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1.
Mol Biotechnol ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727882

RESUMO

Liver fibrosis is a severe liver pathology in response to chronic or iterative liver injury. Senescence has emerged as a protective mechanism against liver fibrosis. Nogo-B has been well established as a significant contributor to liver fibrosis. Nonetheless, researches regarding the role of Nogo-B in cell senescence during liver fibrosis are few. In platelet-derived growth factor-BB (PDGF-BB)-treated human hepatic stellate cell line LX-2, cell proliferation was assayed by CCK-8 method. Western blotting estimated the expression of Nogo-B and fibrosis markers. After Nogo-B was silenced in LX-2 cells pretreated by an autophagy activator Rapamycin and PDGF-BB, CCK-8 method was used to assess cell proliferation. Fibrosis was measured by western blotting and immunofluorescence. Cell cycle was subjected to flow cytometry analysis and cell senescence was evaluated by SA-ß-gal staining. Immunofluorescence staining assessed autophagy. Nogo-B was elevated in PDGF-BB-exposed LX-2 cells. Nogo-B silencing suppressed the proliferation, fibrosis, and autophagy while induced cell cycle arrest and senescence of LX-2 cells. Additionally, pretreatment with Rapamycin partially restored the effects of Nogo-B knockdown on the autophagy, proliferation, fibrosis, cell cycle, and senescence of LX-2 cells upon exposure to PDGF-BB. Collectively, inactivation of autophagy mediated by Nogo-B deficiency might elicit protective activities against the development of liver fibrosis.

2.
Tissue Eng Regen Med ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630369

RESUMO

BACKGROUND: Hepatic fibrosis (HF) is a histopathological change in the process of long-term liver injury caused by cytokine secretion and internal environment disturbance, resulting in excessive liver repair and fiber scar. Nogo-B protein is widely distributed in peripheral tissues and organs and can regulate the migration of endothelial cells by activating TGF-ß1 in vascular remodeling after injury. Nogo-B has been shown to promote organ fibrosis. This study was to determine the role of Nogo-B in HF. METHODS: An HF model was built by intraperitoneal injections with 20% carbon tetrachloride. Localization of Nogo-B was detected by FISH. The interaction between Nogo-B and BACE1 was confirmed by Co-IP. Autophagy flux was analyzed using tandem mRFP-GFP-LC3 fluorescence microscopy, electron microscopy, and western blotting. Detection of serum AST and ALT and H&E staining were utilized to detect the degree of liver injury. The HF was evaluated by Masson trichromatic staining. RT-qPCR, western blotting, and immunofluorescence were employed to detect relevant indicators. RESULTS: Reducing Nogo-B suppressed AST and ALT levels, the accumulation of collagen I and α-SMA, and expressions of pro-fibrotic genes in mouse liver. BACE1 was a potential downstream target of Nogo-B. Nogo-B was upregulated in TGF-ß1-activated hepatic stellate cells (HSCs). Knocking down Nogo-B caused the downregulation of pro-fibrotic genes and inhibited viability of HSCs. Nogo-B knockdown prevented CCL4-induced fibrosis, accompanied by downregulation of extracellular matrix. Nogo-B inhibited HSC autophagy and increased lipid accumulation. BACE1 knockdown inhibited HSC autophagy and activation in LX-2 cells. CONCLUSION: Nogo-B knockdown prevents HF by directly inhibiting BACe1-mediated autophagy.

