Search Results (982)

Background: Prostate cancer remains a leading cause of male cancer-related mortality, largely driven by the dysregulated activation of the androgen receptor (AR) signaling pathway. The emergence of resistance, particularly in castration-resistant prostate cancer (CRPC), necessitates the discovery of innovative therapeutic approaches. This systematic review aims to consolidate contemporary evidence regarding natural products as bioactive alternatives capable of targeting the AR signaling axis. Methods: Adhering to PRISMA guidelines, a systematic search was conducted across PubMed, Scopus, and ScienceDirect databases. The review identified and qualitatively analyzed 15 original research studies that investigated the efficacy and mechanisms of various natural compounds in modulating AR signaling. Results: The analysis reveals that natural products deactivate the AR signaling axis through diverse mechanisms. Neoisoliquiritin and α-terthienyl were found to suppress AR expression, activity, and nuclear translocation. Notably, α-mangostin facilitates the degradation of the AR-V7 splice variant, a key driver of treatment resistance. Manzamine A inhibits AR biosynthesis by targeting the transcription factor E2F8. Furthermore, alternative pathways are modulated through 5-α-reductase inhibition (Annona muricata compounds) and the activation of the non-classical membrane receptor ZIP9 by (-)-epicatechin to induce apoptosis. Conclusions: The emergence of resistance, particularly in castration-resistant prostate cancer (CRPC), necessitates the exploration of innovative therapeutic approaches. This systematic review consolidates contemporary evidence regarding natural products as potential bioactive alternatives for modulating the androgen receptor (AR) signaling axis. Rather than providing a definitive clinical roadmap, this work establishes a preclinical framework for identifying substances that may deactivate the receptor, break down its resistant forms, or prevent nuclear translocation. Full article

In recent years, insect-derived peptides have attracted attention for their potential biological activities, particularly antioxidant properties. This study assessed the antioxidant activity of two widely consumed edible insects, T. molitor and A. diaperinus larvae, using cell-free and cell-based approaches. Whole lyophilized larvae, digestion products from the oral, gastric, and intestinal phases, as well as the <3 kDa permeate fraction (D-P3) derived from the intestinal digestion phase, were evaluated using biochemical antioxidant assays. Overall, digested samples exhibited higher antioxidant capacity than their undigested counterparts. At the cellular level, treatment of LPS-stimulated, PMA-differentiated THP-1 macrophages with A. diaperinus D-P3 was associated with increased mRNA expression of genes related to antioxidant defense, including NFE2-like bZIP transcription factor 2 (NFE2L2, also known as Nrf2), glutathione-disulfide reductase (GSR), superoxide dismutase 1 (SOD1), and catalase (CAT), whereas T. molitor D-P3 preferentially modulated nuclear factor kappa B p50 subunit (NFKB1) and nuclear factor kappa B p65 subunit (RELA). Overall, these findings indicate that gastrointestinal digestion enhances the bioaccessibility of antioxidant components in both edible insect species while revealing species-specific transcriptional responses under in vitro inflammatory conditions. This multilevel assessment provides mechanistic insight into the antioxidant-related biological activity of digestion-derived insect peptides and supports their further investigation as functional ingredients in food and feed systems. Full article

Salt stress is a major environmental constraint affecting plant growth and productivity. Crop wild relatives provide valuable genetic resources for stress tolerance, yet transcriptomic information for forest-derived wild species remains limited. In this study, we analyzed transcriptional responses of V. hirsuta, a crop wild relative (CWR) of legumes, after seven days of salt stress using de novo transcriptome sequencing. Seedlings were exposed to salt stress, and differentially expressed genes (DEGs) were identified between control (Vh_S0) and salt-treated (Vh_S7) plants using an FDR-adjusted threshold (q < 0.05). Gene Ontology and KEGG enrichment analyses revealed that salt-responsive DEGs were mainly involved in regulatory signaling, metabolic adjustment, redox-related processes, and macromolecular organization. Up- and down-regulated DEGs showed distinct yet overlapping enrichment patterns, indicating complex transcriptional reprogramming under salt stress. Transcription factor analysis identified bHLH, MYB, bZIP, NAC, and WRKY families as major regulators, with many families containing both up- and down-regulated members. Notably, genes associated with Na⁺/K⁺ homeostasis were consistently up-regulated and validated by qRT-PCR. These results suggest that continuous seven days salt stress adaptation in V. hirsuta involves coordinated regulation of signaling pathways, transcriptional networks, and transporter-mediated ion homeostasis, providing a valuable transcriptomic resource for crop wild relatives. Full article

