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1.
Anal Chem ; 96(18): 7138-7144, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38676633

RESUMO

Superoxide anion (O2·-) and peroxynitrite (ONOO-), two important oxidants under oxidative stress, coexist in complex cell and organism systems, playing crucial roles in various physiological and pathological processes, particularly in neurodegenerative diseases. Despite the absence of robust molecular tools capable of simultaneously visualizing O2·- and ONOO- in biosystems, the relationship between these two species remains understudied. Herein, we present sequentially activated fluorescent probe, DHX-SP, which exhibits exceptional selectivity and sensitivity toward O2·- and ONOO-. This probe enables precise imaging of these species in living PC12 cells under oxidative stress conditions using distinct fluorescence signal combinations. Furthermore, the probe DHX-SP has the ability to visualize changes in O2·- and ONOO- levels during ferroptosis of PC12 cells and in the Parkinson's disease model. These findings establish a connection between the crosstalk of the phosphorus group of O2·- and ONOO- in PC12 cells under oxidative stress.


Assuntos
Corantes Fluorescentes , Estresse Oxidativo , Ácido Peroxinitroso , Superóxidos , Células PC12 , Ácido Peroxinitroso/análise , Ácido Peroxinitroso/metabolismo , Animais , Ratos , Estresse Oxidativo/efeitos dos fármacos , Corantes Fluorescentes/química , Superóxidos/metabolismo , Superóxidos/análise , Imagem Óptica
2.
BMC Cardiovasc Disord ; 24(1): 111, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365602

RESUMO

OBJECTIVES: The study aims to assess the effect of baseline glycated hemoglobin (HbA1c) levels on atrial fibrillation (AF) recurrence following cryoballoon ablation in patients with and without diabetes. METHODS: Consecutive AF patients receiving first cryoballoon ablation between April 2018 and April 2021 were included. AF recurrence and other clinical outcomes were recorded for a minimum of 12 months post-ablation, with regular assessments at 3, 6, and 12 months, followed by annual check-ups. The primary outcome was AF recurrence after ablation at longest follow-up. Multivariate Cox proportional hazards regression models were utilized to calculate the hazard ratio (HR) and 95% CI per standard deviation (SD) increase of baseline HbA1c level. RESULTS: 335 patients were included in the analysis. The mean age was 61.7 years, 61.8% were male. 12.8% had type 2 diabetes, and 81.7% of patients had paroxysmal AF. The median level of HbA1c was 5.3%, and the mean CHA2DS2-VASc score was 1.8. All cryoballoon ablation procedures, utilizing a 28-mm balloon, achieved successful pulmonary vein isolation. Over a median follow-up of 18 months, 105 patients (31.3%) experienced AF recurrence. In multivariate Cox proportional hazards analysis, a higher HbA1c level, persistent AF (HR 1.91, 95% CI 1.08 to 3.39, P = 0.026), alcohol consumption (HR 2.67, 95% CI 1.33 to 5.37, P = 0.006), and Nadir RSPV (HR 1.04, 95% CI 1.00 to 1.08, P = 0.005) were significant predictors of AF recurrence. Per-SD increase of HbA1c was associated with a 1.75-fold increase risk of AF recurrence (HR 1.75, 95% CI 1.39 to 2.21, P < 0.001). Subgroup analysis revealed that a higher HbA1c level was associated with a higher risk of AF recurrence in patients with and without diabetes, and in patients with paroxysmal and persistent AF. CONCLUSION: Baseline HbA1c level was an independent predictor of AF recurrence following cryoablation, both in patients with and without diabetes.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Criocirurgia , Diabetes Mellitus Tipo 2 , Veias Pulmonares , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Hemoglobinas Glicadas , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Resultado do Tratamento , Fatores de Risco , Criocirurgia/efeitos adversos , Recidiva , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia
3.
BMC Med Imaging ; 24(1): 31, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308230

