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1.
Small ; 20(27): e2310972, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38282180

RESUMO

Recently, aqueous zinc-ion batteries with conversion mechanisms have received wide attention in energy storage systems on account of excellent specific capacity, high power density, and energy density. Unfortunately, some characteristics of cathode material, zinc anode, and electrolyte still limit the development of aqueous zinc-ion batteries possessing conversion mechanism. Consequently, this paper provides a detailed summary of the development for numerous aqueous zinc-based batteries: zinc-sulfur (Zn-S) batteries, zinc-selenium (Zn-Se) batteries, zinc-tellurium (Zn-Te) batteries, zinc-iodine (Zn-I2) batteries, and zinc-bromine (Zn-Br2) batteries. Meanwhile, the reaction conversion mechanism of zinc-based batteries with conversion mechanism and the research progress in the investigation of composite cathode, zinc anode materials, and selection of electrolytes are systematically introduced. Finally, this review comprehensively describes the prospects and outlook of aqueous zinc-ion batteries with conversion mechanism, aiming to promote the rapid development of aqueous zinc-based batteries.

2.
Anticancer Drugs ; 35(2): 195-198, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38018809

RESUMO

Cetuximab [the epidermal growth factor receptor (EGFR)-targeting mAb] improves clinical outcomes when added to standard chemotherapy used in the treatment of metastatic colorectal cancer. Patients with hotspot mutations in Kirsten rat sarcoma viral oncogene ( KRAS ) mutation in exon 2 were not recommended to be treated with cetuximab. However, there is still a lack of clinical data for those unreported non-hotspot KRAS mutations in exon 2 and their response to cetuximab. In this study, we reported a 35-year-old woman who was diagnosed with stage IVA CRC with liver metastases. An exceptionally uncommon KRASP34R mutation in KRAS exon 2 was detected in tumor specimens by next-generation sequencing. This patient obtained limited benefit from first-line chemotherapy and did not respond to cetuximab in the second-line course. In the third-line course, the patient also did not respond to the combination treatment of furaquitinib and cindilimab. The patient died 8 months after treatment initiation. In this study, we found amplification of the rare oncogenic KRASP34R was not only associated with an aggressive phenotype, but also supported cancer resistance to cetuximab, chemotherapy, and immunotherapy.


Assuntos
Antineoplásicos , Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Feminino , Humanos , Adulto , Cetuximab/uso terapêutico , Antineoplásicos/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Mutação
3.
J Org Chem ; 89(11): 7804-7811, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38738759

RESUMO

A straightforward methodology for the assembly of polysubstituted naphthalenes from ortho-alkynyl benzyl alcohols, enabled by using catalytic amounts of Tf2O, has been developed. This transformation not only features transition-metal free and without using other bases and additives but also provides a new synthetic application for ortho-alkynyl benzyl alcohols, i.e., as C6 synthons for the construction of PAHs.

4.
J Environ Manage ; 357: 120828, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38579473

RESUMO

Based on the concept of source separation of brown water (BW, human feces with flushing water) and yellow water (urine) in rural area, anaerobic co-digestion of BW with agricultural waste is a promising and effective method for rural waste treatment and resource recovery. The purpose of this study was to investigate the performance of different agricultural wastes (peanut straw (PST), peanut shell (PSH), swine wastewater acting as co-substrate for anaerobic co-digestion with BW, and the relative mechanisms were explored. When the mixed ratio was uniformly set as 1:1 (mass ratio, measured by volatile solid (VS)) and initial VS load as 20 g/L, the maximum cumulative methane production obtained by co-digestion (21 days) of BW and PST was 688 mL/g-VS, which performed better than the individual substrates (341 mL/g-VS), as well as the average of the sole BW and sole PST groups (531.2 mL/g-VS). The most impactful advantage was ascribed to the promotion of hydrolytic and acidogenic enzyme activities. The addition of PST also reduced the production of endogenous humus, which is difficult for biodegradation. Microbial community analysis showed that different co-substrates would affect the microbial community composition in the reactor. The relative abundance of hydrolytic acidogens in the PST and PSH co-digestion groups were higher than that in the SW co-digestion and sole BW groups, and the methanogenic archaea were dominated by the acetate-trophic Methanotrichaceae. The overall results suggest that anaerobic co-digestion is a feasible method, and co-digestion of BW and PST can improve methane production potential.


