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1.
Cell Syst ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39243757

RESUMEN

The regulation of genes can be mathematically described by input-output functions that are typically assumed to be time invariant. This fundamental assumption underpins the design of synthetic gene circuits and the quantitative understanding of natural gene regulatory networks. Here, we found that this assumption is challenged in mammalian cells. We observed that a synthetic reporter gene can exhibit unexpected transcriptional memory, leading to a shift in the dose-response curve upon a second induction. Mechanistically, we investigated the cis-dependency of transcriptional memory, revealing the necessity of promoter DNA methylation in establishing memory. Furthermore, we showed that the synthetic transcription factor's effective DNA binding affinity underlies trans-dependency, which is associated with its capacity to undergo biomolecular condensation. These principles enabled modulating memory by perturbing either cis- or trans-regulation of genes. Together, our findings suggest the potential pervasiveness of transcriptional memory and implicate the need to model mammalian gene regulation with time-varying input-output functions. A record of this paper's transparent peer review process is included in the supplemental information.

2.
Front Immunol ; 15: 1455730, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234239

RESUMEN

Introduction: Various COVID-19 vaccine trials have shown that vaccines can successfully prevent symptomatic cases of COVID-19 and death. Head-to-head comparisons help to better understand the immune response characteristics of different COVID-19 vaccines in humans. Methods: We randomly selected 20 participants from each of five ongoing Phase II trials of COVID-19 vaccines. Here, SARS-CoV 2-specific immune responses to DNA vaccine (INO-4800), mRNA vaccine (BNT162b2), Adenovirus-vectored vaccine (CONVIDECIA), Protein subunit vaccine (Recombinant COVID- 19 Vaccine (Sf9 Cells)), Inactivated Vaccine (KCONVAC) were examined longitudinally in healthy adults between Jan 15, 2021 and July 5, 2021 for 6 months. RBD-IgG titres were detected by ELISA, neutralising antibody titer were detected by pseudoviral neutralization and immune cell response were detected by flow cytometry. Results: At the first visit (V1), 100% of individuals who received the BNT162b2, CONVIDECIA, or KCONVAC vaccines experienced seroconversion of neutralizing and binding antibodies in the serum. Except for the Recombinant COVID-19 Vaccine (Sf9 Cells) vaccine having the highest neutralizing antibody GMT at the second visit (although there was no statistically significant difference in geometric mean titers between V1 and V2), the rest of the vaccines had the highest levels of binding antibodies and neutralizing antibodies at V1. The neutralizing antibodies GMT of all vaccines showed a significant decrease at V3 compared to V1. The neutralizing antibody GMT against the omicron variant of all vaccines at V1 showed a significant decrease compared to the wild strain. We observed statistically significant differences in Tcm cells and RBD-specific memory B cells among various vaccines. Discussion: BNT162b2 (mRNA vaccine) exhibits the highest antibody levels among the five vaccines evaluated, regardless of whether the target is the wild-type virus or its variants. However, its cellular immune response may be weaker compared to CONVIDECIA (adenovirus type 5 vector vaccine).


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Celular , Inmunidad Humoral , SARS-CoV-2 , Humanos , Vacunas contra la COVID-19/inmunología , Adulto , COVID-19/inmunología , COVID-19/prevención & control , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , SARS-CoV-2/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Masculino , Femenino , China , Persona de Mediana Edad , Adulto Joven , Vacunas de Subunidad/inmunología , Vacunas de ADN/inmunología , Vacuna BNT162/inmunología , Inmunogenicidad Vacunal , Vacunas de Productos Inactivados/inmunología
3.
Adv Sci (Weinh) ; : e2406320, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39248326

