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Lactate dehydrogenase A (LDHA) is known to promote the growth and invasion of various types of tumors, affects tumor resistance, and is associated with tumor immune escape. But how LDHA reshapes the tumor microenvironment and promotes the progression of renal cell carcinoma (RCC) remains unclear. In this study, we found that LDHA was highly expressed in clear cell RCC (ccRCC), and this high expression was associated with macrophage infiltration, while macrophages were highly infiltrated in ccRCC, affecting patient prognosis via M2-type polarization. Our in vivo and in vitro experiments demonstrated that LDHA and M2-type macrophages could enhance the proliferation, invasion, and migration abilities of ccRCC cells. Mechanistically, high expression of LDHA in ccRCC cells upregulated the expression of EPHA2 in exosomes derived from renal cancer. Exosomal EPHA2 promoted M2-type polarization of macrophages by promoting activation of the PI3K/AKT/mTOR pathway in macrophages, thereby promoting the progression of ccRCC. All these findings suggest that EPHA2 may prove to be a potential therapeutic target for advanced RCC.
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Carcinoma de Células Renais , Progressão da Doença , Exossomos , Neoplasias Renais , Macrófagos , Receptor EphA2 , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/genética , Receptor EphA2/metabolismo , Receptor EphA2/genética , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/genética , Exossomos/metabolismo , Animais , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , L-Lactato Desidrogenase/metabolismo , L-Lactato Desidrogenase/genética , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Masculino , Microambiente Tumoral , Prognóstico , Serina-Treonina Quinases TOR/metabolismo , Feminino , Transdução de Sinais , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
In clinical practice, the treatment of colon cancer is faced with the dilemma of metastasis and recurrence, which is related to immunosuppression and hypoxia. Immune checkpoint blockade (ICB) is a negative regulatory pathway of immunity. Immune checkpoint blockade (ICB) is an important immunotherapy method. However, inadequate immunogenicity reduces the overall response rate of ICB. In this study, a tumor microenvironment-responsive nanomedicine (Cu-FACD@MnO2@FA) was prepared to increase host immune response and increase intracellular oxygen levels. Cu-FACD@MnO2@FA preferentially enriched at the tumor site, combined with the immune checkpoint inhibitor alpha PD-L1, induced sufficient immunogenicity to treat colon cancer. Immunofluorescence detection of tumor cells and tissues showed that the expression of hypoxa-inducing factor 1α was significantly down-regulated after treatment and the expression of immunoactivity-related proteins was significantly changed. In vivo treatment in a bilateral tumor mouse model showed complete ablation of the primary tumor and efficient inhibition of the distal tumor. In this study, for the first time, the oxygenation effects of MnO2-coated Cu-doped carbon dots and chemodynamic therapy and a strategy of combining with immuno-blocking therapy were used for treating colon cancer.
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Carbono , Neoplasias do Colo , Cobre , Ácido Fólico , Compostos de Manganês , Óxidos , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Animais , Óxidos/química , Óxidos/farmacologia , Cobre/química , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Camundongos , Carbono/química , Humanos , Ácido Fólico/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Oxigênio/química , Pontos Quânticos/química , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Microambiente Tumoral/efeitos dos fármacosRESUMO
Graphene aerogel (GA) has important application potential as piezoresistive sensors due to its low density, high conductivity, high porosity, and good mechanical properties. However, the fabrication of GA-based sensors with good mechanical properties and excellent sensing performance is still challenging. Herein, liquid- metal-modified GAs (GA/LM) are proposed for the development of an excellent GA-based sensor. GA/LM with three-dimensional interconnected layered structure exhibits excellent compressive stress of 41â KPa and fast response time (<20â ms). While generally flexible GA composites cannot be compressed beyond 80 % strain without plastic deformation, GA/LM demonstrates a high compressive strength of 60â kPa under a strain of 90 %. A real-time pressure sensor was fabricated based on GA/LM-2 to monitor swallowing, pulse beating, finger, wrist and knee bending, and even plantar pressure during walking. These excellent features enable potential applications in health detection.
