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There are a large number of simple landfills in hilly areas, and the results of previous studies have shown that pollutants in landfills can spread via interflow and cause surface source pollution. The hybrid activated sludge-membrane aerated bioreactor (H-MABR) developed in a previous study can be used for the treatment of interflow with a low chemical oxygen demand (COD)/total nitrogen (TN) ratio, and it has been shown to be effective in laboratory simulations. To investigate the effectiveness of the H-MABR in treating interflow around landfills in real-world applications, an in-situ pilot-scale evaluation of the effectiveness of H-MABR operation was conducted at a landfill. The results indicated that the removal efficiencies of COD, TN, and ammonia nitrogen in interflow by H-MABR were 87.1 ± 6.0%, 80.9 ± 7.9%, and 97.9 ± 1.4%, respectively. The removal rate of TN reached 148.6-205.6 g-N/m3·d. The concentration of each pollutant in the effluent was in accordance with China's "Standard for pollution control on the landfill site of municipal solid waste (GB16889-2008)," wherein the COD, TN, and ammonia nitrogen of effluent should be less than 100 mg/L, 40 mg/L, and 25 mg/L, respectively. The results of community composition analysis and PICRUSt analysis based on 16S rRNA gene sequencing showed that there were different dominant functional bacteria between the inner and outer rings, but functional genes involved in the nitrification-denitrification, assimilated nitrate reduction, and dissimilated nitrate reduction pathway were all detected. Furthermore, except for the nitrite oxidation gene narG, the abundance of which did not significantly differ between the inner and outer rings, the abundance of the other functional genes was higher in the outer ring than in the inner ring. An economic evaluation revealed that the operation cost of interflow treatment by the H-MABR was as low as ¥2.78/m3; thus, the H-MABR is a shock-load-resistant and cost-effective technology for interflow treatment.
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Biopelículas , Análisis de la Demanda Biológica de Oxígeno , Reactores Biológicos , Desnitrificación , Nitrificación , Nitrógeno , Aguas del Alcantarillado , Nitrógeno/metabolismo , Eliminación de Residuos Líquidos/métodos , Proyectos PilotoRESUMEN
Emerging contaminants pose a potential risk to aquatic ecosystems in the Pearl River Basin, China, owing to the high population density and active industry. This study investigated samples from eight sewage treatment plants, and five surface water bodies of related watersheds. To screen the risk of emerging contaminants (ECs), and clarify their sources, this study calculated the risk quotient of detected chemical and performed source identification/apportionment using the positive matrix factorization method. In total, 149 organic pollutants were identified. Pharmaceuticals showed significant concentrations in sewage treatment plant samples (120.87 ng/L), compared with surface water samples (1.13 ng/L). The ecological risk assessment identified three chemicals with a heightened risk to aquatic organisms: fipronil sulfide, caffeine, and roxithromycin. Four principal sources of contaminants were identified: pharmaceutical wastewater, domestic sewage, medical effluent, and agricultural runoff. Pharmaceutical wastewater was the primary contributor (60.4 %), to the cumulative EC concentration and to ECs in sewage treatment plant effluent. Agricultural drainage was the main source of ECs in surface water. This study provides a strategy to obtain comprehensive information on the aquatic risks and potential sources of EC species in areas affected by artificial activities, which is of substantial importance to pollutant management and control.
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Monitoreo del Ambiente , Ríos , Aguas del Alcantarillado , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/análisis , Ríos/química , China , Aguas del Alcantarillado/análisis , Medición de Riesgo , Preparaciones Farmacéuticas/análisis , Aguas Residuales/análisis , Aguas Residuales/química , Eliminación de Residuos LíquidosRESUMEN
To overcome challenges in assessing the impact of environmental factors on heavy metal accumulation in soil due to limited comprehensive data, our study in Yangxin County, Hubei Province, China, analyzed 577 soil samples in combination with extensive big data. We used machine learning techniques, the potential ecological risk index, and the bivariate local Moran's index (BLMI) to predict Cr, Pb, Cd, As, and Hg concentrations in cultivated soil to assess ecological risks and identify pollution sources. The random forest model was selected for its superior performance among various machine learning models, and results indicated that heavy metal accumulation was substantially influenced by environmental factors such as climate, elevation, industrial activities, soil properties, railways, and population. Our ecological risk assessment highlighted areas of concern, where Cd and Hg were identified as the primary threats. BLMI was used to analyze spatial clustering and autocorrelation patterns between ecological risk and environmental factors, pinpointing areas that require targeted interventions. Additionally, redundancy analysis revealed the dynamics of heavy metal transfer to crops. This detailed approach mapped the spatial distribution of heavy metals, highlighted the ecological risks, identified their sources, and provided essential data for effective land management and pollution mitigation.
