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1.
Sci Rep ; 14(1): 8642, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622172

RESUMO

Cation exchanger (CAX) genes play an important role in plant growth/development and response to biotic and abiotic stresses. Here, we tried to obtain important information on the functionalities and phenotypic effects of CAX gene family by systematic analyses of their expression patterns, genetic diversity (gene CDS haplotypes, structural variations, gene presence/absence variations) in 3010 rice genomes and nine parents of 496 Huanghuazhan introgression lines, the frequency shifts of the predominant gcHaps at these loci to artificial selection during modern breeding, and their association with tolerances to several abiotic stresses. Significant amounts of variation also exist in the cis-regulatory elements (CREs) of the OsCAX gene promoters in 50 high-quality rice genomes. The functional differentiation of OsCAX gene family were reflected primarily by their tissue and development specific expression patterns and in varied responses to different treatments, by unique sets of CREs in their promoters and their associations with specific agronomic traits/abiotic stress tolerances. Our results indicated that OsCAX1a and OsCAX2 as general signal transporters were in many processes of rice growth/development and responses to diverse environments, but they might be of less value in rice improvement. OsCAX1b, OsCAX1c, OsCAX3 and OsCAX4 was expected to be of potential value in rice improvement because of their associations with specific traits, responsiveness to specific abiotic stresses or phytohormones, and relatively high gcHap and CRE diversity. Our strategy was demonstrated to be highly efficient to obtain important genetic information on genes/alleles of specific gene family and can be used to systematically characterize the other rice gene families.


Assuntos
Oryza , Melhoramento Vegetal , Sequências Reguladoras de Ácido Nucleico , Estresse Fisiológico/genética , Cátions/metabolismo , Variação Genética
2.
Int J Mol Sci ; 25(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38612538

RESUMO

Excessive alcohol intake will aggravate the health risk between the liver and intestine and affect the multi-directional information exchange of metabolites between host cells and microbial communities. Because of the side effects of clinical drugs, people tend to explore the intervention value of natural drugs on diseases. As a flavor substance, spices have been proven to have medicinal value, but they are still rare in treating hepatointestinal diseases caused by alcohol. This paper summarized the metabolic transformation of alcohol in the liver and intestine and summarized the potential value of various perfume active substances in improving liver and intestine diseases caused by alcohol. It is also found that bioactive substances in spices can exert antioxidant activity in the liver and intestine environment and reduce the oxidative stress caused by diseases. These substances can interfere with fatty acid synthesis, promote sugar and lipid metabolism, and reduce liver injury caused by steatosis. They can effectively regulate the balance of intestinal flora, promote the production of SCFAs, and restore the intestinal microenvironment.


Assuntos
Etanol , Fígado Gorduroso , Humanos , Intestinos , Especiarias
3.
J Colloid Interface Sci ; 667: 44-53, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38615622

RESUMO

The construction of high-asymmetrical structures demonstrates significant potential in improving the functionality and distinctness of nanomaterials, but remains a considerable challenge. Herein, we develop a one-pot method to fabricate regioselective super-assembly of Prussian blue analogue (PBA) -- a PBA anisotropic structure (PBA-AS) decorated with epitaxial modules--using a step-by-step epitaxial growth on a rapidly self-assembled cubic substrate guided by thiocyanuric acid (TCA) molecules. The epitaxial growth units manifest as diverse geometric shapes, which are predominantly concentrated on the {100}, {111}, or {100}+{111} crystal plane of the cubic substrate. The crystal plane and morphology of epitaxial module can be regulated by changing the TCA concentration and reaction temperature, enabling a high level of controllability over specific assembly sites and structures. To illustrate the advantage of the asymmetrical structure, phosphated PBA-AS demonstrates improved performance in the oxygen evolution reaction compared to simple phosphated PBA nanocube. This method offers valuable insights for designing asymmetrical nanomaterials with intricate architectures and versatile functionalities.

