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1.
JACC Adv ; 3(4): 100909, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38939657

RESUMO

Background: There is controversy regarding sex differences in short-term mortality in acute type A aortic dissection (ATAAD). Objectives: This study aimed to investigate the impact of sex differences on 30-day operative mortality after ATAAD surgery and to determine if other covariates modify the association. Methods: Consecutive patients (N = 5670) with surgically repaired ATAAD were identified from the multicenter China 5A study. The primary outcome was operative mortality. The age dependency was modeled using a cubic spline curve. Results: There were 1,503 females (26.5%) and 4,167 males (73.5%). Females were older and had a lower percentage of comorbidities compared with males. Females had higher mortality compared to males (10.2% vs 8.2%, P = 0.019); however, there was no difference after propensity analyses (adjusted OR: 1.334 [95% CI: 0.918-1.938]). There was an interaction with sex and age (P interaction = 0.035): older age was associated with higher odds of operative mortality among females (OR: 1.045 [95% CI: 1.029-1.061]) compared with males (OR: 1.025 [95% CI: 1.016-1.035]). The risk of mortality for males and females appears to diverge at 55 years of age (P interaction = 0.019): females under 55 years of age had similar odds to males (OR: 0.852 [95% CI: 0.603-1.205]) but higher odds when over 55 years (OR: 1.420 [95% CI: 1.096-1.839]) compared to males. Conclusions: Under the age of 55 years, females have similar odds of operative mortality compared with males; however, over the age of 55 years females have higher odds than males. Understanding differences in risk allows for individualized treatment strategies. (Additive Anti-inflammatory Action for Aortopathy & Arteriopathy; NCT04398992).

2.
Pest Manag Sci ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940289

RESUMO

BACKGROUND: Succinate dehydrogenase inhibitor (SDHI) fungicides play important roles in the control of plant fungal diseases. However, they are facing serious challenges from issues with resistance and cross-resistance, primarily attributed to their frequent application and structural similarities. There is an urgent need to design and develop SDHI fungicides with novel structures. RESULTS: Aiming to discover novel potent SDHI fungicides, 31 innovative pyrazole ß-ketonitrile derivatives with diphenyl ether moiety were rationally designed and synthesized, which were guided by a 3D-QSAR model from our previous study. The optimal target compound A23 exhibited not only outstanding in vitro inhibitory activities against Rhizoctonia solani with a half-maximal effective concentration (EC50) value of 0.0398 µg mL-1 comparable to that for fluxapyroxad (EC50 = 0.0375 µg mL-1), but also a moderate protective efficacy in vivo against rice sheath blight. Porcine succinate dehydrogenase (SDH) enzymatic inhibitory assay revealed that A23 is a potent inhibitor of SDH, with a half-maximal inhibitory concentration of 0.0425 µm. Docking study within R. solani SDH indicated that A23 effectively binds into the ubiquinone site mainly through hydrogen-bonds, and cation-π and π-π interactions. CONCLUSION: The identified ß-ketonitrile compound A23 containing diphenyl ether moiety is a potent SDH inhibitor, which might be a good lead for novel fungicide research and optimization. © 2024 Society of Chemical Industry.

3.
Small ; : e2402842, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38923165

RESUMO

The nacre-inspired multi-nanolayer structure offers a unique combination of advanced mechanical properties, such as strength and crack tolerance, making them highly versatile for various applications. Nevertheless, a significant challenge lies in the current fabrication methods, which is difficult to create a scalable manufacturing process with precise control of hierarchical structure. In this work, a novel strategy is presented to regulate nacre-like multi-nanolayer films with the balance mechanical properties of stiffness and toughness. By utilizing a co-continuous phase structure and an extensional stress field, the hierarchical nanolayers is successfully constructed with tunable sizes using a scalable processing technique. This strategic modification allows the robust phase to function as nacre-like platelets, while the soft phase acts as a ductile connection layer, resulting in exceptional comprehensive properties. The nanolayer-structured films demonstrate excellent isotropic properties, including a tensile strength of 113.5 MPa in the machine direction and 106.3 MPa in a transverse direction. More interestingly, these films unprecedentedly exhibit a remarkable puncture resistance at the same time, up to 324.8 N mm-1, surpassing the performance of other biodegradable films. The scalable fabrication strategy holds significant promise in designing advanced bioinspired materials for diverse applications.

