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1.
Endocr Metab Immune Disord Drug Targets ; : e060324227740, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38988067

RESUMO

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a highly prevalent, complex, heterogeneous, polygenic endocrine disorder characterized by metabolic and reproductive dysfunction that affects 8-13% of women of reproductive age worldwide. The pathogenesis of PCOS has not been fully clarified and includes genetics, obesity, and insulin resistance (IR). Oxidative stress (OS) of PCOS is independent of obesity. It can induce IR through post-insulin receptor defects, impair glucose uptake in muscle and adipose tissue, and exacerbate IR by reducing insulin secretion from pancreatic ß-cells. OBJECTIVE: To investigate the effects of Calorie Restricted Diet (CRD), High Protein Diet (HPD), and High Protein and High Dietary Fiber Diet (HPD+HDF) on body composition, insulin resistance, and oxidative stress in overweight/obese PCOS patients. METHODS: A total of 90 overweight/obese patients with PCOS were selected to receive an 8- week medical nutrition weight loss intervention at our First Hospital of Peking University, and we randomly divided them into the CRD group (group A), the HPD group (group B), and the HPD+HDF group (group C), with 30 patients in each group. We measured their body composition, HOMA-IR index, and oxidative stress indicators. The t-test, Mann-Whitney U test, analysis of variance (ANOVA), and Kruskal-Wallis H test were used to compare the efficacy of the three methods. RESULTS: After eight weeks, the body weights of the three groups decreased by 6.32%, 5.70% and 7.24%, respectively, and the Visceral Fat Area (VFA) values decreased by 6.8 cm2, 13.4 cm2 and 23.45 cm2, respectively, especially in group C (p >0.05). The lean body mass (LBM), also known as the Fat-Free Mass (FFM) values of group B and group C after weight loss, were higher than that of group A (p >0.05). After weight loss, the homeostatic model assessment of insulin resistance (HOMA-IR) index and malondialdehyde (MDA) were decreased. Superoxide dismutase (SOD) was increased in all three groups (p >0.05), and the changes in SOD and MDA in group B and group C were more significant (p >0.05). HOMA-IR index positively correlated with body mass index (BMI) (r=0.195; p >0.05); MDA positively correlated with percent of body fat (PBF) (r=0.186; p >0.05) and HOMA-IR index (r=0.422; p >0.01); SOD positively correlated with LMI/FFMI (r=0.195; p >0.05), negatively correlated with HOMA-IR index (r=-0.433; p >0.01). CONCLUSION: All three diets were effective in reducing the body weight of overweight/obese patients with PCOS by more than 5% within 8 weeks and could improve both insulin resistance and oxidative stress damage. Compared with CRD, HPD and HPD+HDF diets could better retain lean body mass and significantly improve oxidative stress damage. CLINICAL TRIAL NUMBER: ChiCTR2100054961.

2.
Ann Hematol ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907072

RESUMO

Myelofibrosis is a rare and often fatal hematological neoplasm, and the treatment of myelofibrosis-associated anemia remains suboptimal, with no improved therapies. Luspatercept was shown to display some efficacy in a phase 2 clinical trial for Myelofibrosis with anemia, yet relevant research are limited. Threrfore, data from patients diagnosed with refractory anemic primary or post-essential thrombocythemia/polycythemia vera myelofibrosis, who were treated with luspatercept for at least 9 weeks, were retrospectively collected. Eighteen patients with myelofibrosis treated with luspatercept were enrolled. Median age was 68 years (range, 44-80 years), and 27.8% were males. Ten (55.6%) were transfusion-dependent. Ten (55.6%) were Dynamic International Prognostic Scoring System intermediate-1, and eight (44.4%) were intermediate-2. The median follow-up was 7 (4-16) months. Erythroid response occurred in eight patients (44.4%) at week 12, four patients (30.8%) at week 24, and nine (50%) at the end of follow-up. Patients who were transfusion-dependent and not transfusion-dependent had similar HI-E responses, at different time points (P > 0.05). Patients had a significantly higher hemoglobin level at 12 weeks, 24 weeks, and at the end of follow-up, than at baseline (P = 0.001, P = 0.021, and P = 0.005, respectively). Treatment-related adverse events occurred in five (16.7%) patients, with no serious adverse events. Two (11.1%) patients relapsed at weeks 15 and 31. One patient progressed to acute myeloid leukemia. No patients had died by the end of follow-up. Luspatercept induced a good response in patients with anemic myelofibrosis, with a low relapse rate and good tolerance.

