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T helper cells, particularly T follicular helper (TFH) cells, are essential for the neutralizing antibody production elicited by pathogens or vaccines. However, in immunocompromised individuals, the inefficient support from TFH cells could lead to limited protection after vaccine inoculation. Here we showed that the conjugation of inducible T cell costimulatory (ICOS) onto the nanoparticle, together with immunogen, significantly enhanced the immune response of the vaccines specific for SARS-CoV-2 or human immunodeficiency virus type-1 (HIV-1) in TFH-deficient mice. Further studies indicated that ICOSL on B cells was triggered by ICOS binding, subsequently activated the PKCβ signaling pathway, and enhanced the survival and proliferation of B cells. Our findings revealed that the stimulation of ICOS-ICOSL interaction by adding ICOS on the nanoparticle vaccine significantly substitutes the function of TFH cells to support B cell response, which is significant for the immunocompromised people, such as the elderly or HIV-1-infected individuals. [ABSTRACT FROM AUTHOR]

This study was intended to investigate the macular vascular and photoreceptor changes for diabetic macular edema (DME) at the early stage. A total of 255 eyes of 134 diabetes mellitus patients were enrolled and underwent an ophthalmological and systemic evaluation in this cross-sectional study. Early DME was characterized by central subfoveal thickness (CST) value between 250 and 325 μm, intact ellipsoid zone, and an external limiting membrane. While non-DME was characterized by CST < 250 μm with normal retinal morphology and structure. Foveal avascular zone (FAZ) area ≤ 0.3 mm2 (P < 0.001, OR = 0.41, 95% CI 0.26–0.67 in the multivariate analysis) and HbA1c level ≤ 8% (P = 0.005, OR = 0.37, 95% CI 0.19–0.74 in multivariate analysis) were significantly associated with a higher risk of early DME. Meanwhile, no significant differences exist in cone parameters between non-DME and early DME eyes. Compared with non-DME eyes, vessel diameter, vessel wall thickness, wall-to-lumen ratio, the cross-sectional area of the vascular wall in the upper side were significantly decreased in the early DME eyes (P = 0.001, P < 0.001, P = 0.005, P = 0.003 respectively). This study suggested a vasospasm or vasoconstriction with limited further photoreceptor impairment at the early stage of DME formation. CST ≥ 250 μm and FAZ ≤ 0.3 mm2 may be the indicator for early DME detection. [ABSTRACT FROM AUTHOR]

Even though the capability of aircraft manufacturing has improved, human factors still play a pivotal role in flight accidents. For example, fatigue-related accidents are a common factor in human-led accidents. Hence, pilots' precise fatigue detections could help increase the flight safety of airplanes. The article suggests a model to recognize fatigue by implementing the convolutional neural network (CNN) by implementing flight trainees' face attributions. First, the flight trainees' face attributions are derived by a method called the land-air call process when the flight simulation is run. Then, sixty-eight points of face attributions are detected by employing the Dlib package. Fatigue attribution points were derived based on the face attribution points to construct a model called EMF to detect face fatigue. Finally, the proposed PSO-CNN algorithm is implemented to learn and train the dataset, and the network algorithm achieves a recognition ratio of 93.9% on the test set, which can efficiently pinpoint the flight trainees' fatigue level. Also, the reliability of the proposed algorithm is validated by comparing two machine learning models. [ABSTRACT FROM AUTHOR]

