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1.
Eur Heart J Digit Health ; 5(3): 219-228, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38774374

RESUMEN

Aims: Permanent pacemaker implantation and left bundle branch block are common complications after transcatheter aortic valve replacement (TAVR) and are associated with impaired prognosis. This study aimed to develop an artificial intelligence (AI) model for predicting conduction disturbances after TAVR using pre-procedural 12-lead electrocardiogram (ECG) images. Methods and results: We collected pre-procedural 12-lead ECGs of patients who underwent TAVR at West China Hospital between March 2016 and March 2022. A hold-out testing set comprising 20% of the sample was randomly selected. We developed an AI model using a convolutional neural network, trained it using five-fold cross-validation and tested it on the hold-out testing cohort. We also developed and validated an enhanced model that included additional clinical features. After applying exclusion criteria, we included 1354 ECGs of 718 patients in the study. The AI model predicted conduction disturbances in the hold-out testing cohort with an area under the curve (AUC) of 0.764, accuracy of 0.743, F1 score of 0.752, sensitivity of 0.876, and specificity of 0.624, based solely on pre-procedural ECG images. The performance was better than the Emory score (AUC = 0.704), as well as the logistic (AUC = 0.574) and XGBoost (AUC = 0.520) models built with previously identified high-risk ECG patterns. After adding clinical features, there was an increase in the overall performance with an AUC of 0.779, accuracy of 0.774, F1 score of 0.776, sensitivity of 0.794, and specificity of 0.752. Conclusion: Artificial intelligence-enhanced ECGs may offer better predictive value than traditionally defined high-risk ECG patterns.

3.
Ann Med ; 56(1): 2337739, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38574396

RESUMEN

BACKGROUND AND AIM: This study aims to validate the efficacy of the conventional non-invasive score in predicting significant fibrosis in metabolic-associated fatty liver disease (MAFLD) and to develop a non-invasive prediction model for MAFLD. METHODS: This cross-sectional study was conducted among 7701 participants with MAFLD from August 2018 to December 2023. All participants were divided into a training cohort and a validation cohort. The study compared different subgroups' demographic, anthropometric, and laboratory examination indicators and conducted logistic regression analysis to assess the correlation between independent variables and liver fibrosis. Nomograms were created using the logistic regression model. The predictive values of noninvasive models and nomograms were evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). RESULTS: Four nomograms were developed for the quantitative analysis of significant liver fibrosis risk based on the multivariate logistic regression analysis results. The nomogram's area under ROC curves (AUC) was 0.710, 0.714, 0.748, and 0.715 in overall MAFLD, OW-MAFLD, Lean-MAFLD, and T2DM-MAFLD, respectively. The nomogram had a higher AUC in all MAFLD participants and OW-MAFLD than the other non-invasive scores. The DCA curve showed that the net benefit of each nomogram was higher than that of APRI and FIB-4. In the validation cohort, the AUCs of the nomograms were 0.722, 0.750, 0.719, and 0.705, respectively. CONCLUSION: APRI, FIB-4, and NFS performed poorly predicting significant fibrosis in patients with MAFLD. The new model demonstrated improved diagnostic accuracy and clinical applicability in identifying significant fibrosis in MAFLD.


Asunto(s)
Nomogramas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Estudios Transversales , Cirrosis Hepática/diagnóstico , Antropometría , Área Bajo la Curva , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico
7.
Inflammation ; 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38630167

