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Insufficient exposure to sunlight increases the risk of cardiovascular diseases. Hypertensive left ventricular (LV) hypertrophy exacerbates the risks of myocardial ischemia, ventricular arrhythmias, sudden cardiac death, and heart failure. This study aimed to determine the effects of ultraviolet (UV) irradiation on LV hypertrophy and mitochondrial morphology. Eighteen 7-week-old Dahl salt-sensitive (Dahl S) rats were categorized into three groups (n = 6 each) and fed sodium chloride (NaCl) diets, as follows: UV-irradiated [UVB+A (+), 8% NaCl], non-UV-irradiated [UV (-), 8% NaCl], and control [UV (-), 0.3% NaCl]. UV irradiation was administered at a low intensity of 100 mJ/cm2 for 6 days per week. Echocardiography and mitochondrial analyses were performed to evaluate LV hypertrophy and cardiomyocytes, and skin tissues were stained with hematoxylin and eosin to assess the pathological abnormalities at 12 weeks of age. LV mass was significantly reduced in the UVB+A (+) and control groups compared to that in the UV (-) group. Mitochondrial structural abnormalities in cardiomyocytes were observed only in the UV (-) group, but not in the UVB+A (+) or control group. Pathological skin abnormalities were not observed in any of the three groups. These findings suggest the potential benefits of UV irradiation in hypertensive models.
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Nanoparticles (NPs) can be conjugated with diverse biomolecules and employed in biosensing to detect target analytes in biological samples. This proven concept was primarily used during the COVID-19 pandemic with gold-NP-based lateral flow assays (LFAs). Considering the gold price and its worldwide depletion, here we show that novel plasmonic NPs based on inexpensive metals, titanium nitride (TiN) and copper covered with a gold shell (Cu@Au), perform comparable to or even better than gold nanoparticles. After conjugation, these novel nanoparticles provided high figures of merit for LFA testing, such as high signals and specificity and robust naked-eye signal recognition. Since the main cost of Au NPs in commercial testing kits is the colloidal synthesis, our development with the Cu@Au and the laser-ablation-fabricated TiN NPs is exciting, offering potentially inexpensive plasmonic nanomaterials for various bioapplications. Moreover, our machine learning study showed that biodetection with TiN is more accurate than that with Au.
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Cobre , Ouro , Nanopartículas Metálicas , Titânio , Nanopartículas Metálicas/química , Titânio/química , Ouro/química , Cobre/química , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/economia , Humanos , COVID-19/virologia , COVID-19/diagnóstico , Coloide de Ouro/química , SARS-CoV-2/isolamento & purificaçãoRESUMO
The RNA-binding zinc finger protein 36 (ZFP36) family participates in numerous physiological processes including transition and differentiation through post-transcriptional regulation. ZFP36L1 is a member of the ZFP36 family. This study aimed to evaluate the role of ZFP36L1 in restenosis. We found that the expression of ZFP36L1 was inhibited in VSMC-phenotypic transformation induced by TGF-ß, PDGF-BB, and FBS and also in the rat carotid injury model. In addition, we found that the overexpression of ZFP36L1 inhibited the proliferation and migration of VSMCs and promoted the expression of VSMC contractile genes; whereas ZFP36L1 interference promoted the proliferation and migration of VSMCs and suppressed the expression of contractile genes. Furthermore, the RNA binding protein immunoprecipitation and double luciferase reporter gene experiments shows that ZFP36L1 regulates the phenotypic transformation of VSMCs through the posttranscriptional regulation of KLF16. Finally, our research results in the rat carotid balloon injury animal model further confirmed that ZFP36L1 regulates the phenotypic transformation of VSMCs through the posttranscriptional regulation of KLF16 and further plays a role in vascular injury and restenosis in vivo.
