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1.
Zhongguo Zhong Yao Za Zhi ; 49(14): 3971-3976, 2024 Jul.
Artículo en Chino | MEDLINE | ID: mdl-39099370

RESUMEN

The development of traditional Chinese medicine(TCM) preparations as an incubator for new drugs in medical institutions has flourished, while an evaluation index system remains to be established for comprehensively assessing the development value of these prescriptions. This study established an item pool through literature research, employed the Delphi method to determine the content of evaluation indexes, and adopted the superiority chart to determine the weight of each index. Two-level evaluation index system for the development value of TCM preparations in medical institutions was established, which included 7 first-level items and 36 se-cond-level items, demonstrating scientific validity. The first-level items(weight) were inheritance(10.61%), effectiveness(23.22%), safety(22.71%), innovation(13.21%), economy(10.00%), suitability(8.57%), and accessibility(11.68%). The top three second-level items in terms of weight distribution were adverse reaction monitoring(6.73%), evidence of therapeutic effect(5.71%), and clinical response rate(4.75%). The bottom three second-level items were production advantages(0.86%), medicinal dosage(0.48%), and medicinal smell or taste(0.18%). The content validity of the established system was assessed, which revealed that the index system was reliable, with the overall and average content validity indexes of 0.47 and 0.90, respectively. Furthermore, the established evaluation index system was used to evaluate six TCM preparations in a city-level hospital of TCM in Sichuan Province, which demonstrated that the system had operability. The results indicate that the evaluation index system is scientific, reliable, and operable, providing a reference for developers to selectively develop TCM preparations in medical institutions. In practical application, the system can be adjusted regarding the index weights according to actual conditions.


Asunto(s)
Medicamentos Herbarios Chinos , Medicina Tradicional China , Medicina Tradicional China/normas , Medicamentos Herbarios Chinos/normas , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/química , Humanos
2.
Front Pharmacol ; 15: 1423903, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39101141

RESUMEN

Background: YinChen WuLing Powder (YCWLP) has been recommended by consensus for the treatment of non-alcoholic steatohepatitis (NASH); nevertheless, its specific pharmacological mechanisms remain to be elucidated. This study aims to dissect the mechanisms underlying the therapeutic effects of YCWLP on NASH using a hybrid approach that encompasses network pharmacology, molecular docking, and in vitro experimental validation. Methods: We compiled the chemical constituents of YCWLP from the Traditional Chinese Medicine System Pharmacological Database and Analysis Platform (TCMSP), while potential targets were predicted using the SwissTargetPrediction database. To identify NASH-related candidate targets, comprehensive retrieval was carried out using five authoritative databases. Protein-Protein Interaction (PPI) networks of direct targets of YCWLP in NASH treatment were then constructed using the String database, and functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, were conducted through the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. Core targets were discerned using the Molecular Complex Detection (MCODE) and cytoHubba algorithms. Subsequently, molecular docking of key compounds to core targets was conducted using AutoDock software. Moreover, we established a free fatty acid-induced HepG2 cell model to simulate NASH in vitro, with YCWLP medicated serum intervention employed to corroborate the network pharmacology-derived hypotheses. Furthermore, a combination of enzyme-linked immunosorbent assay (ELISA), and Western blotting analyses was employed to investigate the lipid, hepatic enzyme, SHP2/PI3K/NLRP3 signaling pathway and associated cytokine levels. Results: The network pharmacology analysis furnished a list of 54 compounds from YCWLP and 167 intersecting targets associated with NASH. Through analytic integration with multiple algorithms, PTPN11 (also known as SHP2) emerged as a core target of YCWLP in mitigating NASH. The in vitro experiments validated that 10% YCWLP medicated serum could remarkably attenuate levels of total cholesterol (TC, 1.25 vs. 3.32) and triglyceride (TG, 0.23 vs. 0.57) while ameliorating alanine aminotransferase (ALT, 7.79 vs. 14.78) and aspartate aminotransferase (AST, 4.64 vs. 8.68) leakage in NASH-afflicted cells. In addition, YCWLP significantly enhanced the phosphorylation of SHP2 (0.55 vs. 0.20) and downregulated the expression of molecules within the SHP2/PI3K/NLRP3 signaling axis, including p-PI3K (0.42 vs. 1.02), NLRP3 (0.47 vs. 0.93), along with downstream effectors-cleaved Caspase-1 (0.21 vs. 0.49), GSDMD-NT (0.24 vs. 0.71), mature interleukin-1ß (IL-1ß, 0.17 vs. 0.48), pro-IL-1ß (0.49 vs. 0.89), mature interleukin-18 (IL-18, 0.15 vs. 0.36), and pro-IL-18 (0.48 vs. 0.95). Conclusion: Our research reveals that YCWLP exerts therapeutic effects against NASH by inhibiting lipid accumulation and inflammation, which involves the attenuation of pyroptosis via the SHP2/PI3K/NLRP3 pathway.