3.
Front Cell Dev Biol ; 12: 1383232, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38586304

RESUMO

Studies have shown that bortezomib resistance in multiple myeloma (MM) is mediated by the abnormalities of various molecules and microenvironments. Exploring these resistance mechanisms will improve the therapeutic efficacy of bortezomib. In this study, bone marrow tissues from three patients with MM, both sensitive and resistant to bortezomib, were collected for circRNA high-throughput sequencing analysis. The relationship between circ_0000337, miR-98-5p, and target gene DNA2 was analyzed by luciferase detection and verified by RT-qPCR. We first found that circ_0000337 was significantly upregulated in bortezomib-resistant MM tissues and cells, and overexpression of circ_0000337 could promote bortezomib resistance in MM cells. circ_0000337 may act as a miR-98-5p sponge to upregulate DNA2 expression, regulate DNA damage repair, and induce bortezomib resistance. Furthermore, it was determined that the increased circ_0000337 level in bortezomib-resistant cells was due to an increased N6-methyladenosine (m6A) level, resulting in enhanced RNA stability. In conclusion, the m6A level of circ_0000337 and its regulation may be a new and potential therapeutic target for overcoming bortezomib resistance in MM.

4.
J Biol Chem ; 300(4): 107171, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492776

RESUMO

Gemcitabine-based chemotherapy is a cornerstone of standard care for gallbladder cancer (GBC) treatment. Still, drug resistance remains a significant challenge, influenced by factors such as tumor-associated microbiota impacting drug concentrations within tumors. Enterococcus faecium, a member of tumor-associated microbiota, was notably enriched in the GBC patient cluster. In this study, we investigated the biochemical characteristics, catalytic activity, and kinetics of the cytidine deaminase of E. faecium (EfCDA). EfCDA showed the ability to convert gemcitabine to its metabolite 2',2'-difluorodeoxyuridine. Both EfCDA and E. faecium can induce gemcitabine resistance in GBC cells. Moreover, we determined the crystal structure of EfCDA, in its apo form and in complex with 2', 2'-difluorodeoxyuridine at high resolution. Mutation of key residues abolished the catalytic activity of EfCDA and reduced the gemcitabine resistance in GBC cells. Our findings provide structural insights into the molecular basis for recognizing gemcitabine metabolite by a bacteria CDA protein and may provide potential strategies to combat cancer drug resistance and improve the efficacy of gemcitabine-based chemotherapy in GBC treatment.


Assuntos
Citidina Desaminase , Desoxicitidina , Resistencia a Medicamentos Antineoplásicos , Enterococcus faecium , Neoplasias da Vesícula Biliar , Gencitabina , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/metabolismo , Desoxicitidina/química , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/microbiologia , Neoplasias da Vesícula Biliar/enzimologia , Citidina Desaminase/metabolismo , Citidina Desaminase/genética , Citidina Desaminase/química , Humanos , Enterococcus faecium/enzimologia , Enterococcus faecium/genética , Enterococcus faecium/metabolismo , Linhagem Celular Tumoral , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/metabolismo , Antimetabólitos Antineoplásicos/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química
5.
ACS Omega ; 9(10): 12219-12227, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38497007

RESUMO

A mass transfer model to predict the transport processes of magnesium and lithium ions through porous media in salt lakes has been proposed, which is a combination of the extended Nernst-Planck equation and Donnan effect, accounting for ion diffusion, electromigration, and convection within membrane pores. First, the morphological structure, thickness, surface roughness, and hydrophilicity of the membrane were characterized as fixed parameters, indicating that the surface of the nanofiltration membrane is smooth with low roughness and strong hydrophilicity, resulting in a lower desalination rate but higher water flux. Subsequently, numerical calculations based on the model were conducted to establish a reasonable transport equation for predicting the concentration and retention rate of the main magnesium and lithium ions. When compared with the experimental results, a deviation of less than 5.5% is obtained, confirming the accuracy of the model in describing ion mass transfer. Finally, computational fluid dynamics techniques were employed to simulate the model equations in both the feed and permeate subdomains, demonstrating that the flow characteristics align with reality. Thus, the established transport model exhibits higher predictive accuracy for NF ion separation than one-dimensional models.