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Fator 1 de Resposta a Butirato , Proliferação de Células , Fatores de Transcrição Kruppel-Like , Músculo Liso Vascular , Lesões do Sistema Vascular , Animais , Humanos , Masculino , Ratos , Fator 1 de Resposta a Butirato/metabolismo , Fator 1 de Resposta a Butirato/genética , Movimento Celular/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Ratos Sprague-Dawley , Estabilidade de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/genética , Lesões do Sistema Vascular/patologiaRESUMO
Background: The presence of macrovascular invasion (MVI) is associated with poor prognosis in advanced hepatocellular carcinoma (HCC). This study aims to evaluate the efficacy and safety of Cinobufacini therapy via hepatic arterial infusion (HAI) in advanced HCC patients with MVI. Methods: The clinical records of 130 consecutive patients with unresectable advanced HCC and MVI who had received Cinobufacini or cisplatin plus 5-fluorouracil (CF) treatment via HAI were retrospectively analyzed. The therapeutic efficacy, overall survival (OS), progression-free survival (PFS), and adverse events were compared between the two treatment groups. Results: The Cinobufacini group demonstrated significant curative effects on treatment via HAI compared with the CF group, including the objective response rate (44.9% vs 27.9%, P=0.048), the median OS (14.8 months vs 11.1 months, P=0.010), and the median PFS (10.3 months vs 6.0 months, P=0.006). Result in subgroup analysis of portal vein invasion grade supported the efficacy in Cinobufacini treatment, especially in the median OS of Vp1-2 (18.3 months vs 14.3 months, P=0.043) and Vp3 (15.0 months vs 11.4 months, P=0.046), as well as the median PFS of Vp1-2 (14.8 months vs 10.2 months, P=0.028) and Vp3 (10.8 months vs 6.6 months, P=0.033) compared with CF treatment. Cox proportional hazards model and forest plot analysis of factors confirmed the survival benefit from HAI with Cinobufacini over CF (hazard ratio [HR], 0.61; 95% CI: 0.40-0.91; P=0.010). Multivariable analysis identified portal vein invasion grade (Vp4; HR, 1.78; 95% CI: 1.03-2.16; P=0.032) and AFP (>1000; HR, 1.61; 95% CI: 1.08-1.91; P=0.039) as the independent factors for prognosis. Moreover, the total incidence of adverse events in the Cinobufacini group was significantly lower than in the CF group (60.9% vs 82.0%, P=0.009). Conclusion: Cinobufacini therapy via HAI is a viable strategy for curing advanced HCC with MVI, due to prolonged survival and a superior safety profile.
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OBJECTIVES: To observe the effect of motor evoked potential (MEP)-oriented scalp acupuncture combined with transcranial magnetic stimulation (TMS) on limb motor ability in patients with ischemic stroke hemiplegia. METHODS: A total of 60 patients with ischemic stroke hemiplegia were randomized into an observation group and a control group, 30 cases in each one. In addition to the medication treatment of internal medicine and comprehensive training of hemiplegic limbs, MEP-oriented scalp acupuncture combined with TMS was applied in the observation group, conventional scalp acupuncture at bilateral anterior oblique line of parietal and temporal regions combined with TMS was applied in the control group. The treatment was given once a day, 5 days a week for 4 weeks totally in the two groups. Before and after treatment, the scores of Fugl-Meyer assessment (FMA), modified Ashworth scale (MAS) and modified Barthel index (MBI) were observed in the two groups. RESULTS: After treatment, the FMA and MBI scores were increased compared with those before treatment in the two groups (P<0.001), and the FMA and MBI scores in the observation group were higher than those in the control group (P<0.05). After treatment, the MAS scores of upper and lower limbs in the observation group were decreased compared with those before treatment (P<0.01, P<0.001), the MAS score of lower limb in the control group was decreased compared with that before treatment (P<0.05). CONCLUSIONS: MEP-oriented scalp acupuncture combined with TMS can effectively improve the limb motor ability, daily living ability and limb spasticity in patients with ischemic stroke hemiplegia.
