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1.
Opt Lett ; 49(12): 3448-3451, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38875642

RESUMO

High-power semiconductor lasers with stabilized wavelengths are recognized as exemplary pumping sources for solid-state lasers. This study introduces distributed feedback (DFB) laser diode arrays designed to maintain an extensive temperature locking range. We report experimentally on high-power 808 nm DFB laser diode arrays. The first-order sinusoidal grating was fabricated using nanoimprint lithography, succeeded by inductively coupled plasma (ICP) dry etching and subsequent wet polishing. These 808 nm DFB laser diode arrays have demonstrated a measured output power of 134 W under a pulsed current of 150 A, with the heat sink temperature maintained at 25°C. The slope efficiency was determined to be 1.1 W/A. At a current of 150 A, the laser operated with a narrow spectral width over a wide temperature range, extending from -30 to 90°C, with a temperature drift coefficient of 0.0595 nm/K.

2.
Eur Spine J ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907855

RESUMO

PURPOSE: Prolonged mechanical ventilation (PMV) and reintubation are among the most serious postoperative adverse events associated with malignant cervical tumors. In this study, we aimed to clarify the incidence, characteristics, and risk factors for PMV and reintubation in target patients. METHODS: This retrospective nested case-control study was performed between January 2014 and January 2020 at a large spinal tumor center in China. Univariate analysis was used to identify the possible risk factors associated with PMV and reintubation. Logistic regression analysis was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) with covariates of a probability < 0.05 in univariate analysis. RESULTS: From a cohort of 560 patients with primary malignant (n = 352) and metastatic (n = 208) cervical tumors, 27 patients required PMV and 20 patients underwent reintubation. The incidence rates of PMV and reintubation were 4.82% and 3.57%, respectively. Three variables (all p < 0.05) were independently associated with an increased risk of PMV: Karnofsky Performance Status < 50 compared to ≥ 80, operation duration ≥ 8 h compared to < 6 h, and C4 nerve root encased by the tumor. Longer operative duration and preoperative hypercapnia (all p < 0.05) were independent risk factors for postoperative reintubation, both of which led to longer length of stay (32.6 ± 30.8 vs. 10.7 ± 5.95 days, p < 0.001), with an in-hospital mortality of 17.0%. CONCLUSION: Our results demonstrate the risk factors for PMV or reintubation after surgery for malignant cervical tumors. Adequate assessment, early detection, and prevention are necessary for this high-risk population.

3.
PNAS Nexus ; 3(6): pgae225, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38894878

RESUMO

Myocardial fibrosis is a pathological hallmark of cardiovascular disease (CVD), and excessive fibrosis can lead to new-onset heart failure and increased mortality. Currently, pharmacological therapies for myocardial fibrosis are limited, highlighting the need for novel therapeutic approaches. The particulate guanylyl cyclase B (GC-B) receptor possesses beneficial antifibrotic actions through the binding of its natural ligand C-type natriuretic peptide (CNP) and the generation of the intracellular second messenger, cyclic guanosine 3',5'-monophosphate (cGMP). These actions include the suppression of fibroblast proliferation and reduction in collagen synthesis. With its abundant expression on fibroblasts, the GC-B receptor has emerged as a key molecular target for innovative CVD therapeutics. However, small molecules that can bind and potentiate the GC-B/cGMP pathway have yet to be discovered. From a cell-based high-throughput screening initiative of the NIH Molecular Libraries Small Molecule Repository and hit-to-lead evolution based on a series of structure-activity relationships, we report the successful discovery of MCUF-42, a GC-B-targeted small molecule that acts as a positive allosteric modulator (PAM). Studies herein support MCUF-42's ability to enhance the binding affinity between GC-B and CNP. Moreover, MCUF-42 potentiated cGMP levels induced by CNP in human cardiac fibroblasts (HCFs) and notably also enhanced the inhibitory effect of CNP on HCF proliferation. Together, our findings highlight that MCUF-42 is a small molecule that can modulate the GC-B/cGMP signaling pathway, potentially enhancing the antifibrotic actions of CNP. Thus, these data underscore the continued development of GC-B small molecule PAMs as a novel therapeutic strategy for targeting cardiac fibrosis and CVD.

