Real-world clinical outcomes of tixagevimab/cilgavimab in the Omicron outbreak in China: baseline characteristics and interim analysis of the CLEAR study.

PURPOSE: This study aimed to investigate the real-world use and clinical outcomes of tixagevimab/cilgavimab in China during the Omicron outbreak in late 2022. METHODS: This observational, real-world study included patients who received tixagevimab/cilgavimab from July 9 to December 30, 2022, in Hainan, China. Here, we report the baseline and characteristics and interim analysis results of the clinical outcomes in those receiving at least one dose of tixagevimab/cilgavimab (300 mg) for pre-exposure prophylaxis. RESULTS: Among 248 subjects who received tixagevimab/cilgavimab, 229 subjects were included in this analysis. Until March 28, 2023, the median follow-up was 95 days. The mean age of the subjects was 44.4 ± 15.9 years, 11.8% were ≥ 65 years, and 41.5% were male. Fifty-eight (25.3%) subjects had comorbidities, 16.2% subjects had key immune compromised conditions. Seventy-two (32.6%) patients had laboratory-confirmed SARS-CoV-2 infection and/or received healthcare within three months; 71/72 (98.6%) had mild disease, and one (1.4%) was moderate. No COVID-19-related intensive care unit (ICU) admissions, extracorporeal membrane oxygenation utilizations, or death occurred. Two (0.9%) patients required hospitalization. One (0.4%) serious adverse event occurred, which was considered unrelated to tixagevimab/cilgavimab. CONCLUSION: Among Chinese patients receiving prophylactic tixagevimab/cilgavimab, the incidence of COVID-19-related hospitalization, ICU admission, or death was low during the Omicron surge. Further randomized controlled trials with larger sample sizes are needed to determine the effectiveness of tixagevimab/cilgavimab in preventing severe COVID-19 outcomes. TRIAL REGISTRATION: The study was registered with clinicaltrial.gov (NCT05917951).

Construction of ceRNA Networks at Different Stages of Somatic Embryogenesis in Garlic.

LncRNA (long non-coding RNA) and mRNA form a competitive endogenous RNA (ceRNA) network by competitively binding to common miRNAs. This network regulates various processes of plant growth and development at the post-transcriptional level. Somatic embryogenesis is an effective means of plant virus-free rapid propagation, germplasm conservation, and genetic improvement, which is also a typical process to study the ceRNA regulatory network during cell development. Garlic is a typical asexual reproductive vegetable. Somatic cell culture is an effective means of virus-free rapid propagation in garlic. However, the ceRNA regulatory network of somatic embryogenesis remains unclear in garlic. In order to clarify the regulatory role of the ceRNA network in garlic somatic embryogenesis, we constructed lncRNA and miRNA libraries of four important stages (explant stage: EX; callus stage: AC; embryogenic callus stage: EC; globular embryo stage: GE) in the somatic embryogenesis of garlic. It was found that 44 lncRNAs could be used as precursors of 34 miRNAs, 1511 lncRNAs were predicted to be potential targets of 144 miRNAs, and 45 lncRNAs could be used as eTMs of 29 miRNAs. By constructing a ceRNA network with miRNA as the core, 144 miRNAs may bind to 1511 lncRNAs and 12,208 mRNAs. In the DE lncRNA-DE miRNA-DE mRNA network of adjacent stages of somatic embryo development (EX-VS-CA, CA-VS-EC, EC-VS-GE), by KEGG enrichment of adjacent stage DE mRNA, plant hormone signal transduction, butyric acid metabolism, and C5-branched dibasic acid metabolism were significantly enriched during somatic embryogenesis. Since plant hormones play an important role in somatic embryogenesis, further analysis of plant hormone signal transduction pathways revealed that the auxin pathway-related ceRNA network (lncRNAs-miR393s-TIR) may play a role in the whole stage of somatic embryogenesis. Further verification by RT-qPCR revealed that the lncRNA125175-miR393h-TIR2 network plays a major role in the network and may affect the occurrence of somatic embryos by regulating the auxin signaling pathway and changing the sensitivity of cells to auxin. Our results lay the foundation for studying the role of the ceRNA network in the somatic embryogenesis of garlic.

Abscisic acid induces the expression of AsKIN during the recovery period of garlic cryopreservation.

