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1.
Cardiovasc Diabetol ; 23(1): 138, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664801

RESUMO

BACKGROUND: Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored. The present study sought to investigate whether NCEH1 improved endothelial function in diabetes, and the underlying mechanisms were explored. METHODS: The expression and activity of NCEH1 were determined in obese mice with high-fat diet (HFD) feeding, high glucose (HG)-induced mouse aortae or primary endothelial cells (ECs). Endothelium-dependent relaxation (EDR) in aortae response to acetylcholine (Ach) was measured. RESULTS: Results showed that the expression and activity of NCEH1 were lower in HFD-induced mouse aortae, HG-exposed mouse aortae ex vivo, and HG-incubated primary ECs. HG exposure reduced EDR in mouse aortae, which was exaggerated by endothelial-specific deficiency of NCEH1, whereas NCEH1 overexpression restored the impaired EDR. Similar results were observed in HFD mice. Mechanically, NCEH1 ameliorated the disrupted EDR by dissociating endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to eNOS activation and nitric oxide (NO) release. Moreover, interaction of NCEH1 with the E3 ubiquitin-protein ligase ZNRF1 led to the degradation of Cav-1 through the ubiquitination pathway. Silencing Cav-1 and upregulating ZNRF1 were sufficient to improve EDR of diabetic aortas, while overexpression of Cav-1 and downregulation of ZNRF1 abolished the effects of NCEH1 on endothelial function in diabetes. Thus, NCEH1 preserves endothelial function through increasing NO bioavailability secondary to the disruption of the Cav-1/eNOS complex in the endothelium of diabetic mice, depending on ZNRF1-induced ubiquitination of Cav-1. CONCLUSIONS: NCEH1 may be a promising candidate for the prevention and treatment of vascular complications of diabetes.


Assuntos
Caveolina 1 , Dieta Hiperlipídica , Células Endoteliais , Endotélio Vascular , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo III , Vasodilatação , Animais , Endotélio Vascular/fisiopatologia , Endotélio Vascular/metabolismo , Endotélio Vascular/enzimologia , Endotélio Vascular/efeitos dos fármacos , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Vasodilatação/efeitos dos fármacos , Células Endoteliais/enzimologia , Células Endoteliais/metabolismo , Células Endoteliais/efeitos dos fármacos , Caveolina 1/metabolismo , Caveolina 1/deficiência , Caveolina 1/genética , Células Cultivadas , Esterol Esterase/metabolismo , Esterol Esterase/genética , Camundongos Knockout , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Experimental/fisiopatologia , Transdução de Sinais , Camundongos , Aorta/enzimologia , Aorta/fisiopatologia , Aorta/metabolismo , Aorta/efeitos dos fármacos , Aorta/patologia , Óxido Nítrico/metabolismo , Obesidade/enzimologia , Obesidade/fisiopatologia , Obesidade/metabolismo , Ubiquitinação
2.
Front Pharmacol ; 15: 1337633, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650630

RESUMO

Globally, alcohol-associated liver disease (ALD) has become an increased burden for society. Disulfirams, Benzodiazepines (BZDs), and corticosteroids are commonly used to treat ALD. However, the occurrence of side effects such as hepatotoxicity and dependence, impedes the achievement of desirable and optimal therapeutic efficacy. Therefore, there is an urgent need for more effective and safer treatments. Hovenia dulcis is an herbal medicine promoting alcohol removal clearance, lipid-lowering, anti-inflammatory, and hepatoprotective properties. Hovenia dulcis has a variety of chemical components such as dihydromyricetin, quercetin and beta-sitosterol, which can affect ALD through multiple pathways, including ethanol metabolism, immune response, hepatic fibrosis, oxidative stress, autophagy, lipid metabolism, and intestinal barrier, suggesting its promising role in the treatment of ALD. Thus, this work aims to comprehensively review the chemical composition of Hovenia dulcis and the molecular mechanisms involved in the process of ALD treatment.

