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Background: This study was aimed at investigating the dynamics of lipids and the effect of TAF on the lipid profile of patients including fatty liver disease in CHB patients. Methods: The data of TC, LDL-c, HDL-c, TG, and TC/HDL ratio were collected at baseline, 24 weeks, 48 weeks, 72 weeks, and 96 weeks. CHB patients with fatty liver at baseline were further analyzed in a subgroup. Results: A total of 137 CHB patients treated with TAF were enrolled in this study. During 96 weeks of TAF treatment, there was no significant change in TC, LDL-c, HDL-c, and TG level (P > 0.05). The TC/HDL-c ratio was increased with no significant change (+0.24, P > 0.05). In CHB patients with fatty liver (n = 48), TC, LDL-c, and TC/HDL-c ratio increased gradually during TAF treatment, TG levels increased to 146.63 mg/dL at 48 weeks (P = 0.057) and then decreased, but there was still no significant change compared with the baseline level by 96 weeks (P > 0.05). Conclusion: TAF treatment had a low effect on the lipid profile of CHB patients over the course of 96 weeks, and it was safe even in patients with fatty liver. Clinical trial registration: [https://www.chictr.org.cn/showproj.html?proj=65123], identifier [ChiCTR2000041005].
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Molecular engineering of drug delivering platforms to provide collaborative biological effects with loaded drugs is of great medical significance. Herein, cannabinoid receptor 1 (CB1)- and reactive oxygen species (ROS)-targeting electrosprayed microspheres (MSs) are fabricated by loading with the CB1 agonist arachidonoyl 2'-chloroethylamide (ACEA) and producing ROS in a photoresponsive manner. The synergistic anti-tumor effects of ACEA and ROS released from the MSs are assessed. ACEA inhibits epidermal growth factor receptor signaling and altered tumor microenvironment (TME) by activating CB1 to induce tumor cell death. The MSs are composed of glycidyl methacrylate-conjugated xanthan gum (XGMA) and Fe3+, which form dual molecular networks based on a Fe3+-(COO-)3 network and a CâC addition reaction network. Interestingly, the Fe3+-(COO-)3 network can be disassembled instantly under the conditions of lactate sodium and ultraviolet exposure, and the disassembly is accompanied by massive ROS production, which directly injures tumor cells. Meanwhile, the transition of dual networks to a single network boosts the ACEA release. Together, the activities of the ACEA and MSs promote immunogenic tumor cell death and create a tumor-suppressive TME by increasing M1-like tumor-associated macrophages and CD8+ T cells. In summation, this study demonstrates strong prospects of improving anti-tumor effects of drug delivering platforms through molecular design.
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Antineoplásicos , Ácidos Araquidônicos , Agonistas de Receptores de Canabinoides , Neoplasias Colorretais , Imunoterapia , Receptor CB1 de Canabinoide , Microambiente Tumoral , Hidrogéis/administração & dosagem , Microesferas , Imunoterapia/métodos , Receptor CB1 de Canabinoide/agonistas , Espécies Reativas de Oxigênio/metabolismo , Agonistas de Receptores de Canabinoides/administração & dosagem , Agonistas de Receptores de Canabinoides/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Receptores ErbB/antagonistas & inibidores , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Sistemas de Liberação de Medicamentos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/imunologia , Humanos , Linhagem Celular Tumoral , Raios Ultravioleta , Ácidos Araquidônicos/administração & dosagem , Ácidos Araquidônicos/farmacologia , Polissacarídeos Bacterianos/química , Compostos de Epóxi/química , Metacrilatos/química , Desenho de FármacosRESUMO
Okadaic acid (OA) is one of the main virulence factors of diarrheal shellfish toxins (DSP). It is of great significance to detect OA with an accurate, specific and cost-effective technique in the fields of seafood safety and water quality control. In this work, an electrochemical aptasensor with reverse amplification was developed for the sensitive detection of OA. A two-dimensional graphite-phase nanomaterial (carbon nitride) modified with an anti-OA aptamer and thionine (Th) was immobilized onto the surface of the electrochemical electrode as the sensitive element to capture target OA molecules. ssDNA-modified carbon nitride was used as the reverse amplification element by hybridizing with non-OA linked aptamers. The preparation of the electrochemical aptasensor was well characterized by Scanning Electron Microscopy (SEM), zeta potential detection, UV-Vis absorption, Brunner-Emmet-Teller (BET) measurements, and electrochemical measurements. The quantitative assessment of OA was achieved by differential pulse voltammetry (DPV). Experimental results indicated that this aptasensor showed a concentration-dependent response to OA with a good detection performance including in terms of selectivity, repeatability, reproducibility, and stability. It exhibited 100-fold selectivity between OA and other toxins including dinophysistoxins (DTX), pectenotoxins (PTX), and yessotoxins (YTX). In addition, it showed a much wider quantification range, which is 10-13 M-10-10 M (0.080-80.50 pg mL-1). The detection limit was as low as 10-13 M (0.080 pg mL-1). The aptasensor also successfully achieved significant practicality on real shellfish samples contaminated by OA. All these results demonstrated that the reverse amplification strategy for marine toxin detection may provide a label-free and rapid detection approach for portable applications in the fields of environmental monitoring and food security.