RESUMEN

How consciousness is lost in states such as sleep or anesthesia remains a mystery. To gain insight into this phenomenon, concurrent recordings of electrophysiology signals in the anterior cingulate cortex and whole-brain functional magnetic resonance imaging (fMRI) are conducted in rats exposed to graded propofol, undergoing the transition from consciousness to unconsciousness. The results reveal that upon the loss of consciousness (LOC), there is a sharp increase in low-frequency power of the electrophysiological signal. Additionally, fMRI signals exhibit a cascade of deactivation across a pathway including the hippocampus, thalamus, and medial prefrontal cortex (mPFC) surrounding the moment of LOC, followed by a broader increase in brain activity across the cortex during sustained unconsciousness. Furthermore, sliding window analysis demonstrates a temporary increase in synchrony of fMRI signals across the hippocampus-thalamus-mPFC pathway preceding LOC. These data suggest that LOC may be triggered by sequential activities in the hippocampus, thalamus, and mPFC, while wide-spread activity increases in other cortical regions commonly observed during anesthesia-induced unconsciousness may be a consequence, rather than a cause of LOC. Taken together, the study identifies a cascade of neural events unfolding as the brain transitions into unconsciousness, offering insight into the systems-level neural mechanisms underpinning LOC.

4.
Sci Rep ; 14(1): 20957, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251632

RESUMEN

The mismatch between solar radiation resources and building heating demand on a seasonal scale makes cross-seasonal heat storage a crucial technology, especially for plateau areas. Utilizing phase change materials with high energy density and stable heat output effectively improves energy storage efficiency. This study integrates cascaded phase change with a cross-seasonal heat storage system aimed at achieving low-carbon heating. The simulation analyzes heat distribution and temperature changes from the heat storage system to the heating terminal. The results indicate that although the solar collectors operate for 26.3% of the total heat storage and heating period, the cumulative heat stored is 45.4% higher than the total heating load. Heat transferred by the cross-seasonal heat storage system accounts for up to 61.2% of the total heating load. Therefore, the system reduces fuel consumption by 77.6% compared to conventional fossil fuel heating systems. Moreover, radiant floor heating terminals, with a wide range of operating temperatures, match well with cascaded phase change heat storage and can reduce operation time by 19.5% and heat demand by 5.2% compared to conventional radiators. In addition to demonstrating the feasibility of applying cascaded phase change technology in cross-seasonal heat storage heating, this study reveals the lifecycle sustainability due to the shortened heat storage period. The configuration, parameters, and simulation results provide a reference basis for system application and design.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39228118

RESUMEN

The abundant defects on the perovskite surface greatly impact the efficiency improvement and long-term stability of carbon-based perovskite solar cells. Molecules with electron-donating or electron-withdrawing functional groups have been cited for passivating various defects. However, few studies have investigated the potential adverse effects arising from the synergistic interactions among functional groups. Herein, we investigate the correlation between functional group configurations and passivation strength as well as the potential adverse impacts of strong electrostatic structures by methodically designing three distinct interface molecules functionalized with different ending groups, which both belong to biguanide derivatives, including 1-(3,4-dichlorophenyl) biguanide hydrochloride (DBGCl), metformin hydrochloride (MFCl), and biguanide hydrochloride (BGCl). The results indicate that DBGCl establishes comparatively mild active sites, not only passivates defects but also aids in forming a surface with a uniform potential. Conversely, MFCl exerts a more pronounced adverse effect on the perovskite surface, which is attributable to the electronic state perturbations induced by its functional groups. Due to the lack of hydrophobic groups, devices treated with BGCl demonstrate insufficient moisture resistance. Devices passivated with DBGCl demonstrate superior average efficiency, showcasing a 12% enhancement relative to the pristine. Furthermore, DBGCl-treated devices exhibit enhanced stability in three different environments, respectively, achieving the highest PCE retention rates under nitrogen conditions (25 °C), room-temperature air conditions (25 °C, RH = 40 ± 2%), and high-temperature air conditions (65 °C, RH = 40 ± 2%).

