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1.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(4): 684-691, 2024 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-39218593

RESUMO

This study investigates a brain-computer interface (BCI) system based on an augmented reality (AR) environment and steady-state visual evoked potentials (SSVEP). The system is designed to facilitate the selection of real-world objects through visual gaze in real-life scenarios. By integrating object detection technology and AR technology, the system augmented real objects with visual enhancements, providing users with visual stimuli that induced corresponding brain signals. SSVEP technology was then utilized to interpret these brain signals and identify the objects that users focused on. Additionally, an adaptive dynamic time-window-based filter bank canonical correlation analysis was employed to rapidly parse the subjects' brain signals. Experimental results indicated that the system could effectively recognize SSVEP signals, achieving an average accuracy rate of 90.6% in visual target identification. This system extends the application of SSVEP signals to real-life scenarios, demonstrating feasibility and efficacy in assisting individuals with mobility impairments and physical disabilities in object selection tasks.


Assuntos
Realidade Aumentada , Interfaces Cérebro-Computador , Eletroencefalografia , Potenciais Evocados Visuais , Humanos , Potenciais Evocados Visuais/fisiologia , Estimulação Luminosa , Interface Usuário-Computador , Algoritmos
2.
Parkinsonism Relat Disord ; 128: 107153, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39316934

RESUMO

INTRODUCTION: Anemia may contribute significantly to the onset of Parkinson's disease (PD). Current research on the association between anemia and PD risk is inconclusive, and the relationships between anemia-related blood cell indices and PD incidence require further clarification. This study aims to investigate the relationships between anemia, blood cell indicators, and PD risk using a thorough prospective cohort study. METHODS: We used data from the UK Biobank, a prospective cohort study of 502,649 participants, and ultimately, 365,982 participants were included in the analysis. Cox proportional hazards models were utilized to adjust for confounding factors, aiming to thoroughly explore the associations between anemia and blood cell indices with the risk of incident PD. The interaction between anemia and Polygenic Risk Score (PRS) for PD was also examined. Linear regression and mediation analyses assessed potential mechanisms driven by brain structures, including grey matter volume. RESULTS: During a median follow-up of 14.24 years, 2513 participants were diagnosed with PD. Anemia considerably increased PD risk (hazard ratio [HR] 1.98, 95 % confidence interval [CI]: 1.81-2.18, P < 0.001) after adjustments. Those with high PRS for anemia had an 83 % higher PD incidence compared to low PRS participants. Sensitivity analyses confirmed result robustness. Linear regression showed that anemia correlated with grey matter volumes and most white matter tracts. Furthermore, mediation analyses identified that the volume of grey matter in Thalamus mediates the relationship between anemia and PD risk. CONCLUSION: In summary, we consider there to be a substantial correlation between anemia and increased PD risk.

3.
Int J Biol Macromol ; 280(Pt 1): 135494, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39276887

RESUMO

The active ingredients most commonly employed in sunscreens are compounds containing one or two aromatic rings. Lignin is the most abundant renewable aromatic polymer that has the potential to yield low molecular weight aromatic chemicals when strategically depolymerized. Here, the UV absorbance of a series of monomeric and dimeric lignin model compounds (LMCs) were studied. Specifically, vanillin and ferulic acid demonstrated good absorption in the UVB (280-320 nm) range, while the 5-5 dimer showed efficient absorption in the UVA (320-400 nm) range. Based on this, vanillin, ferulic acid and 5-5 dimer were mixed in pairs and dispersed in the oily isoeugenol to prepare LMC hybrid dispersions. Subsequently, demethylated lignin (DL) was synthesized and used to encapsulate the LMC hybrid dispersions via ultrasonic cavitation to prepare DL-based nano-capsules (DLNCs). The DLNCs were used as the only active ingredient in sunscreens, whose sun protection factor (SPF) value could be up to 55 with a dosage of 10 wt%. Due to anti-photolysis property of DL, the SPF value of DLNCs-based sunscreens increased initially and maintained >8 h under UV irradiation. Additionally, the prepared DLNCs exhibited excellent anti-permeability, antioxidant capacity and biocompatibility, making them a potential substitute for conventional petroleum-based sunscreen agents.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39269797

