Search Results (12,605)

Trophoblast invasion is crucial for the establishment of a functional placenta. Defects in this process can cause adverse pregnancy outcomes, such as miscarriage and preeclampsia. Aldo-keto reductase family 1 member B10 (AKR1B10), a key cytoplasmic oxidoreductase that converts retinoids, retinaldehyde isoprenoids, and lipid peroxidation-derived reactive aldehydes into their corresponding alcohols, regulates cell proliferation, inflammation, and metastasis in cancers. Here, our results demonstrated that AKR1B10 is highly expressed in the ectoplacental cone (EPC) of the mouse placenta. Deficiency of AKR1B10 leads to excessive trophoblast giant cell (TGC) invasion, impaired trophoblast cell differentiation of the junctional zone, and accelerated maternal spiral artery remodeling. Mechanistically, loss of AKR1B10 suppressed extracellular regulated protein kinase (ERK) phosphorylation in both murine placentas and human HTR8/SVneo cells, further promoting HTR8 cell migration and invasion in vitro. Our findings identify AKR1B10 as a critical regulator that restrains trophoblast invasion in the placenta, suggesting it as a new therapeutic target for placental disorders. Full article

Objectives: This study focuses on exploring the mechanism by which Schisandrin B (Sch B) regulates metabolic dysfunction-associated steatotic liver disease (MASLD) mice induced by a high-fat methionine–choline-deficient (MCD) diet through the activation of peroxisome proliferator-activated receptor γ (PPARγ). Methods: Male C57BL/6 mice were fed a high-fat MCD diet for 8 weeks to establish a mouse MASLD model, and the effects of Sch B on MASLD and the mechanisms were investigated. PPARγ overexpression (OE) was induced by adeno-associated virus (AAV) administration via intrahepatic portal vein injection in mice, and a negative control (NC-OE) was also established. Body weight; wet liver weight; hepatic index; serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β); and hepatic triglyceride (TG) levels were measured in the mice. The histopathology and lipid deposition were observed by hematoxylin and eosin (H&E) staining and Oil Red O staining, while the fibrosis was assessed using Masson staining. Western blot was employed to detect the expression levels of PPARγ, sterol regulatory element-binding protein 1c (SREBP-1c), carnitine palmitoyltransferase 1A (CPT1A), transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMA), collagen type I (collagen I), Smad family members 2/3 (Smad2/3), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38), and extracellular signal-regulated kinase 1/2 (ERK1/2), along with the phosphorylation activation status of these kinases. Results: It was confirmed that Sch B caused effects similar to those induced by PPARγ overexpression, reducing the hepatic index, AST, and ALT levels while alleviating lipid accumulation and fibrosis; and upregulating PPARγ and CPT1A while inhibiting SREBP-1c; and the phosphorylation of the TGF-β/Smad and MAPK pathways were involved in the mechanisms. Conclusions: Sch B can alleviate high-fat MCD-induced MASLD by activating PPARγ in mice. Full article

The aim of this study was to summarize current evidence on dust-related diseases of the bronchopulmonary system, medicinal plants, herbal formulations, and their underlying mechanisms of action. A literature review was conducted based on publications indexed in ScienceDirect, Google Scholar, SciFinder, Scopus, and Medline (PubMed), focusing on the mechanisms underlying dust-related diseases of the bronchopulmonary system, pneumoconiosis, and the potential of phytotherapeutic approaches to modulate these processes. The following keywords were used: bronchopulmonary system, pneumoconiosis, dust-related lung diseases, medicinal plants, herbal preparations, pulmonary rehabilitation, and lymphatic sanitation. The pathogenesis of pneumoconiosis involves the deposition of inhaled dust particles in the lung tissue, followed by chronic inflammation, oxidative stress, and progressive fibrosis. In experimental models, flavonoids, alkaloids, terpenoids, glycosides, tannins, and other phytochemical groups have demonstrated therapeutic potential in bronchopulmonary diseases. Among the compounds investigated, emodin, celastrol, kaempferol, sodium tanshinone IIA sulfonate, astragaloside IV, and dioscin have shown promising effects by modulating key signaling pathways and reducing inflammatory responses. Experimental evidence indicates that these phytochemicals can target major pathways involved in inflammation and fibrogenesis, thereby exerting antioxidant, anti-inflammatory, and antifibrotic effects. The lymphatic system also contributes to the pathogenesis of pneumoconiosis by transporting inhaled dust particles to regional lymph nodes, where their accumulation may promote lymph node sclerosis. Therefore, lymphatic sanitation may represent an important therapeutic mechanism of action of herbal formulations in pneumoconiosis. Our proposed lymphotropic herbal formulation enhances physiological lymphatic drainage and may positively influence the motility and functional activity of the tracheobronchial lymph nodes. The therapeutic potential of medicinal plants and herbal formulations in pneumoconiosis is supported by experimental findings for Tripterygium wilfordii (celastrol, through suppression of the EDNRB/Kng1 – (endothelin receptor type B/kininogen1), Delphinium, Camellia, and Berberis species (kaempferol, through inhibition of TLR4 (Toll-like receptor 4 signaling), Astragalus membranaceus (astragaloside IV, through antifibrotic activity mediated by inhibition of the TGF-β1/Smad3 (transforming growth factor beta1)pathway), and Reynoutria japonica Houtt., Rheum, and Aloe species (emodin, through inhibition of Smad3 (Smad family member 3) and NF-κB (nuclear factor kappa B)phosphorylation and reduction of TGF-β1, α-SMA (alpha-smooth muscle actin), collagen I, TNF-α (tumor necrosis factor alpha), and IL-1β (interleukin-1 beta) levels in lung tissue). For these and several other medicinal plants and their flavonoids, antifibrotic activity has been demonstrated through inhibition of the Akt/NF-κB (protein kinase B/nuclear factor kappa B) signaling pathway. A promising direction for future research is to evaluate the combined use of herbal formulations with established antifibrotic agents to determine whether synergistic therapeutic effects can be achieved. Full article

