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1.
Front Psychiatry ; 15: 1378438, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38721612

RESUMEN

Background: Recent studies have shown that regular physical activity (PA) can positively influence mobile phone addiction (MPA) behaviors in college students. However, it remains unknown whether this effect is mediated by other factors. Evidence suggests that resilience and interaction anxiousness may be candidate mediators that partly explain the positive effect of PA on MPA. This study aims to explore the impact of PA on MPA through a mediation model, and the role of resilience and interaction anxiousness in this relationship. Methods: The participants were 590 college students (272 males; mean age = 19.67) who completed a psychosocial battery, including the international physical activity questionnaire-short form (IPAQ-SF), the connor - davidson resilience scale (CD-RISC), the interaction anxiousness scale (IAS), and the mobile phone addiction index (MPAI). Correlations of variables were computed using Pearson's test. Mediation models were tested using SPSSS PROCESS macro with the regression bootstrapping method. Results: PA were negatively associated with MPA behavior (r=-.21, p < 0.01). Resilience and interaction anxiousness moderated the relationship between PA and MPA. More importantly, PA could also influence MPA through the chain-mediating effects of resilience and interaction anxiousness. Conclusion: It is essential to improve resilience and reduce interaction anxiousness to reduce MPA problems through regular engagement in PA among college students.

2.
Comput Biol Med ; 176: 108539, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38728992

RESUMEN

Nested entities and relationship extraction are two tasks for analysis of electronic medical records. However, most of existing medical information extraction models consider these tasks separately, resulting in a lack of consistency between them. In this paper, we propose a joint medical entity-relation extraction model with progressive recognition and targeted assignment (PRTA). Entities and relations share the information of sequence and word embedding layers in the joint decoding stage. They are trained simultaneously and realize information interaction by updating the shared parameters. Specifically, we design a compound triangle strategy for the nested entity recognition and an adaptive multi-space interactive strategy for relationship extraction. Then, we construct a parameter-shared information space based on semantic continuity to decode entities and relationships. Extensive experiments were conducted on the Private Liver Disease Dataset (PLDD) provided by Beijing Friendship Hospital of Capital Medical University and public datasets (NYT, ACE04 and ACE05). The results show that our method outperforms existing SOTA methods in most indicators, and effectively handles nested entities and overlapping relationships.

3.
Bioact Mater ; 37: 477-492, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38698919

RESUMEN

Degradable rotator cuff patches, followed over five years, have been observed to exhibit high re-tear rates exceeding 50%, which is attributed to the inability of degradable polymers alone to restore the post-rotator cuff tear (RCT) inflammatory niche. Herein, poly(ester-ferulic acid-urethane)urea (PEFUU) was developed, featuring prolonged anti-inflammatory functionality, achieved by the integration of ferulic acid (FA) into the polyurethane repeating units. PEFUU stably releases FA in vitro, reversing the inflammatory niche produced by M1 macrophages and restoring the directed differentiation of stem cells. Utilizing PEFUU, hierarchical composite nanofiber patch (HCNP) was fabricated, simulating the natural microstructure of the tendon-to-bone interface with an aligned-random alignment. The incorporation of enzymatic hydrolysate derived from decellularized Wharton jelly tissue into the random layer could further enhance cartilage regeneration at the tendon-to-bone interface. Via rat RCT repairing model, HCNP possessing prolonged anti-inflammatory properties uniquely facilitated physiological healing at the tendon-to-bone interface's microstructure. The alignment of fibers was restored, and histologically, the characteristic tripartite distribution of collagen I - collagen II - collagen I was achieved. This study offers a universal approach to the functionalization of degradable polymers and provides a foundational reference for their future applications in promoting the in vivo regeneration of musculoskeletal tissues.