RESUMEN

Innate immune response is the first line of defense for the host against virus invasion. One important response is the synthesis and secretion of type I interferon (IFN-I) in the virus-infected host cells. Here, we found that respiratory syncytial virus (RSV) infection induced high expression of TRIM25, which belongs to the tripartite motif-containing (TRIM) family of proteins. TRIM25 bound and activated retinoic acid-inducible gene I (RIG-I) by K63-linked ubiquitination. Accordingly, RIG-I mediated the production of IFN-I mainly through the nuclear factor kappa-B (NF-κB) pathway in respiratory epithelial cells. Interestingly, IFN-I, in turn, promoted a high expression of TRIM38 which downregulated the expression of IFN-I by reducing the protein level of RIG-I by K48-linked ubiquitination. More importantly, the binding site of TRIM25 to RIG-I was found in the narrow 25th-43rd amino acid (aa) region of RIG-I N-terminus. In contrast, the binding sites of TRIM38 to RIG-I were found in a much wider amino acid region, which included the binding site of TRIM25 on RIG-I. As a result, TRIM38 inhibits the production of IFN-I by competing with TRIM25 for RIG-I binding. Thus, TRIM38 negatively regulates RIG-I activation to, in turn, downregulate IFN-I expression, thus interfering with host immune response. A negative feedback loop effectively "puts the brakes" on the reaction once host immune response is overactivated and homeostasis is unbalanced. We also discovered that TRIM25 bound RIG-I by a new K63-linked ubiquitination located at K-45 of the first caspase recruitment domain (CARD). Collectively, these results confirm an antagonism between TRIM38 and TRIM25 in regulating IFN-I production by affecting RIG-I activity following RNA virus infection.

8.
J Colloid Interface Sci ; 665: 286-298, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38531274

RESUMEN

Tailoring porous host materials, as an effective strategy for storing sulfur and restraining the shuttling of soluble polysulfides in electrolyte, is crucial in the design of high-performance lithium-sulfur (Li-S) batteries. However, for the widely studied conductive hosts such as mesoporous carbon, how the aspect ratio affects the confining ability to polysulfides, ion diffusion as well as the performances of Li-S batteries has been rarely studied. Herein, ordered mesoporous carbon (OMC) is chosen as a proof-of-concept prototype of sulfur host, and its aspect ratio is tuned from over âˆ¼ 2 down to below âˆ¼ 1.2 by using ordered mesoporous silica hard templates with variable length/width scales. The correlation between the aspect ratio of OMCs and the electrochemical performances of the corresponding sulfur-carbon cathodes are systematically studied with combined electrochemical measurements and microscopic characterizations. Moreover, the evolution of sulfur species in OMCs at different discharge states is scrutinized by small-angle X-ray scattering. This study gives insight into the aspect ratio effects of mesoporous host on battery performances of sulfur cathodes, providing guidelines for designing porous host materials for high-energy sulfur cathodes.

9.
Ir J Med Sci ; 2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38520612

RESUMEN

BACKGROUND AND AIM: Early identification of liver fibrosis is essential for the prognosis of metabolic-associated fatty liver disease (MAFLD), particularly in type 2 diabetes mellitus (T2DM) patients. Here, we explored the association of chitinase-3-like protein 1 (CHI3L1) and liver fibrosis in T2DM-MAFLD patients. METHODS: Liver fibrosis was staged in T2DM-MAFLD patients, and a liver stiffness measurement (LSM) of ≥ 8 kPa was used to differentiate between non-significant (NSLF) and significant liver fibrosis (SLF) subgroups. The two subgroups were compared for serum CHI3L1 and other parameters. Linear correlation, logistic regression, and restricted cubic spline (RCS) analyses were performed to evaluate the association between CHI3L1 and liver fibrosis. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of CHI3L1. RESULTS: Among T2DM-MAFLD, SLF patients had higher CHI3L1 compared to NSLF patients. CHI3L1 was found to be positively correlated with LSM. Multivariate logistic regression analysis suggested that CHI3L1 may be a potential independent risk factor for SLF. Further stratified analysis indicated that the odds ratios of SLF in the high CHI3L1 group were higher than in the low CHI3L1 group in the subgroups. RCS analysis suggested an increasing trend in the incidence of significant fibrosis with the rising level of CHI3L1. The area under the ROC curve for detecting significant fibrosis was 0.749 (95% CI: 0.668-0.829). CONCLUSIONS: Serum CHI3L1 demonstrates an association with significant liver fibrosis. High serum levels of CHI3L1 may indicate the existence of significant liver fibrosis in T2DM-MAFLD patients.

