Zhiwei Wang

Main conclusion A chromosome-scale genome of Capsicum pubescens and comparative pan-TPS analysis support structural characterization and gene-level prioritization of a chromosome−9 terpene-associated candidate locus in this accession. Abstract Capsicum pubescens is one of the five domesticated Capsicum species, mainly cultivated in mid- to high-elevation regions of the Americas. Despite its distinctive morphology and fruit traits, genomic resources for C. pubescens remain less developed than those for the widely cultivated C. annuum. Here, we assembled a chromosome-scale reference genome for accession HNUCP0001, spanning 3.70 Gb with a scaffold N50 of 278.01 Mb. Comparative genomics revealed 679 significantly expanded gene families enriched in sesquiterpenoid and triterpenoid biosynthesis. Genome-wide biosynthetic gene-cluster mining identified multiple terpene-associated candidate loci, which were subsequently prioritized using genome-derived structural criteria and Capsicum pubescens-specific expression evidence. Subsequently, we curated the terpene synthase (TPS) repertoire and, across 16 Capsicum genomes, resolved 36 TPS orthogroups with pronounced presence/absence variation, highlighting dynamic lineage-specific diversification. Together, these analyses establish HNUCP0001 as an accession-specific genomic resource and provide a comparative framework for prioritizing terpene-associated TPS genes and candidate BGCs in Capsicum. These candidate loci, together with accession-level transcriptomic and metabolomic evidence, offer testable hypotheses for future functional studies of specialized terpenoid metabolism in C. pubescens.

Background and aims: Treatment of acute gastric variceal bleeding (AGVB) in patients with large spontaneous portosystemic shunts (SPSS) remains challenging due to the severe, refractory nature of bleeding and the limitations of guideline-recommended therapies, which are associated with difficulty in achieving hemostasis, procedure-related complications, and resource-limited settings. This study aimed to explore the feasibility of balloon-occluded retrograde transvenous obliteration (BRTO)-assisted endoscopic cyanoacrylate injection (ECI) as a potential therapy for AGVB with large SPSS. Methods: This retrospective single-center case series included adult patients (aged 18 or older) who underwent BRTO-assisted ECI for the treatment of AGVB with large SPSS (≥1.2 cm) from March 2022 to December 2024, with a 1-year follow-up. Results: A total of 12 patients were enrolled (mean age 57.8 years; 83.3% male). Among them, 8 were classified as GOV2 and 4 as IGV1, with a median SPSS diameter of 1.6 cm (IQR: 1.2–2.6). All cases of GVs (gastric varices) were attributed to liver cirrhosis, most commonly secondary to hepatitis B virus (58.3%). The majority of patients had Child-Pugh class B (50.0%) or C (41.7%). The clinical success rate was 91.6% (11/12), and no symptomatic embolism or organ dysfunction was observed. There was no early rebleeding (0/12), while the late rebleeding rate was 33.3% (4/12) due to GVs recurrence without regular secondary prophylaxis of bleeding. Although no procedure-related deaths occurred, the 1-year mortality from all causes was 41.7%, primarily from progression of primary liver diseases and co-morbidities. Conclusion: BRTO-assisted ECI appears to be a potential therapy for treating AGVB with large SPSS, with high clinical success and no observed ectopic embolization. Larger prospective multicenter studies are needed to confirm these findings and evaluate long-term outcomes.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) shows marked survival heterogeneity after curative resection, and practical genomic tools for postoperative risk stratification are lacking. We developed and validated a multi-gene mutation panel and microarray assay for prognostic stratification in resected PDAC.Methods: Among 180 patients who underwent R0 resection for PDAC (2015–2019), 169 passed specimen quality control. Ten longest- and ten shortest-survival patients underwent whole-exome sequencing (~200×). Through fold-change ranking, pathway enrichment, and literature curation, 97 candidate genes were subjected to deep targeted sequencing (~1,000×) in all 169 tumors. A 32-gene signature was derived by integrating Cox regression, pathway enrichment, and protein–protein interaction network analyses, then translated into an oligonucleotide microarray and validated in 69 independent patients (surgery 2013–2014).Results: The discovery cohort had a median overall survival (OS) of 28 months. Conventional factors including lymph node status and N stage were not significantly associated with OS, and CA 19-9 discriminated only the ultra-poor prognosis group (<12 months; P=0.963 among remaining groups). The 32-gene signature centered on KRAS, TP53, and FAS hubs spanning nine pathways. In the validation cohort, mutation-score cut-offs delineated four strata with median OS of 7, 15, 40, and 66 months (P<0.001), achieving 75.4% overall and 100% adjacent-category accuracy.Conclusions: A 32-gene mutation panel and microarray assay enable practical, mutation-based postoperative prognostic stratification in PDAC, complementing conventional factors for individualized management.

Giant nodular goiters are hypervascular benign thyroid lesions whose surgical resection carries substantial risks. This study evaluates the feasibility, efficacy, and safety of transarterial chemoembolization (TACE) with bleomycin for symptomatic giant nodular goiter. This single-center retrospective study included patients with giant nodular goiter (≥ 4 cm) treated with TACE using 15,000 U bleomycin and 200-400 μm drug-loaded microspheres between May 2024 and May 2025. Primary outcomes were volumetric reduction and symptom relief. Secondary outcomes included complications and thyroid function changes. Non-parametric paired comparisons were used for statistical analysis. Fifty-one cases (mean age, 58 years [IQR, 42.75-64]) were evaluated. Technical success was achieved in all patients. Median goiter volume decreased from 192.7 cm³ (IQR, 125.4-350.1) to 70.45 cm³ (IQR, 54.04-102.1) at 6-month follow-up (p < 0.0001), representing a median volume reduction rate of 72.13% (IQR, 62.00-78.59). All patients achieved complete symptom remission by 1 month. No major procedure-related adverse events occurred. TACE with bleomycin is a safe and feasible minimally invasive option for symptomatic giant nodular goiter, achieving sustained volume reduction and complete symptom remission without major complications. Question Symptomatic giant nodular goiters pose substantial surgical risk; effective minimally invasive alternatives with durable volume reduction and symptom relief are lacking. Findings TACE with bleomycin-loaded microspheres achieved a median 72.13% volume reduction at 6 months with 100% symptomatic remission and no major complications in all patients. Clinical relevance TACE with bleomycin provides a safe, minimally invasive treatment option for patients with symptomatic giant nodular goiter who are unwilling or medically unfit for surgery, potentially reducing operative morbidity and improving quality of life.