KEY MESSAGE: Abscisic acid induced the expression of AsKIN during the recovery period of garlic cryopreservation. AsKIN was identified as a gene involved in cold and osmotic stress resistance. Cryopreservation has been proven to be effective in removing viruses from garlic. However, oxidative damage in cryopreservation has a significant impact on the survival after preservation. Abscisic acid (ABA) has been shown to reduce oxidative stress and promote the survival after cryopreservation. However, it is not clear which genes play important roles in this process. In this study, we added ABA to the dehydration step and analyzed the transcriptomic divergences between the ABA-treated group and the control group in three cryogenic steps (dehydration, unloading and recovery). By short time-series expression miner (STEM) analysis and weighted gene co-expression network analysis (WGCNA), the recovery step was identified as the period of significant changes in gene expression levels in cryopreservation. The addition of ABA promoted the upregulated expression of microtubule-related genes in the recovery step. We further identified AsKIN as a hub gene in the recovery step and verified its function. The results showed that overexpression of AsKIN enhanced the tolerance of Arabidopsis to oxidative stress in cryopreservation, influenced the expression of genes in response to cold and osmotic stress and promoted plant growth after stress. The AsKIN gene is likely to be involved in the plant response to cold stress and osmotic stress. These results reveal the molecular mechanisms of ABA in cryopreservation and elucidate the potential biological functions of the kinesin-14 subfamily.

Ascorbic acid addition during dehydration improves garlic shoot tip cryopreservation but does not affect viral load.

Cryopreservation is known be an effective method for virus elimination in garlic. However, oxidative damage during the cryopreservation seriously affects the survival of garlic after cryopreservation. Ascorbic acid (AsA) can reduce oxidative damage and improve regrowth following cryopreservation, and its effect may be influenced by the step during which it is added. In this study, AsA was added at the osmoprotection (O) and dehydration (DE) steps of cryopreservation. By observing the dynamic changes in cell viability and reactive oxygen species (ROS) components with different AsA treatments, AsA has been linked to the reduced accumulation of ROS in the shoot tips. Increased gene expression levels of antioxidant enzymes also explained the ROS scavenging effect of AsA. The correlation analysis between cell viability, ROS, membrane lipid peroxidation-related indicators and antioxidant-related indicators showed that membrane lipid peroxidation caused by excess ROS was the main factor affecting cell viability. Ascorbic acid added during dehydration minimized the accumulation of ROS from dehydration to dilution and alleviated the oxidative damage during cryopreservation. Thus, the survival and regrowth of the garlic was significantly improved after cryopreservation. Dehydration was found to be the suitable step for the addition of AsA during garlic cryopreservation. We further evaluated the virus elimination effect under optimal AsA treatment. However, there was no significant difference in virus content in regenerated plants when compared with the control.

Process optimization for microcystin-LR degradation by Response Surface Methodology and mechanism analysis in gas-liquid hybrid discharge system.

A gas-liquid hybrid discharge system was applied to microcystin-LR (MC-LR) degradation. MC-LR degradation was completed after 1 min under a pulsed high voltage of 16 kV, gas-liquid interface gap of 10 mm and oxygen flow rate of 160 L/h. The Box-Behnken Design was proposed in Response Surface Methodology to evaluate the influence of pulsed high voltage, electrode distance and oxygen flow rate on MC-LR removal efficiency. Multiple regression analysis, focused on multivariable factors, was employed and a reduced cubic model was developed. The ANOVA analysis shows that the model is significant and the model prediction on MC-LR removal was also validated with experimental data. The optimum conditions for the process are obtained at pulsed voltage of 16 kV, gas-liquid interface gap of 10 mm and oxygen flow rate of 120 L/h with ta removal efficiency of MC-LR of 96.6%. The addition of catalysts (TiO2 or Fe2+) in the gas-liquid hybrid discharge system was found to enhance the removal of MC-LR. The intermediates of MC-LR degradation were analyzed by liquid chromatography/mass spectrometry. The degradation pathway proposed envisaged the oxidation of hydroxyl radicals and ozone, and attack of high-energy electrons on the unsaturated double bonds of Adda and Mdha, with MC-LR finally decomposing into small molecular products.

Prediction of lymphovascular invasion of gastric cancer based on contrast-enhanced computed tomography radiomics.

