Bacteriophage RNA polymerases: catalysts for mRNA vaccines and therapeutics.

Decades of research on bacteriophage-derived RNA polymerases (RNAPs) were vital for synthesizing mRNA using the transcription (IVT) reaction for vaccines during the COVID-19 pandemic. The future success of mRNA-based products relies on the efficiency of its manufacturing process. mRNA manufacturing is a platform technology that complements the quality by design (QbD) paradigm.

An Experimental and Modeling Approach to Study Tangential Flow Filtration Performance for mRNA Drug Substance Purification.

Following the recent COVID-19 pandemic, mRNA manufacturing processes are being actively developed and optimized to produce the next generation of mRNA vaccines and therapeutics. Herein, the performance of the tangential flow filtration (TFF) was evaluated for high-recovery, and high-purity separation of mRNA from unreacted nucleoside triphosphates (NTPs) from the in vitro transcription (IVT) reaction mixture. For the first time, the fouling model was successfully validated with TFF experimental data to describe the adsorption of mRNA on filtration membrane.

Event-based high-resolution neutron image formation analysis using intensified CMOS cameras.

We present a versatile optical setup for high-resolution neutron imaging with an adaptable field of view and magnification that can resolve individual neutron absorption events with an image intensifier and a CMOS camera. Its imaging performance is characterized by evaluating the resolution limits of the individual optical components and resulting design aspects are discussed. Neutron radiography measurements of a Siemens star pattern were performed in event mode acquisition comparing two common high-resolution neutron scintillators, crystalline Gadolinium Gallium Garnet (GGG) and powdered Gadolinium Oxysulfide (GOS).

Classification of Electronic Waste Components through X-ray and Neutron-Based Imaging Techniques.

In modern society, the amount of e-waste is growing year by year. Waste electronic items are complex, highly heterogeneous systems, containing organic material as well as several exotic, valuable, toxic, mostly metallic elements. In this study, the potential of X-ray and neutron radiography to reveal the inner structure of various complex e-waste was investigated.

Multifaceted activation of STING axis upon Nipah and measles virus-induced syncytia formation.

Activation of the DNA-sensing STING axis by RNA viruses plays a role in antiviral response through mechanisms that remain poorly understood. Here, we show that the STING pathway regulates Nipah virus (NiV) replication in vivo in mice. Moreover, we demonstrate that following both NiV and measles virus (MeV) infection, IFNγ-inducible protein 16 (IFI16), an alternative DNA sensor in addition to cGAS, induces the activation of STING, leading to the phosphorylation of NF-κB p65 and the production of IFNβ and interleukin 6.

Design of a pilot-scale microwave freeze dryer for in situ neutron imaging.

The gentle yet cost-effective drying of sensitive products in the food and pharmaceutical industries is becoming increasingly important. To maintain sensitive ingredients, color, structure, and viability of micro-organisms, often freeze-drying is the only possible way to preserve the product. As many products come in as bulk material, they are dried on heated shelves resulting in poor heat and mass transport through the bed.

Monitoring correlates of SARS-CoV-2 infection in cell culture using a two-photon-active calcium-sensitive dye.

Background: The organism-wide effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection are well studied, but little is known about the dynamics of how the infection spreads in time among or within cells due to the scarcity of suitable high-resolution experimental systems. It has been reported that SARS-CoV-2 infection pathways converge at calcium influx and subcellular calcium distribution changes. Imaging combined with a proper staining technique is an effective tool for studying subcellular calcium-related infection and replication mechanisms at such resolutions.

The redesigned neutron imaging facility, NORMA at BNC, Budapest.

The Budapest Neutron Center operates the cold neutron beam imaging station, Neutron Optics and Radiography for Material Analysis (NORMA), for non-destructive testing. For the NORMA station, there have been increasing requests to reach higher spatial resolution and the ability to follow time-dependent processes. Therefore, the system used successfully so far was completely redesigned and installed for a variety of tasks.

First Broad-Range Serological Survey of Crimean-Congo Hemorrhagic Fever among Hungarian Livestock.

(1) Background: Crimean-Congo hemorrhagic fever (CCHF) is an emerging tick-borne disease endemic in Africa, Asia, the Middle East, and the Balkan and Mediterranean regions of Europe. Although no human CCHF cases have been reported, based on vector presence, serological evidence among small vertebrates, and the general human population, Hungary lies within high evidence consensus for potential CCHF introduction and future human infection. Thus, the aim of our pilot serosurvey was to assess CCHF seropositivity among cattle and sheep as indicator animals for virus circulation in the country.

Quality by Digital Design for Developing Platform RNA Vaccine and Therapeutic Manufacturing Processes.

Quality by digital design (QbDD) utilizes data-driven, mechanistic, or hybrid models to define and optimize a manufacturing design space. It improves upon the QbD approach used extensively in the pharmaceutical industry. The computational models developed in this approach identify and quantify the relationship between the product's critical quality attributes (CQAs) and the critical process parameters (CPPs) of unit operations within the manufacturing process.

Anion exchange HPLC monitoring of mRNA transcription reactions to support mRNA manufacturing process development.

mRNA technology has recently demonstrated the ability to significantly change the timeline for developing and delivering a new vaccine from years to months. The potential of mRNA technology for rapid vaccine development has recently been highlighted by the successful development and approval of two mRNA vaccines for COVID-19. Importantly, this RNA-based approach holds promise for treatments beyond vaccines and infectious diseases, e.

