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Nonsmall cell lung cancer (NSCLC), due to its lack of early symptoms, has become one of the leading causes of cancer-related deaths globally. Exosomes, small membrane vesicles secreted by cells, are widely present in human bodily fluids. In the bodily fluids of NSCLC patients, the quantity of extracellular vesicles is double that of healthy individuals, suggesting their potential as biomarkers for screening NSCLC. This study designed a dual-modal aptasensor that integrated excellent sensitivity in electrochemical detection and portability in fluorescence detection into one device. AuNPs were functionalized with exosome-capturing probes containing thiol-modified CD63 aptamers, which were immobilized on screen-printed gold electrodes. On the other hand, the carboxylated CD63 aptamer was immobilized on the surface of PB-modified g-C3N4 loaded with Co-SANs particles (Co@g-C3N4@PB). By combining these components, a sandwich structure (AuNPs/Apt1/Exo/Apt2- Co@g-C3N4@PB) was constructed, forming a probe for specific exosome recognition. First, the samples were preliminarily assessed for their positive or negative status under a fluorescence inverted microscope. Subsequently, a more in-depth quantitative analysis was conducted on suspected positive samples using electrochemical or fluorescence analysis methods. The detection limits for electrochemical analysis and fluorescence analysis were 66.68 and 33.5particles/mL, respectively. In the analysis of clinical serum exosome samples, the developed dual-modal aptasensor effectively distinguished serum specimens from those of NSCLC patients and healthy volunteers. This highlighted the inspection capability of the dual-modal adapter sensor, especially in point-of-care testing, making it a highly suitable tool for clinical applications.
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BACKGROUND: According to evidences from clinical practices and experiments, renal denervation achieved by removing both the afferent and sympathetic nerves has therapeutic impacts on poor renal function and hypertension in chronic kidney disease (CKD). Epidural anesthesia is presumed to function on the target spine segments with a complete sympathetic block. Based on this perspective, we hypothesized that epidural block with lidocaine could ameliorate renal injury in CKD rats. METHOD AND RESULTS: Male Sprague-Dawley rats weighing 250-300g were randomized into four groups: control, CKD, CKDâ¯+â¯sham, and CKDâ¯+â¯epidural block with lidocaine groups. CKD was induced by resection of the lower and upper thirds of the left kidney followed by right nephrectomy one week later. Significant differences in renal function, sympathetic activation as well as renal fibrosis parameters were observed between CKD and control rats. These parameters corresponded with typical phenotypes of CKD rats. Epidural block with lidocaine improved renal function as well as renal fibrosis, and reversed the abnormalities of the renal function and cardiovascular parameters either fully or partially. CONCLUSION: Epidural block with lidocaine confers renal protection, which is presumably mediated by decreasing sympathetic nerve activities in the renal region and other target organs in CKD.
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BACKGROUND: The association between body shape and depressive symptoms has been reported in adults. The present study aimed to investigate the association between body shape-specific abdominal obesity and depressive symptoms among multi-regional Asian adults. METHODS: The 2011-2012 China Health and Retirement Longitudinal Study and 2022-2023 Hangzhou study were used as the discovery and validation datasets, respectively. Body shape was assessed by body mass index categories. Abdominal obesity was defined as a body shape index (ABSI) ≥ 75th centile. Depression was measured using 10-item Centre for Epidemiological Studies Depression Scale and Geriatric Depression Scale short 15-item version, respectively. General linear and multinomial logistic models were used to explore the association of ABSI, abdominal obesity with depressive scores and presence, respectively. RESULTS: A total of 12,229 and 1210 participants were included in the discovery and validation datasets, respectively. A non-linear reverse L-shaped association was found between ABSI and depressive scores. Participants with abdominal obesity had higher depressive scores (ß = 0.05, 95%CI = 0.01-0.09; and ß = 0.13, 95%CI = 0.01-0.24; respectively). Stratified analyses showed that abdominal obesity was associated with higher depressive scores (ß = 0.09, 95%CI = 0.00-0.17; and ß = 0.25, 95%CI = 0.05-0.46; respectively) and presence (OR = 1.46, 95%CI = 1.02-2.10; and OR = 3.95, 95%CI = 1.58-9.84; respectively) in overweight adults. Furthermore, abdominal obesity was associated with depressive symptoms among overweight females, but not among males. LIMITATION: Causal links weren't addressed because of the observational study design. CONCLUSION: Abdominal obesity exhibited a positive association with depressive symptoms among Asian overweight adults, particularly in females. Prevention and early diagnosis of depressive symptoms should focus on overweight females.
