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A novel mid-infrared methane remote sensor integrated on a movable platform based on a 3.291-µm interband cascade laser (ICL) and wavelength modulation spectroscopy (WMS) is proposed. A transmitting-receiving coaxial, visualized optical layout is employed to minimize laser energy loss. Using a hollow retro-reflector remotely deployed as a cooperative target, the atmospheric average methane concentration over a 100-meter optical range is measured with high sensitivity. A deep neural network (DNN) filter is used for second harmonic (2f) signal denoising to compensate for the performance shortcomings of conventional filtering. Allan deviation analysis indicated that after applying the DNN filter, the limit of detection (LOD) of methane was 86.62 ppb with an average time of 1 s, decreasing to 12.03 ppb with an average time of 229 s, which is a significant promotion compared to similar work reported. The high sensitivity and stability of the proposed sensor are shown through a 24-hour continuous monitoring experiment of atmospheric methane conducted outdoors, providing a new solution for high-sensitivity remote sensing of atmospheric methane.
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We propose a novel methane leakage rate remote sensor that combines a single-photon avalanche diode detector with a near-infrared 1653.7â nm low-power laser. The proposed M sequence and triangle wave signal modulation method simultaneously realizes the detection of methane leakage and target point clouds. Innovatively, the sensor's methane concentration and leakage rate quantification ability were simulated by combining the Gaussian plume diffusion model and the Risley prism. The effects of the prism rotation ratio, wind speed, leakage rate, atmospheric stability (AS), target reflectivity, signal averaging period, and concentration spatial interpolation method on leakage rate are discussed. When plume methane concentrations reduce from 10,000 to 500â ppm·m, the relative concentration bias rise from 1% to 30%, the absolute concentration bias is approximately 100â ppm·m. Two spatial concentration interpolation methods introduced leakage rate bias ranging from 6%-25%. For a low AS, the leakage rate bias under the cubic interpolation method was small (approximately 1.6%). In addition, when the initial leakage rate increased from 100 to 1,000â mg/s, the leakage rate bias was approximately 20% smaller.
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10-Hydroxycamptothecin (HCPT) is a widely used clinical anticancer drug but has a significant side effect profile. Melatonin has a beneficial impact on the chemotherapy of different cancer cells and reproductive processes, but the effect and underlying molecular mechanism of melatonin's involvement in the HCPT-induced side effects in cells, especially in the testicular cells, are poorly understood. In this study, we found that melatonin therapy significantly restored HCPT-induced testicular cell damage and did not affect the antitumor effect of HCPT. Further analysis found that melatonin therapy suppressed HCPT-induced DNA damage associated with ataxia-telangiectasia mutated- and Rad3-related and CHK1 phosphorylation levels in the testis. Changes in apoptosis-associated protein levels (Bax, Bcl-2, p53, and Cleaved caspase-3) and in reactive oxygen species-associated proteins (Nrf2 and Keap1) and index (malondialdehyde and glutathione) suggested that melatonin treatment relieved HCPT-induced cell apoptosis and oxidative damage, respectively. Mechanistically, melatonin-activated autophagy proteins (ATG7, Beclin1, and LC3bII/I) may induce p62-dependent autophagy to degrade Keap1, eliciting Nrf2 from Keap1-Nrf2 interaction to promote antioxidant enzyme expression such as HO-1, which would salvage HCPT-induced ROS production and mitochondrial dysfunction. Collectively, this study reveals that melatonin therapy may protect testicular cells from HCPT-induced damage via the activation of autophagy, which alleviates oxidative stress, mitochondrial dysfunction, and cell apoptosis.