Homeodomain-Leucine Zipper (HD-Zip) constitutes a distinct class of plant-specific transcription factors (TFs) that serves an essential function in mediating plant responses to environmental cues, with the HD-Zip II subfamily recognized as a major regulator of light-intensity adaptation and other environmental responses. However, the involvement of HD-Zip genes in regulating the light response of Juglans mandshurica Maxim. is largely unexplored. In this study, a genome-wide identification, classification, and expression analysis of the HD-Zip gene family in J. mandshurica was conducted. Furthermore, transcriptomic profiling under varying light-intensity conditions was performed to investigate the transcriptional regulation and potential functional networks of differentially expressed HD-Zip genes. The results showed that a total of 57 HD-Zip family genes were identified in J. mandshurica (named as JmHD-Zip) and classified into four subfamilies (HD-Zip I, HD-Zip II, HD-Zip III and HD-Zip IV). Gene structure and phylogenetic analyses indicated that members within the same subfamily exhibited analogous structural characteristics and shared strong homology with closely related species such as Juglans sigillata Dode and Populus trichocarpa. Torr. & A.Gray ex Hook. Promoter cis-acting element analysis revealed that the promoter regions of JmHD-Zip genes were enriched with multiple regulatory motifs associated with light responsiveness, hormone signaling, and stress regulation. Protein–protein interaction network analysis identified JmHDZ57 and JmHDZ43 as the central genes of the differentially expressed HD-Zip genes. Through validation of gene functions, JmHDZ43 promotes plant growth by coordinating shade-responsive morphogenesis via integration of light and hormone signaling pathways. This study offers a theoretical foundation and candidate gene resources for breeding initiatives and molecular investigations of light adaptation in J. mandshurica and potentially other woody species. Full article

Background: International guidelines recommend tight blood pressure (BP) control in patients with thoracic aortic aneurysm (TAA). Hypertension in TAA patients has been associated with an increased rate of aneurysm growth and also with aortic dissection or aortic rupture. We aimed to study BP control in TAA patients referred by a primary or cardiology provider to a tertiary aortic management program. Methods: This retrospective study analyzed 3525 consecutive patients with confirmed TAA diagnosis referred by a primary-care or cardiology provider for management at the Lankenau Aortic Surgical Program between January 2021 and December 2024. Blood pressure was registered using an appropriately sized cuff and a calibrated automated sphygmomanometer. Clinical and demographic data were compared between patients with different stages of hypertension, based on the 2023 ESH guidelines. Results: The overall rate of above-target BP in TAA patients was 54.2% (1911/3525). From the hypertension group, Stage 1 (BP > 140/90) accounted for 53.4% (1020/1911) of patients, with Stage 2 (BP > 160/100) accounting for 12.6% (241/1911) and Stage 3 (BP > 180/110) for 1.8% (35/1911). Among associations of hypertension with demographic data by zip code, no significant differences were observed between groups with respect to race, median household income, or house value. There was a tendency of lower BP in patients from residential areas with higher rates of college graduates compared to those without college education (OR: 0.995; p = 0.059). Conclusions: Hypertension remains both highly prevalent and inadequately controlled in patients with TAA, even within specialized care environments. These findings emphasize the need for a more comprehensive approach to risk factor management to improve outcomes in this high-risk population. Full article

Soil salinization poses a major constraint to global agriculture. Apocynum venetum, a salt-tolerant halophyte, provides an effective model for investigating salt-adaptive strategies; however, the temporal dynamics of its tolerance-associated genes and metabolites remain unclear. In this study, integrated transcriptomics, metabolomics (UHPLC-MS), physiological assays, and weighted gene co-expression network analysis (WGCNA) were conducted to characterize early (7-day) and late (18-day) responses to 200 mM NaCl stress. NaCl stress significantly reduced chlorophyll content while increasing Na⁺ accumulation, MDA levels, antioxidant enzyme activities (SOD and CAT), and total flavonoid content. Early responses (NaCl7) were marked by accumulation of ferulic acid, rhamnetin, and 3,4-dihydrocoumarin, with activation of plant hormone (ABA, auxin, zeatin) and MAPK signaling pathways. Late responses (NaCl18) exhibited increased accumulation of scopoletin, formononetin, and caffeyl-alcohol, with enrichment of phenylpropanoid biosynthesis, glutathione metabolism, and photosynthesis-related pathways. WGCNA identified early-response hub genes, including AOC, MAPKKK17/18, CYP98A, and CCoAOMT, coordinating stress signaling and antioxidant metabolism. Late stress responses involved genes like CPK, GST, CYCD3, and ARF, modulating calcium signaling and ROS detoxification. Genes shared across phases included CYP90C1, HD-ZIP, HSP20, and PP2C, regulating protein stabilization and stress signaling. These findings reveal a two-phase salt tolerance strategy in A. venetum, integrating early signaling and late metabolic adaptation. Full article

