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Accurate estimation of pandemic likelihood in every US state of interest and at any time. Coronavirus disease 2019 (COVID-19) is an infectious illness with a high potential for global dissemination and low rates of fatality and morbidity, placing some strains on national public health systems. This research intends to benchmark a novel technique, that enables hazard assessment, based on available clinical data, and dynamically observed patient numbers while taking into account pertinent territorial and temporal mapping. Multicentre, population-based, and biostatistical strategies have been utilized to process raw/unfiltered medical survey data. The expansion of extreme value statistics from the univariate to the bivariate situation meets with numerous challenges. First, the univariate extreme value types theorem cannot be directly extended to the bivariate (2D) case,-not to mention challenges with system dimensionality higher than 2D. Assessing outbreak risks of future outbreaks in any nation/region of interest. Existing bio-statistical approaches do not always have the benefits of effectively handling large regional dimensionality and cross-correlation between various regional observations. These methods deal with temporal observations of multi-regional phenomena. Apply contemporary, novel statistical/reliability techniques directly to raw/unfiltered clinical data. The current study outlines a novel bio-system hazard assessment technique that is particularly suited for multi-regional environmental, bio, and public health systems, observed over a representative period. With the use of the Gaidai multivariate hazard assessment approach, epidemic outbreak spatiotemporal risks may be properly assessed. Based on raw/unfiltered clinical survey data, the Gaidai multivariate hazard assessment approach may be applied to a variety of public health applications. The study's primary finding was an assessment of the risks of epidemic outbreaks, along with a matching confidence range. Future global COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-COV2) epidemic risks have been examined in the current study; however, COVID-19/SARS-COV2 infection transmission mechanisms have not been discussed.
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Rheumatoid arthritis (RA) is a chronic autoimmune disease with a complex etiology. Neutrophil extracellular traps (NETs are NETwork protein structures activated by neutrophils to induce the cleavage and release of DNA-protein complexes). Current studies have shown the critical involvement of NETs in the progression of autoimmune diseases, Neutrophils mostly gather in the inflammatory sites of patients and participate in the pathogenesis of autoimmune diseases in various ways. NETs, as the activated state of neutrophils, have attracted much attention in immune diseases. Many molecules released in NETs are targeted autoantigens in autoimmune diseases, such as histones, citrulline peptides, and myeloperoxidase. All of these suggest that NETs have a direct causal relationship between the production of autoantigens and autoimmune diseases. For RA in particular, as a disorder of the innate and adaptive immune response, the pathogenesis of RA is inseparable from the generation of RA. In this article, we investigate the emerging role of NETs in the pathogenesis of RA and suggest that NETs may be an important target for the treatment of inflammatory autoimmune diseases.
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Artrite Reumatoide , Progressão da Doença , Armadilhas Extracelulares , Neutrófilos , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Humanos , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/etiologia , Artrite Reumatoide/patologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Animais , Autoantígenos/imunologiaRESUMO
Atherosclerosis is the pathological cause of atherosclerotic cardiovascular disease (ASCVD), which rapidly progresses during the cellular senescence. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce major cardiovascular events in patients with ASCVD and have potential antisenescence effects. Here, we investigate the effects of the SGLT2 inhibitor dapagliflozin on cellular senescence in atherosclerotic mice. Compared with ApoE-/- control mice treated with normal saline, those in the ApoE-/- dapagliflozin group, receiving intragastric dapagliflozin (0.1 mg kg-1 d-1) for 14 weeks, exhibited the reduction in the total aortic plaque area (48.8%±6.6% vs. 74.6%±8.0%, P<0.05), the decrease in the lipid core area ((0.019±0.0037) mm2vs. (0.032±0.0062) mm2, P<0.05) and in the percentage of senescent cells within the plaques (16.4%±3.7% vs. 30.7%±2.0%, P<0.01), while the increase in the thickness of the fibrous cap ((21.6±2.1) µm vs. (14.6±1.5) µm, P<0.01). Transcriptome sequencing of the aortic arch in the mice revealed the involvement of the PPARα and the fatty acid metabolic signaling pathways in dapagliflozin's mechanism of ameliorating cellular aging and plaque progression. In vitro, dapagliflozin inhibited the expression of PPARα and its downstream signal FABP4, by which the accumulation of senescent cells in human aortic smooth muscle cells (HASMCs) was reduced under high-fat conditions. This effect was accompanied by a reduction in the intracellular lipid content and alleviation of oxidative stress. However, these beneficial effects of dapagliflozin could be reversed by the PPARα overexpression. Bioinformatics analysis and molecular docking simulations revealed that dapagliflozin might exert its effects by directly interacting with the RXRA protein, thereby influencing the expression of the PPARα signaling pathway. In conclusion, the cellular senescence of aortic smooth muscle cells is potentially altered by dapagliflozin through the suppression of the RXRA-PPARα-FABP4 signaling pathway, resulting in a deceleration of atherosclerotic progression.
