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1.
Artigo em Inglês | MEDLINE | ID: mdl-38652217

RESUMO

Thrombus age determination in fatal venous thromboembolism cases is an important task for forensic pathologists. In this study, we investigated the time-dependent expressions of formyl peptide receptor 2 (FPR2) and Annexin A1 (ANXA1) in a stasis-induced deep vein thrombosis (DVT) murine model, with the aim of obtaining useful information for thrombus age timing. A total of 75 ICR mice were randomly classified into thrombosis group and control group. In thrombosis group, a DVT model was established by ligating the inferior vena cava (IVC) of mice, and thrombosed IVCs were harvested at 1, 3, 5, 7, 10, 14, and 21 days after modeling. In control group, IVCs without thrombosis were taken as control samples. The expressions of FPR2 and ANXA1 during thrombosis were detected using immunohistochemistry and double immunofluorescence staining. Their protein and mRNA levels in the samples were determined by Western blotting and quantitative real-time PCR. The results reveal that FPR2 was predominantly expressed by intrathrombotic neutrophils and macrophages. ANXA1 expression in the thrombi was mainly distributed in neutrophils, endothelial cells of neovessels, and fibroblastic cells. After thrombosis, the expressions of FPR2 and ANXA1 were time-dependently up-regulated. The percentage of FPR2-positive cells and the level of FPR2 protein significantly elevated at 1, 3, 5 and 7 days after IVC ligation as compared to those at 10, 14 and 21 days after ligation (p < 0.05). Moreover, the mRNA level of FPR2 were significantly higher at 5 days than that at the other post-ligation intervals (p < 0.05). Besides, the levels of ANXA1 mRNA and protein peaked at 10 and 14 days after ligation, respectively. A significant increase in the mRNA level of ANXA1 was found at 10 and 14 days as compared with that at the other post-ligation intervals (p < 0.01). Our findings suggest that FPR2 and ANXA1 are promising as useful markers for age estimation of venous thrombi.

2.
Sci Total Environ ; 928: 172336, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38614350

RESUMO

Nitrous acid (HONO) is an important precursor of the hydroxyl radical (OH) and plays a vital role in atmospheric photochemistry and nitrogen cycling. Soil emissions have been considered as a potential source of HONO. Lately, the HONO emission via soil-atmosphere exchange (ESA-exchange) from soil nitrite has been validated and quantified through chamber experiments, but has not been assessed in the real atmosphere. We coupled ESA-exchange and the other seven potential sources of HONO (i.e., traffic, indoor and soil bacterial emissions, heterogeneous reactions on ground and aerosol surfaces, nitrate photolysis, and acid displacement) into the Weather Research and Forecasting model with Chemistry (WRF-Chem), and found that diurnal variations of the soil emission flux at the Wangdu site were well simulated. During the non-fertilization period, ESA-exchange contributed ∼28 % and âˆ¼35 % of nighttime and daytime HONO, respectively, and enhanced the net ozone (O3) production rate by ∼8 % across the North China Plain (NCP). During the preintensive/intensive fertilization period, the maximum ESA-Exchange contributions attained ∼70 %/83 % of simulated HONO in the afternoon across the NCP, definitely asserting its dominance in HONO production. ESA-Exchange enhanced the OH production rate via HONO photolysis by ∼3.5/7.0 times, and exhibited an increase rate of ∼13 %/20 % in the net O3 production rate across the NCP. The total enhanced O3 due to the eight potential HONO sources ranged from ∼2 to 20 ppb, and ESA-exchange produced O3 enhancements of ∼1 to 6 ppb over the three periods. Remarkably, the average contribution of ESA-exchange to the total O3 enhancements remained ∼30 %. This study suggests that ESA-exchange should be included in three-dimensional chemical transport models and more field measurements of soil HONO emission fluxes and soil nitrite levels are urgently required.