RESUMO

PURPOSE: The tumor immune microenvironment is a valuable source of information for predicting prognosis in breast cancer (BRCA) patients. To identify immune cells associated with BRCA patient prognosis from the Cancer Genetic Atlas (TCGA), we established an MRI-based radiomics model for evaluating the degree of immune cell infiltration in breast cancer patients. METHODS: CIBERSORT was utilized to evaluate the degree of infiltration of 22 immune cell types in breast cancer patients from the TCGA database, and both univariate and multivariate Cox regressions were employed to determine the prognostic significance of immune cell infiltration levels in BRCA patients. We identified independent prognostic factors for BRCA patients. Additionally, we obtained imaging features from the Cancer Imaging Archive (TCIA) database for 73 patients who underwent preoperative MRI procedures, and used the Least Absolute Shrinkage and Selection Operator (LASSO) to select the best imaging features for constructing an MRI-based radiomics model for evaluating immune cell infiltration levels in breast cancer patients. RESULTS: According to the results of Cox regression analysis, M2 macrophages were identified as an independent prognostic factor for BRCA patients (HR = 32.288, 95% CI: 3.100-357.478). A total of nine significant features were selected to calculate the radiomics-based score. We established an intratumoral model with AUCs (95% CI) of 0.662 (0.495-0.802) and 0.678 (0.438-0.901) in the training and testing cohorts, respectively. Additionally, a peritumoral model was created with AUCs (95% CI) of 0.826 (0.710-0.924) and 0.752 (0.525-0.957), and a combined model was established with AUCs (95% CI) of 0.843 (0.723-0.938) and 0.744 (0.491-0.965). The peritumoral model demonstrated the highest diagnostic efficacy, with an accuracy, sensitivity, and specificity of 0.773, 0.727, and 0.818, respectively, in its testing cohort. CONCLUSION: The MRI-based radiomics model has the potential to evaluate the degree of immune cell infiltration in breast cancer patients, offering a non-invasive imaging biomarker for assessing the tumor microenvironment in this disease.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Radiômica , Microambiente Tumoral , Prognóstico , Imageamento por Ressonância Magnética
4.
Int J Environ Health Res ; : 1-19, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38339769

RESUMO

This study aimed to determine dust-phase phthalate levels in 112 dormitories of 14 universities during autumn and winter, investigate their potential sources, and estimate phthalate exposure via dust ingestion. Twelve phthalates were detected, among which di-(2-ethylhexyl) phthalate (DEHP) and dicyclohexyl phthalate (DCHP) were the most abundant, followed by di-isobutyl phthalate (DiBP) and di-n-butyl phthalate (DnBP). The median concentrations and contributions of DCHP and DEHP were the highest. The contributions of di-n-octyl phthalate and di-nonyl phthalate were higher in winter than in autumn. Potential sources included iron furniture, chemical fiber textiles, clothes, and personal care products. Medium-density fiberboard furniture is a potential sink for phthalates. In two seasons, DEHP, DCHP, DiBP, and DnBP were the main phthalates ingested by college students . The median oral exposure of ten phthalates was higher in females than in males. College students have a high risk of exposure to DEHP in dormitories.

5.
J Environ Sci (China) ; 143: 138-147, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38644012

RESUMO

Tetramethylammonium hydroxide (TMAH) is an important compound that utilized and released by the rapidly expanding semiconductor industry, which could hardly be removed by the conventional wastewater treatment techniques. As a cholinergic agonist, the tetramethylammonium ion (TMA+) has been reported to induce toxicity to muscular and respiratory systems of mammals and human, however the toxicity on aquatic biota remains poorly known. We investigated the neurotoxic effects of TMA+ exposure on zebrafish, based on neurobehavior tests and a series of biomarkers. Significant inhibitions on the swimming distance of zebrafish larvae were observed when the exposure level exceeded 50 mg/L, and significant alterations on swimming path angles (straight and deflective movements) occurred even at 10 mg/L. The tested neurobehavioral endpoints of zebrafish larvae were significantly positively correlated with reactive oxygen species (ROS) and malondialdehyde (MDA), significantly negatively related with the activities of antioxidant enzymes, but not significantly correlated with the level of acetylcholinesterase (AChE). Such relationship indicates that the observed neurotoxic effects on swimming behavior of zebrafish larvae is mainly driven by oxidative stress, rather than the alterations of neurotransmitter. At the highest exposure concentration (200 mg/L), TMA+ evoked more severe toxicity on zebrafish juveniles, showing significantly stronger elevation on the MDA activity, and greater inhibitions on the activities of antioxidant enzymes and AChE, suggesting juveniles were more susceptible to TMA+ exposure than larval zebrafish.