6.
Soft Matter ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39239672

RESUMEN

Quantitative investigation of the adhesive behavior between cells and the extracellular matrix (ECM) through molecular bonds is essential for cell culture and bio-medical engineering in vitro. Cell adhesion is a complex multi-scale behavior that includes temporal and spatial scales. However, the influence of the cell and matrix creep effect and the complex spatial morphology characteristics of the matrix on the cell adhesion mechanism is unclear. In the present study, an idealized theoretical model has been considered, where the adhesion of cells and the matrix is simplified into a planar strain problem of homogeneous viscoelastic half-spaces. Furthermore, a new viscoelastic-stochastic model that considers the morphological characteristics of the matrix, the viscoelasticity of the cell and the viscoelasticity of the substrate was developed under the action of a constant external force. The model characterizes the matrix topographical features by fractal dimension (FD), interprets the effects of FD and medium viscoelasticity on the molecular bond force and the receptor-ligand bond re-association rate and reveals a new mechanism for the stable adhesion of molecular bond clusters by Monte Carlo simulation. Based on this model, it was identified that the temporal and spatial distribution of molecular bond force was affected by the matrix FD and the lifetime and stability of the molecular bond cluster could be significantly improved by tuning the FD. At the same time, the viscoelastic creep effect of the cell and matrix increased the re-association rate of open bonds and could expand the window of stable adhesion more flexibly.

7.
Dev Dyn ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39254141

RESUMEN

Twist1 is required for embryonic development and expresses after birth in mesenchymal stem cells derived from mesoderm, where it governs mesenchymal cell development. As a well-known regulator of epithelial-mesenchymal transition or embryonic organogenesis, Twist1 is important in a variety of developmental systems, including mesoderm formation, neurogenesis, myogenesis, cranial neural crest cell migration, and differentiation. In this review, we first highlight the physiological significance of Twist1 in cell differentiation, including osteogenic, chondrogenic, and myogenic differentiation, and then detail its probable molecular processes and signaling pathways. On this premise, we summarize the significance of Twist1 in distinct developmental disorders and diseases to provide a reference for studies on cell differentiation/development-related diseases.

8.
Medicine (Baltimore) ; 103(22): e38371, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-39259101

RESUMEN

BACKGROUND: The impact of intraosseous (IO) access on resuscitation outcomes, as compared to intravenous (IV) administration, is subject to ongoing debate. This review aims to provide a comprehensive evaluation of the methodological, reporting, and evidence quality of existing Systematic Reviews/Meta-Analyses (SRs/MAs) on IO use during resuscitation. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a strategic literature search to identify pertinent SRs/MAs published up until May 6th, 2023. After an extensive screening process, 4 SRs/MAs were included for review. We used the A Measurement Tool to Assess Systematic Reviews-2 tool for assessing methodological quality, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist for evaluating reporting quality, and the Grading of Recommendations Assessment, Development, and Evaluation framework for examining the quality of evidence. RESULTS: The assessment revealed high methodological quality across all the included SRs/MAs but showed significant variability in the quality of evidence. The studies offered conflicting findings on the impact of IO access on resuscitation outcomes such as return of spontaneous circulation, survival rates at hospital discharge, and favorable neurological outcomes. Some studies suggested an association of IO access with poorer outcomes, while others indicated no significant difference between IO and IV routes. CONCLUSIONS: Despite the perceived utility of IO access when IV access is unachievable, the impact of IO on survival, return of spontaneous circulation, and neurological outcomes remains ambiguous due to the inconsistency in the existing evidence. This review underscores the critical need for more rigorous and consistent primary research in this area to strengthen clinical guidelines and improve patient outcomes.


Asunto(s)
Infusiones Intraóseas , Resucitación , Humanos , Infusiones Intraóseas/métodos , Resucitación/métodos , Resucitación/normas , Administración Intravenosa
9.
J Pharm Pharmacol ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39258498