3.
Colloids Surf B Biointerfaces ; 240: 113998, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38823340

RESUMO

Photoactivated therapy has gradually emerged as a promising and rapid method for combating bacteria, aimed at overcoming the emergence of drug-resistant strains resulting from the inappropriate use of antibiotics and the subsequent health risks. In this work, we report the facile fabrication of Zn3[Fe(CN)6]/g-C3N4 nanocomposites (denoted as ZHF/g-C3N4) through the in-situ loading of zinc hexacyanoferrate nanospheres onto two-dimensional g-C3N4 sheets using a simple metal-organic frameworks construction method. The ZHF/g-C3N4 nanocomposite exhibits enhanced antibacterial activity through the synergistic combination of the excellent photothermal properties of ZHF and the photodynamic capabilities of g-C3N4. Under dual-light irradiation (420 nm + 808 nm NIR), the nanocomposites achieve remarkable bactericidal efficacy, eliminating 99.98% of Escherichia coli and 99.87% of Staphylococcus aureus within 10 minutes. Furthermore, in vivo animal experiments have demonstrated the outstanding capacity of the composite in promoting infected wound healing, achieving a remarkable wound closure rate of 99.22% after a 10-day treatment period. This study emphasizes the potential of the ZHF/g-C3N4 nanocomposite in effective antimicrobial applications, expanding the scope of synergistic photothermal/photodynamic therapy strategies.


Assuntos
Antibacterianos , Escherichia coli , Nanocompostos , Staphylococcus aureus , Cicatrização , Nanocompostos/química , Cicatrização/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Fotoquimioterapia , Testes de Sensibilidade Microbiana , Camundongos , Esterilização/métodos , Ferrocianetos/química , Ferrocianetos/farmacologia , Tamanho da Partícula , Zinco/química , Zinco/farmacologia , Terapia Fototérmica , Propriedades de Superfície , Compostos de Nitrogênio/química , Compostos de Nitrogênio/farmacologia , Grafite
4.
J Pharm Pharmacol ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38776436

RESUMO

OBJECTIVES: This study aimed to reveal the anti-fibrotic effects of Botrychium ternatum (Thunb.) Sw. (BT) against idiopathic pulmonary fibrosis (IPF) and to preliminarily analyze its potential mechanism on bleomycin-induced IPF rats. METHODS: The inhibition of fibrosis progression in vivo was assessed by histopathology combined with biochemical indicators. In addition, the metabolic regulatory mechanism was investigated using 1H-nuclear magnetic resonance-based metabolomics combined with multivariate statistical analysis. KEY FINDINGS: Firstly, biochemical analysis revealed that BT notably suppressed the expression of hydroxyproline and transforming growth factor-ß1 in the pulmonary tissue. Secondly, Masson's trichrome staining and hematoxylin and eosin showed that BT substantially improved the structure of the damaged lung and significantly inhibited the proliferation of collagen fibers and the deposition of extracellular matrix. Finally, serum metabolomic analysis suggested that BT may exert anti-fibrotic effects by synergistically regulating tyrosine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; and synthesis and degradation of ketone bodies. CONCLUSIONS: Our study not only clarifies the potential anti-fibrotic mechanism of BT against IPF at the metabolic level but also provides a theoretical basis for developing BT as an effective anti-fibrotic agent.

