Safety, immunogenicity, and efficacy of a modified COVID-19 mRNA vaccine, SW-BIC-213, in healthy people aged 18 years and above: a phase 3 double-blinded, randomized, parallel controlled clinical trial in Lao PDR (Laos).

Background: The mRNA vaccine has demonstrated significant effectiveness in protecting against SARS-CoV-2 during the pandemic, including against severe forms of the disease caused by emerging variants. In this study, we examined safety, immunogenicity, and relative efficacy of a heterologous booster of the lipopolyplex (LPP)-based mRNA vaccine (SW-BIC-213) versus a homologous booster of an inactivated vaccine (BBIBP) in Laos. Methods: In this phase 3 clinical trial, which was randomized, parallel controlled and double-blinded, healthy adults aged 18 years and above were recruited from the Southern Savannakhet Provincial Hospital and Champhone District Hospital. The primary outcomes were safety and immunogenicity, with efficacy as an exploratory endpoint. Participants who were fully immunized with a two-dose inactivated vaccine for more than 6 months were assigned equally to either the SW-BIC-213 group (25 µg) or BBIBP group. The primary safety endpoint was to describe the safety profile of all participants in each group up to 6 months post-booster immunization. The primary immunogenic outcome was to demonstrate the superiority of the neutralizing antibody response, in terms of geometric mean titers (GMTs) of SW-BIC-213, compared with BBIBP 28 days after the booster dose. The exploratory efficacy endpoint aimed to assess the relative efficacy of SW-BIC-213 compared to BBIBP against virologically confirmed symptomatic COVID-19 over a 6-month period. The trial was registered with ClinicalTrials.gov (NCT05580159). Findings: Between October 10, 2022, and January 13, 2023, 1200 participants were assigned to SW-BIC-213 group and 1203 participants in the BBIBP group. All adverse reactions observed during the study were tolerable, transient, and resolved spontaneously. Solicited local reactions were the main adverse reactions in both the SW-BIC-213 group (43.8%) and BBIBP group (14.8%) (p < 0.001). Heterologous boosting with SW-BIC-213 induced higher live virus neutralizing antibodies to SARS-CoV-2 wildtype and BA.5 strains with GMTs reaching 750.1 and 192.9 than homologous boosting with BBIBP with GMTs of 131.5 (p < 0.001) and 47.5 (p < 0.001) on day 29. The statistical findings revealed that, following a period of 14-day to 6-month after booster vaccination, the SW-BIC-213 group exhibited a relative vaccine efficacy (VE) of 70.1% (95% CI: 34.2-86.4) against symptomatic COVID-19 when compared to the BBIBP group. Interpretation: A heterologous booster with the COVID-19 mRNA vaccine SW-BIC-213 manifests a favorable safety profile and proves highly immunogenic and efficacious in preventing symptomatic COVID-19 in individuals who have previously received two doses of inactivated vaccine. Funding: Shanghai Strategic Emerging Industries Development Special Fund, Biomedical Technology Support Special Project of Shanghai "Science and Technology Innovation Action Plan", Shanghai Municipal Science and Technology Commission.

Retrolaminar migration as a complication of intraocular silicone oil injection detected on unenhanced CT.

AIM: To describe the clinical and radiologic features of retrolaminar migration silicone oil (SiO) and observe the dynamic position of ventricular oil accumulation in supine and prone. METHODS: For this retrospective study, 29 patients who had a history of SiO injection treatment and underwent unenhanced head computed tomography (CT) were included from January 2019 to October 2022. The patients were divided into migration-positive and negative groups. Clinical history and CT features were compared using Whitney U and Fisher's exact tests. The dynamic position of SiO was observed within the ventricular system in supine and prone. CT images were visually assessed for SiO migration along the retrolaminar involving pathways for vision (optic nerve, chiasm, and tract) and ventricular system. RESULTS: Intraocular SiO migration was found in 5 of the 29 patients (17.24%), with SiO at the optic nerve head (n=1), optic nerve (n=4), optic chiasm (n=1), optic tract (n=1), and within lateral ventricles (n=1). The time interval between SiO injection and CT examination of migration-positive cases was significantly higher than that of migration-negative patients (22.8±16.5mo vs 13.1±2.6mo, P<0.001). The hyperdense lesion located in the frontal horns of the right lateral ventricle migrated to the fourth ventricle when changing the position from supine to prone. CONCLUSION: Although SiO retrolaminar migration is unusual, the clinician and radiologist should be aware of migration routes. The supine combined with prone examination is the first-choice method to confirm the presence of SiO in the ventricular system.

