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The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Heat stress (HS) poses significant challenges to the dairy industry, resulting in reduced milk production, impaired reproductive performance, and compromised animal welfare. Therefore, understanding the molecular mechanisms underlying cellular responses to HS is crucial for developing effective strategies to mitigate its adverse effects. Heat shock protein 70 (HSP70) has emerged as a potential player involved in cellular thermotolerance in dairy cows. This review provides a comprehensive overview of the role of HSP70 as a molecular chaperone in cellular thermotolerance in dairy cows under HS. HSP70 facilitates proper protein folding and prevents the aggregation of denatured proteins. By binding to misfolded proteins, it helps maintain protein homeostasis and prevents the accumulation of damaged proteins during HS. Additionally, HSP70 interacts with various regulatory proteins and signaling pathways, contributing to the cellular adaptive response to HS. The upregulation of HSP70 expression in response to HS is regulated by a complex network involving heat shock factors (HSF), heat shock element-binding proteins, and HSF co-chaperones. Therefore, HSP70 holds the potential to be a useful indicator of tissue stress due to its role in maintaining cellular balance and because it is released both inside and outside cells in response to stress. Traditional methods of measuring HSP70 in blood samples are labor intensive, and because the process is potentially stressful for the animals, this may subsequently affect the results. Therefore, measuring HSP expression in cow milk has shown promise as an easy, noninvasive, and accurate way to detect HS in dairy cows. Monitoring HSP70 levels in milk can be applied as a supplementary approach to identify HS or HS resistance of individual cows, select suitable animals, and guide targeted management strategies. However, despite the potential advantages of using HSP70 as a biomarker for monitoring HS on dairy cows, challenges remain in standardizing measurement protocols, establishing species-specific reference ranges, addressing interindividual variations, and determining the specificity of changes in HSP70 due to HS. Future research should focus on developing noninvasive techniques for HSP70 detection, with consideration of climatic conditions and unraveling the molecular interactions and regulatory networks involving HSP70. [ABSTRACT FROM AUTHOR]

Background: Gene duplication is a dominant mechanism for the evolution of genomes and plays a key role in genome expansion. Gene duplication via retroposition produces RNA-mediated intron-less copies called retrocopies, that may gain regulatory sequence and biological function to generate retrogenes. Retrocopies dynamics have been reported in several model insect species, but there is still a huge knowledge gap about retrocopies dynamics in most insects, and their role in adaptation. Results: In this study, we reported retrocopy dynamics in 40 species of insect pests of plants belonging to six insect orders. We identified a total of 9,930 retrocopies, which is so far the largest set of retrocopies identified in insects. The identified retrocopies were further grouped into 2,599 Retrogenes, 4,578 Chimeras, 1,241 Intact retrocopies, and 1,512 Pseudogene. We also analyzed all the identified retrogenes that were annotated into 506 gene families. The highest number of retrogenes annotated belong to the heat shock proteins superfamily and are present across all the 40 species from the six orders. We found a significant expansion of the heat shock protein superfamily in the studied species. Almost all the retrogenes, including those belonging to heat shock proteins, are under purifying selection. In summary, we report the retrocopies and retrogenes dynamics in a large set of insect pests of plants and the expansion of the heat shock protein family due to retroposition. Conclusion: This study unveils retrocopy dynamics in the insect pests of plants and highlights the evolution of new genes due to retroposition, and their role in important gene families' expansion. [ABSTRACT FROM AUTHOR]

Heat shock proteins (Hsps), acting as molecular chaperones, play a pivotal role in plant responses to environmental stress. In this study, we found a total of 192 genes encoding Hsps, which are distributed across all 12 chromosomes, with higher concentrations on chromosomes 1, 2, 3, and 5. These Hsps can be divided into six subfamilies (sHsp, Hsp40, Hsp60, Hsp70, Hsp90, and Hsp100) based on molecular weight and homology. Expression pattern data indicated that these Hsp genes can be categorized into three groups: generally high expression in almost all tissues, high tissue-specific expression, and low expression in all tissues. Further analysis of 15 representative genes found that the expression of 14 Hsp genes was upregulated by high temperatures. Subcellular localization analysis revealed seven proteins localized to the endoplasmic reticulum, while others localized to the mitochondria, chloroplasts, and nucleus. We successfully obtained the knockout mutants of above 15 Hsps by the CRISPR/Cas9 gene editing system. Under natural high-temperature conditions, the mutants of eight Hsps showed reduced yield mainly due to the seed setting rate or grain weight. Moreover, the rice quality of most of these mutants also changed, including increased grain chalkiness, decreased amylose content, and elevated total protein content, and the expressions of starch metabolism-related genes in the endosperm of these mutants were disturbed compared to the wild type under natural high-temperature conditions. In conclusion, our study provided new insights into the HSP gene family and found that it plays an important role in the formation of rice quality and yield. [ABSTRACT FROM AUTHOR]

Mitochondria are important organelles in eukaryotes and are involved in various metabolic processes. Mitochondrial proteotoxic stress triggers the mitochondrial unfolded protein response (UPRmt) to restore mitochondrial protein homeostasis and maintain normal life activities. However, the regulatory mechanism of plant UPRmt remains to be revealed in Arabidopsis. Based on the fact that UPRmt activates heat shock protein (HSP) genes, we identified the heat shock transcription factor HSFA6b as a key regulator mediating UPRmt through reverse genetics. HSFA6b responded to mitochondrial proteotoxic stress and regulated mitochondrial heat shock proteins' genes' (mtHSPs) expression. HSFA6b translocated to the nuclear after treatment with doxycycline (Dox)—a mitochondrial ribosome translation inhibitor. HSFA6b binds to the mtHSPs promoters and activates mtHSPs expression. The HSFA6b mutation blocked the UPRmt signals to promote root growth under mitochondrial proteotoxic stress and accelerated leaf senescence during development. Our study reveals a novel signal-regulating mechanism in the UPRmt pathways and provides new insights regarding the regulation of plant growth and development and stress resistance by the UPRmt pathways. [ABSTRACT FROM AUTHOR]

Background: Heat shock proteins (HSPs) play crucial roles in response to temperature changes and biotic stresses. However, the HSP gene family in the pufferfish (Takifugu fasciatus) herring has not been comprehensively investigated. Methods and Results: This study presents a systematic analysis of the HSP70 and HSP90 gene families in T. fasciatus, focusing on gene characterization, conserved structural domains, molecular evolutionary history, and expression patterns of the HSP gene family under stress conditions. The findings reveal that 16 HSP genes are evolutionarily conserved, while hspa4 and hsp90aa appear specific to teleost fish. HSP genes exhibit widespread expression across 11 examined tissues, with most demonstrating high expression levels in the heart, brain, and liver. Furthermore, T. fasciatus was subjected to cryogenic and biotic stresses, revealing distinct expression patterns of HSPs under various stress conditions. The response of HSPs to cold stress and Aeromonas hydrophila infection was sustained. In contrast, gene expression of HSPs significantly changed only in the pre-infection period following Ichthyophthirius multifiliis infection, gradually returning to normal levels in the later stages. Conclusions: These experimental results provide a foundation for further in-depth investigations into the characteristics and functions of HSPs in T. fasciatus. [ABSTRACT FROM AUTHOR]

Summary: The gastrointestinal tract serves as a pivotal physical barrier that prevents the translocation of exogenous substances from the intestinal lumen into the systemic circulation. Dysfunction of intestinal barrier function has been implicated in the pathogenesis of several diseases, such as metabolic disorders. Heat shock proteins (HSPs) play a critical role in maintaining the resilience and viability of epithelial cells when exposed to stressors. Evidence suggests that dietary fibre (DF), a known inducer of HSP production, may be a promising candidate for strengthening the intestinal barrier. Understanding the regulation of intestinal HSPs and the protective effect of DF is critical to defending against environmental threats and preserving human health. To date, six DFs—pectin, chicory, psyllium, guar gum, partially hydrolysed guar gum, and xylooligosaccharide—have been reported to have promotive effects on intestinal HSP induction. DF promotes intestinal HSP induction through gut microbiota‐dependent and independent mechanisms. DF is fermented by gut microbiota to produce short‐chain fatty acids, specifically butyrate and propionate, to promote HSP production. Meanwhile, DF also promotes intestinal HSP induction through direct interaction with intestinal epithelial cells, independent of gut microbiota activity, although the precise mechanism is still unclear. Regulation of intestinal HSP occurs by transcriptional modulation through activation of heat shock transcription factors, primarily heat shock factor 1, or at the post‐transcriptional level by modulation of the translation process. This review highlights recent advances in understanding the role of DF in improving intestinal barrier function, with particular emphasis on the regulatory mechanisms of intestinal HSPs. [ABSTRACT FROM AUTHOR]

