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1.
Nanoscale Adv ; 6(14): 3590-3601, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38989509

RESUMO

Due to the elevated fatality rate of cardiovascular diseases, myocardial fibrosis emerges as a prominent pathological alteration in the majority of heart ailments and their associated pathologies, thereby augmenting the likelihood of sudden cardiac death. Consequently, the prompt and obligatory identification of myocardial fibrosis assumes paramount importance in averting malignant incidents among patients afflicted with cardiac disorders. Herein, with higher expression osteopontin (OPN) found in cardiac fibrosis tissue, we have developed a dual-modality imaging probe, namely OPN targeted nanoparticles (OPN@PFP-DiR NPs), which loaded perfluoropentane (PFP) for ultrasound (US) and 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) for near-infrared fluorescence (NIR) of molecular imaging, to investigate the molecular features of cardiac fibrosis using US and NIR imaging. Subsequently, the OPN@PFP-DiR NPs were administered intravenously to a mouse model of myocardial infarction (MI). The US and NIR molecular imaging techniques were employed to visualize the accumulation of the nanoparticles in the fibrotic myocardium. Hence, this research presents a valuable noninvasive, cost-effective, and real-time imaging method for evaluating cardiac fibrosis, with promising clinical applications.

2.
Saf Health Work ; 15(2): 228-235, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39035801

RESUMO

Background: Glove reuse poses risks, as chemicals can persist even after cleaning. Decontamination methods like thermal aeration, recommended by US OSHA, vary in effectiveness. Some studies show promising results, while others emphasize the importance of considering both permeation and tensile strength changes. This research advocates for informed glove reuse, emphasizing optimal thermal aeration temperatures and providing evidence to guide users in maintaining protection efficiency. Methods: The investigation evaluated Neoprene and Nitrile gloves (22 mils). Permeation tests with toluene and acetone adhered to American Society for Testing Materials (ASTM) F739 standards. Decontamination optimization involved aeration at various temperatures. The experiment proceeded with a maximum of 22 re-exposure cycles. Tensile strength and elongation were assessed following ASTM D 412 protocols. Breakthrough time differences were statistically analyzed using t-test and ANOVA. Results: At room temperature, glove residuals decreased, and standardized breakthrough time (SBT)2 was significantly lower than SBT1, indicating reduced protection. Higher temperature decontamination accelerated residual removal, with ΔSBT (SBT2/SBT1) exceeding 100%, signifying restored protection. Tensile tests showed stable neoprene properties postdecontamination. Results underscore thermal aeration's efficacy for gloves reuse, emphasizing temperature's pivotal role. Findings recommend meticulous management strategies, especially post-breakthrough, to uphold glove-protective performance. Conclusions: Thermal aeration at 100°C for 1 hour proves effective, restoring protection without compromising glove strength. The study, covering twenty cycles, suggests safe glove reuse with proper decontamination, reducing costs significantly. However, limitations in chemical-glove combinations and exclusive focus on specific gloves caution against broad generalization. The absence of regulatory directives on glove reuse highlight the importance of informed selection and rigorous decontamination validation for workplace safety practices.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38870001

RESUMO

Learning universal representations of 3-D point clouds is essential for reducing the need for manual annotation of large-scale and irregular point cloud datasets. The current modus operandi for representative learning is self-supervised learning, which has shown great potential for improving point cloud understanding. Nevertheless, it remains an open problem how to employ auto-encoding for learning universal 3-D representations of irregularly structured point clouds, as previous methods focus on either global shapes or local geometries. To this end, we present a cascaded self-supervised point cloud representation learning framework, dubbed Curriculumformer, aiming to tame curriculum pre-training for enhanced point cloud understanding. Our main idea lies in devising a progressive pre-training strategy, which trains the Transformer in an easy-to-hard manner. Specifically, we first pre-train the Transformer using an upsampling strategy, which allows it to learn global information. Then, we follow up with a completion strategy, which enables the Transformer to gain insight into local geometries. Finally, we propose a Multi-Modal Multi-Modality Contrastive Learning (M4CL) strategy to enhance the ability of representation learning by enriching the Transformer with semantic information. In this way, the pre-trained Transformer can be easily transferred to a wide range of downstream applications. We demonstrate the superior performance of Curriculumformer on various discriminant and generative tasks, outperforming state-of-the-art methods. Moreover, Curriculumformer can also be integrated into other off-the-shelf methods to promote their performance. Our code is available at https://github.com/Fayeben/Curriculumformer.