3.
J Thorac Dis ; 16(2): 935-947, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38505025

RESUMO

Background: Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular tumour, and its early diagnosis remains challenging. This study aims to comprehensively analyse the imaging features of PEH and develop a model for predicting PEH. Methods: Retrospective and pooled analyses of imaging findings were performed in PEH patients at our center (n=25) and in published cases (n=71), respectively. Relevant computed tomography (CT) images were extracted and used to build a deep learning model for PEH identification and differentiation from other diseases. Results: In this study, bilateral multiple nodules/masses (n=19) appeared to be more common with most nodules less than 2 cm. In addition to the common types and features, the pattern of mixed type (n=4) and isolated nodules (n=4), punctate calcifications (5/25) and lymph node enlargement were also observed (10/25). The presence of pleural effusion is associated with a poor prognosis in PEH. The deep learning model, with an area under the receiver operating characteristic curve (AUC) of 0.71 [95% confidence interval (CI): 0.69-0.72], has a differentiation accuracy of 100% and 74% for the training and test sets respectively. Conclusions: This study confirmed the heterogeneity of the imaging findings in PEH and showed several previously undescribed types and features. The current deep learning model based on CT has potential for clinical application and needs to be further explored in the future.

4.
Front Immunol ; 15: 1384548, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533512

RESUMO

Introduction: Colorectal cancer (CRC) presents a substantial challenge characterized by unacceptably high mortality and morbidity, primarily attributed to delayed diagnosis and reliance on palliative care. The immune response of the host plays a pivotal role in carcinogenesis, with IL-38 emerging as a potential protective factor in CRC. However, the precise involvement of IL-38 among various leucocytes, its interactions with PD-1/PD-L1, and its impact on metastasis require further elucidation. Results: Our investigation revealed a significant correlation between IL-38 expression and metastasis, particularly concerning survival and interactions among diverse leucocytes within draining lymph nodes. In the mesentery lymph nodes, we observed an inverse correlation between IL-38 expression and stages of lymph node invasions (TNM), invasion depth, distance, and differentiation. This aligns with an overall survival advantage associated with higher IL-38 expression in CRC patients' nodes compared to lower levels, as well as elevated IL-38 expression on CD4+ or CD8+ cells. Notably, a distinct subset of patients characterized by IL-38high/PD-1low expression exhibited superior survival outcomes compared to other combinations. Discussion: Our findings demonstrate that IL-38 expression in colorectal regional nodes from CRC patients is inversely correlated with PD-1/PD-L1 but positively correlated with infiltrating CD4+ or CD8+ lymphocytes. The combined assessment of IL-38 and PD-1 expression in colorectal regional nodes emerges as a promising biomarker for predicting the prognosis of CRC.


Assuntos
Antígeno B7-H1 , Neoplasias Colorretais , Humanos , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Antígeno CTLA-4/metabolismo , Relevância Clínica , Fatores de Transcrição Forkhead/metabolismo , Linfonodos , Interleucinas/metabolismo
5.
Front Immunol ; 15: 1322256, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524127

RESUMO

Introduction: Wound healing poses a clinical challenge in diabetes mellitus (DM) due to compromised host immunity. CD64, an IgG-binding Fcgr1 receptor, acts as a pro-inflammatory mediator. While its presence has been identified in various inflammatory diseases, its specific role in wound healing, especially in DM, remains unclear. Objectives: We aimed to investigate the involvement of CD64 in diabetic wound healing using a DM animal model with CD64 KO mice. Methods: First, we compared CD64 expression in chronic skin ulcers from human DM and non-DM skin. Then, we monitored wound healing in a DM mouse model over 10 days, with or without CD64 KO, using macroscopic and microscopic observations, as well as immunohistochemistry. Results: CD64 expression was significantly upregulated (1.25-fold) in chronic ulcerative skin from DM patients compared to non-DM individuals. Clinical observations were consistent with animal model findings, showing a significant delay in wound healing, particularly by day 7, in CD64 KO mice compared to WT mice. Additionally, infiltrating CD163+ M2 macrophages in the wounds of DM mice decreased significantly compared to non-DM mice over time. Delayed wound healing in DM CD64 KO mice correlated with the presence of inflammatory mediators. Conclusion: CD64 seems to play a crucial role in wound healing, especially in DM conditions, where it is associated with CD163+ M2 macrophage infiltration. These data suggest that CD64 relies on host immunity during the wound healing process. Such data may provide useful information for both basic scientists and clinicians to deal with diabetic chronic wound healing.