Starch biosynthesis is a fundamental process influencing yield and fruit quality in banana, with ADP-glucose pyrophosphorylase (AGPase) serving as the rate-limiting enzyme catalyzing sucrose conversion into starch. However, the mechanisms underlying functional differentiation of AGPase family genes following polyploidization remain largely unexplored. In this study, eight AGPase genes, including large (MaAPL) and small subunit (MaAPS) members, were identified from the banana (Musa acuminata) genome, all harboring the conserved ADP-glucose pyrophosphorylase domain. Phylogenetic analysis traced their evolutionary origin to the ancient moss Physcomitrella patens, with polyploidization identified as the primary driver of gene family expansion. These genes exhibit conserved codon usage bias and have undergone strong purifying selection. Among them, MaAPS1 displayed distinct functional differentiation, increased intron number, enriched promoter cis-elements, and significantly elevated expression—features likely contributing to its adaptation for enhanced starch accumulation in fruit. Furthermore, the MaAPS1 protein was predominately localized in the chloroplast. Functional validation supported its regulatory involvement: transient silencing in banana fruit reduced starch content, while transient overexpression in banana fruit increased starch levels. Co-expression and molecular docking analyses revealed that transcription factors ERF1, C3H1, bZIP1, and bZIP3 may interact with the MaAPS1 promoter, indicating a multifactorial regulatory network. Overall, this study provides insights into polyploidy-driven functional innovation and transcriptional regulation of MaAPS1 in banana starch biosynthesis, providing valuable molecular targets for genetic improvement of yield and fruit quality. Full article

Background: Lung cancer remains the leading cause of cancer-related morbidity and mortality. Despite advances in surgical management, economically disadvantaged patients experience inequalities in the receipt of treatments. We evaluated the association between socioeconomic status (SES) and type of surgery: robotic-assisted thoracic surgery (RATS), video-assisted thoracic surgery (VATS), and open thoracotomy. Methods: Data came from the National Cancer Database (2015–2022) and included Stage 0–IIIa NSCLC patients. SES was measured by quartiles of median household income in the patient’s zip code. Adjusted multinomial logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: Among 84,931 patients with a mean age of 67.8 years, 38.4% underwent open thoracotomy, 33.3% underwent VATS, and 28.2% underwent RATS. Patients residing in the low-income areas (<$46,277) were significantly less likely to undergo RATS (aOR: 0.79, 95% CI: 0.77–0.86) or VATS (aOR: 0.62, 95% CI: 0.59–0.66) compared to patients living in high-income areas (≥$74,063). Community hospitals were less likely to provide RATS (aOR: 0.32, 95% CI: 0.29–0.35) or VATS (aOR: 0.58, 95% CI: 0.54–0.63) than academic centers. Conclusion: Socioeconomic disadvantage is associated with lower use of minimally invasive surgical approaches for NSCLC. Efforts to expand access to advanced surgical care may be necessary to reduce treatment disparities and improve outcomes. Full article

Oudemansiella raphanipes is a prized edible mushroom renowned for its “three-high, one-low” nutritional profile (high protein, fiber, vitamins; low fat). However, the stage-specific molecular dynamics governing its development and their potential link to its superior nutrition remain unknown, hindering targeted genetic improvement. This study aimed to decipher the first comprehensive transcriptomic atlas across its five key developmental stages and to explore potential molecular signatures linked to its distinctive nutrition. We first confirmed the superior nutritional profile of O. raphanipes via comparative analysis with nine commercial mushrooms. RNA sequencing (RNA-seq) was performed on samples from five defined developmental stages (spores, mycelia, primordia, closed-cap and open-cap fruiting bodies), followed by de novo transcriptome assembly, functional annotation, and differential expression analysis. Results revealed extensive transcriptional reprogramming, with the most dramatic changes occurring at the spore-to-mycelium transition (19,827 differentially expressed genes). Stage-specific pathway enrichment highlighted regulators of germination (e.g., ribosome, transmembrane transport), primordium formation (e.g., glycerophospholipid metabolism, GTPase signaling), fruiting body development (e.g., starch/sucrose metabolism, terpenoid synthesis), and maturation (e.g., glycolysis, fatty acid biosynthesis, transcription factors MADS-box/bZIP). We identified 588 stage-exclusive genes in spores and 515 constitutively upregulated genes linked to energy metabolism and proteostasis. Crucially, integrating nutritional phenotypes with stage-resolved transcriptomics revealed that sustained transcriptional programs in mature fruiting bodies are associated with its nutritional excellence; e.g., upregulation of ribosomal/amino acid metabolic pathways aligns with high protein content, while active fatty acid degradation correlates with low fat levels. Our study provides the first multi-stage transcriptomic blueprint for O. raphanipes development, revealing stage-specific regulators and proposing molecular associations for its nutritional traits. This resource offers a foundational basis and candidate genetic targets for future breeding strategies aimed at enhancing agronomic and nutritional traits in this prized fungus. Full article

