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Backgroud: Intrauterine Adhesions (IUA) is a common gynecological disease which is seriously endangers the reproductive function of women without any ideal treatment. Some researchers found Menstrual Blood-derived Mesenchymal Stem Cells (MenSCs) can repair of damaged endometrium, however, has not been fully clarified. This study aims to evaluate the therapeutic effects of MenSCs in IUA and the repair mechanism in vivo. Methods: This study is Laboratory-based study. To evaluate the therapeutic effects of MenSCs in IUA, We cultivated MenSCs, established mouse endometrial injury model, observed the uterine morphology and degree of endometrial fibrosis and compared the expression of CXC chemokine ligand-13 (CXCL13)、CXC chemokine receptor-5 (CXCR5)、Plasmin Activating Inhibitor-1(Pai-1), Transforming Growth Faction-β1(TGF- β1) and Matrix Metalloproteinase-9 (Mmp-9) among each groups. GraphPad Prism 8.0 was used for statistical processing. Data were expressed as mean ± SD. Statistical comparisons among groups were performed with one-way ANOVA. P < 0.05 were considered statistically significant. Results: We successfully cultured and identified MenSCs and established mice model of uterine adhesion. After treatment with MenSCs, endometrial morphology of mice was partially restored, endometrial thickness was increased, and glands were multipiled. The concentrations of CXCL13 and CXCR5 were significantly increased by immunofluorescence detection compared with the control group. The results of RT-qPCR showed that the expressions of Pai-1 and Mmp-9 were significantly lower than those of the control group. Conclusions: MenSCs may reduce endometrial fibrosis and the down-regulating expression of Pai-1、Mmp-9 and CXCL13-CXCR5 axis were involved in the process of MenSCs repaired IUA. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is a malignant tumor of the digestive tract with a high mortality rate. Erianin has antitumor activity, but the regulatory targets and mechanism of action in pancreatic cancer are unclear. The objective of this study was to evaluate the anti-pancreatic cancer activity of Erianin and explore its underlying mechanisms. Methods: A network pharmacology approach was used to investigate the mechanism of action of Erianin in pancreatic cancer cells. Cell proliferation was analyzed using CCK8, colony-formation, and EdU proliferation assays. Cell migration was evaluated through wound healing and transwell assays, as well as determination of the protein expression levels of EMT markers and β-catenin. Apoptosis and the cell cycle were measured using flow cytometry and JC-1 staining, respectively. The protein expression levels of p-Rb, CyclinB1, P21, Cleaved-PARP, and Cleaved-Caspase3 were assessed using western blotting. RNA sequencing (RNA-seq) and bioinformatics analyses were performed to elucidate the mechanism underlying the action of Erianin in pancreatic cancer. Western blotting was used to examine the expression levels of key proteins in the AKT, JNK, and p38 MAPK signaling pathways. Molecular docking and CETSA were used to test hypotheses. The tumor-suppressive ability of Erianin in vivo was assessed using a tumor-bearing assay in nude mice. Results: Network pharmacology revealed that Erianin inhibited pancreatic cancer through multiple pathways. Erianin significantly inhibited pancreatic cancer cell proliferation and migration while promoting intracellular ROS and inducing apoptosis. Mechanistically, Erianin inhibited pancreatic cancer cell proliferation by regulating the AKT/FOXO1 and ASK1/JNK/p38 MAPK signaling pathways. In vivo experiments showed that Erianin inhibited subcutaneous tumor growth and promoted tumor tissue apoptosis in nude mice. Conclusions: The component-target-pathway network revealed that Erianin exerted anti-cancer effects through multiple components, targets, and pathways. Erianin inhibited the proliferation and migration of pancreatic cancer cells and induced apoptosis through the AKT/FOXO1 and ASK1/JNK/p38 MAPK signaling pathways. These results indicate that Erianin is a promising agent for pancreatic cancer treatment. [ABSTRACT FROM AUTHOR]

Zearalenone (ZEA) is a mycotoxin produced by Fusarium spp. fungi and is widely found in moldy corn, wheat, barley, and other grains. ZEA is distributed to the whole body via blood circulation after metabolic transformation in animals. Through oxidative stress, immunosuppression, apoptosis, autophagy, and mitochondrial dysfunction, ZEA leads to hepatitis, neurodegenerative diseases, cancer, abortion, and stillbirth in female animals, and decreased sperm motility in male animals. In recent years, due to the influence of climate, storage facilities, and other factors, the problem of ZEA pollution in global food crops has become particularly prominent, resulting in serious problems for the animal husbandry and feed industries, and threatening human health. Resveratrol (RSV) is a natural product with therapeutic activities such as anti-inflammatory, antioxidant, and anticancer properties. RSV can alleviate ZEA-induced toxic effects by targeting signaling pathways such as NF-κB, Nrf2/Keap1, and PI3K/AKT/mTOR via attenuating oxidative damage, inflammatory response, and apoptosis, and regulating cellular autophagy. Therefore, this paper provides a review of the protective effect of RSV against ZEA-induced toxicity and its molecular mechanism, and discusses the safety and potential clinical applications of RSV in the search for natural mycotoxin detoxification agents. [ABSTRACT FROM AUTHOR]

The oxalate-carbonate pathway (OCP) involves degradation of soil oxalate to carbonate. To exploit and manage this natural mineralization of assimilated atmospheric CO2 into stable carbonates, improved understanding of this complex biotransformation process is needed. A strain of oxalate-degrading bacteria, Azospirillum sp. OX-1, was isolated from soil, and its secondary products of calcium oxalate degradation were analyzed and characterized using SEM, XRD, TG/DTG-DTA and FTIR-spectroscopy. The molecular mechanism of calcium oxalate degradation was also analyzed using proteomics. The results showed, for the first time, that OX-1 could not only degrade calcium oxalate to calcium carbonate, but also that the process was accompanied by synthesis of methane. Proteomic analysis demonstrated that OX-1 has a dual enzyme system for calcium oxalate degradation, using formyl-CoA transferase (FRC) and thiamine pyrophosphate (ThDP)-dependent oxalyl-CoA decarboxylase (OXC) to form calcium carbonate. Up-regulated expression of enzymes related to methane synthesis was also detected during calcium oxalate degradation. Since methane is also a potent greenhouse gas, these new results suggest that the utility of exploiting the OCP to reduce atmospheric CO2 must be re-evaluated and that further studies should be conducted to reveal how widespread the methane producing capacity of strain OX-1 is in other bacteria and soil environments. [ABSTRACT FROM AUTHOR]

Ependymal cells are arranged along the inner surfaces of the ventricles and the central canal of the spinal cord, providing anatomical, physiological and immunological barriers that maintain cerebrospinal fluid (CSF) homeostasis. Based on this, studies have found that alterations in gene expression, cell junctions, cytokine secretion and metabolic disturbances can lead to dysfunction of ependymal cells, thereby participating in the onset and progression of central nervous system (CNS) infections. Additionally, ependymal cells can exhibit proliferative and regenerative potential as well as secretory functions during CNS injury, contributing to neuroprotection and post-injury recovery. Currently, studies on ependymal cell primarily focus on the basic investigations of their morphology, function and gene expression; however, there is a notable lack of clinical translational studies examining the molecular mechanisms by which ependymal cells are involved in disease onset and progression. This limits our understanding of ependymal cells in CNS infections and the development of therapeutic applications. Therefore, this review will discuss the molecular mechanism underlying the involvement of ependymal cells in CNS infections, and explore their potential for application in clinical treatment modalities. Key points: Ependymal cells play an important role in the maintenance of CSF homeostasis and CNS health by forming physical and immune barriers against pathogen invasion. PPRs signaling pathways, cilia and intercellular junctions, cytokine secretion or senescence of ependymal cells can lead to dysfunction, which in turn is involved in the onset and progression of CNS infection. We propose potential therapeutic applications including gene transfer and novel biomarkers. Studies of ependymal cells have provided new ideas for pathophysiology and treatment, but further research is needed to fully understand their role in CNS infection and evaluate therapeutic effect. [ABSTRACT FROM AUTHOR]

