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1.
Sci Total Environ ; 946: 174428, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964390

RESUMO

Tris(2-chloroethyl) phosphate (TCEP), a chlorinated organophosphate ester, is commonly found in aquatic environments. Due to its various toxic effects, it may pose a risk to the health of aquatic organisms. However, the potential impacts of TCEP exposure on the intestinal microbiota and hepatic function in amphibians have not been reported. This study investigated the impact of long-term exposure to environmentally relevant concentrations of TCEP (0, 3, and 90 µg/L) on the intestinal microbiota and hepatic transcriptome of Polypedates megacephalus tadpoles. The results showed that the body size of the tadpoles decreased significantly with an increase in TCEP concentration. Additionally, TCEP exposure affected the diversity and composition of the intestinal microbiota in tadpoles, leading to significant changes in the relative abundance of certain bacterial groups (the genera Aeromonas decreased and Citrobacter increased) and potentially promoting a more even distribution of microbial species, as indicated by a significant increase in the Simpson index. Moreover, the impact of TCEP on hepatic gene expression profiles in tadpoles was significant, with the majority of differentially expressed genes (DEGs) (709 out of 906 total DEGs in 3 µg/L of TCEP versus control, and 344 out of 387 DEGs in 90 µg/L of TCEP versus control) being significantly down-regulated, which were primarily related to immune response and immune system process. Notably, exposure to TCEP significantly reduced the relative abundance of the genera Aeromonas and Cetobacterium in the tadpole intestine. This reduction was positively correlated with the down-regulated expression of immune-related genes in the liver of corresponding tadpoles. In summary, these findings provide empirical evidence of the potential health risks to tadpoles exposed to TCEP at environmentally relevant concentrations.

2.
Exp Ther Med ; 28(2): 330, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38979021

RESUMO

Chrysanthemum indicum Linnén (C. indicum), a medicinal and food herb with various bioactive components, may be of beneficial use in cosmetics and the treatment of skin-related diseases. However, to date, few studies have been reported on its potential preventive and therapeutic effects on skin cancer. Therefore, the present study aimed to investigate the effect and potential mechanism of action of supercritical carbon dioxide extract from C. indicum (CISCFE) on UV-induced skin cancer in a mouse model. Kunming mice were allocated randomly to five treatment groups: Sham, model, low concentration CISCFE, high concentration CISCFE and positive control nicotinamide groups. The dorsal skin of mice was irradiated with UV light for 31 weeks. Histopathological changes, ELISA assays, immunohistochemical analysis and western blotting were performed to investigate the potential therapeutic effects of CISCFE. The results showed that CISCFE alleviated skin oxidative and inflammatory damage in a UV-induced mouse model of skin cancer. Moreover, CISCFE suppressed abnormal activation of proto-oncogene c-Myc and the overexpression of Ki-67 and VEGF, and increased expression of the anti-oncogene PTEN, thereby reducing abnormal proliferation of the epidermis and blood vessels. Additionally, CISCFE increased the protein expression levels of NAD-dependent protein deacetylase sirtuin-1 (SIRT1), Kelch-like ECH associated protein 1 (Keap1) and inhibited the expression of nuclear factor 2 erythroid 2-related factor 2 (Nrf2), phosphorylated (p)-p62 (Ser 349), p-p65 and acetyl-p65 proteins in a UV-induced skin cancer mouse model. In summary, CISCFE exhibited potent anti-skin cancer activity, which may be attributed its potential effects on the p62/Keap1-Nrf2 and SIRT1/NF-κB pathways.

3.
Tetrahedron Lett ; 1442024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39006392

RESUMO

Thienamycin is a carbapenem antibiotic with potent activity against gram-negative and gram-positive bacteria. Due to its promising activity but lack of chemical stability, thienamycin serves as inspiration for new synthetic antibiotic scaffolds. In this study, we report a nine-step enantioselective formal synthesis of thienamycin. Our route utilizes an asymmetric reduction, enabled by NaBH4 and D-tartaric acid, followed by a series of diastereoselective reactions to access the key azetidinone precursor to thienamycin. This azetidinone precursor could be used as an intermediate to further develop and expand the scope of next-generation beta-lactam antibiotic scaffolds.