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Selenium nanoparticles (SeNPs) are of interest for their versatility and low toxicity, but bare SeNPs are unstable and tend to aggregate and precipitate as black elemental Se, which limits the application of SeNPs. This study evaluated the physicochemical properties, physical stability, antioxidant activities and cytotoxicity of SeNPs stabilized by Grifola frondosa polysaccharides (GFPs) and GFPs-gallic acid conjugates (GFPs-GA). The results showed that the particle size (PZ), polymer index (PDI) and zeta potential (ZP) of the GFPs-SeNPs and GFPs-GA-SeNPs were 58.72 ± 0.53 nm, 0.11, -8.36 ± 0.21 mV and 61.80 ± 0.16 nm, 0.12, -9.37 ± 0.13 mV, respectively. Besides, the GFPs-SeNPs and GFPs-GA-SeNPs remained stable when stored at 4 °C for 70 days in darkness. SeNPs stabilized with GFPs have improved the antioxidant activity and selective toxicity to tumour cells. Interestingly, SeNPs stabilized with GFPs-GA further enhanced these biological activities. This work provided a simple and effective method to construct well-dispersed SeNPs in aqueous systems, demonstrating the important roles of GFPs and GFPs-GA in the size control, dispersion and stabilization of SeNPs. The prepared GFPs-SeNPs and GFPs-GA-SeNPs can serve as good selenium supplements and have potential prospects for antioxidant activity and tumour inhibition.
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Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity. Exposure to noxious stimuli such as hyperoxia, volutrauma, and infection in infancy can have long-reaching impacts on lung health and predispose towards the development of conditions such as chronic obstructive pulmonary disease (COPD) in adulthood. BPD and COPD are both marked by lung tissue degradation, neutrophil influx, and decreased lung function. Both diseases also express a change in microbial signature characterized by firmicute depletion. However, the relationship between pulmonary bacteria and the mechanisms of downstream disease development has yet to be elucidated. We hypothesized that murine models of BPD would show heightened acetylated proline-glycine-proline (Ac-PGP) pathway and neutrophil activity, and through gain- and loss-of-function studies we show that Ac-PGP plays a critical role in driving BPD development. We further test a inhaled live biotherapeutic (LBP) using active Lactobacillus strains in in vitro and in vivo models of BPD and COPD. The Lactobacillus-based LBP is effective in improving lung structure and function, mitigating neutrophil influx, and reducing a broad swath of pro-inflammatory markers in these models of chronic pulmonary disease via the MMP-9/PGP (matrix metalloproteinase/proline-glycine-proline) pathway. Inhaled LBPs show promise in addressing common pathways of disease progression that in the future can be targeted in a variety of chronic lung diseases.