4.
Cryobiology ; 116: 104933, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38925358

RESUMO

Echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA, Liwen procedure) is a novel treatment option for hypertrophic obstructive cardiomyopathy (HOCM). The safety and feasibility of using this procedure for cryoablation are unknown. We aimed to investigate the feasibility and safety of echocardiography-guided percutaneous intramyocardial septal cryoablation (PIMSCA) for septal thickness reduction in a canine model. Eight canines underwent PIMSCA, and had electrocardiography, echocardiography(ECG), myocardial contrast echocardiography (MCE), serological and pathological examinations during the preoperative, immediate postoperative, and 6-month follow-up. All eight canines underwent successful cryoablation and continued to be in sinus rhythm during ablation and without malignant arrhythmias. MCE showed that the ablation area had decreased myocardial perfusion after the procedure. Troponin I levels were significantly elevated [0.010 (0.005, 0.297) ng/mL vs. 3.122 (1.152, 7.990) ng/mL, p < 0.05)]. At 6-month follow-up after the procedure, all animals were alive, with thinning of the interventricular septum (7.26 ± 0.52 mm vs. 3.86 ± 0.29 mm, p < 0.05). Echocardiography showed no significant decrease in the left ventricular ejection fractions (LVEF) (54.32 ± 2.93 % vs. 54.70 ± 2.47 %, p > 0.05) or changes by pulse-wave Doppler E/A (1.17 ± 0.43 vs. 1.07 ± 0.43, p > 0.05), E/e' (8.09 ± 1.49 vs. 10.05 ± 2.68, p > 0.05). Pathological findings proved the effectiveness of cryoablation in myocardial tissues. We observed pericardial effusions and premature ventricular complexes (PVCs) associated with the procedure. Our findings provided preliminary evidence of the safety and feasibility of PIMSCA in reducing interventricular septum, which provides a potentially new treatment option for HOCM.

5.
Int J Cardiovasc Imaging ; 40(7): 1483-1492, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38709352

RESUMO

The data on myocardial perfusion of the percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for obstructive hypertrophic cardiomyopathy (HOCM) are still lacking, although PIMSRA have been proved to be of great safety and efficacy. The aim of this study was to quantitatively analyze the changes in myocardial perfusion after PIMSRA using myocardial contrast echocardiography (MCE). 27 HOCM patients treated with PIMSRA were retrospectively analyzed, and their echocardiographic parameters and perfusion parameters of MCE were collected before and 12 months after PIMSRA. A reperfusion curve was used to quantify microvascular blood volume (A), microvascular flux rate (ß), and microvascular blood flow (MBF) of each segment. Then the value difference (Δ) of parameters between post- and pre-operation were calculated. Finally, the correlation between the changes in MBF and in each echocardiographic parameter was analyzed. (1) Compared with baseline, the global A, ß and MBF were significantly increased in HOCM patients after PIMSRA (all P < 0.001). The ß, MBF were increased in the interventricular septum (P < 0.001, respectively), and the A, ß, MBF were increased in the left ventricular wall (all P < 0.001). (2) Correlation analysis showed that the ΔMBF of interventricular septum was mainly negatively correlated with the maximum interventricular septum thickness (ΔIVSTmax, r=-0.670, P < 0.001), mean interventricular septum thickness (ΔIVSTmean, r=-0.690, P < 0.001), and left ventricular mass index (ΔLVMI, r=-0.774, P < 0.001), while the ΔMBF of left ventricular wall was positively correlated with left ventricular end-diastolic volume index (ΔLVEDVI, r = 0.621, P = 0.001) and stroke volume index (ΔSVI, r = 0.810, P < 0.001). Myocardial perfusion was improved at both interventricular septum and ventricular wall in HOCM patients after PIMSRA. MCE can provide a new dimension for the efficacy evaluation to PIMSRA procedure.


