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1.
Front Genet ; 15: 1380544, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952712

RESUMO

Introduction: Sleep is associated with psychiatric disorders. However, their causality remains unknown. Methods: The study explored the causal relationship between seven sleep parameters (sleep duration, insomnia, sleep apnea, chronotype, daytime dozing, napping during the day, and snoring) and three psychiatric disorders including major depressive disorder (MDD), schizophrenia, and attention-deficit/hyperactivity disorder (ADHD) using two-sample Mendelian randomization (MR). Genome-wide association study (GWAS) summary data for sleep parameters were obtained from the United Kingdom biobank, FinnGen biobank, and EBI databases. MR-Egger, weighted median, inverse-variance weighted (IVW), simple mode, weighted mode, maximum likelihood, penalized weighted median, and IVW(fixed effects) were used to perform the MR analysis. The heterogeneity was detected by Cochran's Q statistic. The horizontal pleiotropy was detected by MR Egger. The sensitivity was investigated by the leave-one-out analysis. Results: Insomnia (OR = 2.02, 95%CI = 1.34-3.03, p = 0.001, False-discovery rate (FDR) corrected p-value = 0.011) and napping during the day (OR = 1.81, 95%CI = 1.34-2.44, FDR corrected p-value<0.001) were associated with an increased risk of MDD. Longer sleep duration (OR = 2.20, 95%CI = 1.24-3.90, FDR corrected p-value = 0.049) had an association with the increased risk of schizophrenia, while daytime dozing (OR = 4.44, 95%CI = 1.20-16.41, corrected p-value = 0.088)and napping during the day (OR = 2.11, 95%CI = 1.11-4.02, FDR corrected p-value = 0.088) had a suggestive association with an increased risk of schizophrenia. Longer sleep duration had a suggestive association with a decreased risk of ADHD (OR = 0.66, 95%CI = 0.42-0.93, FDR corrected p-value = 0.088). Conclusion: This study provides further evidence for a complex relationship between sleep and psychiatric disorders. Our findings highlight the potential benefits of addressing sleep problems in the prevention of psychiatric disorders.

2.
Small ; : e2403221, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012064

RESUMO

Solar interfacial evaporation strategy (SIES) has shown great potential to deal with water scarcity and energy crisis. Biobased hydrogel derived interfacial evaporator can realize efficient evaporation due to the unique structure- properties relationship. As such, increasing studies have focused on water treatment or even potential accompanying advanced energy storage applications with respect of efficiency and mechanism of bio-based hydrogel derived interfacial evaporation from microscale to molecular scale. In this review, the interrelationship between efficient interfacial evaporator and bio-based hydrogel is first presented. Then, special attention is paid on the inherent molecular characteristics of the biopolymer related to the up-to-date studies of promising biopolymers derived interfacial evaporator with the objective to showcase the unique superiority of biopolymer. In addition, the applications of the bio-based hydrogels are highlighted concerning the aspects including water desalination, water decontamination atmospheric water harvesting, energy storage and conversion. Finally, the challenges and future perspectives are given to unveil the bottleneck of the biobased hydrogel derived SIES in sustainable water and other energy storage applications.

3.
Appl Microbiol Biotechnol ; 108(1): 360, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836914

RESUMO

In the fight against hospital-acquired infections, the challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) necessitates the development of novel treatment methods. This study focused on undermining the virulence of S. aureus, especially by targeting surface proteins crucial for bacterial adherence and evasion of the immune system. A primary aspect of our approach involves inhibiting sortase A (SrtA), a vital enzyme for attaching microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) to the bacterial cell wall, thereby reducing the pathogenicity of S. aureus. Verbascoside, a phenylethanoid glycoside, was found to be an effective SrtA inhibitor in our research. Advanced fluorescence quenching and molecular docking studies revealed a specific interaction between verbascoside and SrtA, pinpointing the critical active sites involved in this interaction. This molecular interaction significantly impedes the SrtA-mediated attachment of MSCRAMMs, resulting in a substantial reduction in bacterial adhesion, invasion, and biofilm formation. The effectiveness of verbascoside has also been demonstrated in vivo, as shown by its considerable protective effects on pneumonia and Galleria mellonella (wax moth) infection models. These findings underscore the potential of verbascoside as a promising component in new antivirulence therapies for S. aureus infections. By targeting crucial virulence factors such as SrtA, agents such as verbascoside constitute a strategic and potent approach for tackling antibiotic resistance worldwide. KEY POINTS: • Verbascoside inhibits SrtA, reducing S. aureus adhesion and biofilm formation. • In vivo studies demonstrated the efficacy of verbascoside against S. aureus infections. • Targeting virulence factors such as SrtA offers new avenues against antibiotic resistance.