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Monitoreo del Ambiente , Aprendizaje Automático , Metales Pesados , Contaminantes del Suelo , Contaminantes del Suelo/análisis , Metales Pesados/análisis , Medición de Riesgo , China , Monitoreo del Ambiente/métodos , Suelo/químicaRESUMEN
China's unprecedented rapid urbanization has dramatically reshaped the urban built environment, disrupting the thermal balance of cities. This disruption causes the urban heat island (UHI) effect, adversely affecting urban sustainability and public health. Although studies have highlighted the remarkable impacts of the built environment on UHIs, the specific effects of its various structures and components remain unclear. In this study, a multidimensional remote sensing data set was used to quantify the atmospheric UHIs across 335 Chinese cities from 1980 to 2020. In conjunction with stocks of three end-use sectors and three material groups, the impacts of gridded material stocks on UHI variations were analyzed. The findings reveal that building stocks exert a predominant influence in 48% of cities. Additionally, the extensive use of metal and inorganic materials has increased thermal stress in 220 cities, leading to an average UHI increase of 0.54 °C. The effect of organic materials, primarily arising from mobile heat sources, is continuously increasing. Overall, this study elucidates the effect of the functional structure and material composition of urban landscapes on UHIs, highlighting the complexities associated with the influence of the built environment on the urban heat load.
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Entorno Construido , Ciudades , Calor , Urbanización , ChinaRESUMEN
Background and Objective: Osteoporotic fractures significantly impact individuals's quality of life and exert substantial pressure on the social pension system. This study aims to develop prediction models for osteoporotic fracture and uncover potential risk factors based on Electronic Health Records (EHR). Methods: Data of patients with osteoporosis were extracted from the EHR of Xinhua Hospital (July 2012-October 2017). Demographic and clinical features were used to develop prediction models based on 12 independent machine learning (ML) algorithms and 3 hybrid ML models. To facilitate a nuanced interpretation of the results, a comprehensive importance score was conceived, incorporating various perspectives to effectively discern and mine critical features from the data. Results: A total of 8530 patients with osteoporosis were included for analysis, of which 1090 cases (12.8%) were fracture patients. The hybrid model that synergistically combines the Support Vector Machine (SVM) and XGBoost algorithms demonstrated the best predictive performance in terms of accuracy and precision (above 90%) among all benchmark models. Blood Calcium, Alkaline phosphatase (ALP), C-reactive Protein (CRP), Apolipoprotein A/B ratio and High-density lipoprotein cholesterol (HDL-C) were statistically found to be associated with osteoporotic fracture. Conclusions: The hybrid machine learning model can be a reliable tool for predicting the risk of fracture in patients with osteoporosis. It is expected to assist clinicians in identifying high-risk fracture patients and implementing early interventions.
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Background: IQGAP3 plays a crucial role in regulating cell proliferation, division, and cytoskeletal organization. Abnormal expression of IQGAP3 has been linked to various tumors, but its function in glioma is not well understood. Methods: Various methods, including genetic differential analysis, single-cell analysis, ROC curve analysis, Cox regression, Kaplan-Meier analysis, and enrichment analysis, were employed to analyze the expression patterns, diagnostic potential, prognostic implications, and biological processes involving IQGAP3 in normal and tumor tissues. The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence. Additionally, the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3. Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms. Results: High IQGAP3 expression in gliomas is associated with an unfavorable prognosis, particularly in wild-type IDH and 1p/19q non-codeleted gliomas. Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle, PI3K/AKT signaling, p53 signaling, and PLK1-related pathways. Furthermore, IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma. BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy. In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells, with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression. Conclusion: IQGAP3 shows promise as a valuable biomarker for diagnosis, prognosis, and immunotherapeutic strategies in gliomas.