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BACKGROUND: Extensive research has explored altered structural and functional networks in major depressive disorder (MDD). However, studies examining the relationships between structure and function yielded heterogeneous and inconclusive results. Recent work has suggested that the structure-function relationship is not uniform throughout the brain but varies across different levels of functional hierarchy. This study aims to investigate changes in structure-function couplings (SFC) and their relevance to antidepressant response in MDD from a functional hierarchical perspective. METHODS: We compared regional SFC between individuals with MDD (n = 258) and healthy controls (HC, n = 99) using resting-state functional magnetic resonance imaging and diffusion tensor imaging. We also compared antidepressant non-responders (n = 55) and responders (n = 68, defined by a reduction in depressive severity of >50%). To evaluate variations in altered and response-associated SFC across the functional hierarchy, we ranked significantly different regions by their principal gradient values and assessed patterns of increase or decrease along the gradient axis. The principal gradient value, calculated from 219 healthy individuals in the Human Connectome Project, represents a region's position along the principal gradient axis. RESULTS: Compared to HC, MDD patients exhibited increased SFC in unimodal regions (lower principal gradient) and decreased SFC in transmodal regions (higher principal gradient) (p < 0.001). Responders primarily had higher SFC in unimodal regions and lower SFC in attentional networks (median principal gradient) (p < 0.001). CONCLUSIONS: Our findings reveal opposing SFC alterations in low-level unimodal and high-level transmodal networks, underscoring spatial variability in MDD pathology. Moreover, hierarchy-specific antidepressant effects provide valuable insights into predicting treatment outcomes.
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BACKGROUND: Acute kidney injury (AKI) is a frequent and potentially life-threatening complication after percutaneous coronary intervention (PCI) in patients with ST-segment-elevation myocardial infarction (STEMI). However, the relationship between obesity and the risk of AKI in this specific patient population has not been previously examined. METHODS: We queried the National Inpatient Sample (2016-2019) using ICD-10 codes to obtain a sample of adults with STEMI undergoing PCI. All patients were further subcategorized into obese and nonobese cohorts. The primary outcome was the incidence of AKI. Multivariate regression analysis was performed to assess the impact of obesity on AKI. The consistency of this correlation between subgroups was investigated using subgroup analysis and interaction testing. RESULTS: A total of 62,599 (weighted national estimate of 529,016) patients were identified, of which 9.80% (n = 6137) had AKI. Obesity comprised 19.78% (n = 1214) of the AKI cohort. Obese patients were on average younger, male, white, and had more comorbidities. Additionally, there was a significant positive association between obesity and AKI incidence (adjusted odds ratio [aOR]: 1.24, 95% confidence interval [CI]: 1.15-1.34), which was more pronounced in female patients (aOR: 1.56, 95% CI: 1.33-1.82, p < 0.001, p-interaction = 0.008). The AKI incidence in these patients increased steadily during the 4-year study period, and it was consistently higher in obese patients than in nonobese patients (p-trend < 0.001 for all). CONCLUSIONS: Obesity was independently associated with a greater risk of AKI among adults with STEMI undergoing PCI, particularly in female patients.