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Terapia por Acupuntura , AVC Isquêmico , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Hemiplegia/etiologia , Hemiplegia/terapia , Estimulação Magnética Transcraniana , Couro Cabeludo , Potencial Evocado Motor , Resultado do Tratamento , Extremidade SuperiorRESUMO
Biodegradation is an efficient and cost-effective approach to remove residual penicillin G sodium (PGNa) from the environment. In this study, the effective PGNa-degrading strain SQW1 (Sphingobacterium sp.) was screened from contaminated soil using enrichment technique. The effects of critical operational parameters on PGNa degradation by strain SQW1 were systematically investigated, and these parameters were optimized by response surface methodology to maximize PGNa degradation. Comparative experiments found the extracellular enzyme to completely degrade PGNa within 60 min. Combined with whole genome sequencing of strain SQW1 and LC-MS analysis of degradation products, penicillin acylase and ß-lactamase were identified as critical enzymes for PGNa biodegradation. Moreover, three degradation pathways were postulated, including ß-lactam hydrolysis, penicillin acylase hydrolysis, decarboxylation, desulfurization, demethylation, oxidative dehydrogenation, hydroxyl reduction, and demethylation reactions. The toxicity of PGNa biodegradation intermediates was assessed using paper diffusion method, ECOSAR, and TEST software, which showed that the biodegradation products had low toxicity. This study is the first to describe PGNa-degrading bacteria and detailed degradation mechanisms, which will provide new insights into the PGNa biodegradation.
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Penicilina Amidase , Sphingobacterium , Sphingobacterium/genética , Sphingobacterium/metabolismo , Penicilina Amidase/metabolismo , Penicilina G , Biodegradação AmbientalRESUMO
Radiotherapy is one of the major options currently for cancer treatment. Radiotherapy causes cellular damage inducing cell death, which is expected to be selective for tumor cells. However, side effects that alter the surrounding normal tissue are often hard to be avoided. When radiation involves the hypothalamic-pituitary axis, growth hormone deficiency (GHD) is frequently induced, causing developmental and metabolic-related diseases in childhood cancer survivors. Growth hormone (GH) replacement therapy has been used for these patients and has been shown to be safe in general. However, there are some debating for its long-term safety due to the known roles of GH in inducing cell growth, which could be related to cancer recurrence. In addition, studies have shown that GH is involved in the development of resistance to chemotherapy and radiotherapy through various mechanisms. In this review, we will first discuss the effects of GHD induced after radiotherapy and the safety of the GH replacement treatment. Then, we will discuss the role of the GH-IGF-1 axis in radioresistance via a mechanism of improving DNA repair.
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Hormônio do Crescimento Humano , Hipopituitarismo , Humanos , Hormônio do Crescimento , Fator de Crescimento Insulin-Like I , Terapia de Reposição HormonalRESUMO
Nanoparticles (NPs) can be conjugated with diverse biomolecules and employed in biosensing to detect target analytes in biological samples. This proven concept was primarily used during the COVID-19 pandemic with gold NPs-based lateral flow assays (LFAs). Considering the gold price and its worldwide depletion, here we show that novel plasmonic nanoparticles (NPs) based on inexpensive metals, titanium nitride (TiN) and copper covered with a gold shell (Cu@Au), perform comparable or even better than gold nanoparticles. After conjugation, these novel nanoparticles provided high figures of merit for LFA testing, such as high signals and specificity and robust naked-eye signal recognition. To the best of our knowledge, our study represents the 1st application of laser-ablation-fabricated nanoparticles (TiN) in the LFA and dot-blot biotesting. Since the main cost of the Au NPs in commercial testing kits is in the colloidal synthesis, our development with TiN is very exciting, offering potentially very inexpensive plasmonic nanomaterials for various bio-testing applications. Moreover, our machine learning study showed that the bio-detection with TiN is more accurate than that with Au.
