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Glycosaminoglycan (GAG) lyases are often strictly substrate specific, and it is especially difficult to simultaneously degrade GAGs with different types of glycosidic bonds. Herein, we found a new class of GAG lyases (GAGases) from different bacteria. These GAGases belong to polysaccharide lyase 35 family and share quite low homology with the identified GAG lyases. The most surprising thing is that GAGases can not only degrade three types of GAGs: hyaluronan, chondroitin sulfate, and heparan sulfate but also even one of them can also degrade alginate. Further investigation of structural preferences revealed that GAGases selectively act on GAG domains composed of non/6-O-/N-sulfated hexosamines and d-glucoronic acids as well as on alginate domains composed of d-mannuronic acids. In addition, GAG lyases were once speculated to have evolved from alginate lyases, but no transitional enzymes have been found. The discovery of GAGases not only broadens the category of GAG lyases, provides new enzymatic tools for the structural and functional studies of GAGs with specific structures, but also provides candidates for the evolution of GAG lyases.
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Glicosaminoglicanos , Polisacárido Liasas , Especificidad por Sustrato , Glicosaminoglicanos/metabolismo , Glicosaminoglicanos/química , Polisacárido Liasas/metabolismo , Polisacárido Liasas/química , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Sulfatos de Condroitina/metabolismo , Sulfatos de Condroitina/químicaRESUMEN
Our prior investigations have evidenced that bone marrow mesenchymal stem cell (BMSC) therapy can significantly improve the outcomes of rheumatoid arthritis (RA). This study aims to conduct a comprehensive analysis of the proteomics between BMSCs and BMSCs-Exos, and to further elucidate the potential therapeutic effect of BMSCs-Exos on RA, so as to establish a theoretical framework for the prevention and therapy of BMSCs-Exos on RA. The 4D label-free LC-MS/MS technique was used for comparative proteomic analysis of BMSCs and BMSCs-Exos. Collagen-induced arthritis (CIA) rat model was used to investigate the therapeutic effect of BMSCs-Exos on RA. Our results showed that some homology and differences were observed between BMSCs and BMSCs-Exos proteins, among which proteins highly enriched in BMSCs-Exos were related to extracellular matrix and extracellular adhesion. BMSCs-Exos can be taken up by chondrocytes, promoting cell proliferation and migration. In vivo results revealed that BMSCs-Exos significantly improved the clinical symptoms of RA, showing a certain repair effect on the injury of articular cartilage. In short, our study revealed, for the first time, that BMSCs-Exos possess remarkable efficacy in alleviating RA symptoms, probably through shuttling proteins related to cell adhesion and tissue repair ability in CIA rats, suggesting that BMSCs-Exos carrying expressed proteins may become a useful biomaterial for RA treatment.
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Artritis Reumatoide , Exosomas , Células Madre Mesenquimatosas , Ratas , Animales , Exosomas/metabolismo , Cromatografía Liquida , Proteómica , Espectrometría de Masas en Tándem , Células Madre Mesenquimatosas/metabolismo , Artritis Reumatoide/terapia , Artritis Reumatoide/metabolismoRESUMEN
BACKGROUND: The associations between trajectories of different health conditions and cognitive impairment among older adults were unknown. Our cohort study aimed to investigate the impact of various trajectories, including sleep disturbances, depressive symptoms, functional limitations, and multimorbidity, on the subsequent risk of cognitive impairment. METHODS: We conducted a prospective cohort study by using eight waves of national data from the Health and Retirement Study (HRS 2002-2018), involving 4319 adults aged 60 years or older in the USA. Sleep disturbances and depressive symptoms were measured using the Jenkins Sleep Scale and the Centers for Epidemiologic Research Depression (CES-D) scale, respectively. Functional limitations were assessed using activities of daily living (ADLs) and instrumental activities of daily living (IADLs), respectively. Multimorbidity status was assessed by self-reporting physician-diagnosed diseases. We identified 8-year trajectories at four examinations from 2002 to 2010 using latent class trajectory modeling. We screened participants for cognitive impairment using the 27-point HRS cognitive scale from 2010 to 2018 across four subsequent waves. We calculated hazard ratios (HR) using Cox proportional hazard models. RESULTS: During 25,914 person-years, 1230 participants developed cognitive impairment. In the fully adjusted model 3, the trajectories of sleep disturbances and ADLs limitations were not associated with the risk of cognitive impairment. Compared to the low trajectory, we found that the increasing trajectory of depressive symptoms (HR = 1.39; 95% CI = 1.17-1.65), the increasing trajectory of IADLs limitations (HR = 1.88; 95% CI = 1.43-2.46), and the high trajectory of multimorbidity status (HR = 1.48; 95% CI = 1.16-1.88) all posed an elevated risk of cognitive impairment. The increasing trajectory of IADLs limitations was associated with a higher risk of cognitive impairment among older adults living in urban areas (HR = 2.30; 95% CI = 1.65-3.21) and those who smoked (HR = 2.77; 95% CI = 1.91-4.02) (all P for interaction < 0.05). CONCLUSIONS: The results suggest that tracking trajectories of depressive symptoms, instrumental functioning limitations, and multimorbidity status may be a potential and feasible screening method for identifying older adults at risk of cognitive impairment.
