Search Results (5,699)

Drought seriously affects wheat yield; it is therefore important to study the molecular mechanism of wheat resistance to drought stress to ensure national food security. Plants can remove harmful substances through autophagy, thus improving their drought resistance. The results of previous studies have shown that autophagy is involved in the drought stress response; however, the molecular mechanism of autophagy in response to drought stress has yet to be elucidated. In this study, molecular biological methods such as immunohistochemistry, Co-Immunoprecipitation (Co-IP), and pull-down were used to explain the molecular mechanism of autophagy in response to drought stress at the protein level. We found that a dehydrin protein called cold-regulated 410 (TaCOR410) interacts with autophagy-related 8 (TaATG8, a key protein of wheat autophagy). TaCOR410 interacted with TaATG8 through its ATG8-interacting motif (AIM), and interaction was inhibited after mutation of the AIM. Interference with TaCOR410 inhibited autophagy and reduced the drought resistance of wheat. In contrast, transient transfection of TaCOR410 promoted autophagy. In wheat, overexpression of TaATG8 improved the drought resistance of wheat. Following interference with TaATG5, TaATG7 inhibited autophagy and reduced the drought resistance of wheat. From the above results, it is evident that autophagy can improve the drought resistance of wheat and can respond to drought stress through the interaction of TaCOR410 with TaATG8. Full article

Pharmacotherapy in the geriatric population is one of the greatest challenges in modern medicine. Elderly patients, characterized by multimorbidity and the resulting polypharmacy, are significantly more exposed to adverse drug reactions (ADRs), which often lead to hospitalization and a decline in quality of life. Understanding the reasons for this difference requires an analysis of the physiological changes that occur during the aging process at the molecular level. This article presents a perspective on the molecular aspects of geriatric pharmacotherapy, focusing on the fundamental mechanisms that are modified with age. The analysis covers changes in pharmacokinetics, including the role and regulation of cytochrome P450 (CYP) enzymes, whose activity, especially in phase I reactions, is significantly reduced. The age-dependent dysfunction of drug transporters from the ABC (ATP-binding cassette) and SLC (solute carrier) families in key organs such as the intestines, liver and kidneys is discussed, which affects the absorption, distribution and elimination of xenobiotic compounds, including drugs. The article also provides a comprehensive analysis of the blood–brain barrier (BBB), describing changes in neurovascular integrity, including the dysfunction of tight junctions and a decrease in the activity of P-glycoprotein, sometimes referred to as multidrug resistance protein (MDR). This increases the susceptibility of the central nervous system to the penetration and action of drugs. In the realm of pharmacodynamics, changes in the density and sensitivity of key receptors (serotonergic, dopaminergic, adrenergic) are described based on neuroimaging data, explaining the molecular basis for increased sensitivity to certain drug classes, such as anticholinergics. The paper also explores new research perspectives, such as the role of the gut microbiome in modulating pharmacokinetics by influencing gene expression and the importance of pharmacoepigenetics, which dynamically regulates drug response throughout life via changes in DNA methylation and histone modifications. The clinical implications of these molecular changes are also discussed, emphasizing the potential of personalized medicine, including pharmacogenomics, in optimizing therapy and minimizing the risk of adverse reactions. Such an integrated approach, incorporating data from multiple fields (genomics, epigenomics, microbiomics) combined with a comprehensive geriatric assessment, appears to be the future of safe and effective pharmacotherapy in the aging population. Full article

Cold stress can inhibit the growth of cucurbits, disrupt pollination and fertilization, induce fruit deformities, reduce plant resistance, and increase susceptibility to diseases, ultimately resulting in yield reduction, quality deterioration, or even complete crop failure. This review focuses on the main cucurbits, such as melon, cucumber, and watermelon, systematically expounding the roles of plant hormones, signaling molecules, soluble sugars, key regulatory factors, molecular mechanisms, and network interactions in their response to cold stress. Furthermore, it highlights future research directions and application potential. By analyzing existing challenges and prospective advancements in this field, the review aims to provide a comprehensive reference for facilitating genetic improvement in cold tolerance. Full article