RESUMEN

OBJECTIVES: Hypoxia conditions promote the adaptation and progression of non-small-cell lung cancer (NSCLC) via hypoxia-inducible factors (HIF). HIF-1α may regulate estrogen receptor ß (ERß) and promote the progression of NSCLC. The phytochemical homoharringtonine (HHT) exerts strong inhibitory potency on NSCLC, with molecular mechanism under hypoxia being elusive. METHODS: The effects of HHT on NSCLC growth were determined by cell viability assay, colony formation, flow cytometry, and H460 xenograft models. Western blotting, molecular docking program, site-directed mutagenesis assay, immunohistochemical assay, and immunofluorescence assay were performed to explore the underlying mechanisms of HHT-induced growth inhibition in NSCLC. KEY FINDINGS: HIF-1α/ERß signaling-related E2F1 is highly expressed and contributes to unfavorable survival and tumor growth. The findings in hypoxic cells, HIF-1α overexpressing cells, as well as ERß- or E2F1-overexpressed and knockdown cells suggest that the HIF-1α/ERß/E2F1 feedforward loop promotes NSCLC cell growth. HHT suppresses HIF-1α/ERß/E2F1 signaling via the ubiquitin-proteasome pathway, which is dependent on the inhibition of the protein expression of HIF-1α and ERß. Molecular docking and site-directed mutagenesis revealed that HHT binds to the GLU305 site of ERß. HHT inhibits cell proliferation and colony formation and promotes apoptosis in both NSCLC cells and xenograft models. CONCLUSION: The formation of the HIF-1α/ERß/E2F1 feedforward loop promotes NSCLC growth and reveals a novel molecular mechanism by which HHT induces cell death in NSCLC.

10.
Arq Bras Cardiol ; 121(9): e20240813, 2024.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-39258645

RESUMEN

BACKGROUND: The association between the length of sleep and atherosclerosis has been reported in many observational studies. However, little is known about its significance as a risk factor for atherosclerosis or as a negative consequence of atherosclerosis. OBJECTIVE: This study aimed to assess the causal association between sleep duration and the risk of atherosclerosis using publicly available genome-wide association studies (GWAS) summary statistics. METHODS: We employed a two-sample Mendelian randomization (MR) method with 2 cohorts from MRC-IEU (n=460,099) and UK Biobank (n=361,194) to investigate the causal association between sleep duration and the risk of atherosclerosis. Three methods including the inverse-variance weighted (IVW) technique, Robust adjusted profile score (RAPS), and simple-and weighted-median approach were used to obtain reliable results, and an odds ratio with a 95% confidence interval (CI) was calculated. P<0.05 was considered as a statistical difference. In addition, MR-Egger regression, Radial MR, MR-PRESSO, and leave-one-out analyses were used to assess the possible pleiotropy effects. RESULTS: No causal association of sleep duration with atherosclerosis was found [OR (95%CI): 0.90 (0.98-1.00), p = 0.186]. Leave-one-out, MR-Egger, and MR-PRESSO analyses failed to detect horizontal pleiotropy. CONCLUSIONS: This MR analysis indicated no causal association between genetically predicted sleep duration and atherosclerosis across European populations.


FUNDAMENTO: A associação entre a duração do sono e a aterosclerose foi relatada em muitos estudos observacionais. No entanto, pouco se sabe sobre a sua importância como fator de risco para aterosclerose ou como consequência negativa da aterosclerose. OBJETIVO: Este estudo teve como objetivo avaliar a associação causal entre a duração do sono e o risco de aterosclerose usando estatísticas resumidas de estudos de associação genômica ampla (GWAS) disponíveis publicamente. MÉTODOS: Empregamos um método de randomização mendeliana (RM) de duas amostras com 2 coortes do MRC-IEU (n = 460.099) e do UK Biobank (n = 361.194) para investigar a associação causal entre a duração do sono e o risco de aterosclerose. Três métodos, incluindo a técnica de variância inversa ponderada (IVW), escore de perfil ajustado robusto (RAPS) e abordagem de mediana simples e ponderada, foram usados para obter resultados confiáveis, e uma razão de chances com intervalo de confiança (IC) de 95% foi calculada. P<0,05 foi considerado diferença estatística. Além disso, foram utilizadas análises de regressão: MR-Egger regression, Radial MR, MR-PRESSO e leave-one-out para avaliar os possíveis efeitos de pleiotropia. RESULTADOS: Não foi encontrada associação causal entre duração do sono e aterosclerose [OR (IC95%): 0,90 (0,98-1,00), p = 0,186]. As análises Leave-one-out, MR-Egger, e MR-PRESSO não conseguiram detectar pleiotropia horizontal. CONCLUSÕES: Esta análise de RM não indicou nenhuma associação causal entre a duração do sono geneticamente prevista e a aterosclerose nas populações europeias.