4.
ACS Nano ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012271

RESUMO

The edges of 2D materials have emerged as promising electrochemical catalyst systems, yet their performance still lags behind that of noble metals. Here, we demonstrate the potential of oriented electric fields (OEFs) to enhance the electrochemical activity of 2D materials edges. By atomically engineering the edge of a fluorographene/graphene/MoS2 heterojunction nanoribbon, strong and localized OEFs were realized as confirmed by simulations and spatially resolved spectroscopy. The observed fringing OEF results in an enhancement of the heterogeneous charge transfer rate between the edge and the electrolyte by 2 orders of magnitude according to impedance spectroscopy. Ab initio calculations indicate a field-induced decrease in the reactant adsorption energy as the origin of this improvement. We apply the OEF-enhanced edge reactivity to hydrogen evolution reactions (HER) and observe a significantly enhanced electrochemical performance, as evidenced by a 30% decrease in Tafel slope and a 3-fold enhanced turnover frequency. Our findings demonstrate the potential of OEFs for tailoring the catalytic properties of 2D material edges toward future complex reactions.

5.
J Environ Manage ; 365: 121556, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38936026

RESUMO

Amidst escalating environmental concerns, regional cooperation has emerged as a potent strategy for environmental preservation. Yet, the potency of such cooperation in curbing air pollution remains largely unexplored and nebulous. Drawing upon a decade-long (2010-2019) new data from the dynamic Guangdong-Hong Kong-Macao Greater Bay Area (GBA), this study seeks to fill these knowledge gaps. Our findings underscore the transformative potential of regional cooperation in mitigating air pollution. By catalyzing technological advancements, fostering structural shifts in businesses, and reshaping land-use patterns, regional cooperation paves the way for a cleaner, healthier environment. A deeper dive into the heterogeneity reveals that "top to bottom" city agreements within regional cooperation frameworks significantly enhance air quality. While institutional and economic collaborations prove instrumental in reducing air pollution, social cooperation appears to have a lesser impact. Research findings indicate that the future will necessitate strengthening formal, institutionalized regional cooperation to address potential challenges posed by environmental pollution.


Assuntos
Poluição do Ar , Poluição do Ar/prevenção & controle , Hong Kong , Monitoramento Ambiental/métodos
6.
Int J Med Sci ; 21(7): 1280-1291, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818462

RESUMO

Introduction: An estimated 43% of COVID-19 patients showed sequelae, including fatigue, neurocognitive impairment, respiratory symptoms, and smell or taste disorders. These sequelae significantly affect an individual's health, work capacity, healthcare systems, and socioeconomic aspects. Traditional Chinese herbal medicine (TCHM) management showed clinical benefits in treating patients with COVID-19 sequelae. This study aimed to analyze the effects of personalized TCHM management in patients with COVID-19 sequelae. Methods: After the COVID-19 outbreak in Taiwan, we recorded Chronic Obstructive Pulmonary Disease Assessment Tool (CAT), Chalder Fatigue Questionnaire (CFQ-11), and Brief Symptom Rating Scale (BSRS-5) to assess post-COVID respiratory, fatigue, and emotional distress symptoms, respectively. In this study, we retrospectively reviewed the medical records between July 2022 and March 2023. We analyzed the effects of TCHM administration after 14- and 28-days of treatment. Results: 47 patients were included in this study. The results demonstrated that personalized TCHM treatment significantly improved the CAT, CFQ-11, and BSRS-5 scores after 14 and 28 days. TCHM alleviated physical and psychological fatigue. In logistic regression analysis, there was no statistically significant differences in the severity of the baseline symptoms and TCHM administration effects concerning the duration since the initial confirmation of COVID-19, sex, age, or dietary preference (non-vegetarian or vegetarian). Conclusions: Our study suggested that personalized TCHM treatment notably reduced fatigue, respiratory and emotional distress symptoms after 14- and 28-days of treatment in patients with COVID-19 sequelae. We propose that TCHM should be considered as an effective intervention for patients with COVID-19 sequelae.


