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Infertility has gradually become a global health concern, and evidence suggests that exposure to environmental endocrine-disrupting chemicals (EDCs) represent one of the key causes of infertility. Benzo(a)pyrene (BaP) is a typical EDC that is widespread in the environment. Previous studies have detected BaP in human urine, semen, cervical mucus, oocytes and follicular fluid, resulting in reduced fertility and irreversible reproductive damage. However, the mechanisms underlying the effects of gestational BaP exposure on offspring fertility in male mice have not been fully explored. In this study, pregnant mice were administered BaP at doses of 0, 5, 10 and 20 mg/kg/day via gavage from Days 7.5 to 12.5 of gestation. The results revealed that BaP exposure during pregnancy disrupted the structural integrity of testicular tissue, causing a disorganized arrangement of spermatogenic cells, compromised sperm quality, elevated levels of histone modifications and increased apoptosis in the testicular tissue of F1 male mice. Furthermore, oxidative stress was also increased in the testicular tissue of F1 male mice. BaP activated the AhR/ERα signaling pathway, affected H3K4me3 expression and induced apoptosis in testicular tissue. AhR and Cyp1a1 were overexpressed, and the expression of key molecules in the antioxidant pathway, including Keap1 and Nrf2, was reduced. The combined effects of these molecules led to apoptosis in testicular tissues, damaging and compromising sperm quality. This impairment in testicular cells further contributed to compromised testicular tissues, ultimately impacting the reproductive health of F1 male mice.
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Plants delicately regulate endogenous auxin levels through the coordination of transport, biosynthesis, and inactivation, which is crucial for growth and development. While it is well-established that the actin cytoskeleton can regulate auxin levels by affecting polar transport, its potential role in auxin biosynthesis has remained largely unexplored. Using LC-MS/MS-based methods combined with fluorescent auxin marker detection, we observed a significant increase in root auxin levels upon deletion of the actin bundling proteins AtFIM4 and AtFIM5. Fluorescent observation, immunoblotting analysis, and biochemical approaches revealed that AtFIM4 and AtFIM5 affect the protein abundance of the key auxin synthesis enzyme YUC8 in roots. AtFIM4 and AtFIM5 regulate the auxin synthesis enzyme YUC8 at the protein level, with its degradation mediated by the 26S proteasome. This regulation modulates auxin synthesis and endogenous auxin levels in roots, consequently impacting root development. Based on these findings, we propose a molecular pathway centered on the 'actin cytoskeleton-26S proteasome-YUC8-auxin' axis that controls auxin levels. Our findings shed light on a new pathway through which plants regulate auxin synthesis. Moreover, this study illuminates a newfound role of the actin cytoskeleton in regulating plant growth and development, particularly through its involvement in maintaining protein homeostasis via the 26S proteasome.
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Evidence on the impacts of PM1, PM2.5, and PM10 on the hospital admissions, length of hospital stays (LOS), and hospital expenses among patients with cardiovascular disease (CVD) is still limited in China, especially in rural areas. This study was performed in eight counties of Fuyang from 1 January 2015 to 30 June 2017. We use a three-stage time-series analysis to explore the effects of short-term exposure to PM1, PM2.5, and PM10 on hospital admissions, LOS, and hospital expenses for CVDs. An increment of 10 ug/m3 in PM1, PM2.5, and PM10 corresponded to an increment of 1.82% (95% CI: 1.34, 2.30), 0.96% (95% CI: 0.44, 1.48), and 0.79% (95% CI: 0.63%, 0.95%) in CVD hospital admissions, respectively. We observed that daily concentrations of PMs were associated with an increase in hospital admissions, LOS, and expenses for CVDs. Sustained endeavors are required to reduce air pollution so as to attenuate disease burdens from CVDs.
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BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.