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Aptâmeros de Nucleotídeos , Nitrilas , Ácido Okadáico , Reprodutibilidade dos Testes , Aptâmeros de Nucleotídeos/química , Frutos do Mar , Alimentos Marinhos/análiseRESUMO
The advantage of 3D printing-that is, additive manufacturing (AM) of structural materials-has been severely compromised by their disappointing fatigue properties1,2. Commonly, poor fatigue properties appear to result from the presence of microvoids induced by current printing process procedures3,4. Accordingly, the question that we pose is whether the elimination of such microvoids can provide a feasible solution for marked enhancement of the fatigue resistance of void-free AM (Net-AM) alloys. Here we successfully rebuild an approximate void-free AM microstructure in Ti-6Al-4V titanium alloy by development of a Net-AM processing technique through an understanding of the asynchronism of phase transformation and grain growth. We identify the fatigue resistance of such AM microstructures and show that they lead to a high fatigue limit of around 1 GPa, exceeding the fatigue resistance of all AM and forged titanium alloys as well as that of other metallic materials. We confirm the high fatigue resistance of Net-AM microstructures and the potential advantages of AM processing in the production of structural components with maximum fatigue strength, which is beneficial for further application of AM technologies in engineering fields.
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Background: Smoking is one of the major risk factors for shortened lifespan and disability, while smoking cessation is currently the only guaranteed method to reduce the harm caused by smoking. E-health is a field that utilizes information and communication technology to support the health status of its users. The emergence of this digital health approach has provided a new way of smoking cessation support for smokers seeking help, and an increasing number of researchers are attempting to use e-health for a wide range of effective smoking cessation interventions. We conducted a systematic review and meta-analysis of studies that used e-health as a smoking cessation support tool. Methods: This systematic review and meta-analysis searched the PubMed, Embase, and Cochrane Library databases until December 2022. The included studies were randomized controlled trials (RCTs) comparing the use of e-health interventions and traditional offline smoking cessation care interventions. The primary outcome of the studies was the point smoking cessation rate (7-day and 30-day), and the secondary outcome was sustained smoking cessation rates. Studies were excluded if there was no clear e-health intervention described or if standard-compliant cessation outcomes were not clearly reported. Fixed-effects meta-analysis and meta-regression analyses were performed on the included study data to evaluate the effectiveness of the interventions. The meta-analysis outcome was the risk ratio (RR) and a 95% confidence interval. The study was registered with PROSPERO, CRD42023388667. Findings: We collectively screened 2408 articles, and ultimately included 39 articles with a total of 17,351 eligible participants, of which 44 studies were included in the meta-analysis. The meta-analysis revealed that compared to traditional smoking cessation interventions, e-health interventions can increase point quit rates (RR 1.86, 95% CI 1.69-2.04) as well as sustained quit rates in the long-term (RR 1.79, 95% CI 1.60-2.00) among smokers. Subgroup analysis showed that text and telephone interventions in e-health significantly improved short-term quit rates for up to 7 days (RR 2.10, 95% CI 1.77-2.48). Website and app interventions also had a positive impact on improving short-term quit rates for up to 7 days (RR 1.74, 95% CI 1.56-1.94). The heterogeneity of the study results was low, demonstrating the significant smoking cessation advantages of e-health interventions. Interpretation: We have found that personalized e-health interventions can effectively help smokers quit smoking. The diverse remote intervention methods of e-health can provide more convenient options for further customization. Additionally, further follow-up research is needed to evaluate the sustained effectiveness of interventions on smokers' continuous abstinence over a longer period (greater than one year). In the future, e-health can further optimize smoking cessation strategies. Funding: No funding.
