Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions.

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10-8) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10-5). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue datasets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (false discovery rate <0.05). Finally, by integrating genome-wide HiChIP interactome analysis with transcriptome-wide association study (TWAS), variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by a genome-wide association study.

Role of prebiotics in enhancing the function of next-generation probiotics in gut microbiota.

With the development of high-throughput DNA sequencing and molecular analysis technologies, next-generation probiotics (NGPs) are increasingly gaining attention as live bacterial therapeutics for treatment of diseases. However, compared to traditional probiotics, NGPs are much more vulnerable to the harsh conditions in the human gastrointestinal tract, and their functional mechanisms in the gut are more complex. Prebiotics have been confirmed to play a critical role in improving the function and viability of traditional probiotics. Defined as substrates that are selectively utilized by host microorganisms conferring a health benefit, prebiotics are also important for NGPs. This review summarizes potential prebiotics for use with NGPs and clarifies their characteristics and functional mechanisms. Then we particularly focus on illustrating the protective effects of various prebiotics by enhancing the antioxidant capacity and their resistance to digestive fluids. We also elucidate the role of prebiotics in regulating anti-bacterial effects, intestinal barrier maintenance, and cross-feeding mechanisms of NPGs. With the expanding range of candidate NGPs and prebiotic substrates, more studies need to be conducted to comprehensively elucidate the interactions between prebiotics and NGPs outside and inside hosts, in order to boost their nutritional and healthcare applications.

Evaluation of the Function of Probiotics, Emphasizing the Role of their Binding to the Intestinal Epithelium in the Stability and their Effects on the Immune System.

Due to the importance of using cost-effective methods for therapeutic purposes, the function of probiotics as safe microorganisms and the study of their relevant functional mechanisms have recently been in the spotlight. Finding the mechanisms of attachment and stability and their beneficial effects on the immune system can be useful in identifying and increasing the therapeutic effects of probiotics. In this review, the functional mechanisms of probiotics were comprehensively investigated. Relevant articles were searched in scientific sources, documents, and databases, including PubMed, NCBI, Bactibace, OptiBac, and Bagel4. The most important functional mechanisms of probiotics and their effects on strengthening the epithelial barrier, competitive inhibition of pathogenic microorganisms, production of antimicrobials, binding and interaction with the host, and regulatory effects on the immune system were discussed.In this regard, the attachment of probiotics to the epithelium is very important because the prerequisite for their proper functioning is to establish a proper connection to the epithelium. Therefore, more attention should be paid to the binding effect of probiotics, including sortase A, a significant factor involved in the expression of sortase-dependent proteins (SDP), on their surface as mediators of intestinal epithelial cell binding. In general, by investigating the functional mechanisms of probiotics, it was concluded that the mechanism by which probiotics regulate the immune system and adhesion capacity can directly and indirectly have preventive and therapeutic effects on a wide range of diseases. However, further study of these mechanisms requires extensive research on various aspects.

Membrane lipids are both the substrates and a mechanistically responsive environment of TMEM16 scramblase proteins.

Recent discoveries about functional mechanisms of proteins in the TMEM16 family of phospholipid scramblases have illuminated the dual role of the membrane as both the substrate and a mechanistically responsive environment in the wide range of physiological processes and genetic disorders in which they are implicated. This is highlighted in the review of recent findings from our collaborative investigations of molecular mechanisms of TMEM16 scramblases that emerged from iterative functional, structural, and computational experimentation. In the context of this review, we present new MD simulations and trajectory analyses motivated by the fact that new structural information about the TMEM16 scramblases is emerging from cryo-EM determinations in lipid nanodiscs. Because the functional environment of these proteins in in vivo and in in vitro is closer to flat membranes, we studied comparatively the responses of the membrane to the TMEM16 proteins in flat membranes and nanodiscs. We find that bilayer shapes in the nanodiscs are very different from those observed in the flat membrane systems, but the function-related slanting of the membrane observed at the nhTMEM16 boundary with the protein is similar in the nanodiscs and in the flat bilayers. This changes, however, in the bilayer composed of longer-tail lipids, which is thicker near the phospholipid translocation pathway, which may reflect an enhanced tendency of the long tails to penetrate the pathway and create, as shown previously, a nonconductive environment. These findings support the correspondence between the mechanistic involvement of the lipid environment in the flat membranes, and the nanodiscs. © 2019 Wiley Periodicals, Inc.

