Search Results (3,144)

Background: Chronic kidney disease (CKD) associated vascular calcification (VC) is a leading cause of cardiovascular mortality, partially driven by osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Chaperone-mediated autophagy (CMA) is a selective lysosomal degradation cellular process. However, the precise role and mechanism of CMA in CKD-associated vascular calcification remain unknown. Methods: We studied calcified arteries from CKD patients and rats fed on a high-phosphate diet using histological and ultrastructural methods. VSMCs' calcification was induced by a calcification medium containing high phosphate and calcium. CMA activity was measured by a KFERQ reporter and lysosomal staining. The expression of LAMP2a and HSP90AA1 was knocked down by siRNA, overexpressed by plasmid, and activated by QX77.1. Bioinformatic analysis, protein interaction studies, immunofluorescence and co-immunoprecipitation were performed to investigate the potential mechanism of CMA in VC. Results: The expression of LAMP2a was increased in human calcified radial artery tissues (n = 3, p < 0.05) and rats' calcified aortic tissues (n = 3, p < 0.01), accompanied by lysosomal abnormalities. The activity of CMA was increased during the osteogenic transdifferentiation of VSMCs, as indicated by increased expression of RUNX2 and reduced expression of SM22α (p < 0.05). LAMP2a knockdown attenuated VSMCs’ calcification (p < 0.05), whereas pharmacological activation of CMA aggravated calcification in VSMCs (p < 0.01). Bioinformatic screening identified HSP90AA1 as a candidate involved in CMA in vascular calcification. Elevated HSP90AA1 expression was observed in human calcified radial artery tissues (n = 3, p < 0.01) and rat calcified aortic tissues (n = 3, p < 0.01), which promoted osteogenic transdifferentiation of VSMCs (p < 0.05). HSP90AA1 interacted with LAMP2a and positively regulated its expression (p < 0.01). Conclusions: These findings support an association between CMA activation and CKD vascular calcification. It suggests that HSP90AA1 facilitates vascular calcification in chronic kidney disease involving chaperone-mediated autophagy. Full article

The expansion of fifth-generation (5G) wireless networks has increased environmental exposure to mid-band and millimeter-wave radiofrequency electromagnetic fields (RF-EMF), but their molecular effects on male reproductive tissues remain insufficiently understood. This study evaluated whether repeated exposure to 3.5 GHz and 24 GHz RF-EMF alters testicular stress-associated molecular responses by integrating electromagnetic dosimetry with an in vivo rat model. Whole-body specific absorption rate (SAR) and 10 g peak SAR were estimated using a rat voxel model and scaled to the 20 cm antenna-to-cage geometry used during exposure. Thirty-six adult male Sprague Dawley rats were allocated to sham, 3.5 GHz, or 24 GHz groups and exposed for 1 h/day or 7 h/day over 60 days. Testes were examined histologically and assessed for HSP27, HSP70, and HSP90 protein expression. SAR values were low overall, although absorption was higher at 3.5 GHz than at 24 GHz. Histological evaluation showed preserved seminiferous tubule architecture without consistent structural injury. In contrast, molecular analysis demonstrated frequency- and duration-dependent modulation of heat shock proteins, including early HSP70 downregulation at both frequencies, followed by HSP90 upregulation at 3.5 GHz and HSP27 upregulation at 24 GHz. These findings indicate that low-level 5G-relevant RF-EMF exposure can modify molecular stress responses in testicular tissue even in the absence of overt histological damage. Full article