Asunto(s)
Aterosclerosis , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Sueño , Humanos , Aterosclerosis/genética , Sueño/genética , Sueño/fisiología , Factores de Riesgo , Factores de Tiempo , Femenino , Masculino , Persona de Mediana Edad , Duración del Sueño
11.
Natl Sci Rev ; 11(9): nwae217, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39144746

RESUMEN

This perspective explores detailed structural design and strategies for spin regulation in single-atom spin catalysis, enabling unparalleled efficiency in chemical transformations through the harnessing of spin effects combined with atomic precision of active sites.

12.
Immunology ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39108003

RESUMEN

Group 2 innate lymphoid cells (ILC2s) play a crucial role in the progression of asthma, yet the regulatory mechanisms modulating ILC2 responses in asthma remain underexplored. Human milk oligosaccharides (HMOs), vital non-nutritive components of breast milk, are known to significantly shape immune system development and influence the incidence of allergic diseases. However, their impact on ILC2-driven asthma is not fully understood. Our research reveals that dietary HMOs act as potent inhibitors of ILC2 responses and allergic airway inflammation. Treatment with 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL) significantly reduced ILC2-related airway inflammation induced by papain or Alternaria alternata in mice, evidenced by decreased eosinophil (EOS) infiltration and lower IL-5 and IL-13 levels in BALF. Notably, while ILC2 expresses HMO receptors, HMO did not act directly on ILC2 but potentially modulated their activity through alterations in gut microbiota derived SCFAs. HMO treatments alleviated airway inflammation in SCFA-dependent manners, with SCFA depletion or receptor blocking reversing these beneficial effects. This study reveals the potential of dietary HMOs in managing asthma through modulation of ILC2 activity and the gut-lung axis, proposing a new therapeutic avenue that utilises the immunomodulatory capacities of nutritional components to combat respiratory diseases.

13.
Front Cardiovasc Med ; 11: 1374114, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39165261

RESUMEN

Objectives: The aim of this meta-analysis is to evaluate the effect of astragalus injection (AI) on left ventricular remodeling (LVR) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Methods: The randomized controlled trials (RCTs) of AI in treating HFmrEF were retrieved from 8 major English and Chinese electronic databases, up until November 30, 2023. To evaluate the methodological quality of the included studies, the Cochrane bias risk tool and the Modified Jadad Scale were employed. Stata 17.0 software was utilized for statistical analysis, sensitivity analysis, and assessment of publication bias. Results: Ten RCTs with 995 patients (562 males and 433 females) were identified. Meta-analysis indicated that compared to conventional treatment (CT), AI significantly improved LVR, specifically increasing left ventricular ejection fraction (LVEF, MD = 4.56, 95% CI: 3.68-5.44, p < 0.00001), decreasing left ventricular end-diastolic volume (LVEDV, MD = -7.89, 95% CI: -11.13 to -4.64, p < 0.00001), left ventricular end-diastolic diameter (LVEDD, MD = -4.18, 95% CI: -5.79 to -2.56, p < 0.00001), left ventricular end-systolic volume (LVESV, MD = -8.11, 95% CI: -11.79 to -4.43, p < 0.00001), and left ventricular end-systolic diameter (LVESD, MD = -3.42, 95% CI: -4.90 to -1.93, p < 0.00001). AI also improved clinical efficacy (RR = 4.62, 95% CI: 3.11-6.88, p < 0.00001), reduced N-terminal pro-brain natriuretic peptide (NT-pro BNP, MD = -27.94, 95% CI: -43.3 to -12.36) level, without increasing the incidence of adverse reactions (RR = 1.60, 95% CI: 0.59-4.29, p = 0.35). Sensitivity analysis confirmed the reliability of the merged results, and Begg's and Egger's tests showed no significant publication bias. Conclusion: The systematic review and meta-analysis revealed that combining AI with CT improves LVR without increasing adverse events in HFmrEF patients. However, caution is needed in interpreting the results due to limited evidence. Future high-quality RCTs are needed to support these conclusions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO [CRD42022347248].

