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1.
Adv Mater ; : e2403061, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38782371

RESUMEN

Luminescent materials with narrowband emission have extraordinary significance for developing ultrahigh-definition display. B-N-containing multiple resonance thermally activated delayed fluorescence (MR-TADF) materials are strong contenders. However, their device performances pervasively encounter detrimental aggregation-caused quenching effect that is highly vulnerable to doping concentration, complicating device fabrication. Therefore, constructing highly efficient and concentration-independent MR-TADF emitters is of pragmatic importance for improving device controllability and reproducibility, simplifying manufacturing procedures, and conserving production costs. Here, by systematic arrangement of donor triphenylamine and fluorophore BNCz on distinct bridges, we have developed a spatial confinement strategy with a donor-bridge-fluorophore (D-B-F) architecture. Structurally fine modulation and progressive evolution to construct molecular entities with congested steric hindrance effect that can suppress intermolecular interactions without substantially affecting the luminescence tone of fluorophore BNCz, resulting in highly efficient and concentration-independent narrowband emitters; through isomer engineering, two isomers BN-PCz-TPA and TPA-PCz-BN with different crystal stacking patterns are synthesized by altering the connection mode between triphenylamine and BNCz. As a result, BN-PCz-TPA-based device showcases maximum external quantum efficiency (EQE) of 36.3% with narrow full-width at half-maximum (FWHM) of 27 nm at 10 wt% doping concentration. Even at 20 wt% doping concentration, the maximum EQE remains at 32.5% and the emission spectrum is almost unchanged. This article is protected by copyright. All rights reserved.

2.
Vaccines (Basel) ; 12(2)2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38400198

RESUMEN

Zika virus (ZIKV) is an emerging flavivirus that causes congenital syndromes including microcephaly and fetal demise in pregnant women. No commercial vaccines against ZIKV are currently available. We previously generated a chimeric ZIKV (ChinZIKV) based on the Chaoyang virus (CYV) by replacing the prME protein of CYV with that of a contemporary ZIKV strain GZ01. Herein, we evaluated this vaccine candidate in a mouse model and showed that ChinZIKV was totally safe in both adult and suckling immunodeficient mice. No viral RNA was detected in the serum of mice inoculated with ChinZIKV. All of the mice inoculated with ChinZIKV survived, while mice inoculated with ZIKV succumbed to infection in 8 days. A single dose of ChinZIKV partially protected mice against lethal ZIKV challenge. In contrast, all the control PBS-immunized mice succumbed to infection after ZIKV challenge. Our results warrant further development of ChinZIKV as a vaccine candidate in clinical trials.

3.
ACS Appl Mater Interfaces ; 16(4): 4948-4957, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38235687

RESUMEN

The development of high-performance multiple resonance thermally activated delayed fluorescence (MR-TADF) materials with narrowband yellow emission is highly critical for various applications in industries, such as the automotive, aerospace, and microelectronic industries. However, the modular construction approaches to expeditiously access narrowband yellow-emitting materials is relatively rare. Here, a unique molecular design concept based on frontier molecular orbital engineering (FMOE) of aromatic donor fusion is proposed to strategically address this issue. Donor fusion is a modular approach with a "leveraging effect"; through direct polycyclization of donor attached to the MR parent core, it is facile to achieve red-shifted emission by a large margin. As a result, two representative model molecules, namely BN-Cz and BN-Cb, have been constructed successfully. The BN-Cz- and BN-Cb-based sensitized organic light-emitting diodes (OLEDs) exhibit bright yellow emission with peaks of 560 and 556 nm, full-width at half-maxima (fwhm's) of 49 and 45 nm, Commission Internationale de L'Eclairage coordinates of (0.44, 0.55) and (0.43, 0.56), and maximum external quantum efficiencies (EQEs) of 32.9% and 29.7%, respectively. The excellent optoelectronic performances render BN-Cz and BN-Cb one of the most outstanding yellow-emitting MR-TADF materials.