The oxalate-carbonate pathway (OCP) involves degradation of soil oxalate to carbonate. To exploit and manage this natural mineralization of assimilated atmospheric CO2 into stable carbonates, improved understanding of this complex biotransformation process is needed. A strain of oxalate-degrading bacteria, Azospirillum sp. OX-1, was isolated from soil, and its secondary products of calcium oxalate degradation were analyzed and characterized using SEM, XRD, TG/DTG-DTA and FTIR-spectroscopy. The molecular mechanism of calcium oxalate degradation was also analyzed using proteomics. The results showed, for the first time, that OX-1 could not only degrade calcium oxalate to calcium carbonate, but also that the process was accompanied by synthesis of methane. Proteomic analysis demonstrated that OX-1 has a dual enzyme system for calcium oxalate degradation, using formyl-CoA transferase (FRC) and thiamine pyrophosphate (ThDP)-dependent oxalyl-CoA decarboxylase (OXC) to form calcium carbonate. Up-regulated expression of enzymes related to methane synthesis was also detected during calcium oxalate degradation. Since methane is also a potent greenhouse gas, these new results suggest that the utility of exploiting the OCP to reduce atmospheric CO2 must be re-evaluated and that further studies should be conducted to reveal how widespread the methane producing capacity of strain OX-1 is in other bacteria and soil environments. [ABSTRACT FROM AUTHOR]

The delivery of ultra-high dose rates of radiation, called flash irradiation or flash-RT, has emerged as a new modality of radiotherapy shaking up the paradigm of proportionality of effect and dose whatever the method of delivery of the radiation. The hallmark of flash-RT is healthy tissue sparing from the side effects of radiation without decrease of the antitumor efficiency in animal models. In this review we will define its specificities, the molecular mechanisms underlying the flash effect and the ongoing developments to bring this new modality to patient treatment. [ABSTRACT FROM AUTHOR]

Wheat is the most widely grown crop in the world; its production is severely disrupted by increasing water deficit. Plant roots play a crucial role in the uptake of water and perception and transduction of water deficit signals. In the past decade, the mechanisms of drought tolerance have been frequently reported; however, the transcriptome and metabolome regulatory network of root responses to water stress has not been fully understood in wheat. In this study, the global transcriptomic and metabolomics profiles were employed to investigate the mechanisms of roots responding to water stresses using the drought-tolerant (DT) and drought-susceptible (DS) wheat genotypes. The results showed that compared with the control group, wheat roots exposed to polyethylene glycol (PEG) had 25941 differentially expressed genes (DEGs) and more upregulated genes were found in DT (8610) than DS (7141). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs of the drought-tolerant genotype were preferably enriched in the flavonoid biosynthetic process, anthocyanin biosynthesis and suberin biosynthesis. The integrated analysis of the transcriptome and metabolome showed that in DT, the KEGG pathways, including flavonoid biosynthesis and arginine and proline metabolism, were shared by differentially accumulated metabolites (DAMs) and DEGs at 6 h after treatment (HAT) and pathways including alanine, aspartate, glutamate metabolism and carbon metabolism were shared at 48 HAT, while in DS, the KEGG pathways shared by DAMs and DEGs only included arginine and proline metabolism at 6 HAT and the biosynthesis of amino acids at 48 HAT. Our results suggest that the drought-tolerant genotype may relieve the drought stress by producing more ROS scavengers, osmoprotectants, energy and larger roots. Interestingly, hormone signaling plays an important role in promoting the development of larger roots and a higher capability to absorb and transport water in drought-tolerant genotypes. [ABSTRACT FROM AUTHOR]

Pharmacogenomic analysis based on drug transcriptome characteristics is widely used to identify mechanisms of action. The purpose of this study was to elucidate the molecular mechanism of protective effect against adriamycin (ADM)-induced mpc5 cell injury of Chinese cordyceps aqueous extracts (WCCs) by a systematic transcriptomic analysis. The phytochemicals of WCCs were analyzed via the "phenol–sulfuric acid method", high-performance liquid chromatography (HPLC), and HPLC–mass spectrometry (MS). We analyzed the drug-reaction transcriptome profiles of mpc5 cell after treating them with WCCs. RNA-seq analysis revealed that WCCs alleviated ADM-induced mpc5 cell injury via restoring the expression of certain genes to normal level mainly in the one-carbon pool by the folate pathway, followed by the relaxin, apelin, PI3K-Akt, and nucleotide-binding, oligomerization domain (NOD)-like receptor signaling pathway, enhancing DNA synthesis and repair, cell proliferation, fibrosis reduction, and immune regulation. Otherwise, WCCs also modulated the proliferation and survival of the mpc5 cell by regulating metabolic pathways, and partially restores the expression of genes related to human disease pathways. These findings provide an innovative understanding of the molecular mechanism of the protective effect of WCCs on ADM-induced mpc5 cell injury at the molecular transcription level, and Mthfd2, Dhfr, Atf4, Creb5, Apln, and Serpine1, etc., may be potential novel targets for treating nephrotic syndrome. [ABSTRACT FROM AUTHOR]

• A concise overview on the isolated bioactive compounds from different Annona plant part. • Annona extracts have been shown to exert significant biological and pharmacological activities of isolated compounds with mechanism of its action. • On the current preclinical evidence an association between bioactive component intake with a special focus on human chronic disease prevention. The use of plant derived bioactive substances as a key therapeutic agent to treat various diseases has gained great impetus recently. Annona fruits are currently gaining attention from those who are interested in eating foods that promote health because of its phytochemical composition, whose actions have not before been investigated. A comprehensive search was conducted on scientific databases like Google Scholar, PubMed, Science Direct, Scopus etc to retrieve the relevant literature on Annona species include Annona squamosa, Annona muricata, Annona reticulata, Annona glabra, Annona crassiflora, Annona cherimola, Annona montana, Annona purpurea, Annona senegalensis, Annona dioica and Annona atemoya , their bioactive compounds, biological activity, pharmacology and mechanism from January 2002 to February 2024. According to the available literature data bioactive phytocompound have proven to be a potential alternative to synthetic drugs especially because of their antioxidant, antibacterial and in vitro anticancer properties. This review aims to provide up-to-date information on Annona genus with mode of action on various disease. The literature accessible on this plant species was systematically analysed to extract evidence regarding its phytochemicals, including phenolic, ascorbic acid, fatty acids, essential oils, alkaloids etc. Moreover, the considerable data will be useful for pharmaceutical researchers and other industries looking for up-to-date understandings. Specifically, we provide a concise overview on the isolated bioactive compounds from different Annona part and occurrence of the main classes of compounds as well as on the current preclinical evidence an association between bioactive component intake with a special focus on human chronic disease prevention like neurodegenerative, anti-inflammatory, hyperglycaemic and cancer. Additional investigations are necessary to uncover the underlying mechanisms of its actions and conduct clinical trials to verify its effectiveness and safety in humans. [ABSTRACT FROM AUTHOR]

Boswellic acids is a general term for a series of pentacyclic triterpenoid compounds that are isolated from the oleogin resin of the Boswellia genus and serve as the main active ingredient. It exhibits a wide range of biological activities, such as anti-inflammatory, anti-cancer, antibacterial, antiviral, hepatoprotective, neuroprotective, anti-diabetic, and anti-thrombotic properties. As a result, it has gained significant recognition among practitioners of traditional Chinese and Indian medicine. These biological effects may be associated with multiple molecular targets and signal transduction pathways. However, the poor pharmacokinetic properties of the substance lead to lower bioavailability, which affects its effectiveness. To address this issue, scientists have proposed a number of strategies, such as solid dispersions, phytosome® technologies, and novel drug delivery systems. This article aims to provide a comprehensive overview for boswellic acids on the phytochemistry, molecular mechanisms, potential therapeutic applications, and strategies to improve bioavailability. [ABSTRACT FROM AUTHOR]

As one of the factors regulating tumour angiogenesis, angiopoietin-4 (ANGPT4), which plays an important role in promoting tumour proliferation, survival, expansion and angiogenesis, is highly expressed in some tumours, such as lung adenocarcinoma, glioblastoma and ovarian cancer. This may be related to the fact that ANGPT4 affects the blood vessels and lymphatic system of the tumour. Specifically, ANGPT4 could play an effective role in promoting cancer by affecting the tyrosine kinase receptor TIE2, ERK1/2 and PI3K/AKT signalling pathways. Therefore, ANGPT4 may be an important biomarker for the occurrence and development of cancer and poor prognosis. In addition, the inhibition of ANGPT4 may be a useful cancer treatment. This paper reviews the latest preclinical research on ANGPT4, emphasizes its role in tumourigenesis and broadens our understanding of the carcinogenic function of ANGPT4 and the development of ANGPT4 inhibitors. This is the latest version of the revised version of the previous article. [ABSTRACT FROM AUTHOR]