14.
BMC Public Health ; 24(1): 2171, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39135162

RESUMEN

BACKGROUND: Influenza, an acute infectious respiratory disease, presents a significant global health challenge. Accurate prediction of influenza activity is crucial for reducing its impact. Therefore, this study seeks to develop a hybrid Convolution Neural Network-Long Short Term Memory neural network (CNN-LSTM) model to forecast the percentage of influenza-like-illness (ILI) rate in Hebei Province, China. The aim is to provide more precise guidance for influenza prevention and control measures. METHODS: Using ILI% data from 28 national sentinel hospitals in the Hebei Province, spanning from 2010 to 2022, we employed the Python deep learning framework PyTorch to develop the CNN-LSTM model. Additionally, we utilized R and Python to develop four other models commonly used for predicting infectious diseases. After constructing the models, we employed these models to make retrospective predictions, and compared each model's prediction performance using mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE), and other evaluation metrics. RESULTS: Based on historical ILI% data from 28 national sentinel hospitals in Hebei Province, the Seasonal Auto-Regressive Indagate Moving Average (SARIMA), Extreme Gradient Boosting (XGBoost), Convolution Neural Network (CNN), Long Short Term Memory neural network (LSTM) models were constructed. On the testing set, all models effectively predicted the ILI% trends. Subsequently, these models were used to forecast over different time spans. Across various forecasting periods, the CNN-LSTM model demonstrated the best predictive performance, followed by the XGBoost model, LSTM model, CNN model, and SARIMA model, which exhibited the least favorable performance. CONCLUSION: The hybrid CNN-LSTM model had better prediction performances than the SARIMA model, CNN model, LSTM model, and XGBoost model. This hybrid model could provide more accurate influenza activity projections in the Hebei Province.


Asunto(s)
Predicción , Gripe Humana , Redes Neurales de la Computación , Humanos , China/epidemiología , Gripe Humana/epidemiología , Aprendizaje Profundo , Estudios Retrospectivos , Vigilancia de Guardia
15.
J Biomed Res ; : 1-10, 2024 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-39187911

RESUMEN

Hypertension (HT) is a major risk factor for cardiovascular diseases. Krüppel-like factors (KLFs) are important transcription factors in eukaryotes. Studies have reported that KLF4 and KLF5 are correlated with several cardiovascular diseases, whereas population studies for associations between HT and KLF4 or KLF5 have been rarely reported. Thus, the current study aimed to examines the association of genetic variants and mRNA expression levels of KLF4 and KLF5 with HT, as well as the effect of antihypertensive drugs on the expression levels. The associations of one single-nucleotide polymorphism (SNP) in KLF4 and three SNPs in KLF5 with HT were investigated using a combination of case-control and cohort studies. The study population were selected from a community-based population cohort in four different regions of Jiangsu Province. Risks of HT were estimated through logistic and Cox regression analyses, respectively. In addition, mRNA expression levels of KLF4 and KLF5 were measured in 246 controls and 385 HT cases selected from the cohort study as mentioned above. Among the HT cases, 263 were not taking antihypertensive drugs [AHD(-)] and 122 were taking antihypertensive drugs [AHD(+)]. In the case-control study, SNP rs9573096 (C>T) in KLF5 was significantly associated with an increased risk of HT in the additive model (adjusted odds ratio [OR], 1.106; 95% confidence interval [CI], 1.009 to 1.212). In the cohort study of the normotensive population, rs9573096 in KLF5 was also significantly associated with an increased risk of HT in the additive model (adjusted hazards ratio [HR], 1.199; 95% CI, 1.070 to 1.344). KLF4 and KLF5 mRNA expression levels were significantly higher in the AHD(-) group than in the control group ( P < 0.05), but lower in the AHD(+) group than in the AHD(-) group ( P < 0.05). The current study demonstrated the associations of KLF4 and KLF5 genetic variants with hypertension, and the indicative discriminations of mRNA expression levels of KLF4 and KLF5 for risk of hypertension and antihypertensive treatment.