4.
Nat Biotechnol ; 42(2): 247-252, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37169966

RESUMEN

We present a statistical simulator, scDesign3, to generate realistic single-cell and spatial omics data, including various cell states, experimental designs and feature modalities, by learning interpretable parameters from real data. Using a unified probabilistic model for single-cell and spatial omics data, scDesign3 infers biologically meaningful parameters; assesses the goodness-of-fit of inferred cell clusters, trajectories and spatial locations; and generates in silico negative and positive controls for benchmarking computational tools.


Asunto(s)
Benchmarking , Modelos Estadísticos , Proyectos de Investigación
5.
bioRxiv ; 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-37961332

RESUMEN

Understanding diverse responses of individual cells to the same perturbation is central to many biological and biomedical problems. Current methods, however, do not precisely quantify the strength of perturbation responses and, more importantly, reveal new biological insights from heterogeneity in responses. Here we introduce the perturbation-response score (PS), based on constrained quadratic optimization, to quantify diverse perturbation responses at a single-cell level. Applied to single-cell transcriptomes of large-scale genetic perturbation datasets (e.g., Perturb-seq), PS outperforms existing methods for quantifying partial gene perturbation responses. In addition, PS presents two major advances. First, PS enables large-scale, single-cell-resolution dosage analysis of perturbation, without the need to titrate perturbation strength. By analyzing the dose-response patterns of over 2,000 essential genes in Perturb-seq, we identify two distinct patterns, depending on whether a moderate reduction in their expression induces strong downstream expression alterations. Second, PS identifies intrinsic and extrinsic biological determinants of perturbation responses. We demonstrate the application of PS in contexts such as T cell stimulation, latent HIV-1 expression, and pancreatic cell differentiation. Notably, PS unveiled a previously unrecognized, cell-type-specific role of coiled-coil domain containing 6 (CCDC6) in guiding liver and pancreatic lineage decisions, where CCDC6 knockouts drive the endoderm cell differentiation towards liver lineage, rather than pancreatic lineage. The PS approach provides an innovative method for dose-to-function analysis and will enable new biological discoveries from single-cell perturbation datasets.

6.
Materials (Basel) ; 16(17)2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37687679

RESUMEN

Most natural materials have rotational and hierarchical properties, so they can show excellent mechanical properties such as shear resistance and impact resistance. In order to further improve the energy absorption characteristics of vibration absorbing structures, a new type of honeycomb structure with integral rotation and group rotation is designed and characterized. The effects of the geometrical parameters of rotation Angle on the impact deformation mode, stress response curve and energy absorption characteristics of the honeycomb structure are studied through numerical simulation and experimental design. The results show that the overall honeycomb performance of 15° is better than that of 0°, the specific energy absorption is the results show that the overall honeycomb performance of 15° is better than that of 0°, the specific energy absorption is increased by 6%, the bearing capacity is increased by 320 N, and the crushing force efficiency is increased by 2%. Compared with the whole cell and the group cell, the specific absorption energy increased by 35%, 73% and 71%. The results of this paper provide a new insight into the impact performance of monolithic and grouped rotating honeycomb structures, which is helpful for the results of this paper provide a new insight into the impact performance of monolithic and grouped rotating honeycomb structures, which is helpful for the optimization of crashworthiness structural design.

7.
Angew Chem Int Ed Engl ; 62(52): e202312451, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-37724466

RESUMEN

It is of great strategic significance to develop highly efficient narrowband organic electroluminescent materials that can be utilized to manufacture ultra-high-definition (UHD) displays and meet or approach the requirements of Broadcast Television 2020 (B.T.2020) color gamut standards. This motif poses challenges for molecular design and synthesis, especially for developing generality, diversity, scalability, and robustness of molecular structures. The emergence of multiple resonance thermally activated delayed fluorescence (MR-TADF) emitters has ingeniously solved the problems and demonstrated bright application prospects in the field of UHD displays, sparking a research boom. This Minireview summarizes the research endeavors of narrowband organic electroluminescent materials, with emphasis on the tremendous contribution of frontier molecular orbital engineering (FMOE) strategy. It combines the outstanding advantages of MR framework and donor-acceptor (D-A) structure, and can achieve red-shift and narrowband emission simultaneously, which is of great significance in the development of long-wavelength narrowband emitters with emission maxima especially exceeding 500 nm. We hope that this Minireview would provide some inspiration for what could transpire in the future.