Archaeal group II chaperonins, also known as heat shock proteins (HSPs), are abundantly expressed in Sulfolobales. HSPα and HSPβ gene expression is upregulated during thermal shock. HSPs form large 18-mer complexes that assist in folding nascent proteins and protecting resident proteins during thermal stress. Engineered HSPs have been designed for industrial applications. Since temperature flux in the geothermal habitats of Sulfolobales impacts intracellular temperature, it follows that HSPs have developed thermotolerance. However, despite the low pH (i.e., pH < 4) typical for these habitats, intracellular pH in Sulfolobales is maintained at ~6.5. Therefore, it is not presumed that HSPs have evolved acid-tolerance. To test tolerance to low pH, HSPs were studied at various pH and temperature values. Both circular dichroism and intrinsic fluorescence indicate that HSPα and HSPβ retain structural integrity at neutral pH over a wide range of temperatures. Structural integrity is compromised for all HSPs at ultra-low pH (e.g., pH 2). Secondary structures in HSPs are resilient under mildly acidic conditions (pH 4) but Anilino naphthalene 8-sulfonate binding shows shifts in tertiary structure at lower pH. Trypsin digestion shows that the HSPβ-coh backbone is the most flexible and HSPβ is the most resilient. Overall, results suggest that HSPα and HSPβ exhibit greater thermostability than HSPβ-coh and that there are limits to HSP acid-tolerance. Molecular dynamics (MD) simulations complement the wet lab data. Specifically, MD suggests that the HSPβ secondary structure is the most stable. Also, despite similarities in pH- and temperature-dependent behavior, there are clear differences in how each HSP subtype is perturbed. [ABSTRACT FROM AUTHOR]

The precise and effective activation of the immune response is crucial in promising therapy curing cancer. Photoimmunotherapy (PIT) is an emerging strategy for precise regulation and highly spatiotemporal selectivity. However, this approach faces a significant challenge due to the off‐target effect and the immunosuppressive microenvironment. To address this challenge, a nanoscale full‐active pharmaceutical ingredient (API) photo‐immune stimulator was developed. This formulation overcomes the limitations of PIT by strengthening the ability to penetrate tumors deeply and inducing precise and potent mitochondria‐targeted dual‐mode photodynamic therapy and photothermal therapy. Along with inhibiting overexpressed Hsp90, this nanosensitizer in turn improves the immunosuppressive microenvironment. Ultimately, this mitochondria‐targeted PIT demonstrated potent antitumor efficacy, achieving a remarkable inhibition rate of ≥95% for both established primary tumors and distant abscopal tumors. In conclusion, this novel self‐delivery full‐API nanosystem enhances the efficacy of phototherapy and reprograms the immunosuppressive microenvironment, thereby holding great promise in the development of precise and effective immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Physical inactivity induces insulin resistance (IR) and metabolic imbalances before any significant changes in adiposity. Recent studies suggest that the beneficial effects of exercise can be potentiated if performed while fasting. This work aimed to compare the subacute effects of fed- and fasted-state single-bout exercise on biochemical parameters and cellular signaling in the metabolism. Methods: The animals were allocated into fed rest (FER), fasting rest (FAR), fed exercise (FEE), and fasting exercise (FAE) groups. The exercise protocol was a 30 min treadmill session at 60% of V ˙ O2max. The fasting groups fasted for 8 h before exercise and were killed after 12 h post-exercise. Results: Soleus glycogen concentration increased only in the fasting groups, whereas the triglyceride (TGL) content increased in brown adipose tissue (BAT) and liver in the FAE. The FAE showed decreased plasma total cholesterol concentration compared withthe FAR group. Immunocontent of HSP70, SIRT1, UCP-1, and PGC1-α did not change in any tissue investigated. Conclusions: Our results indicate that physical exercise while fasting can have beneficial metabolic effects on sedentary animals. Remarkably, in the FAE group, there was a reduction in total plasma cholesterol and an increase in the capacity of BAT to metabolize and store nutrients in the form of TGLs. [ABSTRACT FROM AUTHOR]

Background: “Touriga Franca” (TF) and “Touriga Nacional” (TN) are grapevine varieties cultivated in the ‘Douro Superior’ subregion (Northern Portugal) that experience stressful environmental conditions during the summer. Objectives: Aiming to profile the expression of stressresponsive genes by quantitative real-time PCR (qPCR) in TF and TN plants growing naturally, three candidate reference genes were first tested under controlled conditions. Methods: To simulate a summer’s day, TF and TN in vitro plants were exposed to 32 ◦C–3 h (heat acclimation) and 42 ◦C–1 h (severe heat stress, HS) followed by two recovery periods (32 ◦C–3 h and 24 ◦C–24 h). Leaf samples were collected at the end of each phase. Control plants were kept at 24 ◦C. Results: Among the candidate reference genes, the UBC and VAG pair showed the highest stability. The suitability of these genes for qPCR was validated by heat shock protein 17.9A (HSP17.9A) gene profiling. The HSP17.9A expression was up-regulated in both varieties and all experimental phases except in TF control plants. TN showed the highest HSP17.9A relative expression ratio after severe HS. Conclusions: TN responded faster than TF to the induced heat shocks. The UBC, VAG, and HSP17.9A genes revealed to be suitable for further qPCR assays in TF and TN grapevine varieties. [ABSTRACT FROM AUTHOR]

Currently, due to the increasing impact of anthropogenic factors and changes in solar activity, the temperature on Earth is rising, posing a threat to biodiversity. Lichens are among the most sensitive organisms to climate change. Elevated ambient temperatures can have a significant impact on lichens, resulting in more frequent and intense drying events that can impede metabolic activity. It has been suggested that the possession of a diverse sterol composition may contribute to the tolerance of lichens to adverse temperatures and other biotic and abiotic stresses. The major sterol found in lichens is ergosterol (ERG); however, the regulation of the ERG biosynthetic pathway, specifically the step of epoxidation of squalene to 2,3-oxidosqualene catalyzed by squalene epoxidase during stress, has not been extensively studied. In this study, we used lichen Lobaria pulmonaria as a model species that is well known to be sensitive to air pollution and habitat loss. Using in silico analysis, we identified cDNAs encoding squalene epoxidase from L. pulmonaria, designating them as LpSQE1 for the mycobiont and SrSQE1 for the photobiont Symbiochloris reticulata. Our results showed that compared with a control kept at room temperature (+20 °C), mild temperatures (+4 °C and +30 °C) did not affect the physiology of L. pulmonaria, assessed by changes in membrane integrity, respiration rates, and PSII activity. An extreme negative temperature (−20 °C) noticeably inhibited respiration but did not affect membrane stability. In contrast, treating lichen with a high positive temperature (+40 °C) significantly reduced all physiological parameters. Quantitative PCR analysis revealed that exposing thalli to −20 °C, +4 °C, +30 °C, and +40 °C stimulated the expression levels of LpSQE1 and SrSQE1 and led to a significant upregulation of Hsps. These data provide new information regarding the roles of sterols and Hsps in the response of lichens to climate change. [ABSTRACT FROM AUTHOR]

Simple Summary: Fruit flies are major pests that cause extensive damage to fruits and vegetables worldwide. Understanding how these insects respond to heat treatment is crucial for developing effective methods to control them. In this study, we investigated how the Queensland fruit fly and the Mediterranean fruit fly react at a molecular level when exposed to heat. We found that each species responds differently, activating different genes to cope with the stress. By identifying the specific genes involved, we can design targeted heat treatments that are more effective for each species. This tailored approach can improve the efficiency of pest control, reduce the need for harmful chemicals, and minimise damage to the environment. Our findings offer valuable insights for developing better strategies to manage fruit fly populations, ensuring healthier crops and reducing economic losses for farmers. This research highlights the importance of understanding species-specific responses to stress and provides a foundation for future studies aimed at optimising pest management techniques. Invasive Tephritid fruit flies rank among the most destructive agricultural and horticultural pests worldwide. Heat treatment is commonly employed as a post-harvest method to exterminate fruit flies in fruits or vegetables. These pest species exhibit distinct tolerance to heat treatments, suggesting that the molecular pathways affected by heat may differ among species. In this study, the Queensland fruit fly (Qfly), Bactrocera tryoni, was utilised as a model investigate its molecular response to heat stress through heat bioassays. RNA samples from flies before and after heat treatment were extracted and sequenced to identify genes with significant changes in expression. These findings were compared to another serious Tephritid fruit fly species, the Mediterranean fruit fly (Medfly), Ceratitis capitata, under similar heat treatment conditions. The analysis reveals only three common genes: heat shock protein 70 (HSP70), HSP68, and 14-3-3 zeta protein. However, despite these shared genes, their expression patterns differ between Qfly and Medfly. This suggests that these genes might play different roles in the heat responses of each species and could be regulated differently. This study presents the first evidence of differing molecular responses to heat between Qfly and Medfly, potentially linked to their varied origins, habitats, and genetic backgrounds. These findings offer new insights into Tephritid fruit fly responses to heat at the molecular level, which may help refine post-harvest strategies to control these pests in the future. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder that includes non-alcoholic hepatic steatosis without or with moderate inflammation and non-alcoholic steatohepatitis (NASH), characterized by necroinflammation and a more rapid progression of fibrosis. It is the primary pathological basis for hepatocellular carcinoma. With its prevalence escalating annually, NAFLD has emerged as a global health epidemic, presenting a significant hazard to public health worldwide. Existing studies have shown that physical activity and exercise training have a positive effect on NAFLD. However, the extent to which exercise improves NAFLD depends on the type, intensity, and duration. Therefore, the type of exercise that has the best effect on improving NAFLD remains to be explored. To date, the most valuable discussions involve aerobic and anaerobic exercise. Exercise intervenes in the pathological process of NAFLD by regulating physiological changes in cells through multiple signaling pathways. The review aims to summarize the signaling pathways affected by two different exercise types associated with the onset and progression of NAFLD. It provides a new basis for improving and managing NAFLD in clinical practice. [ABSTRACT FROM AUTHOR]