4.
J Am Heart Assoc ; : e031906, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899767

RESUMO

BACKGROUND: Physician transfer is an alternate option to patient transfer for expedient performance of mechanical thrombectomy in patients with acute ischemic stroke. METHODS AND RESULTS: We conducted a systematic review to identify studies that evaluate the effect of physician transfer in patients with acute ischemic stroke who undergo mechanical thrombectomy. A search of PubMed, Scopus, and Web of Science was undertaken, and data were extracted. A statistical pooling with random-effects meta-analysis was performed to examine the odds of reduced time interval between stroke onset and recanalization, functional independence, death, and angiographic recanalization. A total of 12 studies (11 nonrandomized observational studies and 1 nonrandomized controlled trial) were included, with a total of 1894 patients. Physician transfer was associated with a significantly shorter time interval between stroke onset and recanalization with a pooled mean difference estimate of -62.08 (95% CI, -112.56 to -11.61]; P=0.016; 8 studies involving 1419 patients) with high between-study heterogeneity in the estimates (I2=90.6%). The odds for functional independence at 90 days were significantly higher (odds ratio, 1.29 [95% CI, 1.00-1.66]; P=0.046; 7 studies with 1222 patients) with physician transfer with low between-study heterogeneity (I2=0%). Physician transfer was not associated with higher odds of near-complete or complete angiographic recanalization (odds ratio, 1.18 [95% CI, 0.89-1.57; P=0.25; I2=2.8%; 11 studies with 1856 subjects). CONCLUSIONS: Physician transfer was associated with a significant reduction in the mean of time interval between symptom onset and recanalization and increased odds for functional independence at 90 days with physician transfer compared with patient transfer among patients who undergo mechanical thrombectomy.

5.
Microbiol Spectr ; : e0430723, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916339

RESUMO

Mycophenolate mofetil (MMF) is commonly utilized for the treatment of neuromyelitis optica spectrum disorders (NMOSD). However, a subset of patients experience significant gastrointestinal (GI) adverse effects following MMF administration. The present study aims to elucidate the underlying mechanisms of MMF-induced GI toxicity in NMOSD. Utilizing a vancomycin-treated mouse model, we compiled a comprehensive data set to investigate the microbiome and metabolome in the GI tract to elucidate the mechanisms of MMF GI toxicity. Furthermore, we enrolled 17 female NMOSD patients receiving MMF, who were stratified into non-diarrhea NMOSD and diarrhea NMOSD (DNM) groups, in addition to 12 healthy controls. The gut microbiota of stool samples was analyzed using 16S rRNA gene sequencing. Vancomycin administration prevented weight loss and tissue injury caused by MMF, affecting colon metabolomes and microbiomes. Bacterial ß-glucuronidase from Bacteroidetes and Firmicutes was linked to intestinal tissue damage. The DNM group showed higher alpha diversity and increased levels of Firmicutes and Proteobacteria. The ß-glucuronidase produced by Firmicutes may be important in causing gastrointestinal side effects from MMF in NMOSD treatment, providing useful information for future research on MMF. IMPORTANCE: Neuromyelitis optica spectrum disorder (NMOSD) patients frequently endure severe consequences like paralysis and blindness. Mycophenolate mofetil (MMF) effectively addresses these issues, but its usage is hindered by gastrointestinal (GI) complications. Through uncovering the intricate interplay among MMF, gut microbiota, and metabolic pathways, this study identifies specific gut bacteria responsible for metabolizing MMF into a potentially harmful form, thus contributing to GI side effects. These findings not only deepen our comprehension of MMF toxicity but also propose potential strategies, such as inhibiting these bacteria, to mitigate these adverse effects. This insight holds broader implications for minimizing complications in NMOSD patients undergoing MMF therapy.