5.
PLoS One ; 19(5): e0301840, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38787848

RESUMO

Economic resilience provides a new perspective for megacities to achieve sustainable development when facing multiple shocks, and its accurate evaluation is an essential prerequisite for optimizing urban governance. There are currently no generally accepted methods for empirical evaluation or measuring economic resilience, and the present study aims to contribute to in both the research field and methodology. The present study sets dimensions and indicators based on economic resilience's theoretical and empirical research and used Decision Making Trial and Evaluation Laboratory (DEMATEL) and Interactive Structural Modeling (ISM) methods to exclude the effect indicators and divide the indicator hierarchy, respectively. Subsequently, the present study conducts model validation using Chinese megacities as a case study. The game theory weighting method, which combines the Analytic Hierarchy Process (AHP) and Entropy methods, is used to calculate indicator weights, and the VIKOR (VIseKriterijumska Optimizacija i KOmpromisno Resenje) method is used to evaluate and compare economic resilience of megacities. The research findings indicate that the evaluation model constructed in the present study included 15 indicators (after excluding three effect indicators) divided into four levels. After merging the levels, they correspond to three dimensions: resistance, recoverability, and adaptability. In addition, using Chinese megacities as a case study, the evaluation results found that Beijing, Shanghai, and Shenzhen have high economic resilience, Tianjin and Guangzhou have moderate economic resilience, Chengdu has low economic resilience, and Chongqing has the lowest economic resilience. This result is consistent with previous studies and verifies the model's effectiveness. The present study also found that megacities with lower levels of economic resilience exhibit a more significant upward trend, as well as the highest and higher proportion of economic resilience in Chinese megacities depending on time passes, indicating that megacities' economic resilience is weakening. The evaluation result obtained in the present study is more specific, precise, and focused on depicting the distribution differences and development trends of economic resilience at the urban level.


Assuntos
Cidades , Modelos Econômicos , Humanos , China , Desenvolvimento Sustentável/economia
6.
BMC Cancer ; 24(1): 654, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811891

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have demonstrated superior clinical efficacy in prolonging overall survival (OS) as the second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC), and were recommended by the guidelines. However, it remains uncertain which ICI is the most cost-effective. This study assessed the cost-effectiveness of ICIs as the second-line treatment for ESCC based on the perspective of the Chinese healthcare system. METHODS: A network meta-analysis (NMA) was performed to obtain the Hazard ratios (HRs) for indirect comparisons. A three-state Markov model with a 10-year time horizon was conducted to assess the cost-effectiveness. The state transition probabilities were calculated with Kaplan-Meier (KM) curves data from clinical trial and HRs from the NMA. Utilities and costs were derived from local charges or previously published studies. Univariate and probabilistic sensitivity analyses (PSA) were performed to examine model robustness. The results were assessed based on the total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Five clinical trials (ATTRACTION-3, ESCORT, KEYNOTE-181, ORIENT-2, RATIONALE-302) with a total of 1797 patients were included in the NMA. The NMA showed that both camrelizumab and tislelizumab received relatively high rankings for progression-free survival (PFS) and OS. Compared with sintilimab, treatment with tislelizumab and camrelizumab gained 0.018 and 0.034 additional QALYs, resulting in incremental ICERs of $75,472.65/QALY and $175,681.9/QALY, respectively. Nivolumab and pembrolizumab produced lower QALYs and greater costs, suggesting that both were dominated in comparison to sintilimab. HRs and health state utilities were the most influential parameters in most univariate sensitivity analyses of paired comparisons. PSA results suggested that sintilimab had an 84.4% chance of being the most cost-effective treatment regimen at the WTP threshold of $38,223.34/QALY. In the scenario analysis, sintilimab would no longer be cost-effective, if the price of camrelizumab was assumed to decrease by 64.6% or the price of tislelizumab was assumed to decrease by 16.9%. CONCLUSIONS AND RELEVANCE: Among the five potential competing ICIs, sintilimab was likely to be the most cost-effective regimen as the second-line treatment for locally advanced or metastatic ESCC in China.


Assuntos
Análise Custo-Benefício , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Inibidores de Checkpoint Imunológico , Metanálise em Rede , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/economia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/economia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Cadeias de Markov , Nivolumabe/uso terapêutico , Nivolumabe/economia , Análise de Custo-Efetividade
7.
Inorg Chem ; 63(22): 10397-10402, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38767325

RESUMO

A micron-sized long-afterglow material, Sr2MgSi2O7:Eu,Ce, was utilized to conduct the hydrogen evolution reaction and oxygen evolution reaction, two half-reactions of water splitting, in the presence of sacrificial agents under both light and dark conditions for the first time. The as-synthesized Sr2MgSi2O7:Eu,Ce exhibited higher photocatalytic activity compared to that of the referenced Sr2MgSi2O7:Eu and Sr2MgSi2O7:Ce samples. Herein, in addition to benefiting from the long photogenerated carrier lifetime of long-afterglow materials, the higher photocatalytic activity was attributed to the conjugated electronic structure between Eu and Ce ions. This structure facilitates charge and energy transfer between them, leading to an enhanced photocatalytic efficiency. This research provides a new strategy for designing efficient long-afterglow material photocatalysts through the construction of conjugated electronic structures.

