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Green hydrogen from water electrolysis is a key driver for energy and industrial decarbonization. The prediction of the future green hydrogen cost reduction is required for investment and policy-making purposes but is complicated due to a lack of data, incomplete accounting for costs, and difficulty justifying trend predictions. A new AI-assisted data-driven prediction model is developed for an in-depth analysis of the current and future levelized costs of green hydrogen, driven by both progressive and disruptive innovations. The model uses natural language processing to gather data and generate trends for the technological development of key aspects of electrolyzer technology. Through an uncertainty analysis, green hydrogen costs have been shown to likely reach the key target of <$2.5 kg-1 by 2030 via progressive innovations, and beyond this point, disruptive technological developments are required to affect significantly further decease cost. Additionally, the global distribution of green hydrogen costs has been calculated. This work creates a comprehensive analysis of the levelized cost of green hydrogen, including the important balance of plant components, both now and as electrolyzer technology develops, and offers a likely prediction for how the costs will develop over time.
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In the United States, coronavirus disease 2019 (COVID-19) cases have consistently been linked to the prevailing variant XBB.1.5 of SARS-CoV-2 since late 2022. A system has been developed for producing and infecting cells with a pseudovirus (PsV) of SARS-CoV-2 to investigate the infection in a Biosafety Level 2 (BSL-2) laboratory. This system utilizes a lentiviral vector carrying ZsGreen1 and Firefly luciferase (Fluc) dual reporter genes, facilitating the analysis of experimental results. In addition, we have created a panel of PsV variants that depict both previous and presently circulating mutations found in circulating SARS-CoV-2 strains. A series of PsVs includes the prototype SARS-CoV-2, Delta B.1.617.2, BA.5, XBB.1, and XBB.1.5. To facilitate the study of infections caused by different variants of SARS-CoV-2 PsV, we have developed a HEK-293T cell line expressing mCherry and human angiotensin converting enzyme 2 (ACE2). To validate whether different SARS-CoV-2 PsV variants can be used for neutralization assays, we employed serum from rats immunized with the PF-D-Trimer protein vaccine to investigate its inhibitory effect on the infectivity of various SARS-CoV-2 PsV variants. According to our observations, the XBB variant, particularly XBB.1.5, exhibits stronger immune evasion capabilities than the prototype SARS-CoV-2, Delta B.1.617.2, and BA.5 PsV variants. Hence, utilizing the neutralization test, this study has the capability to forecast the effectiveness in preventing future SARS-CoV-2 variants infections.
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Obesity is one of the most common metabolic diseases around the world, which is distinguished by the abnormal buildup of triglycerides within adipose cells. Recent research has revealed that autophagy regulates lipid mobilization to maintain energy balance. TIGAR (Trp53 induced glycolysis regulatory phosphatase) has been identified as a glycolysis inhibitor, whether it plays a role in the metabolism of lipids is unknown. Here, we found that TIGAR transgenic (TIGAR+/+) mice exhibited increased fat mass and trended to obesity phenotype. Non-target metabolomics showed that TIGAR caused the dysregulation of the metabolism profile. The quantitative transcriptome sequencing identified an increased levels of LRRK2 and RAB7B in the adipose tissue of TIGAR+/+ mice. It was confirmed in vitro that TIGAR overexpression increased the levels of LRRK2 by inhibiting polyubiquitination degradation, thereby suppressing macroautophagy and chaperone-mediated autophagy (CMA) while increasing lipid accumulation which were reversed by the LRRK2 inhibitor DNL201. Furthermore, TIGAR drove LRRK2 to interact with RAB7B for suppressing lysosomal degradation of lipid droplets, while the increased lipid droplets in adipocytes were blocked by the RAB7B inhibitor ML282. Additionally, fat-specific TIGAR knockdown of TIGAR+/+ mice alleviated the symptoms of obesity, and adipose tissues-targeting superiority DNL201 nano-emulsion counteracted the obesity phenotype in TIGAR+/+ mice. In summary, the current results indicated that TIGAR performed a vital function in the lipid metabolism through LRRK2-mediated negative regulation of macroautophagy and CMA in adipocyte. The findings suggest that TIGAR has the potential to serve as a viable therapeutic target for treating obesity and its associated metabolic dysfunction.