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Apoptose , Camptotecina , Melatonina , Estresse Oxidativo , Transdução de Sinais , Testículo , Animais , Masculino , Camundongos , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Camptotecina/farmacologia , Camptotecina/análogos & derivados , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Melatonina/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismoRESUMO
OBJECTIVE: To investigate the effect of quick acupuncture combined with rehabilitation therapy on motor and swallowing function of patients with stroke. DESIGN: A retrospective study. SETTING: Single center study. PARTICIPANTS: One hundred and twenty patients with stroke were divided into control and observation group based on the therapeutic regimen. INTERVENTION: Control group (n = 60) only received rehabilitation therapy, and observation group (n = 60) received rehabilitation therapy combined with quick acupuncture. Acupuncture was performed once a day, and 6 times/week for 4 consecutive weeks. MAIN MEASURES: The simplified Fugl-Meyer assessment scale and Barthel index were used to assess limb motor function and daily living ability. The Dysphagia Outcome Severity Scale and Swallowing Quality of Life questionnaire were conducted to estimate the dysphagia severity and life quality of patients with swallowing disorders. The therapeutic efficacy and complications after treatment were analyzed and counted. RESULTS: After treatment, the scores of the observation group were significantly improved compared with the control group (P < 0.05). In the observation group, the therapeutic efficacy was 93% (n = 56); the complication rate was 5% (n = 3); the therapeutic efficacy of the control group was 75% (n = 45); and the complication rate was 25% (n = 15), indicating that the therapeutic efficacy of the observation group is better and the incidence of complications is lower than that of the control group. CONCLUSION: This study suggests that rehabilitation therapy combined with rapid acupuncture therapy has a potential therapeutic effect on the relief of swallowing and motor dysfunction after stroke.
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Terapia por Acupuntura , Transtornos de Deglutição , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Reabilitação do Acidente Vascular Cerebral/métodos , Terapia por Acupuntura/métodos , Pessoa de Meia-Idade , Transtornos de Deglutição/reabilitação , Transtornos de Deglutição/etiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Idoso , Resultado do Tratamento , Terapia Combinada , Qualidade de Vida , Recuperação de Função Fisiológica , Índice de Gravidade de DoençaRESUMO
The transgalactosylase activity of ß-galactosidases offers a convenient and promising strategy for conversion of lactose into high-value oligosaccharides, such as galacto-oligosaccharides (GOS) and human milk oligosaccharides (HMOs). In this study, we cloned and biochemically characterized a novel C-terminally truncated ß-galactosidase (PaBgal2A-D) from Paenibacillus antarcticus with high transglycosylation activity. PaBgal2A-D is a member of glycoside hydrolase (GH) family 2. The optimal pH and temperature of PaBgal2A-D were determined to be pH 6.5 and 50°C, respectively. It was relatively stable within pH 5.0-8.0 and up to 50°C. PaBgal2A-D showed high transglycosylation activity for GOS synthesis, and the maximum yield of 50.8% (wt/wt) was obtained in 2 h. Moreover, PaBgal2A-D could synthesize lacto-N-neotetraose (LNnT) using lactose and lacto-N-triose II (LNT2), with a conversion rate of 16.4%. This study demonstrated that PaBgal2A-D could be a promising tool to prepare GOS and LNnT.
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Perfluorooctane sulfonate (PFOS), an officially listed persistent organic pollutant, is a widely distributed perfluoroalkyl substance. Epidemiological studies have shown that PFOS is intimately linked to the occurrence of insulin resistance (IR). However, the detailed mechanism remains obscure. In previous studies, we found that mitochondrial calcium overload was concerned with hepatic IR induced by PFOS. In this study, we found that PFOS exposure noticeably raised lysosomal calcium in L-02 hepatocytes from 0.5â¯h. In the PFOS-cultured L-02 cells, inhibiting autophagy alleviated lysosomal calcium overload. Inhibition of mitochondrial calcium uptake aggravated the accumulation of lysosomal calcium, while inhibition of lysosomal calcium outflowing reversed PFOS-induced mitochondrial calcium overload and IR. Transient receptor potential mucolipin 1 (TRPML1), the calcium output channel of lysosomes, interacted with voltage-dependent anion channel 1 (VDAC1), the calcium intake channel of mitochondria, in the PFOS-cultured cells. Moreover, we found that ATP synthase F1 subunit beta (ATP5B) interacted with TRPML1 and VDAC1 in the L-02 cells and the liver of mice under PFOS exposure. Inhibiting ATP5B expression or restraining the ATP5B on the plasma membrane reduced the interplay between TRPML1 and VDAC1, reversed the mitochondrial calcium overload and deteriorated the lysosomal calcium accumulation in the PFOS-cultured cells. Our research unveils the molecular regulation of the calcium crosstalk between lysosomes and mitochondria, and explains PFOS-induced IR in the context of activated autophagy.