6.
Pediatr Radiol ; 54(4): 646-652, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38472490

RESUMO

Hand-wrist radiography is the most common and accurate method for evaluating children's bone age. To reduce the scattered radiation of radiosensitive organs in bone age assessment, we designed a small X-ray instrument with radioprotection function by adding metal enclosure for X-ray shielding. We used a phantom operator to compare the scattered radiation doses received by sensitive organs under three different protection scenarios (proposed instrument, radiation personal protective equipment, no protection). The proposed instrument showed greater reduction in the mean dose of a single exposure compared with radiation personal protective equipment especially on the left side which was proximal to the X-ray machine (≥80.0% in eye and thyroid, ≥99.9% in breast and gonad). The proposed instrument provides a new pathway towards more convenient and efficient radioprotection.


Assuntos
Proteção Radiológica , Criança , Humanos , Doses de Radiação , Raios X , Radiografia , Proteção Radiológica/métodos , Fluoroscopia , Imagens de Fantasmas
7.
Anal Bioanal Chem ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443743

RESUMO

In recent years, the energy crisis has made the world realize the importance and need for green energy. Hydrogen safety has always been a primary issue that needs to be addressed for the application and large-scale commercialization of hydrogen energy, and precise and rapid hydrogen gas sensing technology and equipment are important prerequisites for ensuring hydrogen safety. Based on metal oxide semiconductors (MOS), resistive hydrogen gas sensors (HGS) offer advantages, such as low cost, low power consumption, and high sensitivity. They are also easy to test, integrate, and suitable for detecting low concentrations of hydrogen gas in ambient air. Therefore, they are considered one of the most promising HGS. This article provides a comprehensive review of the surface reaction mechanisms and recent research progress in optimizing the gas sensing performance of MOS-based resistive hydrogen gas sensors (MOS-R-HGS). Particularly, the advancements in metal-assisted or doped MOS, mixed metal oxide (MO)-MOS composites, MOS-carbon composites, and metal-organic framework-derived (MOF)-MOS composites are extensively summarized. Finally, the future research directions and possibilities in this field are discussed.

8.
Int J Cardiovasc Imaging ; 40(4): 873-885, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38240854

RESUMO

Cardiovascular disease (CVD) is the leading cause of end-stage mortality in chronic kidney disease (CKD) patients. However, CVD and CKD are inextricably linked, as microalbuminuria is an independent risk factor for CVD. Herein, we investigated changes in cardiac function and its risk factors in CKD patients who had different urine albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs). We prospectively enrolled 182 CKD patients, classified into three groups based on UACRs and eGFRs. Fifty healthy volunteers were included as controls. Changes in clinical and echocardiographic parameters were assessed in each group, and factors independently associated with strain parameters were further analyzed. Compared with those in the control group, the albuminuria but unimpaired renal function (ALB-CKD G1-2), albuminuria and impaired renal function (ALB-CKD G3), and normoalbuminuric CKD (NACKD) groups had decreased left ventricular (LV), right ventricular (RV), and left atrial (LA) strains, the LA contractile strain being the only statistically comparable parameter. Stepwise multiple linear regression analysis revealed varying factors independently correlating with the LV global longitudinal strain. The LA reservoir and conduit strains independently correlated with LV diastolic function in stage 3 CKD associated with comorbid albuminuria or normoalbuminuria. LV function was a partial determinant of LA and RV function in the ALB-CKD G3 group, whereas ventricular and atrial function were independent of each other in the ALB-CKD G1-2 and NACKD groups. Clinical intervention should focus on specific factors affecting cardiac function in patients to reduce the risk of CVD-related death.