Research on the potential association between life-ever gallstones and depressive symptoms is limited. This study aims to evaluate whether the presence of gallstone disease is associated with depressive symptoms. In this cross-sectional study, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020 cycles. The presence of depressive symptoms and gallstone disease was assessed using questionnaire responses. Adjusted odds ratios (OR) were calculated using a multivariate logistic regression model, with adjustments made for age, sex, race, body mass index, history of cardiovascular disease, hypertension, arthritis, and pulmonary disease across different models. Subgroup and sensitivity analyses were conducted to ensure the stability of the results. This study included 6201 adults aged 20 years and above, with 539(8.7%) experiencing depressive symptoms. After adjusting for age, sex, race, body mass index, CVD history, hypertension, arthritis, pulmonary disease, depressive symptoms were possibly associated with life-ever gallstones (OR 1.37, 95% CI 0.91–2.08).When depressive symptoms were categorized as mild, moderate, moderately severe, and severe,life-ever gallstones was possibly associated with mild depressive symptoms (OR 1.12, 95% CI 0.81–1.56), moderate depressive symptoms (OR 1.37, 95% CI 0.89–2.12), moderately severe depressive symptoms (OR 1.93, 95% CI 0.93–3.99), and severe depressive symptoms (OR 0.67, 95% CI 0.16–2.88).As a continuous variable, life-ever gallstones was associated with the PHQ-9 score (OR 0.42, 95% CI 0.02–0.83). The results remained stable after multiple imputation for all missing data. This cross-sectional study demonstrates no significant association between life-ever gallstones and depressive symptoms in US adults. [ABSTRACT FROM AUTHOR]

Objectives: To compare the effectiveness of caries arrest by micro-operative treatment (sealing) to operative treatment (flowable resin composite restoration) through a 2-year randomized controlled clinical trial. Materials and methods: A prospective randomized controlled trial was conducted among 7-9-year-old children. At baseline, 630 subjects were screened and 92 children who had at least one carious lesion classified as ICDAS 3 on the pit and fissure of first permanent molar were included. Then they were randomly assigned to the sealant group (73 lesions) and the flowable resin composite group (76 lesions) to receive the corresponding intervention. Lesions status in each group was evaluated every 6 months up to 24 months. Clinical progression of dental caries and materials retention were the outcomes used for group comparisons at p-value < 0.05. Results: After 24 months, three lesions (4.1%) in the sealant group clinically progressed to dentin caries. No lesion in the flowable composite group was observed a progression. The results of Life-table survival analysis show that the cumulative caries arrest rate had no statistically significant difference between the two groups (p = 0.075). However, the cumulative retention rate was 57.5% in the sealant group and 92.1% in the flowable composite group, with significant differences (p < 0.001). The multilevel mixed model showed the sealant had higher risk of retention failure than the flowable composite (OR = 8.66, p < 0.001), while tooth position did not influence material retention (p = 0.083). In addition, the results of Fisher Exact test show that dentin lesions had more retention failure than enamel lesions in the sealant group (p = 0.026). Conclusion: Although sealing microcavitated carious lesions of the first permanent molar achieved lower retention rate than resin composite restoration, both sealing and restoration effectively arrested caries progression for two years. Clinical relevance: To preserving dental structure and delaying or eliminating the need for operative procedures, microcavitated carious lesion can be arrested by sealing. Trial registration: Registered at ; Feb 15th, 2020; No. ChiCTR2000029862. [ABSTRACT FROM AUTHOR]

Viruses, as opportunistic intracellular parasites, hijack the cellular machinery of host cells to support their survival and propagation. Numerous viral proteins are subjected to host-mediated post-translational modifications. Here, we demonstrate that the SARS-CoV-2 nucleocapsid protein (SARS2-NP) is SUMOylated on the lysine 65 residue, which efficiently mediates SARS2-NP's ability in homo-oligomerization, RNA association, liquid-liquid phase separation (LLPS). Thereby the innate antiviral immune response is suppressed robustly. These roles can be achieved through intermolecular association between SUMO conjugation and a newly identified SUMO-interacting motif in SARS2-NP. Importantly, the widespread SARS2-NP R203K mutation gains a novel site of SUMOylation which further increases SARS2-NP's LLPS and immunosuppression. Notably, the SUMO E3 ligase TRIM28 is responsible for catalyzing SARS2-NP SUMOylation. An interfering peptide targeting the TRIM28 and SARS2-NP interaction was screened out to block SARS2-NP SUMOylation and LLPS, and consequently inhibit SARS-CoV-2 replication and rescue innate antiviral immunity. Collectively, these data support SARS2-NP SUMOylation is critical for SARS-CoV-2 virulence, and therefore provide a strategy to antagonize SARS-CoV-2. Here, the authors show that TRIM28-mediated SUMOylation of SARS-CoV-2 NP is critical for its liquid-liquid phase separation (LLPS) property and subsequent inhibition of innate antiviral immunity. The peptide NSIP-III is applied to unleash such connection by interfering TRIM28 and NP interaction. [ABSTRACT FROM AUTHOR]