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Ácidos Alcanossulfônicos , Autofagia , Cálcio , Fluorocarbonos , Resistência à Insulina , Fígado , Lisossomos , Mitocôndrias , ATPases Mitocondriais Próton-Translocadoras , Ácidos Alcanossulfônicos/toxicidade , Fluorocarbonos/toxicidade , Animais , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Autofagia/efeitos dos fármacos , Cálcio/metabolismo , Camundongos , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Masculino , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Linhagem Celular , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Poluentes Ambientais/toxicidade , Canais de Cátion TRPM/metabolismo , Camundongos Endogâmicos C57BLRESUMO
The incidence of nonalcoholic steatohepatitis (NASH) is related with perfluorooctane sulfonate (PFOS), yet the mechanism remains ill-defined. Mounting evidence suggests that ferroptosis plays a crucial role in the initiation of NASH. In this study, we used mice and human hepatocytes L-02 to investigate the role of ferroptosis in PFOS-induced NASH and the effect and molecular mechanism of PFOS on liver ferroptosis. We found here that PFOS caused NASH in mice, and lipid accumulation and inflammatory response in the L-02 cells. PFOS induced hepatic ferroptosis in vivo and in vitro, as evidenced by the decrease in glutathione peroxidase 4 (GPX4), and the increases in cytosolic iron, acyl-CoA synthetase long-chain family member 4 (ACSL4) and lipid peroxidation. In the PFOS-treated cells, the increases in the inflammatory factors and lipid contents were reversed by ferroptosis inhibitor. PFOS-induced ferroptosis was relieved by autophagy inhibitor. The expression of mitochondrial calcium uniporter (MCU) was accelerated by PFOS, leading to subsequent mitochondrial calcium accumulation, and inhibiting autophagy reversed the increase in MCU. Inhibiting mitochondrial calcium reversed the variations in GPX4 and cytosolic iron, without influencing the change in ACSL4, induced by PFOS. MCU interacted with ACSL4 and the siRNA against MCU reversed the changes in ACSL4ï¼GPX4 and cytosolic iron systemically. This study put forward the involvement of hepatic ferroptosis in PFOS-induced NASH and identified MCU as the mediator of the autophagy-dependent ferroptosis.
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Ácidos Alcanossulfônicos , Autofagia , Cálcio , Coenzima A Ligases , Ferroptose , Fluorocarbonos , Hepatopatia Gordurosa não Alcoólica , Ferroptose/efeitos dos fármacos , Fluorocarbonos/toxicidade , Animais , Ácidos Alcanossulfônicos/toxicidade , Camundongos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/patologia , Autofagia/efeitos dos fármacos , Coenzima A Ligases/metabolismo , Humanos , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Linhagem Celular , Hepatócitos/efeitos dos fármacosRESUMO
High-precision temperature control of large-area blackbodies has a pivotal role in temperature calibration and thermal imaging correction. Meanwhile, it is necessary to correct the temperature difference between the radiating (surface of use) and back surfaces (where the temperature sensor is installed) of the blackbody during the testing phase. Moreover, large-area blackbodies are usually composed of multiple temperature control channels, and manual correction in this scenario is error-prone and inefficient. At present, there is no method that can achieve temperature-automated calibration for a large-area blackbody radiation source. Therefore, this article is dedicated to achieving temperature-automated calibration for a large-area blackbody radiation source. First, utilizing two calibrated infrared thermometers, the optimal temperature measurement location was determined using a focusing algorithm. Then, a three-axis movement system was used to obtain the true temperature at the same measurement location on a large-area blackbody surface from different channels. This temperature was subtracted from the blackbody's back surface. The temperature difference was calculated employing a weighted algorithm to derive the parameters for calibration. Finally, regarding experimental verification, the consistency error of the temperature measurement point was reduced by 85.4%, the temperature uniformity of the surface source was improved by 40.4%, and the average temperature measurement deviation decreased by 43.8%. In addition, this system demonstrated the characteristics of strong environmental adaptability that was able to perform temperature calibration under the working conditions of a blackbody surface temperature from 100 K to 573 K, which decreased the calibration time by 9.82 times.
