Pseudo-linkage or real-linkage of rust resistance genes in a wheat-Thinopyrum intermedium translocation line.

We analysed the chromosomal structures of two wheat-Thinopyrum intermedium addition lines Z4 and Z5 and resolved the linkage relationship between the leaf rust and stripe rust resistance genes in Z4. Wheat addition lines Z4 and Z5 carrying rust resistance genes from Thinopyrum intermedium (JJJJStSt, 2n = 6x = 42) together with three wheat lines involved in the production of these addition lines were analysed by rust response, 90K SNP genotyping, and molecular cytogenetic analysis. Seedling leaf rust (LR) responses to five diverse pathotypes indicated that the LR resistance gene(s) was located in translocation chromosome T3DS-3AS.

A Systematic Method to Detect Next-Generation Sequencing-Based Microsatellite Instability in Plasma Cell-Free DNA: plasmaMSI.

Microsatellite instability (MSI) detection using tumor tissue is a well-established prognostic and predictive biomarker for certain types of cancers. However, tumor tissue samples are less convenient to obtain than blood plasma samples. The main challenge facing next-generation sequencing-based MSI detection in blood plasma samples is the ultralow signal/noise ratio in plasma cell-free DNA (cfDNA).

Retraction Note: MiR-5692a promotes the invasion and metastasis of hepatocellular carcinoma via MMP9.

The article "MiR-5692a promotes the invasion and metastasis of hepatocellular carcinoma via MMP9" by S.-J. Sun, N.

Predicting Futile Recanalization by Cerebral Collateral Recycle Status in Patients with Endovascular Stroke Treatment: The CHANOA Score.

Rationale And Objectives: The correlation between collateral circulation and futile recanalization (FR) is still controversial, and few studies have explored the influence of comprehensive cerebral collateral circulation on FR after endovascular stroke treatment. Therefore, based on cerebral collateral recycle (CCR) status, we aimed to establish an effective scoring system to identify the probability of FR.

Methods: This was a multicenter retrospective cohort study.

The Impact of Sleep Disorders on Glymphatic Function in Parkinson's Disease Using Diffusion Tensor MRI.

Rationale And Objectives: To investigate the impact of sleep disorders on glymphatic system in Parkinson's disease (PD) using a non-invasive imaging technique called diffusion tensor image analysis along perivascular space (DTI-ALPS).

Materials And Methods: A total of 114 PD patients and 54 healthy controls (HCs) underwent sleep questionnaires and MRI examinations as part of data collection from the Parkinson's Progression Markers Initiative cohort. An automated pipeline was proposed for ALPS calculation to reduce biases from manually region delineation.

Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes.

Base editors create precise genomic edits by directing nucleobase deamination or removal without inducing double-stranded DNA breaks. However, a vast chemical space of other DNA modifications remains to be explored for genome editing. Here, we harness the bacterial anti-phage toxin DarT2 to append ADP-ribosyl moieties to DNA, unlocking distinct editing outcomes in bacteria versus eukaryotes.

Disruption of PCSK9 Suppresses Inflammation and Attenuates Abdominal Aortic Aneurysm Formation.

Background: Abdominal aortic aneurysm (AAA) is a chronic vascular inflammatory disease without effective medications. PCSK9 (proprotein convertase subtilisin/kexin 9), a serine protease from the proprotein convertase family, has recently been associated with AAA in human genome-wide association studies. However, its role in AAA is unknown.

In vivo gene editing of T-cells in lymph nodes for enhanced cancer immunotherapy.

Immune checkpoint blockade (ICB) therapy, while promising for cancer treatment, faces challenges like unexpected side effects and limited objective responses. Here, we develop an in vivo gene-editing strategy for improving ICB cancer therapy in a lastingly effective manner. The approach uses a conductive hydrogel-based electroporation system to enable nucleofection of programmed cell death protein 1 (PD1) targeted CRISPR-Cas9 DNAs into T-cells directly within the lymph nodes, and subsequently produces PD1-deficient T-cells to combat tumor growth, metastasis and recurrence in different melanoma models in mice.

Kartogenin-Loaded Exosomes Derived From Bone Marrow Mesenchymal Stem Cells Enhance Chondrogenesis and Expedite Tendon Enthesis Healing in a Rat Model of Rotator Cuff Injury.

Background: The insufficient regeneration of fibrocartilage at the tendon enthesis is the primary cause of retearing after surgical reattachment of the rotator cuff. Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSC-Exos) and kartogenin (KGN) have been demonstrated to induce fibrocartilage formation. Loading drugs into exosomes may lead to a synergistic effect, significantly enhancing the inherent activity of both components.

