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1.
Nano Lett ; 24(7): 2196-2202, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38329428

RESUMO

Antiferromagnetic (AFM) skyrmions are magnetic vortices composed of antiparallell-aligned neighboring spins. In stark contrast to conventional skyrmions based on ferromagnetic order, AFM skyrmions have vanished stray fields, higher response frequencies, and rectified translational motion driven by an external force. Therefore, AFM skyrmions promise highly efficient spintronics devices with high bit mobility and density. Nevertheless, the experimental realization of intrinsic AFM skyrmions remains elusive. Here, we show that AFM skyrmions can be nucleated via interfacial exchange coupling at the surface of a room-temperature AFM material, IrMn, exploiting the particular response from uncompensated moments to the thermal annealing and imprinting effects. Further systematic magnetic characterizations validate the existence of such an AFM order at the IrMn/CoFeB interfaces. Such AFM skyrmions have a typical size of 100 nm, which presents pronounced robustness against field and temperature. Our work opens new pathways for magnetic topological devices based on AFM skyrmions.

2.
Biochem Biophys Res Commun ; 723: 150220, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-38850811

RESUMO

Aging is characterized as the process of functional decline in an organism from adulthood, often marked by a progressive loss of cellular function and systemic deterioration of multiple tissues. Among the numerous molecular, cellular, and systemic hallmarks associated with aging, mitochondrial dysfunction is considered one of the pivotal factors that initiates the aging process. During aging, mitochondria undergo varying degrees of damage, resulting in impaired energy production and disruption of the homeostatic regulation of mitochondrial quality control systems, which in turn affects cellular energy metabolism and results in cellular dysfunction, accelerating the aging process. AMP-activated protein kinase (AMPK) and the mechanistic target of rapamycin complex 1 (mTORC1) are two central kinase complexes responsible for sensing intracellular nutrient levels, regulating metabolic homeostasis, modulating aging and play a crucial role in maintaining the homeostatic balance of mitochondria. Our previous studies found that the novel compound tetramethylpyrazine nitrone (TBN) can protect mitochondria via the AMPK/mTOR pathway in many animal models, extending healthy lifespan through the Nrf2 signaling pathway in nematodes. Building upon this foundation, we have posited a reasonable hypothesis, TBN can improve mitochondrial function to delay aging by regulating the AMPK/mTORC1 signaling pathway. This study focuses on the C. elegans, exploring the impact and underlying mechanisms of TBN on aging and mitochondrial function (especially the mitochondrial quality control system) during the aging process. The present studies demonstrated that TBN extends lifespan of wild-type nematodes and is associated with the AMPK/mTORC1 signaling pathway. TBN elevated ATP and NAD+ levels in aging nematodes while orchestrating mitochondrial biogenesis and mitophagy. Moreover, TBN was observed to significantly enhance normal activities during aging in C. elegans, such as mobility and pharyngeal pumping, concurrently impeding lipofuscin accumulation that were closely associated with AMPK and mTORC1. This study not only highlights the delayed effects of TBN on aging but also underscores its potential application in strategies aimed at improving mitochondrial function via the AMPK/mTOR pathway in C. elegans.


Assuntos
Proteínas Quinases Ativadas por AMP , Envelhecimento , Caenorhabditis elegans , Alvo Mecanístico do Complexo 1 de Rapamicina , Mitocôndrias , Pirazinas , Transdução de Sinais , Animais , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efeitos dos fármacos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Pirazinas/farmacologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Envelhecimento/metabolismo , Envelhecimento/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Óxidos de Nitrogênio/metabolismo
3.
Artigo em Inglês | MEDLINE | ID: mdl-38836739

