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Both copper (Cu) excess and boron (B) deficiency are often observed in some citrus orchard soils. The molecular mechanisms by which B alleviates excessive Cu in citrus are poorly understood. Seedlings of sweet orange (Citrus sinensis (L.) Osbeck cv. Xuegan) were treated with 0.5 (Cu0.5) or 350 (Cu350 or Cu excess) µM CuCl2 and 2.5 (B2.5) or 25 (B25) µM HBO3 for 24 weeks. Thereafter, this study examined the effects of Cu and B treatments on gene expression levels revealed by RNA-Seq, metabolite profiles revealed by a widely targeted metabolome, and related physiological parameters in leaves. Cu350 upregulated 564 genes and 170 metabolites, and downregulated 598 genes and 58 metabolites in leaves of 2.5 µM B-treated seedlings (LB2.5), but it only upregulated 281 genes and 100 metabolites, and downregulated 136 genes and 40 metabolites in leaves of 25 µM B-treated seedlings (LB25). Cu350 decreased the concentrations of sucrose and total soluble sugars, and increased the concentrations of starch, glucose, fructose, and total nonstructural carbohydrates (TNC) in LB2.5, but it only increased the glucose concentration in LB25. Further analysis demonstrated that B addition reduced the oxidative damage and alterations in primary and secondary metabolisms caused by Cu350; and alleviated the impairment of Cu350 to photosynthesis and cell wall metabolism, thus improving leaf growth. LB2.5 exhibited some adaptive responses to Cu350 to meet the increasing need for the dissipation of excessive excitation energy (EEE) and the detoxification of reactive oxygen species (reactive aldehydes) and Cu. Cu350 increased photorespiration, xanthophyll cycle-dependent thermal dissipation, nonstructural carbohydrate accumulation, and secondary metabolite biosynthesis and abundances; and upregulated tryptophan metabolism and related metabolite abundances, and some antioxidant-related gene expression, and some antioxidant abundances. Additionally, this study identified some metabolic pathways, metabolites, and genes that might lead to Cu tolerance in leaves.
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OBJECTIVE: To investigate the reliability and validity of the Chinese version of simplified nutritional appetite questionnaire (SNAQ). METHODS: The SNAQ was translated and back-translated for the study population. We surveyed 122 community-dwelling residents aged ≥60 years in Beijing's residential communities. Participants underwent face-to-face surveys including the SNAQ, mini-nutritional assessment short-form (MNA-SF), FRAIL scale, Sarcopenia-Five (SCAR-F), 15-item Geriatric Depression Scale (GDS-15), 7-item Generalized Anxiety Disorder (GAD-7), 8-item Oral Frailty Index (OFI-8), 10-item Eating Assessment Tool (EAT-10), and Mini-Mental State Examination (MMSE). Cronbach's alpha was used to measure the internal consistency and the relationship between individual items. The construct validity was verified using the KMO-Bartlett. Concurrent validity was established to validate measures of the same constructs. RESULTS: Cronbach's alpha measured the internal consistency of the questionnaire at 0.694. The split-half reliability stood at 0.725. The construct validity of the SNAQ was confirmed using a KMO-Bartlett value of 0.648 (P <0.001). The MNA-SF, as validation benchmark, has a correlation coefficient of 0.345 (P =0.001). CONCLUSION: The Chinese version of the SNAQ has good reliability and validity for older adults in community settings.
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OBJECTIVE: Achieving textbook outcome (TO) implies a smooth recovery post-operation without specified composite complications. This study aimed to evaluate TO in laparoscopic pancreaticoduodenectomy (LPD) and identify independent risk factors associated with achieving TO. METHODS: We conducted a retrospective analysis of data from a randomized controlled trial on LPD at West China Hospital (ChiCTR1900026653). Patients were categorized into the TO and non-TO groups. Perioperative variables were compared between these groups. Multivariate logistic regression was utilized to identify the risk factors. RESULTS: A total of 200 consecutive patients undergoing LPD were included in this study. TO was achieved in 82.5% (n = 165) of the patients. Female patients (OR: 2.877, 95% CI: 1.219-6.790; P = 0.016) and those with a hard pancreatic texture (OR: 2.435, 95% CI: 1.018-5.827; P = 0.046) were associated with an increased likelihood of achieving TO. CONCLUSIONS: TO can be achieved in more than 80% of patients in a high-volume LPD center. Independent risk factors associated with achieving TO included gender (male) and pancreatic texture (soft).
