Robust polyfunctional CD8 and CD4 T cell responses in HLA-A*0201/DR1 transgenic mice following vaccination with modified vaccinia virus Ankara-based vaccines delivering Lassa virus glycoprotein or nucleoprotein.

Lassa virus (LASV) is circulating in rodents in several countries in West Africa and is the causative agent of the zoonotic disease Lassa fever. Several vaccine candidates have been successfully tested in preclinical and clinical research, while no LASV-specific vaccines or antiviral treatments have been licensed to date. Approximately 500,000 human cases of Lassa fever are estimated to occur every year.

Two Hernias, One Patient: A Case of Organoaxial Gastric Volvulus in a Paraesophageal Hernia With an Incisional Hernia.

A 65-year-old male presented with abdominal pain and swelling persisting for five years. On clinical examination, a 15 cm transverse scar was noted above the umbilicus, along with a reducible incisional hernia. Contrast-enhanced CT of the abdomen revealed an incisional hernia with a single defect at the umbilical and epigastric regions with European Hernia Society classification of M2-3, W3, along with a rolling-type paraesophageal hernia.

Engineering TME-gated inducible CAR-T cell therapy for solid tumors.

Autonomous "living drug" chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer medicine. However, concerns about on-target off-tumor T cell activation and resulting toxicities require advanced precise regulatory control systems for CAR-T. Here, we present a novel strategy using a genetic "AND" gate that integrates chemically induced proximity (CIP) and tumor-activated prodrug approaches to generate the next-generation CAR-T cell, TME-iCAR-T cell, that is capable of sensing multiple tumor-specific characteristics (i.

Kit-mediated autophagy suppression driven by a viral oncoprotein emerges as a crucial survival mechanism in Merkel cell carcinoma.

The KIT/c-KIT proto-oncogene is frequently over-expressed in Merkel cell carcinoma (MCC), an aggressive skin cancer commonly caused by Merkel cell polyomavirus (MCPyV). Here, we demonstrated that truncated MCPyV-encoded large T-antigen (LT) suppressed macroautophagy/autophagy by stabilizing and sequestering KIT in the paranuclear compartment via binding VPS39. KIT engaged with phosphorylated BECN1, thereby enhancing its association with BCL2 while diminishing its interaction with the PIK3C3 complex.

Rapid Development of Modified Vaccinia Virus Ankara (MVA)-Based Vaccine Candidates Against Marburg Virus Suitable for Clinical Use in Humans.

Background/objectives: Marburg virus (MARV) is the etiological agent of Marburg Virus Disease (MVD), a rare but severe hemorrhagic fever disease with high case fatality rates in humans. Smaller outbreaks have frequently been reported in countries in Africa over the last few years, and confirmed human cases outside Africa are, so far, exclusively imported by returning travelers. Over the previous years, MARV has also spread to non-endemic African countries, demonstrating its potential to cause epidemics.

A Comprehensive Review of Lavandula stoechas L. (Ustukhuddus) Plant: Phytochemistry, Pharmacology, and In Silico Studies.

Lavandula stoechas L., also referred to as French lavender or Spanish lavender, is a well-known medicinal plant with a strong presence in traditional medicine systems. This review provides an overview of the existing research progress on L.

Implementation of an Immunoassay Based on the MVA-T7pol-Expression System for Rapid Identification of Immunogenic SARS-CoV-2 Antigens: A Proof-of-Concept Study.

The emergence of hitherto unknown viral pathogens presents a great challenge for researchers to develop effective therapeutics and vaccines within a short time to avoid an uncontrolled global spread, as seen during the coronavirus disease 2019 (COVID-19) pandemic. Therefore, rapid and simple methods to identify immunogenic antigens as potential therapeutical targets are urgently needed for a better pandemic preparedness. To address this problem, we chose the well-characterized Modified Vaccinia virus Ankara (MVA)-T7pol expression system to establish a workflow to identify immunogens when a new pathogen emerges, generate candidate vaccines, and test their immunogenicity in an animal model.

A Customizable Platform to Integrate CAR and Conditional Expression of Immunotherapeutics in T Cells.

The potential of chimeric antigen receptor (CAR)-based immunotherapy as a promising therapeutic approach is often hindered by the presence of highly immunosuppressive tumor microenvironments (TME). Combination therapies with either co-administration or built-in expression of additional TME-modulating therapeutic molecules to potentiate the functions of CAR-T cells can cause systemic toxicities due to the lack of control over the delivery of biologics. Here, we present a proof-of-concept engineered platform in human Jurkat T cells that combines CAR with a therapeutic gene circuit capable of sensing -galactosidase (a reported cancer-associated signal) and subsequently activate the production of customized therapeutic gene products.

Single MVA-SARS-2-ST/N Vaccination Rapidly Protects K18-hACE2 Mice against a Lethal SARS-CoV-2 Challenge Infection.