4.
Heliyon ; 10(10): e30594, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38774318

RESUMEN

Aim: Disturbed intestinal microbiota has been implicated in the inflammatory microenvironment of the colon, which usually results in ulcerative colitis (UC). Given the limitations of these drugs, it is important to explore alternative means of protecting the gut health from UC. This study aimed to investigate the potential of polysaccharides as beneficial nutrients in the regulation of the gut microbiota, which determines the inflammatory microenvironment of the colon. Materials and methods: Mice were treated with dextran sulfate sodium (DSS) to evaluate the effects and mechanisms of Lycium barbarum polysaccharide (LBP) in remodeling the inflammatory microenvironment and improving gut health. Body weight and disease activity indices were monitored daily. Hematoxylin and eosin staining was used to analyze colon dynamics. The levels of inflammatory indicators and expression of MUC-2, claudin-1, ZO-1, and G-protein-coupled receptor 5 (TGR5) were determined using assay kits and immunohistochemistry, respectively. 16S rRNA high-throughput sequencing of the intestinal microbiota and liquid chromatography-tandem mass spectrometry for related bile acids were used. Results: LBP significantly improved the colonic tissue structure by upregulating MUC-2, claudin-1, and ZO-1 protein expression. The bacterial genus Dubosiella was dominant in healthy mice, but significantly decreased in mice treated with DSS. LBP rehabilitated Dubosiella in the sick guts of DSS mice to a level close to that of healthy mice. The levels of other beneficial bacterial genera Akkermansia and Bifidobacterium were also increased, whereas those of the harmful bacterial genera Turicibacter, Clostridium_sensu_stricto_1, Escherichia-Shigella, and Faecalibaculum decreased. The activity of beneficial bacteria promoted the bile acids lithocholic and deoxycholic acids in mice with UC, which improved the gut barrier function through the upregulation of TGR5. Conclusion: The inflammatory microenvironment in the gut is determined by the balance of the gut microbiota. LBP showed great potential as a beneficial nutrient for rehabilitating Dubosiella which is dominant in the gut of healthy mice. Nutrient-related LBP may play an important role in gut health management.

5.
Hum Vaccin Immunother ; 20(1): 2345943, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38757492

RESUMEN

Dental caries is a prevalent oral disease that mainly results from Streptococcus mutans. Susceptibility to S. mutans decreased rapidly after weaning in a well-known rat model. However, owing to the lack of time to establish protective immunity ahead of challenge, the weaning rat model is suboptimal for assessing prophylactic vaccines against S. mutans infection. In this study, we found that, in adult rats, S. mutans cultured under air-restricted conditions showed dramatically increased colonization efficacy and accelerated development of dental caries compared with those cultured under air-unrestricted conditions. We propose that S. mutans cultured under air-restricted conditions can be used to develop an optimal caries model, especially for the evaluation of prophylactic efficacy against S. mutans. Therefore, we used the anti-caries vaccine, KFD2-rPAc, to reevaluate the protection against the challenge of S. mutans. In immunized rats, rPAc-specific protective antibodies were robustly elicited by KFD2-rPAc before the challenge. In addition to inhibiting the initial and long-term colonization of S. mutans in vivo, KFD2-rPAc immunization showed an 83% inhibitory efficacy against the development of caries, similar to that previously evaluated in a weaning rat model. These results demonstrate that culturing under air-restricted conditions can promote S. mutans infection in adult rats, thereby helping establish a rat infection model to evaluate the prophylactic efficacy of vaccines and anti-caries drugs.


Asunto(s)
Anticuerpos Antibacterianos , Caries Dental , Modelos Animales de Enfermedad , Streptococcus mutans , Animales , Caries Dental/prevención & control , Caries Dental/microbiología , Caries Dental/inmunología , Streptococcus mutans/inmunología , Ratas , Anticuerpos Antibacterianos/inmunología , Anticuerpos Antibacterianos/sangre , Vacunas Estreptocócicas/inmunología , Vacunas Estreptocócicas/administración & dosificación , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/microbiología , Femenino , Ratas Sprague-Dawley
6.
Trials ; 25(1): 335, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773529

