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1.
Diabetologia ; 67(5): 850-863, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38413438

RESUMO

AIMS/HYPOTHESIS: Type 2 diabetes mellitus is known to contribute to the development of heart failure with preserved ejection fraction (HFpEF). However, identifying HFpEF in individuals with type 2 diabetes early on is often challenging due to a limited array of biomarkers. This study aims to investigate specific biomarkers associated with the progression of HFpEF in individuals with type 2 diabetes, for the purpose of enabling early detection and more effective management strategies. METHODS: Blood samples were collected from individuals with type 2 diabetes, both with and without HFpEF, for proteomic analysis. Plasma integrin α1 (ITGA1) levels were measured and compared between the two groups. Participants were further categorised based on ITGA1 levels and underwent detailed transthoracic echocardiography at baseline and during a median follow-up period of 30 months. Multivariable linear and Cox regression analyses were conducted separately to assess the associations between plasma ITGA1 levels and changes in echocardiography indicators and re-hospitalisation risk. Additionally, proteomic data for the individuals' left ventricles, from ProteomeXchange database, were analysed to uncover mechanisms underlying the change in ITGA1 levels in HFpEF. RESULTS: Individuals with type 2 diabetes and HFpEF showed significantly higher plasma ITGA1 levels than the individuals with type 2 diabetes without HFpEF. These elevated ITGA1 levels were associated with left ventricular remodelling and impaired diastolic function. Furthermore, during a median follow-up of 30 months, multivariable analysis revealed that elevated ITGA1 levels independently correlated with deterioration of both diastolic and systolic cardiac functions. Additionally, higher baseline plasma ITGA1 levels independently predicted re-hospitalisation risk (HR 2.331 [95% CI 1.387, 3.917], p=0.001). Proteomic analysis of left ventricular myocardial tissue provided insights into the impact of increased ITGA1 levels on cardiac fibrosis-related pathways and the contribution made by these changes to the development and progression of HFpEF. CONCLUSIONS/INTERPRETATION: ITGA1 serves as a biomarker for monitoring cardiac structural and functional damage, can be used to accurately diagnose the presence of HFpEF, and can be used to predict potential deterioration in cardiac structure and function as well as re-hospitalisation for individuals with type 2 diabetes. Its measurement holds promise for facilitating risk stratification and early intervention to mitigate the adverse cardiovascular effects associated with diabetes. DATA AVAILABILITY: The proteomic data of left ventricular myocardial tissue from individuals with type 2 diabetes, encompassing both those with and without HFpEF, is available from the ProteomeXchange database at http://proteomecentral.proteomexchange.org .


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/complicações , Função Ventricular Esquerda , Volume Sistólico , Integrina alfa1 , Diabetes Mellitus Tipo 2/complicações , Proteômica , Biomarcadores
2.
Int Arch Allergy Immunol ; 185(3): 274-285, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38029733

RESUMO

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a serious inflammatory condition. Nasal fluids (NFs) present a noninvasive alternative to nasal biopsy for studying CRSwNP pathogenesis. We aimed to compare the protein and mRNA inflammation signature between nasal polyps (NPs) and NFs. METHOD: The performance of polyvinyl alcohol (PVA) sponges and NFs absorbable device (NFAD) for collecting NFs from 20 patients with CRSwNP was compared using the Luminex assay. The other group consisted of four healthy controls and an additional 21 CRSwNP patients (including eosinophilic CRSwNP [ECRSwNP] and non-eosinophilic CRSwNP [NECRSwNP]) for protein quantification by Olink platform and gene expression evaluation by RNA-sequencing. Spearman's analysis was performed to detect correlations between protein expression levels in NFs and clinical assessment variables. RESULTS: NFAD-collected NFs contained at least a 2-fold higher concentration of cytokines than that obtained using PVA sponge, and these cytokines levels are significantly associated with NPs (ρ > 0.45, p < 0.05). Differentially expressed proteins between NFs and NPs were significantly correlated in the ECRSwNP subgroup compared with controls (ρ = 0.41, p < 0.01). Levels of Th2/IL-13, MCP4, and CCL4, characteristic of eosinophilic infiltration, were increased in ECRSwNP patients. A significant correlation between gene and protein expression was observed (ρ = 0.34, p < 0.01). PDL2 levels in NFs were positively correlated with ECRSwNP postoperative recurrence, the nasal VAS, and SNOT-22 scores (ρ > 0.68, p < 0.05 for all). CONCLUSION: Our study revealed similarities and discrepancies in inflammatory signatures between NPs and NFs in the same CRSwNP patient.


