Search Results (1,188)

Petroleum contamination poses a serious threat to human health and ecosystems worldwide, and microbially driven natural attenuation is an effective approach for accelerating hydrocarbon removal. Species of the genus Rhodococcus are recognized for their ability to degrade long chain petroleum hydrocarbons. However, their physiological traits and degradation mechanisms under alkaline conditions remain insufficiently understood. In this study, soil samples were collected from the Dagang oilfield in Tianjin, China, and Rhodococcus sp. A17 was isolated as an active indigenous strain for genomic and physiological characterization under high pH petroleum degradation conditions. The results showed that strain A17 grew optimally at 30 °C, pH 9.0, and 2% salinity. Petroleum hydrocarbon degradation reached 67.8% within 72 h, with a degradation half life of 34.2 h. Genome sequencing identified 18 oxygenase related genes involved in alkane degradation, including alkB, cytochrome P450 monooxygenases, and the long chain alkane monooxygenase ladA, together with four antibiotic resistance genes. Metabolite analysis suggested that alkane degradation might proceed via terminal and subterminal oxidation pathways. Overall, these findings indicate that Rhodococcus sp. A17 exhibits multiple adaptive traits that support its potential application in the bioremediation of petroleum contaminated alkaline environments. Full article

Natural products have emerged as promising multi-target agents for addressing the complex biology of gastric cancer, a malignancy characterized by marked molecular heterogeneity, late clinical presentation, and frequent resistance to systemic therapies. This narrative synthesis integrates primarily preclinical evidence, with emerging clinical data, on how naturally derived compounds modulate three central molecular processes that drive gastric tumor progression and therapeutic failure: evasion of programmed cell death, persistent tumor-promoting inflammation, and chemoresistance. Compounds such as curcumin, resveratrol, berberine, ginsenosides, quercetin, and epigallocatechin gallate restore apoptotic competence by shifting the balance between pro-survival and pro-death proteins, destabilizing mitochondrial membranes, promoting cytochrome c release, and activating caspase-dependent pathways. These agents also exert potent anti-inflammatory effects by inhibiting nuclear factor kappa B and signal transducer and activator of transcription signaling, suppressing pro-inflammatory cytokine production, reducing cyclooxygenase activity, and modulating the tumor microenvironment through changes in immune cell behavior. In parallel, multiple natural compounds function as chemo-sensitizers by inhibiting drug efflux transporters, reversing epithelial–mesenchymal transition, attenuating cancer stem cell-associated traits, and suppressing pro-survival signaling pathways that sustain resistance. Collectively, these mechanistic actions highlight the capacity of natural products to simultaneously target interconnected hallmarks of gastric cancer biology. Ongoing advances in formulation strategies may help overcome pharmacokinetic limitations; however, rigorous biomarker-guided studies and well-designed clinical trials remain essential to define the translational relevance of these compounds. Full article

Saline–alkali stress is one of the important abiotic stresses, which affect plant growth and development. However, the understanding of miRNA pathways in different saline–alkali stress is still limited. In order to better understand the salt–alkali stress response mechanism of wheat, we analyzed miRNA transcription levels in two wheat varieties differing in saline–alkali tolerance (Qingmai 6, QM, tolerant; Meisheng 0308, MS, sensitive) under mixed saline–alkali stress (150 mmol·L¹ and 300 mmol·L¹) for 7 days. High-throughput sequencing identified 11,368 miRNAs (106 conserved, 11,262 non-conserved), among which four miRNAs (miR9653b, miR5384-3p, miR9777, and miR531) exhibited a consistent expression trend across both varieties and all stress concentrations. Additionally, a potential miRNA-mediated regulatory network (including miR408 and miR1135) was predicted to regulate reactive oxygen species (ROS) metabolism via cytochrome P450, plant hormone signal transduction, and MAPK pathways. Saline–alkali-tolerant and sensitive wheat cultivars exhibited distinct miRNA expression patterns under stress. QM maintained higher contents of non-enzymatic antioxidants (ascorbic acid, AsA; reduced glutathione, GSH) and activities of key antioxidant enzymes (ascorbate peroxidase, APX; glutathione reductase, GR), which contributed to balanced ROS homeostasis and enhanced saline–alkali tolerance. Full article

