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Carbonaceous aerosol, including organic carbon (OC) and elemental carbon (EC), has significant influence on human health, air quality and climate change. Accurate measurement of carbonaceous aerosol is essential to reduce the uncertainty of radiative forcing estimation and source apportionment. The accurate separation of OC and EC is controversial due to the charring of OC. Therefore, the development of reference materials (RM) for the validation of OC/EC separation is an important basis for further study. Previous RMs were mainly based on ambient air sampling, which could not provide traceability of OC and EC concentration. To develop traceable RMs with known OC/EC contents, our study applied an improved aerosol generation and mixing technique, providing uniform deposition of particles on quartz filters. To generate OC aerosol with similar pyrolytic property of ambient aerosol, both water soluble organic carbon (WSOC) and water insoluble organic carbon (WIOC) were used, and amorphous carbon was selected for EC surrogate. The RMs were analyzed using different protocols. The homogeneity within the filter was validated, reaching below 2%. The long-term stability of RMs has been validated with RSD ranged from 1.7%-3.2%. Good correlation was observed between nominal concentration of RMs with measured concentration by two protocols, while the difference of EC concentration was within 20%. The results indicated that the newly developed RMs were acceptable for the calibration of OC and EC, which could improve the accuracy of carbonaceous aerosol measurement. Moreover, the laboratory-generated EC-RMs could be suitable for the calibration of equivalent BC concentration by Aethalometers.
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Aerossóis , Poluentes Atmosféricos , Carbono , Monitoramento Ambiental , Carbono/análise , Aerossóis/análise , Monitoramento Ambiental/métodos , Calibragem , Poluentes Atmosféricos/análiseRESUMO
Herein, three supported catalysts, CuO/Al2O3, CeO2/Al2O3, and CuO-CeO2/Al2O3, were synthesized by the convenient impregnation method to reveal the effect of CeO2 addition on catalytic performance and reaction mechanism for toluene oxidation. Compared with CuO/Al2O3, the T50 and T90 (the temperatures at 50% and 90% toluene conversion, respectively) of CuO-CeO2/Al2O3 were reduced by 33 and 39 °C, respectively. N2 adsorption-desorption experiment, XRD, SEM, EDS mapping, Raman, EPR, H2-TPR, O2-TPD, XPS, NH3-TPD, Toluene-TPD, and in-situ DRIFTS were conducted to characterize these catalysts. The excellent catalytic performance of CuO-CeO2/Al2O3 could be attributed to its strong copper-cerium interaction and high oxygen vacancies concentration. Moreover, in-situ DRIFTS proved that CuO-CeO2/Al2O3 promoted the conversion of toluene to benzoate and accelerated the deep degradation path of toluene. This work provided valuable insights into the development of efficient and economical catalysts for volatile organic compounds.
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Cério , Cobre , Oxirredução , Tolueno , Tolueno/química , Catálise , Cobre/química , Cério/química , Modelos Químicos , Poluentes Atmosféricos/químicaRESUMO
Groundwater is one of the chief water sources for agricultural activities in an aggregation of coal mines surrounded by agricultural areas in the Huaibei Plain. However, there have been few reports on whether mining-affected groundwater can be adopted for agricultural irrigation. We attempted to address this question through collecting 71 shallow groundwater samples from 12 coal mining locations. The Piper trilinear chart, the Gibbs diagram, the proportional coefficient of major ions, and principal component analysis were examined to characterize the source, origin, and formation process of groundwater chemical composition. The suitability for agricultural irrigation was evaluated by a final zonation map that establishes a comprehensive weighting model based on analytic hierarchy process and criteria importance though the intercriteria correlation (AHP-CRITIC). The results revealed that the groundwater was classified as marginally alkaline water with a predominant cation of HCO3- and anion of Na+. Total hardness, total dissolved solids, sulfate (SO42-), sodium (Na+), and fluoride (F-) were the primary ions that exceeded the standard. The results also indicated that the dominant hydrochemical facies were Ca-HCO3 and Na-Cl. The dissolution of carbonate, silicate, sulfate minerals, along with cation exchange, were the main natural drivers controlling the hydrogeochemical process of groundwater. The zonation map suggested that 43.17%, 18.85%, and 37.98% of the study area were high, mediate, and low suitability zones, respectively. These results from this study can support policymakers for better managing groundwater associated with a concentration of underground coal mines.