Assuntos
Biomarcadores , Larva , Compostos de Amônio Quaternário , Poluentes Químicos da Água , Peixe-Zebra , Animais , Peixe-Zebra/fisiologia , Poluentes Químicos da Água/toxicidade , Biomarcadores/metabolismo , Compostos de Amônio Quaternário/toxicidade , Larva/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Natação , Comportamento Animal/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
6.
J Biol Chem ; 298(3): 101641, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35090894

RESUMO

Increasing evidence has shown that AdipoRon, a synthetic adiponectin receptor agonist, is involved in the regulation of whole-body insulin sensitivity and energy homeostasis. However, the mechanisms underlying these alterations remain unclear. Here, using hyperinsulinemic-euglycemic clamp and isotopic tracing techniques, we show that short-term (10 days) AdipoRon administration indirectly inhibits lipolysis in white adipose tissue via increasing circulating levels of fibroblast growth factor 21 in mice fed a high-fat diet. This led to reduced plasma-free fatty acid concentrations and improved lipid-induced whole-body insulin resistance. In contrast, we found that long-term (20 days) AdipoRon administration directly exacerbated white adipose tissue lipolysis, increased hepatic gluconeogenesis, and impaired the tricarboxylic acid cycle in the skeletal muscle, resulting in aggravated whole-body insulin resistance. Together, these data provide new insights into the comprehensive understanding of multifaceted functional complexity of AdipoRon.


Assuntos
Fatores de Crescimento de Fibroblastos , Resistência à Insulina , Piperidinas , Animais , Dieta Hiperlipídica , Fatores de Crescimento de Fibroblastos/metabolismo , Técnica Clamp de Glucose , Insulina/metabolismo , Fígado/metabolismo , Camundongos , Piperidinas/farmacologia
7.
Gene Ther ; 30(1-2): 142-149, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35644811

RESUMO

Dystrophin deficiency due to genetic mutations causes cardiac abnormalities in Duchenne's muscular dystrophy. Dystrophin is also shown to be downregulated in conventional failing hearts. Whether restoration of dystrophin expression possesses any therapeutic potential for conventional heart failure (HF) remains to be examined. HF mouse model was generated by transverse aortic constriction (TAC). In vivo activation of dystrophin transcription was achieved by tail-vein injection of adeno-associated virus 9 carrying CRISPR/dCas system for dystrophin. We found that activation of dystrophin expression in TAC mice significantly reduced the susceptibility to arrhythmia of TAC mice and the mortality rate. We further demonstrated that over-expression of dystrophin increased cardiac conduction of hearts in TAC mice by optical mapping evaluation. Activation of dystrophin expression also increased peak sodium current in isolated ventricular myocytes from hearts of TAC mice as recorded by the patch-clamp technique. Immunoblotting and immunofluorescence showed that increased dystrophin transcription restored the membrane distribution of Nav1.5 in the hearts of TAC mice. In summary, correction of dystrophin downregulation by the CRISPR-dCas9 system reduced the susceptibility to arrhythmia of conventional HF mice through restoring Nav1.5 membrane distribution. This study paved the way to develop a new therapeutic strategy for HF-related ventricular arrhythmia.


Assuntos
Insuficiência Cardíaca , Distrofia Muscular de Duchenne , Camundongos , Animais , Distrofina/genética , Distrofina/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Arritmias Cardíacas/genética , Arritmias Cardíacas/terapia , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia
8.
Anal Chem ; 95(19): 7611-7619, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37134014