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Displasia Broncopulmonar , Modelos Animais de Doenças , Lactobacillus , Pulmão , Neutrófilos , Doença Pulmonar Obstrutiva Crônica , Animais , Neutrófilos/imunologia , Camundongos , Administração por Inalação , Humanos , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Pulmão/imunologia , Pulmão/patologia , Pulmão/microbiologia , Displasia Broncopulmonar/imunologia , Displasia Broncopulmonar/microbiologia , Camundongos Endogâmicos C57BL , Feminino , Probióticos/administração & dosagem , Probióticos/uso terapêutico , Pneumonia/microbiologia , Pneumonia/imunologia , Masculino , Prolina/metabolismoRESUMO
INTRODUCTION: The morbidity and mortality of spinal cord injury (SCI) are increasing year by year. It is of vital importance to ascertain the mechanism of SCI. Phosphoglycerate mutase family member 5 (PGAM5) is viewed as a molecular marker of SCI, but its specific role in SCI is elusive. MATERIAL AND METHODS: Following establishment of the SCI mouse model, the pathological examination of the spinal cord was initially assessed using H&E staining. PGAM5 expression in spinal cord tissues was appraised utilizing immunohistochemistry and RT-qPCR. Subsequently, after the expression of PGAM5 in SCI mice was inhibited by adenovirus transfection, the degree of SCI was determined, and the motor ability of hind limbs was estimated with the BBB score. In addition, the apoptosis of neurons, microglia activation and the generation of inflammatory cytokines in the spinal cord of mice were detected. Next, at the cellular level, PGAM5 expression was inhibited in the BV2 microglial cells induced by lipopolysaccharide (LPS), so as to explore the effects of down-regulation of PGAM5 on the activation, inflammation and apoptosis of neurons. Finally, western blot was applied for the appraisement of apoptosis signal-regulating kinase-1 (ASK-1)/p38/nuclear factor-kappa B (NF-kB) signaling-associated proteins. RESULTS: PGAM5 expression in SCI mice was found to be raised. Inhibition of PGAM5 expression in SCI mice can significantly reduce spinal cord pathological injury, SCI-induced neuronal apoptosis, microglial cell activation and inflammation. The above regulatory process might be realized through the ASK-1/p38/NF-kB signaling pathway mediated by PGAM5. CONCLUSIONS: Down-regulation of PGAM5 attenuated SCI-induced neuronal injury by inhibiting ASK-1/p38/NF-kB signaling.
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Background: The ideal timing for commencing enteral nutrition (EN) in critically ill stroke patients in the intensive care unit (ICU) remains a subject of debate, with ongoing controversy regarding the impact of early EN (EEN) initiation. In this study, we investigated the association between the timing of EN initiation and 28-day mortality using data from the MIMIC-IV database. Methods: This study employed a retrospective cohort design using the MIMIC-IV database to identify stroke patients who received EN during their hospital stay. The main focus of this investigation was to examine 28-day mortality among these patients following hospital admission. Various demographic, clinical, laboratory, and intervention variables were considered as covariates. The Cox regression analysis was employed to assess the correlation between the timing of EN initiation and 28-day mortality, and restricted cubic splines (RCS) analysis was used to test for non-linear correlation. Patients were then stratified into two cohorts depending on the timing of EN initiation: within 2 days (n = 564) and beyond 2 days (n = 433). A multivariate Cox regression analysis was used to investigate the difference in 28-day mortality between the groups. Results: A total of 997 participants were included in this study, with 318 (31.9%) dying within 28 days. We observed that the timing of EN initiation correlated with 28-day mortality, but this correlation was not significant after adjusting for covariates (crude HR: 0.94, 95% CI: 0.88-1, p = 0.044; adjusted HR: 0.96, 95% CI: 0.9-1.02, p = 0.178). The RCS analysis showed that the correlation was not non-linear. Notably, in the multivariate regression models, early EN initiation was associated with a higher mortality rate compared to late EN initiation [odds ratio (OR) = 1.34, 95% CI: 1.06-1.67, p = 0.012]. After adjusting for various confounding factors in the multivariate Cox regression models, we identified that patients in the early EN group had a 28% higher risk of mortality than those in the reference group (OR = 1.27, 95% CI: 1-1.61, p = 0.048). These associations remained consistent across various patient characteristics, as revealed through stratified analyses. Conclusions: Early commencement of EN in critically ill stroke patients may be linked to a higher risk of 28-day mortality, highlighting the need for further investigation and a more nuanced consideration of the optimal timing for commencing EN in this patient population.