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Disfunción Cognitiva , Trastornos del Sueño-Vigilia , Humanos , Anciano , Actividades Cotidianas , Estudios de Cohortes , Estudios Prospectivos , Disfunción Cognitiva/epidemiología , Multimorbilidad , Trastornos del Sueño-Vigilia/epidemiologíaRESUMEN
BACKGROUND: Prompt and precise differential diagnosis of biliary atresia (BA) among cholestatic patients is of great importance. Matrix metalloproteinase-7 (MMP-7) holds great promise as a diagnostic marker for BA. This study aimed to investigate the accuracy of age-specific serum MMP-7 for discriminating BA from other cholestatic pediatric patients. METHODS: This was a single center diagnostic accuracy and validation study including both retrospective and prospective cohorts. Serum MMP-7 concentrations were measured using an ELISA kit, the trajectory of which with age was investigated in a healthy infants cohort aged 0 to 365 days without hepatobiliary diseases (n = 284). Clinical BA diagnosis was based on intraoperative cholangiography and subsequent histological examinations. The diagnostic accuracy of age-specific cutoffs of serum MMP-7 were assessed in a retrospective cohort of cholestatic patients (n = 318, with 172 BA) and validated in a prospective cohort (n = 687, including 395 BA). RESULTS: The MMP-7 concentration declines non-linearly with age, showing higher levels in healthy neonates as well as higher cutoff value in neonatal cholestasis. The area under the ROC curve (AUROC) was 0.967 (95% confidence interval [CI]: 0.946-0.988) for the retrospective cohort, and the cutoff of 18 ng/mL yielded 93.0% (95%CI: 88.1-96.3%), 93.8% (95%CI: 88.6-97.1%), 94.7% (95%CI: 90.1-97.5%), and 91.9% (95%CI: 86.4-95.8%) for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), respectively. The performance of MMP-7 was successfully validated in the larger prospective cohort, resulting in a diagnostic sensitivity of 95.9% (379/395; 95% CI: 93.5-97.7%), a specificity of 87.3% (255/292; 95% CI: 83.0-90.9%), a PPV of 91.1% (379/416; 95% CI: 87.9-93.7%), and a NPV of 94.1% (255/271; 95% CI: 90.6-96.6%), respectively. Besides, higher cutoff value of 28.1 ng/mL achieved the best sensitivity, specificity, PPV, and NPV for infants aged 0-30 days, which was 86.4% (95% CI: 75.0-94.0%), 95.5% (95% CI: 77.2-99.9%), 98.1% (95% CI: 89.7-100%), and 72.4% (95% CI: 52.8-87.3%), respectively. CONCLUSIONS: The serum MMP-7 is accurate and reliable in differentiating BA from non-BA cholestasis, showing its potential application in the diagnostic algorithm for BA and significant role in the future research regarding pathogenesis of BA.
