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Risk management has reduced vulnerability to floods and droughts globally1,2, yet their impacts are still increasing3. An improved understanding of the causes of changing impacts is therefore needed, but has been hampered by a lack of empirical data4,5. On the basis of a global dataset of 45 pairs of events that occurred within the same area, we show that risk management generally reduces the impacts of floods and droughts but faces difficulties in reducing the impacts of unprecedented events of a magnitude not previously experienced. If the second event was much more hazardous than the first, its impact was almost always higher. This is because management was not designed to deal with such extreme events: for example, they exceeded the design levels of levees and reservoirs. In two success stories, the impact of the second, more hazardous, event was lower, as a result of improved risk management governance and high investment in integrated management. The observed difficulty of managing unprecedented events is alarming, given that more extreme hydrological events are projected owing to climate change3.
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Sequías , Clima Extremo , Inundaciones , Gestión de Riesgos , Cambio Climático/estadística & datos numéricos , Conjuntos de Datos como Asunto , Sequías/prevención & control , Sequías/estadística & datos numéricos , Inundaciones/prevención & control , Inundaciones/estadística & datos numéricos , Humanos , Hidrología , Internacionalidad , Gestión de Riesgos/métodos , Gestión de Riesgos/estadística & datos numéricos , Gestión de Riesgos/tendenciasRESUMEN
BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.
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Fallo Renal Crónico , Diálisis Peritoneal , Peritonitis , Humanos , Femenino , Estudios Prospectivos , Diálisis Peritoneal/efectos adversos , Diálisis Renal/efectos adversos , Hemoglobinas , Fallo Renal Crónico/epidemiología , Peritonitis/etiología , Estudios RetrospectivosRESUMEN
Artificial intelligence-based methods for predicting drug-target interactions (DTIs) aim to explore reliable drug candidate targets rapidly and cost-effectively to accelerate the drug development process. However, current methods are often limited by the topological regularities of drug molecules, making them difficult to generalize to a broader chemical space. Additionally, the use of similarity to measure DTI network links often introduces noise, leading to false DTI relationships and affecting the prediction accuracy. To address these issues, this study proposes an Adaptive Iterative Graph Optimization (AIGO)-DTI prediction framework. This framework integrates atomic cluster information and enhances molecular features through the design of functional group prompts and graph encoders, optimizing the construction of DTI association networks. Furthermore, the optimization of graph structure is transformed into a node similarity learning problem, utilizing multihead similarity metric functions to iteratively update the network structure to improve the quality of DTI information. Experimental results demonstrate the outstanding performance of AIGO-DTI on multiple public data sets and label reversal data sets. Case studies, molecular docking, and existing research validate its effectiveness and reliability. Overall, the method proposed in this study can construct comprehensive and reliable DTI association network information, providing new graphing and optimization strategies for DTI prediction, which contribute to efficient drug development and reduce target discovery costs.