Key message Strigolactones mitigate Cr(VI) toxicity in Capsicum annuum by limiting chromium uptake and reprogramming photosynthesis and redox metabolism, thereby preserving chloroplast function and cellular integrity. Abstract Agricultural soil contamination and its impact on the crops require alternative strategies to reduce associated environmental risks. Strigolactones (SLs) are emerging phytohormones that regulate plant development and stress adaptation; however, their role in hexavalent chromium [Cr(VI)] tolerance remains poorly understood. Here, we investigated the mechanistic basis of SL-mediated mitigation of Cr(VI) toxicity in Capsicum annuum using the synthetic analog rac-GR24. Cr(VI) stress severely impaired photosynthetic performance by disrupting photosystem efficiency, suppressing Calvin–Benson cycle enzyme activities, and reducing ATP and NADPH production, leading to excessive reactive oxygen species accumulation and cellular damage. rac-GR24 markedly decreased Cr uptake and restored photosynthetic carbon metabolism by enhancing the expression of key Calvin cycle enzymes and genes such as RbcS, RbcL, PGK, GAPDH, and PRK. The regulation of fluorescence parameters such as Fv/Fm, Ф_PSII, and ETR improved PSI and PSII functioning, and rebalanced the adenylate and pyridine nucleotide pools. GR24 reinforced redox homeostasis by activating antioxidant defence, stimulating the ascorbate–glutathione and glyoxalase pathways, resulting in reduced lipid peroxidation and improved cell viability. Ultrastructural observations confirmed improved chloroplast integrity and stomatal behavior under SL treatment. The enhancement of photosynthesis and reduction of stress-related biomarkers are probably the consequences of decreased Cr accumulation in roots and shoots upon rac-GR24 treatment, as indicated by the differential expression of SULTR1.2, SULTR1.3, and SULTR3 genes. These findings demonstrate that GR24 could be highly effective in alleviating Cr-induced toxicity in C. annuum. This protective effect is mediated through the coordinated regulation of photosynthetic carbon metabolism and antioxidant defense system, leading to redox regulation, protection of chloroplasts, and better photosynthetic performance. Graphical abstract The alternative text for this image may have been generated using AI.

Background : Accurate prediction of early recurrence (ER) after radical resection remains a critical challenge in pancreatic ductal adenocarcinoma (PDAC). This study aimed to develop and validate an integrated radiomic‐pathology (Rad‐Path) model for ER prediction and to elucidate its underlying biological mechanisms. Methods : A retrospective cohort of 225 PDAC patients who underwent R0 resection was included. Preoperative CT images and whole‐slide images (WSI) were collected for the extraction of radiomic features and computational pathology features. Selected features were used to develop 11 distinct machine learning models. The SHapley Additive exPlanations (SHAP) algorithm was employed to evaluate feature importance. Single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics (ST) were performed on prospectively collected specimens. Results : The final Rad‐Path model achieved AUCs of 0.851 and 0.814 in the internal and external validation cohorts, respectively. The predicted ER group was specifically linked to the enrichment of fibroblasts and pancreatic stellate cells, as well as dysregulation in extracellular matrix (ECM)‐related pathways. This finding was validated histopathologically, as predicted ER patients predominantly displayed a “reactive‐dominant” phenotype marked by abundant activated fibroblasts and ECM deposition. Conclusion : Our study offers a high‐performance predictive model for ER in PDAC and establishes ECM remodeling as a key biological mechanism underlying the predictions.

Key message Pepper CcSnRK2.5 confers drought adaptation, off ering a key genetic resource for crop improvement. Abstract Drought stress remains a paramount constraint on agricultural productivity, threatening global food security by impairing plant growth and inducing yield instability. As central mediators of plant stress adaptation, sucrose non-fermenting 1-related protein kinase 2 (SnRK2) family members orchestrate complex abiotic stress signaling networks. In this study, we systematically identified SnRK2 orthologs in pepper (Capsicum chinense), which were phylogenetically categorized into three distinct subgroups. Promoter analysis revealed a significant enrichment of ABA-responsive elements (ABREs) and drought-associated cis-regulatory motifs. Spatiotemporal expression profiling uncovered divergent transcript abundance patterns in leaves and roots under progressive drought stress, demonstrating organ-specific regulation of SnRK2-mediated stress perception. Functional validation via virus-induced gene silencing (VIGS) of CcSnRK2.5 in pepper significantly augmented drought susceptibility, evidenced by increased oxidative damage and water loss. Conversely, heterologous overexpression of CcSnRK2.5 in Arabidopsis thaliana enhanced drought tolerance by modulating the expression of key ABA-responsive marker genes. Collectively, these findings elucidate the regulatory role of SnRK2 genes in drought stress adaptation and provide promising genetic targets for the molecular breeding of drought-resilient pepper cultivars.