Assuntos
Diabetes Mellitus Experimental , Úlcera Cutânea , Cicatrização , Animais , Camundongos , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Macrófagos/metabolismo , Pele/metabolismo , Cicatrização/genética
6.
BMC Cancer ; 24(1): 365, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515013

RESUMO

BACKGROUND: To assess the long-term association between organised colorectal cancer (CRC) screening strategies and CRC-relate mortality. METHODS: We systematically reviewed studies on organised CRC screening through PubMed, Ovid Medline, Embase and Cochrane from the inception. We retrieved characteristics of organised CRC screening from included literature and matched mortality (over 50 years) of those areas from the International Agency for Research on Cancer in May 2023. The variations of mortality were reported via the age-standardised mortality ratio. A random-effects model was used to synthesis results. RESULTS: We summarised 58 organised CRC screening programmes and recorded > 2.7 million CRC-related deaths from 22 countries where rollout screening programmes were performed. The CRC screening strategy with faecal tests (guaiac faecal occult blood test (gFOBT) or faecal immunochemical tests (FIT)) or colonoscopy as the primary screening offer was associated with a 41.8% reduction in mortality, which was higher than those offered gFOBT (4.4%), FIT (16.7%), gFOBT or FIT (16.2%), and faecal tests (gFOBT or FIT) or flexible sigmoidoscopy (16.7%) as primary screening test. The longer duration of screening was associated with a higher reduction in the pooled age-standardised mortality ratio. In particular, the pooled age-standardised mortality ratio became non-significant when the screening of FIT was implemented for less than 5 years. CONCLUSIONS: A CRC screening programme running for > 5 years was associated with a reduction of CRC-related mortality. Countries with a heavy burden of CRC should implement sustainable, organised screening providing a choice between faecal tests and colonoscopy as a preferred primary test.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Pré-Escolar , Detecção Precoce de Câncer/métodos , Guaiaco , Colonoscopia/métodos , Programas de Rastreamento/métodos , Neoplasias Colorretais/diagnóstico , Sangue Oculto
7.
Sensors (Basel) ; 24(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38475214

RESUMO

Motor imagery (MI)-based brain-computer interface (BCI) has emerged as a crucial method for rehabilitating stroke patients. However, the variability in the time-frequency distribution of MI-electroencephalography (EEG) among individuals limits the generalizability of algorithms that rely on non-customized time-frequency segments. In this study, we propose a novel method for optimizing time-frequency segments of MI-EEG using the sparrow search algorithm (SSA). Additionally, we apply a correlation-based channel selection (CCS) method that considers the correlation coefficient of features between each pair of EEG channels. Subsequently, we utilize a regularized common spatial pattern method to extract effective features. Finally, a support vector machine is employed for signal classification. The results on three BCI datasets confirmed that our algorithm achieved better accuracy (99.11% vs. 94.00% for BCI Competition III Dataset IIIa, 87.70% vs. 81.10% for Chinese Academy of Medical Sciences dataset, and 87.94% vs. 81.97% for BCI Competition IV Dataset 1) compared to algorithms with non-customized time-frequency segments. Our proposed algorithm enables adaptive optimization of EEG time-frequency segments, which is crucial for the development of clinically effective motor rehabilitation.


Assuntos
Interfaces Cérebro-Computador , Acidente Vascular Cerebral , Humanos , Imaginação , Imagens, Psicoterapia/métodos , Eletroencefalografia/métodos , Algoritmos
8.
Am J Chin Med ; 52(2): 493-512, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38480500

RESUMO

Eugenol (EU) has been shown to ameliorate experimental colitis due to its anti-oxidant and anti-inflammatory bioactivities. In this study, DSS-induced acute colitis was established and applied to clarify the regulation efficacy of EU on intestinal barrier impairment and macrophage polarization imbalance along with the inflammatory response. Besides, the adjusting effect of EU on macrophages was further investigated in vitro. The results confirmed that EU intervention alleviated DSS-induced colitis through methods such as restraining weight loss and colonic shortening and decreasing DAI scores. Microscopic observation manifested that EU maintained the intestinal barrier integrity in line with the mucus barrier and tight junction protection. Furthermore, EU intervention significantly suppressed the activation of TLR4/MyD88/NF-[Formula: see text]B signaling pathways and pro-inflammatory cytokines gene expressions, while enhancing the expressions of anti-inflammatory cytokines. Simultaneously, WB and FCM analyses of the CD86 and CD206 showed that EU could regulate the DSS-induced macrophage polarization imbalance. Overall, our data further elucidated the mechanism of EU's defensive effect on experimental colitis, which is relevant to the protective efficacy of intestinal barriers, inhibition of oxidative stress and excessive inflammatory response, and reprogramming of macrophage polarization. Hence, this study may facilitate a better understanding of the protective action of the EU against UC.