RESUMO

Benefiting from advances in large-scale pre-training, foundation models, have demonstrated remarkable capability in the fields of natural language processing, computer vision, among others. However, to achieve expert-level performance in specific applications, such models often need to be fine-tuned with domain-specific knowledge. In this paper, we focus on enabling vision-language models to unleash more potential for visual understanding tasks under few-shot tuning. Specifically, we propose a novel adapter, dubbed as lusterAdapter, which is based on trainable multiple prototypes clustering algorithm, for tuning the CLIP model. It can not only alleviate the concern of catastrophic forgetting of foundation models by introducing anchors to inherit common knowledge, but also improve the utilization efficiency of few annotated samples via bringing in clustering and domain priors, thereby improving the performance of few-shot tuning. We have conducted extensive experiments on 11 common classification benchmarks. The results show our method significantly surpasses the original CLIP and achieves state-of-the-art (SOTA) performance under all benchmarks and settings. For example, under the 16-shot setting, our method exhibits a remarkable improvement over the original CLIP by 19.6%, and also surpasses TIP-Adapter and GraphAdapter by 2.7% and 2.2%, respectively, in terms of average accuracy across the 11 benchmarks. Code is available at https://github.com/uyzhang/Cluster-Adapter.

5.
Int J Mol Sci ; 25(15)2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39126046

RESUMO

Schizophrenia (SCZ) imposes a significant burden on patients and their families because of its high prevalence rate and disabling nature. Given the lack of definitive conclusions regarding its pathogenesis, physicians heavily rely on patients' subjective symptom descriptions for diagnosis because reliable diagnostic biomarkers are currently unavailable. The role of the inflammatory response in the pathogenesis of SCZ has been supported by some studies. The findings of these studies showed abnormal changes in the levels of inflammatory factors, such as cytokines (CKs), in both peripheral blood and cerebrospinal fluid (CSF) among individuals affected by SCZ. The findings imply that inflammatory factors could potentially function as risk indicators for the onset of SCZ. Consequently, researchers have directed their attention towards investigating the potential utility of CKs as viable biomarkers for diagnosing SCZ. Extracellular vesicles (EVs) containing disease-specific components exhibit remarkable stability and abundance, making them promising candidates for biomarker discovery across various diseases. CKs encapsulated within EVs secreted by immune cells offer valuable insights into disease progression. This review presents a comprehensive analysis summarizing the relationship between CKs and SCZ and emphasizes the vital role of CKs encapsulated within EVs in the pathogenesis and development of SCZ.


Assuntos
Biomarcadores , Citocinas , Vesículas Extracelulares , Esquizofrenia , Humanos , Esquizofrenia/metabolismo , Esquizofrenia/diagnóstico , Citocinas/metabolismo , Vesículas Extracelulares/metabolismo
6.
Molecules ; 29(15)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39125046

RESUMO

Supercapacitors (SCs) are widely recognized as competitive power sources for energy storage. The hierarchical structure of nickel vanadium sulfide nanoparticles encapsulated on graphene nanosheets (NVS/G) was fabricated using a cost-effective and scalable solvothermal process. The reaction contents of the composites were explored and optimized. TEM images displayed the nickel vanadium sulfide nanoparticles (NVS NPs) with 20-30 nm average size anchored to graphene nanosheets. The interconnection of graphene nanosheets encapsulating NVS nanoparticles effectively reduces the ion diffusion path between the electrode and electrolyte, thereby enhancing electrochemical performance. The NVS/G composite demonstrated improved electrochemical performance, achieving a maximum of 1437 F g-1 specific capacitance at 1 A g-1, remarkable rate capability retaining of 1050 F g-1 at 20 A g-1, and exceptional cycle stability with 91.2% capacitance retention following 10,000 cycles. The NVS/G composite was employed as a cathode, and reduced graphene oxide (rGO) was used as an anode material to assemble a device. Importantly, asymmetric SCs using NVS/G//rGO achieved 74.7 W h kg-1 energy density at 0.8 kW kg-1 power density, along with outstanding stability with 88.2% capacitance retention following 10,000 cycles. These superior properties of the NVS/G electrode highlight its significant potential in energy storage applications.