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Injúria Renal Aguda , Bases de Dados Factuais , Obesidade , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Feminino , Masculino , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Pessoa de Meia-Idade , Fatores de Risco , Obesidade/epidemiologia , Obesidade/complicações , Estados Unidos/epidemiologia , Incidência , Idoso , Medição de Risco , Resultado do Tratamento , Fatores de Tempo , Estudos RetrospectivosRESUMO
OBJECTIVE: Antiphospholipid syndrome (APS) is an autoimmune disease mainly affecting young individuals. Testing for antiphospholipid antibodies is recommended for young patients who are suspected to have APS. Yet, it is hard to differentiate APS from other acquired thrombophilia disorders in elderly-onset APS patients. This study aim to investigate the characteristics and prognosis of elderly-onset APS. METHODS: This is an observational cohort study. Thrombotic APS patients who underwent follow-ups between 2009 and 2022 were included. Elderly-onset APS patients (onset age ≥60 years) were compared to non-elderly-onset APS patients (onset age <60 years) and matched cases of elderly non-APS patients (age ≥60 years with thrombosis). RESULTS: A total of 161 APS patients were included in this study, 45 (28.0%) were elderly-onset APS. Stroke (35.6% vs. 18.1%, p = .018) was more common at disease onset in elderly-onset APS patients. Compared to non-elderly-onset patients, elderly-onset APS patients were associated with a higher number of cardiovascular risk factors. Elderly-onset APS patients showed significantly lower positive rate (51.1% vs. 71.6%, p = .014) and ratios [1.24 (1.01-1.38) vs. 1.37 (1.16-1.77), p = .004] of lupus anticoagulant. Elderly-onset APS patients had a significantly higher 10-years cumulative all-cause mortality (p < .001) and APS-related mortality than non-elderly-onset patients (p = .002) and elderly non-APS patients (p = .040). CONCLUSIONS: Elderly-onset APS patients have unique disease characteristics with higher 10-years cumulative all-cause mortality and APS-related mortality. Early recognition and control of comorbidities may reduce the recurrence of thrombosis and mortality in elderly-onset APS patients.
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Although organic-inorganic hybrid Mn2+ halides have advanced significantly, achieving high stability and narrow-band emission remains enormously challenging owing to the weak ionic nature and soft crystal lattice of the halide structure. To address these issues, we proposed a cationic engineering strategy of long-range cation π···π stacking and C-H···π interactions to simultaneously improve the crystal structural stability and rigidity. Herein, two organic zero-dimensional (0D) manganese halide hybrids of (BACQ)2MnX4 [BACQ = 4-(butylamino)-7-chloroquinolin-1-ium; X = Cl and Br] were synthesized. (BACQ)2MnX4 display strong green-light emissions with the narrowest full width at half-maximum (fwhm) of 39 nm, which is significantly smaller than those of commercial green phosphor ß-SiAlON:Eu2+ and most of reported manganese halides. Detailed Hirshfeld surface analyses demonstrate the rigid environment around the [MnX4]2- units originating from the interactions between [BACQ]+. The rigid crystal structure weakens the electron-phonon coupling and renders narrow fwhm of these manganese halides, which is further confirmed by temperature-dependent emission spectra. Remarkably, (BACQ)2MnX4 realizes outstanding structural and luminescence stabilities in various extreme environments. Benefiting from the excellent performance, these Mn2+ halides are used to assemble light-emitting diodes with a wide color gamut of 105% of the National Television System Committee 1931 standard, showcasing the advanced applications in liquid-crystal-display backlighting.
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BACKGROUND: Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis (RA) and is associated with a poor prognosis. However, the role of blood biomarkers in RA-associated interstitial lung disease (RA-ILD) is ill-defined. We aim to evaluate the role of YKL-40 and Krebs von den Lungen-6 (KL-6) in the diagnosis and severity evaluation of RA-ILD. METHODS: 45 RA-non-ILD patients and 38 RA-ILD patients were included. The clinical data and the levels of YKL-40 and KL-6 were measured and collected for all patients. The risk factors for RA-ILD were analyzed and their correlation with relevant indicators and predictive value for RA-ILD was explored. RESULTS: The levels of YKL-40 and KL-6 in RA-ILD patients were higher than RA-non-ILD patients (p < .001). Both YKL-40 and KL-6 were correlated with the incidence of RA-ILD. The predictive power of combined KL-6 and YKL-40 for the presence of ILD was 0.789, with a sensitivity and specificity at 73.7% and 73.3%, respectively. In RA-ILD patients, both YKL-40 and KL-6 were positively correlated with the Scleroderma Lung Study (SLS) I score and negatively correlated with pulmonary function. CONCLUSIONS: KL-6 and YKL-40 might be a useful biomarker in the diagnosis and severity evaluation of RA-ILD.