Assuntos
Reatores Biológicos , Água , Humanos , Animais , Suínos , Anaerobiose , Água/análise , Fezes , Digestão , Metano/análise
5.
J Cell Mol Med ; 27(6): 788-802, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36811277

RESUMO

Pancreatic cancer (PAAD) is a highly malignant tumour characterized of high mortality and poor prognosis. Huntingtin-interacting protein 1-related (HIP1R) has been recognized as a tumour suppressor in gastric cancer, while its biological function in PAAD remains to be elucidated. In this study, we reported the downregulation of HIP1R in PAAD tissues and cell lines, and the overexpression of HIP1R suppressed the proliferation, migration and invasion of PAAD cells, while silencing HIP1R showed the opposite effects. DNA methylation analysis revealed that the promoter region of HIP1R was heavily methylated in PAAD cell lines when compared to the normal pancreatic duct epithelial cells. A DNA methylation inhibitor 5-AZA increased the expression of HIP1R in PAAD cells. 5-AZA treatment also inhibited the proliferation, migration and invasion, and induced apoptosis in PAAD cell lines, which could be attenuated by HIP1R silencing. We further demonstrated that HIP1R was negatively regulated by miR-92a-3p, which modulates the malignant phenotype of PAAD cells in vitro and the tumorigenesis in vivo. The miR-92a-3p/HIP1R axis could regulate PI3K/AKT pathway in PAAD cells. Taken together, our data suggest that targeting DNA methylation and miR-92a-3p-mediated repression of HIP1R could serve as novel therapeutic strategies for PAAD treatment.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , Humanos , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Metilação de DNA , Fosfatidilinositol 3-Quinases/metabolismo , Movimento Celular/genética , Linhagem Celular Tumoral , Neoplasias Pancreáticas/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteínas dos Microfilamentos/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Pancreáticas
6.
J Biol Chem ; 298(12): 102708, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36402444

RESUMO

Fasting hyperglycemia in diabetes mellitus is caused by unregulated glucagon secretion that activates gluconeogenesis (GNG) and increases the use of pyruvate, lactate, amino acids, and glycerol. Studies of GNG in hepatocytes, however, tend to test a limited number of substrates at nonphysiologic concentrations. Therefore, we treated cultured primary hepatocytes with three identical substrate mixtures of pyruvate/lactate, glutamine, and glycerol at serum fasting concentrations, where a different U-13C- or 2-13C-labeled substrate was substituted in each mix. In the absence of glucagon stimulation, 80% of the glucose produced in primary hepatocytes incorporated either one or two 13C-labeled glycerol molecules in a 1:1 ratio, reflecting the high overall activity of this pathway. In contrast, glucose produced from 13C-labeled pyruvate/lactate or glutamine rarely incorporated two labeled molecules. While glucagon increased the glycerol and pyruvate/lactate contributions to glucose carbon by 1.6- and 1.8-fold, respectively, the glutamine contribution to glucose carbon was increased 6.4-fold in primary hepatocytes. To account for substrate 13C carbon loss during metabolism, we also performed a metabolic flux analysis, which confirmed that the majority of glucose carbon produced by primary hepatocytes was from glycerol. In vivo studies using a PKA-activation mouse model that represents elevated glucagon activity confirmed that most circulating lactate carbons originated from glycerol, but very little glycerol was derived from lactate carbons, reflecting glycerol's importance as a carbon donor to GNG. Given the diverse entry points for GNG substrates, hepatic glucagon action is unlikely to be due to a single mechanism.


Assuntos
Glucagon , Gluconeogênese , Camundongos , Animais , Glucagon/metabolismo , Glicerol/metabolismo , Glutamina/metabolismo , Glucose/metabolismo , Fígado/metabolismo , Lactatos/metabolismo , Ácido Láctico/metabolismo , Ácido Pirúvico/metabolismo , Carbono/metabolismo
7.
Small ; 19(50): e2304504, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37635108