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Algoritmos , Simulación del Acoplamiento Molecular , Inteligencia Artificial , Preparaciones Farmacéuticas/química , Preparaciones Farmacéuticas/metabolismo , Descubrimiento de Drogas/métodosRESUMEN
BACKGROUND: Reducing production costs while producing high-quality livestock and poultry products is an ongoing concern in the livestock industry. The addition of oil to livestock and poultry diets can enhance feed palatability and improve growth performance. Emulsifiers can be used as potential feed supplements to improve dietary energy utilization and maintain the efficient productivity of broilers. Therefore, further investigation is warranted to evaluate whether dietary emulsifier supplementation can improve the efficiency of fat utilization in the diet of yellow-feathered broilers. In the present study, the effects of adding emulsifier to the diet on lipid metabolism and the performance of yellow-feathered broilers were tested. A total of 240 yellow-feasted broilers (21-day-old) were randomly divided into 4 groups (6 replicates per group, 10 broilers per replicate, half male and half female within each replicate). The groups were as follows: the control group (fed with basal diet), the group fed with basal diet supplemented with 500 mg/kg emulsifier, the group fed with a reduced oil diet (reduced by 1%) supplemented with 500 mg/kg emulsifier, and the group fed with a reduced oil diet supplemented with 500 mg/kg emulsifier. The trial lasted for 42 days, during which the average daily feed intake, average daily gain, and feed-to-gain ratio were measured. Additionally, the expression levels of lipid metabolism-related genes in the liver, abdominal fat and each intestinal segment were assessed. RESULTS: The results showed that compared with the basal diet group, (1) The average daily gain of the basal diet + 500 mg/kg emulsifier group significantly increased (P < 0.05), and the half-even-chamber rate was significantly increased (P < 0.05); (2) The mRNA expression levels of Cd36, Dgat2, Apob, Fatp4, Fabp2, and Mttp in the small intestine were significantly increased (P < 0.05). (3) Furthermore, liver TG content significantly decreased (P < 0.05), and the mRNA expression level of Fasn in liver was significantly decreased (P < 0.05), while the expression of Apob, Lpl, Cpt-1, and Pparα significantly increased (P < 0.05). (4) The mRNA expression levels of Lpl and Fatp4 in adipose tissue were significantly increased (P < 0.05), while the expression of Atgl was significantly decreased (P < 0.05). (5) Compared with the reduced oil diet group, the half-evading rate and abdominal fat rate of broilers in the reduced oil diet + 500 mg/kg emulsifier group were significantly increased (P < 0.05), and the serum level of LDL-C increased significantly (P < 0.05)0.6) The mRNA expression levels of Cd36, Fatp4, Dgat2, Apob, and Mttp in the small intestine were significantly increased (P < 0.05). 7) The mRNA expression levels of Fasn and Acc were significantly decreased in the liver (P < 0.05), while the mRNA expression levels of Lpin1, Dgat2, Apob, Lpl, Cpt-1, and Pparα were significantly increased (P < 0.05). CONCLUSIONS: These results suggest that dietary emulsifier can enhance the fat utilization efficiency of broilers by increasing the small intestinal fatty acid uptake capacity, inhibiting hepatic fatty acid synthesis and promoting hepatic TG synthesis and transport capacity. This study provides valuable insights for the potential use of emulsifier supplementation to improve the performance of broiler chickens.
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Alimentación Animal , Pollos , Dieta , Suplementos Dietéticos , Emulsionantes , Metabolismo de los Lípidos , Animales , Pollos/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Emulsionantes/farmacología , Alimentación Animal/análisis , Masculino , Femenino , Dieta/veterinaria , Hígado/metabolismo , Hígado/efectos de los fármacosRESUMEN
INTRODUCTION: Autogenous arteriovenous fistula (AVF) is the preferred vascular access in patients undergoing maintenance hemodialysis. However, complications such as thrombosis may occur. This study aimed to construct and validate a machine learning-based risk-prediction model for AVF thrombosis, hypothesizing that such a model can effectively predict occurrences, providing a foundation for early clinical intervention. METHODS: The retrospective longitudinal study included a total of 270 patients who underwent maintenance hemodialysis (MHD) at the Hemodialysis Center of the Second Affiliated Hospital of Harbin Medical University between March 2021 and December 2022. During this study, baseline data and scale information of patients between March 2020 and December 2021 were collected. We recorded outcome indicators between March 2021 and December 2022 for subsequent analyses. Five machine learning models were developed (artificial neural network, logistic regression, ridge classification, random forest, and adaptive boosting). The sensitivity (recall), specificity, accuracy, and precision of each model were evaluated. The effect size of each variable was analyzed and ranked. Models were assessed using the area under the receiver-operating characteristic (AUROC) curve. RESULTS: Among the 270 included patients, 105 had AVF thrombosis (55 male and 50 female patients; age range, 29-79 years; mean age, 56.72 years; standard deviation [SD], ±13.10 years). Conversely, 165 patients did not have AVF thrombosis (99 male and 66 female patients; age range, 23-79 years; mean age, 53.58 years; SD, ±13.33 years). During the observation period, approximately 52.6% of patients with AVF experienced long-term complications. The most common complications associated with AVF were thrombosis (105; 38.9%), aneurysm formation (27; 10%), and excessively high output flow (10; 3.7%). Fifty-four (20%) patients with AVF required intervention because of complications associated with vascular access. The AUROC curve of the testing set was between 0.858 and 0.903. CONCLUSION: In this study, we developed five machine learning models to predict the risk of AVF thrombosis, providing a reference for early clinical intervention.
