Echinacoside regulates the IRE1/XBP1 signaling pathway through HSP72 to reduce endoplasmic reticulum stress and improve diabetic kidney disease.

Genome-wide identification and functional validation of thermal tolerance genes in Mytilus coruscus using a yeast-based functional screening system.

HSP27 mRNA silencing and radiation-driven endosomal-lysosomal escape of lipid nanomicelles synergistically radiosensitize castration-resistant prostate cancer cells

This study aimed to identify key molecules that potentially mediate the mechanisms by which YAP deletion or inhibition attenuates liver fibrosis. C57BL/6 mice were divided into four groups: control, carbon tetrachloride (CCl4), CCl4-YAP-HKO, and CCl4-verteporfin (VP). RNA sequencing (RNA-seq) and proteomic analysis were conducted. Immunohistochemistry and western blotting were also performed to verify the differentially expressed genes (DEGs) identified through the multi-omics approach. Human subjects were enrolled to further assess the identified DEGs. In comparison with the CCl4 group, both the CCl4-YAP-HKO and CCl4-VP groups exhibited liver fibrosis regression. RNA-seq and proteomic analyses identified 12 commonly differentially expressed molecules. Immunohistochemistry and western blotting validated that heat shock protein 27 (HSP27), heat shock protein 70 (HSP70), and p62 expression were significantly reduced, and milk fat globule-epidermal growth factor 8 (MFGE8) expression was elevated in both the CCl4-YAP-HKO and CCl4-VP groups compared with the CCl4 group. Furthermore, plasma p62, HSP27, and HSP70 levels were increased with the occurrence of chronic hepatitis B and HBV-related cirrhosis, whereas MFGE8 levels were decreased. Spearman's correlation analysis further illustrated a significant association between these biomarkers and YAP levels. This study identified HSP27, HSP70, p62, and MFGE8 as crucial YAP-related molecules involved in liver fibrosis.

Heat shock protein 70 (HSP70) and its E3 ligase co-chaperone CHIP (STUB1) form a critical quality-control complex that directs client proteins toward folding or degradation. Phosphorylation of HSP70 at a conserved threonine in the C-terminal tail influences the fate of clients during cellular stress, yet the structural basis for this regulation remains unclear. Here, we present crystal structures of the CHIP tetratricopeptide repeat (TPR) domain bound to unphosphorylated and phosphorylated HSP70 C-terminal peptides at 1.6-1.9Å resolution. Phosphate occupancy at Thr636 (HSPA1A numbering) causes steric clashes and electrostatic repulsion within the TPR-binding groove, decreasing affinity by more than 10-fold, as shown by biolayer interferometry and fluorescence polarization. Molecular dynamics simulations confirm destabilization of key hydrogen bonds. A structure-guided G132N substitution in CHIP introduces new hydrogen bonds to the phosphate group, restoring affinity for phosphorylated peptides in isolated TPR domains without losing native ubiquitination activity. However, in full-length CHIP, interface modifications do not restore phosphorylation-impaired stable binding but yield only partial recovery of transient interactions in cells, indicating additional context-dependent constraints on HSP70-CHIP regulation. These findings reveal the atomic mechanism by which phosphorylation impairs HSP70-CHIP interaction during stress and demonstrate that targeted interface engineering can compensate for post-translational changes in isolated domains. Overall, the results explain how cells switch chaperone-mediated triage pathways and offer a framework for understanding how proteostasis becomes dysregulated in neurodegenerative diseases and cancer.

Thermal desiccation and expression of HSP90 and osmotic avoidance protein genes in an acorn barnacle, Amphibalanus amphitrite.

Loss of TRPV1 may shift capsaicin response from MAPK-CASC11-MYC protection to mitochondrial apoptosis in glioblastoma U87 cells.