Assuntos
Pólipos Nasais , Rinite , Rinossinusite , Sinusite , Humanos , Pólipos Nasais/genética , Pólipos Nasais/metabolismo , Rinite/diagnóstico , Transcriptoma , Sinusite/genética , Sinusite/diagnóstico , Citocinas/metabolismo , Doença Crônica
3.
Artigo em Inglês | MEDLINE | ID: mdl-38880209

RESUMO

BACKGROUND: Despite the large patient base in Asia, the prognostic factors of patients with non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNPs) remain largely undetermined. OBJECTIVE: To systematically investigate the predictive value of clinical and biological variables for non-eosinophilic CRSwNP. METHODS: A total of 51 patients with non-eosinophilic CRSwNP who underwent functional endoscopic surgery were recruited. Clinical information and assessment were comprehensively collected before and after surgery. A broad spectrum of biomarkers was measured in tissue homogenates using multiple assays. A random forest algorithm and stepwise logistic regression were used to construct clinical, biological, and combined models. RESULTS: A total of 41.2% patients with non-eosinophilic CRSwNP were uncontrolled more than 6 months after surgery. We identified 1 clinical variable (22-item Sino-Nasal Outcome Test score) and 4 biomarkers (programmed cell death ligand 1, platelet-derived growth factor subunit ß [PDGF-ß], macrophage inflammatory protein-3b, and PDGF-α) that were significantly predictive of the surgical outcome. The clinical, biological, and combined models had predictive ability with areas under the curve of 0.78, 0.83, and 0.89, respectively. PDGF-ß and programmed cell death ligand 1 were identified as independent biomarkers for the prognosis of patients with CRSwNP without considerable eosinophilic infiltration. CONCLUSION: This study reveals that clinical and biological factors, such as the 22-item Sino-Nasal Outcome Test score and PDGF-ß, are predictive of the postfunctional endoscopic surgical prognosis of patients with non-eosinophilic CRSwNP.

4.
Angew Chem Int Ed Engl ; 61(10): e202114786, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35037354

RESUMO

The production of p-xylene from the methanol to aromatics (MTA) reaction is challenging. The catalytic stability, which is inversely proportional to the particle size of the zeolite, is not always compatible with p-xylene selectivity, which is inversely proportional to the external acid sites. In this study, based on a nano-sized zeolite, we designed hollow triple-shelled Zn/MFI single crystals using the ultra-dilute liquid-phase growth technique. The obtained composites possessed one ZSM-5 layer (≈30 nm) in the middle and two silicalite-1 layers (≈20 nm) epitaxially grown on two sides of ZSM-5, which exhibited a considerably long lifetime (100 % methanol conversion >40 h) as well as an enhanced shape selectivity of p-xylene (>35 %) with a p-xylene/xylene ratio of ≈90 %. Importantly, using this sandwich-like zeolite structure, we directly imaged the Zn species in the micropores of only the ZSM-5 layer and further determined the specific structure and anchor location of the Zn species.

5.
Biochem Biophys Res Commun ; 550: 22-29, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33677132

RESUMO

Autism spectrum disorders (ASD) are a group of neurological disorders which affect approximately 1% of children around the world. Social dysfunction is one of the two core syndromes of ASD, and still lacks effective treatment. Transcranial magnetic stimulation (TMS) is a noninvasive and safe procedure that uses magnetic fields to modulate neural activity. Whether it were effective in modulating social function remains unclear. By using 3-chamber test, ultrasonic vocalization recording and Western-blotting, we demonstrated that FMR1 (fragile X mental retardation protein) mutant mice, a model of ASD, exhibited obvious defects in social preference and ultrasonic communication. In addition, we detected increase of p-Akt (S473) and p-GSK-3ß (S9), and decrease of p-PSD-95 (T19) in the anterior cingulate cortex (ACC) of FMR1-/- mice. Treating FMR1-/- mice with 1 Hz repetitive TMS (rTMS) exerted a long lasting effect in improving both the ultrasonic communication and social preference, as well as restoring the levels of Akt/GSK-3ß activity and spine density in the FMR1-/-ACC. Our data, for the first time, demonstrated a beneficial effect of low frequency rTMS (LF-rTMS) on the social function of FMR1-/- mice and an involvement of Akt/GSK-3ß signaling in this process, indicating LF-rTMS as a potential therapeutic strategy for ASD patients.