The total cavopulmonary anastomosis (Fontan procedure), a palliative procedure for single-ventricle congenital heart disease, improves survival but is associated with progressive multiorgan complications and high long-term morbidity. Prior blood-based proteomic studies in adults have been limited to targeted antibody-based panels or focused on methodological comparisons. Systemic molecular alterations in younger, clinically heterogeneous patients, particularly in untargeted pathways, remain incompletely characterized. Serum samples from 48 Fontan patients and 48 age- and sex-matched healthy controls were analyzed using mass spectrometry with TMT labeling. 2228 proteins were quantified, of which 124 were significantly differentially abundant (fold change > 1.5 or <0.67, FDR-adjusted p < 0.05). Network analysis identified three major functional clusters: extracellular matrix (ECM) organization (predominantly increased), actin cytoskeleton organization, and platelet-related pathways (both predominantly decreased). Stratified analyses showed reduced ECM protein abundance in high-risk patients, suggesting a shift from active remodeling toward a more established fibrotic state, and uniquely elevated cytochrome b5 reductase 3 (CYB5R3), implicating altered redox homeostasis, nitric oxide metabolism, and cellular aging. Overall, our findings extend prior targeted analyses, reveal potential biomarkers such as CYB5R3 and underscore the complexity of the Fontan circulation, with implications for risk stratification and therapeutic targeting. Full article

Acne vulgaris is a chronic inflammatory dermatosis where conventional therapies often face limitations in efficacy and safety, necessitating the development of microbiome-targeted interventions. This study investigated the immunomodulatory potential of microbiome-derived tryptophan metabolites as a novel therapeutic strategy for Cutibacterium acnes (C. acnes)-induced inflammation, focusing on the aryl hydrocarbon receptor (AHR) pathway. We evaluated indole-3-lactic acid (ILA), indole-3-acrylic acid (IAA), and indole-3-propionic acid (IPA) in comparison to tapinarof, utilizing C. acnes-stimulated human epidermal keratinocytes and a C. acnes-induced acne mouse model. In vitro, ILA and IPA significantly suppressed C. acnes-driven inflammatory mediators, including Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1β, and Cyclooxygenase-2 (COX2), whereas IAA demonstrated limited efficacy. In vivo, ILA treatment exhibited superior therapeutic activity, markedly reducing inflammatory cell infiltration, epidermal hyperplasia, and IL-1β expression. Transcriptomic analysis confirmed that ILA attenuates inflammatory signaling (e.g., IL-17 and TNF pathways) while upregulating AHR-responsive genes such as Cytochrome (CYP) 1A1 and CYP1B1. Collectively, these findings establish ILA as a potent postbiotic that mitigates cutaneous inflammation through selective activation of the AHR. Future studies should prioritize the clinical translation of ILA-based topical formulations, with rigorous evaluation of their efficacy and safety in well-designed human trials, to support their development as a non-antibiotic therapeutic alternative for acne management. Full article