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BACKGROUND: In the continuous endeavor to find safe and efficient treatments for Atopic Dermatitis (AD), there remains a considerable focus on dietary adjustments. Nevertheless, the limited availability of research and conflicting findings in the academic literature pose a hurdle in establishing conclusive recommendations. METHOD: Mendelian randomization (MR) was applied to the most comprehensive genome-wide association studies (GWAS) data on tea intake (447 485), green tea intake (n = 64 949), flavored milk intake (n = 64 941), never eat eggs, dairy, wheat, sugar: Wheat products(n = 461 046), never eat eggs, dairy, wheat, sugar: Sugar or foods/drinks containing sugar (n = 461 046), never eat eggs, dairy, wheat, sugar: I eat all of the above (n = 461 046) and atopic dermatitis (n = 218 467). We used the inverse-variance weighted method (IVW) as the primary method. RESULTS: The IVW analyses have demonstrated an increased tea intake was genetically associated with a reduced risk of AD (odds ratio [OR]: 0.646, 95% confidence interval [CI]: 0.430-0.968, p = 0.034). Furthermore, green tea intake was significantly negatively associated with AD (IVW OR: 0.986, 95% CI: 0.975-0.998; p = 0.024) in the IVW model. AD risk could be reduced by never eating wheat products (IVW OR: 8.243E-04, 95% CI: 7.223E-06-9.408E-02, p = 0.003). There was no association between never eating eggs, dairy, wheat, sugar: Sugar, or foods/drinks containing sugar, I eat all of the above and AD. CONCLUSIONS: Our MR study suggests a causal relationship between tea intake, green tea intake, and the avoidance of eating wheat products with atopic dermatitis. Our findings recommend that preventing and managing atopic dermatitis may be achieved by never eating wheat products while increasing tea and green tea intake.
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Dermatitis Atópica , Dieta , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Dermatitis Atópica/genética , Humanos , Dieta/efectos adversos , Té , Huevos , Leche , Triticum/genética , Productos Lácteos , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVE: This study aimed to establish a highly sensitive and rapid single-tube, two-stage, multiplex recombinase-aided qPCR (mRAP) assay to specifically detect the khe, blaKPC-2, and blaNDM-1 genes in Klebsiella pneumoniae. METHODS: mRAP was carried out in a qPCR instrument within 1 h. The analytical sensitivities of mRAP for khe, blaKPC-2, and blaNDM-1 genes were tested using recombinant plasmids and dilutions of reference strains. A total of 137 clinical isolates and 86 sputum samples were used to validate the clinical performance of mRAP. RESULTS: mRAP achieved the sensitivities of 10, 8, and 14 copies/reaction for khe, blaKPC-2, and blaNDM-1 genes, respectively, superior to qPCR. The Kappa value of qPCR and mRAP for detecting khe, blaKPC-2, and blaNDM-1 genes was 1, 0.855, and 1, respectively (p < 0.05). CONCLUSION: mRAP is a rapid and highly sensitive assay for potential clinical identification of khe, blaKPC-2, and blaNDM-1 genes in K. pneumoniae.