Assuntos
Albuminúria , Função do Átrio Esquerdo , Taxa de Filtração Glomerular , Rim , Insuficiência Renal Crônica , Função Ventricular Esquerda , Humanos , Albuminúria/fisiopatologia , Albuminúria/diagnóstico , Masculino , Estudos Prospectivos , Feminino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/urina , Insuficiência Renal Crônica/diagnóstico , Estudos de Casos e Controles , Rim/fisiopatologia , Adulto , Idoso , Fatores de Risco , Função Ventricular Direita , Biomarcadores/urina , Biomarcadores/sangue , Valor Preditivo dos Testes , Fatores de Tempo , Creatinina/urina , Creatinina/sangue , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Ecocardiografia Doppler , Prognóstico
9.
Scand J Gastroenterol ; 59(1): 70-77, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37647217

RESUMO

BACKGROUND: The present study aimed to develop and validate a new nomogram for predicting the incidence of hepatocellular carcinoma (HCC) among chronic hepatitis B (CHB) patients receiving antiviral therapy from real-world data. METHODS: The nomogram was established based on a real-world retrospective study of 764 patients with HBV from October 2008 to July 2020. A predictive model for the incidence of HCC was developed by multivariable Cox regression, and a nomogram was constructed. The predictive accuracy and discriminative ability of the nomogram were assessed by the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Risk group stratification was performed to assess the predictive capacity of the nomogram. The nomogram was compared to three current commonly used predictive models. RESULTS: A total of 764 patients with HBV were recruited for this study. Age, family history of HCC, alcohol consumption, and Aspartate aminotransferase-to-Platelet Ratio Index (APRI) were all independent risk predictors of HCC in CHB patients. The constructed nomogram had good discrimination with a C-index of 0.811. The calibration curve and DCA also proved the reliability and accuracy of the nomogram. Three risk groups (low, moderate, and high) with significantly different prognoses were identified (p < 0.001). The model's performance was significantly better than that of other risk models. CONCLUSIONS: The nomogram was superior in predicting HCC risk among CHB patients who received antiviral treatment. The model can be utilized in clinical practice to aid decision-making on the strategy of long-term HCC surveillance, especially for moderate- and high-risk patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Vírus da Hepatite B/genética , Nomogramas , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Reprodutibilidade dos Testes
10.
J Clin Ultrasound ; 52(1): 3-12, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37864813

RESUMO

PURPOSE: This study aimed to utilize shear wave elastography (SWE) to assess changes in renal stiffness and its influencing factors in patients with chronic kidney disease (CKD) across different estimated glomerular filtration rate (eGFR) categories. It also sought to determine the correlation between perirenal fat (PF) and renal stiffness at various stages of CKD. METHODS: A total of 190 CKD patients and 50 healthy controls were evaluated. Clinical parameters, conventional renal ultrasound measurements, PF, and renal stiffness trends were assessed separately. Factors independently associated with renal stiffness and PF were further analyzed. RESULTS: Renal parenchymal stiffness was significantly higher in the Albumin-CKD G1-2 (ALB-CKD G1-2) and CKD G3 groups than in the control group (p < 0.05). The parenchymal stiffness of the CKD G3 group was higher than that of the ALB-CKD G1-2 group (p < 0.05). The independent factors of renal parenchymal stiffness varied at different stages of disease development, with eGFR and PF being significant factors in the CKD G3 group. PF was elevated in the ALB-CKD G1-2 and CKD G3 groups compared to the control group, and the independent factors of PF varied across different stages, although waist circumference remained a common factor. CONCLUSION: Using SWE to detect renal elastic moduli can effectively assess changes in renal stiffness in patients with CKD with varying eGFRs. PF is an independent factor of renal stiffness in patients with CKD G3, providing a foundation for early diagnosis and clinical treatment.


Assuntos
Técnicas de Imagem por Elasticidade , Insuficiência Renal Crônica , Humanos , Rim/diagnóstico por imagem , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico por imagem , Módulo de Elasticidade
11.
BMJ Paediatr Open ; 7(1)2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38114241

