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.

Energy Storage Triboelectric Nanogenerator Based on Ratchet Mechanism for Random Ocean Energy Harvesting.

The instability of the ocean waves, such as intermittence, randomness, and irregularity, greatly affects the application of a triboelectric nanogenerator (TENG) in its aspects and leads to the irregularity and uncontrollability of its output performance. Hence, the energy storage TENG (ES-TENG) based on the ratchet mechanism is proposed in this work. The ES-TENG uses the ratchet mechanism to store the wave energy in the clockwork spring and then releases it in a centralized way to convert the wave energy into electric energy. When the ES-TENG adopts this method, the change of external excitation does not affect its output performance. Simultaneously, the shell of the ES-TENG is duck-shaped, which can better adapt to the wave environment. The peak power, open-circuit voltage, and short-circuit current of the ES-TENG are 6.2 mW, 495 V, and 19 µA, respectively. In the simulated wave experiment, the ES-TENG can successfully drive a temperature sensor. In summary, this work shows an economic, environmental friendly TENG that can adapt to the wave motion, and its output performance is not affected by wave instability, which has an important guiding significance for the further development and utilization of TENG in ocean energy.

PBPK Modeling on Organs-on-Chips: An Overview of Recent Advancements.

Organ-on-a-chip (OoC) is a new and promising technology, which aims to improve the efficiency of drug development and realize personalized medicine by simulating in vivo environment in vitro. Physiologically based pharmacokinetic (PBPK) modeling is believed to have the advantage of better reflecting the absorption, distribution, metabolism and excretion process of drugs in vivo than traditional compartmental or non-compartmental pharmacokinetic models. The combination of PBPK modeling and organ-on-a-chip is believed to provide a strong new tool for new drug development and have the potential to replace animal testing. This article provides the recent development of organ-on-a-chip technology and PBPK modeling including model construction, parameter estimation and validation strategies. Application of PBPK modeling on Organ-on-a-Chip (OoC) has been emphasized, and considerable progress has been made. PBPK modeling on OoC would become an essential part of new drug development, personalized medicine and other fields.

A Cluster of Bunyavirus-Associated Severe Fever With Thrombocytopenia Syndrome Cases in a Coastal Plain Area in China, 2015: Identification of a Previously Unidentified Endemic Region for Severe Fever With Thrombocytopenia Bunyavirus.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a typical tick-borne, natural focal disease. The natural foci of SFTS were considered to exist in hilly and mountainous areas before 2015. A cluster of 3 patients exposed to a patient with a fulminant disease consistent with SFTS occurred from July to August 2015 in Dongtai County, which is characterized by alluvial plains; this prompted investigation. METHODS: The epidemiological, clinical, and laboratory features of 4 patients in the cluster were analyzed. Serum samples from the indigenous healthy population and native domesticated animals were collected to conduct laboratory tests, along with small wild animals and ticks. RESULTS: In 3 secondary case patients, high fever, thrombocytopenia and leukopenia developed within 8-13 days after contact with blood or bloody secretions from the index patient; SFTS was then diagnosed by means of reverse-transcription polymerase chain reaction. Genomic sequencing and analysis of S and L segments of 2 viral strains isolated from 2 secondary case patients showed that they shared 99.8%-99.9% homology in nucleotide sequence. The seroprevalences among indigenous healthy population, native livestock, native poultry, and small wild animals was 0.74%, 17.54%, 6.67%, and 1.12%, respectively. Three questing ticks, 61 feeding ticks, and 178 small wild animals were collected in August 2015. Survey on tick density and seasonal fluctuation in 2016 showed that ticks were active from March to October. All ticks were identified as Haemaphysalis longicornis. Severe fever with thrombocytopenia bunyavirus (SFTSV)-specific RNA was detected in the ticks collected in 2016, and the minimum SFTSV infection rate in these ticks was 0.54% (1 of 185).Wild mammals and ticks collected in August 2015 tested negative for SFTSV-specific RNA. CONCLUSIONS: Aside from hilly or mountainous area, a coastal plain was identified as the natural foci of SFTSV in Dongtai County, China. The involvement of migration in the evolution of SFTSV might lead to a transregional transmission event of SFTSV.

DNA nanopore functionalized with aptamer and cell-penetrating peptide for tumor cell recognition.

In the present work, DNA nanopore was composed of a bundle of six DNA duplexes folded from six DNA strands and functionalized with Ramos cell aptamer and cell-penetrating peptide (CPP). Herein, we present a unique dually conjugated molecule with an aptamer and cell-penetrating peptide for targeting and recognition of Ramos cells. The aptamer sequence was specific bound to Ramos cell, at the meanwhile the nanopore assembly was taken onto the surface of cell membrane and then got into the cells with the help of CPP. Specific targeting and increased intracellular uptake of nanostructures by Ramos cells were aimed. The intracellular uptake of the structure was determined using confocal microscopy. This study is the first to describe the recognition of tumor cells with functional DNA nanopores, establishing the foundation for the tumor cell detection with low cytotoxic agents. Graphical abstract DNA nanopore was composed of a bundle of six DNA duplexes folded from six DNA strands and functionalized with Ramos cell aptamer and cell-penetrating peptide. The dually conjugated molecule was found to show both improved cellular uptake and effective Ramos cell targeting.

DNA methylation detection with end-to-end nanorod assembly-enhanced surface plasmon resonance.

The Au nanorod (AuNR) assembly-enhanced surface plasmon resonance (SPR) system coupling with polymerization and nicking reactions was developed for amplified detection of DNA methylation and adenine methylation (Dam) methyltransferase (MTase) activity assay. The biosensor showed a good linear relationship between the SPR angle shift and the Dam MTase concentration over a range from 0.5 to 120 U mL(-1), with a detection limit of 0.2 U mL(-1). This study provided a sensitive platform to screen inhibitors for Dam MTase with great potential to be further applied in early clinical diagnosis.