Larix olgensis, a keystone timber species in Northeast China, is increasingly threatened by Neofusicoccum laricinum-induced shoot blight, a devastating disease that compromises forest health and necessitates sustainable management strategies. Here, we demonstrate that the endophytic bacterium Bacillus amyloliquefaciens JL54 elicits multifaceted defense responses in L. olgensis, enhancing resistance to pathogen infection. Greenhouse assays revealed that JL54 pretreatment reduced disease incidence by 12.5% and achieved 43.75% control efficacy while maintaining host vigor. Histochemical analyses identified JL54-induced rapid hydrogen peroxide (H₂O₂) accumulation, extensive lignin deposition, and localized programmed cell death (PCD), indicative of a primed immune response. Transcriptomic analyses uncovered distinct temporal defense patterns: early-stage responses (0 h post-inoculation) were characterized by upregulation of cutin, suberin, and wax biosynthesis pathways, reinforcing physical barriers, whereas late-stage responses (12 h post-inoculation) were dominated by ribosome- and proteostasis-related pathways (e.g., heat shock proteins [HSPs], glutathione S-transferases [GSTs]) to mitigate cellular damage. Biochemical assays corroborated these findings, with JL54 colonization reducing membrane lipid peroxidation (27.2% decrease in malondialdehyde content) and significantly elevating the activity of key defense enzymes, including peroxidase (POD), phenylalanine ammonia-lyase (PAL), and GST. Phytohormone profiling implicated jasmonic acid (JA) as the central mediator of induced systemic resistance (ISR), with JL54-potentiated JA signaling preceding pathogen containment. Collectively, these results demonstrate that JL54 contributes to a coordinated defense strategy in L. olgensis, integrating structural reinforcement (cuticle/lignin), oxidative stress management, and JA-mediated immune priming. These insights advance the understanding of endophyte-conferred resistance in conifers and highlight JL54’s potential as a biocontrol agent for sustainable forestry. Full article

Heat shock proteins 70 (HSP 70) are molecular chaperonins ubiquitously expressed in both prokaryotes and eukaryotes and are involved in the modulation and exacerbation of the immune response. The present study aimed to assess the immunohistochemical expression of HSP70 and apoptosis markers, such as TUNEL and Caspase-3, in 17 cases of cutaneous lupus erythematosus (CLE) in dogs to determine whether HSP70 expression correlates with cell apoptosis and to highlight possible involvement of HSP70 in the pathogenesis of CLE. The results revealed positive HSP70 expression in epidermal and inflammatory cells across all cases, with a significant correlation between HSP70 expression score and TUNEL-positive cells but not with Caspase-3-positive cells. This correlation could indicate a possible role for HSP70 in cell death via a caspase-independent apoptotic mechanism or other programmed cell death mechanisms, such as pyroptosis or necroptosis. The precise mechanisms by which HSP70 acts in this specific pathological context remain incompletely understood, but the results of this study provide important information for future investigations into autoimmune skin disease in dogs. Full article

An algorithm called Dicke state quantum search for the hitting set problem (DSQS-HSP), generates quantum circuits to solve the k-hitting set problem (k-HSP), by initializing the working qubits in an n-qubit Dicke state $\left|D_k^n\right.⟩$ of exactly k qubits in $\left|1\right.⟩$. The quantum circuit reduces the search space size from $2^n$ to D = $\left(\begin{array}{c}n\\ k\end{array}\right)$, the number of symmetric superposition states in $\left|D_k^n\right.⟩$. A quantum-flag oracle checks the hitting condition, and a mirror-readout mechanism projects valid solutions to the output register. The circuit yields two outcome types: the all-zero string with probability (D−M)/D and solution strings, each with probability 1/D, where M is the number of solutions. The resource growth of qubits, gates, circuit depth, and circuit execution repetitions is O($n^k$), which remains polynomial in the best case for min(k, n − k) ≪ n/2. Experimental results using IBM Qiskit Aer Simulator confirm that the DSQS-HSP can produce quantum circuits to successfully solve the k-HSP. Full article