RESUMO

BACKGROUND: Antibacterial therapy plays a crucial role in neonatal infections. The efficacy of antibacterial agents is closely related to the actual dose given to neonates. So we evaluated factors potentially affecting the actual dose of intravenous antibiotics during dispensing process in neonates. METHODS: Meropenem, cefoperazone/sulbactam and piperacillin/tazobactam with two strengths were used to evaluate three methods. Method A (MA) was diluted once and the volumes of 5% glucose for MA were meropenem 4.00 mL, cefoperazone/sulbactam 3.00 mL, piperacillin/tazobactam 9.00 mL. Method B (MB) differed by doubling the volume of 5% glucose. The difference in method C (MC) involved diluting with 5% glucose twice. The concentrations were measured by high-performance liquid chromatography. Relative error (RE) was used to evaluate the preparation accuracy. RESULTS: The RE values using MA/MB/MC were: (1) meropenem 0.5 g: 15.1%, 8.0%, 10.4%; 0.25 g: 7.8%, 3.1%, 6.0%; (2) cefoperazone/sulbactam 1.5 g: 13.6%, 4.2%, 3.4%; 0.75 g: 8.8%, 3.5%, 4.0%; (3) piperacillin/tazobactam 4.5 g: 18.2%, 8.7%, 6.3%; 562.5 mg: 8.1%, 2.8%, 6.1%. MB was better than MA in all three drugs. No difference in RE values was found between single and double dilution, except meropenem with 0.25 g. Using MB, meropenem and piperacillin/tazobactam with small drug strength had higher accuracy in preparation. CONCLUSIONS: MB was suitable for neonatal drug dispensing because of its high accuracy and simple operation. Drugs with small strength were promoted due to the high accuracy.


Assuntos
Antibacterianos , Cefoperazona , Recém-Nascido , Humanos , Antibacterianos/uso terapêutico , Meropeném , Cefoperazona/uso terapêutico , Sulbactam , Piperacilina , Combinação Piperacilina e Tazobactam/uso terapêutico , Glucose
12.
Artigo em Inglês | MEDLINE | ID: mdl-38032026

RESUMO

Surface engineering is an effective strategy to improve the photoelectrochemical (PEC) catalytic activity of hematite, and the defect states with abundant coordinative unsaturation atoms can serve as anchoring sites for constructing intimate connections between semiconductors. On this basis, we anchored an ultrathin FeSe2 layer on Nb5+-doped Fe2O3 (FeSe2/Nb:Fe2O3) via interfacial Se-O chemical bonds to tune the surface potential. Density functional theory (DFT) calculations indicate that amorphous FeSe2 decoration could generate electron delocalization over the composite photoanodes so that the electron mobility was improved to a large extent. Furthermore, electrons could be transferred via the newly formed Se-O bonds at the interface and holes were collected at the surface of electrode for PEC water oxidation. The desired charge redistribution is in favor of suppressing charge recombination and extracting effective holes. Later, work function calculations and Mott-Schottky (M-S) plots demonstrate that a type-II heterojunction was formed in FeSe2/Nb:Fe2O3, which further expedited carrier separation. Except for spatial carrier modulation, the amorphous FeSe2 layer also provided abundant active sites for intermediates adsorption according to the d band center results. In consequence, the target photoanodes attained an improved photocurrent density of 2.42 mA cm-2 at 1.23 V versus the reversible hydrogen electrode (RHE), 2.5 times as that of the bare Fe2O3. This study proposed a defect-anchoring method to grow a close-connected layer via interfacial chemical bonds and revealed the spatial charge distribution effects of FeSe2 on Nb:Fe2O3, giving insights into rational designation in composite photoanodes.

