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1.
Eur J Pharmacol ; 911: 174558, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34634308

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, develops rapidly and has a high mortality rate. Relapsed metastasis is the most important factor affecting prognosis and is also the main cause of death for patients with HCC. Cantharidin is a kind of folk medicine for malignant tumors in China. Because of its cytotoxicity, the application of cantharidin is very limited. Magnesium demethylcantharidate (MDC) is a derivative of cantharidin independently developed by our laboratory. Our results show that MDC has anticancer activity and exhibited lower toxicity than cantharidin. However, whether MDC affects the invasion and metastasis of HCC cells and the underlying molecular mechanisms remain obscure. Transwell and Matrigel assays showed that MDC could effectively inhibit the invasion and metastasis of the HCC cell lines SMMC-7721 and SK-Hep1 in a dose-dependent manner. Moreover, MDC significantly inhibited the expression of invasion and metastasis related proteins MMP-2 and MMP-9. In addition, our study found that MDC inhibited the invasion and metastasis of HCC cell lines SMMC-7721 and SK-Hep1 by activating transcription factor FOXO1. Interestingly, the combination of MDC and sorafenib significantly inhibited the invasion and metastasis of HCC cell lines SMMC-7721 and SK-Hep1 compared with the single drug treatment via the activated transcription factor FOXO1. Our work revealed that MDC obviously inhibited the invasion and metastasis of HCC cells, and suggested that MDC could be a potential candidate molecule against the invasion and metastasis of HCC.

2.
J Integr Plant Biol ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636476

RESUMO

Traditional Chinese Medicine (TCM) belongs to the most elaborate and extensive systems of plant-based healing. The herb Northern Ban Lan (Isatis tinctoria) is famous for its antiviral and anti-inflammatory activity. Although numerous components isolated from I. tinctoria have been characterised so far, their modes of action have remained unclear. Here, we show that extracts from I. tinctoria exert anti-microtubular activity. Using time-lapse microscopy in living tobacco BY-2 (Nicotiana tabacum L. cv Bright Yellow 2) cells expressing GFP-tubulin, we use activity-guided fractionation to screen out the biologically active compounds of I. tinctoria. Among 54 fractions obtained from either leaves or roots of I. tinctoria by methanol (MeOH/H2 O 8:2), or ethylacetate extraction, one specific methanolic root fraction was selected, because it eliminated microtubules efficiently and rapidly. By combination of further purification with ultra-high performance liquid chromatography (UHPLC) and high-resolution (tandem) mass spectrometry (HRMS (/MS)) most of the bio-activity could be assigned to the glucosinolate compound glucobrassicin. Glucobrassicin can also affect microtubules and induce apoptosis in HeLa cells. In the light of these findings, the anti-viral activity of Northern Ban Lan is discussed in the context of microtubules being hijacked by many viral pathogens for cell-to-cell spread. This article is protected by copyright. All rights reserved.

3.
Circ J ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34629373

RESUMO

BACKGROUND: Radiofrequency catheter ablation (RFCA) is an effective therapy for atrial fibrillation (AF). However, it the problem of AF recurrence remains. This study investigates whether a deep convolutional neural network (CNN) can accurately predict AF recurrence in patients with AF who underwent RFCA, and compares CNN with conventional statistical analysis.Methods and Results:Three-hundred and ten patients with AF after RFCA treatment, including 94 patients with AF recurrence, were enrolled. Nine variables are identified as candidate predictors by univariate Cox proportional hazards regression (CPH). A CNNSurv model for AF recurrence prediction was proposed. The model's discrimination ability is validated by a 10-fold cross validation method and measured by C-index. After back elimination, 4 predictors are used for model development, they are N-terminal pro-BNP (NT-proBNP), paroxysmal AF (PAF), left atrial appendage volume (LAAV) and left atrial volume (LAV). The average testing C-index is 0.76 (0.72-0.79). The corresponding calibration plot appears to fit well to a diagonal, and the P value of the Hosmer-Lemeshow test also indicates the proposed model has good calibration ability. The proposed model has superior performance compared with the DeepSurv and multivariate CPH. The result of risk stratification indicates that patients with non-PAF, higher NT-proBNP, larger LAAV and LAV would have higher risks of AF recurrence. CONCLUSIONS: The proposed CNNSurv model has better performance than conventional statistical analysis, which may provide valuable guidance for clinical practice.