The World Health Organization (WHO) recognizes the impact of social determinants of health (SDHs) on human health and wellbeing factors. Limited research has explored how SDHs, such as the social, economic, and environmental conditions in which individuals are born, live, work, and grow older, shape exercise behaviors and chronic health conditions such as cancer in dogs. This study links SDHs identified through owner-provided continental United States zip codes with levels of physical activity. We hypothesized that owners with higher incomes, education, and access to healthcare services positively influence their dog’s health outcomes, specifically owner-reported physical activity. Our study utilized all owner-provided data, collected between 2012 and 2022, from the first seven years of owner surveys for the 3044 Golden Retrievers enrolled in the Morris Animal Foundation Lifetime Study. Sixteen GPBoost Poisson models were built to assess the impact of twenty-three social determinants in Golden Retrievers with and without a diagnosis of cancer. SHAP values were calculated for each dependent variable. Consistently, economic factors, education, ethnicity, and health care access were identified as important variables. Furthermore, our findings suggest that complex interactions between ethnicities and other SDHs should be explored in future studies. Full article

Panax ginseng is a traditional Chinese herbal medicine. Ginsenosides, the main bioactive components responsible for the medicinal value of ginseng, are regulated by transcription factors. Among these regulatory factors, basic leucine zipper (bZIP) transcription factors play crucial roles in plant development and secondary metabolism. To verify that members of the bZIP gene family are involved in regulating ginsenoside biosynthesis and explore their potential mechanisms of action, a correlation analysis was first conducted in this study between the expression levels of PgbZIP genes and ginsenoside content. Additionally, the effects of single-nucleotide polymorphisms (SNPs) and Insertions/Deletions (InDels) on ginsenoside content were analyzed in this study. Through these analyses, PgbZIP48-3, a gene highly associated with ginsenoside biosynthesis, was identified. Subsequently, we systematically analyzed PgbZIP48-3, including its gene structure, protein properties, and phylogenetic relationships. To further verify the function of PgbZIP48-3, an overexpression vector was constructed. Positive ginseng hairy roots were obtained via Agrobacterium-mediated transformation of explants, and the ginsenoside content in these positive hairy roots was determined. The results showed that in the PgbZIP48-3 overexpression positive lines, the contents of ginsenosides Re, Rb2, Rb3, Rc, and Rd were significantly higher than those in the control group, whereas the contents of ginsenosides Rg1, Rf, and Rb1 were lower than those in the control group. Finally, by investigating the SNP/InDel data of PgbZIP48-3 in 346 accessions of a natural P. ginseng population and constructing a predicted interaction map between PgbZIP48-3 and key enzyme genes involved in ginsenoside synthesis, this study preliminarily revealed the potential molecular mechanism by which PgbZIP48-3 regulates ginsenoside biosynthesis from two dimensions: gene mutation and gene expression correlation. Meanwhile, this study provides genetic resources for the breeding of ginseng cultivars with high ginsenoside content. Full article

Sweet potato (Ipomoea batatas L.) is a vital dual-use crop, with some varieties being used as leafy vegetables that are rich in anthocyanins. Nevertheless, salinity stress is a challenge to their production. Homeodomain-leucine zipper (HD-ZIP) gene family members encode proteins participating in the regulation of plant defense and secondary metabolism, while the functional study of HD-ZIP genes in sweet potato is still limited. Herein, a total of 66 IbHD-ZIP genes were identified, which were expanded by segmental duplication. Based upon promoter cis-element information and precedent evidence, IbHD-ZIP61, belonging to subfamily I, was selected for functional studies. Functional characterization was conducted via ectopic expression in transgenic Nicotiana benthamiana. The overexpression of IbHD-ZIP61 significantly increased anthocyanin production under normal growth conditions by promoting anthocyanin biosynthetic genes AN1a, AN2, and DFR. Furthermore, transgenic plants displayed better salinity tolerance, which exhibited reduced growth inhibition, increased water status, decreased oxidative injury, as well as elevated activity of antioxidant enzymes. This study validated the coordinated regulation of anthocyanin pathway genes as well as pivotal pathways (NHX2, NCED1, P5CS) during salinity adaptation. These findings demonstrate that IbHD-ZIP61 is a transcription factor linking anthocyanin synthesis and salinity adaptation, thus making it a potential candidate for improving breeding in nutritionally superior and salinity-adapted edible crops such as sweet potato. Full article

