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2.
Ann Hematol ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39020042

RESUMO

Biallelic mutations of the CEBPA gene (CEBPAbi) are generally associated with favorable prognosis in patients with acute myeloid leukemia (AML). Monoallelic mutations of the CEBPA gene in carboxy-terminal DNA-binding region (CEBPAsmbZIP) and amino-terminal transactivation domains (CEBPAsmTAD) indicate distinct clinical characteristics and therapeutic outcomes. However, further investigation is required to fully understand these differences. In this retrospective study, we enrolled 77 AML patients with CEBPA mutations, including 53 with CEBPAbi, 12 with CEBPAsmbZIP and 12 with CEBPAsmTAD. The clinical characteristics of the three CEBPAmut groups presented significant differences in age, FAB classification, hemoglobin level and platelet count at diagnosis. The CEBPAsmTAD group exhibited shorter 2-year overall survival (OS) and relapse-free survival (RFS) compared to the CEBPAbi group and CEBPAsmbZIP group in AML patients. The most common co-mutations observed in CEBPAmut AML patients were TET2 and GATA2, which had no effect on prognosis. 2-year RFS of 27 CEBPAmut AML patients who underwent allo-HSCT was better than those who did not. MRD3 positive was identified as an influencing factor for 2-year OS and RFS. Allo-HSCT was found to improve the prognosis of CEPBAmut AML patients with positive MRD3 and adverse co-mutations.

3.
Front Endocrinol (Lausanne) ; 15: 1329945, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994012

RESUMO

Introduction: There is a lack of real-world evidence regarding the impact of concomitant metformin and renin-angiotensin system inhibitors (RASis) on sodium-glucose cotransporter-2 inhibitor (SGLT2i)-associated kidney outcomes. This study was aimed to investigate whether SGLT2i-associated kidney outcomes were modified by the concomitant use of metformin or RASis in patients with type 2 diabetes. Methods: SGLT2i users were identified from three electronic health record databases during May 2016 and December 2017 and categorized into those with and without concomitant use of metformin or RASis. Propensity score matching was performed to minimize baseline differences between groups. Study outcomes were mean estimated glomerular filtration rate (eGFR) change and time to 30%, 40%, and 50% eGFR reductions. A meta-analysis was performed to combine the estimates across databases. Results: After matching, there were 6,625 and 3,260 SGLT2i users with and without metformin, and 6,654 and 2,746 SGLT2i users with and without RASis, respectively. The eGFR dip was similar in SGLT2i users with and without metformin therapy, but was greater in SGLT2i users with RASis compared to those without RASis. Neither metformin nor RASi use had a significant effect on SGLT2i-associated eGFR reductions, as evidenced by the hazard ratios (95% CIs) of 30% eGFR reductions for SGLT2is with versus without metformin/RASis, namely 1.02 (0.87-1.20)/1.09 (0.92-1.31). Such findings were also observed in the outcomes of 40% and 50% eGFR reductions. Conclusion: Using metformin or RASis did not modify SGLT2i-associated kidney outcomes in type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Taxa de Filtração Glomerular , Hipoglicemiantes , Metformina , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Metformina/uso terapêutico , Masculino , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Pessoa de Meia-Idade , Hipoglicemiantes/uso terapêutico , Idoso , Rim/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Sistema Renina-Angiotensina/efeitos dos fármacos , Resultado do Tratamento , Estudos Retrospectivos
4.
ACS Appl Mater Interfaces ; 16(28): 36840-36850, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38954505

RESUMO

White Roman goose (Anser anser domesticus) feathers, comprised of oriented conical barbules, are coated with gland-secreted preening oils to maintain a long-term nonwetting performance for surface swimming. The geese are accustomed to combing their plumages with flat bills in case they are contaminated with oleophilic substances, during which the amphiphilic saliva spread over the barbules greatly impairs their surface hydrophobicities and allows the trapped contaminants to be anisotropically self-cleaned by water flows. Particularly, the superhydrophobic behaviors of the goose feathers are recovered as well. Bioinspired by the switchable anisotropic self-cleaning functionality of white Roman geese, superhydrophobic unidirectionally inclined conical structures are engineered through the integration of a scalable colloidal self-assembly technology and a colloidal lithographic approach. The dependence of directional sliding properties on the shape, inclination angle, and size of conical structures is systematically investigated in this research. Moreover, their switchable anisotropic self-cleaning functionalities are demonstrated by Sudan blue II/water (0.01%) separation performances. The white Roman goose feather-inspired coatings undoubtedly offer a new concept for developing innovative applications that require directional transportation and the collection of liquids.