Assuntos
Colite , Eugenol , Animais , Camundongos , Eugenol/farmacologia , Eugenol/uso terapêutico , Fator 88 de Diferenciação Mieloide/genética , Receptor 4 Toll-Like/genética , Colite/induzido quimicamente , Colite/tratamento farmacológico , Proteínas Adaptadoras de Transdução de Sinal , Colo , Citocinas , Macrófagos , Anti-Inflamatórios , Sulfato de Dextrana , NF-kappa B , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
9.
Health Sci Rep ; 7(3): e1964, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38476586

RESUMO

Background and Aims: Unhealthy diets were found to be the main contributor to the overweight problem among adolescents. In this study, we aim to identify the factors causing unhealthy eating habits in adolescents. Methods: School-aged children and adolescents participated in this cross-sectional observational study with additional school and parental consent. A self-administered survey was conducted by 30 primary schools and 25 secondary schools. Participants were asked about the frequency of consuming unhealthy food and the types of unhealthy food consumed. A descriptive analysis was performed to demonstrate the proportions of characteristics. The prevalence of the outcome among participants of various factors was also analyzed using separate binary regression models. Results: A total of 4884 responses were collected. Among primary school students (grade 4, mean age: 10.06), people who (1) were actively gaining weight (aOR: 1.651, 95% CI 1.006-2.708, p = 0.047), (2) went to bed after 11 p.m. (aOR: 1.652, 95% CI 1.065-2.563, p = 0.025), (3) had more than 2 h of gaming (aOR: 2.833, 95% CI 1.913-4.195, p < 0.001), (4) suffered from self-report depressive symptoms (aOR: 1.753, 95% CI 1.233-2.493, p = 0.002) was more likely to consume unhealthy food. As for secondary school students (grade 3, mean age: 15.28), (1) males (aOR: 1.266, 95% CI 1.0004-1.601, p = 0.0496), (2) average-to-high socioeconomic status (Average: aOR: 1.471, 95% CI 1.115-1.941, p = 0.006; High: aOR: 2.253, 95% CI 1.585-3.202. p < 0.001), (3) having more than 2 h of gaming (aOR: 1.342, 95% CI 1.069-1.685, p = 0.011), (4) suffering from psychological distress (aOR: 1.395, 95% CI 1.051-1.852, p = 0.021) were associated with the increased odds of consuming unhealthy food. Conclusion: Several lifestyle and health factors were significantly associated with unhealthy eating behaviors in school-aged children and adolescents in Hong Kong, sharing similarities with many other countries. In conjunction with implementing a policy that addresses factors for unhealthy eating habits, further research should investigate potential interventions targeting these factors to ultimately tackle the overweight and obesity concern for children and adolescents in Hong Kong.

10.
J Cheminform ; 16(1): 29, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475916

RESUMO

Chemical structure segmentation constitutes a pivotal task in cheminformatics, involving the extraction and abstraction of structural information of chemical compounds from text-based sources, including patents and scientific articles. This study introduces a deep learning approach to chemical structure segmentation, employing a Vision Transformer (ViT) to discern the structural patterns of chemical compounds from their graphical representations. The Chemistry-Segment Anything Model (ChemSAM) achieves state-of-the-art results on publicly available benchmark datasets and real-world tasks, underscoring its effectiveness in accurately segmenting chemical structures from text-based sources. Moreover, this deep learning-based approach obviates the need for handcrafted features and demonstrates robustness against variations in image quality and style. During the detection phase, a ViT-based encoder-decoder model is used to identify and locate chemical structure depictions on the input page. This model generates masks to ascertain whether each pixel belongs to a chemical structure, thereby offering a pixel-level classification and indicating the presence or absence of chemical structures at each position. Subsequently, the generated masks are clustered based on their connectivity, and each mask cluster is updated to encapsulate a single structure in the post-processing workflow. This two-step process facilitates the effective automatic extraction of chemical structure depictions from documents. By utilizing the deep learning approach described herein, it is demonstrated that effective performance on low-resolution and densely arranged molecular structural layouts in journal articles and patents is achievable.