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Atresia Biliar , Metaloproteinasa 7 de la Matriz , Curva ROC , Humanos , Atresia Biliar/sangre , Atresia Biliar/diagnóstico , Metaloproteinasa 7 de la Matriz/sangre , Lactante , Masculino , Femenino , Recién Nacido , Reproducibilidad de los Resultados , Estudios Retrospectivos , Diagnóstico Diferencial , Preescolar , Colestasis/sangre , Colestasis/diagnóstico , Estudios ProspectivosRESUMEN
Pseudomonas aeruginosa is often identified as the causative agent in nosocomial infections. Their adapted resistance makes them strong towards antimicrobial treatments. They protect and empower their survival behind strong biofilm architecture that works as their armor toward antimicrobial therapy. Additionally, P. aeruginosa generates virulence factors, contributing to chronic infection and recalcitrant phenotypic characteristics. The current study utilizes the benevolence of nanotechnology to develop an alternate technique to control the spreading of P. aeruginosa by limiting its biofilm and virulence development. This study used a natural compound, tetramethylpyrazine, to generate gold nanoparticles. Tetramethylpyrazine-gold nanoparticles (Tet-AuNPs) were presented in spherical shapes, with an average size of 168 ± 52.49 nm and a zeta potential of -12.22 ± 2.06 mV. The minimum inhibition concentration (MIC) of Tet-AuNPs that proved more than 90 % effective in inhibiting P. aeruginosa was 256 µg/mL. Additionally, it also shows antibacterial activities against Staphylococcus aureus (MIC, 256 µg/mL), Streptococcus mutans (MIC, 128 µg/mL), Klebsiella pneumoniae (MIC, 128 µg/mL), Listeria monocytogenes (MIC, 256 µg/mL), and Escherichia coli (MIC, 256 µg/mL). The sub-MIC values of Tet-AuNPs significantly inhibited the early-stage biofilm formation of P. aeruginosa. Moreover, this concentration strongly affected hemolysis, protease activity, and different forms of motilities in P. aeruginosa. Additionally, Tet-AuNPs destroyed the well-established mature biofilm of P. aeruginosa. The expression of genes linked with the biofilm formation and virulence in P. aeruginosa treated with sub-MIC doses of Tet-AuNPs was shown to be significantly suppressed. Gene expression studies support biofilm- and virulence-suppressing effects of Tet-AuNPs at the phenotypic level.
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Antibacterianos , Biopelículas , Oro , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa , Pirazinas , Factores de Virulencia , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Oro/química , Oro/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/genética , Factores de Virulencia/genética , Antibacterianos/farmacología , Antibacterianos/química , Pirazinas/farmacología , Nanopartículas del Metal/química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Klebsiella pneumoniae/efectos de los fármacos , Streptococcus mutans/efectos de los fármacos , Streptococcus mutans/genética , Listeria monocytogenes/efectos de los fármacos , Listeria monocytogenes/genéticaRESUMEN
Nanomaterials derived from seaweed have developed as an alternative option for fighting infections caused by biofilm-forming microbial pathogens. This research aimed to discover potential seaweed-derived nanomaterials with antimicrobial and antibiofilm action against bacterial and fungal pathogens. Among seven algal species, the extract from Eisenia bicyclis inhibited biofilms of Klebsiella pneumoniae, Staphylococcus aureus, and Listeria monocytogenes most effectively at sub-MIC levels. As a result, in the present study, E. bicyclis was chosen as a prospective seaweed for producing E. bicyclis-gold nanoparticles (EB-AuNPs). Furthermore, the mass spectra of E. bicyclis reveal the presence of a number of potentially beneficial chemicals. The polyhedral shape of the synthesized EB-AuNP with a size value of 154.74 ± 33.46 nm was extensively described. The lowest inhibitory concentration of EB-AuNPs against bacterial pathogens (e.g., L.monocytogenes, S. aureus, Pseudomonas aeruginosa, and K. pneumoniae) and fungal pathogens (Candida albicans) ranges from 512 to >2048 µg/mL. Sub-MIC of EB-AuNPs reduces biofilm formation in P. aeruginosa, K. pneumoniae, L. monocytogenes, and S. aureus by 57.22 %, 58.60 %, 33.80 %, and 91.13 %, respectively. EB-AuNPs eliminate the mature biofilm of K. pneumoniae at > MIC, MIC, and sub-MIC concentrations. Furthermore, EB-AuNPs at the sub-MIC level suppress key virulence factors generated by P. aeruginosa, including motility, protease activity, pyoverdine, and pyocyanin, whereas it also suppresses the production of staphyloxanthin virulence factor from S. aureus. The current research reveals that seaweed extracts and a biocompatible seaweed-AuNP have substantial antibacterial, antibiofilm, and antivirulence actions against bacterial and fungal pathogens.
