Safety and Efficacy of Remote Ischemic Conditioning in Patients With Intravenous Thrombolysis: The SERIC-IVT Trial.

Background: Approximately half of the patients with acute ischemic stroke who receive intravenous thrombolysis (IVT) do not achieve an excellent outcome. Remote ischemic conditioning (RIC) as a promising neuroprotective treatment may improve clinical outcomes in this population. This study aimed to assess the efficacy and safety of RIC in patients with IVT.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

High-performance supercapacitors based on coarse nanofiber bundle and ordered network hydrogels.

Most of the developed flexible hydrogel supercapacitors struggle to maintain their electrochemical stability and structural integrity under tensile strain. Therefore, developing a flexible supercapacitor with excellent mechanical properties and stable electrochemical performance under different strains remains a challenge. Based on the previous cartilage-like structure, we designed a new coarse nanofiber bundle and ordered network.

Referral Networks, Racial Inequity, and Hospital Quality for Open Heart Surgery.

Background: Differences in the quality of hospitals where Black and White patients receive coronary artery bypass grafting (CABG) surgery have been documented. We examined the contributions of physician networks to the gap.

Methods: This was a cross-sectional study of all Medicare fee-for-service Black and White patients undergoing elective CABG during 2017 to 2019; the primary care physicians and cardiologists treating them for 12 months before surgery (the patients' physician network); and CABG-performing hospitals within 100 miles of each patient.

Cell therapy with human IL-10-producing ILC2s limits xenogeneic graft-versus-host disease by inhibiting pathogenic T cell responses.

Interleukin-10 (IL-10)-producing group 2 innate lymphoid cells (ILC2) regulate inflammatory immune responses, yet their therapeutic potential remains largely unexplored. Here, we demonstrate that cell therapy with human ILC2 inhibits pathogenic T cell responses in humanized mouse models of graft-versus-host disease (GVHD), resulting in reduced GVHD severity and improved overall survival without limiting the graft-versus-leukemia effect. ILC2 conferred superior protection from GVHD than IL-10 ILC2s, and blocking IL-10 and IL-4 abrogated ILC2 protective effects, indicating that these cytokines are important for the protective effects of ILC2.

A Wet-Adhesion and Swelling-Resistant Hydrogel for Fast Hemostasis, Accelerated Tissue Injury Healing and Bioelectronics.

Hydrogel bioadhesives with adequate wet adhesion and swelling resistance are urgently needed in clinic. However, the presence of blood or body fluid usually weakens the interfacial bonding strength, and even leads to adhesion failure. Herein, profiting from the unique coupling structure of carboxylic and phenyl groups in one component (N-acryloyl phenylalanine) for interfacial drainage and matrix toughening as well as various electrostatic interactions mediated by zwitterions, a novel hydrogel adhesive (PAAS) is developed with superior tissue adhesion properties and matrix swelling resistance in challenging wet conditions (adhesion strength of 85 kPa, interfacial toughness of 450 J m, burst pressure of 514 mmHg, and swelling ratio of <4%).

Tough Polyurethane Hydrogels with a Multiple Hydrogen-Bond Interlocked Bicontinuous Phase Structure Prepared by In Situ Water-Induced Microphase Separation.

Hydrogels with mechanical performances similar to load-bearing tissues are in demand for in vivo applications. In this work, inspired by the self-assembly behavior of amphiphilic polymers, polyurethane-based tough hydrogels with a multiple hydrogen-bond interlocked bicontinuous phase structure through in situ water-induced microphase separation strategy are developed, in which poly(ethylene glycol)-based polyurethane (PEG-PU, hydrophilic) and poly(ε-caprolactone)-based polyurethane (PCL-PU, hydrophobic) are blended to form dry films followed by water swelling. A multiple hydrogen bonding factor, imidazolidinyl urea, is introduced into the synthesis of the two polyurethanes, and the formation of multiple hydrogen bonds between PEG-PU and PCL-PU can promote homogeneous microphase separation for the construction of bicontinuous phase structures in the hydrogel network, by which the hydrogel features break strength of 12.

Tough and Functional Hydrogel Coating by Electrostatic Spraying.