RESUMO

Objectives: Rheumatoid Arthritis (RA) can accelerate atherosclerosis (AS) plaque formation. High prevalence of AS has been demonstrated in early-stage RA patients. Therefore, there is an urgent need to investigate what mechanisms and key molecules accelerate AS in RA to improve the management of RA. Methods: We retrieved gene expression data for RA (GSE45291) and atherosclerosis (GSE28829) from Gene Expression Omnibus (GEO). Seventeen key genes were identified, and the top one candidate hub gene was SLAM family member 8 (SLAMF8). To investigate the role of SLAMF8 in AS and RA, U937 cells were differentiated into macrophages using Phorbol 12-myristate 13-acetate (PMA) and further transformed into foam cells by oxidized low-density lipoprotein (ox-LDL) treatment and siRNA was manipulated to knock down SLAMF8. Flow Cytometry was employed to assess cell state. The mRNA and protein expressions of the genes were investigated using western blot and RT-qPCR. Results: SLAMF8 was screened as a key gene by bioinformatic methods. Compared to Mφ, SLAMF8, TLR4 and inflammatory cytokines, tumor necrosis factor α (TNF-α), and Interleukin 6 (IL-6) were noticeably expressed in foam cells. Knockdown of SLAMF8 could remarkably curtail TLR4, TNF-α, and IL-6 protein levels. Antagonizing SLAMF8 could attenuate inflammatory factors and apoptosis of foam cells by inhibiting the TLR4 pathway, thus mitigating the severity of AS in RA. Conclusions: Our work demonstrated that SLAMF8 promoted AS in patients with RA by inducing inflammation and apoptosis of foam cells via TLR4 signaling. Therefore, SLAMF8 could be a possible therapeutic spot for AS in RA patients.

4.
Int Endod J ; 57(5): 566-575, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38411530

RESUMO

AIM: This current Mendelian randomization (MR) study aims to comprehensively explore the potential bidirectional link between pulp and periapical disease (PAP) with type 2 diabetes mellitus (T2DM). METHODOLOGY: Summary level data of European-based population genome-wide association studies (GWASs) were employed to undertake this MR study. With the selection of single nucleotide polymorphisms (SNPs) as the instrumental variable, the radial inverse-variance weighted (radial IVW) method with modified second-order weights was applied as the primary method. Additionally, a range of sensitivity analyses were conducted to investigate pleiotropy. Results from different sources of outcome were pooled by meta-analysis with the fixed model. RESULTS: The results of this MR analysis did not suggest a significant impact of pulp and periapical disease on type 2 diabetes (combined OR = 1.04, 95% CI: 1.00-1.07, p = .033) and vice versa (OR = 1.04, 95% CI: 0.96-1.14, p = .329). No significant pleiotropy was detected in the final model after the removal of outliers, demonstrating the reliability of the results in our primary analysis. CONCLUSIONS: With the limitations inherent in the present MR study, there is no significant evidence in either direction to suggest a causal association between pulp and periapical disease and type 2 diabetes mellitus.


Assuntos
Doenças da Polpa Dentária , Diabetes Mellitus Tipo 2 , Doenças Periapicais , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes , Doenças Periapicais/complicações
5.
Hum Mol Genet ; 30(16): 1484-1496, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-33929499

RESUMO

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are serious neurodegenerative diseases. Although their pathogenesis is unclear, the abnormal accumulation of TAR DNA-binding protein of 43 kDa (TDP-43) is a pathological feature that exists in almost all patients. Thus far, there is no drug that can cure ALS/FTLD. Tetramethylpyrazine nitrone (TBN) is a derivative of tetramethylapyrazine, derived from the traditional Chinese medicine Ligusticum chuanxiong, which has been widely proven to have therapeutic effects on models of various neurodegenerative diseases. TBN is currently under clinical investigation for several indications including a Phase II trial of ALS. Here, we explored the therapeutic effect of TBN in an ALS/FTLD mouse model. We injected the TDP-43 M337V virus into the striatum of mice unilaterally and bilaterally, and then administered 30 mg/kg TBN intragastrically to observe changes in behavior and survival rate of mice. The results showed that in mice with unilateral injection of TDP-43M337V into the striatum, TBN improved motor deficits and cognitive impairment in the early stages of disease progression. In mice with bilateral injection of TDP-43M337V into the striatum, TBN not only improved motor function but also prolonged survival rate. Moreover, we show that its therapeutic effect may be through activation of the Akt/mTOR/GSK-3ß and AMPK/PGC-1α/Nrf2 signaling pathways. In summary, TBN is a promising agent for the treatment of ALS/FTLD.