16.
Ecotoxicol Environ Saf ; 284: 116954, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39208572

RESUMEN

Epidemiological studies have suggested a positive association between environmental cadmium (Cd) exposure and type 2 diabetes mellitus (T2DM). Skeletal muscle insulin resistance (IR) plays a critical role in the pathogenesis of T2DM. This study aimed to investigate the effects of chronic low-level Cd exposure on skeletal muscle IR and its potential mechanism. Rats were exposed to drinking water containing 2 or 10 mg/L Cd for 24 weeks. Differentiated L6 myotubes were treated with Cd for 72 h. Immunofluorescence, flow cytometry assay, RNA-sequencing, and Seahorse analysis were conducted to determine the effects of Cd and its underlying mechanism on relevant parameters, including insulin sensitivity, glucose uptake, oxidative stress, mitophagy, and mitochondrial function in skeletal muscle and L6 myotubes. N-acetyl-cysteine (NAC), a scavenger of reactive oxygen species (ROS), and mitophagy inhibitor Cyclosporin A (CsA) were used to confirm the role of oxidative stress in mitophagy and mitochondrial dysfunction caused by Cd. We found that rats exposed to 10 mg/L Cd exhibited hyperglycemia and skeletal muscle IR. Cd markedly increased IRS-1 phosphorylation at Ser612, while decreased levels of phosphorylated PI3K, Akt, AS160, inhibited GLUT4 translocation and glucose uptake. Mechanistically, Cd increased the intracellular ROS, hydrogen peroxide, and malondialdehyde levels and decreased antioxidase activity in L6 myotubes. Furthermore, Cd upregulated the mRNA and protein levels of LC3II/I, PINK1, and Parkin. In addition, Cd induced the formation of mitophagosomes, reduced the mitochondrial membrane potential, decreased the adenosine triphosphate content, and impaired the mitochondrial respiratory capacity. Strikingly, NAC ameliorated oxidative stress, excessive mitophagy, and the associated reduction in myotube insulin sensitivity, while inhibition of mitophagy by CsA alleviated skeletal muscle IR. In conclusion, this study reveals a previously unrecognized mechanism that chronic low-level Cd exposure may induce mitophagy by activating the PINK1/Parkin signal pathway by increasing ROS, thus causing skeletal muscle IR and elevated blood glucose.

17.
Sci Data ; 11(1): 938, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39198467

RESUMEN

This paper describes a two-year high-fidelity dataset for an ultra-low energy office building and living laboratory called HouseZero®. The building integrates multiple low-energy technologies, such as natural ventilation with automatic windows, ground source heat pump, and thermally activated building systems. The building's performance is continuously monitored with an extensive sensor network. The dataset consists of breakdown energy end uses, photovoltaic (PV) production, zone-level indoor environment including indoor air temperature, CO2 concentration, and relative humidity, micro-climatical conditions, building façade temperature, and detailed system operations including zone-level BTU meter, valve status, slab temperature, window/skylight opening status, heat pump, and geothermal well operations. The data can be used to support data analytics of ultra-low-energy building operations, and data-driven modeling of low-energy building systems.