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Antiinfecciosos , Algas Comestibles , Kelp , Nanopartículas del Metal , Algas Marinas , Oro/farmacología , Oro/química , Staphylococcus aureus , Estudios Prospectivos , Nanopartículas del Metal/química , Antibacterianos/farmacología , Antibacterianos/química , Antiinfecciosos/farmacología , Biopelículas , Algas Marinas/química , Factores de Virulencia , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosaRESUMEN
BACKGROUND: Chronic kidney disease (CKD) is a significant risk factor for pulmonary hypertension (PH), a complication that adversely affects patient prognosis. However, the mechanisms underlying this association remain poorly understood. A major obstacle to progress in this field is the lack of a reliable animal model replicating CKD-PH. METHODS: This study aimed to establish a stable rat model of CKD-PH. We employed a combined approach, inducing CKD through a 5/6 nephrectomy and concurrently exposing the rats to a high-salt diet. The model's hemodynamics were evaluated dynamically, alongside a comprehensive assessment of pathological changes in multiple organs. Lung tissues and serum samples were collected from the CKD-PH rats to analyze the expression of angiotensin-converting enzyme 2 (ACE2), evaluate the activity of key vascular components within the renin-angiotensin-aldosterone system (RAAS), and characterize alterations in the serum metabolic profile. RESULTS: At 14 weeks post-surgery, the CKD-PH rats displayed significant changes in hemodynamic parameters indicative of pulmonary arterial hypertension. Additionally, right ventricular hypertrophy was observed. Notably, no evidence of pulmonary vascular remodeling was found. Further analysis revealed RAAS dysregulation and downregulated ACE2 expression within the pulmonary vascular endothelium of CKD-PH rats. Moreover, the serum metabolic profile of these animals differed markedly from the sham surgery group. CONCLUSIONS: Our findings suggest that the development of pulmonary arterial hypertension in CKD-PH rats is likely a consequence of a combined effect: RAAS dysregulation, decreased ACE2 expression in pulmonary vascular endothelial cells, and metabolic disturbances.
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Angiotensina II , Hipertensión Pulmonar , Nefrectomía , Cloruro de Sodio Dietético , Animales , Masculino , Ratas , Angiotensina II/sangre , Enzima Convertidora de Angiotensina 2/metabolismo , Modelos Animales de Enfermedad , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/inducido químicamente , Riñón/metabolismo , Riñón/patología , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Sistema Renina-Angiotensina/fisiología , Cloruro de Sodio Dietético/efectos adversosRESUMEN
Objective: To assess global, regional and national trends in the impact of floods from 1990 to 2022 and determine factors influencing flood-related deaths. Methods: We used data on flood disasters from the International Disaster Database for 1990-2022 from 168 countries. We calculated the annual percentage change to estimate trends in the rates of people affected and killed by floods by study period, World Health Organization (WHO) region, country income level and flood type. We used multivariable logistic regression analysis to assess the factors associated with death from floods. Findings: From 1990 to 2022, 4713 floods were recorded in 168 countries, which affected > 3.2 billion people, caused 218 353 deaths and were responsible for more than 1.3 trillion United States dollars of economic losses. The WHO Western Pacific Region had the most people affected by floods (> 2.0 billion), accounting for 63.19% (2 024 599 380/3 203 944 965) of all affected populations. The South-East Asia Region had the most deaths (71 713, 32.84%). The African and Eastern Mediterranean Regions had the highest number of people affected and killed by floods per 100 000 population in 2022. The odds of floods causing more than 50 deaths were significantly higher in low-income countries (adjusted odds ratio: 14.34; 95% confidence interval: 7.46 to 30.04) compared with high-income countries. Numbers of people affected and mortality due to floods declined over time. Conclusion: Despite the decreases in populations affected and deaths, floods still have a serious impact on people and economies globally, particularly in lower-income countries. Action is needed to improve disaster risk management and flood mitigation.
