Biomedical subjects

Yan Zhang

Publications and source records attributed to Yan Zhang.

At least 19 recordsLinked to original sources

PubMed2026

A transition zone enriched WIF1+ basal cell subtype is associated with benign prostatic hyperplasia.

The cellular composition and disease susceptibilities of the distinct zones of the human prostate remain incompletely understood. Benign prostatic hyperplasia (BPH) is a common condition that causes widespread morbidity and is nearly exclusively localized to the transition zone (TZ). Through extensive single-cell RNA sequencing (scRNA-seq) of benign regions from prostatectomy specimens, we identified a basal cell population expressing WIF1, VCAN, and NRG1, among other genes, that was significantly enriched in the TZ. Analysis of previously published scRNA-seq datasets further confirmed that WIF1+ basal cells were significantly enriched in BPH compared with normal prostate. Pathway and cell-cell communication analyses revealed that this basal subtype is associated with programs related to cell proliferation, epithelial-mesenchymal transition, immune regulation, angiogenesis, and hormone response. Together, the molecular signature, zonal distribution, and pathway enrichment suggest that TZ-enriched WIF1+ basal cells may contribute to BPH pathogenesis by promoting epithelial and stromal remodeling. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

NRG1↗

PubMed2026

Covalent surface coordination enables efficient and stable formaldehyde-water co-electrolysis over non-stoichiometric cuprous oxide.

The activity-stability trade-off of copper-based oxide catalysts in formaldehyde oxidation remains a fundamental challenge. Here, we resolve this trade-off by grafting N-heterocyclic carbenes (NHCs) onto non-stoichiometric Cu2+1O nanocubes (denoted as Cu2+1O, a Cu+-rich single-phase oxide) through covalent CuC bonds. This molecular surface coordination strategy delivers two concurrent benefits. First, strong σ-electron donation from NHCs shifts the Cu d-band center from -2.106 eV to -2.416 eV, weakening intermediate adsorption and lowering the reaction free-energy change of the rate-determining step (CHOOH⁎ desorption) from 2.56 eV to 1.38 eV. Second, the covalent CuC anchors suppress copper leaching in alkaline electrolyte by a factor of 160 (from 8 mg L-1 to 0.05 mg L-1 over 100 h). The resulting Cu2+1O-NHC catalyst drives formaldehyde oxidation at an onset potential of 0.1 V vs. RHE (Tafel slope: 590 ± 2 mV dec-1, versus 96 ± 3 mV dec-1 for unmodified Cu2+1O; mean ± SD, n = 3), achieving near-unity Faradaic efficiency for both formate (98.65 ± 0.32%) and anodic H2 evolution from CH bond cleavage (99.14 ± 0.28%). Isotope-labeled DEMS confirms that anodic H₂ originates predominantly from the CH bond of formaldehyde, as no HD or D2 was detected when the reaction was performed in D2O. After 100 h of continuous operation, the cubic morphology remains largely intact. This work establishes covalent surface coordination as a promising molecular strategy to decouple activity and stability in oxide electrocatalysts, potentially extendable beyond the specific case of Cu2+1O for aldehyde oxidation.

Copper oxide catalyst↗

PubMed2026

Heterologous expression of DobHLH25 from Dendrobium officinale enhances drought tolerance in Arabidopsis.

Drought stress severely constrains the growth, yield, and accumulation of bioactive compounds in Dendrobium officinale (D. officinale), a valuable medicinal orchid, and this challenge is exacerbated under simulated wild cultivation where plants are inevitably exposed to recurring water deficits. Basic helix-loop-helix (bHLH) transcription factors are well-established regulators of plant abiotic stress responses. However, the molecular mechanisms by which bHLH transcription factors respond to drought stress in this species remain largely unknown. In this study, a bHLH transcription factor gene, DobHLH25, was cloned from D. officinale. Phylogenetic analysis revealed that DobHLH25 shares the highest sequence identity with its ortholog in Dendrobium nobile. Additionally, subcellular localization analysis indicated that DobHLH25 is targeted to the nucleus and possesses a functional transcriptional activation domain. Expression pattern analysis showed that DobHLH25 is most abundantly expressed in old leaves, and its expression in roots, stems, and leaves is induced by polyethylene glycol treatments. Heterologous expression of DobHLH25 in Arabidopsis thaliana resulted in higher seed germination rates and longer root lengths under mannitol-induced osmotic stress compared to wild-type plants. Under drought stress, DobHLH25 heterologous expression lines exhibited higher survival rates, reduced leaf water loss, lower malondialdehyde accumulation, and increased proline content. Moreover, the activities of antioxidant enzymes such as superoxide dismutase and peroxidase were significantly enhanced, and the expression levels of multiple drought-responsive genes were markedly upregulated. Collectively, these findings suggest a correlation between DobHLH25 expression and plant drought tolerance, as evidenced by reduced oxidative damage, increased osmolyte accumulation, enhanced antioxidant enzyme activities, and upregulation of drought-responsive genes. Together, these results suggest that DobHLH25 plays a positive role in drought tolerance, and provides a basis for future dissection of its regulatory network in D. officinale.