13.
ACS Appl Mater Interfaces ; 15(43): 50148-50154, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37856670

RESUMO

Various additives have been introduced to assist in film preparation and defect passivation. Herein, fluoroiodobenzene (FIB) molecules with different numbers of F atoms were incorporated into perovskite films to optimize the film quality as well as passivate defects. Based on the calculation and experimental results, it was found that the FIB additives were inclined to exist at the bottom of the film because of the strong affinity between F atoms stemming from FIB molecules and O atoms stemming from TiO2, especially for molecules with more F atoms. By optimization of the FIB molecule, the perovskite film crystallinity was significantly improved, the carrier lifetimes were prolonged, and the charge extraction ability was also enhanced. The device with FIB with one F atom achieved a photoelectrical conversion efficiency as high as 22.89% with a Voc of 1.118 V, fill factor (FF) of 80.44%, and Jsc of 25.45 mA cm-2, which was much higher than that of the control device with an efficiency of 20.87%. Furthermore, FIB molecules with three and five F atoms also achieved higher efficiency than that of the control device. The devices with FIB molecules showed better stability than the devices without additives. The unencapsulated devices with FIB additives held 90% of their original efficiencies in an ambient environment with a temperature of 15-25 °C and a relative humidity of 20-30%, while the control device dropped to 76% after more than 1000 h.

14.
Medicine (Baltimore) ; 102(41): e35419, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37832060

RESUMO

BACKGROUND: The Pilates exercise has recently become an increasingly popular way of exercise in female patients since it is an attractive and low-cost physical exercise modality. Pilates may be a beneficial method of exercise for female patients with depression and anxiety symptoms. However, to date, there has been no attempt to collate this literature. This review aims to systematically assess and meta-analyze the efficacy of Pilates exercise for female patients with depression and anxiety symptoms and inform evidence-based guidelines for exercise prescription. METHODS: Five electronic databases (Scopus, MEDLINE/PubMed, Embase, Web of Science, and the Cochrane Library) were systematically searched up to January 2023 to examine randomized controlled trials (RCTs) focused on the effects of Pilates exercise for female patients with depressive disorders and individuals with elevated levels of depression were included. The primary outcomes were the severity of depression, and the secondary outcomes were anxiety. Statistical analyses were performed using Stata version 15.1 software with a 95% confidence interval (Registration number: CRD42023426522), and the PEDRO Scale was used to evaluate the risk of bias for RCT. RESULTS: 18 RCTs with 827 female patients were included. The methodological quality of the RCTs was considered an A level in 4 studies, B level in 13, studies, and C level in 1 study investigation. The meta-analysis showed that there was moderate evidence for the Pilates exercise significantly improved the severity of depression symptoms (SMD = -0.73; 95% CI -0.86 to -0.59; P < .01) and anxiety symptoms (SMD = -0.62; 95% CI -0.79 to -0.46; P < .01). CONCLUSIONS: Pilates exercise could reduce levels of depression and anxiety in female patients with depression and anxiety symptoms. Pilates exercise can be used as a potential ancillary program to improve depression and anxiety symptoms for female patients.


Assuntos
Depressão , Técnicas de Exercício e de Movimento , Feminino , Humanos , Depressão/terapia , Exercício Físico , Terapia por Exercício/métodos , Ansiedade/terapia , Qualidade de Vida
15.
Psychol Res Behav Manag ; 16: 3907-3924, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37753215

RESUMO

Introduction: Expatriates are facing more stressors, such as cross-cultural adjustment, global political instability, family separation, health concern. The black swan events of the pandemic and the Russian-Ukrainian war have posed significant challenges in the current international environment. Adapting to an expatriate environment as soon as possible is critical to expatriate success. This study aims to examine the factors that affect expatriate adjustment through psychological resilience. Methods: Guided by person-environment (p-e) fit theory, an expatriate adjustment framework based on psychological resilience is proposed, and 309 valid sample data are used for structural equation model (SEM) analysis. Results: The results show that expatriate adjustment is a psychological process based on the development of resilience. Social support plays a buffering role in dealing with environmental deviations induced stressors. The person-environment transactional process is the most critical adjustment process. Discussion: The development of expatriate adjustment is divided into four stages (shock, buffer, adjustment, mastery) consistent with resilience development. Project managers can take different expatriate management strategies from multiple aspects. Finally, this study proposes the U-curve hypothesis of expatriates' psychological resilience development aligned with the U-curve process of expatriate adjustment for future research.