Assuntos
Esclerose Lateral Amiotrófica , Demência Frontotemporal , Degeneração Lobar Frontotemporal , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Animais , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Degeneração Lobar Frontotemporal/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Camundongos
6.
J Endovasc Ther ; : 15266028231209932, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37978877

RESUMO

PURPOSE: This study aimed to compare midterm efficacy between drug-coated balloon (DCB) and bare metal stent (BMS) in the treatment of TASCII C/D femoropopliteal artery lesions. METHODS: The clinical data of patients with TASCII C/D femoropopliteal artery disease admitted to 3 vascular surgery centers from January 2018 to January 2021 were retrospectively analyzed. Patients were divided into DCB group and BMS group. The DCB group was further subdivided into DCB alone subgroup and DCB+BMS subgroup. Study primary outcomes were freedom from clinical-driven target lesion reintervention (FCD-TLR) at 24 months postprocedure. Secondary outcomes included ankle brachial index (ABI), Rutherford classification, major amputation rate, and mortality. RESULTS: A total of 410 consecutive patients were enrolled. At 24 months follow-up, in DCB group (114 patients) relative to BMS group (296 patients), FCD-TLR (86.00% vs 71.91%, p=0.039), and ABI (0.53±0.11 vs 0.47±0.19, p=0.007) were higher; mean Rutherford class was lower (1.57±0.68 vs 3.31±1.39, p=0.000); and major amputation rate (0.87% vs 4.05%, p>0.05) and all-cause mortality (8.92% vs 6.41%, p>0.05) were statistically similar. In DCB alone, subgroup relative to DCB+BMS subgroup, FCD-TLR (90.00% vs 85.00%, p>0.05), major amputation rate (0 vs 1.08%, p>0.05), and all-cause mortality rate (9.09% vs 8.69%, p>0.05) were statistically similar, while FCD-TLR was higher in the DCB+BMS subgroup (90.00% vs 71.91%, p=0.045). CONCLUSION: At midterm follow-up of patients treated for TASCII C/D femoropopliteal artery disease, use of DCB or of DCB combined with rescue BMS appeared similarly efficacious, and yielded more favorable outcomes than use of BMS. CLINICAL IMPACT: The efficacy of drug-coated balloons relative to that of bare metal stents for the treatment of complex femoropopliteal artery lesions, particularly TASCII grade D lesions, remains uncertain. There is a scarcity of multicenter comparative studies, and in this multicenter retrospective study with up to 24-month follow-up, use of drug-coated balloon alone or combined with rescue bare metal stent appeared similarly efficacious while yielding more favorable outcomes than use of bare metal stent alone in the treatment of TASCII grade C/D femoropopliteal artery lesions. Randomized studies are warranted.

7.
J Pept Sci ; 29(9): e3490, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36994602

RESUMO

Antimicrobial peptides (AMPs), a crucial part of the innate immune system, have been exploited as promising candidates for antibacterial agents. Many researchers have been devoting their efforts to develop novel AMPs in recent decades. In this term, many computational approaches have been developed to identify potential AMPs accurately. However, finding peptides specific to a particular bacterial species is challenging. Streptococcus mutans is a pathogen with an apparent cariogenic effect, and it is of great significance to study AMP that inhibit S. mutans for the prevention and treatment of caries. In this study, we proposed a sequence-based machine learning model, namely iASMP, to exactly identify potential anti-S. mutans peptides (ASMPs). After collecting ASMPs, the performances of models were compared by utilizing multiple feature descriptors and different classification algorithms. Among the baseline predictors, the model integrating the extra trees (ET) algorithm and the hybrid features exhibited optimal results. The feature selection method was utilized to remove redundant feature information to improve the model performance further. Finally, the proposed model achieved the maximum accuracy (ACC) of 0.962 on the training dataset and performed on the testing dataset with an ACC of 0.750. The results demonstrated that iASMP had an excellent predictive performance and was suitable for identifying potential ASMP. Furthermore, we also visualized the selected features and rationally explained the impact of individual features on the model output.


