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Immunodeficiency can disrupt normal physiological activity and function. In this study, donkey bone collagen peptide (DP) and its iron chelate (DPI) were evaluated their potential as immunomodulators in cyclophosphamide (Cytoxan®, CTX)-induced Balb/c mice. The femoral tissue, lymphocytes, and serum from groups of mice were subjected to hematoxylin and eosin (H&E) staining, methylthiazolyldiphenyl-tetrazolium bromide (MTT) cell proliferation assays, and enzyme-linked immunosorbent assay (ELISA), respectively. Furthermore, a non-targeted metabolomics analysis based on UPLC-MS/MS and a reverse transcription polymerase chain reaction (RT-qPCR) technology were used to explore the specific metabolic pathways of DPI regulating immunocompromise. The results showed that CTX was able to significantly reduce the proliferative activity of mouse splenic lymphocytes and led to abnormal cytokine expression. After DP and DPI interventions, bone marrow tissue damage was significantly improved. In particular, DPI showed the ability to regulate the levels of immune factors more effectively than Fe2+ and DP. Furthermore, metabolomic analysis in both positive and negative ion modes showed that DPI and DP jointly regulated the levels of 20 plasma differential metabolites, while DPI and Fe2+ jointly regulated 14, and all 3 jointly regulated 10. Fe2+ and DP regulated energy metabolism and pyrimidine metabolism pathways, respectively. In contrast, DPI mainly modulated the purine salvage pathway and the JAK/STAT signaling pathway, which are the key to immune function. Therefore, DPI shows more effective immune regulation than Fe2+ and DP alone, and has good application potential in improving immunosuppression.
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Colágeno , Ciclofosfamida , Equidae , Quelantes del Hierro , Ratones Endogámicos BALB C , Animales , Colágeno/metabolismo , Quelantes del Hierro/farmacología , Ratones , Proliferación Celular/efectos de los fármacos , Péptidos/farmacología , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Inmunosupresores/farmacología , Metabolómica , Citocinas/metabolismo , Masculino , Huesos/efectos de los fármacos , Huesos/metabolismo , Terapia de InmunosupresiónRESUMEN
BACKGROUND: Diabetic eye disease is a common micro-vascular complication of diabetes and a leading cause of decreased vision and blindness in people of working age worldwide.Although previous studies have shown that chemokines system may be a player in pathogenesis of diabetic eye disease, it is unclear which chemokines play the most important role.To date, there is no meta-analysis which has investigated the role of chemokines in diabetic eye disease.We hope this study will contribute to a better understanding of both the signaling pathways of the chemokines in the pathophysiological process, and more reliable therapeutic targets for diabetic eye disease. METHODS: Embase, PubMed, Web of Science and Cochrane Library systematically searched for relevant studies from inception to Sep 1, 2023. A random-effect model was used and standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated to summarize the associated measure between chemokines concentrations and diabetic eye disease. Network meta-analysis to rank chemokines-effect values according to ranked probabilities. RESULTS: A total of 33 different chemokines involving 11,465 subjects (6559 cases and 4906 controls) were included in the meta-analysis. Results of the meta-analysis showed that concentrations of CC and CXC chemokines in the diabetic eye disease patients were significantly higher than those in the controls. Moreover, network meta-analysis showed that the effect of CCL8, CCL2, CXCL8 and CXCL10 were ranked highest in terms of probabilities. Concentrations of CCL8, CCL2, CXCL8 and CXCL10 may be associated with diabetic eye disease, especially in diabetic retinopathy and diabetic macular edema. CONCLUSION: Our study suggests that CCL2 and CXCL8 may play key roles in pathogenesis of diabetic eye disease. Future research should explore putative mechanisms underlying these links, with the commitment to develop novel prophylactic and therapeutic for diabetic eye disease.