3.
Zhongguo Zhong Yao Za Zhi ; 49(4): 884-893, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621895

RESUMO

Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Sepse , Humanos , Medicina Tradicional Chinesa , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Sepse/complicações , Sepse/tratamento farmacológico , Apoptose , Transdução de Sinais , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia
4.
FEBS J ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652546

RESUMO

l-threonine dehydrogenase (Tdh) is an enzyme that links threonine metabolism to epigenetic modifications and mitochondria biogenesis. In vitro studies show that it is critical for the regulation of trimethylation of histone H3 lysine 4 (H3K4me3) levels and cell fate determination of mouse embryonic stem cells (mESCs). However, whether Tdh regulates a developmental process in vivo and, if it does, whether it also primarily regulates H3K4me3 levels in this process as it does in mESCs, remains elusive. Here, we revealed that, in zebrafish hematopoiesis, tdh is preferentially expressed in neutrophils. Knockout of tdh causes a decrease in neutrophil number and slightly suppresses their acute injury-induced migration, but, unlike the mESCs, the level of H3K4me3 is not evidently reduced in neutrophils sorted from the kidney marrow of adult tdh-null zebrafish. These phenotypes are dependent on the enzymatic activity of Tdh. Importantly, a soluble supplement of nutrients that are able to fuel the acetyl-CoA pool, such as pyruvate, glucose and branched-chain amino acids, is sufficient to rescue the reduction in neutrophils caused by tdh deletion. In summary, our study presents evidence for the functional requirement of Tdh-mediated threonine metabolism in a developmental process in vivo. It also provides an animal model for investigating the nutritional regulation of myelopoiesis and immune response, as well as a useful tool for high-throughput drug/nutrition screening.

5.
Sci Rep ; 14(1): 8892, 2024 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632335

RESUMO

There is a lack of studies that concurrently differentiate the effect of the holiday season from the weekend effect on mortality risk in patients with acute myocardial infarction (AMI). We evaluated the mortality risk among patients admitted with AMI who underwent percutaneous coronary intervention, using data from the Taiwan National Health Insurance Research Database. Adult AMI patients admitted during January and February between 2013 and 2020 were enrolled and classified into the holiday season (using the Chinese New Year holiday seasons as an indicator) (n = 1729), weekend (n = 4725), and weekday (n = 14,583) groups according to the first day of admission. A multivariable logistic regression model was used to assess the risk. With the weekday group or the weekend group as the reference, the holiday season group did not have increased risks of in-hospital mortality (adjusted odds ratio [aOR] 1.15; 95% confidence intervals [CI] 0.93-1.42 or aOR 1.23; 95% CI 0.96-1.56) and 7-day mortality (aOR 1.20; 95% CI 0.90-1.58 or aOR 1.24; 95% CI 0.90-1.70). Stratified and subgroup analyses showed similar trends. We conclude that holiday season-initiated admissions were not associated with higher mortality risks in AMI admission cases than weekday or weekend admissions.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Adulto , Humanos , Férias e Feriados , Taiwan , Fatores de Tempo , Fatores de Risco , Mortalidade Hospitalar , Admissão do Paciente , Estudos Retrospectivos
6.
Cardiovasc Endocrinol Metab ; 13(2): e0300, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38633361

RESUMO

Due to the global prevalence of hyperuricemia (HUA), there is growing interest in research on uric acid (UA). HUA is a common condition that has various adverse consequences, including gout and kidney disease. However, recent studies have also implicated UA in the development of cardiovascular diseases (CVD) such as atrial fibrillation (AF) and coronary heart disease (CHD). Experimental and clinical research has extensively demonstrated the detrimental effects of elevated serum UA levels on cardiovascular health. Furthermore, serum UA levels have been identified as predictors of CVD outcomes following percutaneous coronary intervention (PCI) and catheter ablation. Additionally, the use of UA-lowering therapy holds important implications for the management of CVD. This review aims to consolidate the current evidence on the relationship between serum UA and CVD.