Assuntos
Peptídeos Antimicrobianos , Peptídeos , Peptídeos/farmacologia , Antibacterianos/farmacologia , Streptococcus mutans
8.
Occup Environ Med ; 80(9): 529-537, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37468282

RESUMO

Exposure to workplace bullying increases the risk of sickness absence. However, the extent and direction of this relationship for different follow-up lengths are not well established. To provide evidence regarding the direction and extent of the relationship between workplace bullying and different durations of sickness absence. We searched nine databases from their inception to 29 November 2022. Multiple independent observers screened the literature, extracted the data and used the Risk Of Bias In Non-randomised Studies of Exposure to assess the methodological quality. The overall effect sizes of odds ratio, relative risk, hazard ratio and 95% confidence intervals were calculated. Our meta-analysis demonstrated a 26% increased risk of sick leave among workers exposed to workplace bullying for all follow-up lengths (95% CI 1.18 to 1.35), even after adjusting for confounding factors. Moreover, we found a significant association between long-term sickness absence and a higher likelihood of subsequent exposure to workplace bullying, with a pooled OR of 1.63 (95% CI 1.21 to 2.04). Our study established a bidirectional relationship between workplace bullying and long-term sickness absence, highlighting that it increases the risk of sickness absence at different follow-up lengths among employees who have been bullied. Hence, organisations should be mindful of workers who resume work after prolonged absences due to illness and adopt appropriate management strategies to prevent workplace bullying.


Assuntos
Bullying , Estresse Ocupacional , Humanos , Estudos Prospectivos , Local de Trabalho , Absenteísmo , Licença Médica
9.
Acta Pharmacol Sin ; 44(8): 1637-1648, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36882503

RESUMO

Hepatitis C virus (HCV) infection is one of the major factors to trigger a sustained hepatic inflammatory response and hence hepatocellular carcinoma (HCC), but direct-acting-antiviral (DAAs) was not efficient to suppress HCC development. Heat shock protein 90 kDa (HSP90) is highly abundant in different types of cancers, and especially controls protein translation, endoplasmic reticulum stress, and viral replication. In this study we investigated the correlation between the expression levels of HSP90 isoforms and inflammatory response marker NLRP3 in different types of HCC patients as well as the effect of a natural product celastrol in suppression of HCV translation and associated inflammatory response in vivo. We identified that the expression level of HSP90ß isoform was correlated with that of NLRP3 in the liver tissues of HCV positive HCC patients (R2 = 0.3867, P < 0.0101), but not in hepatitis B virus-associated HCC or cirrhosis patients. We demonstrated that celastrol (3, 10, 30 µM) dose-dependently suppressed the ATPase activity of both HSP90α and HSP90ß, while its anti-HCV activity was dependent on the Ala47 residue in the ATPase pocket of HSP90ß. Celastrol (200 nM) halted HCV internal ribosomal entry site (IRES)-mediated translation at the initial step by disrupting the association between HSP90ß and 4EBP1. The inhibitory activity of celastrol on HCV RNA-dependent RNA polymerase (RdRp)-triggered inflammatory response also depended on the Ala47 residue of HSP90ß. Intravenous injection of adenovirus expressing HCV NS5B (pAde-NS5B) in mice induced severe hepatic inflammatory response characterized by significantly increased infiltration of immune cells and hepatic expression level of Nlrp3, which was dose-dependently ameliorated by pretreatment with celastrol (0.2, 0.5 mg/kg, i.p.). This study reveals a fundamental role of HSP90ß in governing HCV IRES-mediated translation as well as hepatic inflammation, and celastrol as a novel inhibitor of HCV translation and associated inflammation by specifically targeting HSP90ß, which could be developed as a lead for the treatment of HSP90ß positive HCV-associated HCC.


Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Camundongos , Animais , Hepacivirus , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Proteínas de Choque Térmico , Proteína 3 que Contém Domínio de Pirina da Família NLR , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Proteínas de Choque Térmico HSP90/metabolismo , Inflamação/tratamento farmacológico
10.
J Cardiothorac Vasc Anesth ; 37(8): 1442-1448, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37120322