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PURPOSE: This study seeks to evaluate the ability of the updated stress strain index (SSIv2) and other Corvis ST biomechanical parameters in distinguishing between keratoconus at different disease stages and normal eyes. DESIGN: Diagnostic accuracy analysis to distinguish disease stages. METHODS: 1084 eyes were included and divided into groups of normal (199 eyes), forme fruste keratoconus (FFKC, 194 eyes), subclinical keratoconus (SKC, 113 eyes), mild clinical keratoconus (CKC-â , 175 eyes), moderate clinical keratoconus (CKC-â ¡, 204 eyes), and severe clinical keratoconus (CKC-â ¢, 199 eyes). Each eye was subjected to a Corvis ST examination to determine the central corneal thickness (CCT), biomechanically corrected intraocular pressure (bIOP), SSIv2 (updated stress-strain index), and other 8 Corvis parameters including the stress-strain index (SSIv1), stiffness parameter at first applanation (SP-A1), first applanation time (A1T), Ambrósio relational thickness to the horizontal profile (ARTh), integrated inverse radius (IIR), maximum deformation amplitude (DAM), ratio between deformation amplitude at the apex and at 2 mm nasal and temporal (DARatio2), and Corvis biomechanical index (CBI). The sensitivity and specificity of these parameters in diagnosing keratoconus were analyzed through receiver operating characteristic curves. RESULTS: Before and after correction for CCT and bIOP, SSIv2 and ARTh were significantly higher and IIR and CBI were significantly lower in the normal group than in the FFKC group, SKC group and the 3 CKC groups (all P < .05). There were also significant correlations between the values of SSIv2, ARTh, IIR, CBI, and the CKC severity (all P < .05). AUC of SSIv2 was significantly higher than all other Corvis parameters in distinguishing normal eyes from FFKC, followed by IIR, ARTh and CBI. CONCLUSION: Corvis ST's updated stress-strain index, SSIv2, demonstrated superior performance in differentiating between normal and keratoconic corneas, and between corneas with different keratoconus stages. Similar, but less pronounced, performance was demonstrated by the IIR, ARTh and CBI.
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Ceratocone , Humanos , Ceratocone/diagnóstico , Topografia da Córnea , Córnea , Tonometria Ocular , Pressão Intraocular , Curva ROC , Fenômenos BiomecânicosRESUMO
Electroplating sludge (ES), a hazardous waste containing heavy metals and Fe/Al/Ca impurities, is conventionally disposed of in landfills. In this study, a pilot-scale vessel with an effective capacity of 20 L was applied to recycle Zn from real ES. The sludge contained 6.3 wt% Fe, 6.9 wt% Al, 2.6 wt% Si, 6.1 wt% Ca, and 17.6 wt% Zn and was treated using a four-step method. First, ES was dissolved in nitric acid after washing in a water bath at 75 °C for 3 h to produce an acidic solution with Fe, Al, Ca, and Zn concentrations of 4527.2, 3116.1, 3357.7, and 21,275 mg/L, respectively. Second, the acidic solution was added with glucose at an Mglucose/Mnitrate ratio of 0.08 and hydrothermally treated at 160 °C for 4 h. During this step, nearly 100 % Fe and 100 % Al were simultaneously removed as a mixture containing 53.1 wt% Fe2O3 and 45.7 wt% Al2O3. This process was repeated five times, during which the Fe/Al removal and Ca/Zn loss rates remained unchanged. Third, the residual solution was adjusted with sulfuric acid, and over 99 % Ca was removed as gypsum. The residual Fe, Al, Ca, and Zn concentrations were 0.44, 0.88, 52.59, and 31,177.1 mg/L, respectively. Finally, Zn in the solution was precipitated as ZnO with a concentration of 94.3 %. Economic calculations showed that each 1 t of ES processed created revenue of about $122. This is the first study of high-value metal resource recovery using real electroplating sludge at the pilot scale. This work highlights the pilot-scale application of resource utilization of real ES and provides new insights into the recycling of heavy metals from hazardous waste.