Assuntos
Proteína do X Frágil da Deficiência Intelectual/genética , Deleção de Genes , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Transtornos do Comportamento Social/prevenção & controle , Transtornos do Comportamento Social/terapia , Estimulação Magnética Transcraniana , Comunicação Animal , Animais , Transtorno do Espectro Autista/prevenção & controle , Transtorno do Espectro Autista/terapia , Feminino , Giro do Cíngulo/metabolismo , Masculino , Camundongos , Fatores de Tempo , Ultrassom
6.
Biochem J ; 477(23): 4655-4674, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33216871

RESUMO

The bi-directional selective low toxicity/high flame retardancy organophosphorus fire retardants (OPFRs) derivatives were designed by a comprehensive effect 3D quantitative structure-activity relationship (QSAR) pharmacophore model, and the toxicity and flame retardancy mechanism of OPFR derivatives were explored. The 3D-QSAR comprehensive pharmacophore model was constructed using the toxicity/flame retardancy comprehensive evaluation values of OPFRs for molecular modifications, which were obtained by the Mamdani fuzzy inference approach. The environment-friendly OPFR derivatives (CDPP-F, CDPP-NO2, TPHP-F, TDCIPP-CH2CH3, and TDCIPP-Br) with high flame retardancy showed significantly reduced multi-toxicity effects (biotoxicity, reproductive toxicity, and neurotoxicity) in the comprehensive model. The spatial overlapping volumes of the toxicity/flame retardancy comprehensive effect model with the toxic effect and with flame retardant effect were 1 : 1. The trend (1 : 1) was similar to the degree of improvement of toxicity and flame retardancy of the OPFR derivatives. The toxicity and flame retardancy were decreased by more than 50%. This indicated that the spatial overlapping volumes in the comprehensive model with the toxic and flame retardant mono-models have significant effects. Based on the 2D-QSAR model, molecular docking, and density functional theory, it was found that, in molecular modification, the introduction of electronegative groups to improve the electronic parameters (q+) can reduce the toxicity of OPFRs. An increase in the bond length and bond angle of the molecular side chain increased the steric parameter (MR) that improved the molecular flame retardancy of OPFRs.


Assuntos
Retardadores de Chama , Simulação de Acoplamento Molecular , Compostos Organofosforados/química , Compostos Organofosforados/toxicidade
7.
J Environ Manage ; 299: 113628, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34461464

RESUMO

The present study attempted to improve the biodegradation removal rate of Fluoroquinolones (FQs) in sewage treatment plants. The similarity index analysis (CoMSIA) model for combined biodegradability was constructed, and 33 kinds of molecular derivatives of FQs suitable for a variety of aerobic biodegradation microorganisms were designed. Further, derivative-20 and derivative-28, with high drug efficiency, drug safety, and environmental friendliness were selected through pharmacokinetics (ADMET), toxicokinetics (TOPKAT), FQs functional characteristics, and environmental friendliness evaluations. Compared with the target molecules, the combined biodegradability of the above two FQ-derivative molecules were increased by 193.57 % and 205.07 %, respectively, while their environment-friendly characteristics were improved to a certain degree. Through molecular docking and molecular dynamic simulation analysis, it showed that van der Waals force (decreased by 2.73 %-61.74 %) was the main factor influencing the binding ability of the modified FQ molecules to the receptor proteins. In addition, the relationship among the non-bonding interaction resultant force, the binding effect of the FQ-derivative molecules, and the receptor protein-related amino acid residues were studied for the first time. It was observed that the higher the value of the non-bonding interaction resultant force, the better was the binding effect, which demonstrating the significantly improved biodegradability of the designed FQ-derivative molecules.


