Genome-wide profiling of tRNA modifications by Induro-tRNAseq reveals coordinated changes.

While all native tRNAs undergo extensive post-transcriptional modifications as a mechanism to regulate gene expression, mapping these modifications remains challenging. The critical barrier is the difficulty of readthrough of modifications by reverse transcriptases (RTs). Here we use Induro-a new group-II intron-encoded RT-to map and quantify genome-wide tRNA modifications in Induro-tRNAseq.

APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence.

Elucidating the relationships between a class I peptide antigen, a CD8 T cell receptor (TCR) specific to that antigen, and the T cell phenotype that emerges following antigen stimulation, remains a mostly unsolved problem, largely due to the lack of large data sets that can be mined to resolve such relationships. Here, we describe Antigen-TCR Pairing and Multiomic Analysis of T-cells (APMAT), an integrated experimental-computational framework designed for the high-throughput capture and analysis of CD8 T cells, with paired antigen, TCR sequence, and single-cell transcriptome. Starting with 951 putative antigens representing a comprehensive survey of the SARS-CoV-2 viral proteome, we utilize APMAT for the capture and single cell analysis of CD8 T cells from 62 HLA A*02:01 COVID-19 participants.

Interaction of N-methylmesoporphyrin IX with a hybrid left-/right-handed G-quadruplex motif from the promoter of the SLC2A1 gene.

Left-handed G-quadruplexes (LHG4s) belong to a class of recently discovered noncanonical DNA structures under the larger umbrella of G-quadruplex DNAs (G4s). The biological relevance of these structures and their ability to be targeted with classical G4 ligands is underexplored. Here, we explore whether the putative LHG4 DNA sequence from the SLC2A1 oncogene promoter maintains its left-handed characteristics upon addition of nucleotides in the 5'- and 3'-direction from its genomic context.

The novel β-hairpin antimicrobial peptide D-G(RF)3 demonstrates exceptional antibacterial efficacy.

The clinical application of most natural antimicrobial peptides (AMPs) is hindered by their lack of a synergistic combination of high antibacterial efficacy, low toxicity, and stability, necessitating frequent complex modifications that incur significant labor and economic costs. Therefore, it is imperative to optimize the antibacterial properties of AMPs using some simplified approach. In this study, we designed a library of β-hairpin AMPs with identical β-turn sequences (-D-Pro-Gly-) and varying repetition units (IR, FR, and WK).

Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor.

Hypoxia-inducible factor prolyl hydroxylase (PHD) inhibitors have been approved for treating renal anemia yet have failed clinical testing for inflammatory bowel disease because of a lack of efficacy. Here we used a multimodel multimodal generative artificial intelligence platform to design an orally gut-restricted selective PHD1 and PHD2 inhibitor that exhibits favorable safety and pharmacokinetic profiles in preclinical studies. ISM012-042 restores intestinal barrier function and alleviates gut inflammation in multiple experimental colitis models.

Cancer cells restrict immunogenicity of retrotransposon expression via distinct mechanisms.

To thrive, cancer cells must navigate acute inflammatory signaling accompanying oncogenic transformation, such as via overexpression of repeat elements. We examined the relationship between immunostimulatory repeat expression, tumor evolution, and the tumor-immune microenvironment. Integration of multimodal data from a cohort of pancreatic ductal adenocarcinoma (PDAC) patients revealed expression of specific Alu repeats predicted to form double-stranded RNAs (dsRNAs) and trigger retinoic-acid-inducible gene I (RIG-I)-like-receptor (RLR)-associated type-I interferon (IFN) signaling.

Cephalopod-inspired jetting devices for gastrointestinal drug delivery.

Needle-based injections currently enable the administration of a wide range of biomacromolecule therapies across the body, including the gastrointestinal tract, through recent developments in ingestible robotic devices. However, needles generally require training, sharps management and disposal, and pose challenges for autonomous ingestible systems. Here, inspired by the jetting systems of cephalopods, we have developed and evaluated microjet delivery systems that can deliver jets in axial and radial directions into tissue, making them suitable for tubular and globular segments of the gastrointestinal tract.

Oncolytic immunotherapy with nivolumab in muscle-invasive bladder cancer: a phase 1b trial.