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Aqueous zinc-ion batteries (AZIBs) suffer from sharp cycling deterioration due to serious interfacial side reactions and corrosion problems on the zinc anode. Herein, an efficacious approach to construct hydrophobic ZnMoO4 coatings on Zn (denoted as Zn@ZMO) is proposed to mitigate direct contact between the zinc anode and electrolyte and enhance its cycle life. The hydrophobic ZnMoO4 layer (contact angle = 128°) with a honeycomb-like structure is prepared by an in situ liquid phase deposition method. The as-prepared ZnMoO4 coating exhibits persistent corrosion protection for Zn through 30 days of immersion in a 2 M ZnSO4 electrolyte, indicating excellent stability of the ZnMoO4 layer and ensuring its available application in AZIBs. Unique microchannels in this kind of honeycomb-like structured coating favor Zn2+ ion diffusion and ease of ion transport, especially at high current cycling. Its robust surface exclusion can effectively counter other side reactions induced by water, simultaneously. As a result, the Zn@ZMO symmetrical cell shows a remarkable cycle lifespan exceeding 2700 h at 1 mA cm-2/1 mA h cm-2, surpassing that of the bare zinc cell by more than 100 folds. At a current density of 5 A g-1, the Zn@ZMO//V2O5 cell can still achieve a specific capacity of 167.0 mA h g-1 after 500 cycles with a capacity retention rate of 88%, which demonstrates its long-term cycling stability.
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OBJECTIVE: To explore the protective effect and the underlying mechanism of silibinin (SIB), one of the active compounds from Silybum marianum (L.) Gaertn in endotoxemia. METHODS: Mouse peritoneal macrophage were isolated via intraperitoneally injection of BALB/c mice with thioglycolate medium. Cell viability was assessed using the cell counting kit-8, while cytotoxicity was determined through lactate dehydrogenase cytotoxicity assay. The protein expressions of interleukin (IL)-1 α, IL-1 ß, and IL-18 were determined by enzyme-linked immunosorbent assay. Intracellular lipopolysaccharide (LPS) levels were measured by employing both the limulus amoebocyte lysate assay and flow cytometry. Additionally, proximity ligation assay was employed for the LPS and caspase-11 interaction. Mice were divided into 4 groups: the control, LPS, high-dose-SIB (100 mg/kg), and low-dose-SIB (100 mg/kg) groups (n=8). Zebrafish were divided into 4 groups: the control, LPS, high-dose-SIB (200 εmol/L), and low-dose-SIB (100 εmol/L) groups (n=30 for survival experiment and n=10 for gene expression analysis). The expression of caspase-11, gasdermin D (GSDMD), and N-GSDMD was determined by Western blot and the expressions of caspy2, gsdmeb, and IL-1 ß were detected using quantitative real-time PCR. Histopathological observation was performed through hematoxylineosin staining, and protein levels in bronchoalveolar lavage fluid were quantified using the bicinchoninicacid protein assay. RESULTS: SIB noticeably decreased caspase-11 and GSDMD-mediated pyroptosis and suppressed the secretion of IL-1 α, IL-1 ß, and IL-18 induced by LPS (P<0.05). Moreover, SIB inhibited the translocation of LPS into the cytoplasm and the binding of caspase-11 and intracellular LPS (P<0.05). SIB also attenuated the expression of caspase-11 and N-terminal fragments of GSDMD, inhibited the relative cytokines, prolonged the survival time, and up-regulated the survival rate in the endotoxemia models (P<0.05). CONCLUSIONS: SIB can inhibit pyroptosis in the LPS-mediated endotoxemia model, at least in part, by inhibiting the caspase-11-mediated cleavage of GSDMD. Additionally, SIB inhibits the interaction of LPS and caspase-11 and inhibits the LPS-mediated up-regulation of caspase-11 expression, which relieves caspase-11-dependent cell pyroptosis and consequently attenuates LPS-mediated lethality.
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Under construction industry upgrading and environmental protection requirements, promoting prefabricated buildings is very important, but its development varies significantly in different regions. For example, it only accounts for 20% of the new construction area in China, and the overall development level is low. The promotion of prefabricated buildings involves multiple interests. Then, how to encourage all stakeholders to work together to promote its development is a crucial issue. This study obtains an evolutionary game model among the government, developers, and purchasers. Then the stability strategies of the stakeholders are given conditions. Finally, numerical simulation is used to validate theoretical findings and determine the sensitivity of key parameters to a subject's behavior. The results show that: (1) There are two key factors that restrict the cooperation of stakeholders to promote prefabricated buildings, including the lack of government subsidies and the weak demand of the purchasers; (2) The government's overall subsidy should not be too high, exceeding the government's expenditure on environmental protection, and the subsidies for developers and purchasers must be reasonably allocated to effectively compensate for development benefits and purchase costs under limited expenditures. (3) Improving the residential environment of prefabricated buildings can significantly enhance the vested interests of purchasers, make up for their purchase costs, increase their willingness to purchase, and thus reduce the sales risk of developers.