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Witnessing violent or traumatic events is common during childhood and adolescence and could cause detrimental effects such as increased risks of psychiatric disorders. This stressor could be modeled in adolescent laboratory animals using the chronic witnessing social defeat (CWSD) paradigm, but the behavioral consequences of CWSD in adolescent animals remain to be validated for cognitive, anxiety-like, and depression-like behaviors and, more importantly, the underlying neural mechanisms remain to be uncovered. In this study, we first established the CWSD model in adolescent male mice and found that CWSD impaired cognitive function and increased anxiety levels and that these behavioral deficits persisted into adulthood. Based on the dorsal-ventral functional division in hippocampus, we employed immediate early gene c-fos immunostaining after behavioral tasks and found that CWSD-induced cognition deficits were associated with dorsal CA3 overactivation and anxiety-like behaviors were associated with ventral CA3 activity reduction. Indeed, chemogenetic activation and inhibition of dorsal CA3 neurons mimicked and reversed CWSD-induced recognition memory deficits (not anxiety-like behaviors), respectively, whereas both inhibition and activation of ventral CA3 neurons increased anxiety-like behaviors in adolescent mice. Finally, chronic administration of vortioxetine (a novel multimodal antidepressant) successfully restored the overactivation of dorsal CA3 neurons and the cognitive deficits in CWSD mice. Together, our findings suggest that dorsal CA3 overactivation mediates CWSD-induced recognition memory deficits in adolescent male mice, shedding light on the pathophysiology of adolescent CWSD-induced adverse effects and providing preclinical evidence for early treatment of stress-induced cognitive deficits.
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The sex difference that females are more vulnerable to depression than males has been recently replicated in an animal model of early-life stress (ES) called the limited bedding and nesting material (LBN) paradigm. Adopting this animal model, we have previously examined the effects of ES on monoamine transporter (MATs) expression in stress-related regions in adult female mice, and the reversal effects of a novel multimodal antidepressant, vortioxetine. In this study, replacing vortioxetine with a classical antidepressant, fluoxetine, we aimed to replicate the ES effects in adult female mice and to elucidate the commonality and differences between fluoxetine and vortioxetine. We found that systemic 30-day treatment with fluoxetine successfully reversed ES-induced depression-like behaviors (especially sucrose preference) in adult female mice. At the molecular level, we largely replicated the ES effects, such as reduced serotonin transporter (SERT) expression in the amygdala and increased norepinephrine transporter (NET) expression in the medial prefrontal cortex (mPFC) and hippocampus. Similar reversal effects of fluoxetine and vortioxetine were observed, including SERT in the amygdala and NET in the mPFC, whereas different reversal effects were observed for NET in the hippocampus and vesicular monoamine transporters expression in the nucleus accumbens. Overall, these results demonstrate the validity of the LBN paradigm to induce depression-like behaviors in female mice, highlight the involvement of region-specific MATs in ES-induced depression-like behaviors, and provide insights for further investigation of neurobiological mechanisms, treatment, and prevention associated with depression in women.
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Experiências Adversas da Infância , Fluoxetina , Humanos , Feminino , Camundongos , Masculino , Animais , Fluoxetina/farmacologia , Vortioxetina , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológicoRESUMO
The AGL6 (AGMOUSE LIKE 6) gene is a member of the SEP subfamily and functions as an E-class floral homeotic gene in the development of floral organs. In this study, we cloned IiAGL6, the orthologous gene of AGL6 in Isatis indigotica. The constitutive expression of IiAGL6 in Arabidopsis thaliana resulted in a late-flowering phenotype and the development of curly leaves during the vegetative growth period. Abnormal changes in floral organ development were observed during the reproductive stage. In woad plants, suppression of IiAGL6 using TRV-VIGS (tobacco rattle virus-mediated virus-induced gene silencing) decreased the number of stamens and led to the formation of aberrant anthers. Similar changes in stamen development were also observed in miRNA-AGL6 transgenic Arabidopsis plants. Yeast two-hybrid and BiFC tests showed that IiAGL6 can interact with other MADS-box proteins in woad; thus, playing a key role in defining the identities of floral organs, particularly during stamen formation. These findings might provide novel insights and help investigate the biological roles of MADS transcription factors in I. indigotica.