Assuntos
Cardiomiopatia Hipertrófica , Circulação Coronária , Microcirculação , Imagem de Perfusão do Miocárdio , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Função Ventricular Esquerda , Humanos , Cardiomiopatia Hipertrófica/fisiopatologia , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/cirurgia , Cardiomiopatia Hipertrófica/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Imagem de Perfusão do Miocárdio/métodos , Resultado do Tratamento , Idoso , Fatores de Tempo , Meios de Contraste , Ecocardiografia , Adulto , Ablação por Radiofrequência/efeitos adversos , Ablação por Cateter/efeitos adversos , Septos Cardíacos/diagnóstico por imagem , Septos Cardíacos/fisiopatologia , Septos Cardíacos/cirurgia
6.
Heart Vessels ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806839

RESUMO

Hypertrophic cardiomyopathy (HCM) patients with sarcomere mutations have an increased risk of heart failure and left ventricular (LV) systolic dysfunction. We hypothesize that sarcomere mutation carriers have abnormal myocardial contractility before LV dysfunction. Therefore, we aimed to associate myocardial contractility with identified sarcomere mutations and predict genotyped HCM patients with sarcomere mutation by three-dimensional speckle tracking imaging (3D-STI). A retrospective analysis of 117 HCM patients identified 32 genotype-positive (G +) and 85 genotype-negative (G-) patients. Genotype-positive patients had higher globe circumferential strain (GCS), globe longitudinal strain (GLS), and globe radial strain (GRS) (p < 0.05), and multivariate logistic regression revealed that these variables were associated with a positive genetic status (p < 0.05). After the propensity matches other possible influencing factors, we developed three models, named Model GCS, Model GLS, and Model GRS, which could identified genotype-positive HCM patients with excellent performance (AUC of 0.855, 0.833, and 0.870 respectively, all p < 0.001). Genotype-positive HCM patients show a higher myocardial hyper-contractility status than patients without sarcomere mutations. When combined with clinical and echocardiographic markers, the 3D-STI parameters can effectively identify the likelihood of genotype-positive HCM.

7.
Cardiology ; : 1-11, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615672

RESUMO

INTRODUCTION: Calcium channel gene variations have been reported to be associated with hypertrophic cardiomyopathy (HCM) in family, but the relationship between calcium channel gene variations and HCM remains undefined in the population. METHODS: A total of 719 HCM unrelated patients were initially enrolled. Finally, 371 patients were identified based on inclusion and exclusion criteria, including 145 patients with gene negative, 28 patients with a single rare calcium channel gene variation (calcium gene variation), 162 patients with a single pathogenic/likely pathogenic sarcomere gene variation (sarcomere gene variation) and 36 patients with a single pathogenic/likely pathogenic sarcomere gene variation and a single rare calcium channel gene variation (double gene variations). Then the demographic, electrocardiographic, echocardiographic, and follow-up data were collected. RESULTS: Patients with double gene variations were at an earlier age and had more percent of family history of HCM, and had thicker walls, higher left ventricular outflow tract pressure gradient, more pathological Q waves, and more bundle branch blocks as compared with those with single sarcomere gene variation. During the follow-up period, patients with double gene variations had more primary endpoints than the other three groups (p = 0.0013). Multivariate analysis showed that double gene variations were the independent predictor of primary endpoint events in patients (HR: 4.82, 95% CI: 1.77-13.2; p = 0.002). CONCLUSION: We found that patients with double gene variations had more severe HCM phenotype and prognosis. The pathogenesis effects of sarcomere gene variation and calcium channel gene variation may be cumulative in HCM populations.