4.
Adv Sci (Weinh) ; : e2101383, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609790

RESUMO

DNA-protein interaction plays an essential role in the storage, expression, and regulation of genetic information. A 1D/3D facilitated diffusion mechanism has been proposed to explain the extraordinarily rapid rate of DNA-binding protein (DBP) searching for cognate sequence along DNA and further studied by single-molecule experiments. However, direct observation of the detailed chronological protein searching image is still a formidable challenge. Here, for the first time, a single-molecule electrical monitoring technique is utilized to realize label-free detection of the DBP-DNA interaction process based on high-gain silicon nanowire field-effect transistors (SiNW FETs). The whole binding process of WRKY domain and DNA has been visualized with high sensitivity and single-base resolution. Impressively, the swinging of hydrogen bonds between amino acid residues and bases in DNA induce the dynamic collective motion of DBP-DNA. This in situ, label-free electrical detection platform provides a practical experimental methodology for dynamic studies of various biomolecules.

5.
Plant Physiol ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34618071

RESUMO

Improving photosynthesis is considered a major and feasible option to dramatically increase crop yield potential. Increased atmospheric CO2 concentration often stimulates both photosynthesis and crop yield, but decreases protein content in the main C3 cereal crops. This decreased protein content in crops constrains the benefits of elevated CO2 on crop yield and affects their nutritional value for humans. To support studies of photosynthetic nitrogen assimilation and its complex interaction with photosynthetic carbon metabolism for crop improvement, we developed a dynamic systems model of plant primary metabolism, which includes the Calvin-Benson cycle, the photorespiration pathway, starch synthesis, glycolysis-gluconeogenesis, the tricarboxylic acid cycle, and chloroplastic nitrogen assimilation. This model successfully captures responses of net photosynthetic CO2 uptake rate (A), respiration rate, and nitrogen assimilation rate to different irradiance and CO2 levels. We then used this model to predict inhibition of nitrogen assimilation under elevated CO2. The potential mechanisms underlying inhibited nitrogen assimilation under elevated CO2 were further explored with this model. Simulations suggest that enhancing the supply of α-ketoglutarate is a potential strategy to maintain high rates of nitrogen assimilation under elevated CO2. This model can be used as a heuristic tool to support research on interactions between photosynthesis, respiration, and nitrogen assimilation. It also provides a basic framework to support the design and engineering of C3 plant primary metabolism for enhanced photosynthetic efficiency and nitrogen assimilation in the coming high-CO2 world.

6.
Org Lett ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609887

RESUMO

An efficient copper-catalyzed cyclization of N-propargyl ynamides with borane adducts through B-H bond insertion has been developed. A series of valuable organoboron compounds are constructed in generally good yields with a wide substrate scope and good functional group tolerance under mild reaction conditions. Importantly, this protocol via vinyl cation intermediates constitutes a novel way of B-H bond insertion.