Waterlogging stress severely limits crop photosynthesis and energy supplies, resulting in significant yield reductions. However, the critical duration of waterlogging stress during the maize jointing stage remains unclear, and the physiological and molecular mechanisms underlying its effects on photosynthetic efficiency and energy synthesis in maize require further investigation. In this study, we systematically analyzed the responses of physiological traits, transcriptomic profiles, and the yield formation in maize (Zea mays L.) to varying waterlogging durations imposed during the jointing stage, including 0 days (CK), 2 days (F2), 4 days (F4), 6 days (F6), 8 days (F8), and 10 days (F10). Our results indicate that the (1) grain weight (GW) showed no significant difference between F2 and CK. However, the GW in F4, F6, F8, and F10 decreased significantly by 17.49%, 26.45%, 60.24%, and 100.00%, respectively, compared to the CK. (2) Compared with the CK, the malondialdehyde content progressively increased from F4 to F10, while antioxidant enzyme activity gradually decreased. The chlorophyll content declined by 29.93% to 57.38%, and net photosynthetic efficiency decreased by 13.82% to 38.93%. Although the leaf sucrose content in from F4 to F10 gradually decreased, the leaf starch content remained stable in F4 and F6. In contrast, the starch content in F8 and F10 leaves was significantly reduced by 37.55% and 47.60%, respectively, compared with CK. (3) A transcriptomic analysis revealed that during from F2 to F4, genes encoding photosystem I subunit protein, such as PSAD, and the cytochrome b6f complex proteingene PETC were downregulated. At F6, these key genes encoding photosynthetic proteins were upregulated. However, at F8 and F10, their expression was significantly downregulated. Concurrently, genes related to ATP synthesis (e.g., ATPD) as well as starch and sucrose metabolism (e.g., SPP2, SS1) were also downregulated. In summary, when waterlogging stress persists for no longer than 6 days, plants can maintain their starch content to supply energy for growth, thereby ensuring basic developmental needs. When waterlogging persists for more than 6 days, energy synthesis is impaired, and the nutrient transport to the grains is significantly inhibited, ultimately resulting in a substantial reduction in yield. Therefore, 6 days of waterlogging can be considered the critical threshold for significant yield loss in maize during the jointing stage. Full article

Artificial metalloenzymes incorporating cobalt protoporphyrin IX (Co-PPIX) are promising for sustainable hydrogen production; however, slow protein preparation and a lack of suitable detection methods limit the systematic optimization of their catalytic performance. Here, we report a streamlined workflow that combines the direct in vivo incorporation of Co-PPIX into cytochrome b₅₆₂ (cyt b₅₆₂) variants with a colorimetric assay for hydrogen evolution, scalable to hundreds of mutants. We screened 103 members of a mutant library and selected the variant Co-Mut25, which displayed activity double than wild type on the screen, and produced over 70% more hydrogen than WT as assessed by gas chromatography. This approach enables the rapid and scalable identification of high-performing cobalt–protein catalysts and expands the toolkit for artificial hydrogenase development. Full article

Limpets are marine gastropod molluscs well adapted to intertidal rocky environments, yet their taxonomic resolution remains challenging due to extensive morphological convergence and the presence of cryptic species. In this study, we applied an integrative taxonomic framework combining multi-locus DNA barcoding and fine-scale morphological characterization to clarify species boundaries within three families of limpets—Nacellidae, Lottiidae, and Siphonariidae. A total of 132 individuals collected from six coastal sites in Shenzhen and adjacent areas of southern China were analyzed using four markers Cytochrome c oxidase subunit I (COI), 16S ribosomal RNA (16S rRNA), Cytochrome b (Cytb) and 28S ribosomal RNA (28S rRNA), together with scanning electron microscopy (SEM) observations of radular morphology. Molecular analyses identified nine distinct species across five genera. Kimura two-parameter distance analyses revealed clear barcode gaps in 16S rRNA, Cytb, and 28S rRNA genes, particularly among Cellana and Nipponacmea, whereas COI exhibited stronger discriminatory power within Siphonaria. Moreover, our study provides newly 16S, 28S references for Nipponacmea formosa and Cytb references for Nipponacmea formosa, Lottia luchuana, Siphonaria atra, Siphonaria sirius, Siphonaria sp. and Siphonaria sirius, enriching the public references and explaining the lack of corresponding records in previous BLAST searches. In addition, we identified misannotated COI references in NCBI which were labelled as Nipponacema schrenckii but belong to Cellana toreuma, highlighting inconsistencies in existing reference data rather than issues with our samples. SEM-based radular features displayed consistent interspecific variation that corroborated molecularly defined clades, offering comprehensive search of the NCBI reliable morphological evidence for species delimitation. Collectively, our findings highlight the value of integrating lineage-specific molecular markers with detailed morphological analyses to resolve taxonomic ambiguities in morphologically conservative marine gastropods. Furthermore, this approach strengthens molecular reference resources essential for future biodiversity and evolutionary research on intertidal limpets. Full article