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BACKGROUND: Abdominal aortic calcification (AAC) is an independent risk factor for cardiovascular disease. We aim to examine the associations between Life's Essential 8 (LE8), the recently updated measurement of cardiovascular health (CVH), and AAC among participants aged ≥40 years. METHODS AND RESULTS: This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey in 2013 to 2014. AAC (AAC score>0) and severe AAC (AAC score>6) were quantified by the Kauppila score system. Multiple linear, multivariable logistic, and restricted cubic spline models were used to assess the associations. A total of 2369 participants were included with a mean AAC score of 1.41 (0.13). Participants in the high-cardiovascular-health group had lower AAC scores, lower prevalence of AAC, and lower prevalence of severe AAC. After the adjustment of potential confounders (age, sex, race and ethnicity, education levels, marital status, poverty income ratio, estimated glomerular filtration rate, serum creatinine, serum uric acid, serum phosphorus, and serum total calcium), higher cardiovascular health was significantly associated with lower risk of AAC. Meanwhile, elevated nicotine exposure score, blood glucose score, and blood pressure score within the LE8 components were significantly associated with lower risk of AAC. Also, nonlinear dose-response relationships were observed. Subgroup analyses (age strata, sex, poverty income ratio, education levels, marital status) indicated the inverse associations of LE8 and AAC were generally similar in different populations. CONCLUSIONS: LE8 was negatively and nonlinearly related to the risk of AAC among middle-aged and older populations. Meanwhile, LE8 components should prioritize higher scores for nicotine exposure, blood glucose, and blood pressure evaluations.
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Glicemia , Calcificação Vascular , Pessoa de Meia-Idade , Humanos , Idoso , Inquéritos Nutricionais , Estudos Transversais , Nicotina , Ácido Úrico , Fatores de RiscoRESUMO
SiZrOC aerogels were synthesized through the pyrolysis of the zirconium source-doped SiOC system using zirconyl chloride octahydrate (ZrOCl2·8H2O) at temperatures ranging from 900 to 1300 °C. This study investigates the microstructure evolution and phase separation of SiOC and SiZrOC aerogels during the pyrolysis process. Upon pyrolysis, both aerogels exhibited a Si-O-C structure with a high thermal stability. The introduction of zirconium elements significantly enhanced the pore volume (3.20 cm3/g) and porosity (96.0%) and reduced the thermal conductivity (0.023 W·m-1·K-1) of the organic-inorganic precursor aerogel. Moreover, the three-dimensional pore structure was retained even under high-temperature pyrolysis conditions. SiZrOC-1100 displayed a high specific surface area of 273.52 m2/g, a high pore volume of 1.70 cm3/g, and a low thermal conductivity of 0.033 W·m-1·K-1. At high temperatures, the SiZrOC phase transformation produces tetragonal ZrO2, which inhibits the graphitization process of free carbon and the growth of SiC grains. Furthermore, the phase separation process of the SiOxCy matrix structure generated oxygen-rich SiOxC4-x units, while carbon-rich SiOxC4-x units were negligible below a pyrolysis temperature of 1200 °C. Between 900 and 1200 °C, SiZrOC is composed of amorphous SiOC, amorphous ZrO2, microcrystalline t-ZrO2, and free carbon phase. These findings provide valuable insights into the preparation of high-performance SiOC aerogels.