8.
Vaccines (Basel) ; 11(7)2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37515065

RESUMEN

The genus Flavivirus is a group of arthropod-borne single-stranded RNA viruses, which includes important human and animal pathogens such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), Dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), and Tick-borne encephalitis virus (TBEV). Reverse genetics has been a useful tool for understanding biological properties and the pathogenesis of flaviviruses. However, the conventional construction of full-length infectious clones for flavivirus is time-consuming and difficult due to the toxicity of the flavivirus genome to E. coli. Herein, we applied a simple, rapid, and bacterium-free circular polymerase extension reaction (CPER) method to synthesize recombinant flaviviruses in vertebrate cells as well as insect cells. We started with the de novo synthesis of the JEV vaccine strain SA-14-14-2 in Vero cells using CPER, and then modified the CPER method to recover insect-specific flaviviruses (ISFs) in mosquito C6/36 cells. Chimeric Zika virus (ChinZIKV) based on the Chaoyang virus (CYV) backbone and the Culex flavivirus reporter virus expressing green fluorescent protein (CxFV-GFP) were subsequently rescued in C6/36 cells. CPER is a simple method for the rapid generation of flaviviruses and other potential RNA viruses. A CPER-based recovery system for flaviviruses of different host ranges was established, which would facilitate the development of countermeasures against flavivirus outbreaks in the future.

9.
Adv Mater ; 35(42): e2305125, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37461260

RESUMEN

Advanced circularly polarized multiple-resonance thermally activated delayed fluorescence (CP-MR-TADF) materials synergize the advantages of circularly polarized luminescence (CPL), narrowband emission, and the TADF characteristic, which can be fabricated into highly efficient circularly polarized organic light-emitting diodes (CP-OLEDs) with high color purity, directly facing the urgent market strategic demand of ultrahigh-definition and 3D displays. In this work, based on an edge-topology molecular-engineering (ETME) strategy, a pair of high-performance CP-MR-TADF enantiomers, (P and M)-BN-Py, is developed, which merges the intrinsically helical chirality into the MR framework. The optimized CP-OLEDs with (P and M)-BN-Py emitters and the newly developed ambipolar transport host PhCbBCz exhibit pure green emission with sharp peaks of 532 nm, full-width at half-maximum (FWHM) of 37 nm, and Commission Internationale de L'Eclairage (CIE) coordinates of (0.29, 0.68). Importantly, they achieve remarkable maximum external quantum efficiencies (EQEs) of 30.6% and 29.2%, and clear circularly polarized electroluminescence (CPEL) signals with electroluminescence dissymmetry factors (gEL s) of -4.37 × 10-4 and +4.35 × 10-4 for (P)-BN-Py and (M)-BN-Py, respectively.

10.
Appetite ; 184: 106512, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36858260

RESUMEN

The current study explored the relationships between retrospective parenting styles and food parenting in childhood (≤ 12 years old) and Chinese adults' current maladaptive and adaptive eating behaviors. We recruited 501 Chinese adults (50.30% men, aged 19-46 years). A set of questionnaires were used to measure retrospective parenting styles (i.e., emotional warmth, rejection, and overprotection), food parenting (i.e., parental concern, monitoring, pressure to eat, and restriction), and current maladaptive (i.e., disordered eating) and adaptive (i.e., intuitive eating) eating behaviors. Correlation and mediation analyses were employed to analyze these data. Results revealed that retrospective parenting styles and food parenting were significantly related to current maladaptive and adaptive eating behaviors in both Chinese men and women. Mediation analyses showed that higher retrospective parental warmth was related to higher retrospective parental concern which, in turn, was related to higher current disordered eating in men (indirect effect = 0.14, 95% CI 0.08, 0.24). Furthermore, higher retrospective parental overprotection was related to higher retrospective parental pressure to eat which, in turn, was related to higher current disordered eating in men (indirect effect = 0.06, 95% CI 0.01, 0.14). For women, higher retrospective parental warmth was associated with higher retrospective parental concern which, in turn, was associated with lower current intuitive eating in women (indirect effect = -0.04, 95% CI = -0.10, -0.01). Furthermore, higher retrospective parental overprotection was associated with higher retrospective parental concern which, in turn, was associated with lower current intuitive eating in women (indirect effect = -0.03, 95% CI = -0.08, -0.004). The findings indicate the importance of including childhood parenting styles and food parenting in future research and intervention of adults' current maladaptive and adaptive eating behaviors.