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Red mud (RM) a solid waste generated by the bauxite smelting industry, is a rich source of metal resources, especially Ti, and its recycling can bring significant environmental and economic benefits. In this study, precious metal Ti was efficiently recovered from red mud using a coupled acid leaching and boiling route for the effective separation of low-value metals. The red mud which contained mainly 10.69% Si, 12.1% Al, 15.2% Ca, 10.99% Fe, and 4.37% Ti, was recovered in five steps. First, a nitric acid solution was used to leach the metals in multiple stages, resulting in an acidic leach solution with high concentrations of Fe, Al, Ti, and Ca ions 2.7 g/L, 4.7 g/L, 5.43 g/L, and 1.8 g/L, respectively. Then, a small amount of sucrose was added as a catalyst to recover Ti from the leach solution under hydrothermal conditions, resulting in the targeted recovery of 98.6% of Ti in the form of high-purity anatase while Fe, Al, and Ca remained in the solution. Next, the Fe in solution was separated as hematite products at a temperature of 110°C and a reaction time of 4 h. Similarly, the Al in the solution was separated and precipitated as boehmite by heating it at 260°C for a reaction time of 20 h. Finally, the remaining Ca in solution was recovered by simple pH regulation. Economic accounting assessment showed that the method yields $101.06 for 1 t of red mud treated, excluding labor costs. This study provides a novel approach to recover precious metals from metal wastes through the whole process resource recovery of solid waste red mud.
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BACKGROUND: Chronic kidney disease (CKD) is characterized as a progressive dysfunction of the kidney, and it might have a close relationship with insulin resistance. We utilized the triglyceride-glucose (TyG) index, a reliable marker of insulin resistance, to evaluate the association between the TyG index and CKD in adults from the general population. METHODS: This was a cross-sectional study obtaining data from the 2015-2018 National Health and Nutrition Examination Survey. The estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) served as kidney function indicators. We defined CKD as the existence of either low eGFR (eGFR < 60 mL/min/1.73 m2 BSA) or albuminuria (UACR > 30 mg/g). Multivariate regressions, correlated subgroup analyses, and interaction terms were performed in this study. RESULTS: For 4361 recruited participants, the mean TyG index was 8.60 ± 0.68, and the prevalence of CKD was 13.35%. Participants with a higher TyG index showed a higher UACR level (ß = 25.10, 95% CI: 6.76, 43.44, P = 0.0074) and higher levels of CKD (OR = 1.34, 95% CI: 1.13, 1.59, P = 0.0006). The positive relationship between the TyG index and CKD became stronger and remained significant in the overweight (OR = 1.61, 95% CI: 1.18, 2.20, P = 0.0027) and obese (OR = 2.48, 95% CI: 1.95, 3.15, P < 0.0001) groups and in people with diabetes (OR = 1.94, 95% CI: 1.46, 2.56, P < 0.0001). CONCLUSIONS: Higher TyG index was strongly associated with a higher UACR level and higher values of albuminuria and CKD, which might be useful in kidney function screening especially among people in disadvantageous socioeconomic conditions with no availability for direct measurement of kidney function. However, more well-designed studies are still needed to validate this relationship.