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In piglets, oxidative stress can exacerbate gut injury caused by pathogens. C-Jun amino-terminal kinase (JNK) is associated with oxidative stress-induced damage to intestinal epithelial barrier. However, it is unclear whether oxidative stress can increase gut injury by Clostridium perfringens type A (CpA) and whether JNK mediates this process. We aimed to investigate if and how the JNK can regulate the effect of oxidative stress on gut injury induced by CpA infection. In this study, the oxidative stress in IPEC-J2 cells was modeled, and the changes in the susceptibility of IPEC-J2 cells to CpA were examined after treatment of oxidative stressed IPEC-J2 cells with JNK inhibitor (SP600125) and JNK siRNA. Pre-injection with the SP600125 solution was also carried out in oxidative stressed mice, followed by CpA infection. Results indicated that compared to that in the Control group, IPEC-J2 cells under oxidative stress showed reduced transmembrane resistance, degraded tight junction (TJ) proteins, increased membrane permeability, and enhanced CpA infection, all of which were reversed by inhibiting or interfering with JNK expression. Similarly, compared to that in the Control group, mice under oxidative stress showed degradation of jejunal TJ proteins, increased intestinal permeability and barrier damage by CpA, while mice pre-injected with the SP600125 solution showed alleviation of these alterations. These results suggested that oxidative stress enhanced the infection of IPEC-J2 cells and the gut injury caused by CpA, which was mediated by JNK. This study provides important insights regarding the mechanism by which oxidative stress enhanced intestinal damage by CpA.
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The development of alternative conductive polymers for the well-known poly (3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) is of great significance for improving the stability in long-term using and high-temperature environments. Herein, an innovative PEDOT:S-ANF aqueous dispersion is successfully prepared by using sulfamic acid (SA) to modified aramid nanofibers (S-ANF) as an alternative dispersant for PSS and the subsequent in situ polymerization of PEDOT. Thanks to the excellent film forming ability and surface negative groups of S-ANF, the PEDOT:S-ANF films show comparable tensile strength and elongation to unmodified PEDOT:ANF. Meanwhile, PEDOT:S-ANF has a high conductivity of 27.87 S cm-1, which is more than 20 times higher than that of PEDOT:PSS. The film exhibits excellent electromagnetic interference (EMI) shielding and thermoelectric performance, with a shielding effectiveness (SE) of 31.14 dB and a power factor (PF) of 0.43 µW m-1K-2. As a substitute for PSS, S-ANF exhibits significant structural and physicochemical properties, resulting in excellent chemical and thermal stability. Even under harsh conditions such as immersing to 0.1 M HCl, 0.1 M NaOH, and 3.5% NaCl solution, or high temperature conditions, the PEDOT:S-ANF films still maintain exceptional EMI shielding performance. Therefore, this multifunctional conductive polymer exhibits enormous potential and even proves its reliability in extreme situations.
