Recent Insights into Nano-mediated siRNA Drug Delivery.

Gene silencing is the characteristic that inhibits gene expression afforded by siRNA interference. The efficacy of the delivery system in terms of precision, efficacy, and stability can be enhanced by genebased drug delivery options. The delivery challenges and their associated side effects create a challenge for the delivery of gene-based drug delivery carriers.

Insecticidal Activity of Fatty Acids From the Fruit Extract of Momordica cymbalaria Fenzl Ex Naudin, Has Insecticidal Activities on Mosquito Larvae.

The fruit and other parts of Momordica cymbalaria are known to have medicinal properties. The study investigates the chemical composition and functional groups of M. cymbalaria fruits to assess the insecticidal potential of its bioactive metabolites.

Discovery of GNE-6893, a Potent, Selective, Orally Bioavailable Small Molecule Inhibitor of HPK1.

Hematopoietic progenitor kinase 1 (HPK1) serves a key immunosuppressive role as a negative regulator of T-cell receptor (TCR) signaling. HPK1 loss-of-function is associated with augmentation of immune function and has demonstrated synergy with immune checkpoint inhibitors in syngeneic mouse cancer models. These data offer compelling evidence for the use of selective small molecule inhibitors of HPK1 in cancer immunotherapy.

Tailoring CuO loading on CoFeO nanocubes photocatalyst for superior photocatalytic degradation of triclosan pollutants under VL irradiation and toxicological evaluation.

In this study, we report the development of a novel CuO(3 wt%)/CoFeO nanocubes (NCs) photocatalyst through simple co-precipitation and wet impregnation methods for the efficient photocatalytic degradation of triclosan (TCS) pollutants. Initially, rod-shaped bare CoFeO was synthesized using a simple co-precipitation technique. Subsequently, CuO was loaded in various percentages (1, 2, and 3 wt%) onto the surface of bare CoFeO nanorods (NRs) via the wet impregnation method.

Accelerating drug development at Bristol Myers Squibb through innovation.

This paper focuses on the use of novel technologies and innovative trial designs to accelerate evidence generation and increase pharmaceutical Research and Development (R&D) productivity, at Bristol Myers Squibb. We summarize learnings with case examples, on how we prepared and continuously evolved to address the increasing cost, complexities, and external pressures in drug development, to bring innovative medicines to patients much faster. These learnings were based on review of internal efforts toward accelerating R&D focusing on four key areas: adopting innovative trial designs, optimizing trial designs, leveraging external control data, and implementing novel methods using artificial intelligence and machine learning.

Atomistic Simulations of Polydisperse Lignin Melts Using Simple Polydisperse Residue Input Generator.

Understanding the physics of lignin will help rationalize its function in plant cell walls as well as aiding practical applications such as deriving biofuels and bioproducts. Here, we present SPRIG (Simple Polydisperse Residue Input Generator), a program for generating atomic-detail models of random polydisperse lignin copolymer melts i.e.

Development of Liposome Systems for Enhancing the PK Properties of Bivalent PROTACs.

Proteolysis-Targeting Chimeras (PROTACs) are a promising new technology in drug development. They have rapidly evolved in recent years, with several of them in clinical trials. While most of these advances have been associated with monovalent protein degraders, bivalent PROTACs have also entered clinical trials, although progression to market has been limited.

Data-driven strategies for increasing patient diversity in Bristol Myers Squibb-sponsored US oncology clinical trials.

Background/aims: Determining whether clinical trial findings are applicable to diverse, real-world patient populations can be challenging when the full demographic characteristics of enrolled patients are not consistently reported. Here, we present the results of a descriptive analysis of racial and ethnic demographic information for patients in Bristol Myers Squibb (BMS)-sponsored oncology trials in the United States (US) and describe factors associated with increased patient diversity.

Methods: BMS-sponsored oncology trials conducted at US sites with study enrollment dates between 1 January 2013 and 31 May 2021 were analyzed.

Non-enzymatic electrochemical detection of creatinine based on a glassy carbon electrode modified with a Pd/CuO decorated polypyrrole (PPy) nanocomposite: an analytical approach.

The major constraints of standard enzymatic biosensors are poor long-term storage stability and high cost. Hence, there is extensive research towards fabrication of reliable enzymeless biosensors based on nanomaterials. In this paper, we present the development of an enzymeless electrochemical biosensor for highly precise detection of creatinine.

Emulating Randomized Controlled Trials with Hybrid Control Arms in Oncology: A Case Study.

This proof-of-concept study retrospectively assessed the feasibility of applying a hybrid control arm design to a completed phase III randomized controlled trial (RCT; CheckMate-057) in advanced non-small cell lung cancer using a real-world data (RWD) source. The emulated trial consists of an experimental arm (patients from the RCT experimental cohort) and a hybrid control arm (patients from the RCT and RWD control cohorts). For the RWD control cohort, this study used a nationwide electronic health record-derived de-identified database.

wnt16 regulates spine and muscle morphogenesis through parallel signals from notochord and dermomyotome.

Bone and muscle are coupled through developmental, mechanical, paracrine, and autocrine signals. Genetic variants at the CPED1-WNT16 locus are dually associated with bone- and muscle-related traits. While Wnt16 is necessary for bone mass and strength, this fails to explain pleiotropy at this locus.