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Neoplasias Encefálicas , Glioma , Humanos , Pronóstico , Neoplasias Encefálicas/patología , Variaciones en el Número de Copia de ADN , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Glioma/patología , Microambiente Tumoral/genética , Proteínas Activadoras de GTPasaRESUMEN
Several mechanisms underlying nephrolithiasis, one of the most common urological diseases, involve calcium oxalate formation, including oxidative stress, inflammatory reactions, fibrosis, pyroptosis, and apoptosis. Although lycopene has strong antioxidant activity, its protective effects against CaOx-induced injury have not yet been reported. This study aimed to systematically investigate the protective effects of lycopene and explore its mechanisms and molecular targets. Crystal deposition, renal function, oxidative stress, inflammatory response, fibrosis, pyroptosis, and apoptosis were assessed to evaluate the renoprotective effects of lycopene against crystal formation in a CaOx rat model and oxalate-stimulated NRK-52E and HK-2 cells. Lycopene markedly ameliorated crystal deposition, restored renal function, and suppressed kidney injury by reducing oxidative stress, apoptosis, inflammation, fibrosis, and pyroptosis in the rats. In cell models, lycopene pretreatment reversed reactive oxygen species increase, apoptotic damage, intracellular lactate dehydrogenase release, cytotoxicity, pyroptosis, and extracellular matrix deposition. Network pharmacology and proteomic analyses were performed to identify lycopene target proteins under CaOx-exposed conditions, and the results showed that Trappc4 might be a pivotal target gene for lycopene, as identified by cellular thermal shift assay and surface plasmon resonance analyses. Based on molecular docking, molecular dynamics simulations, alanine scanning mutagenesis, and saturation mutagenesis, we observed that lycopene directly interacts with Trappc4 via hydrophobic bonds, which may be attributed to the PHE4 and PHE142 residues, preventing ERK1/2 or elevating AMPK signaling pathway phosphorylation events. In conclusion, lycopene might ameliorate oxalate-induced renal tubular epithelial cell injury via the Trappc4/ERK1/2/AMPK pathway, indicating its potential for the treatment of nephrolithiasis.
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Apoptosis , Fibrosis , Licopeno , Nefrolitiasis , Estrés Oxidativo , Piroptosis , Ratas Sprague-Dawley , Solanum lycopersicum , Licopeno/farmacología , Nefrolitiasis/metabolismo , Nefrolitiasis/tratamiento farmacológico , Animales , Estrés Oxidativo/efectos de los fármacos , Ratas , Piroptosis/efectos de los fármacos , Apoptosis/efectos de los fármacos , Masculino , Solanum lycopersicum/química , Humanos , Oxalato de Calcio/metabolismo , Oxalato de Calcio/química , Línea Celular , Riñón/efectos de los fármacos , Riñón/metabolismo , Inflamación/metabolismo , Sustancias Protectoras/farmacologíaRESUMEN
OBJECTIVES: To establish a predictive model for sepsis after percutaneous nephrolithotomy (PCNL) using machine learning to identify high-risk patients and enable early diagnosis and intervention by urologists. METHODS: A retrospective study including 694 patients who underwent PCNL was performed. A predictive model for sepsis using machine learning was constructed based on 22 preoperative and intraoperative parameters. RESULTS: Sepsis occurred in 45 of 694 patients, including 16 males (35.6%) and 29 females (64.4%). Data were randomly segregated into an 80% training set and a 20% validation set via 100-fold Monte Carlo cross-validation. The variables included in this study were highly independent. The model achieved good predictive power for postoperative sepsis (AUC = 0.89, 87.8% sensitivity, 86.9% specificity, and 87.4% accuracy). The top 10 variables that contributed to the model prediction were preoperative midstream urine bacterial culture, sex, days of preoperative antibiotic use, urinary nitrite, preoperative blood white blood cell (WBC), renal pyogenesis, staghorn stones, history of ipsilateral urologic surgery, cumulative stone diameters, and renal anatomic malformation. CONCLUSION: Our predictive model is suitable for sepsis estimation after PCNL and could effectively reduce the incidence of sepsis through early intervention.