Background: Lymphovascular invasion (LVI) is a significant risk factor for lymph node metastasis in gastric cancer (GC) and is closely related to the prognosis and recurrence of GC. This study aimed to establish clinical models, radiomics models and combination models for the diagnosis of GC vascular invasion. Methods: This study enrolled 146 patients with GC proved by pathology and who underwent radical resection of GC. The patients were assigned to the training and validation cohorts. A total of 1,702 radiomic features were extracted from contrast-enhanced computed tomography images of GC. Logistic regression analyses were performed to establish a clinical model, a radiomics model and a combined model. The performance of the predictive models was measured by the receiver operating characteristic (ROC) curve. Results: In the training cohort, the age of LVI negative (-) patients and LVI positive (+) patients were 62.41 ± 8.41 and 63.76 ± 10.08 years, respectively, and there were more male (n = 63) than female (n = 19) patients in the LVI (+) group. Diameter and differentiation were the independent risk factors for determining LVI (-) and (+). A combined model was found to be relatively highly discriminative based on the area under the ROC curve for both the training (0.853, 95% CI: 0.784-0.920, sensitivity: 0.650 and specificity: 0.907) and the validation cohorts (0.742, 95% CI: 0.559-0.925, sensitivity: 0.736 and specificity: 0.700). Conclusions: The combined model had the highest diagnostic effectiveness, and the nomogram established by this model had good performance. It can provide a reliable prediction method for individual treatment of LVI in GC before surgery.

Reinforcement and Deacidification for a Textile Scroll Painting (AD 1881) Using the CNF and MgO Suspensions.

The scroll paintings for ancestor trees have been used to inherit the spirit of ancestor worship as a historical record of family development since the late Ming Dynasty in China. A severely degraded scroll painting of an ancestor tree (made of cotton textiles) needs intervention and conservation treatment to mitigate further deterioration. On the basis of the previously reported characterization results for the painting, in this paper, a suspension that is composed of 0.6% cellulose nanofibril (CNF) and nanosized 0.15% MgO in aqueous solvent (denoted as the CNF-MgO susairpension) was prepared. Conventional characterization methods were used to assess the properties of model samples before and after treatment with the CNF-MgO suspension, as well as before and after degradation under two sets of conditions. The results show that the treated model samples are slightly alkaline, given the deposit of alkaline particles, and demonstrate good mechanical properties before and after degradation due to the increase in fiber-to-fiber bond and mitigation of acid-catalyzed hydrolysis. In spite of the non-transparency of CNF and MgO nanoparticles, they have little impact on the optical properties of textiles, as verified by transmittance data and the determination of color changes. This suspension was then used to reinforce and restore the scroll painting in a practical conservation process. The application of CNF and MgO nanoparticles on textile objects investigated in this study would expand our understanding of the conservation of such objects, especially for those that have already become acidic and degraded.

Variations of arterial compliance and vascular resistance due to plaque or infarct in a single vascular territory of the middle cerebral artery.

Background: Arterial compliance (AC) and vascular resistance (VR) are crucial for the regulation capacity of the vascular system. However, alterations of these features and hemodynamics due to atherosclerosis in a single intracranial artery territory have not been extensively investigated. Thus this study aimed to examine the AC, VR, and hemodynamic variations due to plaque and infarction in the middle cerebral artery (MCA). Methods: Patients with symptomatic MCA atherosclerosis were recruited. Both sides of the MCA were assessed and then classified according to the following scheme: group 0, without plaque; group 1, with plaque but without infarct; group 2, with plaque and infarct in the supplying territories. Data on AC, VR, blood flow, and pulsatility index (PI) were obtained based on 4D flow magnetic resonance imaging (MRI) and the Windkessel model. Results: A total of 63 patients were recruited. After 17 MCAs were excluded (occlusion, n=6; poor image quality, n=11), datasets on 109 MCAs were finally collected and classified into group 0 (n=39), group 1 (n=40), and group 2 (n=30). From groups 0 to 2, there was a decrease in AC (0.0060±0.0031 vs. 0.0052±0.0029 vs. 0.0026±0.0020 mL/mmHg) and an increase in VR [28.65±16.11 vs. 42.59±27.53 vs. 63.21±40.37 mmHg/(mL/s)]. Compared to group 1, group 2 had significantly decreased AC (0.0052±0.0029 vs. 0.0026±0.0020 mL/mmHg; P=0.003) and increased VR [42.59±27.53 vs. 63.21±40.37 mmHg/(mL/s); P=0.021]. From group 0 to group 2, there was a decrease in blood flow (179.29±73.57 vs. 125.11±59.04 vs. 92.05±48.79 mL/min; P<0.001). The PI varied significantly among the 3 groups (0.86±0.20 vs. 1.12±0.50 vs. 0.79±0.16; P<0.001), with group 1 having the highest PI. Conclusions: With the occurrence of plaque and infarct, AC and blood flow progressively decrease while VR increases. The PI was the highest in the group with plaque and without infarct. Assessments of vascular function and hemodynamics in a single artery territory can clarify comprehensive alterations in the cerebral vascular system (CVS).