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Arabidopsis , Isatis , Isatis/genética , Isatis/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Flores , Arabidopsis/metabolismo , Pólen/genética , Pólen/metabolismo , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/metabolismo , FilogeniaRESUMO
The evidence about the effect of non-essential metal mixture on fasting plasma glucose (FPG) levels among older adults without diabetes is limited. This study aims to estimate the individual and joint relationship between five non-essential metals and FPG levels in Chinese older adults without diabetes. This study included 2362 older adults without diabetes. Urinary concentrations of five non-essential metals, i.e., cesium (Cs), aluminum (Al), thallium (Tl), cadmium (Cd), and arsenic (As), were detected by inductively coupled plasma mass spectrometry (ICP-MS). The associations of single metals and the metal mixture with FPG levels were assessed using linear regression and Bayesian kernel machine regression (BKMR) models, respectively. Adjusted single-metal linear regression models showed positive associations of urinary Al (ß = 0.016, 95%CI: 0.001-0.030) and Cs (ß = 0.018, 95%CI: 0.006-0.031) with FPG levels. When comparing the 2th, 3th, and 4th quartiles of urine Cs to its 1th quartile, the significant associations between Cs and FPG levels were found and presented as an "inverted U" trend (ßQ2 vs. Q1: 0.034; ßQ3 vs. Q1:0.054; ßQ4 vs. Q1: 0.040; all P<0.05). BKMR analyses showed urinary level of Cs exhibited an "inverted U" shape association with FPG levels. Moreover, the FPG levels increased linearly with the raised levels of the non-essential metal mixture, and the posterior inclusion probability (PIP) of Cs was the highest (0.92). Potential positive interaction of As and Cs on FPG levels was found in BKMR model. Stratified analysis displayed significant interactions of hyperlipidemia and urine Cs or Tl on FPG levels. An inverse U-shaped association between Cs and FPG was found, individually and as mixture. The FPG levels increased with the raised levels of the non-essential metal mixture, and Cs was the most contributor to FPG levels. Further research is required to confirm the correlation between non-essential metals and FPG levels and to clarify the underlying mechanisms.
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BACKGROUND: Epidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people. METHODS: The study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: In multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (ß = - 0.016, 95 % CI: - 0.030 to - 0.003 for V; ß = - 0.021, 95 % CI: - 0.033 to - 0.009 for Mg), and urine Se was positively related to the FPG levels (ß = 0.024, 95 % CI: 0.014-0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women. CONCLUSIONS: Both Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings.
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Glicemia , Jejum , Metais , Selênio , Idoso , Feminino , Humanos , Teorema de Bayes , Glicemia/análise , Cobalto/urina , População do Leste Asiático , Jejum/sangue , Jejum/urina , Vida Independente , Selênio/urina , Vanádio/urina , Espectrometria de Massas , Cálcio/urina , Magnésio/urina , Molibdênio/urina , Metais/urina , Misturas Complexas/urinaRESUMO
Background: The heterogeneous crosstalk between tumor cells and other cells in their microenvironment means a notable difference in clinical outcomes of head and neck squamous cell carcinoma (HNSCC). CD8+ T cells and macrophages are effector factors of the immune system, which have direct killing and phagocytosis effects on tumor cells. How the evolution of their role in the tumor microenvironment influences patients clinically remains a mystery. This study aims to investigate the complex communication networks in the HNSCC tumor immune microenvironment, elucidate the interactions between immune cells and tumors, and establish prognostic risk model. Methods: 20 HNSCC samples single-cell rna sequencing (scRNA-seq) data and bulk rna-seq data were derived from public databases. The "cellchat" R package was used to identify cell-to-cell communication networks and prognostic related genes, and then cell-cell communication (ccc) molecular subtypes were constructed by unsupervised clustering. Kaplan-Meier(K-M) survival analysis, clinical characteristics analysis, immune microenvironment analysis, immune cell infiltration analysis and CD8+T cell differentiation correlation analysis were performed. Finally, the ccc gene signature including APP, ALCAM, IL6, IL10 and CD6 was constructed based on univariate Cox analysis and multivariate Cox regression. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the model in the train group and the validation group, respectively. Results: With CD8+T cells from naive to exhaustion state, significantly decreased expression of protective factor (CD6 gene) is associated with poorer prognosis in patients with HNSCC. The role of macrophages in the tumor microenvironment has been identified as tumor-associated macrophage (TAM), which can promote tumor proliferation and help tumor cells provide more nutrients and channels to facilitate tumor cell invasion and metastasis. In addition, based on the strength of all ccc in the tumor microenvironment, we identified five prognostic ccc gene signatures (cccgs), which were identified as independent prognostic factors by univariate and multivariate analysis. The predictive power of cccgs was well demonstrated in different clinical groups in train and test cohorts. Conclusion: Our study highlights the propensity for crosstalk between tumors and other cells and developed a novel signature on the basis of a strong association gene for cell communication that has a powerful ability to predict prognosis and immunotherapy response in patients with HNSCC. This may provide some guidance for developing diagnostic biomarkers for risk stratification and therapeutic targets for new therapeutic strategies.
