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1.
J Med Virol ; 96(8): e29859, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39145587

RESUMO

Validation of bioanalytical methods is crucial, especially in the pharmaceutical industry, to determine their suitability for specific purposes and the accuracy of analytical results. The pseudovirion-based neutralization assay (PBNA) is considered the gold standard for detecting and quantifying neutralizing antibodies against human papillomavirus in vaccine development for disease prevention. This paper introduces an improved triple-color PBNA method, capable of simultaneous detection of two or three human papillomavirus (HPV types for use in the development of a 14-valent HPV vaccine candidate. The primary objective was to comprehensively validate the triple-color PBNA method for general vaccine immunogenicity assays. Results show that the method has good specificity, accuracy, precision, linearity, robustness, and applicability. This innovative triple-color PBNA offers an improved approach for large-scale immunogenicity assessment in vaccine development. This study lays a solid foundation that can serve as a guiding paradigm for assessing vaccine responses in preclinical and clinical phases, providing valuable insights to the field.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Testes de Neutralização , Vacinas contra Papillomavirus , Humanos , Testes de Neutralização/métodos , Vacinas contra Papillomavirus/imunologia , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Vacinas Sintéticas/imunologia , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Imunogenicidade da Vacina , Papillomaviridae/imunologia , Sensibilidade e Especificidade
2.
Int J Biol Macromol ; 277(Pt 3): 134296, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39094888

RESUMO

Anthocyanidins and anthocyanins are one subclass of flavonoids in plants with diverse biological functions and have health-promoting effects. Dihydroflavonol 4-reductase (DFR) is one of the important enzymes involved in the biosynthesis of anthocyanidins and other flavonoids. Here, a new MOF-based nano-immobilized DFR enzyme acting as a nano-biocatalyst for the production of anthocyanidins in vitro was designed. We prepared UiO-66-NH2 MOF nano-carrier and recombinant DFR enzyme from genetic engineering. DFR@UiO-66-NH2 nano-immobilized enzyme was constructed based on covalent bonding under the optimum immobilization conditions of the enzyme/carrier ratio of 250 mg/g, 37 °C, pH 6.5 and fixation time of 10 min. DFR@UiO-66-NH2 was characterized and its catalytic function for the synthesis of anthocyanidins in vitro was testified using UPLC-QQQ-MS analysis. Compared with free DFR enzyme, the enzymatic reaction catalyzed by DFR@UiO-66-NH2 was more easily for manipulation in a wide range of reaction temperatures and pH values. DFR@UiO-66-NH2 had better thermal stability, enhanced adaptability, longer-term storage, outstanding tolerances to the influences of several organic reagents and Zn2+, Cu2+ and Fe2+ ions, and relatively good reusability. This work developed a new MOF-based nano-immobilized biocatalyst that had a good prospect of application in the green synthesis of anthocyanins in the future.

3.
Int J Biol Macromol ; 275(Pt 2): 133592, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38960265

RESUMO

Antisense long non-coding RNAs (lncRNAs) played a crucial role in the precise regulation of essential biological processes and were abundantly present in animals. Many of these antisense lncRNAs have been identified as key roles in adipose tissue accumulation in livestock, underscoring their vital role in the regulation of animal physiology. Nonetheless, the functional roles of these antisense lncRNAs in regulating adipogenesis and the specific molecular mechanisms these processes were still unclear, which was a significant gap in current scientific research. In this study, we identified and characterized SERPINE1AS2, a novel natural antisense lncRNA, was highly expressed in the fat tissues of adult cattle and calves. Its expression gradually increased during the differentiation of intramuscular adipocytes. Through functional studies, we observed that knockdown of SERPINE1AS2 inhibited the proliferation and adipogenesis of intramuscular adipocytes, while overexpression of SERPINE1AS2 produced the opposite effect. RNA sequencing (RNA-seq) analysis following SERPINE1AS2 knockdown revealed that differential expression genes (DEGs) were significantly enriched in key signaling pathways, notably the MAPK, Wnt, and mTOR signaling pathways. Furthermore, SERPINE1AS2 interacted with Plasminogen Activator Inhibitor-1 (PAI1), forming RNA dimers through complementary base pairing and consequently influencing PAI1 expression. Interestingly, studies on PAI1 suggested that reduced expression facilitated adipogenesis and the downregulation of PAI1 alleviated the inhibitory effect of reduced SERPINE1AS2 on adipogenesis. In summary, this study suggested that SERPINE1AS2 played a crucial role in the adipogenesis of bovine intramuscular adipocytes by modulating the expression of PAI1. SERPINE1AS2 also regulated adipogenesis by engaging in the MAPK, Wnt, and mTOR signaling pathways. Our results suggested that SERPINE1AS2 had a complex regulatory mechanism on adipogenesis in intramuscular adipocytes.