4.
Biosens Bioelectron ; 261: 116521, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38917514

RESUMO

Oceanic facilities and equipment corrosion present considerable economic and safety concerns, predominantly due to microbial corrosion. Early detection of corrosive microbes is pivotal for effective monitoring and prevention. Yet, traditional detection methods often lack specificity, require extensive processing time, and yield inaccurate results. Hence, the need for an efficient real-time corrosive microbe monitoring technology is evident. Pseudomonas aeruginosa, a widely distributed microorganism in aquatic environments, utilizes its production of quinone-like compounds, specifically pyocyanin (PYO), to corrode metals. Here, we report a novel fiber optic surface plasmon resonance (SPR) sensor modified by the C-terminal of BrlR protein (BrlR-C), which is a specific receptor of PYO molecule, to detect P. aeruginosa in aquatic environments. The results showed that the sensor had a good ability to recognize PYO in the concentration range of 0-1 µg/mL, and showed excellent sensing performance in real-time monitoring the growth status of P. aeruginosa. With a strong selectivity of PYO, the sensor could clearly detect P. aeruginosa against other bacteria in seawater environment, and exhibited excellent anti-interference ability against variations in pH, temperature and pressure and other interfering substances. This study provides a useful tool for monitoring corrosive P. aeruginosa biofilm in aquatic environments, which is a first of its kind example that serves as a laboratory model for the application of fiber optic technology in real-world scenarios to monitoring biofilms in microbial corrosion and biofouling.

5.
Int J Mol Sci ; 25(12)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38928304

RESUMO

Hydrogen sulfide (H2S) is a novel gasotransmitter. Sucrose (SUC) is a source of cellular energy and a signaling molecule. Maize is the third most common food crop worldwide. However, the interaction of H2S and SUC in maize thermotolerance is not widely known. In this study, using maize seedlings as materials, the metabolic and functional interactions of H2S and SUC in maize thermotolerance were investigated. The data show that under heat stress, the survival rate and tissue viability were increased by exogenous SUC, while the malondialdehyde content and electrolyte leakage were reduced by SUC, indicating SUC could increase maize thermotolerance. Also, SUC-promoted thermotolerance was enhanced by H2S, while separately weakened by an inhibitor (propargylglycine) and a scavenger (hypotaurine) of H2S and a SUC-transport inhibitor (N-ethylmaleimide), suggesting the interaction of H2S and SUC in the development of maize thermotolerance. To establish the underlying mechanism of H2S-SUC interaction-promoted thermotolerance, redox parameters in mesocotyls of maize seedlings were measured before and after heat stress. The data indicate that the activity and gene expression of H2S-metabolizing enzymes were up-regulated by SUC, whereas H2S had no significant effect on the activity and gene expression of SUC-metabolizing enzymes. In addition, the activity and gene expression of catalase, glutathione reductase, ascorbate peroxidase, peroxidase, dehydroascorbate reductase, monodehydroascorbate reductase, and superoxide dismutase were reinforced by H2S, SUC, and their combination under non-heat and heat conditions to varying degrees. Similarly, the content of ascorbic acid, flavone, carotenoid, and polyphenol was increased by H2S, SUC, and their combination, whereas the production of superoxide radicals and the hydrogen peroxide level were impaired by these treatments to different extents. These results imply that the metabolic and functional interactions of H2S and sucrose signaling exist in the formation of maize thermotolerance through redox homeodynamics. This finding lays the theoretical basis for developing climate-resistant maize crops and improving food security.


Assuntos
Sulfeto de Hidrogênio , Oxirredução , Sacarose , Termotolerância , Zea mays , Zea mays/metabolismo , Zea mays/fisiologia , Zea mays/genética , Zea mays/efeitos dos fármacos , Sulfeto de Hidrogênio/metabolismo , Sacarose/metabolismo , Regulação da Expressão Gênica de Plantas , Resposta ao Choque Térmico , Plântula/metabolismo , Plântula/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(6): 584-591, 2024 Jun 15.
Artigo em Chinês | MEDLINE | ID: mdl-38926374