Asunto(s)
Conducta Alimentaria , Responsabilidad Parental , Adulto , Niño , Femenino , Humanos , Masculino , Pueblos del Este de Asia , Conducta Alimentaria/psicología , Relaciones Padres-Hijo , Responsabilidad Parental/psicología , Padres/psicología , Estudios Retrospectivos , Encuestas y Cuestionarios
11.
Angew Chem Int Ed Engl ; 62(19): e202301930, 2023 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-36898967

RESUMEN

Advanced multiple resonance induced thermally activated delayed fluorescence (MR-TADF) emitters have emerged as a privileged motif for applications in organic light-emitting diodes (OLEDs), because they furnish highly tunable TADF characteristics and high color purity emission. Herein, based on the unique nitrogen-atom embedding molecular engineering (NEME) strategy, a series of compounds BN-TP-Nx (x=1, 2, 3, 4) have been customized. The nitrogen-atom anchored at different position of triphenylene hexagonal lattice entails varying degrees of perturbation to the electronic structure. The newly-constructed emitters have demonstrated the precise regulation of emission maxima of MR-TADF emitters to meet the actual industrial demand, and further enormously enriched the MR-TADF molecular reservoir. The BN-TP-N3-based OLED exhibits ultrapure green emission, with peak of 524 nm, full-width at half-maximum (FWHM) of 33 nm, Commission Internationale de L'Eclairage (CIE) coordinates of (0.23, 0.71), and maximum external quantum efficiency (EQE) of 37.3 %.

12.
J Environ Manage ; 338: 117757, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-36996567

RESUMEN

Nitrogen fractions in soil, like organic nitrogen, mineral nitrogen, and free amino acids, are sensitive pointers to the soil nitrogen pools involved in nutrient cycling. As a potential improvement measure, biochar might improve soil fertility and nutrient availability. However, few studies have focused on the long-term effects of biochar retention on the soil nitrogen supply capacity of bulk and rhizosphere soil in brown earth. Therefore, a six-year field experiment was conducted in 2013, concentrating on the impact of biochar retention on soil nitrogen fractions. Four biochar rates were tested: no biochar amendment (CK); 15.75 t ha-1 of biochar (BC1); 31.5 t ha-1 of biochar (BC2); 47.25 t ha-1 of biochar (BC3). Our results showed that the elevated application rates significantly enhanced soil organic matter (SOM), and total nitrogen (TN), and improved pH in both bulk and rhizosphere soils. Acid-hydrolyzable nitrogen (AHN) content in biochar treatments was higher than that of CK in bulk and rhizosphere soil. The content of non-hydrolyzable nitrogen (NHN) was increased in 47.25 t ha-1 of biochar retention. Ammonium nitrogen (AN) and amino sugar nitrogen (ASN) contents were higher in bulk soil than in rhizosphere soil. Neutral amino acid contents were the highest both in bulk and rhizosphere soil. Principal component analysis (PCA) showed that soil organic nitrogen was significantly influenced by BC3 treatment in bulk soil, and largely influenced by other treatments in rhizosphere soil. Partial least square path modeling (PLSPM) revealed that NH4+-N was mainly derived from amino acid nitrogen (AAN) and AN in bulk soil and AAN and ASN in rhizosphere soil. These results indicate that different biochar retention rates contributed to improve soil nutrients. Amino acid nitrogen was the prominent nitrogen source of NH4+-N in bulk and rhizosphere soils.