RESUMEN

BACKGROUND: With suicide as a leading cause of death, the issue of children and adolescent suicide risks is in the spotlight today. To empower teachers in primary and secondary schools to serve as gatekeepers and to ensure the safety of children and adolescents, the systematically tailored and localized Life Gatekeeper suicide prevention program was designed for Chinese schools. OBJECTIVE: With the ultimate goal of preventing child and adolescent suicide, we aim to outline a research protocol for examining outcomes of the recently created standardized school-based Life Gatekeeper program in reducing teachers' stigma, increasing their knowledge, willingness to intervene, and perceived competence. METHODS: Participants will be recruited from eligible primary and secondary schools. Cluster sampling will be used to randomly assign each school to either the intervention group or the control group. The primary outcomes are stigma against suicide, suicide literacy, perceived competence, and willingness to intervene with suicidal individuals, which will be measured using the Stigma of Suicide Scale, the Literacy of Suicide Scale, and the Willingness to Intervene Against Suicide Questionnaire, respectively. Measurements will be taken at four time points, including pre-intervention, immediately after the intervention, 6-month follow-up, and 1-year follow-up. CONCLUSIONS: The current study features innovative implementation in the real world, by using a randomized controlled trial design to examine the effectiveness of a school-based gatekeeper program among primary and secondary school teachers, following a sequence of defined and refined steps. The research will also investigate the viability of a school-based gatekeeper program for primary and secondary school teachers that could be quickly and inexpensively implemented in a large number of schools.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Servicios de Salud Escolar , Maestros , Estigma Social , Prevención del Suicidio , Formación del Profesorado , Humanos , China , Adolescente , Niño , Maestros/psicología , Formación del Profesorado/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Suicidio/psicología , Factores de Tiempo , Masculino , Femenino , Conducta del Adolescente , Servicios de Salud Mental Escolar , Evaluación de Programas y Proyectos de Salud , Conducta Infantil
7.
Mater Horiz ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38742392

RESUMEN

Polyurethane (PU) foams, pivotal in modern life, face challenges suh as fire hazards and environmental waste burdens. The current reliance of PU on potentially ecotoxic halogen-/phosphorus-based flame retardants impedes large-scale material recycling. Here, our demonstrated controllable catalytic cracking strategy, using cesium salts, enables self-evolving recycling of flame-retardant PU. The incorporation of cesium citrates facilitates efficient urethane bond cleavage at low temperatures (160 °C), promoting effective recycling, while encouraging pyrolytic rearrangement of isocyanates into char at high temperatures (300 °C) for enhanced PU fire safety. Even in the absence of halogen/phosphorus components, this foam exhibits a substantial increase in ignition time (+258.8%) and a significant reduction in total smoke release (-79%). This flame-retardant foam can be easily recycled into high-quality polyol under mild conditions, 60 °C lower than that for the pure foam. Notably, the trace amounts of cesium gathered in recycled polyols stimulate the regenerated PU to undergo self-evolution, improving both flame-retardancy and mechanical properties. Our controllable catalytic cracking strategy paves the way for the self-evolutionary recycling of high-performance firefighting materials.

8.
Opt Lett ; 49(9): 2417-2420, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691733

RESUMEN

Soliton complexes highlight the particle-like dynamics of dissipative pulses. However, simple and reliable manipulation of bound solitons remains challenging, particularly for all-polarization-maintaining (PM) configurations that are free from random polarization perturbations. Here, we report controllable pulse patterns of robustly coexisting dichromatic soliton complexes in an all-PM fiber laser based on a twistable tapered-fiber filter. According to the twist angle, dichromatic pulses are switched between different patterns, and components at each wavelength can be independently manipulated, extending encodings from the time to the frequency domain. To the best of our knowledge, it is the first experimental demonstration of dual-wavelength soliton complexes that different pulse patterns coexist at separated wavebands.

9.
Opt Lett ; 49(9): 2433-2436, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691737

RESUMEN

We present for the first time, to the best of our knowledge, the pump-power-controlled, all-polarization-maintaining (all-PM), all-fiber configured, wavelength-tunable mode-locked fiber laser in the L-band (1565 to 1625 nm). A tuning range over 20 nm (1568.2  to 1588.9 nm) is attained simply by varying the pump power between 45 and 115 mW. Our work represents the first demonstration of wavelength tuning in all-PM configured nonlinear polarization evolution (NPE) lasers. The non-mechanical and electrically controllable tuning method offers ease of use and cost efficiency within an advanced all-PM, all-fiber design, indicating promising adaptability to diverse wavelength bands.