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Adipocitos , Autofagia , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Obesidad , Monoéster Fosfórico Hidrolasas , Proteínas de Unión al GTP rab , Proteínas de Unión a GTP rab7 , Animales , Obesidad/metabolismo , Obesidad/patología , Autofagia/fisiología , Adipocitos/metabolismo , Proteínas de Unión al GTP rab/metabolismo , Proteínas de Unión al GTP rab/genética , Ratones , Proteínas de Unión a GTP rab7/metabolismo , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/metabolismo , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/genética , Monoéster Fosfórico Hidrolasas/metabolismo , Monoéster Fosfórico Hidrolasas/genética , Ratones Transgénicos , Chaperonas Moleculares/metabolismo , Ratones Endogámicos C57BL , Humanos , Gotas Lipídicas/metabolismo , Metabolismo de los Lípidos/genética , Ubiquitinación , Masculino , Proteínas Reguladoras de la ApoptosisRESUMEN
Acute generalized pustular psoriasis (GPP) is a serious illness. Despite various treatment methods, there is still lack of effective treatment plans for refractory cases with multiple comorbidities. This case report presents a 67-year-old woman with acute GPP, stage 4 chronic kidney disease (CKD), type 2 diabetes, and cardiovascular disease, in whom skin symptom disappearance and kidney function improvement were observed after the use of oral tacrolimus as the sole therapy. This is the first report on the application of tacrolimus in the treatment of acute GPP, especially refractory acute GPP. The successful treatment indicates that there are shared immune pathways between acute GPP and CKD, and the pathways can be interdicted by tacrolimus. Further studies are needed to optimize the therapy to maximize efficacy and minimize toxicity.
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Diabetes Mellitus Tipo 2 , Psoriasis , Insuficiencia Renal Crónica , Femenino , Humanos , Anciano , Tacrolimus/uso terapéutico , Interleucinas , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Psoriasis/complicaciones , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Enfermedad Crónica , Enfermedad Aguda , Insuficiencia Renal Crónica/complicacionesRESUMEN
Bifacial perovskite solar cells have shown great promise for increasing power output by capturing light from both sides. However, the suboptimal optical transmittance of back metal electrodes together with the complex fabrication process associated with front transparent conducting oxides have hindered the development of efficient bifacial PSCs. Here, we present a novel approach for bifacial perovskite devices using single-walled carbon nanotubes as both front and back electrodes. single-walled carbon nanotubes offer high transparency, conductivity, and stability, enabling bifacial PSCs with a bifaciality factor of over 98% and a power generation density of over 36%. We also fabricate flexible, all-carbon-electrode-based devices with a high power-per-weight value of 73.75 W g-1 and excellent mechanical durability. Furthermore, we show that our bifacial devices have a much lower material cost than conventional monofacial PSCs. Our work demonstrates the potential of SWCNT electrodes for efficient, stable, and low-cost bifacial perovskite photovoltaics.
