Multi-omics profiling of retinal pigment epithelium reveals enhancer-driven activation of RANK-NFATc1 signaling in traumatic proliferative vitreoretinopathy.

During the progression of proliferative vitreoretinopathy (PVR) following ocular trauma, previously quiescent retinal pigment epithelial (RPE) cells transition into a state of rapid proliferation, migration, and secretion. The elusive molecular mechanisms behind these changes have hindered the development of effective pharmacological treatments, presenting a pressing clinical challenge. In this study, by monitoring the dynamic changes in chromatin accessibility and various histone modifications, we chart the comprehensive epigenetic landscape of RPE cells in male mice subjected to traumatic PVR.

Unexpected response of terrestrial carbon sink to rural depopulation in China.

China is experiencing large-scale rural-urban migration and rapid urbanization, which have had significant impact on terrestrial carbon sink. However, the impact of rural-urban migration and its accompanying urban expansion on the carbon sink is unclear. Based on multisource remote sensing product data for 2000-2020, the soil microbial respiration equation, relative contribution rate, and threshold analysis, we explored the impact of rural depopulation on the carbon sink and its threshold.

Evaluation of mavacamten in patients with hypertrophic cardiomyopathy.

Aims: We aimed to comprehensively assess the safety and efficacy of mavacamten in hypertrophic cardiomyopathy (HCM) patients.

Methods: A systematic review and meta-analysis was conducted, and efficacy [changes in postexercise left ventricular outflow tract (LVOT) gradient, left ventricular ejection fraction (LVEF), peak oxygen consumption (pVO 2 ), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS), and the proportion of patients exhibiting an improvement of at least one New York Heart Association (NYHA) functional class from baseline)], safety (total count of treatment-emergent adverse events and SAEs, as well as the proportion of patients experiencing at least one adverse event or SAE), and cardiac biomarkers (NT-proBNP and cTnI) outcomes were evaluated.

Results: We incorporated data from four randomized controlled trials, namely EXPLORER-HCM, VALOR-HCM, MAVERICK-HCM, and EXPLORER-CN.

First Observation of a Three-Resonance Structure in e^{+}e^{-}→Nonopen Charm Hadrons.

We report the measurement of the inclusive cross sections for e^{+}e^{-}→nOCH (where nOCH denotes non-open charm hadrons) with improved precision at center-of-mass (c.m.) energies from 3.

Dynamics of carbon and water vapor fluxes in three typical ecosystems of Heihe River Basin, Northwestern China.

Understanding the dynamics of carbon and water vapor fluxes in arid inland river basin ecosystems is essential for predicting and assessing the regional carbon-water budget amid climate change. However, studies aiming to unravel the mechanisms driving the variations and coupling process of regional carbon-water budget in a changing environment in arid regions are limited. Here, we used the eddy covariance technique to analyze the relationship between CO and HO fluxes in three typical ecosystems across the upper, middle, and lower reaches of an arid inland river basin in Northwestern China.

Identification of Potential Crucial Biomarkers in STEMI Through Integrated Bioinformatic Analysis.

Background: ST-segment elevation myocardial infarction (STEMI) is one of the leading causes of fatal cardiovascular diseases, which have been the prime cause of mortality worldwide. Diagnosis in the early phase would benefit clinical intervention and prognosis, but the exploration of the biomarkers of STEMI is still lacking.

Objectives: In this study, we conducted a bioinformatics analysis to identify potential crucial biomarkers in the progress of STEMI.

Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs.

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.

A novel rapamycin cream formulation improves facial angiofibromas associated with tuberous sclerosis complex: a double-blind randomized placebo-controlled trial.

Background: Facial angiofibromas (FAs) are a major feature of tuberous sclerosis complex (TSC). Topical rapamycin can successfully treat FAs. A new stabilized cream formulation that protects rapamycin from oxidation has been developed in 0.

Strategic self-limiting production of infectious HIV particles by CRISPR in permissive cells.

Post-translational glycosylation of the HIV-1 envelope protein involving precursor glycan trimming by mannosyl oligosaccharide glucosidase (MOGS) is critically important for morphogenesis of virions and viral entry. Strategic editing of the MOGS gene in T lymphocytes and myeloid origin cells harboring latent proviral DNA results in the production of non-infectious particles upon treatment of cells with latency reversal agents. Controlled activation of CRISPR-MOGS by rebound HIV-1 mitigates production of infectious particles that exhibit poor ability of the virus to penetrate uninfected cells.

Immunotherapeutic potential of blinatumomab-secreting γ9δ2 T Cells.

Previous studies have explored the use of engineered blinatumomab-secreting autologous αβ T cells for CD19-targeted cancer therapy. To create a more flexible allogeneic delivery system, we utilized γ9δ2 T cells rather than αβ T cells in a similar application. First, we showed that γ9δ2 T cells could serve as effector cells for blinatumomab, and these effector memory cells could survive for at least 7 days after infusion.

Abnormal Conduction Zone Detected by Isochronal Late Activation Mapping Accurately Identifies the Potential Atrial Substrate and Predicts the Atrial Fibrillation Ablation Outcome After Pulmonary Vein Isolation.

Background: The presence of abnormal substrate of left atrium is a predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation. We aimed to investigate the isochronal late activation mapping to access the abnormal conduction velocity for predicting AF ablation outcome.

Methods: Forty-five paroxysmal AF patients (30 males, 57.

Peptide Vaccine Against ADAMTS-7 Ameliorates Atherosclerosis and Postinjury Neointima Hyperplasia.