Assuntos
COVID-19 , Medicamentos de Ervas Chinesas , SARS-CoV-2 , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Taiwan/epidemiologia , Estudos Retrospectivos , Medicamentos de Ervas Chinesas/uso terapêutico , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/psicologia , Idoso , Tratamento Farmacológico da COVID-19 , Fadiga/tratamento farmacológico , Fadiga/etiologia , Adulto , Medicina Tradicional Chinesa/métodos , Resultado do Tratamento
7.
J Am Chem Soc ; 146(10): 6444-6448, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38427590

RESUMO

The first total synthesis of the potent antimicrobial agent dynobactin A is disclosed. This synthesis enlists a singular aziridine ring opening strategy to access the two disparate ß-aryl-branched amino acids present within this complex decapeptide. Featuring a number of unique maneuvers to navigate inherently sensitive and epimerizable functional groups, this convergent approach proceeds in only 16 steps (LLS) from commercial materials and should facilitate the synthesis of numerous analogues for medicinal chemistry studies.


Assuntos
Aminoácidos , Anti-Infecciosos , Anti-Infecciosos/síntese química
8.
Plant J ; 118(6): 1907-1921, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38491869

RESUMO

The sex of dioecious plants is mainly determined by genetic factors, but it can also be converted by environmental cues such as exogenous phytohormones. Gibberellic acids (GAs) are well-known inducers of flowering and sexual development, yet the pathway of gibberellin-induced sex conversion in dioecious spinach (Spinacia oleracea L.) remains elusive. Based on sex detection before and after GA3 application using T11A and SSR19 molecular markers, we confirmed and elevated the masculinization effect of GA on a single female plant through exogenous applications of GA3, showing complete conversion and functional stamens. Silencing of GIBBERELLIC ACID INSENSITIVE (SpGAI), a single DELLA family protein that is a central GA signaling repressor, results in similar masculinization. We also show that SpGAI can physically interact with the spinach KNOX transcription factor SHOOT MERISTEMLESS (SpSTM), which is a homolog of the flower meristem identity regulator STM in Arabidopsis. The silencing of SpSTM also masculinized female flowers in spinach. Furthermore, SpSTM could directly bind the intron of SpPI to repress SpPI expression in developing female flowers. Overall, our results suggest that GA induces a female masculinization process through the SpGAI-SpSTM-SpPI regulatory module in spinach. These insights may help to clarify the molecular mechanism underlying the sex conversion system in dioecious plants while also elucidating the physiological basis for the generation of unisexual flowers so as to establish dioecy in plants.


Assuntos
Regulação da Expressão Gênica de Plantas , Giberelinas , Proteínas de Plantas , Spinacia oleracea , Flores/genética , Flores/fisiologia , Giberelinas/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Spinacia oleracea/genética , Spinacia oleracea/fisiologia , Spinacia oleracea/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
9.
Heliyon ; 10(3): e25825, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38356543

RESUMO

The association between clay minerals and organic carbon is pivotal for understanding transport, burial, and preservation processes of sedimentary organic carbon. However, fine-scale microscopic studies are still limited in assessing the effect of diverse clay mineral structures and properties on organic carbon sequestration. In this study, we employed X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and transmission electron microscopy coupled with energy dispersive spectroscopy and electron energy loss spectroscopy analyses to investigate the nanoscale interaction between clay minerals and organic carbon of two typical fluvial sediment samples with contrasting clay mineral compositions and organic carbon origins. Sample from Taiwan shows abundant illite and chlorite with petrogenic organic carbon, while sample from Luzon has significant smectite with pedogenic organic carbon. We observed that the nanostructure of the clay minerals controls the distribution of organic carbon. In the Luzon sample, the organic carbon is tightly associated with smectite, occupying expandable interlayer spaces. In the Taiwan sample, however, the organic carbon is primarily confined on the surface and edge of illite. These findings offer valuable insights into the selective association of organic carbon with clay minerals and underscore the role of clay mineral nanolayer structures in governing the occurrence and preservation of organic carbon in sediments. A comprehensive understanding of these interactions is crucial for accurate assessments of carbon cycling and sequestration in the natural environment.