7.
BMJ Open Respir Res ; 11(1)2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39089740

RESUMO

OBJECTIVE: To develop a nomogram for predicting occurrence of secondary pulmonary infection in patients with critically traumatic brain injury (TBI) during their stay in the intensive care unit, to further optimise personalised treatment for patients and support the development of effective, evidence-based prevention and intervention strategies. DATA SOURCE: This study used patient data from the publicly available MIMIC-IV (Medical Information Mart for Intensive Care IV) database. DESIGN: A population-based retrospective cohort study. METHODS: In this retrospective cohort study, 1780 patients with TBI were included and randomly divided into a training set (n=1246) and a development set (n=534). The impact of pulmonary infection on survival was analysed using Kaplan-Meier curves. A univariate logistic regression model was built in training set to identify potential factors for pulmonary infection, and independent risk factors were determined in a multivariate logistic regression model to build nomogram model. Nomogram performance was assessed with receiver operating characteristic (ROC) curves, calibration curves and Hosmer-Lemeshow test, and predictive value was assessed by decision curve analysis (DCA). RESULT: This study included a total of 1780 patients with TBI, of which 186 patients (approximately 10%) developed secondary lung infections, and 21 patients died during hospitalisation. Among the 1594 patients who did not develop lung infections, only 85 patients died (accounting for 5.3%). The survival curves indicated a significant survival disadvantage for patients with TBI with pulmonary infection at 7 and 14 days after intensive care unit admission (p<0.001). Both univariate and multivariate logistic regression analyses showed that factors such as race other than white or black, respiratory rate, temperature, mechanical ventilation, antibiotics and congestive heart failure were independent risk factors for pulmonary infection in patients with TBI (OR>1, p<0.05). Based on these factors, along with Glasgow Coma Scale and international normalised ratio variables, a training set model was constructed to predict the risk of pulmonary infection in patients with TBI, with an area under the ROC curve of 0.800 in the training set and 0.768 in the validation set. The calibration curve demonstrated the model's good calibration and consistency with actual observations, while DCA indicated the practical utility of the predictive model in clinical practice. CONCLUSION: This study established a predictive model for pulmonary infections in patients with TBI, which may help clinical doctors identify high-risk patients early and prevent occurrence of pulmonary infections.


Assuntos
Lesões Encefálicas Traumáticas , Unidades de Terapia Intensiva , Nomogramas , Humanos , Masculino , Estudos Retrospectivos , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/mortalidade , Feminino , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Idoso , Medição de Risco , Infecções Respiratórias/epidemiologia , Valor Preditivo dos Testes , Curva ROC
8.
Opt Lett ; 49(15): 4222-4225, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090899

RESUMO

Amid rapid advancements in aerospace science and technology, studying the effects of space radiation on an infrared detector is crucial for enhancing their reliability in radiation environments, particularly against electrons-one of the most damaging charged particles. Barrier structures significantly reduce dark current without any substantial degradation in the optical performance of the devices. Consequently, they are being investigated for use in extreme environments. This paper presents a study on the performance degradation of InAs/GaSb type II superlattice (T2SLs) long-wave infrared (LWIR) detectors with a graded barrier structure under 1 MeV electron irradiation and analyzes potential damage mechanisms. The findings indicate that 1 MeV electron irradiation causes both ionization and displacement damage to the graded barrier InAs/GaSb T2SL LWIR detectors. After irradiation with a fluence of 2 × 1015 e/cm2, the device's dark current density has increased by approximately two orders of magnitude, while the quantum efficiency has decreased by approximately one order of magnitude. As the device mesa shrinks, the sensitivity of dark current to radiation exposure increases. Electron irradiation notably exacerbates surface leakage and bulk dark current, with a pronounced increase in surface leakage current. The study also reveals that electron irradiation primarily enhances the dark current by introducing defect states, thereby leading to device performance degradation.

