Biomedical subjects

Juan Li

Publications and source records attributed to Juan Li.

13 recordsLinked to original sources

PubMed2026

Reframing early gastric carcinogenesis through lineage, niche, and evolution.

Early gastric cancer is still commonly conceptualized as the endpoint of a linear sequence from chronic gastritis to intestinal metaplasia, dysplasia, and invasion. Yet recent single-cell, spatial, genomic, and functional studies indicate that this model incompletely captures the biology of early gastric carcinogenesis. Malignant potential is established progressively within a precancerous gastric field already shaped by somatic evolution, chronic inflammatory injury, and epithelial lineage distortion. Within this field, progression is concentrated in a restricted set of precursor states, particularly incomplete, hybrid, and stem-like metaplastic populations that display plasticity, persistence, and increasing compatibility with a supportive microenvironment. Fibroblast niche remodeling, immune protection loss, endothelial rewiring, genomic instability, epigenetic drift, and selective retention of advantageous molecular alterations further promote malignant commitment. In parallel, diffuse gastric cancer appears to follow a distinct route that may arise independently of conventional intestinal metaplasia through E-cadherin-deficient epithelial transformation and downstream chromatin reprogramming. Here, we synthesize recent evidence to propose an updated framework for early gastric carcinogenesis based on field evolution, lineage instability, ecosystem support, and pathway divergence. Rather than replacing the classical Correa cascade, this framework seeks to refine it by shifting the unit of risk assessment from histologic stage alone to biologically defined precursor states shaped by lineage instability, clonal persistence, niche permissiveness, and pathway-specific molecular constraints. This perspective shifts the emphasis of prevention from detecting smaller cancers to identifying and intercepting biologically committed precursor states before invasion occurs.

Humans↗

PubMed2026

Viscoelastic-Assisted Patient Interface Docking: A Technical Optimization in LenSx Femtosecond Laser-Assisted Cataract Surgery.

PURPOSE: To evaluate the efficacy of viscoelastic-assisted patient interface docking in LenSx (Alcon Laboratories, Inc) femtosecond laser-assisted cataract surgery (FLACS). METHODS: This was a randomized controlled trial. Patients undergoing FLACS from January to August 2025 at Aier Eye Hospital of Wuhan University were randomized via a random number table to receive balanced salt solution (BSS) or visoeleastic as the patient interface docking medium. The primary outcome was docking efficiency, measured by one-time docking success rate, the number of docking attempts, and mean docking time. Secondary outcomes included surgical safety (subconjunctival hemorrhage, capsulotomy completeness/tear rate), laser treatment duration (anterior capsulotomy time, nucleus pretreatment time, total laser emission time), and patient comfort (post-laser pain sensation). RESULTS: A total of 100 patients were enrolled, 50 in each group. Suction loss occurred in 7 patients (14%) in the BSS group and 1 patient (2%) in the viscoelastic group; the one-time docking success rate was significantly higher in the viscoelastic group (98%) than in the BSS group (86%) (chi-square = 3.93, P < .05). The viscoelastic group also had fewer mean docking attempts (1.02 ± 0.14) than the BSS group (1.16 ± 0.42), showing a significant difference (t = 2.23, P < .05). The viscoelastic group exhibited significantly shorter mean docking time (44.66 ± 4.47 seconds) compared to the BSS group (48.62 ± 3.11 seconds) (t = 2.17, P < .05). No significant differences were observed between the groups in subconjunctival hemorrhage, capsulotomy completeness/tear rate, anterior capsulotomy time, nucleus pretreatment time, total femtosecond laser emission time, or patient-reported pain sensation (all P > .05). CONCLUSIONS: Viscoelastic-assisted patient interface docking in FLACS effectively elevates one-time docking success rate, reduces docking attempts, and shortens docking time.

Humans↗

PubMed2026

Development of a highly efficient prime editing platform for cucurbits enables breeding of multi-disease-resistant cucumber.