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Minas de Carvão , Monitoramento Ambiental , Água Subterrânea , Poluentes Químicos da Água , Água Subterrânea/química , China , Poluentes Químicos da Água/análise , AgriculturaRESUMO
BACKGROUND: Optical flow ratio (OFR) is a novel computational fractional flow reserve derived from optical coherence tomography (OCT). However, the impact of combining post-stenting morphology (OCT) and physiology (OFR) remains largely unknown. METHOD: OCT and OFR were analyzed at the independent core laboratory. Target lesion failure (TLF) was defined as the composite of cardiac death, target lesion myocardial infarction and target lesion revascularization. Suboptimal stent deployment was identified with at least one TLF-related OCT or OFR characteristics. RESULTS: A total of 448 ACS patients (459 vessels) were assessed. Stent expansion<80%, MSA<4.5 mm2 and stent edge lipid-rich plaque and OFR<0.90 were independent predictors of TLR (all p value<0.001). Patients with OCT-suboptimal [adjusted hazard ratio (HR): 7.88, 95% CI: 2.73-22.72, p<0.001] or OFR-suboptimal (adjusted HR: 5.78, 95% CI: 2.54-13.14, p<0.001) stent deployment showed significantly higher risk of TLF compared to those with optimal stent deployment with a significant interaction (pinteraction<0.001). OCT and OFR both-suboptimal stent deployment was confirmed as an independent predictor of TLF (adjusted HR: 9.39, 95% CI: 4.25-20.76, p<0.001). CONCLUSION: Combined OCT and OFR conferred an optimal reclassification of stent deployment, which may aid in decision-making regarding a tailored PCI strategy for optimal stent deployment.
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BACKGROUND: Optical fiber sensors have been used to detect glucose owing to advantages such as low cost, small size, and ease of operation etc. phenylboronic acid is one of the commonly used receptors for glucose detection, however phenylboronic acid based regenerative optical fiber sensors are commonly cumulative regeneration, renewable regeneration sensor has been missing from the literature. RESULTS: In this work, instead of using phenylboronic acid, we synthesized succinylaminobenzenoboronic acid molecule (BPOA) by introducing a short chain containing carboxyl group at the other end of phenylboronic acid then covalently bonded BPOA on the surface of excessively tilted fiber grating (Ex-TFG). This provides a very stable platform for renewable regeneration and the regenerative buffer was also optimized. The proposed renewable regeneration method exhibited higher linearity and sensitivity (R2 = 0.9992, 8 pm/mM) in relative to the conventional cumulative regeneration method (R2 = 0.9718, 4.9 pm/mM). The binding affinity between BPOA and glucose was found to be almost constant over 140 bind/release cycles with a variation of less than 0.3 % relative standard deviation. SIGNIFICANCE: The regenerative and label-free sensing capacity of the proposed device provides a theoretical foundation for label-free saccharide detection and the development of wearable glucose monitoring devices based on fiber optic sensors.
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Técnicas Biossensoriais , Ácidos Borônicos , Fibras Ópticas , Ácidos Borônicos/química , Glucose/análise , Tecnologia de Fibra Óptica , Limite de DetecçãoRESUMO
Atherosclerosis (AS) is a chronic progressive inflammatory disease of the vascular wall and the primary pathological basis of cardiovascular and cerebrovascular disease. Focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2), two highly homologous members of the FAK family kinases, play critical roles in integrin signaling. They also serve as scaffolding proteins that contribute to the assembly of cellular signaling complexes that regulate cell survival, cell cycle progression, and cell motility. Research indicates that the FAK family kinases is involved in the gene regulation of vascular cells and that aberrant expression of this family is associated with pathological changes in vascular disease. These findings establish the FAK family kinases as a critical signaling mediator in atherosclerotic lesions and inhibition of its activity has the potential to attenuate the pathological progression of AS. This review highlights the indispensable role of the FAK family kinases in abnormal vascular smooth muscle cell proliferation, endothelial cell dysfunction, inflammation, and lipid metabolism associated with AS. We also summarize therapeutic targets against the FAK family kinases, providing valuable insights into therapeutic strategies for AS.