8.
Adv Sci (Weinh) ; 11(20): e2302379, 2024 May.
Artigo em Italiano | MEDLINE | ID: mdl-38566431

RESUMO

The modification and recognition of 5-methylcytosine (m5C) are involved in the initiation and progression of various tumor types. However, the precise role and potential mechanism of Y-box-binding protein 1 (YBX1) in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, it is found that YBX1 is frequently upregulated in ESCC compared with matched nontumor tissues. Gain- and loss-of-function assays show that YBX1 promoted the proliferation and metastasis of ESCC cells both in vitro and in vivo. Functional studies revealed that NOP2/Sun RNA methyltransferase family member 2 (NSUN2) is a critical RNA methyltransferase that facilitates YBX1-mediated ESCC progression. Mechanistically, integrated analysis based on RNA immunoprecipitation sequencing (RIP-seq) and m5C methylated RNA immunoprecipitation and sequencing (MeRIP-seq) assays identified spermine oxidase (SMOX) as a target gene containing an m5C site in its coding sequence (CDS) region, which coincided well with the binding site of YBX1. Overexpression of SMOX-WT but not SMOX-Mut partially restored the proliferation and invasion ability of ESCC cells curbed by YBX1 knockdown. Moreover, YBX1 activated the mTORC1 signaling pathway by stabilizing SMOX mRNA. The study reveals that YBX1 promotes ESCC development by stabilizing SMOX mRNA in an m5C-dependent manner, thus providing a valuable therapeutic target for ESCC.


Assuntos
Progressão da Doença , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Estabilidade de RNA , Proteína 1 de Ligação a Y-Box , Humanos , Proteína 1 de Ligação a Y-Box/genética , Proteína 1 de Ligação a Y-Box/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Estabilidade de RNA/genética , Camundongos , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Modelos Animais de Doenças , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Metiltransferases
9.
Eur Heart J Case Rep ; 8(4): ytae145, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38590297

RESUMO

Background: Some patients with hypertrophic cardiomyopathy (HCM) re-occur with drug-refractory symptoms but are not eligible for re-operation after the Morrow procedure. Traditional treatment options are limited. We present the first case of the use of ultrasound-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for the treatment of a patient with HCM combined with congenital anatomically corrected malposition of the great arteries (MGA) after Morrow procedure. Case summary: A 61-year-old male patient with congenital MGA, who had been treated with the Morrow procedure for HCM, had worsening symptoms in recent years that were difficult to control medically. He was diagnosed with occult obstructive HCM by stress echocardiography. After multi-disciplinary discussion, this patient was treated with PIMSRA. The post-operative clinical outcome was remarkable, with a significant decrease in septal thickness and disappearance of the left anterior branch conduction block. Conclusion: Percutaneous intramyocardial septal radiofrequency ablation is feasible and can be one of the options for the treatment of patients with HCM, especially those who cannot choose Morrow procedure. However, it still needs a large sample of clinical trials to validate its clinical effectiveness.

10.
PLoS Pathog ; 20(4): e1012075, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38568937

RESUMO

Oropharyngeal microbiomes play a significant role in the susceptibility and severity of COVID-19, yet the role of these microbiomes play for the development of COVID-19 Omicron variant have not been reported. A total of 791 pharyngeal swab samples were prospectively included in this study, including 297 confirmed cases of Omicron variant (CCO), 222 confirmed case of Omicron who recovered (CCOR), 73 confirmed cases of original strain (CCOS) and 199 healthy controls (HC). All samples completed MiSeq sequencing. The results showed that compared with HC, conditional pathogens increased in CCO, while acid-producing bacteria decreased. Based on six optimal oropharyngeal operational taxonomy units (OTUs), we constructed a marker microbial classifier to distinguish between patients with Omicron variant and healthy people, and achieved high diagnostic efficiency in both the discovery queue and the verification queue. At same time, we introduced a group of cross-age infection verification cohort and Omicron variant subtype XBB.1.5 branch, which can be accurately distinguished by this diagnostic model. We also analyzed the characteristics of oropharyngeal microbiomes in two subgroups of Omicron disease group-severity of infection and vaccination times, and found that the change of oropharyngeal microbiomes may affect the severity of the disease and the efficacy of the vaccine. In addition, we found that some genera with significant differences gradually increased or decreased with the recovery of Omicron variant infection. The results of Spearman analysis showed that 27 oropharyngeal OTUs were closely related to 6 clinical indexes in CCO and HC. Finally, we found that the Omicron variant had different characterization of oropharyngeal microbiomes from the original strain. Our research characterizes oropharyngeal microbiomes of Omicron variant cases and rehabilitation cases, successfully constructed and verified the non-invasive diagnostic model of Omicron variant, described the correlation between microbial OTUs and clinical indexes. It was found that the infection of Omicron variant and the infection of original strain have different characteristics of oropharyngeal microbiomes.