3.
Org Lett ; 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39150722

RESUMEN

We disclose herein an asymmetric synthesis of axially chiral oxazepine-containing bridged biaryls via CPA-catalyzed kinetic asymmetric alcoholysis. Control experiments showed that this CPA-catalyzed alcoholysis was reversible, and lowering the reaction temperature could almost suppress the reversible reaction, thus providing a series of axially chiral oxazepine-containing bridged biaryl compounds in good to excellent enantioselectivities. The gram-scale reactions and facile derivatizations of the enantioenriched products demonstrate the practical utility of this reaction.

4.
Anal Chim Acta ; 1319: 342966, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39122278

RESUMEN

BACKGROUND: The abuse of 17ß-estradiol(E2) has aroused wide concern in environmental and biomedical fields, which severely affects the endocrine function of human and animals. Therefore, an ultrasensitive and accurate assay of E2 is critically important. Traditional chromatography or immunoassay techniques exhibited good sensitivity and selectivity, but expensive instruments and antibodies may pose cost and stability issues, as well as difficulties in meeting on-site detection requirements. Ultrasensitive, reliable, and on-site detection of E2 at trace level remains a challenge. Hence, developing a simple, ultrasensitive assay to simultaneously achieve accurate detection and rapid visual analysis of E2 is extremely crucial. RESULTS: We developed a versatile dual-mode photoelectrochemical (PEC) and colorimetric biosensor based on isothermal nucleic acid amplification strategy for the ultrasensitive and accurate detection of E2. The method modified titanium dioxide (TiO2) with tungsten selenide (WSe2) nanoflowers to synthesize WSe2/TiO2 heterostructures as a substrate for signal amplification and nanoprobe modification. Isothermal nucleic acid amplification strategy has been proven to be a powerful tool for strong signal amplification. The presence of a target triggered the nucleic acid amplification reaction, and produced a large amount of tDNA that competed with G-quadruplex immobilized on the electrode surface. The remaining G-quadruplex/hemin catalyzed the 4-chloro-1-naphthol (4-CN) to form biocatalytic precipitation (BCP) and ABTS-H2O2 chromogenic reaction, thus, the dual-mode platform was capable of achieving PEC-colorimetric ultrasensitive detection based on the catalytic activity of G-quadruplex/hemin DNAzyme. Within optimal conditions, the dual-mode biosensor exhibited a remarkable detection limit as low as 0.026 pM. SIGNIFICANCE: Benefiting from the superior performance of WSe2/TiO2 and the power signal amplification of isothermal nucleic acid amplification strategy, this aptasensor achieved the ultrasensitive detection of E2. The independent transmission paths of photoelectrochemical and colorimetric provide mutual support and flexible switching, significantly enhancing the overall sensitivity and accuracy of the detection strategy, which can meet the needs for E2 precise quantification and rapid on-site detection.


Asunto(s)
Técnicas Biosensibles , Colorimetría , Técnicas Electroquímicas , Electrodos , Estradiol , Técnicas de Amplificación de Ácido Nucleico , Titanio , Titanio/química , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Estradiol/análisis , Límite de Detección , Procesos Fotoquímicos , Compuestos de Selenio/química , Humanos
5.
Biomaterials ; 312: 122755, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39151270

RESUMEN

Copper-catalyzed click chemistry offers creative strategies for activation of therapeutics without disrupting biological processes. Despite tremendous efforts, current copper catalysts face fundamental challenges in achieving high efficiency, atom economy, and tissue-specific selectivity. Herein, we develop a facile "mix-and-match synthetic strategy" to fabricate a biomimetic single-site copper-bipyridine-based cerium metal-organic framework (Cu/Ce-MOF@M) for efficient and tumor cell-specific bioorthogonal catalysis. This elegant methodology achieves isolated single-Cu-site within the MOF architecture, resulting in exceptionally high catalytic performance. Cu/Ce-MOF@M favors a 32.1-fold higher catalytic activity than the widely used MOF-supported copper nanoparticles at single-particle level, as first evidenced by single-molecule fluorescence microscopy. Furthermore, with cancer cell-membrane camouflage, Cu/Ce-MOF@M demonstrates preferential tropism for its parent cells. Simultaneously, the single-site CuII species within Cu/Ce-MOF@M are reduced by upregulated glutathione in cancerous cells to CuI for catalyzing the click reaction, enabling homotypic cancer cell-activated in situ drug synthesis. Additionally, Cu/Ce-MOF@M exhibits oxidase and peroxidase mimicking activities, further enhancing catalytic cancer therapy. This study guides the reasonable design of highly active heterogeneous transition-metal catalysts for targeted bioorthogonal reactions.