Assuntos
Fluoroquinolonas , Preparações Farmacêuticas , Bactérias , Biodegradação Ambiental , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade
8.
Ecotoxicol Environ Saf ; 191: 110186, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31954922

RESUMO

A three-dimensional quantitative structure-activity relationship (3D-QSAR) model was established based on molecular structures and docking scores (representing the biodegradability); the scores were obtained for 23 fluoroquinolones (FQs) and the oxidoreductase (PDB ID: 1YZP) of Phanerochaete chrysosporium in the aerobic process of municipal wastewater treatment plants. In the Comparative Molecular Field Analysis (CoMFA) model, q2 was 0.516 and r2pred was 0.727, which showed that the model was reliable and robust. The modification information obtained by the contour maps showed that introducing electronegative, bulky or electropositive groups at different active sites could increase the biodegradability of fluoroquinolone derivatives. Using levofloxacin (LEV) as a modified molecule, 35 fluoroquinolone derivatives with higher biodegradability than LEV were designed. After the evaluation of genotoxicity, bioconcentration and photodegradation, Derivative-15, with higher biodegradability (increased by 27.85%), higher genotoxicity, higher photodegradation and lower bioconcentration, was identified as the most environmentally friendly fluoroquinolone derivative. The 2D-QSAR model of FQ biodegradability was established through the quantization parameters, and q+ was identified as the main parameter affecting the biodegradability of FQs through sensitivity analysis. In addition, the docking results of LEV and Derivative-15 with the oxidoreductase in P. chrysosporium showed that the electrostatic field force between Derivative-15 and the amino acid residues promoted the binding of the donor to the receptor protein, thereby increasing the biodegradability of Derivative-15. Additionally, molecular dynamics simulations revealed that the enhancement of the electrostatic field force with Derivative-15 could promote the binding of the ligand to the receptor, which was basically consistent with the conclusion of molecular docking. Finally, the three microbial degradation pathways of LEV and Derivative-15 were also proposed. The total energy barrier value of the pathway with the lowest total energy barrier of biodegradation was reduced by 32.07%, which was basically consistent with the enhancement of biodegradability of Derivative-15.


Assuntos
Fluoroquinolonas/química , Modelos Moleculares , Poluentes Químicos da Água/química , Basidiomycota/enzimologia , Biodegradação Ambiental , Fluoroquinolonas/farmacocinética , Fluoroquinolonas/toxicidade , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Oxirredutases/química , Relação Quantitativa Estrutura-Atividade , Poluentes Químicos da Água/farmacocinética , Poluentes Químicos da Água/toxicidade
9.
Glycobiology ; 27(9): 861-867, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28810659

RESUMO

Antibiotics such as ß-lactams and aminoglycosides are often subtherapeutic to intracellular infections due to their high hydrophilicity, resulting in low effectiveness against intracellular pathogens and the emergence of antibiotic resistance. Here we reported that an endogenous aminoglycan, hyaluronic acid could be an effective carbohydrate carrier of the aminoglycoside antibiotic, streptomycin against intracellular pathogens. This conjugation could enhance phagocytic activity, and facilitated the entry of streptomycin into host cells via a CD44-mediated pathway. It appeared that this conjugate could clear intracellular bacteria in phagocytic or nonphagocytic cells in a short-term therapy (4 h) at a lower effective dose. In addition, this conjugate was more efficient in reducing bacteria burden in an in vivo acute infection model than streptomycin did. Interestingly, subcutaneous injection of this conjugate at an excess amount had undetectable side effects such as nephrotoxicity. These results suggested that hyaluronic acid might be an efficient Trojan horse for the delivery of hydrophilic antibiotics to deal with intracellular infections.


Assuntos
Glicoconjugados/farmacologia , Ácido Hialurônico/química , Listeriose/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Estreptomicina/farmacologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Sequência de Carboidratos , Permeabilidade da Membrana Celular , Chlorocebus aethiops , Expressão Gênica , Glicoconjugados/química , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Rim/efeitos dos fármacos , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/crescimento & desenvolvimento , Listeria monocytogenes/patogenicidade , Listeriose/microbiologia , Masculino , Camundongos , Células RAW 264.7 , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/patogenicidade , Estreptomicina/química , Testes de Toxicidade Aguda , Células Vero
10.
Int J Mol Sci ; 18(4)2017 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-28397768

RESUMO

Bacteria on living or inert surfaces usually form biofilms which make them highly resistant to antibiotics and immune clearance. Herein, we develop a simple approach to overcome the above conundrum through lysozyme-associated liposomal gentamicin (LLG). The association of lysozyme to the surface of liposomes can effectively reduce the fusion of liposomes and undesirable payload release in regular storage or physiological environments. The LLG was more effective at damaging established biofilms and inhibiting biofilm formation of pathogens including Gram-positive and Gram-negative bacteria than gentamicin alone. This strategy may provide a novel approach to treat infections due to bacterial biofilm.