11.
Cancer Med ; 13(5): e7056, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38477498

RESUMO

BACKGROUND: Non-Hodgkin lymphoma (NHL) accounts for 90% of all malignant lymphomas. This study aimed to evaluate the global incidence, mortality, associated risk factors, and temporal trends of NHL by sex, age, and country. METHODS: Data from 185 countries globally were used for analysis. NHL incidence and mortality were collected via the GLOBOCAN (2020), CI5 series I-X, WHO mortality database, the Nordic Cancer Registries, and the SEER Program. The WHO Global Health Observatory provided country-level, age-standardized prevalence of lifestyle and metabolic risk factors. Trends were examined and reported based on average annual percentage change (AAPC) calculated using Joinpoint regression analysis. Incidence and AAPC are based on data for the last 10 years across countries. RESULTS: Globally, age-standardized incidence and mortality rates for NHL were recorded at 5.8 and 2.6 per 100,000 individuals, respectively. At country-level, NHL incidence was significantly associated with various factors, including HDI (Human Development Index), GDP per capita, prevalence of tobacco and alcohol consumption, sedentary lifestyle, obesity, hypertension, diabetes and hypercholesterolaemia. Rising trend in NHL incidence was observed, with the highest increase recorded in Estonia (AAPCmale = 4.15, AAPCfemale = 5.14), Belarus (AAPCfemale = 5.13), and Lithuania (AAPCfemale = 4.68). While overall NHL mortality has been decreasing, certain populations experienced increased mortality over the decade. In Thailand, AAPC for mortality was 31.28% for males and 30.26% for females. Estonia saw an AAPC of 6.46% for males, while Slovakia experienced an AAPC of 4.24% for females. Colombia's AAPC was 1.29% for males and 1.51% for females. CONCLUSIONS: This study indicates a rising trend of NHL incidence over the past decade- particularly in developed countries, older males, and younger populations. Further research should investigate deeper insights into specific etiology and prognosis of NHL across subtypes, and potential contributors towards these epidemiologic trends.


Assuntos
Linfoma não Hodgkin , Linfoma , Humanos , Masculino , Feminino , Linfoma não Hodgkin/epidemiologia , Linfoma/epidemiologia , Incidência , Sistema de Registros , Fatores de Risco , Saúde Global
12.
Eur J Gen Pract ; 30(1): 2308740, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38407121

RESUMO

BACKGROUND: Reducing avoidable hospital admissions is a global healthcare priority, with optimal primary care recognised as pivotal for achieving this objective. However, in developing systems like China, where primary care is evolving without compulsory gatekeeping, the relationship between patient-perceived primary care quality and hospital utilisation remains underexplored. OBJECTIVES: This study aimed to explore the association between patient-perceived primary care quality and self-reported hospital utilisation in China. METHODS: Data were collected from 16 primary care settings. Patient-perceived quality of primary care was measured using the Assessment Survey of Primary Care scale across six domains (first-contact care, continuity, comprehensiveness, accessibility, coordination, and patient-centredness). Hospital utilisation included patient self-reported outpatient visits, hospital admissions, and emergency department (ED) visits in the last six months. Logistic regression analyses were examined associations between self-reported hospital utilisation and perceived primary care quality adjusted for potential confounders. RESULTS: Of 1,185 patients recruited, 398 (33.6%) reported hospital utilisation. Logistic regression analyses showed that higher total scores for patient-perceived quality of primary care were associated with decreased odds of hospital utilisation (adjusted odds ratio(AOR): 0.417, 95% confidence interval (CI): 0.308-0.565), outpatient visits (AOR: 0.394, 95% CI: 0.275-0.566) and hospital admissions (AOR: 0.496, 95% CI: 0.276-0.891). However, continuity of care was positively associated with ED visits (AOR: 2.252, 95% CI: 1.051-4.825). CONCLUSION: Enhanced patient-perceived quality of primary care in China is associated with a reduction in self-reported overall hospital utilisation, including outpatient visits and hospital admissions. However, better continuity of care may be associated with increased ED visits. Further research is warranted for precise insights and validation of these findings.


Improved patient-perceived primary care quality in China was linked to lower self-reported hospital utilisation, including outpatient visits and hospital admissions.Better primary care accessibility was associated with decreased self-reported emergency department visits and outpatient visits.Continuity of care showed a positive association with emergency department visits, warranting further research.