Assuntos
Plumas , Gansos , Animais , Plumas/química , Anisotropia , Interações Hidrofóbicas e Hidrofílicas , Propriedades de Superfície , Coloides/química
5.
Nutrients ; 16(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38999898

RESUMO

Alpinia officinarum Hance is rich in carbohydrates and is flavored by natives. The polysaccharide fraction 30 is purified from the rhizome of A. officinarum Hance (AOP30) and shows excellent immunoregulatory ability when administered to regulate immunity. However, the effect of AOP30 on the intestinal epithelial barrier is not well understood. Therefore, the aim of this study is to investigate the protective effect of AOP30 on the intestinal epithelial barrier using a lipopolysaccharide (LPS)-induced intestinal epithelial barrier dysfunction model and further explore its underlying mechanisms. Cytotoxicity, transepithelial electrical resistance (TEER) values, and Fluorescein isothiocyanate (FITC)-dextran flux are measured. Simultaneously, the protein and mRNA levels of tight junction (TJ) proteins, including zonula occludens-1 (ZO-1), Occludin, and Claudin-1, are determined using Western blotting and reverse-transcription quantitative polymerase chain reaction methods, respectively. The results indicate that AOP30 restores the LPS-induced decrease in the TEER value and cell viability. Furthermore, it increases the mRNA and protein expression of ZO-1, Occludin, and Claudin-1. Notably, ZO-1 is the primary tight junction protein altered in response to LPS-induced intestinal epithelial dysfunction. Additionally, AOP30 downregulates the production of TNFα via the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. Collectively, the findings of this study indicate that AOP30 can be developed as a functional food ingredient or natural therapeutic agent for addressing intestinal epithelial barrier dysfunction. It sheds light on the role of AOP30 in improving intestinal epithelial function.


Assuntos
Alpinia , Mucosa Intestinal , Lipopolissacarídeos , NF-kappa B , Polissacarídeos , Rizoma , Transdução de Sinais , Receptor 4 Toll-Like , Receptor 4 Toll-Like/metabolismo , Humanos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Rizoma/química , Polissacarídeos/farmacologia , Células CACO-2 , Alpinia/química , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo
6.
Sci Total Environ ; 947: 174537, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38977088

RESUMO

Certain heavy metals have been correlated to an elevated risk of inflammation-related diseases and mortality. Nevertheless, the intricate relationships between metal exposure, inflammation and mortality remain unknown. We included 3741 adults with measurements of ten urinary heavy metals in the National Health and Nutritional Examination Survey (NHANES) 2005-2010, followed up to December 31, 2019. Low-grade systemic inflammation was evaluated by various markers, including C-reactive protein (CRP) and ratios derived from regular blood tests. We assessed associations between heavy metal and all-cause mortality using multivariate COX regressions. Then we assessed the mediation effect of low-grade systemic inflammation on the associations via Sobel Test. To gauge the systemic inflammatory potential of the multi-metal mixture and its correlation with all-cause mortality, a Metal Mixture Inflammatory Index (MMII) was developed using reduced rank regression (RRR) models. The association between MMII and all-cause mortality was explored via multivariate COX regressions. Cadmium, antimony and uranium displayed positive associations with mortality, with hazard ratios (HR) ranging from 1.18 to 1.46 (all P-FDR < 0.05). Mediation analyses revealed that the associations between specific heavy metals (cadmium and antimony) and mortality risk were slightly mediated by the low-grade systemic inflammation markers, with mediation proportions ranging from 3.11 % to 5.38 % (all P < 0.05). MMII, the weighted sum of 9 heavy metals, significantly predicted platelet-to-lymphocyte ratio (PLR) and CRP (ß = 0.10 and 1.16, all P < 0.05), was positively associated with mortality risk (HR 1.28, 95 % CI 1.14 to 1.43). Exposure to heavy metals might increase all-cause mortality, partly mediated by low-grade systemic inflammation. MMII, designed to assess the potential systemic inflammatory effects of exposure to multiple heavy metals, was closely related to the all-cause mortality risk. This study introduces MMII as an approach to evaluating co-exposure and its potential health effects comprehensively.