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Background: Enterobacter cloacae complex (ECC), which includes major nosocomial pathogens, causes urinary, respiratory, and bloodstream infections in humans, for which colistin is one of the last-line drugs. Objective: This study aimed to analyse the epidemiology and resistance mechanisms of colistin-resistant Enterobacter cloacae complex (ECC) strains isolated from Shandong, China. Methods: Two hundred non-repetitive ECC strains were collected from a tertiary hospital in Shandong Province, China, from June 2020 to June 2022. Whole-genome sequencing and bioinformatics analyses were performed to understand the molecular epidemiology of the colistin-resistant ECC strains. The nucleotide sequences of heat shock protein (hsp60) were analyzed by using BLAST search to classify ECC. The gene expression levels of ramA, soxS, acrA, acrB, phoP, and phoQ were assessed using RT-qPCR. MALDI-TOF MS was used to analyse the modification of lipid A. Results: Twenty-three colistin-resistant strains were detected among the 200 ECC clinical strains (11.5%). The hsp60 cluster analysis revealed that 20 of the 23 ECC strains belonged to heterogeneous resistance clusters. Variants of mgrB, phoPQ, and pmrAB, particularly phoQ and pmrB, were detected in the 23 ECC strains. The soxS and acrA genes were significantly overexpressed in all 23 colistin-resistant ECC strains (P < 0.05). Additionally, all 23 ECC strains contained modified lipid A related to colistin resistance, which showed five ion peaks at m/z 1876, 1920, 1955, 2114, and 2158. Among the 23 ECC strains, 6 strains possessed a phosphoethanolamine (pETN) moiety, 16 strains possessed a 4-amino-4-deoxy-L-arabinose (-L-Ara4N) moiety, and one strain had both pETN and -L-Ara4N moieties. Conclusion: This study suggests that diverse colistin resistance existed in ECC, including unknown resistance mechanisms, exist in ECC. Mechanistic investigations of colistin resistance are warranted to optimise colistin use in clinical settings and minimise the emergence of resistance.
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This study investigated the effects of ultrasonic and three chemical individual and dual modification treatments on corn starch's physicochemical, thermal, and rheological properties. Ultrasonication and the three chemical treatments disrupted the starch granules with a decrease in particle size and a significant increase in the ζ-potential. The hydrophilicity of ultrasonic-oxidized dual-modified starch (U-O-CS) was the highest, at 0.854 g/g. The lipophilicity of ultrasonic-esterified dual-modified starch (U-E-CS) was the highest, at 1.485 g/g. The gelatinization temperature of ultrasonic, oxidation, and cross-linking modified starches increased significantly, with cross-linking starches being the largest. Oxidative treatment significantly decreased the starch's G' and G" and weakened the textural properties. The rheological properties of U-O-CS were further weakened. The G' of the starch decreased after the esterification treatment, while the G" increased, and the textural properties were cut. The maximum rheological and textural properties were obtained for crosslinked modification, with a hardness value of 284.70 g.