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Laparoscopía , Pancreaticoduodenectomía , Humanos , Pancreaticoduodenectomía/métodos , Pancreaticoduodenectomía/efectos adversos , Femenino , Masculino , Laparoscopía/métodos , Persona de Mediana Edad , Factores de Riesgo , Estudios Retrospectivos , Anciano , Resultado del Tratamiento , Estudios Prospectivos , China/epidemiología , Adulto , Hospitales de Alto Volumen , Complicaciones Posoperatorias/epidemiologíaRESUMEN
Maintaining and improving ecological resilience is of great practical significance for the Yellow River Basin to reduce potential ecological risks and deliver sustainable development. Based on the essential characteristics of evolutionary resilience, this paper developed an ecological resilience index system of "resistance-recovery-reconstruction-renewal" and calculated the ecological resilience of 75 prefecture-level cities in the Yellow River Basin from 2007 to 2021 with the improved TOPSIS method. Then the spatiotemporal evolution characteristics of ecological resilience were analyzed using the gravity center-standard deviation ellipse, Dagum Gini coefficient decomposition, and spatial autocorrelation analysis. Furthermore, the dynamic spatial Durbin model (DSDM) was used to investigate the influencing factors of ecological resilience. The main results are as follows: (1) The ecological resilience of the Yellow River Basin showed an overall fluctuating upward trend, and the average annual growth rate in the downstream region was larger than in the upstream and midstream regions. (2) Cities with similar levels of ecological resilience were distributed in a "large settlement, small scattered" pattern. The center of gravity shifted to the southeast, and the spatial distribution exhibited a "northwest-southeast" pattern and a trend towards an "east-west" pattern. The primary source of spatial differences was the intensity of transvariation. (3) The ecological resilience in the Yellow River Basin showed significant spatial clustering, with the H-H clustering area shifting from the Hubao-Eyu urban agglomeration to the Shandong Peninsula urban agglomeration, and the L-L clustering area mainly distributed around the Central Plains city cluster. (4) The ecological resilience of the Yellow River Basin exhibited significant snowball, spillover, and siphon effects in time, space, and space-time dimensions, respectively. In the short and long term, population density and openness significantly positively affected the ecological resilience of local and surrounding cities. Urbanization had a long-term effect on ecological resilience without a short-term effect. GDP per capita and industrial structure only imparted a significant positive influence on local ecological resilience. The negative spatial spillover of the intensity of financial investment in technological innovation gradually turned into a positive effect.
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The Helicobacter pylori infection in the stomach is the key reason for gastric mucosal bleeding. Eliminating gastric Helicobacter pylori by oral treatment remains difficult due to the presence of the gastric mucosal layer, which acts as a physical barrier to drugs via oral administration. In this study, a magnetic-navigable microneedle drug delivery platform (MNsD) for oral administration, featuring differential dual-mode drug release rate, was designed to fulfil rapid gastric hemostasis and overcome the gastric barriers for long-lasting Helicobacter pylori inhibition in stomach. MNs-D was created by rationally loading the carrier substrate, which was composed of silk fibroin with variable solubility, with antibiotics and hemostats. In vitro experiments showed MNs-D may sustainably eradicate Helicobacter pylori in stimulated gastric juices with long-lasting drug release (79 % in 24 h) and quickly establish hemostasis with instant drug release (92 % within 60 s). Most importantly, in vivo studies demonstrated MNs-D overcame the unsettling gastric mucosal barrier in traditional therapies of oral administration by insertion into the GML under magnetic navigation, resulting in sustained antibiotic release for long-lasting Helicobacter pylori eradiation (99 %). For differential dual-mode medication release against gastric Helicobacter pylori infections, this study may have firstly examined the effects of magnetic navigated microneedles administered orally.