6.
Chem Commun (Camb) ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39145744

RESUMEN

An unprecedented Pd-catalyzed CO-free double carbonylation using Mo(CO)6 as a safe carbonyl source for the efficient synthesis of 1,4-ketoesters in an atom- and step-economic manner has been developed. The current method features operational safety, a wide substrate range, good functional group compatibility and easy scale-up. The application of carbonylation using a safe carbonyl source for the synthesis of biologically and synthetically useful carbonyl-containing molecules is underway in our lab.

7.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(8): 929-934, 2024 Aug 15.
Artículo en Chino | MEDLINE | ID: mdl-39175313

RESUMEN

Objective: To compare the effectiveness of robot-assisted (RA) minimally invasive surgery versus traditional fluoroscopy-assisted (FA) open posterior fixation surgery in treating thoracolumbar fractures with ankylosing spondylitis (AS). Methods: A clinical data of 21 cases of thoracolumbar fractures with AS who met the selection criteria between December 2016 and December 2023 was retrospectively analyzed. Ten cases underwent RA minimally invasive surgery group (RA group) and 11 cases underwent FA open posterior fixation surgery (FA group). There was no significant difference in gender, age, fracture segment distribution, fracture type, time from injury to surgery, visual analogue scale (VAS) score, and American Spinal Injury Association (ASIA) grading between RA group and FA group ( P>0.05). The operation time, intraoperative blood loss, radiation exposure time, radiation dose, hospital stay, and complications of the two groups were recorded. According to Gertzbein-Robbins criteria, the accuracy of screw implantation was evaluated by CT within 1 week after surgery. During follow-up, pain and nerve function were evaluated by VAS score and ASIA grading. Results: All patients underwent surgery successfully, and there was no significant difference in operation time ( P>0.05). The intraoperative blood loss and hospital stay in the RA group were significantly less than those in the FA group ( P<0.05), and the radiation exposure time and radiation dose were significantly more than those in the FA group ( P<0.05). A total of 249 pedicle screws were implanted in the two groups, including 118 in the RA group and 131 in the FA group. According to the Gertzbein-Robbins criteria, the proportion of clinically acceptable screws (grades A and B) in the RA group was significantly higher than that in the FA group ( P<0.05). Patients in both groups were followed up 3-12 months, with an average of 6.8 months. The VAS scores of the two groups after surgery were significantly lower than those before surgery, and the differences were significant ( P<0.05). The RA group had lower scores than the fluoroscopy group at 1 week and 3 months after surgery ( P<0.05). There was no significant difference in neurological function grading between groups at 1 week and 3 months after surgery ( P>0.05). In the FA group, 1 case of deep infection and 1 case of deep vein thrombosis of lower extremity occurred, while no complication occurred in the RA group, and there was no significant difference in the incidence of complications between groups ( P>0.05). Conclusion: Both RA minimally invasive surgery and FA open posterior fixation surgery can achieve good effectiveness. Compared with the latter, the former has more advantages in terms of intraoperative blood loss, hospital stay, and accuracy of pedicle screw insertion.


Asunto(s)
Fijación Interna de Fracturas , Vértebras Lumbares , Procedimientos Quirúrgicos Robotizados , Fracturas de la Columna Vertebral , Espondilitis Anquilosante , Vértebras Torácicas , Humanos , Estudios Retrospectivos , Espondilitis Anquilosante/cirugía , Fracturas de la Columna Vertebral/cirugía , Fluoroscopía/métodos , Vértebras Torácicas/cirugía , Vértebras Torácicas/lesiones , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/instrumentación , Procedimientos Quirúrgicos Robotizados/métodos , Vértebras Lumbares/cirugía , Vértebras Lumbares/lesiones , Masculino , Resultado del Tratamiento , Femenino , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Tempo Operativo , Persona de Mediana Edad , Adulto , Tornillos Óseos
8.
Front Nutr ; 11: 1395801, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39166131