Assuntos
Adipócitos , Adipogenia , Inibidor 1 de Ativador de Plasminogênio , RNA Longo não Codificante , Adipogenia/genética , Animais , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Bovinos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Adipócitos/metabolismo , Adipócitos/citologia , Regulação da Expressão Gênica , Diferenciação Celular/genética , Proliferação de Células/genética , Transdução de Sinais , Tecido Adiposo/metabolismo , Tecido Adiposo/citologia
4.
Int J Biol Macromol ; 275(Pt 1): 133650, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38971288

RESUMO

Consumers are more inclined to choose beef with a high intramuscular fat content (IMF), which regulated by lots of factors. It is very significant to find a miRNA that plays a key role in the accumulation of IMF. In our study, we found that bta-miR-330 was highly expressed in Japanese black cattle and differentially expressed at intramuscular pre-adipocytes differentiation processes. Furthermore, we transfected the bta-miR-330 mimic & inhibitor in intramuscular pre-adipocytes. The results showed that bta-miR-330 inhibits the proliferation but promotes the adipogenesis of intramuscular pre-adipocytes. Subsequently, our study showed that bta-miR-330 binds to SESN3, which inhibits the adipogenesis of intramuscular pre-adipocytes. Moreover, we established the mechanism that bta-miR-330 promotes the adipogenesis of intramuscular pre-adipocytes by targeting SESN3 to activate the Akt-mTOR signaling pathway. Overall, our results revealed that bta-miR-330-SESN3-Akt-mTOR axis plays an important role in adipogenesis of intramuscular pre-adipocytes, which provides a molecular basis for increasing IMF content in beef cattle.


Assuntos
Adipócitos , Adipogenia , MicroRNAs , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Bovinos , Adipogenia/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Adipócitos/metabolismo , Adipócitos/citologia , Diferenciação Celular , Proliferação de Células
5.
Heliyon ; 10(13): e34127, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39071701

RESUMO

NUAK2 is a member of the AMP-activated protein kinase (AMPK) family, which plays an essential role in cellular processes such as apoptosis, proliferation, and cell fate. Recent studies have already shown that silencing of NUAK2 blocks proliferation and promotes apoptosis of human melanoma cells and liver cancer cells. In addition, NUAK2 is involved in the development of glioblastoma via regulating the expression of cancer stem cell-related genes, and it promotes the cell cycle entry in the glioblastoma cells. However, the expression and the role of NUAK2 in the progress of peripheral nerve regeneration after injury are yet to be elucidated. We observed that NUAK2 was upregulated following distal sciatic nerve crush (SNC). Interestingly, we discovered that NUAK2 showed co-localization with S100 (Schwann cell marker). Furthermore, we found that the NUAK2 had a spatiotemporal protein expression, which was consistent with proliferating cell nuclear-antigen (PCNA). The protein level of NUAK2 and YAP was upregulated in the model of TNF-α-induced Schwann cell (SC) proliferation. Furthermore, flow cytometry analysis, CCK-8, transwell assays, and wound healing assays were all performed with the purpose of exploring the role of NUAK2 in the regulation of SC proliferation and migration. More importantly, we found that NUAK2-deficient SCs showed significantly reduced expression of Yes-associated protein (YAP). Bioinformatic analysis identified upstream regulators of NUAK2 and NUAK2-associated genes (e.g., YAP1). Finally, we investigated the recovery changes during regeneration progress through the walking track analysis. Thus, we speculated that NUAK2 was involved in biochemical and physiological responses of SCs after SNC via YAP-driven proliferation and migration, and this study determined the importance of NUAK2 as a potential target in peripheral nerve regeneration.