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Antibacterianos , Sistemas de Liberación de Medicamentos , Fibroínas , Mucosa Gástrica , Infecciones por Helicobacter , Helicobacter pylori , Agujas , Helicobacter pylori/efectos de los fármacos , Animales , Fibroínas/química , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Administración Oral , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/química , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiología , Mucosa Gástrica/efectos de los fármacos , Liberación de Fármacos , Hemostasis/efectos de los fármacos , Estómago/microbiología , Estómago/efectos de los fármacos , Masculino , RatonesRESUMEN
Acute myeloid leukemia (AML) is a clonal malignancy originating from leukemia stem cells, characterized by a poor prognosis, underscoring the necessity for novel therapeutic targets and treatment methodologies. This study focuses on Ras homolog family member F, filopodia associated (RHOF), a Rho guanosine triphosphatase (GTPase) family member. We found that RHOF is overexpressed in AML, correlating with an adverse prognosis. Our gain- and loss-of-function experiments revealed that RHOF overexpression enhances proliferation and impedes apoptosis in AML cells in vitro. Conversely, genetic suppression of RHOF markedly reduced the leukemia burden in a human AML xenograft mouse model. Furthermore, we investigated the synergistic effect of RHOF downregulation and chemotherapy, demonstrating significant therapeutic efficacy in vivo. Mechanistically, RHOF activates the AKT/ß-catenin signaling pathway, thereby accelerating the progression of AML. Our findings elucidate the pivotal role of RHOF in AML pathogenesis and propose RHOF inhibition as a promising therapeutic approach for AML management.
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BACKGROUND AND PURPOSE: Liver cancer is the fourth leading cause of cancer-related death worldwide, with hepatocellular carcinoma (HCC) being the most common type of primary liver cancer. APG-1252 is a small molecule inhibitor targeting Bcl-2 and Bcl-xl. However, its anti-tumor effects in HCC, alone or in combination with Cabozantinib, have not been extensively studied. EXPERIMENTAL: Approach: TCGA database analysis was used to analysis the gene expression levels of Bcl-2 and Bcl-xl in HCC tissues. Western blot was employed to detect the protein expression levels. And the inhibitory effects of APG-1252 and Cabozantinib on the proliferation of HCC cell lines was detected by CCK-8. The effect on the migration and invasion of HCC cells was verified by transwell assay. Huh7 xenograft model in nude mice was used to investigate the combination antitumor effect in vivo. KEY RESULTS: Our study demonstrated that APG-1252 monotherapy inhibited the proliferation and migration ability of HCC cells, and induced HCC cells apoptosis. The combination of APG-1252 and Cabozantinib showed significant synergistic antitumor effects. Furthermore, the in vivo experiment demonstrated that the combination therapy exerted a synergistic effect in delaying tumor growth, notably downregulating MEK/ERK phosphorylation levels. In terms of mechanism, Cabozantinib treatment caused an increase in the phosphorylation levels of CREB and Bcl-xl proteins, while the combination with APG-1252 mitigated this effect, thereby enhanced the antitumor effect of Cabozantinib. CONCLUSION AND IMPLICATIONS: Our findings suggest that APG-1252 in combination with Cabozantinib offers a more effective treatment strategy for HCC patients, warranting further clinical investigation.
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Anilidas , Carcinoma Hepatocelular , Proliferación Celular , Neoplasias Hepáticas , Ratones Desnudos , Piridinas , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína bcl-X , Animales , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Anilidas/farmacología , Anilidas/uso terapéutico , Piridinas/farmacología , Piridinas/uso terapéutico , Proteína bcl-X/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ratones , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Ratones Endogámicos BALB C , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , MasculinoRESUMEN
The fatigue performance of hard asphalt is an important factor that affects the service life of asphalt pavement. In order to comprehensively explore the influence of chemical components on the fatigue performance of hard asphalt, and to eliminate the chemical instability between the microstructure of asphalt from different oil sources, seven kinds of hard asphalt were designed and prepared with saturates, aromatics, resins, and asphaltenes (SARA) extracted from the same hard asphalt. Rheological, time sweep and linear amplitude sweep (LAS) tests were carried out to evaluate the fatigue properties. The results show that the complex modulus of asphalt binds increased rapidly with an increase of asphaltene and resins and that the colloidal structure was strengthened, which would increase the fatigue factor. In the time sweep test, the strength of the colloidal structure significantly affected the fatigue life, and the fatigue life was different under different test stresses. In the viscoelastic continuum damage (VECD) model, the cumulative damage was related to the modulus, while with the increase of asphaltene and resins, the fatigue life showed a trend of first increasing and then decreasing. The linear regression analysis showed that the fatigue life of hard asphalt had a good correlation with strain sensitivity. This study investigated the applicability of different fatigue evaluation methods and revealed the influence of four components on the fatigue properties of hard asphalt. The results provide significant insights in the improvement of the fatigue performance of both hard asphalt and corresponding mixtures.