Drought Resistance↗

PubMed2026

Phenotypes of Hereditary Diseases Associated With Rauch-Steindl Syndrome.

PURPOSE: Prenatal phenotypic manifestations of genetic disorders associated with NSD2 variants remain poorly characterized. This study presents our institutional experience with the prenatal diagnosis of NSD2-associated genetic disorders, specifically Rauch-Steindl syndrome (RAUST), aiming to improve understanding of both the molecular and clinical features of RAUST. METHODS: We performed a retrospective analysis of six fetuses and one adult diagnosed with RAUST at our institution and thoroughly reviewed the prenatal ultrasound reports of six fetuses. Prenatal and postnatal phenotypes of RAUST cases were summarized alongside findings from previously published literature. Correlations between NSD2 variant locations, variant types, and phenotypes were analyzed. Additionally, protein modeling was used to visualize structural changes in NSD2 protein before and after C-terminal variants. We integrated single-cell transcriptomic and gene expression data from multiple public databases to investigate spatiotemporal expression patterns of NSD2 during human fetal development. RESULTS: Fetal growth restriction (FGR) was the most prevalent prenatal manifestation in RAUST fetuses, followed by microcephaly. Bilateral renal hypoplasia emerged as a novel prenatal ultrasonographic feature. Postnatally, speech and motor developmental delays were the most commonly reported phenotypes, followed by physical developmental delays and intellectual disability. Genotype-phenotype correlation analysis revealed an association between N-terminal truncating variants in NSD2 and impaired fetal growth parameters. Notably, C-terminal truncating variants-predicted not to directly impact NSD2 functional domains-also exerted disease-causing effects. CONCLUSION: This study provides a comprehensive analysis of prenatal phenotypes in RAUST cases, enriching the prenatal phenotypic spectrum of the disease and facilitating early diagnosis and clinical management of RAUST. Furthermore, our genotype-phenotype correlation findings lay a foundational basis for future research into the complex molecular mechanisms underlying NSD2-associated genetic disorders.

Humans↗

PubMed2026

Multivalent cations stabilize DNA duplexes beyond charge neutralization.

Multivalent cations are abundant in cells and play essential roles in DNA duplex stability, genome packaging, and DNA-protein interactions. They can also condense DNA, making it challenging to determine their influence on DNA duplex stability. To overcome this challenge, we studied DNA unpeeling at equilibrium under high tension using magnetic tweezers, thereby preventing condensation. Experiments show that DNA duplex stability first increases and then decreases as cation concentration increases and the maximum DNA duplex stability increases with cation valence. The maximum free energy change of DNA was 3.33 k B T/bp for Na+ and increased to 3.98 k B T/bp for protamine, which is a small arginine-rich protein with a highly positive charge (≈21 for salmon sperm), corresponding to a relative increase of 19.5%. Consistently, all-atom molecular dynamics simulations show that higher-valent cations preferentially embed in the minor groove of DNA and clamp the minor groove, in contrast to the major-groove clamping reported for RNA, thereby stabilizing the helix more efficiently. These findings establish a single-molecule framework for quantifying DNA thermodynamics in complex ionic environments, which contributes to understanding ionic control of genome stability and to designing ion-tunable DNA-based nanostructures and delivery systems.