8.
Anesthesiology ; 141(1): 44-55, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38625679

RESUMO

BACKGROUND: During one-lung ventilation (OLV), positive end-expiratory pressure (PEEP) can improve lung aeration but might overdistend lung units and increase intrapulmonary shunt. The authors hypothesized that higher PEEP shifts pulmonary perfusion from the ventilated to the nonventilated lung, resulting in a U-shaped relationship with intrapulmonary shunt during OLV. METHODS: In nine anesthetized female pigs, a thoracotomy was performed and intravenous lipopolysaccharide infused to mimic the inflammatory response of thoracic surgery. Animals underwent OLV in supine position with PEEP of 0 cm H2O, 5 cm H2O, titrated to best respiratory system compliance, and 15 cm H2O (PEEP0, PEEP5, PEEPtitr, and PEEP15, respectively, 45 min each, Latin square sequence). Respiratory, hemodynamic, and gas exchange variables were measured. The distributions of perfusion and ventilation were determined by IV fluorescent microspheres and computed tomography, respectively. RESULTS: Compared to two-lung ventilation, the driving pressure increased with OLV, irrespective of the PEEP level. During OLV, cardiac output was lower at PEEP15 (5.5 ± 1.5 l/min) than PEEP0 (7.6 ± 3 l/min) and PEEP5 (7.4 ± 2.9 l/min; P = 0.004), while the intrapulmonary shunt was highest at PEEP0 (PEEP0: 48.1% ± 14.4%; PEEP5: 42.4% ± 14.8%; PEEPtitr: 37.8% ± 11.0%; PEEP15: 39.0% ± 10.7%; P = 0.027). The relative perfusion of the ventilated lung did not differ among PEEP levels (PEEP0: 65.0% ± 10.6%; PEEP5: 68.7% ± 8.7%; PEEPtitr: 68.2% ± 10.5%; PEEP15: 58.4% ± 12.8%; P = 0.096), but the centers of relative perfusion and ventilation in the ventilated lung shifted from ventral to dorsal and from cranial to caudal zones with increasing PEEP. CONCLUSIONS: In this experimental model of thoracic surgery, higher PEEP during OLV did not shift the perfusion from the ventilated to the nonventilated lung, thus not increasing intrapulmonary shunt.


Assuntos
Estudos Cross-Over , Ventilação Monopulmonar , Respiração com Pressão Positiva , Animais , Respiração com Pressão Positiva/métodos , Suínos , Feminino , Ventilação Monopulmonar/métodos , Troca Gasosa Pulmonar/fisiologia , Pulmão/fisiologia , Circulação Pulmonar/fisiologia , Distribuição Aleatória , Hemodinâmica/fisiologia
9.
Front Immunol ; 15: 1337241, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481995

RESUMO

Background: Systemic immune-inflammatory biomarkers including systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have been demonstrated to be associated with the risk and severity of various liver diseases. However, studies on their role and clinical significance in metabolic diseases, especially in nonalcoholic fatty liver disease (NAFLD), are limited and results are inconsistent. Methods: 10821 adults aged 20 years or older were enrolled in this cross-sectional study, sourced from six cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted logistic regression was employed to investigate the correlation between systemic immune-inflammatory biomarkers (SII, NLR, PLR, and LMR) and NAFLD risk. Restricted cubic spline regression models and segmented regression models were used to describe nonlinear relationships and threshold effects. Subgroup and sensitivity analyses were also conducted. Results: After adjusting for all confounding variables, there was a significant positive association observed between ln-transformed SII (OR= 1.46, 95% CI: 1.27-1.69, P <0.001), NLR (OR= 1.25, 95% CI: 1.05-1.49, P =0.015), LMR (OR= 1.39, 95% CI: 1.14-1.69, P = 0.002) with NAFLD. A nonlinear dose-response relationship with an inverted "U"-shaped threshold of 4.64 was observed between ln(PLR) and NAFLD risk. When ln(PLR) was below 4.64, each unit increase in ln(PLR) was associated with a 0.55-fold increase in the risk of NAFLD (OR= 1.55, 95% CI: 1.05-2.31, P <0.05). Conversely, when ln(PLR) exceeded 4.64, each unit increase in ln(PLR) was associated with a 0.40-fold decrease in the risk of NAFLD (OR= 0.60, 95% CI. 0.44-0.81, P <0.05). Conclusion: ln-transformed SII, NLR, and LMR were linearly associated with NAFLD risk. ln(PLR) showed an inverted "U"-shaped nonlinear dose-response relationship with the risk of NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Estudos Transversais , Monócitos , Neutrófilos , Inquéritos Nutricionais , Inflamação , Linfócitos
10.
Adv Sci (Weinh) ; 11(16): e2303775, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38327094