10.
Nanoscale ; 16(19): 9509-9515, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38651538

RESUMEN

Scandium oxide (Sc2O3) has a wide range of applications in metallurgy, chemical industry, electronics and many other high-tech fields. However, most Sc2O3 materials exist in the powder or bulk form, while nanostructured Sc2O3 has rarely been reported as there is a lack of a common method to control its dimensionality, hindering the understanding of new properties and potential applications of nano-Sc2O3 materials. In this paper, we establish a procedure to synthesize a two-dimensional (2D) Sc2O3-covalent organic framework (COF) composite film where the crystal size of Sc2O3 domains is as small as ∼3 nm. The composite film is prepared by a Schiff base condensation reaction at the sharp n-pentane/water interface using a combination of surfactant-monolayer-assisted interfacial synthesis and laminar assembly polymerization methods. Then the conditions of nucleation and uniform film formation of the 2D Sc2O3/COF are explored further. Meanwhile, an atomic force microscopy indentation test shows that the material has a high Young's modulus of 89.1 ± 3.8 GPa, which is much higher than those of the majority of reported 2D polymer materials. We further extended this synthesis method to the preparation of Yb2O3 (ytterbium oxide) and/or Er2O3 (erbium oxide)-incorporated 2D COF composite films, verifying the universality of this strategy. This work provides an opportunity to vary the dimensionality of many kinds of metal oxides and explore the potential applications of low-dimensional Sc2O3 materials.

11.
Diabetes Care ; 47(6): 1012-1019, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38623619

RESUMEN

OBJECTIVE: Integrated analyses of plasma proteomics and genetic data in prospective studies can help assess the causal relevance of proteins, improve risk prediction, and discover novel protein drug targets for type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We measured plasma levels of 2,923 proteins using Olink Explore among ∼2,000 randomly selected participants from China Kadoorie Biobank (CKB) without prior diabetes at baseline. Cox regression assessed associations of individual protein with incident T2D (n = 92 cases). Proteomic-based risk models were developed with discrimination, calibration, reclassification assessed using area under the curve (AUC), calibration plots, and net reclassification index (NRI), respectively. Two-sample Mendelian randomization (MR) analyses using cis-protein quantitative trait loci identified in a genome-wide association study of CKB and UK Biobank for specific proteins were conducted to assess their causal relevance for T2D, along with colocalization analyses to examine shared causal variants between proteins and T2D. RESULTS: Overall, 33 proteins were significantly associated (false discovery rate <0.05) with risk of incident T2D, including IGFBP1, GHR, and amylase. The addition of these 33 proteins to a conventional risk prediction model improved AUC from 0.77 (0.73-0.82) to 0.88 (0.85-0.91) and NRI by 38%, with predicted risks well calibrated with observed risks. MR analyses provided support for the causal relevance for T2D of ENTR1, LPL, and PON3, with replication of ENTR1 and LPL in Europeans using different genetic instruments. Moreover, colocalization analyses showed strong evidence (pH4 > 0.6) of shared genetic variants of LPL and PON3 with T2D. CONCLUSIONS: Proteomic analyses in Chinese adults identified novel associations of multiple proteins with T2D with strong genetic evidence supporting their causal relevance and potential as novel drug targets for prevention and treatment of T2D.


Asunto(s)
Diabetes Mellitus Tipo 2 , Proteómica , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudio de Asociación del Genoma Completo , Anciano , Adulto
12.
Int Immunopharmacol ; 132: 111999, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38581994