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Klebsiella pneumoniae , Reacción en Cadena de la Polimerasa Multiplex , beta-Lactamasas , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/aislamiento & purificación , beta-Lactamasas/genética , Humanos , Reacción en Cadena de la Polimerasa Multiplex/métodos , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/diagnóstico , Sensibilidad y Especificidad , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Proteínas Bacterianas/genética , Recombinasas/genética , Recombinasas/metabolismoRESUMEN
Pangolins are susceptible to a variety of gastrointestinal nematodes due to their burrowing lifestyle and feeding habits, and few parasitic nematodes have been reported. Here, a Chinese pangolin with old wounds on its leg and tail was rescued from the Heyuan City, Guangdong Province. The cox1 and SSU rRNA of the worms from the intestine of the Chinese pangolin had the highest sequence identity of 89.58% and 97.95% to the species in the infraorder Spiruromorpha. The complete mitogenome of the worm was further assembled by next-generation sequencing, with a size of 13,708 bp and a GC content of 25.6%. The worm mitogenome had the highest sequence identity of 78.56% to that of Spirocerca lupi, sharing the same gene arrangement with S. lupi and some species in other families under Spiruromorpha. However, the mitogenome between the worm and S. lupi showed differences in codon usage of PCGs, sequences of NCR, and tRNA secondary structures. Phylogenetic analysis showed that the worm mitogenome was clustered with S. lupi in the family Thelaziidae to form a separate branch. However, it is still difficult to identify the worm in the family Thelaziidae because the species in the family Thelaziidae are confused, specifically S. lupi and Thelazia callipaeda in the family Thelaziidae were separated and grouped with species from other families. Thus, the parasitic nematode from the Chinese pangolin may be a novel species in Spiruromorpha and closely related to S. lupi. This study enriches the data on gastrointestinal nematodes in the Chinese pangolin.
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Genoma Mitocondrial , Espirúridos , Thelazioidea , Humanos , Animales , Pangolines , Filogenia , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
PURPOSE: To evaluate the seating accuracy of removable partial denture (RPD) frameworks fabricated by two digital workflows involving selective laser melting (SLM) in comparison to the conventional workflow. MATERIALS AND METHODS: A Kennedy class III modification 1 partially edentulous mandibular arch was used as a master model. Three RPD framework groups were included: (1) a conventional workflow group with conventional impression and casting (CC), (2) a partial digital workflow group with conventional impression and digital fabrication (CD), and (3) a complete digital workflow group with digital impression and digital fabrication (DD). A total of 10 frameworks were produced for each group. The marginal gaps at the occlusal rests, retention arms, and reciprocating arms were measured by a traveling microscope. The data were analyzed with the one-way analysis of variance test. RESULTS: At the framework level, the most superior fit was observed for the CD group (79.5 µm) followed by DD (85.3 µm) and CC (114.2 µm) groups. The CD and DD groups were significantly superior to CC (p < 0.001). This fit pattern was consistent for the retention and reciprocating arms, while the occlusal rest fit was similar among all the groups. CONCLUSIONS: The SLM frameworks had a promising seating accuracy in comparison to conventional frameworks. The type of impression, conventional or digital, did not affect the accuracy of SLM frameworks. The differences observed in the present study are likely to be of minimal clinical significance.