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OBJECTIVE: This study aims to investigate the relationship between midday nap time, nighttime sleep duration, and mild cognitive impairment (MCI) in Chinese older adults and determine the recommended sleep duration to provide a scientific basis for preventing and managing MCI in this population. METHODS: Utilizing the 2020 China Health and Retirement Longitudinal Study database, the demographic data, health status, and lifestyle information of the study participants were collected. A total of 5,314 valid samples were included in the analysis. Logistic regression and restricted cubic spline plots were employed to explore the relationship between sleep patterns and MCI. RESULTS: In the cross-sectional analysis, a linear relationship was observed between midday nap duration and MCI among Chinese elderly. The probability of MCI was lowest among those who napped for less than 30 min at noon. Compared with individuals who napped for30-90 min, those who did not nap were more likely to have MCI (OR = 1.30, 95% CI: 1.05-1.60). Older adults with napping duration < 30 min (OR = 0.73, 95% CI:0.56-0.95) also exhibited lower probability of MCI when compared those without napping habit, Nighttime sleep duration exhibited a U-shaped relationship with MCI. Individuals with less than approximately 6 h of nighttime sleep showed a gradual decrease in the probability of MCI with increasing sleep duration, whereas those with more than 7.5 h demonstrated an increase in the probability of MCI with longer sleep duration. Older adults who slept less than 6 h at night (OR = 1.22, 95% CI: 1.01 ~ 1.46) or more than 8 h (OR = 1.78, 95% CI: 1.35-2.33) were more likely to develop MCI compared with those who slept 6 to 8 h. CONCLUSION: After controlling for potential confounding variables, both nighttime sleep duration and midday nap duration exhibited a nonlinear "U"-shaped relationship with MCI among the elderly. The probability of depression was lower with a nap duration of approximately 60 min, and the optimal nighttime sleep duration was 6-8 h, with around 7 h providing the greatest cognitive benefits.
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Disfunção Cognitiva , Sono , Humanos , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Masculino , Feminino , Idoso , China/epidemiologia , Sono/fisiologia , Fatores de Tempo , Estudos Longitudinais , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Fatores de Risco , Duração do Sono , População do Leste AsiáticoRESUMO
We assessed the diversity, composition, and distribution of bird species in patches of semi-humid evergreen broad-leaved forest by selecting eight natural forest communities in the central Yunnan Plateau, which is a representative distribution area of semi-humid broad-leaved evergreen forest. Field observations were conducted from April to August 2023 by the sample line and sample point method, and eight survey routes of 3-4 km in length were established. The results showed that 1) A total of 1286 birds were recorded, belonging to 102 species in 7 orders and 30 families. The three most abundant families were Muscicapidae (14 species), Leiothrichidae (9 species), and Phylloscopidae (7 species); 2) Species of Oriental origin, Palaearctic origin, and widespread species accounted for 81.4%, 4.9%, and 13.7% of observations, respectively; 3) The average number of bird species surveyed in forest patches was 32.0±3.5; the Shannon index of birds was lower in secondary, semi-humid evergreen broad-leaved forests (1.536±0.110) than in primary forest communities (2.037±0.100); 4) Species composition exhibited considerable variation between patches, with the presence of dominant and common species, and the difference in rare species; 5) Considering the ecological groups of birds based on diet, invertebrate-eating and omnivorous birds, herbivorous birds, and carnivorous birds accounted for 84.3%, 11.8%, and 3.9%, respectively. The coexistence of birds with similar diets was maintained by diluting interspecific competition, mainly through partitioning of the vertical feeding space. For the conservation of bird species diversity and rare species, all patches of native semi-humid evergreenbroad-leaved forest are of conservation value.
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Biodiversidade , Aves , Florestas , Animais , China , Aves/classificação , Árvores/crescimento & desenvolvimento , Árvores/classificação , Conservação dos Recursos NaturaisRESUMO
As one of the research hotspots in recent years, gut microbiota have been proven to be closely related to host metabolism, nutrient absorption, and immune regulation. However, there are still many urgent issues in the research of gut microbiota, such as the localization and tracking of gut microbiota. In this research, two new fluorescent probes, EF and 6F, were developed by optimizing the structure of the positron salt small molecule probe F16. In vitro labeling experiments showed that EF and 6F can quickly label Gram-positive bacteria, Staphylococcus aureus and Lactobacillus reuteri, as well as Gram-negative bacteria, Escherichia coli and Salmonella pullorum. Meanwhile, EF and 6F have little bacterial toxicity and are used at a maximum concentration of 200 µM. Compared with EF, 6F has better hydrophilicity and stronger fluorescence characteristics in aqueous solutions, making it more suitable for imaging within gut microbiota populations. The results of in vivo imaging experiments indicate that EF and 6F can label and image the intestinal microbiota colonized by the mouse intestinal mucosal epithelium without causing any damage to intestinal tissue. Compared with commercially available MitoTracker dyes and fluorescein 5-isothiocyanate (FITC) dyes, EF and 6F exhibit better biocompatibility. Therefore, the compounds EF and 6F synthesized in this study are novel small molecule probes suitable for imaging gut microbiota, providing a better probe selection for exploring complex gut microbiota.