7.
Environ Sci Technol ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656157

RESUMO

Large volumes of water are used in energy production for both primary (e.g., fuel extraction) and secondary energy (e.g., electricity). In countries such as China, with a large internal trade in fuels and long-distance transmission grids, this can result in considerable water inequalities. Previous research focused on the water impacts of energy production at the national and provincial levels, which is too coarse to identify the spatial differences and make specific case studies. Here, we take the next step toward a spatially explicit economically integrated water-use for energy assessment by combining a bottom-up assessment approach with a city-level multiregional input-output model. Specifically, we examine the water consumption of energy production in China, distinguishing between water for primary and secondary energy at the level of coal mines, oil and gas fields, and power plants for the first time. Of the total energy-related freshwater consumption of 4.9 Gm3 in 2017, primary energy accounted for 19% (940 Mm3) and secondary energy accounted for 81% (3955 Mm3). Coal was the largest water consumer for both primary and secondary energy (540 and 3880 Mm3, respectively), with both oil (361, and 0.5 Mm3, respectively) and gas (7 and 69 Mm3, respectively) also consuming large amounts. Intercity virtual water, that is, water embodied in energy trade across cities, reached 54% (2.6 Gm3) of energy-related freshwater consumption. Across China, 32% of cities see a bilateral trade in secondary- and primary-energy-related virtual water (e.g., Daqing city exports virtual water embodied in primary fuel to other cities that is then used to produce electricity in those cities, part of which is used back in Daqing via transmission). For these 32% of cities, 73% export more virtual water than import and 27% import more virtual water than export. This study reveals significant differences in city-level virtual water patterns (e.g., scale and direction) between primary and secondary energy to provide information for cities about their virtual water inflow and outflow and the potential collaboration partners for water management.

8.
Ann Surg Treat Res ; 106(4): 225-230, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38586557

RESUMO

Purpose: Whether a dilated intrahepatic bile duct (IHBD) has any effect on the prognosis of choledochal cyst (CC) remains controversial. We aimed to summarize the clinical characteristics and prognosis of CC with IHBD dilatation. Methods: One hundred ninety-two children diagnosed with CC were identified, including 127 without IHBD dilatation (group A) and 65 with IHBD dilatation (group B). A retrospective analysis was performed to explore the clinical characteristics and prognosis of CC with IHBD dilatation based on clinical indices, symptoms, and complications. Results: Compared with group A, incidences of jaundice and fever were higher in group B (P = 0.010 and P = 0.033). Preoperative total bilirubin, direct bilirubin, and indirect bilirubin were increased in group B compared to group A (P = 0.005, P < 0.001, and P = 0.014), as were preoperative ALT, AST, γ-GT, and total bile acid (P = 0.006, P = 0.025, P < 0.001, and P = 0.024). The risk of liver fibrosis or cirrhosis was significantly increased for group B compared with group A (P = 0.012) and also occurred earlier in group B (P = 0.006). In the dilated IHBDs, 95.4% (62 of 65) recovered to normal, and more than half of dilated IHBDs (37 of 65) recovered to normal in 1 week. Conclusion: Most IHBDs can recover to normal postoperatively in a short time, and proactive treatment is recommended for CC patients with IHBD dilatation for significant abnormal liver functions.

9.
World J Gastroenterol ; 30(10): 1420-1430, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38596496

RESUMO

BACKGROUND: Various animal models have been used to explore the pathogenesis of choledochal cysts (CCs), but with little convincing results. Current surgical techniques can achieve satisfactory outcomes for treatment of CCs. Consequently, recent studies have focused more on clinical issues rather than basic research. Therefore, we need appropriate animal models to further basic research. AIM: To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs. METHODS: Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group, sham surgical group, or control group. A rat model of CC was established by partial ligation of the bile duct. The reliability of the model was confirmed by measurements of serum biochemical indices, morphology of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues. RESULTS: Dilation classified as mild (diameter, ≥ 1 mm to < 3 mm), moderate (≥ 3 mm to < 10 mm), and severe (≥ 10 mm) was observed in 17, 17, and 2 rats in the surgical group, respectively, while no dilation was observed in the control and sham surgical groups. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery, while direct bilirubin, total bilirubin, and gamma-glutamyltransferase were further increased 14 d after surgery. Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery. The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues. CONCLUSION: The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC, which may contribute to investigating the pathogenesis of CC.