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Introduction: Goose astrovirus (GAstV) is a newly emerging pathogen that is currently widespread among geese, causing visceral gout and leading to substantial gosling mortalities, posing a severe threat to the waterfowl industry. GAstV II is the predominant epidemic strain, characterized by its high morbidity and mortality rate. Consequently, there is an urgent necessity to develop an effective diagnostic approach to control the dissemination of GAstV II, particularly in clinical farms with limited laboratory resources. Methods: In this study, a novel multi-enzyme isothermal rapid amplification (MIRA) and lateral flow dipstick (LFD) combined assay was developed. Different primers designed specific targeting a highly conserved region within the viral RdRp gene for the detection of GAstV II. Primers optimized and MIRA-LFD assay analyzed its performance regarding limits of detection, specificity, and efficiency of detection. Results: The developed MIRA amplification is conducted at a constant temperature and accomplished within 10 minutes. Subsequent naked-eye observation of the LFD strips merely takes 5 minutes. The established MIRA-LFD method exhibits high specificity, with no cross-reaction with other pathogens and attains a detection sensitivity of 1 copy/µl, which is consistent with the reverse transcription quantitative PCR (RT-qPCR) assay. Further evaluation with clinical samples indicates that the accuracy of this MIRA-LFD method correlates well with RT-qPCR for the detection of GAstV II. Conclusion: In summary, the convenience, sensitivity, and rapidity of this newly developed detection method offer a significant advantage for on-site diagnosis of GAstV II.
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Infecções por Astroviridae , Gansos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Doenças das Aves Domésticas , Sensibilidade e Especificidade , Animais , Infecções por Astroviridae/diagnóstico , Infecções por Astroviridae/veterinária , Infecções por Astroviridae/virologia , Gansos/virologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Diagnóstico Molecular/métodos , Doenças das Aves Domésticas/diagnóstico , Doenças das Aves Domésticas/virologia , Avastrovirus/genética , Avastrovirus/isolamento & purificação , Primers do DNA/genética , RNA Viral/genéticaRESUMO
A precise radiotherapy plan is crucial to ensure accurate segmentation of glioblastomas (GBMs) for radiation therapy. However, the traditional manual segmentation process is labor-intensive and heavily reliant on the experience of radiation oncologists. In this retrospective study, a novel auto-segmentation method is proposed to address these problems. To assess the method's applicability across diverse scenarios, we conducted its development and evaluation using a cohort of 148 eligible patients drawn from four multicenter datasets and retrospective data collection including noncontrast CT, multisequence MRI scans, and corresponding medical records. All patients were diagnosed with histologically confirmed high-grade glioma (HGG). A deep learning-based method (PKMI-Net) for automatically segmenting gross tumor volume (GTV) and clinical target volumes (CTV1 and CTV2) of GBMs was proposed by leveraging prior knowledge from multimodal imaging. The proposed PKMI-Net demonstrated high accuracy in segmenting, respectively, GTV, CTV1, and CTV2 in an 11-patient test set, achieving Dice similarity coefficients (DSC) of 0.94, 0.95, and 0.92; 95% Hausdorff distances (HD95) of 2.07, 1.18, and 3.95 mm; average surface distances (ASD) of 0.69, 0.39, and 1.17 mm; and relative volume differences (RVD) of 5.50%, 9.68%, and 3.97%. Moreover, the vast majority of GTV, CTV1, and CTV2 produced by PKMI-Net are clinically acceptable and require no revision for clinical practice. In our multicenter evaluation, the PKMI-Net exhibited consistent and robust generalizability across the various datasets, demonstrating its effectiveness in automatically segmenting GBMs. The proposed method using prior knowledge in multimodal imaging can improve the contouring accuracy of GBMs, which holds the potential to improve the quality and efficiency of GBMs' radiotherapy.