Assuntos
Biofilmes/efeitos dos fármacos , Gentamicinas/farmacologia , Lipossomos/metabolismo , Muramidase/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/crescimento & desenvolvimento , Humanos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Microscopia de Fluorescência , Pseudomonas aeruginosa/fisiologia , Pseudomonas aeruginosa/ultraestrutura , Staphylococcus aureus/fisiologia , Staphylococcus aureus/ultraestrutura
11.
Bioorg Med Chem Lett ; 26(10): 2401-2407, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-27072908

RESUMO

Cholesterol derivatives M1-M6 as synthetic cationic lipids were designed and the biological evaluation of the cationic liposomes based on them as non-viral gene delivery vectors were described. Plasmid pEGFP-N1, used as model gene, was transferred into 293T cells by cationic liposomes formed with M1-M6 and transfection efficiency and GFP expression were tested. Cationic liposomes prepared with cationic lipids M1-M6 exhibited good transfection activity, and the transfection activity was parallel (M2 and M4) or superior (M1 and M6) to that of DC-Chol derived from the same backbone. Among them, the transfection efficiency of cationic lipid M6 was parallel to that of the commercially available Lipofectamine2000. The optimal formulation of M1 and M6 were found to be at a mol ratio of 1:0.5 for cationic lipid/DOPE, and at a N/P charge mol ratio of 3:1 for liposome/DNA. Under optimized conditions, the efficiency of M1 and M6 is greater than that of all the tested commercial liposomes DC-Chol and Lipofectamine2000, even in the presence of serum. The results indicated that M1 and M6 exhibited low cytotoxicity, good serum compatibility and efficient transfection performance, having the potential of being excellent non-viral vectors for gene delivery.


Assuntos
Colesterol/química , Terapia Genética/métodos , Lipídeos/química , Lipossomos/química , Relação Estrutura-Atividade , Colesterol/análogos & derivados , Técnicas de Transferência de Genes , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Lipídeos/síntese química , Tamanho da Partícula , Fosfatidiletanolaminas/química , Soro/química , Transfecção/métodos
12.
Biol Pharm Bull ; 39(7): 1112-20, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-27118165

RESUMO

In this work two novel cationic lipids using natural tartaric acid as linking backbone were synthesized. These cationic lipids were simply constructed by tartaric acid backbone using head group 6-aminocaproic acid and saturated hydrocarbon chains dodecanol (T-C12-AH) or hexadecanol (T-C16-AH). The physicochemical properties, gel electrophoresis, transfection activities, and cytotoxicity of cationic liposomes were tested. The optimum formulation for T-C12-AH and T-C16-AH was at cationic lipid/dioleoylphosphatidylethanolamine (DOPE) molar ratio of 1 : 0.5 and 1 : 2, respectively, and N/P charge molar ratio of 1 : 1 and 1 : 1, respectively. Under optimized conditions, T-C12-AH and T-C16-AH showed effective gene transfection capabilities, superior or comparable to that of commercially available transfecting reagent 3ß-[N-(N',N'-dimethylaminoethyl)carbamoyl]cholesterol (DC-Chol) and N-[2,3-dioleoyloxypropyl]-N,N,N-trimethylammonium chloride (DOTAP). The results demonstrated that the two novel tartaric acid-based cationic lipids exhibited low toxicity and efficient transfection performance, offering an excellent prospect as nonviral vectors for gene delivery.


Assuntos
Técnicas de Transferência de Genes , Lipídeos/química , Tartaratos/química , Ácido Aminocaproico , Sobrevivência Celular/efeitos dos fármacos , DNA/administração & dosagem , DNA/química , Proteínas de Fluorescência Verde/genética , Células HEK293 , Células HeLa , Humanos , Lipossomos/química , Lipossomos/farmacologia
13.
BMC Public Health ; 15: 1079, 2015 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-26494015