RESUMEN

Idiopathic pulmonary fibrosis (IPF) is a heterogeneous group of lung diseases with different etiologies and characterized by progressive fibrosis. This disease usually causes pulmonary structural remodeling and decreased pulmonary function. The median survival of IPF patients is 2-5 years. Predominantly accumulation of type II innate immune cells accelerates fibrosis progression by secreting multiple pro-fibrotic cytokines. Group 2 innate lymphoid cells (ILC2) and monocytes/macrophages play key roles in innate immunity and aggravate the formation of pro-fibrotic environment. As a potent immunosuppressant, tacrolimus has shown efficacy in alleviating the progression of pulmonary fibrosis. In this study, we found that tacrolimus is capable of suppressing ILC2 activation, monocyte differentiation and the interaction of these two cells. This effect further reduced activation of monocyte-derived macrophages (Mo-M), thus resulting in a decline of myofibroblast activation and collagen deposition. The combination of tacrolimus and nintedanib was more effective than either drug alone. This study will reveal the specific process of tacrolimus alleviating pulmonary fibrosis by regulating type II immunity, and explore the potential feasibility of tacrolimus combined with nintedanib in the treatment of pulmonary fibrosis. This project will provide new ideas for clinical optimization of anti-pulmonary fibrosis drug strategies.


Asunto(s)
Fibrosis Pulmonar Idiopática , Inmunosupresores , Ratones Endogámicos C57BL , Monocitos , Tacrolimus , Tacrolimus/uso terapéutico , Tacrolimus/farmacología , Animales , Monocitos/efectos de los fármacos , Monocitos/inmunología , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/inmunología , Fibrosis Pulmonar Idiopática/patología , Ratones , Inmunosupresores/uso terapéutico , Inmunosupresores/farmacología , Humanos , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Inmunidad Innata/efectos de los fármacos , Indoles/uso terapéutico , Indoles/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Progresión de la Enfermedad , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Células Cultivadas , Masculino , Citocinas/metabolismo , Miofibroblastos/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad
13.
ACS Appl Mater Interfaces ; 16(15): 19519-19528, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38580622

RESUMEN

The inherent flammability of most polymeric materials poses a significant fire hazard, leading to substantial property damage and loss of life. A universal flame-retardant protective coating is considered as a promising strategy to mitigate such risks; however, simultaneously achieving high transparency of the coatings remains a great challenge. Here, inspired by the moth eye effect, we designed a nanoporous structure into a protective coating that leverages a hydrophilic-hydrophobic interactive assembly facilitated by phosphoric acid protonated amino siloxane. The coating demonstrates robust adhesion to a diverse range of substrates, including but not limited to fabrics, foams, paper, and wood. As expected, its moth-eye-inspired nanoporous structure conferred a high visible light transparency of >97% and water vapor transmittance of 96%. The synergistic effect among phosphorus (P), nitrogen (N), and silicon (Si) largely enhanced the char-forming ability and restricted the decomposition of the coated substrates, which successfully endowed the coating with high fire-fighting performance. More importantly, for both flexible and rigid substrates, the coated samples all possessed great mechanical properties. This work provides a new insight for the design of protective coatings, particularly focusing on achieving high transparency.

14.
Adv Sci (Weinh) ; : e2402915, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38641884

RESUMEN

The silicon (Si) anode is prone to forming a high electric field gradient and concentration gradient on the electrode surface under high-rate conditions, which may destroy the surface structure and decrease cycling stability. In this study, a ferroelectric (BaTiO3) interlayer and field polarization treatment are introduced to set up a built-in field, which optimizes the transport mechanisms of Li+ in solid and liquid phases and thus enhances the rate performance and cycling stability of Si anodes. Also, a fast discharging and slow charging phenomenon is observed in a half-cell with a high reversible capacity of 1500.8 mAh g-1 when controlling the polarization direction of the interlayer, which means a fast charging and slow discharging property in a full battery and thus is valuable for potential applications in commercial batteries. Simulation results demonstrated that the built-in field plays a key role in regulating the Li+ concentration distribution in the electrolyte and the Li+ diffusion behavior inside particles, leading to more uniform Li+ diffusion from local high-concentration sites to surrounding regions. The assembled lithium-ion battery with a BaTiO3 interlayer exhibited superior electrochemical performance and long-term cycling life (915.6 mAh g-1 after 300 cycles at a high current density of 4.2 A g-1). The significance of this research lies in exploring a new approach to improve the performance of lithium-ion batteries and providing new ideas and pathways for addressing the challenges faced by Si-based anodes.