7.
Exp Biol Med (Maywood) ; : 15353702211052036, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34644201

RESUMO

In this study, we aim to identify the clinical significance of basonuclin 1 (BNC1) expression in ovarian carcinoma (OV) and to explore its latent mechanisms. Via integrating in-house tissue microarrays, gene chips, and RNA-sequencing data, we explored the expression and clinical value of BNC1 in OV. Immunohistochemical staining was utilized to confirm the protein expression status of BNC1. A combined SMD of -2.339 (95% CI: -3.649 to -1.028, P < 0.001) identified that BNC1 was downregulated based on 1346 samples, and the sROC (AUC = 0.93) showed a favorable discriminatory ability of BNC1 in OV patients. We used univariate and multivariate Cox regulation to evaluate the prognostic role of BNC1 for OV patients, and a combined hazard ratio of 0.717 (95% CI: 0.445-0.989, P < 0.001) revealed that BNC1 was a protective factor for OV. Furthermore, the fraction of infiltrating naive B cells, memory B cells, and other immune cells showed statistical differences between the high- and low-BNC1 expression groups through cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. Enrichment analysis showed that BNC1 may have a relationship with immune-related items in OV. By predicting the potential regulatory transcription factors (TFs) of BNC1, friend leukemia virus integration 1 (FLI1) may be a potential upstream TF of BNC1. Corporately, a decreasing trend of BNC1 may serve as a tumor suppressor and prognostic biomarker in OV patients. Moreover, BNC1 may take part in immune-related pathways and influence the fraction of tumor-infiltrating immune cells.

8.
Cancer Lett ; 523: 1-9, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34530049

RESUMO

Pancreatic cancer is one of the common malignant tumors of the digestive system, and its clinical treatment is still very challenging. Most of the pancreatic cancer chemotherapeutic drugs have poor plasma stability, low cell uptake efficiency, and are prone to developing drug resistance and toxic side effects. Besides, pancreatic cancer often has a dense extracellular matrix, which consists of collagens, hyaluronic acid, and other proteoglycans. Among them, hyaluronic acid is a key component of the dense matrix, which results in vascular compression and insufficient perfusion, and hinders the delivery of chemotherapeutic drugs. In this study, we explore using hyaluronidase in tumor-bearing mice to eliminate the hyaluronic acid barrier, to reduce blood vessel compression and reshape the tumor microenvironment. In addition, we evaluate using doxorubicin-loaded nanoprobes to improve the stability and local tumor-killing effect of the drug. The nanoprobes have the characteristics of near-infrared optical imaging, which are used to monitor the tumor size in real-time during the treatment process, and dynamically observe the tumor inhibitory effect. The results show that elimination of the hyaluronic acid barrier combined with the doxorubicin-loaded nanoprobes can greatly increase drug penetration into tumor tissue and improve the effectiveness of chemotherapy drugs. This study provides a novel strategy for the treatment of pancreatic cancer.

9.
Sci Rep ; 11(1): 19288, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34588587

RESUMO

Larval metamorphosis in bivalves is a key event for the larva-to-juvenile transformation. Previously we have identified a thyroid hormone receptor (TR) gene that is crucial for larvae to acquire "competence" for the metamorphic transition in the mussel Mytilus courscus (Mc). The mechanisms of thyroid signaling in bivalves are still largely unknown. In the present study, we molecularly characterized the full-length of two iodothyronine deiodinase genes (McDx and McDy). Phylogenetic analysis revealed that deiodinases of molluscs (McDy, CgDx and CgDy) and vertebrates (D2 and D3) shared a node representing an immediate common ancestor, which resembled vertebrates D1 and might suggest that McDy acquired specialized function from vertebrates D1. Anti-thyroid compounds, methimazole (MMI) and propylthiouracil (PTU), were used to investigate their effects on larval metamorphosis and juvenile development in M. coruscus. Both MMI and PTU significantly reduced larval metamorphosis in response to the metamorphosis inducer epinephrine. MMI led to shell growth retardation in a concentration-dependent manner in juveniles of M. coruscus after 4 weeks of exposure, whereas PTU had no effect on juvenile growth. It is hypothesized that exposure to MMI and PTU reduced the ability of pediveliger larvae for the metamorphic transition to respond to the inducer. The effect of MMI and PTU on larval metamorphosis and development is most likely through a hormonal signal in the mussel M. coruscus, with the implications for exploring the origins and evolution of metamorphosis.