6.
J Cancer ; 15(10): 2913-2927, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706894

RESUMO

Purpose: Lung cancer is one of the leading causes with high morbidity and mortality. High mobility group A1 (HMGA1) protein participates in the process of tumorigenesis. This study seeks to explore the specific role of HMGA1 in prognostic value based on The Cancer Genome Atlas (TCGA) database of Lung adenocarcinoma (LUAD) and glycolysis progression in LUAD cells. Patients and Methods: In this research, we compared HMGA1 mRNA expression between tumor tissues and normal samples and evaluated the correlations with clinical characteristics in LUAD patients based on the data of TCGA database. The survival outcome with overall survival (OS), disease-specific survival (DSS) and clinicopathologic characteristics associated were performed using the Kaplan-Meier method and Cox regression. In addition, gene-set enrichment analysis (GSEA) was carried out to explore the biological pathways that related to HMGA1. Cell experiments including cell proliferation assay and glycolysis proteins were performed with A549 and H1299 cells. Results: Our results revealed that HMGA1 mRNA expression was higher in LUAD tissues than in normal tissues. Increased HMGA1 expression in LUAD was associated with Gender (p<0.01), Pathologic stage I&II vs stage III&IV (p<0.001), T1&T2 vs T3&T4 stage (p<0.05), N0 vs N2 stage (p<0.01). Furthermore, multivariate analysis revealed that HMGA1 was an independent risk factor of OS and DSS for LUAD patients (p<0.05). HMGA1 were positively correlated with glycolysis gluconeogenesis pathway and glycolysis markers (HK2, GLUT1, PKM2, LDHA) based on GSEA and Gene Expression Profiling Interactive Analysis (GEPIA) database. At the cellular level, the results of qRT-PCR and western blot assays showed that si-HMGA1 markedly decreased the expression of glycolysis markers. HMGA1 promoted cell glycolysis progression via PI3K/AKT pathway transfected with HMGA1-plasmid and the treatment with 20 µM LY294002. Relevant animal experiments were also synchronously validated and si-HMGA1 groups down-regulated xenograft growth including the weights and size in tumor xenografts. Conclusions: In conclusion, our results suggested that HMGA1 was significantly correlated with poor survival for LUAD tissues and involved in the process of glycolysis in LUAD cells.

7.
Pancreas ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38696438

RESUMO

ABSTRACT: The incidence rate of hypertriglyceridemia pancreatitis (HTGP) has experienced a notable increase in recent years, with eclipsing alcohol as the second leading cause of acute pancreatitis (AP). HTGP is often associated with more severe local and systemic complications. Recognized as a metabolic disorder hypertriglyceridemia (HTG), holds significant relevance in the pathogenesis of HTGP, yet its mechanisms are not fully understood. Both primary (genetic) and secondary (acquired) factors contribute to elevated triglyceride (TG) levels, which concurrently influence the progression of HTGP. This article presents a comprehensive review of the evolving research on HTGP pathogenesis, encompassing lipid synthesis and metabolism, calcium signal transduction, inflammatory mediators, endoplasmic reticulum stress, autophagy, mitochondrial injury by fatty acids, oxidative stress response, genetic factors, and gene mutations. By unraveling the intricate mechanisms underlying HTGP, this article aims to enhance physicians' understanding of the disease and facilitate the development of potential targeted pharmacological interventions for patients.