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OBJECTIVES: We aimed to explore the lived experiences and needs of women after a recent stillbirth event. DESIGN: Qualitative phenomenological study. SETTING: The current study was conducted in a tertiary obstetric hospital in East China between 25 January 2024 and 29 March 2024. PARTICIPANTS: 14 women having experienced a stillbirth within the last 6 months. RESULTS: Researchers agreed on four key themes including individual variations in emotional reaction and recovery, physical recovery and concerns about future pregnancies, the critical role of social support systems and variations in perceptions of stillbirth as the death of a fetus versus a human being, along with related mourning rituals. These themes collectively highlight the multifaceted nature of the stillbirth experience, underscoring the complex interplay between personal, cultural and medical factors that shape women's emotional and physical responses. CONCLUSIONS: Post-stillbirth experiences among Chinese women are deeply individualised and influenced by a complex interplay of personal emotions, cultural contexts and medical interactions. It is imperative for healthcare systems to implement tailored care strategies beyond standard protocols to proactively address their varied emotional landscapes and physical concerns with an enhanced awareness of cultural sensitivities. Specialised training for healthcare providers should be devised to recognise and respond to the unique grief processes. Comprehensive support systems should be established to significantly enhance the recovery journey by providing essential resources and community connections.
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Pesar , Pesquisa Qualitativa , Apoio Social , Natimorto , Humanos , Feminino , Natimorto/psicologia , Adulto , China , Gravidez , Emoções , Adulto Jovem , População do Leste AsiáticoRESUMO
The inorganic matrices such as metal concentrates, steel, cement, glass, clay, coal, graphite, rocks and sediments, ores etc. play a pivotal role in infrastructure development, transportation, and energy. The presence of non-metallic elements particularly halogens influence their quality, processing cost, and environment dynamics. The analysis of non-metals in such matrices is critically challenging due to their hardness, rigidity, and non-digestibility. This comprehensive review provides a critical comparison of various sample preparation methods in conjunction with pros and cons of advanced techniques for the detection of non-metals in complex matrices, particularly focusing on ion chromatography. Moreover, the review also addresses the challenges related to the enrichment and automation of non-metals analysis. In addition, the previous literature on non-metals determination in diverse range of inorganic matrices has been tabulated for the first time. These insights are intended to guide researchers, quality control analysts, environmental scientists, and policymakers in enhancing pollution monitoring and control strategies.
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C-glycosides are a predominant class of flavonoids that demonstrate diverse medical properties and plant physiological functions. The chemical stability, structural diversity, and differential aboveground distribution of these compounds in plants make them ideal protectants. However, little is known about the transcriptional regulatory mechanisms that play these diverse roles in plant physiology. In this study, chard was selected from 69 families for its significantly different flavonoid C-glycosides distributions between the aboveground and underground parts to investigate the role and regulatory mechanism of flavonoid C-glycosides in plants. Our results indicate that flavonoid C-glycosides are affected by various stressors, especially UV-B. Through cloning and validation of key biosynthetic genes of flavonoid C-glycosides in chard (BvCGT1), we observed significant effects induced by UV-B radiation. This finding was further confirmed by resistance testing in BvCGT1 silenced chard lines and in Arabidopsis plants with BvCGT1 overexpression. Yeast one-hybrid and dual-luciferase assays were employed to determine the underlying regulatory mechanisms of BvCGT1 in withstanding UV-B stress. These results indicate a potential regulatory role of BvDof8 and BvDof13 in modulating flavonoid C-glycosides content, through their influence on BvCGT1. In conclusion, we have effectively demonstrated the regulation of BvCGT1 by BvDof8 and BvDof13, highlighting their crucial role in plant adaptation to UV-B radiation. Additionally, we have outlined a comprehensive transcriptional regulatory network involving BvDof8 and BvDof13 in response to UV-B radiation.