RESUMO

BACKGROUND: Although much public scrutiny and academic attention has focused on the evaluations of system implementation since the beginning of New Rural Cooperative Medical System (NRCMS) in China, few studies have systematically evaluated the achievements of the stated policy goals. The purpose of this study is to examine to what extent the policy goals of NRCMS have been achieved. METHODS: Using multistage sampling processes, two rounds of cross-sectional household surveys including 9787 and 7921 rural households were conducted in Eastern China in year 2000 and year 2008, respectively. A pre- and post-implementation comparison was used to evaluate the achievement of policy goals in three measures: impoverishment from major health hazards, household financial risk from medical expenses, and rural income inequity. Intention surveys were also applied to find out potential obstacles in the implementation of NRCMS. RESULTS: The rate of re-impoverishment from health hazard was reduced from 2.69 % ex ante to 2.12 % ex post, a decrease of 21.13 %. The severity of impoverishment fell from a previous 4.66 % to 3.02 %, a decline of 35.18 %. Economic risk of medical treatment population relative to the whole population fell from 2.62 ex ante to 2.03 ex post, a 22.52 % reduction. As indication of effect on improving income equity, the Gini coefficient fell from 0.4629 to 0.4541. The effects of NRCMS were significantly better than those of RCMS. Despite the preliminary achievements, our intention survey of key respondents identified that technical difficulties in actuarial funding and more sustainable reimbursement schedules has become the most challenging barriers in achieving the goals of NRCMS, while raising the insurance premium on NRCMS was no longer as big a barrier. CONCLUSIONS: With NRCMS, China has established a medical security system to reduce the financial burden of healthcare on rural residents. NRCMS has achieved some positive though limited effects; but technical difficulties in the implementation of NRCMS have become barriers to achieve the pre-set policy goals. Efforts should be made to improve the capacity building in the design of the reimbursement schemes for the implementers of NRCMS, such as identifying medical impoverishment, calculating actuarial funding levels for the risk pooling.


Assuntos
Atenção à Saúde/organização & administração , Política de Saúde/economia , Serviços de Saúde Rural/organização & administração , População Rural/estatística & dados numéricos , Logro , Adulto , China/epidemiologia , Estudos Transversais , Atenção à Saúde/economia , Feminino , Apoio Financeiro , Organização do Financiamento/estatística & dados numéricos , Objetivos , Humanos , Masculino , Programas Nacionais de Saúde/organização & administração , Serviços de Saúde Rural/economia
14.
Front Oncol ; 14: 1375373, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38884084

RESUMO

Atypical Parathyroid Adenoma (APA) is a type of tumor that lies somewhere between parathyroid adenoma and parathyroid carcinoma. It often affects adults over the age of 60, and the clinical symptoms are consistent with those of hyperparathyroidism. This condition has a low occurrence, and its ultrasonographic signs are strikingly similar to thyroid malignant tumors, making it easily misdiagnosed. As a result, a case of APA ultrasonography misdiagnosis admitted to our hospital was recorded in order to serve as a reference point for APA diagnosis.

15.
Diabetes Metab Syndr Obes ; 17: 1833-1843, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38680996

RESUMO

Background: Peroxidation is one of the important causes of insulin resistance (IR), and vitamin E is a natural antioxidant, and there may be some correlation between serum vitamin E levels and insulin resistance. Purpose: The correlation between serum vitamin E and insulin resistance in type 2 diabetes mellitus (T2DM) population. Methods: Two hundred and forty-two people (119 with T2DM) were included. One hundred and nineteen patients with T2DM were selected as the case group, and 123 people with non-T2DM were selected as the control group. People insulin resistance was detected by the homeostasis model assessment method (HOMA-IR) greater than 2.69 were included in the diabetic insulin resistance group, and those with HOMA-IR less than 2.69 were included in the diabetic non-insulin resistance group. Record the general body indicators, biochemical indicators, hepatic function indicators, vitamin E, and other indicators. Correlation analysis, logistic regression, trend analysis, and restricted cubic spline (RCS) were performed using SPSS 25.0 and R 4.1.1 software. Correlation analysis, logistic regression, trend analysis, restricted cubic spline (RCS) analysis were conducted on general body indicators, biochemical indicators, hepatic function indicators, vitamin E, and other indicators. Results: The logistic regression results showed that after adjusting for confounding factors, vitamin E was an independent influencing factor for insulin resistance in T2DM patients (P < 0.001). The trend analysis results show that with the decrease of serum vitamin E levels, the risk of insulin resistance in T2DM patients gradually increases. The RCS results showed that the risk of insulin resistance was significantly increased when the serum vitamin E level was lower than 10,575.23 ng/mL. Conclusion: Serum vitamin E levels are lower in T2DM patients than in healthy populations; Vitamin E is an independent influencing factor for HOMA-IR in T2DM patients. The risk of insulin resistance gradually increases in T2DM patients as serum vitamin E levels decrease. Vitamin E is a risk factor for insulin resistance at serum vitamin E levels below 10,575.23 ng/mL. At higher serum vitamin E levels than 10,575.23 ng/mL, vitamin E is a protective factor for insulin resistance.