Chalcone synthase (CHS) is a key enzyme in flavonoid biosynthesis, and its activity strongly influences the efficiency of flavonoid production in plants. By controlling the biosynthesis of secondary metabolites, CHS contributes to plant adaptation to diverse environmental stresses. Here, we identified CHS members across the Phoebe zhennan genome and systematically examined their gene structures, phylogenetic relationships, and potential roles in golden-thread wood color formation and drought response. Genome-wide screening resolved 11 putatively functional PzCHSs, which were unevenly distributed across six chromosomes. Physicochemical analyses indicated that most PzCHS proteins were hydrophilic. Phylogenetic reconstruction divided the PzCHS family into three groups, whose members generally shared similar gene structures. One tandem duplication event and five segmental duplication events were detected. Synteny analysis revealed extensive collinearity between the CHS families of P. zhennan, Phoebe bournei and Cinnamomum camphora, consistent with their close evolutionary relationships. Promoter regions of PzCHS genes were enriched for phytohormone-responsive and growth-related cis-elements, suggesting roles in development and hormonal regulation. Transcriptome profiling showed that PzCHS6 was upregulated in the transition zone of wood and under drought stress, suggesting that this gene may be associated with both golden-thread wood color formation and drought response. These results provide a framework for functional dissection of the CHS members and offer candidate genes for golden-thread wood color improvement and drought response breeding. Full article

Klebsiella grimontii is an emerging pathogen associated with multidrug resistance. Although a single recent study reported phages against K. grimontii, their taxonomic diversity and structural characterisation remained limited. Here, we describe the isolation and characterisation of five novel lytic bacteriophages that specifically target K. grimontii strain K15g, originally isolated from a rotting iris rhizome. Phages Silvester, Lyra, Lyris, Mirion, and Helios were isolated from wastewater samples collected in the Moscow region and represent three distinct morphotypes: podovirus (Silvester), siphovirus (Lyra, Lyris, Mirion), and myovirus (Helios). Whole-genome sequencing revealed that Silvester belongs to the genus Przondovirus (family Autographiviridae); Lyra, Lyris, and Mirion are members of the genus Sugarlandvirus (family Demerecviridae); and Helios falls within the genus Slopekvirus (family Straboviridae). All five phages lack genes associated with lysogeny, virulence factors, or antibiotic resistance, indicating their suitability for therapeutic applications. Structural modelling of the receptor-binding proteins revealed diverse architectures of adsorption apparatuses, including a two-depolymerase complex in Silvester, T5-like tail fibres in the Sugarlandvirus phages, and a set of long and short fibres with a structured cell-puncturing device in Helios. This study presents five novel phages active against Klebsiella grimontii and provides a basis for further evaluation of their potential in phage therapy. Full article

