ROS scavenging and corneal epithelial wound healing by a self-crosslinked tissue-adhesive hydrogel based-on dual-functionalized hyaluronic acid.

Reactive oxygen species (ROS) scavenging is a viable approach to promote corneal epithelium wound healing. This study created a single-component hydrogel (HA Gel) with a novel dual-functionalized hyaluronic acid derivative (HA-GA-PBA) containing gallol and phenylboronic acid (PBA) moieties. Both of these moieties were dual-functional.

Association Between Time to Treatment and Outcomes of Endovascular Therapy vs Medical Management in Patients With Large Ischemic Stroke.

Background And Objectives: Randomized trials have proven the benefit of endovascular therapy (EVT) for acute large ischemic stroke. This study was to characterize the effect of time to treatment on benefit of EVT vs medical management (MM) among patients with large ischemic stroke.

Methods: This was a post hoc analysis of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core randomized trial.

Decision Fusion Model for Predicting Microvascular Invasion in Hepatocellular Carcinoma Based on Multi-MR Habitat Imaging and Machine-Learning Classifiers.

Rationale And Objectives: Accurate prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is crucial for guiding treatment. This study evaluates and compares the performance of clinicoradiologic, traditional radiomics, deep-learning radiomics, feature fusion, and decision fusion models based on multi-region MR habitat imaging using six machine-learning classifiers.

Materials And Methods: We retrospectively included 300 HCC patients.

Assessing the Performance of Models from the 2022 RSNA Cervical Spine Fracture Detection Competition at a Level I Trauma Center.

Purpose To evaluate the performance of the top models from the RSNA 2022 Cervical Spine Fracture Detection challenge on a clinical test dataset of both noncontrast and contrast-enhanced CT scans acquired at a level I trauma center. Materials and Methods Seven top-performing models in the RSNA 2022 Cervical Spine Fracture Detection challenge were retrospectively evaluated on a clinical test set of 1828 CT scans (from 1829 series: 130 positive for fracture, 1699 negative for fracture; 1308 noncontrast, 521 contrast enhanced) from 1779 patients (mean age, 55.8 years ± 22.

Global burden of adult non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) has been steadily increasing over the past decades and is expected to persist in the future.

Background: At present, there is a dearth of comprehensive data at the global, national, and regional levels regarding the adult non-alcoholic fatty liver disease (NAFLD) prevalence. This cross-sectional study aims at ascertaining the prevalence of NAFLD and non-alcoholic steatohepatitis (NASH), utilizing body mass index (BMI) as a determining factor.

Methods: Based on the NHANES database, sigmoidal fitting curves were generated to establish the relationship between BMI and the risk of NAFLD/NASH.

Novel Metabolites Associated With Blood Pressure After Dietary Interventions.

Background: The blood pressure (BP) etiologic study is complex due to multifactorial influences, including genetic, environmental, lifestyle, and their intricate interplays. We used a metabolomics approach to capture internal pathways and external exposures and to study BP regulation mechanisms after well-controlled dietary interventions.

Methods: In the ProBP trail (Protein and Blood Pressure), a double-blinded crossover randomized controlled trial, participants underwent dietary interventions of carbohydrate, soy protein, and milk protein, receiving 40 g daily for 8 weeks, with 3-week washout periods.

Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors.

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841).

Blocking cGAS-STING pathway promotes post-stroke functional recovery in an extended treatment window via facilitating remyelination.

Background: Ischemic stroke is a major cause of worldwide death and disability, with recombinant tissue plasminogen activator being the sole effective treatment, albeit with a limited treatment window. The cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) pathway is emerging as the major DNA-sensing pathway to invoke immune responses in neuroinflammatory disorders.

Methods: By performing a series of neurobehavioral assessments, electrophysiological analysis, high-throughput sequencing, and cell-based assays based on the transient middle cerebral artery occlusion (tMCAO) mouse stroke model, we examined the effects and underlying mechanisms of genetic and pharmacological inhibition of the cGAS-STING pathway on long-term post-stroke neurological functional outcomes.

Pharmacokinetics and pharmacodynamics of mibavademab (a leptin receptor agonist): Results from a first-in-human phase I study.

Mibavademab (previously known as REGN4461), a fully human monoclonal antibody, is being investigated for the treatment of conditions associated with leptin deficiency. Here, we report pharmacokinetics (PKs), pharmacodynamics, and immunogenicity from a phase I study in healthy participants (NCT03530514). In part A, lean or overweight healthy participants were randomized to single-ascending-dose cohorts of 0.

Multi-needle blow-spinning technique for fabricating collagen nanofibrous nerve guidance conduit with scalable productivity and high performance.

Nerve guidance conduits (NGCs) have been widely accepted as a promising strategy for peripheral nerve regeneration. Fabricating ideal NGCs with good biocompatibility, biodegradability, permeability, appropriate mechanical properties (space maintenance, suturing performance, etc.), and oriented topographic cues is still current research focus.

Comparative Analysis of Molecular Landscape in Mouse Models and Patients Reveals Conserved Inflammation Pathways in Age-Related Macular Degeneration.

Purpose: The purpose of this study was to identify key genes and their regulatory networks that are conserved in mouse models of age-related macular degeneration (AMD) and human AMD.

Methods: Retinal RNA-Seq was performed in laser-induced choroidal neovascularization (CNV) mice at day 3 and day 7 after photocoagulation. Mass spectrometry-based proteomic analysis was performed with retinas collected at day 3.

Structural characterization of tin in toothpaste by dynamic nuclear polarization enhanced Sn solid-state NMR spectroscopy.