6.
Front Immunol ; 15: 1362770, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983849

RESUMO

The development of human papillomavirus (HPV) vaccines has made substantive progress, as represented by the approval of five prophylactic vaccines since 2006. Generally, the deployment of prophylactic HPV vaccines is effective in preventing newly acquired infections and incidences of HPV-related malignancies. However, there is still a long way to go regarding the prevention of all HPV infections and the eradication of established HPV infections, as well as the subsequent progression to cancer. Optimizing prophylactic HPV vaccines by incorporating L1 proteins from more HPV subtypes, exploring adjuvants that reinforce cellular immune responses to eradicate HPV-infected cells, and developing therapeutic HPV vaccines used either alone or in combination with other cancer therapeutic modalities might bring about a new era getting closer to the vision to get rid of HPV infection and related diseases. Herein, we summarize strategies for the development of HPV vaccines, both prophylactic and therapeutic, with an emphasis on the selection of antigens and adjuvants, as well as implications for vaccine efficacy based on preclinical studies and clinical trials. Additionally, we outline current cutting-edge insights on formulation strategies, dosing schedules, and age expansion among HPV vaccine recipients, which might play important roles in addressing barriers to vaccine uptake, such as vaccine hesitancy and vaccine availability.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Humanos , Vacinas contra Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/imunologia , Feminino , Desenvolvimento de Vacinas , Adjuvantes Imunológicos , Animais , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/virologia , Papillomaviridae/imunologia , Eficácia de Vacinas
7.
Gynecol Endocrinol ; 40(1): 2375564, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38976721

RESUMO

OBJECTIVE: To comprehensively assess the dose-response association between dietary glycemic index (GI) and glycemic load (GL) and gestational diabetes mellitus (GDM) risk. METHODS: PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, and VIP databases were searched up to May 29, 2024. Studies with at least three exposure categories were included. Dose-response analysis was also performed when covariates were adjusted in the included studies. RESULTS: Thirteen studies involving 39,720 pregnant women were included. A linear relationship was found between GI and the risk of GDM (χ2 = 4.77, Pnon-linearity = .0923). However, association was not significant (χ2 = 0.06, p = .8000). For every unit increase in GI (range 0-30), GDM risk increased by 0.29%. After adjusting for covariates, the linear relationship persisted (χ2 = 4.95, Pnon-linearity = .084) with no significant association (χ2 = 0.08, p = .7775). For GL, a linear relationship was also found (χ2 = 4.17, Pnon-linearity =.1245), but GL was not significantly associated with GDM risk (χ2 = 2.63, p = .1049). The risk of GDM increased by 0.63% per unit increase in GL. After covariate adjustment, a significant association was observed (χ2 = 6.28, p = .0122). CONCLUSION: No significant association between GI and GDM risk was found. After adjusting for covariates, GL shows a significant association with GDM risk. Our findings emphasize the importance of considering dietary GL in managing the risk of GDM. Future research should continue to explore these relationships with standardized diagnostic criteria and robust adjustment for potential confounders.


Assuntos
Diabetes Gestacional , Dieta , Índice Glicêmico , Carga Glicêmica , Humanos , Diabetes Gestacional/epidemiologia , Gravidez , Feminino , Dieta/efeitos adversos , Fatores de Risco
8.
Transplant Proc ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39004579