Journal Article↗

PubMed2026

Protein Profiling Identifies Biomarkers for Predicting Disease Severity in Anti-NMDAR Encephalitis.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune neurological disorder characterized by pathogenic antibodies against the NMDAR. A systematic protein profiling approach is warranted to identify biomarkers capable of predicting disease status. An Olink proximity extension assay (PEA) profiled 91 inflammation-related proteins from anti-NMDAR encephalitis patients. Disease severity or prognosis were assessed by CASE score or mRS score at 6-month follow-up. Patients were stratified into distinct molecular clusters using unsupervised clustering. Logistic regression models incorporating selected biomarkers were developed to predict disease severity and prognosis, followed by absolute quantification using ELISA. Patients were classified into four consensus clusters. Clusters 1 and 2 corresponded to the mild group, while Cluster 3 represented the severe group, consistent with CASE score above 6. Cluster 4 showed heterogeneous clinical features. Elevated serum levels of IL-10, IL-6, and SIRT2, as well as increased CSF levels of CXCL10, CXCL11, and MMP10, were positively associated with severe disease. Conversely, several proteins including LTA and CCL11, CCL8, TGFB1, CXCL6 were associated with severe disease or unfavorable 6-month outcomes. A logistic regression model combining serum CXCL6 and CCL11 with CSF MMP10 achieved an area under the curve (AUC) of 0.95 for predicting disease severity. Serum CCL11 alone showed predictive value for 6-month prognosis, with an AUC of 0.79. These findings delineate distinct protein signatures associated with clinical heterogeneity of anti-NMDAR encephalitis. Prediction models incorporating multiple biomarkers may provide an approach for disease severity stratification and prognosis forecast.

Humans↗

PubMed2026

Discovery of antimicrobial peptides from incomplete biosynthetic gene clusters to combat multidrug-resistant bacteria.

The escalating crisis of multidrug-resistant bacteria necessitates innovative antibiotic discovery platforms. Conventional antimicrobial peptide (AMP) mining often relies on complete biosynthetic gene clusters (BGCs), leaving fragmented genomic resources underexplored. Here, we present an evolution-inspired approach to reconstruct and predict AMPs from partial BGCs. Applying this strategy to 954 Paenibacillus genomes identifies five polymyxin-like peptides, NP001-NP005, with broad in vitro activity. Crucially, in murine models of polymyxin-resistant infection, NP001 reduced bacterial burdens by up to 1,000-fold in a thigh infection model and improved survival (50% vs. 0%) in a lethal peritonitis model. Structural simulations and biophysical assays revealed that NP001 maintains high affinity for bacterial membranes and effectively binds to MCR-1-modified lipid A, a key colistin-resistance mechanism. Moreover, Leu at position 10 of NP001 plays a key role in antibacterial activity against MCR-1-resistant bacteria. Our work establishes a generalizable framework for AMP discovery and introduces a promising therapeutic candidate, NP001, which effectively counteracts polymyxin-resistant pathogens.

Multigene Family↗

PubMed2026

CRISPR-Cas regulates expression of embedded anti-phage defence systems.

Bacteria utilize diverse defence systems to protect against harmful foreign DNA such as bacteriophages1,2, but how these systems coordinate with each other remains poorly understood. Here we uncover CRISIS (CRISPR-supervised immune system), a widespread regulatory paradigm whereby type I CRISPR-Cas loci embed and transcriptionally modulate diverse innate defences. Small non-canonical CRISPR RNA (crRNA)-like RNAs guide the I-C CRISPR-associated complex for antiviral defence (Cascade) effector complex to inhibit promoters of diverse immune cassettes-including composite multi-system clusters-enabling their basal expression for antiviral activity while mitigating fitness costs associated with hyperactivation, such as host growth impairment or exclusion of beneficial plasmids. When CRISPR-Cas is compromised by mutation or anti-CRISPR proteins, there is a burst in transcription of these embedded defence systems, leading to higher-level innate immunity at the expense of host fitness. Together, adaptive CRISPR-Cas systems orchestrate diverse innate immune systems into a layered defence network, comprising a prokaryotic 'immunity guard' strategy.

Bacteriophages↗

PubMed2026

Screening of molecular biomarkers ASPN and LBH and construction of a prediction nomogram for the progression of esophagogastric junction adenocarcinoma.