Asian soybean rust (ASR), caused by Phakopsora pachyrhizi (Syd.), poses a serious threat to global soybean production. The main approach to managing this disease has been through repeated fungicide applications which have reduced efficacy due to fungicide resistance. Recently, spray-induced gene silencing (SIGS) through exogenous application of double-stranded RNA (dsRNA) has emerged as a promising approach for plant disease management. In the present study, twelve different dsRNAs targeting genes important for P. pachyrhizi urediniospore germination, infection of the host plant or resistant to commonly used fungicides were produced in Escherichia coli on a large scale. Nine of these dsRNAs significantly reduced ASR severity (by 24.0% to 81.1%) and fungal biomass (50.5% to 83.1%) compared to the control when applied as a foliar spray in our growth chamber studies. Three of the most effective dsRNAs targeting an acyltransferase (ACE), cytochrome B (CYTB1) and a reductase (S12) also significantly reduced disease severity (78.2 to 82.3%) and fungal growth (79.8 to 85.4%) compared to the control in the greenhouse studies. Further investigation of the P. pachryrhizi urediniospore germination and hyphal growth in the presence of these dsRNAs in vitro revealed these dsRNAs reduced the spore germination rate from 72.1% to 0.0–26.6% at 4.5 h and hyphal growth from 254.0 µm to 2.7–40.5 µm at 9 h, with dsRNA targeting the S12 gene being the most effective. These results highlight the potential of SIGS using selected dsRNAs as a sustainable strategy for managing ASR through suppressing urediniospore germination and hyphal growth. Full article

Macroalgae plays a significant role in the formulation of innovative and environmentally sustainable approaches to address food challenges. Specifically, green macroalgae serve as dietary supplements aimed at improving the health, growth, and feeding efficiency of various species of marine and freshwater fishes, as well as mollusks. The effects of Chaetomorpha linum extract (CLE) on growth performance, physiological responses, and disease resistance are studied in Bellamya bengalensis against Aeromonas hydrophila. In this experiment, adult B. bengalensis (4412 ± 165.25 mg) were randomly divided into 15 rectangular glass aquariums (35 snail/aquaria; 45 L capacity) and their basal diet was supplemented with different levels of CLE, including 0 (CLE0), 1 (CLE1), 2 (CLE2), 3 (CLE3), and 4 (CLE4) g/kg for 60 days. The growth performance in the CLE3 dietary group was significantly higher that of the CLE0 group, exhibiting both linear and quadratic trends in relation to dietary CLE levels (p < 0.05). The activities of pepsin, amylase, and lipase were found to be highest in CLE3 and lowest in CLE0. Both linear and quadratic responses to dietary CLE levels in digestive enzymes were observed (p < 0.05). The activities of superoxide dismutase and catalase in the hepatopancreas were found to be elevated in snails due to the synergistic effect of the supplemented CLE diet. Among different levels of diet given, CLE2-supplemented snails showed an increase in their enzyme activity (p < 0.05). Interestingly, all the CLE-treated snails expressed elevated levels of mucus lysozyme and mucus protein when compared to control (p < 0.05). Additionally, hepatopancreatic acid phosphatase and alkaline phosphatase activity were elevated in snails consuming CLE3 (p < 0.05). The transcription levels of immune-related genes, including mucin-5ac and cytochrome, were significantly elevated in snails that were fed a diet supplemented with 2–4 g of CLE/kg. Furthermore, the transcription level of the acid phosphatase-like 7 protein gene also increased in snails receiving CLE-supplemented diets. After a 14-day period of infection, snails that consumed a diet supplemented with 3–4 g/kg of CLE exhibited a notable increase in survival rates against virulent A. hydrophila. Based on the above findings, it is suggested that a diet supplemented with 3 g/kg of CLE may enhance growth, antioxidant and immune defense, and disease resistance in the freshwater snail B. bengalensis. Full article

