Antagonizing NK-1R modulates pain perception following corneal injury.

Substance P (SP) expressed by corneal nerves, is an 11-amino acid long neuropeptide from the tachykinin family, encoded by the Tac1 gene, and binds to neurokinin receptors. SP overexpression is associated with various pathological responses in the cornea including vasodilation, pain, inflammation, and angiogenesis in the normally avascular tissue. This study investigates the role of neurokinin-1 receptor (NK-1R) mediated signaling in nociception, nerve regeneration, and neuronal activation following mechanical corneal injury in mice.

Activation of α2B/2C adrenergic receptor ameliorates ocular surface inflammation through enhancing regulatory T cell function.

There is an unmet need for effectively treating dry eye disease (DED), a T cell-mediated chronic, inflammatory ocular surface disorder. Given the potential of nonneuronal adrenergic system in modulating T cell response, we herein investigated the therapeutic efficacy and the underlying mechanisms of a specific alpha 2 adrenergic receptor agonist (AGN-762, selective for α2B/2C receptor subtypes) in a mouse model of DED. Experimental DED was treated with the AGN-762 by oral gavage, either at disease induction or after disease establishment, and showed sustained amelioration, along with reduced expression of DED-pathogenic cytokines in ocular surface tissues, decreased corneal MHC-IICD11b cells and lymphoid Th17 cells, and higher function of regulatory T cells (Treg).

Effect of smoking behaviour and related blood DNA methylation on visceral adipose tissues.

Background: Recent studies have found that tobacco smoking is associated with fat distribution, yet limited research has focused on its relationship with visceral adipose tissues (VATs). Furthermore, the cellular and molecular mechanisms underlying the interactions among smoking, epigenetic modifications, and VATs remain unknown.

Method: We performed univariable Mendelian randomization (MR) analysis to elucidate the causal relationship between smoking behaviours and VATs, including epicardial and pericardial adipose tissue (EPAT), liver fat (LF), and pancreas fat (PF).

Substance P regulates memory Th17 cell generation and maintenance in chronic dry eye disease.

Substance P is a neuropeptide expressed by nerves and an array of cells that serves as a critical mediator of neuroinflammation. Our recent work has demonstrated that blocking the preferred receptor for substance P, neurokinin 1 receptor, effectively suppresses the induction of acute dry eye disease by preserving regulatory T-cell function, while inhibiting antigen-presenting cell maturation and subsequent generation of effector Th17 cells. Clinically, dry eye disease is a chronic disorder characterized by sustained ocular surface inflammation, which is mediated by long-lived memory Th17 cells demonstrated in our well-established chronic dry eye disease model.

Oxygen Functional Groups Regulate Cobalt-Porphyrin Molecular Electrocatalyst for Acidic HO Electrosynthesis at Industrial-Level Current.

Electrosynthesis of hydrogen peroxide (HO) based on proton exchange membrane (PEM) reactor represents a promising approach to industrial-level HO production, while it is hampered by the lack of high-efficiency electrocatalysts in acidic medium. Herein, we present a strategy for the specific oxygen functional group (OFG) regulation to promote the HO selectivity up to 92 % in acid on cobalt-porphyrin molecular assembled with reduced graphene oxide. In situ X-ray adsorption spectroscopy, in situ Raman spectroscopy and Kelvin probe force microscopy combined with theoretical calculation unravel that different OFGs exert distinctive regulation effects on the electronic structure of Co center through either remote (carboxyl and epoxy) or vicinal (hydroxyl) interaction manners, thus leading to the opposite influences on the promotion in 2e ORR selectivity.

Neurokinin-1 Receptor Antagonism Reduces Nonallergic Ocular Redness in a Rabbit Model.

To evaluate the therapeutic efficacy of topical application of a neurokinin-1 receptor (NK1R) antagonist in a rabbit model of nonallergic ocular redness. Nonallergic ocular redness was induced in rabbits by a single, topical application of dapiparzole hydrochloride eye drops (0.5%, 1%, 2%, or 5%).

The impact of left-behind experience on urban identity of new-generation migrant workers.