Assuntos
Cisto do Colédoco , Humanos , Feminino , Ratos , Animais , Cisto do Colédoco/cirurgia , Reprodutibilidade dos Testes , Ratos Sprague-Dawley , Modelos Animais , Dilatação Patológica , Bilirrubina , Modelos Animais de Doenças
10.
Clin J Pain ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38595082

RESUMO

OBJECTIVE: The aim of our meta-analysis was to systematically assess the enduring effectiveness and safety of high-frequency spinal stimulation (HF-SCS) in the management of chronic pain. METHODS: We developed a comprehensive literature search strategy to identify clinical trials investigating the efficacy of high-frequency spinal stimulation for chronic pain. The search was conducted in multiple databases, including Web of Science, Cochrane, PubMed, and Embase, covering the period from 2004 to 2023. The inclusion and exclusion criteria established for this study were applied to screen the eligible literature by carefully reviewing abstracts and, when necessary, examining the full text of selected articles. To assess the quality of the included studies, we utilized the risk of bias assessment tool provided by the Cochrane Collaboration.The PRISMA method was followed for the selection of articles, and the quality of the articles was evaluated using the risk assessment table for bias provided by the Cochrane Collaboration.Meta-analysis of the selected studies was performed using Review Manager 5.4 and STATA 16.0. Effect sizes for continuous data were reported as mean differences (MD) or standardized mean differences (SMD), while categorical data were analyzed using relative risks (RR). RESULTS: According to our predefined literature screening criteria, a total of seven English-language randomized controlled trials (RCTs) were included in the meta-analysis. The findings from the meta-analysis demonstrated that high-frequency spinal cord stimulation (HF-SCS) exhibited superior efficacy in the long-term treatment of chronic pain when compared to the control group (RR = 2.44, 95% CI [1.20, 4.96], P = 0.01). Furthermore, HF-SCS demonstrated a statistically significant improvement in the Oswestry Disability Index score (mean difference MD = 3.77, 95% CI [1.17, 6.38], P = 0.005).However, for pain assessment (standardized mean difference SMD = -0.59, 95% CI [-1.28, 0.10], P = 0.09), Patient Global Impression of Improvement (PGI-I) score (MD = 0.11, 95% CI [-0.66, 0.88], P = 0.78 for 6 months; MD = 0.02, 95% CI [-0.42, 0.43], P = 0.97 for 12 months), Clinical Global Impression of Improvement (CGI-I) score (MD = -0.58, 95% CI [-1.62, 0.43], P = 0.27 for 6 months; MD = -0.23, 95% CI [-0.94, 0.48], P = 0.52 for 12 months), and occurrence of adverse effects (odds ratio OR = 0.77, 95% CI [0.23, 2.59], P = 0.67) from a statistical point of view, HF-SCS did not show sufficient effect compared with the control group. Not significant enough to consider it. CONCLUSIONS: The findings from our comprehensive review and meta-analysis, encompassing research from 2004 to 2023, offer encouraging data about the prolonged efficacy and safety of HF-SCS in chronic pain management. Nonetheless, recognizing the constraints of the existing evidence is crucial. Upcoming clinical trials, meticulously planned and stringent, are essential to bolster the current body of evidence and reach more conclusive findings.

11.
Gut ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38621924

RESUMO

OBJECTIVE: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN: Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed. RESULTS: Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial. CONCLUSIONS: This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation. TRIAL REGISTRATION NUMBER: NCT03202498.