Antigen-specific T cell immunotherapy by in vivo mRNA delivery.

Immunotherapy has shown promise for treating patients with autoimmune diseases or cancer, yet treatment is associated with adverse effects associated with global activation or suppression of T cell immunity. Here, we developed antigen-presenting nanoparticles (APNs) to selectively engineer disease antigen (Ag)-specific T cells by mRNA delivery. APNs consist of a lipid nanoparticle core functionalized with peptide-major histocompatibility complexes (pMHCs), facilitating antigen-specific T cell transfection through cognate T cell receptor-mediated endocytosis.

Unravelling mutational signatures with plasma circulating tumour DNA.

The use of circulating tumour DNA (ctDNA) to profile mutational signatures represents a non-invasive opportunity for understanding cancer mutational processes. Here we present MisMatchFinder, a liquid biopsy approach for mutational signature detection using low-coverage whole-genome sequencing of ctDNA. Through analysis of 375 plasma samples across 9 cancers, we demonstrate that MisMatchFinder accurately infers single-base and doublet-base substitutions, as well as insertions and deletions to enhance the detection of ctDNA and clinically relevant mutational signatures.

Targeted Degradation of Receptor-Interacting Protein Kinase 1 to Modulate the Necroptosis Pathway.

Necroptosis is a highly regulated form of necrotic cell death that plays an essential role in pathogen defense and tissue homeostasis. Abnormal regulation of the necroptotic pathway has been implicated in the pathogenesis of various human diseases, including cancer, inflammatory, and neurodegenerative diseases. Receptor-interacting protein kinase 1 (RIPK1) serves as a crucial regulator of the necroptotic signaling pathway and has been identified as a potential therapeutic target.

Enhancing transcription-replication conflict targets ecDNA-positive cancers.

Extrachromosomal DNA (ecDNA) presents a major challenge for cancer patients. ecDNA renders tumours treatment resistant by facilitating massive oncogene transcription and rapid genome evolution, contributing to poor patient survival. At present, there are no ecDNA-specific treatments.

A widespread phage-encoded kinase enables evasion of multiple host antiphage defence systems.

DNA degradation (Dnd) is a widespread bacterial antiphage defence system that relies on DNA phosphorothioate (PT) modification for self/non-self discrimination and subsequent degradation of unmodified DNA. Phages employ counterstrategies to evade host immunity, but anti-Dnd immunity has not been characterized. Here we report an immune evasion protein encoded by the Salmonella phage JSS1 that contributes to subverting Dnd and other defence systems.

Outcomes of Hyperbaric Oxygen Treatment for Central Retinal Artery Occlusion: A Single Center Experience.

Purpose: To describe the outcomes of hyperbaric oxygen therapy (HBOT) for patients with central retinal artery occlusion (CRAO) at a single tertiary care center.

Design: Retrospective clinical cohort study.

Methods: Medical records of all patients diagnosed with CRAO who received HBOT at Mayo Clinic in Rochester, Minnesota from January 1, 2009 to December 31, 2020 were reviewed to confirm diagnosis, time from onset to presentation, exam findings, treatments, and follow-up data.

Evaluation of High-Affinity Monoclonal Antibodies and Antibody-Drug Conjugates by Homogenous Time-Resolved FRET.

The rapid growth of therapeutic monoclonal antibodies demands greater accessibility to scalable methods of evaluating antigen binding. Homogenous TR-FRET is ideal for preliminary screening but has not been reported to assay these interactions due to their high-affinity and complex solution-phase kinetics. Here we report the development of a competition assay to rank-order the relative affinities of these drugs for a common antigen.

Drug-Related Keratitis: A Real-World FDA Adverse Event Reporting System Database Study.

Purpose: This study aimed to assess the drug risk of drug-related keratitis and track the epidemiological characteristics of drug-related keratitis.

Methods: This study analyzed data from the U.S.

Impact of Elevated Serum Triglycerides on Children with Acute Recurrent or Chronic Pancreatitis from INSPPIRE-2.

Objective: To determine if mild-moderate hypertriglyceridemia (HTG) is associated with increased development of chronic pancreatitis (CP) or pancreatitis-associated complications in children with acute recurrent or CP.

Study Design: Longitudinal data from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2) cohort of children with acute recurrent or CP (n = 559) were analyzed. Subjects were divided into normal triglycerides (<150 mg/dL; 1.