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BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a prominent cause of liver-related death that poses a threat to global health and is characterized by severe hepatic steatosis, lobular inflammation, and ballooning degeneration. To date, no Food and Drug Administration-approved medicine is commercially available. The Chaihu Guizhi Ganjiang Decoction (CGGD) shows potential curative effects on regulation of blood lipids and blood glucose, mitigation of organism inflammation, and amelioration of hepatic function. However, the overall regulatory mechanisms underlying its effects on NASH remain unclear. PURPOSE: This study aimed to investigate the efficiency of CGGD on methionine- and choline-deficient (MCD)-induced NASH and unravel its underlying mechanisms. METHODS: A NASH model of SD rats was established using an MCD diet for 8 weeks, and the efficacy of CGGD was evaluated based on hepatic lipid accumulation, inflammatory response, and fibrosis. The effects of CGGD on the intestinal barrier, metabolic profile, and differentially expressed genes (DEGs) profile were analyzed by integrating gut microbiota, metabolomics, and transcriptome sequencing to elucidate its mechanisms of action. RESULTS: In MCD-induced NASH rats, pathological staining demonstrated that CGGD alleviated lipid accumulation, inflammatory cell infiltration, and fibrosis in the hepatic tissue. After CGGD administration, liver index, liver weight, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) contents, liver triglycerides (TG), and free fatty acids (FFAs) were decreased, meanwhile, it down-regulated the level of proinflammatory mediators (TNF-α, IL-6, IL-1ß, MCP-1), and up-regulated the level of anti-inflammatory factors (IL-4, IL-10), and the expression of liver fibrosis markers TGFß, Acta2, Col1a1 and Col1a2 were weakened. Mechanistically, CGGD treatment altered the diversity of intestinal flora, as evidenced by the depletion of Allobaculum, Blautia, norank_f_Erysipelotrichaceae, and enrichment of the probiotic genera Roseburia, Lactobacillus, Lachnoclostridium, etc. The colonic histopathological results indicated that the gut barrier damage recovered in the CGGD treatment group, and the expression levels of colonic short-chain fatty acids (SCFAs)-specific receptors FFAR2, FFAR3, and tight junction (TJs) proteins ZO-1, Occludin, Claudin-1 were increased compared with those in the model group. Further metabolomic and transcriptomic analyses suggested that CGGD mitigated the lipotoxicity caused by glycerophospholipid and eicosanoid metabolism disorders by decreasing the levels of PLA2G4A, LPCAT1, COX2, and LOX5. In addition, CGGD could activate the inhibitory lipotoxic transcription factor PPARα, regulate the proteins of FABP1, APOC2, APOA2, and LPL to promote fatty acid catabolism, and suppress the TLR4/MyD88/NFκB pathway to attenuate NASH. CONCLUSION: Our study demonstrated that CGGD improved steatosis, inflammation, and fibrosis on NASH through enhancing intestinal barrier integrity and alleviating PPARα mediated lipotoxicity, which makes it an attractive candidate for potential new strategies for NASH prevention and treatment.
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Medicamentos Herbarios Chinos , Enfermedad del Hígado Graso no Alcohólico , Ratas , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Ratas Sprague-Dawley , Hígado , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Inflamación/patología , Lípidos/farmacología , Metionina/metabolismo , Ratones Endogámicos C57BLRESUMEN
Current diagnostic methods for diabetic nephropathy (DN) lack precision, especially in early stages and monitoring progression. This study aims to find potential biomarkers for DN progression and evaluate their accuracy. Using serum samples from healthy controls (NC), diabetic patients (DM), early-medium stage DN (DN-EM), and late-stage DN (DN-L), researchers employed quantitative proteomics and Mfuzz clustering analysis revealed 15 proteins showing increased expression during DN progression, hinting at their biomarker potential. Combining Mfuzz clustering with weighted gene co-expression network analysis (WGCNA) highlighted five candidates (HMGB1, CD44, FBLN1, PTPRG, and ADAMTSL4). HMGB1 emerged as a promising biomarker, closely correlated with renal function changes. Experimental validation supported HMGB1's upregulation under high glucose conditions, reinforcing its potential as an early detection biomarker for DN. This research advances DN understanding and identifies five potential biomarkers, notably HMGB1, as a promising early monitoring target. These findings set the stage for future clinical diagnostic applications in DN.