RESUMO

OBJECTIVE: Hematomas of the liver graft, that is, postintervention, subcapsular or intrahepatic are rare yet potentially fatal complications following liver transplantation (LT), necessitating immediate diagnosis and management to avert devastating outcomes. This study was aimed to introduce our approach to manage graft hematoma subsequent to LT. METHODS: Among 131 orthotopic liver transplantations (OLT) conducted at our institution between January 2017 and May 2023, 3 cases of intrahepatic (n = 2) and extrahepatic (n = 1) hematoma were confirmed through computed tomography (CT) within 10 days after LT. The clinical outcomes of various treatment modalities for these three cases were analyzed. RESULTS: Three out of 131 (2.3%) LT recipients developed graft hematoma. Patient 1 developed a spontaneous intrahepatic hematoma, without evident predisposing factors, while patient 2 developed an intrahepatic hematoma following endoscopic retrograde cholangiopancreatography (ERCP). The third case that is extrahepatic hematoma was speculated to be a result of minor hepatic parenchymal injury stemming from compressive and volume-reducing manipulation of a large graft, or secondary to focal ischemic necrosis of the liver. Our management protocol was summarized as follows: (1). Immediate ultrasound and CT, particularly enhanced CT; (2). Puncture and percutaneous drainage (PD) of the hematoma; (3). Arterial embolization if the origin could be identified as a ruptured vessel; (4). Surgical evacuation of the hematoma in the presence of bile leakage, to avoid a compartment respectably secondary infection. All three patients responded favorably to treatment and remained alive to date. CONCLUSION: Prompt diagnosis and sequential individualized management can successfully deal with intra-/extrahepatic graft hematoma after LT. Our results underscored that an individualized management considering potential future complications into account.

10.
Nat Commun ; 15(1): 6255, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39048547

RESUMO

Evolution of SARS-CoV-2 variants emphasizes the need for multivalent vaccines capable of simultaneously targeting multiple strains. SCTV01E is a tetravalent COVID-19 vaccine derived from the spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1. In this double-blinded placebo-controlled pivotal efficacy trial (NCT05308576), the primary endpoint was vaccine efficacy (VE) against COVID-19 seven days post-vaccination in individuals without recent infection. Other endpoints included evaluating safety, immunogenicity, and the VE against all SARS-CoV-2 infections in individuals meeting the study criteria. Between December 26, 2022, and January 15, 2023, 9,223 individuals were randomized at a 1:1 ratio to receive SCTV01E or a placebo. SCTV01E showed a VE of 69.4% (95% CI: 50.6, 81.0) 7 days post-vaccination, with 75 cases in the placebo group and 23 in the SCTV01E group for the primary endpoint. VEs were 79.7% (95% CI: 51.0, 91.6) and 82.4% (95% CI: 57.9, 92.6), respectively, for preventing symptomatic infection and all SARS-CoV-2 infections 14 days post-vaccination. SCTV01E elicited a 25.0-fold higher neutralizing antibody response against Omicron BA.5 28 days post-vaccination compared to placebo. Reactogenicity was generally mild and transient, with no reported vaccine-related SAE, adverse events of special interest (AESI), or deaths. The trial aligned with the shift from dominant variants BA.5 and BF.7 to XBB, suggesting SCTV01E as a potential vaccine alternative effective against present and future variants.


Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Eficácia de Vacinas , Humanos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Método Duplo-Cego , Feminino , Masculino , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , Adulto , Pessoa de Meia-Idade , Anticorpos Antivirais/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Neutralizantes/imunologia , Idoso , Adulto Jovem , Imunogenicidade da Vacina , Adolescente , Vacinação/métodos
11.
BMC Psychiatry ; 24(1): 417, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834965

RESUMO

BACKGROUND: Polypharmacy is common in older adults with psychiatric disorders, but no consensus has reached about the reliable indicators evaluating the benefits and risks of drug-drug interactions (DDIs) in polypharmacy. We aimed to identify indicators suitable for evaluating the clinical significance of DDIs in polypharmacy in older adults with psychiatric disorders. METHODS: The online tools were used to distribute and collect the questionnaires. The Delphi method was applied to analyze experts' opinions. The degree of authority and coordination of experts were analyzed using the coefficient of variation, coefficient of coordination, expert's judgment factor, familiarity with the study content factor, and Kendall coordination coefficient. Statistical analysis was conducted using the IBM SPSS® Statistics Package version 26.0. RESULTS: After three rounds of expert consultation, five primary and eleven secondary indicators were identified. The primary "pharmacodynamic indicator" included "severity of adverse drug reactions", "duration of adverse drug reaction", "symptom relief", "time to onset of symptomatic relief", "number of days in hospital", and "duration of medication". The secondary "pharmacokinetic indicator" contained "dosage administered" and "dosing intervals". The primary "patient tolerance indicator" contained one secondary indicator of "patient tolerability". The primary indicator "patient adherence" contained one secondary indicator of "patient adherence to medication". The primary indicator "cost of drug combination" contained one secondary indicator of "readmission". These indicators were used to determine the clinical significance of DDIs during polypharmacy. CONCLUSIONS: The clinical significance of drug combinations should be taken into account when polypharmacy is used in the elderly. The five primary indicators and eleven secondary indicators might be preferred to evaluate their risks and benefits. Medication management in this population requires a multidisciplinary team, in which nurses play a key role. Future research should focus on how to establish efficient multidisciplinary team workflows and use functional factors to assess DDIs in polypharmacy for psychiatric disorders.