10.
Zhen Ci Yan Jiu ; 46(9): 757-62, 2021 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-34558241

RESUMO

OBJECTIVE: To observe the therapeutic effect of moxa fume in the treatment of chronic rhinosinusitis(CRS) and the effect of acupuncture plus smokeless moxibustion or smoky moxibustion on the expression of thymic stromal lymphopoietin (TSLP) and pituitary adenylate cyclase activating polypeptide (PACAP) proteins in the sinus mucosal tissue in CRS mice. METHODS: Sixty male C57BL/6J mice were randomly divided into 6 groups, namely normal control, sham operation, CRS model, medication, acupuncture plus smokeless moxibustion (Acu+smokeless Moxi) and acupuncture plus smoky moxibustion (Acu+smoky Moxi) groups, with 20 mice in each group. The CRS model was established by inserting a piece of polyporous sponge filled with streptococcus pneumoniae into the maxillary sinus after operation. The mice in the sham operation group received skin incision after opening the maxillary sinus. Mice of the medication group received gavage of clarithromycin 0.103 g·kg-1·d-1 for 21 days. For mice of the Acu+smokeless Moxi and Acu +smoky Moxi groups, manual acupuncture stimulation was applied to bilateral "Zusanli" (ST36), "Shenshu" (BL23) and "Hegu" (LI4) with the needles retained for 30 min, once every other day, and on the following day, moxibustion was applied to "Guanyuan" (CV4) and "Shenque" (BL23) for 20 min, once every other day. The treatment was given for 21 days. Mice of the normal, sham operation and model groups received gavage of normal saline (200 µL/d) for 21 days. Histopathological changes of the nasal mucosa were observed after H.E. staining, the TSLP and PACAP contents and expression were determined by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, separately. RESULTS: At the end of the treatment, mice of the model group still had symptoms of nasal obstruction and runny nose, but those of the 3 treatment groups were obviously relieved in the nasal symptoms. H.E. staining showed an obvious chronic inflammatory reaction in the sinus mucosa, uneven distribution of the mucosal epithelium and necrotic and exfoliated epithelial cells, hyperplasia of fibrous tissue in the submucosa, etc. in the model group, which were relatively milder in the medication, Acu+smokeless Moxi and Acu+smoky Moxi groups, while no obvious inflammation was found in the normal group and sham operation group. In comparison with the normal group, no significant changes were found in the expression levels of PACAP and TSLP in the sham operation group (P>0.05). The expression level of PACAP was significantly lower (P<0.05) and that of TSLP significantly higher in the model group than in the normal and sham operatin groups (P<0.05). Compared with the model group, no significant changes were found in the expression of PACAP in the medication, Acu+smokeless Moxi and Acu+smoky Moxi groups (P>0.05), and the expression of TSLP was further obviously increased in the Acu+smokeless Moxi group (P<0.01), but obviously decreased in the Acu+smoky Moxi group (P<0.01). CONCLUSION: Acupuncture combined with smoky moxibustion can down-regulate the expression of TSLP protein in the nasal sinus mucosa in CRS mice, which maybe contribute to its effect in reducing the inflammatory reaction and nasal symptoms.


Assuntos
Terapia por Acupuntura , Moxibustão , Pontos de Acupuntura , Animais , Imunidade , Lobelina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley , Fumaça
11.
Int J Colorectal Dis ; 36(10): 2237-2245, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34406437

RESUMO

OBJECTIVES: Recently, CAD EYE (Fujifilm, Tokyo, Japan), an artificial intelligence for the lesion recognition (CADe) and the optical diagnosis (CADx) of colorectal polyps, was released. We evaluated the function of CADe and CADx of CAD EYE. METHODS: In this single-center retrospective study, we examined consecutive polyps ≤ 10 mm detected from March to April 2021 to determine whether CAD EYE could recognize them live with both normal- and high-speed observation using white-light imaging (WLI) and linked-color imaging (LCI). We then examined whether the polyps were neoplastic or hyperplastic live with magnified or non-magnified blue-laser imaging (BLI-LASER) or blue-light imaging (BLI-LED) under CAD EYE, comparing the retrospective evaluations with 5 experts and 5 trainees using still images. All polyps were histopathologically examined. RESULTS: We analyzed 100 polyps (mean size 3.9 ± 2.6 mm; 55 neoplastic and 45 hyperplastic lesions) in 25 patients. Regarding CADe, the respective detection rates of CAD EYE with normal- and high-speed observation were 85.0% and 67.0% for WLI (p = 0.002) and 89.0% and 75.0% for LCI (p = 0.009). Regarding CADx for differentiating neoplastic and hyperplastic lesions, the diagnostic accuracy values of CAD EYE with non-magnified and magnified BLI-LASER/LED were 88.8% and 87.8%. Regarding magnified BLI-LASER/LED, the diagnostic accuracy value of CAD EYE was not significantly different from that of experts (92.0%, p = 0.17), but that of trainees (79.0%, p = 0.04). We also found no significant differences in CADe or CADx between LED (53 lesions) and LASER (47 lesions). CONCLUSIONS: CAD EYE was a helpful tool for CADe and CADx in clinical practice.