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The railway fastener, as a crucial component of railway tracks, directly influences the safety and stability of a railway system. However, in practical operation, fasteners are often in low-light conditions, such as at nighttime or within tunnels, posing significant challenges to defect detection equipment and limiting its effectiveness in real-world scenarios. To address this issue, this study proposes an unsupervised low-light image enhancement algorithm, CES-GAN, which achieves the model's generalization and adaptability under different environmental conditions. The CES-GAN network architecture adopts a U-Net model with five layers of downsampling and upsampling structures as the generator, incorporating both global and local discriminators to help the generator to preserve image details and textures during the reconstruction process, thus enhancing the realism and intricacy of the enhanced images. The combination of the feature-consistency loss, contrastive learning loss, and illumination loss functions in the generator structure, along with the discriminator loss function in the discriminator structure, collectively promotes the clarity, realism, and illumination consistency of the images, thereby improving the quality and usability of low-light images. Through the CES-GAN algorithm, this study provides reliable visual support for railway construction sites and ensures the stable operation and accurate operation of fastener identification equipment in complex environments.
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Laparoscopic pancreaticoduodenectomy (LPD) with superior mesenteric/portal vein (SMV/PV) resection and reconstruction was the most technically challenging procedure and had been rarely reported. However, single-incision plus one-port LPD (SILPD +1) with SMV/PV resection and reconstruction has never been reported. In this study, we will demonstrate the feasibility, safety, key surgical procedure, and long-term outcomes for SILPD +1 with SMV/PV resection and reconstruction using video evidence. Two cases of SILPD +1 with SMV/PV wedge resection were carried out by the authors. There was no tumor recurrence during the one-year follow-up. It is worth noting that skilled laparoscopic technicians are necessary to safely complete the procedure with good short-term and long-term outcomes.
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Photodynamic therapy (PDT) is an emerging treatment but often restricted by the availability of oxygen. Enhancing the lifespan of singlet oxygen (1O2) by fractionated generation is an effective approach to improve the efficacy of PDT. Herein, an imine-based nanoscale COF (TpDa-COF) has been synthesized and functionalized with a pyridone-derived structure (Py) to create a 1O2-storing nanoplatform TpDa-COF@Py, which can reversibly capture and release 1O2. Under 660 nm laser exposure, Py interacts with 1O2 produced by the porphyrin motif in COF backbones to generate 1O2-enriched COF (TpDa-COF@Py + hv), followed by the release of 1O2 through retro-Diels-Alder reactions at physiological temperatures. The continuous producing and releasing of 1O2 upon laser exposure leads to an "afterglow" effect and a prolonged 1O2 lifespan. In vitro cytotoxicity assays demonstrates that TpDa-COF@Py + hv exhibits an extremely low half-maximal inhibitory concentration (IC50) of 0.54 µg/mL on 4T1 cells. Remarkably, the Py-mediated TpDa-COF@Py nanoplatform demonstrates enhanced cell-killing capability under laser exposure, attributed to the sustained 1O2 cycling, compared to TpDa-COF alone. Further in vivo assessment highlights the potential of TpDa-COF@Py + hv as a promising strategy to enhance phototheronostics and achieve effective tumor regression. Accordingly, the study supplies a generalized 1O2 "afterglow" nanoplatform to improve the effectiveness of PDT.