7.
Skelet Muscle ; 14(1): 17, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39044305

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron (MN) degeneration, leading to neuromuscular junction (NMJ) dismantling and severe muscle atrophy. The nuclear receptor interaction protein (NRIP) functions as a multifunctional protein. It directly interacts with calmodulin or α-actinin 2, serving as a calcium sensor for muscle contraction and maintaining sarcomere integrity. Additionally, NRIP binds with the acetylcholine receptor (AChR) for NMJ stabilization. Loss of NRIP in muscles results in progressive motor neuron degeneration with abnormal NMJ architecture, resembling ALS phenotypes. Therefore, we hypothesize that NRIP could be a therapeutic factor for ALS. METHODS: We used SOD1 G93A mice, expressing human SOD1 with the ALS-linked G93A mutation, as an ALS model. An adeno-associated virus vector encoding the human NRIP gene (AAV-NRIP) was generated and injected into the muscles of SOD1 G93A mice at 60 days of age, before disease onset. Pathological and behavioral changes were measured to evaluate the therapeutic effects of AAV-NRIP on the disease progression of SOD1 G93A mice. RESULTS: SOD1 G93A mice exhibited lower NRIP expression than wild-type mice in both the spinal cord and skeletal muscle tissues. Forced NRIP expression through AAV-NRIP intramuscular injection was observed in skeletal muscles and retrogradely transduced into the spinal cord. AAV-NRIP gene therapy enhanced movement distance and rearing frequencies in SOD1 G93A mice. Moreover, AAV-NRIP increased myofiber size and slow myosin expression, ameliorated NMJ degeneration and axon terminal denervation at NMJ, and increased the number of α-motor neurons (α-MNs) and compound muscle action potential (CMAP) in SOD1 G93A mice. CONCLUSIONS: AAV-NRIP gene therapy ameliorates muscle atrophy, motor neuron degeneration, and axon terminal denervation at NMJ, leading to increased NMJ transmission and improved motor functions in SOD1 G93A mice. Collectively, AAV-NRIP could be a potential therapeutic drug for ALS.


Assuntos
Esclerose Lateral Amiotrófica , Dependovirus , Modelos Animais de Doenças , Terapia Genética , Camundongos Transgênicos , Neurônios Motores , Atrofia Muscular , Animais , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/terapia , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Terapia Genética/métodos , Atrofia Muscular/genética , Atrofia Muscular/terapia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Dependovirus/genética , Camundongos , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Junção Neuromuscular/metabolismo , Junção Neuromuscular/patologia , Vetores Genéticos/administração & dosagem , Degeneração Neural/genética , Degeneração Neural/terapia , Masculino , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo
8.
EBioMedicine ; 105: 105205, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38918147

RESUMO

BACKGROUND: Birth weight (BW) is associated with risk of cardiometabolic disease (CMD) in adulthood, which may depend on the state of obesity, in particular if developed at a young age. We hypothesised that BW and a polygenic score (PGS) for BW were associated with cardiometabolic risk and related plasma protein levels in children and adolescents. We aimed to determine the modifying effect of childhood obesity on these associations. METHODS: We used data from The cross-sectional HOLBAEK Study with 4263 participants (median [IQR] age, 11.7 [9.2, 14.3] years; 57.1% girls and 42.9% boys; 48.6% from an obesity clinic and 51.4% from a population-based group). We gathered information on BW and gestational age, anthropometrics, cardiometabolic risk factors, calculated a PGS for BW, and measured plasma proteins using Olink Inflammation and Cardiovascular II panels. We employed multiple linear regression to examine the associations with BW as a continuous variable and performed interaction analyses to assess the effect of childhood obesity on cardiometabolic risk and plasma protein levels. FINDINGS: BW and a PGS for BW associated with cardiometabolic risk and plasma protein levels in childhood and adolescence. Childhood obesity modified the associations between BW and measures of insulin resistance, including HOMA-IR (ßadj [95% CI per SD] for obesity: -0.12 [-0.15, -0.08]; normal weight: -0.04 [-0.08, 0.00]; Pinteraction = 0.004), c-peptide (obesity: -0.11 [-0.14, -0.08]; normal weight: -0.02 [-0.06, 0.02]; Pinteraction = 5.05E-04), and SBP SDS (obesity: -0.12 [-0.16, -0.08]; normal weight: -0.06 [-0.11, -0.01]; Pinteraction = 0.0479). Childhood obesity also modified the associations between BW and plasma levels of 14 proteins (e.g., IL15RA, MCP1, and XCL1; Pinteraction < 0.05). INTERPRETATION: We identified associations between lower BW and adverse metabolic phenotypes, particularly insulin resistance, blood pressure, and altered plasma protein levels, which were more pronounced in children with obesity. Developing effective prevention and treatment strategies for this group is needed to reduce the risk of future CMD. FUNDING: Novo Nordisk Foundation (NNF15OC0016544, NNF0064142 to T.H., NNF15OC0016692 to T.H. and A.K., NNF18CC0033668 to S.E.S, NNF18SA0034956 to C.E.F., NNF20SA0067242 to DCA, NNF18CC0034900 to NNF CBMR), The Innovation Fund Denmark (0603-00484B to T.H.), The Danish Cardiovascular Academy (DCA) and the Danish Heart Foundation (HF) (PhD2021007-DCA to P.K.R, 18-R125-A8447-22088 (HF) and 21-R149-A10071-22193 (HF) to M.A.V.L., PhD2023009-HF to L.A.H), EU Horizon (668031, 847989, 825694, 964590 to A.K.), Innovative Health Initiative (101132901 for A.K.), A.P. Møller Foundation (19-L-0366 to T.H.), The Danish National Research Foundation, Steno Diabetes Center Sjælland, and The Region Zealand and Southern Denmark Health Scientific Research Foundation.