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Immobilization of enzymes improves their stability and recoverability and is therefore crucial for scientific research and industrial applications. In this study, phospholipase LM (PLLM) and phospholipase 3G (PL3G) were immobilized using Fe3O4@SiO2@CS-COOH polycarboxylated magnetic nanoparticles (MNPs-COOH) as carriers and then used for degumming soybean crude oil. The immobilization rates and relative enzyme activities of these immobilized phospholipases were evaluated to determine the optimal immobilization parameters. The enzyme activities of PLLM-MNPs-COOH and PL3G-MNPs-COOH were 2830.87 and 1162.25 U/g, respectively. Enzymatic properties of the free and immobilized enzymes were compared. Both immobilized phospholipases exhibited higher condition tolerance and stability after immobilization. After 30-day storage at 4 °C, both immobilized phospholipases retained approximately 1.3 times the residual activity of the corresponding free phospholipases. When the degumming conditions were optimized, the residual phosphorus contents of the PLLM-MNPs-COOH- and PL3G-MNPs-COOH-degummed oils were 4.91 and 7.41 mg/kg, respectively, which were consistent with the safety standards for oil products. After 6 cycles, PLLM-MNPs-COOH and PL3G-MNPs-COOH continued to preserve 71.88 % and 70.00 % of their initial activities, respectively. The immobilized phospholipases are thus suitable for degumming soybean crude oil, and the mixed enzymes exhibited better degumming potential.
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Cell-to-cell interactions are essential for proper development, homeostasis, and complex syncytia/organ formation and function. Intercellular communication are mediated by multiple mechanisms including soluble mediators, adhesion molecules and specific mechanisms of cell to cell communication such as Gap junctions (GJ), tunneling nanotubes (TNT), and exosomes. Only recently, has been discovered that TNTs and exosomes enable the exchange of large signaling molecules, RNA, viral products, antigens, and organelles opening new avenues of research and therapeutic approaches. The focus of this review is to summarize these recent findings in physiologic and pathologic conditions.
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Comunicação Celular , Neoplasias , Humanos , Neoplasias/imunologia , Neoplasias/metabolismo , Comunicação Celular/fisiologia , Animais , Junções Comunicantes/metabolismo , Exossomos/metabolismoRESUMO
This study developed an individual-rearing method to compare the effects of live feed (sandworms Perinereis aibuhitensis), formulated pellet diets, and a mixture of live feed and formula feed on the Kuruma shrimp Penaeus japonicus, aiming to minimize the influence of non-dietary factors on the growth of P. japonicus, like cannibalism. Results indicated that live feed, with its higher protein, essential amino acids, and fatty acid content, led to significantly better growth and feeding performance in P. japonicus (p < 0.05) compared to pellet diets. A mixed diet resulted in a lower average daily protein intake yet maintained a growth and feeding performance comparable to live feed. The intestinal microbiota of shrimp, dominated by Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria, showed significant shifts with diet changes. Specifically, formulated feed increased the relative abundance of Vibrio and Photobacterium while decreasing Shimia and Rhodobacterales (p < 0.05), and feeding live food resulted in a more complex and stable bacterial network. Notably, individual variances in growth and feeding were observed among shrimps, with some on formulated diets showing growth comparable to those on live feed. Each shrimp's final weight, specific growth rate, protein efficiency rate, and average daily food intake positively correlated with its initial body weight (p < 0.05), and daily intake varied cyclically with the molting cycle. These findings suggest that individual-rearing is an effective approach for detailed feed evaluation and monitoring in P. japonicus, contributing to improved feed selection, development, and feeding strategies.