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Inundaciones , Humanos , Salud Global , Desastres , Países en Desarrollo , Modelos Logísticos , Desastres NaturalesRESUMEN
Förster resonance energy transfer (FRET) has been widely applied in fluorescence imaging, sensing and so on, while developing useful strategy of boosting FRET efficiency becomes a key issue that limits the application. Except optimizing spectral properties, promoting orientation factor (κ2) has been well discussed but rarely utilized for boosting FRET. Herein, we constructed binary nano-assembling of two thermally activated delayed fluorescence (TADF) emitters (2CzPN and DMAC-DPS) with J-type aggregate of cyanine dye (C8S4) as doping films by taking advantage of their electrostatic interactions. Time-resolved spectroscopic measurements indicated that 2CzPN/Cy-J films exhibit an order of magnitude higher kFRET than DMAC-DPS/Cy-J films. Further quantitative analysing on kFRET and kDET indicated higher orientation factor (κ2) in 2CzPN/Cy-J films play a key role for achieving fast kFRET, which was subsequently confirmed by anisotropic measurements. Corresponding DFT/TDDFT calculation revealed strong "two-point" electrostatic anchoring in 2CzPN/Cy-J films that is responsible for highly orientated transitions. We provide a new strategy for boosting FRET in nano-assemblies, which might be inspired for designing FRET-based devices of sensing, imaging and information encryption.
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BACKGROUND: This study aimed to evaluate the effect of sacubitril valsartan (SV) on heart failure (HF) hospitalization and cardiovascular mortality in patients on hemodialysis with HF with preserved ejection fraction (EF; HFpEF). METHODS: This single-center, prospective study enrolled 155 stable hemodialysis patients with EF > 40% who were followed up for 12 months. Fifty-nine patients were treated with SV; the others were matched for EF (57.89 ± 9.35 vs. 58.00 ± 11.82, P = 0.9) at a ratio of 1:1 and included as controls. The target dosage of SV was 200 mg/day. RESULTS: Twenty-three (23/155; 14.84%) had HF with mid-range EF (HFmrEF), while 132 (85.16%) had HFpEF. After SV treatment, the peak early diastolic transmitral flow velocity/peak early diastolic mitral annular tissue velocity(E/e') improved from 17.19 ± 8.74 to 12.80 ± 5.52 (P = 0.006), the left ventricular (LV) end-diastolic diameter decreased from 53.14 ± 7.67 mm to 51.56 ± 7.44 mm (P = 0.03), and the LV mass index decreased from 165.7 ± 44.6 g/m2 to 154.8 ± 24.0 g/m2 (P = 0.02). LVEF (P = 0.08) and LV global longitudinal strain (P = 0.7) did not change significantly. The composite outcome of first and recurrent HF hospitalization or cardiovascular death showed no difference between group. However, the Acute Dialysis Quality Initiative Workgroup (ADQI) HF class improved in 39 and 15 patients and worsened in 1 and 11 patients in the SV and control groups, respectively (P < 0.001). Age, diabetes mellitus, and pulmonary arterial pressure were independent risk factors for HF hospitalization and cardiovascular mortality in patients with HFpEF. CONCLUSIONS: SV improved LV hypertrophy, diastolic function, and the ADQI class for HF; however, it failed to reduce the composite endpoints of HF hospitalization and cardiovascular disease-related mortality over 12 months of follow-up in patients on maintenance hemodialysis with EF of > 40%.