The prime editing (PE) system is a precise genome editing technology that works efficiently in monocots; however, its application is limited by low editing efficiency in dicots, particularly Cucurbitaceae and Solanaceae plants. Here, we first significantly improved the transformation efficiency by introducing spectinomycin in cucurbits, then used the tomato elongation factor 1-alpha (SlEF1α) promoter to enhance PE protein expression, and incorporated the Csy4 ribonuclease to process pegRNAs, collectively addressing multiple constraints limiting PE efficiency in cucurbits. The optimized PE systems, particularly Csy4-PE6d, achieved an average desired editing frequency of 80.83% at targeted loci in cucumber via stable genetic transformation, with frequencies reaching up to 100% at certain sites. Moreover, Csy4-PE6d generated homozygous edits in 36.43% of transgenic lines and demonstrated robust editing activity in melon, pumpkin, and potato. Using the Csy4-PE6d tool, we generated heritable edited cucumber lines with dual resistance to bacterial angular leaf spot and downy mildew by targeting the CsSGR gene. Collectively, this optimized system substantially enhances PE efficiency in Cucurbit crops, providing an effective solution to common challenges such as low editing efficiency and limited heritability in these species.

Disease Resistance↗

PubMed2026

Comparison of Medium-Coverage Whole-Genome Sequencing and Chromosomal Microarray in Prenatal Testing of Absence of Heterozygosity.

OBJECTIVE: Absence of heterozygosity (AOH) is a clinically significant genomic feature often associated with uniparental disomy and parental consanguinity in the prenatal settings. Chromosomal microarray analysis (CMA) is commonly used for AOH detection, while sequencing-based approaches may provide complementary genomic information within a single assay. This study evaluated the performance of medium-coverage whole-genome sequencing (CNV-plus) for the detection of prenatal AOH. METHODS: We analyzed 45 prenatal samples (35-CMA-positive, 10-CMA-negative). Concordance between CNV-plus and CMA was assessed at regional, genome-wide, and sample levels, with particular emphasis on the effect of AOH segment size. RESULTS: CNV-plus detected 56 AOH regions compared with 65 by CMA, yielding 68 matched segments. Segment-level sensitivity was 86.8%, showing clear size dependence: 53.3% for 5-10 Mb regions and 96.2% for regions > 10 Mb. Genome-wide overlap was high (global Jaccard index = 0.871), although boundary resolution differed between methods. At the sample level, CNV-plus achieved 97.1% sensitivity and 100% specificity, with no significant difference from CMA. CONCLUSIONS: CNV-plus demonstrates good concordance with CMA for detecting larger AOH regions in prenatal samples and may serve as a complementary approach when considering its size-dependent performance.

Humans↗

PubMed2026

CRISPR screening reveals NPC1L1 as a key driver of glioblastoma progression via cholesterol metabolic regulation.

Glioblastoma (GBM), the most aggressive central nervous system (CNS) malignancy, currently lacks curative therapeutic options. While immunotherapy has revolutionized treatment for many cancers, GBM remains refractory to immune-based interventions due to the absence of effective immunotherapeutic targets. Here, through CRISPR screening, we identify Niemann-Pick C1-like 1 (NPC1L1) as a previously unrecognized key driver of GBM progression. Mechanistically, NPC1L1 modulates cholesterol metabolism to concurrently enhance tumor cell stemness and suppress CD8+ T-cell activation, thus inducing tumor progression. Notably, combined treatment with ezetimibe (NPC1L1 inhibitor) and anti-PD-1 antibody elicited potent antitumor activity in GBM orthotopic mouse models. Collectively, these findings establish NPC1L1 as a critical regulator of GBM pathogenesis, underscoring the translational potential of targeting NPC1L1-mediated cholesterol metabolism for developing novel GBM immunotherapies.

Humans↗

PubMed2026

Characterization of oxidative status in maize protoplasts under temperature and saline-alkali stresses.

