Phase I study of BMS-986299, an NLRP3 agonist, as monotherapy and in combination with nivolumab and ipilimumab in patients with advanced solid tumors.

Purpose: BMS-986299 is a first-in-class, NOD-, LRR-, and pyrin-domain containing-3 (NLRP3) inflammasome agonist enhancing adaptive immune and T-cell memory responses.

Materials And Methods: This was a phase-I (NCT03444753) study that assessed the safety and tolerability of intra-tumoral BMS-986299 monotherapy (part 1A) and in combination (part 1B) with nivolumab, and ipilimumab in advanced solid tumors. Reported here are single-center results.

ADME, Toxicity, Molecular Docking, Molecular Dynamics, Glucokinase activation, DPP-IV, α-amylase, and α-glucosidase Inhibition Assays of Mangiferin and Friedelin for Antidiabetic Potential.

Today the alarming situation of diabetes seeks innovative antidiabetic medications, especially those derived from natural sources, as natural substances are safer than manufactured pharmaceuticals. Therefore, this study investigated the inhibitory properties of mangiferin and friedelin against glucokinase (GK), dipeptidyl peptidase-IV (DPP-IV), α-amylase, and α-glucosidase using computational methods, in vitro enzyme assays, and in-depth ADMET analysis. The study utilized a computer-aided drug design approach to assess the potential therapeutic properties of mangiferin and friedelin as Type 2 diabetes mellitus (T2DM) therapeutic agents.

Isolation and molecular characterization of fowl adenovirus from inclusion body hepatitis cases in Western India during 2019-2021.

Background: Inclusion body hepatitis (IBH) resulted in a substantial economic loss in Western India during 2019 to 2021.

Aims: The study aimed to characterize fowl adenovirus (FAdV) from field outbreaks.

Methods: The study was conducted on 290 liver samples from 66 poultry flocks.

The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2.

SARS-CoV-2 continues to pose a threat to public health. Current therapeutics remain limited to direct acting antivirals that lack distinct mechanisms of action and are already showing signs of viral resistance. The virus encodes an ADP-ribosylhydrolase macrodomain (Mac1) that plays an important role in the coronaviral lifecycle by suppressing host innate immune responses.

NF-κB inhibitor alpha controls SARS-CoV-2 infection in ACE2-overexpressing human airway organoids.

As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that recapitulate the cell-intrinsic response to arising viral variants are needed. Here we describe an adult stem cell-derived human airway organoid model overexpressing the ACE2 receptor (ACE2-OE) that supports robust viral replication while maintaining 3D architecture and cellular diversity of the airway epithelium. ACE2-OE organoids were infected with SARS-CoV-2 variants and subjected to single-cell RNA-sequencing.

Final results of urelumab, an anti-CD137 agonist monoclonal antibody, in combination with cetuximab or nivolumab in patients with advanced solid tumors.

Background: Resistance to immune checkpoint inhibitors and targeted treatments for cancer is common; thus, novel immunotherapy agents are needed. Urelumab is a monoclonal antibody agonist that binds to CD137 receptors expressed on T cells. Here, we report two studies that evaluated urelumab in combination with cetuximab or nivolumab in patients with select, advanced solid tumors.

Seropositivity of dengue cases at a tertiary care centre in Chhindwara, Madhya Pradesh: A three year trend.

Background: During the recent decades, dengue virus infection has been emerged as a major public health problem. Dengue is one of the important mosquito borne infections causing high mortality and morbidity of humans. : This study was carried out from October 2018 to December 2020.

Impact of an Antimicrobial Stewardship Program on Broad Spectrum Antibiotics Consumption in the Intensive Care Setting.

Background And Objectives: Antibiotics are the most commonly exploited agents in intensive care units. An antimicrobial stewardship program (ASP) helps in the optimal utilization of antibiotics and prevents the development of antibiotic resistance. The aim of this study was to assess the impact of ASP on broad-spectrum antibiotic consumption in terms of defined daily dose (DDD) and days of therapy (DOT) before and after the implementation of an ASP.

Previous exposure to Spike-providing parental strains confers neutralizing immunity to XBB lineage and other SARS-CoV-2 recombinants in the context of vaccination.

The emergence of SARS-CoV-2 recombinants is of particular concern as they can result in a sudden increase in immune evasion due to antigenic shift. Recent recombinants XBB and XBB.1.

A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication in vivo.

Despite unprecedented efforts, our therapeutic arsenal against SARS-CoV-2 remains limited. The conserved macrodomain 1 (Mac1) in NSP3 is an enzyme exhibiting ADP-ribosylhydrolase activity and a possible drug target. To determine the role of Mac1 catalytic activity in viral replication, we generated recombinant viruses and replicons encoding a catalytically inactive NSP3 Mac1 domain by mutating a critical asparagine in the active site.

Evaluation of Structural, Magnetic, and Electromagnetic Properties of Co-Substituted NiCuZn Ferrites.

We report citrate gel-assisted autocombusted spinel-type Co-substituted NiCuZn ferrites and their electromagnetic properties. Several complementary techniques were used to investigate the influence of Co on structural and electromagnetic properties of NiCoCuZnFeO with = 0.00-0.