Almost all types of cellular stress induce post‐translational O‐GlcNAc modifications of proteins, and this increase promotes cell survival. We previously demonstrated that O‐GlcNAc on certain small heat shock proteins (sHSPs), including HSP27, directly increases their chaperone activity as one potential protective mechanism. Here, we furthered our use of synthetic proteins to prepare biotinylated sHSPs and show that O‐GlcNAc modification of HSP27 also changes how it interacts within the sHSP system and the broader HSP network. Specifically, we show that O‐GlcNAc modified HSP27 binds more strongly to the co‐chaperone protein BAG3, which then promotes refolding of a model substrate by HSP70. We use proteomics to identify other potential HSP27 interactions that are changed by O‐GlcNAc, including one that we confirm with another sHSP, αB‐crystallin. These findings add additional evidence for O‐GlcNAc as a switch for regulating protein–protein interactions and for modifications of chaperones as one mechanism by which O‐GlcNAc protects against protein aggregation. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is an anthracycline antibiotic widely employed to treat carcinoma. Nevertheless, severe cardiotoxic side effects restrict its clinical use. Esculetin, a natural flavonoid, is found abundantly in plants. This study evaluated the protective effects of esculetin against DOX‐induced hepatotoxicity in rat livers. Forty‐eight rats were randomly divided into six groups with eight rats in each group: control (I), DOX (II), esculetin (III, 50 mg/kg), esculetin (IV, 100 mg/kg), DOX+esculetin 50 (V, DOX+esculetin 50 mg/kg), and DOX+esculetin 100 (VI, DOX+esculetin 100 mg/kg). The administration of esculetin effectively mitigated alterations in the measured biochemical parameters induced by DOX. Gene expression analyses demonstrated that esculetin treatment significantly reduced the DOX‐induced expression of Foxo1, Hspa1a, Hsp4a, Hsp5a, Casp3, and Casp9 while increasing the DOX‐induced expression of Foxo3. These findings suggest that esculetin, with its antioxidant and anti‐inflammatory effects, might be a therapeutic option for protecting against DOX‐induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

ABSTRACT: Heat stress (HS) poses significant challenges to the dairy industry, resulting in reduced milk production, impaired reproductive performance, and compromised animal welfare. Therefore, understanding the molecular mechanisms underlying cellular responses to HS is crucial for developing effective strategies to mitigate its adverse effects. Heat shock protein 70 (HSP70) has emerged as a potential player involved in cellular thermotolerance in dairy cows. This review provides a comprehensive overview of the role of HSP70 as a molecular chaperone in cellular thermotolerance in dairy cows under HS. HSP70 facilitates proper protein folding and prevents the aggregation of denatured proteins. By binding to misfolded proteins, it helps maintain protein homeostasis and prevents the accumulation of damaged proteins during HS. Additionally, HSP70 interacts with various regulatory proteins and signaling pathways, contributing to the cellular adaptive response to HS. The upregulation of HSP70 expression in response to HS is regulated by a complex network involving heat shock factors (HSF), heat shock element-binding proteins, and HSF co-chaperones. Therefore, HSP70 holds the potential to be a useful indicator of tissue stress due to its role in maintaining cellular balance and because it is released both inside and outside cells in response to stress. Traditional methods of measuring HSP70 in blood samples are labor intensive, and because the process is potentially stressful for the animals, this may subsequently affect the results. Therefore, measuring HSP expression in cow milk has shown promise as an easy, noninvasive, and accurate way to detect HS in dairy cows. Monitoring HSP70 levels in milk can be applied as a supplementary approach to identify HS or HS resistance of individual cows, select suitable animals, and guide targeted management strategies. However, despite the potential advantages of using HSP70 as a biomarker for monitoring HS on dairy cows, challenges remain in standardizing measurement protocols, establishing species-specific reference ranges, addressing interindividual variations, and determining the specificity of changes in HSP70 due to HS. Future research should focus on developing noninvasive techniques for HSP70 detection, with consideration of climatic conditions and unraveling the molecular interactions and regulatory networks involving HSP70.

Heat shock proteins (HSPs), also known as heat stress proteins, can be divided into five main families, including HSP100, HSP90, HSP70, HSP60, and small heat shock proteins (sHSPs), according to their molecular weight. Further studies have shown that HSPs represent a class of highly conserved proteins that widely exist in the subcellular compartments of prokaryotic and eukaryotic cells. They have many functions, such as protein folding, repair, and immunity, and play important roles in organism growth and development. For example, Dmhsp70-A and Dmhsp70-B showed similar trends in the development of asexual embryos in Daphnia magna. However, they exhibited different trends in the development of sexual embryos despite high expression in both embryo types. Penaeus japonicus is one of the most important commercial shrimp species in China, Japan, and Southeast Asian countries. Relevant studies have shown that hsp genes widely exist in P. japonicus and play important roles in growth and development. For example, hsp10 and hsp60 were expressed in all tissues of P. japonicus, and the differential expression of hsp60 was identified in the early development stages. However, previous studies were based on single genes, and more systematic studies based on the role of the hsp gene family in the growth and development of P. japonicus have not been published. Our laboratory has completed the genome sequence of P. japonicus, which provides basic data for analyzing the molecular mechanism of hsp in the growth and development of P. japonicus. To further study the characteristics of the hsp gene family in P. japonicus and the expression characteristics of hsp genes during different development stages, the hsp gene family of P. japonicus was identified and analyzed using bioinformatics methods, and variation in its expression during the development of P. japonicus was measured using reverse transcription and quantitative real-time (RT-qPCR). Fifteen members of the hsp gene family were identified from the whole genome of P. japonicus via bioinformatics analysis, and their gene structures, motif compositions, chromosome localizations, and phylogenetic characteristics were analyzed. The expression of hsp genes in maternal-to-zygotic cells, blastocysts, gastrulae, limb buds, intramembranous nauplii, stage 1 nauplii, stage 1 zoeae, stage 1 myses, and stage 1 post-larval juveniles of P. japonicus was measured using qPCR. A total of 15 hsp genes were identified, including 1 hsp10, 2 hsp20, 2 hsp40, 1 hsp60, 6 hsp70, and 3 hsp90 genes. The physicochemical properties of seven proteins were stable, with instability coefficients less than 40. Subcellular localization results showed that most of the hsp gene family members were located in the cytoplasm, as seven hsp genes were localized to the cytoplasm, two to the nucleus, two to the extracellular region, two to the endoplasmic reticulum, and two to the mitochondria. Isoelectric point (pI) is related to the number and proportion of acidic and basic amino acids contained in a protein. Most HSPs exhibited a pI < 7, suggesting they were acidic proteins. The 15 hsp genes were located on 11 chromosomes. Phylogenetic tree analysis showed that most of the HSP family members were first clustered with HSP family members from species such as Penaeus monodon, Litopenaeus vannamei, and Fenneropenaeus chinensis and then with HSP family members of other species, which was consistent with the traditional taxonomic status. A few HSP family members were clustered first with HSP family members from Eriocheir sinensis, D. melanogaster, and other insects, and then with HSP family members from other species. Motif analysis showed that the hsp gene family was highly conserved; however, the functions of different families were quite different. Structural domain analysis showed that the HSP family included cpn10-, metazoan ACD-, DnaJ bact superfamily-, GroEL-, PTZ00009 superfamily-, dnaK-, HSP70 superfamily-, HSP90 superfamily-, PRK14083 superfamily-, and HATpase_HSP90-like domains. Each gene family contained corresponding domains and was important in molecular chaperone processes. hsp genes were expressed in different developmental stages of P. japonicus and played important roles in growth and development. The trend of Pjhsp10-19.517 was similar to that of Pjhsp60-19.518, which was highly expressed during embryonic development and significantly downregulated during larval development. This is consistent with the conclusion of previous studies that HSP60 and HSP10 are molecular chaperones for each other to ensure the correct folding of the target protein. The hsp genes such as Pjhsp40-15.349, Pjhsp70-39.287, Pjhsp70-1.298, and Pjhsp90 were highly expressed in the embryonic period; Pjhsp20, Pjhsp70-3.662, Pjhsp70-15.369, Pjhsp70-32.916, and Pjhsp90-12.759 were highly expressed during the larval period. The hsp genes expressed at high levels during the embryonic period satisfy the high protein requirements of embryos by playing the role of molecular chaperone and regulating the transcription of vitellogenin to meet the embryonic need for vitellin. The hsp genes expressed at high levels during the larval period protect the body from environmental pressure, pathogens, and xenobiotics through a synergistic immune effect. The authors believe that hsp genes play important roles in the growth and development of P. japonicus, and the specific pathways and mechanisms should be further studied. This study provides basic data for further investigations of the role of hsp genes in the growth and development of P. japonicus.