Assuntos
Peso ao Nascer , Doenças Cardiovasculares , Obesidade Infantil , Humanos , Masculino , Feminino , Criança , Adolescente , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Obesidade Infantil/sangue , Estudos Transversais , Fatores de Risco Cardiometabólico , Fatores de Risco , Biomarcadores/sangue , Resistência à Insulina , Índice de Massa Corporal
9.
Clin Child Fam Psychol Rev ; 27(2): 576-601, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38869680

RESUMO

Parental monitoring is a construct of longstanding interest in multiple fields-but what is it? This paper makes two contributions to the ongoing debate. First, we review how the published literature has defined and operationalized parental monitoring. We show that the monitoring construct has often been defined in an indirect and nonspecific fashion and measured using instruments that vary widely in conceptual content. The result has been a disjointed empirical literature that cannot accurately be described as the unified study of a single construct nor is achieving a cumulative scientific character. Second, we offer a new formulation of the monitoring construct intended to remedy this situation. We define parental monitoring as the set of all behaviors performed by caregivers with the goal of acquiring information about the youth's activities and life. We introduce a taxonomy identifying 5 distinct types of monitoring behaviors (Types 1-5), with each behavior varying along five dimensions (performer, target, frequency, context, style). We distinguish parental monitoring from 16 other parenting constructs it is often conflated with and position monitoring as one element within the broader parent-youth monitoring process: the continuous, dyadic interplay between caregivers and youth as they navigate caregivers attempts' to monitor youth. By offering an explicit and detailed conceptualization of monitoring, we aim to foster more rigorous and impactful research in this area.


Assuntos
Relações Pais-Filho , Poder Familiar , Humanos , Criança , Adolescente
10.
Exp Ther Med ; 28(2): 310, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38873041

RESUMO

Chitin degradation products, especially chitosan oligosaccharides (COSs), are highly valued in various industrial fields, such as food, medicine, cosmetics and agriculture, for their rich resources and high cost-effectiveness. However, little is known about the impact of acetylation on COS cellular bioactivity. The present study aimed to compare the differential effects of COS and highly N-acetylated COS (NACOS), known as chitin oligosaccharide, on H2O2-induced cell stress. MTT assay showed that pretreatment with NACOS and COS markedly inhibited H2O2-induced RAW264.7 cell death in a concentration-dependent manner. Flow cytometry indicated that NACOS and COS exerted an anti-apoptosis effect on H2O2-induced oxidative damage in RAW264.7 cells. NACOS and COS treatment ameliorated H2O2-induced RAW264.7 cell cycle arrest. Western blotting revealed that the anti-oxidation effects of NACOS and COS were mediated by suppressing expression of proteins involved in H2O2-induced apoptosis, including Bax, Bcl-2 and cleaved PARP. Furthermore, the antagonist effects of NACOS were greater than those of COS, suggesting that acetylation was essential for the protective effects of COS.