12.
Free Radic Biol Med ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615890

RESUMO

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is one of the liver illnesses that may be affected by mitophagy, which is the selective removal of damaged mitochondria. RNF31, an E3 ubiquitin ligase, is carcinogenic in many malignancies. However, the influence of RNF31 on mitochondrial homeostasis and NAFLD development remains unknown. METHODS: Oleic-palmitic acid treated hepatocytes and high-fat diet (HFD)-fed mice were established to observe the effect of RNF31 on hepatocyte mitophagy and steatosis. Mitophagy processes were comprehensively assessed by mt-Keima fluorescence imaging, while global changes in hepatic gene expression were measured by RNA-seq. RESULTS: The present study discovered a reduction in RNF31 expression in lipotoxic hepatocytes with mitochondrial dysfunction. The observed decrease in RNF31 expression was associated with reduced mitochondrial membrane potential, disturbed mitophagy, and increased steatosis. Additionally, the findings indicated that RNF31 is a pivotal factor in the initiation of mitophagy and the facilitation of mitochondrial homeostasis, resulting in a decrease in steatosis in lipotoxic hepatocytes. Mechanistically, RNF31 enhanced p53 ubiquitination and subsequent proteasomal degradation. Down-regulation of p53 led to increased expression of the mitophagy receptor protein BCL2 and adenovirus E1B 19 kDa-interacting protein 3 (BNIP3), thereby promoting mitophagy in hepatocytes. Furthermore, it was demonstrated that the transportation of RNF31 via small extracellular vesicles derived from mesenchymal stem cells (referred to as sEV) had a substantial influence on reducing hepatic steatosis and restoring liver function in HFD-fed mice. CONCLUSIONS: The findings highlight RNF31's essential role in the regulation of mitochondrial homeostasis in hepatocytes, emphasizing its potential as a therapeutic target for NAFLD.

13.
QJM ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38603614
14.
Front Pharmacol ; 15: 1282480, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38666023

RESUMO

Objective: FL058 is a novel beta-lactamase inhibitor with a broad spectrum of activity and a favorable safety profile. The objective of this study was to evaluate pharmacokinetic/pharmacodynamic (PK/PD) relationships for the combination of FL058 and meropenem in an in vitro infection model. Methods: By simulating human concentration-time profiles in the in vitro model, meropenem combined with FL058 when administered 1 g/0.5 g, 1 g/1 g, 2 g/1 g, and 2 g/2 g q8h by 3-h infusion achieved approximately 2- and 4-log10 kill to KPC/OXA-producing Klebsiella pneumoniae and Escherichia coli; the combination therapy could not inhibit NDM-producing K. pneumoniae but could maintain NDM-producing E. coli around a baseline. Results: The PK/PD indexes that best described the bacterial killing from baseline in log10 CFU/mL at 24 h were the percent time of free drug above the minimal inhibitory concentration (MIC) (%fT > MIC, MIC with FL058 at 4 mg/L) for meropenem and the percent time of free drug above 1 mg/L (%fT > 1 mg/L) for FL058. The targets for achieving a static effect and the 1- and 2-log10 kill were 74, 83, and 99 for %fT > MIC of meropenem and 40, 48, and 64 for %fT > 1 mg/L of FL058, respectively. The PK/PD index of %fT > 1 mg/L can provide a basis for evaluating clinical dosing regimens for FL058 combined with meropenem. Conclusion: FL058 combined with meropenem might be a potential treatment for KPC- and/or OXA-48-producing Enterobacterales infection.

15.
Biotechnol J ; 19(3): e2300706, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38479984

RESUMO

4-cyanobenzoic acid serves as a crucial intermediate for the synthesis of various high-value organic compounds. The enzymatic hydrolysis of terephthalonitrile to produce 4-cyanobenzoic acid using nitrilase offers the advantages of a simple reaction pathway, environmental friendliness, and easy product separation. In order to efficiently develop nitrilases that meet industrial production requirements, the virtual screening method used in the study is established and mature. From a total of 371 amino acids in the nitrilase AfNIT, which exhibits activity in terephthalonitrile hydrolysis, three candidate sites (F168, S192, and T201) were identified, and a "small and accurate" mutant library was constructed. The triple mutant F168V/T201N/S192F was screened from this small mutant library with a specific activity of 227.3 U mg-1 , which was 3.8 times higher than that of the wild-type AfNIT. Using the whole-cell biocatalyst containing the mutant F168V/T201N/S192F, terephthalonitrile was successfully hydrolyzed at a concentration of 150 g L-1 to produce 4-cyanobenzoic acid with a final yield of 170.3 g L-1 and a conversion rate of 98.7%. The obtained nitrilase mutant F168V/T201N/S192F in this study can be effectively applied in the biomanufacturing of 4-cyanobenzoic acid using terephthalonitrile as a substrate. Furthermore, the results also demonstrate the significant improvement in predictive accuracy achieved through the latest AI-assisted computer simulation methods. This approach represents a promising and feasible new technological pathway for assisting enzyme engineering research, laying a theoretical foundation for other related studies.