The Osmotin-Like Protein Gene PdOLP1 Is Involved in Secondary Cell Wall Biosynthesis during Wood Formation in Poplar.

Osmotin-like proteins (OLPs) mediate defenses against abiotic and biotic stresses and fungal pathogens in plants. However, no OLPs have been functionally elucidated in poplar. Here, we report an osmotin-like protein designated PdOLP1 from Populus deltoides (Marsh.). Expression analysis showed that PdOLP1 transcripts were mainly present in immature xylem and immature phloem during vascular tissue development in P. deltoides. We conducted phenotypic, anatomical, and molecular analyses of PdOLP1-overexpressing lines and the PdOLP1-downregulated hybrid poplar 84K (Populus alba × Populus glandulosa) (Hybrid poplar 84K PagOLP1, PagOLP2, PagOLP3 and PagOLP4 are highly homologous to PdOLP1, and are downregulated in PdOLP1-downregulated hybrid poplar 84K). The overexpression of PdOLP1 led to a reduction in the radial width and cell layer number in the xylem and phloem zones, in expression of genes involved in lignin biosynthesis, and in the fibers and vessels of xylem cell walls in the overexpressing lines. Additionally, the xylem vessels and fibers of PdOLP1-downregulated poplar exhibited increased secondary cell wall thickness. Elevated expression of secondary wall biosynthetic genes was accompanied by increases in lignin content, dry weight biomass, and carbon storage in PdOLP1-downregulated lines. A PdOLP1 coexpression network was constructed and showed that PdOLP1 was coexpressed with a large number of genes involved in secondary cell wall biosynthesis and wood development in poplar. Moreover, based on transcriptional activation assays, PtobZIP5 and PtobHLH7 activated the PdOLP1 promoter, whereas PtoBLH8 and PtoWRKY40 repressed it. A yeast one-hybrid (Y1H) assay confirmed interaction of PtoBLH8, PtoMYB3, and PtoWRKY40 with the PdOLP1 promoter in vivo. Together, our results suggest that PdOLP1 is a negative regulator of secondary wall biosynthesis and may be valuable for manipulating secondary cell wall deposition to improve carbon fixation efficiency in tree species.

Computational Approaches for Functional Prediction and Characterisation of Long Noncoding RNAs.

Although a considerable portion of eukaryotic genomes is transcribed as long noncoding RNAs (lncRNAs), the vast majority are functionally uncharacterised. The rapidly expanding catalogue of mechanistically investigated lncRNAs has provided evidence for distinct functional subclasses, which are now ripe for exploitation as a general model to predict functions for uncharacterised lncRNAs. By utilising publicly-available genome-wide datasets and computational methods, we present several developed and emerging in silico approaches to characterise and predict the functions of lncRNAs. We propose that the application of these techniques provides valuable functional and mechanistic insight into lncRNAs, and is a crucial step for informing subsequent functional studies.

The Mechanisms of Pharmacological Activities of Ophiocordyceps sinensis Fungi.

The entomopathogenic fungus Ophiocordyceps sinensis, formerly known as Cordyceps sinensis, has long been used as a traditional Chinese medicine for the treatment of many illnesses. In recent years its usage has increased dramatically because of the improvement of people's living standard and the emphasis on health. Such demands have resulted in over-harvesting of this fungus in the wild. Fortunately, scientists have demonstrated that artificially cultured and fermented mycelial products of O. sinensis have similar pharmacological activities to wild O. sinensis. The availability of laboratory cultures will likely to further expand its usage for the treatment of various illnesses. In this review, we summarize recent results on the pharmacological activities of the components of O. sinensis and their putative mechanisms of actions. Copyright © 2016 John Wiley & Sons, Ltd.