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Aminobutiratos , Compuestos de Bifenilo , Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Estudios Prospectivos , Volumen Sistólico , Tetrazoles/efectos adversos , Valsartán/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Diálisis Renal/efectos adversos , Función Ventricular IzquierdaRESUMEN
Molecularly imprinted polymers, a type of special polymer materials, are widely used in biosensing and other fields due to their ability to specifically recognize target molecules, often called "artificial receptors.". Nowadays, researchers are constantly exploring new design and synthesis methods for molecularly imprinted materials to improve the selectivity and sensitivity of molecularly imprinted materials. Among them, the selection of functional monomers has attracted great attention. This review comprehensively analyzes and discusses the selection methods of functional monomers. The most commonly used functional monomers among different types of templates are screened based on the structural properties of the template molecules, including the selection of functional monomers among ion-imprinted polymers, protein-imprinted polymers, and bacterial imprinted polymers. The rich binding sites and functional group types of multifunctional monomers are also highlighted to advance the development of molecular imprinting technology. The article further explores the current challenges and prospects in the selection of functional monomers and emphasizes multiplex experiments and computer simulations as important directions for future research. This review provides comprehensive information and constructive guidelines for researchers in selecting functional monomers in areas such as analytical chemistry and biosensors.
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Impresión Molecular , Polímeros Impresos Molecularmente , Polímeros Impresos Molecularmente/química , Técnicas Biosensibles , Polímeros/químicaRESUMEN
Osteoarthritis (OA) is characterized by an imbalance between M1 and M2 polarized synovial macrophages. Quercetin has shown protective effects against OA by altering M1/M2-polarized macrophages, but the underlying mechanisms remain unclear. In this study, rat chondrocytes were treated with 10 ng/mL of IL-1ß. To create M1-polarized macrophages in vitro, rat bone marrow-derived macrophages (rBMDMs) were treated with 100 ng/mL LPS. To mimic OA conditions observed in vivo, a co-culture system of chondrocytes and macrophages was established. ATP release assays, immunofluorescence assays, Fluo-4 AM staining, Transwell assays, ELISA assays, and flow cytometry were performed. Male adult Sprague-Dawley (SD) rats were used to create an OA model. Histological analyses, including H&E, and safranin O-fast green staining were performed. Our data showed a quercetin-mediated suppression of calcium ion influx and ATP release, with concurrent downregulation of TRPV1 and P2X7 in the chondrocytes treated with IL-1ß. Activation of TRPV1 abolished the quercetin-mediated effects on calcium ion influx and ATP release in chondrocytes treated with IL-1ß. In the co-culture system, overexpression of P2X7 in macrophages attenuated the quercetin-mediated effects on M1 polarization, migration, and inflammation. Either P2X7 or NLRP3 knockdown attenuated IL-1ß-induced M1/M2 polarization, migration, and inflammation. Moreover, overexpression of TRPV1 reduced the quercetin-mediated suppressive effects on OA by promoting M1/M2-polarized macrophages in vivo. Collectively, our data showed that quercetin-induced suppression of TRPV1 leads to a delay in OA progression by shifting the macrophage polarization from M1 to M2 subtypes via modulation of the P2X7/NLRP3 pathway.
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Osteoartritis , Quercetina , Animales , Masculino , Ratas , Adenosina Trifosfato/metabolismo , Calcio/metabolismo , Inflamación/metabolismo , Macrófagos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Osteoartritis/tratamiento farmacológico , Quercetina/farmacología , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
We investigated the pharmacokinetic pathway of berberine and its metabolites in vitro, in Caco-2 cells, and in human participants following the administration of dihydroberberine (DHB) and micellar berberine (LipoMicel®, LMB) formulations. A pilot trial involving nine healthy volunteers was conducted over a 24 h period; blood samples were collected and subjected to Ultra High-Performance Liquid Chromatography-High Resolution Mass Spectrometry (UHPLC-HRMS) analyses to quantify the concentrations of berberine and its metabolites. Pharmacokinetic correlations indicated that berberrubine and thalifendine follow distinct metabolic pathways. Additionally, jatrorrhizine sulfate appeared to undergo metabolism differently compared to the other sulfated metabolites. Moreover, berberrubine glucuronide likely has a unique metabolic pathway distinct from other glucuronides. The human trial revealed significantly higher blood concentrations of berberine metabolites in participants of the DHB treatment group compared to the LMB treatment group-except for berberrubine glucuronide, which was only detected in the LMB treatment group. Similarly, results from in vitro investigations showed significant differences in berberine metabolite profiles between DHB and LMB. Dihydroberberine, dihydroxy-berberrubine/thalifendine and jatrorrhizine sulfate were detected in LMB-treated cells, but not in DHB-treated cells; thalifendine and jatrorrhizine-glucuronide were detected in DHB-treated cells only. While DHB treatment provided higher blood concentrations of berberine and most berberine metabolites, both in vitro (Caco-2 cells) and in vivo human studies showed that treatment with LMB resulted in a higher proportion of unmetabolized berberine compared to DHB. These findings suggest potential clinical implications that merit further investigation in future large-scale trials.
