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Vanadium redox flow batteries (VRFBs) are of considerable importance in large-scale energy storage systems due to their high efficiency, long cycle life and easy scalability. In this work, chemical vapor deposition (CVD) grown carbon nanotubes (CNTs)-modified electrodes and Nafion 117 membrane are utilised for formulating a vanadium redox flow battery (VRFB). In a CVD chamber, the growth of CNTs is carried out on an acid-treated graphite felt surface. Cyclic voltammetry of CNT-modified electrode and acid-treated electrode revealed that CNTs presence improve the reaction kinetics of V3+/V2+ and VO2+/VO2+ redox pairs. Battery performance is recorded for analysing, the effect of modified electrodes, varying electrolyte flow rates, varying current densities and effect of removing the current collector plates. CNTs presence enhance the battery performance and offered 96.30% of Coulombic efficiency, 79.33% of voltage efficiency and 76.39% of energy efficiency. In comparison with pristine electrodes, a battery consisting CNTs grown electrodes shows a 14% and 15% increase in voltage efficiency and energy efficiency, respectively. Battery configured without current collector plates performs better as compared to with current collector plates which is possibly due to decrease in battery resistance.
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OBJECTIVES: To investigate the ultrasound (US) characteristics of metastatic malignancies (MM) in the major salivary glands and to assess the diagnostic value of the close relationship with the glandular capsule in identifying MM. METHODS: From January 2016 and April 2022, 122 patients with major salivary gland malignancies, including 20 patients with MM and 102 patients with primary malignancies (PM) confirmed by histopathological examination, were enrolled in this study. Their clinicopathologic and US data were recorded and analyzed. The diagnostic performance of the close relationship with the glandular capsule for differentiating MM from PM was analyzed. RESULTS: The mean age of MM were older than that of PM (59.50 ± 14.57 vs. 49.96 ± 15.73, p = 0.013). Compared with PM patients, MM were associated with a higher prevalence of local pain symptoms (p = 0.007) and abnormal facial nerve function (p < 0.001). MM were also more frequently characterized by unclear borders, rough margins, irregular shapes, heterogeneous internal echos, absence of cystic areas, presence of calcifications, close relationship with the glandular capsule, and US-reported positive cervical lymph nodes (all p < 0.05). The close relationship with the glandular capsule showed to be a good indicator in distinguishing between MM and PM, with an area under the receiver operating characteristic curve of 0.863, a sensitivity of 100%, a specificity of 72.5%, and an accuracy of 92.2%. Positive and negative predictive were calculated at 41.7% and 100%, respectively. CONCLUSIONS: The US finding of a close relationship with the glandular capsule is a highly sensitive diagnostic indicator for MM. Following this finding, US-guided needle biopsy should be recommended to further confirm the diagnosis.
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During the past half-century, although numerous interventions for obesity have arisen, the condition's prevalence has relentlessly escalated annually. Obesity represents a substantial public health challenge, especially due to its robust correlation with co-morbidities, such as colorectal cancer (CRC), which often thrives in an inflammatory tumor milieu. Of note, individuals with obesity commonly present with calcium and vitamin D insufficiencies. Transient receptor potential canonical (TRPC) channels, a subclass within the broader TRP family, function as critical calcium transporters in calcium-mediated signaling pathways. However, the exact role of TRPC channels in both obesity and CRC pathogenesis remains poorly understood. This study set out to elucidate the part played by TRPC channels in obesity and CRC development using a mouse model lacking all seven TRPC proteins (TRPC HeptaKO mice). Relative to wild-type counterparts, TRPC HeptaKO mice manifested severe obesity, evidenced by significantly heightened body weights, augmented weights of epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT), increased hepatic lipid deposition, and raised serum levels of total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C). Moreover, TRPC deficiency was accompanied by an decrease in thermogenic molecules like PGC1-α and UCP1, alongside a upsurge in inflammatory factors within adipose tissue. Mechanistically, it was revealed that pro-inflammatory factors originating from inflammatory macrophages in adipose tissue triggered lipid accumulation and exacerbated obesity-related phenotypes. Intriguingly, considering the well-established connection between obesity and disrupted gut microbiota balance, substantial changes in the gut microbiota composition were detected in TRPC HeptaKO mice, contributing to CRC development. This study provides valuable insights into the role and underlying mechanisms of TRPC deficiency in obesity and its related complication, CRC. Our findings offer a theoretical foundation for the prevention of adverse effects associated with TRPC inhibitors, potentially leading to new therapeutic strategies for obesity and CRC prevention.