Pan-Cancer Analysis of GALNT6 with Potential Implications for Prognosis and Tumor Microenvironment in Human Cancer Based on Bioinformatics and qPCR Verification.

Purpose: We explored the expression and prognostic value of GALNT6 and the tumor microenvironment of pan-cancer in humans. Methods: In this study, we explored the expression pattern of GALNT6 pan-cancer across multiple databases. The prognostic value of GALNT6 was evaluated using the Kaplan-Meier method. The types and numbers of GALNT6 gene alterations were exhibited using the cBio Cancer Genomics Portal. The correlations between GALNT6 expression and immune infiltration in cancers were analyzed using the database Tumor Immune Estimation Resource 2. We also used the Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analysis to investigate the molecular mechanisms of the GALNT6 gene in tumorigenesis. The expression of GALNT6 was also further verified by qPCR in lung adenocarcinoma tissues. Results: In general, compared with normal tissue, tumor tissue had a higher expression level of GALNT6. GALNT6 showed a protective effect in colon carcinoma and other cancers; however, a high expression level of GALNT6 was detrimental to survival in bladder cancer and in pheochromocytoma and paraganglioma. Mutation, amplification, and deep deletion were the three main types of GALNT6 mutations in tumors. There was a significant positive correlation between GALNT6 expression and immune infiltration of CD8+ T-cells in skin cutaneous melanoma metastasis, based on most of the algorithms used. Moreover, protein processing- and glycoprotein metabolic-associated functions were involved in the functional mechanisms of GALNT6. Conclusion: This first pan-cancer study offers a relatively comprehensive understanding of the oncogenic roles of GALNT6 across different cancer types.

Distinct gut microbiomes in Thai patients with colorectal polyps.

BACKGROUND: Colorectal polyps that develop via the conventional adenoma-carcinoma sequence [e.g., tubular adenoma (TA)] often progress to malignancy and are closely associated with changes in the composition of the gut microbiome. There is limited research concerning the microbial functions and gut microbiomes associated with colorectal polyps that arise through the serrated polyp pathway, such as hyperplastic polyps (HP). Exploration of microbiome alterations associated with HP and TA would improve the understanding of mechanisms by which specific microbes and their metabolic pathways contribute to colorectal carcinogenesis. AIM: To investigate gut microbiome signatures, microbial associations, and microbial functions in HP and TA patients. METHODS: Full-length 16S rRNA sequencing was used to characterize the gut microbiome in stool samples from control participants without polyps [control group (CT), n = 40], patients with HP (n = 52), and patients with TA (n = 60). Significant differences in gut microbiome composition and functional mechanisms were identified between the CT group and patients with HP or TA. Analytical techniques in this study included differential abundance analysis, co-occurrence network analysis, and differential pathway analysis. RESULTS: Colorectal cancer (CRC)-associated bacteria, including Streptococcus gallolyticus (S. gallolyticus), Bacteroides fragilis, and Clostridium symbiosum, were identified as characteristic microbial species in TA patients. Mediterraneibacter gnavus, associated with dysbiosis and gastrointestinal diseases, was significantly differentially abundant in the HP and TA groups. Functional pathway analysis revealed that HP patients exhibited enrichment in the sulfur oxidation pathway exclusively, whereas TA patients showed dominance in pathways related to secondary metabolite biosynthesis (e.g., mevalonate); S. gallolyticus was a major contributor. Co-occurrence network and dynamic network analyses revealed co-occurrence of dysbiosis-associated bacteria in HP patients, whereas TA patients exhibited co-occurrence of CRC-associated bacteria. Furthermore, the co-occurrence of SCFA-producing bacteria was lower in TA patients than HP patients. CONCLUSION: This study revealed distinct gut microbiome signatures associated with pathways of colorectal polyp development, providing insights concerning the roles of microbial species, functional pathways, and microbial interactions in colorectal carcinogenesis.

Massively parallel reporter assay confirms regulatory potential of hQTLs and reveals important variants in lupus and other autoimmune diseases.