BACKGROUND: Esophagogastric junction adenocarcinoma (EGJA) is an aggressive malignancy of the digestive system with poor prognosis. Early diagnosis and accurate prediction of tumor progression remain major clinical challenges. This study aimed to identify and validate molecular biomarkers and construct a precise diagnostic model, providing a scientific basis for individualized treatment. METHODS: Differentially expressed genes (DEGs) associated with EGJA were identified using The Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was then performed for further screening. The protein expression levels of ASPN and LBH were validated by immunohistochemistry in both tumor and adjacent non-tumor tissues. A nomogram was constructed by integrating clinical and pathological features, and its performance and clinical utility were assessed using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). RESULTS: Immunohistochemistry demonstrated that the protein expression of ASPN was significantly upregulated in tumor tissues, with expression levels increasing with tumor stage. Conversely, LBH was downregulated in tumor tissues and decreased with advancing stages. The predictive model achieved an area under the curve (AUC) value of 0.977, indicating excellent diagnostic and prognostic performance. DCA confirmed the clinical net benefit of the model. CONCLUSIONS: ASPN and LBH are critical molecular biomarkers for EGJA. The nomogram combining these two markers enables accurate distinction between early and advanced-stage tumors, offering significant support for early diagnosis of EGJA.

ASPN↗

PubMed2026

Optimized TadA-derived base editors efficiently manipulate mRNA splicing by A-to-G and C-to-K editing in potato.

Pre-messenger RNA (pre-mRNA) splicing is a critical mechanism for post-transcriptional regulation in plants. Through alternative splicing, plants produce diverse transcriptomes and proteomes that finely regulate development as well as responses to biotic and abiotic stresses. However, modulating the generation of specific splicing isoforms for functional characterization remains challenging, particularly in the non-model crop potato. Here, we show that two optimized TadA-derived base editors efficiently induce diverse mRNA splice variants by targeting specific splice sites. By evaluating multiple adenosine deaminases and performing multi-dimensional optimization, we developed an efficient adenine base editor RTF-ABE8e for potato. RTF-ABE8e achieved 100% editing efficiency at two StDL1 target sites in stable transgenic potato, with homozygous editing frequencies as high as 93.3% and 91.1%, respectively. We also developed RTF-TadDE, a dual-base editor based on a TadA-derived dual deaminase, for A-to-G and C-to-K (K = T/G) mutations in potato with an overall editing efficiency comparable to that of RTF-ABE8e. By targeting different splice sites with these base editors, we obtained diverse splicing isoforms carrying premature termination codons (PTCs) at StDL1 and StPDS and robust mutant phenotypes. These base editors enable efficient and precise editing of splice sites to trigger missplicing, making them powerful tools for manipulating splicing in plants.

Solanum tuberosum↗

PubMed2026

Precision Optimization of Behavioral Activation for Major and Subthreshold Depression: A Meta-Analysis of Exploring Dose-Response Relationships and Moderating Factors.

OBJECTIVE: This meta-analysis evaluated the efficacy of behavioral activation (BA) in adolescents with subthreshold depression (SD) or major depressive disorder (MDD), exploring dose-response relationships and moderating factors. METHOD: We searched PubMed, EMBASE, Web of Science, EBSCO, Scopus, and the Cochrane Library for randomized controlled trials (RCTs) through December 31, 2024. Risk of bias was assessed using RoB-2, and evidence quality with Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Analyses were performed with R, using standardized mean difference (SMD) for continuous variables and meta-regression for dose-response relationships. Subgroup analyses included symptom severity, intervention setting, delivery format, and parental involvement. The primary outcome was the reduction in depressive symptoms (PROSPERO: CRD42023444273). RESULTS: A total of 14 studies were included (11 RCTs meta-analyzed, comprising 572 participants). BA demonstrated a moderate effect size compared to treatment-as-usual (SMD = -0.42) and a large effect size compared to no-treatment controls (SMD = -0.87). BA was more effective for mild depressive symptoms (SMD = -0.93) than severe symptoms (SMD = -0.43), with significant efficacy in university settings (SMD = -0.94). Intervention without parental involvement exhibited significantly larger effects than those with parental participation (SMD = -0.94 vs -0.38; p < .0001), although this finding was likely confounded by age, symptom severity, and intervention setting. BA moderately improved both behavioral activation levels and functioning (SMD = 0.49). CONCLUSION: Short-term, school-based BA is significantly beneficial for older adolescents with mild depressive symptoms. Findings provide practical guidance for optimizing BA implementation and highlight directions for future research, including the need for larger sample sizes, standardized follow-up assessments, and more representative samples. PLAIN LANGUAGE SUMMARY: This meta-analysis evaluated the effectiveness of behavioral activation (BA), a therapeutic approach focused on improving positive activities, in adolescents with subthreshold depression or major depressive disorder. Based on 14 included studies and 572 participants, BA was found to be more effective for subthreshold compared to major depression. These findings suggest a promising role for BA as an early intervention tool in adolescent depression. STUDY REGISTRATION INFORMATION: Precision Optimization of Behavioral Activation for Major and Subthreshold Depression: A Meta-Analysis of Exploring Dose-response Relationships and Moderating Factors; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023444273. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. Diverse cell lines and/or genomic datasets were not available. We actively worked to promote sex and gender balance in our author group.

