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Famoxadone is a chiral fungicide frequently found in the environment and agricultural products. However, the health risks of famoxadone enantiomers are not well understood. This study investigated the stereoselective cytotoxicity and metabolic behavior of famoxadone enantiomers in mammals. Results showed that R-famoxadone was 1.5 times more toxic to HepG2 cells than S-famoxadone. R-famoxadone induced more pronounced ferroptosis compared to S-famoxadone. It caused greater upregulation of genes related to iron transport and lipid peroxidation, and greater downregulation of genes related to peroxide clearance. Furthermore, R-famoxadone induced more severe lipid peroxidation and reactive oxygen species (ROS) accumulation through ACSL4 activation and GPX4 inhibition. Additionally, the bioavailability of R-famoxadone in mice was six times higher than that of S-famoxadone. Liver microsome assays, cytochrome P450 (CYP450) inhibition assays, human recombinant CYP450 assays, and molecular docking suggested that the lower binding affinities of CYP2C8, CYP2C19, and CYP2E1 for R-famoxadone caused its preferential accumulation. Overall, R-famoxadone poses a higher risk than S-famoxadone due to its greater cytotoxicity and persistence. This study provides the first evidence of ferroptosis-induced stereoselective toxicity, offering insights for the comprehensive health risk assessment of chiral famoxadone and valuable references for the application of high-efficiency, low-risk pesticide enantiomers.
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Ferroptosis , Fungicidas Industriales , Estrobilurinas , Fungicidas Industriales/toxicidad , Fungicidas Industriales/química , Animales , Humanos , Ferroptosis/efectos de los fármacos , Células Hep G2 , Estereoisomerismo , Medición de Riesgo , Estrobilurinas/toxicidad , Estrobilurinas/química , Simulación del Acoplamiento Molecular , Ratones , Masculino , Sistema Enzimático del Citocromo P-450/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Supervivencia Celular/efectos de los fármacosRESUMEN
Background: The prognosis of AIDS after active antiretroviral therapy (ART) and the quality of life of people living with HIV (PLWH) are both affected by non-AIDS-related diseases such as cardiovascular disease (CVD). However, the specific risk ratios between PLWH and individuals negative for HIV are poorly understood. We aimed to systematically review and investigate the CVD risk factors associated with HIV. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library databases between 1 January 2015, and 12 May 2023 for articles reported the prevalence and risk factors of CVD such as hypertension, dyslipidaemia, coronary artery disease (CAD), and myocardial infarction (MI). Due to the high heterogeneity, we used a random-effects model to analyse the data. All statistical analyses were performed using Stata/MP 17.0 with 95% confidence intervals (CIs). Results: We analysed 31 eligible studies including 312 913 PLWH. People living with HIV had higher risks of dyslipidaemia (hazard ratio (HR) = 1.53; 95% CI = 1.29, 1.82), CAD (HR = 1.37; 95% CI = 1.24, 1.51), and MI (HR = 1.47; 95% CI = 1.28, 1.68) compared to individuals without HIV. However, there were no significant differences in the prevalence of hypertension between groups (HR = 1.17; 95% CI = 0.97, 1.41). Subgroup analysis revealed that men with HIV, PLWH who smoked and the elderly PLWH had a high prevalence of CVD. Moreover, the disease prevalence patterns varied among regions. In the USA and Europe, for instance, some HRs for CVD were higher than in other regions. Active ART initiation after 2015 appears to have a lower risk of CVD (hypertension, hyperlipidaemia, CAD). All outcomes under analysis showed significant heterogeneity (I2>70%, P < 0.001), which the available study-level variables could only partially account for. Conclusions: People living with HIV had a higher CVD risk than the general population; thus, CVD prevention in PLWH requires further attention. Rapid initiation of ART may reduce the incidence of CVD in PLWH. For timely screening of CVD high-risk individuals and thorough disease management to prevent CVD, further studies are required to evaluate the risk factors for CVD among PLWH, such as age, region, etc. Registration: PROSPERO (CRD42021255508).