Background/Objectives: This review integrates evolutionary, metabolic, genetic, and nutritional perspectives to explain how sterol-derived vitamin D pathways shape human physiology and inter-individual variability in vitamin D status. Methods: The literature on sterol and vitamin D metabolism across animals, plants, fungi, and algae was synthesized with data from metabolomics databases, genome-wide association studies, RNA-seq resources (including GTEx), structural biology, and functional genomics. Results: Vitamin D₂ and vitamin D₃ likely emerged early in evolution as non-enzymatic photochemical sterol derivatives and were later co-opted into a tightly regulated endocrine system in vertebrates. In humans, cytochrome P450 enzymes coordinate vitamin D activation and degradation and intersect with oxysterol production, thereby linking vitamin D signaling to cholesterol and bile acid metabolism. Tissue-specific gene expression and regulatory genetic variants, particularly in the genes DHCR7, CYP2R1, CYP27B1, and CYP27A1, contribute to population-level differences in vitamin D status and metabolic outcomes. Structural analyses reveal selective, high-affinity binding of 1,25-dihydroxyvitamin D₃ to VDR, contrasted with broader, lower-affinity ligand recognition by LXRs. Dietary patterns modulate nuclear receptor signaling through distinct yet convergent ligand sources, including cholesterol-derived oxysterols, oxidized phytosterols, and vitamin D₂ versus vitamin D₃. Conclusions: Sterol and vitamin D metabolism constitute an evolutionarily conserved, adaptable network shaped by UV exposure, enzymatic control, genetic variation, and diet. This framework explains inter-individual variability in vitamin D biology and illustrates how evolutionary and dietary modulation of sterol-derived ligands confers functional flexibility to nuclear receptor signaling in human health. Full article

The Asian tiger mosquito (Aedes albopictus) is an important vector of arboviruses, including dengue, chikungunya, and Zika. Its rapid global expansion has been facilitated by climate change and human activities. Phylogenetic studies of Ae. albopictus have largely relied on mitochondrial cytochrome c oxidase subunit 1 (COX1) and NADH dehydrogenase subunit 5 (ND5) markers, while the utility of cytochrome b (CYTB) remains underexplored. We collected Ae. albopictus from 13 sites in seven provinces of South Korea and analyzed COX1, ND5, and CYTB sequences. Genetic diversity indices were calculated, and phylogenetic relationships were reconstructed using maximum-likelihood trees and haplotype networks with a dataset obtained from GenBank. COX1 revealed 46 haplotypes, including six novel variants, with the highest diversity in southern coastal regions such as Busan and Suncheon. ND5 showed limited variation, with only two haplotypes. CYTB revealed three haplotypes, including region-specific variants in Busan and Wonju, supporting its role as a complementary marker. The Busan haplotype H41 bridged domestic and international lineages, suggesting Busan as a likely entry point. This study demonstrates that integrating COX1, ND5, and CYTB improves the resolution of Ae. albopictus phylogeography in Korea and highlights the need for continued molecular surveillance to guide vector control strategies. Full article

Testosterone (T) produced by Leydig cells (LCs) is essential for male reproduction; yet, the regulatory mechanisms underlying steroidogenesis remain incompletely understood. Here, we investigated the role of cyclin-dependent kinase 5 regulatory subunit-associated protein 3 (CDK5RAP3) in Leydig cell development and steroidogenesis, based on its identification by immunoprecipitation-mass spectrometry (IP-MS) as a protein associated with steroidogenesis and cholesterol metabolism in mouse testicular tissue. Using human samples, we found that CDK5RAP3 expression was significantly reduced in Leydig cells from patients with spermatogenic failure (T < 10.4 nmol/L). Notably, CDK5RAP3 expression increased during mouse postnatal Leydig cell maturation and regeneration in an ethane dimethanesulfonate (EDS)-induced rat model. Functional analyses in primary LCs and MLTC-1 cells showed that hCG stimulation triggered CDK5RAP3 nuclear translocation without altering its overall expression, while CDK5RAP3 knockdown markedly impaired hCG-induced testosterone production and reduced the expression of the steroidogenic regulator steroidogenic acute regulatory (STAR) protein, as well as key steroidgenic enzymes, including cytochrome P450 family 11 subfamily A member 1 (CYP11A1), 17a-hydroxylase (CYP17A1), and 3β-hydroxysteroid dehydrogenase (HSD3B). Conversely, CDK5RAP3 overexpression enhanced testosterone production in the absence of hCG. In vivo, AAV2/9-mediated CDK5RAP3 silencing in adult mouse testes resulted in a significant reduction in serum testosterone levels compared with controls (3.60 ± 0.38 ng/mL vs. 1.83 ± 0.37 ng/mL). Mechanistically, CDK5RAP3 interacted with SMAD4 and CEBPB, and BMP pathway inhibition by Noggin rescued the testosterone deficit caused by CDK5RAP3 loss. Together, these findings identify CDK5RAP3 as an essential regulator of Leydig cell steroidogenesis and provide insight into its potential relevance to male infertility associated with low testosterone. Full article