Humans↗

PubMed2026

Integrative Analysis Uncover the Effects and Multi-Omics Features of Thigh Muscle Fat Infiltration.

The health impacts and underlying biological pathways of thigh muscle fat infiltration (TMFI) remain incompletely understood. In this study, we analyzed TMFI measured by magnetic resonance imaging in 55,120 UK Biobank participants and found that higher TMFI was significantly associated with all-cause mortality as well as with all major system-specific diseases examined (p values ranged from 2.50 × 10-88 to 9.97 × 10-04). TMFI also mediated the effects of lifestyle factors on health-related outcomes, with mediation proportions ranging from 6.7% to 71.7%. A genome-wide association study (GWAS) identified 79 lead single nucleotide polymorphisms (SNPs) linked to TMFI, and the polygenic risk score for TMFI was significantly associated with mortality and all incident diseases across examined organ systems in an independent subset of UK Biobank participants of European ancestry who were not included in the TMFI GWAS (n = 362,286, all p < 0.05). Gene-drug interactions identified multiple drugs that could potentially modulate TMFI. Analysis of single-cell transcriptomic data indicated that myogenic cells were strongly linked to TMFI (p = 7.08 × 10-08). Summary-data-based Mendelian randomization and Transcriptome-Wide Association Study analyses revealed numerous genes whose expression in specific tissues was associated with TMFI. Proteomic and metabolomic profiling uncovered a broad array of circulating biomarkers associated with TMFI, many of which mediated the effects of modifiable factors and genetic risk on TMFI. Overall, our results highlight the biological relevance of TMFI to human health and provide insights into the multi-omics mechanisms underlying TMFI, identifying potential targets for interventions.

Humans↗

PubMed2025

Integrative oral and gut microbiome profiling highlights microbial correlates of complications in type 1 diabetes: a cross-sectional analysis.

BACKGROUND/OBJECTIVE: Chronic vascular complications are the primary threat in long-standing type 1 diabetes (T1D) patients. We examined the associations between oral-gut microbiome dysbiosis and these complications, offering novel insights into therapeutic strategies and underlying mechanisms. METHODS: This cross-sectional study enrolled 75 T1D participants (disease duration ≥ 10 years) and 43 healthy controls who underwent comprehensive clinical assessment, including blood glucose, lipid profile, and complication-related examinations. Fecal and oral rinse samples were collected for shotgun metagenomic sequencing. T1D participants were stratified by the presence of microvascular (retinopathy, nephropathy, or neuropathy) or macrovascular complications separately. Microbial differences across groups were assessed. RESULTS: Significant differences in oral and gut microbiota compositions were observed between T1D participants with and without complications (both microvascular and macrovascular). A core set of 26 gut and 8 oral microbial species was specifically associated with vascular complications. Butyrate-producing gut bacteria (Blautia wexlerae, Anaerobutyricum hallii, Roseburia inulinivorans, A. soehngenii) and specific oral Neisseria species were enriched in T1D without complications individuals, suggesting protective effects against complications. Mediation analysis indicated associations consistent with partial mediation between certain microbial species and the relationships of glycemic control or insulin resistance (HbA1c, glucose risk index, estimated glucose disposal rate) with complication risk. Moreover, potential oral-gut microbiome interconnections were implicated in complication development. Finally, classification models integrating both oral and gut microbial features significantly outperformed models based on either site alone in distinguishing T1D patients with complications. CONCLUSIONS: Distinct oral and gut microbiome features are associated with chronic vascular complications in T1D. These findings highlight the potential of microbiome-targeted strategies for understanding and preventing T1D-related complications.