Hydrogel coatings impart superior surface properties to materials, but their application on large and complicated substrates is hindered by two challenges: limited wetting conditions and intricate curing processes. To overcome the challenges, lyophilized adhesive hydrogel powders (LAHPs) are developed, which consist of poly(acrylic acid-co-3-(trimethoxysilyl)propyl methacrylate) crosslinked with chitosan. These powders are electrostatic sprayed onto substrates to address wetting issues and rehydrated to form bulk hydrogel coatings to circumvent curing challenges.

Activation of Imprinted Gene Promotes Cardiac Fibrosis After Ischemic Injury.

Background: Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition in the myocardium, is an important target for heart disease treatments. (paternally expressed gene 3) is an imprinted gene expressed from the paternal allele, and de novo purine biosynthesis (DNPB) is a crucial pathway for nucleotide synthesis. However, the roles of PW1 and DNPB in ECM production by cardiac fibroblasts during myocardial ischemia are not yet understood.

Diagnostic Efficacy of Ventilation-Perfusion Single Photo Emission Computed Tomography/Computed Tomography for Pulmonary Hypertension due to Fibrinous Mediastinitis.

Rationale And Objectives: Comprehensive data on the use of ventilation-perfusion single-photo emission computed tomography/computed tomography (V/Q SPECT/CT), an established diagnostic tool for chronic thromboembolic pulmonary hypertension, in identifying pulmonary hypertension secondary to fibrinous mediastinitis (PH-FM) is scarce. This study aimed to assess its diagnostic efficacy for PH-FM.

Materials And Methods: Patients with PH due to pulmonary artery stenosis were assessed using V/Q SPECT/CT, computed tomography pulmonary angiography (CTPA), and digital subtraction pulmonary angiography (PAG).

Hendersines J-M: Isoquinoline alkaloids from Corydalis hendersonii Hemsl. with cardiomyocyte protective and NO production inhibitory effects.

Six isoquinoline alkaloids were identified from the alkaloid-rich fraction of Corydalis hendersonii Hemsl, including five previously undescribed isoquinoline alkaloids hendersines J-M (1a, 1b, and 2-4) and isobicuculline (5), a compound reported for the first time from a natural source. Their structures were elucidated based on spectroscopic analysis of HR-ESI-MS, 1D and 2D NMR, X-ray diffraction, and ECD. Compounds 1a and 1b represent a pair of rare three-nitrogen isoquinoline alkaloid enantiomers, while 2 and 3 are isoquinoline alkaloids featuring a benzo-fused N-heterocycle.

Follistatin From hiPSC-Cardiomyocytes Promotes Myocyte Proliferation in Pigs With Postinfarction LV Remodeling.

Background: When human induced pluripotent stem cells (hiPSCs) that CCND2-OE (overexpressed cyclin-D2) were differentiated into cardiomyocytes (hiPSC-CMs) and administered to the infarcted hearts of immunodeficient mice, the cells proliferated after administration and repopulated >50% of the scar. Here, we knocked out human leukocyte antigen class I and class II expression in hiPSC-CMs (hiPSC-CMs) to reduce the cells' immunogenicity and then assessed the therapeutic efficacy of hiPSC-CMs for the treatment of myocardial infarction.

Methods: hiPSC-CM and wild-type hiPSC-CM (hiPSC-CM) spheroids were differentiated in shaking flasks, purified, characterized, and intramyocardially injected into pigs after ischemia/reperfusion injury; control animals were injected with basal medium.

METTL4-Mediated Mitochondrial DNA N6-Methyldeoxyadenosine Promoting Macrophage Inflammation and Atherosclerosis.

Background: Mitochondrial dysfunction is a key factor in the development of atherogenesis. METTL4 (methyltransferase-like protein 4) mediates N6- methyldeoxyadenosine (6mA) of mammalian mitochondrial DNA (mtDNA). However, the role of METTL4-mediated mitoepigenetic regulation in atherosclerosis is still unknown.

Lack of dominant-negative activity for tumor-related ZNRF3 missense mutations at endogenous levels.

ZNRF3, a negative regulator of β-catenin signaling, removes Wnt receptors from the membrane. Currently, it is unknown which tumor-associated variants can be considered driver mutations and through which mechanisms they contribute to cancer. Here we show that all truncating mutations analyzed at endogenous levels exhibit loss-of-function, with longer variants retaining partial activity.

Haematological setpoints are a stable and patient-specific deep phenotype.

