Search Results (943)

Background: Lycium ruthenicum, commonly known as Black goji berry, is a shrub species native to western China and is rich in bioactive compounds that contribute to its nutritional and health-promoting effects. However, the transcriptional dynamics associated with fruit development and quality formation in black goji berry remain incompletely understood. This study aimed to investigate transcriptional dynamics during fruit development and identify candidate genes associated with sugar accumulation and fruit enlargement. Methods: Fruits were sampled at five developmental stages (S1–S5), and RNA-seq was performed to investigate the alterations in gene expression. Differential expression analysis, temporal expression-pattern analysis, functional enrichment analysis, and weighted gene co-expression network analysis (WGCNA) were performed, followed by the integration of differential expression, temporal expression patterns, co-expression relationships, and functional annotation. Results: Fruit diameter, fresh weight, and total soluble sugar content increased markedly during the later developmental stages. Differential expression analysis revealed extensive transcriptional changes across successive developmental transitions, while temporal expression-pattern analysis identified distinct increasing and decreasing gene clusters. Functional enrichment analysis showed that the DEGs were mainly associated with carbohydrate metabolism, sugar transport, hormone-related processes, photosynthesis, and cell-wall modification. WGCNA identified 13 co-expression modules, among which MEyellow and MEbrown showed strong but opposite associations with developmental stage, total soluble sugar content, fruit diameter, and fruit fresh weight. The integrated analysis highlighted several candidate genes associated with sugar metabolism and transport during late fruit development. Conclusions: These findings provide a transcriptomic perspective on the coordinated changes in sugar accumulation and fruit enlargement during L. ruthenicum fruit development. Full article

Persistent Müllerian duct syndrome (PMDS) is a rare disorder of sex development characterized by the persistence of Müllerian duct derivatives in genetically and phenotypically male animals. This report describes the clinical presentation, diagnostic work-up, surgical management, histopathological findings, and cytogenetic characterization of a 9-year-old intact male Schnauzer dog presented with a 3-day history of progressively worsening vomiting, diarrhea, unilateral testicular enlargement, oliguria, and dysuria. Diagnostic evaluation included abdominal radiography, ultrasonography, exploratory laparotomy, histopathology, and cytogenetic analysis using R-replicative banding after bromodeoxyuridine incorporation. Imaging and surgical exploration revealed cryptorchidism, persistent Müllerian duct derivatives, including uterine horn-like structures, and an abnormal gonadal structure. Histopathological examination confirmed severe seminiferous tubular atrophy, persistence of Müllerian-derived tissues, and a unilateral Sertoli cell tumor. Cytogenetic analysis demonstrated a normal male karyotype (78,XY) without evidence of chromosomal mosaicism or structural abnormalities, supporting the diagnosis of a 78,XY disorder of sex development and excluding major chromosomal defects. This case highlights the importance of integrating clinical evaluation, diagnostic imaging, histopathology, and cytogenetic analysis to identify findings compatible with PMDS and emphasizes that this condition should be considered in the differential diagnosis of cryptorchid male dogs presenting with reproductive tract abnormalities or associated testicular neoplasia. Full article

The post-anthesis sepal inflation forming a Chinese lantern in Physalis pubescens represents a striking morphological novelty, whereas in the related genus Solanum lycopersicum var. cerasiforme, the sepals remain non-enclosing, providing an ideal comparative system to study reproductive organ divergence. This study aimed to systematically compare the reproductive development between Physalis pubescens L. and Solanum lycopersicum var. cerasiforme. We integrated phylogenetic analysis, light and scanning electron microscopy, semi-thin sectioning, and quantitative RT-qPCR analysis of six MADS-box genes. Phylogenetic analysis placed P. pubescens in a clade with P. alkekengi (L.) and P. ixocarpa (Brot. ex Hornem.), distinct from tomato. Floral organs differed markedly in petal color, anther morphology, and dehiscence type. Microspore development was delayed before the tetrad stage but accelerated thereafter in P. pubescens; S. lycopersicum anthers exhibited pronounced connective tissue proliferation absent in P. pubescens. P. pubescens sepals expanded 6.92-fold by 17 days post anthesis and enclosed the fruit, while S. lycopersicum sepals grew minimally. Sepal expansion was driven by inner epidermal cell enlargement and intercellular space formation, producing a hollow structure with a trichome-free inner epidermis. Expression of six MADS-box genes exhibited diversity: PfMPF2 and PfAGL1 were upregulated during sepal growth, PfMPF3, PfSEP1 and PfSEP3 exhibited a high–low–high pattern with minima at peak growth, and PfAGL6 declined. These findings reveal that coordinated epidermal cell expansion, parenchyma cavity formation, and a dynamic MADS-box gene network govern the inflated sepal syndrome, and highlight key divergences in anther morphogenesis, providing a cellular and molecular framework for reproductive evolution in Solanaceae. Full article