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Introduction: This study aimed to explore the transcriptomic profile of premature ovarian insufficiency (POI) by investigating alterations in gene expression. Methods: A total of sixty-one women, comprising 31 individuals with POI in the POI group and 30 healthy women in the control group (HC group), aged between 24 and 40 years, were recruited for this study. The transcriptomic profiles of peripheral blood samples from all study subjects were analyzed using RNA-sequencing. Results: The results revealed 39 differentially expressed genes in individuals with POI compared to healthy controls, with 10 upregulated and 29 downregulated genes. Correlation analysis highlighted the relationship between the expression of SLC25A39, CNIH3, and PDZK1IP1 and hormone levels. Additionally, an effective classification model was developed using SLC25A39, CNIH3, PDZK1IP1, SHISA4, and LOC389834. Functional enrichment analysis demonstrated the involvement of these differentially expressed genes in the "haptoglobin-hemoglobin complex," while KEGG pathway analysis indicated their participation in the "Proteoglycans in cancer" pathway. Conclusion: The identified genes could play a crucial role in characterizing the genetic foundation of POI, potentially serving as valuable biomarkers for enhancing disease classification accuracy.
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BACKGROUND: Glycopeptide antibiotics (GPAs) represented by vancomycin (VAN) are clinically used as a first-line treatment for serious infections caused by Gram-positive pathogens. The use and dosing methods of GPAs are rigorously managed for safety considerations, which calls for fast and accurate quantification approaches. RESULT: A new sort of fluorescent probes for GPAs has been proposed, each of which was integrated by a fluorescein-based reporter and a GPAs' recognition peptide D-alanyl-D-alanine (D-Ala-D-Ala). These probes work as dynamic molecular switches, which mainly exist as non-fluorescent spirolactam forms in the absence of GPAs. GPAs binding with the dipeptide regulates the dynamic balance between fluorescence OFF lactam form and fluorescence ON ring-opened form, rendering these probes capable of GPAs detecting. The most promising one P1 exhibits excellent sensitivity and selectivity towards GPAs detection. SIGNIFICANCE: Different to previous developments, P1 consists of a single fluorophore without the need of a fluorescence-quenching group or a secondary dye, which is the smallest fluorescent probe for GPAs up to now. P1 realizes direct VAN quantification from complex biological samples including real serums, dispensing with additional drug extraction. More interestingly, both P1 and P6 can distinguish GPAs with different peptide backbones, which has not been achieved previously.