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At present, the optimal therapeutic approach for the treatment of platinum-resistant recurrent ovarian cancer remains to be fully elucidated. The present systematic review and network meta-analysis aimed to elucidate the relative efficacy and safety of apatinib, administered either as monotherapy or in conjunction with chemotherapy, compared with chemotherapy alone, for the treatment of platinum-resistant recurrent ovarian cancer. The PubMed, Embase and Wanfang Data electronic databases were searched, where the search spanned from the conception of the databases until April 2023. A quality evaluation was conducted and R software was used for network meta-analysis. Following inclusion and exclusion criteria screening, the present analysis included 17 clinical trials, combining data from 1,228 patients with platinum-resistant recurrent ovarian cancer categorized into the following three treatment cohorts: i) 555 patients who received apatinib plus chemotherapy; ii) 229 patients who received apatinib alone; and iii) 444 patients who underwent conventional chemotherapy. Results of the present study demonstrated that the co-administration of apatinib with either tegiol [odds ratio (OR), 2.54; 95% CI, 1.06-6.11] or etoposide (OR, 2.12; 95% CI, 1.20-3.74) significantly improved the objective response rate (ORR) compared with that following apatinib monotherapy. By contrast, gemcitabine monotherapy resulted in inferior ORR efficacy compared with that following apatinib (OR, 0.47; 95% CI, 0.23-0.95). In addition, combinations of apatinib with etoposide (OR, 1.32; 95% CI, 1.06-1.64) or paclitaxel (OR, 1.52; 95% CI, 1.04-2.23) demonstrated a significantly improved disease control rates (DCR) compared with those following apatinib alone. According to the area under the cumulative ranking analysis, apatinib and paclitaxel in combination was the most efficacious treatment modality in terms of DCR. In terms of safety, the incidence of adverse events, such as hand-foot syndrome [relative risk (RR), 4.23; 95% CI, 1.80-9.95] and hypertension (RR, 4.80; 95% CI, 1.53-15.05), was found to be significantly higher in patients treated with apatinib-containing therapies, compared with those treated with chemotherapy alone. Consequently, the present meta-analysis highlighted the potential of apatinib, particularly in combination with chemotherapy, as a therapeutic strategy for patients with platinum-resistant recurrent ovarian cancer.
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A cascade oxidation/Pictet-Spengler condensation/annulation process has been developed for the one-pot total synthesis of nitramarine, nitraridine, and their analogues. The procedure proceeded with easily available quinolines and tryptophan derivatives. A simple and metal-free approach, wide substrate scope, and functional group tolerance make it applicable for the synthesis of diverse bioactive nitramarine, nitraridine, and their derivatives. Furthermore, the bioactivity evaluation has identified two promising leading compounds 5d and 5e with potent antitumor proliferative activity against breast cancer cells.
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Luminescent coupling (LC) is a key phenomenon in monolithic tandem solar cells. This study presents a nondestructive technique to quantitatively evaluate the LC effect, addressing a gap in the existing predictions made by optical modeling. The method involves measuring the ratio of photons emitted from the high bandgap top cell that escape through the rear, contributing additional current to the bottom cell, and to those escaping from the front side of top cell. The findings indicate that in the analyzed monolithic perovskite/silicon tandem solar cells, more than 85% of the emitted photons escaping from the perovskite top cell are used to generate additional current in the bottom cell. This process notably reduces the mismatch in the generated current between each subcell, particularly when the current is limited by the low bandgap subcell. The presented method is applicable to a variety of monolithic tandem structures, providing vital information for subcell characterization, providing vital information for predicting energy output and optimization for outdoor applications.
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As a chronic autoimmune disease with complex aetiology, rheumatoid arthritis (RA) has been demonstrated to be associated with mitochondrial dysfunction since mitochondrial dysfunction can affect the survival, activation, and differentiation of immune and non-immune cells involved in the pathogenesis of RA. Nevertheless, the mechanism behind mitochondrial dysfunction in RA remains uncertain. Accordingly, this review addresses the possible role and mechanisms of mitochondrial dysfunction in RA and discusses the potential and challenges of mitochondria as a potential therapeutic strategy for RA, thereby providing a breakthrough point in the prevention and treatment of RA.