RESUMO

Aqueous zinc-ion batteries (AZIBs) are considered to be one of the most promising devices for large-scale energy storage systems owing to their high theoretical capacity, environmental friendliness, and safety. However, the ionic intercalation or surface redox mechanisms in conventional cathode materials generally result in unsatisfactory capacities. Conversion-type aqueous zinc-tellurium (Zn-Te) batteries have recently gained widespread attention owing to their high theoretical specific capacities. However, it remains an enormous challenge to improve the slow kinetics of the aqueous Zn-Te batteries. Here, MoO2 nanoclusters embedded in hierarchical nitrogen-doped carbon nanoflower (MoO2 /NC) hosts are successfully synthesized and loaded with Te in aqueous Zn-Te batteries. Benefitting from the highly dispersed MoO2 nanoclusters and hierarchical nanoflower structure with a large specific surface area, the electrochemical kinetics of the Te redox reaction are significantly improved. As a result, the Te-MoO2 /NC electrode exhibits superior cycling stability and a high specific capacity of 493 mAh g-1 at 0.1 A g-1 . Meanwhile, the conversion mechanism is systematically explored using a variety of ex situ characterization methods. Therefore, this study provides a novel approach for enhancing the kinetics of the Te redox reaction in aqueous Zn-Te batteries.

8.
BMC Gastroenterol ; 23(1): 195, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37277756

RESUMO

BACKGROUND: At present, the relationship between severe acute pancreatitis (SAP) and albumin infusion is not clear. We aimed to identify the impact of serum albumin on the prognosis of SAP and the association between albumin infusions and mortality for hypoalbuminemia patients. METHODS: This was a retrospective cohort study that analyzed 1000 patients with SAP who were admitted to the First Affiliated Hospital of Nanchang University between January 2010 and December 2021 using data from a prospectively maintained database. Multivariate logistic regression analysis was conducted to reveal the relationship between serum albumin within 1 week after admission and poor prognosis of SAP. Propensity score matching (PSM) analysis was adopted to evaluate the effect of albumin infusion for hypoalbuminemia patients with SAP. RESULTS: The prevalence of hypoalbuminemia (≤ 30 g/L) was 56.9% within 1 week after admission. Multivariate logistic regression identified that age (OR: 1.02; 95% CI: 1.00-1.04; P = 0.012), serum urea (OR: 1.08; 95% CI: 1.04-1.12; P < 0.001), serum calcium (OR: 0.27; 95% CI: 0.14-0.50; P < 0.001), lowest albumin level within 1 week after admission (OR: 0.93; 95% CI: 0.89-0.97; P = 0.002), and APACHE II score ≥ 15 (OR: 1.73; 95% CI: 1.19-2.51; P = 0.004) were independently associated with mortality. The PSM analysis demonstrated that mortality (OR: 0.52, 95% CI: 0.29-0.92, P = 0.023) was less common in albumin-infused than non-albumin-infused hypoalbuminemia patients. In subgroup analyses, doses > 100 g within 1 week after admission for hypoalbuminemia patients with albumin infusions was associated with lower mortality than doses ≤ 100 g (OR: 0.51, 95% CI: 0.28-0.90, P = 0.020). CONCLUSIONS: Hypoalbuminemia in early-stage SAP is significantly related to poor prognosis. However, albumin infusions could significantly decrease mortality in hypoalbuminemia patients with SAP. Additionally, infusing sufficient albumin within a week after admission may decrease mortality in hypoalbuminemia patients.


Assuntos
Hipoalbuminemia , Pancreatite , Humanos , Pancreatite/complicações , Pancreatite/tratamento farmacológico , Estudos Retrospectivos , Doença Aguda , Albumina Sérica , Prognóstico , Fatores de Risco
9.
Can Assoc Radiol J ; 74(2): 455-461, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36301082

RESUMO

Purpose: To evaluate a novel laser angle selection system (LASS) for improving the efficiency of a computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB). Methods: Thirty-eight patients referred for CT-guided PTNB were randomly separated into a LASS-assisted puncture group (18 patients) or conventional freehand control group (20 patients). The puncture time, number of control CT scans, and patients' radiation dose were compared for each group. Results: The lesion size, target-to-pleural distance, planned puncture depth, and angle of the two groups were not significantly different. LASS-assisted PTNB significantly reduced the number of control scans (1.7 ± 0.8 vs 3.5 ± 1.5, P < .001) and the mean operation time (12.0 ± 4.3 min vs 28.8 ± 13.3 min, P < .001) compared with the conventional method. The corresponding room time (27.1 ± 6.6 min vs 44.1 ± 14.4 min, P < .001) and total radiation dose (7.9 ± 1.0 mSv vs 10.1 ± 1.7 mSv, P < .001) of each procedure also decreased significantly. Fifty-six percent (10/18) of the operations hit the target on the first needle pass when using LASS compared with 10% (2/20) using the conventional method. Conclusions: Compared with a conventional method, this novel laser angle simulator improves puncture efficiency with fewer needle readjustments and reduces patient radiation dose.