The spatial and temporal variation of green economic efficiency and its driving factors are of great significance for the construction of high-efficiency and low-consumption green development model and sustainable socio-economic development. The research focused on the Yangtze River Economic Belt (YREB) and employed the miniumum distance to strong efficient frontier DEA (MinDs) model to measure the green economic efficiency of the municipalities in the region between 2008 and 2020. Then, the spatial autocorrelation model was used to analyze the evolution characteristics of its spatial pattern. Finally, Geodetector was applied to reveal the drivers and their interactions on green economic efficiency. It is found that: 1) the overall green economic efficiency of the YREB from 2008 to 2020 shows a W-shaped fluctuating upward trend, green economic efficiency is greater in the downstream and smallest in the upstream; 2) the spatial distribution of green economic efficiency shows clustering characteristics, with multi-core clustering based on ‘city clusters-central cities’ becoming more obvious over time; the High-High agglomeration type is mainly clustered in Jiangsu and Zhejiang, while the Low-Low agglomeration type is clustered in the western Sichuan Plateau area and southwestern Yunnan; 3) from input-output factors, whether it is the YREB as a whole or the upper, middle and lower reaches regions, the economic development level, labor input, and capital investment are the leading factors in the spatial-temporal evolution of green economic efficiency, with the comprehensive influence of economic development level and pollution index being the most important interactive driving factor; 4) from socio-economic factors, information technology drivers such as government intervention, transportation accessibility, information infrastructure, and Internet penetration are always high impact influencers and dominant interaction factors for green economic efficiency in the YREB and the three major regions in the upper, middle and lower reaches. Accordingly, the article puts forward relevant policy recommendations in terms of formulating differentiated green transformation strategies, strengthening network leadership and information technology construction and coordinating multi-factor integrated development, which could provide useful reference for promoting synergistic green economic efficiency in the YREB. [ABSTRACT FROM AUTHOR]

: Circulating neutrophil extracellular trap (NET) formation is an adaptive process during acute lung injury (ALI). The important role of plasminogen activator inhibitor (PAI)-1 in NET formation during ALI remains unclear. This research intends to examine the impacts of the decrease in PAI-1 levels on NET formation and the underlying mechanism. We found a relative association between the increase in plasma NET levels and thromboinflammation-induced lung damage in patients with ARDS. PAI-1 knockout (KO) mice exhibited significant increases in Pseudomonas aeruginosa (PAO1 strain)-induced ALI, inflammation, inflammatory cell accumulation, and proinflammatory cytokine secretion, and wild-type mice exhibited the opposite changes. During PAO1-induced ALI, PAI-1 KO increased NET release and the levels of prothrombotic markers in mice. PAI-1 deficiency also promoted NET formation and NET-mediated pyroptosis and ferroptosis by activating the PI3K/MAPK/AKT pathway in a PAO1-induced ALI mouse model. In conclusion, PAI-1 KO exacerbated PAO1-induced pneumonia-associated injury and contributed to NET-mediated pyroptosis and ferroptosis through PI3K/MAPK/AKT pathway activation. Thus, targeting PAI-1 and NETs may be a promising therapeutic approach for ameliorating pneumonia and thromboinflammation-associated ALI. [ABSTRACT FROM AUTHOR]