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Most of studies relating ambient nitrogen dioxide (NO2) exposure to hospital admissions for cardiovascular diseases (CVDs) were conducted among urban population. Whether and to what extent these results could be generalizable to rural population remains unknown. We addressed this question using data from the New Rural Cooperative Medical Scheme (NRCMS) in Fuyang, Anhui, China. Daily hospital admissions for total CVDs, ischaemic heart disease, heart failure, heart rhythm disturbances, ischaemic stroke, and haemorrhagic stroke in rural regions of Fuyang, China, were extracted from NRCMS between January 2015 and June 2017. A two-stage time-series analysis method was used to assess the associations between NO2 and CVD hospital admissions and the disease burden fractions attributable to NO2. In our study period, the average number (standard deviation) of hospital admissions per day were 488.2 (117.1) for total CVDs, 179.8 (45.6) for ischaemic heart disease, 7.0 (3.3) for heart rhythm disturbances, 13.2 (7.2) for heart failure, 267.9 (67.7) for ischaemic stroke, and 20.2 (6.4) for haemorrhagic stroke. The 10-µg/m3 increase of NO2 was related to an elevated risk of 1.9% (RR: 1.019, 95% CI: 1.005 to 1.032) for hospital admissions of total CVDs at lag0-2 days, 2.1% (1.021, 1.006 to 1.036) for ischaemic heart disease, and 2.1% (1.021, 1.006 to 1.035) for ischaemic stroke, respectively, while no significant association was observed between NO2 and hospital admissions for heart rhythm disturbances, heart failure, and haemorrhagic stroke. The attributable fractions of total CVDs, ischaemic heart disease, and ischaemic stroke to NO2 were 6.52% (1.87 to 10.94%), 7.31% (2.19 to 12.17%), and 7.12% (2.14 to 11.85%), respectively. Our findings suggest that CVD burdens in rural population are also partly attributed to short-term exposure to NO2. More studies across rural regions are required to replicate our findings.
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Poluentes Atmosféricos , Poluição do Ar , Isquemia Encefálica , Doenças Cardiovasculares , Insuficiência Cardíaca , Acidente Vascular Cerebral Hemorrágico , AVC Isquêmico , Isquemia Miocárdica , Acidente Vascular Cerebral , Humanos , Doenças Cardiovasculares/epidemiologia , Dióxido de Nitrogênio/análise , Poluição do Ar/análise , Isquemia Encefálica/epidemiologia , População Rural , Acidente Vascular Cerebral/epidemiologia , China/epidemiologia , Isquemia Miocárdica/epidemiologia , Poluentes Atmosféricos/análise , Material Particulado/análise , Exposição Ambiental/análiseRESUMO
The effects of interactions between the toxic and essential metal mixtures on cognitive function are poorly understood. This study aims to identify the joint association of arsenic (As), cadmium (Cd), and lead (Pb) with cognitive function in older adults and the moderating role of selenium (Se), zinc (Zn), and copper (Cu) in this association. This study included 1000 community-dwelling older adults. Cognitive function was assessed by the Mini-Mental State Examination (MMSE). Blood concentrations of As, Cd, Pb, Se, Zn, and Cu were measured using inductively coupled plasma mass spectrometry. Linear regression and Bayesian kernel machine regression (BKMR) models were applied to assess the individual and joint associations of As, Cd, and Pb with cognitive function and to examine whether Se, Zn, and Cu (individually and as a mixture) modified these associations. In the adjusted single-metal models, both Cd (ß = - 0.37, 95% CI: - 0.73 to - 0.01) and Pb (ß = - 0.44, 95% CI: - 0.86 to - 0.02) were associated with MMSE scores, while Se (ß = 0.71, 95% CI: 0.30 to 1.13) exhibited a positive relationship with MMSE scores. Univariate exposure-response functions from BKMR models showed similar results. Moreover, the toxic metal mixture (As, Cd, and Pb) exhibited a significant negative association with MMSE scores in a dose-response pattern, with Pb being the greatest contributor within the mixture. The negative association of Pb alone or the toxic metal mixture with MMSE scores became weaker at higher concentrations of Se within its normal range, especially when Se levels were greater than the median (89.18 µg/L). Our findings support that Se can attenuate the negative associations of exposure to single Pb or the As, Cd, and Pb mixtures with cognitive function. Future prospective studies are needed to replicate our findings.