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Comercio , Industria de la Construcción , China , Simulación por Computador , AmbienteRESUMEN
BACKGROUND: Liver fibrosis caused by chronic liver injury, eventually develops into liver cirrhosis and hepatocellular carcinoma. Currently, there are no effective drugs to relieve liver fibrosis due to the lack of molecular pathogenesis characteristics. Former research demonstrates that the hepatic immune microenvironment plays a key role in the pathogenesis of liver fibrosis, thus macrophages are important immune cells in the liver. Our previous study has found that IDO1 plays an important role in the liver immune microenvironment. CRG is a gallic acid tannin found in medicinal plants of many ethnicities that protects against inflammation, tumors and chronic liver disease. However, the mechanism of by which CRG mediates the interaction of IDO1 with macrophages during hepatic immune maturation is not clear. PURPOSE: To investigate the regulatory mechanism of CRG in liver fibrosis and the intrinsic relationship between IDO1 and macrophage differentiation. METHODS: Zebrafish, RAW264.7 cells and mice were used in the study. IDO1 overexpression and knockdown cell lines were constructed using lentiviral techniques. RESULTS: We discovered that CRG remarkably reduced the AST and ALT serum levels. Histological examination revealed that CRG ameliorates CCL4-induced liver fibrosis and depressed the expression of α-SMA, Lamimin, Collagen-Ι and fibronectin. Besides, we found that CRG promoted increased MerTK expression on partly macrophages. Interestingly, in vitro, we found that CRG suppressed IDO1 expression and regulated macrophage differentiation by upregulating CD86, CD80 and iNOS, while downregulating CD206, CD163, IL-4 and IL-10 expression. Additionally, we found that CRG could inhibit hepatic stellate cell activation by direct or indirect action. CONCLUSION: Our findings suggest that CRG alleviates liver fibrosis by mediating IDO1-mediated M2 macrophage repolarization.
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Neoplasias Hepáticas , Pez Cebra , Animales , Ratones , Cirrosis Hepática/tratamiento farmacológico , Macrófagos , Microambiente TumoralRESUMEN
The concentration of circulating tumor cells (CTCs) in peripheral blood is strongly correlated with the progress of certain metastatic cancers. In this study, we have developed a novel and facile electrochemical biosensor for the detection of CTCs based on the use of manganese dioxide nanosheets (MnO2 NSs) and gold nanoparticles (AuNPs). Aptamer sequence of target cell is modified on the surface of AuNPs for specifical recognition. With low-speed centrifugation, numerous AuNPs@DNA can be removed from the supernatant. On the other hand, MnO2 NSs are modified on the electrode surface to capture unreacted AuNPs@DNA. The declined electrochemical signal intensity can be used to reflect the level of CTCs. This biosensor achieves a wide linear range from 10 to 104 cells mL-1 and a limit of detection as low as 3 cells mL-1. Due to the specific aptamer as the recognition element, interfering cells can be successfully distinguished and this method performs satisfactorily in clinical samples. Therefore, it has great potential to be used as a powerful tool benefiting rare cells analysis and the investigation of dynamics of cellular interactions.
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Técnicas Biosensibles , Oro , Compuestos de Manganeso , Nanopartículas del Metal , Células Neoplásicas Circulantes , Óxidos , Humanos , Técnicas Electroquímicas , Comunicación CelularRESUMEN
Background: The 2019 novel coronavirus (COVID-19) pandemic remains rampant in many countries/regions. Improving the positive detection rate of COVID-19 infection is an important measure for the control and prevention of this pandemic. This meta-analysis aims to systematically summarize the current characteristics of the computed tomography (CT) auxiliary screening methods for COVID-19 infection in the real world. Methods: Web of Science, Cochrane Library, Embase, PubMed, CNKI, and Wanfang databases were searched for relevant articles published prior to 1 September 2022. Data on specificity, sensitivity, positive/negative likelihood ratio, area under curve (AUC), and diagnostic odds ratio (dOR) were calculated purposefully. Results: One hundred and fifteen studies were included with 51,500 participants in the meta-analysis. Among these studies, the pooled estimates for AUC of CT in confirmed cases, and CT in suspected cases to predict COVID-19 diagnosis were 0.76 and 0.85, respectively. The CT in confirmed cases dOR was 5.51 (95% CI: 3.78-8.02). The CT in suspected cases dOR was 13.12 (95% CI: 11.07-15.55). Conclusion: Our findings support that CT detection may be the main auxiliary screening method for COVID-19 infection in the real world.