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BACKGROUND: Ensuring that the scale and hierarchical structure of health human resources are rational, and that medical services are efficient and fair, is an important task of practical significance. On this basis, examining the impact of health human resources on the level of medical services presents a new and formidable challenge. This study aims to delve into how the scale and hierarchical structure of health human resources in China's four major economic regions affect the fairness and efficiency of medical services, and to identify optimization strategies. METHODS: This study utilizes provincial panel data from China's four major economic regions spanning the years 2009 to 2021. Initially, it provides a statistical description of the current state of health human resources and the level of medical services. Subsequently, it employs a fixed-effects model to analyze the impact of the scale and hierarchical structure of health human resources, as well as their interactive effects, on the fairness and efficiency of medical services, and discusses the interactive mechanisms between medical service fairness and medical service efficiency. Furthermore, after conducting a comprehensive evaluation of the level of medical services using the entropy weight method, it explores the regional heterogeneity and temporal dynamics in the influence of the scale and hierarchical structure of health human resources on the level of medical services. Finally, the study examines the scientific validity and rationality of the research findings through various robustness checks, including the substitution of research variables and models. RESULTS: The study found that the scale of health human resources has a promoting effect on the equity of medical services (ß ≤ 0.643, p ≤ 0.01), but exhibits an inhibitory effect on the efficiency of medical services (ß ≥ -0.079, p ≤ 0.1); the hierarchical structure of health human resources shows a positive impact on both the equity and efficiency of medical services (ßequity ≤ 0.160, p ≤ 0.01; ßefficiency ≤ 0.341, p ≤ 0.05); at the same time, the results indicate that the interactive effect of the scale and hierarchical structure of health human resources promotes equity in medical services (ß = 0.067, p ≤ 0.01), but restricts the efficiency of medical services (ß ≥ -0.039, p ≤ 0.01); the mechanism by which health human resources affect the level of medical services in China's western and northeastern regions is more pronounced than in the central and eastern regions; after the implementation of the "Healthy China 2030" Planning Outline, the role of health human resources in the level of medical services has been strengthened; in the robustness tests, the model remains robust after replacing the core explanatory variables, with R2 maintained between 0.869 and 0.972, and the dynamic GMM model test shows a significant second-order lag in the level of medical services (ßequity ≤ 0.149, p ≤ 0.01; ßefficiency ≤ 0.461, p ≤ 0.01); the channel test results prove that managerial personnel and other technical personnel are key pathways in regulating the impact of medical staff on the level of medical services. CONCLUSION: This study provides an in-depth analysis of the impact of health human resources on the level of medical services, revealing that both the scale and hierarchical structure of health human resources significantly affect the equity and efficiency of medical services. Furthermore, the influence of health human resources on the level of medical services exhibits regional heterogeneity and temporal characteristics. Robustness tests ensure the scientific validity and robustness of the research conclusions. This provides effective references for optimizing the allocation of health human resources and improving the level of medical services.
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Mão de Obra em Saúde , China , Humanos , Recursos em Saúde , Serviços de Saúde/economia , Serviços de Saúde/normas , Atenção à Saúde/economiaRESUMO
Periodontitis is a chronic inflammatory disease caused by plaque that destroys the alveolar bone tissues, resulting in tooth loss. Poor eradication of pathogenic microorganisms, persistent malignant inflammation and impaired osteo-/angiogenesis are currently the primary challenges to control disease progression and rebuild damaged alveolar bone. However, existing treatments for periodontitis fail to comprehensively address these issues. Herein, an injectable composite hydrogel (SFD/CS/ZIF-8@QCT) encapsulating quercetin-modified zeolitic imidazolate framework-8 (ZIF-8@QCT) is developed. This hydrogel possesses thermo-sensitive and adhesive properties, which can provide excellent flowability and post-injection stability, resist oral fluid washout as well as achieve effective tissue adhesion. Inspirationally, it is observed that SFD/CS/ZIF-8@QCT exhibits a rapid localized hemostatic effect following implantation, and then by virtue of the sustained release of zinc ions and quercetin exerts excellent collective functions including antibacterial, immunomodulation, pro-osteo-/angiogenesis and pro-recruitment, ultimately facilitating excellent alveolar bone regeneration. Notably, our study also demonstrates that the inhibition of osteo-/angiogenesis of PDLSCs under the periodontitis is due to the strong inhibition of energy metabolism as well as the powerful activation of oxidative stress and autophagy, whereas the synergistic effects of quercetin and zinc ions released by SFD/CS/ZIF-8@QCT are effective in reversing these biological processes. Overall, our study presents innovative insights into the advancement of biomaterials to regenerate alveolar bone in periodontitis.
