Early Versus Delayed Antihypertensive Treatment After Acute Ischemic Stroke by Hypertension History.

Background: We performed a prespecified subgroup analysis of the CATIS-2 trial (China Antihypertensive Trial in Acute Ischemic Stroke II) to compare the effect of early versus delayed antihypertensive treatment on death and disability in patients with and without medical history of hypertension.

Methods: CATIS-2 is a multicenter randomized clinical trial conducted in 106 hospitals in China. The trial randomized 4810 patients with acute ischemic stroke within 24 to 48 hours of symptom onset and elevated systolic blood pressure between 140 and <220 mm Hg to receive antihypertensive treatment immediately after randomization or to discontinue antihypertensive medications for 7 days and then receive treatment on day 8.

SOX2-induced IL1α-mediated immune suppression drives epithelial dysplasia malignant transformation.

Squamous cell carcinomas (SCC) are often preceded by potentially malignant precursor lesions, most of which remain benign. The terminal exhaustion phenotypes of effector T-cells and the accumulation of myeloid-derived suppressor cells (MDSC) have been thoroughly characterized in established SCC. However, it is unclear what precancerous lesions harbor a bona fide high risk for malignant transformation and how precancerous epithelial dysplasia drives the immune system to the point of no return.

Scalable production of ultraflat and ultraflexible diamond membrane.

Diamond is an exceptional material with great potential across various fields owing to its interesting properties. However, despite extensive efforts over the past decades, producing large quantities of desired ultrathin diamond membranes for widespread use remains challenging. Here we demonstrate that edge-exposed exfoliation using sticky tape is a simple, scalable and reliable method for producing ultrathin and transferable polycrystalline diamond membranes.

Computational evaluation of interactive dynamics for a full transcatheter aortic valve device in a patient-specific aortic root.

Transcatheter aortic valve implantation (TAVI) has become a key treatment for severe aortic stenosis, especially for patients unsuitable for surgery. Since its introduction in 2002, TAVI has advanced significantly due to improvements in imaging, operator skills, and device engineering. Despite these innovations, challenges in device sizing and positioning remain, complicating outcome predictions.

Two versus three to four cycles of neoadjuvant immunochemotherapy for locally advanced esophageal squamous cell carcinoma in real-world practice.

Background: There is currently no consensus on whether intensive cycles of neoadjuvant immunochemotherapy provide greater benefit than do less intensive cycles (two cycles) in esophageal cancer (EC). Therefore, in this study, we assessed the efficacy and safety of three to four cycles of neoadjuvant immunochemotherapy compared to two cycles for treating patients with locally advanced esophageal squamous cell carcinoma (ESCC).

Methods: This is a retrospective study of patients enrolled on previous clinical studies involving locally/regionally advanced ESCC (St.

Deep generative design of RNA aptamers using structural predictions.

RNAs represent a class of programmable biomolecules capable of performing diverse biological functions. Recent studies have developed accurate RNA three-dimensional structure prediction methods, which may enable new RNAs to be designed in a structure-guided manner. Here, we develop a structure-to-sequence deep learning platform for the de novo generative design of RNA aptamers.

Patient-derived tumor-like cell clusters for personalized chemo- and immunotherapies in non-small cell lung cancer.

Many patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100-5,000 drug tests within 10 days.

Global cellular proteo-lipidomic profiling of diverse lysosomal storage disease mutants using nMOST.

Lysosomal storage diseases (LSDs) comprise ~50 monogenic disorders marked by the buildup of cellular material in lysosomes, yet systematic global molecular phenotyping of proteins and lipids is lacking. We present a nanoflow-based multi-omic single-shot technology (nMOST) workflow that quantifies HeLa cell proteomes and lipidomes from over two dozen LSD mutants. Global cross-correlation analysis between lipids and proteins identified autophagy defects, notably the accumulation of ferritinophagy substrates and receptors, especially in and mutants, where lysosomes accumulate cholesterol.

Hu8F4-CAR T cells with mutated Fc spacer segment improve target-specificity and mediate anti-leukemia activity .

Hu8F4 is a T cell receptor (TCR)-like antibody with high affinity for leukemia-associated antigen PR1/HLA-A2 epitope. Adapted into a chimeric antigen receptor (CAR) format, Hu8F4-CAR is comprised of the Hu8F4 scFv, the human IgG1 CH2CH3 extracellular spacer domain, a human CD28 costimulatory domain, and the human CD3ζ signaling domain. We have demonstrated high efficacy of Hu8F4-CAR-T cells against PR1/HLA-A2-expressing cell lines and leukemic blasts from AML patients .

The association of long-term trajectories of BMI, its variability, and metabolic syndrome: a 30-year prospective cohort study.

Background: Limited data exists on how early-life weight changes relate to metabolic syndrome (MetS) risk in midlife. This study examines the association between long-term trajectories of body mass index (BMI), its variability, and MetS risk in Chinese individuals.

Methods: In the Hanzhong Adolescent Hypertension study (March 10, 1987-June 3, 2017), 1824 participants with at least five BMI measurements from 1987 to 2017 were included.

Multicenter Evaluation of a Weakly Supervised Deep Learning Model for Lymph Node Diagnosis in Rectal Cancer at MRI.