Xylem formation of Populus euphratica and its response to water-heat factors in the lower reaches of Tarim River, China.

To deeply understand the effects of water and temperature factors on the xylem formation of Populus euphratica, taking the Yingsu section in the lower reaches of Tarim River as an example, we selected micro-coring samples of P. euphratica around monitoring wells F2 and F10 in the 100 and 1500 m distance from the channel of Tarim River. We used wood anatomy method to analyze the xylem anatomy of P. euphratica and its response to water and temperature factors. The results showed that the changes of the total anatomical vessel area and the vessel number of P. euphratica in the two plots were basically consistent during the whole growing season. The vessel number of xylem conduits of P. euphratica increased slowly with the increases of groundwater depth, while the total conduit area increased firstly and then decreased. The total vessel area, minimum vessel area, average vessel area, and maximum vessel area of P. euphratica xylem increased significantly with the increases of temperature in the growing season. The contribution of groundwater depth and air temperature to P. euphratica xylem varied among different growth stages. In the early growing season, air temperature had the largest contribution to the number and total area of xylem conduits of P. euphratica. During the middle growing season, air temperature and groundwater depth jointly affected the parameters of each conduit. During the later growing season, groundwater depth had the largest contribution to the number and total area of conduits. Results of the sensitivity analysis indicated that the groundwater depth sensitive to xylem vessel number change of P. euphratica was 5.2 m and that to the change in the total conduit area was 5.9 m. The temperature sensitive to total vessel area of P. euphratica xylem was 22.0 ℃, and that to average vessel area was 18.5 ℃. Therefore, the sensitive groundwater depth affecting xylem growth was at the range of 5.2-5.9 m, and the sensitive temperature was at the range of 18.5-22 ℃. This study could provide scientific basis for the restoration and protection of P. euphratica forest in the lower reaches of Tarim River.

Independent and Correlated Role of Apolipoprotein E ɛ4 Genotype and Herpes Simplex Virus Type 1 in Alzheimer's Disease.

The ɛ4 allele of the Apolipoprotein E (APOE) gene in individuals infected by Herpes simplex virus type 1 (HSV-1) has been demonstrated to be a risk factor in Alzheimer's disease (AD). APOE-ɛ4 reduces the levels of neuronal cholesterol, interferes with the transportation of cholesterol, impairs repair of synapses, decreases the clearance of neurotoxic peptide amyloid-ß (Aß), and promotes the deposition of amyloid plaque, and eventually may cause development of AD. HSV-1 enters host cells and can infect the olfactory system, trigeminal ganglia, entorhinal cortex, and hippocampus, and may cause AD-like pathological changes. The lifecycle of HSV-1 goes through a long latent phase. HSV-1 induces neurotropic cytokine expression with pro-inflammatory action and inhibits antiviral cytokine production in AD. It should be noted that interferons display antiviral activity in HSV-1-infected AD patients. Reactivated HSV-1 is associated with infectious burden in cognitive decline and AD. Finally, HSV-1 DNA has been confirmed as present in human brains and is associated with APOEɛ4 in AD. HSV-1 and APOEɛ4 increase the risk of AD and relate to abnormal autophagy, higher concentrations of HSV-1 DNA in AD, and formation of Aß plaques and neurofibrillary tangles.

[Advances in the study of the rat model of aging induced by D-galactose]

D-galactose (D-gal)-induced aging model is widely used in the study of the pharmacodynamics of antiaging drugs. The model has a shorter life-span, disorders in learning and memory, reduced immune function and other aging characteristics. Regular and quantitative injection of D-gal solution to rats can produce symptoms of natural aging models that are used in screening of antiaging drugs, and their pharmacological activities. This paper provides a summary of the mechanism of rat model induced with D-gal solution. The methods of building and evaluation of the aging models are provided. The theoretical basis is included to facilitate the subsequent research and experiment in the mechanism study of aging and antiaging medicines.

[Ideal white organic light emitting devices based on doped PFO].

In the present paper, the electroluminescence emission from a doped polymer layer was studied. The blue fluorene PFO was used as the host material and MEH-PPV as the dopant. The spectral characteristics and color stability of the emission on CIE chromaticity diagram were investigated. With the doping ratio of 2.5 Wt%, the device shows turn-on voltage of 3 V, and color coordinates of (0.33, 0.33) at 11 V. The color coordinates of the device was stable with changing voltage in a large range, and located in the ideal white area in the range of 5-20 V voltage.