Xudong Wang,1– 3,&ast; Zhiyong Li,1,&ast; Jianhong Xu,1 Jun Wang,1 Ying Li,1 Qiang Li,4 Jianrong Niu,5 Rongya Yang2 1Outpatient Department of Yangfangdian, Southern Medical District of Chinese PLA General Hospital, Beijing, 100843, People’s Republic of China; 2Department of Dermatology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100010, People’s Republic of China; 3Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 4Medical Health Care Dept, Air Force Medical Center PLA, Beijing, 100142, People’s Republic of China; 5Department of Dermatology, Air Force Medical Center PLA, Beijing, 100142, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongya Yang, Department of Dermatology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100010, People’s Republic of China, Email yangrya@sina.com Qiang Li, Medical Health Care Department, Air Force Medical Center PLA, Beijing, 100142, People’s Republic of China, Email 16585260@qq.comPurpose: Heat shock protein A4 (HSPA4) is associated with a variety of human diseases. However, its function in cutaneous malignant melanoma (CMM) remains uncertain.Patients and Methods: The gene and protein expression level of HSPA4 in CMM was investigated with public databases. Cell Counting Kit-8 (CCK8) assay was performed to assess the effect of HSPA4 on the proliferation of melanoma cells. Then, the diagnostic and prognostic value of HSPA4 in CMM were analyzed. Gene variations and methylation levels, and the correlation between HSPA4 expression and immune cell infiltration were evaluated, followed by the construction of HSPA4 related protein-protein interaction networks and functional enrichment analysis.Results: The mRNA and protein expression level of HSPA4 was significantly higher in CMM. Knocking down HSPA4 in A-375 cell line could inhibit tumor cell growth. The receiver operating characteristic (ROC) curve analysis confirmed the diagnostic value of HSPA4. Survival analysis showed that high expression of HSPA4 was associated with poor prognosis. HSPA4 gene alterations were observed in 3% of CMM patients. Five CpG sites are associated with the prognosis of CMM. HSPA4 is negatively correlated with most immune cells in CMM. The protein interaction network shows that HSPA4 is closely related to proteins such as DnaJ heat shock protein family (Hsp40) member B1 (DNAJB1) and DnaJ heat shock protein family (Hsp40) member B6 (DNAJB6), and the expression of DNAJB1 is positively correlated with HSPA4. Functional enrichment analysis indicated that HSPA4 may be associated with immune suppression and immune escape within the tumor microenvironment of CMM.Conclusion: HSPA4 may participate in the regulation of tumor development and microenvironment, which may be a potential diagnostic and prognostic marker of CMM.Keywords: heat shock protein, melanoma, HSPA4, TCGA, bioinformatics

Abstract Background Gene duplication is a dominant mechanism for the evolution of genomes and plays a key role in genome expansion. Gene duplication via retroposition produces RNA-mediated intron-less copies called retrocopies, that may gain regulatory sequence and biological function to generate retrogenes. Retrocopies dynamics have been reported in several model insect species, but there is still a huge knowledge gap about retrocopies dynamics in most insects, and their role in adaptation. Results In this study, we reported retrocopy dynamics in 40 species of insect pests of plants belonging to six insect orders. We identified a total of 9,930 retrocopies, which is so far the largest set of retrocopies identified in insects. The identified retrocopies were further grouped into 2,599 Retrogenes, 4,578 Chimeras, 1,241 Intact retrocopies, and 1,512 Pseudogene. We also analyzed all the identified retrogenes that were annotated into 506 gene families. The highest number of retrogenes annotated belong to the heat shock proteins superfamily and are present across all the 40 species from the six orders. We found a significant expansion of the heat shock protein superfamily in the studied species. Almost all the retrogenes, including those belonging to heat shock proteins, are under purifying selection. In summary, we report the retrocopies and retrogenes dynamics in a large set of insect pests of plants and the expansion of the heat shock protein family due to retroposition. Conclusion This study unveils retrocopy dynamics in the insect pests of plants and highlights the evolution of new genes due to retroposition, and their role in important gene families’ expansion.

Abstract Heat shock proteins are essential molecular chaperones that play crucial roles in stabilizing protein structures, facilitating the repair or degradation of damaged proteins, and maintaining proteostasis and cellular functions. Extensive research has demonstrated that heat shock proteins are highly expressed in cancers and closely associated with tumorigenesis and progression. The "Hallmarks of Cancer" are the core features of cancer biology that collectively define a series of functional characteristics acquired by cells as they transition from a normal state to a state of tumor growth, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, enabled replicative immortality, the induction of angiogenesis, and the activation of invasion and metastasis. The pivotal roles of heat shock proteins in modulating the hallmarks of cancer through the activation or inhibition of various signaling pathways has been well documented. Therefore, this review provides an overview of the roles of heat shock proteins in vital biological processes from the perspective of the hallmarks of cancer and summarizes the small-molecule inhibitors that target heat shock proteins to regulate various cancer hallmarks. Moreover, we further discuss combination therapy strategies involving heat shock proteins and promising dual-target inhibitors to highlight the potential of targeting heat shock proteins for cancer treatment. In summary, this review highlights how targeting heat shock proteins could regulate the hallmarks of cancer, which will provide valuable information to better elucidate and understand the roles of heat shock proteins in oncology and the mechanisms of cancer occurrence and development and aid in the development of more efficacious and less toxic novel anticancer agents. Graphic abstract

Abstract Photothermal therapy is an alternative cancer therapy that uses a photothermal agent with light irradiation to induce fatal hyperthermia in cancer cells. In a previous study, we found that ex vivo photothermal (PT) treatment induced expression of heat shock proteins (HSPs), such as HSP70, HSP27, and HSP90, in cancer cells; moreover, immunization with lysates from PT-treated tumor cells resulted in significant tumor growth inhibition in tumor-bearing mice. In this study, we hypothesized that sublethal PT treatment of antigen-presenting cells regulates their immunogenicity. We observed the upregulation of expression of intracellular HSP70 and surface activation markers, such as CD40, CD80, CD86, and MHC class II, in sublethal PT-treated cells. The protumoral activity of myeloid-derived suppressor cells (MDSCs) was reduced by sublethal hyperthermia. Furthermore, poorly immunogenic MDSCs were converted into immunogenic antigen-presenting cells by PT treatment. The differences in immunogenicity between MDSCs untreated or treated with the PT technique were evaluated using the Student’s t-test or Mann–Whitney rank sum test. Collectively, direct hyperthermic treatment resulted in phenotypic changes and the functional regulation of immune cells.

[Objective] Trypanosoma cruzi, a causal agent of Chagas’ disease, is a parasite whose life cycle alternates between an invertebrate (triatomine) and a vertebrate (mammal) host. Various studies have shown that in T. cruzi, HSP83 (a homolog of HSP90) is essential for cell division and control of the response to thermal stress. This investigation focused on studying the cloning, bioinformatic characterization, and expression of the heat shock protein HSP83 T. cruzi gene for further cell signaling studies. [Methodology] RNA was extracted from T. cruzi epimastigotes (EPm6 clone, MHOM/VE/2007/ 6c) using a commercial kit. The cDNA encoding HSP83 was determined using RT-PCR on extracted mRNA, for which the primers were designed based on the HSP83 sequence of T. cruzi strain CL Brener. Cloning was performed using pGEM®T-Easy and subcloned into the expression vector pQE30. Sequence and bioinformatic characterization were performed. The gene was expressed, and the recombinant protein was purified using affinity chromatography and identified through immunoblotting. [Results] Sequence analysis showed similarity to the gene encoding HSP83 from Trypanosoma cruzi, and HSP domains and B epitopes in the sequence were also observed. After 3 hours of induction with IPTG, a recombinant protein with an approximate weight of 83 kDa was obtained. The immunoblotting reaction with hyperimmune anti-T. cruzi epimastigote serum helped detect a single band with a molecular weight of nearly 83 kDa. [Conclusions] All results indicate that the cloning and characterization of HSP83 from Trypanosoma cruzi was achieved.

