Determining the Optimal Age for Extracranial-Intracranial Bypass Surgery: A Post Hoc Analysis of the CMOSS Randomized Trial.

Background: Previous trials have failed to demonstrate the benefits of extracranial-intracranial (EC-IC) bypass surgery for patients with carotid or middle cerebral artery occlusion. However, little evidence has focused on the effect of age on prognosis. This study aimed to explore whether EC-IC bypass surgery can provide greater benefits than medical therapy alone in specific age groups.

A Multi-Enzyme Nanocascade to Target Disease-Relevant Metabolites.

Metabolic processes in living organisms depend on the synergistic actions of enzymes working in proximity and in concert, catalyzing reactions effectively while regulating the formation of metabolites. This enzyme synergy offers promising therapeutic application for diseases such as alcohol intoxication, cancer, and hyperinflammation. Despite their potential, the clinical translation of enzyme cascades is restricted by challenges including poor enzyme stability, short half-life, and a lack of delivery strategies that maintain enzyme proximity.

Myeloid clonal hematopoiesis of indeterminate potential in patients with chronic lymphocytic leukemia.

Clonal hematopoiesis of indeterminate potential (CHIP) in patients with chronic lymphocytic leukemia (CLL) has not been extensively characterized. The objective of this study was to describe the prevalence of myeloid CHIP (M-CHIP) in patients with CLL, and to determine its association with time to first treatment (TTFT) and overall survival (OS). We retrospectively analyzed data from patients participating in a prospective CLL database at the Dana-Farber Cancer Institute who had standard-of-care targeted 95-gene next-generation sequencing (NGS) performed.

Treatment of Vedolizumab With Exclusive Enteral Nutrition in Adult Patients With Moderate to Severe Crohn's Disease (Crohn Exclusive Enteral Nutrition Study).

Introduction: Despite increasing studies confirming the efficacy of vedolizumab (VDZ) in Crohn's disease (CD), improving the responses to this biologic agent remains challenging in clinical practice. In this article, we investigated the efficacy of combined treatment of VDZ and 16-week exclusive enteral nutrition (EEN) in moderately to severely active CD.

Methods: From October 2020 to October 2023, 81 patients with moderately to severely active CD treated with VDZ from 2 inflammatory bowel disease centers were retrospectively selected.

Sub-regional Radiomics Analysis for Predicting Metastasis Risk in Clear Cell Renal Cell Carcinoma: A Multicenter Retrospective Study.

Rationale And Objectives: Clear cell renal cell carcinoma (ccRCC) is the most common malignant neoplasm affecting the kidney, exhibiting a dismal prognosis in metastatic instances. Elucidating the composition of ccRCC holds promise for the discovery of highly sensitive biomarkers. Our objective was to utilize habitat imaging techniques and integrate multimodal data to precisely predict the risk of metastasis, ultimately enabling early intervention and enhancing patient survival rates.

Identifying the Mechanisms of a Peripherally Limited Exercise Phenotype in Patients With Heart Failure With Preserved Ejection Fraction.

Background: We identified peripherally limited patients using cardiopulmonary exercise testing and measured skeletal muscle oxygen transport and utilization during invasive single leg exercise testing to identify the mechanisms of the peripheral limitation.

Methods: Forty-five patients with heart failure with preserved ejection fraction (70±7 years, 27 females) completed seated upright cardiopulmonary exercise testing and were defined as having a (1) peripheral limitation to exercise if cardiac output/oxygen consumption (VO) was elevated (≥6) or 5 to 6 with a stroke volume reserve >50% (n=31) or (2) a central limitation to exercise if cardiac output/VO slope was ≤5 or 5 to 6 with stroke volume reserve <50% (n=14). Single leg knee extension exercise was used to quantify peak leg blood flow (Doppler ultrasound), arterial-to-venous oxygen content difference (femoral venous catheter), leg VO, and muscle oxygen diffusive conductance.

Glycoengineering-based anti-PD-1-iRGD peptide conjugate boosts antitumor efficacy through T cell engagement.

Despite the important breakthroughs of immune checkpoint inhibitors in recent years, the objective response rates remain limited. Here, we synthesize programmed cell death protein-1 (PD-1) antibody-iRGD cyclic peptide conjugate (αPD-1-(iRGD)) through glycoengineering methods. In addition to enhancing tissue penetration, αPD-1-(iRGD) simultaneously engages tumor cells and PD-1 T cells via dual targeting, thus mediating tumor-specific T cell activation and proliferation with mild effects on non-specific T cells.

Divergent Learning-Related Transcriptional States of Cortical Glutamatergic Neurons.

Experience-dependent gene expression reshapes neural circuits, permitting the learning of knowledge and skills. Most learning involves repetitive experiences during which neurons undergo multiple stages of functional and structural plasticity. Currently, the diversity of transcriptional responses underlying dynamic plasticity during repetition-based learning is poorly understood.

Endoplasmic Reticulum Protein 72 Regulates Integrin Mac-1 Activity to Influence Neutrophil Recruitment.