Assuntos
Aminoaciltransferases , Antibacterianos , Aderência Bacteriana , Proteínas de Bactérias , Biofilmes , Cisteína Endopeptidases , Glucosídeos , Staphylococcus aureus Resistente à Meticilina , Simulação de Acoplamento Molecular , Fenóis , Infecções Estafilocócicas , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/antagonistas & inibidores , Aminoaciltransferases/antagonistas & inibidores , Aminoaciltransferases/metabolismo , Cisteína Endopeptidases/metabolismo , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Glucosídeos/farmacologia , Animais , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Fenóis/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Mariposas/microbiologia , Virulência/efeitos dos fármacos , Modelos Animais de Doenças , Fatores de Virulência/metabolismo , Inibidores Enzimáticos/farmacologia , Polifenóis
4.
Biol Reprod ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38938081

RESUMO

Ovarian theca cells produce testosterone, which acts as a vital precursor substance for synthesizing estrogens during follicular development. Nerve growth factor (NGF) has been shown to participate in reproductive physiology, specifically to follicular development and ovulation. There is currently no available data on the impact of NGF on testosterone synthesis in porcine theca cells. Furthermore, m6A modification is the most common internal modification in eukaryotic mRNAs that are closely associated with female gametogenesis, follicle development, ovulation, and other related processes. It is also uncertain whether the three main enzymes associated with m6A, such as Writers, Erasers and Readers, play a role in this process. The present study, with an in vitro culture model, investigated the effect of NGF on testosterone synthesis in porcine theca cells and the role of Writers-METTL14 in this process. It was found that NGF activates the PI3K/AKT signaling pathway through METTL14, which regulates testosterone synthesis in porcine theca cells. This study will help to further elucidate the mechanisms by which NGF regulates follicular development and provide new therapeutic targets for ovary-related diseases in female animals.

5.
Sci Rep ; 14(1): 14219, 2024 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902308

RESUMO

A network meta-analysis of randomized controlled trials was conducted to compare and rank the effectiveness of various noninvasive brain stimulation (NIBS) for Parkinson's disease (PD). We searched PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), and Chinese Biomedical Literature Service System (SinoMed) databases from the date of database inception to April 30th, 2024. Two researchers independently screened studies of NIBS treatment in patients with PD based on inclusion and exclusion criteria. Two researchers independently performed data extraction of the included studies using an Excel spreadsheet and assessed the quality of the literature according to the Cochrane Risk of Bias Assessment Tool (RoB2). Network meta-analysis was performed in StataMP 17.0. A total of 28 studies involving 1628 PD patients were included. The results showed that HF-rTMS over the SMA (SMD = - 2.01; 95% CI [- 2.87, - 1.15]), HF-rTMS over the M1 and DLPFC (SMD = - 1.80; 95% CI [- 2.90, - 0.70]), HF-rTMS over the M1 (SMD = - 1.10; 95% CI [- 1.55, - 0.65]), a-tDCS over the DLPFC (SMD = - 1.08; 95% CI [- 1.90, - 0.27]), HF-rTMS over the M1 and PFC (SMD = - 0.92; 95% CI [- 1.71, - 0.14]), LF-rTMS over the M1 (SMD = - 0.72; 95% CI [- 1.17, - 0.28]), and HF-rTMS over the DLPFC (SMD = - 0.70; 95% CI [- 1.21, - 0.19]) were significantly improved motor function compared with sham stimulation. The SUCRA three highest ranked were HF-rTMS over the SMA (95.1%), HF-rTMS over the M1 and DLPFC (89.6%), and HF-rTMS over the M1 (73.0%). In terms of enhanced cognitive function, HF-rTMS over the DLPFC (SMD = 0.80; 95% CI [0.03,1.56]) was significantly better than sham stimulation. The SUCRA three most highly ranked were a-tDCS over the M1 (69.8%), c-tDCS over the DLPFC (66.9%), and iTBS over the DLPFC (65.3%). HF-rTMS over the M1 (SMD = - 1.43; 95% CI [- 2.26, - 0.61]) and HF-rTMS over the DLPFC (SMD = - 0.79; 95% CI [- 1.45, - 0.12)]) significantly improved depression. The SUCRA three highest ranked were HF-rTMS over the M1 (94.1%), LF-rTMS over the M1 (71.8%), and HF-rTMS over the DLPFC (69.0%). HF-rTMS over the SMA may be the best option for improving motor symptoms in PD patients. a-tDCS and HF-rTMS over the M1 may be the NIBS with the most significant effects on cognition and depression, separately.Trial registration: International Prospective Register of Systematic Review, PROSPERO (CRD42023456088).