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Supervivencia Celular , Estructuras Metalorgánicas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Oxígeno Singlete , Oxígeno Singlete/metabolismo , Oxígeno Singlete/química , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/síntesis química , Animales , Ratones , Supervivencia Celular/efectos de los fármacos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Tamaño de la Partícula , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Propiedades de Superficie , Humanos , Proliferación Celular/efectos de los fármacos , Femenino , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Astragaloside IV (AS-IV) is one of the basic components of Astragali radix, that has been shown to have preventive effects against various diseases, including cancers. This study aimed to explore the role of AS-IV in hepatocellular carcinoma (HCC) and its underlying mechanism. METHODS: The cell viability, glucose consumption, lactate production, and extracellular acidification rate (ECAR) in SNU-182 and Huh7 cell lines were detected by specific commercial kits. Western blot was performed to analyze the succinylation level in SNU-182 and Huh7 cell lines. The interaction between lysine acetyltransferase (KAT) 2 A and phosphoglycerate mutase 1 (PGAM1) was evaluated by co-immunoprecipitation and immunofluorescence assays. The role of KAT2A in vivo was explored using a xenografted tumor model. RESULTS: The results indicated that AS-IV treatment downregulated the protein levels of succinylation and KAT2A in SNU-182 and Huh7 cell lines. The cell viability, glucose consumption, lactate production, ECAR, and succinylation levels were decreased in AS-IV-treated SNU-182 and Huh7 cell lines, and the results were reversed after KAT2A overexpression. KAT2A interacted with PGAM1 to promote the succinylation of PGAM1 at K161 site. KAT2A overexpression promoted the viability and glycolysis of SNU-182 and Huh7 cell lines, which were partly blocked following PGAM1 inhibition. In tumor-bearing mice, AS-IV suppressed tumor growth though inhibiting KAT2A-mediated succinylation of PGAM1. CONCLUSION: AS-IV inhibited cell viability and glycolysis in HCC by regulating KAT2A-mediated succinylation of PGAM1, suggesting that AS-IV might be a potential and suitable therapeutic agent for treating HCC.
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Carcinoma Hepatocelular , Supervivencia Celular , Glucólisis , Neoplasias Hepáticas , Fosfoglicerato Mutasa , Saponinas , Triterpenos , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Animales , Fosfoglicerato Mutasa/metabolismo , Ratones , Glucólisis/efectos de los fármacos , Triterpenos/farmacología , Supervivencia Celular/efectos de los fármacos , Saponinas/farmacología , Línea Celular Tumoral , Histona Acetiltransferasas/metabolismo , Ratones Desnudos , Proliferación Celular/efectos de los fármacosRESUMEN
Cuproptosis is a newly defined form of programmed cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis and metastasis. However, whether cuproptosis-related lncRNAs are involved in the pathogenesis of diffuse large B cell lymphoma (DLBCL) remains unclear. This study aimed to identify the prognostic signatures of cuproptosis-related lncRNAs in DLBCL and investigate their potential molecular functions. RNA-Seq data and clinical information for DLBCL were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Cuproptosis-related lncRNAs were screened out through Pearson correlation analysis. Utilizing univariate Cox, least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analysis, we identified seven cuproptosis-related lncRNAs and developed a risk prediction model to evaluate its prognostic value across multiple groups. GO and KEGG functional analyses, single-sample GSEA (ssGSEA), and the ESTIMATE algorithm were used to analyze the mechanisms and immune status between the different risk groups. Additionally, drug sensitivity analysis identified drugs with potential efficacy in DLBCL. Finally, the protein-protein interaction (PPI) network were constructed based on the weighted gene co-expression network analysis (WGCNA). We identified a set of seven cuproptosis-related lncRNAs including LINC00294, RNF139-AS1, LINC00654, WWC2-AS2, LINC00661, LINC01165 and LINC01398, based on which we constructed a risk model for DLBCL. The high-risk group was associated with shorter survival time than the low-risk group, and the signature-based risk score demonstrated superior prognostic ability for DLBCL patients compared to traditional clinical features. By analyzing the immune landscapes between two groups, we found that immunosuppressive cell types were significantly increased in high-risk DLBCL group. Moreover, functional enrichment analysis highlighted the association of differentially expressed genes with metabolic, inflammatory and immune-related pathways in DLBCL patients. We also found that the high-risk group showed more sensitivity to vinorelbine and pyrimethamine. A cuproptosis-related lncRNA signature was established to predict the prognosis and provide insights into potential therapeutic strategies for DLBCL patients.