Assuntos
Técnica Delphi , Interações Medicamentosas , Transtornos Mentais , Polimedicação , Humanos , Transtornos Mentais/tratamento farmacológico , Idoso , Masculino , Feminino , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Pessoa de Meia-Idade , Inquéritos e Questionários , Relevância Clínica
12.
Microbiol Spectr ; 12(8): e0030924, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-38888361

RESUMO

The tumor suppressor p53, primarily functioning as a transcription factor, has exhibited antiviral capabilities against various viruses in chickens, including infectious bursal disease virus (IBDV), avian leukosis virus subgroup J (ALV-J), and avian infectious laryngotracheitis virus (ILTV). Nevertheless, the existence of a universal antiviral mechanism employed by chicken p53 (chp53) against these viruses remains uncertain. This study conducted a comprehensive comparison of molecular networks involved in chp53's antiviral function against IBDV, ALV-J, and ILTV. This was achieved through an integrated analysis of ChIP-seq data, examining chp53's genome-wide chromatin occupancy, and RNA-seq data from chicken cells infected with these viruses. The consistent observation of chp53 target gene enrichment in metabolic pathways, confirmed via ChIP-qPCR, suggests a ubiquitous regulation of host cellular metabolism by chp53 across different viruses. Further genome binding motif conservation analysis and transcriptional co-factor prediction suggest conserved transcriptional regulation mechanism by which chp53 regulates host cellular metabolism during viral infection. These findings offer novel insights into the antiviral role of chp53 and propose that targeting the virus-host metabolic interaction through regulating p53 could serve as a universal strategy for antiviral therapies in chickens.IMPORTANCEThe current study conducted a comprehensive analysis, comparing molecular networks underlying chp53's antiviral role against infectious bursal disease virus (IBDV), avian leukosis virus subgroup J (ALV-J), and avian infectious laryngotracheitis virus (ILTV). This was achieved through a combined assessment of ChIP-seq and RNA-seq data obtained from infected chicken cells. Notably, enrichment of chp53 target genes in metabolic pathways was consistently observed across viral infections, indicating a universal role of chp53 in regulating cellular metabolism during diverse viral infections. These findings offer novel insights into the antiviral capabilities of chicken p53, laying a foundation for the potential development of broad-spectrum antiviral therapies in chickens.


Assuntos
Vírus da Leucose Aviária , Galinhas , Herpesvirus Galináceo 1 , Vírus da Doença Infecciosa da Bursa , RNA-Seq , Proteína Supressora de Tumor p53 , Animais , Galinhas/virologia , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Vírus da Leucose Aviária/genética , Vírus da Leucose Aviária/fisiologia , Vírus da Doença Infecciosa da Bursa/genética , Vírus da Doença Infecciosa da Bursa/fisiologia , Herpesvirus Galináceo 1/genética , Sequenciamento de Cromatina por Imunoprecipitação , Antivirais/farmacologia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/genética , Regulação da Expressão Gênica
13.
Virology ; 597: 110159, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38943781

RESUMO

Therapies targeting virus-host interactions are seen as promising strategies for treating gallid alphaherpesvirus 1 (ILTV) infection. Our study revealed a biphasic activation of two MAPK cascade pathways, MEK/ERK and p38 MAPK, as a notably activated host molecular event in response to ILTV infection. It exhibits antiviral functions at different stages of infection. Initially, the MEK/ERK pathway is activated upon viral invasion, leading to a broad suppression of metabolic pathways crucial for ILTV replication, thereby inhibiting viral replication from the early stage of ILTV infection. As the viral replication progresses, the p38 MAPK pathway activates its downstream transcription factor, STAT1, further hindering viral replication. Interestingly, ILTV overcomes this biphasic antiviral barrier by hijacking host p38-AKT axis, which protects infected cells from the apoptosis induced by infection and establishes an intracellular equilibrium conducive to extensive ILTV replication. These insights could provide potential therapeutic targets for ILTV infection.