10.
Virology ; 592: 109995, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38290415

RESUMO

The aim of this study was to investigate the effects of vaccination, COVID-19 pandemic and migration of migratory birds on the avian influenza positivity rate in Shangrao City and to predict the future avian influenza positivity rate. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to detect nucleic acids of avian influenza A viruses. 1795 samples were collected between 2016 and 2022, of which 1086 were positive. In addition, there were seven human cases of avian influenza. The results showed that the positivity rate of H9 subtype in Shangrao City was higher than usual during the COVID-19 pandemic and migratory birds. Predictions suggest that the H9 subtype positivity rate in Shangrao City will be on the rise in the future. In recent years, the H5 positivity rate has gradually increased. Migratory birds and the COVID-19 pandemic have led to an increase in H9 subtype positivity. Therefore, the prevention and control of them should be strengthened.


Assuntos
COVID-19 , Influenza Aviária , Animais , Humanos , Influenza Aviária/epidemiologia , Pandemias , Aves , China/epidemiologia
11.
Ann Surg Treat Res ; 106(1): 31-37, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38205097

RESUMO

Purpose: Polyacrylamide hydrogel (PAHG), which had been used widely for breast augmentation, has been banned for more than 15 years. Patients who had been injected PAHG for breast augmentation need evacuation surgery to remove as much as possible. To provide a series of diagnosis and treatment process MRI and intraoperative color Doppler ultrasound are combined for maximal removal of PAHG. Methods: The patients who received evacuation surgery in Peking University Third Hospital from 2010 to 2022 after PAHG injection for breast augmentation were included in this research. MR scanning was performed preoperatively and postoperatively in some of these patients and color Doppler ultrasound was applied to help evacuate PAHG intraoperatively. The mean clearance rate of PAHG was calculated according to the MRI outcomes. Results: Two hundred and 4 patients had received evacuation surgery after PAHG injection for breast augmentation with an average age of 42.8 years and an average body mass index of 21.2 kg/m2. The average PAHG retention time was 13.5 years. Among them, 52 patients underwent pre- and postoperative MRI scanning. The mean three-dimensional (3D) volume of PAHG was 684.8 mL (range, 350.0-1,123.9 mL), and the average residual 3D volume of PAHG was 53.7 mL (range, 12.4-98.3 mL). The mean clearance rate was 92.1%. Conclusion: MRI and intraoperative color Doppler ultrasound can provide effective and precise location information of PAHG for evacuation surgery, which is a reliable method to ensure the maximal removal of PAHG.

12.
J Dig Dis ; 24(12): 691-701, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37994615

RESUMO

OBJECTIVE: To estimate the performance of the FibroTouch-based ultrasound attenuation parameter (UAP) for assessing hepatic steatosis in nonalcoholic fatty liver disease (NAFLD), with magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. METHODS: This prospective, cross-sectional study included 275 individuals in the training group and 110 individuals in the validation group, all of whom completed a standardized research visit, laboratory tests, MRI-PDFF, and UAP measurements over 1 month. Pearson correlation coefficient and Bland-Altman analysis were used to assess the agreement between UAP and MRI-PDFF for the detection of hepatic steatosis. The diagnostic value of UAP was evaluated by the area under the receiver operating characteristic (ROC) curve (AUROC). Confounding factors to UAP performance were identified by ROC curves and regression analyses. RESULTS: The AUROC of UAP for detecting MRI-PDFF at ≥5%, ≥10%, and ≥20% were 0.95 (95% confidence interval [CI] 0.92-0.97), 0.86 (95% CI 0.81-0.90), and 0.90 (95% CI 0.86-0.93), respectively, and their optimal thresholds were 259, 274, and 295 dB/m, respectively. The UAP measurements had higher diagnostic accuracy in participants with lower waist circumference (≤90 cm for men and ≤80 cm for women) compared to those with higher waist circumference (AUROC values: 0.97 vs 0.84, P < 0.05). Bland-Altman analysis showed good agreement between UAP and MRI-PDFF (bias 0.00021). According to established regression analyses, hepatic steatosis could be accurately diagnosed using UAP estimation. CONCLUSIONS: FibroTouch-UAP has a high diagnostic potential for hepatic steatosis in NAFLD patients and helps clinical assessment and monitoring.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Masculino , Humanos , Feminino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Fígado/diagnóstico por imagem , Fígado/patologia , Estudos Transversais , Estudos Prospectivos , Curva ROC , Imageamento por Ressonância Magnética/métodos , Padrões de Referência
13.
J Dig Dis ; 24(11): 630-637, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37823361