RESUMO

OBJECTIVES: To review the efficacy of 2 score tools for identifying pulmonary complications after cardiac surgery. DESIGN: A retrospective observational study. SETTING: At the West China Hospital of Sichuan University General Hospital. PARTICIPANTS: Patients who underwent elective cardiac surgery (N = 508). INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A total of 508 patients who underwent elective cardiac surgery between March 2021 and December 2021 were included in this observational study. Three independent physiotherapists used 2 different sets of score tools, as described by Kroenke et al. (Kroenke Score) and Reeve et al. (Melbourne Group Scale), to evaluate clinically defined pulmonary complications according to the European Perioperative Clinical Outcome definitions (including atelectasis, pneumonia, and respiratory failure) daily after surgery at midday. The incidence of postoperative pulmonary complications (PPCs) was 51.6% (262/508) with the Kroenke Score and 21.9% (111/508) with the Melbourne Group Scale. The clinically observed incidence of atelectasis was 51.4%, pneumonia was 20.9%, and respiratory failure at 6.5%. The receiver operator characteristics curve showed that the overall validity of the Kroenke Score was better than that of the Melbourne Group Scale in atelectasis (area under the curve [AUC], 91.5% v 71.3%). The Melbourne Group Scale performed better in pneumonia (AUC, 99.4% v 80.0%) and respiratory failure (AUC, 88.5% v 75.9%) than the Kroenke Score. CONCLUSION: The incidence of PPCs after cardiac surgery was highly prevalent. Both the Kroenke Score and the Melbourne Group Scale are effective in identifying patients with PPCs. Kroenke Score can identify patients with mild pulmonary adverse events, whereas the Melbourne Group Scale is more dominant in identifying moderate-to-severe pulmonary complications.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Pneumonia , Atelectasia Pulmonar , Insuficiência Respiratória , Humanos , Pulmão , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Pneumonia/etiologia , Atelectasia Pulmonar/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Insuficiência Respiratória/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
11.
Nano Lett ; 22(17): 6857-6865, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-35849087

RESUMO

Perpendicularly magnetized structures that are switchable using a spin current under field-free conditions can potentially be applied in spin-orbit torque magnetic random-access memory (SOT-MRAM). Several structures have been developed; however, new structures with a simple stack structure and MRAM compatibility are urgently needed. Herein, a typical structure in a perpendicular spin-transfer torque MRAM, the Pt/Co multilayer and its synthetic antiferromagnetic counterpart with perpendicular magnetic anisotropy, was observed to possess an intrinsic interlayer chiral interaction between neighboring magnetic layers, namely, the interlayer Dzyaloshinskii-Moriya interaction (DMI) effect. Furthermore, using a current parallel to the eigenvector of the interlayer DMI, we switched the perpendicular magnetization of both structures without a magnetic field, owing to the additional symmetry breaking introduced by the interlayer DMI. This SOT switching scheme realized in the Pt/Co multilayer and its synthetic antiferromagnet structure may open a new avenue toward practical perpendicular SOT-MRAM and other SOT devices.

12.
Nurs Health Sci ; 25(4): 530-542, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37941525

RESUMO

This qualitative systematic review aims to comprehensively understand the experiences and perspectives of nurses infected with COVID-19, addressing a significant gap in the current literature. Following the JBI meta-synthesis approach, a rigorous search was conducted across nine electronic databases and references until January 16, 2023. Seventeen eligible studies underwent quality assessment using the JBI critical checklist. Data were synthesized using standardized tools, and the ConQual tool evaluated confidence in the findings. Seven key findings emerged, providing valuable insights into emotional experiences, adaptation to COVID-19 challenges, influence of support systems, coping strategies, posttraumatic growth perceptions, and effects on professional identity and career advancement. The findings highlight emotional toll, adaptive strategies, and professional implications for nurses. Moreover, they emphasize the importance of support systems, coping mechanisms, and posttraumatic growth in promoting nurses' well-being and resilience. These insights have practical implications for targeted interventions and support mechanisms to enhance infected nurses' well-being and improve healthcare outcomes.


Assuntos
COVID-19 , Resiliência Psicológica , Humanos , Pesquisa Qualitativa , Papel do Profissional de Enfermagem/psicologia
13.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 40(6): 1117-1125, 2023 Dec 25.
Artigo em Zh | MEDLINE | ID: mdl-38151934

RESUMO

In recent years, wearable devices have seen a booming development, and the integration of wearable devices with clinical settings is an important direction in the development of wearable devices. The purpose of this study is to establish a prediction model for postoperative pulmonary complications (PPCs) by continuously monitoring respiratory physiological parameters of cardiac valve surgery patients during the preoperative 6-Minute Walk Test (6MWT) with a wearable device. By enrolling 53 patients with cardiac valve diseases in the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, the grouping was based on the presence or absence of PPCs in the postoperative period. The 6MWT continuous respiratory physiological parameters collected by the SensEcho wearable device were analyzed, and the group differences in respiratory parameters and oxygen saturation parameters were calculated, and a prediction model was constructed. The results showed that continuous monitoring of respiratory physiological parameters in 6MWT using a wearable device had a better predictive trend for PPCs in cardiac valve surgery patients, providing a novel reference model for integrating wearable devices with the clinic.