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The association between serum pentraxin-3 (PTX-3) levels and chronic obstructive pulmonary disease (COPD) has been explored in several studies. However, the results remain inconsistent. This meta-analysis aims to evaluate the differences in serum PTX-3 levels between COPD patients and healthy controls, as well as between patients with acute exacerbations of COPD (AECOPD) and stable COPD. Databases including PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) were systematically searched. A random-effects model was used to pool the results, accounting for the potential impact of heterogeneity. Subgroup and meta-regression analyses were performed to evaluate the influence of study characteristics on the outcome. The initial search identified 274 articles, with 17 studies meeting the inclusion criteria. These studies included a total of 996 AECOPD patients, 1414 stable COPD patients, and 1016 healthy controls. The meta-analysis showed significantly higher serum PTX-3 levels in COPD patients compared to healthy controls (standardized mean difference [SMD]: 0.51, 95% confidence interval [CI]: 0.30 to 0.73, P < 0.001; I² = 85%). Subgroup and meta-regression analyses suggested that the results were not significantly affected by the age, sex, or smoking status of the patients. Additionally, serum PTX-3 levels were higher in AECOPD patients compared to stable COPD patients (SMD: 0.58, 95% CI: 0.41 to 0.74, P < 0.001; I² = 59%). In conclusion, serum PTX-3 levels are elevated in COPD patients, particularly during acute exacerbations, compared to stable COPD patients and healthy controls. PTX-3 may serve as a potential biomarker for COPD severity and exacerbation status.
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OBJECTIVE: This study aimed to validate the iScore, ASTRAL score, DRAGON score, and THRIVE score for assessing large vessel occlusion-acute ischemic stroke (AIS-LVO) and establish a predictive model for AIS-LVO patients that has better performance to guide clinical practice. METHODS: We retrospectively included 439 patients with AIS-LVO and collected baseline data from all of them. External validation of the iScore, ASTRAL score, DRAGON score, and THRIVE score was performed. All variables were compared between groups via univariate analysis, and the results are expressed as ORs and 95â¯% CIs. Independent variables with P < 0.25 were included in the multivariate logistic analysis, and statistically significant differences (P < 0.05) were identified as risk factors for prognosis in AIS-LVO patients. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the predictive value of our model. RESULTS: Our external validation resulted in an iScore under the curve (AUC) of 0.8475, an ASTRAL AUC of 0.8324, a DRAGON AUC of 0.8196, and a THRIVE AUC of 0.8039. In our research, multivariate Cox regression revealed 8 independent predictors. We used a nomogram to visualize the results of the data analysis. The AUC for the training cohort was 0.8855 (95â¯% CI, 0.8487-0.9222), and that in the validation cohort was 0.8992 (95â¯% CI, 0.8496-0. 9488). CONCLUSIONS: In this study, we verified that the above scores have excellent efficacy in predicting the prognosis of AIS-LVO patients. The nomogram we developed was able to predict the prognosis of AIS-LVO more accurately and may contribute to personalized clinical decision-making and treatment for future clinical work.
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The shrinkage of metal oxide semiconductor field effect transistor (MOSFET) to the small size of the nanoscale results in changes in their channel current noise composition. This paper determines the channel current noise composition of 90 nm MOSFET through experiments, and according to the device material and noise characteristics analysis, the channel current noise of 90 nm and below is obtained, which not only contains thermal noise and suppressed channel shot noise, but also adds suppressed gate tunneling shot noise and cross-correlation noise. Then, Monte Carlo simulation of 10 nm MOSFET noise is further used to determine the channel current composition of small size nanoscale devices. Subsequently, based on the device structure and fundamental characteristics of channel current noise, the channel current noise model is established. Finally, this model is employed to analyze the relationship between thermal noise, suppressed shot noise, cross-correlation noise, and channel current noise in relation to bias parameters and device characteristics. The theoretical results are basically consistent with the experimental and the simulated results, and the channel noise increases with the increase of bias voltage. This achievement holds promise for enhancing the operational efficiency, reliability, and lifetime of nanoscale small-sized MOSFET devices.