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Acute myeloid leukemia (AML) is one of the most aggressive hematological malignancies with a low 5-year survival rate and high rate of relapse. Developing more efficient therapies is an urgent need for AML treatment. Accumulating evidence showed that ferroptosis, an iron-dependent form of programmed cell death, is closely correlated with cancer initiation and clinical outcome through reshaping the tumor microenvironment. However, understanding of AML heterogeneity based on extensive profiling of ferroptosis signatures remains to be investigated yet. Herein, five independent AML transcriptomic datasets (TCGA-AML, GSE37642, GSE12417, GSE10358, and GSE106291) were obtained from the GEO and TCGA databases. Then, we identified two ferroptosis-related molecular subtypes (C1 and C2) with distinct prognosis and tumor immune microenvironment (TIME) by consensus clustering. Patients in the C1 subtype were associated with favorable clinical outcomes and increased cytotoxic immune cell infiltration, including CD8+/central memory T cells, natural killer (NK) cells, and non-regulatory CD4+ T cells while showing decreased suppressive immune subsets such as M2 macrophages, neutrophils, and monocytes. Functional enrichment analysis of differentially expressed genes (DEGs) implied that cell activation involved in immune response, leukocyte cell-cell adhesion and migration, and cytokine production were the main biological processes. Phagosome, antigen processing and presentation, cytokine-cytokine receptor interaction, B-cell receptor, and chemokine were identified as the major pathways. To seize the distinct landscape in C1 vs. C2 subtypes, a 5-gene prognostic signature (LSP1, IL1R2, MPO, CRIP1, and SLC24A3) was developed using LASSO Cox stepwise regression analysis and further validated in independent AML cohorts. Patients were divided into high- and low-risk groups, and decreased survival rates were observed in high- vs. low-risk groups. The TIME between high- and low-risk groups has a similar scenery in C1 vs. C2 subtypes. Single-cell-level analysis verified that LSP1 and CRIP1 were upregulated in AML and exhausted CD8+ T cells. Dual targeting of these two markers might present a promising immunotherapeutic for AML. In addition, potential effective chemical drugs for AML were predicted. Thus, we concluded that molecular subtyping using ferroptosis signatures could characterize the TIME and provide implications for monitoring clinical outcomes and predicting novel therapies.
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BACKGROUND: Cardiovascular complications significantly augment the overall COVID-19 mortality, largely due to the susceptibility of human cardiomyocytes (CMs) to SARS-CoV-2 virus. SARS-CoV-2 virus encodes 27 genes, whose specific impacts on CM health are not fully understood. This study elucidates the deleterious effects of SARS-CoV-2 genes Nsp6, M, and Nsp8 on human CMs. METHODS: CMs were derived from human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent stem cells, using 2D and 3D differentiation methods. We overexpressed Nsp6, M, or Nsp8 in hPSCs and then applied whole mRNA-seq and mass spectrometry for multi-omics analysis. Co-immunoprecipitation mass spectrometry was utilized to map the protein interaction networks of Nsp6, M, and Nsp8 within host hiPSC-CMs. RESULTS: Nsp6, Nsp8, and M globally perturb the transcriptome and proteome of hPSC-CMs. SARS-CoV-2 infection and the overexpression of Nsp6, Nsp8, or M coherently upregulated genes associated with apoptosis and immune/inflammation pathways, whereas downregulated genes linked to heart contraction and functions. Global interactome analysis revealed interactions between Nsp6, Nsp8, and M with ATPase subunits. Overexpression of Nsp6, Nsp8, or M significantly reduced cellular ATP levels, markedly increased apoptosis, and compromised Ca2+ handling in hPSC-CMs. Importantly, administration of FDA-approved drugs, ivermectin and meclizine, could restore ATP levels, thereby mitigating apoptosis and dysfunction in hPSC-CMs overexpressing Nsp6, Nsp8, or M. CONCLUSION: Overall, our findings uncover the extensive damaging effects of Nsp6, Nsp8, and M on hPSC-CMs, underlining the crucial role of ATP homeostasis in CM death and functional abnormalities induced by these SARS-CoV-2 genes, and reveal the potential therapeutic strategies to alleviate these detrimental effects with FDA-approved drugs.