Association of Alzheimer's disease and periodontitis - a systematic review and meta-analysis of evidence from observational studies.

The relationship between periodontitis (or periodontal disease) with Alzheimer's disease has been reported by various primary sources in the past decade, but not with a solid secondary research statement. A systematic review and meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and registered (Reference number: CRD42020185264) with PROSPERO (International prospective register for systematic reviews). A literature search was conducted on specific databases for suitable articles in English language.

Expression of ABC transporters during syncytialization in preeclampsia.

Preeclampsia complicates 2-8% of pregnancies and is associated with prematurity and intrauterine growth restriction. Cholesterol and sterol transport is a key function of the placenta and it is elicited through ATP binding cassette (ABC) transporters. ABCA1 expression changes during trophoblast cell fusion, a process required to form the placental syncytium that enables maternal-fetal nutrient transfer.

Fast and versatile analysis of liposome encapsulation efficiency by nanoParticle exclusion chromatography.

Liposomes are an attractive drug delivery platform for a wide variety of pharmaceutical molecules. Encapsulation efficiency, which refers to the amount of drug contained inside liposomes compared with the total amount of drug, is a critical quality attribute of liposome products, as the free drug in a liposomal formulation may cause toxicity or undesired biodistribution. The determination of encapsulation efficiency requires the measurement of at least two of the three drug populations: total drug, encapsulated drug and free drug.

Efficacy of Combined Rifampicin Formulations Delivered by the Pulmonary Route to Treat Tuberculosis in the Guinea Pig Model.

Liposomes, as vehicles alone or in combination with rifampicin (RIF) microparticles (RMs), were evaluated as vehicles to enhance the permeation of RIF into granulomas. RIF liposomes (RLs) were extruded through a 0.1 µm polypropylene membrane.

Safety and pharmacodynamics of an engineered E. coli Nissle for the treatment of phenylketonuria: a first-in-human phase 1/2a study.

Phenylketonuria (PKU) is a rare disease caused by biallelic mutations in the PAH gene that result in an inability to convert phenylalanine (Phe) to tyrosine, elevated blood Phe levels and severe neurological complications if untreated. Most patients are unable to adhere to the protein-restricted diet, and thus do not achieve target blood Phe levels. We engineered a strain of E.

Crystallographic investigation, Hirshfeld surface analysis, NLO characterization and experimental spectral (UV and NMR) studies with DFT probe on(R)-9-(2-hydroxy propyl)adenine.

In this study, (R)-9-(2-hydroxy propyl)adenine (HPA) is the molecule of interest for investigation. The XRD from single crystal of HPA has been used to extract its structural features. Since HPA crystallised in a non-centro symmetric space group P222, its NLO property was studied and it was found to exhibit very good SHG activity.

Discovery and Optimization of DNA Gyrase and Topoisomerase IV Inhibitors with Potent Activity against Fluoroquinolone-Resistant Gram-Positive Bacteria.

Herein, we describe the discovery and optimization of a novel series that inhibits bacterial DNA gyrase and topoisomerase IV binding to, and stabilization of, DNA cleavage complexes. Optimization of this series led to the identification of compound , which has potent activity against Gram-positive bacteria, a favorable safety profile, and excellent pharmacokinetic properties. Compound was found to be efficacious against fluoroquinolone-sensitive infection in a mouse thigh model at lower doses than moxifloxacin.

Bayesian Optimization of Bose-Einstein Condensates.

Machine Learning methods are emerging as faster and efficient alternatives to numerical simulation techniques. The field of Scientific Computing has started adopting these data-driven approaches to faithfully model physical phenomena using scattered, noisy observations from coarse-grained grid-based simulations. In this paper, we investigate data-driven modelling of Bose-Einstein Condensates (BECs).

Recent Progress in Stimuli-Responsive Intelligent Nano Scale Drug Delivery Systems: A Special Focus Towards pH-Sensitive Systems.

Stimuli-responsive nanocarriers are gaining much attention due to their versatile multifunctional activities, including disease diagnosis and treatment. Recently, clinical applications of nano-drug delivery systems for cancer treatment pose a challenge due to their limited cellular uptake, low bioavailability, poor targetability, stability issues, and unfavourable pharmacokinetics. To overcome these issues, researchers are focussing on stimuli-responsive systems.

Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk.

Epidemiological studies indicate that elevated alkaline phosphatase activity is associated with increased cardiovascular disease risk. Other epidemiological data demonstrate that mothers giving multiple childbirths (multipara) are also at increased risk of developing late-onset cardiovascular disease. We hypothesized that these two associations stem from a common cause, the insufficient plasma level of the ectopic mineralization inhibitor inorganic pyrophosphate, which is a substrate of alkaline phosphatase.

Assessing Patient Participation Burden Based on Protocol Design Characteristics.

Background: Although a number of studies have quantitatively measured investigative site burden to administer increasingly complex protocol designs, robust scholarly research has not been performed to quantify the burden that patients face as participants in clinical trials.

Methods: This paper presents the results of a cross-sectional pilot study conducted by the Tufts Center for the Study of Drug Development and ZS Associates among nearly 600 patients via an online survey conducted between February and March 2019. Respondents rated the perceived burden of 60 commonly administered protocol procedures.