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Enfermedades Cardiovasculares , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Enfermedades Cardiovasculares/epidemiología , Factores de Riesgo , Factores de Riesgo de Enfermedad CardiacaRESUMEN
BACKGROUND: The experimental autoimmune myocarditis (EAM) model is valuable for investigating myocarditis pathogenesis. M1-type macrophages and CD4+T cells exert key pathogenic effects on EAM initiation and progression. Baicalein (5,6,7-trihydroxyflavone, C15H10O5, BAI), which is derived from the Scutellaria baicalensis root, is a primary bioactive compound with potent anti-inflammatory and antioxidant properties. BAI exerts good therapeutic effects against various autoimmune diseases; however, its effect in EAM has not been thoroughly researched. PURPOSE: This study aimed to explore the possible inhibitory effect of BAI on M1 macrophage polarisation and CD4+T cell differentiation into Th1 cells via modulation of the JAK-STAT1/4 signalling pathway, which reduces the secretion of pro-inflammatory factors, namely, TNF-α and IFN-γ, and consequently inhibits TNF-α- and IFN-γ-triggered apoptosis in cardiomyocytes of the EAM model mice. STUDY DESIGN AND METHODS: Flow cytometry, immunofluorescence, real-time quantitative polymerase chain reaction (q-PCR), and western blotting were performed to determine whether BAI alleviated M1/Th1-secreted TNF-α- and IFN-γ-induced myocyte death in the EAM model mice through the inhibition of the JAK-STAT1/4 signalling pathway. RESULTS: These results indicate that BAI intervention in mice resulted in mild inflammatory infiltrates. BAI inhibited JAK-STAT1 signalling in macrophages both in vivo and in vitro, which attenuated macrophage polarisation to the M1 type and reduced TNF-α secretion. Additionally, BAI significantly inhibited the differentiation of CD4+T cells to Th1 cells and IFN-γ secretion both in vivo and in vitro by modulating the JAK-STAT1/4 signalling pathway. This ultimately led to decreased TNF-α and IFN-γ levels in cardiac tissues and reduced myocardial cell apoptosis. CONCLUSION: This study demonstrates that BAI alleviates M1/Th1-secreted TNF-α- and IFN-γ-induced cardiomyocyte death in EAM mice by inhibiting the JAK-STAT1/4 signalling pathway.
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Apoptosis , Modelos Animales de Enfermedad , Flavanonas , Interferón gamma , Quinasas Janus , Miocarditis , Miocitos Cardíacos , Factor de Transcripción STAT1 , Transducción de Señal , Factor de Necrosis Tumoral alfa , Animales , Factor de Transcripción STAT1/metabolismo , Transducción de Señal/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Quinasas Janus/metabolismo , Ratones , Flavanonas/farmacología , Masculino , Interferón gamma/metabolismo , Apoptosis/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Miocarditis/tratamiento farmacológico , Factor de Transcripción STAT4/metabolismo , Enfermedades Autoinmunes/tratamiento farmacológico , Ratones Endogámicos BALB C , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Scutellaria baicalensis/química , Células TH1/efectos de los fármacos , Diferenciación Celular/efectos de los fármacosRESUMEN
Antibiotics can be accidentally introduced into farmland by wastewater irrigation, and the environmental effects are still unclear. In this study, the effects of oxytetracycline on the residue of imidacloprid in soil and radishes were investigated. Besides, the rhizosphere microbiome and radish metabolome were analyzed. It showed that the persistence of imidacloprid in soil was unchanged, but the content of olefin-imidacloprid was increased by oxytetracycline. The residue of imidacloprid in radishes was increased by nearly 1.5 times, and the hazard index of imidacloprid was significantly raised by 1.5-4 times. Oxytetracycline remodeled the rhizosphere microbiome, including Actinobe, Elusimic, and Firmicutes, and influenced the metabolome of radishes. Especially, some amino acid metabolic pathways in radish were downregulated, which might be involved in imidacloprid degradation. It can be assumed that oxytetracycline increased the imidacloprid residue in radish through disturbing the plant-rhizosphere microbiome holobiont and, thus, increased the pesticide dietary risk.