There is a critical unmet need for safe and efficacious neoadjuvant treatment for cisplatin-ineligible patients with muscle-invasive bladder cancer. Here we launched a phase 1b study using the combination of intravesical cretostimogene grenadenorepvec (oncolytic serotype 5 adenovirus encoding granulocyte-macrophage colony-stimulating factor) with systemic nivolumab in cisplatin-ineligible patients with cT2-4aN0-1M0 muscle-invasive bladder cancer. The primary objective was to measure safety, and the secondary objective was to assess the anti-tumor efficacy as measured by pathologic complete response along with 1-year recurrence-free survival.

Effects of Creatine Supplementation and Resistance Training on Muscle Strength Gains in Adults <50 Years of Age: A Systematic Review and Meta-Analysis.

Background: Numerous meta-analyses have assessed the efficacy of creatine supplementation in increasing muscle strength. However, most have not considered the effect of the participants' age, training duration, or other confounding variables on strength outcomes. Therefore, the purpose of this study was to consider the effect of these variables on the potential efficacy of creatine supplementation and resistance training for improving measures of muscle strength.

How to recognize clustering of luminescent defects in single-wall carbon nanotubes.

Semiconducting single-wall carbon nanotubes (SWCNTs) are a promising material platform for near-infrared imaging, optical sensing, and single-photon emission at telecommunication wavelengths. The functionalization of SWCNTs with luminescent defects can lead to significantly enhanced photoluminescence (PL) properties due to efficient trapping of highly mobile excitons and red-shifted emission from these trap states. Among the most studied luminescent defect types are oxygen and aryl defects that have largely similar optical properties.

The epithelial barrier theory and its associated diseases.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide.

Macrocyclic trichothecenes from Myrothecium verrucaria PA 57 and their cytotoxic activity.

Four novel macrocyclic trichothecenes, termed mytoxins D-G (1-4), along with four known analogs (5-8), were isolated from the ethyl acetate extract of fermented rice inoculated with the fungus Myrothecium verrucaria PA57. Each compound features a tricyclic 12,13-epoxytrichothec-9-ene (EPT) core. Notably, mytoxin G (4) represents the first instance of a macrocyclic trichothecene incorporating a glucosyl unit within the trichothecene structure.

Mitochondrial phylogeography of grassland caterpillars (Lepidoptera: Lymantriinae: ) endemic to the Qinghai-Tibetan plateau.

Grassland caterpillars (Lepidoptera: Lymantriinae: ) are the most damaging pests to alpine meadows in the Qinghai-Tibetan Plateau (QTP). Here, we conducted extensive sampling from 39 geographic populations covering almost the entire distribution of the eight QTP (Hübner) species to investigate phylogeographic patterns and speciation based on two mitochondrial genes ( and ). A total of 40 haplotypes were detected in the 39 populations, with >70% of all haplotypes not shared between populations.

Methylation of KSHV vCyclin by PRMT5 contributes to cell cycle progression and cell proliferation.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus that encodes numerous cellular homologs, including cyclin D, G protein-coupled protein, interleukin-6, and macrophage inflammatory proteins 1 and 2. KSHV vCyclin encoded by ORF72, is the homolog of cellular cyclinD2. KSHV vCyclin can regulate virus replication and cell proliferation by constitutively activating cellular cyclin-dependent kinase 6 (CDK6).

Development of the APBD-SQ, a novel patient-reported outcome for health-related quality of life in adult polyglucosan body disease.

Adult polyglucosan body disease (APBD) is a rare autosomal recessive glycogen storage disorder that leads to slowly progressive multi-organ dysfunction in adulthood. A novel disease-specific patient-reported outcome measure was created and administered to assess symptom burden and health-related quality of life (HR-QOL) in APBD. Thirty-six participants between 30 and 79 years of age (83% ≥60 years, 56% male) completed the anonymous questionnaire independently or with a caregiver proxy (75% self-report).

Cannabis use and patient-reported outcomes among patients at a comprehensive cancer center.

Background: Patients with cancer report increasing rates of cannabis use, often to manage symptoms and toxicities. The efficacy and safety of cannabis, however, for some use cases remains unclear. To better understand characteristics of patients with cancer who report using cannabis, we examined data from a cannabis use survey of among patients with cancer seen at a National Cancer Institute-Designated Cancer Center.