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The relational triple extraction of unstructured medical texts about Parkinson's disease is critical for the construction of a medical knowledge graph. However, the triple entities in Parkinson's disease are usually complicated and overlapped, which impedes the accuracy of triple extraction, especially in the case of rarely available corpus. Therefore, this study first builds a corpus about Parkinson's disease. Then, a tagging-based three-stage relational triple extraction model is proposed, named ParTRE. To enhance the contextual representation of sentences, the proposed model employs BiLSTM modules to capture fine-grained semantic information. Additionally, a conditional normalization layer is used so that entity pairs can be extracted accurately from two complementary directions. As for the imbalanced relationship categories, an adaptive loss function strategy based on focal loss is derived by assigning different weights to relationship categories and reducing the loss of easy-to-classify samples. The model performance is evaluated on the Parkinson's corpus and public datasets. The results indicate that the proposed model achieves an overall F1-score of 93.3 % on the Parkinson's corpus and comparable performance on public datasets compared with the state-of-the-art methods. Moreover, a satisfactory result is achieved by the proposed model on conquering the overlapped entities and imbalanced relationship categories. Owing to demonstrated availability and validity, the proposed method can be integrated with medical knowledge graphs and therefore benefits medical intelligence.
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Doença de Parkinson , Humanos , Idioma , Semântica , ConhecimentoRESUMO
Previous studies about anhedonia symptoms in bipolar depression (BD) ignored the unique role of gender on brain function. This study aims to explore the regional brain neuroimaging features of BD with anhedonia and the sex differences in these patients. The resting-fMRI by applying fractional amplitude of low-frequency fluctuation (fALFF) method was estimated in 263 patients with BD (174 high anhedonia [HA], 89 low anhedonia [LA]) and 213 healthy controls. The effects of two different factors in patients with BD were analyzed using a 3 (group: HA, LA, HC) × 2 (sex: male, female) ANOVA. The fALFF values were higher in the HA group than in the LA group in the right medial cingulate gyrus and supplementary motor area. For the sex-by-group interaction, the fALFF values of the right hippocampus, left medial occipital gyrus, right insula, and bilateral medial cingulate gyrus were significantly higher in HA males than in LA males but not females. These results suggested that the pattern of high activation could be a marker of anhedonia symptoms in BD males, and the sex differences should be considered in future studies of BD with anhedonia symptoms.
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In this article, chiral covalent organic framework core-shell composite CCOF-TpPa-Py@SiO2 was facilely synthesized by induction at room temperature. The CCOF-TpPa-Py@SiO2 core-shell composite was used as a chiral stationary phase for the separation of the racemates by high-performance liquid chromatography, which exhibits good separation performance for chiral compounds including ketones, alcohols, esters, epoxides, carboxylic acids, amides, and amines. The effects of analyte injection mass on the enantioseparation were studied. The reproducibility and stability of the CCOF-TpPa-Py@SiO2 chiral column were explored. The intra-day (n = 5), inter-day (n = 5), and inter-column (n = 3) relative standard deviations for the migration times and resolution of benzoin were 0.32%-0.54%, 0.45%-0.61%, and 1.21%-1.53%, respectively. In addition, the chiral separation ability of the CCOF-TpPa-Py@SiO2 chiral column (column A) was compared with that of the MDI-ß-CD-Modified COF@SiO2 (column B) as well as a commercial chiral column (Chiralpak AD-H). The chiral recognition ability of column A is complementary to that of column B and AD-H column. The resolution mechanism of CCOF-TpPa-Py@SiO2 stationary phase towards chiral analyte was explored. Hence, the synthesis of CCOF-TpPa-Py@SiO2 core-shell composite by induction at room temperature as chiral stationary phases for chromatographic separation has important research potential and application prospects.
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Maslinic acid has a variety of biological activities, such as anti-tumor, hypoglycemic, anti-inflammatory, and anti-parasitic. In order to enhance the biological activity of maslinic acid, scholars have carried out a lot of structural modifications, and found some more valuable maslinic acid derivatives. In this paper, the structural modification, biological activity, and structure-activity relationship of maslinic acid were reviewed, providing references for the development of maslinic acid.
