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.

Sesquiterpenoids from Vitex pierreana.

A new germacrane sesquiterpenoid with an epoxy moiety, pierreanin A (1), and a pair of unique cyclobutyl-containing sesquiterpenoid diastereoisomers, pierreanins B and C (2 and 3), were isolated from the branches and leaves of Vitex pierreana, together with 2 known analogues, identified as germacrone (4) and epiprocurcumenol (5). The structures of all isolates were evaluated by detailed analyses of NMR, IR, and MS data. The absolute configurations of 1-3 were determined by comparison of the experimental ECD spectra with reported data of analogues containing the same chromophore. The ability of three new compounds to inhibit the growth of DU145 prostate cancer cells was also evaluated, as well as their inhibitory effects against the production of NO in LPS-stimulated RAW264.7 cells.

Flavonoids from Caragana pruinosa roots.

A new pterocarpan derivative, pruinosanone D (1), a new isoflavonoid, pruinosanone E (2), and a new chalcone, pruinosanone F (3), were isolated from Caragana pruinosa roots, along with four known analogues (4-7), identified as 2,4-dihydroxy-3'-methoxy-4'-ethoxychalcone, 7,4-dihydroxyflavanone, butin and scutellaprostin C, respectively. Their structures were elucidated by detailed analyses of NMR, IR, and MS data. The ability of the isolated compounds to prevent nitric oxide (NO) production by LPS-stimulated RAW 264.7 macrophages was also studied. Compound 1 were among the most potent NO production inhibitor, with IC50 value of 0.62µM.

Therapeutic effects of Caragana pruinosa Kom. roots extract on type II collagen-induced arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Caragana pruinosa Kom. is a deciduous shrub belonging to the genus of Caragana (Leguminosae), and Caragana plants exhibit a wide range of interesting pharmacological properties including anti-inflammatory, analgesic, and anti-arthritis activity, etc. AIM OF THE STUDY: This study was aimed to investigate the anti-arthritic effect of 80% EtOH extract from the roots of C. pruinosa (ERCP) on arthritis and explore the potential pharmacological mechanism. MATERIALS AND METHODS: After collagen induced arthritis (CIA) were established in rats, the animals were orally administered with ERCP (130, 260 and 520mg/kg) for 30 days. During the treatment, the rats' body weights, arthritis indices and paw volumes were measured every 5 days. Subsequently, rats' blood samples were collected to determine TNF-α, IL-1ß, IL-6, IL-10, and C-reactive protein (CRP) contents in serum. Then, rats were sacrificed and the hind paws and knee joints were collected for histopathological examination. RESULTS: Our results indicated that ERCP significantly suppressed the inflammatory reactions and destructions in joints and synovial tissues. ERCP inhibited the paw swelling and arthritis index in CIA rats. Additionally, it decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) and CRP, whereas increased that of IL-10. CONCLUSION: Our results suggested ERCP has significant anti-arthritic effect on CIA rats, and the pharmacological mechanisms are related to the down-regulation of TNF-α, IL-1ß, IL-6 and CRP and the up-regulation of IL-10.

Electrochemical Surface Plasmon Resonance Fiber-Optic Sensor: In Situ Detection of Electroactive Biofilms.

Spectroelectrochemistry has been found to be an efficient technique for revealing extracellular electron transfer (EET) mechanism of electroactive biofilms (EABs). Herein, we propose a novel electrochemical surface plasmon resonance (EC-SPR) optical fiber sensor for monitoring EABs in situ. The sensor uses a tilted fiber Bragg grating (TFBG) imprinted in a commercial single-mode fiber and coated with nanoscale gold film for high-efficiency SPR excitation. The wavelength shift of the surface plasmon resonance (SPR) over the fiber surface clearly identifies the electrochemical activity of the surface localized (adjacent to the electrode interface) bacterial cells in EABs, which differs from the "bulk" detections of the conventional electrochemical measurements. A close relationship between the variations of redox state of the EABs and the changes of the SPR under potentiostatic conditions has been achieved, pointing to a new way to study the EET mechanism of the EABs. Benefiting from its compact size, high sensitivity, and ease of use, together with remote operation ability, the proposed sensor opens up a multitude of opportunities for monitoring EABs in various hard-to-reach environments.

Highly sensitive detection of urinary protein variations using tilted fiber grating sensors with plasmonic nanocoatings.

Surface plasmon resonance (SPR) optical fiber biosensors can be used as a cost-effective and relatively simple-to-implement alternative to well established bulky prism configurations for high sensitivity biological sample measurements. The miniaturized size and remote operation ability offer them a multitude of opportunities for single-point sensing in hard-to-reach spaces, even possibly in vivo. The biosensor configuration reported in this work uses a tilted fiber Bragg grating (TFBG) in a commercial single mode fiber coated with a nanometer scale silver film. The key point is that by reducing the silver film thickness to around 20-30 nm (rather than 50 nm for optimal SPR excitation), different modes of the TFBG spectrum present very high but opposite sensitivities to refractive index (RI) changes around the TFBG. Experimental results obtained with the coated TFBG embedded inside a microfluidic channel show an amplitude sensitivity greater than 8000 dB/RIU (Refractive Index Unit) and a limit of detection of 10(-5)RIU. Using this device, the effect of different concentrations of protein in rat urine was clearly differentiated between healthy samples, nephropatic samples and samples from individuals under treatment, with a protein concentration sensitivity of 5.5 dB/(mg/ml) and a limit of detection of 1.5 × 10(-3)mg/ml. Those results show a clear relationship between protein outflow and variations in the RI of the urine samples between 1.3400 and 1.3408, pointing the way to the evaluation and development of new drugs for nephropathy treatments. The integration of TFBGs with microfluidic channels enables precise measurement control over samples with sub-microliter volumes and does not require accurate temperature control because of the elimination of the temperature cross-sensitivity inherent in TFBG devices. Integration of the TFBG with a hypodermic needle on the other hand would allow similar measurements in vivo. The proposed optical fiber/microfluidic plasmonic biosensor represents an appealing solution for rapid, low consumption and highly sensitive detection of analytes at low concentrations in medicine as well as in chemical and environmental monitoring.