Assuntos
Pólipos do Colo , Inteligência Artificial , Pólipos do Colo/diagnóstico por imagem , Colonoscopia , Humanos , Imagem de Banda Estreita , Estudos Retrospectivos
12.
Int J Mol Sci ; 22(16)2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34445219

RESUMO

In the heart, TRPM4 is most abundantly distributed in the conduction system. Previously, a single mutation, 'E7K', was identified in its distal N-terminus to cause conduction disorder because of enhanced cell-surface expression. It remains, however, unclear how this expression increase leads to conduction failure rather than abnormally enhanced cardiac excitability. To address this issue theoretically, we mathematically formulated the gating kinetics of the E7K-mutant TRPM4 channel by a combined use of voltage jump analysis and ionomycin-perforated cell-attached recording technique and incorporated the resultant rate constants of opening and closing into a human Purkinje fiber single-cell action potential (AP) model (Trovato model) to perform 1D-cable simulations. The results from TRPM4 expressing HEK293 cells showed that as compared with the wild-type, the open state is much preferred in the E7K mutant with increased voltage-and Ca2+-sensitivities. These theoretical predictions were confirmed by power spectrum and single channel analyses of expressed wild-type and E7K-mutant TRPM4 channels. In our modified Trovato model, the facilitated opening of the E7K mutant channel markedly prolonged AP duration with concomitant depolarizing shifts of the resting membrane potential in a manner dependent on the channel density (or maximal activity). This was, however, little evident in the wild-type TRPM4 channel. Moreover, 1D-cable simulations with the modified Trovato model revealed that increasing the density of E7K (but not of wild-type) TRPM4 channels progressively reduced AP conduction velocity eventually culminating in complete conduction block. These results clearly suggest the brady-arrhythmogenicity of the E7K mutant channel which likely results from its pathologically enhanced activity.


Assuntos
Mutação com Ganho de Função , Modelos Biológicos , Canais de Cátion TRPM , Células HEK293 , Humanos , Potenciais da Membrana , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo
13.
J Neurooncol ; 154(2): 131-144, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34357490

RESUMO

BACKGROUND: Circular RNA (circRNA) has been demonstrated to play key roles in regulating glioma progression. Understanding the regulatory mechanism of circRNA in glioma is vital to reveal the pathogenesis of glioma and develop novel therapeutic strategies. Therefore, our study focuses on the role and underlying mechanism of Circ_CLIP2 in glioma. METHODS: The expression of Circ_CLIP2, miR-195-5p and HMGB3 in glioma cells and tissues were analyzed using qRT-PCR. Cell proliferation was determined with colony formation and MTT assays. Cell cycle and apoptosis were examined by flow cytometry. Western blot was conducted for analyzing HMGB3, PCNA, Bax, Bcl-2, cleaved-caspase 3, Wnt-1 and ß-catenin. Dual-luciferase reporter assay was measured to investigate the interaction among Circ_CLIP2, miR-195-5p and HMGB3. RESULTS: The expression of Circ_CLIP2 and HMGB3 were increased while miR-195-5p was down-regulated in glioma cells and patients. Silencing of Circ_CLIP2 inhibited cell proliferation, enhanced cell apoptosis and inhibited the Wnt/ß-catenin signaling pathway. Circ_CLIP2 suppressed miR-195-5p expression by directly sponging miR-195-5p. MiR-195-5p inhibited HMGB3 expression via directly targeting HMGB3. Knockdown of miR-195-5p facilitated cell proliferation, inhibited cell apoptosis and activated Wnt/ß-catenin signaling, which were reversed by silencing of HMGB3. CONCLUSION: Knockdown of Circ_CLIP2 suppresses glioma progression by targeting miR-195-5p/HMGB3 thus inhibiting Wnt/ß-catenin signaling. This study may provide potential therapeutic targets against glioma.