RESUMEN

Background and objectives: Lactose intolerance and coeliac disease are common clinical nutrient malabsorption disorders, with an unclear pathogenesis and limited therapeutic options. It is widely believed that the gut microbiota plays an important role in many digestive disorders, but its role in lactose intolerance and coeliac disease is not yet clear. This study aimed to investigate the correlation between gut microbiota and lactose intolerance and coeliac disease. Materials and methods: This study utilized the genome-wide association study database to investigate the association between gut microbiota and lactose intolerance and coeliac disease using Mendelian randomization (MR). The robustness of our findings was confirmed through subsequent analyses including Cochrane's Q statistic, MR-Egger Intercept Regression, MR-PRESSO Global Test and Leave-one-out methods. Results: By employing the inverse variance weighted method, we identified that family Veillonellaceae, genus Oxalobacter and Senegalimassilia were protective against lactose intolerance, whereas genus Anaerotruncus, Eubacterium rectale group and Ruminococcus2 were found to be risk factors for lactose intolerance. Regarding coeliac disease, class Bacilli and Gammaproteobacteria, family FamilyXIII and Veillonellaceae, genus Eisenbergiella, Lachnoclostridium, RuminococcaceaeUCG014 and Ruminococcus2 were identified as protective factors, while class Betaproteobacteria, genus Eubacterium xylanophilum group and Blautia were risk factors. Furthermore, reverse the MR analysis did not reveal any evidence of a causal relationship between lactose intolerance or coeliac disease and the bacteria identified in our study. Conclusion: This study provides novel insights into exploring the role of gut microbiota in lactose intolerance and coeliac disease; however, further experiments investigations are required to elucidate the specific underlying mechanisms.

9.
Food Chem ; 461: 140884, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39167951

RESUMEN

This study investigated the effects of sodium pyrophosphate (SPP) and catechin (C) on the in vitro enzymatic digestion of oxidatively damaged myofibrillar protein (MP) gel. The results indicated that SPP increased the ß-sheet content and the gastric digestibility of the MP gel, while C hindered the transition from α-helix to ß-sheet structure, leading to decreased digestibility. Notably, neither compound significantly affected intestinal digestibility. Furthermore, SPP and C significantly enhanced the antioxidant activity of MP gel digestion products. Notably, their synergistic hydrolysis products, simulating both gastric and gastrointestinal stages, chelated 91.4 % and 89.1 % of Fe2+ and scavenged 59.4 % and 77.6 % of hydroxyl radicals, respectively. Moreover, the final digestion products of the MP gel treated with SPP and C exhibited the highest content of negatively charged amino acids and absolute Zeta potential values. Overall, this study demonstrated that incorporating SPP and C could positively impact the digestion of oxidatively damaged MP gels.

10.
Eur J Gastroenterol Hepatol ; 36(9): 1133-1140, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39101442

RESUMEN

OBJECTIVE: This study explored the mediating effect of diabetes on the relationship between nonalcoholic fatty liver disease (NAFLD) and atherosclerotic cardiovascular disease (ASCVD). METHODS: In this prospective community cohort study, 82 975 participants were enrolled, with the primary outcome being the incidence of new-onset ASCVD. Using the Cox proportional hazards model, the hazard ratio (HR) and 95% confidence interval (CI) for ASCVD occurrence were computed between NAFLD and non-NAFLD groups. The correlation between NAFLD and diabetes was assessed using a binary logistic regression model, and that between NAFLD, diabetes and ASCVD using a mediation model. RESULTS: During follow-up, 9471 ASCVD cases were observed. Compared with individuals without NAFLD, those with NAFLD showed an increased ASCVD risk (HR: 1.424; 95% CI: 1.363-1.488; P < 0.001). Stratifying NAFLD based on metabolic subphenotypes revealed a higher ASCVD risk in the NAFLD combined with diabetes subgroup than in the non-NAFLD subgroup (HR: 1.960; 95% CI: 1.817-2.115; P < 0.001). NAFLD was positively associated with baseline diabetes (odds ratio: 2.983; 95% CI: 2.813-3.163; P < 0.001). Furthermore, NAFLD severity was positively correlated with diabetes risk. Mediation analysis indicated that diabetes partially mediated the effect of NAFLD on ASCVD incidence, accounting for 20.33% of the total effect. CONCLUSION: NAFLD is an independent predictor of increased ASCVD risk, which may be slightly mediated by diabetes in patients with NAFLD. Evaluating NAFLD and diabetes may be crucial in the early screening and prevention of ASCVD.