11.
Pestic Biochem Physiol ; 202: 105918, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879320

RESUMO

Transcription factors play an important role in regulating the expression of detoxification genes (e.g. P450s) that confer insecticide resistance. Our previous study identified a series of candidate transcription factors (CYP6B7-fenvalerate association proteins, CAPs) that may be related to fenvalerate-induced expression of CYP6B7 in a field HDTJ strain of H. armigera. Whether these CAPs can mediate the transcript of CYP6B7 induced by fenvalerate in a susceptible HDS strain of H. armigera remains unknown. Further study showed that the expression levels of multiple CAPs were significantly induced by fenvalerate in HDS strain. Knockdown of CAP19 [fatty acid synthase-like (FAS)], CAP22 [polysaccharide biosynthesis domain-containing protein 1 (PBDC1)], CAP24 [5-formyltetrahydrofolate cycloligase (5-FCL)], CAP30 [peptidoglycan recognition protein LB-like (PGRP)] and CAP33 [NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 (NDUFA11)] resulted in significant inhibition of CYP6B7 and some other P450 genes expression; meanwhile, the sensitivity of HDS strain larvae to fenvalerate was significantly increased. In addition, PBDC1, PGRP and NDUFA11, either alone or in combination, could significantly enhance the activity of CYP6B7 promoter in HDS strain, as well as the expression level of CYP6B7 gene in Sf9 cells line. These results suggested that PBDC1, PGRP and NDUFA11 may be involved in the transcript regulation of key detoxifying genes in response to fenvalerate in HDS strain of H. armigera.


Assuntos
Proteínas de Insetos , Inseticidas , Mariposas , Nitrilas , Piretrinas , Animais , Piretrinas/farmacologia , Piretrinas/toxicidade , Nitrilas/farmacologia , Nitrilas/toxicidade , Inseticidas/farmacologia , Inseticidas/toxicidade , Mariposas/genética , Mariposas/efeitos dos fármacos , Mariposas/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Resistência a Inseticidas/genética , Família 6 do Citocromo P450/genética , Família 6 do Citocromo P450/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Helicoverpa armigera
12.
Hemasphere ; 8(6): e90, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38903535

RESUMO

Transcriptional cofactors of the ETO family are recurrent fusion partners in acute leukemia. We characterized the ETO2 regulome by integrating transcriptomic and chromatin binding analyses in human erythroleukemia xenografts and controlled ETO2 depletion models. We demonstrate that beyond its well-established repressive activity, ETO2 directly activates transcription of MYB, among other genes. The ETO2-activated signature is associated with a poorer prognosis in erythroleukemia but also in other acute myeloid and lymphoid leukemia subtypes. Mechanistically, ETO2 colocalizes with EP300 and MYB at enhancers supporting the existence of an ETO2/MYB feedforward transcription activation loop (e.g., on MYB itself). Both small-molecule and PROTAC-mediated inhibition of EP300 acetyltransferases strongly reduced ETO2 protein, chromatin binding, and ETO2-activated transcripts. Taken together, our data show that ETO2 positively enforces a leukemia maintenance program that is mediated in part by the MYB transcription factor and that relies on acetyltransferase cofactors to stabilize ETO2 scaffolding activity.

13.
PLoS One ; 19(6): e0305531, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38917135

RESUMO

BACKGROUND: Opioids administered in hospital during the immediate postoperative period are likely to influence post-surgical outcomes, but inpatient prescribing during the admission is challenging to access. Modified-release(MR) preparations have been especially associated with harm, whilst certain populations such as the elderly or those with renal impairment may be vulnerable to complications. This study aimed to assess postoperative opioid utilisation patterns during hospital stay for people admitted for major/orthopaedic surgery. METHODS: Patients admitted to a teaching hospital in the North-West of England between 2010-2021 for major/orthopaedic surgery with an admission for ≥1 day were included. We examined opioid administrations in the first seven days post-surgery in hospital, and "first 48 hours" were defined as the initial period. Proportions of MR opioids, initial immediate-release(IR) oxycodone and initial morphine milligram equivalents (MME)/day were calculated and summarised by calendar year. We also assessed the proportion of patients prescribed an opioid at discharge. RESULTS: Among patients admitted for major/orthopaedic surgery, 71.1% of patients administered opioids during their hospitalisation. In total 50,496 patients with 60,167 hospital admissions were evaluated. Between 2010-2017 MR opioids increased from 8.7% to 16.1% and dropped to 11.6% in 2021. Initial use of oxycodone IR among younger patients (≤70 years) rose from 8.3% to 25.5% (2010-2017) and dropped to 17.2% in 2021. The proportion of patients on ≥50MME/day ranged from 13% (2021) to 22.9% (2010). Of the patients administered an opioid in hospital, 26,920 (53.3%) patients were discharged on an opioid. CONCLUSIONS: In patients hospitalised with major/orthopaedic surgery, 4 in 6 patients were administered an opioid. We observed a high frequency of administered MR opioids in adult patients and initial oxycodone IR in the ≤70 age group. Patients prescribed with ≥50MME/day ranged between 13-22.9%. This is the first published study evaluating UK inpatient opioid use, which highlights opportunities for improving safer prescribing in line with latest recommendations.