10.
Diabetes Metab Syndr Obes ; 17: 943-957, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38435634

RESUMEN

Purpose: This research aims to examine and scrutinize gender variations in the incidence of diabetic nephropathy (DN) and the trajectory of renal function in type 2 diabetes mellitus (T2DM) patients. Patients and Methods: We conducted a retrospective cohort study that enrolled 1549 patients diagnosed with T2DM from May 2015 to July 2023. We separately compared the clinical characteristics of male and female participants with and without DN. We utilized the Kaplan-Meier method to examine the cumulative incidence of DN among T2DM patients of varying genders. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using univariable and multivariable Cox proportional hazards regression analysis to evaluate the correlation between various factors and the risk of DN incidence. Multiple linear regression was utilized to investigate the relationship between ΔeGFR% and each factor. Logistic regression with cubic spline function and smooth curve fitting was employed to analyze the nonlinear link between ΔeGFR% and the risk of DN among participants of different genders. Results: The prevalence of DN was higher in female participants (17.31%) than in male participants (12.62%), with a significant cumulative risk ratio (1.33 [1.02-1.73], P = 0.034). Multiple linear regression analysis revealed that creatinine, female gender, blood urea nitrogen, alkaline phosphatase, and total cholesterol had a significant impact on ΔeGFR% in T2DM patients, with standardized ß coefficients of -0.325, -0.219, -0.164, -0.084, and 0.071, respectively. The restricted cubic spline analysis demonstrated a strong negative association between ΔeGFR% and the risk of developing DN (P < 0.001). Conclusion: Both male and female patients with T2DM had a higher prevalence of DN over the 5-year follow-up period. However, women had a greater risk of developing DN and a faster decline in renal function compared to men.

11.
Aquac Nutr ; 2024: 6337005, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38298207

RESUMEN

The effects of plant protein sources (PPSs) on the health of the liver and intestine of the largemouth bass, Micropterus salmoides, were compared to verify the potential damaging effects of dietary fiber (DF). A diet containing 55% fish meal (FM) was used as the control. The test diets contained 25% soybean meal (SBM), rapeseed meal (RSM), cottonseed meal, or peanut meal, and the FM content was decreased to 30%. The protein and lipid contents of these five diets were balanced by casein and oil. Fish were raised for 8 weeks. The fish fed the diet containing PPS showed a trend of decreasing growth and apparent digestibility coefficients. The contents of total bile acid, lipid, and collagen in the liver were increased, and the mRNA expression levels of genes encoding inflammatory factors and enzymes involved in de novo fatty acid synthesis and bile acid synthesis were upregulated. Both the lipid and collagen contents in the liver were positively correlated with the DF content in the diet significantly. Morphology and histology showed reduced liver size, hepatic steatosis, and fibrosis in fish fed diets containing PPS. The lowest hepatosomatic index was observed in fish fed the SBM diet, and the most severe damage was observed in fish fed the RSM diet. No obvious histological abnormalities were observed in the hindgut. The bile acid profile in the liver could be used to distinguish the types of PPS very well by Fisher discriminant analysis. These results indicated that 25% of each of the four PPSs in the diet exceeded the tolerance range of largemouth bass and caused liver damage, which might be mediated by bile acid. DF in PPS might be an important agent contributing to liver damage.