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Antibacterianos , Glicopeptídeos , Fluorescência , Antibacterianos/química , Glicopeptídeos/química , Vancomicina/química , AlaninaRESUMO
Acute-on-chronic liver failure (ACLF) implies high short-term mortality rates and usually requires intensive care unit (ICU) admission. Proper prognosis for these patients is crucial for early referral for liver transplantation. The superiority of CLIF-C ACLF score in Asian patients with ACLF admitted to an ICU remains inconclusive when compared to other scoring systems. The purpose of the study is (i) to compare the predictive performance of original MELD, MELD-Lactate, CLIF-C ACLF, CLIF-C ACLF-Lactate, and APACHE-II scores for short-term mortality assessment. (ii) to build and validate a novel scoring system and to compare its predictive performance to that of the original five scores. Two hundred sixty-five consecutive cirrhotic patients with ACLF who were admitted to our ICU were enrolled. The prognostic values for mortality were assessed by ROC analysis. A novel model was developed and internally validated using fivefold cross-validation. Alcohol abuse was identified as the primary etiology of cirrhosis. The AUROC of the five prognostic scores were not significantly superior to each other in predicting 1-month and 3-month mortality. The newly developed prognostic model, incorporating age, alveolar-arterial gradient (A-a gradient), BUN, total bilirubin level, INR, and HE grades, exhibited significantly improved performance in predicting 1-month and 3-month mortality with AUROC of 0.863 and 0.829, respectively, as compared to the original five prognostic scores. The novel ACLF model seems to be superior to the original five scores in predicting short-term mortality in ACLF patients admitted to an ICU. Further rigorous validation is required.
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Insuficiência Hepática Crônica Agudizada , Unidades de Terapia Intensiva , Humanos , Insuficiência Hepática Crônica Agudizada/mortalidade , Masculino , Feminino , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Curva ROC , Índice de Gravidade de Doença , Valor Preditivo dos Testes , APACHERESUMO
Colorectal cancer development and outcome are impacted by modifiable risk factors, including psychologic stress. The gut microbiota has also been shown to be linked to psychologic factors. Here, we found a marked deteriorative effect of chronic stress in multiple colorectal cancer models, including chemically induced (AOM/DSS), genetically engineered (APCmin/+), and xenograft tumor mouse models. RNA sequencing data from colon tissues revealed that expression of stemness-related genes was upregulated in the stressed colorectal cancer group by activated ß-catenin signaling, which was further confirmed by results from ex vivo organoid analyses as well as in vitro and in vivo cell tumorigenicity assays. 16S rRNA sequencing of the gut microbiota showed that chronic stress disrupted gut microbes, and antibiotic treatment and fecal microbiota transplantation abolished the stimulatory effects of chronic stress on colorectal cancer progression. Stressed colorectal cancer mice displayed a significant decrease in Lactobacillus johnsonii (L. johnsonii) abundance, which was inversely correlated with tumor load. Moreover, protocatechuic acid (PCA) was identified as a beneficial metabolite produced by L. johnsonii based on metabolome sequencing and LC/MS-MS analysis. Replenishment of L. johnsonii or PCA blocked chronic stress-induced colorectal cancer progression by decreasing ß-catenin expression. Furthermore, PCA activated the cGMP pathway, and the cGMP agonist sildenafil abolished the effects of chronic stress on colorectal cancer. Altogether, these data identify that stress impacts the gut microbiome to support colorectal cancer progression. SIGNIFICANCE: Chronic stress stimulates cancer stemness by reducing the intestinal abundance of L. johnsonii and its metabolite PCA to enhance ß-catenin signaling, forming a basis for potential strategies to circumvent stress-induced cancer aggressiveness. See related commentary by McCollum and Shah, p. 645.
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Neoplasias Colorretais , Microbioma Gastrointestinal , Lactobacillus johnsonii , Humanos , Animais , Camundongos , Neoplasias Colorretais/metabolismo , beta Catenina/genética , Lactobacillus johnsonii/genética , RNA Ribossômico 16S/genéticaRESUMO
We report a case of fetal nasal chondromesenchymal hamartoma (NCMH) first noted on prenatal ultrasound at 34 weeks. A solid-cystic mass which predominantly hyperechoicgenic and relatively clear margin, was located on the left nasal cavity and pharynx, with anterior extension and moderate blood flow. Further follow-up ultrasound examination depicted an enlargement of the tumor. Fetal magnetic resonance imaging (MRI) showed an inhomogeneous signal lesion involving the ethmoid sinuses, nasal cavity, and pharynx. The infant, delivered via cesarean section at 37 + 5 weeks, required urgent neonatology intervention due to respiratory difficulties. Neonatal MRI and computer tomography were subsequently performed at 1 day after birth. Surgical excision occurred at 7 days, confirming NCMH via histological examination. Awareness of this entity, is essential to avoid potentially harmful therapies, especially in prenatal period. Considered NCMH in diagnosis when fetal nasal masses presenting with predominantly high-level echo, well-defined margins and moderate vascularity.