RESUMO

OBJECTIVES: To explore the value of different endoscopic scoring methods in assessing disease activity in pediatric Crohn's disease (CD). METHODS: A total of 70 children diagnosed with CD at the Children's Hospital of Chongqing Medical University from January 2018 to January 2023 were included. Clinical disease activity was assessed using the Pediatric Crohn's Disease Activity Index (PCDAI), while different endoscopic scores were assigned based on endoscopic findings. Spearman rank correlation analysis was used to evaluate the correlation between each endoscopic scoring method and PCDAI as well as laboratory indicators. Kappa test was used to assess the consistency between colonoscopy/capsule endoscopy scoring methods and PCDAI in determining CD activity. Receiver operating characteristic curve analysis was performed to assess the diagnostic efficacy of laboratory indicators in predicting endoscopic activity. RESULTS: The PCDAI score showed a moderate positive correlation with the scores of Crohn's Disease Endoscopic Index of Severity (CDEIS) (rs=0.696, P<0.01), Simple Endoscopic Score for Crohn's Disease (SES-CD) (rs=0.680, P<0.01), Lewis Score (rs=0.540, P<0.01), and Capsule Endoscopy-Crohn's Disease Index (CE-CD) (rs=0.502, P<0.01). The consistency between all endoscopic scoring methods and PCDAI in determining CD activity was poor (Kappa=0.069-0.226). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hematocrit (HCT), and serum albumin (ALB) levels showed a moderate correlation with the PCDAI score and the scores of colonoscopy scoring methods (CDEIS and SES-CD) (|rs|=0.581-0.725, P<0.01), but a weak correlation with the scores of capsule scoring methods (P<0.05). ESR and CRP had higher area under the curve (AUC) values in predicting disease activity based on PCDAI, CDEIS, SES-CD, and Lewis Score compared to HCT and ALB (P<0.05). CONCLUSIONS: CDEIS, SES-CD, Lewis Score, and CE-CD can be used to evaluate disease activity in pediatric CD, but they do not fully correspond with disease activity assessed by PCDAI. Elevated levels of ESR and CRP can predict clinical and endoscopic disease activity in children with CD.


Assuntos
Colonoscopia , Doença de Crohn , Índice de Gravidade de Doença , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Doença de Crohn/sangue , Criança , Masculino , Feminino , Adolescente , Pré-Escolar , Endoscopia por Cápsula , Proteína C-Reativa/análise , Sedimentação Sanguínea , Curva ROC
7.
Orphanet J Rare Dis ; 19(1): 225, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844943

RESUMO

BACKGROUND: Infantile liver failure syndrome type 1 (ILFS1, OMIM #615,438), caused by leucyl-tRNA synthase 1 (LARS1, OMIM *151,350) deficiency, is a rare autosomal-recessive disorder. The clinical manifestations, molecular-genetic features, and prognosis of LARS1 disease remain largely elusive. METHODS: Three new instances of ILFS1 with confirmed variants in LARS1, encoding LARS1, were identified. Disease characteristics were summarized together with those of 33 reported cases. Kaplan-Meier analysis was performed to assess prognostic factors in ILFS1 patients. RESULTS: The 3 new ILFS1 patients harbored 6 novel variants in LARS1. Among the 36 known patients, 12 died or underwent liver transplantation. The main clinical features of ILFS1 were intrauterine growth restriction (31/32 patients in whom this finding was specifically described), failure to thrive (30/31), hypoalbuminemia (32/32), microcytic anemia (32/33), acute liver failure (24/34), neurodevelopmental delay (25/30), seizures (22/29), and muscular hypotonia (13/27). No significant correlations were observed between genotype and either presence of liver failure or clinical severity of disease. Kaplan-Meier analysis indicated that age of onset < 3mo (p = 0.0015, hazard ratio = 12.29, 95% confidence interval [CI] = 3.74-40.3), like liver failure (p = 0.0343, hazard ratio = 6.57, 95% CI = 1.96-22.0), conferred poor prognosis. CONCLUSIONS: Early age of presentation, like liver failure, confers poor prognosis in ILFS1. Genotype-phenotype correlations remain to be established.