Spike density is an important component of wheat spike architecture and is determined by the combined effects of spike-axis elongation and spikelet number. In this study, we characterized an ethyl methanesulfonate (EMS)-induced recessive dense-spike mutant, ds, which was obtained from EMS mutagenesis of the wheat cultivar YN21 in 2013 and displays a field-visible compact spike architecture associated with a shortened spike axis, reduced spike internode spacing, and increased spikelet number. Genetic analysis showed that all F₁ plants exhibited normal spikes and that segregation in the F₂ population fitted a 3:1 ratio, supporting control by a single recessive nuclear gene. Through genome-wide marker-based linkage screening, enlarged-population validation, and fine mapping, ds was delimited to an approximately 864.819 kb interval between ID2B2796 and ID2B7615 on chromosome 2B. This interval contains 11 high-confidence annotated genes, including F-box protein, actin, ubiquitin-conjugating enzyme, ribosomal protein L16, RecX, plant cysteine oxidase, PI4KIIγ, and two adjacent GA3OX-family-related genes. Integrated RNA-seq and RT-qPCR analyses showed that the two adjacent GA3OX-family-related genes were expressed in young spikes and exhibited reduced expression in ds-sib relative to WT-sib. These expression data support their retention as plausible, non-exclusive candidates but do not establish causality. Transcriptome analysis further revealed changes in hormone-related pathways, cell-wall organization, carbohydrate metabolism, and transcription-factor regulation. These results provide a reliable genetic basis for further molecular cloning of ds and suggest that altered hormone- and growth-related transcriptional responses may be associated with dense-spike formation in wheat. Full article

Disruptions in folate (vitamin B9) and vitamin B12 metabolism, including nutritional deficiency, folate receptor alpha (FRα) autoantibodies, and MTHFR/DHFR polymorphisms, impair one-carbon metabolism and produce measurable retinal structural, microvascular, and functional changes, offering a non-invasive window into systemic and cerebral metabolic dysfunction, particularly cerebral folate deficiency (CFD). This review synthesizes peer-reviewed evidence on retinal alterations linked to folate/B12 deficiency, hyperhomocysteinemia, FRα autoantibody syndromes, and MTHFR/DHFR variants, alongside artificial intelligence (AI) and machine learning (ML) approaches applied to retinal imaging for metabolic, anemic, and nutritional optic neuropathy detection. Three convergent phenotypes emerge: structural changes (retinal nerve fiber layer and ganglion cell complex thinning, optic disc pallor, chorioretinal atrophy), microvascular abnormalities (reduced vessel density, foveal avascular zone enlargement, capillary dropout), and functional deficits (centrocecal scotoma, dyschromatopsia, reduced contrast sensitivity); they arise from homocysteine-mediated endothelial toxicity, mitochondrial impairment, and eNOS uncoupling. Existing AI/ML models for anemia and optic neuropathy establish technical feasibility but do not target folate-specific phenotypes. We propose a dedicated multimodal ML framework integrating structural, perfusion, functional, and biochemical/genetic data as a research agenda for automated, non-invasive CFD detection. Given the established folate–autism spectrum disorder (ASD) risk association reported in FRAA-positive cohorts, such a framework, once validated, could support prenatal and neonatal screening in FRAA-positive or genetically high-risk pregnancies, enabling earlier leucovorin treatment and reducing neurodevelopmental risk. Full article