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BACKGROUND: As a common disabling disease, irreversible neuronal death due to spinal cord injury (SCI) is the root cause of functional impairment; however, the capacity for neuronal regeneration in the developing spinal cord tissue is limited. Therefore, there is an urgent need to investigate how defective neurons can be replenished and functionally integrated by neural regeneration; the reprogramming of intrinsic cells into functional neurons may represent an ideal solution. METHODS: A mouse model of transection SCI was prepared by forceps clamping, and an adeno-associated virus (AAV) carrying the transcription factors NeuroD1 and Neurogenin-2(Ngn2) was injected in situ into the spinal cord to specifically overexpress these transcription factors in astrocytes close to the injury site. 5-bromo-2´-deoxyuridine (BrdU) was subsequently injected intraperitoneally to continuously track cell regeneration, neuroblasts and immature neurons marker expression, neuronal regeneration, and glial scar regeneration. In addition, immunoprotein blotting was used to measure the levels of transforming growth factor-ß (TGF-ß) pathway-related protein expression. We also evaluated motor function, sensory function, and the integrity of the blood-spinal cord barrier(BSCB). RESULTS: The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord was achieved by specific AAV vectors. This intervention led to a significant increase in cell regeneration and the proportion of cells with neuroblasts and immature neurons cell properties at the injury site(p < 0.0001). Immunofluorescence staining identified astrocytes with neuroblasts and immature neurons cell properties at the site of injury while neuronal marker-specific staining revealed an increased number of mature astrocytes at the injury site. Behavioral assessments showed that the intervention did not improve The BMS (Basso mouse scale) score (p = 0.0726) and gait (p > 0.05), although the treated mice had more sensory sensitivity and greater voluntary motor ability in open field than the non-intervention mice. We observed significant repair of the BSCB at the center of the injury site (p < 0.0001) and a significant improvement in glial scar proliferation. Electrophysiological assessments revealed a significant improvement in spinal nerve conduction (p < 0.0001) while immunostaining revealed that the levels of TGF-ß protein at the site of injury in the intervention group were lower than control group (p = 0.0034); in addition, P70 s6 and PP2A related to the TGF-ß pathway showed ascending trend (p = 0.0036, p = 0.0152 respectively). CONCLUSIONS: The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord after spinal cord injury can reprogram astrocytes into neurons and significantly enhance cell regeneration at the injury site. The reprogramming of astrocytes can lead to tissue repair, thus improving the reduced threshold and increasing voluntary movements. This strategy can also improve the integrity of the blood-spinal cord barrier and enhance nerve conduction function. However, the simple reprogramming of astrocytes cannot lead to significant improvements in the striding function of the lower limbs.
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Astrócitos , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Modelos Animais de Doenças , Proteínas do Tecido Nervoso , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Astrócitos/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Camundongos , Regeneração Nervosa/fisiologia , Neurônios , Feminino , Camundongos Endogâmicos C57BL , Medula Espinal/metabolismoRESUMO
Per- and polyfluoroalkyl substances (PFASs) have attracted increasing attention due to their persistence in the environment and potential adverse effects on human and animal health. The detection and quantification of PFASs in livestock could substantially contribute to monitoring their presence within the food chain. We developed a targeted quantification method for 34 PFASs in livestock serum by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). We used protein precipitation for serum sample extraction and accurate mass measurement of targeted PFAS compounds for quantification. We validated the method with various analytical parameters, achieving accuracy of 70-120% and precision of <20%. The method also demonstrated good analytical sensitivity, with a limit of detection of <0.051 ng/mL and a limit of quantification of <0.175 ng/mL. When applying the developed method to actual serum samples from a variety of livestock, we successfully identified and quantified various PFASs in different livestock species. Our method has the potential to be a valuable tool for veterinary laboratory analysis of PFAS contamination in livestock.
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Metallic lithium is the most competitive anode material for next-generation high-energy batteries. Nevertheless, the extensive volume expansion and uncontrolled Li dendrite growth of lithium metal not only cause potential safety hazards but also lead to low Coulombic efficiency and inferior cycling lifespan for Li metal batteries. Herein, a multifunctional dendrite-free composite anode (Li/SnS2) is proposed through an in situ melt-infusion strategy. In this configuration, the 3D cross-linked porous Li2S/Li22Sn5 framework facilitates the rapid penetration of electrolytes and accommodates the volume expansion during the repeated Li-plating process. Meanwhile, the lithiophilic Li2S phases with a low Li+ transport barrier ensure preferential Li deposition, effectively avoiding uneven electron distribution. Moreover, the Li22Sn5 electron conductors with appropriate Li+ bonding ability guarantee rapid charge transport and mass transfer. Most importantly, the steady multifunctional skeleton with sufficient inner interfaces (Li2S/Li22Sn5) in the whole electrode, not only realizes the redistribution of the localized free electron, contributing to the decomposition of Li clusters, but also induces a planar deposition model, thus restraining the generation of Li dendrites. Consequently, an unprecedented cyclability of over 6 500 h under an ultrahigh areal capacity of 10 mAh cm-2 and a current rate of 20 mA cm-2 is achieved for the prepared Li2S/Li22Sn5 composite anode. Moreover, the assembled Li/SnS2||LiFePO4 (LFP) pouch full-cells also demonstrate remarkable rate capability and a convincing cycling lifespan of more than 2 000 cycles at 2 C.