Assuntos
Infecções por Herpesviridae , Sistema de Sinalização das MAP Quinases , Replicação Viral , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Infecções por Herpesviridae/virologia , Infecções por Herpesviridae/metabolismo , Alphaherpesvirinae/fisiologia , Alphaherpesvirinae/genética , Alphaherpesvirinae/metabolismo , Interações Hospedeiro-Patógeno , Linhagem Celular , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT1/genética
14.
Diabetol Metab Syndr ; 16(1): 134, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890685

RESUMO

BACKGROUND: The aim of this study was to investigate whether a causal relationship exists between serum uric acid (SUA) and diabetic microvascular complications using a two-sample Mendelian randomization (MR) method. METHODS: We used the MR approach, utilizing genome-wide association study (GWAS) summary statistics, to estimate the causal effect of SUA on diabetic microvascular complications in European individuals. The summary statistical data of SUA were obtained from the open database (IEU OPEN GWAS PROJECT) (p < 5 × 10- 8), and data on diabetic microvascular complications (diabetic nephropathy, diabetic neuropathy, diabetic retinopathy) were obtained from the FinnGen consortium. F-statistics were calculated to assess the correlation between instrumental variables (IVs) and SUA, and single nucleotide polymorphisms (SNPs) associated with confounders or outcomes were excluded by consulting the PhenoScanner database. Inverse variance weighting (IVW) was used for primary estimation, and MR‒Egger, weighted median (WM), and Mendelian randomization pleiotropy residuals sum and outliers (MR-PRESSO) were used for additional assessment. Heterogeneity was assessed using the Cochran's Q test, and polytropy was assessed using the MR‒Egger intercept. RESULTS: MR analysis revealed a causal relationship between a genetically predicted increase in SUA and diabetic nephropathy [OR = 1.32, 95%(CI) = 1.07-1.63, p = 0.008]. The results were consistent with those after MR-PRESSO [OR = 1.30, 95%(CI) = 1.07-1.58, p = 0.008]. There was a causal relationship between type 2 diabetes mellitus (T2DM) and renal complication IVW [OR = 1.27, 95%(CI) = 1.00-1.62, p = 0.049]. These results were consistent with those after MR-PRESSO [OR = 1.27, 95%(CI) = 1.00-1.62, p = 0.050]. There was no significant causal relationship between the genetically predicted increase in SUA and diabetic retinopathy [OR 1.09, 95%(CI) = 0.94-1.26, p = 0.249] or diabetic neuropathy [OR = 1.08, 95%(CI) = 0.84-1.40, p = 0.549]. CONCLUSIONS: This MR analysis suggests a causal relationship between genetically predicted uric acid increases and diabetic microvascular complications. A significant causal relationship exists between SUA and diabetic nephropathy but not between SUA and diabetic retinopathy or diabetic neuropathy.

15.
J Org Chem ; 89(12): 8342-8356, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38819657

RESUMO

A mild and transition-metal-free defluorinative alkylation of benzyl amines with trifluoromethyl alkenes is reported. The features of this protocol are easy-to-obtain starting materials, a wide range of substrates, and functional group tolerance as well as high atom economy, thus offering a strategy to access a variety of gem-difluorohomoallyl amines, which are extensively distributed in pharmaceuticals and bioactive agents, with excellent chemoselectivity. The primary products can be further transformed to a diversity of 2-fluorinated pyrroline compounds.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38775884