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Regulación Neoplásica de la Expresión Génica , Linfoma de Células B Grandes Difuso , ARN Largo no Codificante , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Humanos , ARN Largo no Codificante/genética , Pronóstico , Biomarcadores de Tumor/genética , Mapas de Interacción de Proteínas/genética , Masculino , Femenino , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Persona de Mediana EdadRESUMEN
The large open circuit voltage (VOC) loss and phase segregation are two main obstacles hindering the development of wide-bandgap perovskite solar cells (PSCs). Even though substantial progress has been made through crystallization regulation and surface modification on perovskite, the mechanism of VOC loss and phase segregation has rarely been studied. In this paper, we first investigate the halide ions distribution along the out-of-plane direction and find the initial inhomogeneous distribution of halide ions during the crystallization process is an important reason. It leads to the formation of an unfavorable potential well in PSCs, resulting in VOC loss as well as generation of strong strain exacerbating phase segregation. Through introducing melatonin (MT) into perovskite precursors, a homogeneous distribution of halide anions is realized due to the well-regulated crystallization. Consequently, the treated PSCs exhibit an optimized power conversion efficiency (PCE) of 22.88% with a VOC loss as low as 0.38 V, which are the best values for wide-bandgap PSCs up to now.
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Multiple studies have shown knockdown of chromobox 7 (CBX7) promotes the regenerative capacity of various cells or tissues. We examined the effect of CBX7 on hepatocyte proliferation and liver regeneration after 2/3 hepatectomy in a mouse model. For in vitro experiments, NCTC 1469 and BNL CL.2 hepatocytes were co-transfected with siRNA-CBX7-1 (si-CBX7-1), siRNA-CBX7-2 (si-CBX7-2), pcDNA-CBX7, si-BMI1-1, si-BMI1-2, pcDNA-BMI1, or their negative control. For in vivo experiments, mice were injected intraperitoneally with lentivirus-packaged shRNA and shRNA CBX7 before hepatectomy. Our results showed that CBX7 was rapidly induced in the early stage of liver regeneration. CBX7 regulated hepatocyte proliferation, cell cycle, and apoptosis of NCTC 1469 and BNL CL.2 hepatocytes. CBX7 interacted with BMI1 and inhibited BMI1 expression in hepatocytes. Silencing BMI1 aggregated the inhibitory effect of CBX7 overexpression on hepatocyte viability and the promotion of apoptosis. Furthermore, silencing BMI1 enhanced the regulatory effect of CBX7 on Nrf2/ARE signaling in HGF-induced hepatocytes. In vivo, CBX7 silencing enhanced liver/body weight ratio in PH mice. CBX7 silencing promoted the Ki67-positive cell count and decreased the Tunel-positive cell count after hepatectomy, and also increased the expression of nuclear Nrf2, HO-1, and NQO-1. Our results suggest that CBX7 silencing may increase survival following hepatectomy by promoting liver regeneration.
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Apoptosis , Proliferación Celular , Hepatocitos , Regeneración Hepática , Factor 2 Relacionado con NF-E2 , Complejo Represivo Polycomb 1 , Transducción de Señal , Animales , Ratones , Apoptosis/genética , Silenciador del Gen , Hepatectomía , Hepatocitos/metabolismo , Hígado/metabolismo , Regeneración Hepática/genética , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Complejo Represivo Polycomb 1/metabolismo , Complejo Represivo Polycomb 1/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismoRESUMEN
Surface ozone is an important air pollutant detrimental to human health and vegetation productivity, particularly in China. However, high resolution surface ozone concentration data is still lacking, largely hindering accurate assessment of associated environmental impacts. Here, we collected hourly ground ozone observations (over 6 million records), remote sensing products, meteorological data, and social-economic information, and applied recurrent neural networks to map hourly surface ozone data (HrSOD) at a 0.1° × 0.1° resolution across China during 2015-2020. The coefficient of determination (R2) values in sample-based, site-based, and by-year cross-validations were 0.72, 0.65 and 0.71, respectively, with the root mean square error (RMSE) values being 11.71 ppb (mean = 30.89 ppb), 12.81 ppb (mean = 30.96 ppb) and 11.14 ppb (mean = 31.26 ppb). Moreover, it exhibits high spatiotemporal consistency with ground-level observations at different time scales (diurnal, seasonal, annual), and at various spatial levels (individual sites and regional scales). Meanwhile, the HrSOD provides critical information for fine-resolution assessment of surface ozone impacts on environmental and human benefits.