Polyploidization can generate morphological and physiological variation in plants, but the molecular basis underlying leaf trait changes after genome doubling in grapevine remains insufficiently understood. This study aimed to characterize phenotypic, physiological, transcriptomic, and metabolomic differences between diploid and induced autotetraploid plants of ‘Thompson Seedless’ and to identify biological processes potentially associated with the observed leaf trait variation. In this study, autotetraploid plants were induced from axillary buds of ‘Thompson Seedless’ using colchicine treatment, and ploidy levels were confirmed by flow cytometry and chromosome counting. Phenotypic, physiological, transcriptomic, and metabolomic analyses were performed to compare diploid and tetraploid plants. Compared with diploids, tetraploids exhibited enlarged leaves, reduced plant stature, larger but less dense stomata, increased chloroplast number in guard cells, and higher total chlorophyll and carotenoid contents. Fv/Fm remained unchanged, whereas increased Vj and decreased ψEo and φEo suggested differences in electron transport-related characteristics beyond QA. Transcriptomic analysis identified 1564 differentially expressed genes, and metabolomic profiling detected 618 differentially accumulated metabolites. Integrated analyses highlighted coordinated molecular differences associated mainly with cell-wall processes, secondary metabolism, redox-related functions, and carbon-related pathways. These findings identify candidate biological processes for future functional validation and provide a basis for evaluating the potential value of autotetraploid germplasm in grapevine breeding. Full article

Background/Objectives: Intraductal papillary neoplasm of the bile duct (IPNB) is a premalignant lesion of cholangiocarcinoma. Currently, its tumor immune microenvironment (TIME) remains poorly characterized. Occupational cholangiocarcinoma provides a unique setting wherein multiple IPNBs arise in a background of chronic biliary injury caused by organic solvents. This study evaluated TIME alternations in IPNB lesions in occupational cholangiocarcinoma, focusing on histological subclassifications, phenotypes, invasive status, and tumor size. Methods: Thirteen IPNB lesions in six patients with occupational cholangiocarcinoma were immunohistochemically stained for CD8, CD163, programmed death protein 1 (PD-1), and programmed death ligand 1 (PD-L1). CD8-, CD163-, and PD-1-positive cells were counted in the most densely infiltrated areas. PD-L1 expression was assessed using the combined positive score (CPS), and associations with each status were analyzed. Results: Within the occupational IPNB cohort, type 2 IPNBs demonstrated significantly higher CD8, CD163, and PD-1 expression levels than type 1 IPNBs. Invasive lesions showed significantly higher CD8 expression and CPS than noninvasive lesions. Tumor size was positively correlated with CD163 expression (R = 0.504), CD8 expression (R = 0.627), and CPS (R = 0.569) in the TIME. When stratified by tumor size (<10 vs. ≥10 mm), lesions ≥ 10 mm in size demonstrated significantly higher CD163 expression and CPS. Notably, all lesions with CPS ≥1 were ≥10 mm in size. Conclusions: In IPNB arising from occupational cholangiocarcinoma, tumor enlargement is associated with progressive TIME alterations. Lesions ≥ 10 mm in size may represent a threshold at which immunoediting and invasive potential become more prominent. Full article

Copines are a family of calcium-dependent phospholipid-binding proteins conserved across numerous eukaryotes. The expression of multiple copine genes is dysregulated in several human cancers, yet their molecular functions remain poorly understood. We are investigating copine genes (cpnA-cpnF) in the amoeba Dictyostelium discoideum, a well-established model for studying conserved signaling pathways that regulate chemotaxis. During development, individual amoebae release and move toward cAMP. cAMP chemotaxis utilizes Ras/PI3K signaling, a pathway that is highly conserved in mammalian cells and often dysregulated in cancer. Using two cpnD mutants that were generated via restriction enzyme-mediated integration (REMI), we found that cpnD mutants exhibited increased cellular proliferation, precocious development, and larger fruiting bodies. Additionally, we found that cpnD mutants had increased cell spreading, producing a flattened morphology and larger cell area. Because activated Ras has been shown to promote this phenotype, we measured Ras activity and found that cpnD mutants exhibited increased Ras activation. cpnD mutants also formed significantly smaller contractile vacuoles during osmotic stress. Inhibition of PI3K suppressed both the enlarged cell area and reduced contractile vacuole phenotypes, indicating that these defects result from increased Ras/PI3K signaling. Finally, we found that GFP-tagged CpnD transiently localized to the plasma membrane following cAMP stimulation, suggesting CpnD may have a role in cAMP signaling. Together, these findings identify CpnD as a potential negative regulator of Ras signaling and provide the first evidence of copine involvement in the Ras/PI3K pathway, suggesting a conserved mechanism that may help explain how altered copine expression contributes to cancer progression. Full article