4.
Hum Vaccin Immunother ; 20(1): 2330770, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38602539

RESUMO

The immunogenicity and safety of the concomitant administration of recombinant COVID-19 vaccine and quadrivalent inactivated influenza vaccine (Split Virion) (QIIV) in Chinese adults are unclear. In this open-label, randomized controlled trial, participants aged ≥ 18 years were recruited. Eligible healthy adults were randomly assigned (1:1) to receive QIIV at the same time as the first dose of COVID-19 vaccine (simultaneous-group) or 14 days after the second dose of COVID-19 vaccine (non-simultaneous-group). The primary outcome was to compare the difference in immunogenicity of QIIV (H1N1, H3N2, Yamagata, and Victoria) between the two groups. A total of 299 participants were enrolled, 149 in the simultaneous-group and 150 in the non-simultaneous-group. There were no significant differences in geometric mean titer (GMT) [H1N1: 386.4 (95%CI: 299.2-499.0) vs. 497.4 (95%CI: 377.5-655.3); H3N2: 66.9 (95%CI: 56.1-79.8) vs. 81.4 (95%CI: 67.9-97.5); Yamagata: 95.6 (95%CI: 79.0-115.8) vs. 74.3 (95%CI: 58.6-94.0); and Victoria: 48.5 (95%CI: 37.6-62.6) vs. 65.8 (95%CI: 49.0-88.4)] and seroconversion rate (H1N1: 87.5% vs. 90.1%; H3N2: 58.1% vs. 62.0%; Yamagata: 75.0% vs. 64.5%; and Victoria: 55.1% vs. 62.8%) of QIIV antibodies between the simultaneous and non-simultaneous groups. For the seroprotection rate of QIIV antibodies, a higher seroprotection rate of Yamagata antibody was observed only in the simultaneous-group than in the non-simultaneous-group [86.0% vs. 76.0%, p = .040]. In addition, no significant difference in adverse events was observed between the two groups (14.2% vs. 23.5%, p = .053). In conclusion, no immune interference or safety concerns were found for concomitant administration of COVID-19 vaccine with QIIV in adults aged ≥ 18 years.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Adulto , Humanos , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Vírus da Influenza A Subtipo H3N2 , Vacinas contra Influenza/efeitos adversos , Anticorpos , China
5.
Front Oncol ; 14: 1286426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38571492

RESUMO

Familial non-medullary thyroid carcinoma (FNMTC) is a type of thyroid cancer characterized by genetic susceptibility, representing approximately 5% of all non-medullary thyroid carcinomas. While some cases of FNMTC are associated with familial multi-organ tumor predisposition syndromes, the majority occur independently. The genetic mechanisms underlying non-syndromic FNMTC remain unclear. Initial studies utilized SNP linkage analysis to identify susceptibility loci, including the 1q21 locus, 2q21 locus, and 4q32 locus, among others. Subsequent research employed more advanced techniques such as Genome-wide Association Study and Whole Exome Sequencing, leading to the discovery of genes such as IMMP2L, GALNTL4, WDR11-AS1, DUOX2, NOP53, MAP2K5, and others. But FNMTC exhibits strong genetic heterogeneity, with each family having its own pathogenic genes. This is the first article to provide a chromosomal landscape map of susceptibility genes associated with non-syndromic FNMTC and analyze their potential associations. It also presents a detailed summary of variant loci, characteristics, research methodologies, and validation results from different countries.

6.
iScience ; 27(4): 109456, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38591005

RESUMO

Spermiogenesis defines the final phase of male germ cell differentiation. While multiple deubiquitinating enzymes have been linked to spermiogenesis, the impacts of deubiquitination on spermiogenesis remain poorly characterized. Here, we investigated the function of UAF1 in mouse spermiogenesis. We selectively deleted Uaf1 in premeiotic germ cells using the Stra8-Cre knock-in mouse strain (Uaf1 sKO), and found that Uaf1 is essential for spermiogenesis and male fertility. Further, UAF1 interacts and colocalizes with USP1 in the testes. Conditional knockout of Uaf1 in testes results in disturbed protein levels and localization of USP1, suggesting that UAF1 regulates spermiogenesis through the function of the deubiquitinating enzyme USP1. Using tandem mass tag-based proteomics, we identified that conditional knockout of Uaf1 in the testes results in reduced levels of proteins that are essential for spermiogenesis. Thus, we conclude that the UAF1/USP1 deubiquitinase complex is essential for normal spermiogenesis by regulating the levels of spermiogenesis-related proteins.