Background: The metalloprotease ADAMTS-7 (a disintegrin and metalloproteinase with thrombospondin type 1 motif 7) is a novel locus associated with human coronary atherosclerosis. ADAMTS-7 deletion protects against atherosclerosis and vascular restenosis in rodents.

Methods: We designed 3 potential vaccines consisting of distinct B cell epitopic peptides derived from ADAMTS-7 and conjugated with the carrier protein KLH (keyhole limpet hemocyanin) as well as aluminum hydroxide as an adjuvant.

A GIS-based method for modeling methane emissions from paddy fields by fusing multiple sources of data.

Quantification of regional methane (CH) gas emission in the paddy fields is critical under climate warming. Mechanism models generally require numerous parameters while empirical models are too coarse. Based on the mechanism and structure of the widely used model CH4MOD, a GIS-based Regional CH Emission Calculation (GRMC) method was put forward by introducing multiple sources of remote sensing images, including MOD09A1, MOD11A2, MOD15A2H as well as local water management standards.

Deep Underground Laboratory Measurement of ^{13}C(α,n)^{16}O in the Gamow Windows of the s and i Processes.

The ^{13}C(α,n)^{16}O reaction is the main neutron source for the slow-neutron-capture process in asymptotic giant branch stars and for the intermediate process. Direct measurements at astrophysical energies in above-ground laboratories are hindered by the extremely small cross sections and vast cosmic-ray-induced background. We performed the first consistent direct measurement in the range of E_{c.

Seasonal and Inter-Annual Variations of Carbon Dioxide Fluxes and Their Determinants in an Alpine Meadow.

The alpine meadow is one of the most important ecosystems on the Qinghai-Tibet Plateau (QTP) due to its huge carbon storage and wide distribution. Evaluating the carbon fluxes in alpine meadow ecosystems is crucial to understand the dynamics of carbon storage in high-altitude areas. Here, we investigated the carbon fluxes at seasonal and inter-annual timescales based on 5 years of observations of eddy covariance fluxes in the Zoige alpine meadow on the eastern Tibetan Plateau.

Spacer prioritization in CRISPR-Cas9 immunity is enabled by the leader RNA.

CRISPR-Cas systems store fragments of foreign DNA, called spacers, as immunological recordings used to combat future infections. Of the many spacers stored in a CRISPR array, the most recent are known to be prioritized for immune defence. However, the underlying mechanism remains unclear.

Clinical and biomarker analyses of sintilimab versus chemotherapy as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma: a randomized, open-label phase 2 study (ORIENT-2).

This randomized, open-label, multi-center phase 2 study (NCT03116152) assessed sintilimab, a PD-1 inhibitor, versus chemotherapy in patients with esophageal squamous cell carcinoma after first-line chemotherapy. The primary endpoint was overall survival (OS), while exploratory endpoint was the association of biomarkers with efficacy. The median OS in the sintilimab group was significantly improved compared with the chemotherapy group (median OS 7.

Sinking Rate and Community Structures of Autumn Phytoplankton Responses to Mesoscale Physical Processes in the Western South China Sea.

To examine the influence of mesoscale eddy on the natural phytoplankton community and its sinking rate changes, a comprehensive investigation cruise was carried out in the western South China Sea in autumn 2016. A total of 108 phytoplankton species were found, which belong to 54 phytoplankton genera; most of them were dominated by Dinophyta (54 genera), followed by Bacillariophyta (50 genera), Cyanophyta (3 genera), and Chrysophyta (1 genus). Bacillariophyta and Dinophyta were the main phytoplankton communities in the investigated sea area.

Integrated Metabolic Profiling and Transcriptional Analysis Reveals Therapeutic Modalities for Targeting Rapidly Proliferating Breast Cancers.

Unlabelled: Metabolic dysregulation is a prominent feature in breast cancer, but it remains poorly characterized in patient tumors. In this study, untargeted metabolomics analysis of triple-negative breast cancer (TNBC) and patient with estrogen receptor (ER)-positive breast cancer samples, as well as TNBC patient-derived xenografts (PDX), revealed two major metabolic groups independent of breast cancer histologic subtypes: a "Nucleotide/Carbohydrate-Enriched" group and a "Lipid/Fatty Acid-Enriched" group. Cell lines grown in vivo more faithfully recapitulated the metabolic profiles of patient tumors compared with those grown in vitro.

Exercise for Neuropathic Pain: A Systematic Review and Expert Consensus.

Neuropathic pain (NP), a severe and disruptive symptom following many diseases, normally restricts patients' physical functions and leads to anxiety and depression. As an economical and effective therapy, exercise may be helpful in NP management. However, few guidelines and reviews focused on exercise therapy for NP associated with specific diseases.

Prehospital shock index and systolic blood pressure are highly specific for pediatric massive transfusion.

Background: While massive transfusion protocols (MTPs) are associated with decreased mortality in adult trauma patients, there is limited research on the impact of MTP on pediatric trauma patients. The purpose of this study was to compare pediatric trauma patients requiring massive transfusion with all other pediatric trauma patients to identify triggers for MTP activation in injured children.

Methods: Using our level I trauma center's registry, we retrospectively identified all pediatric trauma patients from January 2015 to January 2018.

Automatic Detection of the Circulating Cell-Free Methylated DNA Pattern of , and for Detection of Early Breast Cancer and Surgical Treatment Response.

The early detection of cancer can reduce cancer-related mortality. There is no clinically useful noninvasive biomarker for early detection of breast cancer. The aim of this study was to develop accurate and precise early detection biomarkers and a dynamic monitoring system following treatment.