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Neoplasias , Ácido Oleanólico/análogos & derivados , Triterpenos , Humanos , Relação Estrutura-Atividade , Anti-Inflamatórios/farmacologia , Triterpenos/farmacologia , Triterpenos/químicaRESUMO
Visual simultaneous localization and mapping (VSLAM) enhances the navigation of autonomous agents in unfamiliar environments by progressively constructing maps and estimating poses. However, conventional VSLAM pipelines often exhibited degraded performance in dynamic environments featuring mobile objects. Recent research in deep learning led to notable progress in semantic segmentation, which involves assigning semantic labels to image pixels. The integration of semantic segmentation into VSLAM can effectively differentiate between static and dynamic elements in intricate scenes. This paper provided a comprehensive comparative review on leveraging semantic segmentation to improve major components of VSLAM, including visual odometry, loop closure detection, and environmental mapping. Key principles and methods for both traditional VSLAM and deep semantic segmentation were introduced. This paper presented an overview and comparative analysis of the technical implementations of semantic integration across various modules of the VSLAM pipeline. Furthermore, it examined the features and potential use cases associated with the fusion of VSLAM and semantics. It was found that the existing VSLAM model continued to face challenges related to computational complexity. Promising future research directions were identified, including efficient model design, multimodal fusion, online adaptation, dynamic scene reconstruction, and end-to-end joint optimization. This review shed light on the emerging paradigm of semantic VSLAM and how deep learning-enabled semantic reasoning could unlock new capabilities for autonomous intelligent systems to operate reliably in the real world.
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The pipeline ground-penetrating radar stands as an indispensable detection device for ensuring underground space security. A wheeled pipeline robot is deployed to traverse the interior of urban underground drainage pipelines along their central axis. It is subject to influences such as resistance, speed, and human factors, leading to deviations in its posture. A guiding wheel is employed to rectify its roll angle and ensure the precise spatial positioning of defects both inside and outside the pipeline, as detected by the radar antenna. By analyzing its deflection factors and correction trajectories, the intelligent correction control of the pipeline ground-penetrating radar falls into the realm of nonlinear multi-constraint optimization. Consequently, a time-series-based correction angle prediction algorithm is proposed. The application of the long short-term memory (LSTM) deep learning model facilitates the prediction of correction angles and torque for the guiding wheel. This study compares the performance of LSTM with an autoregressive integrated moving average model under identical dataset conditions. The subsequent findings reveal a reduction of 4.11° and 8.25 N·m in mean absolute error, and a decrease of 10.66% and 7.27% in mean squared error for the predicted correction angles and torques, respectively. These outcomes are achieved utilizing the three-channel drainage pipeline ground-penetrating radar device with top antenna operating at 1.2 GHz and left/right antennas at 750 MHz. The LSTM prediction model intelligently corrects its posture. Experimental results demonstrate an average correction speed of 5 s and an average angular error of ±1°. It is verified that the model can correct its attitude in real-time with small errors, thereby enhancing the accuracy of ground-penetrating radar antennas in locating pipeline defects.
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This study aimed to assess the effect of a phase-change material (PCM) cooling blanket for cooling between exercise bouts on recovery of physiological parameters and subsequent exercise performance in the heat. Eighteen male volunteers were recruited to participate in human trials involving two exhaustive treadmill running bouts (Bout1 for 3 km and Bout2 for 1.5 km) in a climate chamber (temperature = 33 °C; relative humidity = 40%). Participants were randomly subjected to one of two cooling conditions for a 10-min period between exercise bouts: CON: natural cooling; 10-min PCM: with a PCM cooling blanket for 10 min. Several physiological parameters including mean skin temperature (Tskin), oral temperature (Toral), core temperature (Tcore), heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), peripheral capillary oxygen saturation (SpO2), average running speed and rating of perceived exertion (RPE) scale score were analyzed. The results showed that compared to the CON group, participants in the 10-min PCM group had a significant lower Tskin, Tcore, HR and RR at post-cooling, as well as greater reductions in mean skin temperature (ΔTskin) and core temperature (ΔTcore) from post-Bout1 to post-cooling. Additionally, the 10-min PCM group exhibited significantly lower peak Tcore, peak HR and RPE scale score during Bout2, while the average running speed during Bout2 was significantly higher. The present study suggests that cooling with a PCM cooling blanket can enhance physiological recovery and subsequent exercise performance in the heat.