15.
Opt Lett ; 49(8): 1911-1914, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38621037

RESUMEN

Coherent beam combining (CBC) of two femtosecond third-harmonic (TH) generators is proposed and demonstrated. By applying phase modulation to one of the fundamental laser pulses, the feedback loop effectively eliminates both phase and pointing errors between the two TH femtosecond laser beams. The system delivers 345-nm femtosecond laser pulses with 22-W average power at 1-MHz repetition rate. The average combining efficiency is 91.5% over approximately 1 h of testing. The beam quality of the combined ultraviolet (UV) laser beam is near-diffraction-limited with M2 factors of M X2=1.36, M Y2=1.24, which are similar to those of the individual channels. This scheme exhibits promising potential for increasing high-beam-quality UV laser power.

16.
Biochem Cell Biol ; 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38567768

RESUMEN

Cell-in-cell (CIC) structures have been suggested to mediate intracellular substance transport between cells and have been found widely in inflammatory lung tissue of asthma. The aim of this study was to investigate the significance of CIC structures in inflammatory progress of asthma. CIC structures and related inflammatory pathways were analyzed in asthmatic lung tissue and normal lung tissue of mouse model. In vitro, the activation of inflammatory pathways by CIC-mediated intercellular communication was analyzed by RNA-Seq and verified by Western blotting and immunofluorescence. Results showed that CIC structures of lymphocytes and alveolar epithelial cells in asthmatic lung tissue mediated intercellular substance (such as mitochondria) transfer and promoted pro-inflammation in two phases. At early phase, internal lymphocytes triggered inflammasome-dependent pro-inflammation and cell death of itself. Then, degraded lymphocytes released cellular contents such as mitochondria inside alveolar epithelial cells, further activated multi-pattern-recognition receptors and NF-kappa B signaling pathways of alveolar epithelial cells, and thereby amplified pro-inflammatory response in asthma. Our work supplements the mechanism of asthma pro-inflammation progression from the perspective of CIC structure of lymphocytes and alveolar epithelial cells, and provides a new idea for anti-inflammatory therapy of asthma.

17.
Signal Transduct Target Ther ; 9(1): 114, 2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38678055

RESUMEN

Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the epidemic. Here, we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain (RBD) scaffold protein (3R-NC) adjuvanted with a flagellin protein (KFD) (3R-NC + KFDi.n). In mice, the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a year. This long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG- and IgA-producing plasma cells, alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD adjuvant. Based upon these preclinical findings, an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2 (IAV) vaccine. With a favorable safety profile, the 3R-NC + KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary secretions. To meet the challenge of frequently emerged variants, we further designed an updated triple-RBD scaffold protein with mutated RBD combinations, which can induce adaptable antibody responses to neutralize the newly emerging variants, including JN.1. Our findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.


Asunto(s)
Administración Intranasal , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Flagelina , SARS-CoV-2 , SARS-CoV-2/inmunología , Humanos , Flagelina/inmunología , Flagelina/genética , Flagelina/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , Animales , Ratones , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Anticuerpos Neutralizantes/inmunología , Femenino , Anticuerpos Antivirales/inmunología , Vacunación , Masculino , Adulto , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina A/inmunología , Persona de Mediana Edad
18.
Pharmacol Res ; 203: 107178, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38583686

RESUMEN

Idiopathic pulmonary fibrosis (IPF) is one of the most fatal chronic interstitial lung diseases with unknown pathogenesis, current treatments cannot truly reverse the progression of the disease. Pulmonary macrophages, especially bone marrow derived pro-fibrotic macrophages, secrete multiple kinds of profibrotic mediators (SPP1, CD206, CD163, IL-10, CCL18…), thus further promote myofibroblast activation and fibrosis procession. IL20Rb is a cell-surface receptor that belongs to IL-20 family. The role of IL20Rb in macrophage activation and pulmonary fibrosis remains unclear. In this study, we established a bleomycin-induced pulmonary fibrosis model, used IL4/13-inducing THP1 cells to induce profibrotic macrophage (M2-like phenotype) polarization models. We found that IL20Rb is upregulated in the progression of pulmonary fibrosis, and its absence can alleviate the progression of pulmonary fibrosis. In addition, we demonstrated that IL20Rb promote the activation of bone marrow derived profibrotic macrophages by regulating the Jak2/Stat3 and Pi3k/Akt signaling pathways. In terms of therapeutic strategy, we used IL20Rb neutralizing antibodies for animal administration, which was found to alleviate the progression of IPF. Our results suggest that IL20Rb plays a profibrotic role by promoting profibrotic macrophage polarization, and IL20Rb may become a potential therapeutic target for IPF. Neutralizing antibodies against IL20Rb may become a potential drug for the clinical treatment of IPF.