Gliomas are primary brain tumors known for their resistance to radiotherapy and frequent recurrence. This might result from the high heterogeneity and transcriptional plasticity of gliomas. Heat shock proteins are associated with unfavorable tumor outcomes and protect tumors from the effects of radiotherapy. However, their influence on brain tumors is not fully understood. Initial analyses of glioma patients from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases who had undergone radiotherapy identified HSP90B1 as a crucial gene affecting patient prognosis. Subsequent investigations revealed that HSP90B1 enhanced the proliferation, migration, and invasion of glioma cells. It was also found to protect glioma cells from radiotherapy-induced apoptosis. Co-immunoprecipitation (CO-IP) found that HSP90B1 directly interacted with RhoC and protected it from degradation via the ubiquitin-proteasome pathway. Rescue experiments indicated that HSP90B1 might facilitate glioma migration, invasion, and radiotherapy resistance by modulating RhoC expression. A mouse model further demonstrated that gliomas expressing high levels of HSP90B1 exhibited decreased sensitivity to radiotherapy. Overall, our research revealed that HSP90B1 significantly impacts the prognosis of glioma patients treated with radiotherapy. Additionally, HSP90B1 might enhance glioma metastasis and resistance to radiotherapy by regulating RhoC expression. This regulatory effect was achieved by the directly binding of HSP90B1 to RhoC, thereby preventing its degradation through the ubiquitin-proteasome pathway.

Simultaneous exposure to thermal stress and agrochemicals represents a realistic yet understudied toxicological scenario for pollinators. Honey bees (Apis mellifera) increasingly face intense heat waves while foraging in pesticide-treated landscapes. Understanding the cumulative impact of these stressors is therefore critical for predicting pollinator health. We investigated the combined effects of simulated heat waves (exposed to 42 °C for two hours over three consecutive days) and chronic sublethal exposure to the neonicotinoid acetamiprid on honey bee immunity and physiology. By subjecting bees to a subsequent mechanical challenge, we assessed both their baseline physiological state and their capacity to mount an active immune defense under stress. Using a comprehensive panel of biomarkers - including antimicrobial peptides (AMPs: abaecin, apidaecin, defensin-1, hymenoptaecin), heat shock proteins, and oxidative stress markers - we evaluated the bees' immune and physiological resilience. Strikingly, while heat stress alone significantly reduced total hemocyte counts, indicating compromised cellular immunity, it did not trigger a humoral immune response. In contrast, combining heat stress with acetamiprid led to a significant overexpression of all tested AMP genes and elevated AMP concentrations in the hemolymph. Furthermore, this combined treatment upregulated catalase expression, signaling enhanced oxidative stress, and increased total hemolymph protein levels, suggesting altered physiological homeostasis. These results indicate that the interplay between thermal stress and pesticide exposure lowers the threshold for immune activation. We conclude that even sublethal pesticide doses can become immunologically burdensome during heat events. This stressor interaction risks physiological exhaustion and energy trade-offs, potentially compromising colony resilience against ubiquitous parasites in a warming world.

Pharmacological activation of HSF1 by HSF1A mitigates heatstroke-induced acute kidney injury via ferroptosis inhibition.

SiO2 nanoparticle–based seed priming enhances lettuce seed germination and seedling growth under heat stress

TGEV infection activates pro‑inflammatory signaling via the YY1/HSP40/NF‑κB pathway in intestinal epithelial cells and organoids.

Treatment with anti-Hsp90 antibody mitigates fibronectin-related cardiac fibrosis induced by pressure overload in mice.

Small heat shock protein HSPB8 interacts with a pre-fibrillar TDP43 low complexity domain species to delay fibril formation.

Thermal stress disrupts development, physiology, and immune responses in large yellow croaker (Larimichthys crocea).

Embryonic thermal manipulation reshapes hepatic transcriptome profiles of heat-stressed broiler chickens.

Fluorogenic probes are valuable tools for rapid detection and bioimaging of target molecules without requiring bound/free separation. Although antibody-based probes are widely used, their large size, reliance on secondary labeling, and limited accessibility to some intracellular regions can restrict their utility. In contrast, fluorogenic peptide aptamers-compact, chemically synthesizable, and self-reporting-offer a promising alternative. Here, we developed a method to prepare a fluorophore-conjugated peptide library using cDNA display and applied it to the selection of fluorogenic peptides targeting heat shock protein 90α (Hsp90α), a clinically relevant biomarker. As the solvatochromic reporter, we used an environmentally sensitive fluorophore, 4-N, N-dimethylamino-1,8-naphthalimide (4-DMN). One selected peptide, Peptide2, exhibited fluorescence enhancement in the presence of Hsp90α while remaining largely unresponsive to the homologous Hsp70. In fixed cells, Peptide2 produced intracellular fluorescence patterns that partially overlapped with those obtained using an anti-Hsp90α antibody, supporting its ability to detect intracellular Hsp90α-related signals. Peptide2 and the antibody also showed partially distinct staining distributions, suggesting differences in epitope accessibility and/or intracellular accessibility. These results establish a proof of concept for generating target-responsive, self-reporting peptide probes using bioorthogonal cDNA display.