Zero-inflated count data are characterized by an excessive frequency of zeros that cannot be adequately analyzed by a single distribution, such as Poisson or negative binomial. This problem is pervasive in many practical applications, including document–keyword matrix derived from text corpora, where most keyword frequencies are zero. Conventional statistical approaches, such as the zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB) models, explicitly separate a structural zero component from a count component, but they typically assume independent observations and can be unstable when covariates are high-dimensional and sparse. To address these limitations, this paper proposes a graph-based zero-inflated learning framework that combines simple graph convolution (SGC) with zero-inflated count regression heads such as ZIP and ZINB. We first construct an observation graph by connecting similar samples, and then apply SGC to propagate and smooth features over the graph, producing convolutional representations that incorporate neighborhood information while remaining computationally lightweight. The resulting representations are used as covariates in ZIP and ZINB heads, which preserve probabilistic interpretability through maximum likelihood learning. Our experiments on simulated zero-inflated datasets with controlled zero ratios demonstrate that the proposed ZIP+SGC and ZINB+SGC consistently reduce prediction errors compared with their non-graph baselines, as measured by mean absolute error and root mean squared error. Overall, the proposed approach provides an efficient and interpretable way to integrate graph neural computation with zero-inflated modeling for sparse count prediction problems. Full article

Background: AMP-activated protein kinase (AMPK) acts as a key energy sensor that negatively regulates skeletal muscle mass. Zinc is an essential trace element that is required for myogenic differentiation and protein synthesis, while zinc deficiency has been associated with muscle atrophy in vivo. However, how zinc status modulates AMPK activation itself or alters downstream responses to AMPK signaling in muscle cells remains unclear. Methods: C2C12 myotubes were cultured under zinc-depleted (ZnD), zinc-sufficient (20 μM; Zn20), or zinc-supplemented (40 μM; Zn40) conditions. AMPK was activated by AICAR, and zinc status–dependent responses were evaluated using molecular and morphological analyses. Results: AICAR increased intracellular zinc levels in Zn20 and Zn40 but not in ZnD. Zinc transporter expression exhibited gene-specific regulation: Zip3 was upregulated across all zinc conditions, Zip14 was significantly induced in ZnD and Zn40, and Zip10 was selectively upregulated in Zn40. AICAR induced myotube atrophy in all groups; however, the reduction in myotube diameter was significantly greater under zinc-depleted conditions. Zinc depletion was associated with transcriptional upregulation of FoxO1, FoxO3, Atrogin-1, and MuRF1 in response to AICAR, while AMPK activation and suppression of S6K1 phosphorylation occurred to a similar extent regardless of zinc status. Conclusions: These findings indicate that zinc availability does not alter AMPK activation itself but modulates downstream atrophic responses to AMPK signaling. Under conditions of AMPK activation, adequate zinc availability is accompanied by increased intracellular zinc levels and stress-responsive ZIP regulation, which may limit excessive atrophic gene induction, whereas zinc depletion increases susceptibility to AMPK-induced atrophic responses in skeletal muscle cells. Full article

Drought stress severely limits maize growth, and enhancing drought resistance remains a central objective of crop improvement. Plant-specific NAC (NAM/ATAF/CUC) transcription factors are critical regulators of abiotic stress responses. Previously, we identified ZmNAC20—a gene rapidly induced by both drought and abscisic acid (ABA)—as a positive regulator of stomatal closure and drought survival when over-expressed; however, its direct target genes and downstream regulatory network remained elusive. Here, we used DAP-seq to identify 3537 ZmNAC20 binding peaks genome-wide, revealing four enriched cis-motifs and 1439 target genes. GO and KEGG analyses showed pronounced enrichment in intracellular signal transduction. The intersection of RNA-seq of drought-stressed ZmNAC20-over-expressing and wild-type B104 seedlings with DAP-seq outputs defined 80 potential direct targets (48 up-, 32 down-regulated). Among the activated genes, ZmNAC20 binds and up-regulates genes of the ROS-producing enzyme ZmRBOH8, BURP domain-containing protein ZmBURP4, gibberellin (GA) catabolic enzyme ZmGA2OX6, and HD-Zip transcription factor ZmHB56. These results unveil a multi-layered drought-responsive network through which ZmNAC20 integrates hormone and ROS signaling, providing a molecular blueprint for breeding drought-resilient maize. Full article