RESUMO

Emodin has been proven to have weight-reducing and lipid-lowering effects. In order to make emodin play a better anti-obesity role, we designed and developed an emodin loaded dissolving microneedle patch, in which emodin existed in the form of emodin-polyvinylpyrrolidone co-precipitate (Emodin-PVP). Meanwhile, polydopamine (PDA) was added to the microneedle patch (PDA-Emodin-PVP-MN) for photothermal-enhanced chemotherapy of obesity. The average weight of the patch was 0.1 ± 0.05 g and the drug loading was 0.37 ± 0.031 mg. After 5 min of NIR irradiation (808 nm, 0.6 W/cm2), the rat abdominal temperature could reach 48 ℃, and the cumulative release of emodin reached 96.25%. The diffusion coefficient of emodin in the in vitro agar diffusion experiment was 249.27 mm2 h-1. No obvious toxicity was observed in hemolysis test, CCK-8 assay and microscopic histopathological analysis. The patch significantly reduced the percent of body weight ( P < 0.01), lipid-body ratio ( P < 0.001), serum FFAs ( P < 0.01) and the cell volume of peritesticular adipose tissue in the high-fat diet induced obese rats, indicating the patch had good anti-obesity effect. The mechanism of action may be related to the up-regulation of HSL and LPL protein levels in rat peritesticular adipose tissue.

17.
Sci Rep ; 14(1): 12110, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802473

RESUMO

Copper mineralization in the Pulang (PL) porphyry deposit, Langdu (LD) porphyry-skarn deposit and Songnuo (SN) porphyry prospect in northwestern Yunnan, China, is closely related to the emplacement of quartz monzonite porphyries. The chemical compositions of biotite and apatite from those porphyries were analyzed to calculate the halogen fugacity and to constrain mineralized and barren porphyries. Our data show that biotites from the PL deposit have higher MgO, SiO2, TiO2 and F contents than those from the LD deposit or SN prospect. Compared to those in the LD deposit and SN prospect, the Mg (atoms per formula unit (apfu)) and AlVI (apfu) value in biotite is greater, and the F content is greater and the SO3 and Ce2O3/Y2O3 ratio in apatite are lower in the PL deposit. Ti-biotite thermometry and apatite-biotite geothermometry show that the crystallization temperature of biotite from the PL deposit is higher than that from the SN prospect or LD deposit. The results suggest that oxygen fugacity, magmatic sulfur, and H2O contents cannot be used to efficiently distinguish the PL deposit from the LD deposit and SN prospect. However, the halogen chemistry of biotite from the PL deposit is distinctly different from that of the LD deposit or SN prospect according to the lower IV (F), indicating that mineralized quartz monzonite porphyries in the PL deposit formed during the late magmatic stage, which is in contrast to those in the LD deposit and SN prospect. The mineralized porphyries display a remarkable negative linear relationship (r = - 0.96) with the log (f HF/f HCl) and log (f H2O/f HF) ratio, which can be used to distinguish the mineralized and barren porphyries. Compared with other typical porphyry Cu systems, there is a remarkable positive linear relationship between IV (Cl) and log (f H2O/f HCl). In addition, the linear slope and intercept for log (f H2O/f HCl) ratios and the IV (Cl) of biotite from the potassic and phyllic alteration zones are significantly greater than those from other porphyries.

18.
Front Neurosci ; 18: 1387266, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38784091

RESUMO

Background: Evaluating the correlation between serum potassium and Parkinson's disease (PD) in US adults. Methods: A cross-sectional study was conducted on 20,495 adults aged 40 years or older using NHANES data from 2005 to 2020. The study utilized one-way logistic regression and multifactorial logistic regression to examine the correlation between serum potassium levels and PD. Additionally, a smoothed curve fitting approach was employed to assess the concentration-response relationship between serum potassium and PD. Stratified analyses were carried out to investigate potential interactions between serum potassium levels and PD with variables such as age, sex, race, marital status, education, BMI, smoking and medical conditions like coronary, stroke, diabetes, hypertension, and hypercholesterolemia. Results: In this study, a total of 20,495 participants, comprising 403 PD and 20,092 non-PD individuals, were included. After adjusted for covariates, multivariable logistic regression revealed that high serum potassium level was an independent risk factor for PD (OR:1.86, 95% CI:1.45 ~ 2.39, p < 0.01).The linear association between serum potassium and PD was described using fitted smoothing curves. Age, sex, race, education, marital, BMI, coronary, stroke, diabetes, hypertension and hypercholesterolemia were not significantly correlated with this positive connection, according to subgroup analysis and interaction testing (P for interaction >0.05). Conclusion: Serum potassium levels are elevated in patients with Parkinson's disease compared to non-PD patients. Additional prospective studies are required to explore the significance of serum potassium levels in individuals with Parkinson's disease.