We designed a massively parallel reporter assay (MPRA) in an Epstein-Barr virus transformed B cell line to directly characterize the potential for histone post-translational modifications, i.e., histone quantitative trait loci (hQTLs), expression QTLs (eQTLs), and variants on systemic lupus erythematosus (SLE) and autoimmune (AI) disease risk haplotypes to modulate regulatory activity in an allele-dependent manner. Our study demonstrates that hQTLs, as a group, are more likely to modulate regulatory activity in an MPRA compared with other variant classes tested, including a set of eQTLs previously shown to interact with hQTLs and tested AI risk variants. In addition, we nominate 17 variants (including 11 previously unreported) as putative causal variants for SLE and another 14 for various other AI diseases, prioritizing these variants for future functional studies in primary and immortalized B cells. Thus, we uncover important insights into the mechanistic relationships among genotype, epigenetics, and gene expression in SLE and AI disease phenotypes.

CircRNA-miRNA-VEGFA: an important pathway to regulate cancer pathogenesis.

Cancers, especially malignant tumors, contribute to high global mortality rates, resulting in great economic burden to society. Many factors are associated with cancer pathogenesis, including vascular endothelial growth factor-A (VEGFA) and circular RNAs (circRNA). VEGFA is a pivotal regulator of vascular development such as angiogenesis, which is an important process in cancer development. CircRNAs have covalently closed structures, making them highly stable. CircRNAs are widely distributed and participate in many physiological and pathological processes, including modulating cancer pathogenesis. CircRNAs act as transcriptional regulators of parental genes, microRNA (miRNA)/RNA binding protein (RBP) sponges, protein templates. CircRNAs mainly function via binding to miRNAs. CircRNAs have been shown to influence different diseases such as coronary artery diseases and cancers by regulating VEGFA levels via binding to miRNAs. In this paper, we explored the origin and functional pathways of VEGFA, reviewed the current understanding of circRNA properties and action mechanisms, and summarized the role of circRNAs in regulating VEGFA during cancer pathogenesis.

The Mechanism Underlying the ncRNA Dysregulation Pattern in Hepatocellular Carcinoma and Its Tumor Microenvironment.

HCC is one of the most common malignant tumors and has an extremely poor prognosis. Accumulating studies have shown that noncoding RNA (ncRNA) plays an important role in hepatocellular carcinoma (HCC) development. However, the details of the related mechanisms remain unclear. The heterogeneity of the tumor microenvironment (TME) calls for ample research with deep molecular characterization, with the hope of developing novel biomarkers to improve prognosis, diagnosis and treatment. ncRNAs, particularly microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), have been found to be correlated with HCC neogenesis and progression. In this review, we summarized the aberrant epigenetic and genetic alterations caused by dysregulated ncRNAs and the functional mechanism of classical ncRNAs in the regulation of gene expression. In addition, we focused on the role of ncRNAs in the TME in the regulation of tumor cell proliferation, invasion, migration, immune cell infiltration and functional activation. This may provide a foundation for the development of promising potential prognostic/predictive biomarkers and novel therapies for HCC patients.

Research Progress of Soil Microorganisms in Response to Heavy Metals in Rice.

Soil heavy-metal pollution leads to excessive heavy metals in rice and other food crops, which has caused serious impacts on the ecological environment and on human health. In recent years, environmental friendly treatment methods that reduce the bioavailability of heavy metals in soil by soil microorganisms improving the tolerance of heavy metals in rice and reducing the transfer of heavy metals from the roots to the above-ground parts of rice have attracted much attention. This paper reviews the role and mechanism of soil microorganisms in alleviating heavy-metal stress in rice at home and abroad in recent years. At present, microorganisms tolerant to heavy metals mainly include bacteria and fungi, and their mechanisms include the adsorption of heavy metals by microorganisms, the secretion of growth-promoting substances (growth hormone, ACC deaminase, IAA), changing the physical and chemical properties of the soil and the composition of the microbial community, changing the transport mode of heavy metals in soil, the improvement of the antioxidant capacity of rice, etc. Hence, soil microorganisms have good application value and prospects in rice and other crops. However, the vast majority of current research focuses on a single strain, the screening principles of strains are limited, the pathogenicities of the strains have not been evaluated, and there are still few field experiments under natural conditions. In the future, we should strengthen the action of soil microorganisms on rice in response to the above problems in heavy metals, to better promote the microbial remediation technology.