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Resistência à Insulina , Insuficiência Renal Crônica , Humanos , Adulto , Albuminúria/epidemiologia , Albuminúria/urina , Glucose , Triglicerídeos , Estudos Transversais , Inquéritos Nutricionais , Taxa de Filtração GlomerularRESUMO
This study investigated the pharmacological mechanism of kaempferol in the treatment of oxaliplatin-induced neuropathic pain by network pharmacological method and cells experiment. The kaempferol and disease target genes were obtained from several databases, including TCMSP, SwissTargetPrediction, GeneCards, and CTD. Then, the common target genes of drugs and diseases were obtained using Venny online tools. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses were carried out to obtain the enriched molecular pathways associated with the kaempferol and disease. Finally, we constructed a neuropathic pain cell experiment to confirm the findings. 138 intersection targets were identified between targets of kaempferol and oxaliplatin-induced neurotoxicity. Enrichment analyses revealed that the IL-17 signaling pathway was associated with the therapeutic effects of kaempferol. Kaempferol down-regulated the mRNA expression levels of TNF-α, IL-6, and CCL2 in oxaliplatin-treated astrocytes. Our findings showed that kaempferol alleviated oxaliplatin-induced neurotoxicity via regulation of inflammation-related genes.
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Medicamentos de Ervas Chinesas , Neuralgia , Síndromes Neurotóxicas , Humanos , Quempferóis/farmacologia , Oxaliplatina/toxicidade , Astrócitos , Bases de Dados Factuais , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/prevenção & controle , Simulação de Acoplamento MolecularRESUMO
PURPOSE: The objective of this paper is to design a protocol for a systematic review and meta-analysis on the effectiveness of self-management interventions in patients with chronic heart failure. METHODS: The protocol is developed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol has been registered in PROSPERO (CRD42021246973). Base on the population, intervention, comparator, and outcome (PICO) framework, our research questions are: 1) What are the effects of eHealth self-management interventions on patients with chronic heart failure? 2) What factors of interventions might affect outcomes? The process includes: 1) search strategy and inclusion criteria; 2) data extraction; 3) risk of bias assessment and 4) data analysis. Searching process and data extraction will be guided by Cochrane Handbook for Systematic Reviews of Interventions. We will use Cochrane Risk of Bias tool to assess the risk of bias. The data analysis will be performed using Metafor package in R. CONCLUSIONS: This systemic review will synthesize the current evidence and identify gaps. Findings in the meta-analysis will provide guidance for designing a more effective self-management intervention for patients with chronic heart failure in future.
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Insuficiência Cardíaca , Autogestão , Telemedicina , Doença Crônica , Insuficiência Cardíaca/terapia , Humanos , Metanálise como Assunto , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Heart failure (HF) is a common clinical syndrome associated with substantial morbidity, a heavy economic burden, and high risk of readmission. eHealth self-management interventions may be an effective way to improve HF clinical outcomes. OBJECTIVE: The aim of this study was to systematically review the evidence for the effectiveness of eHealth self-management in patients with HF. METHODS: This study included only randomized controlled trials (RCTs) that compared the effects of eHealth interventions with usual care in adult patients with HF using searches of the EMBASE, PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), and CINAHL databases from January 1, 2011, to July 12, 2022. The Cochrane Risk of Bias tool (RoB 2) was used to assess the risk of bias for each study. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria were used to rate the certainty of the evidence for each outcome of interest. Meta-analyses were performed using Review Manager (RevMan v.5.4) and R (v.4.1.0 x64) software. RESULTS: In total, 24 RCTs with 9634 participants met the inclusion criteria. Compared with the usual-care group, eHealth self-management interventions could significantly reduce all-cause mortality (odds ratio [OR] 0.83, 95% CI 0.71-0.98, P=.03; GRADE: low quality) and cardiovascular mortality (OR 0.74, 95% CI 0.59-0.92, P=.008; GRADE: moderate quality), as well as all-cause readmissions (OR 0.82, 95% CI 0.73-0.93, P=.002; GRADE: low quality) and HF-related readmissions (OR 0.77, 95% CI 0.66-0.90, P<.001; GRADE: moderate quality). The meta-analyses also showed that eHealth interventions could increase patients' knowledge of HF and improve their quality of life, but there were no statistically significant effects. However, eHealth interventions could significantly increase medication adherence (OR 1.82, 95% CI 1.42-2.34, P<.001; GRADE: low quality) and improve self-care behaviors (standardized mean difference -1.34, 95% CI -2.46 to -0.22, P=.02; GRADE: very low quality). A subgroup analysis of primary outcomes regarding the enrolled population setting found that eHealth interventions were more effective in patients with HF after discharge compared with those in the ambulatory clinic setting. CONCLUSIONS: eHealth self-management interventions could benefit the health of patients with HF in various ways. However, the clinical effects of eHealth interventions in patients with HF are affected by multiple aspects, and more high-quality studies are needed to demonstrate effectiveness.