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Cálculos Renales , Nefrolitotomía Percutánea , Nefrostomía Percutánea , Sepsis , Masculino , Femenino , Humanos , Nefrolitotomía Percutánea/efectos adversos , Nefrostomía Percutánea/efectos adversos , Cálculos Renales/cirugía , Cálculos Renales/complicaciones , Estudios Retrospectivos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Sepsis/diagnóstico , Sepsis/etiología , Aprendizaje AutomáticoRESUMEN
BACKGROUND: Active health is a new concept, model, and system to maintain the state of whole-person health. In the context of the increasingly serious health problems of primary and secondary school teachers, it is of great significance to explore the relationship between physical activity and primary and secondary school teachers' health based on the active health perspective. METHODS: The survey involving 741 primary and secondary school teachers across representative provinces in China utilized the International Physical Activity Scale, Body Imagery State Scale, and General Self-Efficacy Scale. Data analysis employed SPSS 25.0 and Amos 24.0 software. RESULTS: While no significant gender disparities were observed in body image and self-efficacy, age groups exhibited a bipartite and "V" shaped distribution. Female teachers demonstrated higher physical activity levels (2456.46) and superior physical fitness compared to males (2297.86). A positive correlation emerged between physical activity, body image, self-efficacy, and health status. Importantly, body image and self-efficacy partially mediated the relationship between physical activity and health status, accounting for 82.31% of the total effect. CONCLUSIONS: Primary and secondary school teachers have real problems such as teachers' physical activity is generally insufficient, teachers' body image status is generally poor, and teachers' self-efficacy is low; physical activity is an important factor in promoting primary and secondary school teachers' health status, and low, medium, and high levels of activity all have a promoting effect on the health of primary and secondary school teachers, and the more active primary and secondary school teachers are in terms of physical activity, the better their body image, self-efficacy, and health status are, and the more active primary and secondary school teachers are in terms of physical activity, the more positive the physical activity, self-efficacy, and health status are. The more physically active primary and secondary school teachers are, the better their physical intention, self-efficacy and health status are. SUGGESTIONS: improve the quality and effectiveness, promote the concept of active health among teachers; empower teachers, strengthen the institutional protection of teachers' health; reduce the burden and increase the quantity,and optimise the supply of health services for teachers.
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Imagen Corporal , Autoeficacia , Masculino , Humanos , Femenino , Ejercicio Físico , Estado de Salud , Maestros , Instituciones AcadémicasRESUMEN
This study collected data on waste generation and management in China between 1979 and 2020 from government statistics and literature and reviewed the development of municipal solid waste (MSW) management in China. The extended stochastic impact by regression on population, affluence and technology (STIRPAT) model was employed to identify the driving forces of MSW generation, and the cointegration analysis showed that economy (0.35, t = -3.47), industrial structure (3.34, t = -20.77) and urbanization (-1.5, t = 5.678) were the significant socioeconomic driving forces in the long run. By employing the framework of evolutionary economics, this study then investigated the internal rules of long-term interaction between socioeconomic factors and MSW management. The results indicate that, in the long run, MSW management development can be viewed as an evolutionary process that includes a continuous adaptation to external socioeconomic factors and the co-evolution of internal institutions and technologies. Adaptation and diversity of institutions and technologies play an important role in achieving sustainable waste management and circular economy (CE). This study offers a novel evolutionary perspective for explaining dynamic changes of MSW management in China, as well as recommendations for emerging economies to achieve sustainable waste management and CE goals.
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Background: Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune disease that can affect any organ or tissue in the body, and is characterized by intensive infiltration of IgG4-positive plasma cells, and elevated serum IgG4 levels. IgG4-RD causes renal impairment of unknown pathogenesis that may progress to kidney failure. However, few case of IgG4-RD mimicking malignant ureter tumor leading to severe hydronephrosis. Case Description: This report describes a 38-year-old male patient who was hospitalized for sudden waist pain. Enhanced abdominal computed tomography (CT) revealed a mass involving the right ureter. He presented to the urologist with severe right hydronephrosis. Urinalysis revealed occult blood (3+), and atypical cells were observed in urine cytology, raising the possibility of a ureteral malignancy. After that, the patient underwent diagnostic ureteroscopy instead of direct nephroureterectomy and was found not to have any malignancy. The patient received laparoscopic partial ureteral resection and anastomosis. Histologically, there were observations of IgG4-positive plasma cell infiltration exceeding 10 cells per high-power field, as well as a high ratio of IgG4-positive/IgG-positive cells exceeding 40%. And histopathology revealed ureteral IgG4-related disease, with no evidence of urothelial carcinoma. Conclusions: IgG4-RD has previously been reported in lesions involving the ureters, but misdiagnosis and subsequent radical nephroureterectomy can cause lifelong regret for the patient in having lost one side of the urinary tract. To avoid such misdiagnoses, clinicians should consider IgG4-RD as a potential condition.