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COVID-19 , Humanos , Sensibilidad y Especificidad , Prueba de COVID-19 , Tomografía Computarizada por Rayos X , SARS-CoV-2RESUMEN
BACKGROUND: Licorice (Glycyrrhiza uralensis Fisch.), a well-known traditional medicine, is traditionally used for the treatment of respiratory disorders, such as cough, sore throat, asthma and bronchitis. We aim to investigate the effects of liquiritin (LQ), the main bioactive compound in licorice against acute lung injury (ALI) and explore the potential mechanism. METHODS: Lipopolysaccharide (LPS) was used to induce inflammation in RAW264.7 cells and zebrafish. Intratracheal instillation of 3 mg/kg of LPS was used for induction an ALI mice model. The concentrations of IL-6 and TNF-α were tested using the enzyme linked immunosorbent assay. Western blot analysis was used to detect the expression of JNK/Nur77/c-Jun related proteins. Protein levels in bronchoalveolar lavage fluid (BALF) was measured by BCA protein assay. The effect of JNK on Nur77 transcriptional activity was determined by luciferase reporter assay, while electrophoretic mobility shift assay was used to examine the c-Jun DNA binding activity. RESULTS: LQ has significant anti-inflammatory effects in zebrafish and RAW264.7 cells. LQ inhibited the expression levels of p-JNK (Thr183/Tyr185), p-Nur77 (Ser351) and p-c-Jun (Ser63), while elevated the Nur77 expression level. Inhibition of JNK by a specific inhibitor or small interfering RNA enhanced the regulatory effect of LQ on Nur77/c-Jun, while JNK agonist abrogated LQ-mediated effects. Moreover, Nur77-luciferase reporter activity was suppressed after JNK overexpression. The effects of LQ on the expression level of c-Jun and the binding activity of c-Jun with DNA were attenuated after Nur77 siRNA treatment. LQ significantly ameliorated LPS-induced ALI with the reduction of lung water content and BALF protein content, the downregulation of TNF-α and IL-6 levels in lung BALF and the suppression of JNK/Nur77/c-Jun signaling, which can be reversed by a specific JNK agonist. CONCLUSION: Our results indicated that LQ exerts significant protective effects against LPS-induced inflammation both in vivo and in vitro via suppressing the activation of JNK, and consequently inhibiting the Nur77/c-Jun signaling pathway. Our study suggests that LQ may be a potential therapeutic candidate for ALI and inflammatory disorders.
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Alcoholic liver disease (ALD) is associated with hepatic inflammatory activation and iron overload. The receptor for advanced glycation end products (RAGE) is an important metabolic mediator during the development of ALD. The aim of this study was to determine the effect of RAGE on iron homeostasis in ALD. We found increased circulating transferrin, hepcidin and ferritin in ALD patients and positively correlated with RAGE level. RAGE knockout (RAGE-/-) and wild-type mice were subjected to chronic alcoholic feeding for 6 weeks to induce ALD, and RAGE inhibitor, iron chelator or lipid peroxidation inhibitor were administered. We showed that chronic alcohol administration triggered hepatic steatosis, inflammation, and oxidative stress, which were eliminated by deficiency or inhibition of RAGE. Surprisingly, pathways of hepatic iron metabolism were significantly altered, including increased iron uptake (Tf/TfR) and storage (Ferritin), as well as decreased iron export (FPN1/Hepcidin). In vitro experiments confirmed that RAGE had different effects on the mechanism of iron metabolism of hepatocytes and macrophages respectively. In conclusion, our data revealed preclinical evidence for RAGE inhibition as an effective intervention for alleviating alcohol-induced liver injury.