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The northeastern margin of the Tibetan Plateau (NE Tibetan Plateau) exhibits active geological structures and has experienced multiple strong earthquakes, with M ≥ 7, throughout history. Particularly noteworthy is the 1920 M81/2 earthquake in the Haiyuan region that occurred a century ago and is documented as one of the deadliest earthquakes. Consequently, analyzing seismic risks in the northeastern margin of the Tibetan Plateau holds significant importance. The b value, a crucial parameter for seismic activity, plays a pivotal role in seismic hazard analyses. This study calculates the spatial b values in this region based on earthquake catalogs since 1970. The study area encompasses several major active faults, and due to variations in b values across different fault types, traditional grid-search methods may introduce significant errors in calculating the spatial b value within complex fault systems. To address this, we employed the hierarchical space-time point-process (HIST-PPM) method proposed by Ogata. This method avoids partitioning earthquake samples, optimizes parameters using Akaike's Bayesian Information Criterion (ABIC) with entropy maximization, and theoretically allows for a higher spatial resolution and more accurate b value calculations. The results indicate a high spatial heterogeneity in b values within the study area. The northwestern and southeastern regions exhibit higher b values. Along the Haiyuan fault zone, the central rupture zone of the Haiyuan earthquake has relatively higher b values than other regions of this fault zone, which is possibly related to the sufficient release of stress during the main rupture of the Haiyuan earthquake. The b values vary from high in the west to low in the east along the Zhongwei fault. On the West Qinling fault zone, the epicenter of the recent Minxian-Zhangxian earthquake is associated with a low b value. In general, regions with low b values correspond well to areas with moderate-strong seismic events in the past 50 years. The spatial differences in b values may reflect variances in seismic hazards among fault zones and regions within the same fault zone.
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An eco-friendly adsorbent was prepared by reverse suspension crosslinking method to remove multiple pollutants from aqueous solution. Both raw materials, derived from humus (HS) and chitosan (CS), are biodegradable and low-cost natural biopolymers. After combining HS with CS, the adsorption capacity was significantly improved due to compensation effects between the two components. HS/CS exhibited the features of amphoteric adsorption through pH adjustment, enabling it to adsorb not only anionic pollutants (Methyl Orange (MO) and Cr(VI)), but also cationic ones (Methylene Blue (MB) and Pb(II)). The adsorption capacities were approximately 242 mg/g, 69 mg/g, 188 mg/g and 57 mg/g for MO, Cr(VI), MB and Pb(II), respectively. HS/CS showed a slight preference for MO in MO/Cr(VI) co-adsorption system, whereas strong selectivity for MB over Pb(II) in MB/Pb(II) system under acidic condition (pH<3.0). This selective behavior would allow for potential applications in separating MB/Pb(II) effluents and selectively recycling Pb(II) in acidic environment. The isothermal and kinetic adsorption behaviors followed Langmuir model and pseudo-second-order model, respectively. The density functional theory (DFT) confirmed that the interaction between metal ions and adsorbents was primarily attributed to chelation and electrostatic adsorption, owing to nitric and oxygenic functional groups. Whereas, the adsorption mechanisms for dyes were involved in electrostatic attraction, H-bond and π-π bond, due to available hydrogen, oxygen, nitrogen atoms and aromatic groups on the surface of adsorbent and adsorbates. The adsorbent could be efficiently regenerated and retained over 90% of its adsorption capacity after five cycles, which has a potential for practical applications in water treatment.
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Quitosano , Colorantes , Hidrogeles , Metales Pesados , Contaminantes Químicos del Agua , Quitosano/química , Contaminantes Químicos del Agua/química , Adsorción , Metales Pesados/química , Hidrogeles/química , Colorantes/química , Sustancias Húmicas , Cinética , Eliminación de Residuos Líquidos/métodos , Modelos Químicos , Purificación del Agua/métodosRESUMEN
Nanomaterial-based in vivo tumor imaging and therapy have attracted extensive attention; however, they suffer from the unintelligent "always ON" or single-parameter responsive signal output, substantial off-target effects, and high cost. Therefore, achieving in vivo easy-to-read tumor imaging and precise therapy in a multi-parameter responsive and intelligent manner remains challenging. Herein, an intelligent DNA nanoreactor (iDNR) was constructed following the "AND" Boolean logic algorithm to address these issues. iDNR-mediated in situ deposition of photothermal substance polydopamine (PDA) can only be satisfied in tumor tissues with abundant membrane protein biomarkers "AND" hydrogen peroxide (H2 O2 ). Therefore, intelligent temperature-based in vivo easy-to-read tumor imaging is realized without expensive instrumentation, and its diagnostic performance matches with that of flow cytometry, and photoacoustic imaging. Moreover, precise photothermal therapy (PTT) of tumors could be achieved via intelligent heating of tumor tissues. The precise PTT of primary tumors in combination with immune checkpoint blockade (ICB) therapy suppresses the growth of distant tumors and inhibits tumor recurrence. Therefore, highly programmable iDNR is a powerful tool for intelligent biomedical applications.