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Early brain injury (EBI) is the leading cause of poor prognosis for patients suffering from subarachnoid hemorrhage (SAH), particularly learning and memory deficits in the repair phase. A recent report has involved calcium/calmodulin-dependent protein kinase II (CaMKII) in the pathophysiological process underlying SAH-induced EBI. Alpha-asarone (ASA), a major compound isolated from the Chinese medicinal herb Acorus tatarinowii Schott, was proven to reduce secondary brain injury by decreasing CaMKII over-phosphorylation in rats' model of intracerebral hemorrhage in our previous report. However, the effect of ASA on SAH remains unclear, and the role of CaMKII in both acute and recovery stages of SAH needs further investigation. In this work, we first established a classic SAH rat model by endovascular perforation and intraperitoneally administrated different ASA doses (10, 20, and 40 mg/kg) 2 h after successful modeling. Then, the short- and long-term neurobehavioral performances were blindly evaluated to confirm ASA's efficacy against SAH. Subsequently, we explored ASA's therapeutic mechanism in both acute and recovery stages using histopathological examination, TUNEL staining, flow cytometry, Western-blot, double-immunofluorescence staining, and transmission electron microscopy (TEM) observation. Finally, KN93, a selective CaMKII inhibitor, was applied in oxyhemoglobin-damaged HT22 cells to explore the role of CaMKII in ASA's neuroprotective effect. The results demonstrated that ASA alleviated short- and long-term neurological dysfunction, reduced mortality and seizure rate within 24 h, and prolonged 14-day survival in SAH rats. Histopathological examination showed a reduction of neuronal damage and a restoration of the hippocampal structure after ASA treatment in both acute and recovery phases of SAH. In the acute stage, the Western-blot and flow cytometer analyses showed that ASA restored E/I balance, reduced calcium overload and CaMKII phosphorylation, and inhibited mitochondrion-involved apoptosis, thus preventing neuronal damage and apoptosis underlying EBI post-SAH. In the recovery stage, the TEM observation, double-immunofluorescence staining, and Western-blot analyses indicated that ASA increased the numbers of synapses and enhanced synaptic plasticity in the ipsilateral hippocampi, probably by promoting NR2B/CaMKII interaction and activating subsequent CREB/BDNF/TrkB signaling pathways. Furthermore, KN93 notably reversed ASA's neuroprotective effect on oxyhemoglobin-damaged HT22 cells, confirming CaMKII a potential target for ASA's efficacy against SAH. Our study confirmed for the first time that ASA ameliorated the SAH rats' neurobehavioral deterioration, possibly via modulating CaMKII-involved pathways. These findings provided a promising candidate for the clinical treatment of SAH and shed light on future drug discovery against SAH.