Humans↗

PubMed2025

Multi-omics reveals cross-tissue regulatory mechanisms of autism risk loci via gut microbiota-immunity-brain axis.

Autism Spectrum Disorder (ASD) involves a multi-system interaction mechanism among genetics, immunity, and gut microbiota, yet its regulatory network remains undefined. This study conducted a meta-analysis on Genome-Wide Association Study data from four independent ASD cohorts to identify potential genetic loci. By integrating Polygenic Priority Score, brain region, and brain cell eQTL enrichment analyses, and combining summary-data-based Mendelian Randomisation (SMR) analyses of brain cis-eQTL and mQTL, bidirectional Mendelian Randomisation analyses of 473 gut microbiota, and SMR analysis of blood eQTL, SNPs such as rs2735307 and rs989134 with significant multi-dimensional associations were identified. These loci exert cross-tissue regulatory effects by participating in gut microbiota regulation, involving immune pathways such as T cell receptor signal activation and neutrophil extracellular trap formation, as well as cis-regulating neurodevelopmental genes (HMGN1 and H3C9P), or synergistically influencing epigenetic methylation modifications to regulate the expression of BRWD1 and ABT1. The cross-scale evidence chain constructed in this study provides a theoretical foundation for precision medicine research in ASD, holding promise to advance the development of innovative therapeutic strategies.

Autism spectrum disorder↗

PubMed2025

Cross-species phenotypic profiling uncovers functional determinants of bacterial cold shock adaptation.

Temperature shifts impose broad physiological stress, requiring precise and dynamic regulatory programs to restore cellular homeostasis. While the heat shock response is well characterized, the mechanisms underlying cold shock response (CSR) remain less understood. To identify genes critical for cold adaptation, we applied transposon sequencing (Tn-seq) to monitor mutant fitness across the full course of CSR and sustained low-temperature growth in two mesophilic bacteria, Escherichia coli and Bacillus subtilis. In B. subtilis, phenotypic profiling revealed a temporally structured program: membrane fluidity and cell wall remodeling were most critical in the early stage of CSR, whereas post-transcriptional regulation became essential during late-stage recovery to reprogram gene expression and restore growth. Cross-species comparison uncovered both conserved and species-specific mechanisms, with RNA metabolism and ribosome/translation regulators playing broad roles. Specifically, we identified a conserved synergy between two ribosomal RNA methyltransferases, RsmA and RsmH, in promoting cold adaptation. In B. subtilis, mutants lacking these enzymes exhibited significant delay in translation recovery following cold-induced global inhibition. Together, these findings provide a comparative, systems-level view of bacterial cold adaptation and establish a framework for exploring stress responses in pathogens and extremophiles.

Cell envelope↗

PubMed2025

Genome-Wide Identification, Phylogenetic Analysis, and Expression Pattern of Polyamine Biosynthesis Gene Family in Pepper.

Polyamines (PAs), including putrescine, spermidine, spermine, and thermospermine, play essential roles in plant growth, development, and responses to stress. However, the structure and function of PA biosynthetic genes in pepper remain poorly characterized. This study aimed to identify PA biosynthesis genes in the pepper genome using bioinformatics approaches and to assess their expression under various stress conditions. A total of 16 PA biosynthesis-related genes were identified, representing members of the arginine decarboxylase (ADC), ornithine decarboxylase (ODC), agmatine iminohydrolase (AIH), N-carbamoylputrescine amidohydrolase (CPA), S-adenosylmethionine decarboxylase (SAMDC), spermidine synthase (SPDS), spermine synthase (SPMS), and ACAULIS5 (ACL5) gene families. These genes encode proteins with an average molecular weight of approximately 40 kDa, primarily localized in the mitochondria and cytoplasm. Promoter analysis revealed multiple cis-acting elements associated with stress and phytohormone responsiveness. Gene expression was induced by various abiotic stresses, including saline-alkaline, drought, heat, cold, and hydrogen peroxide, as well as by phytohormones such as abscisic acid, ethylene, salicylic acid, auxin, and gibberellin. Overall, this study provides a comprehensive analysis of PA biosynthesis genes in pepper and highlights their potential roles in stress adaptation and hormone signalling, offering a foundation for further exploration of PA-mediated stress tolerance mechanisms.