This article presents a two-way convolution of the Mittag-Leffler function with Sheffer polynomials via the umbral algebraic method, thereby introducing the Mittag-Leffler–Sheffer polynomials (MLSPs) and the Sheffer–Mittag-Leffler function (SMLF). We establish their generating functions, series definitions, quasi-monomial properties, and differential equations. Using Wronskian and Pascal functional matrices, we derive recursive formulas and differential recursive identities for these hybrid polynomials. Various special cases including Mittag-Leffler–Appell, Mittag-Leffler–Hermite, and Mittag-Leffler–Miller–Lee polynomials are examined. Additionally, a graphical investigation of the zero distributions of selected members of these polynomial families is presented using computational tools. Full article

Background: The mangrove ecosystem serves as a vital coastal ecotone, providing essential ecological services, such as water purification, shoreline protection, and biodiversity maintenance. Fungal pathogens threaten mangrove health and contribute to ecosystem degradation, but the molecular mechanisms underlying disease resistance in mangroves remain poorly explored. Introdustion: Thaumatin-like proteins (TLPs), belonging to the pathogenesis-related-5 (PR-5) family, play a crucial role in antifungal defense in plants. Method and results: In this study, we identified 23 TLP family members in the mangrove Aegiceras corniculatum. The genes encoding TLP family members were unevenly distributed on chromosomes. Collinearity analyses showed that TLP family members in A. corniculatum underwent multiple gene duplication events, and Ka/Ks calculations revealed that these duplicated genes were predominantly under purifying selection. Among the 23 TLPs, AcTLP19 was significantly upregulated after Botrytis cinerea infection. Subcellular localization prediction and experiments revealed the extracellular localization of AcTLP19. Conclusions: Heterologous expression and antibacterial tests showed that recombinant AcTLP19 had no direct antifungal activity against B. cinerea or Fusarium oxysporum under the tested conditions, leaving open the possibility that it contributes to mangrove defense through indirect mechanisms, or that its antifungal activity was not captured under the specific assay conditions. This study advances our knowledge of mangrove stress responses and may contribute to future conservation strategies. Full article

Background: Transition from upper-secondary school is a significant milestone for people with intellectual and developmental disabilities and represents a time of possibilities—including opportunities to pursue career interests in the job market or further education, deciding where and with whom to live, and identifying further education. The purpose of this qualitative study was to better understand student career and life goals and the support they receive to achieve those goals. Method: Data was collected in spring of 2022 through face-to-face focus group interviews with 11 youth with intellectual and developmental disabilities attending a secondary education program in Iceland and seven family members. We used reflexive thematic analysis to analyze focus group transcripts. Results: Our findings indicate that students have goals for their post-school life; however, they do not feel they have the support or opportunities to achieve their goals. Conclusion: We discuss strategies that schools and communities can use to enhance support and preparation for post-secondary life. Full article

Objective: Heritable thoracic aortic disease (HTAD) is an important cause of thoracic aortic aneurysm and dissection, yet remains underdiagnosed. We aimed to summarize the prevalence of syndromic and non-syndromic HTAD, describe variants of uncertain significance (VUS), and evaluate the impact of family screening in a contemporary cardiothoracic surgical cohort. Methods: Between 2018 and 2026, 163 patients underwent genetic testing for suspected HTAD at our institution. A total of 139 patients with completed genetic testing were included in the analysis. Indications for testing included root aneurysm or acute aortic dissection before the age of 60 years with or without positive family history, aneurysms involving multiple vascular territories, or syndromic features suggestive of a heritable aortopathy. Results: The mean age at testing was 45.8 ± 15.1 years and 33% of patients were female. Aortic dissection represented the initial manifestation of disease in 40% of patients. Positive family history was present in 60% of patients. Pathogenic variants were identified in 24%. Twenty-three patients were diagnosed with syndromic HTAD, most commonly Marfan syndrome, while 10 patients were found to have non-syndromic HTAD. Variants of uncertain significance were detected in 27 patients (19%), predominantly affecting MYLK and MYH11. Following diagnosis, 87 relatives underwent screening, resulting in 18 prophylactic aortic operations. Conclusions: Cardiac surgeons should be aware of the importance of genetic testing in patients with aortic disease. Beyond the individual patient, the broader goal is to identify at-risk family members and prevent acute aortic syndromes. Continued collection of genotype–phenotype data is essential to improve interpretation of variants of uncertain significance and optimize future patient care. Full article