8.
Front Cell Infect Microbiol ; 14: 1378331, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38817447

RESUMO

Brucellosis is a zoonotic disease caused by a Gram-negative coccus a facultative intracellular pathogen. Neurobrucellosis has an incidence rate of 3-7% among all patients with brucellosis, while spinal cord involvement is rare and carries a significant mortality risk. This report describes a case of brucellosis myelitis in a 55-year-old male patient who presented with recurrent paralysis, incontinence, and damage to the visual and auditory nerves. The diagnosis of neurobrucellosis involves a serum tube agglutination test, cerebrospinal fluid analysis, a physical examination of the nervous system, and a comprehensive review of the patient's medical history. The presence of brucellosis was confirmed in cerebrospinal fluid using MetaCAP™ sequencing. Treatment with a combination of rifampicin, doxycycline, ceftriaxone sodium, amikacin, compound brain peptide ganglioside, and dexamethasone resulted in significant improvement of the patient's clinical symptoms and a decrease in the brucellosis sequence count in cerebrospinal fluid. For the first time, MetaCAP™ sequencing has been used to treat pathogenic microbial nucleic acids, which could be a valuable tool for early diagnosis and treatment of neurobrucellosis.


Assuntos
Antibacterianos , Brucelose , Mielite , Humanos , Masculino , Brucelose/complicações , Brucelose/tratamento farmacológico , Brucelose/diagnóstico , Brucelose/microbiologia , Pessoa de Meia-Idade , Mielite/microbiologia , Mielite/diagnóstico , Mielite/tratamento farmacológico , Antibacterianos/uso terapêutico , Resultado do Tratamento , Imageamento por Ressonância Magnética
9.
J Med Chem ; 67(11): 8791-8816, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38775356

RESUMO

The spread of the influenza virus has caused devastating pandemics and huge economic losses worldwide. Antiviral drugs with diverse action modes are urgently required to overcome the challenges of viral mutation and drug resistance, and targeted protein degradation strategies constitute excellent candidates for this purpose. Herein, the first degradation of the influenza virus polymerase acidic (PA) protein using small-molecule degraders developed by hydrophobic tagging (HyT) technology to effectively combat the influenza virus was reported. The SAR results revealed that compound 19b with Boc2-(L)-Lys demonstrated excellent inhibitory activity against A/WSN/33/H1N1 (EC50 = 0.015 µM) and amantadine-resistant strain (A/PR/8/H1N1), low cytotoxicity, high selectivity, substantial degradation ability, and good drug-like properties. Mechanistic studies demonstrated that the proteasome system and autophagic lysosome pathway were the potential drivers of these HyT degraders. Thus, this study provides a powerful tool for investigating the targeted degradation of influenza virus proteins and for antiviral drug development.


Assuntos
Antivirais , Interações Hidrofóbicas e Hidrofílicas , Tioureia , Antivirais/farmacologia , Antivirais/química , Antivirais/síntese química , Humanos , Cães , Animais , Tioureia/farmacologia , Tioureia/análogos & derivados , Tioureia/química , Relação Estrutura-Atividade , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Células Madin Darby de Rim Canino , Proteólise/efeitos dos fármacos , Proteínas Virais/metabolismo , Proteínas Virais/química , Proteínas Virais/antagonistas & inibidores , RNA Polimerase Dependente de RNA/antagonistas & inibidores , RNA Polimerase Dependente de RNA/metabolismo , Farmacorresistência Viral/efeitos dos fármacos
10.
Appl Opt ; 63(8): 1947-1951, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38568633

RESUMO

Three samples whose growth temperatures were 450°C, 500°C, and 560°C for S E S A M 1, S E S A M 2, and S E S A M 3, respectively, were tested by femto-second time-resolved transient absorption spectroscopy. The results indicate that the carrier dynamics of excited state absorption were dominant, and the lifetimes of carriers trapped by defect levels were about tens of pico-seconds. To further study the influence of carrier dynamics and recovery time of samples by ion-implantation, B + ions of 80 and 130 KeV were implanted into the samples with dose of 1014/c m 2. The modified samples showed a dominance of ultra-fast carrier dynamics of ground-state bleaching and direct recombination, which lasted for hundreds of femto-seconds, over excited state absorption. Additionally, carrier fast trapping was observed to be competitive with the excited state absorption process. After ion-implantation, the carrier dynamics of carrier trapping were enhanced, which contributed to forming an ultra-short laser, while the carrier dynamics of absorption of the excited state were suppressed. The conclusion that defect levels were partially eliminated by B + ion-implantation can be drawn.