Assuntos
Analgésicos Opioides , Prescrição Eletrônica , Procedimentos Ortopédicos , Dor Pós-Operatória , Humanos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Dor Pós-Operatória/tratamento farmacológico , Adulto , Prescrição Eletrônica/estatística & dados numéricos , Pacientes Internados/estatística & dados numéricos , Inglaterra , Hospitalização/estatística & dados numéricos , Idoso de 80 Anos ou mais , Oxicodona/administração & dosagem , Oxicodona/uso terapêutico , Adolescente
14.
Front Endocrinol (Lausanne) ; 15: 1284283, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919485

RESUMO

Background: Clinically, the diagnosis and treatment of cholangiocarcinoma are generally different according to the location of occurrence, and the studies rarely consider the differences between different pathological types. Cholangiocarcinomas in large- and middle-sized intrahepatic bile ducts are mostly mucinous, while in small sized bile duct are not; mucinous extrahepatic cholangiocarcinomas are also more common than mucinous intrahepatic cholangiocarcinoma. However, it is unclear whether these pathological type differences are related to the prognosis. Methods: Data of total 22509 patients was analyzed from Surveillance, Epidemiology, and End Results program database out of which 22299 patients were diagnosed with common adeno cholangiocarcinoma while 210 were diagnosed with mucinous cholangiocarcinoma. Based on the propensity score matching (PSM) analysis, between these two groups' clinical, demographic, and therapeutic features were contrasted. The data were analyzed using Cox and LASSO regression analysis and Kaplan-Meier survival curves. Ultimately, overall survival (OS) and cancer specific survival (CSS) related prognostic models were established and validated in test and external datasets and nomograms were created to forecast these patients' prognosis. Results: There was no difference in prognosis between mucinous cholangiocarcinoma and adeno cholangiocarcinoma. Therefore, we constructed prognostic model and nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time. By comparing the 9 independent key characteristics i.e. Age, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy, risk scores were calculated for each individual. By integrating these two pathological types in OS and CSS prognostic models, effective prognosis prediction results could be achieved in multiple datasets (OS: AUC 0.70-0.87; CSS: AUC 0.74-0.89). Conclusion: Age, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy are the independent prognostic factors in OS or CSS of the patients with mucinous and ordinary cholangiocarcinoma. Nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time is of significance in clinical practice and management of cholangiocarcinoma.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Nomogramas , Humanos , Masculino , Colangiocarcinoma/terapia , Colangiocarcinoma/patologia , Colangiocarcinoma/mortalidade , Feminino , Prognóstico , Pessoa de Meia-Idade , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Neoplasias dos Ductos Biliares/mortalidade , Estudos Retrospectivos , Idoso , Programa de SEER , Adulto
15.
Sci Total Environ ; 946: 174301, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38942305

RESUMO

Livestock and poultry products are an essential human food source. However, the rapid development of the livestock sector (LS) has caused it to become a significant source of greenhouse gas (GHG) emissions. Consequently, investigating the spatio-temporal characteristics and evolution of GHG emissions is crucial to facilitate the green development of the LS and achieve "peak carbon and carbon neutrality". This study combined life cycle assessment (LCA) with the IPCC Tier II method to construct a novel GHG emissions inventory. The GHG emissions of 31 provinces in China from 2000 to 2021 were calculated, and their spatio-temporal characteristics were revealed. Then, the stochastic impacts by regression on population, affluence, and technology (STIRPAT) model was used to identify the main driving factors of GHG emissions in six regions of China and explore the emission reduction potential. The results showed that GHG emissions increased and then decreased from 2000 to 2021, following a gradual and steady trend. The peak of 628.55 Mt CO2-eq was reached in 2006. The main GHG-producing segments were enteric fermentation, slaughtering and processing, and manure management, accounting for 45.39 %, 26.34 %, and 23.08 % of total GHG emissions, respectively. Overall, the center of gravity of GHG emissions in China migrated northward, with spatial aggregation observed since 2016. The high emission intensity regions were mainly located west of the "Hu Huanyong line". Economic efficiency and emissions intensity were the main drivers of GHG emissions. Under the baseline scenario, GHG emissions are not projected to peak until 2050. Therefore, urgent action is needed to promote the low-carbon green development of the LS in China. The results can serve as scientific references for the macro-prevention and control of GHG emissions, aiding strategic decision-making. Additionally, they can provide new ideas for GHG accounting in China and other countries around the world.


Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Gases de Efeito Estufa , Gado , Gases de Efeito Estufa/análise , China , Animais , Poluentes Atmosféricos/análise , Criação de Animais Domésticos/métodos , Poluição do Ar/estatística & dados numéricos
16.
Front Public Health ; 12: 1320863, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818444

RESUMO

Background: The rise in e-cigarette use among youth is a significant global public health issue. It is important to identify those at increased risk and implement effective strategies to reduce e-cigarette popularity among the youth. Objective: This study aims to identify predictors of e-cigarette uptake in youths with no prior tobacco use, considering individual, familial and the broader societal environmental factors. Methods: For this investigation, a group of 2,487 tobacco-free youths was selected from 15 high schools in Shenzhen, China. Susceptibility to e-cigarettes was determined by assessing the possibility of future use and the openness to trying e-cigarettes if presented by friends. Both chi-square tests and logistic regression were applied to identify factors linked to susceptibility to e-cigarette use. Results: Among the respondents, 5.5% (n = 136) were found to be susceptible to e-cigarette use. The analysis revealed factors tied to this risk: perceptions of e-cigarettes, the impact of vaping peers, paternal parenting styles, the extent of social support, exposure to messages both for and against e-cigarettes use, and secondhand smoke (SHS) exposure. Youths who downplayed the addictive nature of e-cigarettes (aOR = 2.01; 95% CI: 1.14-3.55; p = 0.016), those with friends who engaged in vaping (aOR = 3.43-7.64; 95%CI: 2.36-20.42; p < 0.001), those experiencing over-protective or rejective maternal parenting (aOR = 1.68-3.01; 95%CI: 1.11-5.77; p = 0.001-0.014) or rejective paternal parenting (aOR = 3.63; 95%CI: 1.99-6.59; p < 0.001), those aware of e-cigarette advertisements (aOR = 1.82; 95%CI: 1.28-2.60; p = 0.001), and those exposed to SHS at home (aOR = 1.68; 95%CI: 1.17-2.41; p = 0.005) or at public places (aOR = 1.72-1.79; 95%CI: 1.21-2.57; p = 0.002-0.003) were more prone to e-cigarettes. In contrast, youths who believed using e-cigarettes reduces one's attractiveness (aOR = 0.34; 95%CI: 0.16-0.72; p = 0.005) or perceived that vaping made social interactions less enjoyable (aOR = 0.26; 95%CI: 0.12-0.58; p = 0.001), those who benefited from high social support (aOR = 0.30-0.60; 95%CI: 0.17-0.97; p < 0.001), and those who noticed message about e-cigarettes' adverse consequence (aOR = 0.54; 95%CI: 0.38-0.77; p = 0.001) were less likely to be inclined toward e-cigarette use. Conclusion: The propensity of the youth to e-cigarette usage is shaped by a multiple element. An all-encompassing strategy that addresses the individual, familial, and the broader societal aspects is imperative for the effective prevention of e-cigarette initiation among youth.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Vaping , Humanos , China/epidemiologia , Masculino , Adolescente , Feminino , Estudos Transversais , Vaping/epidemiologia , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Inquéritos e Questionários , Grupo Associado , Poluição por Fumaça de Tabaco/estatística & dados numéricos
18.
Environ Res ; 256: 119245, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38810821

RESUMO

Microalgae have been renowned as the most promising energy organism with significant potential in carbon fixation. In the large-scale cultivation of microalgae, the 3D porous substrate with higher specific surface area is favorable to microalgae adsorption and biofilm formation, whereas difficult for biofilm detachment and microalgae harvesting. To solve this contradiction, N-isopropylacrylamide, a temperature-responsive gels material, was grafted onto the inner surface of the 3D porous substrate to form temperature-controllable interface wettability. The interfacial free energy between microalgae biofilm and the substrates increased from -63.02 mJ/m2 to -31.89 mJ/m2 when temperature was lowered from 32 °C to 17 °C, weakening the adsorption capacity of cells to the surface, and making the biofilm detachment ratio increased to 50.8%. When further cooling the environmental temperature to 4 °C, the detachment capability of microalgae biofilm kept growing. 91.6% of the cells in the biofilm were harvesting from the 3D porous substrate. And the biofilm detached rate was up to 19.84 g/m2/h, realizing the temperature-controlled microalgae biofilm harvesting. But, microalgae growth results in the secretion of extracellular polymeric substances (EPS), which enhanced biofilm adhesion and made cell detachment more difficult. Thus, ultrasonic vibration was used to reinforce biofilm detachment. With the help of ultrasonic vibration, microalgae biofilm detached rate increased by 143.45% to 41.07 g/m2/h. These findings provide a solid foundation for further development of microalgae biofilm detachment and harvesting technology.