[Display omitted] Although photothermal therapy (PTT) is effective at killing tumor cells, it can inadvertently damage healthy tissues surrounding the tumor. Nevertheless, lowering the treatment temperature will reduce the therapeutic effectiveness. In this study, we employed 2,2′-((2Z,2′Z)-((4,4,9,9-Tetrahexyl-4,9-dihydro-s-indaceno[1,2- b :5,6- b ']dithiophene-2,7-diyl)bis(methanylylidene))bis(3-oxo-2,3-dihydro-1H-indene-2,1-diylidene)) dimalononitrile (IDIC), a molecule possessing a conventional acceptor–donor-acceptor (A-D-A) structure, as a photothermal agent (PTA) to facilitate effective mild photothermal therapy (mPTT). IDIC promotes intramolecular charge transfer under laser irradiation, making it a promising candidate for mPTT. To enhance the therapeutic potential of IDIC, we incorporated quercetin (Qu) into IDIC to form IDIC-Qu nanoparticles (NPs), which can inhibit heat shock protein (HSP) activity during the process of mPTT. Moreover, IDIC-Qu NPs exhibited exceptional water dispersibility and passive targeting abilities towards tumor tissues, attributed to its enhanced permeation and retention (EPR) effect. These advantageous properties position IDIC-Qu NPs as a promising candidate for targeted tumor treatment. Importantly, the IDIC-Qu NPs demonstrated controllable photothermal effects, leading to outstanding in vitro cytotoxicity against cancer cells and effective in vivo tumor ablation through mPTT. IDIC-Qu NPs nano-system enriches the family of organic PTAs and holds significant promise for future clinical applications of mPTT. [ABSTRACT FROM AUTHOR]

Heat shock proteins are essential molecular chaperones that play crucial roles in stabilizing protein structures, facilitating the repair or degradation of damaged proteins, and maintaining proteostasis and cellular functions. Extensive research has demonstrated that heat shock proteins are highly expressed in cancers and closely associated with tumorigenesis and progression. The "Hallmarks of Cancer" are the core features of cancer biology that collectively define a series of functional characteristics acquired by cells as they transition from a normal state to a state of tumor growth, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, enabled replicative immortality, the induction of angiogenesis, and the activation of invasion and metastasis. The pivotal roles of heat shock proteins in modulating the hallmarks of cancer through the activation or inhibition of various signaling pathways has been well documented. Therefore, this review provides an overview of the roles of heat shock proteins in vital biological processes from the perspective of the hallmarks of cancer and summarizes the small-molecule inhibitors that target heat shock proteins to regulate various cancer hallmarks. Moreover, we further discuss combination therapy strategies involving heat shock proteins and promising dual-target inhibitors to highlight the potential of targeting heat shock proteins for cancer treatment. In summary, this review highlights how targeting heat shock proteins could regulate the hallmarks of cancer, which will provide valuable information to better elucidate and understand the roles of heat shock proteins in oncology and the mechanisms of cancer occurrence and development and aid in the development of more efficacious and less toxic novel anticancer agents. [ABSTRACT FROM AUTHOR]

[Objective) The role of heat shock protein Hsp70 gene in the adaptation of Sogatella furcifera to abiotic stresses (insecticide, high/ low temperature, and UV-A) was revealed, which provided a reference for the green prevention and control of S. furcifera. [Method) Based on genomic and transcriptomic data, the Hsp70 gene in the S. furcifera was cloned and identified, and its transcription levels treated with insecticide, high/low temperature and UV-A stress were measured using RT-qPCR. [Result] A Hsp70 gene was successfully obtained and designated as SfHsp70-1. Its full-length sequence was determined to be 2322 bp, with an open reading frame of 2001 bp, encoding 666 amino acid residues, a molecular weight of approximately 72.91 kDa and a theoretical isoelectric point of 5. 11. There were three conserved domains of the Hsp70 family proteins in SfHsp70-1, with a conserved C-terminal endoplasmic reticulum Hsp70 sequence 'HDEL'. The sublethal concentration of thiamethoxam showed a significant dose effect, and LC10 significantly induced the transcriptional level of the SfHsp70-1 gene to 2.59 fold that of the control (acetone treatment), whereas LC25 concentration stress showed no significant impact. Additionally, temperature stress at 10 °C (30 min), 20 °C (30,60 min), and 40 ℃ (10,30,60 min) significantly induced the transcriptional levels of the SfHsp70-1 gene by 77.24%,62.00%,85.89%,138.96%,75.67% and 61.10% compared to the control (25 °C). UV-A (300 μW/cm²) stress significantly inhibited the transcriptional levels of the SfHsp70-1 gene, with a reduction of 87.85%,88.74%, 91.91%,89.78%,93.04% and 91. 16%, respectively, compared to the control (0 min exposure), and the expression level showed a gradually downward trend with the extension of treatment time. (Conclusion] The overexpression of the SfHsp70-1 gene contributes to the S. furcifera adaptation to thiamethoxam and high/low temperature stress. These findings provide a foundation for further investigating the role of the Hsp70 gene in the adaptation of the S. furcifera to abiotic stress and providing a reference for the green prevention development and control technology for S. furcifera. [ABSTRACT FROM AUTHOR]

Simple Summary: Hippodamia variegata is a key natural enemy of cotton-growing regions in northwestern China. In this study, transcriptome sequencing analysis was performed on H. variegata, after beetles were exposed to different temperatures (from 32 to 38 °C) for 24 h, using high-throughput sequencing technology. We found the largest number of differentially expressed genes (DEGs) in the 35 °C vs. 32 °C group (1151); the fewest DEGs were found in the 38 °C vs. 35 °C group (901), indicating that H. variegata expressed the largest number of newly mobilized genes under medium-high temperature (35 °C). Gene functional analysis showed that the DEGs were mainly involved in "Catalytic activity", "Oxidoreductase activity", "Metabolic pathways", and "Longevity regulating pathway-multiple species" gene groups. The results from qRT-PCR were consistent with the transcriptome data, confirming their reliability. Finally, the RNAi results showed that adult survival, longevity, and fecundity were lower in the group in which gene expression of the heat shock proteins (Hsp70-01 and Hsp68) was suppressed than in the control group (injection ds-GFP) at all the experimental temperatures (32, 35, and 38 °C). Our results indicate the important role of the heat shock proteins (Hsp70-01 and Hsp68) in resistance to high-temperature stress in H. variegata and provide a molecular basis for analyzing the thermotolerance mechanism of H. variegata. Previous studies have shown that the survival and reproduction of Hippodamia variegata are increasingly harmed by progressive increases in temperature (from 32 °C to 35 °C and 38 °C). In this study, transcriptome sequencing analysis was performed on H. variegata, after being exposed to different temperatures (from 32 to 38 °C) for 24 h, using high-throughput sequencing technology. We found the largest number of differentially expressed genes (DEGs) in the 35 °C vs. 32 °C group (1151) followed by the 38 °C vs. 32 °C group (1054) and then the 38 °C vs. 35 °C group (901), indicating that H. variegata expressed the largest number of newly mobilized genes under medium-high temperature (35 °C). Gene functional analysis showed that a large number of DEGs were involved in "Catalytic activity", "Oxidoreductase activity", "Metabolic pathways", and "Longevity regulating pathway-multiple species" gene groups. We randomly selected nine DEGs for validation using qRT-PCR. The results of qRT-PCR were consistent with the transcriptome data, confirming their reliability. Finally, the RNAi results showed that adult survival, longevity, and fecundity were lower in the group in which gene expression of the heat shock proteins (Hsp70-01 and Hsp68) was suppressed than in the control group (injection ds-GFP) at all the experimental temperatures (32, 35, and 38 °C). Our results indicate the important role of the heat shock proteins (Hsp70-01 and Hsp68) in resistance to high-temperature stress in H. variegata and provide a molecular basis for analyzing its thermotolerance mechanism. [ABSTRACT FROM AUTHOR]

Rice, a staple crop that feeds more than one-third of the world's population, encounters a wide range of biotic and abiotic stresses due to climate change. Rising temperature is one of the significant abiotic stresses affecting rice productivity worldwide. The development of heat-tolerant rice cultivars is critical in this regard. Weedy rice could potentially serve as a natural resource for genes conferring agronomically important traits beneficial to cultivated rice. However, heat tolerance in both cultivated and weedy rice is still understudied. This study screened a set of 180 weedy rice accessions for heat stress tolerance and further characterised them using genome-wide single-nucleotide polymorphisms (SNPs) analysis. Five heat-tolerant (HT) accessions (MU244, MU235, MU249, MU260 and MU237), along with five heat-susceptible (HS) accessions (MU100, MU114, MU264, MU251 and MU005), were subjected to relative electrical conductivity (REC) test and reactive oxidative species assay (ROS). These tests verified that the five HT accessions performed better under heat stress than their HS counterparts. In addition, whole-genome sequences of three HT (MU235, MU237 and MU066) and four HS (MU100, MU114, MU022 and MU005) accessions were selected for the genome-wide SNPs comparison, revealing substantial amino acid variation in the heat-tolerance-related genes between the HT and HS rice groups. The proposed genes and genome-wide SNP markers may help rice breeders better understand how different rice cultivars respond to heat stress. [ABSTRACT FROM AUTHOR]

Appropriate responses to environmental challenges are imperative for the survival of all living organisms. Exposure to low‐dose stresses is recognized to yield increased cellular fitness, a phenomenon termed hormesis. However, our molecular understanding of how cells respond to low‐dose stress remains profoundly limited. Here we report that histone variant H3.3‐specific chaperone, HIRA, is required for acquired tolerance, where low‐dose heat stress exposure confers resistance to subsequent lethal heat stress. We found that human HIRA activates stress‐responsive genes, including HSP70, by depositing histone H3.3 following low‐dose stresses. These genes are also marked with histone H3 Lys‐4 trimethylation and H3 Lys‐9 acetylation, both active chromatin markers. Moreover, depletion of HIRA greatly diminished acquired tolerance, both in normal diploid fibroblasts and in HeLa cells. Collectively, our study revealed that HIRA is required for eliciting adaptive stress responses under environmental fluctuations and is a master regulator of stress tolerance. [ABSTRACT FROM AUTHOR]