14.
Medicine (Baltimore) ; 100(34): e26909, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449457

RESUMO

RATIONALE: Bladder paraganglioma is characterized by headache, palpitations, hypertension, blurred vision, or sweating during voiding. Transurethral holmium laser resection is a safe and efficacious alternative method for the resection of bladder neoplasms. PATIENT CONCERNS: A 24-year-old female had a 2-year history of intermittent headaches, palpitation, and sweating during micturition. DIAGNOSIS: Physical examination revealed a rise in the patient's blood pressure to 180/90 mmHg after micturition. Laboratory examination found that the blood catecholamine metabolites were significantly increased. Abdominal ultrasound and computed tomography (CT) scan indicated a 37 mm × 31 mm paraganglioma situated at the right anterolateral wall of the bladder. A diagnosis of bladder paraganglioma was considered based on a comprehensive evaluation of the physical examination, laboratory examination, ultrasound and computerized tomography scan. INTERVENTIONS: Preoperative oral administration of a nonselective α-adrenergic receptor antagonist (phenoxybenzamine, 10 mg three times a day,) accompanied by a high-sodium diet and generous fluid intake, was initiated 2 weeks before the surgery to stabilize intraoperative hemodynamics. As the patient was newly married and nulligravid, management with transurethral resection was considered superior to open or partial cystectomy and was selected as the treatment method. OUTCOMES: Transurethral holmium resection of the bladder paraganglioma was successfully performed with blood loss less than 20 ml and well-controlled intraoperative blood pressure. The 1-year follow-up results demonstrated well-controlled symptoms. Cystoscopy and evaluation of blood catecholamine metabolites revealed no disease recurrence. LESSONS: Transurethral holmium laser resection is a good alternative approach for the resection of bladder paraganglioma, given its advantages of safety and efficacy.


Assuntos
Lasers de Estado Sólido/uso terapêutico , Paraganglioma/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Feminino , Humanos , Paraganglioma/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Procedimentos Cirúrgicos Urológicos , Adulto Jovem
15.
Environ Res ; 203: 111843, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34364864

RESUMO

Ag3PO4/BiPO4 heterojunction photocatalysts with an intergrowth structure composed of sphere-shaped Ag3PO4 and nanorod BiPO4 were synthesized via a facile combination of solvothermal method and in-situ deposition process. They exhibit enhanced photocatalytic activities under sunlight irradiation, and the heterojunction composite with the 10 wt% loading amounts of Ag3PO4 presented the highest photocatalytic activities against norfloxacin (NFX), ofloxacin (OFXL) and ciprofloxacin (CIP), with high degradation efficiencies of 94.7%, 95.4% and 92.1%, respectively. Additionally, the Ag3PO4/BiPO4 photocatalyst demonstrates outstanding structural and photocatalytic stability. The superior performance was attributed to the effective charge transfer across the p-n heterojunction interface and the enhancement of light absorption. This work provides a new insight into the development of novel BiPO4-based heterojunction composites and meets the remediation for contaminated aqueous environment.