12.
Environ Sci Technol ; 58(3): 1563-1576, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38183415

RESUMEN

Uncertain chemical mechanisms leading to brown carbon (BrC) formation affect the drivers of the radiative effects of aerosols in current climate predictions. Herein, the aqueous-phase reactions of methylglyoxal (MG) and typical reduced nitrogen species (RNSs) are systematically investigated by using combined quantum chemical calculations and laboratory experiments. Imines and diimines are identified from the mixtures of methylamine (MA) and ammonia (AM) with MG, but not from dimethylamine (DA) with the MG mixture under acidic conditions, because deprotonation of DA cationic intermediates is hindered by the amino groups occupied by two methyl groups. It leads to N-heterocycle (NHC) formation in the MG + MA (MGM) and MG + AM (MGA) reaction systems but to N-containing chain oligomer formation in the MG + DA (MGD) reaction system. Distinct product formation is attributed to electrostatic attraction and steric hindrance, which are regulated by the methyl groups of RNSs. The light absorption and adverse effects of NHCs are also strongly related to the methyl groups of RNSs. Our finding reveals that BrC formation is mainly contributed from MG reaction with RNSs with less methyl groups, which have more abundant and broad sources in the urban environments.


Asunto(s)
Contaminantes Atmosféricos , Dimetilaminas , Piruvaldehído , Carbono , Nitrógeno , Metilaminas , Aerosoles/análisis
13.
Cell Biol Int ; 48(2): 174-189, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37853939

RESUMEN

Geranylgeranyltransferase type I (GGTase-I) significantly affects Rho proteins, such that the malignant progression of several cancers may be induced. Nevertheless, the effect and underlying mechanism of GGTase-I in the malignant progression of salivary adenoid cystic carcinoma (SACC) remain unclear. This study primarily aimed to investigate the role and mechanism of GGTase-I in mediating the malignant progression of SACC. The level of GGTase-I gene in cells was stably knocked down by short hairpin RNA-EGFP-lentivirus. The effects of GGTase-I silencing on the migration, invasion, and spread of cells were examined, the messenger RNA levels of GGTase-I and RhoA genes of SACC cells after GGTase-I knockdown were determined, and the protein levels of RhoA and RhoA membrane of SACC cells were analyzed. Moreover, the potential underlying mechanism of silencing GGTase-I on the above-mentioned aspects in SACC cells was assessed by examining the protein expression of ROCK1, MLC, p-MLC, E-cadherin, Vimentin, MMP2, and MMP9. Furthermore, the underlying mechanism of SACC cells proliferation was investigated through the analysis of the expression of cyclinD1, MYC, E2F1, and p21CIP1/WAF1 . Besides, the change of RhoA level in SACC tissues compared with normal paracancer tissues was demonstrated through quantitative reverse-transcription polymerase chain reaction and western blot experiments. Next, the effect after GGTase-I silencing was assessed through the subcutaneous tumorigenicity assay. As indicated by the result of this study, the silencing of GGTase-I significantly reduced the malignant progression of tumors in vivo while decreasing the migration, invasion, and proliferation of SACC cells and RhoA membrane, Vimentin, ROCK1, p-MLC, MMP2, MMP9, MYC, E2F1, and CyclinD1 expression. However, the protein expression of E-cadherin and p21CIP1/WAF1 was notably upregulated. Subsequently, no significant transform of RhoA and MLC proteins was identified. Furthermore, RhoA expression in SACC tissues was significantly higher than that in paracancerous tissues. As revealed by the results of this study, GGTase-I shows a correlation with the proliferation of SACC through the regulation of cell cycle and may take on vital significance in the migration and invasion of SACC by regulating RhoA/ROCK1/MLC signaling pathway. GGTase-I is expected to serve as a novel exploration site of SACC.