16.
Aging (Albany NY) ; 15(18): 9572-9589, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37724903

RESUMO

Idiopathic pulmonary fibrosis (IPF), a fatal disorder associated with aging, has a terrible prognosis. However, the potential causes of IPF remain a riddle. In this study, we designed to explore whether the modification of the core fucosylation (CF) can ameliorate pulmonary fibrosis by targeting alveolar epithelial cells (AECs) senescence. First, we verified that cellular senescence occurs in the bleomycin-induced lung fibrosis mice models and CF modifications accompanying senescent AECs in pulmonary fibrosis. Next, both gain- and loss- of function research on CF were performed to elucidate its role in promoting AECs senescence and triggering pulmonary fibrosis in vitro. Notably, using alveolar epithelial cell-specific FUT8 conditional knockout mouse models, however, inhibition of cellular senescence by deleting the FUT8 gene could attenuate pulmonary fibrosis in vivo. Finally, blocking the CF modification of transforming growth factor -ß type I receptor (TGF-ßR I) could reduce the activation of downstream transforming growth factor -ß (TGF-ß) pathways in AECs senescence both in vivo and in vitro. This study reveals that CF is a crucial interventional target for the treatment of pulmonary fibrosis. Blocking CF modification contributes importantly to inhibiting AECs senescence resulting in pulmonary fibrosis lessen.

17.
Phys Chem Chem Phys ; 25(35): 23847-23854, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37641862

RESUMO

We discovered the composition of ternary AB3Si3 (A = Na/K/Rb/Cs) compounds in the moderate pressure range of 0-100 GPa using first-principles structural prediction and systematically analyzed their structures, stability, electronic and optical properties within the framework of density functional theory. The AB3Si3 compounds exhibit a diverse phase diagram, including nine structures that are selected based on formation energies, along with a known clathrate RbB3Si3 structure with Pm3̄n symmetry. All predicted phases are thermodynamically and dynamically stable within the studied pressure range. In particular, the KB3Si3 compound with a direct band gap of 1.0 eV is identified as a promising candidate for photovoltaic materials beyond silicon-based materials, among which boron atoms form a unique regular octahedral structure; in contrast, NaB3Si3 and RbB3Si3 compounds are shown to have metallicity. Our findings enrich crystal structures of alkali-metal borosilicides and provide valuable insights into their potential applications.

18.
Jpn J Infect Dis ; 76(6): 343-350, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37518069

RESUMO

Mycobacterium tuberculosis (M.tb) infection causes the communicable disease tuberculosis (TB), a major disease and one of the leading causes of death worldwide. The protein encoded by the region of deletion (RD) in M.tb mediates the pathogenic properties of M.tb by inducing an inflammatory response or disrupting host cell metabolism. We cloned and purified the Rv2653 protein from RD13 to explore its regulatory effects on host macrophages. We found that Rv2653 promoted glycolysis and upregulated the expression of key glycolytic enzymes, namely, hexokinase 2 (HK2) and lactate dehydrogenase-A (LDHA) in human leukemia monocytic (THP1) cells. Furthermore, the induction of glycolysis by Rv2653 contributes to the activation of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome. Rv2653 activated the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, and the mTORC1 inhibitor NR1 blocked Rv2653-induced HK2, LDHA, and NLRP3 expression. siRNA interfering with HK2 or LDHA significantly inhibited the activation of NLRP3 inflammasome by Rv2653, blocked Rv2653-triggered inflammatory factors interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), and nitric oxide (NO), and promoted the survival of Bacillus Calmette-Guerin (BCG) in THP1 cells. Overall, Rv2653 promoted glycolysis by activating the mTORC1 signaling pathway, activating the NLRP3 inflammasome, and releasing inflammatory factors, ultimately inhibiting the intracellular survival of BCG in THP1 cells. Therefore, we revealed that anti-M.tb immune mechanisms induced by Rv2653 contribute to the development of new anti-TB strategies.


