 7, cardiac function and left ventricular wall motion were assessed using transthoracic echocardiography and speckle-tracking strain imaging, followed by histopathological evaluation with H&E and Masson's trichrome staining. Representative results showed that Cracd-deficient mice exhibited reduced ventricular dilation and preserved systolic function compared to WT controls. This protocol provides a reliable experimental platform for mechanistic studies of CRACD in cardiac pathophysiology.

Animals↗
PubMed2026

Efficient homologous replacement and deletion of large genomic fragments through template-jumping prime editing in rice.

Homologous replacement of genomic sequences with large DNA fragments (> 100 bp) holds great potential for crop breeding, yet an efficient method to achieve such edits is lacking in plants. Here, in rice, we developed template-jumping prime editing (TJ-PE), a recently reported PE strategy for large targeted insertion, as an efficient tool for homologous replacement with DNA fragments ranging from dozens to hundreds of base pairs, and using TJ-PE, we replaced genomic fragments of up to 340 bp with homologous fragments of the same length. In addition, our TJ-PE tool also enabled precise deletion of 944- to 2024-bp fragments in rice, with efficiencies of up to 34.6% for c. 2000-bp precise deletions. Collectively, this study expands the editing scope of PE in rice and establishes TJ-PE as a generalist tool for precise deletion and replacement of large DNA fragments.

Oryza↗
PubMed2026

Therapeutic-drug-monitoring-based ATG Targeted Dosing Strategy in Unmanipulated Haploidentical Haematopoietic Stem Cell Transplantation: a randomized, multicenter, phase 3 clinical trial.

Anti-thymocyte globulin (ATG) has been a standard prophylaxis for graft-versus-host disease (GVHD). However, the pharmacokinetics of ATG in vivo vary significantly, and weight-based fixed dosing may not optimize efficacy while minimizing toxicity. We investigated the clinical results of a therapeutic-drug-monitoring (TDM)-based, dose-optimized ATG strategy versus weight-based fixed dosing in haploidentical haematopoietic stem cell transplantation (NCT05166967). Patients were randomly assigned in a 1:1 ratio to receive a targeted dose of ATG or a fixed dose of 10&#x202f;mg/kg. The primary endpoint was the 365-day graft-versus-host disease-free and relapse-free survival (GRFS). From January 1, 2022, to January 16, 2024, 204 patients were enrolled, with 102 patients in each group. The 365-day GRFS was higher in the targeted dose group (66.7%) than in the fixed dose group (50.0%; hazard ratio [HR], 0.666; 95% confidence interval [CI], 0.4456 to 0.9954; P&#x202f;=&#x202f;0.048). The cumulative incidence of moderate to severe chronic GVHD at day 365 was significantly lower in the targeted dose group (9.8%; 95% CI, 5.0 to 16.5) compared with the fixed dose group (22.5%; 95% CI, 15.0 to 31.1; P&#x202f;=&#x202f;0.026). Fewer grade 3-5 infections were reported in the targeted dose group (44.1%) than in the fixed dose group (70.6%; P&#x202f;<&#x202f;0.001). More patients in the targeted dose group achieved optimal ATG exposure (P&#x202f;=&#x202f;0.007) and superior CD4+ T-cell reconstitution (P&#x202f;=&#x202f;0.002). These findings support the clinical utility of a TDM-based individualized ATG dosing strategy that balances efficacy and toxicity for GVHD prophylaxis in allogeneic stem cell transplantation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05166967.

Humans↗
PubMed2026

Recent advances in immunotherapy for breast cancer: An updated review.