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Cesárea , Hamartoma , Gravidez , Lactente , Recém-Nascido , Humanos , Feminino , Diagnóstico Diferencial , Hamartoma/diagnóstico por imagem , Hamartoma/patologia , Feto/patologia , Diagnóstico Pré-Natal , Imageamento por Ressonância MagnéticaRESUMO
This study aims to investigate the effect of maternal nicotine exposure on the gene expression profiles in the liver of offspring mice. Pregnant mice were subcutaneously injected with either saline vehicle or nicotine twice a day on gestational days 11-21. Total RNA from the liver samples which collected from the offspring mice of postnatal day 7 and 21 was subjected to RNA sequencing. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis were conducted to identify the functions of differentially expressed genes (DEGs). Four genes were selected for further validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A total of 448 DEGs and 186 DEGs were identified on postnatal day 7 and 21, respectively. GO analysis revealed that the DEGs on postnatal day 7 mainly participated in the biological functions of cell growth and proliferation, and the DEGs on postnatal day 21 mainly participated in ion transport/activity. KEGG enrichment analysis showed that the DEGs on postnatal day 7 were mainly enriched in the cell cycle, cytokine-cytokine receptor interactions, hypertrophic cardiomyopathy, and the p53 signaling pathway, while the DEGs on postnatal day 21 were mainly enriched in neuroactive ligand-receptor interactions, the calcium signaling pathway, retinol metabolism, and axon guidance. The qRT-PCR results were consistent with the RNA sequencing data. The DEGs may affect the growth of liver in early postnatal period while may affect ion transport/activity in late postnatal period.
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Perfilação da Expressão Gênica , Transcriptoma , Animais , Camundongos , Perfilação da Expressão Gênica/métodos , Nicotina/toxicidade , Análise de Sequência de RNA , FígadoRESUMO
Dissolved organic matter (DOM) and iron minerals widely existing in the natural aquatic environment can mediate the migration and transformation of organic pollutants. However, the mechanism of interaction between DOM and iron minerals in the microbial degradation of pollutants deserves further investigation. In this study, the mechanism of 17 alpha-ethinylestradiol (EE2) biodegradation mediated by humic acid (HA) and three kinds of iron minerals (goethite, magnetite, and pyrite) was investigated. The results found that HA and iron minerals significantly accelerated the biodegradation process of EE2, and the highest degradation efficiency of EE2 (48%) was observed in the HA-mediated microbial system with pyrite under aerobic conditions. Furthermore, it had been demonstrated that hydroxyl radicals (HOâ¢) was the main active substance responsible for the microbial degradation of EE2. HO⢠is primarily generated through the reaction between hydrogen peroxide secreted by microorganisms and Fe(II), with aerobic conditions being more conducive. The presence of iron minerals and HA could change the microbial communities in the EE2 biodegradation system. These findings provide new information for exploring the migration and transformation of pollutants by microorganisms in iron-rich environments.