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Hierro , Hepatopatías Alcohólicas , Animales , Ratones , Etanol , Ferritinas/metabolismo , Hepcidinas/genética , Hierro/metabolismo , Metabolismo de los Lípidos , Hígado/metabolismo , Hepatopatías Alcohólicas/metabolismo , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Transferrina/metabolismoRESUMEN
Xiaoheiyao is the rhizome of Inula nervosa Wall., a traditional spice and medicinal herb in China. In this study, the creatinine inhibitor from Xiaoheiyao extract and also the effects and mechanism on the production of heterocyclic aromatic amines (HAAs) were investigated. Xiaoheiyao extract inhibited the total contents of seven detected HAAs in grilled beef patties, particularly aminoimidazole-azaarenes (AIAs) in a dose-dependent manner, reaching a maximum inhibition rate of 62% for total HAAs and 73% for AIAs. The most effective subfraction of Xiaoheiyao extract (IER80) contained abundant potential creatinine inhibitors, as revealed by immobilized creatinine probe, HPLC and UPLC-MS/MS analyses. Moreover, electrophilic p-coumaric acid derivatives were discovered from IER80 by feature based molecular networking. p-Coumaric acid was demonstrated to inhibit the contents of total HAAs and AIAs in grilled beef patties and model system. Quantitative analyses of the precursor and intermediates of AIAs in model system revealed that p-coumaric acid mainly affected the generation of AIAs by inhibiting creatinine.
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Compuestos Heterocíclicos , Inula , Bovinos , Animales , Creatinina , Compuestos Heterocíclicos/análisis , Cromatografía Liquida , Rizoma/química , Espectrometría de Masas en Tándem , Aminas/análisis , Extractos Vegetales , Culinaria , Carne/análisisRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Biejiajian pill (BJJP) is a canonical formula that is clinically used to treat chronic liver disease, especially to decrease the incidence of hepatocellular carcinoma (HCC). However, the mechanisms underlying the prevention of HCC progression by BJJP remain unclear. AIM OF THE STUDY: This study aimed to determine whether BJJP inhibits HCC progression by downregulating platelet-derived growth factor receptor beta (PDGFRß) signaling in cancer-associated fibroblasts (CAFs) in a mouse model of diethylnitrosamine (DEN)/carbon tetrachloride (CCl4)-induced HCC. MATERIALS AND METHODS: C57BL/6 male mice were intraperitoneally injected with DEN 2 weeks after birth, followed by repeated injections of CCl4 weekly from 6 weeks of age onwards, to recapitulate features of HCC. At week 14, BJJP was orally administered to mice. The effects of BJJP on HCC progression were evaluated using histology, immunohistochemistry, and serum biochemical marker levels. Transcriptome analysis, molecular docking, quantitative real-time PCR, and Western blot were used to study the genes targeted by BJJP and the associated signaling pathway. The effects of BJJP on PDGFRß signaling in CAFs and the underlying mechanism were demonstrated. RESULTS: BJJP treatment significantly suppressed carcinogenesis and cancer progression, and it ameliorated liver inflammation in mice with HCC. A total of 176 genes, including PDGFRß, were significantly downregulated after BJJP treatment and five components of BJJP with high binding affinity to PDGFRß were identified. BJJP inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and glycogen synthase kinase 3 beta (GSK3ß) by suppressing PDGFRß expression in CAFs, and it also downregulated the expression of the downstream proteins hepatocyte growth factor (HGF) and vascular endothelial growth factor A (VEGF-A). Furthermore, BJJP-containing serum consistently reduced PDGFRß, HGF, and VEGF-A expression levels in HSC-derived CAFs in vitro. Importantly, PDGF-BB induced PDGFRß activation in CAFs and both BJJP and sunitinib (a kinase inhibitor) inhibited PDGF-BB/PDGFRß signaling. CONCLUSION: BJJP inhibits the progression of HCC through suppressing VEGF-A and HGF expression in CAFs by downregulating PDGFRß signaling.
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Fibroblastos Asociados al Cáncer , Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Ratones , Animales , Carcinoma Hepatocelular/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Becaplermina , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias Hepáticas/metabolismo , Ratones Endogámicos C57BL , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Transducción de Señal/fisiologíaRESUMEN
Background: To assess the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) used as an adjunct to insulin therapy in adults with type 1 diabetes. Methods: A search of electronic databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) from 1 January 1950 to 23 May 2021 was conducted to find randomized controlled trials. The primary outcome was the change in HbA1c. Eight efficacy and six safety secondary endpoints were evaluated via meta-analysis. Weighted mean difference (WMD) and odds ratio (OR), alongside 95% confidence interval (CI), were calculated using the random effects model. Results: Among 1,379 candidate studies, 11 trials comprising 2,856 participants satisfied the inclusion criteria. Overall, GLP-1 RA adjunctive therapy reduced HbA1c by -0.21% (95% CI, -0.33 to -0.10), weight by -4.04 kg (-4.8 to -3.27), systolic pressure by -2.57 mmHg (-4.11 to -1.03), and diastolic blood pressure by -1.02 mmHg (-1.99 to -0.06). In addition, there was a decrease in prandial insulin dose (WMD, -4.23 IU; 95% CI, -5.26 to -3.20), basal insulin dose (-2.40 IU; -3.93 to -0.87), and total insulin dose (-5.73 IU; -10.61 to -0.86). Moreover, GLP-1 RAs did not increase the incidence of severe hypoglycemia, diabetic ketoacidosis, or severe adverse events. However, GLP-1 RAs increased the incidence of gastrointestinal adverse events (OR, 2.96; 95% CI, 2.33-3.77). Conclusion: Our meta-analysis of randomized clinical trials suggests moderate beneficial effects of GLP-1 RAs on the metabolic profile in patients with type 1 diabetes, without an increased risk of serious adverse events. Clinical Trial Registration: https://www.crd.york.ac.uk/PROSPERO; Identifier: CRD 42020199840.
