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1.
Front Immunol ; 15: 1424933, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39086485

RESUMO

Introduction: Immunotherapies targeting T cells in solid cancers are revolutionizing clinical treatment. Novel immunotherapies have had extremely limited benefit for acute myeloid leukemia (AML). Here, we characterized the immune microenvironment of t(8;21) AML patients to determine how immune cell infiltration status influenced prognosis. Methods: Through multi-omics studies of primary and longitudinal t(8;21) AML samples, we characterized the heterogeneous immune cell infiltration in the tumor microenvironment and their immune checkpoint gene expression. Further external cohorts were also included in this research. Results: CD8+ T cells were enriched and HAVCR2 and TIGIT were upregulated in the CD34+CD117dim%-High group; these features are known to be associated with immune exhaustion. Data integration analysis of single-cell dynamics revealed that a subset of T cells (cluster_2) (highly expressing GZMB, NKG7, PRF1 and GNLY) evolved and expanded markedly in the drug-resistant stage after relapse. External cohort analysis confirmed that the cluster_2 T-cell signature could be utilized to stratify patients by overall survival outcome. Discussion: In conclusion, we discovered a distinct T-cell signature by scRNA-seq that was correlated with disease progression and drug resistance. Our research provides a novel system for classifying patients based on their immune microenvironment.


Assuntos
Cromossomos Humanos Par 8 , Leucemia Mieloide Aguda , Análise de Célula Única , Microambiente Tumoral , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Análise de Célula Única/métodos , Prognóstico , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Cromossomos Humanos Par 8/genética , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Feminino , Translocação Genética , Cromossomos Humanos Par 21/genética , Linfócitos T CD8-Positivos/imunologia , Adulto , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética
2.
Int Immunopharmacol ; 139: 112615, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39032475

RESUMO

BACKGROUND AND PURPOSE: Liver cancer is the fourth leading cause of cancer-related death worldwide, with hepatocellular carcinoma (HCC) being the most common type of primary liver cancer. APG-1252 is a small molecule inhibitor targeting Bcl-2 and Bcl-xl. However, its anti-tumor effects in HCC, alone or in combination with Cabozantinib, have not been extensively studied. EXPERIMENTAL: Approach: TCGA database analysis was used to analysis the gene expression levels of Bcl-2 and Bcl-xl in HCC tissues. Western blot was employed to detect the protein expression levels. And the inhibitory effects of APG-1252 and Cabozantinib on the proliferation of HCC cell lines was detected by CCK-8. The effect on the migration and invasion of HCC cells was verified by transwell assay. Huh7 xenograft model in nude mice was used to investigate the combination antitumor effect in vivo. KEY RESULTS: Our study demonstrated that APG-1252 monotherapy inhibited the proliferation and migration ability of HCC cells, and induced HCC cells apoptosis. The combination of APG-1252 and Cabozantinib showed significant synergistic antitumor effects. Furthermore, the in vivo experiment demonstrated that the combination therapy exerted a synergistic effect in delaying tumor growth, notably downregulating MEK/ERK phosphorylation levels. In terms of mechanism, Cabozantinib treatment caused an increase in the phosphorylation levels of CREB and Bcl-xl proteins, while the combination with APG-1252 mitigated this effect, thereby enhanced the antitumor effect of Cabozantinib. CONCLUSION AND IMPLICATIONS: Our findings suggest that APG-1252 in combination with Cabozantinib offers a more effective treatment strategy for HCC patients, warranting further clinical investigation.


Assuntos
Anilidas , Carcinoma Hepatocelular , Proliferação de Células , Neoplasias Hepáticas , Camundongos Nus , Piridinas , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína bcl-X , Animais , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Anilidas/farmacologia , Anilidas/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Proteína bcl-X/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Camundongos , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Camundongos Endogâmicos BALB C , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Masculino
3.
Med Oncol ; 41(6): 155, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744773