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Hepatocellular carcinoma (HCC) is the major cause of cancer-associated mortality worldwide. Despite great advances have been made on the treatment of HCC, the survival rate of patients remains poor. Spindle apparatus coiled-coil protein 1 (SPDL1) is involved in the development of various cancers in humans. However, the role of SPDL1 in HCC remains unclear. In this study, we found high expression of SPDL1 in HCC tissues as compared to normal samples. In vitro, silencing of SPDL1 induced HCC cell apoptosis, and suppressed HCC cell propagation and migration. In vivo, knockdown of SPDL1 inhibited the tumor growth of HCC cells. These findings indicated the tumor-promoting role of SPDL1 in HCC. Mechanistically, we identified farnesyltransferase-beta (FNTB) as the downstream target protein of SPDL1 based on immunoprecipitation and mass spectrometry, which were confirmed by western blotting. Rescue assay determined that FNTB played a tumor promoting role in SPDL1-trigger HCC cell growth. Overexpression of FNTB recovered HCC cell viability and migration in SPDL1 knockdown cells. We also found that silencing of SPDL1 increased the sensitivity of Huh7 cells to sorafenib and lenvatinib, suggesting that SPDL1 is a new therapeutic target in HCC. Collectivity, the present study identified a new axis SPDL1/FNTB involved in the progression of HCC. Hence, SPDL1/FNTB is a potential target for the treatment of HCC.
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Calcination of MgCO3 is an important industrial reaction, but it causes significant and unfavorable CO2 production. Calcination in a reducing green hydrogen atmosphere can substantially reduce CO2 release and produce high value-added products such as CO or hydrocarbons, but the mechanism is still unclear. Here, the in situ transformation process of MgCO3 interacting with hydrogen and the specific formation mechanism of the high value-added products are thoroughly investigated based on reaction thermodynamic, ab initio molecular dynamics (AIMD) simulations, and density functional theory (DFT) calculations. The reaction thermodynamic parameters of MgCO3 coupled with hydrogen to produce CO or methane are calculated, revealing that increasing and decreasing the thermal reductive decomposition temperature favors the production of CO and methane, respectively. Kinetically, the energy barriers of each possible production pathway for the dominant products CO and methane are further calculated in conjunction with the AIMD simulation results of the transformation process. The results suggest that CO is produced via the MgO catalytic-carboxyl pathway (CO2*â COOH*transâ COOH*cisâ CO*â CO), which is autocatalyzed by MgO derived from the thermal reductive decomposition of MgCO3. For the mechanism of methane formation, it prefers to be produced by the stepwise interaction of carbonates in the MgCO3 laminates with hydrogen adsorbed on their surfaces (direct conversion pathway: sur-O-CO â sur-O-HCO â sur-O-HCOH â sur-O-HC â sur-O-CH2 â sur-O-CH3 â sur-O + CH4*).
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Gyrovirus galga1 (GyVg1), formerly known as AGV2, was initially identified in chickens in southern Brazil. The prevalence of GyVg1 from 2021 to 2024 in 28 out of the 63 poultry farms located in Jiangsu, Anhui, Henan, Hunan, Shandong, and Hubei provinces in eastern and central China was detected via PCR. The complete genomes of the 28 strains were sequenced and exhibited a full length of 2,376 bp. Similarity analysis of these strains did not suggest definite correlation with evolutionary branching and geographical distribution. Compared with the reference GyVg1 strains, HN2202 shared the highest similarity of 99.71% with HLJ1511 (chicken-originated) from northeastern China in 2015 to 2016. Recombination analysis revealed that AH2102 was a potential recombinant of peafowl-originated HN2019-PF1 and chicken-originated HLJ1506-2, whereas HN2304 was a recombinant of peafowl-originated HN2019-PF1 and the Hungarian ferret strain G13. Mutation site analysis of the capsid protein revealed that highly mutated regions occurred between sites 288 to 316 and 383 to 419. These results indicate that GyVg1 may have undergone an interspecies transmission, which involved complex mutations and recombination. This study may provide a reference for subsequent investigations targeting the molecular epidemiology and viral evolution of GyVg1.