Assuntos
COVID-19 , Infecção Hospitalar , Microbiota , Humanos , SARS-CoV-2/genética , Bactérias , Microbiota/genética
11.
Lancet Reg Health West Pac ; 46: 101062, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38623390

RESUMO

Background: The public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood. Methods: This study adopted a multi-stage sampling method for hospital selection. In the first stage, nationwide tertiary hospital recruitment was performed. As a result, 88 hospitals with the consent of the director of cardiology and access to an established electronic medical records system, were recruited. In the second stage, we sampled 66 hospitals within each geographic-economic stratification through a random sampling process. Data on (1) the outpatient and inpatient visits for cardiomyopathies between 2017 and 2021 and (2) the competency in the management of patients with cardiomyopathies, were collected. The competency of a hospital to provide cardiomyopathy care was evaluated using a specifically devised scale. Findings: The outpatient and inpatient visits for cardiomyopathies increased between 2017 and 2021 by 38.6% and 33.0%, respectively. Most hospitals had basic facilities for cardiomyopathy assessment. However, access to more complex procedures was limited, and the integrated management pathway needs improvement. Only 4 (6.1%) of the 66 participating hospitals met the criteria for being designated as a comprehensive cardiomyopathy center, and only 29 (43.9%) could be classified as a primary cardiomyopathy center. There were significant variations in competency between hospitals with different administrative and economic levels. Interpretation: The health burden of cardiomyopathies has increased significantly between 2017 and 2021 in China. Although most tertiary hospitals in China can offer basic cardiomyopathy care, more advanced facilities are not yet universally available. Moreover, inconsistencies in the management of cardiomyopathies across hospitals due to differing administrative and economic levels warrants a review of the nation allocation of medical resources. Funding: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2023-I2M-1-001) and the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17).

13.
Methods ; 227: 27-34, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38679187

RESUMO

Lysine ß-hydroxybutyrylation is an important post-translational modification (PTM) involved in various physiological and biological processes. In this research, we introduce a novel predictor KbhbXG, which utilizes XGBoost to identify ß-hydroxybutyrylation modification sites based on protein sequence information. The traditional experimental methods employed for the identification of ß-hydroxybutyrylated sites using proteomic techniques are both costly and time-consuming. Thus, the development of computational methods and predictors can play a crucial role in facilitating the rapid identification of ß-hydroxybutyrylation sites. Our proposed KbhbXG model first utilizes machine learning algorithm XGBoost to predict ß-hydroxybutyrylation modification sites. On the independent test set, KbhbXG achieves an accuracy of 0.7457, specificity of 0.7771, and an impressive area under the curve (AUC) score of 0.8172. The high AUC score achieved by our method demonstrates its potential for effectively identifying novel ß-hydroxybutyrylation sites, thereby facilitating further research and exploration of the ß-hydroxybutyrylation process. Also, functional analyses have revealed that different organisms preferentially engage in distinct biological processes and pathways, which can provide valuable insights for understanding the mechanism of ß-hydroxybutyrylation and guide experimental verification. To promote transparency and reproducibility, we have made both the codes and dataset of KbhbXG publicly available. Researchers interested in utilizing our proposed model can access these resources at https://github.com/Lab-Xu/KbhbXG.