Assuntos
Biópsia Guiada por Imagem , Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Biópsia Guiada por Imagem/métodos , Biópsia por Agulha/métodos , Tomografia Computadorizada por Raios X/métodos , Lasers , Neoplasias Pulmonares/patologia , Pulmão/patologia , Radiografia Intervencionista/métodos
10.
Hum Mol Genet ; 29(9): 1405-1416, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31373354

RESUMO

Dominant TBX5 mutation causes Holt-Oram syndrome (HOS), which is characterized by limb defects in humans, but the underlying mechanistic basis is unclear. We used a mouse model with Tbx5 conditional knockdown in Hh-receiving cells (marked by Gli1+) during E8 to E10.5, a previously established model to study atrial septum defects, which displayed polydactyly or hypodactyly. The results suggested that Tbx5 is required for digit identity in a subset of limb mesenchymal cells. Specifically, Tbx5 deletion in this cell population decreased cell apoptosis and increased the proliferation of handplate mesenchymal cells. Furthermore, Tbx5 was found to negatively regulate the Hh-signaling activity through transcriptional regulation of Ptch1, a known Hh-signaling repressor. Repression of Hh-signaling through Smo co-mutation in Tbx5 heterozygotes rescued the limb defects, thus placing Tbx5 upstream of Hh-signaling in limb defects. This work reveals an important missing component necessary for understanding not only limb development but also the molecular and genetic mechanisms underlying HOS.


Assuntos
Anormalidades Múltiplas/genética , Cardiopatias Congênitas/genética , Comunicação Interatrial/genética , Proteínas Hedgehog/genética , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas das Extremidades Inferiores/genética , Receptor Patched-1/genética , Proteínas com Domínio T/genética , Deformidades Congênitas das Extremidades Superiores/genética , Anormalidades Múltiplas/patologia , Animais , Apoptose/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Cardiopatias Congênitas/patologia , Comunicação Interatrial/patologia , Humanos , Deformidades Congênitas dos Membros/patologia , Deformidades Congênitas das Extremidades Inferiores/patologia , Camundongos , Mutação/genética , Transdução de Sinais/genética , Receptor Smoothened/genética , Deformidades Congênitas das Extremidades Superiores/patologia
11.
BMC Cancer ; 22(1): 163, 2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35148700

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common malignancies worldwide. Noninvasive imaging techniques, such as magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET), have been involved in increasing evolution to detect RCC. This meta-analysis aims to compare to compare the performance of MRI, SPECT, and PET in the detection of RCC in humans, and to provide evidence for decision-making in terms of further research and clinical settings. METHODS: Electronic databases including PubMed, Web of Science, Embase, and Cochrane Library were systemically searched. The keywords such as "magnetic resonance imaging", "MRI", "single-photon emission computed tomography", "SPECT", "positron emission tomography", "PET", "renal cell carcinoma" were used for the search. Studies concerning MRI, SPECT, and PET for the detection of RCC were included. Pooled sensitivity, specificity, and the area under the summary receiver operating characteristic (SROC) curve (AUC), etc. were calculated. RESULTS: A total of 44 articles were finally detected for inclusion in this study. The pooled sensitivities of MRI, 18F-FDG PET and 18F-FDG PET/CT were 0.80, 0.83, and 0.89, respectively. Their respective overall specificities were 0.90, 0.86, and 0.88. The pooled sensitivity and specificity of MRI studies at 1.5 T were 0.86 and 0.94, respectively. With respect to prospective PET studies, the pooled sensitivity, specificity and AUC were 0.90, 0.93 and 0.97, respectively. In the detection of primary RCC, PET studies manifested a pooled sensitivity, specificity, and AUC of 0.77, 0.80, and 0.84, respectively. The pooled sensitivity, specificity, and AUC of PET/CT studies in detecting primary RCC were 0.80, 0.85, and 0.89. CONCLUSION: Our study manifests that MRI and PET/CT present better diagnostic value for the detection of RCC in comparison with PET. MRI is superior in the diagnosis of primary RCC.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Detecção Precoce de Câncer/estatística & dados numéricos , Neoplasias Renais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Idoso , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Adulto Jovem
12.
Org Biomol Chem ; 20(36): 7221-7225, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36053155

RESUMO

A new synthetic methodology for the synthesis of 5H-dibenzo[a,d]cycloheptenes from ortho-aryl alkynyl benzyl alcohols and arenes via a Tf2O-mediated formal [5 + 2] annulation reaction has been achieved. From this transformation, structurally diverse 5H-dibenzo[a,d]cycloheptenes were achieved in moderate to good yields. This transformation probably involves an intermolecular Friedel-Crafts-type alkylation and a subsequent intramolecular 7-endo-dig cyclization in one pot, highlighting the high efficiency, regioselectivity, and step-economy of this protocol.