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Matéria Orgânica Dissolvida , Poluentes Ambientais , Ferro , Minerais , Substâncias Húmicas , Etinilestradiol/análise , OxirreduçãoRESUMO
We have investigated whether inflammasomes and pyroptosis are activated in maternal nicotine exposure (MNE) offspring mice and whether they are involved in MNE-promoted metabolic associated fatty liver disease (MAFLD) in adult offspring. We injected pregnant mice subcutaneously with saline vehicle or nicotine twice a day on gestational days 11-21. Offspring mice from both groups were fed with a normal diet (ND) or a high-fat diet (HFD) for 6 months at postnatal day 21 to develop the MAFLD model. Serum biochemical indices were analyzed, and liver histology was performed. The expression levels of inflammasome and pyroptosis proteins were detected by western blot. We found MNE significantly aggravated the injury of MAFLD in adult offspring mice. MNE activated inflammasomes and pyroptosis in both infant and adult offspring mice. HFD treatment activated inflammasomes but not pyroptosis at 3 months, while it showed no effect at 6 months. However, pyroptosis was more severe in MNE-HFD mice than in MNE-ND mice at 6 months. Taken together, our data suggest MNE promotes MAFLD progression in adult offspring mice. MNE also induces NLRP3 and NLRP6 inflammasome activation and pyroptosis in both infant and adult offspring mice, which may be involved in MNE-promoted progression of MAFLD.
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BACKGROUND: Astrocytes have been demonstrated to undergo conversion into functional neurons, presenting a promising approach for stroke treatment. However, the development of small molecules capable of effectively inducing this cellular reprogramming remains a critical challenge. METHODS: Initially, we introduced a glial cell marker gene, GFaABC1D, as the promoter within an adeno-associated virus vector overexpressing miR-124 into the motor cortex of an ischemia-reperfusion model in rats. Additionally, we administered NeuroD1 as a positive control. Lentiviral vectors overexpressing miR-124 were constructed and transfected into primary rat astrocytes. We assessed the cellular distribution of GFAP, DCX, and NeuN on days 7, 14, and 28, respectively. RESULTS: In rats with ischemic stroke, miR-124-transduced glial cells exhibited positive staining for the immature neuron marker doublecortin (DCX) and the mature neuron marker NeuN after 4 weeks. In contrast, NeuroD1-overexpressing model rats only expressed NeuN, and the positive percentage was higher in co-transfection with miR-124 and NeuroD1. Overexpression of miR-124 effectively ameliorated neurological deficits and motor functional impairment in the model rats. In primary rat astrocytes transduced with miR-124, DCX was not observed after 7 days of transfection, but it appeared at 14 days, with the percentage further increasing to 44.6% at 28 days. Simultaneously, 15.1% of miR-124-transduced cells exhibited NeuN positivity, which was not detected at 7 and 14 days. In vitro, double fluorescence assays revealed that miR-124 targeted Dll4, and in vivo experiments confirmed that miR-124 inhibited the expression of Notch1 and DLL4. CONCLUSIONS: The overexpression of miR-124 in astrocytes demonstrates significant potential for improving neurological deficits following ischemic stroke by inhibiting DLL4 expression, and it may facilitate astrocyte-to-neuronal transformation.
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Isquemia Encefálica , AVC Isquêmico , MicroRNAs , Acidente Vascular Cerebral , Ratos , Animais , Astrócitos/metabolismo , AVC Isquêmico/genética , AVC Isquêmico/metabolismo , Neurônios/metabolismo , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Isquemia Encefálica/metabolismoRESUMO
Hepatocellular carcinoma (HCC) is associated with high mortality, especially in Asian populations where chronic HBV infection is a major cause. Accurate prediction of mortality can assist clinical decision-making. We aim to (i) compare the predicting ability of Barcelona Clinic Liver Cancer classification (BCLC) stage, neutrophil-to-lymphocyte ratio (NLR), and Albumin-Bilirubin (ALBI) score in predicting short-term mortality (one- and two-year) and (ii) develop a novel model with improved accuracy compared to the conventional models. This study enrolled 298 consecutive HCC patients from our hepatology department. The prognostic values for mortality were assessed by area under the receiver operating characteristic curve (AUROC) analysis. A novel model was established and internally validated using 5-fold cross-validation, followed by external validation in a cohort of 100 patients. The primary etiology of cirrhosis was hepatitis B virus (HBV), with 81.2% of HCC patients having preserved liver function. Significant differences were observed in hemoglobin (Hb) and serum albumin levels, which reflect patients' nutrition status, between patients who survived for one year and those who died. BCLC exhibited superior predictive accuracy compared to NLR but had borderline superiority to the ALBI score. Therefore, a novel model incorporating BCLC, Hb, and serum albumin was developed, internally and externally validated, as well as subgroup sensitivity analysis. The model exhibited significantly higher predictive accuracy for one- and two-year mortality than conventional prognostic predictors, with AUROC values of 0.841 and 0.805, respectively. The novel "BCLC-Nutrition Model", which incorporates BCLC, Hb, and serum albumin, may provide improved predictive accuracy for short-term mortality in HCC patients compared to commonly used prognostic scores. This emphasizes the importance of nutrition in the management of HCC patients.