Assuntos
Pulmão , Caminhada , Humanos , Caminhada/fisiologia , Teste de Caminhada , Valvas Cardíacas/cirurgia , Período Pós-Operatório , Complicações Pós-Operatórias/etiologia
14.
Biochem Biophys Res Commun ; 614: 107-113, 2022 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-35576681

RESUMO

SKN-1, the ortholog of mammalian Nrf2 proteins, is a transcription factor that plays an important role in oxidative stress resistance and longevity. Similar to other defense systems, the Nrf2-mediated stress response is compromised in aging and neurodegenerative diseases. Our previous studies demonstrated that tetramethylpyrazine nitrone (TBN), a derivative of tetramethylpyrazine armed with a potent free radical-scavenging nitrone moiety, exerted multifunctional neuroprotection in neurological and other diseases. However, the ability of TBN to extend a healthy lifespan and its underlying mechanisms of action are not yet clear. C. elegans have become a popular animal model in aging research. Herein, we demonstrate that TBN can extend the lifespan, promote age-associated health indicators, and restore mitochondrial function in C. elegans. TBN also significantly reduced ROS levels and superoxide accumulation in C. elegans. We show that TBN-mediated lifespan extension is SKN-1dependent. The present study provides valuable insights into the mechanisms by which TBN inhibits aging via the Nrf2/SKN-1 pathway in C. elegans.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Modelos Animais de Doenças , Proteínas de Ligação a DNA/metabolismo , Longevidade/fisiologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Pirazinas , Transdução de Sinais , Fatores de Transcrição/metabolismo
15.
J Chem Inf Model ; 62(10): 2617-2629, 2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35533298

RESUMO

Although peptides are regarded as ideal therapeutic agents, only a small proportion of the marketed drugs are peptides. In the past decade, pharmacists have paid great attention to the development of peptide therapeutics. Except a few approved chemically/rationally designed peptides, most attempts failed due to unsatisfactory efficacy or safety. Luckily, computation methods, such as artificial intelligence, have been utilized to accelerate the discovery of therapeutic peptides by predicting the activity, toxicity, and absorption, distribution, metabolism, and excretion of polypeptides. Usually, a specific biological activity of a peptide could be accurately determined by an interest-oriented binary classification constructed of a positive set and another un-experimentally validated negative set regardless of other characteristics, which suggests that it could be challenging to realize the comprehensive evaluation of the research object in the early stage of drug research and development. Herein, we proposed an integrated method (GM-Pep) that contained a conditional variational autoencoder model (CVAE) and a positive sample training multiclassifier (Deep-Multiclassifier) to effectively generate a single bioactive peptide sequence without toxicity and referential side effects. The results showed that our Deep-Multiclassifier model gave a sequence accuracy of up to 96.41% [toxicity (94.48%), antifungal (96.58%), antihypertensive (97.18%), and antibacterial (96.91%), respectively]. The properties of Deep-Multiclassifier and CVAE were validated through 12 first synthesized antibacterial peptides or compared to random peptides. The source code and data sets are available at https://github.com/TimothyChen225/GM-Pep.


Assuntos
Peptídeos , Análise de Sequência de Proteína , Inteligência Artificial , Humanos , Peptídeos/química , Peptídeos/toxicidade , Análise de Sequência de Proteína/métodos
16.
Pharmacology ; 107(3-4): 206-215, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35021174