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The split-Hopkinson pressure bar technique is widely used to determine the dynamic mechanical behavior of materials. However, spike-like stress features appear in the initial stress behavior of ultra-soft materials tested with a split-Hopkinson bar. These features are not intrinsic characteristics of the materials. Potential causes were investigated through experiments and numerical simulations. It was found that the spike feature represents derived stress resulting from the radial inertia effect during dynamic loading. In this work, we propose and experimentally verify effective methods to reduce this effect. The influences of density, strain acceleration, ratio between inner and outer diameter, and Poisson's ratio on the radial inertia effect were investigated. The spike stress was found to change linearly with density and strain acceleration but decrease significantly when the inner/outer diameter ratio was below 0.3, after which it remained nearly constant. A parabolic stress distribution was observed along the radial direction due to the Poisson effect, especially when the ratio exceeded 0.3, leading to higher spike stress. Finally, suggestions were proposed as experimental guidance when testing ultra-soft materials.
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Terpenoids play a crucial role in plant growth and development, as well as in regulating resistance mechanisms. Terpene synthase (TPS) serves as the final step in the synthesis process of terpenoids. However, a comprehensive bioinformatics analysis of the TPS gene family in Triticum plants had not previously been systematically undertaken. In this study, a total of 531 TPS members were identified in Triticum plants. The evolutionary tree divided the TPS proteins into five subfamilies: Group1, Group2, Group3, Group4, and Group5. The results of the duplication events analysis showed that TD and WGD were major driving forces during the evolution of the TPS family. The cis-element analysis showed that the TPS genes were related to plant growth and development and environmental stress. Moreover, the GO annotation displayed that the biological function of TPS was relatively conserved in wheat plants. The RNA-seq data showed that the rice and wheat TPS genes responded to low-temperature stress and exhibited significantly different expression patterns. This research shed light on the functions of TPSs in responding to abiotic stress and demonstrated their modulatory potential during root development. These findings provide a foundation for further and deeper investigation of the TPSs' functions in Triticum plants.
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Alquil e Aril Transferases , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Família Multigênica , Filogenia , Proteínas de Plantas , Triticum , Triticum/genética , Triticum/crescimento & desenvolvimento , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Genoma de Planta , Oryza/genética , Oryza/crescimento & desenvolvimento , Perfilação da Expressão GênicaRESUMO
Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an epigenetic regulator that plays critical roles in tumours. However, the DNA methylation alteration patterns driven by UHRF1 and the related differentially expressed tumour-related genes remain unclear. In this study, a UHRF1-shRNA MCF-7 cell line was constructed, and whole-genome bisulfite sequencing and RNA sequencing were performed. The DNA methylation alteration landscape was elucidated, and DNA methylation-altered regions (DMRs) were found to be distributed in both gene bodies and adjacent regions. The DMRs were annotated and categorized into 488 hypermethylated/1696 hypomethylated promoters and 1149 hypermethylated/5501 hypomethylated gene bodies. Through an integrated analysis with the RNA sequencing data, 217 methylation-regulated upregulated genes and 288 downregulated genes were identified, and these genes were primarily enriched in nervous system development and cancer signalling pathways. Further analysis revealed 21 downregulated oncogenes and 15 upregulated TSGs. We also showed that UHRF1 silencing inhibited cell proliferation and migration and suppressed tumour growth in vivo. Our study suggested that UHRF1 and the oncogenes or TSGs it regulates might serve as biomarkers and targets for breast cancer treatment.