9.
Arch Toxicol ; 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39096369

RESUMO

Nano-plastics (NPs) have emerged as a significant environmental pollutant, widely existing in water environment, and pose a serious threat to health and safety with the intake of animals. Skeletal muscle, a vital organ for complex life activities and functional demands, has received limited attention regarding the effects of NPs. In this study, the effects of polystyrene NPs (PS-NPs) on skeletal muscle development were studied by oral administration of different sizes (1 mg/kg) of PS-NPs in mice. The findings revealed that PS-NPs resulted in skeletal muscle damage and significantly hindered muscle differentiation, exhibiting an inverse correlation with PS-NPs particle size. Morphological analysis demonstrated PS-NPs caused partial disruption of muscle fibers, increased spacing between fibers, and lipid accumulation. RT-qPCR and western blots analyses indicated that PS-NPs exposure downregulated the expression of myogenic differentiation-related factors (Myod, Myog and Myh2), activated PPARγ/LXRß pathway, and upregulated the expressions of lipid differentiation-related factors (SREBP1C, SCD-1, FAS, ACC1, CD36/FAT, ADIPOQ, C/EBPα and UCP-1). In vitro experiments, C2C12 cells were used to confirm cellular penetration of PS-NPs (0, 100, 200, 400 µg/mL) through cell membranes along with activation of PPARγ expression. Furthermore, to verify LXRß as a key signaling molecule, silencing RNA transfection experiments were conducted, resulting in no increase in the expressions of PPARγ, LXRß, SREBP1C, FAS, CD36/FAT, ADIPOQ, C/EBPα and UCP-1 even after exposure to PS-NPs. However, the expressions of SCD-1and ACC1 remained unaffected. The present study evidenced that exposure to PS-NPs induced lipid accumulation via the PPARγ/LXRß pathway thereby influencing skeletal muscle development.

10.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(8): 893-898, 2024 Aug 15.
Artigo em Chinês | MEDLINE | ID: mdl-39148397

RESUMO

Pharyngitis can be caused by various pathogens, including viruses and bacteria. Group A streptococcus (GAS) is the most common bacterial cause of pharyngitis. However, distinguishing GAS pharyngitis from other types of upper respiratory tract infections is challenging in clinical settings. This often leads to empirical treatments and, consequently, the overuse of antimicrobial drugs. With the advancement of antimicrobial drug management and healthcare payment reform initiatives in China, reducing unnecessary testing and prescriptions of antimicrobial drugs is imperative. To promote standardized diagnosis and treatment of GAS pharyngitis, this article reviews various international guidelines on the clinical diagnosis and differential diagnosis of GAS pharyngitis, particularly focusing on clinical scoring systems guiding laboratory testing and antimicrobial treatment decisions for GAS pharyngitis and their application recommendations, providing a reference for domestic researchers and clinical practitioners.


Assuntos
Faringite , Infecções Estreptocócicas , Streptococcus pyogenes , Humanos , Faringite/microbiologia , Faringite/tratamento farmacológico , Faringite/diagnóstico , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico
11.
Front Public Health ; 12: 1403196, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39171301

RESUMO

Background: Multimorbidity has become a major public health problem among Chinese middle-aged and older adults, and the most costly to the health care system. However, most previous population-based studies of multimorbidity have focused on a limited number of chronic diseases, and diagnosis was based on participants' self-report, which may oversimplify the problem. At the same time, there were few reports on the relationship between multimorbidity patterns and health care costs. This study analyzed the multimorbidity patterns and changes among middle-aged and older people in China over the past decade, and their association with medical costs, based on representative hospital electronic medical record data. Methods: Two cross-sectional surveys based on representative hospital data were used to obtain adults aged 45 years and older in Xiangyang in 2013 (n = 20,218) and 2023 (n = 63,517). Latent Class Analysis was used to analyze changes in the patterns of multimorbidity, gray correlation analysis and ordered logistics model were used to assess the association of multimorbidity patterns with medical expenses. The diagnosis and classification of chronic diseases were based on the International Classification of Diseases, Tenth Revision codes (ICD-10). Results: The detection rate of chronic disease multimorbidity has increased (70.74 vs. 76.63%, p < 0.001), and multimorbidity patterns have increased from 6 to 9 (2013: Malignant tumors pattern, non-specific multimorbidity pattern, ischemic heart disease + hypertension pattern, cerebral infarction + hypertension pattern, kidney disease + hypertension pattern, lens disease + hypertension pattern; new in 2023: Nutritional metabolism disorders + hypertension pattern, chronic lower respiratory diseases + malignant tumors pattern, and gastrointestinal diseases pattern) in China. The medical cost of all multimorbidity patients have been reduced between 2013 and 2023 (RMB: 8216.74 vs. 7247.96, IQR: 5802.28-15,737 vs. 5014.63-15434.06). The top three specific multimorbidity patterns in both surveys were malignancy tumor pattern, ischemic heart disease + hypertension pattern, and cerebral infarction + hypertension pattern. Hypertension and type 2 diabetes are important components of multimorbidity patterns. Compared with patients with a single disease, only lens disorders + hypertension pattern were at risk of higher medical costs in 2013 (aOR:1.23, 95% CI: 1.03, 1.47), whereas all multimorbidity patterns were significantly associated with increased medical costs in 2023, except for lens disorders + hypertension (aOR:0.35, 95% CI: 0.32, 0.39). Moreover, the odds of higher medical costs were not consistent across multimorbidity patterns. Among them, ischemic heart disease + hypertension pattern [adjusted odds ratio (aOR):4.66, 95%CI: 4.31, 5.05] and cerebral infarction + hypertension pattern (aOR: 3.63, 95% CI: 3.35, 3.92) were the two patterns with the highest risk. Meanwhile, men (aOR:1.12, 95CI:1.09, 1.16), no spouse (aOR:1.09, 95CI: 1.03, 1.16) had a positive effect on medical costs, while patients with total self-pay (aOR: 0.45, 95CI: 0.29, 0.70), no surgery (aOR: 0.05, 95CI: 0.05, 0.05), rural residence (aOR: 0.92, 95CI: 0.89, 0.95), hospitalization days 1-5 (aOR: 0.04, 95CI: 0.04, 0.04), and hospitalization days 6-9 (aOR: 0.15, 95CI: 0.15, 0.16) had a negative impact on medical costs. Conclusion: Multimorbidity patterns among middle-aged and older adults in China have diversified over the past decade and are associated with rising health care costs in China. Smart, decisive and comprehensive policy and care interventions are needed to effectively manage NCDS and their risk factors and to reduce the economic burden of multimorbidity on patients and the country.