RESUMO

Interleukin-6 (IL-6) and hypoxia-inducible factor-1α (HIF-1α) play important roles in epithelial-mesenchymal transformation (EMT) and tumor development. Previous studies have demonstrated that IL-6 promotes EMT, invasion, and metastasis in epithelial ovarian cancer (EOC) cells by activating the STAT3/HIF-1α pathway. MicroRNA (miRNA) is non-coding small RNAs that also play an important role in tumor development. Notably, Let-7 and miR-200 families are prominently altered in EOC. However, whether IL-6 regulates the expression of Let-7 and miR-200 families through the STAT3/HIF-1α signaling to induce EMT in EOC remains poorly understood. In this study, we conducted in vitro and in vivo investigations using two EOC cell lines, SKOV3, and OVCAR3 cells. Our findings demonstrate that IL-6 down-regulates the mRNA levels of Let-7c and miR-200c while up-regulating their target genes HMGA2 and ZEB1 through the STAT3/HIF-1α signaling in EOC cells and in vivo. Additionally, to explore the regulatory role of HIF-1α on miRNAs, both exogenous HIF blockers YC-1 and endogenous high expression or inhibition of HIF-1α can be utilized. Both approaches can confirm that the downstream molecule HIF-1α inhibits the expression and function of Let-7c and miR-200c. Further mechanistic research revealed that the overexpression of Let-7c or miR-200c can reverse the malignant evolution of EOC cells induced by IL-6, including EMT, invasion, and metastasis. Consequently, our results suggest that IL-6 regulates the expression of Let-7c and miR-200c through the STAT3/HIF-1α pathway, thereby promoting EMT, invasion, and metastasis in EOC cells.


Assuntos
Carcinoma Epitelial do Ovário , Transição Epitelial-Mesenquimal , Subunidade alfa do Fator 1 Induzível por Hipóxia , Interleucina-6 , MicroRNAs , Invasividade Neoplásica , Neoplasias Ovarianas , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Feminino , Humanos , Camundongos , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Interleucina-6/metabolismo , Interleucina-6/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica/genética , Metástase Neoplásica , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética
4.
Adv Sci (Weinh) ; 11(17): e2309392, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38403451

RESUMO

MXene-based thermal camouflage materials have gained increasing attention due to their low emissivity, however, the poor anti-oxidation restricts their potential applications under complex environments. Various modification methods and strategies, e.g., the addition of antioxidant molecules and fillers have been developed to overcome this, but the realization of long-term, reliable thermal camouflage using MXene network (coating) with excellent comprehensive performance remains a great challenge. Here, a MXene-based hybrid network comodified with hyaluronic acid (HA) and hyperbranched polysiloxane (HSi) molecules is designed and fabricated. Notably, the presence of appreciated HA molecules restricts the oxidation of MXene sheets without altering infrared stealth performance, superior to other water-soluble polymers; while the HSi molecules can act as efficient cross-linking agents to generate strong interactions between MXene sheets and HA molecules. The optimized MXene/HA/HSi composites exhibit excellent mechanical flexibility (folded into crane structure), good water/solvent resistance, and long-term stable thermal camouflage capability (with low infrared emissivity of ≈0.29). The long-term thermal camouflage reliability (≈8 months) under various outdoor weathers and the scalable coating capability of the MXene-coated textile enable them to disguise the IR signal of various targets in complex environments, indicating the great promise of achieved material for thermal camouflage, IR stealth, and counter surveillance.

5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1016548

RESUMO

ObjectiveThree methods were applied to conduct occupational health risk assessment for the working positions exposed to silicon dusts in a sanitary ceramic manufacturing factory, and the evaluation results were compared to explore the applicability of different occupational health risk assessment methods. MethodsOne large sanitary ceramic product manufacturing enterprise in Songjiang District, Shanghai was selected to conduct occupational health risk assessment for the working positions exposed to silicon dusts, using occupational hazard risk index evaluation method, exposure ratio evaluation method, and International Council on Mining and Metals (ICMM) quantitative occupational health risk assessment method . The consistency of the evaluation results of the three methods was tested using weighted Kappa method. ResultsFourteen working positions exposed to silicon dusts were identified, and three positions had excessive dust concentration: composite forming position of phase 2 workshop (0.80 mg·m-3), addition forming position of phase 2 workshop (1.00 mg·m-3), and glazing position of 1F in phase 2 workshop (1.50 mg·m-3), with an excessive rate of 21.42%. The occupational hazard risk index evaluation method assessed 6 positions with no harm, 6 positions with mild harm, and 2 positions with moderate harm. The ICMM quantitative occupational health risk assessment method assessed 6 positions with potential risks, 2 positions with tolerable risks, and 6 positions with intolerable risks. The exposure ratio evaluation method assessed 8 positions with medium risk, 5 positions with high risk, and 1 position with extremely high risk. The consistency test results of the three evaluation methods were poor. The Kappa coefficient between the occupational hazard risk index evaluation method and the ICMM quantitative occupational health risk assessment method was 0.15. The Kappa coefficient between the occupational hazard risk index evaluation method and the exposure ratio evaluation method was -0.09. The Kappa coefficient between the ICMM quantitative occupational health risk assessment method and the exposure ratio evaluation method was 0.04. The RR values obtained by the three evaluation methods were significantly correlated: the correlation coefficients between RRICMM quantitative assessment method and RRexposure ratio evaluation method, RROccupational hazard risk index evaluation method and RRICMM quantitative assessment method, RROccupational hazard risk index evaluation method and RRexposure ratio evaluation method were 0.915, 0.604, and 0.594, respectively. The correlation between the assessment result level and CTWA was strong. ConclusionThe occupational hazard risk index evaluation method is suitable for the working positions with low silicon dust exposure concentration, the ICMM quantitative occupational health risk assessment method and the exposure ratio evaluation method are suitable for the positions with high silicon dust exposure concentration, but all these three evaluation methods have limitations. It is more reasonable to use multiple methods at the same time in actual evaluation work.