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ETHNOPHARMACOLOGICAL RELEVANCE: Da Chuanxiong Formula (DCX) is a traditional herbal compound composed of Gastrodia elata Bl. and Ligusticum chuanxiong Hort, which could significantly enhance blood circulation and neuroprotection, showing promise in treating Vascular Cognitive Impairment (VCI). AIM OF STUDY: This study aims to elucidate the potential of DCX in treating VCI and its underlying mechanism. MATERIALS AND METHODS: Firstly, the cognitive behavior level, blood flow changes, and brain pathology changes were evaluated through techniques such as the Morris water maze, step-down, laser speckle, coagulation analysis, and pathological staining to appraise the DCX efficacy. Then, the DCX targeting pathways were decoded by merging metabolomics with transcriptomics. Finally, the levels of reactive oxygen species (ROS), Fe2+, and lipid peroxidation related to the targeting signaling pathways of DCX were detected by kit, and the expression levels of mRNAs or proteins related to ferroptosis were determined by qPCR or Western blot assays respectively. RESULTS: DCX improved cognitive abilities and cerebral perfusion significantly, and mitigated pathological damage in the hippocampal region of VCI model rats. Metabolomics revealed that DCX was able to call back 33 metabolites in plasma and 32 metabolites in brain samples, and the majority of the differential metabolites are phospholipid metabolites. Transcriptomic analysis revealed that DCX regulated a total of 3081 genes, with the ferroptosis pathway exhibiting the greatest impact. DCX inhibited ferroptosis of VCI rates by decreasing the levels of ferrous iron, ROS, and malondialdehyde (MDA) while increasing the level of superoxide dismutase (SOD) and glutathione (GSH) in VCI rats. Moreover, the mRNA and protein levels of ACSL4, LPCAT3, ALOX15, and GPX4, which are related to lipid metabolism in ferroptosis, were also regulated by DCX. CONCLUSION: Our research findings indicated that DCX could inhibit ferroptosis through the ACSL4/GPX4 signaling pathway, thereby exerting its therapeutic benefits on VCI.
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Disfunción Cognitiva , Ferroptosis , Animales , Ratas , Especies Reactivas de Oxígeno , Metabolómica , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/genética , Perfilación de la Expresión Génica , GlutatiónRESUMEN
Α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are crucial for properties of synaptic plasticity, such as long-term potentiation (LTP). LTP impairment can occur early in the onset of Alzheimer's disease (AD). The downregulation or decreased abundance of AMPAR expression in the postsynaptic membrane is closely associated with LTP impairment. Ceftriaxone (Cef) can improve LTP impairment in the early stages of AD in a mouse model. The purpose of this study was to explore the mechanism underlying this process from the aspects of AMPAR expression and ubiquitination degree. In this study, we found that ß-amyloid (Aß) treatment induced hippocampal LTP impairment and AMPAR downregulation and ubiquitination. Cef pretreatment ameliorated Aß-induced hippocampal LTP impairment, reduced AMPAR ubiquitination, and increased AMPAR expression, especially in the plasma membrane, in Aß-treated mice. Administration of USP46 siRNA and DHK (a specific blocker of glutamate transporter-1) significantly inhibited the above effects of Cef, suggesting a role for anti-AMPAR ubiquitination and upregulation of glutamate transporter-1 (GLT-1) in the Cef-induced improvements mentioned above. The above findings demonstrate that pretreatment with Cef effectively mitigated Aß-induced impairment of hippocampal LTP by suppressing the ubiquitination process of AMPARs in a GLT-1-dependent manner. These results provide novel insights into the underlying mechanisms elucidating the anti-AD by Cef.
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Long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) has been shown to be a regulator for many cancers, including non-small cell lung cancer (NSCLC). Therefore, its role and mechanism in the process of NSCLC deserve to be further revealed. The expression levels of GAS5, fat mass and obesity-associated protein (FTO) and bromodomain-containing protein 4 (BRD4) were detected by quantitative real-time PCR. Western blot analysis was used to examine the protein expression of FTO, BRD4, up-frameshift protein 1 (UPF1) and autophagy-related markers. Methylated RNA immunoprecipitation was used to assess the m6A level of GAS5 regulated by FTO. Cell proliferation and apoptosis were determined using MTT assay, EdU assay and flow cytometry. Autophagy ability was assessed by immunofluorescence staining and transmission electron microscope. Xenograft tumor model was constructed to explore the effects of FTO and GAS5 on NSCLC tumor growth in vivo. The interaction between UPF1 and GAS5 or BRD4 was confirmed by pull-down assay, RIP assay, dual-luciferase reporter assay, and chromatin immunoprecipitation. Fluorescent in situ hybridization was used to analyze the co-localization of GAS5 and UPF1. Actinomycin D treatment was employed to evaluate BRD4 mRNA stability. GAS5 was downregulated in NSCLC tissues and was associated with poor prognosis in NSCLC patients. FTO was highly expressed in NSCLC, and it inhibited GAS5 expression by reducing GAS5 m6A methylation level. GAS5 suppressed by FTO could promote the autophagic death of NSCLC cells in vitro and inhibit NSCLC tumor growth in vivo. In addition, GAS5 was able to interact with UPF1 to reduce the mRNA stability of BRD4. Knockdown of BRD4 reversed the inhibition of GAS5 or UPF1 silencing on the autophagic cell death of NSCLC. The findings of the study showed that lncRNA GAS5 mediated by FTO could contribute to the autophagic cell death of NSCLC by interacting with UPF1 to reduce BRD4 mRNA stability, suggesting that GAS5 might be a vital therapy target for NSCLC progression.