Effect of tixagevimab/cilgavimab for pre-exposure prophylaxis during the China Omicron outbreak.

OBJECTIVES: By the end of 2022, China had made a pivotal decision to optimize the COVID-19 policy. The dominant Omicron variant in China at that time was highly transmissible. In this study, we aimed to evaluate the real-world safety and efficacy of tixagevimab and cilgavimab against this background in China. METHODS: Participants were enrolled if they were over 12 years old and were planning to receive tixagevimab or cilgavimab. All participants received intramuscular administration of tixagevimab (150 mg) and cilgavimab (150 mg). Data were collected on demographics, underlying illness, prior infection, vaccination, adverse events, and COVID-19 outcomes (e.g., infection rate, hospitalization rate, and severe disease). RESULTS: During the study period, 168 (37.9%) of 443 who received tixagevimab/cilgavimab were diagnosed with SARS-CoV-2 infection. All infected patients had mild COVID-19. Two patients (0.5%) were hospitalized for COVID-19, but none of them were admitted to the ICU. None of the patients died during this study. 4 (0.9%) reported mild local adverse events, and no severe systemic adverse reactions were reported. CONCLUSION: Tixagevimab/cilgavimab may have protected high-risk populations against infection with the Omicron variant, hospitalization and severe disease during the China COVID-19 pandemic.

Evaluation of 3D multi-contrast carotid vessel wall MRI: a comparative study.

BACKGROUND: Conventional reference multi-contrast black-blood (BB) MRI can be used for measuring luminal stenosis severity and plaque components, and its performance has been validated by intra- and inter-reader reproducibility test and histology. Recently, a set of 3D multi-contrast BB sequences have been developed, but its accuracy and reliability have not been well investigated. In this study, we evaluated the performance of 3D multi-contrast MRI (3D-MERGE, T2-VISTA, and SNAP) by comparing it with reference multi-contrast vessel wall MRI and assessing the inter-reader reproducibility. METHODS: In total, 27 patients were recruited in this study. Twenty-six participants underwent reference and 3D multi-contrast imaging in a 3.0T MR scanner. One participant underwent carotid endarterectomy (CEA) after 3D MR imaging. Two trained reviewers interpreted reference and 3D datasets. Lumen area (LA), wall area (WA), normalized wall index (NWI), maximum wall thickness (MaxWT), and mean wall thickness (MWT) were measured, and the presence of lipid-rich necrotic core (LRNC), intra-plaque hemorrhage (IPH) and calcification (CA) were identified. Inter-reader reproducibility of 3D interpretation was assessed. RESULTS: 3D imaging provided comparable measurements with reference imaging in LA (43.81±25.74 vs. 43.35±24.66 mm2) and MaxWT (1.65±1.33 vs. 1.62±1.10 mm), with a lower NWI (0.40±0.15 vs. 0.43±0.11), WA (29.40±21.92 vs. 30.64±16.17 mm2) and MWT (1.09±0.69 vs. 1.14±0.47), and showed good agreement for identification of LRNC (κ=0.66, 95% CI: 0.30-1.00) and CA (κ=0.69, 95% CI: 0.42-0.97), and excellent agreement for IPH (κ=1.00, 95% CI: 1.00-1.00). Inter-reader agreement of 3D analysis was good (LRNC, κ=0.87, 95% CI: 0.61-1.00; CA, κ=0.66, 95% CI: 0.36-0.96; IPH, κ=1.00, 95% CI: 1.00-1.00). CONCLUSIONS: 3D multi-contrast vessel wall imaging provides comparable performance in morphological measurements and identification of carotid plaque components as reference multi-contrast MRI, with good inter-reader reproducibility.