Asunto(s)
Aterosclerosis , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Incidencia , Aterosclerosis/epidemiología , Factores de Riesgo , Anciano , Diabetes Mellitus/epidemiología , Modelos de Riesgos Proporcionales , Análisis de Mediación , Medición de Riesgo , Modelos Logísticos , Adulto
11.
J Colloid Interface Sci ; 676: 33-44, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39018808

RESUMEN

Ideal wave-absorbing materials are required to possess the characteristics such as being "broad, lightweight, thin, and strong." Biomass-derived materials for absorbing electromagnetic waves (EMWs) are widely explored due to their low cost, lightweight, environmentally friendly, high specific surface area, and porous structure. In this study, wood was used as the raw material, and N-doped carbon nanotubes were grown in situ in porous carbon derived from wood, loaded with magnetic metal Co nanoparticles through chemical vapor deposition. The Fir@Co@CNT composite material exhibited a three-dimensional conductive electromagnetic network structure and excellent impedance matching, thereby demonstrating excellent wave absorption performance. By controlling the introduction of carbon nanotubes, the roles of polarization loss and conduction loss in the Fir@Co@CNT composite material were precisely regulated. The Fir@Co@CNT 1:5 composite material achieved a minimum reflection loss (RLmin) of -43.03 dB in the low-frequency region and a maximum effective absorption bandwidth (EABmax) of 4.3 GHz (1.5 mm). Meanwhile, the Fir@Co@CNT 1:10 composite material achieved a RLmin of -52 dB with a thickness of only 2.3 mm, along with an EABmax of 4.2 GHz (1.6 mm). Both materials collectively cover the entire C-band, X-band, and Ku-band in terms of EAB. This work introduces a method for regulating polarization loss and conduction loss, showcasing the potential of biomass carbon materials as low-frequency EMW absorption materials for the first time. It also provides a new direction for the development and application of environmentally friendly, lightweight, high-performance wave-absorbing materials.

12.
Environ Geochem Health ; 46(9): 309, 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39002061

RESUMEN

Groundwater near a sulfuric acid plant in Xingyang, Henan, China was sampled from seven distinct sites to explore the prevalence of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs). Results showed that genes aadA, blaCTX-M, tetA, qnrA, and sul1 were detected with 100% frequency followed by aac(6')-Ib (85.71%), ermB (85.71%), and tetX (71.42%). Most abundant ARGs were sul1 in LSA2 (1.15 × 1011 copies/mL), tetA in LSA6 (4.95 × 1010 copies/mL), aadA in LSA2 (4.56 × 109 copies/mL), blaCTX-M in LSA4 (1.19 × 109 copies/mL), and ermB in LSA5 (1.07 × 109 copies/mL). Moreover, in LSA2, intl1 as a marker of class 1 integron emerged as the most abundant gene as part of MGE (2.25 × 1011 copies/mL), trailed by ISCR1 (1.57 × 109 copies/mL). Environmental factors explained 81.34% of ARG variations, with a strong positive correlation between the intl2 and blaCTX-M genes, as well as the ISCR1 gene and qnrA, tetA, intl2, and blaCTX-M. Furthermore, the intI1 gene had a strong positive connection with the aadA, tetA, and sul1 genes. Moreover, the aac(6')-Ib gene was associated with As, Pb, Mg, Ca, and HCO3-. The intl2 gene was also shown to be strongly associated with Cd. Notably, network analysis highlighted blaCTX-M as the most frequently appearing gene across networks of at least five genera. Particularly, Lactobacillus, Plesiomonas, and Ligilactobacillus demonstrated correlations with aadA, qnrA, blaCTX-M, intI2, and ISCR1. Based on 16S rRNA sequencing, the dominant phyla were Proteobacteria, Firmicutes, Bacteroidota, Acidobacteriota, and Actinobacteriota, with dominant genera including Pseudomonas, Ligilactobacillus, Azoarcus, Vogesella, Streptococcus, Plesiomonas, and Ferritrophicum. These findings enhance our understanding of ARG distribution in groundwater, signaling substantial contamination by ARGs and potential risks to public health.


Asunto(s)
Genes Bacterianos , Agua Subterránea , China , Agua Subterránea/microbiología , Ácidos Sulfúricos , Monitoreo del Ambiente , Farmacorresistencia Bacteriana/genética , Antibacterianos , Secuencias Repetitivas Esparcidas , Bacterias/genética , Bacterias/efectos de los fármacos , Microbiología del Agua , Farmacorresistencia Microbiana/genética , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis
13.
Sci Total Environ ; 947: 174569, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38977092