Assuntos
Falência Hepática , Humanos , Feminino , Masculino , Lactente , Prognóstico , Falência Hepática/genética , Falência Hepática/patologia , Recém-Nascido , Falência Hepática Aguda/genética , Falência Hepática Aguda/mortalidade
8.
Food Chem ; 456: 139624, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38850608

RESUMO

The limited availability of phospholipase A1 (PLA1) has posed significant challenges in enzymatic degumming. In this study, a novel PLA1 (UM2) was introduced to address this limitation, which had a unique thermo-responsive ability to switch phospholipase and lipase activities in response to temperature variations. Remarkably, UM2 displayed an unprecedented selectivity under optimized conditions, preferentially hydrolyzing phospholipids over triacylglycerols-a specificity superior to that of commercial PLA1. Moreover, UM2 demonstrated high efficiency in hydrolyzing phospholipids with a predilection for phosphatidylcholine (PC) and phosphatidylethanolamine (PE). A practical application of UM2 on crude flaxseed oil led to a dramatic reduction in phosphorus content, plummeting from an initial 384.06 mg/kg to 4.38 mg/kg. Broadening its industrial applicability, UM2 effectively performed enzymatic degumming for other distinct crude vegetable oils with a unique phospholipid composition. Collectively, these results highlighted the promising application of UM2 in the field of oil degumming.

9.
PLoS One ; 19(6): e0304629, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38829867

RESUMO

OBJECTIVE: To dynamically observe the occurrence of deep vein thrombosis (DVT) after a hip fracture and analyze of the risk factors affecting the dynamic alteration of DVT. METHODS: Data of patients with hip fractures from January 1, 2017 to August 31, 2021 were collected. Patients were divided into DVT and non-DVT groups according to their daily Doppler ultrasonography findings. Survival analysis was used to describe dynamic changes in DVT occurrence with time. Log-rank tests were used to compare the influence of individual factors of patients with DVT occurrence, and a Cox proportional hazards regression model was used to identify the risk factors affecting the dynamic alteration of DVT occurrence. RESULTS: A total of 331 patients were included: 148(44.7%) had preoperative DVT, and 143 (96.6%) had DVT in the first 3days after admission. The probability of DVT was 0.42 on Day 1, 0.11 on Day 2, 0.10 on Day 3, 0.08 on Day 4, 0.20 on Day 5, and 0.00 on Day 6-7, with a median survival time of 3.30 d. Age>70 years, intertrochanteric fracture, admission hemoglobin<130g/L, and admission hematocrit<40% had a significantly higher occurrence rate of DVT. A hematocrit level of <40% (Hazard Ratio 2.079, 95% Confidence Interval:1.148-3.764, P = 0.016) was an independent risk factor for DVT. CONCLUSION: DVT after hip fractures mainly occurred in the first three days after admission, the trend was stabilized within one week, and day 1 had the highest rate of DVT incidence. Age, fracture type, HGB level, and Hct level affected dynamic occurrence of DVT. At constant other factors, Hct<40% was 2.079-fold incidence in the risk of preoperative DVT formation than those with Hct≥40% after hip fracture.


Assuntos
Fraturas do Quadril , Trombose Venosa , Humanos , Fraturas do Quadril/complicações , Trombose Venosa/etiologia , Trombose Venosa/epidemiologia , Masculino , Feminino , Fatores de Risco , Idoso , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos
10.
Int J Ophthalmol ; 17(6): 1007-1017, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895685

RESUMO

AIM: To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity. METHODS: A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited. Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals. Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery. The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software. Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2 (EPHA2). Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins. The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assay, respectively. The cell migration was analyzed by wound healing assay. Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo. RESULTS: A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif (SAM) domain of EPHA2. Functional studies demonstrated the variant's impact: reduced EPHA2 protein expression, altered subcellular localization, and disrupted interactions with other lens membrane proteins. This mutant notably enhanced human lens epithelial cell migration, and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast (DIC) optics. CONCLUSION: Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.

11.
BMC Musculoskelet Disord ; 25(1): 483, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898453

RESUMO

INTRODUCTION: The Ilizarov bone transport technique is widely recognised as an effective method for treating large segment bone defects in clinical practice. However, axial deviation is a common complication in the treatment of tibial large segment bone defects, which can have a serious impact on the clinical efficacy of bone transport. Our study aims to construct and validate a nomogram for predicting axial deviation of tibial bone transport. METHOD: This study retrospectively collected data from 363 patients who underwent the tibial Ilizarov technique for bone transport. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for axial deviation, which were later used to construct a nomogram. The nomogram was evaluated using the decision curve analysis (DCA), the calibration curve, and the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 363 patients who underwent Ilizarov tibial bone transport, 31.7% (115/363) experienced axial deviation. Multivariate logistic regression analysis showed that gender, height, defect site, and external fixation index were important risk factors for axial deviation. The AUC value of the nomogram model was 0.705. The calibration curve and the decision curve analysis showed a good consistency between the actual axial deviation and the predicted probability. CONCLUSION: The model assigns a quantitative risk score to each variable, which can be used to predict the risk of axial deviation during tibial bone transport.