Assuntos
Metanálise em Rede , Doença de Parkinson , Doença de Parkinson/terapia , Doença de Parkinson/fisiopatologia , Humanos , Estimulação Magnética Transcraniana/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
6.
Cell Transplant ; 33: 9636897241262992, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38910431

RESUMO

Transplantation of mesenchymal stem cells (MSCs) is one of the hopeful treatments for spinal cord injury (SCI). Most current studies are in animals, and less in humans, and the optimal transplantation strategy for MSCs is still controversial. In this article, we explore the optimal transplantation strategy of MSCs through a network meta-analysis of the effects of MSCs on SCI in animal models. PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), and Chinese Biomedical Literature Service System (SinoMed) databases were searched by computer for randomized controlled studies on MSCs for SCI. Two investigators independently completed the literature screening and data extraction based on the inclusion and exclusion criteria. RevMan 5.4 software was used to assess the quality of the included literature. Stata 16.0 software was used for standard meta-analysis and network meta-analysis. Standardized mean difference (SMD) was used for continuous variables to combine the statistics and calculate 95% confidence interval (95% CI). P < 0.05 was considered a statistically significant difference. Cochrane's Q test and the I2 value were used to indicate the magnitude of heterogeneity. A random-effects model was used if I2 > 50% and P < 0.10 indicated significant heterogeneity between studies, and conversely, a fixed-effects model was used. Evidence network diagrams were drawn based on direct comparisons between various interventions. The surface under the cumulative ranking curve area (SUCRA) was used to predict the ranking of the treatment effects of each intervention. A total of 32 animal studies were included in this article for analysis. The results of the standard meta-analysis showed that MSCs improved motor ability after SCI. The network meta-analysis showed that the best treatment effect was achieved for adipose tissue-derived mesenchymal stromal cells (ADMSCs) in terms of cell source and intrathecal (IT) in terms of transplantation modality. For transplantation timing, the best treatment effect was achieved when transplantation was performed in the subacute phase. The available literature suggests that IT transplantation using ADMSCs in the subacute phase may be the best transplantation strategy to improve functional impairment after SCI. Future high-quality studies are still needed to further validate the results of this study to ensure the reliability of the results.


Assuntos
Modelos Animais de Doenças , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Animais , Humanos , Ratos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Metanálise em Rede , Traumatismos da Medula Espinal/terapia
7.
Exp Ther Med ; 28(1): 295, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38827477

RESUMO

Ammonia (NH3) is an irritating and harmful gas that affects cell apoptosis and autophagy. Sirtuin 5 (SIRT5) has multiple enzymatic activities and regulates NH3-induced autophagy in tumor cells. In order to determine whether SIRT5 regulates NH3-induced bovine mammary epithelial cell apoptosis and autophagy, cells with SIRT5 overexpression or knockdown were generated and in addition, bovine mammary epithelial cells were treated with SIRT5 inhibitors. The results showed that SIRT5 overexpression reduced the content of NH3 and glutamate in cells by inhibiting glutaminase activity in glutamine metabolism, and reduced the ratio of ADP/ATP. The results in the SIRT5 knockdown and inhibitor groups were comparable, including increased content of NH3 and glutamate in cells by activating glutaminase activity, and an elevated ratio of ADP/ATP. It was further confirmed that SIRT5 inhibited the apoptosis and autophagy of bovine mammary epithelial cells through reverse transcription-quantitative PCR, western blot, flow cytometry with Annexin V FITC/PI staining and transmission electron microscopy. In addition, it was also found that the addition of LY294002 or Rapamycin inhibited the PI3K/Akt or mTOR kinase signal, decreasing the apoptosis and autophagy activities of bovine mammary epithelial cells induced by SIRT5-inhibited NH3. In summary, the PI3K/Akt/mTOR signal involved in NH3-induced cell autophagy and apoptosis relies on the regulation of SIRT5. This study provides a new theory for the use of NH3 to regulate bovine mammary epithelial cell apoptosis and autophagy, and provides guidance for improving the health and production performance of dairy cows.