RESUMO

Mitochondrial viscosity affects metabolite diffusion and mitochondrial metabolism and is associated with many diseases. However, the accuracy of mitochondria-targeting fluorescent probes in measuring viscosity is unsatisfactory because these probes can diffuse from mitochondria during mitophagy with a decreased mitochondrial membrane potential (MMP). To avoid this problem, by incorporating different alkyl side chains into dihydroxanthene fluorophores (denoted as DHX), we developed six near-infrared (NIR) probes for the accurate detection of mitochondrial viscosity, and the sensitivity to viscosity and the mitochondrial targeting and anchoring capability of these probes increased by increasing the alkyl chain length. Among them, DHX-V-C12 had a highly selective response to viscosity variations with minimum interference from polarity, pH, and other biologically relevant species. Furthermore, DHX-V-C12 was used to monitor the mitochondrial viscosity changes of HeLa cells treated by ionophores (nystatin, monensin) or under starvation conditions. We hope that this mitochondrial targeting and anchoring strategy based on increasing the alkyl chain length will be a general strategy for the accurate detection of mitochondrial analytes, enabling the accurate study of mitochondrial functions.


Assuntos
Corantes Fluorescentes , Mitocôndrias , Humanos , Corantes Fluorescentes/química , Viscosidade , Células HeLa , Mitocôndrias/metabolismo , Mitofagia
9.
Small ; 19(18): e2206991, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36772898

RESUMO

Regulating the crystal structure by A-site cation substitution is one of the effective methods to explore high-performance nonlinear optical (NLO) materials. Herein, two non-centrosymmetric (NCS) compounds, α-MZnPO4 (M = Li, K) with short UV absorption edges 221 and 225 nm, are obtained by performing A-site cation substitution method. It is noteworthy that α-LiZnPO4 (α-LZPO) achieves >10 times second harmonic generation (SHG) response (2.3 × KDP) enhancement compared with that of α-KZnPO4 (α-KZPO) (0.2 × KDP), which is the only case among phosphates with different A-site cations. By structural comparison, it is found that the A-site cations play important roles for anion rearrangements, and further the structure features of the two compounds by designing two suppositional crystal models as well as performing other theoretical calculations are analyzed. The study confirms the feasibility to design promising NLO materials with strengthen SHG response and structural stability in orthophosphate system.

10.
Chemistry ; 29(34): e202300626, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37037794

RESUMO

In the work, four new Sb-based phosphates, K4 (SbO2 )5 (PO4 )3 , Rb(SbO2 )2 PO4 , Rb3 (SbO2 )3 (PO4 )2 and Cs3 (SbO2 )3 (PO4 )2 (H2 O)1.32 , were successfully synthesized by a high-temperature melt method. Among them, Rb(SbO2 )2 PO4 and Rb3 (SbO2 )3 (PO4 )2 are the first reported examples of Rb-containing alkali metal Sb-based phosphates. They show three-dimensional (3D) frameworks composed of [Sb8 P4 O30 ]∞ layer for K4 (SbO2 )5 (PO4 )3 and [Sb6 P2 O20 ]∞ layer for Rb(SbO2 )2 PO4 , and 2D lamellar structure composed of [Sb3 P2 O10 ]∞ for Rb3 (SbO2 )3 (PO4 )2 and Cs3 (SbO2 )3 (PO4 )2 (H2 O)1.32 . A detailed structural comparison shows that the structure dimensions for them transfer from 1D to complex 3D framework with the increase of (Sb+P)/O ratio, which affects performances of the compounds. Optical property and energy band structure calculations were also carried out based on the density functional theory (DFT). The present study enriches the diversity of Sb-based phosphates and paves the way for further explore their optical properties in the future.

11.
Appl Opt ; 62(9): 2357-2366, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-37132875

RESUMO

This paper focuses on the rapid charge transfer of lock-in pixels in time of flight 3D image sensors. Through the principal analysis, a mathematical model of potential distribution in a pinned photodiode (PPD) in different comb shapes is established. Based on this model, the influence of different comb shapes on the accelerating electric field in PPD is analyzed. The semiconductor device simulation tool SPECTRA is applied to verify the effectiveness of the model, and the simulation results are analyzed and discussed. When the width of comb tooth is in narrow and medium range, the potential changes more obviously with the increase of comb tooth angle α, whereas the potential becomes stable even if the comb tooth angle α increases sharply with the wide comb tooth width. The proposed mathematical model contributes to instructing the design of pixel transferring electrons rapidly and resolving image lag.