RESUMO

OBJECTIVES: Laser lithotripsy under fluoroscopic guidance is difficult to perform and risky due to its invisibility. In this study we aimed to investigate the efficacy and safety of a novel endoscopic auxiliary system (NEAS)-assisted lithotripsy under fluoroscopy for treating difficult common bile duct (CBD) stones. METHODS: Patients with difficult CBD stones who were treated with NEAS-assisted laser lithotripsy (NEAS group) or conventional mechanical lithotripsy (ML) under fluoroscopy (ML group) were retrospectively evaluated. The primary outcome was the complete stone clearance rate and the secondary outcomes included operation time, complications, and medical cost. RESULTS: Seventeen patients were treated with NEAS-assisted laser lithotripsy and 144 patients underwent ML. Using the propensity score matching analysis, 17 pairs of cases treated with NEAS-assisted lithotripsy and ML were included. Patients in the NEAS group showed a higher stone clearance rate than the ML group (94.1% vs 58.8%, P = 0.039), as well as shorter operation time (41.9 min vs 49.4 min, P < 0.001) and lower medical cost (USD 4607 vs USD 5014, P < 0.001). There was no significant difference in the complication rate between the two groups (5.9% vs 17.6%, P = 0.601). CONCLUSION: NEAS-assisted fluoroscopy-guided laser lithotripsy is feasible and safe, which may be a promising technique in fluoroscopy-guided laser lithotripsy for difficult CBD stones.


Assuntos
Cálculos Biliares , Litotripsia , Humanos , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/terapia , Cálculos Biliares/etiologia , Projetos Piloto , Estudos Retrospectivos , Resultado do Tratamento , Litotripsia/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Fluoroscopia
14.
Eur J Radiol ; 168: 111073, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37741058

RESUMO

PURPOSE: To explore the effect of epinephrine mixed with local anaesthetic injection on blood flow control in early stage arteriovenous malformation (AVM) and explore suitable cases. METHODS: Twenty-five patients with early stage (Schobinger clinical stage I/II) AVM were selected between September 2019 and March 2022. Local anaesthetics containing epinephrine were injected around the nourishing artery and into lesions under the guidance of ultrasound, and the blood flow distribution grade in the lesions as well as the changes in diameter, peak systolic velocity (PSV), and resistance index (RI) of the nourishing arteries and vessels in the lesions were observed to determine the type of AVM suitable for epinephrine injection. After blood flow was controlled, sclerosant agents were injected into the lesions for sclerotherapy. RESULTS: After local injection of the epinephrine mixture, the blood flow distribution in the lesion decreased by one to three grades; the diameter and PSV also decreased, while RI increased. There were statistically significant differences before and after the injection (P < 0.05). The efficacy of the injection was 80% (20/25), especially in patients with lesion vessels, a nourishing artery lumen diameter <2 mm, and a PSV <40 cm/s in the lesion. Patients with Schobinger clinical stage I AWM showed good results. CONCLUSIONS: Local anaesthetics containing epinephrine play a positive role in reducing the distribution and velocity of blood flow in patients with AVM lesions and may be used as an experimental method for the treatment of AVM, which is beneficial for sclerotherapy in patients with early AVM.