7.
Plant Biotechnol J ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593377

RESUMO

Fusarium head blight (FHB) and the presence of mycotoxin deoxynivalenol (DON) pose serious threats to wheat production and food safety worldwide. DON, as a virulence factor, is crucial for the spread of FHB pathogens on plants. However, germplasm resources that are naturally resistant to DON and DON-producing FHB pathogens are inadequate in plants. Here, detoxifying bacteria genes responsible for DON epimerization were used to enhance the resistance of wheat to mycotoxin DON and FHB pathogens. We characterized the complete pathway and molecular basis leading to the thorough detoxification of DON via epimerization through two sequential reactions in the detoxifying bacterium Devosia sp. D6-9. Epimerization efficiently eliminates the phytotoxicity of DON and neutralizes the effects of DON as a virulence factor. Notably, co-expressing of the genes encoding quinoprotein dehydrogenase (QDDH) for DON oxidation in the first reaction step, and aldo-keto reductase AKR13B2 for 3-keto-DON reduction in the second reaction step significantly reduced the accumulation of DON as virulence factor in wheat after the infection of pathogenic Fusarium, and accordingly conferred increased disease resistance to FHB by restricting the spread of pathogenic Fusarium in the transgenic plants. Stable and improved resistance was observed in greenhouse and field conditions over multiple generations. This successful approach presents a promising avenue for enhancing FHB resistance in crops and reducing mycotoxin contents in grains through detoxification of the virulence factor DON by exogenous resistance genes from microbes.

8.
Sci Rep ; 14(1): 8335, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594318

RESUMO

Enhancing information security has become increasingly significant in the digital age. This paper investigates the concept of physical layer security (PLS) within a relay-aided power line communication (PLC) system operating over a multiple-input multiple-output (MIMO) channel based on MK model. Specifically, we examine the transmission of confidential signals between a source and a distant destination while accounting for the presence of multiple eavesdroppers, both colluding and non-colluding. We propose a two-phase jamming scheme that leverages a full-duplex (FD) amplify-and-forward (AF) relay to address this challenge. Our primary objective is to maximize the secrecy rate, which necessitates the optimization of the jamming precoding and transmitting precoding matrices at both the source and the relay while adhering to transmit power constraints. We present a formulation of this problem and demonstrate that it can be efficiently solved using an effective block coordinate descent (BCD) algorithm. Simulation results are conducted to validate the convergence and performance of the proposed algorithm. These findings confirm the effectiveness of our approach. Furthermore, the numerical analysis reveals that our proposed algorithm surpasses traditional schemes that lack jamming to achieve higher secrecy rates. As a result, the proposed algorithm offers the benefit of guaranteeing secure communications in a realistic channel model, even in scenarios involving colluding eavesdroppers.

9.
Food Funct ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38590277

RESUMO

Lactiplantibacillus plantarum NCUH001046 (LP)-fermented tomatoes exhibited the potential to alleviate obesity in our previous study. This subsequent study further delves deeper into the effects of LP fermentation on the physicochemical properties, bioactivities, and hepatic lipid metabolism modulation of tomatoes, as well as the analysis of potential bioactive compounds exerting obesity-alleviating effects. Results showed that after LP fermentation, viable bacterial counts peaked at 9.11 log CFU mL-1 and sugar decreased, while organic acids, umami amino acids, total phenols, and total flavonoids increased. LP fermentation also improved the inhibition capacities of three digestive enzyme activities and Enterobacter cloacae growth, as well as antioxidant activities. Western blot results indicated that fermented tomatoes, especially live probiotic-fermented tomatoes (LFT), showed improved effects compared to unfermented tomatoes in reducing hepatic lipid accumulation by activating the AMPK signal pathway. UHPLC-Q-TOF/MS-based untargeted metabolomics analysis showed that chlorogenic acid, capsiate, tiliroside, irisflorentin, and homoeriodictyol levels increased after fermentation. Subsequent cell culture assays demonstrated that irisflorentin and homoeriodictyol reduced lipid accumulation via enhancing AMPK expression in oleic acid-induced hyperlipidemic HepG2 cells. Furthermore, Spearman's correlation analysis indicated that the five phenols were positively associated with hepatic AMPK pathway activation. Consequently, it could be inferred that the five phenols may be potential bioactive compounds in LFT to alleviate obesity and lipid metabolism disorders. In summary, these findings underscored the transformative potential of LP fermentation in enhancing the bioactive profile of tomatoes and augmenting its capacity to alleviate obesity and lipid metabolism disorders. This study furnished theoretical underpinnings for the functional investigation of probiotic-fermented plant-based foods.