12.
J Sci Food Agric ; 103(4): 1874-1884, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36468888

RESUMO

BACKGROUND: The poor gelling and emulsification properties of pea protein (PeaP) limit its application in gel-based products. In this study, a strong hydrogel and a high internal phase emulsion (HPLE) gel of PeaP were constructed by covalent cross-linking of transglutaminase (TGase) assisted by high-intensity ultrasound. RESULTS: Ultrasound promoted the catalytic efficiency of TGase, with the gel-point temperature dropping from 44 °C to 28 °C after 10 min of ultrasound. As the ultrasound time increased from 1 min to 10 min, the microstructure of the hydrogel also changed from an irregular macropore structure to a relatively homogeneous honeycomb structure. This was accompanied by an improvement in gel strength, water holding capacity, and ultimate stress. Ultrasound enhanced the binding of water to PeaP, but had little effect on the water-locking ability of the network structure. Ultrasonication improved the self-supporting ability of the HPIE gels. The oil droplets within the HPIE gels were closely aligned to form a hexagonal structure. The PeaP layer was further cross-linked by TGase, strengthening the network structure. High internal phase emulsion gel displayed a higher gel strength, viscosity, and good self-healing ability under 1 min ultrasound. Meanwhile, HPIE gel at 1 min of ultrasound could be printed with the highest clarity. CONCLUSION: This work provided some insights into improving the functional properties of PeaP, which is helpful for the design and development of PeaP-based gel products. © 2022 Society of Chemical Industry.


Assuntos
Hidrogéis , Proteínas de Ervilha , Emulsões/química , Transglutaminases/química , Géis/química , Água/química , Reologia
13.
Angew Chem Int Ed Engl ; 62(11): e202218970, 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36688728

RESUMO

Although great progress has been made in new electrolytes for lithium metal batteries (LMBs), the intrinsic relationship between electrolyte composition and cell performance remains unclear due to the lack of valid quantization method. Here, we proposed the concept of negative center of electrostatic potential (NCESP) and Mayer bond order (MBO) to describe solvent capability, which highly relate to solvation structure and oxidation potential, respectively. Based on established principles, the selected electrolyte with 1.7 M LiFSI in methoxytrimethylsilane (MOTMS)/ (trifluoromethyl)trimethylsilane (TFMTMS) shows unique hyperconjugation nature to stabilize both Li anode and high-voltage cathode. The 4.6 V 30 µm Li||4.5 mAh cm-2 lithium cobalt oxide (LCO) (low N/P ratio of 1.3) cell with our electrolyte shows stable cycling with 91 % capacity retention over 200 cycles. The bottom-up design concept of electrolyte opens up a general strategy for advancing high-voltage LMBs.

14.
Pharmacol Res ; 182: 106284, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35661710

RESUMO

Pathological cardiac hypertrophy is a process characterized by significant disturbance of protein turnover. Cullin-associated and Neddylation-dissociated 1 (CAND1) acts as a coordinator to modulate substrate protein degradation by promoting the formation of specific cullin-based ubiquitin ligase 3 complex in response to substrate accumulation, which thereby facilitate the maintaining of normal protein homeostasis. Accumulation of calcineurin is critical in the pathogenesis of cardiac hypertrophy and heart failure. However, whether CAND1 titrates the degradation of hypertrophy related protein eg. calcineurin and regulates cardiac hypertrophy remains unknown. Therefore, we aim to explore the role of CAND1 in cardiac hypertrophy and heart failure and the underlying molecular mechanism. Here, we found that the protein level of CAND1 was increased in cardiac tissues from heart failure (HF) patients and TAC mice, whereas the mRNA level did not change. CAND1-KO+ /- aggravated TAC-induced cardiac hypertrophic phenotypes; in contrast, CAND1-Tg attenuated the maladaptive cardiac remodeling. At the molecular level, CAND1 overexpression downregulated, whereas CAND1-KO+ /- or knockdown upregulated calcineurin expression at both in vivo and in vitro conditions. Mechanistically, CAND1 overexpression favored the assembly of Cul1/atrogin1/calcineurin complex and rendered the ubiquitination and degradation of calcineurin. Notably, CAND1 deficiency-induced hypertrophic phenotypes were partially rescued by knockdown of calcineurin, and application of exogenous CAND1 prevented TAC-induced cardiac hypertrophy. Taken together, our findings demonstrate that CAND1 exerts a protective effect against cardiac hypertrophy and heart failure partially by inducing the degradation of calcineurin.