6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1032320

RESUMO

ObjectiveTo investigate the entrance surface dose (ESD) of digital radiography (DR)adult examinees in a grade A tertiary hospital in Shanghai, to analyze the dose level of the DR adult examinees, and to provide data for the development of DR typical dose reference. MethodsA DR equipment in the hospital was selected and the irradiation parameters and dose were determined in two randomly selected age groups (15‒39 years and 40‒69 years) of DR adult examinees. The examinations included chest PA, chest LAT, abdominal AP, pelvic AP, lumbar AP, lumbar LAT, thoracic AP, and thoracic LAT. The number of examinees in each exposure position was 20. ESD and effective dose were calculated for each age group and each position. ResultsA total of 320 examinees were investigated. The 75th percentiles of ESD in different exposure positions were as follows: chest PA 0.19 mGy;chest LAT 0.96 mGy;abdominal AP 3.63 mGy;pelvic AP 3.16 mGy;lumbar AP 9.27 mGy;lumbar LAT 18.29 mGy;thoracic AP 6.85 mGy;and thoracic LAT 13.40 mGy. ConclusionsThe differences between the estimated ESD and effective dose were large in different exposure positions、in the same exposure positions、and in the same positions with different exposure types, and there were statistically significant differences in ESD of examinees with different exposure positions. The estimated typical values of different exposure positions were apparently lower than the diagnostic reference level.

7.
Korean J Physiol Pharmacol ; 28(1): 59-72, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38154965

RESUMO

To investigate the mechanism of Wenshen Xuanbi Decoction (WSXB) in treating osteoarthritis (OA) via network pharmacology, bioinformatics analysis, and experimental verification. The active components and prediction targets of WSXB were obtained from the TCMSP database and Swiss Target Prediction website, respectively. OA-related genes were retrieved from GeneCards and OMIM databases. Protein-protein interaction and functional enrichment analyses were performed, resulting in the construction of the Herb-Component-Target network. In addition, differential genes of OA were obtained from the GEO database to verify the potential mechanism of WSXB in OA treatment. Subsequently, potential active components were subjected to molecular verification with the hub targets. Finally, we selected the most crucial hub targets and pathways for experimental verification in vitro. The active components in the study included quercetin, linolenic acid, methyl linoleate, isobergapten, and beta-sitosterol. AKT1, tumor necrosis factor (TNF), interleukin (IL)-6, GAPDH, and CTNNB1 were identified as the most crucial hub targets. Molecular docking revealed that the active components and hub targets exhibited strong binding energy. Experimental verification demonstrated that the mRNA and protein expression levels of IL-6, IL-17, and TNF in the WSXB group were lower than those in the KOA group (p < 0.05). WSXB exhibits a chondroprotective effect on OA and delays disease progression. The mechanism is potentially related to the suppression of IL-17 and TNF signaling pathways and the down-regulation of IL-6.