13.
BMC Pediatr ; 22(1): 568, 2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36192715

RESUMO

We tend to investigate the connection between time to appropriate therapy (TTAT) and prognosis in pediatric patients with nosocomial Klebsiella pneumoniae (K. pneumoniae) bloodstream infection, and find the optimal cutoff point for the empirical administration of antimicrobials. This retrospective study was conducted in Children's Hospital of Chongqing Medical University, and inpatients with nosocomial K. pneumoniae bloodstream infection were finally enrolled. We applied the Classification and Regression Tree (CART) analysis to find the TTAT cutoff point and the Logistic Regression analysis to evaluate prognostic indicators. The incidence of septic shock and mortality was 17.91% (12/67) and 13.43% (9/67), respectively. The CART-derived TTAT cutoff point was 10.7 h. The multivariate logistic regression analysis indicated delayed therapy (TTAT ≥ 10.7 h), pediatric risk of mortality (PRISM) III scores ≥ 10, time to positivity (TTP) ≤ 13 h, and requiring for invasive mechanical ventilation were independently associated with the incidence of septic shock (Odds ratio [OR] 9.87, 95% Confidence interval [CI] 1.46-66.59, P = 0.019; OR 9.69, 95% CI 1.15-81.39, P = 0.036; OR 8.28, 95% CI 1.37-50.10, P = 0.021; OR 6.52, 95% CI 1.08-39.51, P = 0.042; respectively) and in-hospital mortality (OR 22.19, 95% CI 1.25-393.94, P = 0.035; OR 40.06, 95% CI 2.32-691.35, P = 0.011; OR 22.60, 95% CI 1.78-287.27, P = 0.016; OR 12.21, 95% CI 1.06-140.67, P = 0.045; respectively).Conclusions: TTAT is an independent predictor of poor outcomes in children with nosocomial K. pneumoniae bloodstream infection. Initial appropriate antimicrobial therapy should be administrated timely and within 10.7 h from the onset of bloodstream infection is recommended.


Assuntos
Bacteriemia , Infecção Hospitalar , Infecções por Klebsiella , Choque Séptico , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Criança , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Humanos , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológico
14.
Liver Int ; 41(6): 1305-1319, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33529448

RESUMO

BACKGROUND & AIMS: Pregnant women may transmit their metabolic phenotypes to their offspring, enhancing the risk for nonalcoholic fatty liver disease (NAFLD); however, the molecular mechanisms remain unclear. METHODS: Prior to pregnancy female mice were fed either a maternal normal-fat diet (NF-group, "no effectors"), or a maternal high-fat diet (HF-group, "persistent effectors"), or were transitioned from a HF to a NF diet before pregnancy (H9N-group, "effectors removal"), followed by pregnancy and lactation, and then offspring were fed high-fat diets after weaning. Offspring livers were analysed by functional studies, as well as next-generation sequencing for gene expression profiles and DNA methylation changes. RESULTS: The HF, but not the H9N offspring, displayed glucose intolerance and hepatic steatosis. The HF offspring also displayed a disruption of lipid homeostasis associated with an altered methionine cycle and abnormal one-carbon metabolism that caused DNA hypermethylation and L-carnitine depletion associated with deactivated AMPK signalling and decreased expression of PPAR-α and genes for fatty acid oxidation. These changes were not present in H9N offspring. In addition, we identified maternal HF diet-induced genes involved in one-carbon metabolism that were associated with DNA methylation modifications in HF offspring. Importantly, the DNA methylation modifications and their associated gene expression changes were reversed in H9N offspring livers. CONCLUSIONS: Our results demonstrate for the first time that maternal HF diet disrupted the methionine cycle and one-carbon metabolism in offspring livers which further altered lipid homeostasis. CpG islands of specific genes involved in one-carbon metabolism modified by different maternal diets were identified.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Efeitos Tardios da Exposição Pré-Natal , Animais , Carbono/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Humanos , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Gravidez
15.
J Org Chem ; 86(1): 1002-1011, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33284023