10.
Food Funct ; 15(8): 4462-4474, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38563684

RESUMO

Fermented soymilk (FSM4) has attracted much attention due to its nutritional and health characteristics. Exploring FSM4 products to alleviate diarrhea can ensure their effectiveness as a therapeutic food for alleviating gastrointestinal disorders. However, the relationship between gut microbiota and gut metabolite production remains unknown during diarrheal episodes. Therefore, the diarrhea-alleviating role and mechanisms of FSM4 in diarrhea rats were investigated via biochemical, gut microbiota, and serum metabolite analyses. The findings showed that consuming FSM4 improved diarrhea symptoms and reduced systemic inflammation better than non-fermented soymilk (NFSM). It is worth noting that FSM4 promoted the diversity, richness, structure, and composition of gut microbiota. It increased the ability to reduce inflammation associated with harmful bacteria (Anaerofilum, Flavonifractor, Bilophila, Anaerostipes, [Ruminococcus]_torques_group, Clostridium_sensu_stricto_1, Turicibacter, Ruminococcus_1, Ruminiclostridium_6, Prevotellaceae_NK3B31_group and Fusicatenibacter), while stimulating the growth of healthy species (Lactobacillus, Ruminococcaceae_UCG-014, Oscillibacter, [Eubacterium]_coprostanoligenes_group, Negativibacillus, and Erysipelotrichaceae_UCG-003). Moreover, metabolomics analysis showed that lipid metabolites such as lysophosphatidylethanolamine (LysoPE) and sphingolipids were upregulated in the NG group, closely related to pro-inflammatory cytokines (IL-6, IL-1ß, TNF-α, and IFN-γ) and the aforementioned pathogenic bacteria. Notably, in treatment groups, especially FSM4, the accumulation of L-ornithine, aspartic acid, ursocholic acid, 18-oxooleate, and cyclopentanethiol was increased, which was robustly associated with the anti-inflammatory factor IL-10 and beneficial bacteria mentioned above. Therefore, it can be inferred that the amino acids, bile acid, 18-oxooleate, and cyclopentanethiol produced in the FSM4 group can serve as metabolic biomarkers, which synergistically act with the gut microbiota to help alleviate inflammation for diarrhea remission. Overall, FSM4 may provide a new alternative, as an anti-inflammatory diet, to alleviate diarrhea.

11.
BMC Infect Dis ; 24(1): 413, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641791

RESUMO

Considering that neutralizing antibody levels induced by two doses of the inactivated vaccine decreased over time and had fallen to low levels by 6 months, and homologous and heterologous booster immunization programs have been implemented in adults in China. The booster immunization of recombinant COVID-19 vaccine (ZF2001) after priming with inactivated vaccine in healthy children and adolescents has not been reported. We performed an open-labeled, single-arm clinical trial to evaluate the safety and immunogenicity of heterologous booster immunization with ZF2001 after priming with inactivated vaccine among 240 population aged 3-17 years in China. The primary outcome was immunogenicity, including geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates of SARS-CoV-2 neutralizing antibodies against prototype SARS-CoV-2 and Omicron BA.2 variant at 14 days after vaccination booster. On day 14 post-booster, a third dose booster of the ZF2001 provided a substantial increase in antibody responses in minors, and the overall occurrence rate of adverse reactions after heterologous vaccination was low and all adverse reactions were mild or moderate. The results showed that the ZF2001 heterologous booster had high immunogenicity and good safety profile in children and adolescents, and can elicit a certain level of neutralizing antibodies against Omicron.Trial registration NCT05895110 (Retrospectively registered, First posted in ClinicalTrials.gov date: 08/06/2023).