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Microbiota , Neonicotinoides , Nitrocompuestos , Oxitetraciclina , Raphanus , Raphanus/química , Oxitetraciclina/metabolismo , Oxitetraciclina/farmacología , Rizosfera , Suelo/químicaRESUMEN
As chlorfenapyr is a commonly used insecticide in agriculture, the health risks of subchronic exposure to chlorfenapyr remained unclear. This study aimed to extensively probe the health risks from subchronic exposure to chlorfenapyr at the NOAEL and 10-fold NOAEL dose in mice. Through pathological and biochemical examinations, the body metabolism, hepatic toxicity, and intestinal homeostasis were systematically assessed. After 12 weeks, a 10-fold NOAEL dose of chlorfenapyr resulted in weight reduction, increased daily food intake, and blood lipid abnormalities. Concurrently, this dosage induced hepatotoxicity and amplified oxidative stress in hepatocytes, a finding further supported in HepG2 cells. Moreover, chlorfenapyr resulted in intestinal inflammation, evidenced by increased inflammatory factors (IL-17a, IL-10, IL-1ß, IL-6, IL-22), disrupted immune cells (RORγt, Foxp3), and compromised intestinal barriers (ZO-1 and occludin). By contrast, the NOAEL dose presented less toxicity in most evaluations. Serum metabolomic analyses unveiled widespread disruptions in pathways related to hepatotoxicity and intestinal inflammation, including NF-κB signaling, Th cell differentiation, and bile acid metabolism. Microbiomic analysis showed an increase in Lactobacillus, a decrease in Muribaculaceae, and diminished anti-inflammatory microbes, which further propelled the inflammatory response and leaded to intestinal inflammation. These findings revealed the molecular mechanisms underlying chlorfenapyr-induced hepatotoxicity and intestinal inflammation, highlighting the significant role of the gut microbiota.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Inflamación , Piretrinas , Ratones , Animales , Inflamación/inducido químicamente , Inflamación/patología , Estrés Oxidativo , HomeostasisRESUMEN
Structurally defined arabinogalactan (LBP-3) from Lycium barbarum have effect on improving intestinal barrier function. However, whether its intestinal barrier function depended on the changes of intestinal mucin O-glycans have not been investigated. A dextran sodium sulfate-induced acute colitis mouse model was employed to test prevention and treatment with LBP-3. The intestinal microbiota as well as colonic mucin O-glycan profiles were analyzed. Supplementation with LBP-3 inhibited harmful bacteria, including Desulfovibrionaceae, Enterobacteriaceae, and Helicobacteraceae while significantly increased the abundance of beneficial bacteria (e.g., Lachnospiraceae, Ruminococcaceae, and Lactobacillaceae). Notably, LBP-3 augmented the content of neutral O-glycans by stimulating the fucosylation glycoforms (F1H1N2 and F1H2N2), short-chain sulfated O-glycans (S1F1H1N2, S1H1N2, and S1H2N3), and sialylated medium- and long-chain O-glycans (F1H2N2A1, H2N3A1, and F1H3N2A1). In summary, we report that supplement LBP-3 significantly reduced pathological symptoms, restored the bacterial community, and promoted the expression of O-glycans to successfully prevent and alleviate colitis in a mouse model, especially in the LBP-3 prevention testing group. The underlying mechanism of action was investigated using glycomics to better clarify which the structurally defined LBP-3 were responsible for its beneficial effect against ulcerative colitis and assess its use as a functional food or pharmaceutical supplement.
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Colitis , Galactanos , Lycium , Ratones , Animales , Mucinas/metabolismo , Lycium/metabolismo , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Polisacáridos/efectos adversos , Bacterias/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de EnfermedadRESUMEN
Perovskite materials and their applications in optoelectronics have attracted intensive attentions in recent years. However, in-depth understanding about their anisotropic behavior in ultrafast carrier dynamics is still lacking. Here we explore the ultrafast dynamical evolution of photo-excited carriers and photoluminescence based on differently-oriented MAPbBr3 wafers. The distinct in-plane polarization of carrier relaxation dynamics of the (100), (110) and (111) wafers and their out-of-plane anisotropy in a picosecond time scale were found by femtosecond time- and polarization-resolved transient transmission measurements, indicating the relaxation process dominated by optical/acoustic phonon interaction is related to photoinduced transient structure rearrangements. Femtosecond laser two-photon fabricated patterns exhibit three orders of magnitude enhancement of emission due to the formation of tentacle-like microstructures. Such a ultrafast dynamic study carried on differently-oriented crystal wafers is believed to provide a deep insight about the photophysical process of perovskites and to be helpful for developing polarization-sensitive and ultrafast-response optoelectronic devices.