Assuntos
Custos de Cuidados de Saúde , Multimorbidade , Humanos , Estudos Transversais , China/epidemiologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Custos de Cuidados de Saúde/estatística & dados numéricos , Doença Crônica/epidemiologia , Idoso de 80 Anos ou mais , Inquéritos e Questionários , População do Leste Asiático
12.
J Neurointerv Surg ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043583

RESUMO

BACKGROUND: Valvular diseases are widely recognized as important etiologies for large vessel occlusion stroke (LVO) but their impact on outcomes among patients with LVO receiving endovascular treatment (EVT) are less well delineated. METHODS: This study was a post hoc exploratory analysis of the RESCUE-BT trial, DEVT trial and BASILAR prospective registry. Outcome measures included the modified Rankin Scale (mRS) score at 90 days, symptomatic intracranial hemorrhage, and post-stroke early acute heart failure (EAHF). Chronic significant mitral regurgitation (csMR) was defined as a long-existing mitral regurgitation (MR) with moderate-to-severe MR grade examined by the transthoracic echocardiography. Adjusted odds ratio (aOR) and 95% confidence interval (CI) were obtained by logistic regression models. RESULTS: Among 2011 patients in these three studies, 837 individuals receiving EVT with available information for valvular status were included in this study. In all categories of chronic valvular disorders, only csMR was related to very poor outcomes (mRS 5-6, aOR 2.76 (95% CI 1.59 to 4.78), P<0.001). CsMR (aOR 7.65 (95% CI 4.33 to 13.49), P<0.001) was an independent predictor of post-stroke EAHF. Mediation analysis showed that csMR increased EAHF instead of reocclusion events or venous thrombosis mediated its effects on functional outcome (49.50% (95% CI 24.83% to 90.00%)). Identical results of csMR on clinical outcomes and post-stroke EAHF were detected in novel cohorts constructed by propensity score matching and sensitivity analysis. CONCLUSION: Our study demonstrated that csMR was a mediator of heart-brain interaction associated with poor outcomes of LVO after EVT by increasing the frequency of post-stroke EAHF. Replication of these findings in a larger cohort is warranted.

14.
Inorg Chem ; 63(29): 13558-13567, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38962945

RESUMO

The α-diimine-ligated Zn-Zn-bonded compound [K(THF)2]2[LZn-ZnL] (1, L = [(2,6-iPr2C6H3)NC(Me)]22-) displays diverse reactivities toward a variety of ketones. In the reaction of 1 with benzophenone or 4,4'-di-tert-butylbenzophenone, a multielectron transfer process was observed to give bimetallic (Zn/K) complexes with both ketyl radical fragments and C-C coupled pinacolate moieties (products 2 and 3). In contrast, treating 1 with 9-fluorenone only afforded pinacolate complex 5. Moreover, the reactions of 1 with N- or O-heterocycle-functionalized ketones, i.e., di(2-pyridyl)ketone, 2,2-pyrrolidinone, 9-xanthenone, or 10-methyl-9(10H)-acridone, were also carried out. Besides different transformations of the ketone moiety, the heteroatoms (nitrogen or oxygen) are also involved in coordination with zinc or potassium ions, yielding discrete aggregates or polymeric structures of products 6-9.