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Insuficiência Cardíaca , Autogestão , Telemedicina , Adulto , Insuficiência Cardíaca/terapia , Humanos , Adesão à Medicação , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
This work studied the relationship between biodegradation rate and grain size itself, excluding other structural factors such as segregations, impure inclusions, second phase particles, sub-structures, internal stresses and textures caused by alloying additions and deformation processing for pure Mg. A spectrum of grain size was obtained by annealing through changing the annealing temperature. Grain boundary influenced the hardness and the biodegradation behavior. The hardness was grain size-dependent, following a typical Hall-Petch relation: HV=18.45+92.31d-12. The biodegradation rate decreased with decreasing grain size, following a similar Hall-Petch relation: Pi=0.17-0.68d-12 or Pw=1.34-6.17d-12. This work should be helpful for better controlling biodegradation performance of biodegradable Mg alloys through varying their grain size.
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The mechanism of oxidizing reaction in the preparation of graphene oxide (GO) by a chemical oxidation method remains unclear. The main oxidant of graphite oxide has not been determined. Here, we show a new mechanism in which Mn2O7, the main oxidant, is heated to decompose oxygen atoms and react with graphite. The whole preparation process constitutes of four distinct independent steps, different from the three steps of literature registration, and each step has its own chemical oxidation reaction. In the first step, concentrated sulfuric acid and nitric acid are intercalated between graphite layers in the form of a molecular thermal motion to produce HNO3-H2SO4-GIC. In the second step, Mn2O7 is intercalated between graphite layers in the molecular convection-diffusion to Mn2O7-H2SO4-GIC. In the third step, Mn2O7 is decomposed by heat. Oxygen atoms are generated to oxidize the defects in the graphite layer to PGO. This discovery is the latest and most important. In the fourth step, PGO is purified with deionized water, hydrogen peroxide, and hydrochloric acid to GO. Optical microscopy, ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction spectrometry, and scanning electron microscopy analytical evidence was used for confirming Mn2O7 as the main oxidant and the structure of GO. This work provides a more plausible explanation for the mechanism of oxidizing reaction in the preparation of GO by a chemical oxidation method.
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Cancer-associated fibroblasts secreted exosomes (CAFs-exo) are important for tumor carcinogenesis and chemoresistance, but its underlying mechanism in colorectal cancer (CRC) has not yet been clarified. In this study, we investigated the regulatory mechanism of CAFs-exo cricN4BP2L2 on the proliferation, apoptosis, stemness and chemoresistance of LoVo cells. We found that CAFs-exo promoted the oxaliplatin resistance and stemness of LoVo cells, while inhibited the LoVo cell apoptosis. Moreover, knockdown of cricN4BP2L2 in CAFs-exo inhibited the oxaliplatin resistance and stemness characteristics of LoVo cells. Mechanistically, cricN4BP2L2 regulated PI3K/AKT/mTOR axis by binding to EIF4A3. Rescue experiments proved that CAFs-derived exosomal cricN4BP2L2 promoted CRC cells stemness and oxaliplatin resistance by upregulating EIF4A3. Moreover, in vivo experiments showed that depletion of cricN4BP2L2 suppressed CRC tumorigenesis growth. In conclusion, CAFs-exo cricN4BP2L2 promoted the CRC cells stemness and oxaliplatin resistance through EIF4A3/PI3K/AKT/mTOR pathway.