Schisantherin D from Schisandra chinensis (Turcz.) Baill. exhibits anti-liver fibrosis capacity via modulating ETBR involved signaling, an in vitro and in vivo study.

Excess levels of chemical hepatotoxicants (alcohol, aflatoxin B1), oxidative drugs (acetaminophen) and some cytokines (ET-1, TGF-ß1) can induce chronic or acute liver injury. After these, the severe hepatic disease, especially the liver fibrosis (LF) occurs without taking measures, which brings threat to human health. The dibenzocyclooctadiene lignans of S. chinensis (SCDLs) were found to act as the hepatoprotective components via blocking endothelin B receptor (ETBR). While study on its anti-LF mechanisms especially for its refined compound of schisantherin D (SC-D) is still a lack. So this study aims to investigate the anti-fibrosis effect of SC-D with in vitro and in vivo assays. Bioinformatics analysis revealed the close relations of ETBR to Smad2, Smad3, Nrf2, etc. in LF-related signaling pathways (such as TGF-ß/Smad and Nrf2/ARE). Histopathological staining on livers showed the recovery trend in SC-D treated LF mice. SC-D also modulated expressions of ETBR and fibrosis or anti-oxidative related proteins (such as TIMP1, p-Smad2/3, Nrf2, Smad7, etc.) in LF mice livers. Serum levels of TNF-α, COLI, ALT, AST and LDH in SC-D treated mice were also downregulated compared with LF mice, and upregulated expression of GSH. In vitro studies, SC-D also modulated expressions of LF-related proteins to the normal tendency in LX-2 cell, while weakened its anti- LX-2 proliferation effect by transfections of si-Smad7 or si-Nrf2. Accordingly the anti-LF approach of SC-D showed relations with modulating ETBR linked fibrosis and anti-oxidative related signaling. Also, Smad7 and Nrf2 might be the key factors for SC-D mediated anti-LF effect.

Subcellular localization of X-linked inhibitor of apoptosis protein (XIAP) in cancer: Does that matter?

X-linked inhibitor of apoptosis protein (XIAP) finely tunes the balance between survival and death to control homeostasis. XIAP is found aberrantly expressed in cancer, which has been shown to promote resistance to therapy-induced apoptosis and confer poor outcome. Despite its predominant cytoplasmic localization in human tissues, growing evidence implicates the expression of XIAP in other subcellular compartments in sustaining cancer hallmarks. Herein, we review our current knowledge on the prognostic role of XIAP localization and discuss molecular mechanisms underlying differential biological functions played in each compartment. The comprehension of XIAP subcellular shuttling and functional dynamics might provide the rationale for future anticancer therapeutics.

Functional Mechanisms of Health Behavior Change Techniques: A Conceptual Review.

Background: Health behavior change is among the top recommendations for improving health of patients with lifestyle-related chronic diseases. An array of behavior change techniques (BCTs) have been developed to support behavior change initiation and maintenance. These BCTs often show limited success when they are not informed by theory, leading to a mismatch between the intention of the BCT and patients' needs or expectations. Previous studies have identified a number of resources (domains) which patients may require to initiate and maintain health behavior change. Indeed, not yet well established is how BCTs address these resources, i.e., the functional mechanisms of BCTs. Purpose: Provide a theoretical framework of the functional mechanisms of BCTs for developing and implementing successful interventions for health behavior change. Methods: Conceptual review, including literature analysis and synthesis as well as conceptualization of a new model based on the synthesis. Results: Through the integration of dual-process models as well as reward and motivation proceeding, i.e., affective, emotional, or intuitive neurobiological cues, into the rational framework of rather linear cognitive or task-related decision progress, we categorize previously identified resources into three distinct sets: external, internal reflective, and internal affective resources. Based on this triad, we classify BCTs according to their functional mechanisms into facilitating (=providing external resources), boosting (=strengthening internal reflective resources), and nudging (=activating internal affective resources). Consequently, we present a simplified Behavior Change Resource Model (BCRM) that is centered on patients' resources. Conclusion: The model can be applied to develop health behavior change interventions, which promote engagement and empowerment. Future studies should aim at testing the applicability and practicality of the BCRM.