PMTR1 is essential for melatonin-improved plant broad-spectrum disease resistance to bacterial pathogens and viruses. Melatonin plays vital roles in various plant stress responses, and the identification of phytomelatonin receptor 1 (PMTR1) in recent decades further extends the phytomelatonin signaling pathway. However, whether and how PMTR1 participates in plant broad-spectrum disease resistance has remained unclear. Here, we confirmed that exogenous melatonin enhanced disease resistance to bacterial blight and mosaic disease, indicating the crucial role of melatonin in cassava broad-spectrum disease resistance. In addition, the transcription of MePMTR1 was induced by Xanthomonas axonopodis pv. manihotis (Xam), common mosaic virus (CMV) and exogenous melatonin, suggesting that MePMTR1 may be involved in cassava immunity. Further investigation illustrated that MePMTR1 was a positive regulator in disease resistance to Xam and CMV, and it was necessary for melatonin-improved broad-spectrum disease resistance to the bacterial pathogen and the virus. Moreover, RNA-sequencing identified many differentially expressed genes (DEGs) in melatonin-improved disease resistance through MePMTR1, including calmodulin-like proteins (CMLs), calmodulin-binding proteins (CaMBPs), transcription factors WRKYs and MYBs, respiratory burst oxidase homolog protein C (RBOHC), heat shock protein 20, pathogenesis-related protein (PR10), etc. In total, this study provides new light on the theoretical foundation of melatonin in modulating broad-spectrum disease resistance in cassava, extending the understanding of the melatonin signaling pathway in plant immunity.

Aging is commonly viewed as a passive consequence of accumulated damage; however, emerging evidence suggests that it may also represent an adaptive response to environmental stress. Here, we combined transcriptomic and metabolomic profiling of Saccharomyces cerevisiae to investigate how short-term, long-term, and recovery phases of stress exposure shape cellular physiology and lifespan. Short-term stress-induced protective pathways and longevity-associated metabolites, including trehalose and 5'-methylthioadenosine, consistent with enhanced stress resilience and proteostasis. In contrast, prolonged stress activated heat shock proteins and epigenetic regulators, coupled with metabolic signatures associated with loss of proteostasis, reduced energy homeostasis, and shortened chronological lifespan. Upon recovery, beneficial metabolites such as S-adenosylhomocysteine were restored, highlighting the reversibility of stress-induced aging trajectories. Phylogenetic analysis demonstrated conservation of these stress- and aging-related genes across eukaryotes and prokaryotes, suggesting an evolutionary basis for aging as a long-term stress adaptation. Together, these findings suggest that aging-associated molecular changes are closely linked to conserved stress response pathways, with implications for understanding the hallmarks of aging.

Host cell proteins (HCPs) are critical process-related impurities of recombinant protein biopharmaceuticals that have the potential to impact product safety and efficacy. In this study, two residual HCPs, heat shock protein 90 beta and perilipin-4-like, produced from a CHO cell line, were identified during the development of a late-stage platform Immunoglobulin G subclass 1 (IgG1)monoclonal antibody process. A risk assessment was performed that included identification of HCPs, homology with their human protein counterparts, and prior non-clinical and clinical experience. The outcome deemed these two species as "problematic" and target levels were established to guide approaches for removal. Given the high productivity of the upstream and downstream platform processes, the goal was to explore conditions that minimize deviations from the platform. An end-to-end approach was performed that evaluated downstream levers, including Protein A washes, polishing chromatography operational parameters, and exploration of depth filter media. Upstream levers were also explored, evaluating effects of temperature shift and modulation of iron and citrate to help control levels of both HCP species. The results presented in this study demonstrated the upstream and downstream conditions achieved effective removal of the two HCP species to meet drug substance targets.