Photothermal therapy is an alternative cancer therapy that uses a photothermal agent with light irradiation to induce fatal hyperthermia in cancer cells. In a previous study, we found that ex vivo photothermal (PT) treatment induced expression of heat shock proteins (HSPs), such as HSP70, HSP27, and HSP90, in cancer cells; moreover, immunization with lysates from PT-treated tumor cells resulted in significant tumor growth inhibition in tumor-bearing mice. In this study, we hypothesized that sublethal PT treatment of antigen-presenting cells regulates their immunogenicity. We observed the upregulation of expression of intracellular HSP70 and surface activation markers, such as CD40, CD80, CD86, and MHC class II, in sublethal PT-treated cells. The protumoral activity of myeloid-derived suppressor cells (MDSCs) was reduced by sublethal hyperthermia. Furthermore, poorly immunogenic MDSCs were converted into immunogenic antigen-presenting cells by PT treatment. The differences in immunogenicity between MDSCs untreated or treated with the PT technique were evaluated using the Student's t-test or Mann–Whitney rank sum test. Collectively, direct hyperthermic treatment resulted in phenotypic changes and the functional regulation of immune cells. [ABSTRACT FROM AUTHOR]

Pakchoi is a kind of nonheading Chinese cabbage being widely cultivated not only in China but also all over Asia. High temperature is a major limiting factor influencing the yield and quality of pakchoi, while the mechanism of pakchoi dealing with high-temperature challenges remains largely elusive. In the present study, we conducted a comparative transcriptomic analysis, which was also validated by qPCR, of the heat-tolerant Xinxiaqing (XXQ) variant and Suzhouqing (SZQ) variant, which are heat-sensitive under high-temperature treatment. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggest that high-temperature-induced phytohormones signal transduction, especially auxin signal transduction, regulates the heat responses of pakchoi. Our further investigations imply that high-temperature-activated auxin signal plays a positive role in helping pakchoi deal with high-temperature challenge; IAA-pretreated pakchoi plants exhibited greater resistance to the high-temperature treatment, probably due to the induction of antioxidant activity. In addition, our study also identified six heat shock proteins/factors (HSPs/HSFs) whose up-regulation correlates with the elevated heat tolerance of pakchoi. Notably, among these high-temperature-induced heat-responsive factors, HSP20 and HSP26.5 are under the regulation of auxin signal, and this signal cascade contributes to enhancing the thermostability of pakchoi. In the present study, we identified crucial high-temperature-responsive factors and signaling pathways in pakchoi, which help in understanding the mechanism of pakchoi coping with high-temperature challenge. [ABSTRACT FROM AUTHOR]

Purpose: To determine if 7d of New Zealand blackcurrant (NZBC) extract alters the heat shock, inflammatory and apoptotic response during prolonged exertional-heat stress. Methods: Ten men (Age: 29 ± 2 years, Stature: 1.82 ± 0.02 m, Mass: 80.3 ± 2.7 kg, V̇O2max: 56 ± 2 mL·kg−1·min−1) ingested two capsules of CurraNZ™ (NZBC extract: 210 mg anthocyanins·day−1) or PLACEBO for 7d prior to 1 h treadmill run (65% V̇O2max) in hot ambient conditions (34 °C/40% RH). Blood samples were collected before (Pre), immediately after (Post), 1 h after (1-Post), and 4 h after (4-Post) exercise. Heat shock proteins (HSP90, HSP70, HSP32) were measured in plasma. HSP and protein markers of inflammatory capacity (TLR4, NF-κB) and apoptosis (BAX/BCL-2, Caspase 9) were measured in peripheral blood mononuclear cells (PBMC). Results: eHSP32 was elevated at baseline in NZBC(+ 31%; p < 0.001). In PLACEBO HSP32 content in PBMC was elevated at 4-Post(+ 98%; p = 0.002), whereas in NZBC it fell at Post(− 45%; p = 0.030) and 1-Post(− 48%; p = 0.026). eHSP70 was increased at Post in PLACEBO(+ 55.6%, p = 0.001) and NZBC (+ 50.7%, p = 0.010). eHSP90 was increased at Post(+ 77.9%, p < 0.001) and 1-Post(+ 73.2%, p < 0.001) in PLACEBO, with similar increases being shown in NZBC (+ 49.0%, p = 0.006 and + 66.2%, p = 0.001; respectively). TLR4 and NF-κB were both elevated in NZBC at PRE(+ 54%, p = 0.003 and + 57%, p = 0.004; respectively). Main effects of study condition were also shown for BAX/BCL-2(p = 0.025) and Caspase 9 (p = 0.043); both were higher in NZBC. Conclusion: 7d of NZBC extract supplementation increased eHSP32 and PBMC HSP32 content. It also increased inflammatory and apoptotic markers in PBMC, suggesting that NZBC supports the putative inflammatory response that accompanies exertional-heat stress. [ABSTRACT FROM AUTHOR]

Summary: The clade III subfamily of OsSWEETs includes transmembrane proteins necessary for susceptibility to bacterial blight (BB). These genes are targeted by the specific transcription activator‐like effector (TALE) of Xanthomonas oryzae pv. oryzae and mediate sucrose efflux for bacterial proliferation. However, the mechanism through which OsSWEETs regulate rice immunity has not been fully elucidated. Here, we demonstrated that the cytosolic carboxyl terminus of OsSWEET11a/Xa13 is required for complementing susceptibility to PXO99 in IRBB13 (xa13/xa13). Interestingly, the C‐terminus of ZmXa13, the maize homologue of OsSWEET11a/Xa13, could perfectly substitute for the C‐terminus of OsSWEET11a/Xa13. Furthermore, OsSWEET11a/Xa13 interacted with the high‐mobility group B1 (OsHMGB1) protein and the small heat shock‐like protein OsHsp20L through the same regions in the C‐terminus. Consistent with the physical interactions, knockdown or knockout of either OsHMGB1 or OsHsp20L caused an enhanced PXO99‐resistant phenotype similar to that of OsSWEET11a/OsXa13. Surprisingly, the plants in which OsHMGB1 or OsHsp20L was repressed developed increased resistance to PXO86, PXO61 and YN24, which carry TALEs targeting OsSWEET14/Xa41 or OsSWEET11a/Xa13. Additionally, OsHsp20L can interact with all six members of clade III OsSWEETs, whereas OsHMGB1 can interact with five other members in addition to OsSWEET12. Overall, we revealed that OsHMGB1 and OsHsp20L mediate conserved BB susceptibility by interacting with clade III OsSWEETs, which are candidates for breeding broad‐spectrum disease‐resistant rice. [ABSTRACT FROM AUTHOR]

Heat shock proteins (HSPs) play an important role in all living organisms under stress conditions by acting as molecular chaperones. The expression of different HSPs during stress varies depending on their protective functions and anti-apoptotic activities. The application of HSPs improves the efficiency and decreases the economic cost of animal breeding. By upregulating the expression of HSPs, feed supplements can improve stress tolerance in farm animals. In addition, high expression of HSPs is often a feature of tumor cells, and inhibiting the expression of HSPs is a promising novel method for killing these cells and treating cancers. In the present review, the findings of previous research on the application of HSPs in animal breeding and veterinary medicine are summarized, and the knowledge of the actions of HSPs in animals is briefly discussed. [ABSTRACT FROM AUTHOR]

JRK is a DNA‐binding protein of the pogo superfamily of transposons, which includes the well‐known centromere binding protein B (CENP‐B). Jrk null mice exhibit epilepsy, and growth and reproductive disorders, consistent with its relatively high expression in the brain and reproductive tissues. Human JRK DNA variants and gene expression levels are implicated in cancers and neuropsychiatric disorders. JRK protein modulates β‐catenin–TCF activity but little is known of its cellular functions. Based on its homology to CENP‐B, we determined whether JRK binds centromeric or other satellite DNAs. We show that human JRK binds satellite III DNA, which is abundant at the chromosome 9q12 juxtacentromeric region and on Yq12, both sites of nuclear stress body assembly. Human JRK‐GFP overexpressed in HeLa cells strongly localises to 9q12. Using an anti‐JRK antiserum we show that endogenous JRK co‐localises with a subset of centromeres in non‐stressed cells, and with heat shock factor 1 following heat shock. Knockdown of JRK in HeLa cells proportionately reduces heat shock protein gene expression in heat‐shocked cells. A role for JRK in regulating the heat shock response is consistent with the mouse Jrk null phenotype and suggests that human JRK may act as a modifier of diseases with a cellular stress component. [ABSTRACT FROM AUTHOR]