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OBJECTIVE: To compare the effects of exercise training under hypoxia versus normoxia on cognitive function in clinical and non-clinical populations. DATA SOURCES: From inception to June 13th, 2022, a systematic search was performed on PubMed, Web of Science, Embase, Scopus, and Cochrane Central Register of Controlled Trials. STUDY SELECTION: Randomized controlled trials comparing the effects of exercise under hypoxic vs normoxic on cognition in clinical and non-clinical populations were included. The systematic search generated 14,894 relevant studies, of which 12 were finally included. DATA EXTRACTION: Two reviewers independently extracted data from included studies. Results were expressed as standardized mean difference (SMD). Each included study was assessed using the Cochrane Risk of Bias 1.0 (RoB1.0) tool. Finally, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to rate the certainty of evidence for each outcome. DATA SYNTHESIS: Overall, 12 studies with a total of 338 participants met the inclusion criteria. The pooled results suggested that hypoxia exercise had a small but not statistically significant positive effect on overall cognitive function (SMD=0.064, 95% confidence interval (CI): -0.156-0.284, P=.567, very low-certainty evidence), when compared with normoxic exercise. Regarding the domain-specific cognitive functions, there was a medium and significant positive effect on memory (SMD=0.594, 95% CI: 0.068 to 1.120, P=.027, very low-certainty evidence), while effects on visuospatial function (SMD=0.490, 95% CI: -0.030 to 1.010, P=.065, very low-certainty evidence), attention (SMD=0.037, 95% CI: -0.340 to 0.414, P=.847, very low-certainty evidence), executive function (SMD=0.096, 95% CI: -0.268 to 0.460, P=.605, very low-certainty evidence), and processing speed (SMD=-0.145, 95% CI: -0.528 to 0.239, P=.459, very low-certainty evidence) were not statistically significant. CONCLUSIONS: The current pooled results revealed that hypoxic exercise was related to improved cognitive performance. Nevertheless, exercise under hypoxia did not have a significant advantage in cognitive promotion when compared with exercise under normoxia.
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BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a severe complication in cirrhosis patients with ascites, leading to high mortality rates if not promptly treated. However, specific prediction models for SBP are lacking. AIMS: This study aimed to compare commonly used cirrhotic prediction models (CTP score, MELD, MELD-Na, iMELD, and MELD 3.0) for short-term mortality prediction and develop a novel model to improve mortality prediction. METHODS: Patients with the first episode of SBP were included. Prognostic values for mortality were assessed using AUROC analysis. A novel prediction model was developed and validated. RESULTS: In total, 327 SBP patients were analyzed, with HBV infection as the main etiologies. MELD 3.0 demonstrated the highest AUROC among the traditional models. The novel model, incorporating HRS, exhibited superior predictive accuracy for in-hospital in all patients and 3-month mortality in HBV-cirrhosis, with AUROC values of 0.827 and 0.813 respectively, surpassing 0.8. CONCLUSIONS: MELD 3.0 score outperformed the CTP score and showed a non-significant improvement compared to other MELD-based scores, while the novel SBP model demonstrated impressive accuracy. Internal validation and an HBV-related cirrhosis subgroup sensitivity analysis supported these findings, highlighting the need for a specific prognostic model for SBP and the importance of preventing HRS development to improve SBP prognosis.