Understanding the coordinated regulation of growth and metabolism during fruit development is essential for improving crop quality and harvest management. This study investigated changes in morphological traits, endogenous phytohormones, soluble sugars, anthocyanins, and water-soluble vitamins in eggplant (Solanum melongena L.) fruit from 3 to 15 days after anthesis (DAA). Fruit length, diameter, and fresh weight increased significantly, with fresh weight increasing 16.6-fold. Cellular analysis showed that fruit enlargement was driven predominantly by cell expansion. Total soluble sugars increased 2.8-fold, with glucose and fructose as the predominant sugars. Delphinidin-based anthocyanins increased sharply during mid-development (9–12 DAA) and then declined slightly, whereas water-soluble vitamins decreased progressively. Based on integrated data, fruit development was classified into three phases: early (3 DAA, initiation and defense), mid (6–9 DAA, rapid growth and pigmentation), and late (12–15 DAA, functional maturation). Notably, 15 DAA was identified as a critical candidate stage with maximum sugar content, high anthocyanin levels, and completed seed development, suggesting its utility as a potential indicator of optimal harvest timing under the present conditions. These results provide an integrated understanding of developmental and metabolic processes in eggplant fruit and offer practical insights for optimizing harvest strategies. Full article

Background: 2,3,3,3-Tetrafluoro-2-(heptafluoropropoxy)propanoic acid (GenX) is a perfluoroether carboxylic acid that has been detected in drinking water sources. Its potential hepatotoxicity has raised concern, although the associated molecular alterations remain incompletely understood. Chlorogenic acid (CGA), a naturally occurring polyphenol, has been reported to affect oxidative stress and metabolic homeostasis. Methods: Adult male C57BL/6J mice were exposed to GenX (2 mg/kg/day) with or without CGA (30 mg/kg/day) by gavage for 12 weeks. AML12 cells were treated with GenX (10–800 μM) for 24 or 48 h to assess cell viability, and intracellular lipid accumulation was evaluated after exposure to 200 μM GenX for 24 h. Results: GenX exposure induced hepatomegaly, microvesicular steatosis, inflammatory cell infiltration, and a reduction in hepatic glycogen stores. It also decreased hepatic glutathione concentrations and increased hepatic malondialdehyde concentrations. Serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, and triglyceride levels were elevated. In AML12 cells, GenX increased intracellular lipid accumulation, as assessed by Oil Red O staining. Transcriptomic analysis identified significant enrichment of the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Consistently, GenX altered the expression of genes and proteins involved in lipogenesis, fatty acid uptake, lipid storage, and fatty acid oxidation, suggesting disturbed PPAR-related lipid metabolic regulation. Moreover, the decreased p-mTOR/mTOR ratio, increased LC3-II/I, and overexpression of Beclin1, p62, and inflammatory mediators in the GenX group might suggest changes in autophagy-related proteins and inflammatory response. CGA coadministration partially attenuated several GenX-induced hepatic alterations, including liver enlargement, hepatic lipid accumulation, lipid peroxidation, and changes in selected autophagy- and inflammation-related proteins. Conclusions: Subchronic GenX exposure-induced adverse hepatic effects might be associated with disrupted PPAR-related lipid metabolic regulation, oxidative stress, inflammatory responses, and changes in autophagy-related proteins. CGA might exert potential modulatory effects. Full article