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Food-derived electrophilic compounds (FECs) are small molecules with electrophilic groups with potential cytoprotective effects. This study investigated the differential effects of six prevalent FECs on colitis in dextran sodium sulfate (DSS)-induced mice and the underlying relationship with molecular characteristics. Fumaric acid (FMA), isoliquiritigenin (ISO), cinnamaldehyde (CA), ferulic acid (FA), sulforaphane (SFN), and chlorogenic acid (CGA) exhibited varying improvements in colitis on clinical signs, colonic histopathology, inflammatory and oxidative indicators, and Nrf2 pathway in a sequence of SFN, ISO > FA, CA > FMA, CGA. Representative molecular characteristics of the "penetration-affinity−covalent binding" procedure, logP value, Keap1 affinity energy, and electrophilic index of FECs were theoretically calculated, among which logP value revealed a strong correlation with colitis improvements, which was related to the expression of Nrf2 and its downstream proteins. Above all, SFN and ISO possessed high logP values and effectively improving DSS-induced colitis by activating the Keap1−Nrf2 pathway to alleviate oxidative stress and inflammatory responses.
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We propose the inverse design of ultracompact, broadband focusing spectrometers based on adaptive diffractive optical networks (a-DONs). Specifically, we introduce and characterize two-layer diffractive devices with engineered angular dispersion that focus and steer broadband incident radiation along predefined focal trajectories with the desired bandwidth and nanometer spectral resolution. Moreover, we systematically study the focusing efficiency of two-layer devices with side length L=100µ m and focal length f=300µ m across the visible spectrum and demonstrate accurate reconstruction of the emission spectrum from a commercial superluminescent diode. The proposed a-DONs design method extends the capabilities of efficient multi-focal diffractive optical devices to include single-shot focusing spectrometers with customized focal trajectories for applications to ultracompact spectroscopic imaging and lensless microscopy.
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BACKGROUND: To investigate whether metformin monotherapy or adjunctive therapy improves the prognosis in patients with any type of cancer compared to non-metformin users (age ≥18). METHODS: Databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) and clinical trial registries ( ClinicalTrials.gov ; the World Health Organization International Clinical Trials Registry Platform) were screened for randomized, controlled trials (RCT) reporting at least progression-free survival (PFS) and/or overall survival (OS). Main outcome measures included hazard ratios (HR), and combined HRs and 95% confidence intervals (CI) were calculated using random-effects models. RESULTS: Of the 8419 records screened, 22 RCTs comprising 5943 participants were included. Pooled HRs were not statistically significant in both PFS (HR 0.97, 95% CI 0.82-1.15, I2 = 50%) and OS (HR 0.98, 95% CI 0.86-1.13, I2 = 33%) for patients with cancer between the metformin and control groups. Subgroup analyses demonstrated that metformin treatment was associated with a marginally significant improvement in PFS in reproductive system cancers (HR 0.86, 95% CI 0.74-1.00) and a significantly worse PFS in digestive system cancers (HR 1.45, 95% CI 1.03-2.04). The PFS or OS was observed consistently across maintenance dose, diabetes exclusion, median follow-up, risk of bias, and combined antitumoral therapies. CONCLUSION: Metformin treatment was not associated with cancer-related mortality in adults compared with placebo or no treatment. However, metformin implied beneficial effects in the PFS of the patients with reproductive system cancers but was related to a worse PFS in digestive system cancers. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42022324672.