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Although cotton dressing is one of the most commonly used wound management materials, it lacks antimicrobial and healing-promoting activity. This work developed a multilayer electroactive composite cotton dressing (Ag/Zn@Cotton/Paraffin) with exudate-activated electrical stimulation and antibacterial activity by the green and sustainable magnetron-sputtering and spraying methods. The inner hydrophilic layer of the cotton dressing was magnetron sputtered with silver/zinc galvanic couple arrays (Ag/Zn), which can be activated by wound exudate, generating an electrical stimulation (ES) into the wound. The Ag/Zn@Cotton showed efficient antibacterial activities against S. aureus and E. coli. Meanwhile, the paraffin-sprayed outer surface showed excellent antibacterial adhesion rates for S. aureus (99.82 %) and E. coli (97.92 %). The in vitro cell experiments showed that the ES generated by Ag/Zn@Cotton/Paraffin increased the migration of fibroblasts, and the in vivo mouse model indicated that the Ag/Zn@Cotton/Paraffin could enhance wound healing via re-epithelialization, inflammatory inhibition, collagen deposition, and angiogenesis. MTT method and live/dead staining showed that Ag/Zn@Cotton/Paraffin had no significant cytotoxic effects. This work may shed some light on designing and fabricating multi-functional electroactive composited dressings based on traditional biomedical textiles.
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Fibra de Algodón , Staphylococcus aureus , Ratones , Animales , Escherichia coli , Parafina , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Cicatrización de Heridas , VendajesRESUMEN
Microplastic is an emerging environmental pollutant with potential health risks. Recent studies have shown that microplastic could impair gut homeostasis in mammals. Although it has been widely demonstrated that gut dyshomeostasis could impact renal health through the gut-kidney axis, the effects of microplastic-induced gut dyshomeostasis on renal health and underlying mechanisms are still largely unknown. In the current work, we found that polystyrene microplastics (PS-MPs) treatment impaired the gut barrier, increased urinary complement-activated product C5a levels and renal C5aR expression, leading to chronic kidney disease-related symptoms in mice. Restoring the gut barrier using an antibiotic mixture effectively alleviated PS-MPs-induced kidney injury, indicating the involvement of the gut-kidney axis in PS-MPs-induced renal injury. Moreover, it also mitigated PS-MPs-induced alterations in urinary C5a levels and renal C5aR expression, suggesting that the renal C5a/C5aR pathway might be involved in PS-MPs' impacts on the gut-kidney axis. Further experiments using a C5aR inhibitor, PMX53, verified the vital role of renal C5a/C5aR pathway activation in the development of kidney injury induced by PS-MPs. Collectively, our results suggest that PS-MPs induce kidney injury in mice by impairing the gut barrier, increasing C5a levels, and ultimately activating the renal C5a/C5aR pathway, highlighting the crucial role of the gut-kidney axis in PS-MPs-induced kidney injury.
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Microplásticos , Plásticos , Animales , Ratones , Microplásticos/toxicidad , Microplásticos/metabolismo , Plásticos/metabolismo , Poliestirenos/toxicidad , Poliestirenos/metabolismo , Riñón/metabolismo , MamíferosRESUMEN
To improve the consumption of wind energy and reduce carbon emission, this paper proposes a wind-thermal interconnected low-carbon power system integrated with hydrogen storage. An energy scheduling optimization model aiming at minimizing the daily operation cost of the system is constructed considering environmental operation cost quantification, and whale optimization algorithm is used to optimize multiple variables. Finally, in simulation example, various scenarios are set considering the application way of hydrogen and the scenarios with and without the carbon capture and storage (CCS) are optimized, respectively. The horizontal comparison results show that the system with hydrogen production (S2) and the system with hydrogen fuel cell (S3) have higher economic operation cost than that of wind-thermal interconnected power system only (S1), but the environmental cost is reduced; the system's daily operating costs are reduced. The wind curtailment rate decreases from 11.0% (S1) to 3.8% (S2 and S3) without CCS, and from 9.0% (S1) to 2.1% (S2 and S3) with CCS. The longitudinal comparison shows that the thermal power output is reduced and the wind power consumption is improved with CCS. The addition of CCS increases total operating costs but significantly reduces environmental costs. Configuring hydrogen storage system in the wind-thermal interconnected power system can effectively promote the consumption of wind energy and reduce the system operation cost; however, the utilization of CCS is economic unfriendly at present.