8.
Huan Jing Ke Xue ; 44(12): 6551-6563, 2023 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-38098383

RESUMO

Ozone was one of the major pollutants affecting the environmental air quality in China. The accurate apportionment of key sources and their contributions of ambient ozone and its precursor VOCs played an important role in the effective prevention and control of ozone pollution. Therefore, this study utilized the photochemical-age-based parameterization method to estimate the initial concentrations of ambient VOCs data collected from January 1 to February 28, 2021 in Jiaozhou, Qingdao and corrected the photochemical losses of ambient VOC species. The positive matrix factorization(PMF) and ozone formation potential(OFP) models were used to conduct source apportionment of ambient VOCs and their OFPs so as to provide data support for the prevention and control of ozone pollution in Qingdao. The results showed that the average values of ambient ρ(TVOCs) and OFP in Qingdao during the study period were 65.9 µg·m-3 and 176.7 µg·m-3, respectively. Propane had the highest concentration(12.4 µg·m-3) and percentage(18.9%), whereas m/p-xylene had the highest OFP(24.6 µg·m-3) and percentage(13.9%). The mean initial concentration of TVOCs during the study was 153.1 µg·m-3, and its photochemical loss rate reached 63.8%. Alkenes were the VOC species with the highest photochemical loss rate(92.1%), and the photochemical loss rate of isoprene reached 98.6%, which was substantially higher than that of other VOC species. According to the source apportionment results of initial concentrations(IC-PMF), liquefied petroleum gas(24.2%), solvent use(17.8%), natural gas and petrochemical-related enterprises(16.6%), gasoline volatilization(13.2%), combustion and gasoline vehicle emissions(12.2%), biogenic emissions(8.6%), and diesel vehicle emissions(7.4%) were the main contributing sources of the ambient VOCs in Jiaozhou. Compared with the apportioned results of IC-PMF, the contribution of biogenic emissions was underestimated by 38.9% in the apportioned results based on observed concentrations(OC-PMF), and the contribution of natural gas and petrochemical-related enterprises was underestimated by 28.5%, and the underestimations of their contributions were substantially higher than those of other sources. Compared with that before the Spring Festival, the contribution of gasoline volatilization to ambient VOCs increased markedly during the Spring Festival, whereas the contributions of solvent use, combustion, and gasoline vehicle emissions to ambient VOCs increased most significantly after the Spring Festival. The main contributing sources of ambient ozone during the study period were solvent use(31.3%), natural gas and petrochemical-related enterprises(16.1%), biogenic emissions(14.5%), and combustion and gasoline vehicle emissions(13.2%). The primary contributors of ambient ozone in different Spring Festival periods showed substantial differences. Before the Spring Festival, solvent use had the highest contribution(71.1 µg·m-3), and gasoline volatilization was the highest contributor during the Spring Festival(34.4 µg·m-3), whereas biogenic emissions after the Spring Festival were the highest contributor(39.1 µg·m-3).

9.
Zhen Ci Yan Jiu ; 48(9): 890-7, 2023 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-37730259

RESUMO

OBJECTIVE: To investigate the effect of electroacupuncture(EA) stimulation on proliferation and diffe-rentiation of endogenous neural stem cells as well as Jagged1/Notch1 pathway in AD model mice, so as to explore its mechanism underlying amelioration of AD. METHODS: A total of 40 6-week-old male APP/PS1 transgenic AD mice were randomly divided into EA group (n=20) and AD model group ( n=20), and other 20 normal C57BL/6J mice of the same age were used as the normal control group. The mice in the EA group received EA (10 Hz, 2 mA) at "Baihui"(GV20), "Fengfu"(GV16) and bilateral "Shenshu" (BL23) for 20 min, once daily, 6 days a week for 16 weeks. The mice's learning-memory ability was detected by Morris water maze tests. The Aß senile plaques in the hippocampal CA1 region were detected by Congo red staining, the immunofluorescence double label of BrdU, neuronal nuclear antigen (NeuN) and astrocyte specific protein GFAP in dentate gyrus of hippocampus was performed for detecting the proliferation and differentiation of the endogenous neural stem cells. The expression levels of Nestin (neuron specific protein) and GFAP were detected by Western blot, and those of Jagged1 and Notch1 mRNAs and proteins in the hippocampus were detected by real-time fluorescence quantifative PCR and Western blot. RESULTS: Compared with the normal control group, the escape latencies at 2nd, 3rd and 4th day, and Aß senile plaques were significantly increased (P<0.05, P<0.01), whereas the platform crossing times and time spent in the target quadrant, the expression levels of Jagged1 mRNA and Nestin protein were remarkably down-regulated (P<0.05) in the model group. Following EA intervention, the escape latencies at the 3rd and 4th day, Aß senile plaques, immunofluorescence density of BrdU/GFAP, and GFAP protein expression were pronouncedly decreased (P<0.05, P<0.01), while the platform crossing times, platform quadrant residence time, immunofluorescence density of BrdU/NeuN, expression levels of Jagged1 and Notch1 mRNAs and proteins and Nestin protein evidently increased (P<0.05, P<0.01), suggesting an enhancement of proliferation and diffe-rentiation of endogenous neural stem cells into neurons and a suppression of the proliferation and differentiation towards astrocytes in the hippocampus. CONCLUSION: EA at GV20, GV16 and BL23 can improve the learning-memory ability, promote the proliferation and differentiation of endogenous neural stem cells towards neurons and inhibit the proliferation and differentiation of endogenous neural stem cells towards astrocytes in the hippocampus, which may be achieved by regulating Jagged1/Notch1 pathway.