Phytophthora fruit rot caused by Phytophthora capsici is a devastating disease in many solanaceous vegetables, resulting in tremendous yield and economic losses. However, the underlying resistance or susceptibility to P. capsici in eggplant remains obscure. In this study, the transcriptomic analysis was performed between the resistant (G42) and susceptible (EP28) eggplant genotypes at 0, 1, 3 and 5 days post-inoculation (dpi). Taking 0 dpi as the control, a total of 4111, 7496 and 7325 DEGs were expressed at 1, 3 and 5 dpi, respectively, in G42 and 5316, 12675 and 12048 DEGs were identified at 1, 3 and 5 dpi, respectively, in EP28. P. capsici infection induced substantial transcriptional changes in the inoculated fruits. The analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) identified defense-related pathways including ‘plant-pathogen interactions’, ‘mitogen-activated protein kinase (MAPK)’ and ‘hormone biosynthesis and signal transduction’. The hormone-related genes encompassing ethylene, abscisic acid, auxins and gibberellins showed differential expression between G42 and EP28 eggplant genotypes, signifying their important roles in plant disease resistance. P. capsici infection induced the expression of major transcription factors such as MYB, NAC/NAM, bHLH, WRK, HSF, HD-ZIPAP2/ERF and Mad-box. qRT-PCR validation of the selected genes corroborates with RNA-seq, depicting the precision and consistency of the transcriptomic data. According to qRT-PCR and RNA-seq analyses, the expression of the pathogenesis-related gene transcriptional activator, SmPTI6 (Smechr0603020), is upregulated in G42 and downregulated in EP28. This differential expression suggests a potential role in the resistance to P. capsici. Functional analysis via a virus-induced gene silencing (VIGS) system found that silencing SmPTI6 in G42 enhanced infection by P. capsici, indicating that SmPTI6 performs a critical role in response to pathogen attack. The comprehensive results obtained in this study provide a valuable resource for understanding the molecular mechanisms underlying eggplant resistance to P. capsici and for establishing breeding resistant eggplant genotypes to P. capsici. Full article

Radioactive wastewater generated from nuclear energy, medical, and industrial sectors poses persistent ecological and health risks, necessitating the development of safe and sustainable treatment strategies. Compared with conventional physicochemical approaches, bioremediation using radiation-resistant bacteria (RRB) provides distinct advantages, including lower energy requirements, reduced secondary pollution, and superior ecological compatibility. This review synthesizes current knowledge on RRB’s biological characteristics, molecular resistance mechanisms, and applications in radioactive wastewater treatment. Moreover, potential applications in non-radioactive wastewater treatment—such as selective removal of heavy metals, degradation of refractory organics, and mitigation of antibiotic resistance—are discussed. Evidence from existing studies indicates that RRB share fundamental adaptive traits, including extraordinary radiotolerance, unique morphological modifications, and cross-tolerance to multiple stressors, which are underpinned by specialized DNA repair systems, potent antioxidant defenses, and radiation-responsive regulatory networks. These mechanisms collectively confer the ability to withstand and mitigate radiation-induced damage. Future research should responsibly prioritize the genetic engineering of RRB and its integration with complementary technologies, such as microbial fuel cells, to achieve synergistic pollutant removal and energy recovery. This synthesis provides a theoretical basis and technical reference for advancing RRB-enabled bioremediation toward sustainable wastewater management. Full article

The emergence of bacterial resistance has spurred an urgent need to develop effective alternatives to traditional antibiotics. Phenylethyl alcohol from plants exhibits potential antimicrobial properties, but its efficacy is limited due to its compromised dispersion in water and structural stability in ambient conditions. Herein, for the first time, a polymerization-induced self-assembly strategy was employed to obtain different morphological nanogels with phenylethyl alcohol moieties as hydrophobic cores through in situ reversible addition–fragmentation chain-transfer (RAFT) polymerization. The well-defined copolymers of PTEG_x-co-PPMA_y with controllable molecular weights and narrow polydispersity were confirmed by a combination of techniques. The generated phenylethyl alcohol-based nanogels demonstrated potent antibacterial activity, particularly PTEG₃₀-co-PPMA₇₀ with a one-dimensional linear architecture, which achieved a minimum inhibitory concentration of 62 μg mL⁻¹ against E. coli. SEM revealed membrane disruption as the bactericidal mechanism, highlighting enhanced efficacy against Gram-negative bacteria due to structural differences in cell envelopes. This study establishes a robust platform for designing phenylethyl alcohol-based nanogels with controllable structures toward achieving potent antimicrobial performance, offering a promising strategy for combating bacterial resistance while addressing the dilemma of conventional antibiotic drug systems. Full article