Assuntos
Lisina , Aprendizado de Máquina , Processamento de Proteína Pós-Traducional , Lisina/metabolismo , Lisina/química , Biologia Computacional/métodos , Humanos , Algoritmos , Software , Proteômica/métodos
14.
Medicine (Baltimore) ; 103(11): e37423, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489731

RESUMO

BACKGROUND: Sarcoma is a heterogeneous malignancy arising from interstitial tissue. Anthracycline-based therapy is the first-line treatment recommended by guidelines for patients with locally advanced or metastatic unresectable sarcoma. Recently, targeted therapies, in particular tyrosine kinase inhibitors (TKIs), have made significant progress in the treatment of sarcoma, and their efficacy has been investigated in randomized controlled trials. The aim of this meta-analysis is to evaluate the efficacy of TKIs in patients with advanced or metastatic sarcoma who have previously received chemotherapy. METHODS: We completed a meta-analysis after conducting literature searches in PubMed, Embase, and Cochrane. The single-drug, placebo-controlled, randomized controlled clinical trials of TKIs in patients with advanced or progressive sarcoma who have previously received chemotherapy are available for inclusion in the study. The observation results were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The subgroup analysis was performed according to histological subtypes of sarcoma. RESULTS: This study included 6 studies, including 1033 patients. The ORR (OR: 7.99, 95% CI: 3.62-19.61, P < .00001), DCR (OR: 2.54, 95% CI: 1.27-5.08, P = .009), PFS (HR: 0.46, 95% CI: 0.34-0.62, P < .00001), and OS (HR: 0.80, 95% CI: 0.67-0.96, P = .02) of patients treated with TKIs were better than those in the placebo group. CONCLUSIONS: In patients with advanced sarcoma, TKIs have been shown to have advantages in terms of ORR, DCR and PFS and OS. Multi-targeted TKIs may be considered as one of the second-line treatment options for sarcoma patients who have received prior chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Segunda Neoplasia Primária , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Segunda Neoplasia Primária/tratamento farmacológico , Inibidores de Proteínas Quinases , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico
15.
Chem Commun (Camb) ; 60(32): 4342-4345, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38545842

RESUMO

Activity-based ubiquitin probes (Ub-ABPs) have recently been developed as effective tools for studying the capabilities of E1-E2-E3 enzymes, but most of them can only be used in cell lysates. Here, we report the first cell-penetrating Ub-Dha probes based on thiazolidine-protected cysteines, which enable successful delivery into cells confirmed by a fluorophore at the N-terminus of Ub and live-cell fluorescence microscopy. A total of 18 E1-E2-E3 enzymes in live cells were labelled and enriched in combination with label-free quantification (LFQ) mass spectrometry. This work provided a new cell-penetrating Ub tool for studying the activity and function of Ub-related enzymes.


Assuntos
Ubiquitina-Proteína Ligases , Ubiquitina , Ubiquitina/química , Ubiquitina-Proteína Ligases/metabolismo , Corantes Fluorescentes , Ubiquitinação
16.
J Org Chem ; 89(8): 5401-5408, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38546539

RESUMO

A synthetically useful approach to functionalized triazoles is described via the reaction of ß-carbonyl phosphonates and azides. 1,4- and 1,5-disubstituted and 1,4,5-trisubstituted triazoles can be regio- and chemoselectively accessed under mild conditions in good to excellent yields (31 examples, up to 99%). A mechanism is proposed that rationalizes the avoidance of the 4-phosphonate byproducts, which is aligned with crystallographic and experimental evidence.