Intensive aquaculture induces severe environmental stress and disease susceptibility in Pacific white shrimp (Litopenaeus vannamei). Cannabidiol (CBD) offers significant potential as a bioactive stress-mitigating additive. This study evaluated the effects of dietary CBD supplementation (0, 10, 20, 40, and 80 mg/kg) on the growth, intestinal microecology, and stress tolerance of juvenile L. vannamei over an 8-week feeding trial, followed by a combined chronic ammonia and acute hypoxia challenge. Moderate CBD supplementation (10–40 mg/kg) significantly promoted growth, minimized feed conversion ratios, and enriched muscle eicosapentaenoic (EPA) and docosahexaenoic acids (DHA). Furthermore, CBD restructured the intestinal microbiota by suppressing opportunistic pathogens and enriching beneficial taxa. Under combined stress, moderate CBD prolonged the median lethal time (LT₅₀) by up-regulating hypoxia-inducible factor 1-alpha (hif-1α) and heat shock protein 70 (hsp70) transcription and boosting systemic antioxidant capacity to neutralize lipid peroxidation. Conversely, the highest dose (80 mg/kg) induced metabolic exhaustion and hepatopancreatic toxicity, evidenced by drastically elevated serum transaminases and diminished stress tolerance. Conclusively, dietary CBD exerts a classic biphasic effect in L. vannamei. Inclusion at 10–40 mg/kg safely promotes the best comprehensive effects on growth, immune homeostasis, and environmental resilience within the concentration range tested in this study, whereas excessive administration provokes severe metabolic burden, highlighting the critical need for strict dosage regulation. Full article

Objective: The purpose of this study was to determine the biological association between host-derived HSP47 and fungal-derived HSP90 in the context of vulvovaginal candidiasis (VVC) and to examine their relationships with clinical, inflammatory, and metabolic phenotypes in infected and healthy women. Methods: This study followed a six-month case–control design (February–July 2025) and was conducted at the University of Tabuk Hospital in Tabuk, Saudi Arabia. A total of 84 women aged 18–45 years were recruited, of which 42 were VVC-infected, and 42 were healthy controls. ELISA kits were used to test vaginal swabs for HSP47 and HSP90. Clinical, hematological, cytokine, and metabolic markers were also evaluated. Mann–Whitney U, Spearman correlation, and multiple linear regression tests were performed to analyze the data. Results: The levels of HSP47 and HSP90 were significantly higher among infected patients (2.29 ng/mL and 3341 ng/mL, respectively) when compared with controls (0.58 ng/mL and 1025.7 ng/mL; p < 0.001). Women who were infected were older (p = 0.02), but there were no significant differences in terms of BMI (p = 0.29). The levels of vitamin D and adiponectin were significantly decreased (p < 0.001), while pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ, TGF-β, and IL-8) and WBC counts were higher compared to the control group. The hematology results were characterized by inflammation-related anemia and disturbed protein metabolism. The ROC analysis demonstrated good diagnostic performance, with an AUC of 1.0 in the case of HSP47 and 0.905 in the case of HSP90. In the case of the infected patients, the regression models were found to be weak (HSP90 R² = 0.154; HSP47 R² = 0.273), although HSP47 retained significant connections with IL-8 (p = 0.005) and IFN-γ (p = 0.028). Conclusions: High levels of HSP47 and HSP90 are observed in VVC, reflecting an epithelial stress response and fungal persistence. These HSPs have high diagnostic accuracy, which justifies their potential as biomarkers for the timely detection of VVC; they also have further implications as early biomarkers for prognostic and treatment monitoring support, despite the poor predictive models. This study has some limitations that must be addressed; in particular, the regression analyses failed to provide statistically significant predictive models, likely due to the limited sample size. In addition, the specificity of HSP90 and HSP47 for VVC in comparison with other vaginal infections was not evaluated. Full article

Background/Objectives: The significant negative correlation between protein and oil content in soybean seeds is a long-standing bottleneck for conventional breeding. Its root cause lies in insufficient understanding of related molecular regulatory processes. Methods: We selected the CSSL_R19, a chromosome segment substitution line, to thoroughly investigate the intrinsic effects of the substituted segment on the high seed storage protein (SSP) and low fatty acid (FA) phenotype. Transcriptomic, proteomic, and metabolomic analyses were performed on the recurrent parent and R19. Results: A total of 1821 differentially expressed genes (DEGs), 12 differentially expressed proteins (DEPs), and 10 differentially accumulated metabolites (DEMs) were detected. Subsequently, an integrative examination of the data demonstrated that 28 DEGs, 5 DEPs, and 4 DEMs participated in biological processes such as carbohydrate metabolism, lipid degradation, as well as protein synthesis and transport. Mechanistically, down-regulation of PGM reduces the carbon source supply for FA synthesis; up-regulation of LOX, LACS, ACX, and KAT promotes FA degradation. SRP, SAR1, and HSP70 are involved in the synthesis and transport of SSP. Crucially, qRT-PCR validation performed on all 28 core DEGs showed that their expression trends were highly consistent with the transcriptome data, confirming the reliability of the findings. Conclusions: In conclusion, we propose a potential regulatory network that enhances SSP accumulation and reduces FA content. Altogether, these findings advance our understanding of storage compound accumulation in soybeans and guide future breeding strategies. Full article