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Metais Pesados , Selênio , Idoso , Humanos , Arsênio/toxicidade , Teorema de Bayes , Cádmio/toxicidade , Cognição , População do Leste Asiático , Intoxicação por Metais Pesados , Chumbo/toxicidade , Metais Pesados/toxicidade , Selênio/farmacologiaRESUMO
Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.
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Transtornos do Sono-Vigília , Estresse Psicológico , Animais , Camundongos , Hormônio Liberador da Corticotropina/metabolismo , Núcleo Accumbens/metabolismo , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Sono , Estresse Psicológico/complicaçõesRESUMO
Background: Diabetes can increase the risk of coronary heart disease, and also increase the mortality rate of coronary heart disease in diabetic patients. Although reperfusion therapy can preserve the viable myocardium, fatal reperfusion injury can also occur. Studies have shown that diabetes can aggravate myocardial ischemia-reperfusion injury, ERK1/2 can reduce myocardial ischemia-reperfusion injury, but its mechanism in hyperglycemic myocardial ischemia-reperfusion injury is unclear. This study sought to explore the mechanism of extracellular signal-regulated kinase 1/2 (ERK1/2) in hyperglycemic myocardial ischemia reperfusion (I/R) injury. Methods: H9C2 cardiomyocytes were treated with high-glucose (HG) medium plus I/R stimulation to establish a hyperglycemia I/R model in vitro. The cells were treated with LM22B-10 (an ERK activator) or transfected with the constitutive activation of the mitogen-activated protein kinase 1 (CaMEK) gene. Myocardial cell apoptosis, mitochondria functional-related indicators, the oxidative stress indexes, and the expression levels of ERK1/2 protein were detected. Results: The HG I/R injury intervention caused an increase in the ratio of apoptotic cardiomyocytes (P<0.05), but the phosphorylation level of the ERK1/2 protein did not increase further. Administering LM22B-10 or transfecting the CaMEK gene significantly activated the phosphorylation levels of ERK1/2 protein and reduced the proportion of cardiomyocyte apoptosis (P<0.05). HG I/R injury increased mitochondrial fission and reduced membrane potential. The intervention reduced the number of punctate mitochondria, increased the average network structure size and median branch length (P<0.01), increased the median network structure size and average branch length (P<0.05), and reduced the colocalization of Drp1 (Dynamin-Related protein1)/TOMM20 (Mitochondrial outer membrane translocation enzyme 20) (P<0.05) and Drp1 with serine 616 phosphorylation (Drp1s616) phosphorylation (P<0.01), thereby reducing mitochondrial fission, increasing membrane potential and mitochondrial function. HG I/R injury increased the level of oxidative stress, while administering LM22B-10 or transfecting the CaMEK gene reduced the level of oxidative stress (P<0.01). Conclusions: Targeting the activation of ERK1/2 protein phosphorylation reduced mitochondrial fission, increased membrane potential and mitochondrial function, reduced oxidative stress and myocardial cell apoptosis, and alleviated hyperglycemia myocardial I/R injury.
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Messenger RNA (mRNA) is being developed by researchers as a novel drug for the treatment or prevention of many diseases. However, to enable mRNA to fully exploit its effects in vivo, researchers need to develop safer and more effective mRNA delivery systems that improve mRNA stability and enhance the ability of cells to take up and release mRNA. To date, lipid nanoparticles are promising nanodrug carriers for tumor therapy, which can significantly improve the immunotherapeutic effects of conventional drugs by modulating mRNA delivery, and have attracted widespread interest in the biomedical field. This review focuses on the delivery of mRNA by lipid nanoparticles for cancer treatment. We summarize some common tumor immunotherapy and mRNA delivery strategies, describe the clinical advantages of lipid nanoparticles for mRNA delivery, and provide an outlook on the current challenges and future developments of this technology.