BACKGROUND: Protoplasts have emerged as a powerful model system in plant functional genomics, offering significant utility in functional gene analysis, protein interaction studies, and transient expression platforms for gene editing. Despite their versatility, inherent limitations restrict their broader application, highlighting the need for systematic investigations into their responses to abiotic stressors, such as temperature fluctuations and saline-alkali conditions (200 mM saline mixture: 170mM NaCl and 30mM Na2CO3, pH = 9.1). RESULTS: In this study, we comprehensively examined the effects of varying temperatures and saline-alkali stress on the integrity, viability, and reactive oxygen species (ROS) metabolism of maize protoplasts. Key markers of oxidative stress-including ROS accumulation, lipid peroxidation (measured as malondialdehyde, MDA), antioxidant enzyme activity (superoxide dismutase, SOD), and hydrogen peroxide (H2O2) levels-were quantified to assess the oxidative stress response. Protoplasts maintained at 4 °C demonstrated enhanced stability and antioxidant capacity, preserving cell viability and endogenous protein integrity for up to 16 h. Conversely, exposure to 37 °C significantly compromised protoplast viability, while incubation at 28 °C exerted minimal effects within 16 h. CONCLUSIONS: Our study investigated the effects of various temperature stresses and salt-alkali stress on maize protoplasts. The results demonstrated that both temperature and salt-alkali stress significantly impacted protoplast production, viability, and the expression of endogenous proteins. These findings not only characterize the redox response of maize protoplasts, but also provide guidance for protoplast isolation and other procedures: 4 °C is suitable for short-term maintenance, 25-28 °C for routine functional assays, and 37 °C should be avoided. These findings provide valuable insights into the stress responses of protoplasts and establish a foundation for future research aimed at improving plant stress tolerance through protoplast-based techniques.

Zea mays↗

PubMed2026

Comparison of the clinical efficacy, safety and EEG functional connectivity changes between 18-Hz rTMS and iTBS of accelerated dTMS treatment for major depressive disorder: a randomized controlled trial.

Although the antidepressant efficacy of 18-Hz deep transcranial magnetic stimulation (dTMS) has been validated, its prolonged treatment duration has considerable limitations for treatment capacity and patient adherence. Therefore, novel short-course protocols such as accelerated dTMS and intermittent theta burst stimulation (iTBS) present promising alternative options. Here we addressed the question of whether iTBS of accelerated dTMS achieves comparable therapeutic and electrophysiological effects to accelerated dTMS with the conventional 18-Hz rTMS protocol in patients with major depressive disorder (MDD). In a randomized controlled trial (n = 73), participants received either 18-Hz rTMS of accelerated dTMS (rTMS-dTMS group), iTBS of accelerated dTMS (iTBS-dTMS group), or pharmacotherapy alone (drug group). Both dTMS protocols were administered twice daily for 10 days targeting the left lateral prefrontal cortex including the dorsolateral region. Results showed that Hamilton Depression Rating Scale (HAMD) score of the iTBS-dTMS group decreased significantly from 22.5 ± 3.7 before treatment to 8.2 ± 4.1 after treatment (t = 15.900, p < 0.001). HAMD score of the rTMS-dTMS group decreased significantly from 21.3 ± 2.9 before treatment to 8.0 ± 3.8 after treatment (t = 17.232, p < 0.001). The drug group also exhibited significantly improved patients' mood symptoms, and the HAMD score decreased from 24.7 ± 6.8 to 14.0 ± 5.0 (t = 6.363, p < 0.001). The treatment response rate was 85.7% in the iTBS-dTMS group and 76.9% in the rTMS-dTMS group, which was much higher than that of the drug group (42.1%). The remission rate was 50.0% in the iTBS-dTMS group and 42.3% in the rTMS-dTMS group, which was significantly higher than 10.5% of the drug group. We demonstrate here that both accelerated dTMS protocols significantly reduced HAMD scores, improved the response rates, and remission rates, outperforming pharmacotherapy alone. Resting-state EEG analysis further revealed unique frequency-specific functional connectivity (FC) modulation effects: the rTMS-dTMS group primarily exhibited weakened alpha-band functional connectivity within the fronto-occipital, fronto-temporal and fronto-central networks after treatment, whereas the iTBS-dTMS group predominantly demonstrated reduced theta-band functional connectivity within the fronto-parietal, fronto-occipital and fronto-temporal pathways after treatment. These findings indicate that iTBS of accelerated dTMS demonstrates comparable efficacy and tolerability to 18-Hz rTMS of accelerated dTMS, whilst inducing treatment-specific network-level neurophysiological alterations. In the rTMS-dTMS group, relative changes in FC between the frontal and temporal/precentral regions showed significant negative correlation with HAMD score reduction rates, while relative changes in FC between the frontal lobe and parietal lobe showed a significant positive correlation with the rate of HAMD score reduction for the iTBS-dTMS group. This study revealed novel mechanisms by which accelerated dTMS protocols modulate brain networks, providing evidence for the clinical application of accelerated iTBS-dTMS as an efficient, evidence-based treatment for MDD.

Humans↗

PubMed2026

Optimizations of Cas12a- and Cas12i-based adenine base editors for efficient precision editing in the plant genome.