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Li3VO4 (LVO) is a highly promising anode material for lithium-ion batteries, owing to its high capacity and stable discharge plateau. However, LVO faces a significant challenge due to its poor rate capability, which is mainly attributed to its low electronic conductivity. To enhance the kinetics of lithium ion insertion and extraction in LVO anode materials, a conductive polymer called poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is applied to coat the surface of LVO. This uniform coating of PEDOT:PSS improves the electronic conductivity of LVO, thereby enhancing the corresponding electrochemical properties of the resulting PEDOT:PSS-decorated LVO (P-LVO) half-cell. The charge/discharge curves between 0.2 and 3.0 V (vs. Li+/Li) indicate that the P-LVO electrode displays a capacity of 191.9 mAh/g at 8 C, while the LVO only delivers a capacity of 111.3 mAh/g at the same current density. To evaluate the practical application of P-LVO, lithium-ion capacitors (LICs) are constructed with P-LVO composite as the negative electrode and active carbon (AC) as the positive electrode. The P-LVO//AC LIC demonstrates an energy density of 107.0 Wh/kg at a power density of 125 W/kg, along with superior cycling stability and 97.4% retention after 2000 cycles. These results highlight the great potential of P-LVO for energy storage applications.
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OBJECTIVE: To review the evidence for the effectiveness of multicomponent exercise (an exercise program combining aerobic, endurance, balance, and flexibility exercises) on cognition, physical function, and activities of daily living in people with dementia and mild cognitive impairment (MCI). DATA SOURCES AND STUDY SELECTION: We conducted this study under the guidance of a designated protocol (PROSPERO CRD42022324641). Pertinent randomized controlled trials were selected from PubMed, Embase, Web of Science, and the Cochrane Library by 2 independent authors through May 2022. DATA EXTRACTION: Two authors independently extracted the data and assessed the quality of the included studies following the Cochrane Risk of Bias tool. Outcome data were extracted in a random effects model and estimated as Hedges' g and 95% confidence interval (CI). To validate specific results, the Egger test combined the Duval and Tweedie "trim and fill" method and sensitivity analysis with study removed were performed. DATA SYNTHESIS: A total of 21 publications were eligible for the quantitative analysis. In dementia, estimates of Hedges' g showed effects on global cognition (g=0.403; 95% CI, 0.168-0.638; P<.05), especially executive function (g=0.344; 95% CI, 0.111-0.577; P<.05), flexibility (g=0.671; 95% CI, 0.353-0.989; P<.001), agility and mobility (g=0.402; 95% CI, 0.089-0.714; P<.05), muscle strength (g=1.132; 95% CI, 0.420-1.845; P<.05), and activities of daily living (g=0.402; 95% CI, 0.188-0.615; P<.05). Also, a positive trend was observed in gait speed. Additionally, multicomponent exercise had positive effects on global cognition (g=0.978; 95% CI, 0.298-1.659; P<.05) and executive function (g=0.448; 95% CI, 0.171-0.726; P<.05) in patients with MCI. CONCLUSIONS: Our findings confirm the viability of multicomponent exercise as a management strategy for patients with dementia and MCI.