Assuntos
Eletroacupuntura , Células-Tronco Neurais , Masculino , Camundongos , Animais , Camundongos Endogâmicos C57BL , Nestina , Bromodesoxiuridina , Placa Amiloide , Hipocampo , Diferenciação Celular/genética , Camundongos Transgênicos , Proliferação de Células
11.
Medicine (Baltimore) ; 102(24): e33957, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37327299

RESUMO

Neuroinflammation plays an essential role in the process of acute ischemic stroke (AIS) injury repair. The current study seeks to investigate the relationship between the neutrophil/lymphocyte ratio (NLR) and neutrophil/high-density lipoprotein cholesterol ratio (NHR) and AIS disease severity and short-term prognosis. As such, the primary aim of this study is to improve AIS diagnosis and treatment. A total of 136 patients with AIS at the Nantong Third People's Hospital were retrospectively analyzed. The inclusion criteria comprised patients with ischemic stroke admitted to the hospital <24 hours after symptom onset. Baseline, clinical, and laboratory data were collected from all patients within 24 hours of admission. Univariate, multivariate and receiver operating characteristic curve analysis were performed to determine the relationship between NLR, NHR, AIS severity, and short-term prognosis. NLR (odds ratio [OR] = 1.448, 95% confidence interval [CI] 1.116-1.878, P = .005) and NHR (OR = 1.480, 95% CI 1.158-1.892, P = .002) were identified as independent risk factors for stroke severity. Additionally, the correlation between combined NLR and NHR and AIS severity achieved a sensitivity of 81.4% and specificity of 60.4% with a best cutoff value of 6.989. This outcome was superior to that of the single composite inflammatory index. Moreover, NLR (OR = 1.252, 95% CI 1.008-1.554, P = .042) was an independent risk factor for poor short-term prognosis in patients with AIS. When the optimal cutoff value was 2.605, the sensitivity of NLR correlation with the short-term prognosis of AIS was 82.2%, and the specificity was 59.3%. NLR combined with NHR exhibits a strong correlation with disease severity in AIS. Meanwhile, an elevated NLR in patients with AIS can predict a poor short-term prognosis.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/complicações , Neutrófilos/patologia , Estudos Retrospectivos , Prognóstico , Linfócitos/patologia , Acidente Vascular Cerebral/etiologia
12.
Huan Jing Ke Xue ; 44(4): 1962-1973, 2023 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-37040947

RESUMO

The ambient concentration of ozone is high in Qingdao, and ozone pollution episodes occur frequently in summer. The refined source apportionment of ambient volatile organic compounds (VOCs) and their ozone formation potential (OFP) during ozone pollution episodes and non-ozone pollution periods can play an important role in effectively reducing air ozone pollution in coastal cities and continuously improving ambient air quality. Therefore, this study applied the online VOCs monitoring data with hourly resolution in summer (from June to August) in 2020 in Qingdao to analyze the chemical characteristics of ambient VOCs during the ozone pollution episodes and non-ozone pollution periods and conducted the refined source apportionment of ambient VOCs and their OFP using a positive matrix factorization (PMF) model. The results showed that the average mass concentration of ambient VOCs in Qingdao in summer was 93.8 µg·m-3, and compared with that during the non-ozone pollution period, the mass concentration of ambient VOCs during the ozone pollution episodes increased by 49.3%, and the mass concentration of aromatic hydrocarbons increased by 59.7%. The total OFP of ambient VOCs in summer was 246.3 µg·m-3. Compared with that in the non-ozone pollution period, the total OFP of ambient VOCs in the ozone pollution episodes increased by 43.1%; that of alkanes increased the most, reaching 58.8%. M-ethyltoluene and 2,3-dimethylpentane were the species with the largest increase in OFP and its proportion during the ozone pollution episodes. The main contributors of ambient VOCs in Qingdao in summer were diesel vehicles (11.2%), solvent use (4.7%), liquefied petroleum gas and natural gas (LPG/NG) (27.5%), gasoline vehicles (8.9%), gasoline volatilization (26.6%), emissions of combustion- and petrochemical-related enterprises (16.4%), and plant emissions (4.8%). Compared with that in the non-ozone pollution period, the contribution concentration of LPG/NG in the ozone pollution episodes increased by 16.4 µg·m-3, which was the source category with the largest increase. The contribution concentration of plant emissions increased by 88.6% in the ozone pollution episodes, which was the source category with the highest increase rate. In addition, emissions from combustion- and petrochemical-related enterprises were the largest contributor to the OFP of ambient VOCs in summer in Qingdao, with its OFP and contribution proportion being 38.0 µg·m-3and 24.5%, respectively, followed by that of LPG/NG and gasoline volatilization. Compared with the non-ozone pollution period, the total contributions of LPG/NG, gasoline volatilization, and solvent use to the increase in OFP for ambient VOCs in the ozone pollution episodes were 74.1%, which were the main contribution source categories.