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Temperatura Alta , Corrida , Humanos , Masculino , Temperatura Corporal/fisiologia , Regulação da Temperatura Corporal/fisiologia , Temperatura Baixa , Exercício Físico/fisiologia , Frequência Cardíaca/fisiologia , Corrida/fisiologia , Temperatura Cutânea , Estudos Cross-OverRESUMO
PURPOSE: Perioperative vision loss (POVL) is a rare and devastating complication following prone spine surgery. Due to the rare nature of this complication, there is limited research available about patient and surgical risk factors that increase the risk of POVL. The objective of this study was to investigate associated risk factors for POVL with use of the National Surgical Quality Improvement Program (NSQIP) database. DESIGN: This study used a case-control secondary data analysis methodology that included five cases of POVL and 250 controls from the American College of Surgeons National Surgical Quality Improvement Program database who all underwent prone spine surgery between 2010 and 2020. METHODS: Each POVL case was matched to 50 randomly selected controls (n = 250) based on type and year of surgery. Demographics and variables of interest were compared among the POVL cases, among POVL cases and the aggregate control group (n = 250), and POVL cases against their matched control group. Univariate and multivariate conditional logistic regression were then used to estimate the odds of developing POVL in relation to potential patient and surgical risk factors. FINDINGS: When POVL cases were compared to the 250 control cases using univariate analysis, patients who developed POVL were more likely to have received a blood transfusion within 72 hours of surgery (P < .0001). and have longer operative times (odds ratio = 1.01, 95% CI [1.003, 1.017], P = .003). CONCLUSIONS: Two surgical risk factors were determined to be statistically significant, including the need for perioperative blood transfusion and prolonged operative time. These findings support previous research on POVL which often identified blood loss and prolonged operative times as surgical risk factors. The narrow patient population used in this project may have limited the ability to perform a more robust study on POVL. Therefore, further research on POVL using the National Surgical Quality Improvement Program database is strongly encouraged.
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Accelerating sulfur conversion catalysis to alleviate the shuttle effect has become a novel paradigm for effective Li-S batteries. Although nitrogen-coordinated metal single-atom (M-N4) catalysts have been investigated, further optimizing its utilization rate and catalytic activities is urgently needed for practical applications. Inspired by the natural alveoli tissue with interconnected structure and well-distributed enzyme catalytic sites on the wall for the simultaneously fast diffusion and in situ catalytic conversion of substrates, here, we proposed the controllable synthesis of bioinspired carbon cathode with interconnected porous structure and asymmetric coordinated V-S1N3 sites for efficient and stable Li-S batteries. The enzyme-mimetic V-S1N3 shows asymmetric electronic distribution and high tunability, therefore enhancing in situ polysulfide conversion activities. Experimental and theoretical results reveal that the high charge asymmetry degree and large atom radius of S in V-S1N3 result in sloping adsorption for polysulfide, thereby exhibiting low thermodynamic energy barriers and long-range stability (0.076 % decay over 600â cycles).
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OBJECTIVES: To explore the effects of iris xanthin on airway inflammation, airway remodeling, and the high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in asthmatic young mice. METHODS: Sixty male BALB/c young mice were randomly assigned into six groups: a blank group, a model group, a dexamethasone group, and low, medium, and high dose groups of iris xanthin, with ten mice per group. Asthma models were induced through intraperitoneal injections of a sensitizing agent [ovalbumin (OVA) 20 µg + aluminum hydroxide gel 2 mg], followed by 4% OVA aerosol inhalation. Lung function was measured using a pulmonary function tester to determine lung volume (LV), resting ventilation per minute (VE), and airway reactivity (Penh value). Hematoxylin-eosin (HE) staining was employed to examine and analyze airway remodeling. The contents of interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha (TNF-α) in bronchoalveolar lavage fluid were quantified using ELISA. Real-time fluorescence quantitative polymerase chain reaction and Western blot analysis were used to assess the expression of HMGB1/TLR4/NF-κB pathway-related mRNA and proteins in lung tissues. RESULTS: Compared to the model group, the dexamethasone and iris xanthin-treated groups (low, medium, and high doses) exhibited significant increases in LV and VE (P<0.05), with incremental dose-dependent increases observed in the iris xanthin groups. Additionally, Penh values, IL-1ß, IL-6, TNF-α, and airway remodeling indicators, along with mRNA levels of HMGB1, TLR4, and NF-κB p65 and protein levels of HMGB1, TLR4, and p-NF-κB p65, were all reduced (P<0.05) in a dose-dependent manner. When compared to the dexamethasone group, the low and medium dose iris xanthin groups showed decreases in LV and VE (P<0.05), whereas Penh values, IL-1ß, IL-6, TNF-α, and airway remodeling indicators, along with mRNA levels of HMGB1, TLR4, NF-κB p65 and protein levels of HMGB1, TLR4, and p-NF-κB p65, were increased (P<0.05). No significant differences were noted in these indices between the high dose iris xanthin group and the dexamethasone group (P>0.05). CONCLUSIONS: Iris xanthin can effectively alleviates airway inflammation and inhibits airway remodeling in asthmatic young mice, possibly through the suppression of the HMGB1/TLR4/NF-κB pathway.