Assuntos
Inflamassomos , Mycobacterium tuberculosis , Humanos , Inflamassomos/genética , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Mycobacterium tuberculosis/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Inflamação , Glicólise
19.
BMC Cardiovasc Disord ; 23(1): 353, 2023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37460997

RESUMO

BACKGROUND: This study aimed to analysis the clinical characteristics and prognosis of acute STEMI in patients aged ≤ 45 years. METHODS: Seven hundred and one patients with STEMI from Liaocheng People's Hospital from January 2018 to March 2021 were included in this study. Clinical characteristics, management, and outcomes (average follow-up: 11.5 months) were compared between patients aged ≤ 45 years and those aged > 45 years. RESULTS: Of the patients with STEMI who underwent primary percutaneous coronary intervention, 108 (15.4%) were aged ≤ 45 years. Compared to the older group, the younger patient group included more males, current smokers, and those with alcohol use disorder (AUD) or a family history of ischaemic heart disease (IHD). The culprit vessel in young patients was the left anterior descending (LAD) artery (60% vs. 45.9%, P = 0.031), which may have been due to smoking (odds ratio, 3.5; 95% confidence interval: 1.12-10.98, P = 0.042). Additionally, young patients presented with higher low-density lipoprotein and lower high-density lipoprotein levels than older patients; uric acid levels were also significantly higher in younger patients than that in the older group. Diabetes showed a trend toward major adverse cardiovascular events (MACE) in both groups; age and sex were both independent predictors of MACE in older patients. CONCLUSION: More patients who were smokers, had AUD, or a family history of IHD were present in the young patient group. Hyperuricaemia (but not dyslipidaemia) was a prevalent risk factor in patients aged ≤ 45 years. Diabetes should be controlled to reduce cardiovascular events in young patients.


Assuntos
Infarto Miocárdico de Parede Anterior , Doença da Artéria Coronariana , Isquemia Miocárdica , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Masculino , Humanos , Idoso , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Fatores de Risco , Infarto Miocárdico de Parede Anterior/etiologia , Doença da Artéria Coronariana/etiologia , Isquemia Miocárdica/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Arritmias Cardíacas/etiologia
20.
Cancer Med ; 12(16): 17005-17017, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37455599

RESUMO

BACKGROUND AND AIMS: Endoscopic ultrasonography-guided fine-needle aspiration/biopsy (EUS-FNA/B) is considered to be a first-line procedure for the pathological diagnosis of pancreatic cancer owing to its high accuracy and low complication rate. The number of new cases of pancreatic ductal adenocarcinoma (PDAC) is increasing, and its accurate pathological diagnosis poses a challenge for cytopathologists. Our aim was to develop a hyperspectral imaging (HSI)-based convolution neural network (CNN) algorithm to aid in the diagnosis of pancreatic EUS-FNA cytology specimens. METHODS: HSI images were captured of pancreatic EUS-FNA cytological specimens from benign pancreatic tissues (n = 33) and PDAC (n = 39) prepared using a liquid-based cytology method. A CNN was established to test the diagnostic performance, and Attribution Guided Factorization Visualization (AGF-Visualization) was used to visualize the regions of important classification features identified by the model. RESULTS: A total of 1913 HSI images were obtained. Our ResNet18-SimSiam model achieved an accuracy of 0.9204, sensitivity of 0.9310 and specificity of 0.9123 (area under the curve of 0.9625) when trained on HSI images for the differentiation of PDAC cytological specimens from benign pancreatic cells. AGF-Visualization confirmed that the diagnoses were based on the features of tumor cell nuclei. CONCLUSIONS: An HSI-based model was developed to diagnose cytological PDAC specimens obtained using EUS-guided sampling. Under the supervision of experienced cytopathologists, we performed multi-staged consecutive in-depth learning of the model. Its superior diagnostic performance could be of value for cytologists when diagnosing PDAC.


Assuntos
Carcinoma Ductal Pancreático , Aprendizado Profundo , Neoplasias Pancreáticas , Humanos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Citologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas
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