Inhalable hybrid nanovaccines with virus-biomimetic structure boost protective immune responses against SARS-CoV-2 variants.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with different antigenic variants, has posed a significant threat to public health. It is urgent to develop inhalable vaccines, instead of injectable vaccines, to elicit mucosal immunity against respiratory viral infections. METHODS: We reported an inhalable hybrid nanovaccine (NVRBD-MLipo) to boost protective immunity against SARS-CoV-2 infection. Nanovesicles derived from genetically engineered 293T cells expressing RBD (NVRBD) were fused with pulmonary surfactant (PS)-biomimetic liposomes containing MPLA (MLipo) to yield NVRBD-MLipo, which possessed virus-biomimetic structure, inherited RBD expression and versatile properties. RESULTS: In contrast to subcutaneous vaccination, NVRBD-MLipo, via inhalable vaccination, could efficiently enter the alveolar macrophages (AMs) to elicit AMs activation through MPLA-activated TLR4/NF-κB signaling pathway. Moreover, NVRBD-MLipo induced T and B cells activation, and high level of RBD-specific IgG and secretory IgA (sIgA), thus elevating protective mucosal and systemic immune responses, while reducing side effects. NVRBD-MLipo also demonstrated broad-spectrum neutralization activity against SARS-CoV-2 (WT, Delta, Omicron) pseudovirus, and protected immunized mice against WT pseudovirus infection. CONCLUSIONS: This inhalable NVRBD-MLipo, as an effective and safe nanovaccine, holds huge potential to provoke robust mucosal immunity, and might be a promising vaccine candidate to combat respiratory infectious diseases, including COVID-19 and influenza.

An efficient TOF-SIMS image analysis with spatial correlation and alternating non-negativity-constrained least squares.

MOTIVATION: Advances in analytical instrumentation towards acquiring high-resolution images of mass spectrometry constantly demand efficient approaches for data analysis. This is particularly true of time-of-flight secondary ion mass spectrometry imaging where recent advances enable acquisition of high-resolution data in multiple dimensions. In many applications, the distribution of different species from a sampled surface is spatially continuous in nature and a model that incorporates the spatial correlation across the surface would be preferable to estimations at discrete spatial locations. A key challenge here is the capability to analyse the high-resolution multidimensional data to extract relevant information reliably and efficiently. RESULTS: We propose a framework based on alternating non-negativity-constrained least squares which accounts for the spatial correlation across the sample surface. The proposed method also decouples the computational complexity of the estimation procedure from the image resolution, which significantly reduces the processing time. We evaluate the performance of the algorithm with biochemical image datasets generated from mixture of metabolites.

Is Azvudine Comparable to Nirmatrelvir-Ritonavir in Real-World Efficacy and Safety for Hospitalized Patients with COVID-19? A Retrospective Cohort Study.

INTRODUCTION: Azvudine and nirmatrelvir-ritonavir are more extensively used to treat COVID-19 in China due to their earlier approval by the National Medical Products Administration. However, there has been a scarcity of research directly comparing the clinical outcomes between azvudine and nirmatrelvir-ritonavir till now. We aimed to make a head-to-head comparison of the efficacy and safety of azvudine or nirmatrelvir-ritonavir in hospitalized patients with COVID-19 in China. METHODS: This retrospective cohort study was conducted using data collected from Tongde Hospital of Zhejiang Province between December 2022 and January 2023. All-cause mortality, risk of progressing to a critical condition, proportion with nucleic-acid negative conversion (PNANC), time to first nucleic-acid negative conversion (TFNANC), length of hospital stay and incidence of adverse events were systematically assessed as outcomes. Multi-model regression analysis, propensity-score-matching analysis, subgroup analysis and several sensitivity analyses were applied to compare these outcomes. RESULTS: This study included a total of 1571 hospitalized patients with COVID-19, among whom 272 received nirmatrelvir-ritonavir and 156 received azvudine. We found no significant differences in all-cause mortality (HR 1.41; 95% CI 0.56-3.56; P = 0.471), risk of progressing to critical COVID-19 (HR 1.67; 95% CI 0.78-3.60; P = 0.189), PNANC (HR 0.87; 95% CI 0.69-1.09; P = 0.220), length of stay (ß - 0.82; 95% CI - 2.78 to 1.15; P = 0.414) and adverse event rate (3.21% vs. 4.41%, P = 0.538) between the two groups, although azvudine was slightly less effective than nirmatrelvir-ritonavir. Meanwhile, the azvudine group exhibited a significantly longer TFNANC (ß 2.53; 95% CI 0.76-4.29; P = 0.005) than the nirmatrelvir-ritonavir group. Results were similar for propensity-score matching and multiple sensitivity analyses. CONCLUSION: Azvudine probably possessed comparable efficacy and safety to nirmatrelvir-ritonavir, although it was less effective than nirmatrelvir-ritonavir for some outcomes.

Implementation of CT Image Segmentation Based on an Image Segmentation Algorithm.