Phoebe bournei is an economically and ecologically important woody species native to China. As a core component of colchicine-triggered polyploid breeding, the tubulin genes (TUA and TUB) have been identified and functionally analyzed in many plants, but not yet in P. bournei. Here, tubulin family members in P. bournei were identified through sequence alignment and subsequently characterized using comprehensive bioinformatic analyses. In particular, a total of six PbTUA and ten PbTUB members were identified and grouped into two and five subfamilies, respectively, according to phylogenetic relationships. Most tubulin proteins were small (414–522 aa) with predicted stability. Furthermore, 36 collinear gene pairs were identified, suggesting a possible contribution to the evolutionary expansion of this family. For different tissues, the expression levels of most tubulin genes were generally lower in leaves but higher in roots. Besides, treatment with 1.0% colchicine inhibited the expression of all 15 tubulin genes except PbTUB6. These results provide preliminary insights into tubulin genes associated with polyploid induction and supply candidate genes for future functional studies toward polyploid germplasm creation of P. bournei. Full article

Background: Cunninghamia lanceolata (Lamb.) Hook. (C. lanceolata) is an important timber tree species in southern China. However, the molecular regulatory mechanisms underlying adventitious root formation during cutting propagation remain largely unclear. The lack of genetic resources has hindered molecular breeding efforts in this species. Methods: In this study, transcriptome analysis was performed on the root systems of scions from elite C. lanceolata clones at 7, 30, and 60 d after cutting. Results: Approximately 69.30 Gb of clean data were obtained. De novo assembly and gene prediction yielded 43,433 protein-coding genes, of which 32,886 (75.7%) were functionally annotated. Temporal clustering and comparative functional enrichment analyses revealed a distinct temporal functional shift during adventitious root development in C. lanceolata. Early stages were dominated by metabolic processes such as pyrimidine metabolism and carbohydrate biosynthesis, whereas later stages were governed by phytohormone signal transduction. Key components of the auxin pathway, including AUX1, AFB, IAA, and SAUR, exhibited dynamic and differential expression, which may be associated with adventitious root growth. Based on the transcriptome data, we identified nine members of the PIN gene family. Both transcriptomic expression profiles and qRT-PCR validation demonstrated that these PIN genes showed divergent expression trends across developmental stages, suggesting that they may participate in rooting by regulating polar auxin transport. Conclusions: This study systematically elucidates the molecular network underlying adventitious root formation in C. lanceolata cuttings. It enriches the omics resources for conifers and provides a theoretical foundation and omics basis for molecular breeding and efficient propagation of elite C. lanceolata clones. Full article

Background: Acute alcohol intoxication causes liver injury and delays recovery via oxidative stress, ferroptosis, inflammation, and gut dysbiosis. This study investigated whether pretreatment with an Alcohol Relief Formula (ARF), composed of soybean peptides, botanical extracts, and probiotics, protects against alcohol-induced liver damage in a preventive model and explored the underlying mechanisms. Methods: Mice with acute alcohol intoxication were pretreated with ARF. Liver damage, hepatic alcohol-metabolizing enzymes, antioxidant capacity, inflammatory cytokines, and lipid peroxidation were measured. Ferroptosis markers and AMP-activated protein kinase (AMPK) signaling were assessed. Gut microbiota composition and cecal short-chain fatty acids (SCFAs) were analyzed. Correlations between SCFAs, ferroptosis suppression, and AMPK activation were evaluated. Results: ARF pretreatment alleviated acute liver damage and accelerated sobriety. It enhanced alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities, inhibited CYP2E1 expression, and improved alcohol metabolism. ARF pretreatment restored antioxidant capacity, decreased pro-inflammatory cytokines and lipid peroxidation, and ameliorated hepatic histopathological changes. Notably, ARF pretreatment was associated with suppressed ethanol-induced ferroptosis markers, including increased glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and ferroptosis suppressor protein 1 (FSP1) expression, elevated AMPK phosphorylation, and reduced hepatic total iron content. In parallel, ARF pretreatment was associated with modulation of the alcohol-disrupted gut microbiota, increased short-chain fatty acid (SCFA)-producing bacteria, and maintained cecal acetate, propionate, and butyrate levels. Correlation analysis revealed that SCFA restoration was positively associated with ferroptosis marker modulation and AMPK activation, suggesting a potential link between gut metabolites and hepatic protection. Conclusions: ARF may serve as a potential preventive nutritional strategy for acute alcohol intoxication by promoting recovery and mitigating liver damage in this acute binge pretreatment model. The observed effects may involve the modulation of gut microbiota-derived SCFAs and AMPK signaling associated with ferroptosis markers. Full article