The sudden emergence of SARS-CoV-2 demonstrates the need for new vaccines that rapidly protect in the case of an emergency. In this study, we developed a recombinant MVA vaccine co-expressing SARS-CoV-2 prefusion-stabilized spike protein (ST) and SARS-CoV-2 nucleoprotein (N, MVA-SARS-2-ST/N) as an approach to further improve vaccine-induced immunogenicity and efficacy. Single MVA-SARS-2-ST/N vaccination in K18-hACE2 mice induced robust protection against lethal respiratory SARS-CoV-2 challenge infection 28 days later.

Estrone-Based Derivatives Stabilize the and G-Quadruplex DNA Structures.

G-rich sequences are present across the genome and can fold to form dynamic secondary structures, namely, G-quadruplexes (G4). These structures play a pivotal role in regulating numerous biological processes including replication, transcription, and translation. Therefore, targeting these structures using molecular scaffolds is an attractive approach to modulating their functions.

Solanum tuberosum tuber-driven starch-mediated green-hydrothermal synthesis of cerium oxide nanoparticles for efficient photocatalysis and antimicrobial activities.

In this study, we are reporting for the first time the utilization of Solanum tuberosum tuber-driven, starch-mediated, green-hydrothermally synthesized cerium oxide nanoparticles (G-CeO NPs) for the antibacterial activity and photodegradation of cationic (methylene blue, MB) and anionic (methyl orange, MO) dyes separately and in combination, aimed at environmental remediation. The XRD analysis confirms the fluorite structure of G-CeO NPs, displaying an average crystallite size of 9.6 nm.

Management of Non-union Distal Femur Fractures With Augmentation Nail Plate Construct.

Background and objective A non-union distal femur fracture is a challenging fracture to treat. Common treatment modalities for non-union distal femur fractures include dual plating, intramedullary nails, ilizarov, and hybrid fixators. Despite the availability of a wide armamentarium of constructs, the clinical and functional outcome of these modalities is often complicated by significant morbidity, joint stiffness, and delayed union.

Targeting Parallel Topology of G-Quadruplex Structures by Indole- Fused Quindoline Scaffolds.

Preferential stabilization of G-quadruplex (G4) structures using small-molecule ligands has emerged as an effective approach to develop anticancer drugs. Herein, we report the synthesis of three indole-fused quindoline derivatives with varying lengths of side chains (, , ) as selective ligands for promoter G4 structures. The ligands stabilize the parallel topology of and promoter G4 DNAs over telomeric and duplex DNAs, as evident from the circular dichroism melting and polymerase stop-assay experiments.

A Cross-Sectional Study of the Impact of the COVID-19 Pandemic on Previously Diagnosed Patients With Fibromyalgia.

Introduction Coronavirus disease 2019 (COVID-19) was a one-of-its-kind pandemic due to its high infectivity and mortality rate. Prolonged lockdown periods imposed during the pandemic saved many lives but, on the other hand, had a huge psychological and clinical impact on patients suffering from chronic medical illnesses. Aims This study aimed to find the impact of the COVID-19 pandemic on patients with previously diagnosed fibromyalgia.

Distribution, sources, and pollution levels of toxic metal(loid)s in an urban river (Ichamati), Bangladesh using SOM and PMF modeling with GIS tool.

Indexical assessment coupled with a self-organizing map (SOM) and positive matrix factorization (PMF) modeling of toxic metal(loid)s in sediment and water of the aquatic environment provides valuable information from the environmental management perspective. However, in northwest Bangladesh, indexical and modeling assessments of toxic metal(loid)s in surface water and sediment are still rare. Toxic metal(loid)s were measured in sediment and surface water from an urban polluted river (Ichamati) in northwest Bangladesh using an atomic absorption spectrophotometer to assess distribution, pollution levels, sources, and potential environmental risks to the aquatic environment.

Assessment of dengue virus inactivation in random donor platelets using amotosalen and ultraviolet A illumination.

Objectives: The study objective was evaluation of amotosalen and ultraviolet A (UVA) illumination-based inactivation of dengue virus (DENV) in blood platelets.

Materials And Methods: Whole blood was collected from healthy donors and platelet concentrates were prepared at a tertiary care hospital in Gurugram, India. Platelet units collected from five blood group matched individuals were pooled and spiked with DENV.

Enhanced luminescence of tris(carboxylato)uranyl(VI) complexes and energy transfer to Eu(III): a combined spectroscopic and theoretical investigation.

Complex formation between uranyl and carboxylate ligands (benzoate, nicotinate and isonicotinate) has been studied extensively by absorption and luminescence spectroscopy in acetonitrile medium. Experimental data had indicated the existence of stable and enhanced luminescent tris(carboxylato) uranyl(VI) complexes [UO(L)] with symmetry. The high luminescence of these complexes was due to the sensitization of the O → U ligand to metal charge transfer (LMCT) emission by extremely intense equatorial (carboxylate ligands) LMCT bands.

Bisindolylmaleimide Ligands Stabilize G-Quadruplex DNA Structure and Downregulate Gene Expression.