We investigate the impact of left-behind experiences on the urban identity of new-generation migrant workers using data from the 2017 China Migrants Dynamic Survey. The results show the following: (1) The left-behind experience is an important factor undermining the urban identity of new-generation migrant workers, and the conclusion remains consistent after robustness checks, such as propensity score matching. (2) Left-behind experiences of both parents away from home had the most significant negative impact on urban identity.

SET domain containing 2 promotes megakaryocyte polyploidization and platelet generation through methylation of α-tubulin.

Background: Megakaryocytes (MKs) are polyploid cells responsible for producing ∼10 platelets daily in humans. Unraveling the mechanisms regulating megakaryopoiesis holds the promise for the production of clinical-grade platelets from stem cells, overcoming significant current limitations in platelet transfusion medicine. Previous work identified that loss of the epigenetic regulator SET domain containing 2 (SETD2) was associated with an increased platelet count in mice.

Myeloid-derived suppressor cells promote allograft survival by suppressing regulatory T cell dysfunction in high-risk corneal transplantation.

Highly inflamed and neovascularized corneal graft beds are known as high-risk (HR) environments for transplant survival. One of the primary factors leading to this rejection is reduction in the suppressive function of regulatory T cells (Treg). Our results show that myeloid-derived suppressor cells (MDSC) counteract interleukin-6-mediated Treg dysfunction by expressing interleukin-10.

Therapeutic Effects of Stimulating the Melanocortin Pathway in Regulating Ocular Inflammation and Cell Death.

Alpha-melanocyte-stimulating hormone (α-MSH) and its binding receptors (the melanocortin receptors) play important roles in maintaining ocular tissue integrity and immune homeostasis. Particularly extensive studies have demonstrated the biological functions of α-MSH in both immunoregulation and cyto-protection. This review summarizes the current knowledge of both the physiological and pathological roles of α-MSH and its receptors in the eye.

The BK Channel Limits the Pro-Inflammatory Activity of Macrophages.

Macrophages play a crucial role in the innate immune response, serving as key effector cells in the defense against pathogens. Although the role of the large-conductance voltage and calcium-activated potassium channel, also known as the K1.1 or BK channel, in regulating neurotransmitter release and smooth muscle contraction is well known, its potential involvement in immune regulation remains unclear.

The protective effect of vagus nerve stimulation against myocardial ischemia/reperfusion injury: pooled review from preclinical studies.

Myocardial ischemia-reperfusion (I/R) injury markedly undermines the protective benefits of revascularization, contributing to ventricular dysfunction and mortality. Due to complex mechanisms, no efficient ways exist to prevent cardiomyocyte reperfusion damage. Vagus nerve stimulation (VNS) appears as a potential therapeutic intervention to alleviate myocardial I/R injury.

Insights into mustard gas keratopathy- characterizing corneal layer-specific changes in mice exposed to nitrogen mustard.

Exposure to mustard agents, such as sulfur mustard (SM) and nitrogen mustard (NM), often results in ocular surface damage. This can lead to the emergence of various corneal disorders that are collectively referred to as mustard gas keratopathy (MGK). In this study, we aimed to develop a mouse model of MGK by using ocular NM exposure, and describe the subsequent structural changes analyzed across the different layers of the cornea.

Tele-Instruction Tool for Multiple Lay Responders Providing Cardiopulmonary Resuscitation in Telehealth Emergency Dispatch Services: Mixed Methods Study.

Background: Telephone-assisted cardiopulmonary resuscitation (T-CPR) has proven to be a crucial intervention in enhancing the ability of lay responders to perform cardiopulmonary resuscitation (CPR) during telehealth emergency services. While the majority of established T-CPR protocols primarily focus on guiding individual rescuers, there is a lack of emphasis on instructing and coordinating multiple lay responders to perform resuscitation collaboratively.

Objective: This study aimed to develop an innovative team-based tele-instruction tool to efficiently organize and instruct multiple lay responders on the CPR process and to evaluate the effectiveness and feasibility of the tool.

The impact of donor diabetes on corneal transplant immunity.