15.
J Virol ; 98(7): e0033424, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38829137

RESUMO

Porcine deltacoronavirus (PDCoV) is an enteric pathogenic coronavirus that causes acute and severe watery diarrhea in piglets and has the ability of cross-species transmission, posing a great threat to swine production and public health. The interferon (IFN)-mediated signal transduction represents an important component of virus-host interactions and plays an essential role in regulating viral infection. Previous studies have suggested that multifunctional viral proteins encoded by coronaviruses antagonize the production of IFN via various means. However, the function of these viral proteins in regulating IFN-mediated signaling pathways is largely unknown. In this study, we demonstrated that PDCoV and its encoded nucleocapsid (N) protein antagonize type I IFN-mediated JAK-STAT signaling pathway. We identified that PDCoV infection stimulated but delayed the production of IFN-stimulated genes (ISGs). In addition, PDCoV inhibited JAK-STAT signal transduction by targeting the nuclear translocation of STAT1 and ISGF3 formation. Further evidence showed that PDCoV N is the essential protein involved in the inhibition of type I IFN signaling by targeting STAT1 nuclear translocation via its C-terminal domain. Mechanistically, PDCoV N targets STAT1 by interacting with it and subsequently inhibiting its nuclear translocation. Furthermore, PDCoV N inhibits STAT1 nuclear translocation by specifically targeting KPNA2 degradation through the lysosomal pathway, thereby inhibiting the activation of downstream sensors in the JAK-STAT signaling pathway. Taken together, our results reveal a novel mechanism by which PDCoV N interferes with the host antiviral response.IMPORTANCEPorcine deltacoronavirus (PDCoV) is a novel enteropathogenic coronavirus that receives increased attention and seriously threatens the pig industry and public health. Understanding the underlying mechanism of PDCoV evading the host defense during infection is essential for developing targeted drugs and effective vaccines against PDCoV. This study demonstrated that PDCoV and its encoded nucleocapsid (N) protein antagonize type I interferon signaling by targeting STAT1, which is a crucial signal sensor in the JAK-STAT signaling pathway. Further experiments suggested that PDCoV N-mediated inhibition of the STAT1 nuclear translocation involves the degradation of KPNA2, and the lysosome plays a role in KPNA2 degradation. This study provides new insights into the regulation of PDCoV N in the JAK-STAT signaling pathway and reveals a novel mechanism by which PDCoV evades the host antiviral response. The novel findings may guide us to discover new therapeutic targets and develop live attenuated vaccines for PDCoV infection.


Assuntos
Deltacoronavirus , Proteínas do Nucleocapsídeo , Fator de Transcrição STAT1 , Transdução de Sinais , Animais , Suínos , Fator de Transcrição STAT1/metabolismo , Deltacoronavirus/metabolismo , Proteínas do Nucleocapsídeo/metabolismo , Humanos , Janus Quinases/metabolismo , Doenças dos Suínos/virologia , Doenças dos Suínos/metabolismo , alfa Carioferinas/metabolismo , Interferon Tipo I/metabolismo , Infecções por Coronavirus/virologia , Infecções por Coronavirus/metabolismo , Células HEK293 , Linhagem Celular , Proteólise , Interações Hospedeiro-Patógeno
16.
Microbiol Spectr ; 12(8): e0031124, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-38916312