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Berberina , Micelas , Humanos , Berberina/análogos & derivados , Berberina/farmacocinética , Berberina/sangre , Berberina/metabolismo , Células CACO-2 , Proyectos Piloto , Masculino , Adulto , Femenino , Cromatografía Líquida de Alta PresiónRESUMEN
Although the literature predominantly emphasises the crucial role of technological innovation in alleviating resource dependence, limited attention has been given to the pivotal role of capital in driving such innovation. As a critical factor in technological advancements and productivity enhancement, venture capital has a substantial function in the utilisation of resources and the development of sustainable energy sources. Drawing upon panel data from 30 provinces in China, this study explores how venture capital and resource dependence are interrelated. Our research reveals that venture capital effectively mitigates regional resource dependence by facilitating increased investment in innovation channels. However, the weakening of regional human resources mitigates venture capital's diminishing impacts on resource dependence. These findings provide valuable insights for countries seeking to reduce their dependence on natural resources and achieve long-term economic sustainability.
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Inversiones en Salud , Recursos Naturales , Humanos , China , Fuentes Generadoras de Energía , Invenciones , Desarrollo EconómicoRESUMEN
Study investigating mpox infection and its association with sexual behavior among men who have sex with men (MSM) in China was lacking. This observational survey aimed to provide evidence on detail characteristics of mpox cases and sexual behavior, then analyze their relationship among MSM in China to help formulate prevention and control policies. An anonymous cross-sectional study was conducted in 27 MSM social organizations across 21 provinces, municipalities, and autonomous regions from July 31 to August 4, 2023. A safe sexual behavior index was constructed based on three risky sexual behaviors in the last month, including condomless anal intercourse, commercial sex and group sex. High safe sexual behavior indicated that the participant engaged in none of the three, and low safe sexual behavior indicated that they engaged in all three behaviors; otherwise, moderate safe sexual behavior was indicated. Among 7538 MSM, the prevalence of mpox was 0.73% (55/7538). The proportion of high safe sexual behavior was 79.64% (6003/7538). The crude prevalence of mpox was lower in the high safe sexual behavior group (0.35%, 21/6003), compared with the low (12.12%, 8/66) and moderate safe (1.78%, 26/1469) sexual behavior group. In the multivariable-adjusted analysis, after adjusting for all covariates, compared with low safe sexual behavior group, moderate safe sexual behavior group (aOR = 0.21; 95% CI = 0.08, 0.54) and high safe sexual behavior group (aOR = 0.04; 95% CI = 0.02, 0.12) both had lower risk of mpox. Of three sexual behaviors, MSM who reported no commercial sex had the lowest risk of mpox (aOR = 0.23; 95% CI = 0.13, 0.41), compared with those who reported commercial sex in the last month. The other two safe sexual behaviors both were associated with lower risk of mpox (no group sex vs. group sex: aOR = 0.15; 95% CI = 0.08, 0.28; no condomless anal intercourse vs. condomless anal intercourse: aOR = 0.23; 95% CI = 0.13, 0.41). The prevalence of mpox virus infection was nearly 1% among MSM in China. Strengthening mpox surveillance, emphasizing safe sexual behavior in health education are essential for the control of mpox among MSM in China.