13.
Chem Biol Drug Des ; 102(1): 76-87, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37005089

RESUMO

Islet ß-cell damage and dysfunction represent the pathophysiological basis of diabetes. Excessive activation of cyclin-dependent kinase 5 (CDK5) is involved in the pathogenesis of type 2 diabetes mellitus (T2DM), although the exact mechanism remains unclear. Therefore, this study investigated the role of a CDK5 inhibitor (TFP5) in islet ß-cell damage under diabetic conditions by regulating the expression of CDK5 in vitro and in vivo. CDK5 was upregulated under high glucose conditions in vivo and in vitro, which resulted in inflammation, oxidative stress, and apoptosis of islet ß-cells, thereby decreasing insulin secretion. However, TFP5 treatment inhibited the overexpression of CDK5; reduced the inflammatory response, oxidative stress, and apoptosis of islet ß cells; and restored insulin secretion. In conclusion, CDK5 is involved in islet ß-cell damage under high glucose conditions, and TFP5 may represent a promising candidate for the development of treatments for T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Apoptose , Quinase 5 Dependente de Ciclina/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose/farmacologia , Insulina/metabolismo , Estresse Oxidativo
14.
Acta Anatomica Sinica ; (6): 628-634, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1015174

RESUMO

Objective To explore the protective effect of fosinopril (Fos) on streptozotocin ( STZ) induced diabetic retinopatfry( DR) mice and on the expression of angiotensin converting enzyme 2(ACE2) and vascular endothelial growth factor (VEGF) in DR mice. Methods Totally forty-eight healthy male Kunming mice, thirty-six were randomly selected, and a diabetic mouse model induced by STZ was constructed after 6 weeks of high-fat diet. After the successful establishment of the model, the thirty-six mice were randomly divided into three groups: model group, Fos low concentration ( 5 mg/kg) group, and Fos high concentration ( 10 mg/kg) group. The remaining twelve mice were served as the control group. After 8 weeks administration, the bod)' weight and blood glucose level of mice in each group were determined. The change in the retinal structure was verified by HE staining. The serum level of VEGF was measured by ELISA. The expression of ACE2 in the retina tissue was verified by immunohistochemistry. The expression of ACE2 mRNA in diabetic retinopatlry was analyzed by Real-time PCR. The levels of ACE2 and VEGF protein in diabetic retinopatlry were detected by Western blotting. Results Fos ( 5 mg/kg, 10 mg/kg ) reduced significantly the proliferation of neovascularization in the inner boundaiy layer, down-regulated the expression of VEGF in the serum of diabetic mice and promoted the expression of ACE2 in the retina tissue of diabetic mice. In addition, the effect of the high concentration group of Fos had a stronger effect than the lower concentration group (P<0. 0 5 ) . Conclusion Fos has a protective effect on the retinopatlry of diabetic mice. This protective effect ma)' be mediated through the increased expression of ACE2 and the reduction of VEGF expression.

15.
Dalton Trans ; 52(1): 136-146, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36472123

RESUMO

The effective detection of organic amines is particularly important for environmental protection and human health. Herein, according to hard and soft acid base theory, a novel three-dimensional (3D) butterfly shaped Eu4(OH)2 cluster-based metal-organic framework with Lewis basic triazole sites, {[Eu4(taip)4(ox)(OH)2(H2O)4]·3H2O}n (1) (H2taip = 5-(1,2,4-triazol-1-yl) isophthalic acid, H2ox = oxalic acid), was successfully synthesized under solvothermal conditions, and was characterized by single crystal X-ray diffraction, powder X-ray diffraction, elemental analysis, infrared spectroscopy and thermogravimetric analysis. Structural analysis reveals that compound 1 is a 3D net constructed from butterfly shaped Eu4(OH)2 clusters and contains isosceles triangular channels with dimensions of 8.84 × 8.84 × 8.63 Å3, which shows an unprecedented 8-connected topology with a Schläfli symbol {36·418·53·6}. Fluorescence experiments of compound 1 show sensitive luminescence quenching responses to organic amines such as diethylamine (DEA), trimethylamine (TMA), triethylamine (TEA), ethylenediamine (EDA) and aniline, and the quenching constants (KSV) decrease in the following order: EDA > DEA > TMA > TEA > aniline. The fluorescence quenching responses may be attributed to the energy gap between the LUMO energy values of H2taip and organic amines, which hinders the transfer of excited state energy to the emission state of Eu3+ and results in luminescence quenching. The fluorescence lifetimes of compound 1 in ethanol and organic anilines indicate that the fluorescence recognition process of organic amines was static.