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Muerte Celular Autofágica , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , ARN Largo no Codificante , Animales , Humanos , Adenina/análogos & derivados , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Muerte Celular Autofágica/genética , Proteínas que Contienen Bromodominio/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proteínas de Ciclo Celular , Proliferación Celular/genética , Desmetilación , Modelos Animales de Enfermedad , Hibridación Fluorescente in Situ , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , MicroARNs/genética , Proteínas Nucleares/metabolismo , ARN Helicasas/metabolismo , ARN Largo no Codificante/metabolismo , Transactivadores/genética , Transactivadores/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
The association between HIV pre-exposure prophylaxis (PrEP) and the natural history of human papillomavirus (HPV) has not been well documented. Our objective was to evaluate the impact of PrEP on the prevalence, incidence, and clearance of anal HPV among men who have sex with men (MSM). Sexually active, HIV-negative MSM aged 18 years and older in Xinjiang, China since September 1, 2016, were enrolled in an ongoing observational cohort study of HPV. At baseline and every 6 months, an anal swab was taken to test for HPV and a questionnaire on sociodemographic characteristics and sexual behaviors was collected. Those who consented to receive PrEP were enrolled in an open-label PrEP intervention study from November 1, 2019, to June 30, 2021. This study analyzed data from participants present in the HPV cohort between November 1, 2019, and June 30, 2021. We compared the prevalence, incidence, and clearance of anal HPV between men who received PrEP (PrEP users) and those who did not (non-PrEP users), and compared men before and after initiating PrEP. We calculated prevalence ratios (PRs), incidence rate ratios (IRRs), and clearance rate ratios (CRRs) for both comparisons. Of the 870 participants present in the HPV cohort during the period between November 1, 2019, and June 30, 2021, 859 had adequate ß-globin for HPV genotype testing and were included in our study. Among them, 429 were PrEP users, while 430 were non-PrEP users. Median age was 32 years (interquartile range [IQR]: 26-38). Among PrEP users, 217 were tested for anal HPV before PrEP initiation. PrEP users had lower prevalence of HPV 45, 51, and 54 (PRs: 0.27 [95% CI: 0.09-0.80], 0.42 [0.21-0.85], and 0.41 [0.17-0.99], respectively) and lower clearance of HPV 16 (CRR: 0.31 [0.10-0.91]) compared with non-PrEP users. PrEP users exhibited lower prevalence of HPV 51 (PR: 0.31 [0.12-0.84]), lower incidence of HPV 6, 11, 16, 39 and 61 (IRRs: 0.34 [0.13-0.90], 0.26 [0.08-0.87], 0.44 [0.21-0.91], 0.21 [0.05-0.93], and 0.19 [0.04-0.82], respectively), as well as higher clearance of HPV 52 (CRR: 2.17 [1.08-4.35]) after PrEP initiation. PrEP use may lower the risk of HPV infection among MSM in Xinjiang, China. Our findings further extend the knowledge of the impact of PrEP on sexually transmitted infections.