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COVID-19 , Células-Tronco Pluripotentes , Humanos , Miócitos Cardíacos , SARS-CoV-2 , Genes Virais , Trifosfato de AdenosinaRESUMO
BACKGROUND: Aging is associated with an increased prevalence of non-communicable chronic diseases (NCDs), functional impairments, and diverse demands for health services. This study analyzed the trends in older adults' needs and utilization of health services from 1993 to 2018 in China, as well as chronic disease-related economic burdens. METHODS: The research data were collected from the six cross-sectional National Health Service Survey (NHSS), implemented every 5 years from 1993 to 2018. A multi-stage stratified random cluster sampling method has been adopted in the NHSS. The data on the older population's socio-economic characteristics, health service needs, and utilization were collected from the 6 waves National Health Service Survey (NHSS) 1993-2018. In the 2013 and 2018 NHSSs, EQ-5D-3L and visual analogue scale were used to evaluate the health condition. And the prevalence of NCDs and related Out-of-pocket (OOP) expenditures were collected. Functional dependency and impairment were collected in 2018. The Katz Activities of Daily Living scale was used to evaluate six functions, including self-feeding, dressing, bathing, transferring, toilet hygiene, and controlling bowel movements. RESULTS: The two-week morbidity rate and prevalence of NCDs showed a rapid upward trend in older adults. With the development of health system reform and universal health insurance coverage, older adults' two-week medical consultation rate increased from 25.6% in 1993 to 40.1% in 2018, and the hospitalization rate rose from 6.1% to 24.9%. The difference in health service needs and utilization between urban and rural areas decreased, and the hospitalization rate in rural areas (26.3%) exceeded that in urban areas (23.6%) for the first time in 2018. Functional independence become more severe as aged. The proportion of severe functional impairment was 6.9% and 2% in the group aged 80 or over and group 70-79 years, respectively. Regarding disability status, 32.5% had hearing problems and 31.4% had visual impairment. The highest prevalence rates of NCDs in older adults were found in hypertension (36.9%), followed by diabetes (10.6%), cerebrovascular disease (5.4%), ischemic heart disease (4.5%), and intervertebral disc disease (4.2%). The average annual OOP expenditures attributed to NCDs increased from ¥2481.8 RMB in 2013 to ¥8255.9 RMB in 2018 for older adults. About 90.7% of older adults prefer to live in the residential community, leading to the demands for preventive healthcare (30.4%), medical treatment (14.1%), and elderly education (8.6%). CONCLUSION: The elevated risks of age-related impairments and chronic morbidities, and increased demands for preventive healthcare are critical public health issues. Policymakers should strengthen primary healthcare and move towards integrated delivery to improve access and quality of care for older adults. The integration of healthcare and social security constitutes an adaptive trend in meeting the multi-level demands of an aging society.
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Doenças não Transmissíveis , Medicina Estatal , Idoso , Humanos , Doenças não Transmissíveis/epidemiologia , Doenças não Transmissíveis/terapia , Atividades Cotidianas , Estudos Transversais , China/epidemiologiaRESUMO
BACKGROUND: Over the past 25 years, the spectrum of diseases in China has rapidly changed from infectious to non-communicable diseases (NCDs). This study aimed to identify the prevalence of chronic diseases over the past 25 years in China and estimate the trends and changes in risk factors related to NCDs. METHODS: We conducted a descriptive analysis based on the National Health Service Survey (NHSS) from 1993 to 2018. The survey year (in parentheses) and its respective number of respondents were (1993) 215,163; (1998) 216,101; (2003) 193,689; (2008) 177,501; (2013) 273,688; and (2018) 256,304. In each survey, approximately half the participants were male. In addition, we estimated the trends in the prevalence and risk factors of NCDs from 1993 to 2018 and described their coefficient of variation in the provisions. RESULTS: The prevalence of NCDs has risen rapidly, from 17.0% in 1993 to 34.3% 2018. Hypertension and diabetes were the two main NCDs accounting for 53.3% in 2018. Similarly, the prevalence of hypertension and diabetes have also increased rapidly, increasing 15.1 and 27.0 times respectively from 1993 to 2018. Moreover, from 1993 to 2018, the proportion of smoking decreased from 32.0% to 24.7%, and the proportion of drinking and physical activity increased from 18.4% and 8.0% to 27.6% and 49.9%, respectively. The proportion of obesity increased from 5.4% in 2013 to 9.5% in 2018. The prevalence of NCDs in rural areas (35.2%) in 2018 was slightly higher than that in urban areas (33.5%). Changes in the prevalence of NCDs in rural were larger than those in urban. However, from 2013 to 2018, the provincial gaps for these metrics narrowed, except for that of smoking (Coefficient of Variation from 0.14 to 0.16). CONCLUSIONS: The prevalence of NCDs increased rapidly in China and was similar in urban and rural areas in 2018. Two key risk factors (drinking and obesity) increased in prevalence, while the other two (smoking and physical inactivity) decreased. These results indicate that China is facing considerable challenges in curbing chronic diseases to achieve the United Nations Sustainable Development Goals or the Healthy China 2030 goals. The government should take more active measures to change unhealthy lifestyles, improve efficiency in risk factor management, and pay more attention and allocate more health resources to rural areas.