RESUMEN

BACKGROUND: Organophosphate esters (OPEs) exposure could affect offspring health. However, the underlying mechanisms are not well documented. OBJECTIVES: Based on a birth cohort study, we aimed to investigate the associations among gestational OPEs exposure, placental DNA methylation levels of peroxisome proliferator-activated receptor (PPAR) signaling pathway-related genes, and fetal growth. METHODS: We measured the concentrations of eight OPE metabolites in maternal urine samples and neonatal anthropometric measurements in 733 mother-child pairs. In 327 placental samples, we assessed the DNA methylation levels of 14 genes which were involved in the PPARs signaling pathway and expressed in placenta. Multiple linear regression models were used to examine the associations of OPEs exposure with placental DNA methylation, and of OPEs and placental DNA methylation with neonatal anthropometric measurements. Causal mediation analyses were conducted to examine the potential mediating role of placental DNA methylation in the pathway between OPEs exposure and fetal growth. RESULTS: We observed a general pattern of OPEs exposure being associated with hypermethylation of candidate genes, with statistically significant associations identified for several OPEs with RXRA, ACAA1, ACADL, ACADM, PLTP, and NR1H3 methylation. Further, gestational exposure to BCIPP, DPP, BBOEP, ∑NCl-OPEs, and ∑OPEs tended to be associated with lower anthropometric measurements, with more significant associations observed on arm circumference, and abdominal and back skinfold thickness. Notably, RXRA, ACAA1, ACOX1, CPT2, ACADM, and NR1H3 methylation tended to be associated with lower neonatal anthropometric measurements, especially for abdominal and back skinfold thickness. Moreover, mediation analyses showed that 19.42 % of the total effect of DPP on the back skinfold thickness was mediated by changes in RXRA methylation, and there was a significant indirect effect of RXRA methylation. CONCLUSIONS: Gestational OPEs exposure could disrupt the placental DNA methylation levels of PPAR signaling pathway-related genes, which might contribute to the effect of OPEs on fetal growth.


Asunto(s)
Metilación de ADN , Exposición Materna , Organofosfatos , Receptores Activados del Proliferador del Peroxisoma , Placenta , Transducción de Señal , Femenino , Embarazo , Humanos , Receptores Activados del Proliferador del Peroxisoma/genética , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Placenta/metabolismo , Ésteres , Adulto , Desarrollo Fetal/efectos de los fármacos , Estudios de Cohortes , Recién Nacido , Contaminantes Ambientales
14.
Org Lett ; 26(28): 5905-5910, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-38980194

RESUMEN

Herein, we present a straightforward approach to access hydroindoline-5-one-based 6/5/3-fused polycyclic ring structures through multistep cascade reactions involving α-aryl vinylsulfoniums and para-quinamines. The reactions proceed smoothly under mild conditions to deliver the desired products in generally good isolated yields. This protocol is also applicable to the cascade cycloaddition reactions of α-aryl vinylsulfoniums and para-quinols, effectively generating complex tricyclic scaffolds. In addition, the scale-up synthesis and further derivatizations demonstrate the potential synthetic application of the protocol.

15.
Front Artif Intell ; 7: 1321884, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38952409

RESUMEN

Background: Carotid plaques are major risk factors for stroke. Carotid ultrasound can help to assess the risk and incidence rate of stroke. However, large-scale carotid artery screening is time-consuming and laborious, the diagnostic results inevitably involve the subjectivity of the diagnostician to a certain extent. Deep learning demonstrates the ability to solve the aforementioned challenges. Thus, we attempted to develop an automated algorithm to provide a more consistent and objective diagnostic method and to identify the presence and stability of carotid plaques using deep learning. Methods: A total of 3,860 ultrasound images from 1,339 participants who underwent carotid plaque assessment between January 2021 and March 2023 at the Shanghai Eighth People's Hospital were divided into a 4:1 ratio for training and internal testing. The external test included 1,564 ultrasound images from 674 participants who underwent carotid plaque assessment between January 2022 and May 2023 at Xinhua Hospital affiliated with Dalian University. Deep learning algorithms, based on the fusion of a bilinear convolutional neural network with a residual neural network (BCNN-ResNet), were used for modeling to detect carotid plaques and assess plaque stability. We chose AUC as the main evaluation index, along with accuracy, sensitivity, and specificity as auxiliary evaluation indices. Results: Modeling for detecting carotid plaques involved training and internal testing on 1,291 ultrasound images, with 617 images showing plaques and 674 without plaques. The external test comprised 470 ultrasound images, including 321 images with plaques and 149 without. Modeling for assessing plaque stability involved training and internal testing on 764 ultrasound images, consisting of 494 images with unstable plaques and 270 with stable plaques. The external test was composed of 279 ultrasound images, including 197 images with unstable plaques and 82 with stable plaques. For the task of identifying the presence of carotid plaques, our model achieved an AUC of 0.989 (95% CI: 0.840, 0.998) with a sensitivity of 93.2% and a specificity of 99.21% on the internal test. On the external test, the AUC was 0.951 (95% CI: 0.962, 0.939) with a sensitivity of 95.3% and a specificity of 82.24%. For the task of identifying the stability of carotid plaques, our model achieved an AUC of 0.896 (95% CI: 0.865, 0.922) on the internal test with a sensitivity of 81.63% and a specificity of 87.27%. On the external test, the AUC was 0.854 (95% CI: 0.889, 0.830) with a sensitivity of 68.52% and a specificity of 89.49%. Conclusion: Deep learning using BCNN-ResNet algorithms based on routine ultrasound images could be useful for detecting carotid plaques and assessing plaque instability.