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Remodelação das Vias Aéreas , Asma , Proteína HMGB1 , Camundongos Endogâmicos BALB C , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Animais , Remodelação das Vias Aéreas/efeitos dos fármacos , Asma/tratamento farmacológico , Asma/metabolismo , Masculino , Camundongos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Chitin, a polymer of ß-1,4-linked N-acetylglucosamine (GlcNAc), can be degraded into valuable oligosaccharides by various chitinases. In this study, the genome of Shewanella khirikhana JW44, displaying remarkable chitinolytic activity, was investigated to understand its chitin-degradation potential. A chitinase gene SkChi65 from this strain was then cloned, expressed, and purified to characterize its enzymatic properties and substrate hydrolysis. Genome analysis showed that, of the 14 genes related to chitin utilization in JW44, six belonged to glycoside hydrolase (GH) families because of their functional domains for chitin binding and catalysis. The recombinant chitinase SkChi65, consisting of 1129 amino acids, was identified as a member of the GH18 family and possessed two chitin-binding domains with a typical motif of [A/N]KWWT[N/S/Q] and one catalytic domain with motifs of DxxDxDxE, SxGG, YxR, and [E/D]xx[V/I]. SkChi65 was heterologously expressed as an active protein of 139.95 kDa best at 37 °C with 1.0 mM isopropyl-ß-d-thiogalactopyranoside induction for 6 h. Purified SkChi65 displayed high stability over the ranges of 30-50 °C and pH 5.5-8.0 with optima at 40 °C and pH 7.0. The kinetic parameters Km, Vmax, and kcat of SkChi65 towards colloidal chitin were 27.2 µM, 299.2 µMs-1, and 10,203 s-1, respectively. In addition to colloidal chitin, SkChi65 showed high activity towards glycol chitosan and crystalline chitin. After analysis by thin-layer chromatography, the main products were N,N'-diacetylchitobiose, and GlcNAc with (GlcNAc)2-6 used as substrates. Collectively, SkChi65 could exhibit both exo- and endochitinase activities towards diverse substrates, and strain JW44 has a high potential for industrial application with an excellent capacity for chitin bioconversion.
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President Xi set a long-term mitigation target of carbon neutrality by 2060 in September 2020 to cut carbon emissions and improve environmental performance. As a result, the current study aims to investigate how green human resource management and green innovation affect environmental performance in pursuit of the ultimate objective of carbon neutrality. Furthermore, the research considers the potential mediating effect of a green competitive advantage to clarify the mechanisms by which GHRM and green innovation impact environmental performance. Data from 278 employees in the manufacturing industry of Heilongjiang Province were collected through a questionnaire, for which we used a quantitative random sampling technique. The study employed the Smart PLS-4 structural equation modeling technique and revealed that all three factors significantly influenced environmental performance: green HRM, innovation, and competitive advantage. Resource-based view (RBV) theory served as the theoretical foundation for the study. The study uniquely contributes to the literature on GHRM, green innovation, competitive advantage, and environmental performance.