Assuntos
Hospitais , Atenção Primária à Saúde , Humanos , Autorrelato , Estudos Transversais , China
13.
Angew Chem Int Ed Engl ; 63(17): e202317794, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38424035

RESUMO

Tin halide perovskites (THPs) have demonstrated exceptional potential for various applications owing to their low toxicity and excellent optoelectronic properties. However, the crystallization kinetics of THPs are less controllable than its lead counterpart because of the higher Lewis acidity of Sn2+, leading to THP films with poor morphology and rampant defects. Here, a colloidal zeta potential modulation approach is developed to improve the crystallization kinetics of THP films inspired by the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. After adding 3-aminopyrrolidine dihydro iodate (APDI2) in the precursor solution to change the zeta potential of the pristine colloids, the total interaction potential energy between colloidal particles with APDI2 could be controllably reduced, resulting in a higher coagulation probability and a lower critical nuclei concentration. In situ laser light scattering measurements confirmed the increased nucleation rate of the THP colloids with APDI2. The resulting film with APDI2 shows a pinhole-free morphology with fewer defects, achieving an impressive efficiency of 15.13 %.

14.
Poult Sci ; 103(4): 103496, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38330890

RESUMO

The avian influenza virus is infected through the mucosal route, thus mucosal barrier defense is very important. While the inactivated H9N2 vaccine cannot achieve sufficient mucosal immunity, adjuvants are needed to induce mucosal and systemic immunity to prevent poultry from H9N2 influenza virus infection. Our previous study found that polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles (AMP-ZnONPs) had immune-enhancing effects in vitro. This study aimed to evaluate the mucosal immune responses of oral whole-inactivated H9N2 virus (WIV)+AMP-ZnONPs and its impact on the animal challenge protection, and the corresponding changes of pulmonary metabolomics after the second immunization. The results showed that compared to the WIV, the combined treatment of WIV and AMP-ZnONPs significantly enhanced the HI titer, IgG and specific sIgA levels, the number of goblet cells and intestinal epithelial lymphocytes (iIELs) as well as the expression of J-chain, polymeric immunoglobulin receptor (pIgR), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and transforming growth factor-ß (TGF-ß). In viral attack experiments, WIV combing with AMP-ZnONPs effectively reduced lung damage and viral titers in throat swabs. Interestingly, significant changes of both the IgA intestinal immune network and PPAR pathway could also be found in the WIV+AMP-ZnONPs group compared to the non-infected group. Taken together, these findings suggest that AMP-ZnONPs can serve as a potential mucosal vaccine adjuvant, thereby avoiding adverse stress and corresponding costs caused by vaccine injection.


Assuntos
Vírus da Influenza A Subtipo H9N2 , Vacinas contra Influenza , Influenza Aviária , Vacinas , Animais , Imunidade nas Mucosas , Galinhas , Anticorpos Antivirais , Adjuvantes Imunológicos/farmacologia , Administração Oral , Vacinas de Produtos Inativados , Influenza Aviária/prevenção & controle
15.
Vaccine ; 42(7): 1549-1560, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38320931

RESUMO

Tumor subunit vaccines have great potential in personalized cancer immunotherapy. They are usually administered with adjuvant owing to their low immunogenicity. Cholera toxin (CT) is a biological adjuvant with diverse biological functions and a long history of use. Our earlier study revealed that a CT-like chimeric protein co-delivered with murine granulocyte-macrophage colony stimulating factor (mGM-CSF) and prostate cancer antigen epitope could co-stimulate dendritic cells (DCs) and enhance cross presentation of tumor epitope. To further study the molecular mechanism of CT-like chimeric protein in cross presentation, major histocompatibility complex class I (MHC I)-restricted epitope 257-264 of ovalbumin (OVAT) was used as a model antigen peptide in this study. Recombinant A subunit and pentameric B subunit of CT protein were respectively genetically constructed and purified. Then both assembled into AB5 chimeric protein in vitro. Three different chimeric biomacromolecules containing mGM-CSF and OVAT were constructed according to the different fusion sites and whether the endoplasmic reticulum (ER) retention sequence was included. It was found that A2 domain and B subunit of CT were both available for loading epitopes and retaining GM1 affinity. The binding activity of GM1 was positively correlated with antigen endocytosis. Once internalized, DCs became mature and cross-presented antigen. KDEL helped the whole molecule to be retained in the ER, and this improved the cross presentation of antigen on MHC I molecules. In conclusion, hexameric CT-like chimeric protein with dual effects of GM1 affinity and ER retention sequence were potential in improvement of cross presentation. The results laid a foundation for designing personalized tumor vaccine based on CT-like chimeric protein molecular structure.