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Infecciones por VIH , Infecciones por Papillomavirus , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Masculino , Humanos , Adulto , Virus del Papiloma Humano , Incidencia , Homosexualidad Masculina , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Prevalencia , Estudios de Cohortes , Papillomaviridae/genética , China/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & controlRESUMEN
The study of the currently known >3,000 species of snakes can provide valuable insights into the evolution of their genomes. Deinagkistrodon acutus, also known as Sharp-nosed Pit Viper, one hundred-pacer viper or five-pacer viper, is a venomous snake with significant economic, medicinal and scientific importance. Widely distributed in southeastern China and South-East Asia, D. acutus has been primarily studied for its venom. Here, we employed next-generation sequencing to assemble and annotate a highly continuous genome of D. acutus. The genome size is 1.46 Gb; its scaffold N50 length is 6.21 Mb, the repeat content is 42.81%, and 24,402 functional genes were annotated. This study helps to further understand and utilize D. acutus and its venom at the genetic level.
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To assess the prevalence and exacerbating factors of intimate partner violence in people with human immunodeficiency virus (PWH) in China, we conducted a cross-sectional study, involving 2792 PWH in 4 provinces in China from 1 September 2020 to 1 June 2021. The categories of intimate partner violence (IPV) included physical violence, sexual violence, emotional abuse, and controlling behavior. The severity of a violent act was divided into mild, moderate, and severe. Among PWH, the prevalence of IPV was 15.4% (95% confidence interval, 14.1%-16.8%). The severity of physical violence was mainly moderate, and the severity of sexual violence, emotional abuse, and controlling behavior was mainly mild. The prevalence of IPV in men was higher than that in women. Results from the multivariable logistic regression showed that age, ethnic, registered residence, education, and duration of HIV antiretroviral therapy were factors related to IPV in PWH (P < .05).
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Infecciones por VIH , Violencia de Pareja , Masculino , Humanos , Femenino , VIH , Estudios Transversales , Prevalencia , Violencia de Pareja/psicología , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Factores de Riesgo , Parejas Sexuales/psicologíaRESUMEN
OBJECTIVES: This study aimed to assess the effects of COVID-19 nonpharmaceutical interventions (NPIs) on the human papillomavirus (HPV) epidemic among men who have sex with men (MSM) in Xinjiang, China. METHODS: In our cohort study, we enrolled and followed HIV-negative MSM in Xinjiang, China, between 2016 and 2022. Anal swab samples were collected to test for HPV DNA. We used interrupted time series analysis to characterize the temporal trends in HPV prevalence, incidence, and clearance before (September 01, 2016, to July 16, 2020) and during the implementation of COVID-19 NPIs in Xinjiang (July 17, 2020, to March 31, 2022). We used binomial segmented regression models to estimate the impact of COVID-19 NPIs on HPV prevalence, incidence, and clearance. RESULTS: We recruited 1296 MSM who contributed to a total of 5374 HPV tests in our study. COVID-19 NPIs were associated with a 37.9% decrease in the prevalence (prevalence ratio, 0.621; 95% confidence interval, 0.465-0.830), 52.2% decrease in the incidence (risk ratio, 0.478; 0.377-0.606), and 40.4% increase in the clearance (risk ratio, 1.404; 1.212-1.627) of HPV of any genotype after the implementation of COVID-19 NPIs in Xinjiang. CONCLUSION: COVID-19 NPIs may lead to lower transmission and higher clearance of HPV among MSM. Future studies are needed to clarify the longer-term impact of COVID-19 on the transmission and natural history of HPV among MSM.