Alpha-mangostin (AM), a xanthone from Garcinia mangostana, has shown promising nephroprotective properties, but its mechanisms in acute kidney injury (AKI) remain incompletely defined. In this study, we applied an integrative network pharmacology pipeline combined with molecular docking to clarify AM’s multi-target mechanisms in AKI. We identified 128 predicted AM targets and intersected them with AKI-related genes, yielding 122 shared targets. Protein–protein interaction analysis identified ten hub genes—TNF, AKT1, IL6, SRC, CTNNB1, HSP90AA1, NFKB1, HIF1A, PPARG, and PTGS2—implicating inflammatory, hypoxia, and cell-survival pathways. KEGG enrichment highlighted HIF-1 signaling, PI3K–Akt signaling, chemokine signaling, AGE–RAGE signaling, and pathways related to cellular senescence and oxidative stress, while GO terms emphasized responses to chemical/oxygen-containing compounds, kinase activity, signal transduction, and apoptosis. Molecular docking against the ten hub proteins showed favorable binding energies across multiple targets. The strongest predicted affinities were observed for PTGS2 (−11.13 kcal/mol), TNF (−9.74 kcal/mol), and AKT1 (−9.48 kcal/mol). Docking positioned AM within the COX-2 catalytic pocket, engaging key catalytic and hydrophobic residues similar to known inhibitors. MD simulation interaction analysis confirmed that AM maintained stable contacts with key human PTGS2 residues, characterized by dominant hydrogen bonds and water-bridge interactions with SER353, TYR355, ARG513, and SER530, along with consistent hydrophobic contacts, and persistent interactions sustained throughout the 200 ns trajectory. Collectively, these results suggest that AM modulates interconnected inflammatory, hypoxic, and survival pathways relevant to AKI, acting as a multi-target ligand with notable interaction involving COX-2, TNF, and AKT1. Further experimental validation and formulation strategies to improve bioavailability are recommended for the advancement of AM toward therapeutic evaluation in AKI. Full article

For a protein to perform its biological functions, it must adopt a specific three-dimensional conformation. In addition, many proteins require the assistance of other protein complexes known as chaperonins to fold —i.e., to acquire such a specific conformation—, although the exact mechanisms whereby the chaperonins act and assist the folding process have not been completely determined. In this work, we characterize the physical environment at the interior of the chaperonin HSP60/HSP10 via Molecular Dynamics Simulations. We found that, inside the cavity of the chaperonin (within a region covering much of the cavity’s volume), the long-range electrostatic potential presents a structured pattern that, except for small fluctuations, does not change in time. The electrostatic potential generates an electric field that can be modeled, as a first approximation, as constant and unidirectional $(\mathit{E}/\left(\mathrm{V}·{\AA }^{-1}\right)\approx -0.0054\widehat{𝚤}+0.010\widehat{\mathit{𝚥}}-0.162\widehat{k}$, here the chaperonin’s main axis is aligned along $\widehat{k})$, which can produce large deformations in the structure of a heated protein (Rhodanese); the long-range approximated $\mathit{E}\left(\mathit{r}\right)$ can in fact unfold the Rhodanese, when applied as an external field. Finally, we discuss the possible implications of such an electric field for the protein folding problem, within the context of proteins whose folding is assisted by chaperones. The existence and effects of the electric field are consistent with several theories and experimental observations related to the protein folding problem, in particular with the foldon view. Full article