Background/Objectives: Fibrous dysplasia (FD) is a benign fibro-osseous disorder characterized by the replacement of normal bone with fibrous tissue and immature woven bone, most commonly involving the craniofacial skeleton. It typically presents as an intraosseous lesion in children and young adults. Fibrous dysplasia may rarely present with predominant gingival involvement and minimal radiographic evidence of intraosseous disease. We report an unusual case of craniofacial fibrous dysplasia that clinically mimicked an exophytic gingival mass in the anterior maxilla of a middle-aged patient. Methods: A middle-aged patient presented with a slowly enlarging gingival mass extending from the right canine to the left central incisor region. After being lost to follow-up for approximately 4.5 years, the patient returned with increased swelling, pain, spacing of the anterior teeth, and functional impairment affecting mastication and speech. Clinical, radiographic, surgical, and histopathologic findings were evaluated. Surgical management included excision of the lesion, extraction of non-restorable teeth, and bone grafting under general anesthesia. Results: Radiographic examination demonstrated minimal osseous involvement without a clearly defined intraosseous expansile lesion. Histopathologic analysis revealed irregular curvilinear trabeculae of woven bone within a fibrous stroma containing bland spindle cell proliferation, consistent with FD. At the six-month follow-up, the patient remained asymptomatic without complications and was undergoing prosthetic rehabilitation with plans for future implant placement. Conclusions: FD may rarely present as a predominantly gingival lesion with minimal radiographic evidence of bone involvement, posing a diagnostic challenge. Recognition of this atypical presentation is important to avoid misdiagnosis and to facilitate appropriate management through comprehensive clinicoradiologic and histopathologic correlation. Full article

Atriplex halimus is a medicinal plant traditionally used for various therapeutic purposes. This study evaluated the antioxidant, anti-inflammatory, cytotoxic, genotoxic, and anti-arthritic activities of the A. halimus aqueous extract (AHA). Anti-arthritic effects were investigated in Complete Freund’s Adjuvant (CFA)-induced arthritic rats treated with AHA (150 or 300 mg/kg) for 21 days. AHA significantly reduced paw swelling and arthritis severity and improved body weight, while a non-significant reduction in spleen enlargement was observed. Hematological and biochemical parameters were restored toward normal values, indicating anti-inflammatory, hepatoprotective, and nephroprotective effects. The extract also reduced oxidative stress by decreasing nitric oxide (NO) and malondialdehyde (MDA) levels and increasing glutathione (GSH) content and catalase (CAT) activity. Histopathological examination confirmed reduced inflammatory infiltration and protection against bone damage. Phytochemical analysis revealed polyphenols, flavonoids, and tannins, consistent with its antioxidant activity in DPPH, ABTS, CUPRAC, and o-phenanthroline assays. AHA also showed anti-inflammatory activity by inhibiting bovine serum albumin denaturation. The extract induced a moderate concentration-dependent reduction in HeLa cell viability without cytotoxicity toward HaCaT cells. Comet assay results demonstrated DNA damage in HeLa cells at higher concentrations, while AHA significantly suppressed zymosan-induced IL-1β gene expression. These findings indicate that AHA is a promising natural source of bioactive compounds with diverse biological activities. Full article

The development of highly efficient and low-cost electrocatalysts for the urea oxidation reaction (UOR) is crucial for advancing urea fuel cell technologies. In this work, MgZnFe-layered double hydroxide (LDH), LDH/BDC-MOF, and LDH/1,2,4-triazole (LDH/TZ) nanocomposites were successfully synthesized via a simple one-pot co-precipitation method. The structural, morphological, textural, and thermal properties of the prepared materials were investigated using XRD, FTIR, SEM, EDX, BET, and TGA analyses. SEM observations revealed that pristine LDH consisted of stacked thin nanosheets with significant layer aggregation, whereas LDH/BDC-MOF exhibited MOF-pillared structures and LDH/TZ formed a highly porous interconnected three-dimensional network that effectively suppressed nanosheet restacking. BET analysis showed a remarkable enlargement in pore size from 6.7 nm for LDH to 34.5 nm for LDH/TZ. The electrocatalytic performance toward UOR was evaluated by cyclic voltammetry, chronoamperometry, and electrochemical impedance spectroscopy in 1.0 M KOH, containing different urea concentrations. Among all investigated electrodes, LDH/TZ exhibited the highest catalytic activity, delivering anodic current densities of 106, 132, 166, 180, and 202 mA cm⁻² at urea concentrations of 0.2, 0.4, 0.6, 0.8, and 1.0 M, respectively. Furthermore, LDH/TZ displayed a lower onset potential of 0.41 V compared with 0.49 V for LDH/BDC-MOF and 0.56 V for pristine LDH. The enhanced activity was further supported by a high double-layer capacitance of 9.7 μF cm⁻², a large electrochemically active surface area of 0.24 cm², and a low charge-transfer resistance of 2.9 Ω. Chronoamperometric measurements demonstrated excellent durability with a stable current density of approximately 73 mA cm⁻² after 3600 s, while cyclic stability reached 94% after 100 cycles. The superior performance of LDH/TZ is attributed to the synergistic effect of the nitrogen-rich triazole ligand, enlarged pore structure, enhanced active-site exposure, and accelerated charge-transfer kinetics, highlighting its strong potential as an efficient electrocatalyst for direct urea fuel cell applications. Full article