RESUMO

An efficient method for the direct preparation of 3-aceto(cyano)methyl-substituted benzothio(seleno)phenes has been achieved through C(sp3)-H bond activation of easily available acetone or acetonitrile and cascade radical cyclization reaction. In this cascade radical cyclization reaction, C(sp2)-C(sp3) and C(sp2)-S bonds, as well as benzenethio(seleno)phene skeletons, can be built along with the cleavage of the C(sp3)-S bond, demonstrating the high step-economics and efficiency of this approach.

16.
J Environ Manage ; 296: 113152, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34217942

RESUMO

Anaerobic digestion (AD) comprises a series of biochemical reactions, with methane as one of the target products. Amino acids (AAs) are important molecular and primary intermediate products when protein is the main component of organic waste/wastewater. The L (levorotatory, left-handed)-configuration is natural for AAs, while D (dextrorotatory, right-handed) -AAs also widely exist in the natural environment and can be generated by racemization. However, the effects and underlying mechanisms of natural AAs and their enantiomers on the methane yield and the underlying mechanisms remain unclear. In this study, the effects of certain widespread L-AAs and their enantiomers on two-stage AD and the mechanisms therein were investigated. The AAs enantiomers showed variable or even opposite effects on different processes. The methane yield from a model monosaccharide (glucose) decreased by 57% with D-leucine addition. The butyrate generation and the methane yield from propionate were sensitive to the AA configuration and were inhibited by D-leucine by 80% and 61.8%, respectively, with D-leucine addition, while the volatile fatty acids concentration was slightly increased with the addition of L-leucine. The related mechanisms were further investigated in terms of key enzymes and microbial communities. The addition of D-Leucine decreased acetic acid production from homoacetogens by 30.2% due to the inhibition of key enzymes involved in hydrogen generation and consumption. The transform of butyryl CoA to butyryl phosphate was the rate-limiting step, with the related enzyme (phosphotransbutylase) was inhibited by D-leucine. Furthermore, the bacteria related to butyric acid generation and organic matter degradation were inhibited by D-leucine, while the methanogenic archaea remained stable irrespective of leucine addition. The effect of D-AAs on microorganisms is related to the type of sludge. In this study, the methanogenetic seed sludge was granular and did not dissociate after treatment; however, the D-AAs could trigger biofilm disassembly and reduce the stability of the sludge floc. The study provides a novel method for regulating AD by adding specific AAs with L or D configuration.


Assuntos
Reatores Biológicos , Metano , Aminoácidos , Anaerobiose , Biotransformação , Ácidos Graxos Voláteis , Esgotos
17.
J Biol Chem ; 294(48): 18017-18028, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31645433

RESUMO

Gluconeogenesis (GNG) is de novo production of glucose from endogenous carbon sources. Although it is a commonly studied pathway, particularly in disease, there is a lack of consensus about substrate preference. Moreover, primary hepatocytes are the current gold standard for in vitro liver studies, but no direct comparison of substrate preference at physiological fasting concentrations has been performed. We show that mouse primary hepatocytes prefer glycerol to pyruvate/lactate in glucose production assays and 13C isotope tracing studies at the high concentrations commonly used in the literature, as well as at more relevant fasting, physiological concentrations. In addition, when glycerol, pyruvate/lactate, and glutamine are all present, glycerol is responsible for over 75% of all glucose carbons labeled. We also found that glycerol can induce a rate-limiting enzyme of GNG, glucose-6-phosphatase. Lastly, we suggest that glycerol is a better substrate than pyruvate to test in vivo production of glucose in fasting mice. In conclusion, glycerol is the major carbon source for GNG in vitro and in vivo and should be compared with other substrates when studying GNG in the context of metabolic disease states.