Global warming has profound effects on the living conditions and metabolism of organisms, including fish. The metabolic rate of fish increases as the temperature increases within its thermal tolerance range. Temperature changes can trigger a range of physiological reactions, including the activation of the stress axis and the production of HSPs. Under stress conditions, HSPs play a crucial role in antioxidant systems, immune responses, and enzyme activation. This study examined the effects of heat shock products (HSPs) on fish under temperature stress. Various HSP inducers (HSPis), including Pro-Tex®, amygdalin, and novel synthetic compounds derived from pirano piranazole (SZ, MZ, HN-P1, and HN-P2), were evaluated in isolated cells of sterlet sturgeon (Acipenser ruthenus) treated with temperature changes (18, 22, and 26 °C). Cells from the liver, kidney, and gills were cultured in vitro in the presence and absence of temperature stress and treated with HSPi compounds. To assess HSP27, HSP70, and HSP90 expression patterns, Western blotting was used. The HSPis and HSPi + temperature stress treatments affected the antioxidant capacity and immune parameters, among other enzyme activities. The results showed that HSPi compounds increase cell survival in vitro, positively modulate HSP expression and antioxidant levels, and decrease immune parameters. HSPi can increase A. ruthenus tolerance to temperature stress. In addition, the results indicate that these compounds can reverse adverse temperature effects. Further research is needed to determine how these ecological factors affect fish species' health in vivo and in combination with other stressors. [ABSTRACT FROM AUTHOR]

The study aims to investigate the protective effect of chlorogenic acid on the intestinal barrier of broiler under chronic heat stress. 240 AA broilers were randomly divided into 4 groups: control group with a feeding temperature of (22±2） ℃, and the other three groups with a feeding temperature of (30± 2) ℃. The chronic heat stress group (HS group) was fed with the basic diet daily, while the low-dose (LCA group) and high-dose chlorogenic acid groups (HCA group) were supplemented with chlorogenic acid at 300 mg/kg and 600 mg/kg, respectively. The production performance, intestinal antioxidant indicators, inflammatory factors, heat shock proteins, and barrier integrity-related protein expression were tested. The results showed that 600 mg/kg chlorogenic acid in the basic diet could promote the growth performance of heat-stressed broilers and significantly increase the ADG (P<0.05), significantly improved the activity of SOD and CAT in the intestinal tract of heat-stressed broilers (P<0.05), significantly reduced the content of peroxides MDA (P< 0.05), significantly inhibited the concentration of IL-1β, IL-6, and TNF- α (P<0.05), significantly increased the content of IL-10 (P<0.05), significantly reduced the gene expression of HSP27, HSP70, and HSP90 (P<0.05), and significantly promoted the gene expression of Claudin1, Occludin, and ZO-1 (P<0.05). In summary, the chlorogenic acid can reduce oxidative stress caused by high temperature environments on the intestines of broiler, reduce the secretion of inflammatory factors in the intestines, significantly improve the ability of intestinal tissues to resist heat stress, and maintain the integrity of the intestinal tissue barrier. [ABSTRACT FROM AUTHOR]

Hsp40–Hsp70 typically function in concert as molecular chaperones, and their roles in post-infection immune responses are increasingly recognized. However, in the economically important fish species Scophthalmus maximus (turbot), there is still a lack in the systematic identification, interaction models, and binding site analysis of these proteins. Herein, 62 Hsp40 genes and 16 Hsp70 genes were identified in the turbot at a genome-wide level and were unevenly distributed on 22 chromosomes through chromosomal distribution analysis. Phylogenetic and syntenic analysis provided strong evidence in supporting the orthologies and paralogies of these HSPs. Protein–protein interaction and expression analysis was conducted to predict the expression profile after challenging with Aeromonas salmonicida. dnajb1b and hspa1a were found to have a co-expression trend under infection stresses. Molecular docking was performed using Auto-Dock Tool and PyMOL for this pair of chaperone proteins. It was discovered that in addition to the interaction sites in the J domain, the carboxyl-terminal domain of Hsp40 also plays a crucial role in its interaction with Hsp70. This is important for the mechanistic understanding of the Hsp40–Hsp70 chaperone system, providing a theoretical basis for turbot disease resistance breeding, and effective value for the prevention of certain diseases in turbot. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is most commonly diagnosed worldwide. Liquiritigenin is a flavonoid found in various species of the Glycyrrhiza genus, showing anti-tumor activity. This article was to explore the influences of liquiritigenin on the biological behaviors of BC cells and its underlying mechanism. BC cells were treated with liquiritigenin alone or transfected with oe-HSP90 before liquiritigenin treatment. RTqPCR and Western blotting were employed to examine the levels of HSP90, Snail, Ecadherin, HSC70, and LAMP-2A. Cell viability, proliferation, migration, and invasion were evaluated by performing MTT, colony formation, scratch, and Transwell assays, respectively. Liquiritigenin treatment reduced HSP90 and Snail levels and enhanced E-cadherin expression as well as inhibiting the proliferation, migration, and invasion of BC cells. Moreover, liquiritigenin treatment decreased the expression of HSC70 and LAMP-2A, proteins related to chaperone-mediated autophagy (CMA). HSP90 overexpression promoted the CMA, invasion, and migration of BC cells under liquiritigenin treatment. Liquiritigenin inhibits HSP90-mediated CMA, thereby suppressing BC cell growth. [ABSTRACT FROM AUTHOR]

The Ti 3 C 2 @Qu nanocomposites are constructed by utilizing the high photothermal conversion ability of Ti 3 C 2 nanosheets in combination with quercetin (Qu) as an inhibitor of heat shock protein 70 (HSP70). Qu molecules are loaded onto the nanoplatform in a pH-sensitive controlled release manner. The acidic environment of the tumor causes the burst-release of Qu molecules, which deplete the level of HSP70 in tumor cells and leave the tumor cells out from the protection of the heat-resistant survival pathway in advance, thus sensitizing the hyperthermia efficacy. [Display omitted] Photothermal therapy (PTT) has attracted much attention due to its less invasive, controllable and highly effective nature. However, PTT also suffers from intrinsic cancer resistance mediated by cell survival pathways. These survival pathways are regulated by a variety of proteins, among which heat shock protein (HSP) triggers thermotolerance and protects tumor cells from hyperthermia-induced apoptosis. Confronted by this challenge, we propose and validate here a novel MXene-based HSP-inhibited mild photothermal platform, which significantly enhances the sensitivity of tumor cells to heat-induced stress and thus improves the PPT efficacy. The Ti 3 C 2 @Qu nanocomposites are constructed by utilizing the high photothermal conversion ability of Ti 3 C 2 nanosheets in combination with quercetin (Qu) as an inhibitor of HSP70. Qu molecules are loaded onto the nanoplatform in a pH-sensitive controlled release manner. The acidic environment of the tumor causes the burst-release of Qu molecules, which deplete the level of heat shock protein 70 (HSP70) in tumor cells and leave the tumor cells out from the protection of the heat-resistant survival pathway in advance, thus sensitizing the hyperthermia efficacy. The nanostructure, photothermal properties, pH-responsive controlled release, synergistic photothermal ablation of tumor cells in vitro and in vivo, and hyperthermia effect on subcellular structures of the Ti 3 C 2 @Qu nanocomposites were systematically investigated. [ABSTRACT FROM AUTHOR]

Background. Investigating deaths related to chronic cocaine abuse can be a difficult task, particularly when they occur suddenly and without explanation. Cocaine abuse can trigger biological effects similar to physiological stressors, causing the body to produce heatshock proteins (HSPs). However, there is still limited information on the specific levels of each HSP type. This systematic review aims to comprehensively collect and analyze all existing literature data regarding the relationship between HSPs and cocaine abuse to investigate whether HSPs can be utilized as forensic markers for accurately diagnosing cocaine-related deaths. Materials and Methods. The Authors conducted the literature search using PubMed and Scopus databases, searching for articles published between 1 January 1992 and 1 April 2024 using the text string: "heat shock protein" AND "cocaine". Conclusion. Twenty articles were collected, but only nine were included in the systematic review. The data gathered pertained to both human and murine species. The majority of the analyzed articles revealed an elevation in HSP25, HSP27, HSP60, HSP70, HSP72, and HSP73 levels in the brain, cerebellum, and liver, indicating cocaine-induced stress. The relationship between HSP and cocaine has been unclear over time. However, recent studies have shown that cocaine consumption leads to an increase in HSP levels, particularly in the central nervous system. This correlation can also be observed in certain types of liver cells that are capable of binding cocaine metabolites. In conclusion, HSP brain levels, along with other biomarkers, may be used to diagnose sudden, unexpected death related to cocaine abuse. [ABSTRACT FROM AUTHOR]

Misfolded and aggregated proteins build up in neurodegenerative illnesses, which causes neuronal dysfunction and ultimately neuronal death. In the last few years, there has been a significant upsurge in the level of interest towards the function of molecular chaperones in the control of misfolding and aggregation. The crucial molecular chaperones implicated in neurodegenerative illnesses are covered in this review article, along with a variety of their different methods of action. By aiding in protein folding, avoiding misfolding, and enabling protein breakdown, molecular chaperones serve critical roles in preserving protein homeostasis. By aiding in protein folding, avoiding misfolding, and enabling protein breakdown, molecular chaperones have integral roles in preserving regulation of protein balance. It has been demonstrated that aging, a significant risk factor for neurological disorders, affects how molecular chaperones function. The aggregation of misfolded proteins and the development of neurodegeneration may be facilitated by the aging-related reduction in chaperone activity. Molecular chaperones have also been linked to the pathophysiology of several instances of neuron withering illnesses, enumerating as Parkinson's disease, Huntington's disease, and Alzheimer's disease. Molecular chaperones have become potential therapy targets concerning with the prevention and therapeutic approach for brain disorders due to their crucial function in protein homeostasis and their connection to neurodegenerative illnesses. Protein homeostasis can be restored, and illness progression can be slowed down by methods that increase chaperone function or modify their expression. This review emphasizes the importance of molecular chaperones in the context of neuron withering disorders and their potential as therapeutic targets for brain disorders. [ABSTRACT FROM AUTHOR]