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COVID-19 , Infecciones por VIH , Infecciones por Papillomavirus , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Infecciones por VIH/complicaciones , Virus del Papiloma Humano , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/complicaciones , Factores de Riesgo , Estudios de Cohortes , Prevalencia , Incidencia , Análisis de Series de Tiempo Interrumpido , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/complicaciones , Papillomaviridae/genéticaRESUMEN
SET and MYND domain protein 2 (SMYD2) can methylate histone H3 at lysine36 (H3K36) and some non-histone substrates to play a role in tumorigenesis. However, It is unclear how SMYD2 contributes to chronic kidney disease (CKD). Here, AZ505 or LLY507, which could inhibit SMYD2, were used in cisplatin-induced CKD to investigate the effects and possible mechanisms by which they might act. We found that high expression of SMYD2 in cisplatin-induced CKD. However, AZ505 or LLY507 can significantly inhibit its expression, improve renal function injury and fibrosis induced by cisplatin, inhibit the transition of epithelial cells to a fibrogenic phenotype and fibrosis-related proteins, inhibit the expression of Inflammatory Cytokines (such as IL-6 and TNF-α), And inhibit the phosphorylation of pro-fibrosis molecule Smad3 and signal transduction and transcription activator-3 (STAT3) and up-regulated the expression of renal protective factor Smad7. In cultured tubular epithelial cells, AZ505 also can inhibit the expression of EMT, fibrosis-related proteins, and inflammatory cytokines in cisplatin-induced tubular epithelial cells. Based on these findings, SMYD2 may be a critical regulator of cisplatin-induced CKD and targeted pharmacological inhibition of SMYD2 may prevent cisplatin-induced CKD through Smad3 or STAT3-related signaling pathways.
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MicroRNAs (miRNAs) are a large class of non-coding RNAs that play important roles in the proliferation and differentiation of adipocytes. Our previous sequencing analysis revealed higher expression of miR-369-3p in the longissimus muscle of 2-month-old Aohan fine-wool sheep (AFWS) compared to 12-month-old sheep (P<0.05), suggesting that miR-369-3p may regulate fat deposition in AFWS. To test this, miR-369-3p mimics, inhibitors, and negative controls (NCs) were constructed and transfected into AFWS preadipocytes. After transfection with miR-369-3p mimics, we found a decrease (P<0.05) in the expression of genes and proteins related to cell proliferation and differentiation, detected by RT-qPCR (quantitative reverse transcription PCR) and western blot analyses. Moreover, EdU (5-ethynyl-2'-deoxyuridine) detection and Oil Red O staining showed a decrease (P<0.05) in cell proliferation and lipid accumulation, respectively. The opposite trends (P<0.05) were obtained after transfection with miR-369-3p inhibitors. In conclusion, the results showed that miR-369-3p can inhibit the proliferation and differentiation of AFWS preadipocytes, providing a theoretical basis to further explore the molecular mechanism of fat deposition in sheep and other domestic animals.
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As one of the most challenging environment issues worldwide, climate change has posed a serious threat to habitat, species, and people's livelihoods. In this study, a sector-disaggregated cross-regional emission analysis model is developed to systematically analyze enviro-economic effects of sector-level carbon mitigation efforts from both production and consumption perspectives for supporting climate change-related policymaking. A special case study of Hubei Province, China, is conducted to demonstrate the potential benefits of its use in the climate change related policymaking field. The power generation sector has been disaggregated into five subsectors based on different power generation technologies to help investigate the potential of such technologies to carbon emission mitigations. The carbon mitigation policy scenarios from both industry optimization and demand substitute perspectives will further be explored to provide bases for decision makers to formulate the desired carbon mitigation policy aimed at different regions and sectors. Results indicate that dominant direct and indirect CO2 emissions in Hubei Province are from the Production and supply of fossil-fuel power sector and Construction sector, respectively. When industry optimization policies on the fossil-fuel power sector (in Hubei), there are significant effects on the CO2 emission mitigation whichever regions. Therefore, industry optimization policies are suggested for implementation in specific sectors with close intersectoral/interprovince trade contacts and significant emissions to achieve joint carbon emission mitigations.