16.
Heliyon ; 10(11): e32522, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38961909

RESUMEN

Objectives: Dihydroartemisinin (DHA), an artemisinin derivative extracted from the traditional Chinese medicinal herb Artemisia annua, has the potential to suppress head and neck squamous cell carcinoma (HNSCC) progression. However, the mechanisms underlying these effects remain unclear. Therefore, we aimed to examine the mechanisms underlying the effects of DHA on tumor invasion and migration. Methods: Human HNSCC cell lines CAL-27 and FaDu were exposed to varying DHA concentrations (0, 5, 20, and 80 µM) for 24 h. Cell proliferation, invasion, and migration were assessed using CCK8, transwell, and wound-healing assays, respectively. Quantitative real-time PCR, western blotting, and immunofluorescence were used to assess the expression levels of the target genes and proteins. Results: DHA suppressed the invasion and migration of CAL-27 and FaDu cells. Additionally, miR-195-5p suppressed the invasion and migration of HNSCC cells. This study revealed significant differences in the expression of miR-195-5p and TENM2 between clinical samples and multiple public databases. DHA treatment and miR-195-5p overexpression significantly reduced TENM2 expression in HNSCC cells, which suggested that miR-195-5p overexpression enhanced the inhibitory effect of DHA on TENM2. Conclusions: This study provides the first evidence that DHA inhibits cell invasion and migration by regulating the miR-195-5p/TENM2 axis in HNSCC cells, suggesting it as a potentially effective treatment strategy for HNSCC.

17.
Eur J Prev Cardiol ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38946352

RESUMEN

AIMS: The relationship between uric acid (UA) concentrations and the risk of cardiovascular disease (CVD), especially for subtypes of CVD among individuals with chronic kidney disease (CKD) is not well understood. This study aimed to investigate whether uric acid concentration was associated with subtypes of CVD and all-cause mortality among individuals with CKD. METHODS: A total of 27,707 individuals with CKD, free of CVD at recruitment from the Kailuan Study, were included. Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a median follow-up of 11-12 years, we documented 674 myocardial infarctions, 1197 heart failures, 2406 strokes, and 5676 total deaths. Among participants with CKD, compared with those in the lowest tertile of UA, the HRs (95% CIs) of participants in the highest UA tertile were 1.38 (1.13-1.67) for myocardial infarction, 1.60 (1.38-1.85) for heart failure, 1.01 (0.91-1.12) for stroke, and 1.29 (1.21-1.38) for all-cause mortality. Subgroup analyses showed that the associations between UA and heart failure and all-cause mortality were stronger in individuals with eGFR <45 mL/min/1.73m2 compared to their counterparts (Pinteraction<0.05). Additionally, the association between UA and all-cause mortality was stronger among individuals without diabetes than those with diabetes (Pinteraction<0.05). CONCLUSIONS: In individuals with CKD, a higher concentration of UA was associated with a higher risk of myocardial infarction, heart failure, and all-cause mortality, following a dose-response relationship. Our data underscore the importance of UA screening among individuals with CKD for CVD and premature death prevention.


This study investigated the relationship between uric acid (UA) concentrations and the risk of cardiovascular disease and all-cause mortality in individuals with chronic kidney disease (CKD) using the Kailuan Study. A higher concentration of UA was associated with a higher risk of myocardial infarction, heart failure, and all-cause mortality among individuals with CKD, following a dose-response manner.The associations between concentrations of UA and the risk of heart failure and all-cause mortality were more pronounced in individuals with severe kidney impairment (estimated glomerular filtration rate <45 mL/min/1.73m2). Furthermore, the association between UA and all-cause mortality was stronger among individuals without diabetes compared to those with the condition.