8.
PLoS Comput Biol ; 20(5): e1011200, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38709852

RESUMO

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.


Assuntos
COVID-19 , Previsões , Pandemias , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/transmissão , Humanos , Previsões/métodos , Estados Unidos/epidemiologia , Pandemias/estatística & dados numéricos , Biologia Computacional , Modelos Estatísticos
9.
Sci Total Environ ; 937: 173305, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38777056

RESUMO

Heat stress (HS) poses a substantial challenge to livestock. Studies have demonstrated that HS reduces fertility and leads to gut microbiota dysbiosis in bulls. However, the impact of the gut microbiota on fertility in bulls during HS is still unclear. Our research revealed that HS exposure decreased semen quality in bulls, and fecal microbiota transplantation (FMT) from heat-stressed bulls to recipient mice resulted in a significant decrease in number of testicular germ cells and epididymal sperm. Untargeted metabolomics methodology and 16S rDNA sequencing conjoint analysis revealed that Akkermansia muciniphila (A. muciniphila) seemed to be a key bacterial regulator of spermatogenesis after HS exposure. Moreover, the research indicated that A. muciniphila regulated secondary bile acid metabolism by promoting the colonization of bile salt hydrolase (BSH)-metabolizing bacteria, leading to increase of retinol absorption in the host gut and subsequently elevation of testicular retinoic acid level, thereby improving spermatogenesis. This study sheds light on the relationship between HS-induced microbiota dysbiosis and spermatogenesis, offering a potential therapeutic approach for addressing bull spermatogenic dysfunction triggered by HS exposure.


Assuntos
Ácidos e Sais Biliares , Disbiose , Microbioma Gastrointestinal , Espermatogênese , Animais , Microbioma Gastrointestinal/fisiologia , Espermatogênese/fisiologia , Masculino , Ácidos e Sais Biliares/metabolismo , Camundongos , Bovinos , Resposta ao Choque Térmico/fisiologia , Akkermansia/fisiologia , Transplante de Microbiota Fecal , Testículo/metabolismo
10.
Medicine (Baltimore) ; 103(19): e38017, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728499

RESUMO

Numerous inflammatory indicators have been demonstrated to be strongly correlated with tumor prognosis. However, the association between inflammatory indicators and the prognosis of patients with nasopharyngeal carcinoma (NPC) receiving treatment with programmed death receptor-1 (PD-1) immunosuppressant monoclonal antibodies remains uncertain. Inflammatory indicators in peripheral blood were collected from 161 NPC patients at 3 weeks after initial PD-1 treatment. Through univariate and multivariate analyses, as well as nomogram and survival analyses, we aimed to identify independent prognostic factors related to 1-year progression-free survival (PFS). Subsequently, a prognostic nomogram was devised, and its predictive and discriminating abilities were assessed utilizing calibration curves and the concordance index. Our univariate and multivariate analyses indicated that age (P = .012), M stage (P < .001), and systemic immune-inflammation index (SII) during the third week following initial PD-1 treatment (SII3, P = .005) were independently correlated with the 1-year PFS of NPC patients after PD-1 treatment. Notably, we constructed a novel nomogram based on the SII3, age, and M stage. Importantly, utilizing the derived cutoff point from the nomogram, the high-risk group exhibited significantly shorter PFS than did the low-risk group (P < .001). Furthermore, the nomogram demonstrated a greater concordance index for PFS than did the tumor node metastasis stage within the entire cohort. We successfully developed a nomogram that integrates the SII3 and clinical markers to accurately predict the 1-year PFS of NPC patients receiving PD-1 inhibitor treatment.