Assuntos
Calcineurina , Cardiomegalia , Proteínas Culina , Insuficiência Cardíaca , Animais , Calcineurina/metabolismo , Cardiomegalia/genética , Proteínas Culina/química , Proteínas Culina/genética , Proteínas Culina/metabolismo , Insuficiência Cardíaca/genética , Humanos , Camundongos , Fatores de Transcrição
15.
J Interv Cardiol ; 2022: 2345584, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463209

RESUMO

Objective: At present, the use of particular radial hemostatic devices after coronary angiography (CAG) or percutaneous coronary intervention (PCI) has become the primary method of hemostasis. Most control studies are based on the products already on the market, while only a few studies are on the new hemostatic devices. The aim of this study is to compare a new radial artery hemostasis device which is transformed based on the invention patent (Application number: CN201510275446) with TR Band (Terumo Medical) to evaluate its clinical effects. Methods: In a prospective randomized clinical trial, 60 patients after CAG or PCI were randomly divided into two groups, patients in the trial group (CD group) using a new radial artery hemostasis device to stop bleeding and the control group (TR group) using the TR Band. The method is to collect relevant data of the two groups and compare the differences in hemostasis, local complications, and patient discomfort between the two groups. Results: The hemostatic devices in both groups achieved adequate hemostasis, and there was no failure to stop bleeding. The new radial artery hemostasis device was better than the TR band in pain and swelling (P < 0.05). There were no significant differences in bleeding, hematoma, ecchymosis, skin damage, and local infection between the two groups (P > 0.05). Conclusions: The sample of the new radial artery hemostasis device can stop bleeding effectively at the puncture site after CAG or PCI and is not inferior to the TR Band balloon hemostatic device in safety and is better in comfort.


Assuntos
Hemostáticos , Intervenção Coronária Percutânea , Angiografia Coronária/efeitos adversos , Hemorragia/etiologia , Hemorragia/prevenção & controle , Hemostasia , Técnicas Hemostáticas , Hemostáticos/uso terapêutico , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Estudos Prospectivos , Artéria Radial , Resultado do Tratamento
16.
Acta Pharmacol Sin ; 43(2): 307-315, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33911193

RESUMO

Interleukin-17A (IL-17), a potent proinflammatory cytokine, has been shown to participate in cardiac electrical disorders. Diabetes mellitus is an independent risk factor for ventricular arrhythmia. In this study, we investigated the role of IL-17 in ventricular arrhythmia of diabetic mice. Diabetes was induced in both wild-type and IL-17 knockout mice by intraperitoneal injection of streptozotocin (STZ). High-frequency electrical stimuli were delivered into the right ventricle to induce ventricular arrhythmias. We showed that the occurrence rate of ventricular tachycardia was significantly increased in diabetic mice, which was attenuated by IL-17 knockout. We conducted optical mapping on perfused mouse hearts and found that cardiac conduction velocity (CV) was significantly decreased, and action potential duration (APD) was prolonged in diabetic mice, which were mitigated by IL-17 knockout. We performed whole-cell patch clamp recordings from isolated ventricular myocytes, and found that the densities of Ito, INa and ICa,L were reduced, the APDs at 50% and 90% repolarization were increased, and early afterdepolarization (EAD) was markedly increased in diabetic mice. These alterations were alleviated by the knockout of IL-17. Moreover, knockout of IL-17 alleviated the downregulation of Nav1.5 (the pore forming subunit of INa), Cav1.2 (the main component subunit of ICa,L) and KChIP2 (potassium voltage-gated channel interacting protein 2, the regulatory subunit of Ito) in the hearts of diabetic mice. The expression of NF-κB was significantly upregulated in the hearts of diabetic mice, which was suppressed by IL-17 knockout. In neonatal mouse ventricular myocytes, knockdown of NF-κB significantly increased the expression of Nav1.5, Cav1.2 and KChIP2. These results imply that IL-17 may represent a potential target for the development of agents against diabetes-related ventricular arrhythmias.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Cardiomiopatias Diabéticas/metabolismo , Interleucina-17/metabolismo , NF-kappa B/metabolismo , Remodelação Ventricular , Animais , Western Blotting , Técnicas de Inativação de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Patch-Clamp , Reação em Cadeia da Polimerase em Tempo Real
17.
Sensors (Basel) ; 22(4)2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35214528