A strategy coupling high-activity nucleases with dimeric TadA-8e optimizes plant Cas12-based adenine base editors, boosts editing efficiency, and provides precise editors for crop breeding and genomics research.

Adenine↗

PubMed2026

A Bibliometric Analysis of Systematic Reviews in the Field of Ankylosing Spondylitis from 2007 to 2025.

BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory autoimmune disease and the most common clinical form of spinal arthritis. Over the past decades, tremendous progress has been made in systematic reviews on AS. This study aimed to conduct a bibliometric analysis of AS-related meta-analyses to visualize the hotspots and trends in the field. METHODS: A comprehensive search was conducted for publications of AS meta-analysis from 2007 to 2025 using the Web of Science Core Collection database. Bibliometric analysis was performed using the Bibliometrix software package, VOSviewer, and CiteSpace. RESULTS: In total, 1073 articles were identified, and the number of relevant publications showed annual growth. China, the USA, and England were the most productive countries. Annals of the Rheumatic Diseases was the most productive journal (54, 10.65%), Pan Faming was the most productive author (23, 4.54%), and Anhui Medical University (45, 8.88%) was the most productive institution. High-frequency keywords were mainly grouped into five themes: complications, biologics, physical therapy exercises, gut microbiota, and analytical methods. DISCUSSION: This first bibliometric analysis of AS-related EBM research showed a 20-year upward trend in AS meta-analyses, consistent with prior studies. CiteSpace revealed that China (top since 2014) and the USA led in publications (53 countries) but had limited collaboration. Pan Faming (23 articles) was the most active author, and Annals of the Rheumatic Diseases published the most articles. Keyword analysis identified five themes (e.g., AS complications, biologics) and research frontiers: pre-2012 genome-AS links, post-2012 multi-center RCTs, and the recent focus on AS patients' HRQoL. Limitations included database and English-language bias; future meta-analyses should adopt standardized outcomes. CONCLUSION: In recent years, there has been a remarkable surge in the number of meta-analyses on AS. This significant increase underscores the importance of this research area. Studies in this field have mainly focused on several key aspects: risk factors, network meta-analysis, and quality- of-life studies. These findings are highly valuable for understanding advancements in ASrelated research and can also encourage researchers and clinicians to focus on both effective medical treatments and the well-being of AS patients.

Spondylitis, Ankylosing↗

PubMed2025

CsMYB219 and CsMYB196 influence epigallocatechin gallate biosynthesis in tea plant (Camellia sinensis) by regulating CsSCPL1A gene expression.

Epigallocatechin gallate (EGCG) is the most abundant and biologically active catechin in tea leaves and has been widely utilized in the development of functional foods. EGCG is catalyzed by serine carboxypeptidase-like 1A (CsSCPL1A) acyltransferases in tea plants. Although CsSCPL family genes are regulated by several transcription factors (TFs), systematic studies on their regulation by MYB TFs are lacking. This study integrates targeted metabolomics, transcriptomics, DNA-protein, and protein-protein interaction analyses to elucidate the transcriptional regulation of EGCG biosynthesis-related genes CsSCPL4 and CsSCPL5-1 by R2R3-MYB TFs. CsMYB219 and CsMYB196 can specifically bind to CsSCPL4 and CsSCPL5-1 promoters and activate their expression. CsMYB196 also interacted with CsTT8a and CsTTG1 to activate the transcription activity of CsSCPL4 and CsSCPL5-1 promoters by forming a MYB/bHLH/WD40 (MBW) complex. Promoter truncation assays delineated MYB-responsive cis-elements in CsSCPL4 (-613 to -1 bp with enhancers at -1967 to -1622) and CsSCPL5-1 (-503 to -296 bp). Silencing of CsMYB219 and CsMYB196 by virus-induced gene silencing (VIGS) assay significantly reduced the expression levels of CsSCPL4 and CsSCPL5-1 and EGCG content in tea leaves. Transient overexpression of CsMYB219 and CsMYB196 in tea leaves upregulated CsSCPL4 and CsSCPL5-1 expression and elevated EGCG content. These findings enhance our understanding of the regulatory network underlying EGCG biosynthesis in tea plants and provide a solid foundation for future genetic improvement of tea plant cultivars.

Catechin↗

PubMed2011

Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector.