Assuntos
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nomogramas , Humanos , Masculino , Feminino , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/sangue , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/sangue , Adulto , Idoso , Inibidores de Checkpoint Imunológico/uso terapêutico , Prognóstico , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Adulto Jovem
11.
Bio Protoc ; 14(7): e4966, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38618175

RESUMO

Contractile injection systems (CISs), one of the most important bacterial secretion systems that transport substrates across the membrane, are a collection of diverse but evolutionarily related macromolecular devices. Numerous effector proteins can be loaded and injected by this secretion complex to their specific destinations. One group of CISs called extracellular CIS (eCIS) has been proposed as secretory molecules that can be released from the bacterial cytoplasm and attack neighboring target cells from the extracellular environment. This makes them a potential delivery vector for the transportation of various cargos without the inclusion of bacterial cells, which might elicit certain immunological responses from hosts. We have demonstrated that the Photorhabdus virulence cassette (PVC), which is a typical eCIS, could be applied as an ideal vector for the translocation of proteinaceous cargos with different physical or chemical properties. Here, we describe the in-depth purification protocol of this mega complex from Escherichia coli. The protocol provided is a simpler, faster, and more productive way of generating the eCIS complexes than available methodologies reported previously, which can facilitate the subsequent applications of these nanodevices and other eCIS in different backgrounds.

12.
J Cell Physiol ; 239(6): e31289, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38685566

RESUMO

Follicular cysts are a common reproductive disorder in domestic animals that cause considerable economic losses to the farming industry. Effective prevention and treatment methods are lacking because neither the pathogenesis nor formation mechanisms of follicular cysts are well-understood. In this study, we first investigated the granulosa cells (GCs) of cystic follicles isolated from pigs. We observed a significant reduction in the expression of methyltransferase-like 3 (METTL3). Subsequent experiments revealed that METTL3 downregulation in GCs caused a decrease in m6A modification of pri-miR-21. This reduction further inhibited DGCR8 recognition and binding to pri-miR-21, dampening the synthesis of mature miR-21-5p. Additionally, the decrease in miR-21-5p promotes IL-1ß expression in GCs. Elevated IL-1ß activates the NFκB pathway, in turn upregulating apoptotic genes TNFa and BAX/BCL2. The subsequent apoptosis of GCs and inhibition of autophagy causes downregulation of CYP19A1 expression. These processes lower oestrogen secretion and contribute to follicular cyst formation. In conclusion, our findings provide a foundation for understanding and further exploring the mechanisms of follicular-cyst development in farm animals. This work has important implications for treating ovarian disorders in livestock and could potentially be extended to humans.


Assuntos
Apoptose , Células da Granulosa , Metiltransferases , MicroRNAs , Animais , Feminino , Apoptose/genética , Células Cultivadas , Regulação para Baixo , Cisto Folicular/genética , Cisto Folicular/patologia , Cisto Folicular/metabolismo , Células da Granulosa/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Metiltransferases/metabolismo , Metiltransferases/genética , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/metabolismo , NF-kappa B/genética , Transdução de Sinais , Suínos , Proteínas de Ligação a RNA/metabolismo
13.
Pestic Biochem Physiol ; 201: 105874, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685243

RESUMO

In insects, chemosensory proteins (CSPs) play an important role in the perception of the external environment and have been widely used for protein-binding characterization. Riptortus pedestris has received increased attention as a potential cause of soybean staygreen syndrome in recent years. In this study, we found that RpedCSP4 expression in the antennae of adult R. pedestris increased with age, with no significant difference in expression level observed between males and females, as determined through quantitative real-time polymerase chain reaction (qRT-PCR). Subsequently, we investigated the ability of RpedCSP4 to bind various ligands (five aggregated pheromone components and 13 soybean volatiles) using a prokaryotic expression system and fluorescence competitive binding assays. We found that RpedCSP4 binds to three aggregated pheromone components of R. pedestris, namely, ((E)-2-hexenyl (Z)-3-hexenoate (E2Z3), (E)-2-hexenyl (E)-2-hexenoate (E2E2), and (E)-2-hexenyl hexenoate (E2HH)), and that its binding capacities are most stable under acidic condition. Finally, the structure and protein-ligand interactions of RpedCSP4 were further analyzed via homology modeling, molecular docking, and targeted mutagenesis experiments. The L29A mutant exhibited a loss of binding ability to these three aggregated pheromone components. Our results show that the olfactory function of RpedCSP4 provides new insights into the binding mechanism of RpedCSPs to aggregation pheromones and contributes to discover new target candidates that will provide a theoretical basis for future population control of R. pedestris.