Assuntos
Anestésicos Locais , Malformações Arteriovenosas Intracranianas , Humanos , Escleroterapia , Hemodinâmica/fisiologia , Artérias
15.
Environ Sci Pollut Res Int ; 30(43): 98271-98287, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37608166

RESUMO

How to reduce air pollution is an essential topic of environmental governance. Existing research has predominantly concentrated on the decentralization effect within the environmental field, leaving a gap in exploring non-environmental decentralization effects. This paper exploits a quasi-experiment of "counties power expansion (CPE)" reform in China to examine the effect of administrative decentralization on air pollution. Administrative decentralization will reorganize authority in economic and social matters and redistribute fiscal responsibility and resources for specific targets among multilevel governments. Employing a county-level dataset from 1999 to 2019 in China, we find that administrative decentralization significantly raises air pollution by about 2%. Our results further suggest that air pollution is mainly attributed to the increment of resource input and firm expansion. We find that geographical location will influence the air pollution effect. The policymaker should consider an inclusive intuitional design when launching administrative decentralization.


Assuntos
Poluição do Ar , Conservação dos Recursos Naturais , Política Ambiental , China , Política
16.
J Plast Reconstr Aesthet Surg ; 84: 79-86, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37327736

RESUMO

BACKGROUND: The facial artery (FA) is the main blood vessel supplying blood to the face. It is essential to understand the anatomy of FA around the nasolabial fold (NLF). This study aimed to provide the detailed anatomy and relative positioning of FA to help avoid unexpected complications in plastic surgery. METHODS: FA was observed from the inferior border of the mandible to the end of its terminal branch in 66 hemifaces of 33 patients with Doppler ultrasonography. The evaluation parameters were: (1) location, (2) diameter, (3) FA-skin depth, (4) relationship between the NLF and FA, (5) distance between the FA and significant surgical landmarks, and (6) the running layer. The FA course is classified based on the terminal branch. RESULTS: The most common FA course was Type 1, which had an angular branch as the final branch (59.1%). The most common FA-NLF relationship was that the FA was situated inferior to the NLF (50.0%). The mean FA diameter was 1.56 ± 0.36 mm at the mandibular origin, 1.40 ± 0.37 mm at the cheilion, and 1.32 ± 0.34 mm at the nasal ala. The FA diameter on the right hemiface was thicker than that on the left hemiface (p < 0.05). CONCLUSION: The FA mainly terminates in the angular branch, running in the medial NLF and in dermis and subcutaneous tissue, with a blood supply advantage in the right hemisphere. We suppose that a deep injection into periosteum around the NLF may be safer than an injection into the superficial musculoaponeurotic system (SMAS) layer.


Assuntos
Angiografia , Artérias , Humanos , Artérias/anatomia & histologia , Nariz , Sulco Nasogeniano , Ultrassonografia Doppler
17.
Materials (Basel) ; 16(9)2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37176258

RESUMO

A high-pressure (HP) GaN nucleation layer (NL) was inserted between AlGaN buffer and an unintentionally doped (UID) GaN layer of an AlGaN/GaN HEMT on Si. The XRD and TEM showed that when the V/III ratio was optimized during the HP-GaN NL growth, the edge dislocation density in the HP-GaN NL layer could be reduced significantly. Experimental results exhibited a lower off-state leakage current, higher maximum ID and Gm (corresponding to 22.5% and 21.7% improvement, respectively), and lower on-state resistance. These results demonstrate that the electrical properties of the AlGaN/GaN HEMT can be improved through the insertion of a HP-GaN NL.

18.
J Med Chem ; 66(8): 5820-5838, 2023 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-37053384

RESUMO

GPR84 is a proinflammatory G protein-coupled receptor that mediates myeloid immune cell functions. Blocking GPR84 with antagonists is a promising approach for treating inflammatory and fibrotic diseases. Previously, a GPR84 antagonist 604c, with a symmetrical phosphodiester structure, has displayed promising efficacy in a mouse model of ulcerative colitis. However, the low blood exposure resulting from physicochemical properties prevented its uses in other inflammatory diseases. In this study, a series of unsymmetrical phosphodiesters with lower lipophilicity were designed and tested. The representative compound 37 exhibited a 100-fold increase in mouse blood exposure compared to 604c while maintaining in vitro activity. In a mouse model of acute lung injury, 37 (30 mg/kg, po) significantly reduced the infiltration of proinflammatory cells and the release of inflammatory cytokines and ameliorated pathological changes equally or more effectively than N-acetylcysteine (100 mg/kg, po). These findings suggest that 37 is a promising candidate for treating lung inflammation.