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Carbono , Viento , Dióxido de Carbono/análisis , AlgoritmosRESUMEN
Angiogenesis is the process by which new blood vessels form and is required for tumour growth and metastasis. It helps in supplying oxygen and nutrients to tumour cells and plays a crucial role in the local progression and distant metastasis of, and development of treatment resistance in, breast cancer. Tumour angiogenesis is currently regarded as a critical therapeutic target; however, anti-angiogenic therapy for breast cancer fails to produce satisfactory results, owing to issues such as inconsistent efficacy and significant adverse reactions. As a result, new anti-angiogenic drugs are urgently needed. Flavonoids, a class of natural compounds found in many foods, are inexpensive, widely available, and exhibit a broad range of biological activities, low toxicity, and favourable safety profiles. Several studies find that various flavonoids inhibit angiogenesis in breast cancer, indicating great therapeutic potential. In this review, we summarize the role of angiogenesis in breast cancer and the potential of natural flavonoids as anti-angiogenic agents for breast cancer treatment. We discuss the value and significance of nanotechnology for improving flavonoid absorption and utilization and anti-angiogenic effects, as well as the challenges of using natural flavonoids as drugs.
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Adjuvants are an indispensable component of vaccines, but there are few adjuvants for human vaccines. H2 receptor blockers, inhibiting gastric acid secretion, have immune enhancement effects. Ranitidine (RAN) is a water-soluble H2 receptor blocker, and whether it has an immune-enhancing effect is still unknown. In this study, flow cytometry, western blotting, and immunofluorescence methods were used to analyze whether RAN could activate macrophage polarization to the M1 phenotype in vivo and in vitro. Here, we found that the M1 inflammatory cytokine levels and surface markers in RAW264.7 cells were upregulated by NF-κB activation, possibly through the PI3K-Akt2 signaling pathway, after RAN treatment. Endocytic function was also enhanced by feedback regulation of Akt2/GSK3ß/Dynmin1 signaling. Furthermore, to evaluate the adjuvant function of RAN, we used OVA plus RAN as a vaccine to inhibit the growth of B16-OVA tumors in mice. We also found that in the RAN adjuvant group, macrophage polarization to M1, Th1 cell differentiation, and cytotoxic T lymphocyte (CTL) activation were significantly upregulated. The tumor growth of mice was inhibited, and the survival rate of mice was significantly improved. This study provides new evidence for the mechanism by which RAN activates the immune response and is expected to provide a new strategy for the research and development of tumor vaccine adjuvants.
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Adyuvantes Inmunológicos , Macrófagos , Neoplasias , Ranitidina , Linfocitos T Citotóxicos , Animales , Humanos , Ratones , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ranitidina/farmacología , Ranitidina/uso terapéutico , Células RAW 264.7 , Transducción de Señal , Linfocitos T Citotóxicos/efectos de los fármacos , Linfocitos T Citotóxicos/inmunología , Vacunas , Activación de Macrófagos/efectos de los fármacos , Activación de Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéuticoRESUMEN
To simultaneously achieve the objectives of waste resource utilization and clean production, a novel approach involving the utilization of corn straw-sludge hybrid biochar was proposed for the adsorption of VOCs emitted from biomass power plants. This study analyzed the effect of straw-sludge biochar on the adsorption characteristics of VOCs (toluene, isopentane, and ethylene) under different preparation conditions (raw material ratio, activation temperature, and activation time). The findings revealed that the adsorption efficiency of the mixed biochar was significantly superior to that of individual corn straw biochar and sludge biochar. The adsorption of methylbenzene, isopentane, and ethylene was 78.32, 40.81, and 41.18% higher, respectively, compared to the control groups consisting of pure sludge biochar and pure corn straw biochar. Moreover, the adsorption performance of the activated biochar followed the sequence of ethylene < isopentane < methylbenzene in terms of both saturation time and adsorption capacity. The adsorption capacity of VOCs on straw biochar-sludge biochar demonstrated a consistent correlation with the boiling point and molecular weight of the adsorbate, with higher adsorption capacities observed for adsorbates with larger boiling points and molecular weights, specifically methylbenzene > isopentane > ethylene.