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OBJECTIVE: Designing physiologically adequate microvascular trees is of crucial relevance for bioengineering functional tissues and organs. Yet, currently available methods are poorly suited to replicate the morphological and topological heterogeneity of real microvascular trees because the parameters used to control tree generation are too simplistic to mimic results of the complex angiogenetic and structural adaptation processes in vivo. METHODS: We propose a method to overcome this limitation by integrating a conditional deep convolutional generative adversarial network (cDCGAN) with a local fractal dimension-oriented constrained constructive optimization (LFDO-CCO) strategy. The cDCGAN learns the patterns of real microvascular bifurcations allowing for their artificial replication. The LFDO-CCO strategy connects the generated bifurcations hierarchically to form microvascular trees with a vessel density corresponding to that observed in healthy tissues. RESULTS: The generated artificial microvascular trees are consistent with real microvascular trees regarding characteristics such as fractal dimension, vascular density, and coefficient of variation of diameter, length, and tortuosity. CONCLUSIONS: These results support the adoption of the proposed strategy for the generation of artificial microvascular trees in tissue engineering as well as for computational modeling and simulations of microcirculatory physiology.
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Simulación por Computador , Microcirculación , Microvasos , Microvasos/fisiología , Microvasos/anatomía & histología , Humanos , Microcirculación/fisiología , Modelos Cardiovasculares , FractalesRESUMEN
Nitrous oxide (N2O) emissions from livestock manure contribute significantly to the growth of atmospheric N2O, a powerful greenhouse gas and dominant ozone-depleting substance. Here, we estimate global N2O emissions from livestock manure during 1890-2020 using the tier 2 approach of the 2019 Refinement to the 2006 IPCC Guidelines. Global N2O emissions from livestock manure increased by ~350% from 451 [368-556] Gg N year-1 in 1890 to 2042 [1677-2514] Gg N year-1 in 2020. These emissions contributed ~30% to the global anthropogenic N2O emissions in the decade 2010-2019. Cattle contributed the most (60%) to the increase, followed by poultry (19%), pigs (15%), and sheep and goats (6%). Regionally, South Asia, Africa, and Latin America dominated the growth in global emissions since the 1990s. Nationally, the largest emissions were found in India (329 Gg N year-1), followed by China (267 Gg N year-1), the United States (163 Gg N year-1), Brazil (129 Gg N year-1) and Pakistan (102 Gg N year-1) in the 2010s. We found a substantial impact of livestock productivity, specifically animal body weight and milk yield, on the emission trends. Furthermore, a large spread existed among different methodologies in estimates of global N2O emission from livestock manure, with our results 20%-25% lower than those based on the 2006 IPCC Guidelines. This study highlights the need for robust time-variant model parameterization and continuous improvement of emissions factors to enhance the precision of emission inventories. Additionally, urgent mitigation is required, as all available inventories indicate a rapid increase in global N2O emissions from livestock manure in recent decades.
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Ganado , Estiércol , Óxido Nitroso , Óxido Nitroso/análisis , Estiércol/análisis , Animales , Contaminantes Atmosféricos/análisisRESUMEN
Purpose: To compare the efficacy and safety of Kangfuxin solution and lvpao powder on mucositis induced by radiation therapy in head and neck carcinoma patients. We retrospectively analyzed 114 patients with head and neck malignant tumors in our center. Methods and Materials: Patients were given Kangfuxin solution to rinse the mouth or Lvpao powder sprayed on oral mucosa after the solution use. The side effect was evaluated by Common Terminology Criteria for Adverse Events version 4.0. Results: The grade 3 mucositis occurred in 32.9% (23/70) and 11.4% (5/44) in Kangfuxin solution group and Kangfuxin solution + lvpao powder group, respectively (P = .009). The pain score of the Kangfuxin solution group was significantly higher than that of the Kangfuxin solution and lvpao powder group, with 4.26 ± 0.81 versus 3.75 ± 1.03 (P = .007). The time of symptom relief in the combined group was significantly shorter than that in the single drug group, with 3 days versus 6 days (P = .000). The weight loss of the former groups was bigger than that of the latter group (6.67 ± 1.20 kg vs 5.95 ± 0.94 kg; P = .001). There was no statistical difference in the limitations in mouth opening (P = .164). Conclusions: Lvpao powder is safe and effective as a mucosal repair drug in accelerating the recovery of patients and reducing their body weight.