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Nanopartículas , Nanoestructuras , Neoplasias , Humanos , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Neoplasias/patología , Fototerapia/métodos , Nanotecnología , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Cell division cycle associated 7 (CDCA7) is a copy number amplification gene that contributes to the metastasis and invasion of tumors, including esophageal squamous cell carcinoma (ESCC). This present study aimed at clarifying whether high expression of CDCA7 promotes the metastasis and invasion of ESCC cell lines and exploring the underlying mechanisms implicated in epithelial-mesenchymal transition (EMT) of ESCC. The role of CDCA7 in the regulation of ESCC metastasis and invasion was evaluated using ESCC cell lines. Expression of EMT-related markers including E-cadherin, N-cadherin, Vimentin, Snail, and Slug, transforming growth factor ß (TGF-ß) signaling pathway including Smad2/3, p-Smad2/3, Smad4, and Smad7 were detected in CDCA7 knockdown and overexpressed cell lines. Dual-luciferase reporter assay and rescue assay were used to explore the underlying mechanisms that CDCA7 contributed to the metastasis and invasion of ESCC. High CDCA7 expression significantly promoted the metastasis and invasion of ESCC cell lines both in vivo and in vitro. Additionally, the expression of CDCA7 positively correlated with the expression of N-cadherin, Vimentin, Snail, Slug, TGF-ß signaling pathway and negatively correlated with the expression of E-cadherin. Furthermore, CDCA7 transcriptionally regulated the expression of Smad4 and Smad7. Knockdown of CDCA7 inhibited the TGF-ß signaling pathway and therefore inhibited EMT. Our data indicated that CDCA7 was heavily involved in EMT by regulating the expression of Smad4 and Smad7 in TGF-ß signaling pathway. CDCA7 might be a new therapeutic target in the suppression of metastasis and invasion of ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/genética , Factor de Crecimiento Transformador beta/metabolismo , Vimentina/genética , Vimentina/metabolismo , Neoplasias Esofágicas/patología , Transición Epitelial-Mesenquimal/genética , Línea Celular Tumoral , Cadherinas/genética , Cadherinas/metabolismo , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Proteína Smad4/genética , Proteína Smad4/metabolismo , Proteínas Nucleares/genética , Proteína smad7/genética , Proteína smad7/metabolismoRESUMEN
Activation of hepatic stellate cells (HSCs) is the main course of liver fibrosis which is positively correlated with adverse clinical outcomes in non-alcoholic steatohepatitis (NASH). Diethyldithiocarbamate (DDC) attenuates NASH related liver fibrosis in mice, but its underlying mechanisms remains unclear. In this study, the data showed that DDC inhibited the activation of HSCs in high fat choline-deficient, L-amino acid-defined (CDAA) diet induced NASH. Double Immunofluorescence analysis showed that the baseline expression of peroxisome proliferator-activated receptor α (PPARα) is high in HSCs in normal mouse liver and notably decreases in the NASH liver, indicating that PPARα might be associated with the activation of HSCs. While, DDC upregulated PPARα in HSCs in the NASH liver. Mixture of free fatty acid was used to induce steatosis of hepatocytes. Human HSCs (LX-2 cells) were activated after co-cultured with steatotic hepatocytes, and DDC inhibited the activation of LX-2 cells. Meanwhile, DDC upregulated PPARα and FABP1, and promoted the accumulation of LDs in LX-2 cells. PPARα small interfering RNA blocked these effect of DDC. These findings suggest that PPARα is associated with the activation of HSCs in the context of NASH. DDC improves NASH related fibrosis through inhibiting the activation of HSCs via PPARα/FABP1.