Sensor-Based Measurement Method to Support the Assessment of Robot-Assisted Radiofrequency Ablation.

Digital surgery technologies, such as interventional robotics and sensor systems, not only improve patient care but also aid in the development and optimization of traditional invasive treatments and methods. Atrial Fibrillation (AF) is the most common cardiac arrhythmia with critical clinical relevance today. Delayed intervention can lead to heart failure, stroke, or sudden cardiac death.

Engineering an Escherichia coli based in vivo mRNA manufacturing platform.

Synthetic mRNA is currently produced in standardized in vitro transcription systems. However, this one-size-fits-all approach has associated drawbacks in supply chain shortages, high reagent costs, complex product-related impurity profiles, and limited design options for molecule-specific optimization of product yield and quality. Herein, we describe for the first time development of an in vivo mRNA manufacturing platform, utilizing an Escherichia coli cell chassis.

Strategic Planning of a Joint SARS-CoV-2 and Influenza Vaccination Campaign in the UK.

The simultaneous administration of SARS-CoV-2 and influenza vaccines is being carried out for the first time in the UK and around the globe in order to mitigate the health, economic, and societal impacts of these respiratory tract diseases. However, a systematic approach for planning the vaccine distribution and administration aspects of the vaccination campaigns would be beneficial. This work develops a novel multi-product mixed-integer linear programming (MILP) vaccine supply chain model that can be used to plan and optimise the simultaneous distribution and administration of SARS-CoV-2 and influenza vaccines.

A novel ACE2 decoy for both neutralization of SARS-CoV-2 variants and killing of infected cells.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to millions of infections and deaths worldwide. As this virus evolves rapidly, there is a high need for treatment options that can win the race against new emerging variants of concern. Here, we describe a novel immunotherapeutic drug based on the SARS-CoV-2 entry receptor ACE2 and provide experimental evidence that it cannot only be used for (i) neutralization of SARS-CoV-2 and in SARS-CoV-2-infected animal models but also for (ii) clearance of virus-infected cells.

Long-Term Efficacy and Safety of Left Atrial Appendage Closure Procedures.

The aim of the present single-center, nonrandomized, retrospective study was to assess the safety and long-term efficacy of percutaneous left atrial appendage closure (LAAC) procedures and to compare the different LAAC devices and therapeutic regimes in this respect.Medical data of 136 patients (pts) (mean age, 72.5 ± 7.

Arylnaphthalene Lignans with Anti-SARS-CoV-2 and Antiproliferative Activities from the Underground Organs of and .

Diphyllin () and justicidin B () are arylnaphthalene lignans with antiviral and antiproliferative effects. Compound is also known as an effective inhibitor of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To evaluate the antiviral and cytotoxic potency of both lignans in SARS-CoV-2 -infected cells and various cancer cell lines, respectively, and were isolated from the underground organs of and .

Vaccines on demand, part II: future reality.

Introduction: Prior to the emergence of SARS-CoV-2, the potential use of mRNA vaccines for a rapid pandemic response had been well described in the scientific literature, however during the SARS-CoV-2 outbreak we witnessed the large-scale deployment of the platform in a real pandemic setting. Of the three RNA platforms evaluated in clinical trials, including 1) conventional, non-amplifying mRNA (mRNA), 2) base-modified, non-amplifying mRNA (bmRNA), which incorporate chemically modified nucleotides, and 3) self-amplifying RNA (saRNA), the bmRNA technology emerged with superior clinical efficacy.

Areas Covered: This review describes the current state of these mRNA vaccine technologies, evaluates their strengths and limitations, and argues that saRNA may have significant advantages if the limitations of stability and complexities of manufacturing can be overcome.

SARS-CoV-2 variant detection from wastewater: rapid spread of B.1.1.7 lineage in Hungary.

Wastewater-based epidemiology (WBE) is a recognised tool for tracking community transmission of COVID-19. From the second half of 2020, the emergence of new, highly infective, more pathogenic or vaccine-escape SARS-CoV-2 variants is the major public health concern. Variant analysis in sewage might assist the early detection of new mutations.

Evaluation of Isolation Area, Myocardial Injury and Left Atrial Function Following High-Power Short-Duration Radiofrequency or Second-Generation Cryoballoon Ablation for Atrial Fibrillation.

This randomized study aims to compare the left atrial (LA) lesion size, function, and tissue damage following pulmonary vein isolation (PVI) by high-power short-duration (HPSD) radiofrequency (RF) and second-generation cryoballoon (CB2) ablation. We enrolled 40 patients with paroxysmal atrial fibrillation who underwent PVI by HPSD RF (n = 21) or CB2 (n = 19). Every patient underwent LA CT angiography and transthoracic echocardiography (TTE) to assess the LA anatomy and function.

Characterization of Simulated Liquid Radioactive Waste in a New Type of Cement Mixture.

There is still a safety challenge for the long-term stabilization of nuclear waste. Due to its affordable price and easy manufacturing, cement is one of the most promising materials to immobilize a large volume of low- and intermediate-level radioactive liquid waste. To investigate the effect of borate on the cementation of radioactive evaporator concentrates and to provide more data for solidification formula optimization, simulated liquid waste in various concentrations was prepared.