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Proteínas Estimuladoras de Ligação a CCAAT , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Ubiquitina-Proteína Ligases , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Humanos , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Células MCF-7 , Feminino , Proliferação de Células/genética , Animais , Regiões Promotoras Genéticas , Camundongos , Epigênese Genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Movimento Celular/genéticaRESUMO
The mitochondrial pyruvate carrier (MPC) is a specific protein complex located in the inner mitochondrial membrane. Comprising a heterodimer of two homodimeric membrane proteins, mitochondrial pyruvate carrier 1 and mitochondrial pyruvate carrier 2, MPC connects cytoplasmic metabolism to mitochondrial metabolism by transferring pyruvate from the cytoplasm to the mitochondria. The nervous system requires substantial energy to maintain its function, and the mitochondrial energy supply is closely linked to neurological function. Mitochondrial dysfunction can induce or exacerbate intracerebral pathologies. MPC influences mitochondrial function due to its specific role as a pyruvate transporter. However, recent studies on MPC and mitochondrial dysfunction in neurological disorders have yielded controversial results, and the underlying mechanisms remain unclear. In this brief review, we provide an overview of the structure and function of MPC. We further discuss the potential mechanisms and feasibility of targeting MPC in treating Parkinson's disease, Alzheimer's disease, and cerebral ischemia/hypoxia injury. This review aims to offer insights into MPC as a target for clinical treatment.
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Aloperine (ALO), a quinolizidine-type alkaloid isolated from a natural Chinese herb, has shown promising antitumor effects. Nevertheless, its common mechanism of action and specific target remain elusive. Here, it is demonstrated that ALO inhibits the proliferation and migration of non-small cell lung cancer cell lines in vitro and the tumor development in several mouse tumor models in vivo. Mechanistically, ALO inhibits the fusion of autophagosomes with lysosomes and the autophagic flux, leading to the accumulation of sequestosome-1 (SQSTM1) and production of reactive oxygen species (ROS), thereby inducing tumor cell apoptosis and preventing tumor growth. Knockdown of SQSTM1 in cells inhibits ROS production and reverses ALO-induced cell apoptosis. Furthermore, VPS4A is identified as a direct target of ALO, and the amino acids F153 and D263 of VPS4A are confirmed as the binding sites for ALO. Knockout of VPS4A in H1299 cells demonstrates a similar biological effect as ALO treatment. Additionally, ALO enhances the efficacy of the anti-PD-L1/TGF-ß bispecific antibody in inhibiting LLC-derived subcutaneous tumor models. Thus, ALO is first identified as a novel late-stage autophagy inhibitor that triggers tumor cell death by targeting VPS4A.
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Autofagossomos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Lisossomos , Quinolizidinas , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Autofagossomos/metabolismo , Autofagossomos/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Lisossomos/metabolismo , Lisossomos/efeitos dos fármacos , Linhagem Celular Tumoral , Quinolizidinas/farmacologia , Modelos Animais de Doenças , Proteínas de Transporte Vesicular/metabolismo , Proteínas de Transporte Vesicular/genética , Progressão da Doença , Proliferação de Células/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacosRESUMO
The urban heat island (UHI) effect in arid cities can be small or even negative, the latter known as the urban cool island (UCI) effect. Differences in defining urban and rural areas can introduce uncertainties in detecting UHI or UCI, especially when the UHI signal is small. Here, we compared the surface UHI intensity (SUHII) estimated by a dozen different methods (with multiple urban and/or rural definitions) across 104 arid cities globally, providing a comprehensive evaluation of the uncertainty in SUHII estimates. Results show that the absolute difference in annual average SUHII (∆SUHII) among methods exceeded 1 °C in about half of the arid cities during both daytime and nighttime. The overall annual mean ∆SUHII for all arid cities was 1.35 °C during daytime and 1.03 °C at night. The uncertainty arising from simultaneous variations in urban and rural definitions was generally higher than that resulting from their individual changes. It was observed that, with varying definitions of urban and rural areas, nearly 50 % of arid cities experienced a sign reversal in daytime SUHII estimates, while approximately 15 % exhibited a sign reversal in nighttime SUHII. Variations in urban-rural differences in surface properties, such as vegetation index and albedo, due to differing urban and rural definitions, contributed strongly to the observed SUHII uncertainties. Overall, our results offer new insights into the ongoing debate on heat and cold islands in arid cities, emphasizing a critical need to standardize SUHII estimation frameworks.