Despite the success of AlphaFold2 approaches in predicting single protein structures, these methods showed intrinsic limitations in predicting multiple functional conformations of allosteric proteins and have been challenged to accurately capture the effects of single point mutations that induced significant structural changes. We examined several implementations of AlphaFold2 methods to predict conformational ensembles for state-switching mutants of the ABL kinase. The results revealed that a combination of randomized alanine sequence masking with shallow multiple sequence alignment subsampling can significantly expand the conformational diversity of the predicted structural ensembles and capture shifts in populations of the active and inactive ABL states. Consistent with the NMR experiments, the predicted conformational ensembles for M309L/L320I and M309L/H415P ABL mutants that perturb the regulatory spine networks featured the increased population of the fully closed inactive state. The proposed adaptation of AlphaFold can reproduce the experimentally observed mutation-induced redistributions in the relative populations of the active and inactive ABL states and capture the effects of regulatory mutations on allosteric structural rearrangements of the kinase domain. The ensemble-based network analysis complemented AlphaFold predictions by revealing allosteric hotspots that correspond to state-switching mutational sites which may explain the global effect of regulatory mutations on structural changes between the ABL states. This study suggested that attention-based learning of long-range dependencies between sequence positions in homologous folds and deciphering patterns of allosteric interactions may further augment the predictive abilities of AlphaFold methods for modeling of alternative protein sates, conformational ensembles and mutation-induced structural transformations. [ABSTRACT FROM AUTHOR]

ABSTRACT In recent years, a significant breakthrough has emerged in biology, the identification of lactylation, a novel post‐translational process. This intriguing modification is not limited to a specific class of proteins but occurs across a diverse range, including histones, signalling molecules, enzymes, and substrates. It can exert a broad regulatory role in various diseases, ranging from developmental anomalies and neurodegenerative disorders to inflammation and cancer. Thus, it presents exciting opportunities for exploring innovative treatment approaches. As a result, there has been a recent surge of research interest, leading to a deeper understanding of the molecular mechanisms and regulatory functions underlying lactylation within physiological and pathological processes. Here, we review the detection and molecular mechanisms of lactylation, from biological functions to disease effects, providing a systematic overview of the mechanisms and functions of this post‐translational modification. [ABSTRACT FROM AUTHOR]

Fenugreek (Trigonella foenum‐graecum) is a widely grown dietary herb in Asia, and its seeds are traditionally used for several diseases, including diabetes. The seeds and leaves possess a variety of compounds that play an important role in regulating their hypoglycemic effect. However, so far, no extensive systematic review exists on its antidiabetic effect, highlighting the molecular mechanisms and isolated compounds. The purpose of this review is to summarize the preclinical and clinical antidiabetic properties of fenugreek and its isolated compounds by focusing on underlying mechanisms. PubMed, Google Scholar, Science Direct, and Scopus databases were searched to retrieve articles until June, 2024. Preclinical studies demonstrated that the antidiabetic effect of fenugreek was mostly associated with enhanced glucose transporter type‐4 (GLUT4) translocation and hexokinase activity, decreased glucose‐6‐phosphatase and fructose‐1,6‐bisphosphatase activities, inhibited α‐amylase and maltase activities, protected β cells, and increased insulin release. Furthermore, few studies have reported its role as a glucagon‐like peptide‐1 (GLP‐1) modulator, 5′‐AMP‐activated kinase (AMPK) activator, and dipeptidyl peptidase‐IV (DPP‐IV) inhibitor. Further clinical trials showed that fenugreek seeds improved blood glucose levels, insulin resistance, insulin sensitivity, and lipid profiles. This study highlights significant evidence of the antidiabetic effect of fenugreek and its isolated compounds; therefore, it could be a potential therapy for diabetes. [ABSTRACT FROM AUTHOR]

Simple Summary: Rice production is strongly affected by environmental stresses such as drought, heat and salt. Rice plants have developed intricate molecular mechanisms to deal with these challenges. Researchers have identified crucial genes, proteins and metabolic pathways involved in these responses through transcriptomic and proteomic studies. Understanding these molecular mechanisms can help in developing new stress-resistant varieties, thus ensuring stable production under adverse environmental conditions. This review aims to provide a straightforward summary of the progress in understanding the molecular mechanisms of rice's response to various environmental stresses through transcriptomic and proteomic studies. Rice (Oryza sativa L.) is grown nearly worldwide and is a staple food for more than half of the world's population. With the rise in extreme weather and climate events, there is an urgent need to decode the complex mechanisms of rice's response to environmental stress and to breed high-yield, high-quality and stress-resistant varieties. Over the past few decades, significant advancements in molecular biology have led to the widespread use of several omics methodologies to study all aspects of plant growth, development and environmental adaptation. Transcriptomics and proteomics have become the most popular techniques used to investigate plants' stress-responsive mechanisms despite the complexity of the underlying molecular landscapes. This review offers a comprehensive and current summary of how transcriptomics and proteomics together reveal the molecular details of rice's response to environmental stresses. It also provides a catalog of the current applications of omics in comprehending this imperative crop in relation to stress tolerance improvement and breeding. The evaluation of recent advances in CRISPR/Cas-based genome editing and the application of synthetic biology technologies highlights the possibility of expediting the development of rice cultivars that are resistant to stress and suited to various agroecological environments. [ABSTRACT FROM AUTHOR]

Simple Summary: Diapause is a state in which insects respond to environmental changes, leading to developmental stagnation, which is crucial in the life history of insects. miRNA regulates the expression of genes after transcription and participates in the regulation of important biological processes of insect growth and development. In this study, we screened differentially expressed miRNAs (DEMs) in non-diapause/diapause and diapause/non-diapause comparison groups of Ostrinia furnacalis and predicted their target genes. The expression patterns of key target genes Kr-h, JHE, JHEH, FOXO, Cry, and Per in diapause-related metabolic pathways at different stages of diapause were opposite to those of miRNAs, suggesting their regulatory roles in the diapause process. This study improves the scientific understanding of diapause in O. furnacalis; the learning can be applied to other insects. microRNAs (miRNAs) function as vital regulators of diapause in insects through their ability to post-transcriptionally suppress target gene expression. In this study, the miRNA of Ostrinia furnacalis, an economically important global crop pest species, was characterized. For the included analyses, 9 small RNA libraries were constructed using O. furnacalis larvae in different diapause states (non-diapause, ND; diapause, D; diapause-termination, DT). The results identified 583 total miRNAs, of which 256 had previously been identified, whereas 327 were novel. Furthermore, comparison analysis revealed that 119 and 27 miRNAs were differentially expressed in the D vs. ND and DT vs. D, respectively. Moreover, the expression patterns of their miRNAs were also analyzed. GO and KEGG analysis of the target genes of differentially expressed miRNAs highlighted the importance of these miRNAs as diapause regulators in O. furnacalis, especially through metabolic processes, endocrine processes, 20-hydroxyecdysone, and circadian clock signaling pathways. In summary, this study highlighted the involvement of specific miRNAs in the control of diapause in O. furnacalis. To the best of our knowledge, this is the first study to identify miRNA expression patterns in O. furnacalis, thereby providing reference and novel evidence enhancing our current understanding of how small RNAs influence insect diapause. [ABSTRACT FROM AUTHOR]