Purpose To develop a Weakly supervISed model DevelOpment fraMework (WISDOM) model to construct a lymph node (LN) diagnosis model for patients with rectal cancer (RC) that uses preoperative MRI data coupled with postoperative patient-level pathologic information. Materials and Methods In this retrospective study, the WISDOM model was built using MRI (T2-weighted and diffusion-weighted imaging) and patient-level pathologic information (the number of postoperatively confirmed metastatic LNs and resected LNs) based on the data of patients with RC between January 2016 and November 2017. The incremental value of the model in assisting radiologists was investigated.

PI3Kγ maintains the self-renewal of acute myeloid leukemia stem cells by regulating the pentose phosphate pathway.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy originating from transformed hematopoietic stem or progenitor cells. AML prognosis remains poor owing to resistance and relapse driven by leukemia stem cells (LSCs). Targeting molecules essential for LSC function is a promising therapeutic approach.

CD147 Sparks Atherosclerosis by Driving M1 Phenotype and Impairing Efferocytosis.

Background: Atherosclerosis is a globally prevalent chronic inflammatory disease with high morbidity and mortality. The development of atherosclerotic lesions is determined by macrophages. This study aimed to investigate the specific role of myeloid-derived CD147 (cluster of differentiation 147) in atherosclerosis and its translational significance.

Clinical Outcomes of Deferred Lesions by IVUS Versus FFR-Guided Treatment Decision.

Background: There are limited data regarding the safety of deferral of percutaneous coronary intervention based on intravascular ultrasound (IVUS) findings. The current study sought to compare the prognosis between deferred lesions based on IVUS and fractional flow reserve (FFR)-guided treatment decision.

Methods: This study is a post hoc analysis of the FLAVOUR randomized trial (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients With Intermediate Stenosis) that compared 2-year clinical outcomes between IVUS- and FFR-guided treatment decision on intermediate coronary artery lesions using predefined criteria.

Human Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ASC42, a Novel Farnesoid X Receptor Agonist.

Background: ASC42 is a non-steroidal farnesoid X receptor agonist currently in clinical development for chronic liver diseases, such as nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) and primary biliary cirrhosis (PBC).

Objective: The objective of this study was to assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ASC42 in healthy subjects.

Methods: We conducted the first-in-human study of ASC42 following single and multiple ascending doses (SAD/MAD) and food effect in healthy subjects.

Transcriptomic analysis of the ocular posterior segment completes a cell atlas of the human eye.

Although the visual system extends through the brain, most vision loss originates from defects in the eye. Its central element is the neural retina, which senses light, processes visual signals, and transmits them to the rest of the brain through the optic nerve (ON). Surrounding the retina are numerous other structures, conventionally divided into anterior and posterior segments.

Fractalkine Enhances Hematoma Resolution and Improves Neurological Function via CX3CR1/AMPK/PPARγ Pathway After GMH.

Background: Hematoma clearance has been a proposed therapeutic strategy for hemorrhagic stroke. This study investigated the impact of CX3CR1 (CX3C chemokine receptor 1) activation mediated by r-FKN (recombinant fractalkine) on hematoma resolution, neuroinflammation, and the underlying mechanisms involving AMPK (AMP-activated protein kinase)/PPARγ (peroxisome proliferator-activated receptor gamma) pathway after experimental germinal matrix hemorrhage (GMH).

Methods: A total of 313 postnatal day 7 Sprague Dawley rat pups were used.

Deep Learning-Based Fully Automated Segmentation of Regional Muscle Volume and Spatial Intermuscular Fat Using CT.

Rationale And Objectives: We aim to develop a CT-based deep learning (DL) system for fully automatic segmentation of regional muscle volume and measurement of the spatial intermuscular fat distribution of the gluteus maximus muscle.

Materials And Methods: A total of 472 subjects were enrolled and randomly assigned to one of three groups: a training set, test set 1, and test set 2. For each subject in the training set and test set 1, we selected six slices of the CT images as the region of interest for manual segmentation by a radiologist.

Improved Structural Characterization of Glycerophospholipids and Sphingomyelins with Real-Time Library Searching.

In mass spectrometry-based lipidomics, complex lipid mixtures undergo chromatographic separation, are ionized, and are detected using tandem MS (MS) to simultaneously quantify and structurally characterize eluting species. The reported structural granularity of these identified lipids is strongly reliant on the analytical techniques leveraged in a study. For example, lipid identifications from traditional collisionally activated data-dependent acquisition experiments are often reported at either species level or molecular species level.

Super Enhancer-Associated Circular RNA-CircKrt4 Regulates Hypoxic Pulmonary Artery Endothelial Cell Dysfunction in Mice.

Background: Circular RNAs (circRNAs) have been implicated in pulmonary hypertension progression through largely unknown mechanisms. Pulmonary artery endothelial cell (PAEC) dysfunction is a hallmark in the pathogenesis of pulmonary hypertension. However, the specific role of circular RNAs in PAEC injury caused by hypoxia remains unclear.

Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct.

Background: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations.

Methods: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone.

Morphological and molecular evidence gives insight into the taxonomic position of (Apiaceae, Selineae).

In this study, morphological and molecular evidences were combined to determine the taxonomic position of Hand.-Mazz. Morphologically, is similar to the species of the genus in having fibrous remnant sheaths at the stem base, pinnate and linear coexisted bracts, strongly compressed dorsally mericarps, filiform median and lateral ribs, winged marginal ribs, numerous vittae in each furrow and commissure, but can also be easily distinguished from members of by its hispid fruit and linear-lanceolate bracteoles.