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ABSTRACT: Fluoride is one of the essential trace elements for body. However, excessive fluoride poses a major threat to human and animal health. Fluorosis may cause pathological damage of the duodenum, but the underlying mechanism needs to be further studied. This study was to investigate the effects of long-term exposure to sodium fluoride (0, 500, 1,000, 2,000 mg/kg) on the duodenum of chickens. The results showed that after NaF exposure, intestinal epithelial cells were disarranged, necrotic or even exfoliated, goblet cells and mucus secretion were increased, and inflammatory response was induced in duodenal tissue. Oxidative stress, endoplasmic reticulum stress (ERs), and heat shock proteins (HSPs) are an adaptive response, however long-term, excessive changes are detrimental. Fluorosis activates ERs through IRE1, PERK and ATF6 pathways, increases the expression of HSP60, HSP70 and HSP90, and causes apoptosis and oxidative damage in duodenal tissue. In addition, fluorosis can activate the MAPK signaling pathway. This article can provide a reference for exploring the potential duodenal toxicity of sodium fluoride.

Background: Heat shock proteins (HSPs) play a critical role in cellular stress responses and have been implicated in numerous diseases, including Parkinson's disease (PD) and various cancers. Understanding the differential expression and functional implications of HSPs in these conditions is crucial for identifying potential therapeutic targets and biomarkers for diagnosis and prognosis. Methods: We utilized combined datasets (GSE6613 and GSE72267) to identify and analyze the heat shock-related genes differentially expressed in PD. Gene Set Variation Analysis (GSVA) was performed to explore functional profiles, while LASSO regression was employed to screen potential PD biomarkers. In glioma, prognostic value, immune infiltration, and pathway enrichment associated with HSPA1L gene expression were assessed via Kaplan-Meier plots, ssGSEA, and enrichment analyses. Results: In PD, we identified 17 differentially expressed HSPs. Enrichment analysis revealed significant pathways related to protein homeostasis and cellular stress responses. LASSO regression pinpointed 12 genes, including HSPA1L, as significant markers for PD, with nomogram and calibration plots indicating predictive accuracy. Stratification based on HSPA1L expression in PD highlighted differentially active biological processes, immune responses, and metabolic disruptions. In the pan-cancer analysis, HSPA1L showed variable expression across cancer types and a significant correlation with patient survival and immune infiltration. In glioma, low HSPA1L expression was associated with worse overall survival, distinct immune infiltration patterns, and altered pathway activities. Conclusion: This integrative study reveals the substantial role of HSPs, especially HSPA1L, in the pathogenesis and prognosis of PD and glioma. Our findings offer new perspectives on the molecular mechanisms underlying these diseases and propose HSPA1L as a potential prognostic biomarker and a target for therapeutic intervention.

The rise in world temperature has led to remarkable changes in global climate patterns, eventually devastating the crops. Climate change has led to the emergence of various abiotic factors which has decreased the crop’s productivity. Heat stress has a great role in crop production reduction among various abiotic factors. Rise in temperature at different stages of crop growth beyond threshold level has caused significant crop damage remarkably in wheat. Heat stress causes immense disturbance to the morphological, physiological, and biochemical processes of crops, eventually leading to a decrease in wheat yield. Each degree increase in global temperature has led to a 6% decline in the wheat yield. Heat stress causes a significant decrease in the plant height, photosynthesis rate, dehiscence of the anther, floret fertility, kernel weight, CO2 absorption and assimilation, photosynthesis activity, and chlorophyll content, and starch synthesis in endosperm. Among other stages of the wheat crop, the flowering stage is so prone to heat stress which decreases the seed set. The wheat crop has several tolerance mechanisms to overcome heat stress such as leaf senescence, canopy temperature depression, and heat shock protein. The effect of heat stress is minimized by the production of heat shock protein. Various biochemical and molecular approaches can aid in understanding the effects created by heat stress.

AbstractHeat shock proteins (HSP) have been associated with a range of persistent inflammatory disorders; however, little research has been conducted on the involvement of HSP in the development of ankylosing spondylitis (AS). The research aims to identify a diagnostic signature based on HSP-related genes and determine the molecular subtypes of AS. We gathered the transcriptional data of patients with AS from the GSE73754 dataset and conducted a literature search for HSP-related genes (HRGs). The logistic regression model was utilized for the identification of hub HRGs associated with AS. Subsequently, these HRGs were employed in the construction of a nomogram prediction model. We employed a consensus clustering approach to identify novel molecular subgroups. Subsequently, we conducted functional analyses, encompassing GO, KEGG, and GSEA, to elucidate the underlying mechanisms between these subgroups. To assess the immunological landscape, we employed the xCell algorithm. Through logistic regression analysis, the four core HRGs (CCT2, HSPA6, DNAJB14, and DNAJC5) were confirmed as potential biomarkers for AS. Subsequent stratification revealed two distinct molecular phenotypes, designated as Cluster 1 and Cluster 2. Notably, Cluster 2 was characterized by the upregulation of pathways pertinent to immune response and inflammation. Our research suggests that the CCT2, HSPA6, DNAJB14, and DNAJC5 exhibit potential as effective blood-based diagnostic biomarkers for AS. These findings contribute to a deeper comprehension of the underlying mechanisms involved in the development of AS and offer potential targets for personalized therapeutic interventions.

Abstract The precise and effective activation of the immune response is crucial in promising therapy curing cancer. Photoimmunotherapy (PIT) is an emerging strategy for precise regulation and highly spatiotemporal selectivity. However, this approach faces a significant challenge due to the off‐target effect and the immunosuppressive microenvironment. To address this challenge, a nanoscale full‐active pharmaceutical ingredient (API) photo‐immune stimulator was developed. This formulation overcomes the limitations of PIT by strengthening the ability to penetrate tumors deeply and inducing precise and potent mitochondria‐targeted dual‐mode photodynamic therapy and photothermal therapy. Along with inhibiting overexpressed Hsp90, this nanosensitizer in turn improves the immunosuppressive microenvironment. Ultimately, this mitochondria‐targeted PIT demonstrated potent antitumor efficacy, achieving a remarkable inhibition rate of ≥95% for both established primary tumors and distant abscopal tumors. In conclusion, this novel self‐delivery full‐API nanosystem enhances the efficacy of phototherapy and reprograms the immunosuppressive microenvironment, thereby holding great promise in the development of precise and effective immunotherapy.

Hsp70 is a key cellular system counteracting protein misfolding and aggregation, associated with stress, ageing, and disease. Hsp70 solubilises aggregates and aids protein refolding through substrate binding and release cycles regulated by co-chaperones: J-domain proteins (JDPs) and nucleotide exchange factors (NEFs). Here, we elucidate the collaborative impact of Hsp110 NEFs and different JDP classes throughout Hsp70-dependent aggregate processing. We show that Hsp110 plays a major role at initial stages of disaggregation, determining its final efficacy. The NEF catalyses the recruitment of thick Hsp70 assemblies onto aggregate surface, which modifies aggregates into smaller species more readily processed by chaperones. Hsp70 stimulation by Hsp110 is much stronger with class B than class A JDPs and requires the auxiliary interaction between class B JDP and the Hsp70 EEVD motif. Furthermore, we demonstrate for the first time that Hsp110 disrupts the JDP-Hsp70 interaction. Such destabilisation of chaperone complexes at the aggregate surface might improve disaggregation, but also lead to the inhibition above the sub-stoichiometric Hsp110 optimum. Thus, balanced interplay between the co-chaperones and Hsp70 is critical to unlock its disaggregating potential.

Escherichia coli ClpB and Saccharomyces cerevisiae Hsp104 are AAA+ motor proteins essential for proteome maintenance and thermal tolerance. ClpB and Hsp104 have been proposed to extract a polypeptide from an aggregate and processively translocate the chain through the axial channel of its hexameric ring structure. However, the mechanism of translocation and if this reaction is processive remains disputed. We reported that Hsp104 and ClpB are non-processive on unfolded model substrates. Others have reported that ClpB is able to processively translocate a mechanically unfolded polypeptide chain at rates over 240 amino acids (aa) per second. Here, we report the development of a single turnover stopped-flow fluorescence strategy that reports on processive protein unfolding catalyzed by ClpB. We show that when translocation catalyzed by ClpB is challenged by stably folded protein structure, the motor enzymatically unfolds the substrate at a rate of ~0.9 aa s−1 with a kinetic step-size of ~60 amino acids at sub-saturating [ATP]. We reconcile the apparent controversy by defining enzyme catalyzed protein unfolding and translocation as two distinct reactions with different mechanisms of action. We propose a model where slow unfolding followed by fast translocation represents an important mechanistic feature that allows the motor to rapidly translocate up to the next folded region or rapidly dissociate if no additional fold is encountered.