11.
IEEE Trans Cybern ; PP2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598405

RESUMO

Uncertainty estimation in real-world scenarios is challenged by complexities arising from peaking phenomena and measurement noises. This article introduces a novel scheme for practical uncertainty estimation to mitigate peaking dynamics and enhance overall dynamic behavior. A fusion estimation framework for lumped uncertainties using multiple extended state observers (ESOs) is constructed, and the low-frequency adaptive parameter learning technique is employed to approximate the optimal fusion. The adaptive fusion estimation not only attenuates transient peaks in uncertainty estimation but also attains fast convergence and high accuracy under the high-gain scheduling of ESOs. Furthermore, the robustness of uncertainty estimation against measurement noises is enhanced by cascading filters in the proposed adaptive fusion framework for multiple ESOs. Extensive theoretical analyses are executed to verify practical applicability in peak and noise rejection. Finally, simulations and experiments on the wheel velocity system of a mobile robot are conducted to test the validity and feasibility.

12.
Eur J Med Res ; 29(1): 230, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609977

RESUMO

BACKGROUND: Photodynamic therapy (PDT) is a promising interventional treatment approach that contributes to antitumor immunity. It has been reported that PDT can enhance the effectiveness of immune checkpoint inhibitors (ICIs), but its mechanism is yet unclear. Herein, we implemented bioinformatics analysis to detect common pathways and potential biomarkers in non-small cell lung cancer (NSCLC), PDT, and NSCLC immunotherapy to investigate potential links between PDT, immunotherapy and NSCLC, and their clinical impact. METHODS: Differentially expressed genes in NSCLC- and NSCLC immunotherapy-related data in the GEO database were intersected with PDT-related genes in the GeneCards database to obtain candidate genes and shared pathways. Enrichment analysis and protein-protein interaction were established to identify key genes in functionally enriched pathways. The expression profiles and the prognostic significance of key genes were depicted. RESULTS: Bioinformatics analysis showed that HIF-1α was screened as a prognostic gene in hypoxia, HIF-1, and PD-L1-related signaling pathways, which was associated with clinical response in NSCLC patients after PDT and immunotherapy. In vivo experiments showed that PDT could inhibit tumor growth and upregulate HIF-1α and PD-L1 expressions in NSCLC tissues with a positive correlation, which might influence the blocking activity of ICIs on the HIF-1, and PD-L1-related signaling pathways. CONCLUSIONS: PDT might improve the clinical response of ICIs by upregulating tumor HIF-1α and PD-L1 expressions in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Fotoquimioterapia , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Relevância Clínica , Antígeno B7-H1/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética
13.
Digit Health ; 10: 20552076241247374, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665889

RESUMO

Background: Consumer wearable devices such as wristbands and smartwatches have potential application value in communicable disease surveillance. Objective: We investigated the ability of wearable devices to monitor COVID-19 patients of varying severity. Methods: COVID-19 patients with mobile phones supporting wearable device applications were selected from Dalian Sixth People Hospital. Physiological parameters from the wearable devices and electronic questionnaires were collected from the device wearing until 14 days post-discharge. Clinical information during hospitalization was also recorded. Based on imaging data, the patients were categorized into the milder group without pneumonia and the more severe group with pneumonia. We plotted the curves of the physiological parameters of the two groups to compare the differences and changes. Results: Ninety-eight patients were included in the analysis. The mean age was 39.6 ± 10.5 years, including 45 males (45.9%). There were 24 asymptomatic patients, 10 mild patients, 60 moderate patients, and 4 severe patients. Compared with the milder group, the more severe group had higher heart rate-related parameters, while the heart rate variability (HRV) was the opposite. In the more severe group, the heart rate-related parameters showed a downward trend from 0 to 7 days after the fever resolution. Among them, the resting heart rate and sleep heart rate decreased on the 25th day after the onset and were close to the milder group 1 week after discharge. Conclusions: Consumer wearable devices have the potential to monitor respiratory infections. Heart rate-related parameters obtained from these devices can be sensitive indicators of COVID-19 severity and correlate with disease evolution. Trial registration: ClinicalTrials.gov NCT04459637.