Background: Integrins mediate the adhesion, crawling, and migration of neutrophils during vascular inflammation. Thiol exchange is important in the regulation of integrin functions. ERp72 (endoplasmic reticulum-resident protein 72) is a member of the thiol isomerase family responsible for the catalysis of disulfide rearrangement.

Clonal Hematopoiesis of Indeterminate Potential in Chronic Thromboembolic Pulmonary Hypertension: A Multicenter Study.

Background: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is multifactorial and growing evidence has indicated that hematological disorders are involved. Clonal hematopoiesis of indeterminate potential (CHIP) has recently been associated with an increased risk of both hematological malignancies and cardiovascular diseases. However, the prevalence and clinical relevance of CHIP in patients with CTEPH remains unclear.

Application of synthetic lipid droplets in metabolic diseases.

Background: The study and synthesis of membrane organelles are becoming increasingly important, not only as simplified cellular models for corresponding molecular and metabolic studies but also for applications in synthetic biology of artificial cells and drug delivery vehicles. Lipid droplets (LDs) are central organelles in cellular lipid metabolism and are involved in almost all metabolic processes. Multiple studies have also demonstrated a high correlation between LDs and metabolic diseases.

Potassium Magnesium Citrate Is Superior to Potassium Chloride in Reversing Metabolic Side Effects of Chlorthalidone.

Background: Thiazide diuretics (TD) are the first-line treatment of hypertension because of its consistent benefit in lowering blood pressure and cardiovascular risk. TD is also known to cause an excess risk of diabetes, which may limit long-term use. Although potassium (K) depletion was thought to be the main mechanism of TD-induced hyperglycemia, TD also triggers magnesium (Mg) depletion.

Organization and replicon interactions within the highly segmented genome of Borrelia burgdorferi.

Borrelia burgdorferi, a causative agent of Lyme disease, contains the most segmented bacterial genome known to date, with one linear chromosome and over twenty plasmids. How this unusually complex genome is organized, and whether and how the different replicons interact are unclear. We recently demonstrated that B.

MAGT1 Deficiency Dysregulates Platelet Cation Homeostasis and Accelerates Arterial Thrombosis and Ischemic Stroke in Mice.

Background: MAGT1 (magnesium transporter 1) is a subunit of the oligosaccharide protein complex with thiol-disulfide oxidoreductase activity, supporting the process of N-glycosylation. MAGT1 deficiency was detected in human patients with X-linked immunodeficiency with magnesium defect syndrome and congenital disorders of glycosylation, resulting in decreased cation responses in lymphocytes, thereby inhibiting the immune response against viral infections. Curative hematopoietic stem cell transplantation of patients with X-linked immunodeficiency with magnesium defect causes fatal bleeding and thrombotic complications.

Reduced Adenoma Miss Rate With 9-Minute vs 6-Minute Withdrawal Times for Screening Colonoscopy: A Multicenter Randomized Tandem Trial.

Introduction: Although the 9-minute mean withdrawal time (m-WT) is often reported to be associated with the optimal adenoma detection rate (ADR), no randomized trials of screening colonoscopy have confirmed the impact of a 9-minute m-WT on adenoma miss rate (AMR) and ADR.

Methods: A multicenter tandem trial was conducted in 11 centers. Seven hundred thirty-three asymptomatic participants were randomized to receive segmental tandem screening colonoscopy with a 9-minute withdrawal, followed by a 6-minute withdrawal (9-minute-first group, 9MF, n = 366) or vice versa (6-minute-first group, 6MF, n = 367).

In vivo non-invasive confocal fluorescence imaging beyond 1,700 nm using superconducting nanowire single-photon detectors.

Light scattering by biological tissues sets a limit to the penetration depth of high-resolution optical microscopy imaging of live mammals in vivo. An effective approach to reduce light scattering and increase imaging depth is to extend the excitation and emission wavelengths to the second near-infrared window (NIR-II) at >1,000 nm, also called the short-wavelength infrared window. Here we show biocompatible core-shell lead sulfide/cadmium sulfide quantum dots emitting at ~1,880 nm and superconducting nanowire single-photon detectors for single-photon detection up to 2,000 nm, enabling a one-photon excitation fluorescence imaging window in the 1,700-2,000 nm (NIR-IIc) range with 1,650 nm excitation-the longest one-photon excitation and emission for in vivo mouse imaging so far.

AAV-delivered suppressor tRNA overcomes a nonsense mutation in mice.

Gene therapy is a potentially curative medicine for many currently untreatable diseases, and recombinant adeno-associated virus (rAAV) is the most successful gene delivery vehicle for in vivo applications. However, rAAV-based gene therapy suffers from several limitations, such as constrained DNA cargo size and toxicities caused by non-physiological expression of a transgene. Here we show that rAAV delivery of a suppressor tRNA (rAAV.

Design of a mutation-integrated trimeric RBD with broad protection against SARS-CoV-2.

The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen.

Resolvin E1 Attenuates Pulmonary Hypertension by Suppressing Wnt7a/β-Catenin Signaling.

[Figure: see text].