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Metformina , Neoplasias , Adulto , Humanos , Metformina/uso terapéutico , Neoplasias/tratamiento farmacológico , Terapia Combinada , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
In order to investigate how the addition of two common ingredients in chocolate, sugar and milk powder, affects the mechanical properties of solid chocolate, uniaxial compression tests and wedge fracture tests were carried out using four ratios of chocolate as the experimental material. Mechanical properties such as Young's modulus and fracture toughness were directly correlated with textural properties such as hardness, elasticity, and brittleness. The results show that adding sugar increases Young's modulus and fracture toughness of chocolate, while milk powder is the opposite. In equal amounts of both, sugar played a more substantial role. In combination with the properties exhibited by chocolate in the above tests, data from creep tests were collected to improve the classical Bingham model and develop a new constitutive model for predicting the mechanical behaviour of solid chocolate with different ratios of added sugar and milk powder. The new four-component constitutive model allows for a more accurate fit to the creep test data and this work provides some suggestions for making different tasting chocolates by adjusting the addition of ingredients.
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Cacao , Chocolate , Animales , Polvos , Leche , Azúcares , CarbohidratosRESUMEN
Background: The 2019 novel coronavirus (COVID-19) pandemic remains rampant in many countries/regions. Improving the positive detection rate of COVID-19 infection is an important measure for control and prevention of this pandemic. This meta-analysis aims to systematically summarize the current characteristics of the auxiliary screening methods by serology for COVID-19 infection in real world. Methods: Web of Science, Cochrane Library, Embase, PubMed, CNKI, and Wangfang databases were searched for relevant articles published prior to May 1st, 2022. Data on specificity, sensitivity, positive/negative likelihood ratio, area under curve (AUC), and diagnostic odds ratio (dOR) were calculated purposefully. Results: Sixty-two studies were included with 35,775 participants in the meta-analysis. Among these studies, the pooled estimates for area under the summary receiver operator characteristic of IgG and IgM to predicting COVID-19 diagnosis were 0.974 and 0.928, respectively. The IgG dOR was 209.78 (95% CI: 106.12 to 414.67). The IgM dOR was 78.17 (95% CI: 36.76 to 166.25). Conclusion: Our findings support serum-specific antibody detection may be the main auxiliary screening methods for COVID-19 infection in real world.
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COVID-19 , COVID-19/diagnóstico , COVID-19/epidemiología , Prueba de COVID-19 , Humanos , Inmunoglobulina G , Inmunoglobulina M , Sensibilidad y EspecificidadRESUMEN
Flammability is a great challenge in the fields of electronics. The emergence of triboelectric nanogenerators (TENGs) provides a safe way to harvest environmentalally friendly energy and convert it into more secure power sources. Especially, polymer-based TENGs significantly accelerate the practical application of self-powered flexible electronics. However, most of the existing polymeric materials for TENGs are easily flammable and melt, dripping, in a fire scenario, and cannot be reused after combustion, which greatly limits the application of TENGs under extreme conditions. Herein, a fire-resistant TENG based on all-aromatic liquid crystalline poly(aryl ether ester) (LCPAEE ) synthesized via simple and efficient one-pot melt polycondensation is reported. The highly rigid main chain of LCPAEE endows the LCP-TENG with outstanding anti-dripping, temperature- and fire-resistance. The resultant LCP-TENG exhibits excellent electrical output performance, which is attributed to the high dielectric constant (ε' = 4.8) and fibrous-structured morphology of LCPAEE . The device can maintain over 65% of open-circuit voltage even after 16 s combustion (≈520 °C). Consequently, this work offers a novel strategy for tailoring the TENGs toward a secure power generator and electronics with fire hazard reduction, and potential application in firefighting, personal protection, and other extreme temperature environments.
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We propose an efficient inverse design approach for multifunctional optical elements based on adaptive deep diffractive neural networks (a-D2NNs). Specifically, we introduce a-D2NNs and design two-layer diffractive devices that can selectively focus incident radiation over two well-separated spectral bands at desired distances. We investigate focusing efficiencies at two wavelengths and achieve targeted spectral line shapes and spatial point-spread functions (PSFs) with optimal focusing efficiency. In particular, we demonstrate control of the spectral bandwidths at separate focal positions beyond the theoretical limit of single-lens devices with the same aperture size. Finally, we demonstrate devices that produce super-oscillatory focal spots at desired wavelengths. The proposed method is compatible with current diffractive optics and doublet metasurface technology for ultracompact multispectral imaging and lensless microscopy applications.