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Objective: In order to address the issues of inconvenience, high medical costs, and lack of universality associated with traditional knee rehabilitation equipment, a portable intelligent wheelchair for knee rehabilitation was designed in this study. Methods: Based on the analysis of the knee joint's structure and rehabilitation mechanisms, an electric pushrod-driven rehabilitation institution was developed. A multi-functional module was designed with a modular approach, and the control of the wheelchair body and each functional module was implemented using an STM32 single-chip microcomputer. A three-dimensional model was established using SolidWorks software. In conjunction with Adams and Ansys simulation software, kinematic and static analyses were conducted on the knee joint rehabilitation institution and its core components. A prototype was constructed to verify the equipment's actual performance. Results: According to the prototype testing, the actual range of motion for the knee joint swing rod is 15.1°~88.9°, the angular speed of the swing rod ranges from -7.9 to 8.1°/s, the angular acceleration of the swing rod varies from -4.2 to 1.6°/s², the thrust range of the electric pushrod is -82.6 to 153.1 N, and the maximum displacement of the load pedal is approximately 1.7 mm, with the leg support exhibiting a maximum deformation of about 1.5 mm. Conclusion: The intelligent knee joint rehabilitation wheelchair meets the designed functions and its actual performance aligns with the design criteria, thus validating the rationality and feasibility of the structural design.
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Desenho de Equipamento , Articulação do Joelho , Cadeiras de Rodas , Humanos , Fenômenos Biomecânicos , Amplitude de Movimento Articular , SoftwareRESUMO
BACKGROUND: Silver sulfadiazine (SSD) is commonly formulated into otic preparations to treat otitis externa, although evidence of stability and antimicrobial efficacy with long-term storage is lacking. OBJECTIVES: To evaluate the effect of storage time on chemical stability and in vitro antimicrobial activity of SSD diluted in sterile water, including two 1% suspensions using SSD pharmaceutical-grade powder stored at room temperature (RT) in plastic or sterile glass bottles, and a 1:9 dilution using prescription SSD 1% cream stored at RT in a sterile glass bottle. MATERIALS AND METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assessed chemical stability. Trimethoprim/sulfamethoxazole-susceptible and trimethoprim/sulfamethoxazole-resistant strains of Staphylococcus pseudintermedius (SP), meticillin-resistant (MR) SP, S. schleiferi (SS), MRSS, Pseudomonas aeruginosa, Proteus mirabilis and Escherichia coli evaluated by 24 h time-kill analysis assessed in vitro antimicrobial efficacy. Each assessment was performed at zero, one, three and six months of storage. RESULTS: LC-MS/MS showed no significant change in concentration over time for any suspension. When adjusted for time and species/strain, all SSD suspensions showed significant reductions in colony forming units (cfu)/mL at 24 h (p < 0.001). Including all suspensions, a bactericidal effect (minimum 3-log cfu/mL reduction at 24 h) occurred against 94% of total isolates, with failure against 33 of 552 isolates (6%). Bactericidal failure was more likely with the cream-based suspension (p < 0.05) and at six months (p < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Powder-based and cream-based SSD/sterile water suspensions showed no significant change in concentration and demonstrated in vitro antimicrobial activity for six months. Bactericidal failure was more likely with the cream-based suspension and after six months of storage.
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Fibrosis is a public health issue of great concern characterized by the excessive deposition of extracellular matrix, leading to the destruction of parenchymal tissue and organ dysfunction that places a heavy burden on the global healthcare system due to its high incidence, disability, and mortality. Salvianolic acid B (SalB) has positively affected various human diseases, including fibrosis. In this review, we concentrate on the anti-fibrotic effects of SalB from a molecular perspective while providing information on the safety, adverse effects, and drug interactions of SalB. Additionally, we discuss the innovative SalB formulations, which give some references for further investigation and therapeutic use of SalB's anti-fibrotic qualities. Even with the encouraging preclinical data, additional research is required before relevant clinical trials can be conducted. Therefore, we conclude with recommendations for future studies. It is hoped that this review will provide comprehensive new perspectives on future research and product development related to SalB treatment of fibrosis and promote the efficient development of this field.