Assuntos
Técnica de Ilizarov , Nomogramas , Tíbia , Humanos , Feminino , Masculino , Estudos Retrospectivos , Adulto , Tíbia/cirurgia , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem , Adolescente , Idoso , Complicações Pós-Operatórias/etiologia
12.
Chin J Integr Med ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910191

RESUMO

OBJECTIVE: To explore the neuroprotective effects and mechanism of Tanreqing Injection (TRQ) on treating ischemic stroke based on network pharmacology and in vivo experimental validation. METHODS: The chemical compounds of TRQ were retrieved based on published data, with targets retrieved from PubChem, Therapeutic Target Database and DrugBank. Network visualization and analysis were performed using Cytoscape, with protein-protein interaction networks derived from the STRING database. Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis. In in vivo experiments, the middle cerebral artery occlusion (MCAO) model was used. Infarct volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot. Molecular docking was performed to predict ligand-receptor interactions. RESULTS: We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets. Of the targets, 116 were therapeutic targets for stroke. The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke. Furthermore, in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats (P<0.05). In addition, protein levels of the apelin receptor (APJ)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were increased by TRQ (P<0.05). In addition, 41 chemical compounds in TRQ could bind to APJ. CONCLUSIONS: The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway. However, further studies are needed to confirm the findings.

13.
BMC Infect Dis ; 24(1): 550, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824508

RESUMO

BACKGROUND: Influenza A virus infections can occur in multiple species. Eurasian avian-like swine influenza A (H1N1) viruses (EAS-H1N1) are predominant in swine and occasionally infect humans. A Eurasian avian-like swine influenza A (H1N1) virus was isolated from a boy who was suffering from fever; this strain was designated A/Shandong-binzhou/01/2021 (H1N1). The aims of this study were to investigate the characteristics of this virus and to draw attention to the need for surveillance of influenza virus infection in swine and humans. METHODS: Throat-swab specimens were collected and subjected to real-time fluorescent quantitative polymerase chain reaction (RT‒PCR). Positive clinical specimens were inoculated onto Madin-Darby canine kidney (MDCK) cells to isolate the virus, which was confirmed by a haemagglutination assay. Then, whole-genome sequencing was carried out using an Illumina MiSeq platform, and phylogenetic analysis was performed with MEGA X software. RESULTS: RT‒PCR revealed that the throat-swab specimens were positive for EAS-H1N1, and the virus was subsequently successfully isolated from MDCK cells; this strain was named A/Shandong-binzhou/01/2021 (H1N1). Whole-genome sequencing and phylogenetic analysis revealed that A/Shandong-binzhou/01/2021 (H1N1) is a novel triple-reassortant EAS-H1N1 lineage that contains gene segments from EAS-H1N1 (HA and NA), triple-reassortant swine influenza H1N2 virus (NS) and A(H1N1) pdm09 viruses (PB2, PB1, PA, NP and MP). CONCLUSIONS: The isolation and analysis of the A/Shandong-binzhou/01/2021 (H1N1) virus provide further evidence that EAS-H1N1 poses a threat to human health, and greater attention should be given to the surveillance of influenza virus infections in swine and humans.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Filogenia , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H1N1/classificação , China/epidemiologia , Humanos , Masculino , Animais , Influenza Humana/virologia , Influenza Humana/epidemiologia , Cães , Células Madin Darby de Rim Canino , Criança , Suínos , Sequenciamento Completo do Genoma , Infecções por Orthomyxoviridae/virologia , Infecções por Orthomyxoviridae/veterinária , Infecções por Orthomyxoviridae/epidemiologia , Genoma Viral
14.
Adv Sci (Weinh) ; : e2402170, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38885373