Asunto(s)
Bleomicina , Activación de Macrófagos , Macrófagos , Ratones Endogámicos C57BL , Animales , Humanos , Macrófagos/metabolismo , Macrófagos/inmunología , Bleomicina/toxicidad , Ratones , Masculino , Receptores de Interleucina/metabolismo , Fibrosis Pulmonar Idiopática/patología , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/inmunología , Transducción de Señal , Factor de Transcripción STAT3/metabolismo , Janus Quinasa 2/metabolismo , Células THP-1 , Pulmón/patología , Pulmón/metabolismo , Pulmón/inmunología , Pulmón/efectos de los fármacos , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/inmunología , Fibrosis Pulmonar/inducido químicamente , Ratones Noqueados , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo
19.
Brief Bioinform ; 25(3)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38581422

RESUMEN

Reliable cell type annotations are crucial for investigating cellular heterogeneity in single-cell omics data. Although various computational approaches have been proposed for single-cell RNA sequencing (scRNA-seq) annotation, high-quality cell labels are still lacking in single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) data, because of extreme sparsity and inconsistent chromatin accessibility between datasets. Here, we present a novel automated cell annotation method that transfers cell type information from a well-labeled scRNA-seq reference to an unlabeled scATAC-seq target, via a parallel graph neural network, in a semi-supervised manner. Unlike existing methods that utilize only gene expression or gene activity features, HyGAnno leverages genome-wide accessibility peak features to facilitate the training process. In addition, HyGAnno reconstructs a reference-target cell graph to detect cells with low prediction reliability, according to their specific graph connectivity patterns. HyGAnno was assessed across various datasets, showcasing its strengths in precise cell annotation, generating interpretable cell embeddings, robustness to noisy reference data and adaptability to tumor tissues.


Asunto(s)
Cromatina , Redes Neurales de la Computación , Reproducibilidad de los Resultados
20.
J Int Med Res ; 52(3): 3000605241236278, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38483140

RESUMEN

OBJECTIVE: To assess the efficacy of dynamic changes in lymphocyte-C-reactive protein ratio (LCR) on differentiating disease severity and predicting disease progression in adult patients with Coronavirus disease 2019 (COVID-19). METHODS: This single-centre retrospective study enrolled adult COVID-19 patients categorized into moderate, severe and critical groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (ninth edition). Demographic and clinical data were collected. LCR and sequential organ failure assessment (SOFA) score were calculated. Lymphocyte count and C-reactive protein (CRP) levels were monitored on up to four occasions. Disease severity was determined concurrently with each LCR measurement. RESULTS: This study included 145 patients assigned to moderate (n = 105), severe (n = 33) and critical groups (n = 7). On admission, significant differences were observed among different disease severity groups including age, comorbidities, neutrophil proportion, lymphocyte count and proportion, D-Dimer, albumin, total bilirubin, direct bilirubin, indirect bilirubin, CRP and SOFA score. Dynamic changes in LCR showed significant differences across different disease severity groups at different times, which were significantly inversely correlated with disease severity of COVID-19, with correlation coefficients of -0.564, -0.548, -0.550 and -0.429 at four different times. CONCLUSION: Dynamic changes in LCR can effectively differentiate disease severity and predict disease progression in adult COVID-19 patients.


Asunto(s)
COVID-19 , Adulto , Humanos , COVID-19/diagnóstico , Estudios Retrospectivos , Proteína C-Reactiva/análisis , SARS-CoV-2 , Biomarcadores , Gravedad del Paciente , Índice de Severidad de la Enfermedad , Linfocitos/metabolismo , Progresión de la Enfermedad , Bilirrubina
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