Enhancement strategies for photo-fermentative biohydrogen production: A review.

Biohydrogen production by photo fermentation is an attractive clean energy production approach with less environmental pollution and higher substrate conversion. In recent years, various measures have been used to improve biohydrogen production performance, but there is a lack of systematic and comprehensive summary and analysis. Hence, the recent literatures on enhancing biohydrogen production by photo fermentation were summarized, and the functional mechanisms of enhancement strategies were explained. In this work, these measures were divided into four categories according to their roles in photo fermentation, including substrate pretreatment, bacterial modification and immobilization, additive addition, reactor design optimization. It can be concluded that the optimal enhancement conditions of each strategy were affected by substrate type, strain and process parameters. According to the results of this work, it was expected to give readers a clear understanding and provide a scientific reference of the research of photosynthetic biohydrogen production.

Current Findings Regarding Natural Components With Potential Anti-2019-nCoV Activity.

COVID-19, a novel coronavirus pneumonia (named by the World Health Organization, WHO), has spread widely since the end of 2019. Research on synthetic drugs and vaccines has become a focus of attention in China and other countries, as such approaches are regarded as key tools for disease prevention and control; however, the development of these therapeutics will take months, or even years. Under such circumstances, development of coronavirus specific therapeutics is urgent. For this specific indication, the rapid performance of natural products, such as plant compounds, herbal extracts, and traditional Chinese medicine, could contribute as alternative measures. Recent investigations have provided evidence that these natural products are potential candidates for development as therapeutic agents against the virus that causes COVID-19, 2019-nCoV. Targeting the structural proteins or cellular receptors of 2019-nCoV, including coronavirus chymotrypsin-like (3CLpro or Mpro), helicase (nsP13), S protein, and human angiotensin converting enzyme 2 (ACE2), holds promise for preventing infection. In this review, we summarize some representative natural products and their active components that have potential anti-2019-nCoV effects. We focus on the basic structural elements of 2019-nCoV, its main mechanisms of action, and the feasibility and potential of products to inhibit the novel coronavirus. In addition, the relative advantages, additional functions, and precautions that should be used with typical natural products are also discussed. The aim is to make the case that natural products could be a valuable pool for the development of active compounds for treating 2019-nCoV infection, which may contribute to mitigation of the spread of the pandemic.

Food Legumes and Rising Temperatures: Effects, Adaptive Functional Mechanisms Specific to Reproductive Growth Stage and Strategies to Improve Heat Tolerance.

Ambient temperatures are predicted to rise in the future owing to several reasons associated with global climate changes. These temperature increases can result in heat stress- a severe threat to crop production in most countries. Legumes are well-known for their impact on agricultural sustainability as well as their nutritional and health benefits. Heat stress imposes challenges for legume crops and has deleterious effects on the morphology, physiology, and reproductive growth of plants. High-temperature stress at the time of the reproductive stage is becoming a severe limitation for production of grain legumes as their cultivation expands to warmer environments and temperature variability increases due to climate change. The reproductive period is vital in the life cycle of all plants and is susceptible to high-temperature stress as various metabolic processes are adversely impacted during this phase, which reduces crop yield. Food legumes exposed to high-temperature stress during reproduction show flower abortion, pollen and ovule infertility, impaired fertilization, and reduced seed filling, leading to smaller seeds and poor yields. Through various breeding techniques, heat tolerance in major legumes can be enhanced to improve performance in the field. Omics approaches unravel different mechanisms underlying thermotolerance, which is imperative to understand the processes of molecular responses toward high-temperature stress.