Using nitrogen-doped graphene quantum dots (N-GQDs) and 3-aminophenylboronic acid (APBA), a novel fluorescence nanosensor was developed. This nanosensor exhibits high selectivity and sensitivity for lysine detection. Its sensing mechanism involves the suppression of electron transfer from APBA to the N-GQDs unit, thereby inhibiting photoinduced electron transfer and initiating internal charge transfer. At an optimal pH of 7, the protonated α-amine and ε-amine groups of lysine interact with the amide and boronic acid moieties, respectively. This interaction results in a redshift of fluorescence, substantially enhancing the response signal. A linear response was observed within a concentration range 0.40–3.01 μM, with the detection limit being 0.005 μM. A similar linear range was also achieved for the determination of lysine in human serum. Density functional theory calculations correlating molecular orbits and geometries support UV–vis and fluorescence findings. Additionally, the nanosensor was successfully applied to detect lysine in living cells and real samples, including milk and honey. For practical application, we construct a lysine-specific sensing platform using a commercial chip (TCS34725) that collects red, blue, and green signals, thereby facilitating the convenient use of the nanosensor. Overall, this study offers new perspectives on the development and application of fluorescent nanosensors for detecting individual amino acids. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is the leading sight-threatening disease in developed countries. On the other hand, recent studies indicated an ethnic variation in the phenotype of AMD. For example, several reports demonstrated that the incidence of drusen in AMD patients is less in Asians compared to Caucasians though the reason has not been clarified yet. In the last decades, several genome association studies have disclosed many susceptible genes of AMD and revealed that the association strength of some genes was different among races and AMD phenotypes. In this review article, the essential findings of the clinical studies and genome association studies for the most significant genes CFH and ARMS2/HTRA1 in AMD of different races are summarized, and theoretical hypotheses about the molecular mechanisms underlying the ethnic variation in the AMD manifestation mainly focused on those genes between Caucasians and Asians are discussed. [ABSTRACT FROM AUTHOR]

Background: Methamphetamine (METH) is a highly addictive drug that directly affects the central nervous system. METH use not only harms the user's health but also poses risks and costs to society. Prolonged METH dependence has been shown to impair cognition, which may be the primary factor in impulsive drug-seeking behaviors and high relapse rates. However, the molecular mechanisms underlying METH addiction and METH-induced cognitive decline remain poorly understood. Methods: To illuminate the potential molecular mechanisms underpinning METH addiction, we compared serum protein expression levels between 12 long-term METH users and 12 healthy controls using label-free quantitative proteomics. Bioinformatic analyses were conducted to determine functional networks and protein-protein interactions. Results: In total, 23 differentially expressed proteins were identified between the two groups. The differentially expressed proteins were related to cognitive dysfunction, neuroinflammation, immune impairment, metabolic disturbances, and calcium binding and regulation. Conclusions: These 23 proteins may underpin the multi-system damage induced by chronic METH exposure. Our findings provide novel insights into the molecular basis of METH addiction and inform potential prevention and treatment strategies for individuals with METH dependence. [ABSTRACT FROM AUTHOR]

The F1-ATPase enzyme is the smallest-known molecular motor that rotates in 120° steps, driven by the hydrolysis of ATP. It is a multi-subunit enzyme that contains three catalytic sites. A central question is how the elementary chemical reactions that occur in the three sites are coupled to mechanical rotation. Various models and coupling schemes have been formulated in an attempt to answer this question. They can be classified as 2-site (bi-site) models, exemplified by Boyer's binding change mechanism first proposed 50 years ago, and 3-site (tri-site) models such as Nath's torsional mechanism, first postulated 25 years ago and embellished 1 year back. Experimental data collated using diverse approaches have conclusively shown that steady-state ATP hydrolysis by F1-ATPase occurs in tri-site mode. Hence older models have been continually modified to make them conform to the new facts. Here, we have developed a pure mathematical approach based on combinatorics and conservation laws to test if proposed models are 2-site or 3-site. Based on this novel combinatorial approach, we have proved that older and modified models are effectively bi‒site models in that catalysis and rotation in F1-ATPase occurs in these models with only two catalytic sites occupied by bound nucleotide. Hence these models contradict consensus experimental data. The recent 2023 model of ATP hydrolysis by F1-ATPase has been proved to be a true tri-site model based on our novel mathematical approach. Such pure mathematical proofs constitute an important step forward for ATP mechanism. However, in what must be considered an aspect with great scientific potential, the power of such mathematical proofs has not been fully exploited to solve molecular biological problems, in our opinion. We believe that the creative application of pure mathematical proofs (for another example see Nath in Theory Biosci 141:249–260, 2022) can help resolve with finality various longstanding molecular-level issues that arise as a matter of course in the analysis of fundamental biological problems. Such issues have proved extraordinarily difficult to resolve by standard experimental, theoretical, or computational approaches. [ABSTRACT FROM AUTHOR]

The extraction of targets from biological samples for immunoassays using organic solvents, such as methanol, is often necessary. However, high concentrations of organic solvents in extracts invariably lead to instability of the employed antibody, resulting in poor performance of the immunoassay. Evaluating the tolerance ability and exploring the molecular mechanisms of antibody tolerance in organic solvents are essential for the development of robust immunoassays. In this work, 25 monoclonal antibodies and methanol are utilized as models to address these questions. A novel protocol is initially established to precisely and rapidly determine antibody tolerance in methanol, identifying two distinct methanol effect patterns. Through a detailed investigation of the structural basis, a novel hypothesis regarding methanol effect patterns is proposed, termed "folding‐aggregation," which is subsequently validated through molecular dynamics simulations. Furthermore, the investigation of sequence basis reveals significant differences in residue types within the complementarity‐determining regions and ligand‐binding residues, distinguishing the two antibody methanol effect patterns. Moreover, the methanol effect patterns of the antibodies are defined by germline antibodies. This work represents the first exploration of antibody methanol effect patterns and associated molecular mechanisms, with potential implications for the discovery and engineering of tolerant antibodies for the development of robust immunoassays. [ABSTRACT FROM AUTHOR]

With the continuous improvement in living standards, people's demand for high-quality meat is increasing. Ningxiang pig has delicious meat of high nutritional value, and is loved by consumers. However, its slow growth and low meat yield seriously restrict its efficient utilization. Gene expression is the internal driving force of life activities, so in order to fundamentally improve its growth rate, it is key to explore the molecular mechanism of skeletal muscle development in Ningxiang pigs. In this paper, Ningxiang boars were selected in four growth stages (30 days: weaning period, 90 days: nursing period, 150 days: early fattening period, and 210 days: late fattening period), and the longissimus dorsi (LD) muscle was taken from three boars in each stage. The fatty acid content, amino acid content, muscle fiber diameter density and type of LD were detected by gas chromatography, acidolysis, hematoxylin eosin (HE) staining and immunofluorescence (IF) staining. After transcription sequencing, weighted gene co-expression network analysis (WGCNA) combined with the phenotype of the LD was used to explore the key genes and signaling pathways affecting muscle development. The results showed that 10 modules were identified by WGCNA, including 5 modules related to muscle development stage, module characteristics of muscle fiber density, 5 modules characteristic of muscle fiber diameter, and a module characteristic of palmitoleic acid (C16:1) and linoleic acid (C18:2n6C). Gene ontology (GO) enrichment analysis found that 52 transcripts relating to muscle development were enriched in these modules, including 44 known genes and 8 novel genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that these genes were enriched in the auxin, estrogen and cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) pathways. Twelve of these genes were transcription factors, there were interactions among 20 genes, and the interactions among 11 proteins in human, pig and mouse were stable. To sum up, through the integrated analysis of phenotype and transcriptome, this paper analyzed the key genes and possible regulatory networks of skeletal muscle development in Ningxiang pigs at various stages, to provide a reference for the in-depth study of skeletal muscle development. [ABSTRACT FROM AUTHOR]

Polyacrylamide (PAM) is a high-molecular-weight polymer with extensive applications. However, the inefficient natural degradation of PAM results in environmental accumulation of the polymer. Biodegradation is an environmentally friendly approach in the field of PAM treatment. The first phase of PAM biodegradation is the deamination of PAM, forming the product poly(acrylic acid) (PAA). The second phase of PAM biodegradation involves the cleavage of PAA into small molecules, which is a crucial step in the degradation pathway of PAM. However, the enzyme that catalyzes the degradation of PAA and the molecular mechanism remain unclear. Here, a novel monooxygenase PCX02514 is identified as the key enzyme for PAA degradation. Through biochemical experiments, the monooxygenase PCX02514 oxidizes PAA with the participation of NADPH, causing the cleavage of carbon chains and a decrease in the molecular weight of PAA. In addition, the crystal structure of the monooxygenase PCX02514 is solved at a resolution of 1.97 Å. The active pocket is in a long cavity that extends from the C-terminus of the TIM barrel to the protein surface and exhibits positive electrostatic potential, thereby causing the migration of oxygen-negative ions into the active pocket and facilitating the reaction between the substrates and monooxygenase PCX02514. Moreover, Arg10-Arg125-Ser186-Arg187-His253 are proposed as potential active sites in monooxygenase PCX02514. Our research characterizes the molecular mechanism of this monooxygenase, providing a theoretical basis and valuable tools for PAM bioremediation. [ABSTRACT FROM AUTHOR]