16.
Huan Jing Ke Xue ; 42(9): 4116-4125, 2021 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-34414710

RESUMO

Organic carbon (OC), elemental carbon (EC), and PM2.5 concentration data obtained from Shanxi Super Station in Jiashan County of Jiaxing City, in the winter of 2018 and 2019, were analyzed to determine the variation and potential source areas of carbonaceous aerosols. The results show that OC concentrations in the winter of 2018 and 2019 were 6.90 µg·m-3 and 5.63 µg·m-3, respectively, while EC concentrations were 2.47 µg·m-3 and 1.57 µg·m-3, respectively. The concentrations of OC and EC in the winter of 2019 were lower than those in the winter of 2018, by approximately 18.4% and 36.4%, respectively. In 2018 and 2019, the concentrations of secondary organic carbon (SOC), calculated using the minimum R-squared (MRS) method, were 1.49 µg·m-3 and 1.97 µg·m-3, respectively, and the concentrations of primary organic carbon (POC) were 5.41 µg·m-3 and 3.66 µg·m-3, respectively. The proportion of POC in OC showed a downward trend, from 96.0% in December 2018 to 64.9% in February 2020, indicating a decrease of 31.1 percentage points. SOC showed an upward trend, increasing by 31.1 percentage points from 4.0% in December 2018 to 35.1% in February 2020. It is worth noting that with the increase in PM2.5 concentration, the concentration of OC and EC increased by 474.7% and 408.2%, respectively, although the proportion of OC in PM2.5 decreased from 18.8% to 12.3%. and the percentage of OC decreased from 5.8% to 3.3%. The contribution of POC to PM2.5 did not fluctuate, and only decreased significantly above 150 µg·m-3, while the contribution of SOC to PM2.5 first decreased and then increased. In Jiaxing, the potential sources of OC and EC were mainly southern Jiangsu, southeastern Anhui, local Jiaxing, and northern Zhejiang. In the winter of the contribution concentrations of OC and EC in the main potential source regions were approximately 2 µg·m-3 and 6 µg·m-3 lower, respectively, than in winter 2018. The range of high values in the potential source regions also decreased in 2019. Before the COVID-19 epidemic, it was affected by both motor vehicle exhaust emissions and coal burning. During the Spring Festival and home isolation, due to traffic control and other reasons, motor vehicle emissions were reduced, which leaving coal burning as the main contributor.


Assuntos
Poluentes Atmosféricos , COVID-19 , Aerossóis/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Humanos , Material Particulado/análise , SARS-CoV-2
17.
Acta Pharmacol Sin ; 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376812

RESUMO

Peroxisome proliferator-activated receptor α (PPARα), a ligand-activated nuclear receptor critical for systemic lipid homeostasis, has been shown closely related to cardiac remodeling. However, the roles of cardiomyocyte PPARα in pressure overload-induced cardiac remodeling remains unclear because of lacking a cardiomyocyte-specific Ppara-deficient (PparaΔCM) mouse model. This study aimed to determine the specific role of cardiomyocyte PPARα in transverse aortic constriction (TAC)-induced cardiac remodeling using an inducible PparaΔCM mouse model. PparaΔCM and Pparafl/fl mice were randomly subjected to sham or TAC for 2 weeks. Cardiomyocyte PPARα deficiency accelerated TAC-induced cardiac hypertrophy and fibrosis. Transcriptome analysis showed that genes related to fatty acid metabolism were dramatically downregulated, but genes critical for glycolysis were markedly upregulated in PparaΔCM hearts. Moreover, the hypertrophy-related genes, including genes involved in extracellular matrix (ECM) remodeling, cell adhesion, and cell migration, were upregulated in hypertrophic PparaΔCM hearts. Western blot analyses demonstrated an increased HIF1α protein level in hypertrophic PparaΔCM hearts. PET/CT analyses showed an enhanced glucose uptake in hypertrophic PparaΔCM hearts. Bioenergetic analyses further revealed that both basal and maximal oxygen consumption rates and ATP production were significantly increased in hypertrophic Pparafl/fl hearts; however, these increases were markedly blunted in PparaΔCM hearts. In contrast, hypertrophic PparaΔCM hearts exhibited enhanced extracellular acidification rate (ECAR) capacity, as reflected by increased basal ECAR and glycolysis but decreased glycolytic reserve. These results suggest that cardiomyocyte PPARα is crucial for the homeostasis of both energy metabolism and ECM during TAC-induced cardiac remodeling, thus providing new insights into potential therapeutics of cardiac remodeling-related diseases.