Immunotherapy has revolutionized the treatment landscape of breast cancer, particularly for triple-negative breast cancer (TNBC), yet primary and acquired resistance remain formidable obstacles limiting durable clinical benefit. This review provides a comprehensive update on recent advances in breast cancer immunotherapy, with a focused emphasis on the molecular and cellular mechanisms driving treatment resistance and emerging strategies to overcome them. We dissect tumor-intrinsic resistance pathways, including loss of tumor antigens, defects in antigen processing and presentation machinery, insensitivity to interferon-&#x3b3; signaling, metabolic reprogramming, and epigenetic dysregulation. Tumor-extrinsic mechanisms, such as infiltration of immunosuppressive cells, abnormal angiogenesis, extracellular matrix remodeling, and FGF/FGFR genomic amplification, are highlighted as key barriers to effective immune checkpoint blockade. Emerging evidence implicates novel resistance mediators, including the DUSP22-LGALS1 axis, THSD4-driven T cell exclusion, and the MTDH-SND1 complex impairing antigen presentation, etc. We critically evaluate current strategies to surmount resistance, encompassing combination regimens with chemotherapy, targeted therapies, radiotherapy, and novel immunomodulators. The review also addresses challenges in managing immune-related adverse events, controversies surrounding patient selection biomarkers, and the urgent need for optimized efficacy evaluation systems beyond RECIST criteria. Finally, we discuss future directions, including novel immune checkpoints, microbiome modulation, artificial intelligence-assisted decision-making, and innovative trial designs. By integrating mechanistic insights with clinical evidence, this review provides a framework for understanding and overcoming immunotherapy resistance, advancing the paradigm from "effective" to "precise" immuno-oncology in breast cancer.

Humans↗
PubMed2026

A multi-model genome-wide association study identifies genetic variants underlying resistance to Largemouth Bass Ranavirus (LMBV) in Micropterus salmoides.

Largemouth bass (Micropterus salmoides) is an economically important freshwater aquaculture species, yet recurrent outbreaks of Largemouth Bass Ranavirus (LMBV) continue to impair production and cause substantial losses. The genetic basis of host variation in LMBV resistance remains insufficiently characterized. Here, we applied a multi-model genome-wide association study (GWAS) to identify loci associated with resistance following a controlled challenge with the LMBV-23PY strain. Whole-genome resequencing was performed for 146 phenotyped fish, including 72 susceptible and 74 resistant individuals. After stringent quality control, 877,262 high-quality variants were retained and tested using six GWAS models. Across binary survival status and survival time phenotypes, 32 shared suggestive variants were consistently detected across models, representing suggestive loci for LMBV-23PY resistance. Genes within &#xb1;50&#xa0;kb of these loci were annotated, and functional enrichment highlighted immune- and redox-related biological processes. Three prioritized candidates-GSTT3L (glutathione S-transferase theta-3-like), CGRP2 (calcitonin gene-related peptide 2), and NPPC (natriuretic peptide C)-were associated with pathways involved in oxidative stress responses and immune regulation. Collectively, these results provide insight into the genetic architecture of LMBV-23PY resistance in largemouth bass and identify suggestive variants and associated candidate genes for downstream validation, functional interrogation, and the development of marker-assisted and genome-enabled breeding strategies.

Animals↗
PubMed2026

Incidence of silent cerebral lesions during pulsed field ablation for paroxysmal atrial fibrillation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is a first-line treatment for paroxysmal atrial fibrillation (PAF). Complications such as silent cerebral lesion (SCL) may occur during ablation. Pulsed field ablation (PFA) is a non-thermal method thatablates cardiac tissue via irreversible electroporation. Limited studies have reported the incidence of SCL during PFA, with highly variable results. However, randomized controlled trials (RCTs) remain scarce. The objective of this study was to compare perioperative SCL incidence between PFA and RFCA, and to identify risk factors for SCL during PFA. METHODS: In this prospective pilot RCT (ChiCTR2400088774), 62 patients with PAF were randomized 1:1 to undergo PFA or RFCA. Cerebral MRI (3.0 T) was performed preoperatively and 24-48h postoperatively. SCL was defined as a new acute brain lesion on MRI without neurological deficits. Baseline and surgical data of the patients were collected. RESULTS: SCL was detected post-procedure in 6.45% (2/31) in the RFCA group, 12.90% (4/31) in the PFA group. No statistically significant difference in the incidence of postoperative SCL was detected between the two groups (p&#x2009;=&#x2009;0.67). Left atrium dimension (LAD), left atrial operation time (LAOT), left ventricular end-diastolic dimension (LVEDD), and total operation time (TOT) were significantly higher in SCL group than those in no-SCL group (p&#x2009;<&#x2009;0.05) through univariate analyses. CONCLUSIONS: SCL incidence was 12.90% in the PFA group versus 6.45% in the RFCA group. While no statistically significant difference was detected between two groups, the numerically higher rate in the PFA group warrants larger studies to evaluate cerebral safety associated with PFA.

Humans↗
PubMed2026

Association between 1400 blood metabolites and the risk of ankylosing spondylitis: A 2-stage, 2-sample Mendelian randomization study.