19.
Environ Sci Pollut Res Int ; 31(26): 38288-38297, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38797757

RESUMO

A simple, low-cost, and highly sensitive method using a modified QuECHERS procedure based on a liquid chromatography-tandem mass spectrometer (LC-MS/MS) was established to simultaneously quantify lufenuron and chlorfenapyr and the corresponding metabolite tralopyril in cabbage for the first time. On the basis of this method, terminal residue and dietary risk of lufenuron and chlorfenapyr in cabbage were investigated. The recoveries of lufenuron, chlorfenapyr, and tralopyril ranged from 88 to 110%, with relative standard deviation of less than 12.4%. The field trial results showed that at the pre-harvest interval (PHI) of 21 days, the terminal residues of lufenuron, chlorfenapyr, and tralopyril in the supervised trials were not higher than 0.02 mg/kg, and the highest detected residue levels of lufenuron, chlorfenapyr, and tralopyril were 0.047, 0.055, and <0.02 mg·kg-1 at 14-day pre-harvest respectively, which were lower than the maximum residue limits (MRLs) for cabbage established in China. For the dietary risk assessment, the national estimated daily intakes (NEDIs) as proportion of acceptable daily intakes (ADIs) were 80.4% and 29.9% for chlorfenapyr and lufenuron respectively indicating an acceptable dietary risk to Chinese population.


Assuntos
Benzamidas , Brassica , Brassica/química , Medição de Risco , Piretrinas , Resíduos de Praguicidas , China , Espectrometria de Massas em Tandem , Cromatografia Líquida , Humanos , Exposição Dietética , Fluorocarbonos
20.
Front Public Health ; 12: 1380290, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818439

RESUMO

Background: Engaging in regular physical activity has been consistently linked to improved physical health and academic performance. Despite its known benefits, there is a concerning trend of decreased physical activity among children globally. The study primarily aims to investigate the level of physical activity among junior high school students in Taiyuan and analyse the main affecting factors from a socio-ecological perspective. Methods: A cross-sectional study was conducted, involving 650 junior high school students from 7 schools in Taiyuan, and 648 valid questionnaires were ultimately collected. The data on students' physical activity levels were collected through the Children's Leisure Activities Study Survey Questionnaire, and the data on factors affecting students' physical activity were collected through the Student Perceived Factors Affecting Physical Activity Questionnaire. Results: In this study, students from the 7th, 8th, and 9th grades participated in physical activities, averaging 214.500 min per week in moderate-intensity and 25.000 min in high-intensity activities, cumulatively averaging 280.000 min weekly. Notably, a significant disparity (p = 0.012) was observed in the combined duration of moderate and high-intensity activities, with male students engaging more time compared to their female counterparts (307.500 vs. 255.000 min). This variance extended across different grades, particularly evident in 8th graders who recorded the highest weekly high-intensity activity duration (31.000 min) and overall physical activity time (320.500 min), surpassing the 7th graders(p = 0.007 for high-intensity activities). Furthermore, an exploratory factor analysis of a 32-item questionnaire, designed to identify determinants of physical activity, revealed six principal components. These components were found to positively correlate with both moderate and high-intensity physical activities. Conclusion: Results emphasize that educational institutions and community programs should collaborate to offer engaging weekend physical activity programs. Schools should develop and implement tailored physical education curricula addressing gender and grade differences. Furthermore, schools and local governments should invest in high-quality sports equipment and facilities.


Assuntos
Exercício Físico , Instituições Acadêmicas , Estudantes , Humanos , Estudos Transversais , Masculino , Feminino , Adolescente , Inquéritos e Questionários , Estudantes/estatística & dados numéricos , China , Criança , Fatores Sexuais
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