The continuous increase in microbial resistance to therapeutic agents has become one of the greatest challenges to global health. In this context, the present study investigated the bioactivity of 25 chroman-4-one and homoisoflavonoid derivatives—17 of which are novel—against pathogenic microorganisms, including Staphylococcus epidermidis, Pseudomonas aeruginosa, Salmonella enteritidis, Candida albicans, C. tropicalis, Nakaseomyces glabratus (formerly C. glabrata), Aspergillus flavus, and Penicillium citrinum. Antimicrobial assay was performed using the microdilution technique in 96-well microplates to determine the minimum inhibitory concentration (MIC). Thirteen compounds exhibited antimicrobial activity, with compounds 1, 2, and 21 demonstrating greater potency than the positive control, especially against Candida species. Molecular modeling suggested distinct mechanisms of action in Candida albicans: 1 potentially inhibits cysteine synthase, while 2 and 21 possibly target HOG1 kinase and FBA1, key proteins in fungal virulence and survival. Our findings indicated that the addition of alkyl or aryl carbon chains at the hydroxyl group at position 7 reduces antimicrobial activity, whereas the presence of methoxy substituents at the meta position of ring B in homoisoflavonoids enhances bioactivity. These findings highlight key structural features of these compound classes, which may aid in the development of new bioactive agents against pathogenic microorganisms. Full article

High-Density Polyethylene (HDPE) plays a crucial role in the life of every human being due to its properties such as chemical resistance, light weight, and ease of forming, among others. Its usage ranges from bottles for beverages and other liquids, to pipes, wire and cable insulation, and prosthetics. As it undergoes several thermal cycles during its life cycle, it is essential to maintain its qualities, even after undergoing thermal and thermo-oxidative degradation. Here, various dosages of synthetic (Irganox 1010) and natural (vitamin E) antioxidants are added to HDPE formulations to study their impacts on HDPE stability. The antioxidants are mixed physically with HDPE before the mixtures are melt-mixed three times to represent their life cycles. Samples are taken after each time and used to analyze the molecular weight distribution, rheological behavior, mechanical properties, and thermal stability. The results show that vitamin E is superior to Irganox 1010 in these tests, as vitamin E performance exceeds that of Irganox 1010, even at lower doses. The only drawback of using vitamin E is the yellow color it causes, which may necessitate the addition of another additive to enhance the color stability of HDPE in color-sensitive applications. Full article

Newcastle Disease (ND) is an important and notable disease among the avian infectious diseases, because of its high contagiousness, and the most virulent strains of ND virus (NDV) have impacted poultry breeders all over the world. Immunization and biosecurity measures are used to reduce ND; however, vaccination has been shown to offer protection against clinical signs but not against virus proliferation and shedding, which could have an adverse effect on the environment. The genetic basis for inherent resistance to NDV has been established, and genetic selection on existing resistance-related genetic variation can help to mitigate virus propagation. Further, understanding the genes and processes that drive the response to NDV will lay the groundwork for genetic improvement in poultry. The majority of studies on NDV susceptibility make use of phenotypic indicators such as body weight, morbidity, mortality, antibody response, and viral load. According to recent advancements in molecular genetic research, many different genes are diversely regulated in different chicken lines to NDV infection, which might be used in the future to establish disease-resistant breeding approaches. It is possible that many more genes linked to illness and resistance are still to be discovered, because the precise mechanism of resistance is not entirely understood. The enhanced genetic knowledge of chickens and the development of more advanced transgenic techniques would lead to pathogen resistance. Hence, this paper summarizes the current understanding of genetic resistance to Newcastle Disease, and we additionally highlight a few possible genes/markers connected with NDV that may improve chicken resistance to NDV infections and can be used to produce NDV-resistant chicken breeds/strains in the near future. Full article