14.
Sci Total Environ ; 929: 172656, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38653420

RESUMO

There has been increasing concern regarding the adverse environmental and health effects of organic pollutants. A list of priority control organic pollutants (PCOPs) can provide regulatory frameworks for the use and monitoring of organic compounds in the environment. In this study, 20,010 groundwater samples were collected from 15 "first level" groundwater resource zones in China. Fifty (50) organic compounds were analyzed based on their prevalence, occurrence, and physicochemical properties (persistence, bioaccumulation, and toxicity). Results showed that 16 PCOPs, including 12 pesticides, 3 aromatic hydrocarbons (AHs), and 1 phthalate ester, were recognized. Pesticides and AHs accounted for 75 % and 18.75 % of the high-priority pollutants, respectively. There were significant differences in PCOPs between confined and phreatic groundwater. Higher concentrations of pesticides were mainly detected in phreatic groundwater. PCOPs detected in samples from the 15 groundwater resource zones were mainly pesticides and AHs. The groundwater data indicate that the organic compounds detected in the Yellow River Basin (YRB), Yangtze River Basin (YZB), Liaohe River Basin (LRB), and Songhua River Basin (SRB) are mainly categorized as Q1 (high priority) and Q2 (medium priority) pollutants based on the contaminants ranking system in China. The findings from this study offer a snapshot of the wide distribution of PCOPs in the surveyed regions, and are expected to establishing treatment and prevention measures at both the regional and national levels in China.


Assuntos
Monitoramento Ambiental , Água Subterrânea , Poluentes Químicos da Água , China , Poluentes Químicos da Água/análise , Água Subterrânea/química , Bioacumulação , Praguicidas/análise , Compostos Orgânicos/análise
15.
Arch Virol ; 169(5): 94, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594417

RESUMO

Considering that avian leukosis virus (ALV) infection has inflicted massive economic losses on the poultry breeding industry in most countries, its early diagnosis remains an important measure for timely treatment and control of the disease, for which a rapid and sensitive point-of-care test is required. We established a user-friendly, economical, and rapid visualization method for ALV amplification products based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) combined with an immunochromatographic strip in a lateral flow device (LFD). Using the ALVp27 gene as the target, five RT-LAMP primers and one fluorescein-isothiocyanate-labeled probe were designed. After 60 min of RT-LAMP amplification at 64 °C, the products could be visualized directly using the LFD. The detection limit of this assay for ALV detection was 102 RNA copies/µL, and the sensitivity was 100 times that of reverse transcription polymerase chain reaction (RT-PCR), showing high specificity and sensitivity. To verify the clinical practicality of this assay for detecting ALV, the gold standard RT-PCR method was used for comparison, and consistent results were obtained with both assays. Thus, the assay described here can be used for rapid detection of ALV in resource-limited environments.


Assuntos
Vírus da Leucose Aviária , Técnicas de Diagnóstico Molecular , Transcrição Reversa , Animais , Vírus da Leucose Aviária/genética , Sensibilidade e Especificidade , Técnicas de Amplificação de Ácido Nucleico/métodos
16.
Phytomedicine ; 129: 155582, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38608595