RESUMO

Oxazocines are key structural intermediates in the synthesis of natural products and pharmaceutical molecules. However, the synthesis of oxazocines especially in a highly enantioselective manner, is a long-standing formidable challenge due to unfavorable energetics involved in cyclization. Herein, a series of new PNP-Ligand P-chiral stereocenter is first designed and synthesized, called MQ-Phos, and successfully applied it in the Pd-catalyzed enantioselective higher-order formal [4+4]-cycloaddition of α, ß-unsaturated imines with 2-(hydroxymethyl)-1-arylallyl carbonates. The reaction features mild conditions, excellent regio- and enantiocontrol and a broad substrate scope (54 examples). Various medium-sized rings can be afforded in moderate to excellent yields (up to 92%) and excellent enantioselectivity (up to 99% ee). The newly developed MQ-Phos is critical for synthesis of the medium-sized ring in excellent catalytic reactivity and enantioselectivity.

15.
Angew Chem Int Ed Engl ; : e202405520, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896428

RESUMO

Functionalization of Si-bound methyl group provides an efficient access to diverse organosilanes. However, the asymmetric construction of silicon-stereogenic architectures by functionalization of Si-bound methyl group has not yet been described despite recent significant progress in producing chiral silicon. Herein, we disclosed the enantioselective silylmethyl functionalization involving the aryl to alkyl 1,5-palladium migration to access diverse naphthalenes possessing an enantioenriched stereogenic silicon center, which are inaccessible before. It is worthy to note that the realization of asymmetric induction at the step of metal migration itself remains challenging. Our study constitutes the first enantioselective aryl to alkyl 1,5-palladium migration reaction. The key to the success is the discovery and fine-tuning of the different substituents of α,α,α,α-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL)-based phosphoramidites, which ensure the enantioselectivity and desired reactivity.

16.
Clin Nutr ESPEN ; 63: 2-12, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38879879

RESUMO

BACKGROUND & AIMS: Several medicinal plant extracts have demonstrated hepatoprotective effects. However, data are scarce regarding their combined effects on non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the effects of tablets containing Silybum marianum, Pueraria lobata, and Salvia miltiorrhiza (SPS) on NAFLD progression in Chinese adults. METHODS: In this randomized, triple-blind, placebo-controlled clinical trial, 121 NAFLD patients (60 female and 61 male), diagnosed via magnetic resonance imaging (MRI) and aged 18-65 years, were enrolled. Participants were randomly allocated to receive SPS tablets (n = 60; three tablets per dose, twice daily) or placebo (n = 61) for 24 weeks. Each SPS tablet contained approximately 23.0 mg of silybin, 11.4 mg of puerarin, and 10.9 mg of salvianolic acid. There were no differences in appearance, taste and odour between the SPS tablets and placebo manufactured by BYHEALTH Co., LTD (Guangzhou, China). The primary endpoints were changes in the liver fat content (LFC) and steatosis grade from baseline to 24 weeks. Secondary outcomes included changes in biomarkers/scores of liver fibrosis and steatosis, oxidative stress, inflammatory cytokines, alcohol metabolism, and glucose metabolism. RESULTS: A total of 112 participants completed the research. The intention-to-treat results showed a trend toward reduction in both absolute LFC (-0.52%) and percentage of LFC (-4.57%) in the SPS group compared to the placebo group after 24 weeks, but these changes didn't reach statistical significance (p > 0.05). The SPS intervention (vs. placebo) significantly decreased hypersensitive C-reactive protein level (-6.76%) and increased aldehyde dehydrogenase activity (+18.1%) at 24 weeks post-intervention (all p < 0.05). Per-protocol analysis further supported these effects. This trial is registered at Clinical Trials.gov (NCT05076058). CONCLUSION: SPS supplementation may have potential benefits in improving NAFLD, but further larger-scale trials are necessary to confirm these findings.