Assuntos
Toxina da Cólera , Neoplasias , Camundongos , Animais , Humanos , Toxina da Cólera/metabolismo , Apresentação Cruzada , Gangliosídeo G(M1)/metabolismo , Gangliosídeo G(M1)/farmacologia , Proteínas Recombinantes/farmacologia , Adjuvantes Imunológicos/farmacologia , Proteínas Recombinantes de Fusão/genética , Epitopos , Apresentação de Antígeno
16.
Entropy (Basel) ; 26(2)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38392427

RESUMO

Compound droplets have received increasing attention due to their applications in many several areas, including medicine and materials. Previous works mostly focused on compound droplets on planar surfaces and, as such, the effects of curved walls have not been studied thoroughly. In this paper, the influence of the properties of curved solid wall (including the shape, curvature, and contact angle) on the wetting behavior of compound droplets is explored. The axisymmetric lattice Boltzmann method, based on the conservative phase field formulation for ternary fluids, was used to numerically study the wetting and spreading of a compound droplet of the Janus type on various curved solid walls at large density ratios, focusing on whether the separation of compound droplets occurs. Several types of wall geometries were considered, including a planar wall, a concave wall with constant curvature, and a convex wall with fixed or variable curvature (specifically, a prolate or oblate spheroid). The effects of surface wettability, interfacial angles, and the density ratio (of droplet to ambient fluid) on the wetting process were also explored. In general, it was found that, under otherwise identical conditions, droplet separation tends to happen more likely on more hydrophilic walls, under larger interfacial angles (measured inside the droplet), and at larger density ratios. On convex walls, a larger radius of curvature of the surface near the droplet was found to be helpful to split the Janus droplet. On concave walls, as the radius of curvature increases from a small value, the possibility to observe droplet separation first increases and then decreases. Several phase diagrams on whether droplet separation occurs during the spreading process were produced for different kinds of walls to illustrate the influences of various factors.

17.
Int J Gen Med ; 17: 471-483, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38344679

RESUMO

Background: Stomach adenocarcinoma (STAD) presents a challenge given its advanced stage at diagnosis and poor prognosis. Integrin subunit alpha 11 (ITGA11) encodes alpha integrin and has been implicated in promoting tumorigenesis and development by participating in cell proliferation and invasion. However, the precise mechanism of ITGA11 in STAD remains unclear. Methods: The differences in ITGA11 expression levels between 375 gastric cancer samples and 32 paracancerous tissue samples from the Cancer Genome Atlas (TCGA) database were examined. The relationship between ITGA11 expression and clinical features and ITGA11 diagnostic and prognostic value were evaluated using the chi-square test and receiver operating characteristic (ROC) assay. Differentially expressed genes were identified based on ITGA11 expression. Subsequently, functional enrichment analyses were conducted using Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis. Furthermore, immune infiltration and the expression of ITGA11-associated immune checkpoints in patients with tumors were assessed using CIBERSORT, single-sample gene set enrichment analysis, and the TIMER database. Drug sensitivity associated with ITGA11 expression was analyzed using the R oncoPredict package to guide treatment decisions. Finally, the difference in ITGA11 expression between cancer tissue and the adjacent tissues was validated using quantitative PCR (qPCR) and immunohistochemistry. Results: The gastric cancer tissue had significantly upregulated ITGA11 expression compared to paracancerous tissues. ITGA11 demonstrated robust diagnostic and prognostic value in gastric cancer (GC) and was an independent risk factor for adverse outcomes. The patients with STAD with elevated ITGA11 expression levels had heightened immune cell infiltration and increased immune checkpoint marker expression. Notably, patients with increased ITGA11 expression demonstrated reduced responsiveness to oxaliplatin and afatinib. Conclusion: The results indicated the pivotal role of ITGA11 in shaping the tumor immune microenvironment, ultimately establishing ITGA11 as an immune-related prognostic predictor within the intricate landscape of STAD.