18.
Front Public Health ; 12: 1362884, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38947356

RESUMEN

Introduction: Hospital affiliated green spaces can help patients recover and recover their physical functions, promote physical and mental relaxation, enhance health awareness, and improve overall health. However, there are still significant questions about how to scientifically construct hospital affiliated green spaces. This study examines the impact of hospital green spaces on patient rehabilitation through scientific evaluation methods, providing reference for the scientific construction of hospital affiliated green spaces. Applicability evaluation was conducted on the affiliated green spaces of three hospitals in Harbin. An evaluation system covering plants, space, accessibility, rehabilitation functions, and promotional and educational functions has been constructed. The entropy weight method is used to determine the weight of indicators, and the grey correlation analysis method is used to evaluate the suitability of green space for patient rehabilitation. Methods: The experimental results showed that the landscape accessibility index had the highest weight (0.3005) and the plant index had the lowest weight (0.1628), indicating that caring for special needs is the foundation of hospital landscapes, and plants have subtle and long-term effects on physical and mental health. In the evaluation of the rehabilitation applicability of the affiliated green spaces of various hospitals, the second hospital has the highest grey correlation degree (0.8525), followed by the tumor hospital (0.5306) and the fifth hospital (0.4846). It can be seen that the green space of the second hospital has high applicability for patient rehabilitation, but the green space of the tumor hospital and the fifth hospital needs to be improved and developed. Results and discussion: The evaluation criteria used in this study are comprehensive. The landscaping at the Third Hospital is well-planned with good plant configuration and reasonable spatial layout. However, there is insufficient consideration for accessibility in the landscape design, and the details are lacking. The rehabilitation and educational functions of the landscape are inadequate, with limited outdoor activities and low road safety. The hospital's affiliated green spaces should adhere to the principle of "appropriate scale, comprehensive functionality, and educational leisure," integrating rehabilitation and educational functions while increasing the variety of outdoor activities. In the future, emphasis should be placed on exploring the integration of landscape and rehabilitation to provide a functional site that is convenient for visiting, with improved rehabilitation facilities and an educational and enjoyable environment. The design should incorporate elements that contribute to a sense of well-being, including roads and.


Asunto(s)
Entropía , Humanos , Hospitales , China , Arquitectura y Construcción de Hospitales
19.
Small ; : e2402655, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949408

RESUMEN

Solution Gated Graphene Field-Effect Transistors (SGGT) are eagerly anticipated as an amplification platform for fabricating advanced ultra-sensitive sensors, allowing significant modulation of the drain current with minimal gate voltage. However, few studies have focused on light-matter interplay gating control for SGGT. Herein, this challenge is addressed by creating an innovative photoelectrochemical solution-gated graphene field-effect transistor (PEC-SGGT) functionalized with enzyme cascade reactions (ECR) for Organophosphorus (OPs) detection. The ECR system, consisting of acetylcholinesterase (AChE) and CuBTC nanomimetic enzymes, selectively recognizes OPs and forms o-phenylenediamine (oPD) oligomers sediment on the PEC electrode, with layer thickness related to the OPs concentration, demonstrating time-integrated amplification. Under light stimulation, the additional photovoltage generated on the PEC gate electrode is influenced by the oPD oligomers sediment layer, creating a differentiated voltage distribution along the gate path. PEC-SGGT, inherently equipped with built-in amplification circuits, sensitively captures gate voltage changes and delivers output with an impressive thousandfold current gain. The seamless integration of these three amplification modes in this advanced sensor allows a good linear range and highly sensitive detection of OPs, with a detection limit as low as 0.05 pm. This work provides a proof-of-concept for the feasibility of light-assisted functionalized gate-controlled PEC-SGGT for small molecule detection.

20.
Sensors (Basel) ; 24(13)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-39000834

RESUMEN

The fusion of multi-modal medical images has great significance for comprehensive diagnosis and treatment. However, the large differences between the various modalities of medical images make multi-modal medical image fusion a great challenge. This paper proposes a novel multi-scale fusion network based on multi-dimensional dynamic convolution and residual hybrid transformer, which has better capability for feature extraction and context modeling and improves the fusion performance. Specifically, the proposed network exploits multi-dimensional dynamic convolution that introduces four attention mechanisms corresponding to four different dimensions of the convolutional kernel to extract more detailed information. Meanwhile, a residual hybrid transformer is designed, which activates more pixels to participate in the fusion process by channel attention, window attention, and overlapping cross attention, thereby strengthening the long-range dependence between different modes and enhancing the connection of global context information. A loss function, including perceptual loss and structural similarity loss, is designed, where the former enhances the visual reality and perceptual details of the fused image, and the latter enables the model to learn structural textures. The whole network adopts a multi-scale architecture and uses an unsupervised end-to-end method to realize multi-modal image fusion. Finally, our method is tested qualitatively and quantitatively on mainstream datasets. The fusion results indicate that our method achieves high scores in most quantitative indicators and satisfactory performance in visual qualitative analysis.

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