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Fibroblastos Associados a Câncer , Neoplasias Colorretais , Exossomos , MicroRNAs , Fibroblastos Associados a Câncer/patologia , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , RNA Helicases DEAD-box/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fator de Iniciação 4A em Eucariotos/metabolismo , Exossomos/metabolismo , Humanos , MicroRNAs/metabolismo , Oxaliplatina , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
Our previous research has demonstrated that colorectal cancer (CRC) progression was promoted by circN4BP2L2. This study aimed to further explore the mechanism of circN4BP2L2 in the development of CRC from the perspective of small extracellular vesicles (sEVs). Cancer-associated fibroblasts cell (CAFs) and normal fibroblasts cell (NFs) were isolated from CRC tissues and adjacent tissues, respectively. The ultra-centrifugation was used for extraction of their related sEVs. Cell proliferation and apoptosis were analyzed using CCK-8 and flow cytometry, respectively. Transwell assay was conducted to measure cell migration. The tube formation ability was assessed by tube formation assay. The target relationships between circN4BP2L2 and miR-664b-3p, and miR-664b-3p and HMGB3 were validated by dual-luciferase reporter detection. The effect of CAFs-derived sEV (CAFs-sEVs) circN4BP2L2 on CRC was further studied in nude mice. CAFs-exo promoted cell proliferation, migration, tube formation ability, and inhibited apoptosis of CRC cells. CAFs-sEV circN4BP2L2 knockdown reversed the above results. CircN4BP2L2 directly targeted miR-664b-3p, and HMGB3 was targeted by miR-664b-3p. Moreover, subcutaneous tumorigenesis and liver metastasis of nude mice with CRC were repressed by CAFs-sEV circN4BP2L2 knockdown. CAFs-sEV circN4BP2L2 knockdown restrained CRC cell proliferation and migration by regulating miR-664b-3p/HMGB3 pathway.
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Neoplasias Colorretais , Vesículas Extracelulares , MicroRNAs , Animais , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
Cannabinoid receptors, CB1 and CB2, have been implicated as emerging targets for cancer therapy. Herein, we investigated the potential regulation mechanism of CB1 and its implications in colorectal cancer. CB1 and EGFR expression were examined in colorectal cancer cell lines. The effects of CB1 agonist ACEA and its antagonist AM251 on the proliferation, migration and invasion of colorectal cancer cells and the expression of M1 and M2 macrophage markers were examined. EGFR overexpression was performed with plasmids containing EGFR gene. Tumor xenografts were constructed to explore the effects of CB1 activation on tumorigenesis. We showed that CB1 was downregulated while EGFR was upregulated in colorectal cancer cells. The activation of CB1 suppressed the proliferation, migration and invasion of colorectal cancer cells and the differentiation of M2 macrophages, while CB1 inhibition had opposite effects. Moreover, the alterations in tumorigenesis and M2 macrophage activation induced by CB1 activation were counteracted by EGFR overexpression. Besides, CB1 silencing promoted tumor cell proliferation and M2 polarization which was counteracted by EGFR knockdown. In vivo, CB1 activation also repressed tumorigenesis and M2 macrophage activation. The present study demonstrated that CB1 activation suppressed M2 macrophage through EGFR downregulation in colorectal cancers. These findings first unveiled the potential avenue of CB1 as a targeted therapy for colorectal cancer.
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BACKGROUND: The migration of bone marrow-derived mesenchymal stem cells (BMSCs) to the wound site played an important role in tissue repair. Substance P (SP) has been studied and reported to be involved in tissue repair by promoting the growth of endothelial cells and the migration of BMSCs. However, the complicated process and the molecular mechanisms were not fully understood. Thus, we aimed to investigate the effect of SP-induced BMSCs migration on tissue repair and its possible mechanism. METHODS AND RESULTS: Western blot and q-PCR assay revealed that SP could induce the BMSCs migration through overexpression of CXCR4 and upregulation of Akt phosphorylation. And the upregulation was related to the activation of neurokinin-1 receptor (NK-1R). Besides, we found that the increased phosphorylation Akt caused by SP could be canceled by the inhibition of CXCR4 both in vitro and in vivo. Furthermore, a skin-injury animal model was established and used to observe the tissue repair process. Results showed that SP could accelerate wound closure, gain more granulation tissue accumulation, and more collagen deposition through the promotion of angiogenesis and induction of the BMSCs migration to the wound site. And these effects could be impaired by inhibition of CXCR4 and p-Akt. CONCLUSIONS: Our results suggested that SP promoted tissue repair through BMSCs migration via upregulation of CXCR4 and p-Akt. The expression of CXCR4 and p-Akt were regulated by NK-1R activation. These findings add more evidence in understanding the mechanisms of SP-induced BMSCs migration and highlight the potential for clinical implementation of SP in tissue repair.