Assuntos
Proteínas de Insetos , Feromônios , Animais , Feromônios/metabolismo , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/química , Masculino , Feminino , Ligação Proteica , Heterópteros/metabolismo , Heterópteros/genética
14.
Sci Rep ; 14(1): 9032, 2024 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641704

RESUMO

CSF1R is a receptor tyrosine kinase responsible for the growth/survival/polarization of macrophages and overexpressed in some AML patients. We hypothesized that a novel multi-kinase inhibitor (TKi), narazaciclib (HX301/ON123300), with high potency against CSF1R (IC50 ~ 0.285 nM), would have anti-AML effects. We tested this by confirming HX301's high potency against CSF1R (IC50 ~ 0.285 nM), as well as other kinases, e.g. FLT3 (IC50 of ~ 19.77 nM) and CDK6 (0.53 nM). An in vitro proliferation assay showed that narazaciclib has a high growth inhibitory effect in cell cultures where CSF1R or mutant FLT3-ITD variants that may be proliferation drivers, including primary macrophages (IC50 of 72.5 nM) and a subset of AML lines (IC50 < 1.5 µM). In vivo pharmacology modeling of narazaciclib using five AML xenografts resulted in: inhibition of MV4-11 (FLT3-ITD) subcutaneous tumor growth and complete suppression of AM7577-PDX (FLT3-ITD/CSF1Rmed) systemic growth, likely due to the suppression of FLT3-ITD activity; complete suppression of AM8096-PDX (CSF1Rhi/wild-type FLT3) growth, likely due to the inhibition of CSF1R ("a putative driver"); and nonresponse of both AM5512-PDX and AM7407-PDX (wild-type FLT3/CSF1Rlo). Significant leukemia load reductions in bone marrow, where disease originated, were also achieved in both responders (AM7577/AM8096), implicating that HX301 might be a potentially more effective therapy than those only affecting peripheral leukemic cells. Altogether, narazaciclib can potentially be a candidate treatment for a subset of AML with CSF1Rhi and/or mutant FLT3-ITD variants, particularly second generation FLT3 inhibitor resistant variants.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Inibidores de Proteínas Quinases , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/metabolismo , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Tirosina Quinase 3 Semelhante a fms/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Receptores Proteína Tirosina Quinases , Receptores de Fator Estimulador de Colônias/antagonistas & inibidores , Receptores de Fator Estimulador de Colônias/metabolismo , Piridonas/farmacologia , Pirimidinas/farmacologia
15.
Molecules ; 29(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38675681

RESUMO

Alpha-ketoglutaric acid (α-KG), as an intermediate product of the tricarboxylic acid cycle, plays a crucial role in peptide and amino acid synthesis. In order to reduce costs and improve efficiency in the oxidative production of α-ketoglutaric acid, this study successfully synthesized and expressed L-glutamate oxidase (LGOXStr) from Streptomyces viridosporus R111 and catalase (KatGEsc) from Escherichia coli H736. Two immobilization methods and the conditions for one-step whole-cell catalysis of α-ketoglutaric acid were investigated. α-Ketoglutaric acid has broad applications in the pharmaceutical, food, and chemical industries. The specific research results are as follows: (1) By fusing the sfGFP tag, L-glutamate oxidase (LGOXStr r) and catalase (KatGEsc) were successfully anchored to the outer membrane of Escherichia coli cells, achieving one-step whole-cell catalysis of α-ketoglutaric acid with a conversion efficiency of up to 75%. (2) Through the co-immobilization of LGOXStr and KatGEsc, optimization of the preparation parameters of immobilized cells, and exploration of the immobilization method using E.coli@ZIF-8, immobilized cells with conversion rates of over 60% were obtained even after 10 cycles of reuse. Under the optimal conditions, the production rate of α-ketoglutaric acid reached 96.7% in a 12 h reaction, which is 1.1 times that of E. coli@SA and 1.29 times that of free cells.