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Soil respiration (RS) is crucial for releasing carbon dioxide (CO2) from terrestrial ecosystems to atmosphere. Prescribed burning (a common forest management tool), along with its important by-product pyrogenic carbon (PyC), can influence the carbon cycle of forest soil. However, few studies explore RS and PyC spatial correlation after prescribed burning. In this study, we investigated the spatial pattern of RS and its influencing factors by conducting prescribed burnings in a temperate artificial Pinus koraiensis forest. RS was measured 1 day (1 d) pre-prescribed burning, 1 d, 1 year (1 yr) and two years (2 yr) after prescribed burning. Significant decrease in RS were observed 1-2 yr After burning (reductions of 65.2% and 41.7% respectively). The spatial autocorrelation range of RS decreased pre-burning (2.72m), then increased post-burning (1 d: 2.44m; 1 yr: 40.14m; 2 yr: 9.8m), indicating a more homogeneous distribution of patch reduction. Pyrogenic carbon (PyC) in the soil gradually decreased in the short term after burning with reductions of 19%, 52%, and 49% (1d., 1 yr And 2 yr After the fire, respectively). However, PyC and RS exhibited a strong spatial positive correlation from 1 d.- 1 yr post-burning. The spatial regression model of dissolved organic carbon (DOC) on RS demonstrated significant positive spatial correlation in all measurements (pre- and post-burning). Microbial carbon to soil nitrogen ratio (MCN) notably influenced RS pre-burning and 1-2 yr post-burning. RS also showed significant spatial correlation in cross-variance with NH4+-N and NO3--N post-burning. The renewal of the PyC positively influenced RS, subsequently affecting its spatial distribution in 1d.- 1yr. Introducing PyC into RS studies helps enhances understanding of prescribed fire effects on forest soil carbon (C) pools, and provides valuable information regarding regional or ecosystem C cycling, facilitating a more accurate prediction of post-burning changes in forest soil C pools.
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A novel ß-galactosidase (TsGal48) from Thermus scotoductus was cloned, and the enzyme was biochemically characterized. TsGal48 catalyzed the synthesis of lacto-N-neotetraose (LNnT) from lactose via the transglycosylation reaction with a maximal yield of 20%, which is the highest yield for the synthesis of LNnT so far. To further improve the yield of LNnT, TsGal48 was successfully engineered by directed evolution and site-saturation mutagenesis. A mutated ß-galactosidase (mTsGal48) was selected and characterized. mTsGal48 produced LNnT with a yield of 27.7 g/L, which is 1.4-fold higher than that of TsGal48 (19.7 g/L). Then, a developed strategy for LNnT synthesis from chitin powder was provided in a 30 L bioreactor. The reaction process included chitin powder hydrolysis, lacto-N-triose II (LNT2) synthesis, and LNnT synthesis. The reaction time was reduced from 44 to 17 h in chitin powder hydrolysis and LNT2 synthesis. The content of LNnT was up to 25 g/L in the multienzyme system. The green and efficient route may be suitable for large-scale production of LNnT from chitin powder.
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Background: Oesophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths worldwide because existing treatments are often insufficient. Therefore, new, reliable biomarkers must be identified. CTSL overexpression is closely associated with tumour progression and poor prognosis. However, the role and mechanism of CTSL as an oncogene in ESCC remain unclear. Methods: Genome-wide association study (GWAS) data were used for Mendelian randomization analysis to investigate the possible relationships between CTSL and ESCC. The correlation between CTSL expression and prognosis was analysed using GEO, TCGA, and GEPIA data. We compared CTSL expression among the cell types using single-cell sequencing. Correlations between CTSL and the tumour microenvironment, immune cell infiltration, tumour mutational load, immunological checkpoints, and treatment sensitivity in patients with ESCC were investigated. Finally, using mouse models and cellular investigations, we assessed the effects of CTSL on the growth, apoptosis, and metastasis of ESCC tumour cells. Results: CTSL was overexpressed in ESCC and correlated with prognosis. We also discovered its close association with cell immunity, especially with tumour-associated macrophages and immune checkpoints in the tumour microenvironment. CTSL may play a key role in ESCC development by affecting M2 macrophage polarisation. CTSL and the M2 macrophage marker genes showed significant positive correlations. Mendelian randomization analysis confirmed a relationship between CTSL and ESCC. Finally, our in vitro and in vivo experiments demonstrated that CTSL promoted the proliferation and migration of ESCC cells, validating our bioinformatic analysis. Conclusion: CTSL emerged as a crucial gene in ESCC that influences patient prognosis and immunity, particularly in association with M2 macrophages. Therefore, targeting or modulating CTSL levels may provide new therapeutic strategies for patients with ESCC.