Assuntos
Aminoidrolases , Benzoatos , Simulação por Computador , Aminoidrolases/genética , Aminoidrolases/química
16.
World J Pediatr ; 20(4): 325-339, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38509432

RESUMO

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a relatively uncommon but severe pediatric complication, is associated with coronavirus disease 2019 (COVID-19). A variety of treatment approaches, including intravenous immunoglobulins (IVIGs), glucocorticoids (GCs) and biologic agents, such as anakinra and infliximab, have been described for the management of COVID-19-related MIS-C. Anticoagulant therapy is also important. However, a well-developed treatment system has not been established, and many issues remain controversial. Several recently published articles related to the treatment of MIS-C have been released. Hence, in this review, we identified relevant articles published recently and summarized the treatment of MIS-C more comprehensively and systematically. DATA SOURCES: We reviewed the literature on the treatment of MIS-C through 20 September 2023. The PubMed/Medline, Web of Science, EMBASE, and Cochrane Library databases were searched with the combination of the terms "multisystem inflammatory syndrome", "MIS-C", "PIMS-TS", "therapy", "treatment", "drug", "IVIG", "GCs", "intravenous immunoglobulin", "corticosteroids", "biological agent", and "aspirin". RESULTS: The severity of MIS-C varies, and different treatment schemes should be used according to the specific condition. Ongoing research and data collection are vital to better understand the pathophysiology and optimal management of MIS-C. CONCLUSIONS: MIS-C is a disease involving multiple systems and has great heterogeneity. With the accumulation of additional experience, we have garnered fresh insights into its treatment strategies. However, there remains a critical need for greater standardization in treatment protocols, alongside the pressing necessity for more robust and meticulously conducted studies to deepen our understanding of these protocols. Supplementary file1 (MP4 208044 kb).


Assuntos
COVID-19/complicações , Glucocorticoides , Imunoglobulinas Intravenosas , Síndrome de Resposta Inflamatória Sistêmica , Humanos , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Criança , Imunoglobulinas Intravenosas/uso terapêutico , Glucocorticoides/uso terapêutico , Tratamento Farmacológico da COVID-19
17.
Chem Commun (Camb) ; 60(28): 3798-3801, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38483079

RESUMO

Herein, we report a scandium-catalyzed chemoselective carbene insertion into a N-H bond over a S-H bond with disulfide formation. This reaction represents the first example of the synthesis of o-alkylamine-diaryl disulfides through the N-alkylation of o-aminobenzenethiol, while also undergoing oxidative coupling to form a S-S bond. Control experiments explain the chemo-selectivity of this rare-earth-metal Lewis acid-induced catalysis by a carbene outer-sphere nucleophilic addition mechanism. This method holds tremendous potential as a valuable tool for functionalizing advanced-synthetic-intermediates, offering numerous applications in medicinal and materials chemistry.