Assuntos
Aminas , Estruturas Metalorgânicas , Humanos , Luminescência , Bases de Lewis , Ácido Oxálico
16.
Front Psychol ; 13: 968154, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36312162

RESUMO

Background: Breast cancer patients and their families are under various pressures in the process of disease diagnosis and treatment, which seriously threaten their physical and mental health. Findings from existing research suggest that good family resilience can help breast cancer families better adapt and cope with adversity and challenges. However, there are only a few intervention studies on family resilience and no intervention studies on resilience among the families of breast cancer patients. Therefore, this study aims to explore appropriate measures to improve the resilience level of breast cancer families and help them better cope with the disease. Objective: The purpose of this study protocol is to demonstrate a coping-focused family resilience intervention to increase the level of resilience in the families of breast cancer patients and help them better cope with adversity. Methods: The trial will recruit 80 breast cancer families and randomly assign them to experimental and control groups in a 1:1 ratio. The control group will receive routine care, and the intervention group will receive a 6-week one-on-one online family resilience intervention based on the control group. Two groups of subjects will be assessed at baseline and at 1 week, 1 month, and 3 months after the intervention. The primary outcome is family resilience, and the secondary outcomes are coping style, social support, family disease burden, and levels of anxiety and depression. Expected results: We hypothesized that after the intervention, the intervention group would have significantly higher levels of family resilience than the preintervention and control groups. In the intervention group, other aspects related to family resilience, such as family disease burden and anxiety and depression levels of patients and their families, were significantly alleviated, and disease coping and social support levels were improved accordingly. Discussion: If the program works, it can help breast cancer families identify family strengths and resources to proactively address challenges so that families can successfully navigate the crisis and patient and family recovery can be facilitated. It can also provide a practical path for clinical workers to help breast cancer families adjust rationally. Clinical Trial Registration: This study has been registered in the Chinese Clinical Trials Registry (Registration Number: http://www.chictr.org.cn/ChiCTR2100052108).

17.
J Neurophysiol ; 128(5): 1168-1180, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36197012

RESUMO

Secondary brain injury (SBI) refers to new or worsening brain insult after primary brain injury (PBI). Neurophysiological experiments show that calcium (Ca2+) is one of the major culprits that contribute to neuronal damage and death following PBI. However, mechanistic details about how alterations of Ca2+ levels contribute to SBI are not well characterized. In this paper, we first build a biophysical model for SBI related to calcium homeostasis (SBI-CH) to study the mechanistic details of PBI-induced disruption of CH, and how these disruptions affect the occurrence of SBI. Then, we construct a coupled SBI-CH model by formulating synaptic interactions to investigate how disruption of CH affects synaptic function and further promotes the propagation of SBI between neurons. Our model shows how the opening of voltage-gated calcium channels (VGCCs), decreasing of plasma membrane calcium pump (PMCA), and reversal of the Na+/Ca2+ exchanger (NCX) during and following PBI, could induce disruption of CH and further promote SBI. We also show that disruption of CH causes synaptic dysfunction, which further induces loss of excitatory-inhibitory balance in the system, and this might promote the propagation of SBI and cause neighboring tissue to be injured. Our findings offer a more comprehensive understanding of the complex interrelationship between CH and SBI.NEW & NOTEWORTHY We build a mechanistic model SBI-CH for calcium homeostasis (CH) to study how alterations of Ca2+ levels following PBI affect the occurrence and propagation of SBI. Specifically, we investigate how the opening of VGCCs, decreasing of PMCA, and reversal of NCX disrupt CH, and further induce the occurrence of SBI. We also present a coupled SBI-CH model to show how disrupted CH causes synaptic dysfunction, and further promotes the propagation of SBI between neurons.