RESUMO

The spread of prion-like protein aggregates is a common driver of pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit a clear progressive spreading pattern that correlates with disease severity. Clinical observation combined with complementary experimental studies has shown that Tau preformed fibrils (PFF) are prion-like seeds that propagate pathology by entering cells and templating misfolding and aggregation of endogenous Tau. While several cell surface receptors of Tau are known, they are not specific to the fibrillar form of Tau. Moreover, the underlying cellular mechanisms of Tau PFF spreading remain poorly understood. Here, it is shown that the lymphocyte-activation gene 3 (Lag3) is a cell surface receptor that binds to PFF but not the monomer of Tau. Deletion of Lag3 or inhibition of Lag3 in primary cortical neurons significantly reduces the internalization of Tau PFF and subsequent Tau propagation and neuron-to-neuron transmission. Propagation of Tau pathology and behavioral deficits induced by injection of Tau PFF in the hippocampus and overlying cortex are attenuated in mice lacking Lag3 selectively in neurons. These results identify neuronal Lag3 as a receptor of pathologic Tau in the brain,and for AD and related Tauopathies, a therapeutic target.


Assuntos
Proteína do Gene 3 de Ativação de Linfócitos , Neurônios , Tauopatias , Proteínas tau , Animais , Humanos , Camundongos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Antígenos CD/metabolismo , Antígenos CD/genética , Modelos Animais de Doenças , Neurônios/metabolismo , Proteínas tau/metabolismo , Proteínas tau/genética , Tauopatias/metabolismo , Tauopatias/genética , Tauopatias/patologia
11.
FASEB J ; 38(5): e23501, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38411462

RESUMO

In the adult mammalian brain, new neurons are continuously generated from neural stem cells (NSCs) in the subventricular zone (SVZ)-olfactory bulb (OB) pathway. YAP, a transcriptional co-activator of the Hippo pathway, promotes cell proliferation and inhibits differentiation in embryonic neural progenitors. However, the role of YAP in postnatal NSCs remains unclear. Here, we showed that YAP was present in NSCs of the postnatal mouse SVZ. Forced expression of Yap promoted NSC maintenance and inhibited differentiation, whereas depletion of Yap by RNA interference or conditional knockout led to the decline of NSC maintenance, premature neuronal differentiation, and collapse of neurogenesis. For the molecular mechanism, thyroid hormone receptor-interacting protein 6 (TRIP6) recruited protein phosphatase PP1A to dephosphorylate LATS1/2, therefore inducing YAP nuclear localization and activation. Moreover, TRIP6 promoted NSC maintenance, cell proliferation, and inhibited differentiation through YAP. In addition, YAP regulated the expression of the Sonic Hedgehog (SHH) pathway effector Gli2 and Gli1/2 mediated the effect of YAP on NSC maintenance. Together, our findings demonstrate a novel TRIP6-YAP-SHH axis, which is critical for regulating postnatal neurogenesis in the SVZ-OB pathway.