Tripterygium glycoside tablets (TGT), a representative formulation derived from Tripterygium wilfordii Hook F, have limited clinical application due to adverse reproductive toxicity. In previous studies investigating the effects of TGT on chronic kidney disease (CKD), it was found that both TGT and its alkaloid-enriched fraction (AEF) induced testicular atrophy, suggesting that AEF may be the material basis for the reproductive toxicity of TGT. Therefore, the reproductive toxicity of AEF was investigated in depth. This study established a CKD rat model to investigate the toxic effects of TGT, AEF, and the non-alkaloid-enriched fraction (NAEF) on the reproductive system during CKD treatment. Network toxicology and metabolomics were combined to elucidate the underlying mechanisms of AEF-induced reproductive toxicity. The results showed that both TGT and AEF significantly reduced testicular index and sperm concentration, causing seminiferous tubule atrophy and disrupting the levels of testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Furthermore, TGT, AEF, and NAEF all significantly inhibited the proliferation of GC-1 cells. Network toxicology indicated that AEF modulates targets such as SRC, AKT, and HSP90AA1, thereby influencing pathways including the PI3K-AKT signaling pathway and pathways in cancer. Metabolomics obtained 89 differential metabolites of AEF, which were enriched in glycerophospholipid, linoleic acid, and arachidonic acid metabolism, a finding consistent with the constructed “metabolite–enzyme–reaction–gene” network. In summary, AEF exerts reproductive toxicity primarily by disrupting hypothalamic–pituitary–testicular axis homeostasis and perturbing glycerophospholipid, linoleic acid, and arachidonic acid metabolism. Full article

Background and Objectives: Deltamethrin (DLM), a widely used pyrethroid insecticide, has been linked to cardiotoxic effects in non-target organisms. Hesperidin (HSP), a dietary bioflavonoid with antioxidant and cardioprotective properties, may counteract these effects. This study investigated the protective role of HSP against DLM-induced cardiotoxicity in male Wistar Albino rats. Materials and Methods: Thirty-two rats were divided into four groups: Control, DLM, DLM + HSP 100, and DLM + HSP 300. At the end of the experiment, serum ischemia-modified albumin (IMA), glucose, cholesterol, triglyceride, and HDL levels were analyzed. Cardiac and aortic tissues were assessed histopathologically. Masson’s trichrome staining evaluated cardiac fibrosis, Verhoeff–Van Gieson staining examined elastin and tunica media thickness, and caspase-3 expression in the aorta was determined immunohistochemically. Results: DLM administration caused cardiac and aortic damage by increasing IMA, glucose, caspase 3 activities, and tunica media thickness. HSP treatment, particularly at 300 mg/kg, reduced IMA (0.28 ± 0.02 vs. 0.60 ± 0.03 AU), glucose (141.12 ± 11.70 vs. 207.06 ± 9.85 mg/dL), cardiac histopathological damage score (2.17 ± 0.41 vs. 9.02 ± 1.35), tunica media thickness (95.29 ± 4.29 vs. 114.95 ± 17.20 µm), and caspase-3 expression score (0.62 ± 0.74 vs. 2.87 ± 0.35). All results showed significance at the p < 0.05 level. Conclusions: HSP exhibited dose-dependent protective effects against DLM-induced oxidative stress, apoptosis, and cardiovascular injury, suggesting its potential as a therapeutic candidate against pesticide-related cardiotoxicity. Full article

The bean bug Riptortus pedestris (Hemiptera: Alydidae) is a major soybean pest in Asia, increasingly threatened by rising temperatures. It is crucial to clarify the high-temperature lethal thresholds of R. pedestris for predicting population dynamics under climate warming. Previous physiological data showed that female adults have significantly higher heat tolerance than males, with HLT₅₀ values of 39.76 °C versus 38.45 °C and HLT₉₀ values of 42.99 °C versus 42.44 °C. This sex-specific difference suggests distinct molecular responses to thermal stress. To test this hypothesis, we performed transcriptome sequencing of adults exposed to 24 °C (control), 40 °C (sublethal), and 44 °C (lethal), with males and females treated separately. A high-quality assembly yielded 270,199 unigenes, with 71 heat shock protein (HSP) genes identified across six subfamilies (sHSP, HSP40, HSP60, HSP70, HSP90, HSFs). HSPs exhibited a dual strategy: constitutive expression for basal proteostasis and strong induction—especially at 44 °C—for stress defense. Notably, responses were sexually dimorphic: females upregulated multiple stress-responsive HSPs (e.g., RpedHsp15.5-3, RpedHsp30.8) to protect reproduction, while males specifically induced RpedHsp83.6, possibly for signaling regulation. Phylogenetic analysis confirmed conservation within Hemiptera. These findings reveal the molecular basis of thermal adaptation in R. pedestris and identify key HSPs as potential targets for RNAi, HSP inhibitors, or precision thermal control. Full article