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacinas de Subunidades , Adulto , Criança , Humanos , Adolescente , Vacinas contra COVID-19/efeitos adversos , Vacinas de Produtos Inativados/efeitos adversos , COVID-19/prevenção & controle , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Imunogenicidade da Vacina
12.
Adv Mater ; : e2312369, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581648

RESUMO

Traditional noble metal oxide, such as RuO2, is considered a benchmark catalyst for acidic oxygen evolution reaction (OER). However, its practical application is limited due to sluggish activity and severe electrochemical corrosion. In this study, Ru-Fe nanoparticles loading on carbon felt (RuFe@CF) is synthesized via an ultrafast Joule heating method as an active and durable OER catalyst in acidic conditions. Remarkably low overpotentials of 188 and 269 mV are achieved at 10 and 100 mA cm-2, respectively, with a robust stability up to 620 h at 10 mA cm-2. When used as an anode in a proton exchange membrane water electrolyzer, the catalyst shows more than 250 h of stability at a water-splitting current of 200 mA cm-2. Experimental characterizations reveal the presence of a Ru-based oxide nanosheath on the surface of the catalyst during OER tests, suggesting a surface reconstruction process that enhances the intrinsic activity and inhibits continuous metal dissolution. Moreover, density functional theory calculations demonstrate that the introduction of Fe into the RuFe@CF catalyst reduces the energy barrier and boosts its activities. This work offers an effective and universal strategy for the development of highly efficient and stable catalysts for acidic water splitting.

13.
Food Chem ; 450: 139335, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38642533

RESUMO

Laotan Suancai, a popular traditional Chinese fermented vegetable, is manufactured in the industry via four fermentation rounds. However, the differences in flavor quality of Laotan Suancai from the four fermentation rounds and the causes of this variation remain unclear. Metabolome analysis indicated that the different content of five taste compounds and 31 aroma compounds caused the differences in flavor quality among the variated fermentation rounds of Laotan Suancai. Amplicon sequencing indicated that the microbial succession exhibited a certain pattern during four fermentation rounds and further analysis unveiled that organic acids drove the microbiota shift to more acid-resistant populations. Spearman correlation analysis highlighted that seven core microbes may be involved in the formation of differential flavor and the corresponding metabolic pathways were reconstructed by function prediction. Our findings offer a novel perspective on comprehending the deterioration of flavor quality across the fermentation rounds of Laotan Suancai.

14.
Proteomics ; : e2300371, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38643379

RESUMO

Forecasting alterations in protein stability caused by variations holds immense importance. Improving the thermal stability of proteins is important for biomedical and industrial applications. This review discusses the latest methods for predicting the effects of mutations on protein stability, databases containing protein mutations and thermodynamic parameters, and experimental techniques for efficiently assessing protein stability in high-throughput settings. Various publicly available databases for protein stability prediction are introduced. Furthermore, state-of-the-art computational approaches for anticipating protein stability changes due to variants are reviewed. Each method's types of features, base algorithm, and prediction results are also detailed. Additionally, some experimental approaches for verifying the prediction results of computational methods are introduced. Finally, the review summarizes the progress and challenges of protein stability prediction and discusses potential models for future research directions.

