Huntingtin is an RNA binding protein and participates in -mediated paraspeckles.

Huntingtin protein, mutated in Huntington's disease, is implicated in nucleic acid-mediated processes, yet the evidence for direct huntingtin-nucleic acid interaction is limited. Here, we show wild-type and mutant huntingtin copurify with nucleic acids, primarily RNA, and interact directly with G-rich RNAs in in vitro assays. Huntingtin RNA-immunoprecipitation sequencing from patient-derived fibroblasts and neuronal progenitor cells expressing wild-type and mutant huntingtin revealed long noncoding RNA as a significantly enriched transcript.

Tumor-Tailored Ionizable Lipid Nanoparticles Facilitate IL-12 Circular RNA Delivery for Enhanced Lung Cancer Immunotherapy.

The advancement of message RNA (mRNA) -based immunotherapies for cancer is highly dependent on the effective delivery of RNA (Ribonucleic) payloads using ionizable lipid nanoparticles (LNPs). However, the clinical application of these therapies is hindered by variable mRNA expression among different cancer types and the risk of systemic toxicity. The transient expression profile of mRNA further complicates this issue, necessitating frequent dosing and thus increasing the potential for adverse effects.

Confidence score: a data-driven measure for inclusive systematic reviews considering unpublished preprints.

Objectives: COVID-19, since its emergence in December 2019, has globally impacted research. Over 360 000 COVID-19-related manuscripts have been published on PubMed and preprint servers like medRxiv and bioRxiv, with preprints comprising about 15% of all manuscripts. Yet, the role and impact of preprints on COVID-19 research and evidence synthesis remain uncertain.

Rational design and combinatorial chemistry of ionizable lipids for RNA delivery.

In 2018, LNPs enabled the first FDA approval of a siRNA drug (Onpattro); two years later, two SARS-CoV-2 vaccines (Comirnaty, Spikevax) based on LNPs containing mRNA also arrived at the clinic, saving millions of lives during the COVID-19 pandemic. Notably, each of the three FDA-approved LNP formulations uses a unique ionizable lipid while the other three components, , cholesterol, helper lipid, and PEGylated lipid, are almost identical. Therefore, ionizable lipids are critical to the delivery efficiency of mRNA.

Simultaneous determination of monocrotaline and its N-oxide metabolite in rat plasma using LC-MS/MS: Application to a pharmacokinetic study.

Monocrotaline (MCT) is a pyrrolizidine alkaloid that can induce hepatic sinusoidal damage, pulmonary hypertension, renal toxicity, and heart disease. Monocrotaline N-oxide (MNO), the primary metabolite of MCT, is less toxic; however, it can convert back to MCT to exhibit its toxicity. This study developed and validated a rapid and sensitive LC-MS/MS method for the simultaneous determination of MCT and monocrotaline N-oxide in rat plasma.

Quantification of Usaramine and its N-Oxide Metabolite in Rat Plasma Using Liquid Chromatography-Tandem Mass Spectrometry.

A sensitive, fast and robust liquid chromatography--tandem mass spectrometry (LC-MS-MS) method was developed and validated for the determination of usaramine (URM) and usaramine N-oxide (UNO) in rat plasma. The separation was conducted on an ACQUITY UPLC BEH C18 Column (50 × 2.1 mm, 1.

Quantitative imaging of intracellular nanoparticle exposure enables prediction of nanotherapeutic efficacy.

Nanoparticle internalisation is crucial for the precise delivery of drug/genes to its intracellular targets. Conventional quantification strategies can provide the overall profiling of nanoparticle biodistribution, but fail to unambiguously differentiate the intracellularly bioavailable particles from those in tumour intravascular and extracellular microenvironment. Herein, we develop a binary ratiometric nanoreporter (BiRN) that can specifically convert subtle pH variations involved in the endocytic events into digitised signal output, enabling the accurately quantifying of cellular internalisation without introducing extracellular contributions.

Evaluating HIFU-mediated local drug release using thermal strain imaging: Phantom and preliminary in-vivo studies.

Purpose: High-intensity focused ultrasound (HIFU)-mediated drug release becomes a promising therapeutic technique for treatment of cancer, which has merits of deep penetration, noninvasive approach and nonionizing radiation. However, conventional thermocouple-based approach for treatment monitoring would encounter big challenges such as the viscous heating artifact and difficulty in monitoring in the deep region. In this study, we develop an effective method based on thermal strain imaging (TSI) for the evaluation of HIFU-mediated drug release.

Localized co-delivery of collagenase and trastuzumab by thermosensitive hydrogels for enhanced antitumor efficacy in human breast xenograft.

Modulation of the collagen-rich extracellular matrix (ECM) in solid tumors by the treatment with collagenase has been proved effective in enhancement of the interstitial transport and antitumor efficacy of antibodies. We, therefore, developed a PLGA-PEG-PLGA polymer-based thermosensitive hydrogel, which incorporated a HER2-targeted monoclonal antibody trastuzumab and collagenase (Col/Tra/Gel) for peritumoral administration. HER2-positvie BT474 tumor-bearing mice were selected as a model.