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Derivados de Alilbenceno , Anisoles , Bencenosulfonamidas , Bencilaminas , Lesiones Encefálicas , Fármacos Neuroprotectores , Hemorragia Subaracnoidea , Humanos , Ratas , Animales , Ratas Sprague-Dawley , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/patología , Calcio/uso terapéutico , Oxihemoglobinas/uso terapéutico , Lesiones Encefálicas/etiologíaRESUMEN
Lessening energy-related carbon emissions has become a crucial measure to achieve Chinese carbon neutrality. This study is the first to construct a Difference in Carbon pressures-adjusted Human Development Index (DCHDI) model for the purpose of exploring the coupling effect between carbon emissions and human development variety from 2000 to 2019 in Chinese provinces. We demonstrate the following. (1) The total energy-related carbon footprint of 30 provinces in China reached 10.2 billion tons in 2019, with an average annual growth rate of 6.93% over the past two decades; and the provinces with the highest carbon emissions per capita are InnerMongolia, Ningxia, and Shanxi. (2) At the provincial level, we observed that the Human Development Index (HDI), which includes life expectancy, education, and income, has been rising, while Beijing, Shanghai, and Tianjin entered the super-high HDI level before 2008. (3) The entire coupling effect of 30 Chinese provinces has been broadly fortified in the last 20 years, but the growth rate of DCHDI values in 2011-2019 has slowed down compared with that in 2000-2010; the clustering phenomenon demonstrated that this discovery is associated with historical peaks in total carbon emissions. (4) The coordination degree of carbon emissions per capita and HDI was verified, and 96% of the data points were found in the range of super high coupling coordination degree. Overall, this study provides the government with worthwhile guidance for decision-making and carbon reduction strategies for other countries struggling to advance human sustainable development.
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Carbono , Desarrollo Económico , Humanos , China , Carbono/análisis , Beijing , Dióxido de Carbono/análisisRESUMEN
As the largest beer producer and consumer in the world, China's endeavors to reduce solid waste generation (SWG) and carbon emissions (CEs) in the course of beer production assume paramount significance. This study aims to assess the SWG and CEs in beer production within China at both national and provincial levels, and further delves into the spatial distribution characteristics and evolving patterns across the country. Key findings of the study include:(1) Peak SWG and CEs were recorded in 2013, reaching 861.62 million tons and 2315.10 tCO2e, respectively, followed by a consistent decline. (2) Among the three types of solid waste, spent grain exhibited the highest generation rate, contributing to 94.38% of the total. (3) The emergence of China's beer industry dates back to the 1980s in the northeastern region, expanding to the southeastern and the Yangtze River Basin during the 1990s, ultimately extending nationwide. (4) The spatial distribution of beer production revealed significant regional disparities and notable industry concentration. Notably, many provinces witnessed reduced CEs from beer production starting in 2015, although the extent of reduction varied in different provinces. These findings serve as a scientific foundation for formulating emission reduction strategies in beer producing and offer insights for other food industries in China.
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Carbono , Residuos Sólidos , Residuos Sólidos/análisis , Carbono/análisis , Cerveza/análisis , Industrias , China , Dióxido de Carbono/análisis , Desarrollo EconómicoRESUMEN
Material stocks have created alternative perspectives in many environmental and climate studies. Their significance nonetheless may be under-explored, partially due to scarcity of more precise, timely and higher-resolution information. To address this limitation, our present study developed a gridded material stocks dataset for China in Year 2000 and 2020, by examining the geographical distribution and geometric configurations of the human-made stock-containing environment. The stocks of twelve materials embodied in five end-use sectors and 104 products and constructions were assessed at a resolution of 1 × 1 km grid. Material intensity in each product or construction component was carefully evaluated and tagged with its geometric conformation. The gridded stocks aggregately are consistent with the stock estimation across 337 prefectures and municipalities. The reliability of our assessment was also validated by previous studies from national, regional, to grid levels. This gridded mapping of material stocks may offer insights for urban-rural disparities, urban mining opportunity, and climate and natural disaster resilience.