The BRAF protein regulates cell growth and division through key signaling pathways. Mutations in BRAF, particularly the V600E variant, are frequently observed in colorectal cancer (CRC) and are associated with poor prognosis and therapeutic challenges. Tumors harboring certain BRAF mutations often exhibit primary resistance to BRAF inhibitor monotherapies. Over time, these tumors can also develop acquired resistance, further complicating treatment. In this study, we employed replica exchange molecular dynamics simulations combined with machine learning techniques to investigate the structural alterations induced by BRAF mutations and their contribution to drug resistance. Our analyses revealed that conformational changes in mutant BRAF proteins associated with dabrafenib residues psi494, phi600, phi644, phi663, psi675, and phi677 were sufficient for classifying drug-resistant vs. drug-sensitive variants. Similarly, for vemurafenib, residues psi450, phi484, phi495, phi518, psi622, and phi622 were the key residues that influence drug binding and resistance mechanisms. These residues are located in the N-lobe of CR3, which is responsible for ATP binding and the regulation of BRAF kinase activity. These findings offer deeper insights into the molecular basis of BRAF-driven resistance and provide predictive models for phenotypic outcomes of various BRAF mutations. The study underscores the importance of targeting specific BRAF variants for more effective, personalized therapeutic strategies in drug-resistant CRC patients. Full article

Background/Objectives: Obesity and type 2 diabetes mellitus (T2DM) profoundly disrupt lipid metabolism within local microenvironments of skeletal muscle and its associated connective tissues, including adipose tissue, bone, and fascia. However, the role of local communication between skeletal muscle and its proximal connective tissues in propagating metabolic dysfunction is incompletely understood. This narrative review synthesizes current evidence on these local metabolic interactions, highlighting novel insights and existing gaps. Methods: We conducted a comprehensive literature analysis of primary research published in the last decade, sourced from PubMed, Web of Science, and ScienceDirect. Studies were selected for relevance to skeletal muscle, adipose tissue, fascia, and bone lipid metabolism in the context of obesity and T2DM, with emphasis on molecular, cellular, and paracrine mechanisms of local crosstalk. Findings were organized into thematic sections addressing physiological regulation, pathological remodeling, and inter-organ signaling pathways. Results: Our synthesis reveals that local lipid dysregulation in obesity and T2DM involves altered fatty acid transporter dynamics, mitochondrial overload, fibro-adipogenic remodeling, and compartment-specific adipose tissue dysfunction. Crosstalk via myokines, adipokines, osteokines, bioactive lipids, and exosomal miRNAs integrates metabolic responses across these tissues, amplifying insulin resistance and lipotoxic stress. Emerging evidence highlights the underappreciated roles of fascia and marrow adipocytes in regional lipid handling. Conclusions: Collectively, these insights underscore the pivotal role of inter-tissue crosstalk among skeletal muscle, adipose tissue, bone, and fascia in orchestrating lipid-induced insulin resistance, and highlight the need for integrative strategies that target this multicompartmental network to mitigate metabolic dysfunction in obesity and T2DM. Full article

Background: Histone deacetylase 6 (HDAC6) is a unique class IIb HDAC isozyme characterized by two catalytic domains and a zinc finger ubiquitin-binding domain. It plays critical roles in various cellular processes, including protein degradation, autophagy, immune regulation, and cytoskeletal dynamics. Due to its multifunctional nature and overexpression in several cancer types, HDAC6 has emerged as a promising therapeutic target. Methods: In this study, we employed a ligand-based pharmacophore modeling approach using a structurally diverse set of known HDAC6 inhibitors. This was followed by the virtual screening of over 140,000 commercially available compounds from both the MolPort and Asinex databases. The screening workflow incorporated pharmacophore filtering, molecular docking, and molecular dynamic (MD) simulations. Binding free energies were estimated using Molecular Mechanics Generalized Born Surface Area (MM-GBSA) analysis to prioritize top candidates. A fluorometric enzymatic assay was used to measure HDAC6 activity, while cell viability assay by Cell Titer Glo was used to assess the anti-tumor activity against drug-sensitive and -resistant multiple myeloma (MM) cells. Western blotting was used to evaluate the acetylation of tubulin or histone H4 after treatment with selected compounds. Results: Three promising compounds were identified based on stable binding conformations and favorable interactions within the HDAC6 catalytic pocket. Among them, Molecular Mechanics Generalized Born Surface Area (MM-GBSA) analysis identified Compound 10 (AKOS030273637) as the top theoretical binder, with a ΔG_bind value of −45.41 kcal/mol. In vitro enzymatic assays confirmed its binding to the HDAC6 catalytic domain and inhibitory activity. Functional studies on MM cell lines, including drug-resistant variants, showed that Compound 10 reduced cell viability. Increased acetylation of α-tubulin, a substrate of HDAC6, likely suggested on-target mechanism of action. Conclusions: Compound 10, featuring a benzyl 4-[4-(hydroxyamino)-4-oxobutylidene] piperidine-1-carboxylate scaffold, demonstrates potential drug-like properties and a predicted bidentate zinc ion coordination, supporting its potential as an HDAC6 inhibitor for further development in hematologic malignancies. Full article