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Disfunção Cognitiva , Demência , Humanos , Idoso , Atividades Cotidianas , Cognição , Exercício FísicoRESUMO
Colorectal cancer (CRC) stands as the second leading cause of cancer-related deaths worldwide with limited available medicines. While drug repurposing comes as a promising strategy for cancer treatment, we discovered that propranolol (Prop), a non-selective ß1 and ß2 adrenergic receptor blocker, significantly inhibited the development of subcutaneous CT26 CRC and AOM/DSS-induced CRC models. The RNA-seq analysis highlighted the activated immune pathways after Prop treatment, with KEGG analysis enriched in T-cell differentiation. Routine analyses of blood revealed a decrease in neutrophil to lymphocyte ratio, a biomarker of systemic inflammation, and a prognostic indicator in the Prop-treated groups in both CRC models. Analysis of the tumor-infiltrating immune cells exhibited that Prop regressed the exhaustion of CD4+ and CD8+ T cells in the CT26-derived graft models, which was further corroborated in the AOM/DSS-induced models. Furthermore, bioinformatic analysis fitted well with the experimental data, showing that ß2 adrenergic receptor (ADRB2) was positively correlated with T-cell exhaustion signature in various tumors. The in vitro experiment showed no direct effect of Prop on CT26 cell viability, while T cells were activated with significantly-upregulated production of IFN-γ and Granzyme B. Consistently, Prop was unable to restrain CT26 tumor growth in nude mice. At last, the combination of Prop and the chemotherapeutic drug Irinotecan acted out the strongest inhibition in CT26 tumor progress. Collectively, we repurpose Prop as a promising and economical therapeutic drug for CRC treatment and highlight T-cell as its target.
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Neoplasias Colorretais , Propranolol , Animais , Camundongos , Propranolol/farmacologia , Propranolol/uso terapêutico , Irinotecano/farmacologia , Irinotecano/uso terapêutico , Linfócitos T CD8-Positivos , Camundongos Nus , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Neoplasias Colorretais/patologia , Linhagem Celular TumoralRESUMO
The main purpose of this study was to compare the antioxidant and anticancer activities of lycopene samples with different ratios of Z-isomers. Lycopene samples containing 5%, 30%, and 55% Z-isomers were successfully prepared by using thermal treatment combined with anti-solvent crystallization. The in vitro bio-accessibility of lycopene was estimated by the determination of partition factor (PF) and the results showed that lycopene with 55% Z-isomers possessed the highest bio-accessibility. Moreover, DPPH and ABTS assays suggested that the antioxidant activity of lycopene increased with the Z-isomers content from 5% to 55%. However, lycopene inhibited the survival of human hepatocellular carcinoma cells (HepG2) in a dose and time-dependent manner. The highest inhibition of HepG2 cell lines was achieved by 55% Z-ratio of lycopene. The cell viability was 22.54% at 20 µg/mL after incubating for 24 h, the number of cells was significantly reduced and the morphology was shrunk. Furthermore, molecular docking was introduced to compare the binding ability between different lycopene isomers with Scavenger Receptor class B type I (SR-BI), and the results revealed that the affinity of (all-E)-lycopene with SR-BI was lower compared to 5Z-lycopene and 13Z-lycopene, providing the reasons for different bioavailability of the above-mentioned lycopene isomers. All the above results demonstrated that Z-isomers-rich lycopene could enhance bio-accessibility and biological functionality.
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ABSTRACT: We aimed to plot the growth curve of the fetal clavicle, identify gestational date-independent parameters. Using 2-dimensional ultrasonography, we obtained the clavicle lengths (CLs) from 601 normal fetuses between 12 and 40 gestational age (GA). The CL/fetal growth parameters ratio was calculated. Moreover, 27 cases of fetal growth restriction (FGR) and 9 cases of small for GA (SGA) were detected. In normal fetuses, the mean CL (mm) = -68.2 + 29.80 × ln(GA) ± Z × (1.07 + 0.02 × GA). A linear relationship was detected between CL and head circumference (HC), biparietal diameter, abdominal circumference and femoral length with R2 values of 0.973, 0.970, 0.962, and 0.972, respectively. The CL/HC ratio (mean value 0.130) showed no significant correlation with GA. Clavicle lengths in the FGR group significantly decreased compared with the SGA group ( P < 0.01). This study determined a reference range of fetal CL in a Chinese population. Furthermore, the CL/HC ratio, which is independent of GA, is a novel parameter for the evaluation of the fetal clavicle.