Human blood metabolites have been closely linked to ankylosing spondylitis (AS) in observational studies, yet direct causal evidence remains limited. This study aims to use Mendelian randomization (MR) to pinpoint causal metabolites associated with AS and to predict potential side effects of metabolite interventions. Genetic instruments for exposure were sourced from a genome-wide association study of 1400 blood metabolites, while genome-wide association study data for AS outcomes were derived from the FinnGen cohort. The primary MR analysis was conducted using the inverse variance weighted method. Supplemental analyses were conducted using weighted median, MR-Egger, simple mode, and weighted mode methods, while sensitivity analyses were performed to evaluate heterogeneity and pleiotropy. A replication analysis using an additional the UK Biobank cohort was also performed to determine metabolites associated with AS. The Steiger test and linkage disequilibrium score regression were used to further strengthen causal inference. Lastly, a phenome-wide Mendelian randomization analysis was performed to investigate the potential on-target side effects of metabolite interventions. After comprehensive analyses, 3 metabolites (the 2'-deoxyuridine levels, the hate to mannose ratio, and the Uridine to 2'-deoxyuridine ratio) were identified as being genetically associated with AS. The phenome-wide Mendelian randomization analysis revealed that the hate to mannose ratio might have deleterious effects on 4 other diseases, while no significant associations were found for the 2'-deoxyuridine levels or the uridine to 2'-deoxyuridine ratio with other diseases. This systematic MR analysis unveiled the potential role of the 2'-deoxyuridine levels, hate to mannose ratio and uridine to 2'-deoxyuridine ratio as the causal mediator in the development of AS. Considering the advantages and disadvantages, 2'-deoxyuridine appears as the most promising prospective therapeutic target for the prevention of AS.

Humans↗
PubMed2025

Intraocular pressure is a promising target for myopia control.

BACKGROUND: Myopia presents a noteworthy global health concern, urging exploration of innovative treatments. The role of intraocular pressure (IOP) in regulating the progression of myopia has been controversial. METHODS: To investigate the impact of reducing IOP to varying extents on myopia progression, three groups receiving distinct IOP-lowering medications (Brinzolamide, Latanoprost, and a combination of Brinzolamide and Latanoprost) were designed in a form-deprived myopic guinea pig model. Additionally, proteomics analyses were conducted to identify differentially expressed proteins in the sclera. RESULTS: Based on 24-h and 4-week IOP monitoring, the group receiving both Brinzolamide and Latanoprost exhibited the greatest magnitude of IOP reduction and the most significant inhibition of axial length (AL) growth. Moreover, the administration of IOP-lowering medications increased choroidal thickness and induced alterations in the structure of scleral collagen fibrils. Notably, scleral proteomics revealed remodeling processes associated with key mechanisms, including proteolysis, fibrinolysis, and metal ion binding. CONCLUSIONS: Our findings highlight that pressure-dependent scleral remodeling contributes to the deceleration of AL elongation. These results underscore the efficacy of IOP reduction in mitigating the progression of myopia, providing a promising alternative strategy for myopia management.

Myopia↗
PubMed2025

LKB1 inactivation promotes epigenetic remodeling-induced lineage plasticity and antiandrogen resistance in prostate cancer.

Epigenetic regulation profoundly influences the fate of cancer cells and their capacity to switch between lineages by modulating essential gene expression, thereby shaping tumor heterogeneity and therapy response. In castration-resistant prostate cancer (CRPC), the intricacies behind androgen receptor (AR)-independent lineage plasticity remain unclear, leading to a scarcity of effective clinical treatments. Utilizing single-cell RNA sequencing on both human and mouse prostate cancer samples, combined with whole-genome bisulfite sequencing and multiple genetically engineered mouse models, we investigated the molecular mechanism of AR-independent lineage plasticity and uncovered a potential therapeutic strategy. Single-cell transcriptomic profiling of human prostate cancers, both pre- and post-androgen deprivation therapy, revealed an association between liver kinase B1 (LKB1) pathway inactivation and AR independence. LKB1 inactivation led to AR-independent lineage plasticity and global DNA hypomethylation during prostate cancer progression. Importantly, the pharmacological inhibition of TET enzymes and supplementation with S-adenosyl methionine were found to effectively suppress AR-independent prostate cancer growth. These insights shed light on the mechanism driving AR-independent lineage plasticity and propose a potential therapeutic strategy by targeting DNA hypomethylation in AR-independent CRPC.

Male↗