Assuntos
Lesões Encefálicas , Cálcio , Humanos , Cálcio/metabolismo , Trocador de Sódio e Cálcio/metabolismo , Canais de Cálcio/metabolismo , Lesões Encefálicas/metabolismo , Homeostase
18.
Sensors (Basel) ; 22(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36080892

RESUMO

Automatic power line extraction from aerial images of unmanned aerial vehicles is one of the key technologies of power line inspection. However, the faint power line targets and complex image backgrounds make the extraction of power lines a greater challenge. In this paper, a new power line extraction method is proposed, which has two innovative points. Innovation point one, based on the introduction of the Mask RCNN network algorithm, proposes a block extraction strategy to realize the preliminary extraction of power lines with the idea of "part first and then the whole". This strategy globally reduces the anchor frame size, increases the proportion of power lines in the feature map, and reduces the accuracy degradation caused by the original negative anchor frames being misclassified as positive anchor frames. Innovation point two, the proposed connected domain group fitting algorithm solves the problem of broken and mis-extracted power lines even after the initial extraction and solves the problem of incomplete extraction of power lines by background texture interference. Through experiments on 60 images covering different complex image backgrounds, the performance of the proposed method far exceeds that of commonly used methods such as LSD, Yolact++, and Mask RCNN. DSCPL, TPR, precision, and accuracy are as high as 73.95, 81.75, 69.28, and 99.15, respectively, while FDR is only 30.72. The experimental results show that the proposed algorithm has good performance and can accomplish the task of power line extraction under complex image backgrounds. The algorithm in this paper solves the main problems of power line extraction and proves the feasibility of the algorithm in other scenarios. In the future, the dataset will be expanded to improve the performance of the algorithm in different scenarios.

19.
Anal Chem ; 94(30): 10722-10729, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35853240

RESUMO

Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, is a vital ligand-activated transcriptional factor, which is highly expressed in the liver, intestine, and adrenal gland. However, FXR homeostasis is influenced by many factors, such as diet and circadian rhythm, and the expression of FXR differs in diverse organs. Currently, there is no method to monitor the FXR homeostasis in real time, which restricts us from further investigating the function of FXR under physiological and pathological conditions. In this project, classic FXR agonists were selected to be modified to targeting FXR. The photo-cross-linking diazirine group and alkynyl, a click reaction group, were incorporated to the ligands. Through biorthogonal reaction, fluorophore was linked to the ligands to realize the monitoring of FXR expression in cells.


Assuntos
Fígado , Receptores Citoplasmáticos e Nucleares , Células Cultivadas , Regulação da Expressão Gênica , Fígado/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Transcrição/metabolismo
20.
Abdom Radiol (NY) ; 47(10): 3615-3627, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35821274

RESUMO

PURPOSE: This study aimed to investigate whether underdilated transjugular intrahepatic portosystemic shunt (TIPS) could reduce the risk of hepatic encephalopathy (HE) and ameliorate impaired hepatic function in patients with a history of splenectomy. METHODS: A retrospective case-control study was conducted with 96 patients who had prior splenectomy and TIPS placement from August 2016 to May 2022. All patients were divided into two groups based on the diameter of expansion balloon catheters, the underdilated group (6-mm balloon catheter, n = 60) and a control group (8-mm balloon catheter, n = 36). Following the 1:1 propensity score matching (PSM), 33 patients in the underdilated group and 33 patients in the control group were included. RESULTS: During a median follow-up of 36 months, a quicker recovery in liver function after TIPS placement was showed in the underdilated group. The mean TBIL content (16.562 ± 6.549 µmol/L vs 23.871 ± 11.609 µmol/L, P = 0.019) and the mean CLIF-C AD score (41.108 ± 5.223 vs 45.100 ± 4.429, P = 0.033) in the underdilated group were significantly lower than those in the control group during 6 to 12 months after the procedure. In line with the control group, the ability to reduce portal pressure gradient (PPG) and achieve a significantly clinical remission of PVT and ascites severity was showed in the underdilated group 3 months after TIPS creation (P < 0.001). The Kaplan-Meier analysis demonstrated that no statistically significant differences were found in the cumulative incidence of no overt HE (OHE) (log-rank P = 0.383), cumulative incidence without shunt dysfunction (log-rank P = 0.283), cumulative incidence of no variceal rebleeding (log-rank P = 0.696), and survival (log-rank P = 0.341) (log-rank P = 0.341) between the two groups during the follow-up period. CONCLUSION: For patients with prior splenectomy, it is safe to employ underdilated TIPS, as the stents will eventually self-expand to 8 mm. The present study has shown some degree of liver function preservation in the underdilated group, which may be related to slower progressive changes in the portal hemodynamics.


Assuntos
Varizes Esofágicas e Gástricas , Encefalopatia Hepática , Hipertensão Portal , Derivação Portossistêmica Transjugular Intra-Hepática , Estudos de Casos e Controles , Encefalopatia Hepática/complicações , Encefalopatia Hepática/epidemiologia , Humanos , Hipertensão Portal/cirurgia , Cirrose Hepática/complicações , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Esplenectomia/efeitos adversos , Resultado do Tratamento
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