Assuntos
Pneumonia , Receptores Acoplados a Proteínas G , Camundongos , Animais , Citocinas
19.
Acta Pharmacol Sin ; 44(8): 1665-1675, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37016043

RESUMO

Acute lung injury (ALI) is an acute, progressive hypoxic respiratory failure that could develop into acute respiratory distress syndrome (ARDS) with very high mortality rate. ALI is believed to be caused by uncontrolled inflammation, and multiple types of immune cells, especially neutrophils, are critically involved in the development of ALI. The treatment for ALI/ARDS is very limited, a better understanding of the pathogenesis and new therapies are urgently needed. Here we discover that GPR84, a medium chain fatty acid receptor, plays critical roles in ALI development by regulating neutrophil functions. GPR84 is highly upregulated in the cells isolated from the bronchoalveolar lavage fluid of LPS-induced ALI mice. GPR84 deficiency or blockage significantly ameliorated ALI mice lung inflammation by reducing neutrophils infiltration and oxidative stress. Further studies reveal that activation of GPR84 strongly induced reactive oxygen species production from neutrophils by stimulating Lyn, AKT and ERK1/2 activation and the assembly of the NADPH oxidase. These results reveal an important role of GPR84 in neutrophil functions and lung inflammation and strongly suggest that GPR84 is a potential drug target for ALI.


Assuntos
Lesão Pulmonar Aguda , Pneumonia , Síndrome do Desconforto Respiratório , Animais , Camundongos , Neutrófilos/patologia , Pneumonia/patologia , Inflamação/tratamento farmacológico , Lesão Pulmonar Aguda/tratamento farmacológico , Síndrome do Desconforto Respiratório/patologia , Lipopolissacarídeos/efeitos adversos
20.
BMC Geriatr ; 23(1): 116, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36864383

RESUMO

BACKGROUND: This research aimed to investigate the associations of anthropometric measurements, physiological parameters, chronic disease comorbidities, and social and lifestyle factors with cognitive function amongst community-dwelling older adults in Taiwan. METHODS: This was an observational, cross-sectional study involving 4,578 participants at least 65 years old, recruited between January 2008 and December 2018 from the Annual Geriatric Health Examinations Program. Cognitive function was assessed using the short portable mental state questionnaire (SPMSQ). Multivariable logistic regression was done to analyze the factors associated with cognitive impairment. RESULTS: Among the 4,578 participants, 103 people (2.3%) with cognitive impairment were identified. Associated factors were age (odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.13,1.20), male gender (OR = 0.39, 95% CI = 0.21,0.72), diabetes mellitus (DM) (OR = 1.70, 95% CI = 1.03, 2.82), hyperlipidemia (OR = 0.47, 95% CI = 0.25, 0.89), exercise (OR = 0.44, 95% CI = 0.34, 0.56), albumin (OR = 0.37, 95% CI = 0.15, 0.88), and high-density lipoprotein (HDL) (OR = 0.98, 95% CI = 0.97, 1.00). Whereas waistline, alcohol intake in recent six months, and hemoglobin was not significantly associated with cognitive impairment (all p > 0.05). CONCLUSIONS: Our findings suggested that people with older age and a history of DM had a higher risk of cognitive impairment. Male gender, a history of hyperlipidemia, exercise, a high albumin level, and a high HDL level seemed to be associated with a lower risk of cognitive impairment amongst older adults.


Assuntos
Disfunção Cognitiva , Vida Independente , Masculino , Humanos , Idoso , Taiwan/epidemiologia , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Albuminas
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