Assuntos
Catalase , Escherichia coli , Ácidos Cetoglutáricos , Ácidos Cetoglutáricos/metabolismo , Ácidos Cetoglutáricos/química , Escherichia coli/enzimologia , Catalase/metabolismo , Catalase/química , Aminoácido Oxirredutases/metabolismo , Aminoácido Oxirredutases/química , Streptomyces/enzimologia , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo
16.
Front Endocrinol (Lausanne) ; 15: 1361906, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505745

RESUMO

Aim: To examine the association between napping characteristics and glycemic control in people with type 2 diabetes. Design: This study used a cross-sectional design. Methods: A convenience sample of people with type 2 diabetes (N=226) were included. Glycemic control was indicated by HbA1c which was measured by A1C Now®+. Napping characteristics including napping frequency, duration, timing, and type were measured by validated questionnaires. Other variables, such as insomnia, cognitive impairment, and depression were measured by the Insomnia Severity Index, Montreal Cognitive Assessment, and Patient Health Questionnaire-9, respectively. Multivariate linear regression analyses were performed. Results: The sample consisted of 122 women (54.0%), with a median age of 67 years. Their median HbA1c was 6.8%. No significant relationship was found between napping frequency and HbA1c. Among nappers, after controlling for covariates, long napping duration (≥60 min) and morning napping were both associated with poorer glycemic control. Compared with appetitive napping, restorative napping was associated with better glycemic control. Conclusion: Daytime napping (e.g., duration and type) is an important modifiable factor for glycemic control in people with type 2 diabetes. This study provides new insights into the relationship between napping and glucose management among people with diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Distúrbios do Início e da Manutenção do Sono , Humanos , Feminino , Idoso , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/complicações , Distúrbios do Início e da Manutenção do Sono/complicações , Hemoglobinas Glicadas , Estudos Transversais , Controle Glicêmico
17.
Diabetes Res Clin Pract ; 209: 111570, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38341040

RESUMO

AIMS: To examine whether sleep health in the first trimester could predict glucose metabolism in the second trimester. METHODS: Pregnant women (N = 127) during the first trimester were recruited (August 2022 to March 2023). Overall sleep health was assessed by the Sleep Health Index. Various dimensions of sleep health were measured using a 7-day sleep diary and questionnaires. The outcomes, including diagnosis of gestational diabetes mellitus (GDM) and HbA1c, were obtained from the medical records in the second trimester. Poisson regression analysis and multiple linear regression were used for data analysis. RESULTS: The average age of the participants was 32.6 years. The incidence of GDM was 28.3 % and the mean HbA1c was 5.2 % (33 mmol/mol). Sleep duration regularity (RR = 1.808; 95 %CI 1.023, 3.196) was associated with GDM after controlling for confounders. SHI total score (ß = -0.278; 95 %CI -0.022, -0.005) and sleep duration regularity (ß = 0.243; 95 %CI 0.057, 0.372) were associated with HbA1c. CONCLUSIONS: Worse sleep health, particularly lower sleep regularity, predicted worse glucose metabolism among pregnant women. Healthcare professional may consider adding sleep-related assessment to prenatal care. Maintaining regular sleep should be encouraged. Studies examining the impact of sleep intervention on glucose metabolism among pregnant women are warranted.


Assuntos
Diabetes Gestacional , Gestantes , Gravidez , Humanos , Feminino , Adulto , Hemoglobinas Glicadas , Estudos Prospectivos , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/diagnóstico , Primeiro Trimestre da Gravidez , Sono , Glucose , Glicemia/metabolismo
18.
Mater Horiz ; 11(9): 2180-2190, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38406864

RESUMO

Achieving programmable and reversible deformations of soft materials is a long-standing goal for various applications in soft robotics, flexible electronics and many other fields. Swelling-induced shape morphing has been intensively studied as one of the potential mechanisms. However, achieving an extremely large swelling ratio (>1000% in volume) remains challenging with existing swellable soft materials (e.g., hydrogels and water-swellable rubbers). Inspired by the shape change enabled by the osmosis-driven swelling in living organisms, herein, we report a polymer composite system composed of fine sodium chloride (NaCl) particles embedded in Ecoflex00-10 polymer. This Ecoflex00-10/NaCl polymer composite can achieve controllable volumetric swelling up to 3000% while maintaining a relatively high elastic stiffness. We demonstrate that this swellable polymer composite can serve as an active component to drive the shape morphing of various structures. By controlling the geometric design and the fraction of the NaCl particle, morphing structures capable of deforming sequentially are created. Finally, by encapsulating 3D printed polymer composite patterns using water-permeable PDMS membrane, a programmable braille with visual and tactile regulation is demonstrated for the purpose of information encryption. Our study provides a facile approach to generate customizable shape-morphing structures, aiming to broaden the range of techniques and applications for morphing devices.