Corneal transplantation is the most common form of solid tissue grafting, with an approximately 80% to 90% success rate. However, success rates may decline when donor tissues are derived from patients with a history of diabetes mellitus (DM). To evaluate the underlying immunopathologic processes that cause graft rejection, we used streptozotocin-induced type 1 DM (DM1) and transgenic Lep type 2 DM (DM2) diabetic murine models as donors and nondiabetic BALB/c as recipients.

Intracardiac echocardiographic imaging with a cartosound module for guidance of left atrial appendage closure: a comparative study with transesophageal echocardiographic imaging.

Purpose: In most clinical trials, intracardiac echocardiography (ICE) has provided fewer views than the four standard views provided by transesophageal echocardiography (TEE) when assessing left atrial appendage closure (LAAC) devices. This study aimed to determine if ICE guided by the CartoSound system achieve adequate high-quality views and similar clinical outcomes as TEE during LAAC.

Methods: This study prospectively enrolled 202 patients who underwent LAAC using either ICE (n = 69), TEE (n = 121), or a combination of ICE and TEE (n = 12) as the procedural imaging under local anesthesia.

Insights into mustard gas keratopathy: Characterizing corneal layer-specific changes in mice exposed to nitrogen mustard.

Exposure to mustard agents, such as sulfur mustard (SM) and nitrogen mustard (NM), often results in ocular surface damage. This can lead to the emergence of various corneal disorders that are collectively referred to as mustard gas keratopathy (MGK). In this study, we aimed to develop a mouse model of MGK by using ocular NM exposure, and describe the subsequent structural changes analyzed across the different layers of the cornea.

Long-lived autoreactive memory CD4 T cells mediate the sustained retinopathy in chronic autoimmune uveitis.

Chronic uveitis comprises heterogeneous clinical entities characterized by sustained and recurrent intraocular inflammation that is believed to be driven by autoimmune responses. The management of chronic uveitis is challenging with the limited availability of efficacious treatments, and the underlying mechanisms mediating disease chronicity remain poorly understood as the majority of experimental data are derived from the acute phase of the disease (the first 2-3 weeks post-induction). Herein, we investigated the key cellular mechanisms underlying chronic intraocular inflammation using our recently established murine model of chronic autoimmune uveitis.

Reduced- or Half-Dose Rivaroxaban Following Left Atrial Appendage Closure: A Feasible Antithrombotic Therapy in Patients at High Risk of Bleeding?

The optimal antithrombotic strategy after percutaneous left atrial appendage closure (LAAC) has not yet been established. The advisability of administering low-dose direct oral anticoagulation after LAAC to patients at high risk of bleeding is uncertain. Thus, in the present study, we evaluated the safety and effectiveness of reduced-(15 mg) or half-dose rivaroxaban (10 mg) versus warfarin regarding real-world risks of thromboembolism, bleeding, and device-related thrombosis (DRT) after LAAC.

Conventional type I migratory CD103 dendritic cells are required for corneal allograft survival.

Corneal transplant rejection primarily occurs because of the T helper 1 (Th1) effector cell-mediated immune response of the host towards allogeneic tissue. The evidence suggests that type 1 migratory conventional CD103 dendritic cells (CD103DC1) acquire an immunosuppressive phenotype in the tumor environment; however, the involvement of CD103DC1 in allograft survival continues to be an elusive question of great clinical significance in tissue transplantation. In this study, we assess the role of CD103DC1 in suppressing Th1 alloreactivity against transplanted corneal allografts.

Amplified Natural Killer Cell Activity and Attenuated Regulatory T-cell Function Are Determinants for Corneal Alloimmunity in Very Young Mice.

Background: Corneal transplantation outcomes are generally less favorable in young children compared with adults. The purpose of this study was to determine the immunological mechanisms underlying this difference.

Methods: A murine model of allogeneic corneal transplantation was used in the study, and graft survival was determined by evaluating opacity scores for 8 wk.

The relationship between MUC19 copy number variation and growth traits of Chinese cattle.

Copy number variation (CNV), as one of the important variations in the biological genome, refers to the deletion and duplication of genomic segments between 1 kb and 50 kb caused by genomic rearrangements. Currently, many copy number variations have been found to be significantly associated with important economic traits such as growth, development and reproduction of cattle. However, the study of MUC19 gene has not been reported.