Background: Cardiac involvement in cryoglobulinemia (CG) is rare but potentially fatal, and its clinical spectrum remains poorly characterized. Methods: This retrospective study enrolled 11 patients with cardiac involvement among 885 patients with CG at Peking Union Medical College Hospital between January 2015 and March 2026. We analyzed its clinical characteristics, radiological features and management. Results: Among 885 CG patients, 11 (1.2%; 4 type I, 7 type II) had cardiac involvement. Cardiac symptoms included dyspnea (n = 6), chest tightness (n = 4), edema (n = 3), and orthopnea (n = 1). All patients had elevated N-terminal pro-B-type natriuretic peptide (median 29,799 pg/mL). Echocardiography, performed in all 11 patients, revealed left heart enlargement (n = 9), reduced left ventricular ejection fraction (n = 7), myocardial disease (n = 6), pericardial effusion (n = 4), and pulmonary hypertension (n = 3). Cardiac magnetic resonance in 5 of 11 patients showed non-ischemic late gadolinium enhancement in two cases. For first-line therapy, 6 of 11 patients received rituximab-based regimens, 3 of 11 received bortezomib-based regimens, and 1 of 11 received antiviral therapy with corticosteroids; 1 patient declined treatment. All 10 treated patients achieved initial cardiac improvement, with 5 relapsing and 2 dying during a median follow-up of 57 months (range 9–130 months). The estimated 4-year overall and progression-free survival rates were 77.9% (95% CI: 0.546–1.000) and 50.0% (95% CI: 0.269–0.929), respectively. Conclusions: Cardiac involvement in CG is rare and associated with diverse structural and functional abnormalities. Cardiac involvement should be considered in CG patients presenting with unexplained cardiac manifestations after excluding alternative causes. B-cell-targeted therapy induced an initial response, but relapse is common. Early intervention is essential given the substantial relapse burden and potential for severe morbidity. Full article

Regular endurance exercise is consistently associated with lower cardiovascular mortality, a favorable cardiometabolic profile, and superior cardiorespiratory fitness. However, coronary imaging studies in master endurance athletes have raised a clinically relevant paradox: despite a low burden of conventional risk factors, some athletes—particularly older men with high lifetime exercise exposure—show a greater prevalence of coronary artery calcium and subclinical coronary plaque than sedentary or less active controls. This observation has challenged the long-standing assumption that high-volume endurance exercise is uniformly protective against coronary artery disease. A binary interpretation of this literature is inadequate. Coronary flow reserve and ischemic threshold may remain adequate in some athletes, although this concept is supported by limited functional and outcome data. Based on experimental vascular biology and indirect human evidence, repetitive high-flow states during endurance exercise generate sustained laminar shear stress, cyclic wall strain, and marked increases in coronary blood flow, thereby activating endothelial mechanotransduction pathways and influencing vascular smooth muscle cell behavior, extracellular matrix remodeling, and calcification biology. These adaptations may culminate in positive arterial remodeling, luminal enlargement, and, in some individuals, a predominantly calcified plaque phenotype. Importantly, structural remodeling does not necessarily equate to functional impairment. In selected athletes, when outward remodeling and endothelial responsiveness are preserved, coronary flow reserve and ischemic threshold may remain adequate, although this concept remains supported by limited functional and outcome data. This narrative review integrates the clinical imaging literature with current concepts in vascular mechanobiology to propose that coronary remodeling in endurance athletes exists along an adaptive–maladaptive continuum shaped by cumulative exercise load, aging, sex, conventional risk factors, and biological susceptibility. This framework may help clinicians interpret CAC/CCTA findings in athletes more appropriately and avoid equating plaque burden with equivalent functional or prognostic significance. Full article