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Abnormal activation of the extrasynaptic N-methyl-d-aspartate receptor (NMDAR) contributes to the pathogenesis of Alzheimer's disease (AD). Ceftriaxone (Cef) can improve cognitive impairment by upregulating glutamate transporter-1 and promoting the glutamate-glutamine cycle in an AD mouse model. This study aimed to investigate the effects of Cef on synaptic plasticity and cognitive-behavioral impairment and to unravel the associated underlying mechanisms. We used an APPswe/PS1dE9 (APP/PS1) mouse model of AD in this study. Extrasynaptic components from hippocampal tissue homogenates were isolated using density gradient centrifugation. Western blot was performed to evaluate the expressions of extrasynaptic NMDAR and its downstream elements. Intracerebroventricular injections of adeno-associated virus (AAV)-striatal enriched tyrosine phosphatase 61 (STEP61 ) and AAV-STEP61 -shRNA were used to modulate the expressions of STEP61 and extrasynaptic NMDAR. Long-term potentiation (LTP) and Morris water maze (MWM) tests were performed to evaluate the synaptic plasticity and cognitive function. The results showed that the expressions of GluN2B and GluN2BTyr1472 in the extrasynaptic fraction were upregulated in AD mice. Cef treatment effectively prevented the upregulation of GluN2B and GluN2BTyr1472 expressions. It also prevented changes in the downstream signals of extrasynaptic NMDAR, including increased expressions of m-calpain and phosphorylated p38 MAPK in AD mice. Furthermore, STEP61 upregulation enhanced, whereas STEP61 downregulation reduced the Cef-induced inhibition of the expressions of GluN2B, GluN2BTyr1472 , and p38 MAPK in the AD mice. Similarly, STEP61 modulation affected Cef-induced improvements in induction of LTP and performance in MWM tests. In conclusion, Cef improved synaptic plasticity and cognitive behavioral impairment in APP/PS1 AD mice by inhibiting the overactivation of extrasynaptic NMDAR and STEP61 cleavage due to extrasynaptic NMDAR activation.
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Enfermedad de Alzheimer , Ratones , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Ceftriaxona/farmacología , Ceftriaxona/uso terapéutico , Modelos Animales de Enfermedad , Plasticidad Neuronal/fisiología , Cognición , Ratones Transgénicos , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
This paper examines the effects of interventions to reduce air pollution during two international events on air quality in Beijing and its neighbor cities. Air quality data were gathered from China's Ministry of Environmental Protection, meteorological data from the China Meteorological Administration and economic data from the China Statistical Yearbook. The paper uses fixed-effect panel data models to empirically evaluate air quality improvement in Beijing and other affected cities before, during, and after the 2008 Olympic Games and the 2014 Asia-Pacific Economic Cooperation summit. Results show substantial improvement in air quality in Beijing and neighboring cities during the two events. However, some of the air quality improvement achieved reverted within a year after the games and within a week after the summit. Furthermore, the improvement achieved during the summit completely reverted and air quality deteriorated severely five days after the summit. It is also found that air quality in China, at least in the cities included in this study, gradually improved over the past 15 years or so. The findings suggest that sustainable interventions and incentive-based programs to reduce emissions from industry production and traffic are the key to maintaining the air pollution reduction achieved during the events.
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We report on charge state measurements of laser-accelerated carbon ions in the energy range of several MeV penetrating a dense partially ionized plasma. The plasma was generated by irradiation of a foam target with laser-induced hohlraum radiation in the soft x-ray regime. We use the tricellulose acetate (C_{9}H_{16}O_{8}) foam of 2 mg/cm^{3} density and 1 mm interaction length as target material. This kind of plasma is advantageous for high-precision measurements, due to good uniformity and long lifetime compared to the ion pulse length and the interaction duration. We diagnose the plasma parameters to be T_{e}=17 eV and n_{e}=4×10^{20} cm^{-3}. We observe the average charge states passing through the plasma to be higher than those predicted by the commonly used semiempirical formula. Through solving the rate equations, we attribute the enhancement to the target density effects, which will increase the ionization rates on one hand and reduce the electron capture rates on the other hand. The underlying physics is actually the balancing of the lifetime of excited states versus the collisional frequency. In previous measurement with partially ionized plasma from gas discharge and z pinch to laser direct irradiation, no target density effects were ever demonstrated. For the first time, we are able to experimentally prove that target density effects start to play a significant role in plasma near the critical density of Nd-glass laser radiation. The finding is important for heavy ion beam driven high-energy-density physics and fast ignitions. The method provides a new approach to precisely address the beam-plasma interaction issues with high-intensity short-pulse lasers in dense plasma regimes.