18.
BMC Genomics ; 25(1): 145, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321406

RESUMO

BACKGROUND: Schizothorax o'connori is an endemic fish distributed in the upper and lower reaches of the Yarlung Zangbo River in China. It has experienced a fourth round of whole gene replication events and is a good model for exploring the genetic differentiation and environmental adaptability of fish in the Qinghai-Tibet Plateau. The uplift of the Qinghai-Tibet Plateau has led to changes in the river system, thereby affecting gene exchange and population differentiation between fish populations. With the release of fish whole genome data, whole genome resequencing has been widely used in genetic evolutionary analysis and screening of selected genes in fish, which can better elucidate the genetic basis and molecular environmental adaptation mechanisms of fish. Therefore, our purpose of this study was to understand the population structure and adaptive characteristics of S. o'connori using the whole-genome resequencing method. RESULTS: The results showed that 23,602,746 SNPs were identified from seven populations, mostly distributed on chromosomes 2 and 23. There was no significant genetic differentiation between the populations, and the genetic diversity was relatively low. However, the Zangga population could be separated from the Bomi, Linzhi, and Milin populations in the cluster analysis. Based on historical dynamics analysis of the population, the size of the ancestral population of S. o'connori was affected by the late accelerated uplift of the Qinghai Tibet Plateau and the Fourth Glacial Age. The selected sites were mostly enriched in pathways related to DNA repair and energy metabolism. CONCLUSION: Overall, the whole-genome resequencing analysis provides valuable insights into the population structure and adaptive characteristics of S. o'connori. There was no obvious genetic differentiation at the genome level between the S. o'connori populations upstream and downstream of the Yarlung Zangbo River. The current distribution pattern and genetic diversity are influenced by the late accelerated uplift of the Qinghai Tibet Plateau and the Fourth Ice Age. The selected sites of S. o'connori are enriched in the energy metabolism and DNA repair pathways to adapt to the low temperature and strong ultraviolet radiation environment at high altitude.


Assuntos
Cyprinidae , Raios Ultravioleta , Animais , Tibet , China , Cyprinidae/genética , Análise de Sequência de DNA
19.
Int J Obes (Lond) ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336864

RESUMO

BACKGROUND: Little is known about the degrees and shapes of associations of changes in obesity indices with cardiovascular disease (CVD) and mortality risks. We aimed to conduct a dose-response meta-analysis for the associations of changes in weight, body mass index (BMI), waist circumference (WC), waist-to-hip ratio, and waist-to-height ratio with CVD events, CVD-specific deaths, and all-cause mortality. METHODS: We searched MEDLINE via OvidSP, Embase via OvidSP, Web of Science, CINAHL, and Scopus for articles published before January 8th, 2023. Dose-response relationships were modeled using the one-stage mixed-effects meta-analysis. Random-effects models were used to pool the relative risk (RR) and 95% confidence interval (CI). RESULTS: We included 122 articles. Weight change was negatively associated with deaths from CVD and any cause, while WC change elevated CVD-specific mortality. Non-linear relationships also confirmed the adverse effects of increased WC on CVD-specific mortality. Additionally, gains of 5 kg in weight and 1 kg/m2 in BMI or more were associated with elevated CVD events, especially among young adults and individuals without CVD. Conversely, reductions of 5 kg in weight and 1 kg/m2 in BMI or more were associated with higher CVD-specific and all-cause deaths than increased counterparts, particularly among old adults and individuals with CVD. Similar non-linear relationships between relative changes in weight and BMI and deaths from CVD and any cause were observed. CONCLUSIONS: The effects of changes in weight and BMI on CVD outcomes were affected by age and cardiovascular health. Tailored weight management and avoidance of increased WC should be recommended.

20.
Polymers (Basel) ; 16(3)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38337293

RESUMO

Excessive settlement of the subgrade seriously reduces the service quality of slab tracks and threatens trains' running safety. While the utilization of foamed polyurethane is recognized as an effective solution, previous research on its expansion mechanism and its impact on track lifting requires further refinement. Accordingly, a series of full-scale tests, including expansion force tests on foamed polyurethane with diverse qualities and lifting tests of polyurethane grouting with varied qualities on the track structure, have been conducted. The expansion development process of foamed polyurethane is meticulously elucidated, and key expansion parameters are analyzed. Simultaneously, this research explores the lifting behavior of foamed polyurethane grouting under the slab tracks, yielding new insights into essential lifting parameters for track formation repair and maintenance. Based on the experimental data, this study proposes new empirical formulas to comprehensively describe both the expansion mechanism of foam polyurethane and its lifting behavior under the slab tracks. The outcomes of this research offer a new breakthrough for the design of lifting mechanism for maintaining slab track structures through the utilization of foam polyurethane slurry grouting, such as determining the optimal grouting quantity. In addition, these results are instrumental to the evaluation of lifting effects and service life, enhancing the circular economy of railway track systems.

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