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Nanopartículas , Neoplasias , Sistemas de Liberação de Medicamentos , Humanos , Imunoterapia , Lipossomos , Nanopartículas/uso terapêutico , Neoplasias/genética , Neoplasias/terapia , RNA Mensageiro/genéticaRESUMO
The evidence about the association of the essential trace element (ETE) mixture with atherosclerotic cardiovascular disease (ASCVD) amongst older adults is limited. This study aims to evaluate the associations of single ETEs and the ETE mixture with the 10-year ASCVD risks and its predicting factors in Chinese community-dwelling older adults. A total of 607 community-dwelling older adults were included in this study. Blood levels of vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), and selenium (Se) were assessed by inductively coupled plasma mass spectrometry. The predicted 10-year ASCVD risk was calculated using the Prediction for ASCVD Risk in China (China-PAR) equations. Traditional linear regressions and Bayesian kernel machine regression (BKMR) were used to assess the associations of single ETEs and the ETE mixture with the 10-year ASCVD risks and its predicting factors such as systolic blood pressure (SBP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), diabetes, and waist circumference (WC). In linear regression models, blood Cr levels were negatively associated with the 10-year ASCVD risks after adjustment for covariates (ß = - 0.07, 95% CI = - 0.11 ~ - 0.03); The 3th quartile (Q3) of Se levels was also associated with a lower 10-year ASCVD risks when compared with the lowest quartile (Q1) of Se levels (ßQ3 vs. Q1: - 0.12, 95% CI = - 0.22 ~ - 0.02). In BKMR models, the negative associations of Cr and Se with the 10-year ASCVD risks were observed. Higher blood levels of ETE mixture were associated with decreased 10-year ASCVD risks in a dose-response pattern, with Cr having the highest value of the posterior inclusion probability (PIP) within the mixture. Furthermore, a positive association between Cr and HDL-C and a negative association between Se and SBP were found in both linear regression and BKMR models. Cr and Se were negatively associated with the 10-year ASCVD risks, individually and as a mixture. ETE mixture showed a linear dose-response association with decreased 10-year ASCVD risks, with Cr being the most important component within the mixture. The negative association of the ETE mixture with the 10-year ASCVD risks may be attributed to Cr and Se, mainly mediated by HDL-C and SBP, respectively. Further cohort studies are needed to clarify this association.
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Doenças Cardiovasculares , Oligoelementos , Humanos , Idoso , Vida Independente , Teorema de Bayes , População do Leste Asiático , ColesterolRESUMO
With the continuous development of air pollution control measures, the concentration of PM2.5 in Shanghai has shown a conspicuous downward trend in recent years. However, frequent O3 pollution events have highlighted the urgent need to explore the occurrence patterns of O3 pollution and develop scientific strategies for reducing O3 peaks. This study examines data from July 2017, when the cumulative number of O3 pollution days in 17 cities in the Yangtze River Delta was 165 days, of which Shanghai was the most serious, with an exceedance rate of 64.5%. During this period, the average concentration of NO2 in Shanghai was 27.1 µg·m-3 and volatile organic copunds (VOCs) mixing ratio was 22.5×10-9. By analyzing ozone precursor concentrations and meteorological factors, we determined that these events mainly resulted from a combination of unfavorable meteorological conditions such as high temperature, low humidity, low wind speed, and high precursor emissions. WRF-CMAQ scenario simulations showed that a reduction in precursor emissions in Shanghai alone would have a limited controlling effect on regional O3 pollution. Thus, regional joint control is recommended when widespread pollution events occur. Our analysis shows that if VOCs in Shanghai and nine neighboring cities can be reduced by 30%, the maximum 8-h O3 concentration in Shanghai could be reduced by 7.2%. If the reduction number of these cities rises to 17, the maximum 8-h O3 concentration reduction rate in Shanghai will increase to 7.8%. It is also recommended that the VOCs:NOx reduction ratio should be strictly controlled at more than 3:1, or else the O3 concentration in some areas will increase.