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Human babesiosis is a tick-borne disease caused by Babesia pathogens. The disease, which presents with malaria-like symptoms, can be life-threatening, especially in individuals with weakened immune systems and the elderly. The worldwide prevalence of human babesiosis has been gradually rising, prompting alarm among public health experts. In other pathogens, genetic techniques have proven to be valuable tools for conducting functional studies to understand the importance of specific genes in development and pathogenesis as well as to validate novel cellular targets for drug discovery. Genetic manipulation methods have been established for several non-human Babesia and Theileria species and, more recently, have begun to be developed for human Babesia parasites. We have previously reported the development of a method for genetic manipulation of the human pathogen Babesia duncani. This method is based on positive selection using the hDHFR gene as a selectable marker, whose expression is regulated by the ef-1aB promoter, along with homology regions that facilitate integration into the gene of interest through homologous recombination. Herein, we provide a detailed description of the steps needed to implement this strategy in B. duncani to study gene function. It is anticipated that the implementation of this method will significantly improve our understanding of babesiosis and facilitate the development of novel and more effective therapeutic strategies for the treatment of human babesiosis. Key features This protocol provides an effective means of transfection of B. duncani, enabling genetic manipulation and editing to gain further insights into its biology and pathogenesis. The protocol outlined here for the electroporation of B. duncani represents an advancement over previous methods used for B. bovis [1]. Improvements include higher volume of culture used during the electroporation step and an enhancement in the number of electroporation pulses. These modifications likely enhance the efficiency of gene editing in B. duncani, allowing for quicker and more effective selection of transgenic parasites.
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Drunk-driving events often escalate into drunk-driving crashes, however, the contributing factors of this progression remain elusive. To mitigate the likelihood of crashes stemming from drunk-driving events, this paper introduces the notion of 'the severity of drunk-driving event' and examines the complex relationship between the severity and its contributing factors, considering spatiotemporal heterogeneity. The study utilizes a Geographically and Temporally Weighted Binary Logistic Regression (GTWBLR) model to conduct spatiotemporal analysis based on police-reported drunk-driving events in Beijing, China. The results show that most factors passed the non-stationary test, indicating their effects on the severity of drunk-driving event vary significantly across different spatial and temporal domains. Notably, during non-workday, drunk-driving events in northeast of Beijing are more likely to escalate into crashes. Furthermore, severe weather during winter in the northwest of Beijing is associated with high risk of drunk-driving crashes. Based on these insights, the authorities can strengthen drunk-driving checks in the northeast region of Beijing, particularly during non-workdays. And it is crucial to promptly clear accumulated snow on the roads during severe winter weather to improve road safety. These insights and recommendations are highly valuable for reducing the risk of drunk-driving crashes.
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Acidentes de Trânsito , Dirigir sob a Influência , Análise Espaço-Temporal , Humanos , Acidentes de Trânsito/estatística & dados numéricos , Pequim , Dirigir sob a Influência/estatística & dados numéricos , Dirigir sob a Influência/legislação & jurisprudência , Modelos Logísticos , Masculino , Feminino , Condução de Veículo , Tempo (Meteorologia) , AdultoRESUMO
Traffic violation is one of the leading causes of traffic crashes. In the context of global aging, it is important to study traffic violations by elderly drivers for improving traffic safety in preparation for a worldwide aging population. In this study, a hybrid approach of Latent Class Analysis (LCA) and XGBoost based SHAP is proposed to identify hidden clusters and to understand the key contributing factors on the severity of traffic violations by elderly drivers, based on the police-reported traffic violation dataset of Beijing (China). First, LCA is applied to segment the dataset into several latent homogeneous clusters, then XGBoost based SHAP is established on each cluster to identify feature contributions and the interaction effects of the key contributing factors on the severity of traffic violations by elderly drivers. Two comparison groups were set up to analyze factors, which are responsible for the different severities of traffic violations. The results show that elderly drivers can be classified into four groups by age, urban or not, license, and season; factors such as less annual number of traffic violations, national & provincial highway, night and winter are key contributing factors for higher severity of traffic violations, which are consistent with common cognition; key contributing factors for all clusters are similar but not identical, for example, more annual number of traffic violations contribute to more severe violation for all clusters except for Cluster 2; some factors which are not key contributing factors may affect the severity of traffic violations when they are combined with other factors, for example, the combination of lower annual number of traffic violations and county & township highway contributes to more severe violation for Cluster 1. These findings can help government to formulate targeted countermeasures to decrease the severity of traffic violations by specific elderly groups and improve road service for the driving population.