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Hipertensão , Doenças não Transmissíveis , Masculino , Humanos , Feminino , Medicina Estatal , Fatores de Risco , Obesidade/epidemiologia , China/epidemiologia , Doença Crônica , Hipertensão/epidemiologia , Doenças não Transmissíveis/epidemiologiaRESUMO
Lipid droplets (LDs) are cellular organelles critical for lipid homeostasis, with intramyocyte LD accumulation implicated in metabolic disorder-associated heart diseases. Here we identify a human long non-coding RNA, Lipid-Droplet Transporter (LIPTER), essential for LD transport in human cardiomyocytes. LIPTER binds phosphatidic acid and phosphatidylinositol 4-phosphate on LD surface membranes and the MYH10 protein, connecting LDs to the MYH10-ACTIN cytoskeleton and facilitating LD transport. LIPTER and MYH10 deficiencies impair LD trafficking, mitochondrial function and survival of human induced pluripotent stem cell-derived cardiomyocytes. Conditional Myh10 deletion in mouse cardiomyocytes leads to LD accumulation, reduced fatty acid oxidation and compromised cardiac function. We identify NKX2.5 as the primary regulator of cardiomyocyte-specific LIPTER transcription. Notably, LIPTER transgenic expression mitigates cardiac lipotoxicity, preserves cardiac function and alleviates cardiomyopathies in high-fat-diet-fed and Leprdb/db mice. Our findings unveil a molecular connector role of LIPTER in intramyocyte LD transport, crucial for lipid metabolism of the human heart, and hold significant clinical implications for treating metabolic syndrome-associated heart diseases.
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Cardiopatias , Metabolismo dos Lipídeos , RNA Longo não Codificante , Animais , Humanos , Camundongos , Cardiopatias/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos/genética , Lipídeos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
What is already known about this topic?: Chronic pain has been identified as a risk factor for cardiovascular diseases. Evidence shows that adopting a healthy lifestyle can help reduce the cardiometabolic risks associated with chronic pain. What is added by this report?: Results from this cohort study suggest a positive association between chronic pain and the development of new-onset metabolic-related multimorbidity, specifically metabolic multimorbidity and cardiometabolic comorbidity, within middle-aged and older Chinese adults. Furthermore, adopting healthy lifestyles can potentially mitigate or even reverse these associations. What are the implications for public health practice?: The results of our study emphasize the importance of promoting healthy lifestyles among older Chinese adults as a preventative measure against the medical burdens and cardiometabolic risks associated with chronic pain.
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BACKGROUND: Changes in China's health care system in the last three decades was remarkable. The current study aims on examine the change of equality of health care utilization in mainland China based on a nationwide household interview survey. METHODS: We used household interview data extracted from six waves of National Health Service Survey between 1993 and 2018. Changes of health care utilization were descripted. Equality of the utilization were examined with univariate meta-regression across urban and rural areas, socioeconomic development regions and income groups. RESULTS: The proportion of outpatient visits within last two weeks experienced a decrease from 17.0% in 1993 to 13.0% in 2013 and bounced back to 24.0% in 2018. The age-standardized trend remained unchanged. Hospitalization in the last 12 month increased from 2.6% in 1998 to 13.8% in 2018. The perceived unmet need of hospital admission fell from 35.9% in 1998 to 21.5% in 2018. The gaps in health care utilization between urban and rural areas, across regions and by income groups have been narrowed, implying improved equality of using medical services in the last two and a half decades. CONCLUSION: China has experienced significant increases in health care utilization over the past 25 years. Meanwhile, the unmet needs for health care decreased remarkably and the equality of health care utilization improved significantly. These results imply significant achievements in health service accessibility in China.