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Infecciones por VIH , Mpox , Minorías Sexuales y de Género , Humanos , Masculino , China/epidemiología , Estudios Transversales , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Mpox/epidemiología , Prevalencia , Trabajo Sexual , Conducta Sexual , Pueblos del Este de AsiaRESUMEN
We aimed to assess the burden and trend of the HIV/AIDS epidemic among older adults over the past three decades at different geographical levels, based on the data collected from the Global Burden of Diseases (GBD) study 2019. This assessment identified the average annual percentage changes (AAPCs) using Joinpoint regression analysis. Globally, the incidence of HIV/AIDS has decreased (AAPC = -3.107); however, the overall prevalence has consistently increased (AAPC = 5.557). Additionally, both mortality (AAPC = 2.166) and disability-adjusted life years (DALYs; AAPC = 2.429) have increased. The highest increasing trends in female HIV/AIDS incidence and prevalence were observed in the Central Asia region. However, for males, these trends were observed in the Oceania region and the high-income Asia Pacific region, respectively. In recent decades, females aged 70-74 years had the highest incidence and prevalence, while males aged 70-74 years had highest mortality and DALYs in low social development index (SDI) regions. Unsafe sex resulted in 15 381.16 deaths, accounting for 90.73% of all HIV/AIDS deaths, and 331 140.56 DALYs, accounting for 91.12% of all HIV/AIDS DALYs. The HIV/AIDS disease burden differs by region, age, and sex among older adults. Sexual health education and targeted screening for older adults are recommended.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Carga Global de Enfermedades , Masculino , Humanos , Femenino , Anciano , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Años de Vida Ajustados por Calidad de Vida , Factores de Riesgo , Costo de Enfermedad , Salud GlobalRESUMEN
BACKGROUND: The potential mutual effect of physical and psychological disorders on cognitive function is critical for preventing cognitive impairment among older adults. We aimed to investigate the mediating role of physical and psychological disorders in their associations with cognitive function. METHODS: We conducted a prospective cohort study using the Health and Retirement Study, involving 5308 adults aged 60 years or older. Physical disorders included seven self-reported physician-diagnosed conditions. Psychological disorder and cognitive function were ascertained using the 8-item Centers for Epidemiologic Research Depression scale and the 27-point HRS cognitive scale, respectively. Multivariable linear regression models were used to assess the association of the baseline scores of physical and psychological disorders with subsequent cognitive scores. Second-order cross-lagged panel models (CLPM) were used to assess the longitudinal mediating roles, respectively. RESULTS: The higher psychological disorder scores (ß = -0.15; P < 0.0001) and physical disorders scores (ß = -0.18; P < 0.0001) were, the worse the cognitive function was. CLPM revealed a significant longitudinal mediating effect of baseline physical disorders through changes in psychological disorder from 2002 to 2010 on the cognitive scores changes from 2002 to 2010 (ß = -0.02; P < 0.0001). Meanwhile, the longitudinal mediating effect of baseline psychological disorder scores through physical disorders changes from 2002 to 2010 on the cognitive scores changes from 2002 to 2010 was significant (ß = -0.004; P = 0.005). CONCLUSIONS: The mutual longitudinal mediating effects of psychological disorder and physical disorder indicate that among older adults, physical and psychological disorders accelerate cognitive impairment as a whole and mutually reinforcing process.
Asunto(s)
Disfunción Cognitiva , Humanos , Anciano , Femenino , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Disfunción Cognitiva/epidemiología , Estudios Longitudinales , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Anciano de 80 o más Años , Trastornos del Conocimiento/psicología , Trastornos del Conocimiento/epidemiología , ComorbilidadRESUMEN
The issue of material failure attributed to microbiologically influenced corrosion (MIC) is escalating in seriousness. Microorganisms not only facilitate corrosion but certain beneficial microorganisms also impede its occurrence. This study explored the impact of marine B. velezensis on the corrosion behavior of X65 steel in simulated offshore oilfield produced water. B. velezensis exhibited rapid growth in the initial stages, and the organic acid metabolites were found to promote corrosion. Subsequently, there was an increase in cross-linked "networked" biofilms products, a significant rise in the prismatic shape of corrosion products, and a tendency for continuous development in the middle and late stages. The organic/inorganic mineralized film layer formed on the surface remained consistently complete. Metabolic products of amino acid corrosion inhibitors were also observed to be adsorbed into the film. B. velezensis altered the kinetics of the X65 steel cathodic reaction, resulting in a deceleration of the electrochemical reaction rate. The mineralization induced by B. velezensis effectively slowed down the corrosion rate of X65 steel.