Photobiomodulation (PBM) therapy has been effectively used to relieve pain and inflammation and promote tissue healing and regeneration in a broad range of ailments. Prior work has focused on intracellular mitochondrial cytochrome c oxidase, while extracellular latent TGF-β1 activation had been noted. This work investigated the role of PBM-generated redox signaling and integration in normal oral keratinocytes, using Western blots and pathway-specific small molecule inhibitors. We observed that PBM primarily generates ROS intracellularly within mitochondria, which then diffuse extracellularly to activate latent TGF-β1. This activation triggers ATF-4 expression through both canonical (Smad3) and non-canonical (p38, ERK) TGF-β signaling pathways. We observed a critical role for NFκB as an essential integrator, coordinating these responses as evidenced by the loss of ATF-4 expression following NFκB inhibition (BAY II) after both PBM and TGF-β1 treatments. Proteomic pathway analysis revealed that PBM downregulates inflammatory and apoptotic pathways while activating stress-adaptive responses in the NFκB pathway. A core set of PBM-induced redox, NFκB, and TGF-β signaling targets was identified. These findings suggest that optimal PBM treatment responses require a coordinated action of multiple signaling pathways that optimize cellular adaptation to stress and promote tissue repair rather than protracted inflammation and cell death. Full article

AflatoxinB1 (AFB1) is a hepatotoxic mycotoxin whose bioactivation by cytochrome P450 (CYP450) enzymes generates reactive metabolites that drive oxidative stress, inflammation, and apoptosis. Propolis is a bee-derived product with antioxidant and immunomodulatory properties. To investigate whether propolis supplementation attenuates AFB1-induced hepatic injury by modulating inflammatory mediators, Nrf2–HO-1 signaling, mitochondrial apoptosis, and CYP450 expression in rats, twenty-four male Sprague-Dawley rats were randomly allocated to four groups (n = 6): control, AFB1 (25 µg/kg/day), propolis (250 mg/kg/day), and AFB1 + propolis. Treatments were given by oral gavage for 28 days. Hepatic IL-1β, IL-6, TNF-α, Nrf2 and HO-1 levels were measured by ELISA. Histopathology was assessed on H&E-stained sections. Bax, Bcl-2, caspase-3, CYP1A2, CYP3A4, CYP2C19 and cytochrome P450 reductase expressions were evaluated immunohistochemically and quantified by ImageJ. Data were analyzed using one-way ANOVA with Tukey’s post hoc test. AFB1 significantly increased hepatic IL-1β and IL-6 and reduced Nrf2 levels, while propolis supplementation restored Nrf2, elevated HO-1 and significantly lowered IL-6 compared with AFB1 alone (p < 0.05). AFB1 induced marked hydropic degeneration, sinusoidal congestion, and mononuclear infiltration, alongside increased Bax and caspase-3 and decreased Bcl-2 expression; these changes were largely reversed in propolis-treated groups. AFB1 upregulated CYP1A2, CYP3A4 and cytochrome P450 reductase, whereas propolis co-treatment significantly suppressed their expression without affecting CYP2C19. Propolis supplementation attenuated AFB1-induced liver injury through coordinated anti-inflammatory, antioxidant, anti-apoptotic and metabolic regulatory effects, notably via restoration of Nrf2–HO-1 signaling and down-regulation of key CYP450 isoenzymes. Propolis may represent a promising natural dietary strategy against AFB1-associated hepatotoxicity, warranting further translational research. Full article