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BACKGROUND: Urinary extracellular vesicles (EVs) have gained increasing interest in recent years as a potential source of noninvasive biomarkers of diseases related to urinary organs, but knowledge of the mechanism is still limited. The current study sought to clarify the mechanism of urinary EVs behind di-(2-ethylhexyl) phthalate (DEHP)-induced hypospadias via PFN2 delivery. METHOD: PFN2 expression in hypospadias was predicted by bioinformatics analysis. Following the induction of a hypospadias rat model using DEHP, rats were injected with EVs and/or underwent alteration of PFN2 and TGF-ß1 to assess their effects in vivo. The extracted rat urothelial cells (UECs) were co-cultured with EVs extracted from urine for in vitro experiments. RESULT: Microarray analysis predicted poor PFN2 expression in hypospadias. Upregulated PFN2 was found in urinary EVs, and restrained epithelial-mesenchymal transition (EMT) was observed in DEHP-exposed rats. Urinary EVs or PFN2 overexpression increased SMAD2, SMAD3, and TGF-ß1 protein expression and SMAD2 and SMAD3 phosphorylation in UECs and DEHP-exposed rats. UEC migration, invasion, and EMT were augmented by EV co-culture or upregulation of PFN2. Of note, the silencing of TGF-ß1 counterweighed the effect of PFN2. Besides, EV co-culture or overexpression of PFN2 or TGF-ß1 elevated the body weight, anal-genital distance (AGD), anal-genital index (AGI), and EMT of DEHP-exposed rats. CONCLUSION: In summary, urinary EVs activated the SMAD/TGF-ß1 pathway to induce EMT via PFN2 delivery, thus protecting against DEHP-induced hypospadias. (1) EMT in epithelial cells inhibits DEHP-induced hypospadias. (2) Urine-derived EVs deliver PFN2 to promote EMT in epithelial cells. (3) PFN2 can activate the SMAD/TGF-ß1 signaling axis. (4) Urine-derived EVs can transmit PFN2 to activate the SMAD/TGF-ß1 signaling axis, thus promoting EMT and inhibiting the occurrence of hypospadias.
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Dietilhexil Ftalato , Hipospadias , Humanos , Masculino , Ratas , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Transición Epitelial-Mesenquimal , Hipospadias/inducido químicamente , Dietilhexil Ftalato/toxicidad , Profilinas/farmacologíaRESUMEN
Gas-phase NbMgn (n = 2-12) clusters were fully searched by CALYPSO software, and then the low-energy isomers were further optimized and calculated under DFT. It is shown that the three lowest energy isomers of NbMgn (n = 3-12) at each size are grown from two seed structures, i.e., tetrahedral and pentahedral structures, and the transition size occurs at the NbMg8 cluster. Interestingly, the relative stability calculations of the NbMg8 cluster ground-state isomer stand out under the examination of several parameters' calculations. The charge-transfer properties of the clusters of the ground-state isomers of various sizes had been comprehensively investigated. In order to be able to provide data guidance for future experimental probing of these ground-state clusters, this work also predicted infrared and Raman spectra at the same level of theoretical calculations. The results show that the multipeak nature of the IR and Raman spectra predicts that it is difficult to distinguish them directly. Finally, the optical properties of these clusters were investigated by calculating the static linear, second-order nonlinear, and third-order nonlinear coefficients. Importantly and interestingly, the NbMg8 cluster was shown to have superior nonlinear optical characteristics to all other clusters; thus, it is a powerful candidate for a potentially ultrasensitive nonlinear optical response device for some special purpose.
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STUDY DESIGN: Prospective cohort study. OBJECTIVES: Diabetes mellitus (DM) is associated with unfavourable patient-reported outcomes after spine surgery. Chronic low back pain (CLBP) with Modic Changes (MCs) in the lumbar vertebrae, as observed on MRI, forms a specific subgroup. This study aims to investigate the potential influence of DM on CLBP with MCs. METHODS: This study involved 259 patients with CLBP accompanied MCs. We recorded the patient-reported outcomes (visual analogue scale (VAS), Oswestry Disability Index (ODI), and Roland-Morris Disability Questionnaire (RMDQ)) at baseline, 3, 6, and 12 months. Multivariable linear regression analyses were performed to determine predictors of patient-reported outcomes. RESULTS: 103 patients had DM. Patients with DM exhibited higher VAS (P < .05), ODI (P < .001), and RMDQ (P < .001) scores at 3, 6, and 12 months, while patients without DM experienced more significant improvements in the scores over time (P < .001). Patients with DM reported longer durations of physical exercise (P = .007). Additionally, patients without DM had a significantly higher patient satisfaction index (P < .001) and a lower prevalence of hypertension (P < .001). Notably, significant differences were observed in the distribution of MCs of lumbar vertebrae (P = .034) and Pfirrmann grades of intervertebral disc degeneration between two groups (P < .001). CONCLUSION: Patients with DM demonstrated poorer patient-reported outcomes compared to those without DM in 1-year. DM emerged as an independent predictor of adverse patient-reported outcomes. It can be utilized to enhance the management and treatment of CLBP in patients with MCs.