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Poluentes Atmosféricos , Poluição do Ar , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Cidades , Monitoramento Ambiental , Ozônio/análise , Compostos Orgânicos Voláteis/análiseRESUMO
Continuous on-line observation of particulate matter and PM2.5 chemical composition was conducted from October 15th to November 7th 2019 in East China. During the observation period, a wide range of dust-related processes took place. According to supplementary urban air quality assessment affected by dust (hereafter referred to as supplementary provisions), the observations were divided into four stages including pre-dust event, dust â , dust â ¡, and post-dust event. The dust â stage represented the processes of transportation and retention, while the dust â ¡ stage represented processes of backflow from the sea and scavenging. The start time of the studied dust event was October 29th 08:00-09:00 based on the supplementary provisions, dust tracers, and air quality models; however, disagreements existed between these data sources with respect to the finishing time. The supplementary provisions could not effectively distinguish backflow dust from sea, and results from different dust tracers were variable. The WRF-CMAQ model simulated dust variation trends well but overestimated short-term suspended dust and backflow dust. PM10, PM2.5, and trace element concentrations were much higher during dust events than during non-dust periods, with highest daily concentrations of (234.8±125.5), (76.8±22.5), and (17.54±10.5) µg·m-3, respectively, which occurred on October 29th. During the dust event, concentration of crustal elements were remarkably high in PM2.5. At the same time, secondary ions (SO42-, NO3-, and NH4+) contributed less to PM2.5 mass concentrations. Four major crustal elements (Al, Si, Ca, and Fe) accounted for 23.5% and 13.7% of the mass concentration of PM2.5 and secondary ions accounted for 24.3% and 41.9% during dust â and dust â ¡ stages, respectively. Based on PMF source apportionment, Ca abundance, PM2.5/PM10 in dust sources, and the reconstruction of crustal material, dust particulates accounted for 43.4%-50.0% of PM2.5 and backflow dust accounted for 19.2%-24.7% of PM2.5.
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Volatile organic compounds (VOCs) play important roles in the formation of ozone and fine particles in the troposphere. Industrial parks emit significant amounts of VOCs in China, while few studies have characterized them. In the present study, a mobile platform was employed to measure the levels and composition VOCs around industrial parks in the Yangzte River Delta region. The average concentration of VOCs ranged from 39 µg·m-3 (5% percentile) to 533 µg·m-3 (95% percentile) with an average of 183 µg·m-3, which was three times that of ambient concentrations. Maximum VOC concentrations ranged from 307 µg·m-3 (5% percentile) to 12006 µg·m-3 (95% percentile) with an average of 2812 µg·m-3. The frequency of abnormal peak values was as high as 64% across all the industrial parks, of which toluene (32%), xylene (18%), benzene (9%), and>C9 aromatics (19%) were the most common species. Differences in VOC characteristics were observed among the different types of industrial parks. Specifically, highest concentrations of VOCs were observed in textile industrial parks followed by chemical, painting, and petrochemical industrial parks, and VOC concentrations in electronics industrial parks were the lowest. Importantly, species measured using the mobile platform only contributed~50% of VOCs present in ambient samples, indicating that the concentrations of VOCs in the industrial parks were underestimated overall. These results can inform measures to control VOC pollution in industrial parks in China.
RESUMO
In this work, a new quantitative analysis method of multi-components analysis via a single marker strategy coupled with high-performance liquid chromatography (HPLC) analysis, was proposed to analyze nine nucleosides (cytidine, uridine, 2'-deoxyuridine, inosine, guanosine, 2'-deoxyguanosine, thymidine, adenosine, and 2'-deoxyadenosine) as quality control markers in Rhizoma Paridis. Guanosine was set as the internal reference substance, whose content in Rhizoma Paridis was determined using conventional external standard method. Then, relative correction factors between guanosine and the other eight nucleosides were measured respectively. The amounts of the other eight components were calculated according to the relative correction factors by the quantitative analysis of multi-components via a single marker method. Finally, the result of vector angle cosine analysis showed that there was no significant difference of the contents between the external standard method and the quantitative analysis of multi-components via a single marker method, indicating that the quantitative analysis of multi-components via a single marker method can be applied for the quality control of Rhizoma Paridis. As far as we know, this is also the first report to analyze nucleosides by the quantitative analysis of multi-components via a single marker method, providing an efficient and promising quality assessment method for other traditional Chinese medicine containing nucleosides.