Asunto(s)
Rizosfera , Suelo , Suelo/química , Fertilizantes/análisis , Nitrógeno/análisis , Carbón Orgánico , Aminoácidos
13.
J Food Prot ; 86(1): 100029, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36916588

RESUMEN

Plasma-activated water (PAW) is considered a novel sanitizer for the food industry due to the antimicrobial mechanisms exhibited by reactive oxygen and nitrogen species. The plasma operation parameters can affect the chemistry of PAW and can therefore influence its microbial inactivation efficacy. This study statistically optimized the operating conditions of PAW (activation time, distance from nozzle, and volume of water) using response surface methodology. Two optimized conditions of PAW were identified for the inactivation of planktonic cells of the avirulent strain of Salmonella Typhimurium MHM112 providing a minimum reduction of 6.3 log. All three operating parameters significantly affected the physicochemical characteristics (pH, ORP, EC, nitrite, and nitrate) and microbial inactivation efficacy of PAW. Mixing of small batches using the two optimized conditions to obtain larger volumes did not significantly change the microbial inactivation. However, there were significant reductions in nitrite and nitrate concentrations in PAW due to the mixing of batches while the pH and ORP values remained unaffected. The storage of large volumes of PAW for 25 min at 40-46°C, which is the commercial egg washing temperature in the United States, did not significantly impact S. Typhimurium MHM112 inactivation or the physicochemical characteristics of PAW. A validation study using a cocktail of six pathogenic strains of Salmonella revealed no significant differences in inactivation between the avirulent S. Typhimurium MHM112 and the pathogenic strains, suggesting that the avirulent S. Typhimurium MHM112 may serve as a surrogate for sanitation of S. enterica at the optimized conditions of PAW. The results obtained from this study are useful for our long-term goal of evaluating PAW efficacy in surface egg washing to inactivate Salmonella.


Asunto(s)
Gases em Plasma , Salmonella , Viabilidad Microbiana , Nitratos , Industria de Alimentos
14.
Diagn Pathol ; 18(1): 21, 2023 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-36782249

RESUMEN

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare, non-Langerhans cell histiocytosis of unknown etiology. we report a very rare case of recurrent central nervous system RDD with KRAS gene mutation and review the literature to improve our understanding of this disease. CASE PRESENTATION: A 19-year-old male patient was admitted to our hospital for headache. Cranial magnetic resonance imaging revealed a mass of abnormal signal shadows in the prepontine cistern. The mass was surgically removed and the patient was consequently diagnosed with intracranial Rosai-Dorfman disease. Seven months later, pathological examination confirmed that the RDD had recurred. Next-generation sequencing found KRAS mutation in exon 4 (C.351A > C. P. K117n). CONCLUSION: RDD of the CNS has no distinct clinical manifestations and imaging characteristics, and the final diagnosis should be based on the results of the pathological examination. Although RDD is not currently classified as a neoplastic disorder, some evidence of clonality has changed our understanding of it. Follow up examinations over a long period are necessary to determine the efficacy of treatment.


Asunto(s)
Histiocitosis Sinusal , Humanos , Masculino , Adulto Joven , Sistema Nervioso Central/patología , Diagnóstico Diferencial , Histiocitosis Sinusal/diagnóstico , Histiocitosis Sinusal/genética , Histiocitosis Sinusal/patología , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética
15.
Chemistry ; 29(12): e202203414, 2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36585378

RESUMEN

Circularly polarized luminescence (CPL) materials that concurrently exhibit high efficiency and narrowband emission are extremely promising applications in 3D and wide color gamut display. By merging the CPL optical property and multiple resonance (MR) induced thermally activated delayed fluorescence (TADF) characteristic into one molecule, a new strategy, namely CP-MR-TADF, is proposed to generate organic emitters with CPL activity, TADF and narrowband emission. High-performance red, green and blue CP-MR-TADF emitters have been developed following this strategy. Herein, the present status and progress of CP-MR-TADF materials in the field of organic light-emitting diodes (OLEDs) is summarized. Finally, for this rapidly growing new research field, the future opportunities are forecasted and the present challenges are discussed.