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Lentinula edodes (Shiitake) is an important edible mushroom and polysaccharides are its major constituents with proven health benefits. The study was to investigate the gut bacterial fermentation and subsequent effects on gut barrier function of a glucan-rich polysaccharide, LePS40 precipitated from the mushroom water extract with 40 % (v/v) ethanol. LePS40 consisted of a ß-(1â3)-glucan main chain with substitution in the C-6 position with side chains mainly composed of (1 â 6)-linked ß-Glcp residues, (1 â 6)-linked α-Galp residues and terminal residues of ß-Glcp. LePS40 was found highly resistant to digestive enzymes and gastric acid in simulated human gastrointestinal tract, but highly fermentable during in vitro human fecal fermentation. The fecal fermentation degradation of LePS40 appeared to selectively break the glucoside linkage in view of the dramatic decrease in the glucose molar ratio (12.68 to 1.07). Compared with the prebiotic reference FOS, LePS40 led to much higher levels of butyric, and propionic acid and a lower level of acetic acid. Moreover, LePS40 enhanced the abundance of some beneficial bacterial populations, but decreased the bacteria possibly linked with fatty-liver disease and colorectal cancer. Furthermore, the fecal fermentation products of LePS40 showed a potential protective effect on intestinal barrier function against inflammatory damage in Caco-2/Raw264.7 co-culture model. These findings suggest the potential of LePS40 for improvement of gut health through modulation of gut microbiota.
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Fermentação , Microbioma Gastrointestinal , Cogumelos Shiitake , Cogumelos Shiitake/química , Cogumelos Shiitake/metabolismo , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Células CACO-2 , Animais , Fezes/microbiologia , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/metabolismo , Digestão/efeitos dos fármacos , Peso Molecular , Camundongos , Mucosa Intestinal/metabolismo , PrebióticosRESUMO
Vancomycin-resistant enterococcus (VRE) is a major nosocomial pathogen that exhibits enhanced infectivity due to its robust virulence and biofilm-forming capabilities. In this study, 6-methoxyldihydrochelerythrine chloride (6-MDC) inhibited the growth of exponential-phase VRE and restored VRE's sensitivity to vancomycin. 6-MDC predominantly suppressed the de novo biosynthetic pathway of pyrimidine and purine in VRE by the RNA-Seq analysis, resulting in obstructed DNA synthesis, which subsequently weakened bacterial virulence and impeded intracellular survival. Furthermore, 6-MDC inhibited biofilm formation, eradicated established biofilms, reduced virulence, and enhanced the host immune response to prevent intracellular survival and replication of VRE. Finally, 6-MDC reduced the VRE load in peritoneal fluid and cells significantly in a murine peritoneal infection model. This paper provides insight into the potential antimicrobial target of benzophenanthridine alkaloids for the first time.
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Objectives: The purpose of this paper is to explore the relationship between blood levels of cadmium, lead, and mercury and anxiety in American adults. Methods: Blood metals and self-reported anxiety days were extracted from laboratory data and questionnaire data, respectively, using NHANES data from 2007-2012. Weighted logistic regression was used to assess the relationship between cadmium, lead and mercury with anxiety. Restricted cubic spline was used to visualize the non-linear relationship between metal concentrations and anxiety. Weighted quantile sum (WQS) regression was used to investigate the effect of combined exposure to the three metals on anxiety. Results: The prevalence of anxiety in adults was 26.0%. After adjusting for potential confounding variables, cadmium levels in the highest quartile (Q4) were associated with a higher risk of anxiety compared to the lowest quartile (Q1) (OR = 1.279, 95% CI: 1.113-1.471, p < 0.01). Restricted cubic spline analysis indicated a positive association between blood cadmium levels and anxiety. Furthermore, co-exposure to multiple heavy metals was positively associated with anxiety risk (WQS positive: OR = 1.068, 95% CI: 1.016-1.160, p < 0.05), with cadmium contributing the most to the overall mixture effect. Compared to the Light RPA, the Vigorous/Moderate RPA group had a relatively low risk of anxiety after cadmium exposure. Conclusion: High levels of blood cadmium are positively associated with the development of anxiety disorders, which needs to be further verified in future studies.