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Acidentes de Trânsito , Condução de Veículo , Análise de Classes Latentes , Humanos , Idoso , Acidentes de Trânsito/prevenção & controle , Masculino , Pessoa de Meia-Idade , Feminino , Idoso de 80 Anos ou mais , Pequim , Fatores Etários , China , SegurançaRESUMO
The protective efficacy of chemically bonded phosphate ceramic coatings (CBPC) is notably diminished owing to the presence of micropores and inadequate self-healing capacity in prolonged corrosive environments. Consequently, it is imperative to augment the corrosion and wear resistance of phosphate ceramic coatings while imbuing them with self-healing capabilities. In this work, a novel self-healing phosphate ceramic coating (MC-PTx@CBPC, x = 0.5, 1.0, 1.5) is designed by urea-formaldehyde (UF) in situ polymerization of nanoscale microcapsules encapsulated with 1H,1H,2H,2H-perfluorodecyltriethoxysilane (PFDTES) and evaluated in detail for corrosion and wear resistance. The corrosion inhibition efficiencies of all formulated MC-PTx@CBPC (x = 0.5, 1.0, 1.5) coatings exceed 90%, with the impedance modulus at the lowest frequency (|Z|f=0.01) showing enhancements of 1-2 orders of magnitude compared to pure CBPC. Moreover, the self-healing function becomes active during prolonged immersion. This can be primarily ascribed to the formation of a unique micronanostructure facilitated by nanoscale microcapsules and micrometer-sized alumina ceramics, bonded via the AlPO4 phase. This structure enhances both the hydrophobicity and the bonding strength of the coating. Specifically, following prolonged immersion, the encapsulated PFDTES is liberated from the microcapsules, undergoing hydrolysis and subsequent polymerization upon contact with the electrolyte to form a protective thin film. This film efficiently obstructs the ingress of corrosive agents. Furthermore, the special micronanostructure enhances the hardness of the coating and the releasing PFDTES can form a lubricating film at the interface of abrasion, thus reducing the wear rate and friction coefficient of the MC-PTx@CBPC (x = 0.5, 1.0, 1.5). Therefore, MC-PTx@CBPC (x = 0.5, 1.0, 1.5) possesses excellent corrosion protection, tribological properties, and self-healing capabilities, which provide thought-provoking ideas for phosphate ceramic coatings to protect metals in harsh environments.
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BACKGROUND: Heart failure (HF) is the last stage in the progression of various cardiovascular diseases. Although it is documented that CD151 contributes to regulate the myocardial infarction, the function of CD151 on HF and involved mechanisms are still unclear. METHOD AND RESULTS: In the present study, we found that the recombinant adeno-associated virus (rAAV)-mediated endothelial cell-specific knockdown of CD151-transfected mice improved transverse aortic constriction (TAC)-induced cardiac function, attenuated myocardial hypertrophy and fibrosis, and increased coronary perfusion, whereas overexpression of the CD151 protein aggravated cardiac dysfunction and showed the opposite effects. In vitro, the cardiomyocytes hypertrophy induced by PE were significantly improved, while the proliferation and migration of cardiac fibroblasts (CFs) were significantly reduced, when co-cultured with the CD151-silenced endothelial cells (ECs). To further explore the mechanisms, the exosomes from the CD151-silenced ECs were taken by cardiomyocyte (CMs) and CFs, verified the intercellular communication. And the protective effects of CD151-silenced ECs were inhibited when exosome inhibitor (GW4869) was added. Additionally, a quantitative proteomics method was used to identify potential proteins in CD151-silenced EC exosomes. We found that the suppression of CD151 could regulate the PPAR signaling pathway via exosomes. CONCLUSION: Our observations suggest that the downregulation of CD151 is an important positive regulator of cardiac function of heart failure, which can regulate exosome-stored proteins to play a role in the cellular interaction on the CMs and CFs. Modulating the exosome levels of ECs by reducing CD151 expression may offer novel therapeutic strategies and targets for HF treatment.