RESUMO

INTRODUCTION: Doxorubicin (DOX), an anthracycline antitumor agent, has been widely used against various solid tumors and hematological malignancies. However, the clinical application of DOX is restricted by its multiple organ toxicity including nephrotoxicity. This study investigated the protective effects and mechanisms of dexrazoxane (DZR) against DOX-induced nephropathy in rats. METHODS: Male Sprague Dawley rats received 2.5 mg/kg DOX once a week for 5 consecutive weeks. 24-h urinary protein and renal function injury biomarkers were determined to evaluate the renal function. Histopathological changes and glomerulosclerosis were examined by hematoxylin and eosin and periodic acid-Schiff staining. The change of renal ultrastructure in the DOX-induced rats was observed by the electron microscopy. The renal apoptosis was detected by TUNEL staining and measured the protein expression of Caspase-3, Bcl-2, and Bax. Renal interstitial fibrosis was determined by Masson staining and immunohistochemistry examination. The levels of vimentin, alpha-smooth muscle actin (α-SMA), and transforming growth factor ß (TGF-ß) in kidney tissue were detected by Western blot. RESULTS: DZR pretreatment markedly raised the survival rate and improved the renal dysfunction in DOX-treated rats. DZR ameliorated DOX-induced histopathological lesion of glomerular and tubular and apoptosis. DZR restored the oxidant/antioxidant balance via regulating the levels of MDA, SOD, and TAC. DZR reduced DOX-induced collagen IV deposition and renal interstitial fibrosis and downregulated the fibrosis-related protein expressions of vimentin, α-SMA, and TGF-ß1. CONCLUSION: Our results suggest DZR exerted its protective effects against DOX-induced nephropathy through inhibition of lipid peroxidation, apoptosis, and fibrosis.


Assuntos
Dexrazoxano , Nefropatias , Animais , Antibióticos Antineoplásicos/efeitos adversos , Dexrazoxano/efeitos adversos , Doxorrubicina/toxicidade , Fibrose , Rim/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Nefropatias/prevenção & controle , Masculino , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/metabolismo
17.
Sensors (Basel) ; 22(2)2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35062513

RESUMO

This article examines the positioning effect of integrated navigation after adding an LEO constellation signal source and a 5G ranging signal source in the context of China's new infrastructure construction. The tightly coupled Kalman federal filters are used as the algorithm framework. Each signal source required for integrated navigation is simulated in this article. At the same time, by limiting the range of the azimuth angle and visible height angle, different experimental scenes are simulated to verify the contribution of the new signal source to the traditional satellite navigation, and the positioning results are analyzed. Finally, the article compares the distribution of different federal filtering information factors and reveals the method of assigning information factors when combining navigation with sensors with different precision. The experimental results show that the addition of LEO constellation and 5G ranging signals improves the positioning accuracy of the original INS/GNSS by an order of magnitude and ensures a high degree of positioning continuity. Moreover, the experiment shows that the federated filtering algorithm can adapt to the combined navigation mode in different scenarios by combining different precision sensors for navigation positioning.


Assuntos
Algoritmos , Projetos de Pesquisa , Simulação por Computador , Registros
18.
J Nurs Manag ; 30(7): 2854-2868, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36122417

RESUMO

AIM: This review examined the association between workplace violence and the risk of post-traumatic stress disorder (PTSD) and burnout among nurses. BACKGROUND: The extent to which workplace violence is associated with an increased risk of PTSD and burnout in nurses remains unclear. EVALUATION: We searched nine electronic databases (PubMed, Cochrane, Embase, Web of Science, CINAHL, PsycINFO, Chinese Biomedical, China National Knowledge Internet and WANFANG). KEY ISSUES: Overall, 114 full-text studies were identified; 43 met the inclusion criteria, of which 10 were included in the meta-analysis. Compared to their counterparts with non-exposure to workplace violence, nurses experiencing it had 2.13 and 2.25 times higher odds of reporting PTSD and burnout after adjusting the confounding factors. Additionally, the moderator and mediator factors might help reduce the risk of both in this population. CONCLUSION: This study indicated that workplace violence increases the risk of PTSD and burnout. IMPLICATIONS FOR NURSING MANAGEMENT: Our review identified the magnitude of the association between exposure to workplace violence and the reported symptoms of PTSD and burnout in nurses. Furthermore, multi-targeted efforts directed at the identified social/organizational, task-related and individual resources might help mitigate their harmful impact in the aforementioned population.


Assuntos
Esgotamento Profissional , Transtornos de Estresse Pós-Traumáticos , Violência no Trabalho , Humanos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/etiologia , Esgotamento Psicológico , China , Local de Trabalho
19.
J Proteome Res ; 18(4): 1542-1552, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30484658