RESUMO

Helicobacter pylori is a microaerophilic Gram-negative bacterium that resides in the human stomach and is classified as a class I carcinogen for gastric cancer. Numerous studies have demonstrated that H. pylori infection plays a role in regulating the function of host cells, thereby contributing to the malignant transformation of these cells. However, H. pylori infection is a chronic process, and short-term cellular experiments may not provide a comprehensive understanding of the in vivo situation, especially when considering the lower oxygen levels in the human stomach. In this study, we aimed to investigate the mechanisms underlying gastric cell dysfunction after prolonged exposure to H. pylori under hypoxic conditions. We conducted a co-culture experiment using the gastric cell line GES-1 and H. pylori for 30 generations under intermittent hypoxic conditions. By closely monitoring cell proliferation, migration, invasion, autophagy, and apoptosis, we revealed that sustained H. pylori stimulation under hypoxic conditions significantly influences the function of GES-1 cells. This stimulation induces epithelial-mesenchymal transition and contributes to the propensity for malignant transformation of gastric cells. To confirm the in vitro results, we conducted an experiment involving Mongolian gerbils infected with H. pylori for 85 weeks. All the results strongly suggest that the Nod1 receptor signaling pathway plays a crucial role in H. pylori-related apoptosis and autophagy. In summary, continuous stimulation by H. pylori affects the functioning of gastric cells through the Nod1 receptor signaling pathway, increasing the likelihood of cell carcinogenesis. The presence of hypoxic conditions further exacerbates this process.IMPORTANCEDeciphering the collaborative effects of Helicobacter pylori infection on gastric epithelial cell function is key to unraveling the development mechanisms of gastric cancer. Prior research has solely examined the outcomes of short-term H. pylori stimulation on gastric epithelial cells under aerobic conditions, neglecting the bacterium's nature as a microaerophilic organism that leads to cancer following prolonged stomach colonization. This study mimics a more genuine in vivo infection scenario by repeatedly exposing gastric epithelial cells to H. pylori under hypoxic conditions for up to 30 generations. The results show that chronic exposure to H. pylori in hypoxia substantially increases cell migration, invasion, and epithelial-mesenchymal transition, while suppressing autophagy and apoptosis. This highlights the significance of hypoxic conditions in intensifying the carcinogenic impact of H. pylori infection. By accurately replicating the in vivo gastric environment, this study enhances our comprehension of H. pylori's pathogenic mechanisms in gastric cancer.


Assuntos
Transformação Celular Neoplásica , Células Epiteliais , Transição Epitelial-Mesenquimal , Mucosa Gástrica , Gerbillinae , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Helicobacter pylori/patogenicidade , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Animais , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Humanos , Células Epiteliais/microbiologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Hipóxia/microbiologia , Linhagem Celular , Proliferação de Células , Apoptose , Movimento Celular , Autofagia , Estômago/microbiologia , Estômago/patologia
17.
Phytochemistry ; 225: 114197, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38945281

RESUMO

Five undescribed monoterpene-chalcone conjugates (1-5), one undescribed hypothetical precursor of diarylheptanoid (6), two undescribed diarylheptanoids (7-8), and fourteen known compounds (9-22) were isolated from the seeds of Alpinia katsumadai. Their structures were elucidated through the interpretation of HRESIMS, NMR, ECD, and X-ray diffraction data. MTT assays on human cancer cell lines (HepG2, A549, SGC7901, and SW480) revealed that compounds 3-8, 11, and 13 exhibited broad-spectrum antiproliferative activities with IC50 values ranging from 3.59 to 21.78 µM. B cell lymphoma 2 was predicted as the target of sumadain C (11) by network pharmacology and verified by homogeneous time-resolved fluorescence assay and molecular docking.


Assuntos
Alpinia , Antineoplásicos Fitogênicos , Proliferação de Células , Diarileptanoides , Ensaios de Seleção de Medicamentos Antitumorais , Monoterpenos , Sementes , Alpinia/química , Humanos , Diarileptanoides/química , Diarileptanoides/farmacologia , Diarileptanoides/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Sementes/química , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Monoterpenos/química , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Relação Estrutura-Atividade , Chalconas/química , Chalconas/farmacologia , Chalconas/isolamento & purificação , Chalcona/química , Chalcona/farmacologia , Chalcona/isolamento & purificação , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Simulação de Acoplamento Molecular
18.
Front Aging Neurosci ; 16: 1403077, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903900