17.
J Agric Food Chem ; 72(22): 12469-12477, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38771932

RESUMO

Photopharmacology can be implemented in a way of regulating drug activities by light-controlling the molecular configuations. Three photochromic ligands (PCLs) that bind on one or two sites of GABARs and nAChRs were reported here. These multiphoton PCLs, including FIP-AB-FIP, IMI-AB-FIP, and IMI-AB-IMI, are constructed with an azobenzene (AB) bridge that covalently connects two fipronil (FIP) and imidacloprid (IMI) molecules. Interestingly, the three PCLs as well as FIP and IMI showed great insecticidal activities against Aedes albopictus larvae and Aphis craccivora. IMI-AB-FIP in both trans/cis isomers can be reversibly interconverted depending on light, accompanied by insecticidal activity decrease or increase by 1.5-2.3 folds. In addition, IMI-AB-FIP displayed synergistic effects against A. craccivora (LC50, IMI-AB-FIP = 14.84-22.10 µM, LC50, IMI-AB-IMI = 210.52-266.63 µM, LC50, and FIP-AB-FIP = 36.25-51.04 µM), mainly resulting from a conceivable reason for simultaneous targeting on both GABARs and nAChRs. Furthermore, modulations of wiggler-swimming behaviors and cockroach neuron function were conducted and the results indirectly demonstrated the ligand-receptor interactions. In other words, real-time regulations of receptors and insect behaviors can be spatiotemporally achieved by our two-photon PCLs using light.


Assuntos
Aedes , Compostos Azo , Inseticidas , Neonicotinoides , Nitrocompostos , Pirazóis , Animais , Nitrocompostos/química , Nitrocompostos/farmacologia , Inseticidas/química , Inseticidas/farmacologia , Compostos Azo/química , Compostos Azo/farmacologia , Neonicotinoides/química , Neonicotinoides/farmacologia , Pirazóis/química , Pirazóis/farmacologia , Aedes/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Comportamento Animal/efeitos dos fármacos , Luz , Receptores Nicotínicos/química , Receptores Nicotínicos/metabolismo , Receptores de GABA/metabolismo , Receptores de GABA/química
18.
Environ Int ; 188: 108770, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38821016

RESUMO

BACKGROUND: The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone levels in cross-sectional studies. Few studies have assessed longitudinal associations between urinary phthalate metabolite concentrations and sex hormone levels during menopausal transition. METHODS: Pre- and perimenopausal women from the Midlife Women's Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally. RESULTS: We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: -4.51%; 95% CI: -6.72%, -2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures. CONCLUSIONS: Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period.


Assuntos
Poluentes Ambientais , Perimenopausa , Ácidos Ftálicos , Humanos , Ácidos Ftálicos/urina , Feminino , Pessoa de Meia-Idade , Estudos Longitudinais , Perimenopausa/sangue , Poluentes Ambientais/sangue , Poluentes Ambientais/urina , Estradiol/sangue , Adulto , Hormônios Esteroides Gonadais/sangue , Progesterona/sangue , Progesterona/urina , Exposição Ambiental/estatística & dados numéricos , Saúde da Mulher , Testosterona/sangue
19.
Chem Commun (Camb) ; 60(47): 6063-6066, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38780308

RESUMO

In this study, a benzoselenadiazole- and pyridine-bifunctionalized hydrogen-bonded arylamide foldamer was synthesized. A co-crystallization experiment with 1,4-diiodotetrafluorobenzene showed that a new type of supramolecular double helices, which were induced by three orthogonal interactions, namely, three-center hydrogen bonding (O⋯H⋯O), I⋯N halogen bonding and Se⋯N chalcogen bonding, have been constructed in the solid state. This work presents a novel instance of multiple non-covalent interactions that work together to construct supramolecular architectures.

20.
ACS Appl Mater Interfaces ; 16(22): 29069-29076, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38795038

RESUMO

The development of granular carbon materials with outstanding selectivity for the separation of alkenes and alkanes is highly desirable in the petrochemical industry but remains a significant challenge due to closely similar molecular sizes and physical properties of adsorbates. Herein, we report a facile approach of using natural biomass to prepare novel granular carbon molecule sieves with a molecular recognition accuracy of 0.44 Å and propose a new three-region model for the pore size distribution of amorphous porous carbons. Coffee bean-based granule carbon molecular sieves (CFGCs) were prepared with precise micropore regulation with subangstrom accuracy and characterized using molecular probes to reveal the evolution of carbon structure during preparation. The CFGC-0.09-750 demonstrates exceptional selectivity adsorption toward C3H6 while excluding C3H8, with an uptake ratio of 106.75 and a C3H6 uptake of 1.88 mmol/g at 298 K and 100 kPa, showcasing its immense potential in industrial applications for separating C3H6 and C3H8. The novel three-region model established in this work can clearly and reasonably elucidate why the samples CFGCs can screen propylene from propane at the subangstrom level. This study provides important guidance for the development of new carbon molecular sieves with subangstrom accuracy in molecular recognition and separation capacity.

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