Assuntos
Gluconeogênese/efeitos dos fármacos , Glucose-6-Fosfatase/biossíntese , Glicerol/farmacologia , Hepatócitos/metabolismo , Animais , Indução Enzimática/efeitos dos fármacos , Hepatócitos/citologia , Ácido Láctico/metabolismo , Camundongos , Ácido Pirúvico/metabolismo
18.
Lab Invest ; 100(4): 553-569, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31748681

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has a developmental origin and is influenced in utero. We aimed to evaluate if maternal diet intervention before pregnancy would be beneficial to reduce the risk of offspring NAFLD. In our study, female mice were either on a normal-fat diet (NF group), or a high-fat diet for 12 weeks and continued on this diet throughout pregnancy and lactation (HF group), or switched from HF-to-NF diet 1 week (H1N group), or 9 weeks (H9N group) before pregnancy. Compared with the NF offspring, the H1N and HF, but not the H9N offspring, displayed more severe hepatic steatosis and glucose intolerance. More specifically, an abnormal blood lipid panel was seen in the H1N offspring and abnormal hepatic free fatty acid composition was present in both the HF and H1N offspring, while the H9N offspring displayed both at normal levels. These physiological changes were associated with desensitized hepatic insulin/AKT signaling, increased expression of genes and proteins for de novo lipogenesis and cholesterol synthesis, decreased expression of genes and proteins for fatty acid oxidation, increased Pcsk9 expression, and hypoactivation of 5' AMP-activated protein kinase (AMPK) signaling in the HF and H1N offspring. However, these effects were completely or partially rescued in the H9N offspring. In summary, we found that early maternal diet intervention is effective in reducing the risk of offspring NAFLD caused by maternal HF diet. These findings provide significant support to develop effective diet intervention strategies and policies for prevention of obesity and NAFLD to promote optimal health outcomes for mothers and children.


Assuntos
Dieta Hiperlipídica , Metabolismo dos Lipídeos , Fígado/metabolismo , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Feminino , Insulina/metabolismo , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/fisiologia , Lipogênese , Masculino , Camundongos , Gravidez , Transcriptoma , Aumento de Peso/fisiologia
19.
BMC Infect Dis ; 20(1): 665, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907533

RESUMO

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a major Gram-negative pathogen, which has been reported to result in high mortality. We aim to investigate the prognostic value and optimum cut-off point of time-to-positivity (TTP) of blood culture in children with P. aeruginosa bacteremia. METHODS: From August 2014 to November 2018, we enrolled the inpatients with P. aeruginosa bacteremia in a 1500-bed tertiary teaching hospital in Chongqing, China retrospectively. Receiver operating characteristic (ROC) analysis was used to determine the optimum cut-off point of TTP, and logistic regression were employed to explore the risk factors for in-hospital mortality and septic shock. RESULTS: Totally, 52 children with P. aeruginosa bacteremia were enrolled. The standard cut-off point of TTP was18 h. Early TTP (≤18 h) group patients had remarkably higher in-hospital mortality (42.9% vs 9.7%, P = 0.014), higher incidence of septic shock (52.4% vs12.9%, P = 0.06), higher Pitt bacteremia scores [3.00 (1.00-5.00) vs 1.00 (1.00-4.00), P = 0.046] and more intensive care unit admission (61.9% vs 22.6%, P = 0.008) when compared with late TTP (> 18 h) groups. Multivariate analysis indicated TTP ≤18 h, Pitt bacteremia scores ≥4 were the independent risk factors for in-hospital mortality (OR 5.88, 95%CI 1.21-21.96, P = 0.035; OR 4.95, 95%CI 1.26-27.50, P = 0.024; respectively). The independent risk factors for septic shock were as follows: TTP ≤18 h, Pitt bacteremia scores ≥4 and hypoalbuminemia (OR 6.30, 95%CI 1.18-33.77, P = 0.032; OR 8.15, 95%CI 1.15-42.43, P = 0.014; OR 6.46, 95% CI 1.19-33.19 P = 0.031; respectively). CONCLUSIONS: Early TTP (≤18 hours) appeared to be associated with worse outcomes for P. aeruginosa bacteremia children.


Assuntos
Bacteriemia/diagnóstico , Hemocultura , Infecções por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/isolamento & purificação , Bacteriemia/mortalidade , Criança , Pré-Escolar , China , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Lactente , Unidades de Terapia Intensiva , Modelos Logísticos , Masculino , Prognóstico , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/mortalidade , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Choque Séptico/mortalidade , Centros de Atenção Terciária , Fatores de Tempo
20.
Eur J Pediatr ; 179(11): 1699, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32488736

RESUMO

The authors regrets that there is a typo error on the Abbreviation section of their published paper. "Area under the curve" should have been abbreviated to "AUC" instead of "A". The authors have requested that this be noted. The original article has been corrected.

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