18.
Small ; : e2405592, 2024 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-39155416

RESUMEN

Aqueous ammonium ion batteries (AAIBs) have garnered significant attention due to their unique energy storage mechanism. However, their progress is hindered by the relatively low capacities of NH4 + host materials. Herein, the study proposes an electrodeposited tungsten oxide@polyaniline (WOx@PANI) composite electrode as a NH4 + host, which achieves an ultrahigh capacity of 280.3 mAh g-1 at 1 A g-1, surpassing the vast majority of previously reported NH4 + host materials. The synergistic interaction of coordination chemistry and hydrogen bond chemistry between the WOx and PANI enhances the charge storage capacity. Experimental results indicate that the strong interfacial coordination bonding (N: →W6+) effectively modulates the chemical environment of W atoms, enhances the protonation level of PANI, and thus consequently the conductivity and stability of the composites. Spectroscopy analysis further reveals a unique NH4 +/H+ co-insertion mechanism, in which the interfacial hydrogen bond network (N-H···O) accelerates proton involvement in the energy storage process and activates the Grotthuss hopping conduction of H+ between the hydrated tungsten oxide layers. This work opens a new avenue to achieving high-capacity NH4 + storage through interfacial chemistry interactions, overcoming the capacity limitations of NH4 + host materials for aqueous energy storage.

19.
Huan Jing Ke Xue ; 45(8): 4540-4552, 2024 Aug 08.
Artículo en Chino | MEDLINE | ID: mdl-39168674

RESUMEN

To explore the relationship between land use and water quality in basins with different land use patterns at different spatial and temporal scales, the Wuding River Basin and Yanhe River Basin were taken as research objects. Based on land use data in 2020 and water quality monitoring data during two periods, the redundancy analysis method was adopted to quantitatively explore the impact of land use on water quality at multiple scales. The results showed that: ① The main land use types in the two basins were cultivated land and grassland, and the difference was mainly in the proportion of bare land and forest land. ② The water quality in spring was better than that in autumn, and the water quality in the middle and lower reaches was worse. ③ The interpretation rate of land use on the riparian scale was the highest in the two basins. ④ The effect of land use on water quality was more significant in the Wuding River Basin in autumn than in spring, whereas the Yanhe River Basin showed the opposite trend. ⑤ Different land uses had different impacts on water quality. Bare land, cultivated land, and Shannon diversity index (SHDI) in the Wuding River Basin had significant impacts on water quality, whereas grassland, cultivated land, artificial surface, patch density (PD), and SHDI were significant in the Yanhe River Basin. Cultivated land and artificial surfaces in the Wuding River Basin had a negative impact on water quality. Grassland and bare land had a negative correlation with most chemical indicators. Artificial surfaces and grasslands in the Yanhe River Basin had a negative impact on water quality, whereas forest land had a significant purification effect. The research results provide important information for sustainable land use and multi-scale landscape planning, which can be used to improve water quality.

20.
Nat Commun ; 15(1): 7214, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39174541

RESUMEN

It is challenging to attain strong near-infrared (NIR) emissive gold nanoclusters. Here we show a rod-shaped cluster with the composition of [Au28(p-MBT)14(Hdppa)3](SO3CF3)2 (1 for short, Hdppa is N,N-bis(diphenylphosphino)amine, p-MBT is 4-methylbenzenethiolate) has been synthesized. Single crystal X-ray structural analysis reveals that it has a rod-like face-centered cubic (fcc) Au22 kernel built from two interpenetrating bicapped cuboctahedral Au15 units. 1 features NIR luminescence with an emission maximum at 920 nm, and the photoluminescence quantum yield (PLQY) is 12%, which is 30-fold of [Au21(m-MBT)12(Hdppa)2]SO3CF3 (2, m-MBT is 3-methylbenzenethiolate) with a similar composition and 60-fold of Au30S(S­t­Bu)18 with a similar structure. time-dependent DFT(TDDFT)calculations reveal that the luminescence of 1 is associated with the Au22 kernel. The small Stokes shift of 1 indicates that it has a very small excited state structural distortion, leading to high radiative decay rate (kr) probability. The emission of cluster 1 is a mixture of phosphorescence and thermally activated delayed fluorescence(TADF), and the enhancement of the NIR emission is mainly due to the promotion of kr rather than the inhibition of knr. This work demonstrates that the metal kernel and the surface structure are both very important for cluster-based NIR luminescence materials.

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