16.
ACS Omega ; 9(24): 26708-26718, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38911737

RESUMO

Y-H bond functionalization has always been the focus of research interest in the area of organic synthesis. Direct hydrogen atom transfer (HAT) from the Y-H bond is one of the most efficient and practical methods to activate the Y-H bond. Recently, nitrogen centered radical cations were broadly utilized as H-abstraction catalysts to activate Y-H bonds via the HAT process. As a type of HAT catalyst, the H-affinity of nitrogen centered radical cations is a significant thermodynamic parameter to quantitatively evaluate the thermodynamic H-abstraction potentials of nitrogen centered radical cations. In this work, the pK a values of 120 protonated N-containing compounds in acetonitrile (AN) are predicted, and the H-affinities of 120 nitrogen centered radical cations in AN are derived from the reduction potentials of nitrogen centered radical cations and pK a of protonated N-containing compounds using Hess' law. This work focuses on the H-abstraction abilities of 120 nitrogen centered radical cations in AN to enrich the molecule library of novel HAT catalysts or H-abstractors and provides valuable thermodynamic guidelines for the application of nitrogen centered radical cations in Y-H bond functionalization.

17.
Materials (Basel) ; 17(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38255516

RESUMO

The epoxy resin-based (ESB) intumescent flame-retardant coatings were modified with 1,4-butanediol diglycidyl ether (14BDDE) and butyl glycidyl ether (BGE) as diluents and T403 and 4,4'-diaminodiphenylmethane (DDM) as curing agents, respectively. The effects of different diluents and curing agents on the flame-retardant and mechanical properties, as well as the composition evolution of the coatings, were investigated by using large-plate combustion, the limiting oxygen index (LOI), vertical combustion, a cone calorimeter, X-ray diffraction, FTIR analysis, a N2 adsorption and desorption test, a scanning electron microscope (SEM), a tensile strength test, and a viscosity test. The results showed that the addition of 14BBDE and T403 promoted the oxidation of B4C and the formation of boron-containing glass or ceramics, increased the residual mass of char, densified the surface char layer, and increased the specific surface area of porous residual char. When their dosage was 30%, ESB-1T-3 coating exhibited the most excellent flame-retardant properties. During the 2 h large-plate combustion test, the backside temperature was only 138.72 °C, without any melting pits. In addition, the peak heat release rate (PHRR), total heat release rate (THR), total smoke production (TSP), and peak smoke production (PSPR) were reduced by 13.15%, 13.9%, 5.48%, and 17.45%, respectively, compared to the blank ESB coating. The LOI value reached 33.4%, and the vertical combustion grade was V-0. In addition, the tensile strength of the ESB-1T-3 sample was increased by 10.94% compared to ESB. In contrast, the addition of BGE and DDM promoted the combustion of the coating, affected the ceramic process of the coating, seriously affected the formation of borosilicate glass, and exhibited poor flame retardancy. The backside temperature reached 190.93 °C after 2 h combustion. A unified rule is that as the amount of diluent and curing agent increases, the flame retardancy improves while the mechanical properties decrease. This work provides data support for the preparation and process optimization of resin-based coatings.

18.
Front Behav Neurosci ; 18: 1387447, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38813469

RESUMO

Introduction: Autism spectrum disorder (ASD) is a group of diseases often characterized by poor sociability and challenges in social communication. The anterior cingulate cortex (ACC) is a core brain region for social function. Whether it contributes to the defects of social communication in ASD and whether it could be physiologically modulated to improve social communication have been poorly investigated. This study is aimed at addressing these questions. Methods: Fragile X mental retardation 1 (FMR1) mutant and valproic acid (VPA)-induced ASD mice were used. Male-female social interaction was adopted to elicit ultrasonic vocalization (USV). Immunohistochemistry was used to evaluate USV-activated neurons. Optogenetic and precise target transcranial magnetic stimulation (TMS) were utilized to modulate anterior cingulate cortex (ACC) neuronal activity. Results: In wild-type (WT) mice, USV elicited rapid expression of c-Fos in the excitatory neurons of the left but not the right ACC. Optogenetic inhibition of the left ACC neurons in WT mice effectively suppressed social-induced USV. In FMR1-/-- and VPA-induced ASD mice, significantly fewer c-Fos/CaMKII-positive neurons were observed in the left ACC following USV compared to the control. Optogenetic activation of the left ACC neurons in FMR1-/- or VPA-pretreated mice significantly increased social activity elicited by USV. Furthermore, precisely stimulating neuronal activity in the left ACC, but not the right ACC, by repeated TMS effectively rescued the USV emission in these ASD mice. Discussion: The excitatory neurons in the left ACC are responsive to socially elicited USV. Their silence mediates the deficiency of social communication in FMR1-/- and VPA-induced ASD mice. Precisely modulating the left ACC neuronal activity by repeated TMS can promote the social communication in FMR1-/- and VPA-pretreated mice.