Cognitive decline covers a broad spectrum of disorders, not only resulting from brain diseases but also from systemic diseases, which seriously influence the quality of life and life expectancy of patients. As a highly selective anatomical and functional interface between the brain and systemic circulation, the blood-brain barrier (BBB) plays a pivotal role in maintaining brain homeostasis and normal function. The pathogenesis underlying cognitive decline may vary, nevertheless, accumulating evidences support the role of BBB disruption as the most prevalent contributing factor. This may mainly be attributed to inflammation, metabolic dysfunction, cell senescence, oxidative/nitrosative stress and excitotoxicity. However, direct evidence showing that BBB disruption causes cognitive decline is scarce, and interestingly, manipulation of the BBB opening alone may exert beneficial or detrimental neurological effects. A broad overview of the present literature shows a close relationship between BBB disruption and cognitive decline, the risk factors of BBB disruption, as well as the cellular and molecular mechanisms underlying BBB disruption. Additionally, we discussed the possible causes leading to cognitive decline by BBB disruption and potential therapeutic strategies to prevent BBB disruption or enhance BBB repair. This review aims to foster more investigations on early diagnosis, effective therapeutics, and rapid restoration against BBB disruption, which would yield better cognitive outcomes in patients with dysregulated BBB function, although their causative relationship has not yet been completely established. [ABSTRACT FROM AUTHOR]

The incidence of kidney diseases is increasing globally, posing a serious threat to human health. Studies have shown that apigenin, a natural dietary flavonoid with multiple bioactivities, may be effective in protecting the kidneys and treating a variety of kidney diseases. This review collates and discusses the available evidence on the therapeutic effects of apigenin on common kidney diseases. In addition, the specific molecular mechanisms by which apigenin exerts its renoprotective effects are described, which informs further research and clinical nutritional applications of apigenin in the field of renal diseases. [ABSTRACT FROM AUTHOR]

Purpose: Targeting inflammatory crosstalk between tumors and their microenvironment has emerged as a crucial method for suppressing pancreatic adenocarcinoma (PAAD) progression. Berberine (BBR) is a natural pentacyclic isoquinoline alkaloid known for its anti-inflammatory and antitumor pharmacological effects; however, the mechanism underlying PAAD suppression remains unclear. We aim to investigate the effects of BBR on PAAD progression and their underlying mechanisms. Methods: The prognostic value of inflammation-related genes in PAAD was assessed using bioinformatics analyses, then the pharmacological effects and potential mechanisms of BBR on PAAD will be investigated in silico, in vitro, and in vivo. Results: Fifty-eight prognostic inflammation-related genes were identified in PAAD, which were shown to have good sensitivity and specificity using a novel inflammation-related gene risk-prognosis prediction model. Among these, four candidate genes (CAPS3, PTGS2, ICAM1, and CXCR4) were predicted as targets of BBR in PAAD in silico. Molecular docking simulations showed that the four key targets docked well with BBR. Further BBR treatment suppressed cell proliferation, colony formation, and induced cell cycle arrest in vitro. Moreover, BBR exhibited a significant tumor-suppressive effect in murine subcutaneous xenografts without macroscopic hepatic and renal toxicities. In addition, BBR downregulated CAPS3, PTGS2, ICAM1, and CXCR4 protein expression. Conclusion: This study not only elucidated the prognostic value of inflammation-related genes in PAAD but also demonstrated the potential of BBR to inhibit PAAD by targeting these genes. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are endogenous non-coding RNAs that play significant roles in the chemoresistance mechanisms of colorectal cancer (CRC). Chemotherapy is a crucial treatment modality for CRC, but resistance to chemotherapy remains a major challenge. Various studies have demonstrated that lncRNAs contribute to CRC chemoresistance through different mechanisms. Consequently, targeting lncRNAs to overcome CRC chemoresistance has been proposed as a therapeutic strategy. This review summarizes the recent advances in research on the mechanisms by which lncRNAs contribute to chemoresistance in CRC. [ABSTRACT FROM AUTHOR]

Bone tissue defects present a major challenge in orthopedic surgery. Bone tissue engineering using multiple versatile bioactive materials is a potential strategy for bone‐defect repair and regeneration. Due to their unique physicochemical and mechanical properties, biofunctional materials can enhance cellular adhesion, proliferation, and osteogenic differentiation, thereby supporting and stimulating the formation of new bone tissue. 3D bioprinting and physical stimuli‐responsive strategies have been employed in various studies on bone regeneration for the fabrication of desired multifunctional biomaterials with integrated bone tissue repair and regeneration properties. In this review, biomaterials applied to bone tissue engineering, emerging 3D bioprinting techniques, and physical stimuli‐responsive strategies for the rational manufacturing of novel biomaterials with bone therapeutic and regenerative functions are summarized. Furthermore, the impact of biomaterials on the osteogenic differentiation of stem cells and the potential pathways associated with biomaterial‐induced osteogenesis are discussed. [ABSTRACT FROM AUTHOR]

Desert strains of the genus Chroococcidiopsis are among the most desiccation-resistant cyanobacteria capable of anhydrobiosis. The accumulation of two sugars, sucrose and trehalose, facilitates the entrance of anhydrobiotes into a reversible state of dormancy by stabilizing cellular components upon water removal. This study aimed to evaluate, at the atomistic level, the role of trehalose in desiccation resistance by using as a model system the 30S ribosomal subunit of the desert cyanobacterium Chroococcidiopsis sp. 029. Molecular dynamic simulations provided atomistic evidence regarding its protective role on the 30S molecular structure. Trehalose forms an enveloping shell around the ribosomal subunit and stabilizes the structures through a network of direct interactions. The simulation confirmed that trehalose actively interacts with the 30S ribosomal subunit and that, by replacing water molecules, it ensures ribosomal structural integrity during desiccation, thus enabling protein synthesis to be carried out upon rehydration. [ABSTRACT FROM AUTHOR]

Pathogenic Bacillus and clostridial (i.e., Clostridium and Clostridioides) bacteria express a diverse repertoire of effector proteins to promote disease. This includes production of binary toxins, which enter host epithelial cells and seriously damage the intestinal tracts of insects, animals, and humans. In particular, binary toxins form an AB-type complex composed of a catalytic subunit that is toxic (A) and an oligomeric cell-binding and delivery subunit (B), where upon delivery of A into the cytoplasm of the host cell it catalytically ADP-ribosylates actin and rapidly induces host cell death. In this review, binary toxins expressed by Bacillus thuringiensis, Clostridioides difficile, and Clostridium perfringens will be discussed, with particular focus placed upon the structural elucidations of their respective B subunits and how these findings help to deconvolute how toxic enzyme delivery into target host cells is achieved by these deadly bacteria. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by irreversible scarring of lung tissue, leading to death. Despite recent advancements in understanding its pathophysiology, IPF remains elusive, and therapeutic options are limited and non-curative. This review aims to synthesize the latest research developments, focusing on the molecular mechanisms driving the disease and on the related emerging treatments. Unfortunately, several phase 2 studies showing promising preliminary results did not meet the primary endpoints in the subsequent phase 3, underlying the complexity of the disease and the need for new integrated endpoints. IPF remains a challenging condition with a complex interplay of genetic, epigenetic, and pathophysiological factors. Ongoing research into the molecular keystones of IPF is critical for the development of targeted therapies that could potentially stop the progression of the disease. Future directions include personalized medicine approaches, artificial intelligence integration, growth in genetic insights, and novel drug targets. [ABSTRACT FROM AUTHOR]

Intense and prolonged physical activity can lead to a decrease in muscle capacity, making it difficult to maintain the desired exercise intensity and resulting in exercise fatigue. The long‐term effects of exercise fatigue can be very damaging to the body, so it is an urgent problem to be addressed. The intervention of foodborne active substances will be an effective measure. There is growing evidence that the molecular structure and function of curcumin have a positive effect on relieving fatigue. In this review, we summarize curcumin's molecular structure, which enables it to bind to a wealth of molecular targets, regulate signaling pathways, and thus alleviate exercise fatigue through a variety of mechanisms, including reducing oxidative stress, inhibiting inflammation, reducing metabolite accumulation, and regulating energy metabolism. The effects of curcumin on fatigue‐related markers were analyzed from the perspective of animal models and human models and based on the bidirectional interaction between curcumin and intestinal microbiota: Intestinal microbiota can transform curcumin, and curcumin regulates gut microbiota through metabolic pathways, providing a new perspective for alleviating fatigue. This review contributes to a more comprehensive understanding of the possible molecular mechanisms of curcumin in anti‐fatigue and provides a new possibility for the development of functional foods in the future. [ABSTRACT FROM AUTHOR]