Assuntos
Proteínas Hedgehog , Células-Tronco Neurais , Animais , Camundongos , Neurônios , Neurogênese , Encéfalo , Mamíferos
12.
mSystems ; 9(1): e0108723, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38078774

RESUMO

Borrelia burgdorferi, the pathogen of Lyme disease, differentially produces many outer surface proteins (Osp), some of which represent the most abundant membrane proteins, such as OspA, OspB, and OspC. In cultured bacteria, these proteins can account for a substantial fraction of the total cellular or membrane proteins, posing challenges to the identification and analysis of non-abundant proteins, which could serve as novel pathogen detection markers or as vaccine candidates. Herein, we introduced serial mutations to remove these abundant Osps and generated a B. burgdorferi mutant deficient in OspA, OspB, and OspC in an infectious 297-isolate background, designated as OspABC- mutant. Compared to parental isolate, the mutant did not reflect growth defects in the cultured medium but showed differential mRNA expression of representative tested genes, in addition to gross changes in cellular and membrane protein profiles. The analysis of differentially detectable protein contents of the OspABC- mutant, as compared to the wild type, by two-dimensional gel electrophoresis followed by liquid chromatography-mass spectrometry, identified several spirochete proteins that are dominated by proteins of unknown functions, as well as membrane transporters, chaperons, and metabolic enzymes. We produced recombinant forms of two of these represented proteins, BBA34 and BB0238, and showed that these proteins are detectable during spirochete infection in the tick-borne murine model of Lyme borreliosis and thus serve as potential antigenic markers of the infection.IMPORTANCEThe present manuscript employed a systemic approach to identify non-abundant proteins in cultured Borrelia burgdorferi that are otherwise masked or hidden due to the overwhelming presence of abundant Osps like OspA, OspB, and OspC. As these Osps are either absent or transiently expressed in mammals, we performed a proof-of-concept study in which their removal allowed the analysis of otherwise less abundant antigens in OspABC-deficient mutants and identified several immunogenic proteins, including BBA34 and BB0238. These antigens could serve as novel vaccine candidates and/or genetic markers of Lyme borreliosis, promoting new research in the clinical diagnosis and prevention of Lyme disease.


Assuntos
Borrelia burgdorferi , Doença de Lyme , Camundongos , Animais , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Lipoproteínas/genética , Vacinas Bacterianas/genética , Antígenos de Superfície/genética , Doença de Lyme/diagnóstico , Borrelia burgdorferi/genética , Mamíferos
13.
Talanta ; 269: 125484, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38043338

RESUMO

Ethylene is a hormone for fruit ripening control, and for the purpose of maintaining plant quality, ethylene monitoring is crucial. Due to the simple structure and limited functionality, the technical realization of ethylene detection by an artificial sensor remains a challenge. In this paper, we present a metal-organic frameworks (MOFs) array based electronic nose (e-nose) for rapid and accurate determination of ethylene. Six zirconium-based MOFs with systematically modified pore sizes and π-π binding sites have been prepared and fabricated into a sensor array using quartz crystal microbalance (QCM) technology. By virtue of the synergistic features of six MOF sensors, selectivity detection of ethylene has been achieved. The detection limit reaches to 0.27 ± 0.02 ppm, and high selectivity and stability (98.29 % ± 0.88 %) could also be confirmed. By submitting data to machine learning algorithm, an e-nose system could be established for discriminating ethylene from mixtures with a qualitative accuracy of 90.30 % and quantitative accuracy of 98.89 %. Practical evaluation suggests that the e-nose could index the fruit quality based on the accurate detection of ethylene released during fruit ripeness. This work demonstrates the promising potential of fabricating MOFs based e-nose systems for practical monitoring applications by selectively detecting challengeable target molecules.

14.
Respir Res ; 24(1): 280, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37964270

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic fatal disease with limited therapeutic options. The infiltration of monocytes and fibroblasts into the injured lungs is implicated in IPF. Enolase-1 (ENO1) is a cytosolic glycolytic enzyme which could translocate onto the cell surface and act as a plasminogen receptor to facilitate cell migration via plasmin activation. Our proprietary ENO1 antibody, HL217, was screened for its specific binding to ENO1 and significant inhibition of cell migration and plasmin activation (patent: US9382331B2). METHODS: In this study, effects of HL217 were evaluated in vivo and in vitro for treating lung fibrosis. RESULTS: Elevated ENO1 expression was found in fibrotic lungs in human and in bleomycin-treated mice. In the mouse model, HL217 reduced bleomycin-induced lung fibrosis, inflammation, body weight loss, lung weight gain, TGF-ß upregulation in bronchial alveolar lavage fluid (BALF), and collagen deposition in lung. Moreover, HL217 reduced the migration of peripheral blood mononuclear cells (PBMC) and the recruitment of myeloid cells into the lungs. In vitro, HL217 significantly reduced cell-associated plasmin activation and cytokines secretion from primary human PBMC and endothelial cells. In primary human lung fibroblasts, HL217 also reduced cell migration and collagen secretion. CONCLUSIONS: These findings suggest multi-faceted roles of cell surface ENO1 and a potential therapeutic approach for pulmonary fibrosis.