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Exossomos , Insuficiência Cardíaca , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Células Endoteliais , Regulação para Baixo , Exossomos/metabolismo , Cardiomegalia/genética , Cardiomegalia/metabolismo , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismoRESUMO
The causes of traffic violations by elderly drivers are different from those of other age groups. To reduce serious traffic violations that are more likely to cause serious traffic crashes, this study divided the severity of traffic violations into three levels (i.e., slight, ordinary, severe) based on point deduction, and explore the patterns of serious traffic violations (i.e., ordinary, severe) using multi-source data. This paper designed an interpretable machine learning framework, in which four popular machine learning models were enhanced and compared. Specifically, adaptive synthetic sampling method was applied to overcome the effects of imbalanced data and improve the prediction accuracy of minority classes (i.e., ordinary, severe); multi-objective feature selection based on NSGA-II was used to remove the redundant factors to increase the computational efficiency and make the patterns discovered by the explainer more effective; Bayesian hyperparameter optimization aimed to obtain more effective hyperparameters combination with fewer iterations and boost the model adaptability. Results show that the proposed interpretable machine learning framework can significantly improve and distinguish the performance of four popular machine learning models and two post-hoc interpretation methods. It is found that six of the top ten important factors belong to multi-scale built environment attributes. By comparing the results of feature contribution and interaction effects, some findings can be summarized: ordinary and severe traffic violations have some identical influencing factors and interactive effects; have the same influencing factors or the same combinations of influencing factors, but the values of the factors are different; have some unique influencing factors and unique combinations of influencing factors.
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BACKGROUND: Stromal cell derived factor-1 (SDF-1) plays a pivotal role in the recruitment of stem cells to injured livers. However, the changes of SDF-l in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) have yet to be elucidated. AIM: To study the SDF-1 changes in patients with HBV-related ACLF. METHODS: 30 patients with HBV-related ACLF, 27 patients with chronic hepatitis B and 20 healthy individuals are involved in our study. The SDF-l mRNA expression in liver tissue was detected by quantitative real-time polymerase chain reaction. Immunohistochemical staining was performed to illustrate the expression of SDF-l, CXC receptor 4 (CXCR4) and Ki67. The serum SDF-l concentrations were also detected by enzyme-linked immunosorbent assays. RESULTS: The expression of SDF-1 mRNA from ACLF patients was remarkably higher than that from other patients (both P < 0.05). The expression of SDF-l, CXCR4 and Ki67 from ACLF were the highest among the three groups (all P < 0.01). The serum SDF-l levels in ACLF patients were significantly lower than that in other patients (both P < 0.01). Moreover, in ACLF patients, the serum SDF-1 Levels were positively correlated with serum total bilirubin and international normalized ratio. In addition, the serum SDF-l levels in survival were significantly lower compared with the non-survivals (P < 0.05). The area under the curve for the serum SDF-1 level in predicting 28-d mortality was 0.722 (P < 0.05). CONCLUSION: This study provides the SDF-1 changes in patients with HBV-related ACLF. The SDF-1 Level at admission may serve as a promising prognostic marker for predicting short-term prognosis.
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Ultra-compact spectrometers are becoming increasingly popular for their promising applications in biomedical analysis, environmental monitoring, and food safety. In this work, we report a single-pixel-photodetector spectrometer with a spectral range from 480 nm to 820 nm, based on the AlGaAs/GaAs p-graded-n junction with a voltage-tunable optical response. To reconstruct the optical spectrum, we propose a tailored method called Neural Spectral Fields (NSF) that leverages the unique wavelength and bias-dependent responsivity matrix. Our spectrometer achieves a high spectral wavelength accuracy of up to 0.30 nm and a spectral resolution of up to 10 nm. Additionally, we demonstrate the high spectral imaging performance of the device. The compatibility of our demonstration with the standard III-V process greatly accelerates the commercialization of miniaturized spectrometers.