The genome of tomato spotted wilt virus (TSWV) can encode various proteins, including RdRp, NSm, NSs, Gc, Gn, and N. Existing research primarily focuses on plant (tomato and chili pepper) resistance to TSWV mediated by resistance genes (Sw-5b and Tsw). Furthermore, the inhibitory effects of agents on the TSWV N proteins have been investigated. TSWV proteins have the potential to be used as molecular targets for pharmaceutical agents, however, the mechanism of action between TSWV proteins and pharmaceutical agents has not been systematically and comprehensively reported. This study presents a detailed analysis of the three-dimensional structures of resolved TSWV proteins and predicts the structures of four unresolved TSWV proteins using AlphaFold2 modeling. It also summarizes the advancement and application of TSWV resistance genes and TSWV inhibitors in plant protection. The potential molecular mechanisms of ningnanmycin, moroxydine, and ribavirin on TSWV proteins were analyzed, along with their possible sites of action. The aim is to establish a theoretical foundation for subsequent comprehensive excavation and exploration of novel agents with anti-TSWV properties. [ABSTRACT FROM AUTHOR]

Rhododendron simsii Planchon is an important ornamental species in the northern hemisphere. Flower color is an important objective of Rhododendron breeding programs. However, information on anthocyanin synthesis in R. simsii is limited. In this research, the regulatory mechanism of anthocyanin biosynthesis in R. simsii was performed through the integrated analysis of metabolome and RNA-seq. A total of 805 and 513 metabolites were screened by positive and negative ionization modes, respectively, In total, 79 flavonoids contained seven anthocyanidins, 42 flavanones, 10 flavans, 13 flavones, and seven flavonols. Methylated and glycosylated derivatives took up the most. Differentially accumulated metabolites were mainly involved in "flavone and flavonol biosynthesis", "cyanoamino acid metabolism", "pyrimidine metabolism", and "phenylalanine metabolism" pathways. For flavonoid biosynthesis, different expression of shikimate O-hydroxycinnamoyltransferase, caffeoyl-CoA O-methyltransferase, flavonoid 3′-monooxygenase, flavonol synthase, dihydroflavonol 4-reductase/flavanone 4-reductase, F3′5′H, chalcone synthase, leucoanthocyanidin reductase, and 5-O-(4-coumaroyl)-D-quinate 3′-monooxygenase genes ultimately led to different accumulations of quercetin, myricetin, cyanidin, and eriodictyol. In flavone and flavonol biosynthesis pathway, differential expression of F3′5′H, flavonoid 3′-monooxygenase and flavonol-3-O-glucoside/galactoside glucosyltransferase genes led to the differential accumulation of quercetin, isovitexin, and laricitrin. This research will provide a biochemical basis for further modification of flower color and genetic breeding in R. simsii and related Rhododendron species. [ABSTRACT FROM AUTHOR]

1. Tibial dyschondroplasia (TD) is a skeletal disorder in broilers that has financial implications, necessitating dietary modifications to reduce the prevalence of this disease. This study explored how arginine silicate inositol complex (ASI) supplementation affected tibial growth plate (TGP) and overall bone health in broilers with manganese (Mn) deficiency-induced TD. 2. A total of 240 broiler chicks were divided into four groups, each consisting of 60 birds (15 replicates of four broilers each) as follows: i) Control, with 60 mg Mn per kg of diet; ii) ASI, with 60 mg Mn and 1 g ASI per kg of diet; iii) TD, with 22 mg Mn per kg of diet, and iv) TD+ASI, with 22 mg Mn and 1 g ASI per kg of diet. 3. It was found that ASI supplementation increased tibial bone length in Mn-deficient TD broilers (p = 0.007). There was no Mn x ASI interaction for other bone morphometry variables (p > 0.05). However, both tibial bone mineral content and density were affected by Mn and ASI (p < 0.05). With ASI supplementation, serum bone-specific alkaline phosphatase and osteocalcin levels were elevated in the TD+ASI group compared to the TD group (p < 0.001). In the TD group, osteoprotegerin (OPG) levels in the TGP decreased compared to the control groups (p < 0.001). 4. In contrast, ASI supplementation in the TD broilers counteracted the decrease in OPG compared to TD broilers without ASI supplementation (p < 0.001). The Mn level and ASI supplementation significantly influenced the OPG/receptor activator of the nuclear factor-κB ligand ratio (p < 0.001). 5. In conclusion, the results demonstrated that inclusion of ASI in broiler diets could enhance bone formation variables by controlling OPG levels in the TGP, potentially serving as an effective method to decrease the occurrence of TD. [ABSTRACT FROM AUTHOR]

Malignant pleural mesothelioma (MPM) is a rare, highly aggressive, and lethal tumor with poor prognosis. Its survival period ranges from four months to one year, and the 5-year survival rate is only about 10%. MPM is highly resistant to chemotherapy, and conventional treatments such as cisplatin combined with pemetrexed or raltitrexed only have a certain effect in about 20% of patients. In recent years, with the continuous in-depth understanding of the genetic variation characteristics of MPM, some progress has been made in the molecular mechanism underlying the chemotherapy resistance of MPM. This article will summarize the research progress of the molecular mechanism underlying the chemotherapy resistance of MPM, including BAP1 gene mutation, microRNA, MTA1-mediated DNA damage repair pathway, GITRGITRL pathway, TGFa pathway, tumor stem cell, EGFR, and PTEN. The aim of this work is to provide a reference for exploring new therapeutic targets and combined treatment options for MPM. [ABSTRACT FROM AUTHOR]

Key message: This review provides a thorough and comprehensive perspective on the topic of cucumber sexual expression. Specifically, insights into sex expression mediated by pathways other than ethylene are highlighted. Cucumber (Cucumis sativus L.) is a common and important commercial crop that is cultivated and consumed worldwide. Additionally, this species is commonly used as a model for investigating plant sex expression. Cucumbers exhibit a variety of floral arrangements, comprising male, female, and hermaphroditic (bisexual) flowers. Generally, cucumber plants that produce female flowers are typically preferred due to their significant impact on the overall output. Various environmental conditions, such as temperature, light quality, and photoperiod, have been also shown to influence the sex expression in this species. Multiple lines of evidence indicate that ethylene and its biosynthesis genes are crucial in regulating cucumber sex expression. Gibberellins, another well-known phytohormone, can similarly influence cucumber sex expression via an ethylene-independent route. Further studies employing the next-generation sequencing technology also visualized a deeper slice of the molecular mechanism such as the role of the cell cycle program in the cucumber sex expression. This review aims to provide an overview of the sex expression of cucumber including its underlying molecular mechanism and regulatory aspects based on recent investigations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Increasing studies have found that estrogen has a certain correlation with tendinopathy, but for a long time, there are few experiments and summaries of estrogen in tendinopathy, which makes it difficult for specialists and scholars in related fields to fully understand the research status. OBJECTIVE: To summarize the current clinical or preclinical original research, so as to summarize the role of estrogen in tendinosis, and make a certain prospect for the evaluation and management of estrogen in tendinosis in the future. METHODS: Relevant literature in PubMed, Web of Science, CNKI, WanFang, and VIP databases were searched by computer. Search time was from January 2008 to September 2023. The search terms were “oestrogen, estrogen, estrogen receptor, tendinopathy, tendonopathy, sinew, tendon, tendons, myotenositis” in English and “estrogen, estrogen receptor, tendinosis, tendon, tendinitis” in Chinese. According to the selection criteria, the search results were screened and excluded, and finally 60 documents were included for review and analysis. RESULTS AND CONCLUSION: In vivo studies have shown that estrogen can promote tendon anabolism. In vitro experiments have also proved that various estrogens can promote the proliferation of tendon cells and reduce inflammation and apoptosis, but most of the experiments are limited to animal models. Estrogen receptor β acts more in tendon injury and repair processes, but estrogen receptor α has not been found to have a major impact on tendon injury. The expression of estrogen receptor β can repair the tendon by affecting the formation of fat, the deposition of type I collagen and reducing the apoptosis of tendon cells, while its over-expression may promote inflammation and angiogenesis, thus promoting the inflammatory process and playing a role in tendon injury. Animal studies have shown that estrogen deficiency may reduce the synthesis efficiency of collagen in the tendon, decrease the elasticity of tendon, inhibit the synthesis and metabolism of the tendon, which is not conducive to the repair of tendon injury, while normal level of estrogen may stimulate the synthesis of type I collagen in tendon and promote the proliferation and metabolism of tendon cells. At present, the molecular mechanism of estrogen in tendon injury has not been fully explained. More experiments focus on tendon collagen synthesis, cell proliferation and apoptosis. Only a few documents have studied the molecular mechanisms of estrogen receptor β deficiency regulating interferon regulatory factor 5-chemokine ligand 3 axis, E2 regulating estrogen receptor α and PI-3K-Akt signaling pathways, and high levels of estradiol reducing the level of free-circulating insulin-like growth factor. Various estrogens, including endogenous estrogens and phytoestrogens, are beneficial to the repair of tendinopathy at normal levels, and estrogen receptor β mainly affects the formation of fat, the deposition of type I collagen and the reduction of apoptosis of tendon cells through, which lays a foundation for the future treatment of tendinopathy with different subtypes of estrogens in vivo and the influence of estrogen membrane receptors on tendinopathy. [ABSTRACT FROM AUTHOR]