Background: Nudix hydrolases (NHs), characterized by the conserved Nudix motif (GX₅EX₇REUXEEXGU), hydrolyze nucleoside diphosphate derivatives and play vital roles in plant stress responses and cellular homeostasis. However, the NH gene family has not been systematically characterized in maize (Zea mays L.). Methods: We performed a genome-wide analysis of ZmNH (Nudix hydrolase) genes using a maize pan-genome encompassing 26 high-quality genomes. Results: A total of 73 ZmNH members were identified, comprising 22 core genes (present in all 26 lines), 28 dispensable genes (present in 2–25 lines), and 23 private genes (present in only one line). Phylogenetic analysis clustered them into three subgroups (Type-I, -II, and -III), with Type-III being the largest (28 members). Gene structure and motif analyses revealed conserved exon–intron architectures and 10 conserved motifs. Nonsynonymous/synonymous substitution ratio (Ka/Ks) calculations across the 26 inbred lines indicated that most ZmNH genes were under purifying selection (Ka/Ks < 1), whereas ZmNH2 and ZmNH12 showed evidence of positive selection in some lines. Expression profiling under four stress conditions—Fusarium graminearum, Cercospora zeina, Exserohilum turcicum, and Ostrinia furnacalis—identified 20 differentially expressed ZmNH genes. Notably, ZmNH9 was consistently responsive across multiple pathogen treatments, suggesting a potential role in broad-spectrum disease resistance. Conclusions: These findings provide a foundation for future functional studies of the maize NH gene family. Full article

G. barbadense represents an indispensable germplasm resource for high-quality textile fiber and disease resistance; nevertheless, systematic information regarding its ZRT/IRT-like protein (ZIP) gene family remains limited. Here, a total of 46 GbZIP genes were identified across the G. barbadense genome. Comprehensive bioinformatic investigations revealed uneven chromosomal distribution and confirmed that segmental/whole-genome duplications, supplemented by localized tandem duplications, drove family expansion. Members clustered within the same phylogenetic clades shared conserved motif organization and gene architecture, while promoter regions harbored abundant cis-acting elements associated with phytohormone and stress signaling. Transcriptome profiling indicated distinct expression patterns across vegetative/reproductive tissues, fiber and ovule developmental stages, and diverse abiotic stress conditions (cold, hot, drought, and salt). Quantitative Real-Time PCR (qRT-PCR) further validated that several GbZIP candidates exhibited temporal expression variations upon exposure to cadmium toxicity, V. dahliae infection, and combined Cd-V. dahliae stress. Specifically, GbZIP13, GbZIP18, GbZIP27, and GbZIP36 displayed prominent broad-spectrum responses to all three stress conditions, whereas GbZIP16, GbZIP29, and GbZIP30 showed stress-specific regulatory divergence. Overall, this study aims to systematically analyze the evolutionary characteristics and expression patterns of the GbZIP family, and to specifically evaluate the response differences under Cd stress, V. dahliae stress, and combined stress, in order to identify potential key candidate genes. Full article

Endometrial cancer (EC) is the most common gynecological malignancy with rising incidence, yet reliable non-invasive prognostic biomarkers for preoperative risk stratification and treatment guidance are needed. This pilot study investigated whether plasma levels of aldo-keto reductase family 1 member B1 (AKR1B1) and aldo-keto reductase family 1 member B10 (AKR1B10) could serve as non-invasive prognostic biomarkers in EC. Plasma samples were collected preoperatively from 78 postmenopausal women with histologically confirmed EC alongside clinicopathological data including histological grade, depth of myometrial invasion, lymphovascular invasion, and metastatic status. AKR1B1 and AKR1B10 protein levels were quantified using enzyme-linked immunosorbent assays (ELISAs) in 72 and 64 plasma samples, respectively, and data were analyzed using R v4.3.0. Plasma AKR1B10 levels were significantly higher in Grade 3 compared to Grade 1–2 EC patients; and should be considered with caution given the limited Grade 3 sample size. A model combining both AKR1B1 and AKR1B10 with clinical variables (BMI, age, smoking, parity, hormone replacement therapy, previous use of contraceptives) showed limited discriminative ability for preoperative lymphovascular invasion prediction and is not suitable for clinical use in its current form. Survival analysis revealed that patients with plasma levels of both AKR1B1 and AKR1B10 below the median showed significantly better overall (p = 0.04, hazard ratio (HR) = 0.33, 95% confidence interval (CI): 0.10–1.01) and recurrence-free survival (p = 0.005, HR = 0.09, 95% CI: 0.02–0.49) compared to the remainder of the cohort. These preliminary, hypothesis-generating findings suggest the potential of circulating AKR1B proteins as candidate prognostic biomarkers in EC, requiring prospective validation in larger cohorts. Full article