18.
Ying Yong Sheng Tai Xue Bao ; 35(1): 203-211, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38511457

RESUMO

Liangshan Prefecture is one of the three major forest areas in Sichuan Province and one of the three major disaster areas of forest fire. We measured the physicochemical properties and combustion performances of different organs (leaves and branches) of 15 main economic tree species in Liangshan, and analyzed the bioecology characteristics, silviculture characteristics and value characteristics of different tree species. We investigated the fire resistance of different tree species to screen out fire-resistant species suitable for economic forest development in Liangshan Prefecture, and improve the biological fire prevention ability. The seven physicochemical properties and combustion performances indices of 15 tree species showed significant differences. Except for crude ash and lignin, the weights of moisture content, caloric value, ignition point, crude fat, and crude fibre of leaves were higher than those of branches. Crude fibre index of leaves (9.6%) and the crude ash index of branches (9.9%) were the highest weight indices of the two organs, respectively. Based on the fire resistance, we divided all the species into three classes, i.e., class Ⅰ (excellent fire-resistance trees) Juglans regia and Morus alba; class Ⅱ (better fire-resistant trees) Sapium sebiferum, Mangifera indica, Phyllanthus emblica, Eriobotrya japonica, Ligustrum lucidum, Castanea mollissima, and Punica granatum; class Ⅲ (poor fire-resistant trees) Pinus armandii, Illicium simonsii, Morella rubra, Sapindus mukorossi, Olea europaea and Camellia oleifera. J. regia and M. alba had fireproof solid performance and could be used as the preferred species for fireproof economic forest in Liangshan region. It was suggested that to use class Ⅰ to Ⅱ fire-resistant tree species built the main fireproof isolated forest belt, and pay attention to fire prevention after planting class Ⅲ tree species in a large area.


Assuntos
Incêndios , Incêndios Florestais , Árvores , Florestas , China
19.
Artigo em Chinês | MEDLINE | ID: mdl-38297864

RESUMO

Objective:To study the feasibility and efficacy of using a tympanic cartilage shaping device in endoscopic type Ⅰ tympanoplasty. Methods:A tympanic cartilage shaper was designed and manufactured by measuring tympanic membrane dimensions with HRCT imaging for cutting and shaping cartilage to repair the tympanic membrane. From August 2019 to October 2021, 66 patients(72 ears) with chronic suppurative otitis media in Xiangya Hospital underwent endoscopic type Ⅰ tympanoplasty with this tympanic cartilage shaping device, and were observed the tympanic membrane healing and hearing recovery effect after surgery. Postoperative follow-up ranged from 3-24 months, with an average of 9 months. The data were analyzed by the SPSS 26.0 software. Results:According to the imaging measurements, tympanic pars tensa width(8.60±0.20) mm, height(8.64±0.19) mm, design and manufacture a cylindrical cartilage shaping device with inner diameter 8.60 mm. After tympanoplasty, the healing rate of tympanic membrane was 100%; The average air-bone gap before surgery was(23.10±7.33) dB, then(14.30±6.40) dB 1 month after surgery, which were significant reduced compared with those before surgery. The average air-bone gap was(14.30±6.40) dB 3 month after surgery compared with 1 month after surgery, the difference was also statistically significant(t=6.630, P<0.05). Conclusion:The tympanic membrane cartilage shaper shaping cartilage in endoscopic tympanoplasty is simple, stable and reliable, which can reduce the time of graft cartilage processing, improve the efficiency of surgery, and restore the tympanic membrane morphology and function in the postoperative period.


Assuntos
Perfuração da Membrana Timpânica , Membrana Timpânica , Humanos , Membrana Timpânica/cirurgia , Timpanoplastia/métodos , Perfuração da Membrana Timpânica/cirurgia , Resultado do Tratamento , Cartilagem/transplante , Estudos Retrospectivos
20.
Crit Rev Food Sci Nutr ; : 1-11, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38356229

RESUMO

Immunoassay based on the antibodies specific for targets has advantages of high sensitivity, simplicity and low cost, therefore it has received more attention in recent years, especially for the rapid detection of small molecule chemicals present in foods, diagnostics and environments. However, limited by low molecular weight and only one antigenic determinant existed, immunoassays for these small molecule chemicals, namely hapten substances, were commonly performed in a competitive immunoassay format, whose sensitivities were obviously lower than the sandwich enzyme-linked immunosorbent assay generally adaptable for the protein targets. In order to break through the bottleneck of detection format, researchers have designed and established several novel noncompetitive immunoassays for the haptens in the past few years. In this review, we focused on the four representative types of noncompetitive immunoassay formats and described their characteristics and applications in rapid detection of small molecules. Meanwhile, a systematic discussion on the current technologies challenges and the possible solutions were also summarized. This review aims to provide an updated overview of the current state-of-the-art in noncompetitive immunoassay for small molecules, and inspire the development of novel designs for small molecule detection.

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