Efficient and widespread gene transfer is required for successful treatment of Duchenne muscular dystrophy (DMD). Here, we performed the first clinical trial using a chimeric adeno-associated virus (AAV) capsid variant (designated AAV2.5) derived from a rational design strategy. AAV2.5 was generated from the AAV2 capsid with five mutations from AAV1. The novel chimeric vector combines the improved muscle transduction capacity of AAV1 with reduced antigenic crossreactivity against both parental serotypes, while keeping the AAV2 receptor binding. In a randomized double-blind placebo-controlled phase I clinical study in DMD boys, AAV2.5 vector was injected into the bicep muscle in one arm, with saline control in the contralateral arm. A subset of patients received AAV empty capsid instead of saline in an effort to distinguish an immune response to vector versus minidystrophin transgene. Recombinant AAV genomes were detected in all patients with up to 2.56 vector copies per diploid genome. There was no cellular immune response to AAV2.5 capsid. This trial established that rationally designed AAV2.5 vector was safe and well tolerated, lays the foundation of customizing AAV vectors that best suit the clinical objective (e.g., limb infusion gene delivery) and should usher in the next generation of viral delivery systems for human gene transfer.

Amino Acid Sequence↗

PubMed2011

A versatile adeno-associated virus vector producer cell line method for scalable vector production of different serotypes.

Application of adeno-associated virus (AAV) vector in large animal studies and clinical trials often requires high-titer and high-potency vectors. A number of currently used vector production methods, based on either transient transfection or helper virus infection of cell lines, have their advantages and limitations. We previously developed a 293-cell-based producer cell line method for high-titer and high-potency AAV2 vectors. Similar to several other methods, however, it requires multiple cloning steps for the vector and packaging plasmids and a two-step transfection and selection for stable cell lines. Here we report a simplified method with several key improvements and advantages: (1) a one-step cloning of AAV vector cassette into the serotype-specific packaging plasmid; (2) a single plasmid transfection and selection for stable AAV vector producer cell lines; (3) high vector yields of different serotypes, e.g., AAV2, 8, and 9, upon infection with an E1A/E1B-deleted helper adenovirus; (4) efficient packaging of both single-stranded and double-stranded (self-complementary) AAV vectors; and (5) efficient packaging of large AAV cassettes such as a mini-dystrophin vector (5.0 kb). All cell lines were stable with growth rates identical to the parental 293 cells. The vector yields were consistent among serotypes, with 5 × 10(13) to 8 × 10(13) vector genome particles per Nunc cell factory (equivalent to 40 15-cm plates). The vectors showed high potency for in vitro and in vivo transduction. In conclusion, the simple and versatile AAV producer cell line method can be useful for large scale AAV vector production in preclinical and clinical studies.

Biotechnology↗

PubMed2009

A myocardium tropic adeno-associated virus (AAV) evolved by DNA shuffling and in vivo selection.

To engineer gene vectors that target striated muscles after systemic delivery, we constructed a random library of adeno-associated virus (AAV) by shuffling the capsid genes of AAV serotypes 1 to 9, and screened for muscle-targeting capsids by direct in vivo panning after tail vein injection in mice. After 2 rounds of in vivo selection, a capsid gene named M41 was retrieved mainly based on its high frequency in the muscle and low frequency in the liver. Structural analyses revealed that the AAVM41 capsid is a recombinant of AAV1, 6, 7, and 8 with a mosaic capsid surface and a conserved capsid interior. AAVM41 was then subjected to a side-by-side comparison to AAV9, the most robust AAV for systemic heart and muscle gene delivery; to AAV6, a parental AAV with strong muscle tropism. After i.v. delivery of reporter genes, AAVM41 was found more efficient than AAV6 in the heart and muscle, and was similar to AAV9 in the heart but weaker in the muscle. In fact, the myocardium showed the highest gene expression among all tissues tested in mice and hamsters after systemic AAVM41 delivery. However, gene transfer in non-muscle tissues, mainly the liver, was dramatically reduced. AAVM41 was further tested in a genetic cardiomyopathy hamster model and achieved efficient long-term delta-sarcoglycan gene expression and rescue of cardiac functions. Thus, direct in vivo panning of capsid libraries is a simple tool for the de-targeting and retargeting of viral vector tissue tropisms facilitated by acquisition of desirable sequences and properties.

Animals↗