The complete blood count (CBC) is an important screening tool for healthy adults and a common test at periodic exams. However, results are usually interpreted relative to one-size-fits-all reference intervals, undermining the precision medicine goal to tailor care for patients on the basis of their unique characteristics. Here we study thousands of diverse patients at an academic medical centre and show that routine CBC indices fluctuate around stable values or setpoints, and setpoints are patient-specific, with the typical healthy adult's nine CBC setpoints distinguishable as a group from those of 98% of other healthy adults, and setpoint differences persist for at least 20 years.

Developing high-performance and sustainable polylactic acid/recycled polyolefin blends: Tuning the degree of functional group reaction and performance optimization.

In the current development of the plastics industry, the use of biodegradable and recycled plastics not only effectively reduces the volume of landfills and incineration but also significantly decreases environmental damage. However, the extensive application of biodegradable polylactic acid (PLA) is limited by its poor toughness and thermal properties. The study introduced recycled linear low-density polyethylene (R-LLDPE) and ethylene-octene copolymer (POE) to modify PLA, primarily based on their excellent toughness and thermal resistance.

Development of tough and stiff elastomers by leveraging hydrophilic-hydrophobic supramolecular segment interaction.

The presence of supramolecular interactions plays a crucial role in the formation of resilient multifunctional elastomers. Nevertheless, achieving elastomers with fabulous mechanical properties remains a significant challenge due to the incomplete understanding of the underlying principles. In this study, we have presented a simple yet efficient approach for manipulating the microstructure, resulting in a significant enhancement of the mechanical properties of the elastomers.

Orthostatic and Standing Hypertension and Risk of Cardiovascular Disease.

Background: Orthostatic hypertension is an emerging risk factor for adverse events. Recent consensus statements combine an increase in blood pressure upon standing with standing hypertension, but whether these 2 components have similar risk associations with cardiovascular disease (CVD) is unknown.

Methods: The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing blood pressure during visit 1 (1987-1989).

Self-Reinforcing Ionogel Bioadhesive Interface for Robust Integration and Monitoring of Bioelectronic Devices with Hard Tissues.

Integrating bioelectronic devices with hard tissues, such as bones and teeth, is essential for advancing diagnostic and therapeutic technologies. However, stable and durable adhesion in dynamic, moist environments remains challenging. Traditional bioadhesives often fail to maintain strong bonds, especially when interfacing with metal electrodes and hard tissues.

Tracking the gene expression programs and clonal relationships that underlie mast, myeloid, and T lineage specification from stem cells.

T cells develop from hematopoietic progenitors in the thymus and protect against pathogens and cancer. However, the emergence of human T cell-competent blood progenitors and their subsequent specification to the T lineage have been challenging to capture in real time. Here, we leveraged a pluripotent stem cell differentiation system to understand the transcriptional dynamics and cell fate restriction events that underlie this critical developmental process.

Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia.

Background: Obecabtagene autoleucel (obe-cel) is an autologous 41BB-ζ anti-CD19 chimeric antigen receptor (CAR) T-cell therapy which uses an intermediate-affinity CAR to reduce toxic effects and improve persistence.

Methods: We conducted a phase 1b-2 multicenter study of obe-cel in adults (≥18 years of age) with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). The main cohort, cohort 2A, included patients with morphologic disease; patients in cohort 2B had measurable residual disease.

Structural-Functional Integrated Graphene-Skinned Aramid Fibers for Electromagnetic Interference Shielding.

Structural-functional integrated polymer fibers with exciting properties are increasingly important for next-generation technologies. Herein, we report the structural-functional integrated graphene-skinned aramid fiber (GRAF) featuring high conductivity, high strength, and light weight, which is weaved for efficient electromagnetic interference (EMI) shielding. Graphene was self-assembled onto the surface of aramid fibers through a dip-coating strategy using an aramid polyanion (APA) as the binder and the etchant.

Weaning of non COPD patients at high-risk of extubation failure assessed by lung ultrasound: the WIN IN WEAN multicentre randomised controlled trial.

Background: Postextubation respiratory failure (PRF) frequently complicates weaning from mechanical ventilation and may increase morbidity/mortality. Noninvasive ventilation (NIV) alternating with high-flow nasal oxygen (HFNO) may prevent PRF.

Methods: Ventilated patients without chronic obstructive pulmonary disease (COPD) and at high-risk of PRF defined as a lung ultrasound score (LUS) ≥ 14 assessed during the spontaneous breathing trial, were included in a French-Chinese randomised controlled trial.