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Atenção à Saúde , Medicina Estatal , Humanos , Aceitação pelo Paciente de Cuidados de Saúde , Renda , China , População RuralRESUMO
Among many supercapacitor electrode materials, carbon materials are widely used due to their large specific surface area, good electrical conductivity and high economic efficiency. However, carbon-based supercapacitors face the challenges of low energy density and limited operating environment. This work reports a facile self-assembled method to prepare three-dimensional carbon nanotubes/reduced graphene oxide (CNTs/rGO) aerogel material, which was applied as both positive and negative electrodes in a symmetric superacapacitor. The fabricated supercapacitor exhibited prominent capacitive performance not only at room temperature, but also at extreme temperatures (-20 â¼ 80 °C). The specific capacitances of the symmetric supercapacitors based on CNTs/rGO at a weight ratio of 2:5 respectively reached 107.8 and 128.2 F g-1 at 25 °C and 80 °C with KOH as the electrolyte, and 80.0 and 144.6 F g-1 at -20 °C and 60 °C with deep eutectic solvent as the electrolyte. Notably, the capacitance retention and coulombic efficiency of the assembled supercapacitors remained almost unchanged after 20,000 cycles of charge/discharge test over a wide temperature range. The work uncovered a possibility for the development of high-performance supercapacitors flexibly operated at extreme temperatures.
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The endoplasmic reticulum (ER) plays an important role in the regulation of protein synthesis. Alterations in the folding capacity of the ER induce stress, which activates three ER sensors that mediate the unfolded protein response (UPR). Components of the pathways regulated by these sensors have been shown to regulate autophagy. The last corresponds to a mechanism of self-eating and recycling important for proper cell maintenance. Ultraviolet radiation (UV) is an external damaging stimulus that is known for inducing oxidative stress, and DNA, lipid and protein damage. Many controversies exist regarding the role of UV-inducing ER stress or autophagy. However, a connection between the three of them has not been addressed. In this review, we will discuss the contradictory theories regarding the relationships between UV radiation with the induction of ER stress and autophagy, as well as hypothetic connections between UV, ER stress and autophagy.
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Autofagia , Estresse do Retículo Endoplasmático , Raios Ultravioleta , Resposta a Proteínas não Dobradas , Estresse Oxidativo , Humanos , AnimaisRESUMO
BACKGROUND: Job burnout has become a widespread phenomenon in school settings. However, little is known about the mental health condition of the growing cohort of generalist teachers in rural primary schools. Drawing on the job demands-resource model and social exchange theory, this study examines the correlation between job burnout and job satisfaction through perceived organizational support and work engagement. METHODS: We recruited 639 Chinese generalist teachers in rural primary schools as the study subjects and developed a serial mediation model to assess the hypothesized construct. The data acquired online via Wenjuanxing Software were confirmed as valid and analyzed with SPSS and SmartPLS. RESULTS: The participants scored above the median in perceived organizational support, work engagement, and job satisfaction, and had scores close to the median for job burnout. Statistically significant differences among the investigated variables were found in gender, age, experience, and degree. Job burnout was negatively predictive of perceived organizational support, work engagement, and job satisfaction (each p = 0.000). Perceived organizational support mediated the association between job burnout and work engagement (p = 0.000) and the connection between job burnout and job satisfaction (p = 0.000), while work engagement mediated the association between job burnout and job satisfaction (p = 0.000) and the association between perceived organizational support and job satisfaction (p = 0.000). CONCLUSIONS: Perceived organizational support and work engagement as two sequential mediators buffered the detrimental impact of job burnout on job satisfaction among Chinese generalist teachers in rural primary schools. Targeted strategies should be implemented to diminish generalist teachers' feelings of burnout, being unsupported by organizations, disengagement at work, and dissatisfaction with the job.