With the increasingly important role of image segmentation in the field of computed tomography (CT) image segmentation, the requirements for image segmentation technology in related industries are constantly improving. When the hardware resources can fully meet the needs of the fast and high-precision image segmentation program system, the main means of how to improve the image segmentation effect is to improve the related algorithms. Therefore, this study has proposed a combination of genetic algorithm (GA) and Great Law (OTSU) algorithm to form an image segmentation algorithm-immune genetic algorithm (IGA) algorithm. The algorithm has improved the segmentation accuracy and efficiency of the original algorithm, which is beneficial to the more accurate results of CT image segmentation. The experimental results in this study have shown that the operating efficiency of the OTSU segmentation algorithm is up to 75%. The operating efficiency of the GA algorithm is up to 78%. The operating efficiency of the IGA algorithm is up to 92%. In terms of operating efficiency, the OTSU segmentation algorithm has more advantages. In terms of segmentation accuracy, the highest accuracy rate of OTSU segmentation algorithm is 45%. The accuracy of the GA algorithm is 80%. The highest accuracy of the IGA algorithm is 97%. The IGA algorithm is more powerful in terms of operating efficiency and accuracy. Therefore, the application of the IGA algorithm to CT image segmentation is beneficial to doctors to better judge the lesions and improve the diagnosis rate.

Bioactive dammarane triterpenoid saponins from the leaves of Cyclocarya paliurus.

Thirteen undescribed dammarane triterpenoid saponins (cypaliurusides A-M), including eleven seco-dammarane type triterpenoids, were isolated from Cyclocarya paliurus. Each of these compounds has the unique feature of having a monosaccharide attached to C-11, rather than C-12, compared to the same type of saponins found in this plant. The structures of them were determined by comprehensive analysis of 1D, 2D NMR and HRESIMS data. Cypaliuruside J showed significant α-glucosidase inhibitory effect with IC50 value of 2.22 ± 0.13 µM. In addition, Cypaliurusides F and K exhibited modest cytotoxic activities against selected human cancer cell lines in vitro, with IC50 values ranging from 4.61 ± 0.13 to 15.23 ± 3.88 µM.

L-carnitine's role in KAATSU training- induced neuromuscular fatigue.

KAATSU training at greatly reduced intensities has been proven to result in substantial increases in both muscle hypertrophy and strength. Nevertheless, this revolutionary training method (combined with the restriction of venous blood flow from the working muscle) may cause underlying hypoxia and neurotransmitter dysfunction, which are linked to neuromuscular fatigue. Hence, an exploration of KAATSU training-induced hypoxic and neurodegenerative events is of utmost importance before promoting this training mode, although KAATSU has been shown to result in numerous positive training adaptations. Furthermore, based on substantial evidence, L-carnitine supplementation exerts neuroprotective effects by attenuating hypoxic stress and neurotransmitter dysfunction. However, studies directly examining the effects of KAATSU exercise on both hypoxia and neurotransmitter dysfunction, which would aggravate the detrimental effects of neuromuscular fatigue, are lacking. In addition, an expansion of the applications of L-carnitine to a smaller-molecule field for treating KAATSU training-evoked neuromuscular fatigue requires further clarification. Therefore, this review aims to present the current evidence for the effectiveness of exogenous L-carnitine at reducing the amount of hypoxic damage and its neuroprotective effects mediated by increasing cerebral acetylcholine levels. Simply, L-carnitine administration may be an important contributor to the mechanisms curtailing KAATSU training-induced neuromuscular fatigue.

CsPbBr3:xEu3+ perovskite QD borosilicate glass: a new member of the luminescent material family.

Eu3+ ions were introduced into the lattices of CsPbBr3 perovskite QDs and a tunable multicolour emission from CsPbBr3:xEu3+ perovskite QD glass was successfully obtained. Multicolour LEDs that were fabricated by combining the as-prepared CsPbBr3:xEu3+ QD glasses with a UV chip were also researched in this study.

Dexmedetomidine versus propofol on the sedation of pediatric patients during magnetic resonance imaging (MRI) scanning: a meta-analysis of current studies.

Magnetic resonance imaging (MRI) is a widely applied diagnostic approach for detection of pediatric diseases. Sedatives are commonly used to acquire the accurate MRI images. Dexmedetomidine and propofol serve as sole or combined sedatives in pediatric MRI scanning. This meta-analysis aimed to compare the efficacy of dexmedetomidine and propofol in children ubdergoing MRI. Pubmed, Cochrane Library and Web of Science were searched up to June, 2017. Onset of sedation time, recovery time, sedation time, MRI time, MRI quality and emergence delirium were analyzed. 6 studies with 368 subjects were enrolled in this meta-analysis. The pooling data showed that propofol had a shorter onset of sedation time (WMD: 6.05, 95% CI: 3.12 - 8.98, P < 0.0001) and recovery time (WMD: 1.01, 95% CI: 0.36-1.67, P < 0.001) than dexmedetomidine. But for sedation time and MRI scanning time, there were no differences between the two groups (sedation time: P = 0.29; MRI scanning time: P = 0.50). There were no significance between dexmedetomidine and propofol on MRI quality (MRI quality 1: P = 1.00; MRI quality 2: P = 0.68; MRI quality 3: P = 0.45). Two studies using Pediatric Anesthesia Emergence Delirium (PAED) to assess emergence delirium 10 minutes after awakening showed that propofol had a lower PAED than dexmedetomidine (WMD: 2.57, 95% CI: 0.15-5.00, P = 0.04). Thus, propofol should be encouraged in pediatric patients undergoing MRI for its better sedative effects and a low incidence of emergence delirium.