19.
Int J Mol Sci ; 25(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38396642

RESUMO

Restricted production of fungal secondary metabolites hinders the ability to conduct comprehensive research and development of novel biopesticides. Okaramine B from Penicillium demonstrates remarkable insecticidal efficacy; however, its biosynthetic yield is low, and its regulatory mechanism remains unknown. The present study found that the yield difference was influenced by fermentation modes in okaramine-producing strains and performed genomic and comparative transcriptome analysis of P. daleae strain NBP-49626, which exhibits significant features. The NBP-49626 genome is 37.4 Mb, and it encodes 10,131 protein-encoding genes. Up to 5097 differentially expressed genes (DEGs) were identified during the submerged and semi-solid fermentation processes. The oka gene cluster, lacking regulatory and transport genes, displayed distinct transcriptional patterns in response to the fermentation modes and yield of Okaramine B. Although transcription trends of most known global regulatory genes are inconsistent with those of oka, this study identified five potential regulatory genes, including two novel Zn(II)2Cys6 transcription factors, Reg2 and Reg19. A significant correlation was also observed between tryptophan metabolism and Okaramine B yields. In addition, several transporter genes were identified as DEGs. These results were confirmed using real-time quantitative PCR. This study provides comprehensive information regarding the regulatory mechanism of Okaramine B biosynthesis in Penicillium and is critical to the further yield improvement for the development of insecticides.


Assuntos
Azetidinas , Azocinas , Alcaloides Indólicos , Penicillium , Penicillium/metabolismo , Perfilação da Expressão Gênica , Genômica/métodos
20.
Int J Mol Sci ; 25(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38338986

RESUMO

Root knot nematodes cause serious damage to global agricultural production annually. Given that traditional chemical fumigant nematicides are harmful to non-target organisms and the environment, the development of biocontrol strategies has attracted significant attention in recent years. In this study, it was found that the Bacillus thuringiensis Berliner strain NBIN-863 exhibits strong fumigant nematicidal activity and has a high attraction effect on Meloidogyne incognita (Kofoid and White) Chitwood. Four volatile organic compounds (VOCs) produced by NBIN-863 were identified using solid-phase microextraction and gas chromatography-mass spectrometry. The nematicidal activity of four VOCs, namely, N-methylformamide, propenamide, 3-(methylthio)propionic acid, and phenylmalonic acid, was detected. Among these compounds, 3-(methylthio)propionic acid exhibited the highest direct contact nematicidal activity against M. incognita, with an LC50 value of 6.27 µg/mL at 24 h. In the fumigant bioassay, the mortality rate of M. incognita treated with 1 mg/mL of 3-(methylthio)propionic acid for 24 h increased to 69.93%. Furthermore, 3-(methylthio)propionic acid also exhibited an inhibitory effect on the egg-hatching of M. incognita. Using chemotaxis assays, it was determined that 3-(methylthio)propionic acid was highly attractive to M. incognita. In pot experiments, the application of 3-(methylthio)propionic acid resulted in a reduction in gall numbers, decreasing the number of galls per gram of tomato root from 97.58 to 6.97. Additionally, the root length and plant height of the treated plants showed significant increases in comparison with the control group. The current study suggests that 3-(methylthio)propionic acid is a novel nematicidal virulence factor of B. thuringiensis. Our research provides evidence for the potential use of NBIN-863 or its VOCs in biocontrol against root knot nematodes.


Assuntos
Bacillus thuringiensis , Praguicidas , Propionatos , Tylenchoidea , Compostos Orgânicos Voláteis , Animais , Antinematódeos/farmacologia , Praguicidas/farmacologia , Compostos Orgânicos Voláteis/farmacologia
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