Asunto(s)
Transferasas Alquil y Aril , Carcinoma Adenoide Quístico , Neoplasias de las Glándulas Salivales , Quinasas Asociadas a rho , Humanos , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Vimentina/metabolismo , Carcinoma Adenoide Quístico/genética , Carcinoma Adenoide Quístico/metabolismo , Carcinoma Adenoide Quístico/patología , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/metabolismo , Neoplasias de las Glándulas Salivales/patología , Invasividad Neoplásica/genética , Puntos de Control del Ciclo Celular , Transducción de Señal , Proliferación Celular , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica
14.
Environ Sci Pollut Res Int ; 30(58): 122364-122380, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37966646

RESUMEN

Massive amount of food waste has been generated annually, posing a threat to ecological sustainability and the social economy due to current disposal methods. Urgent action is needed worldwide to convert the traditional pathway for treating food waste into a sustainable bioeconomy, as this will significantly benefit food chain management. This study explores the use of pyrolysis to produce different types of food waste biochars and investigates their adsorption capabilities for removing Cd2+ and Pb2+ in aqueous solution. The results indicated that co-pyrolysis biochar from fresh food waste and rice husk (FWRB) exhibited superior adsorption performance for Cd2+ (61.84 mg·g-1) and Pb2+ (245.52 mg·g-1), respectively. Pseudo-second-order kinetics (0.74 ≤ R2 ≤ 0.98) and Langmuir isotherms (0.87 ≤ R2 ≤ 0.98) indicated that the immobilized Cd2+ and Pb2+ on biochars were mainly attributed to the chemisorption, including precipitation with minerals (e.g., carbonates, silicates, and phosphate), complexation with functional groups (-OH), cation exchange (-COO-), and coordination with π-electrons. Furthermore, FWRB demonstrated reduced EC and Na content in comparison to food waste digestate biochar (FWDB) and food waste digestate co-pyrolysis with sawdust biochar (FWSB), with levels of Cd and Pb falling below China's current guideline thresholds. These findings suggested that co-pyrolysis of fresh food waste with rice husk could be applicable to the recycling of food waste into biochar products for heavy metal stabilization in contaminated water and soils.


Asunto(s)
Cadmio , Eliminación de Residuos , Cadmio/análisis , Alimento Perdido y Desperdiciado , Plomo , Alimentos , Carbón Orgánico , Adsorción , Agua
15.
J Org Chem ; 88(19): 13956-13966, 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37699255

RESUMEN

An environmentally benign multicomponent strategy for the amidosulfenylation of alkenes for the synthesis of ß-succinimide sulfides is disclosed. In this process, common disulfides smoothly act as a sulfur-based source, and N-iodosuccinimide (NIS) is used not only as a free radical initiator but also as an N-nucleophile. A broad range of functional groups are tolerated in this reaction system.

16.
Diabetes Metab Syndr Obes ; 16: 2255-2268, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37545743

RESUMEN

Purpose: The identification of significant fibrosis is critical for predicting the prognosis of non-alcoholic fatty liver disease (NAFLD). This study aimed to compare the predictive value of chitinase-3-like protein 1 (CHl3L1) and other non-invasive biomarkers, as well as to establish a novel non-invasive diagnostic model for assessing the risk of significant fibrosis in NAFLD. Patients and Methods: A total of 71 patients with confirmed NAFLD based on liver biopsy were included in this study. Serum CHI3L1 levels and other non-invasive fibrosis assessment measures were determined. The aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 Index (FIB-4) were calculated to assess the diagnostic superiority of serum CHI3L1 compared to other non-invasive fibrosis assessment measures. Multivariate logistic regression analysis was conducted to identify relevant variables for constructing a diagnostic model. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of each index, including the area under ROC curve (AUC), sensitivity, and specificity. A nomogram was established based on the logistic regression model. Results: Serum CHI3LI levels were found to be higher in NAFLD patients with significant fibrosis compared to those without significant fibrosis. Multivariate logistic regression analysis revealed that aspartate aminotransferase (AST), type IV collagen (IV-C), CHI3L1, and liver stiffness measurement (LSM) were identified as potential independent risk factors associated with significant fibrosis in patients. The AUC of CHI3L1 for diagnosing significant liver fibrosis was 0.716 (0.596,0.836), with the optimal cut-off point of 125.315. The nomogram incorporating CHI3LI, AST, IV-C, and LSM further improved the potential predictive value, with an AUC for diagnosing significant fibrosis of 0.864 (0.766,0.962). This was superior to IV-C, CHI3L1, LSM, and APRI (all p < 0.05). Conclusion: The diagnostic model constructed by CHI3L1 combined with the existing non-invasive markers AST, IV-C, and LSM can help assess the risk of significant liver fibrosis in NAFLD.