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Enfermedad del Hígado Graso no Alcohólico , Ratones , Humanos , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Células Estrelladas Hepáticas/metabolismo , PPAR alfa/metabolismo , Hígado/metabolismo , Cirrosis Hepática/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismoRESUMEN
Carboxylic acids are abundant, low cost and environmentally friendly, direct convert carboxylic acids into valued-added compounds are in high demand. Herein, we report a Rh(I) catalyzed direct decarbonylative borylation of aryl and alkyl carboxylic acid using TFFH as activator. This protocol features excellent functional-group tolerance and a broad substrate scope including natural product and drugs. A gram-scale decarbonylative borylation reaction of Probenecid is also presented. In addition, the utility of this strategy is highlighted by a one-pot decarbonylative borylation/ derivatization sequence.
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Using a hemispherical directional reflectance factor instrument, spectral data of dirty snow containing black carbon (BC), mineral dust (MD), and ash was collected from multiple locations to investigate the impact of these light-absorbing impurities (LAIs) on snow reflectance characteristics. The findings revealed that the perturbation of snow reflectance caused by LAIs is characterized by nonlinear deceleration, indicating that the reduction in snow reflectance per unit ppm of LAIs declines as snow contamination increases. The reduction in snow reflectance caused by BC may reach saturation at elevated particle concentrations (thousands of ppm) on snow. Snowpacks loaded with MD or ash initially exhibit a significant reduction in spectral slope around 600 and 700 nm. The deposition of numerous MD or ash particles can increase snow reflectance beyond the wavelength of 1400 nm, with an increase of 0.1 for MD and 0.2 for ash. BC can darken the entire measurement range (350-2500 nm), while MD and ash can only affect up to 1200 nm (350-1200 nm). This study enhances our understanding of the multi-angle reflection characteristics of various dirty snow, which can guide future snow albedo simulations and improve the accuracy of LAIs' remote sensing retrieval algorithms.
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Monitoreo del Ambiente , Nieve , Polvo/análisis , Luz Solar , Hollín/análisis , CarbonoRESUMEN
This study focuses on the cation intercalation of structurally unique compounds synthesized from the partial dehydration and deprotonation of coordinated water molecules in hydrous materials. Partial dehydration can potentially result in hydrous materials with a porous nature, which maintains the parent structure of the material, and deprotonation causes oxidation in the hydrous materials. Li-intercalation experiments were conducted on the hydrous iron(II) phosphate mineral, vivianite (Fe2+3(PO4)2·8H2O), and its oxidized and partially dehydrated product, santabarbaraite. Vivianite comprises two-dimensional Fe3(PO4)2 sheets and coordinated water molecules. The oxidation progress of the Fe2+ of vivianite increased cathodic capacities up to 156 mA h g-1. The Li-intercalation reaction rate increased significantly owing to dehydration because the partial dehydration of vivianite created structural space for the diffusion of Li+. Furthermore, X-ray diffraction measurements revealed that Li intercalation did not cause the formation of byproducts.
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Microbiologically influenced corrosion (MIC) caused by biofilm is a serious problem in many industries. D-amino acids could be a potential strategy to enhance traditional corrosion inhibitors due to their roles in biofilm reduction. However, the synergistic mechanism of D-amino acids and inhibitors remains unknown. In this study, D-Phenylalanine (D-Phe) and 1-hydroxyethane-1,1-diphosphonic acid (HEDP) were selected as the typical D-amino acid and corrosion inhibitor to evaluate their effect on the corrosion caused by Desulfovibrio vulgaris. The combination of HEDP and D-Phe obviously slowed down the corrosion process by 32.25%, decreased the corrosion pit depth and retarded cathodic reaction. SEM and CLSM analysis indicated that D-Phe reduced the content of extracellular protein and thus inhibited the biofilm formation. The molecular mechanism of D-Phe and HEDP on corrosion inhibition was further explored via transcriptome. The combination of HEDP and D-Phe down-regulated the gene expression of peptidoglycan, flagellum, electron transfer, ferredoxin and quorum sensing (QS) molecules, leading to less peptidoglycan synthesis, weaker electron transfer and stronger QS factor inhibition. This work provides a new strategy for improving traditional corrosion inhibitors, retarding MIC and mitigating subsequent water eutrophication.