RESUMO

Accurate and fast rolling bearing fault diagnosis is required for the normal operation of rotating machinery and equipment. Although deep learning methods have achieved excellent results for rolling bearing fault diagnosis, the performance of most methods declines sharply when the working conditions change. To address this issue, we propose a one-dimensional lightweight deep subdomain adaptation network (1D-LDSAN) for faster and more accurate rolling bearing fault diagnosis. The framework uses a one-dimensional lightweight convolutional neural network backbone for the rapid extraction of advanced features from raw vibration signals. The local maximum mean discrepancy (LMMD) is employed to match the probability distribution between the source domain and the target domain data, and a fully connected neural network is used to identify the fault classes. Bearing data from the Case Western Reserve University (CWRU) datasets were used to validate the performance of the proposed framework under different working conditions. The experimental results show that the classification accuracy for 12 tasks was higher for the 1D-LDSAN than for mainstream transfer learning methods. Moreover, the proposed framework provides satisfactory results when a small proportion of the unlabeled target domain data is used for training.


Assuntos
Redes Neurais de Computação , Vibração , Aclimatação , Humanos , Aprendizado de Máquina , Modalidades de Fisioterapia
18.
Angew Chem Int Ed Engl ; 61(17): e202200850, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35182094

RESUMO

Owing to the strong nucleophilicity of the NH2 group, free-NH2 glycinates react with MBH acetates to usually deliver N-allylated products even in the absence of catalysts. Without protection of the NH2 group, chiral pyridoxal catalysts bearing an amide side chain at the C3 position of the naphthyl ring switched the chemoselectivity of the glycinates from intrinsic N-allylation to α-C allylation. The reaction formed chiral multisubstituted glutamic acid esters as SN 2'-SN 2' products in good yields with excellent stereoselectivity (up to 86 % yield, >20 : 1 dr, 97 % ee). As compared to pyridoxal catalysts bearing an amide side arm at the C2 position, the pyridoxals in this study have a bigger catalytic cavity to enable effective activation of larger electrophiles, such as MBH acetates and related intermediates. The reaction is proposed to proceed via a cooperative bifunctional catalysis pathway, which accounts for the high level of diastereo- and enantiocontrol of the pyridoxal catalysts.


Assuntos
Acetatos , Piridoxal , Amidas , Catálise , Estereoisomerismo
19.
Environ Sci Technol ; 55(9): 5763-5771, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33818073

RESUMO

Coal and coal gangue spontaneous combustion (CGSC) occurs globally, causing significant environmental pollution. However, its emissions are poorly quantified and are overlooked in global or regional air pollutant emission inventories in previous studies, resulting in the underestimation of its impacts on climate, environment, and public health. This study quantified the emissions of various air pollutants originating from CGSC in Wuhai, a city in China, investigated emission characteristics, and estimated the contribution of CGSC emissions to fine particulate matter (PM2.5) air pollution and related health impacts on a regional scale. The results revealed that the CGSC-related PM2.5 emissions were approximately 4643 t a-1 (95% confidence interval (95% CI): 721; 10447), accounting for 26.3% of the total PM2.5 emissions. Alkanes, alkenes, and aromatics accounted for 69.4, 17.9, and 2.9%, respectively, of the total emissions of volatile organic compounds (VOCs). Due to CGSC emissions, the ambient PM2.5 concentration in Wuhai increased by 5.7 µg m-3 on average, while the nitrate concentration decreased. The number of premature deaths caused by exposure to ambient PM2.5 associated with CGSC reached 381 (95% CI: 290; 452) in Wuhai and surrounding cities in 2017. Urgent control strategies and engineering techniques are needed to mitigate CGSC to protect public health.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Cidades , Carvão Mineral/análise , Monitoramento Ambiental , Material Particulado/análise , Combustão Espontânea
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