16.
Adv Mater ; 35(3): e2205166, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36325646

RESUMEN

It is of important strategic significance to develop high-efficiency narrowband organic electroluminescent materials that can be employed to fabricate ultrahigh-definition displays with wide color gamut. This topic implies a great challenge to molecular design and synthesis, especially for the development of universality, diversity, scalability, and robustness of molecular architectonics. In this work, a synthetic methodology is demonstrated for functionalizing brominated BN-containing multiple-resonance (MR) frameworks with multifarious functional groups, such as donors, acceptors, and moieties without obvious push-pull electron properties. The m-DPAcP-BNCz-based organic light-emitting diode (OLED) exhibits green emission with a full-width at half-maximum (FWHM) of 28 nm and a maximum external quantum efficiency (EQE) of 40.6%. The outstanding performance of m-DPAcP-BNCz is attributed to the perfect integration of the inherent advantages of the MR framework and the donor-acceptor configuration, which can not only achieve bathochromic shift and narrowband emission, but also obtain high photoluminescence (PL) quantum yield (ΦPL ) and horizontal emitting dipole orientation ratio (Θ// ). This straightforward and efficient approach provides insightful guidance for the construction and enrichment of more high-efficiency narrowband emitters.

17.
Cell Rep ; 41(6): 111592, 2022 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-36351383

RESUMEN

Steady-state extramedullary hematopoiesis during adulthood is an emerging field of great interest. The meninges contain both innate and adaptive immune cells, which provide immunosurveillance of the central nervous system (CNS). Hematopoietic progenitors that give rise to meningeal immune cells remain elusive. Here, we report that steady-state meninges of adult mice host hematopoietic stem cells (HSCs), as defined by long-term, efficient, multi-lineage reconstitution and self-renewal capacity in the meninges, blood, spleen, and bone marrow of sublethally irradiated adult recipients. HSCs lodge in the meninges after birth with local expression of pro-hematopoietic niche factors. Meningeal HSCs are locally maintained in homeostasis and get replenished from the blood only when the resident pool is reduced. With a tissue-specific expression profile, meningeal HSCs can provide the CNS with a constant supply of leukocytes more adapted to local microenvironment.


Asunto(s)
Hematopoyesis , Células Madre Hematopoyéticas , Ratones , Animales , Células Madre Hematopoyéticas/metabolismo , Hematopoyesis/fisiología , Médula Ósea , Bazo , Meninges , Ratones Endogámicos C57BL
18.
Int Immunopharmacol ; 113(Pt A): 109308, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36274487

RESUMEN

BACKGROUND: A large-scale outbreak of Zika virus (ZIKV) has occurred in Brazil and other South American countries, and has rapidly spread to 60 countries and regions worldwide since 2015, but no approved anti-ZIKV vaccines are available as of 2021. METHODS: We developed four types of anti-ZIKV DNA vaccine candidates: VPC-NS1, VPC-prME, VPC-prME-NS1, and VPC-EIII-NS1. They were developed against the structural proteins prM and E, and non-structural protein 1 (NS1) of ZIKV using the mammalian cell expression vector pcDNA3.1(+) as the backbone. For immunization, we intramuscularly injected mice with each vaccine candidate (n = 12 to 15 per group) on day 0 and day 14, with mice injected with phosphate-buffered saline (PBS) and pcDNA3.1(+) backbone vector as controls. On day 7, 21, and 35 after initial immunization, the effect of DNA vaccines was evaluated by ZIKV-specific humoral immunity determined by enzyme-linked immunosorbent assay (ELISA), ZIKV-specific T cell immunity determined by intracellular cytokine staining by flow cytometry and serum neutralization capacity determined by plaque reduction neutralization test (PRNT50) assay. RESULTS: The sequencing results showed that DNA vaccine vectors were successfully constructed. Western blotting and immunofluorescence results demonstrated the successful expression of immunogens carried by the DNA vaccines. On day 21 and 35 after the initial immunization, the levels of serum total immunoglobulin (Ig)G in all vaccine-given groups were slightly higher (approximately 1.5- to 2-fold) than those in the control groups. By contrast, ZIKV-specific IgG levels of all vaccine-given groups were significantly higher (approximately 10- to 1000- fold) than those of the control groups. The PRNT50 assay showed that the average serum dilution factors for neutralizing half ZIKV virions from vaccine-given groups were at least 32-fold (highest, 93-fold), while the sera from control group showed no protection. For cellular immunity, the proportions of CD11b+ myeloid cells, CD19+ B lymphocytes and CD3+ T lymphocytes in the mouse spleens as well as the percentages of CD4+ and CD8+ subsets of T cell were not changed 35 days after initial immunization. By contrast, the proportions of ZIKV-specific CD4+T cell and CD8+T cell in all vaccine-given groups were 2- to 10-folds and 2- to 30-fold than those in the control groups, respectively. CONCLUSION: All four DNA vaccines designed for the ZIKV induced neutralizing IgGs and cellular immune responses against ZIKV. Particularly, VPC-EIII-NS1 induced high level of humoral response comparable to the vaccine candidate containing prM, E and NS1 polyprotein, suggesting a potent reduced ADE effect and reserved neutralizing activity. Our findings may provide guidance for improving safety of anti-ZIKV vaccines in the future.