15.
J Gastrointest Surg ; 28(4): 458-466, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38583896

RESUMO

Computed tomography (CT) imaging has the potential to assist in predicting the prognosis and treatment strategies for pancreatic cancer (PC). This study aimed to develop and validate a radio-clinical model based on preoperative multiphase CT assessments to predict the overall survival (OS) of PC and identify differentially expressed genes associated with OS. METHODS: Patients with PC who had undergone radical pancreatectomy (R0 resection) were divided into development and external validation sets. Independent predictors of OS were identified using Cox regression analyses and included in the nomogram, which was externally validated. The area under the curve was used to measure the model's accuracy in estimating OS probability. RNA sequencing data from The Cancer Genome Atlas were used for gene expression analysis. RESULTS: In the development and external validation sets, survival was estimated respectively for 132 and 27 patients. Multivariate Cox regression analysis identified 5 independent OS predictors: age (P = .049), sex (P = .001), bilirubin level (P = .005), tumor size (P = .020), and venous invasion (P = .041). These variables were incorporated into the nomogram. Patients were divided into high- and low-risk groups for OS and survival curves showed that all patients in the low-risk group had better OS than that of those in the high-risk group (P < .001). Differentially expressed genes in patients with a poor prognosis were involved in neuroactive ligand-receptor interaction. CONCLUSION: The radio-clinical model may be clinically useful for successfully predicting PC prognosis.


Assuntos
Produtos Biológicos , Neoplasias Pancreáticas , Humanos , Prognóstico , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia , Tomografia Computadorizada por Raios X , Nomogramas
16.
Diabetes Metab Res Rev ; 40(4): e3803, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38581399

RESUMO

AIMS: We aimed to examine the longitudinal associations of birth weight with plasma metabolites in adulthood, and further quantify the proportions of the links between birth weight and incident adult type 2 diabetes (T2D) that were mediated by plasma metabolites. MATERIALS AND METHODS: A total of 62,033 participants with complete nuclear magnetic resonance metabolomics and birth weight data from the UK Biobank were included in this study. Linear regression was used to assess the associations between birth weight and metabolites. Cox regression was used to estimate hazard ratios for T2D associated with metabolites. We further performed mediation analyses to estimate the extent to which metabolites might mediate the association between birth weight and T2D risk. RESULTS: Low birth weight was associated with the adverse metabolic responses across multiple metabolic pathways, including lipoprotein subclasses, amino acids, fatty acids (FA), and inflammation. Metabolites associated with higher birth weight tended to be associated with a lower risk of T2D (Pearson correlation coefficient: -0.85). A total of 62 metabolites showed statistically significant mediation effects in the protective association of higher birth weight and T2D risk, including large-sized very low-density lipoprotein particles and triglyceride concentrations as well as saturated, and monounsaturated FA and glycoprotein acetyls. CONCLUSIONS: We identified a range of metabolites that reflect the adult metabolic response to birth weight, some of which might lie on the pathway between birth weight and adult T2D risk.


Assuntos
Diabetes Mellitus Tipo 2 , Adulto , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Peso ao Nascer , Biomarcadores , Metaboloma , Metabolômica
17.
Photochem Photobiol ; 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644599

RESUMO

The aim of the present research is to investigate anti-UVB radiation activity of total flavonoids from Ilex latifolia Thunb. (namely large-leaved Kuding tea) on human keratinocyte cell line (HaCaT cells) based on network pharmacology and molecular docking technique. Network pharmacology was used to screen target genes of active ingredients from Ilex latifolia Thunb. associated with UVB irradiation. The possible signaling pathways were analyzed by KEGG enrichment and verified by cellular experiments. Molecular docking was used to assess the affinity between the active ingredients and the core targets. The prediction of network pharmacology and molecular docking was identified by series experiment in UVB-irradiated HaCaT cells. Network pharmacology results showed that the active ingredients of Ilex latifolia Thunb. for anti-UVB irradiation were mainly flavonoids, and the possible signaling pathways were involved in PI3K-AKT, apoptosis, MAPKs, NF-κB, and JAK-STAT3. Molecular docking indicated key binding activity between AKT1-Glycitein, STAT3-Formononetin, CASP3-Formononetin, TNF-Kaempferol, CASP3-Luteolin, and AKT1-Quercetin. The total flavonoid pretreatment (0.25-1.0 mg/mL) down-regulated the expression of IL-6, IL-1ß, and TNF-α in the cells determined by ELISA. The expression of phosphor PI3K, phosphor AKT, phosphor JAK, phosphor STAT3, phosphor JNK, and phosphor p38 MAPKs and COX-2 proteins in cytosolic and NF-κB p65 protein in nucleus were down-regulated and determined by western blot. It also protected UVB-irradiated cells from apoptosis by reducing apoptosis rate and down-regulating active-caspase 3. In a word, the total flavonoid treatment protected HaCaT cells from UVB injuries effectively, and the potential mechanism involves PI3K-AKT, JAK-STAT3, MAPK, and NF-κB pathway by anti-inflammatory and apoptosis action in cells. The mechanism in vivo experiment needs to be further confirmed in future.