RESUMO

Introduction: Alzheimer's disease (AD) is the most widespread neurodegenerative disease in the world. Previous studies have shown that peripheral immune dysregulation plays a paramount role in AD, but whether there is a protective causal relationship between peripheral immunophenotypes and AD risk remains ambiguous. Methods: Two-sample Mendelian randomization (MR) was performed using large genome-wide association study (GWAS) genetic data to assess causal effects between peripheral immunophenotypes and AD risk. Utilizing the genetic associations of 731 immune cell traits as exposures. We adopted the inverse variance weighted method as the primary approach. The Weighted median and MR-Egger regression methods were employed as supplements. Various sensitivity analyses were performed to assess the robustness of the outcomes. Results: Based on the IVW method, we identified 14 immune cell traits that significantly reduced the risk of AD, of which six demonstrated statistical significance in both IVW and Weighted median methods. Among the seven immune traits, four were related to regulatory T (Treg) cells : (1) CD25++ CD45RA- CD4 not regulatory T cell % T cell (odds ratio (OR) [95% confidence interval (CI)] = 0.96 [0.95, 0.98], adjusted P = 1.17E-02), (2) CD25++ CD45RA- CD4 not regulatory T cell % CD4+ T cell (OR [95% CI] = 0.97 [0.96, 0.99], adjusted P = 3.77E-02), (3) Secreting CD4 regulatory T cell % CD4 regulatory T cell (OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E-03), (4) Activated & secreting CD4 regulatory T cell % CD4 regulatory T cell(OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E-03). In addition, HLA DR++ monocyte % monocyte (OR [95% CI] = 0.93 [0.89, 0.98], adjusted P = 4.87E-02) was associated with monocytes, and HLA DR on myeloid Dendritic Cell (OR [95% CI] = 0.93 [0.89, 0.97], adjusted P = 1.17E-02) was related to dendritic cells (DCs). Conclusion: These findings enhance the comprehension of the protective role of peripheral immunity in AD and provide further support for Treg and monocyte as potential targets for immunotherapy in AD.

19.
Int J Biol Macromol ; 274(Pt 1): 133334, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38908626

RESUMO

Tannic acid, a bioactive polyphenol found in various phytogenic foods and medicinal plants, has potential prevention effects on colitis, though more evidence and mechanistic studies are required to substantiate this. In this study, we investigated the effects of different doses from 0 to 3 mg/mL of tannic acid on mice, ultimately selecting a dose of 3 mg/mL for the anti-colitis trial based on growth and intestinal morphology assessments. Using the DSS-induced colitis model, we found that tannic acid may alleviate colitis by inhibiting the IL-17 - NF-κB p65 signaling pathway and modulating epigenetic pathways, particularly methylation modifications. Additionally, tannic acid altered the gut microbiota, increasing the abundances of Prevotella, Eubacterium_siraeum_group, and Enterorhabdus in the colon. Supplementation with Eubacterium siraeum via gavage also inhibited colitis, accompanied by increased folate and methylation regulators in the colon. These findings suggest that tannic acid may inhibit colitis through the suppression of the IL-17 - NF-κB pathway and the enhancement of microbiota-mediated methylation pathways.


Assuntos
Colite , Microbioma Gastrointestinal , Interleucina-17 , NF-kappa B , Transdução de Sinais , Taninos , Animais , Taninos/farmacologia , Colite/induzido quimicamente , Colite/metabolismo , Colite/tratamento farmacológico , Colite/microbiologia , Camundongos , NF-kappa B/metabolismo , Interleucina-17/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Metilação/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Colo/microbiologia , Masculino , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Sulfato de Dextrana , Polifenóis
20.
Nat Commun ; 15(1): 4940, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858370

RESUMO

Dielectric capacitors offer great potential for advanced electronics due to their high power densities, but their energy density still needs to be further improved. High-entropy strategy has emerged as an effective method for improving energy storage performance, however, discovering new high-entropy systems within a high-dimensional composition space is a daunting challenge for traditional trial-and-error experiments. Here, based on phase-field simulations and limited experimental data, we propose a generative learning approach to accelerate the discovery of high-entropy dielectrics in a practically infinite exploration space of over 1011 combinations. By encoding-decoding latent space regularities to facilitate data sampling and forward inference, we employ inverse design to screen out the most promising combinations via a ranking strategy. Through only 5 sets of targeted experiments, we successfully obtain a Bi(Mg0.5Ti0.5)O3-based high-entropy dielectric film with a significantly improved energy density of 156 J cm-3 at an electric field of 5104 kV cm-1, surpassing the pristine film by more than eight-fold. This work introduces an effective and innovative avenue for designing high-entropy dielectrics with drastically reduced experimental cycles, which could be also extended to expedite the design of other multicomponent material systems with desired properties.

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