Assuntos
Biofilmes , Géis , Microalgas , Temperatura , Biofilmes/crescimento & desenvolvimento , Microalgas/crescimento & desenvolvimento , Porosidade , Géis/química , Acrilamidas/química
19.
Chin J Integr Med ; 30(8): 692-700, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38733455

RESUMO

OBJECTIVE: To explore the rapid antidepressant potential and the underlying mechanism of Chaihu Shugan San (CSS) in female mice. METHODS: Liquid chromatography mass spectrometry (LC-MS)/MS was used to determine the content of main components in CSS to determine its stability. Female C57BL/6J mice were randomly divided into 4 groups, including control (saline), vehicle (saline), CSS (4 g/kg) and ketamine (30 mg/kg) groups. Mice were subjected to irregular stress stimulation for 4 weeks to establish the chronic mild stress (CMS) model, then received a single administration of drugs. Two hours later, the behavioral tests were performed, including open field test, tail suspension test (TST), forced swimming test (FST), novelty suppression feeding test (NSF), and sucrose preference test (SPT). Western blot analysis was used to detect the expression levels of N-methyl-D-aspartate receptor (NMDA) subtypes [N-methyl-D-aspartate receptor 1 (NR1), NR2A, NR2B], synaptic proteins [synapsin1 and post synaptic density protein 95 (PSD95)], and brain-derived neurotrophic factor (BDNF). Moreover, the rapid antidepressant effect of CSS was tested by pharmacological technologies and optogenetic interventions that activated glutamate receptors, NMDA. RESULTS: Compared with the vehicle group, a single administration of CSS (4 g/kg) reversed all behavioral defects in TST, FST, SPT and NSF caused by CMS (P<0.05 or P<0.01). CSS also significantly decreased the expressions of NMDA subtypes (NR1, NR2A, NR2B) at 2 h in hippocampus of mice (all P<0.01). In addition, similar to ketamine, CSS increased levels of synaptic proteins and BDNF (P<0.05 or P<0.01). Furthermore, the rapid antidepressant effects of CSS were blocked by transient activation of NMDA receptors in the hippocampus (all P<0.01). CONCLUSION: Rapid antidepressant effects of CSS by improving behavioral deficits in female CMS mice depended on rapid suppression of NMDA receptors and activation of synaptic proteins.


Assuntos
Antidepressivos , Ácido Glutâmico , Hipocampo , Camundongos Endogâmicos C57BL , Transmissão Sináptica , Animais , Feminino , Antidepressivos/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ácido Glutâmico/metabolismo , Transmissão Sináptica/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Comportamento Animal/efeitos dos fármacos , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Extratos Vegetais/farmacologia , Estresse Psicológico/tratamento farmacológico , Depressão/tratamento farmacológico
20.
J Exp Bot ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38808519

RESUMO

Strawberry (Fragaria×ananassa) is a model plant for studying non-climacteric fruit ripening regulated by abscisic acid (ABA). However, the signaling of ABA in the regulation of fruit coloration is not fully understood. Here, a transcription factor FabHLH3 key to fruit coloration is identified by yeast two hybrid library screening using FaSnRK2.6 as a bait, an ABA core signaling component negative to ripening. Indeed, this interaction is also confirmed by firefly luciferase complementation assay and pull-down assay. RT-qPCR and Western blotting analysis confirm FabHLH3 is expressed ubiquitously in strawberry and stably during fruit development. Manipulating both FabHLH3 and FaSnRK2.6 expression by overexpression and interference demonstrates that FabHLH3 and FaSnRK2.6 promote and inhibit strawberry fruit coloration, respectively, using the marker gene FaUFGT, key to anthocyanin biosynthesis. FaSnRK2.6 can phosphorylate FabHLH3, which promotes FaUFGT expression by the directly binding to its promoter. The phosphorylation inhibits the binding of FabHLH3 to FaUFGT promoter, consequently suppressing FaUFGT expression. Altogether, FaSnRK2.6, a negative kinase in ripening, interacts with and phosphorylates FabHLH3 to suppress FaUFGT expression. With the increase of ABA content in strawberry fruit ripening, the expression of FaSnRK2.6 decreased, which released FabHLH3 transcription activity and enhanced FaUFGT expression, finally promoting the coloration. Thus, our findings fill a gap how FaSnRK2.6 negatively regulates strawberry fruit coloration and ripening by FabHLH3.

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