Assuntos
Fibrose Pulmonar Idiopática , Pneumonia , Camundongos , Humanos , Animais , Leucócitos Mononucleares/metabolismo , Anticorpos Monoclonais/uso terapêutico , Células Endoteliais/metabolismo , Fibrinolisina/metabolismo , Fibrinolisina/farmacologia , Fibrinolisina/uso terapêutico , Pulmão/metabolismo , Fibrose , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/metabolismo , Pneumonia/metabolismo , Colágeno/metabolismo , Bleomicina/toxicidade , Fibroblastos/metabolismo , Fosfopiruvato Hidratase/metabolismo , Fosfopiruvato Hidratase/farmacologia , Fosfopiruvato Hidratase/uso terapêutico , Camundongos Endogâmicos C57BL
15.
PLoS One ; 18(11): e0294108, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37943771

RESUMO

Social resilience is a key factor in disaster management, but compared to resilience in other fields, research on social resilience is still limited to assessment or evaluation, and there is still a lack of dynamic and procedural research, which is also a challenge. This article constructs a causal feedback model and a system dynamics model of social resilience during the COVID-19 epidemic, so as to analyze the dynamic characteristics and improvement path of social resilience. After verifying the effectiveness of the model, model simulation is conducted and the following important conclusions are drawn: social resilience dynamically changes during the research cycle and is influenced by social entity behavior and social mechanisms; The sensitivity factors for the two variables that measure social resilience, namely panic degree and damage degree, are the real-time information acquisition of public and the epidemic awareness of local government, respectively. Therefore, the path to enhancing social resilience should be pursued from both the public and government perspectives, including improving the public's ability to access real-time information, increasing the timeline of government information disclosure, and enhancing local governments' understanding and awareness of the epidemic.


Assuntos
COVID-19 , Desastres , Epidemias , Humanos , COVID-19/epidemiologia , Epidemias/prevenção & controle , Modelos Teóricos , Governo Local
18.
BMC Womens Health ; 23(1): 408, 2023 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-37542252

RESUMO

BACKGROUND: 17α-hydroxylase deficiency, which is caused by a CYP17A1 gene mutation, is a rare type of congenital adrenocortical hyperplasia that mainly manifests as hypertension, hypokalaemia and sexual dysplasia. To date, few pregnancies associated with this syndrome have been reported. CASE PRESENTATION: We describe a 35-year-old Chinese woman with nonclassical congenital adrenal hyperplasia (NCCAH) due to 17α-hydroxylase/17,20-lyase deficiency who achieved pregnancy after in vitro fertilization (IVF) and frozen-thawed embryo transfer. She had secondary amenorrhea since she was 27, and subsequently, high level of progesterone in the follicular phase was found during a blood test. A compound heterozygous mutation was found in the CYP17A1 gene, c.1263G > A and c.985_987delinsAA. The patient was given standardized treatment with dexamethasone. Due to ovulation disorder, IVF was performed. She underwent whole embryo vitrification freezing. Frozen-thawed embryo transplantation was performed following the artificial cycle protocol of endometrium preparation, resulting in a singleton pregnancy. At 39 weeks and 1 day of gestation, caesarean section was performed due to the breech position of the foetus. CONCLUSION: A high level of progesterone reduces endometrial receptivity. Standardized treatment with dexamethasone and frozen-thawed embryo transfer with an artificial cycle protocol of endometrium preparation should be the choice for infertile female patients with CYP17A1 deficiency.