Post-acute immunological and behavioral sequelae in mice after Omicron infection.

Progress in understanding long COVID and developing effective therapeutics is hampered in part by the lack of suitable animal models. Here we used ACE2-transgenic mice recovered from Omicron (BA.1) infection to test for pulmonary and behavioral post-acute sequelae.

Mercapto-pyrimidines are reversible covalent inhibitors of the papain-like protease (PLpro) and inhibit SARS-CoV-2 (SCoV-2) replication.

The papain-like protease (PLpro) plays a critical role in SARS-CoV-2 (SCoV-2) pathogenesis and is essential for viral replication and for allowing the virus to evade the host immune response. Inhibitors of PLpro have great therapeutic potential, however, developing them has been challenging due to PLpro's restricted substrate binding pocket. In this report, we screened a 115 000-compound library for PLpro inhibitors and identified a new pharmacophore, based on a mercapto-pyrimidine fragment that is a reversible covalent inhibitor (RCI) of PLpro and inhibits viral replication in cells.

Mild SARS-CoV-2 infection results in long-lasting microbiota instability.

Viruses targeting mammalian cells can indirectly alter the gut microbiota, potentially compounding their phenotypic effects. Multiple studies have observed a disrupted gut microbiota in severe cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that require hospitalization. Yet, despite demographic shifts in disease severity resulting in a large and continuing burden of non-hospitalized infections, we still know very little about the impact of mild SARS-CoV-2 infection on the gut microbiota in the outpatient setting.

Paranasal Sinus Malignant Peripheral Nerve Sheath Tumour: A Rare Case Report.

Malignant Peripheral Nerve Sheath Tumour (MPNST) is a neoplastic lesion rarely reported in literature. In approximately 5% of cases it is associated with Neurofibromatosis type 1 syndrome. Pathognomic features of MPNST include slow growth rate, aggressive nature, nearly circumscribed, unencapsulated arising from non myelinated Schwann cells.

A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication and pathogenesis .

Despite unprecedented efforts, our therapeutic arsenal against SARS-CoV-2 remains limited. The conserved macrodomain 1 (Mac1) in NSP3 is an enzyme exhibiting ADP-ribosylhydrolase activity and a possible drug target. To determine the therapeutic potential of Mac1 inhibition, we generated recombinant viruses and replicons encoding a catalytically inactive NSP3 Mac1 domain by mutating a critical asparagine in the active site.

Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6.

Although the SARS-CoV-2 Omicron variant (BA.1) spread rapidly across the world and effectively evaded immune responses, its viral fitness in cell and animal models was reduced. The precise nature of this attenuation remains unknown as generating replication-competent viral genomes is challenging because of the length of the viral genome (~30 kb).

Surface decorated quantum dots: Synthesis, properties and role in herbal therapy.

Quantum dots are the serendipitous outcome of materials research. It is the tiny carbonaceous nanoparticles with diameters ranging from 1 to 10 nm. This review is a brief discussion of the synthesis, properties, and biomedical applicability of quantum dots, especially in herbal therapy.

Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6.

Although the SARS-CoV-2 Omicron variant (BA.1) spread rapidly across the world and effectively evaded immune responses, its viral fitness in cell and animal models was reduced. The precise nature of this attenuation remains unknown as generating replication-competent viral genomes is challenging because of the length of the viral genome (30kb).

Angiomatous Nasal Polyp: The Great Emulator-A Case Report.

Angiomatous nasal polyps are rare, benign and non-neoplastic lesions rarely reported in literature. Clinically and radiologically it mimics sinonasal neoplasm. In 5% of inflammatory or allergic sinonasal polyps, extensive vascularisation and ectasia with pseudoamyloid deposition is noted.

Facile and scalable synthesis of un-doped, doped and co-doped graphene quantum dots: a comparative study on their impact for environmental applications.

In recent years, graphene quantum dots (GQDs) received huge attention due to their unique properties and potential applicability in different area. Here, we report simple and facile method for the synthesis of GQDs and their functionalization by doping and co-doping using different heteroatom under the optimized conditions. The doping and co-doping of GQDs using boron and nitrogen have been confirmed by FTIR and TEM.

Isolation and molecular characterization of infectious bursal disease virus circulating in western and central India.

Background: Infectious bursal disease (IBD) caused substantial economic loss in central and western India during 2020 and 2021.

Aims: The study was conducted to characterize IBD virus (IBDV) from field outbreaks.

Methods: The study was conducted on 360 samples from 42 poultry flocks.

Mild SARS-CoV-2 infection results in long-lasting microbiota instability.

Unlabelled: Viruses targeting mammalian cells can indirectly alter the gut microbiota, potentially compounding their phenotypic effects. Multiple studies have observed a disrupted gut microbiota in severe cases of SARS-CoV-2 infection that require hospitalization. Yet, despite demographic shifts in disease severity resulting in a large and continuing burden of non-hospitalized infections, we still know very little about the impact of mild SARS-CoV-2 infection on the gut microbiota in the outpatient setting.