Stannous fluoride (SnF) is an effective fluoride source and antimicrobial agent that is widely used in commercial toothpaste formulations. The antimicrobial activity of SnF is partly attributed to the presence of Sn(II) ions. However, it is challenging to directly determine the Sn speciation and oxidation state within commercially available toothpaste products due to the low weight loading of SnF (0.

Genomic Innovation in Early Life Cardiovascular Disease Prevention and Treatment.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally. Although CVD events do not typically manifest until older adulthood, CVD develops gradually across the life-course, beginning with the elevation of risk factors observed as early as childhood or adolescence and the emergence of subclinical disease that can occur in young adulthood or midlife. Genomic background, which is determined at zygote formation, is among the earliest risk factors for CVD.

Design of Orally-bioavailable Tetra-cyclic phthalazine SOS1 inhibitors with high selectivity against EGFR.

KRAS mutations (G12C, G12D, etc.) are implicated in the oncogenesis and progression of many deadliest cancers. Son of sevenless homolog 1 (SOS1) is a crucial regulator of KRAS to modulate KRAS from inactive to active states.

Towards precision medicine based on a continuous deep learning optimization and ensemble approach.

We developed a continuous learning system (CLS) based on deep learning and optimization and ensemble approach, and conducted a retrospective data simulated prospective study using ultrasound images of breast masses for precise diagnoses. We extracted 629 breast masses and 2235 images from 561 cases in the institution to train the model in six stages to diagnose benign and malignant tumors, pathological types, and diseases. We randomly selected 180 out of 3098 cases from two external institutions.

Targeted Expression of Retinoschisin by Retinal Bipolar Cells in XLRS Promotes Resolution of Retinoschisis Cysts Sans RS1 From Photoreceptors.

Purpose: Loss of retinoschisin (RS1) function underlies X-linked retinoschisis (XLRS) pathology. In the retina, both photoreceptor inner segments and bipolar cells express RS1. However, the loss of RS1 function causes schisis primarily in the inner retina.

Insights From a Large-Scale Whole-Genome Sequencing Study of Systolic Blood Pressure, Diastolic Blood Pressure, and Hypertension.

Background: The availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure.

Methods: We conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants.

Analysis of microbial community structure and volatile compounds in pit mud used for manufacturing Taorong-type Baijiu based on high-throughput sequencing.

In this study, the pit mud used in manufacturing Taorong-type Baijiu was collected from the upper, middle, lower and bottom layers of pits at Henan Yangshao Liquor Co., LTD. High-throughput sequencing (HTS) technology was used to analyze the microbial community structure of the pit mud.

Optogenetics for light control of biological systems.

Optogenetic techniques have been developed to allow control over the activity of selected cells within a highly heterogeneous tissue, using a combination of genetic engineering and light. Optogenetics employs natural and engineered photoreceptors, mostly of microbial origin, to be genetically introduced into the cells of interest. As a result, cells that are naturally light-insensitive can be made photosensitive and addressable by illumination and precisely controllable in time and space.

Pancreatic cancer cells render tumor-associated macrophages metabolically reprogrammed by a GARP and DNA methylation-mediated mechanism.

How tumor-associated macrophages transit from a predominant antitumor M1-like phenotype to a protumoral M2-like phenotype during the development of pancreatic ductal adenocarcinoma (PDA) remains to be elucidated. We thus conducted a study by employing a PDA-macrophage co-culture system, an "orthotopic" PDA syngeneic mouse model, and human PDA specimens, together with macrophages derived from GARP knockout mice and multiple analytic tools including whole-genome RNA sequencing, DNA methylation arrays, multiplex immunohistochemistry, metabolism measurement, and invasion/metastasis assessment. Our study showed that PDA tumor cells, through direct cell-cell contact, induce DNA methylation and downregulation of a panel of glucose metabolism and OXPHOS genes selectively in M1-like macrophages, leading to a suppressed glucose metabolic status in M1-like but not in M2-like macrophages.

RBD-homodimer, a COVID-19 subunit vaccine candidate, elicits immunogenicity and protection in rodents and nonhuman primates.

The pandemic of COVID-19 caused by SARS-CoV-2 has raised a new challenges to the scientific and industrious fields after over 1-year spread across different countries. The ultimate approach to end the pandemic is the timely application of vaccines to achieve herd immunity. Here, a novel SARS-CoV-2 receptor-binding domain (RBD) homodimer was developed as a SARS-CoV-2 vaccine candidate.

Development of a Sensitive Diagnostic Assay for Parkinson Disease Quantifying α-Synuclein-Containing Extracellular Vesicles.

Objective: To develop a reliable and fast assay to quantify the α-synuclein (α-syn)-containing extracellular vesicles (EVs) in CSF and to assess their diagnostic potential for Parkinson disease (PD).

Methods: A cross-sectional, multicenter study was designed, including 170 patients with PD and 131 healthy controls (HCs) with a similar distribution of age and sex recruited from existing center studies at the University of Washington and Oregon Health and Science University. CSF EVs carrying α-syn or aggregated α-syn were quantified using antibodies against total or aggregated α-syn, respectively, and highly specific, sensitive, and rapid assays based on the novel Apogee nanoscale flow cytometry technology.

Association Between the Types of Posterior Staphyloma and Their Risk Factors in Pathological Myopia.

Purpose: The purpose of this study was to investigate the relationship of posterior staphyloma (PS) types in pathological myopia (PM) with age, best-corrected visual acuity (BCVA), spherical equivalent (SE), axial length (AL), and myopic retinoschisis (MRS) using three-dimensional magnetic resonance imaging (3D-MRI) and optical coherence tomography (OCT).

Methods: This retrospective, cross-sectional study included 108 eyes of 59 patients with PM from the Henan Eye Institute, China. We classified the PS types based on current international classification criteria and analyzed the risk factors (age, AL, MRS, and BCVA).