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Background: The coronavirus disease 2019 (COVID-19) pandemic has created more devastation among dialysis patients than among the general population. Patient-level prediction models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are crucial for the early identification of patients to prevent and mitigate outbreaks within dialysis clinics. As the COVID-19 pandemic evolves, it is unclear whether or not previously built prediction models are still sufficiently effective. Methods: We developed a machine learning (XGBoost) model to predict during the incubation period a SARS-CoV-2 infection that is subsequently diagnosed after 3 or more days. We used data from multiple sources, including demographic, clinical, treatment, laboratory, and vaccination information from a national network of hemodialysis clinics, socioeconomic information from the Census Bureau, and county-level COVID-19 infection and mortality information from state and local health agencies. We created prediction models and evaluated their performances on a rolling basis to investigate the evolution of prediction power and risk factors. Result: From April 2020 to August 2020, our machine learning model achieved an area under the receiver operating characteristic curve (AUROC) of 0.75, an improvement of over 0.07 from a previously developed machine learning model published by Kidney360 in 2021. As the pandemic evolved, the prediction performance deteriorated and fluctuated more, with the lowest AUROC of 0.6 in December 2021 and January 2022. Over the whole study period, that is, from April 2020 to February 2022, fixing the false-positive rate at 20%, our model was able to detect 40% of the positive patients. We found that features derived from local infection information reported by the Centers for Disease Control and Prevention (CDC) were the most important predictors, and vaccination status was a useful predictor as well. Whether or not a patient lives in a nursing home was an effective predictor before vaccination, but became less predictive after vaccination. Conclusion: As found in our study, the dynamics of the prediction model are frequently changing as the pandemic evolves. County-level infection information and vaccination information are crucial for the success of early COVID-19 prediction models. Our results show that the proposed model can effectively identify SARS-CoV-2 infections during the incubation period. Prospective studies are warranted to explore the application of such prediction models in daily clinical practice.
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Due to the reduction of the thermal efficiency and output fluctuation of the boiler system caused by the high moisture in biomass, dewatering of fuels using low-cost processes is an important step in feedstock pretreatment for biomass power plants. In the present study, a steel ball was used as the spherical heat carrier (SHC). The effects of the SHC temperature on the dewatering of different biomasses were investigated by a mixture-drying device at 40% moisture content of biomass, and the drying process of peanut shells was analyzed. Results showed that the moisture content was effectively reduced, and the combustion performance of the biomass was significantly promoted. The work is likely to provide an economically feasible approach for biomass drying in further studies.
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This study aimed to investigate the transgenerational impacts of maternal intake of polysorbate 80 (P80), an emulsifier widely used in modern society, on the development of offspring immunity. Our results revealed that maternal P80 treatment led to impaired differentiation of innate lymphoid cells (ILCs) and CD4+ T cells in the small intestinal lamina propria (SiLP), resulting in intestinal dyshomeostasis in female offspring. Furthermore, we found that SiLP ILCs abundances were significantly altered in 0-day-old fetuses from P80-treated mothers, indicating a prenatal impact of P80-treated mothers on offspring immunity. Additionally, cesarean section and foster-nursing studies demonstrated that P80-induced altered SiLP ILCs in 0-day-old fetuses could further induce dysregulation of ILCs and CD4+ T cells in the SiLP, thus promoting intestinal dysregulation in offspring later in life. Overall, our findings suggest that maternal P80 intake could prenatally program the development of offspring immunity, exerting a significant and long-lasting impact.
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Triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous subtype of breast cancer, lacks effective treatment options. Sophora flavescens Aiton, a Chinese medicinal plant, is often used in traditional Chinese medicine to treat cancer. Matrine (MAT) is an alkaloid extracted from Sophora flavescens. It has good anticancer effects, and thus can be explored as a new therapeutic agent in TNBC research. We performed bioinformatics analysis to analyze the differentially expressed genes between normal breast tissues and TNBC tissues, and comprehensive network pharmacology analyses. The activity and invasion ability of TNBC cells treated with MAT were analyzed. Apoptosis and cell cycle progression were determined using cytometry. We used Monodansylcadaverine (MDC) staining to determine the condition of autophagosomes. Finally, the expression levels of the key target proteins of the PI3K/AKT pathway were determined using western blotting. The proliferation and invasion ability of MDA-MB-231 and MDA-MB-468 can be effectively inhibited by MAT. The results of flow cytometry indicated that MAT arrested the TNBC cell cycle and induced apoptosis. In addition, we confirmed that MAT inhibited the expression of BCL-2 while up-regulating the expression of cleaved caspase-3. Moreover, enhanced intensity of MDC staining and high LC3-II expression were observed, which confirmed that MAT induced autophagy in TNBC cells. Western blotting showed that MAT inhibited the PI3K/AKT pathway and downregulated the expressions of PI3K, AKT, p-AKT, and PGK1. This study provides feasible methods, which include bioinformatics analysis and in vitro experiments, for the identification of compounds with anti-TNBC properties. MAT inhibited the PI3K/AKT signaling pathway, arrested cell cycle, as well as promoted cell apoptosis and autophagy. These experiments provide evidence for the anti-TNBC effect of MAT and identified potential targets against TNBC.