18.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(4): 359-364, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34374254

RESUMO

Objective: To observe the effects of acupuncture on the endoplasmic reticulum (ER) functional enzymes sarcoplasmic reticulum Ca2+-ATPase (SERCA), protein disulfide isomerase (PDI), glucose-regulated protein 78(GRP78) and PERK pathways in rats with exercise-induced skeletal muscle damage, and to explore the mechanisms of acupuncture in preventing and treating exercise-induced skeletal muscle damage. Methods: Eight-week-old male SD rats were randomly divided into control group (group C, n=6), exercise group (group E, n=30), acupuncture group (group A, n=30) and exercise acupuncture group (group EA, n=30). Among them, the E and EA group were established an exercise-induced skeletal muscle damage model by a single eccentric exercise, and acupuncture intervention was applied 0.5 cm above the Achilles tendon of the rat's calf immediately after EA exercise, and in group A, acupuncture intervention was applied during the same period. Each group was divided into 0 h/12 h/24 h/48 h/72 h (n=6) according to different sampling time points after exercise and acupuncture intervention, and soleus muscle was collected at the corresponding time for index test. The ultrastructure of muscle fibers was observed by transmission electron microscopy; the contents of SERCA and PDI were determined by ELISA; and the expressions of ER stress marker proteins GRP78 and p-PERK and p-eIF2α were detected by Western blot. Results: Compared with group C, there were no significant differences in the indicators of group A at all time points (P> 0.05), the ultrastructure of muscle fibers in group E showed different damages, SERCA content was significantly decreased from 0 h to 48 h (P<0.05), PDI content was significantly increased from 0 h to 72 h (P<0.05), GRP78 expression was significantly increased from 0 h to 72 h (P<0.05), p-PERK expression was significantly increased from 0 h to 24 h (P<0.05), and p-eIF2α expression was consistent with p-PERK. Compared with the corresponding times in group E, the ultrastructure of muscle fibers in group EA was significantly alleviated, SERCA content was significantly increased from 48 h and 72 h (P<0.05), PDI content was significantly increased from 0 h to 72 h (P<0.05), and GRP78 expression was significantly decreased from 0 h to 72 h (P<0.05). Conclusion: Acupuncture can effectively ameliorate exercise-induced skeletal muscle damage and alleviate ER stress after a large load eccentric exercise. The mechanism of them may be related to the up-regulation of protein disulfide isomerase PDI and the inhibition of ER stress PERK pathway.


Assuntos
Terapia por Acupuntura , Condicionamento Físico Animal , Animais , Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Masculino , Músculo Esquelético , Ratos , Ratos Sprague-Dawley
19.
Sci Rep ; 11(1): 15618, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34341365

RESUMO

C4 photosynthesis is a remarkable complex trait, elucidations of the evolutionary trajectory of C4 photosynthesis from its ancestral C3 pathway can help us better understand the generic principles of the evolution of complex traits and guide the engineering of C3 crops for higher yields. Here, we used the genus Flaveria that contains C3, C3-C4, C4-like and C4 species as a system to study the evolution of C4 photosynthesis. We first mapped transcript abundance, protein sequence and morphological features onto the phylogenetic tree of the genus Flaveria, and calculated the evolutionary correlation of different features; we then predicted the relative changes of ancestral nodes of those features to illustrate the major events during the evolution of C4 photosynthesis. We found that gene expression and protein sequence showed consistent modification patterns in the phylogenetic tree. High correlation coefficients ranging from 0.46 to 0.9 among gene expression, protein sequence and morphology were observed. The greatest modification of those different features consistently occurred at the transition between C3-C4 species and C4-like species. Our results show highly coordinated changes in gene expression, protein sequence and morphological features, which support evolutionary major events during the evolution of C4 metabolism.

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