19.
Front Endocrinol (Lausanne) ; 14: 1136048, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37152935

RESUMO

Background: Non-fasting lipid assessment can help predict cardiovascular disease risks and is linked to multiple diseases, particularly diabetes. The significance of non-fasting lipid levels in routine screening and postprandial lipid tests for potential dyslipidemia has not been conclusively determined. Various new lipid-lowering strategies have been developed to improve non-fasting dyslipidemia. Therefore, analysis of scientific outputs over the past decade is essential to reveal trends, hotspots, and frontier areas for future research in this field. Methods: The Science Citation Index Expanded in the Web of Science Core Collection database was searched for publications related to non-fasting lipid research from 2012 to 2022. The regional distributions, authors, disciplines, journals, references, and keywords of the studies were analyzed using the bibliometric software VOSviewer and CiteSpace. Results: A total of 4160 articles and reviews that met the inclusion criteria were included in this study. The output trend was established to be stable and the number of citation indices has been persistently increasing. A total of 104 countries/regions, 4668 organizations, and 20782 authors were involved in this research area. In terms of country, the United States had the largest number of publications (979). The University of Copenhagen was the most productive institution, publishing 148 papers. Professor Børge G Nordestgaard has made the most significant contribution to this field. Nutrients was the most productive journal while the American Journal of Clinical Nutrition was the highest co-cited journal. Analysis of co-cited references indicated that lipid-lowering strategies, statin therapy, high-fat meals, insulin resistance, physical exercise, and fructose were hotspots. Analysis of co-cited keywords revealed that apolipoprotein B, especially apolipoprotein B48, is becoming a key research focus. The keywords "gut microbiota" and "meal timing" were the most extensively studied. Conclusion: The causal relationship between non-fasting dyslipidemia and diseases is currently being explored and the standards for non-fasting or postprandial lipid assessment are continuously being updated. Among the hotspots, lipid-lowering strategies are a potential research direction. Apolipoprotein B48, gut microbiota, and chrononutrition are the research frontiers. This initial bibliometric analysis of non-fasting lipids will enable researchers to monitor swift transformations and recognize novel concepts for upcoming research.


Assuntos
Apolipoproteínas B , Bibliometria , Apolipoproteína B-48 , Bases de Dados Factuais , Exercício Físico
20.
Diabetes Metab Syndr Obes ; 16: 1481-1491, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37229352

RESUMO

Background: Adequate intake of folic acid (FA) has been proven essential for metabolism, cellular homeostasis, and antioxidant effects in diabetic patients. Our aim was to evaluate the association between serum folate levels and the risk of insulin resistance in patients with type 2 diabetes mellitus (T2DM) and to provide new ideas and approaches for reducing the risk of T2DM. Methods: This was a case-control study involving 412 participants (206 with T2DM). Anthropometric parameters, islet function, biochemical parameters and body composition of T2DM group and control group were determined. Correlation analysis and logistic regression were used to evaluate the risk factors associated with the onset of insulin resistance in T2DM. Results: The folate levels in type 2 diabetic patients with insulin resistance were significantly lower than those in patients without insulin resistance. Logistic regression showed that FA and high-density lipoprotein were independent influencing factors for insulin resistance in diabetic patients (P < 0.05). After adjusting for confounding factors, the degree of insulin resistance in diabetic patients was in a significant inverse relationship with folate levels (P< 0.05). We also found that below the serum FA threshold of 7.09 ng/mL insulin resistance was significantly more elevated. Conclusion: Our findings suggest that the risk of insulin resistance increases with the decrease in serum FA levels in T2DM patients. Monitoring folate levels in these patients and FA supplementation are warranted preventive measures.

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