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Ácido Etidrónico , Fenilalanina , Ácido Etidrónico/farmacología , Fenilalanina/farmacología , Corrosión , Peptidoglicano/farmacología , Biopelículas , Aminoácidos/farmacología , Acero/química , Acero/farmacologíaRESUMEN
Objective: This study aims to investigate the main types of oculocutaneous albinism (OCA) and the distribution characteristics of mutations in the Chinese population. Additionally, genetic diagnosis and prenatal diagnosis were conducted for Chinese OCA families. Methods: A total of 116 blood DNA samples were collected from 40 unrelated families with suspected albinism. OCA gene testing and mutation screening were performed to identify mutated genes and genotypes. The prenatal genetic diagnosis was conducted on 20 fetal DNA samples (17 amniotic fluid DNA samples, 2 villus DNA samples, and 1 umbilical cord blood DNA sample). Follow-up was conducted on the born fetuses, and the feasibility and accuracy of prenatal genetic diagnosis were assessed based on the clinical phenotype of the fetuses. Results: Analysis of 40 pedigrees led to a molecular diagnosis for the patients or their parents: 24 (60%) had OCA1, 12 (30%) had OCA2, 1 (2.5%) had OCA3, and 2 (5%) had OCA4. Furthermore, 2.5% of the patients harbored only one heterozygous mutation in OCA2. The most common form of albinism observed was OCA1, followed by OCA2, OCA4, and OCA3. Prenatal diagnosis was performed on 20 fetuses, and the clinical phenotype of the fetuses aligned with the predictions of prenatal genetic diagnosis after follow-up. Conclusions: The results of gene mutation analysis in 40 families with oculocutaneous albinism indicate that OCA1 is the predominant type of albinism in the Chinese population, with all four types of OCA identified. Further research is needed to expand the understanding of pathogenic mutations associated with different types of OCA. Prenatal genetic testing, based on determining the albinism type and genotype of the proband and their parents, proves to be the most accurate and least traumatic method in eugenics. This study provides valuable insights into identifying novel therapeutic targets.
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Albinismo Oculocutáneo , Pueblos del Este de Asia , Embarazo , Femenino , Humanos , Mutación , Albinismo Oculocutáneo/genética , Albinismo Oculocutáneo/diagnóstico , Fenotipo , Proteínas de Transporte de Membrana/genética , Glicoproteínas de Membrana/genética , Oxidorreductasas/genética , Antígenos de Neoplasias/genéticaRESUMEN
Observations and numerical models are mainly used to investigate the spatiotemporal distribution and vertical structure characteristics of aerosols to understand aerosol pollution and its effects. However, the limitations of observations and the uncertainties of numerical models bias aerosol calculations and predictions. Data assimilation combines observations and numerical models to improve the accuracy of the initial, analytical fields of models and promote the development of atmospheric aerosol pollution research. Numerous studies have been conducted to integrate multi-source data, such as aerosol optical depth and aerosol extinction coefficient profile, into various chemical transport models using various data assimilation algorithms and have achieved good assimilation results. The definition of data assimilation and the main algorithms will be briefly presented, and the progress of aerosol assimilation according to two types of aerosol data, namely, aerosol optical depth and extinction coefficient, will be presented. The application of vertical aerosol data assimilation, as well as the future trends and challenges of aerosol data assimilation, will be further analysed.