Scutellarin, one of natural flavonoids from Scutellaria barbata D. Don and Erigeron breviscapus (vant) Hand.-Mazz. Modern pharmacological studies have shown that scutellarin has a good anti-tumor effect. According to the literature review at home and abroad, scutellarin can inhibit the growth and metastasis of tumor cells, block the cell cycle at various stages, induce apoptosis and autophagy, interfere with tumor metabolism, reverse drug resistance of tumor cells and enhance the sensitivity of chemotherapy drugs. In this paper, the anti-tumor mechanism of scutellarin was reviewed, and the shortcomings of current studies and future research directions were analyzed, so as to provide a basis for further exploration of the anti-tumor potential of scutellarin and its further development and utilization. [ABSTRACT FROM AUTHOR]

[Display omitted] • Selective autophagy is characterized by its ability to specifically degrade a certain substrate, rather than causing widespread cell autophagy. • The mechanisms underlying selective autophagy can be broadly dispersed in three steps: designation, targeting and sequestration, and degradation. • Numerous human diseases and their progression are closely linked to aberrant selective autophagy. • Deciphering the molecular mechanisms underlying selective autophagy provides a theoretical framework for treating relevant clinical disorders. • Regulation of selective autophagy by discovering and developing small-molecule agents has great clinical application prospects for the treatment of related diseases. Autophagy is an evolutionarily conserved turnover process for intracellular substances in eukaryotes, relying on lysosomal (in animals) or vacuolar (in yeast and plants) mechanisms. In the past two decades, emerging evidence suggests that, under specific conditions, autophagy can target particular macromolecules or organelles for degradation, a process termed selective autophagy. Recently, accumulating studies have demonstrated that the abnormality of selective autophagy is closely associated with the occurrence and progression of many human diseases, including neurodegenerative diseases, cancers, metabolic diseases, and cardiovascular diseases. This review aims at systematically and comprehensively introducing selective autophagy and its role in various diseases, while unravelling the molecular mechanisms of selective autophagy. By providing a theoretical basis for the development of related small-molecule drugs as well as treating related human diseases, this review seeks to contribute to the understanding of selective autophagy and its therapeutic potential. In this review, we systematically introduce and dissect the major categories of selective autophagy that have been discovered. We also focus on recent advances in understanding the molecular mechanisms underlying both classical and non-classical selective autophagy. Moreover, the current situation of small-molecule drugs targeting different types of selective autophagy is further summarized, providing valuable insights into the discovery of more candidate small-molecule drugs targeting selective autophagy in the future. On the other hand, we also reveal clinically relevant implementations that are potentially related to selective autophagy, such as predictive approaches and treatments tailored to individual patients. [ABSTRACT FROM AUTHOR]

Dishevelled, EGL-10 and pleckstrin domain-containing 1 (DEPDC1) has been identified as a crucial factor in the development and progression of various types of cancer. This protein, which is largely undetectable in normal tissues but is highly expressed in numerous tumor types, serves a significant role in cell mitosis, proliferation, migration, invasion, angiogenesis, autophagy and apoptosis. Furthermore, DEPDC1 is implicated in several key signaling pathways, such as NF-κB, PI3K/Akt, Wnt/β-catenin and Hippo pathways, which are essential for cell proliferation and survival. The expression of DEPDC1 has been linked to poor prognosis and survival rates in multiple types of cancer, including hepatocellular carcinoma, lung adenocarcinoma, colorectal cancer and breast cancer. Notably, DEPDC1 has been suggested to have potential as a diagnostic and prognostic marker, as well as a therapeutic target. Its involvement in critical signaling pathways suggests that targeting DEPDC1 could inhibit tumor growth and metastasis, thereby improving patient outcomes. In addition, clinical trials have shown promising results for DEPDC1-derived peptide vaccines, indicating their safety and potential efficacy in cancer treatment. To the best of our knowledge, this is the first comprehensive review addressing the role of DEPDC1 in cancer. Through a critical analysis of existing studies, the present review aimed to consolidate existing knowledge and highlight gaps in understanding, paving the way for future research to elucidate the complex interactions of DEPDC1 in the context of cancer biology. [ABSTRACT FROM AUTHOR]

AbstractDiabetes has become a serious public health crisis, presenting significant challenges to individuals worldwide. As the largest organ in the human body, skeletal muscle is a significant target of this chronic disease, yet muscle wasting as a complication of diabetes is still not fully understood and effective treatment methods have yet to be developed. Here, we discuss the targets involved in inducing muscle wasting under diabetic conditions, both validated targets and emerging targets. Diabetes-induced skeletal muscle wasting is known to involve changes in various signaling molecules and pathways, such as protein degradation pathways, protein synthesis pathways, mitochondrial function, and oxidative stress inflammation. Recent studies have shown that some of these present potential as promising therapeutic targets, including the neuregulin 1/epidermal growth factor receptor family, advanced glycation end-products, irisin, ferroptosis, growth differentiation factor 15 and more. This study’s investigation and discussion of such pathways and their potential applications provides a theoretical basis for the development of clinical treatments for diabetes-induced muscle wasting and a foundation for continued focus on this disease. [ABSTRACT FROM AUTHOR]

The research is aimed to elucidate the role of plant hormones in regulating the development of hybrid embryos in Hydrangea macrophylla. Fruits from the intraspecific cross of H. macrophylla 'Otaksa' × 'Coerulea' were selected at the globular, heart, and torpedo stages of embryo development. Transcriptome sequencing and differential gene expression analysis were conducted. The results showed that fruit growth followed a single "S-shaped growth curve, with globular, heart, and torpedo embryos appearing at 30, 40, and 50 d post-pollination, respectively, and the embryo maintaining the torpedo shape from 60 to 90 d. A total of 12,933 genes was quantified across the three developmental stages, with 3359, 3803, and 3106 DEGs in the S1_vs_S2, S1_vs_S3, and S2_vs_S3 comparisons, respectively. Among these, 133 genes related to plant hormone biosynthesis and metabolism were differentially expressed, regulating the synthesis and metabolism of eight types of plant hormones, including cytokinin, auxin, gibberellin, abscisic acid, and jasmonic acid. The pathways with the most differentially expressed genes were cytokinin, auxin, and gibberellin, suggesting these hormones may play crucial roles in embryo development. In the cytokinin pathway, CKX (Hma1.2p1_0579F.1_g182670.gene, Hma1.2p1_1194F.1_g265700.gene, and NewGene_12164) genes were highly expressed during the globular embryo stage, promoting rapid cell division in the embryo. In the auxin pathway, YUC (Hma1.2p1_0271F.1_g109005.gene and Hma1.2p1_0271F.1_g109020.gene) genes were progressively up-regulated during embryo growth; the early response factor AUX/IAA (Hma1.2p1_0760F.1_g214260.gene) was down-regulated, while the later transcriptional activator ARF (NewGene_21460, NewGene_21461, and Hma1.2p1_0209F.1_g089090.gene) was up-regulated, sustaining auxin synthesis and possibly preventing the embryo from transitioning to maturity. In the gibberellin pathway, GA3ox (Hma1.2p1_0129F.1_g060100.gene) expression peaked during the heart embryo stage and then declined, while the negative regulator GA2ox (Hma1.2p1_0020F.1_g013915.gene) showed the opposite trend; and the gibberellin signaling repressor DELLA (Hma1.2p1_1054F.1_g252590.gene) increased over time, potentially inhibiting embryo development and maintaining the torpedo shape until fruit maturity. These findings preliminarily uncover the factors affecting the development of hybrid H. macrophylla embryos, laying a foundation for further research into the regulatory mechanisms of H. macrophylla hybrid embryo development. [ABSTRACT FROM AUTHOR]