17.
BMC Cardiovasc Disord ; 24(1): 177, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519968

RESUMO

BACKGROUND: Estimated plasma volume status (ePVS) estimated by the Duarte formula is associated with clinical outcomes in patients with heart failure. It remains unclear the predictive value of the ePVS to the postoperative hypotension (POH) in percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) treating hypertrophic obstructive cardiomyopathy (HOCM). METHODS: Data of HOCM patients who underwent PIMSRA were retrospectively collected. Preoperative ePVS was calculated using the Duarte formulas which derived from hemoglobin and hematocrit ratios. Clinical variables including physical assessment, biological and echocardiographic parameters were recorded. Patients were labeled with or without POH according to the medical record in the hospital. Univariable and multivariable logistic regression were performed to evaluate the association between ePVS and POH. Using different thresholds derived from quartiles and the best cutoff value of the receiver operating characteristic curve, the diagnostic performance of ePVS was quantified. RESULTS: Among the 405 patients included in this study, 53 (13.1%) patients were observed with symptomatic POH. Median (IQR) of ePVS in overall patients was 3.77 (3.27~4.40) mL/g and in patients with POH were higher than those without POH. The ePVS was associated with POH, with the odds ratio of 1.669 (95% CI 1.299 ~ 2.144) per mL/g. After adjusted by potential confounders, ePVS remained independently associated with POH, with the approximate odds ratio in different models. CONCLUSION: The preoperative ePVS derived from the Duarte formulas was independently associated with postoperative hypotension in HOCM patients who underwent PIMSRA and showed prognostic value to the risk stratification of postoperative management. TRIAL REGISTRATION: NCT06003478 (22/08/2023).


Assuntos
Cardiomiopatia Hipertrófica , Hipotensão , Ablação por Radiofrequência , Humanos , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/cirurgia , Hipotensão/diagnóstico , Hipotensão/etiologia , Volume Plasmático , Estudos Retrospectivos , Resultado do Tratamento , Estudos Clínicos como Assunto
18.
Nanotechnology ; 35(19)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38306686

RESUMO

Piezoresistive layered two-dimensional (2D) crystals offer intriguing promise as pressure sensors for microelectromechanical systems (MEMS) due to their remarkable strain-induced conductivity modulation. However, integration of the conventional chemical vapor deposition grown 2D thin films onto a micromachined silicon platform requires a complex transfer process, which degrades their strain-sensing performance. In this study, we present a differential pressure sensor built on a transfer-free piezoresistive PdSe2polycrystalline film deposited on a SiNxmembrane by plasma-enhanced selenization of a metal film at a temperature as low as 200 °C. Based on the resistance change and finite element strain analysis of the film under membrane deflection, we show that a 7.9 nm thick PdSe2film has a gauge factor (GF) of -43.3, which is ten times larger than that of polycrystalline silicon. The large GF enables the development of a diaphragm pressure sensor with a high sensitivity of 3.9 × 10-4kPa-1within the differential pressure range of 0-60 kPa. In addition, the sensor with a Wheatstone bridge circuit achieves a high voltage sensitivity of 1.04 mV·kPa-1, a rapid response time of less than 97 ms, and small output voltage variation of 8.1 mV in the temperature range of 25 °C to 55 °C. This transfer-free and low-temperature grown PdSe2piezoresistive thin film is promising for MEMS transducer devices.

20.
Heliyon ; 10(4): e25861, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38384504

RESUMO

Objective: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with a high incidence of complications in the mid and late stages of gestation. This study investigates differences in the composition of intestinal flora among pregnant women diagnosed with ICP, employing Illumina MiSeq high-throughput sequencing technology. Methods: This case-control study obtained patient data from the hospital information system (HIS) and the laboratory information system (LIS). Fecal samples were collected from 25 pregnant women who did not undergo intestinal preparation before delivery between December 2020 and March 2021. Whole-genome analysis was performed. PCR was used to amplify the 16S rRNA V3-V4 variable region, which was then sequenced. Alpha and beta diversity were computed, and the maternal intestinal flora's abundance and composition characteristics were analyzed. Differences in intestinal flora between the two sample groups were examined. Results: Bacteroides and Proteobacteria exhibited positive correlations with TBIL and IBIL. Betaproteobacteria, Gammaproteobacteria, and Erysipeiotrichi showed positive correlations with TBIL, IBIL, and DBIL, while Lactobacillus, Delftia, and Odoribacter demonstrated positive correlations with ALT. Conclusion: The ICP group displayed significantly higher levels of total bile acid and ALT compared to the control group. The intestinal flora composition comprised four primary phyla: Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria. ICP patients exhibited a lower relative abundance of intestinal flora across different levels of community composition when compared to the control group. Specific correlations between certain intestinal flora and clinical liver parameters were identified.

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