Assuntos
Transplante de Células-Tronco Mesenquimais , Receptores da Neurocinina-1 , Animais , Células da Medula Óssea , Movimento Celular , Quimiocina CXCL12/metabolismo , Células Endoteliais/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Receptores da Neurocinina-1/genética , Receptores da Neurocinina-1/metabolismo , Substância P/farmacologiaRESUMO
Background: Employees who are physically present but work insufficiently because of illness are deemed as having presenteeism. In the health care setting, the issue has taken on greater importance because of the impairment of the physical and mental health of nurses and the nursing safety of the patients. According to the Job Demand-Resource Model, burnout may link emotional labor with presenteeism. Thus, this study analyzed the role of burnout as a mediating factor between the three types of emotional labor strategies and presenteeism among nurses in tertiary-level hospitals. Methods: A cross-sectional study of 1,038 nurses from six Chinese hospitals was conducted. The questionnaires, including the 14-item emotional labor strategies scale, 22-item Maslach Burnout Inventory scale, 6-item Stanford Presenteeism Scale, and items about demographic characteristics and work-related factors, were used to collect data. A multivariable linear regression was used to predict work-related factors and investigate the correlation of emotional labor, burnout, and presenteeism. The structural equation model was implemented to test the mediating effects of job burnout. Results: The results of the study showed that the average presenteeism score of the participants was 14.18 (4.33), which is higher than in Spanish, Portuguese, and Brazilian nurses. Presenteeism was explained by 22.8% of the variance in the final model in multivariable linear regression (P < 0.01). Presenteeism was found to be positively correlated with surface acting, emotionally expressed demands, deep acting, emotional exhaustion, depersonalization, and low personal accomplishment (P < 0.01). Notably, presenteeism was negatively correlated with deep acting (P < 0.01). In addition, burnout partially mediated the correlation between emotionally expressed demands, deep acting, and presenteeism with a mediatory effect of 24 and 63.31% of the total effect. Burnout completely mediated the association between surface acting and presenteeism, a mediating effect of 86.44% of the total effect. Conclusions: The results of this study suggested that different emotional labor strategies affect presenteeism, either directly or indirectly. Nursing managers should intervene to reduce presenteeism by improving the ability of the nurses to manage emotions, thereby alleviating burnout.
Assuntos
Esgotamento Profissional , Enfermeiros Administradores , Esgotamento Profissional/epidemiologia , China/epidemiologia , Estudos Transversais , Emoções , Humanos , Presenteísmo , Centros de Atenção TerciáriaRESUMO
Electroplating sludge is a hazardous waste produced in large quantities in the electroplating industry during production. It is rich in heavy metal resources and can be recovered as value-added heavy metal products. To recover Zn in electroplating sludge, Fe/Al/Ca impurities were effectively removed as hematite, boehmite, and calcium sulfate, respectively, via a facile hydrothermal method with reduction of nitric acid by addition of glucose. After the sludge was dissolved in nitric acid, the generated solution contained 6.1 g/L of Zn, 2.2 g/L of Fe, 2.5 g/L of Al, and 2.9 g/L of Ca. First, approximately 100% Fe was extracted as hematite nanoparticles containing 94.6 wt% Fe2O3 after the solution was treated at 190 °C for 6 h. Second, when the temperature was elevated to 270 °C, nearly 99% Al was isolated as boehmite particles containing 95.2 wt% Al2O3. Third, more than 98% Ca was removed as anhydrite, which contained 95.9 wt% CaSO4, by adding sulfuric acid. During the steps, the total loss of Zn was less than 3%, and 5.75 g/L of residual Zn was recovered as zincite containing 92.2 wt% ZnO by adjusting the pH to 8. The dissolved Fe, Al, and Ca impurities were successfully removed as purified hematite, boehmite, and anhydrite, respectively, through the stepwise separation method by adjusting reaction temperatures and pH. The high content of Zn in the electroplating sludge was finally purified as zincite.