17.
Front Plant Sci ; 14: 1213807, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37416884

RESUMEN

Heavy ion beam (HIB) is an effective physical mutagen that has been widely used in plant mutational breeding. Systemic knowledge of the effects caused by different HIB doses at developmental and genomic levels will facilitate efficient breeding for crops. Here we examined the effects of HIB systematically. Kitaake rice seeds were irradiated by ten doses of carbon ion beams (CIB, 25 - 300 Gy), which is the most widely used HIB. We initially examined the growth, development and photosynthetic parameters of the M1 population and found that doses exceeding 125 Gy caused significant physiological damages to rice. Subsequently, we analyzed the genomic variations in 179 M2 individuals from six treatments (25 - 150 Gy) via whole-genome sequencing (WGS). The mutation rate peaks at 100 Gy (2.66×10-7/bp). Importantly, we found that mutations shared among different panicles of the same M1 individual are at low ratios, validating the hypothesis that different panicles may be derived from different progenitor cells. Furthermore, we isolated 129 mutants with distinct phenotypic variations, including changes in agronomic traits, from 11,720 M2 plants, accounting for a 1.1% mutation rate. Among them, about 50% possess stable inheritance in M3. WGS data of 11 stable M4 mutants, including three lines with higher yields, reveal their genomic mutational profiles and candidate genes. Our results demonstrate that HIB is an effective tool that facilitates breeding, that the optimal dose range for rice is 67 - 90% median lethal dose (LD50), and that the mutants isolated here can be further used for functional genomic research, genetic analysis, and breeding.

18.
Plants (Basel) ; 12(7)2023 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-37050050

RESUMEN

MADS-box is a class of transcriptional regulators that are ubiquitous in plants and plays important roles in the process of plant growth and development. Identification and analysis of blueberry MADS-box genes can lay a foundation for their function investigations. In the present study, 249 putative MADS-box genes were identified in the blueberry genome. Those MADS-box genes were distributed on 47 out of 48 chromosomes. The phylogenetic and evolutionary analyses showed that blueberry MADS-box genes were divided into 131 type I members and 118 type II members. The type I genes contained an average of 1.89 exons and the type II genes contained an average of 7.83 exons. Motif analysis identified 15 conserved motifs, of which 4 were related to the MADS domain and 3 were related to the K-box domain. A variety of cis-acting elements were found in the promoter region of the blueberry MADS-box gene, indicating that the MADS-box gene responded to various hormones and environmental alterations. A total of 243 collinear gene pairs were identified, most of which had a Ka/Ks value of less than 1. Nine genes belonging to SEP, AP3/PI, and AGL6 subfamilies were screened based on transcriptomic data. The expression patterns of those nine genes were also verified using quantitative PCR, suggesting that VcMADS6, VcMADS35, VcMADS44, VcMADS58, VcMADS125, VcMADS188, and VcMADS212 had potential functions in blueberry fruit ripening. The results of this study provide references for an in-depth understanding of the biological function of the blueberry MADS-box genes and the mechanism of blueberry fruit ripening.