18.
bioRxiv ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38562900

RESUMO

Motile cilia have essential cellular functions in development, reproduction, and homeostasis. Genetic causes for motile ciliopathies have been identified, but the consequences on cellular functions beyond impaired motility remain unknown. Variants in CCDC39 and CCDC40 cause severe disease not explained by loss of motility. Using human cells with pathological variants in these genes, Chlamydomonas genetics, cryo-electron microscopy, single cell RNA transcriptomics, and proteomics, we identified perturbations in multiple cilia-independent pathways. Absence of the axonemal CCDC39/CCDC40 heterodimer results in loss of a connectome of over 90 proteins. The undocked connectome activates cell quality control pathways, switches multiciliated cell fate, impairs microtubule architecture, and creates a defective periciliary barrier. Both cilia-dependent and independent defects are likely responsible for the disease severity. Our findings provide a foundation for reconsidering the broad cellular impact of pathologic variants in ciliopathies and suggest new directions for therapies.

19.
ACS Omega ; 9(11): 12734-12742, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38524500

RESUMO

RNA-binding proteins (RBPs) can interact with RNAs to regulate RNA translation, modification, splicing, and other important biological processes. The accurate identification of RBPs is of paramount importance for gaining insights into the intricate mechanisms underlying organismal life activities. Traditional experimental methods to predict RBPs require a lot of time and money, so it is important to develop computational methods to predict RBPs. However, the existing approaches for RBP prediction still require further improvement due to unidentified RBPs in many species. In this study, we present Seq-RBPPred (predicting RBPs from sequence), a novel method that utilizes a comprehensive feature representation encompassing both biophysical properties and hidden-state features derived from protein sequences. In the results, comprehensive performance evaluations of Seq-RBPPred its superiority compare with state-of-the-art methods, yielding impressive performance including 0.922 for overall accuracy, 0.926 for sensitivity, 0.903 for specificity, and Matthew's correlation coefficient (MCC) of 0.757 as ascertained from the evaluation of the testing set. The data and code of Seq-RBPPred are available at https://github.com/yaoyao-11/Seq-RBPPred.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38491763

RESUMO

Low birth weight and unhealthy lifestyle are both associated with an increased risk of hypertension. The authors aimed to assess the joint association and interaction of birth weight and lifestyle with incident hypertension. The authors included 205 522 participants free of hypertension at baseline from UK Biobank. A healthy lifestyle score was constructed using information on body mass index, physical activity, diet, smoking status and alcohol intake. Cox proportional hazard models were used to investigate the impact of birth weight, healthy lifestyle score and their joint effect on hypertension. The authors documented 13 548 (6.59%) incident hypertension cases during a median of 8.6 years of follow-up. The multivariate adjusted hazard ratios and 95% confidence intervals were 1.12 (1.09, 1.15) per kg lower birth weight and 0.76 (0.75, 0.77) per score increment in healthy lifestyle score. Healthy lifestyle reduced the risk of hypertension in any category of different birth weight groups. The preventive effect of healthy lifestyle on hypertension was the most pronounced at lower birth weight with <2500 g and 2500-2999 g, respectively. Addictive interaction between birth weight and healthy lifestyle score was observed with the relative excess risk due to interaction of 0.04 (0.03, 0.05). Our findings emphasized the importance of healthy lifestyle for hypertension prevention, especially among the high-risk population with lower birth weight.

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