G-Quadruplex (G4) structures play a pivotal role in diverse biological functions, including essential processes, such as telomere maintenance and gene regulation. G4 structures formed in functional regions of genomes are actively pursued toward therapeutics and are targeted by small-molecule ligands that alter their structure and/or stability. Herein, we report the synthesis of bisindolylmaleimide-based () ligands, which preferentially stabilize parallel G4 structures of and oncogenes over the telomeric G4 and duplex DNAs.

Post synthetically modified IRMOF-3 for efficient recovery and selective sensing of U(vi) from aqueous medium.

A simple and efficient route to develop various novel functionalized MOF materials for rapid and excellent recovery of U(vi) from aqueous medium, along with selective sensing has been demonstrated in the present study. In this connection, a set of four distinct post synthetically modified (PSM) iso-reticular metal organic frameworks were synthesized from IRMOF-3 namely, IRMOF-PC (2-pyridine carboxaldehyde), IRMOF-GA (glutaric anhydride), IRMOF-SMA (sulfamic acid), and IRMOF-DPC (diphenylphosphonic chloride) for the recovery and sensing of U(vi) from aqueous medium. The MOFs were characterized by Fourier transform infrared spectroscopy (FTIR), powder XRD, BET surface area analysis, thermogravimetric analysis (TGA), NMR (C, H and P), Scanning Electron Microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX).

Unraveling the coordination approach of Eu(III) in cyphos nitrate ionic liquid - a comprehensive luminescence spectroscopy study.

In consideration of the mounting attention drawn by the ionic liquid cyphos 101 (trihexyl(tetradecyl)phosphonium chloride: [P][Cl]) in the recovery of rare earth metals and other valuable species from their waste matrices, an effort was made using luminescence spectroscopy to study the detailed liquid-liquid extraction and coordination behavior of Eu(III) using the nitrate form of cyphos 101 (cyphos nitrate: [P][NO]) in its undiluted form. Eu(III) complexation with [P][NO] at each stage of the extraction process was investigated using the luminescence spectroscopy technique. Various extraction parameters such as aqueous phase acidity, concentrations of ionic liquid extractant and initial Eu(III) ion, extraction time, experimental temperature, were tuned to discover their impact on the complexation process.

Method to Eliminate Fluoride Interference in the Spectrophotometric Estimation of Zirconium: Application to U-Zr Alloys.

In the estimation of Zr using the ultraviolet-visible (UV-Vis) spectrophotometric technique, fluoride interference is a decade-old unsolved problem. The process of repeated fuming with strong acids is often used to remove fluoride from the solution in order to estimate Zr using spectrophotometry analysis. For the first time, in this work, a simple use of AlCl is reported as a suppressing reagent to eliminate the interference of fluoride in the estimation of Zr.

Potentially toxic elemental contamination in Wainivesi River, Fiji impacted by gold-mining activities using chemometric tools and SOM analysis.

Potentially toxic element (PTE) contamination in Wainivesi River, Fiji triggered by gold-mining activities is a major public health concern deserving attention. However, chemometric approaches and pattern recognition of PTEs in surface water and sediment are yet hardly studied in Pacific Island countries like Fijian urban River. In this study, twenty-four sediment and eight water sampling sites from the Wainivesi River, Fiji were explored to evaluate the spatial pattern, eco-environmental pollution, and source apportionment of PTEs.

Comparative evaluation of ADVIA Centaur® XP chemiluminescence system for screening of HBV, HCV, HIV and syphilis in Indian blood donors.

Background: The introduction of chemiluminescent immunoassay (CLIA) in blood donor screening has led to a gradual replacement of enzyme-linked-immunosorbent assay (ELISA) as the former offers automation, higher sensitivity and lower turn-around-time. However, only a few CLIA platforms are used for blood donor screening in India. The present study evaluated one such newer platform viz.

Preliminary assessment of heavy metals in surface water and sediment in Nakuvadra-Rakiraki River, Fiji using indexical and chemometric approaches.

River water and sediment embody environmental characteristics that give valuable environmental management information. However, indexical and chemometric appraisal of heavy metals (HMs) in river water and sediment is very scarce in Island countries including Fiji. In this research, forty-five sediment and fifteen water samples from the Nakuvadra-Rakiraki River, Fiji were analyzed for appraising spatial distribution, pollution, and source identification of selected heavy metals (HMs) using the coupling tools of self-organizing map (SOM), compositional data analysis (CDA), and sediment and water quality indices.

Water resources pollution associated with risks of heavy metals from Vatukoula Goldmine region, Fiji.

Although mining is essential for human economic development, is amongst the most polluting anthropogenic sources that influence seriously in water resources. Thus, understanding the presence and concentration of heavy metals in water and sediment in the vicinity of mines is important for the sustainability of the ecosystem. In this work, a multidisciplinary approach was developed to characterize the contamination level, source apportionment, co-existence, and degree of ecological and human health risks of HMs on water resources in the Vatukoula Goldmine region (VGR), Fiji.