Capsicum↗

PubMed2025

Ossifying Spindled and Epithelioid Tumor: A Novel Soft Tissue Tumor.

This investigation describes the clinicoradiologic, pathologic, and molecular features of a unique soft tissue tumor characterized by a peripheral shell of bone and composed of bland myoid spindle and epithelioid cells that are keratin-positive. Our study cohort consists of 6 men and 6 women, with a mean age of 32 years. The tumors arose in the extremities (n = 9) and proximal limb girdle (n = 3) and were equally distributed between deep and superficial soft tissues. Patients reported dull painless masses of several months to >10 years duration (mean: 2.9 years). Imaging demonstrated a complete or partial peripheral shell of bone that could extend centrally, and the tumor's mean size was 5.7 cm. Histologically, the tumors were composed of uniform, eosinophilic myoid spindled cells growing in sheets and intersecting fascicles, surrounded by mature lamellar and/or woven bone. Also present was an admixed component of intermediate-sized epithelioid cells with eosinophilic cytoplasm. Mitotic activity was consistently low. Immunohistochemistry showed strong multifocal staining for keratins, and 50% (5/10) showed focal staining for S100; however, all were negative for SMA, desmin, SOX10, ERG, and CD34. Genetic analysis by multiple targeted RNA sequencing panels was negative (n = 10); however, whole transcriptome sequencing (n = 8) revealed a recurrent and novel in-frame SRSF7::NFATC3 fusion in 4 tumors. Dual fluorescence in situ hybridization probes for SRSF7::NFATC3 successfully confirmed this fusion and identified a fifth case, which had not undergone whole transcriptome sequencing but was negative by a targeted RNA fusion panel. Methylation profiling (n = 8) demonstrated a shared epigenetic profile distinct from other entities. Clinical follow-up (n = 11) showed no evidence of recurrence after primary excision with a mean of 41.6 months. In summary, we describe a novel soft tissue tumor designated "ossifying spindled and epithelioid tumor" as a descriptive histologic term that also emphasizes its close radiologic mimic, ossifying fibromyxoid tumor. All cases have behaved in a benign fashion without recurrence following simple excision. Awareness of this entity is important, so that it can be distinguished from other neoplasms that have more aggressive biological potential.

Humans↗

PubMed2025

An advanced cytosine base editor enabled the generation of cattle with a stop codon in the β-lactoglobulin gene.

β-Lactoglobulin (BLG) is an allergen present in milk that can induce an acute immune response in certain individuals. The successful use of cytosine base editors (CBEs) can introduce stop codons into premature mRNA, thereby generating animals with disrupted genes that negatively regulate target traits. In this study, we employed a CBE system to target the major milk allergen BLG in bovine embryos, mammary epithelial cells, and live cattle. First, the precise single-base editing of the BLG gene in bovine embryos was achieved by designing an effective sgRNA to induce a c.61C > T substitution in the coding region, converting codon 21Gln (p.21Gln) to a premature stop codon. Sanger sequencing revealed an editing efficiency of 83.3% (20 out of 24 embryos), including two homozygous edits. Second, a bovine mammary epithelial cell line harboring BLG edits was constructed using the same CBE system. Sequencing showed that the designed sgRNA1 enabled the simultaneous conversion of three consecutive cytosines (c.59-61CCC > TTT) to thymines. At position c.61, single-cell clones exhibited monoallelic or biallelic editing (BLGc.61C > T), with monoallelic edits at positions c.59 and c.60 (CC > TT). Gene expression analysis confirmed that the BLGc.61C > T mutation effectively suppressed BLG expression at both the mRNA and protein levels, even in monoallelically edited cells. Finally, we successfully generated a heterozygous BLGc.61C > T single-base-edited dairy cow that despite its heterozygosity, showed significantly reduced BLG expression in the mammary epithelial cells and milk. Collectively, this study demonstrates the feasibility of using CBEs to disrupt BLG expression in dairy cows and provides a foundation for application in generating hypoallergenic dairy products.

Animals↗