The solubility values of polyphenolic compounds in different extraction solvents are crucial for their recovery from natural matrices. Hansen solubility parameters (HSPs) stand out as a predictive tool for evaluating solute-solvent affinity and thus rational solvent selection for extraction processes. In this study, HSPs of trans-resveratrol and hesperetin were calculated using a semi-empirical method to assess the capability to predict the solubility behavior of both polyphenols in organic binary solvent mixtures. Experimental solubility of both polyphenols was determined in up to 21 monosolvents at 298.15 K and 0.1 MPa and used to classify them to iteratively calculate HSPs. Calculated HSPs were compared and discussed with literature values in terms of molecular interactions, demonstrating a fair agreement. Solubility of trans-resveratrol and hesperetin was then determined in methanol + MEK, ethanol + MEK, methanol + MiBK, ethanol + MiBK, and methanol + ethanol binary solvent mixtures. trans-Resveratrol achieved higher mole fraction solubility than hesperetin in all binary mixtures across the whole molar fraction range except in methanol + MiBK. Both compounds exhibited enhanced solubility in all alcohols + ketone binary mixtures, attributed to synergistic solvent effects. HSP analysis revealed a minimum Hansen distance between solute and solvent mixtures at compositions corresponding to the solubility maximum in synergistic systems. Additionally, calculated HSPs proved to effectively estimate the concentration at which this phenomenon occurs in all tested systems, reaching a robust correlation between maximum solubility and minimum Hansen distance. Overall, insights from this study underscore the effectiveness of experimentally derived HSPs in predicting the solubility behavior of polyphenols and seek to provide valuable guidance on solvent selection strategies for the recovery of bioactive compounds. Full article

Background/Objectives: Salinity stress limits agricultural production and threatens global food security. Faba bean (Vicia faba L.) is an important legume crop, and identifying salt-stress-responsive genes may support an improvement in salt response. This study aimed to identify intronless genes in faba bean, screen candidate genes associated with salt-stress responses, and develop a KASP marker for salt-response evaluation. Methods: Intronless genes were identified from the faba bean reference genome. Transcriptome analysis was conducted in roots and leaves of two cultivars, Sucan 4 and Yundou 1183, under 150 mM NaCl treatment and control conditions. Candidate genes were examined by expression analysis, functional annotation, PPI prediction, and a luciferase complementation assay. A KASP marker was developed from an SNP within the VfERF1A locus and tested in 97 accessions. Results: A total of 7581 intronless genes were identified, accounting for 20.69% of annotated genes. Fifteen intronless genes were significantly differentially expressed in both roots and leaves of the two cultivars under salt treatment. Functional annotation suggested that VfERF1A and VfHSP17.8 may be involved in salt-stress responses. PPI prediction and the LUC assay provided preliminary support for a possible association of VfERF1A with VfEIN2. The VfERF1A-based KASP marker showed clear genotype clustering, and the two homozygous classes differed significantly in QYmax, relative shoot fresh weight, and relative plant height under salt treatment (p < 0.05). The preliminary predictive accuracy for QYmax was 86.36%. Conclusions: These results provide a genome-wide resource of intronless genes in faba bean, identify candidate genes associated with salt-stress responses, and describe a preliminary KASP marker associated with salt-response traits. Further validation in independent populations, under diverse environmental conditions, and with additional functional evidence is still required. Full article