Melanoma is one of the most aggressive skin cancers, with increasing rates of occurrence. Although it has not traditionally been considered hormonally driven, recent evidence links androgen receptor (AR) signaling to important aspects of melanoma biology, including tumor growth, metastasis, immune evasion, and resistance to therapy. Mechanistically, AR promotes melanoma progression by activating a pro-metastatic gene program, suppressing anti-tumor immune responses, and altering the tumor microenvironment. Additionally, emerging data indicate AR’s involvement in resistance to chemotherapy and immune-based therapies. This review provides a comprehensive overview of AR’s intricate role in melanoma, focusing on its molecular mechanisms, its impact on immune evasion and therapy resistance, and its potential clinical applications. We also assess AR-targeted strategies, including androgen deprivation therapy and AR antagonists, to improve the effectiveness of chemotherapy, targeted therapy, and immunotherapy. Understanding AR’s role in melanoma could lead to new treatment options, particularly for sex-specific patient groups. Full article

Steel fiber reinforced concrete in marine environments often suffers from stress corrosion coupling. Under mechanical loading, the formation of penetrating cracks in the matrix increases susceptibility to seawater penetration and interfacial degradation. Using molecular dynamics simulations, this study investigated the effects of calcium-to-silicon (Ca/Si) ratios on the interfacial bonding and transport properties of a γ-FeOOH/CSH system. The results show that higher Ca/Si ratios strengthen ionic bonding between CSH and γ-FeOOH, thereby improving interfacial adhesion. Additionally, increased Ca/Si ratios significantly slow the transport of water molecules and ions (Na⁺, Cl⁻, SO₄²⁻) within γ-FeOOH/CSH nanopores. It was observed that Cl⁻ and SO₄²⁻ exhibited pronounced filtration effects at Ca/Si = 2.0. These findings suggest that optimizing the Ca/Si ratio in concrete can simultaneously enhance interfacial strength and reduce permeability. This provides an effective strategy for improving the marine erosion resistance of steel fiber reinforced concrete structures. Full article

This study investigated the physicochemical, structural, and functional characteristics of foxtail millet starches (FMSs), including five non-waxy varieties (N-HXMS, N-LXMS, N-QZHS, N-JG21S, N-BLGS) and one waxy control (W-HJGS). All FMSs exhibited polygonal granules with surface pores and an orthorhombic crystalline structure (A-type X-ray diffraction pattern). Compared with the waxy FMSs, non-waxy starches exhibited higher amylose content (32.4–34.04%), reduced crystallinity (37.01–39.21%) and short-range molecular order, and lower hydration capacity and molecular weight (1.01 × 10⁵–2.81 × 10⁵ g/mol). The non-waxy FMSs also demonstrated enhanced resistance to mechanical shear, better structural stability, stronger recovery behavior, and reduced enzymatic susceptibility. Varieties like N-LXMS, with higher amylose and resistant starch contents (31.17%), are more suitable for functional foods targeting glycemic control, while W-HJGS, with higher swelling power (22.76 g/g) and solubility (92.30%), is well suited as a thickener. This study provides a foundation for future research on the modification of FMSs and their utilization as starch-based matrices in various applications, such as functional food development, biodegradable packaging materials, and targeted delivery systems for bioactive compounds. Full article