RESUMO

Donepezil is a clinically approved acetylcholinesterase inhibitor (AChEI) for cognitive improvement in Alzheimer's disease (AD). Donepezil has been used as a first-line agent for the symptomatic treatment of AD, but its ability to modify disease pathology and underlying mechanisms is not clear. We investigated the protective effects and underlying mechanisms of donepezil in AD-related triple transgenic (APPSwe/PSEN1M146V/MAPTP301L) mouse model (3×Tg-AD). Mice (8-month old) were treated with donepezil (1.3 mg/kg) for 4 months and evaluated by behavioral tests for assessment of cognitive functions, and the hippocampal tissues were examined by protein analysis and quantitative proteomics. Behavioral tests showed that donepezil significantly improved the cognitive capabilities of 3×Tg-AD mice. The levels of soluble and insoluble amyloid beta proteins (Aß1-40 and Aß1-42) and senile plaques were reduced in the hippocampus. Golgi staining of the hippocampus showed that donepezil prevented dendritic spine loss in hippocampal neurons of 3×Tg-AD mice. Proteomic studies of the hippocampal tissues identified 3131 proteins with altered expression related to AD pathology, of which 262 could be significantly reversed with donepezil treatment. Bioinformatics with functional analysis and protein-protein interaction (PPI) network mapping showed that donepezil significantly elevated the protein levels of PINK 1, NFASC, MYLK2, and NRAS in the hippocampus, and modulated the biological pathways of axon guidance, mitophagy, mTOR, and MAPK signaling. The substantial upregulation of PINK 1 with donepezil was further verified by Western blotting. Donepezil exhibited neuroprotective effects via multiple mechanisms. In particular, PINK 1 is related to mitophagy and cellular protection from mitochondrial dysfunction, which might play important roles in AD pathogenesis and represent a potential therapeutic target.


Assuntos
Doença de Alzheimer/metabolismo , Donepezila/farmacologia , Hipocampo , Proteínas Quinases/metabolismo , Proteoma , Peptídeos beta-Amiloides/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Cognição , Modelos Animais de Doenças , Feminino , Hipocampo/química , Hipocampo/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Fármacos Neuroprotetores/farmacologia , Proteoma/análise , Proteoma/efeitos dos fármacos , Proteômica
20.
Med Sci Monit ; 25: 5580-5588, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31350990

RESUMO

BACKGROUND The factors associated with osteoporosis are poorly understood in the Chinese population. This study aimed to examine the factors associated with osteoporosis and with fractures in a Chinese elderly population. MATERIAL AND METHODS This was a cross-sectional study of elderly people living in Tianjin between 2012 and 2014. Bone mineral density was measured by dual X-ray absorptiometry. The subjects completed a questionnaire about lifestyle habits, personal and family medical history, calcium intake, and exercising. Data were gathered on occurrence of fracture at 5 years or August 2018, whichever occurred first. RESULTS There were 298 individuals with osteoporosis (18.5% male, median age 67 years) and 397 without (46.3% male, median age 62 years). Male sex (OR=0.051, 95% CI: 0.021-0.126), age (OR=1.049, 95% CI: 1.099-1.202), being divorced/widowed (OR=2.445, 95% CI: 1.219-4.904), digestive ulcer history (OR=3.805, 95% CI: 1.539-9.405), family history of hunchback (OR=2.659, 95% CI: 1.145-6.175), family history of osteoarthropathy (OR=4.222, 95% CI: 2.128-8.375), fracture history (OR=2.138, 95% CI: 1.307-3.496), drinking green tea (OR=0.352, 95% CI: 0.217-0.574), and exercising (OR=0.303, 95% CI: 0.193-0.475) were independently associated with osteoporosis. Digestive ulcer history (OR=3.183, 95% CI: 1.178-8.5992), exercising (OR=0.354, 95% CI: 0.139-0.903), and taking calcium supplements during follow-up (OR=0.262, 95% CI: 0.112-0.611) were independently associated with fractures in patients with osteoporosis. CONCLUSIONS Female sex, age, marital status, history of digestive ulcer and fracture, and family history of hunchback and osteoarthropathy are associated with osteoporosis among elderly subjects, while drinking green tea and exercising are inversely associated. Among the patients with osteoporosis, a history of digestive ulcer is associated with fractures, while exercising and taking calcium supplements are inversely associated.


Assuntos
Fraturas Ósseas/etiologia , Osteoporose/epidemiologia , Osteoporose/fisiopatologia , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Densidade Óssea , Cálcio/metabolismo , China , Estudos Transversais , Suplementos Nutricionais , Exercício Físico , Feminino , Fraturas Ósseas/fisiopatologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Fatores de Risco
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