Asunto(s)
Vacunas de ADN , Vacunas Virales , Infección por el Virus Zika , Virus Zika , Ratones , Animales , Virus Zika/genética , Virus Zika/química , Anticuerpos Antivirales , Infección por el Virus Zika/prevención & control , Brasil , Anticuerpos Neutralizantes , Mamíferos
19.
Sci Immunol ; 7(73): eabm6931, 2022 07 29.
Artículo en Inglés | MEDLINE | ID: mdl-35905286

RESUMEN

Intraepithelial T cells (IETs) are in close contact with intestinal epithelial cells and the underlying basement membrane, and they detect invasive pathogens. How intestinal epithelial cells and basement membrane influence IET survival and function, at steady state or after infection, is unclear. The herpes virus entry mediator (HVEM), a member of the TNF receptor superfamily, is constitutively expressed by intestinal epithelial cells and is important for protection from pathogenic bacteria. Here, we showed that at steady-state LIGHT, an HVEM ligand, binding to epithelial HVEM promoted the survival of small intestine IETs. RNA-seq and addition of HVEM ligands to epithelial organoids indicated that HVEM increased epithelial synthesis of basement membrane proteins, including collagen IV, which bound to ß1 integrins expressed by IETs. Therefore, we proposed that IET survival depended on ß1 integrin binding to collagen IV and showed that ß1 integrin-collagen IV interactions supported IET survival in vitro. Moreover, the absence of ß1 integrin expression by T lymphocytes decreased TCR αß+ IETs in vivo. Intravital microscopy showed that the patrolling movement of IETs was reduced without epithelial HVEM. As likely consequences of decreased number and movement, protective responses to Salmonella enterica were reduced in mice lacking either epithelial HVEM, HVEM ligands, or ß1 integrins. Therefore, IETs, at steady state and after infection, depended on HVEM expressed by epithelial cells for the synthesis of collagen IV by epithelial cells. Collagen IV engaged ß1 integrins on IETs that were important for their maintenance and for their protective function in mucosal immunity.


Asunto(s)
Linfocitos Intraepiteliales , Animales , Colágeno , Células Epiteliales/metabolismo , Integrinas/metabolismo , Ligandos , Ratones
20.
Am J Clin Exp Urol ; 10(2): 73-81, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35528467

RESUMEN

INTRODUCTION: Pelvic lymph node dissection (PLND) is widely performed for staging in men undergoing radical prostatectomy (RP) for prostate cancer. Our goal was to synthesize all available evidence and data to evaluate perioperative complications for two templates of PLND, standard (sPLND) vs extended (ePLND), at the time of RP in patients with prostate cancer. METHODS: A meta-analysis was performed on relevant literature about complications during PLND. Pubmed, Scopus, WebofScience, and Cochrane Library were systematically searched through July 2021. Meta-analysis was conducted with both fixed-effects and random-effects models to estimate risk ratios (RRs) between treatments. A subgroup analysis was also conducted based on surgery type - open vs robotic. RESULTS: 13 (1 randomized clinical trial and 12 observational studies) studies published between 1997 and 2019 with a total of 7,036 patients were analyzed. Pooled data showed complications in a random-effects model was lower in the sPLND group than the ePLND group (RR, 0.62; 95% CI 0.40-0.97). In a subgroup analysis, neither the open surgery subgroup nor the robotic surgery subgroup showed significant differences in complication rate between sPLND and ePLND. CONCLUSION: ePLND is associated with a significantly greater risk of perioperative complication compared to sPLND, but not when comparing these templates performed via a robotic approach. Additional studies comparing the complication rates of sPLND and ePLND when utilizing a robotic approach should be conducted.

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