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Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Matrinas , Línea Celular Tumoral , Apoptosis , Proliferación CelularRESUMEN
As two commonly used fungicides, carbendazim and tebuconazole are widely found in the environment and in foods. Studies have reported that these fungicides can induce hepatic oxidative stress and other health risks. Nevertheless, the influences of exposure to carbendazim and tebuconazole at their acceptable daily intake (ADI) doses on hepatic oxidative stress, and the residual distributions in mice remain unclear. To fill these gaps, ICR (CD-1) mice were exposed to carbendazim and tebuconazole at their ADI doses by oral administration for 4 weeks in this study. The results showed that tebuconazole accumulated primarily in the epididymal fat of mice (16.84 µg/kg), whereas no significant residues of carbendazim in the tissues were observed. In addition, exposure to ADI doses of tebuconazole significantly reduced liver coefficients and induced hepatic oxidative stress in mice, including elevating the levels of glutathione and malonaldehyde. However, no significant impacts were observed on the hepatic redox homeostasis in mice after exposure to carbendazim at its ADI dose. The results could be helpful for understanding the exposure risks of carbendazim and tebuconazole in terms of low doses and long term.
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Objective: The study aims to explore the correlation mechanism among metacognition, attitude toward physical exercise, and health-related behavior in high school students. Methods: A total of 869 students (17 ± 1.70) from Anhui, Zhejiang, Shandong, and Fujian provinces were selected by stratified sampling to complete the Metacognition Questionnaire, Health-Related Behavior Self-Rating Scale, Attitude Toward Physical Exercise Scale, and Depression-Anxiety-Stress Scale (Simplified Chinese version, DASS-21). Results: (1) Metacognition was negatively predictive of attitude toward physical exercise and health-related behavior (ß = -0.236, P < 0.01; ß = -0.239, P < 0.01) but positively predictive of negative emotion (ß = 0.496, P < 0.01); (2) attitude toward physical exercise was positively predictive of health-related behavior (ß = 0.533, P < 0.01) but negatively predictive of negative emotion (ß = -0.336, P < 0.01); and (3) negative emotion was negatively predictive of health-related behavior (ß = -0.389, P < 0.01). Conclusions: Metacognition not only has a directly predictive effect on health-related behavior but also predicts it through attitude toward physical exercise. Negative emotion also mediates the relationship between metacognition and attitude toward physical exercise.
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Metacognición , Humanos , Conductas Relacionadas con la Salud , Actitud , Encuestas y Cuestionarios , Estudiantes/psicologíaRESUMEN
Polyphenol compounds are natural antioxidants, which are rich in anti-inflammatory and antioxidant components. They have a wide range of medicinal benefits that are believed to improve human health across various aspects; especially its anticancer effect has been gradually confirmed. The anticancer effect of polyphenols is mainly based on their strong antioxidant and immunomodulatory effects. The innate and adaptive immune responses as well as the development and maintenance of cells and tissues of the immune system are regulated by the NF-κB family of transcription factors. Dysregulation of NF-κB can lead to autoimmune diseases, chronic inflammation, and even cancer. Polyphenol compounds can exert antioxidant and immunomodulatory effects by targeting NF-κB, thus hindering the occurrence and development of tumors.Polyphenol compounds have unique advantages over conventional anticancer therapies such as chemotherapy because they have few side effects and do not cause toxicity to healthy cells. Additionally, they can attenuate the toxic effects of current anticancer therapies. Based on these characteristics, polyphenols have great potential in the prevention and treatment of cancer. This article systematically summarizes the mechanism of NF-κB in tumor genesis, progression, metastasis, angiogenesis, and drug resistance. In addition, we present the anticancer effect of polyphenol compounds by targeting NF-κB during the different stages of tumorigenesis.