Assuntos
Nascido Vivo , Esteroide 17-alfa-Hidroxilase , Humanos , Feminino , Gravidez , Adulto , Esteroide 17-alfa-Hidroxilase/genética , Progesterona , Oxigenases de Função Mista , Cesárea , Dexametasona
19.
Front Physiol ; 14: 1204531, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601645

RESUMO

Background. Global and regional transpulmonary pressure (PL) during one-lung ventilation (OLV) is poorly characterized. We hypothesized that global and regional PL and driving PL (ΔPL) increase during protective low tidal volume OLV compared to two-lung ventilation (TLV), and vary with body position. Methods. In sixteen anesthetized juvenile pigs, intra-pleural pressure sensors were placed in ventral, dorsal, and caudal zones of the left hemithorax by video-assisted thoracoscopy. A right thoracotomy was performed and lipopolysaccharide administered intravenously to mimic the inflammatory response due to thoracic surgery. Animals were ventilated in a volume-controlled mode with a tidal volume (VT) of 6 mL kg-1 during TLV and of 5 mL kg-1 during OLV and a positive end-expiratory pressure (PEEP) of 5 cmH2O. Global and local transpulmonary pressures were calculated. Lung instability was defined as end-expiratory PL<2.9 cmH2O according to previous investigations. Variables were acquired during TLV (TLVsupine), left lung ventilation in supine (OLVsupine), semilateral (OLVsemilateral), lateral (OLVlateral) and prone (OLVprone) positions randomized according to Latin-square sequence. Effects of position were tested using repeated measures ANOVA. Results. End-expiratory PL and ΔPL were higher during OLVsupine than TLVsupine. During OLV, regional end-inspiratory PL and ΔPL did not differ significantly among body positions. Yet, end-expiratory PL was lower in semilateral (ventral: 4.8 ± 2.9 cmH2O; caudal: 3.1 ± 2.6 cmH2O) and lateral (ventral: 1.9 ± 3.3 cmH2O; caudal: 2.7 ± 1.7 cmH2O) compared to supine (ventral: 4.8 ± 2.9 cmH2O; caudal: 3.1 ± 2.6 cmH2O) and prone position (ventral: 1.7 ± 2.5 cmH2O; caudal: 3.3 ± 1.6 cmH2O), mainly in ventral (p ≤ 0.001) and caudal (p = 0.007) regions. Lung instability was detected more often in semilateral (26 out of 48 measurements; p = 0.012) and lateral (29 out of 48 measurements, p < 0.001) as compared to supine position (15 out of 48 measurements), and more often in lateral as compared to prone position (19 out of 48 measurements, p = 0.027). Conclusion. Compared to TLV, OLV increased lung stress. Body position did not affect stress of the ventilated lung during OLV, but lung stability was lowest in semilateral and lateral decubitus position.

20.
Adv Mater ; 35(38): e2304046, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37269216

RESUMO

Chiral sensors have attracted growing interest due to their application in health monitoring. However, rational design of wearable logic chiral sensors remains a great challenge. In this work, a dual responsive chiral sensor RT@CDMOF is prepared through in situ self-assembly of chiral γ-cyclodextrin metal-organic framework (CDMOF), rhodamine 6G hydrazide (RGH), and tetracyanovinylindane (TCN). The embedded RGH and TCN inherit the chirality of host CDMOF, producing dual changes both in fluorescence and reflectance. RT@CDMOF is explored as a dual channel sensor for chiral discrimination of lactate enantiomers. Comprehensive mechanistic studies reveal the chiral binding process, and carboxylate dissociation is confirmed by impedance and solid-state 1 H nuclear magnetic resonance (NMR). A flexible membrane sensor is successfully fabricated based on RT@CDMOF for wearable health monitoring. Practical evaluation confirms the potential of fabricated membrane sensor in point-of-care health monitoring by indexing the exercise intensity. Based on above, a chiral IMPLICATION logic unit can be successfully achieved, demonstrating the promising potential of RT@CDMOF in design and assembly of novel smart devices. This work may open a new avenue to the rational design of logic chiral sensors for wearable health monitoring applications.


Assuntos
Ciclodextrinas , Estruturas Metalorgânicas , Dispositivos Eletrônicos Vestíveis , Estereoisomerismo , Ácidos Carboxílicos
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