The transient receptor potential melastatin (TRPM) tetrameric cation channels are involved in a wide range of biological functions, from temperature sensing and taste transduction to regulation of cardiac function, inflammatory pain, and insulin secretion. The structurally conserved TRPM cytoplasmic domains make up >70 % of the total protein. To investigate the mechanism by which the TRPM cytoplasmic domains contribute to gating, we employed electrophysiology and cryo-EM to study TRPM5--a channel that primarily relies on activation via intracellular Ca2+. Here, we show that activation of mammalian TRPM5 channels is strongly altered by Ca2+-dependent desensitization. Structures of rat TRPM5 identify a series of conformational transitions triggered by Ca2+ binding, whereby formation and dissolution of cytoplasmic interprotomer interfaces appear to control activation and desensitization of the channel. This study shows the importance of the cytoplasmic assembly in TRPM5 channel function and sets the stage for future investigations of other members of the TRPM family. [ABSTRACT FROM AUTHOR]

Pyroptosis is a programmed cell death with inflammatory response. Gasdermin D (GSDMD) is a key protein that mediates pyroptosis and is the main executor. When inflammasomes are stimulated by pathogenic microorganisms, the pyroptosis signal caspase is activated, which cuts GSDMD. Then the amino terminal (N terminal) of GSDMD is transferred to the cell membrane to form intracellular pores that allow water molecules and other substances to enter, causing cell swelling and cracking, leading to cell death, that is, cell pyroptosis. In recent years, scientific research has demonstrated that GSDMD may be involved in the pathogenesis of bone metabolic diseases, especially osteoporosis, by mediating osteoblast pyroptosis. Inhibition of osteoblast pyroptosis may regulate the development of osteoporosis. Osteoblast pyroptosis may interfere with bone metabolism as a pro-inflammatory way to regulate osteocyte death, and its research is a new research hot spot. In this paper, the molecular mechanism of GSDMD-mediated osteoblast pyroptosis is analyzed and discussed, and the relationship between GSDMD-mediated osteoblast pyroptosis and the field of cell pyroptosis is reviewed. The relationship between osteoblast pyroptosis and osteoporosis is analyzed, which provides a key target protein factor mechanism for the research and diagnosis and treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Purpose: Employing polymer additives is an effective strategy to realize the manipulation of polymorphic transformation. However, the manipulation mechanism is still not clear, which limit the precise selection of polymeric excipients and the development of pharmaceutical formulations. Methods: The solubility of cimetidine (CIM) in acetonitrile/water mixtures were measured. And the polymorphic transformation from CIM form A to form B with the addition of different polymers was monitored by Raman spectroscopy. Furthermore, the manipulation effect of polymers was determined based on the results of experiments and molecular simulations. Results: The solubility of form A is consistently higher than that of form B, which indicate that form B is the thermodynamically stable form within the examined temperature range. The presence of polyvinylpyrrolidone (PVP) of a shorter chain length could have a stronger inhibitory effect on the phase transformation process of metastable form, whereas polyethylene glycol (PEG) had almost no impact. The nucleation kinetics experiments and molecular dynamic simulation results showed that only PVP molecules could significantly decrease the nucleation rate of CIM, due to the ability of reducing solute molecular diffusion and solute–solute molecular interaction. A combination of crystal growth rate measurements and calculations of the interaction energies between PVP and the crystal faces of CIM indicate that smaller molecular weight PVP can suppress crystal growth more effectively. Conclusion: PVP K16-18 has more impact on the stabilization of CIM form A and inhibition of the phase transformation process. The manipulation mechanism of polymer additives in the polymorphic transformation of CIM was proposed. [ABSTRACT FROM AUTHOR]

Maize (Zea mays L.) is an important food crop with a wide range of uses in both industry and agriculture. Drought stress during its growth cycle can greatly reduce maize crop yield and quality. However, the molecular mechanisms underlying maize responses to drought stress remain unclear. In this work, a WRKY transcription factor‐encoding gene, ZmWRKY30, from drought‐treated maize leaves was screened out and characterized. ZmWRKY30 gene expression was induced by dehydration treatments. The ZmWRKY30 protein localized to the nucleus and displayed transactivation activity in yeast. Compared with wild‐type (WT) plants, Arabidopsis lines overexpressing ZmWRKY30 exhibited a significantly enhanced drought stress tolerance, as evidenced by the improved survival rate, increased antioxidant enzyme activity by superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), elevated proline content, and reduced lipid peroxidation recorded after drought stress treatment. In contrast, the mutator (Mu)‐interrupted ZmWRKY30 homozygous mutant (zmwrky30) was more sensitive to drought stress than its null segregant (NS), characterized by the decreased survival rate, reduced antioxidant enzyme activity (SOD, POD, and CAT) and proline content, as well as increased malondialdehyde accumulation. RNA‐Seq analysis further revealed that, under drought conditions, the knockout of the ZmWRKY30 gene in maize affected the expression of genes involved in reactive oxygen species (ROS), proline, and myo‐inositol metabolism. Meanwhile, the zmwrky30 mutant exhibited significant downregulation of myo‐inositol content in leaves under drought stress. Combined, our results suggest that ZmWRKY30 positively regulates maize responses to water scarcity. This work provides potential target genes for the breeding of drought‐tolerant maize. [ABSTRACT FROM AUTHOR]

Background: Candida vulturna is an emerging pathogen belonging to the Metshnikowiaceae family together with Candida auris and Candida haemulonii species complex. Some strains of this species were reported to be resistant to several antifungal agents. Objectives: This study aims to address identification difficulties, evaluate antiungal susceptibilities and explore the molecular mechanisms of azole resistance of Candida vulturna. Methods: We studied five C. vulturna clinical strains isolated in three Colombian cities. Identification was performed by phenotypical, proteomic and molecular methods. Antifungal susceptibility testing was performed following CLSI protocol. Its ERG11 genes were sequenced and a substitution was encountered in azole resistant isolates. To confirm the role of this substitution in the resistance phenotype, Saccharomyces cerevisiae strains with a chimeric ERG11 gene were created. Results: Discrepancies in identification methods are highlighted. Sequencing confirmed the identification as C. vulturna. Antifungal susceptibility varied among strains, with four strains exhibiting reduced susceptibility to azoles and amphotericin B. ERG11 sequencing showed a point mutation (producing a P135S substitution) that was associated with the azole‐resistant phenotype. Conclusions: This study contributes to the understanding of C. vulturna's identification challenges, its susceptibility patterns, and sheds light on its molecular mechanisms of azole resistance. [ABSTRACT FROM AUTHOR]

Objective: Brusatol (BT) is a quassinoid compound extracted from Brucea javanica that is a traditional Chinese herbal medicine. Brusatol possesses biological and medical activity, including antitumor, antileukemia, anti-inflammatory, antitrypanosomal, antimalarial, and antitobacco mosaic virus activity. To summarize and discuss the antitumor effects of BT and its mechanisms of actions, we compiled this review by combining the extensive relevant literature and our previous studies. Methods: We searched and retrieved the papers that reported the pharmacological effects of BT and the mechanism of BT antitumor activity from PubMed until July 2023. Key findings: Numerous studies have shown that BT is a unique nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor that acts on various signaling pathways and has good antitumor properties. Brusatol shows great potential in cancer therapy by inhibiting cell proliferation, blocking the cell cycle, promoting tumor cell differentiation, accelerating tumor cell apoptosis, inducing autophagy, suppressing angiogenesis, inhibiting tumor invasion and metastasis, and reversing multidrug resistance. Conclusion: This review summarizes recent updates on the antitumor activity and molecular mechanisms of BT and provides references for future development and clinical translation of BT and its derivatives as antitumor drugs. [ABSTRACT FROM AUTHOR]