RESUMO

BACKGROUND: Recent studies have shown that harringtonine (HT) could specifically bind with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein and host cell transmembrane serine protease 2 (TMPRSS2) to block membrane fusion, which is an effective antagonist for SARS-CoV-2. PURPOSE: Our study focused on in-depth exploration of in vitro pharmacokinetic characteristics of HT in lung. METHODS: HPLC-fluorescence detection method was used to detect changes of HT content. Incubation systems of lung microsomes for phase I metabolism and UGT incubation systems for phase II metabolism were performed to elucidate metabolites and metabolic mechanisms of HT, and then the metabolic enzyme phenotypes for HT were clarified by chemical inhibition method and recombinant enzyme method. Through metabolomics, we comprehensively evaluated the physiological dynamic changes in SD rat and human lung microsomes, and revealed the relationship between metabolomics and pharmacological activity of HT. RESULTS: HPLC-fluorescence detection method showed strong specificity, high accuracy, and good stability for rapid quantification of HT. We confirmed that HT mainly underwent phase I metabolism, and the metabolites of HT in different species were all identified as 4'-demethyl HT, with metabolic pathway being hydrolysis reaction. CYP1A2 and CYP2E1 participated in HT metabolism, but as HT metabolism was not NADPH dependent, the esterase HCES1 in lung also played a role. The main KEGG pathways in SD rat and human lung microsomes were cortisol synthesis and secretion, steroid hormone biosynthesis and linoleic acid metabolism, respectively. The downregulated key biomarkers of 11-deoxycortisol, 21-deoxycortisol and 9(10)-EpOME suggested that HT could prevent immunosuppression and interfere with infection and replication of SARS-CoV-2. CONCLUSION: HT was mainly metabolized into 4'-demethyl HT through phase I reactions, which was mediated by CYP1A2, CYP2E1, and HCES1. The downregulation of 11-deoxycortisol, 21-deoxycortisol and 9(10)-EpOME were key ways of HT against SARS-CoV-2. Our study was of great significance for development and clinical application of HT in the treatment of COVID-19.


Assuntos
Tratamento Farmacológico da COVID-19 , Pulmão , Ratos Sprague-Dawley , Animais , Humanos , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Ratos , Administração por Inalação , SARS-CoV-2 , Masculino , Microssomos/metabolismo , Microssomos/efeitos dos fármacos , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo
17.
Appl Opt ; 63(6): A24-A31, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38437354

RESUMO

Rapid testing of cement raw meal plays a crucial role in the cement production process, so there is an urgent need for a fast and accurate testing method. In this paper, a method based on the Savitzky-Golay (SG) smoothing and sample set partitioning based on joint x-y distance (SPXY) spectral data pre-processing is proposed to improve the accuracy of the laser-induced breakdown spectroscopy (LIBS) technique for quantitative analysis of cement raw meal components. Firstly, the spectral data is denoised by SG smoothing, which effectively reduces the noise and baseline variations in the spectra. Then, the denoised data is divided into sample sets by combining the SPXY sample division method, which improves the efficiency of data analysis. Finally, the delineated data set is modeled for quantitative analysis by a back-propagation (BP) neural network. Compared to the modeling effect of the four oxide contents of CaO, S i O 2, A l 2 O 3, and F e 2 O 3 in the Hold-Out method, the correlation coefficient (R) was improved by 26%, 10%, 17%, and 4%, respectively. The root mean square error (RMSE) was reduced by 47%, 33%, 43%, and 21%, respectively. The mean absolute percentage error (MAPE) was reduced by 63%, 60%, 36%, and 51%, respectively. The results show that there is a significant improvement in the model effect, which can effectively improve the accuracy of quantitative analysis of cement raw meal composition by LIBS. This is of great significance for the real-time detection of cement raw meal composition analysis.