19.
J Virol ; 97(3): e0176422, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-36779760

RESUMEN

Respiratory syncytial virus (RSV) infects more than 60% of infants in their first year of life. Since an experimental formalin-inactivated (FI) RSV vaccine tested in the 1960s caused enhanced respiratory disease (ERD), few attempts have been made to vaccinate infants. ERD is characterized by Th2-biased responses, lung inflammation, and poor protective immune memory. Innate immune memory displays an increased nonspecific effector function upon restimulation, a process called trained immunity, or a repressed effector function upon restimulation, a process called tolerance, which participates in host defense and inflammatory disease. Mycobacterium bovis bacillus Calmette-Guérin (BCG) given at birth can induce trained immunity as well as heterologous Th1 responses. We speculate that BCG given at birth followed by FI-RSV may alleviate ERD and enhance protection through promoting trained immunity and balanced Th immune memory. Neonatal mice were given BCG at birth and then vaccinated with FI-RSV+Al(OH)3. BCG/FI-RSV+Al(OH)3 induced trained macrophages, tissue-resident memory T cells (TRM), and specific cytotoxic T lymphocytes (CTL) in lungs and inhibited Th2 and Th17 cell immune memory, all of which contributed to inhibition of ERD and increased protection. Notably, FI-RSV+Al(OH)3 induced tolerant macrophages, while BCG/FI-RSV+Al(OH)3 prevented the innate tolerance through promoting trained macrophages. Moreover, inhibition of ERD was attributed to trained macrophages or TRM in lungs but not memory T cells in spleens. Therefore, BCG given at birth to regulate trained immunity and TRM may be a new strategy for developing safe and effective RSV killed vaccines for young infants. IMPORTANCE RSV is the leading cause of severe lower respiratory tract infection of infants. ERD, characterized by Th2-biased responses, inflammation, and poor immune memory, has been an obstacle to the development of safe and effective killed RSV vaccines. Innate immune memory participates in host defense and inflammatory disease. BCG given at birth can induce trained immunity as well as heterologous Th1 responses. Our results showed that BCG/FI-RSV+Al(OH)3 induced trained macrophages, TRM, specific CTL, and balanced Th cell immune memory, which contributed to inhibition of ERD and increased protection. Notably, FI-RSV+Al(OH)3 induced tolerant macrophages, while BCG/FI-RSV+Al(OH)3 prevented tolerance through promoting trained macrophages. Moreover, inhibition of ERD was attributed to trained macrophages or TRM in lungs but not memory T cells in spleens. BCG at birth as an adjuvant to regulate trained immunity and TRM may be a new strategy for developing safe and effective RSV killed vaccines for young infants.


Asunto(s)
Vacuna BCG , Infecciones por Virus Sincitial Respiratorio , Vacunas contra Virus Sincitial Respiratorio , Animales , Ratones , Vacuna BCG/administración & dosificación , Vacuna BCG/inmunología , Pulmón/inmunología , Macrófagos/inmunología , Ratones Endogámicos BALB C , Infecciones por Virus Sincitial Respiratorio/prevención & control , Vacunas contra Virus Sincitial Respiratorio/administración & dosificación , Vacunas contra Virus Sincitial Respiratorio/inmunología , Virus Sincitial Respiratorio Humano/inmunología , Bazo/inmunología , Células TH1/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/inmunología
20.
ACS Appl Mater Interfaces ; 15(3): 4398-4407, 2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36514844

RESUMEN

Elastomer-based wearables can improve people's lives; however, frictional wear caused by manipulation may pose significant concerns regarding their durability and sustainability. To address the aforementioned issue, a new class of advanced scalable supersoft elastic transparent material (ASSETm) is reported, which offers a unique combination of scalability (20 g scale), stretchability (up to 235%), and enzymatic degradability (up to 65% in 30 days). The key feature of our design is to render native dextrin hydrophobic, which turns it into a macroinitiator for bulk ring-opening polymerization. Based on ASSETm, a self-powered touch sensor (ASSETm-TS) for touch sensing and non-contact approaching detection, possessing excellent electrical potential (up to 65 V) and rapid response time (60 ms), is fabricated. This work is a step toward developing sustainable soft electronic systems, and ASSETm's tunability enables further improvement of electrical outputs, enhancing human-interactive applications.

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