18.
Small ; : e2401506, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38431925

RESUMO

Reaching rapid reaction kinetics of oxygen reduction (ORR) and oxygen evolution reactions (OER) is critical for realizing efficient rechargeable zinc-air batteries (ZABs). Herein, a novel CoNi-CoN3 composite site containing CoNi alloyed nanoparticles and CoN3 moieties is first constructed in N-doped carbon nanosheet matrix (CoNi-CoN3 /C). Benefiting from the high electroactivity of CoNi-CoN3 composite sites and large surface area, CoNi-CoN3 /C shows a superior half-wave potential (0.88 V versus RHE) for ORR and a small overpotential (360 mV) for OER at 10 mA cm-2 . Theoretical calculations have demonstrated that the introduction of CoNi alloys has modulated the electronic distributions near the CoN3 moiety, inducing the d-band center of CoNi-CoN3 composite site to shift down, thus stabilizing the valence state of Co active sites and balancing the adsorption of OER/ORR intermediates. Accordingly, the reaction energy trends exhibit optimized overpotentials for OER/ORR, leading to superior battery performances. For aqueous and flexible quasi-solid-state rechargeable ZABs with CoNi-CoN3 /C as catalyst, a large power density (250 mW cm-2 ) and high specific capacity (804 mAh g-1 ) are achieved. The in-depth understanding of the electroactivity enhancement mechanism of interactive metal nanoparticles and metal coordinated with nitrogen (MNx ) moieties is crucial for designing novel high-performance metal/nitrogen-doped carbon (M─N─C) catalysts.

19.
RSC Adv ; 14(12): 8445-8453, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38476179

RESUMO

Fenton catalytic medicine that catalyzes the production of ·OH without external energy input or oxygen as a substrate has reshaped the landscape of conventional cancer therapy in recent decades, yet potential biosafety concerns caused by non-safety-approved components restrict their clinical translation from the bench to the bedside. Herein, to overcome this dilemma, we elaborately utilizate safety-approved hetastarch, which has been extensively employed in the clinic as a plasma substitute, as a stabilizer participating in the copper chloride-initiated polymerization of pyrrole monomer before loading it with DOX. The constructed DOX-loaded hetastarch-doped Cu-based polypyrrole (HES@CuP-D) catalyzes the excess H2O2 in tumor cells to ·OH through a Cu+-mediated Fenton-like reaction, which not only causes oxidative damage to tumor cells but also leads to the structural collapse and DOX release. Additionally, HES@CuP-D together with laser irradiation reinforces tumor killing efficiency by hyperthermia-enhanced catalytic activity and -accelerated drug release. As a result, the developed HES@CuP-D provides a promising strategy for Fenton catalytic therapy with negligible toxicity to the body.

20.
BMJ Open Respir Res ; 11(1)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38479820

RESUMO

BACKGROUND: No studies have investigated whether high-sensitivity C reactive protein (hsCRP) can be used to predict the forced expiratory volume in 1 s (FEV1)/estimated value of FEV1 (FEV1%pred). This study aimed to assess the association between hsCRP and FEV1%pred in middle-aged and elderly individuals without underlying lung disease. METHODS: The data for this study were obtained from a prospective cohort study that included 1047 middle-aged and elderly citizens from Beijing aged 40-75 years without any evidence of underlying lung diseases with FEV1 >70% after receiving inhalational bronchodilators. The baseline analysis of the participants was performed from 30 May 2018 to 31 October 2018. Restricted cubic spline regression and multivariate linear regression models were used to assess the non-linear association and linear association between hsCRP and FEV1/FEV in 6 s (FEV6) and FEV1%pred, respectively. RESULTS: The hsCRP values of 851 participants were recorded; the values were normal in 713 (83.8%) participants. The remaining 196 participants (18.7%) had missing data. A non-linear association was observed between normal hsCRP values and FEV1/FEV6. hsCRP was linearly and negatively correlated with FEV1%pred, and each 1 SD increase in hsCRP was significantly associated with a 2.4% lower in FEV1%pred. Significantly higher FEV1/FEV6 differences were observed in the female subgroup than those in the male subgroup (p=0.011 for interaction). CONCLUSIONS: hsCRP had a non-linear association with FEV1/FEV6 and a linear negative association with FEV1%pred in individuals with normal hsCRP values. hsCRP can be used to predict FEV1%pred, which can be used to predict the development of chronic obstructive pulmonary disease. hsCRP has a stronger association with lung function in women than that in men. TRIAL REGISTRATION NUMBER: NCT03532893.


Assuntos
Pneumopatias , Pulmão , Idoso , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Volume Expiratório Forçado , Pequim/epidemiologia , Estudos Prospectivos , Proteína C-Reativa
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