Repulsive interactions instruct synaptic partner matching in an olfactory circuit.

Neurons exhibit extraordinary precision in selecting synaptic partners. Whereas cell-surface proteins (CSPs) mediating attractive interactions between developing axons and dendrites have been shown to instruct synaptic partner matching , it is less clear the degree to which repulsive interactions play a role. Here, using a genetic screen guided by single cell transcriptomes , we identified three CSP pairs-Toll2-Ptp10D, Fili-Kek1, and Hbs/Sns-Kirre-in mediating repulsive interactions between non-partner olfactory receptor neuron (ORN) axons and projection neuron (PN) dendrites in the developing olfactory circuit.

Model-Informed Recommendation of Mavacamten Posology for Chinese Adults With Obstructive Hypertrophic Cardiomyopathy.

Mavacamten is a cardiac myosin inhibitor for adults with obstructive hypertrophic cardiomyopathy (HCM). Dose optimization is performed 4 weeks after starting mavacamten, guided by periodic echo measurements of Valsalva left ventricular outflow tract gradient (VLVOTg) and left ventricular ejection fraction (LVEF). Previously, a population pharmacokinetic (PPK) model was developed and exposure-response (E-R) of VLVOTg (efficacy) and LVEF (safety) was used to identify the mavacamten titration regimen with the optimal benefit/risk ratio, now included in the US prescribing information.

Pharmacokinetics of infigratinib and its active metabolites in Chinese patients with advanced gastric cancer harboring FGFR2 gene amplification.

Infigratinib, an FGFR1-3 selective oral tyrosine kinase inhibitor, has shown clinical activity in cancers with FGFR alterations. The pharmacokinetics (PK) of infigratinib and its major metabolites have been characterized in global populations. This study examined the PK profile of infigratinib and its metabolites in Chinese patients.

Integrated single-cell transcriptome and TCR profiles of hepatocellular carcinoma highlight the convergence on interferon signaling during immunotherapy.

Background: Despite the success of immune checkpoint inhibitor (ICI)-based combination therapies in hepatocellular carcinoma (HCC), its effectiveness remains confined to a subset of patients. The development of reliable, predictive markers is important for accurate patient stratification and further mechanistic understanding of therapy response.

Methods: We comprehensively analyzed paired single-cell RNA transcriptome and T-cell repertoire profiles from 14 HCC ascites samples, collected from 7 patients before and after treatment with the combination of sintilimab (anti-PD-1) and bevacizumab (anti-VEGF).

The role of intelligent technology in the development of urban air mobility systems: A technical perspective.

Urban Air Mobility (UAM) is an emerging transportation system that aims at revolutionizing urban mobility through the deployment of small electric vertical takeoff and landing (eVTOL) aircraft. The development of UAM is largely driven by advances in Intelligent Technology (IT). This review article provides an overview of the UAM system and discusses the application of IT in UAM.

Electrodeposition and Optimisation of Amorphous NiS Catalyst for Hydrogen Evolution Reaction in Alkaline Environment.

Anion exchange membrane (AEM) water electrolysers have shown their potential in green hydrogen production. One of the crucial tasks is to discover novel cost-effective and sustainable electrocatalyst materials. In this study, a low-cost Ni-S-based catalyst for hydrogen evolution reaction was prepared via a simple electrodeposition process from a modified Watts bath recipe.

Dimensionality reduction simplifies synaptic partner matching in an olfactory circuit.

The distribution of postsynaptic partners in three-dimensional (3D) space presents complex choices for a navigating axon. Here, we discovered a dimensionality reduction principle in establishing the 3D glomerular map in the fly antennal lobe. Olfactory receptor neuron (ORN) axons first contact partner projection neuron (PN) dendrites at the 2D spherical surface of the antennal lobe during development, regardless of whether the adult glomeruli are at the surface or interior of the antennal lobe.

Pharmacokinetics and safety of mavacamten in healthy Chinese participants with different CYP2C19 phenotypes.

Obstructive hypertrophic cardiomyopathy (oHCM) is a subtype of HCM characterized by left ventricular outflow tract obstruction resulting from cardiac muscle hypertrophy and anatomic alterations in the mitral valve and apparatus. Mavacamten, a cardiac myosin inhibitor metabolized primarily by CYP2C19 in the liver, is the first and only targeted medication approved for the treatment of symptomatic New York Heart Association (NYHA) class II-III oHCM. Previous pharmacokinetic (PK) results of mavacamten in healthy Caucasian, Japanese, and Asian participants demonstrated that mavacamten exposure was affected by CYP2C19 metabolism status.

Modified Zhenwu Decoction improved intestinal barrier function of experimental colitis through activation of sGC-mediated cGMP/PKG signaling.

Background: The invasion of luminal antigens and an aberrant immune response resulting from a disrupted physical epithelial barrier are the key characteristics of ulcerative colitis (UC). The restoration of damaged epithelial function is crucial for maintaining mucosal homeostasis and disease quiescence. Current therapies for UC primarily focus on suppressing inflammation.

Molecular and cellular mechanisms of teneurin signaling in synaptic partner matching.

In developing brains, axons exhibit remarkable precision in selecting synaptic partners among many non-partner cells. Evolutionarily conserved teneurins are transmembrane proteins that instruct synaptic partner matching. However, how intracellular signaling pathways execute teneurins' functions is unclear.

[Research progress of traditional Chinese and Western medicine non-pharmacological prevention strategies for acute high altitude disease].

Acute high altitude disease (AHAD) is a general term for a series of clinical reactions that occur when the body fails to adapt to the low-pressure hypoxic environment of high altitudes. Mild cases can cause symptoms such as headache, nausea and vomiting, while more severe cases can lead to life-threatening conditions such as pulmonary edema, cerebral edema and other critical conditions that can be fatal. With the increasing demand for high altitudes deployment, understanding the common preventive measures of AHAD can reduce its morbidity or mortality to a certain extent, which is of great benefit to those who reside temporarily at high altitudes.

Integrated metabolomics and serum-feces pharmacochemistry-based network pharmacology to reveal the mechanisms of an herbal prescription against ulcerative colitis.

Background: CDD-2103 is an herbal prescription used to treat ulcerative colitis (UC). This study aimed to uncover its mechanism by integrating metabolomics and serum-feces pharmacochemistry-based network pharmacology.

Methods: A DSS-induced chronic colitis mice model was used to evaluate the anti-colitis effect of CDD-2103.

Modified Zhenwu Decoction suppresses chronic colitis via targeting macrophage CCR2/Fyn/p38 MAPK signaling axis.

Background: Ulcerative colitis (UC) is associated with intestinal macrophage infiltration due to disruption of the mucosal barrier and bacterial invasion. Therefore, it is crucial to identify therapeutic agents capable of attenuating the macrophage-induced inflammatory response to preserve mucosal homeostasis and immune tolerance. The modified Zhenwu decoction (CDD-2103) is a novel herbal formulation developed based on the principles of Traditional Chinese medicine.

A new framework for exploratory network mediator analysis in omics data.

Omics methods are widely used in basic biology and translational medicine research. More and more omics data are collected to explain the impact of certain risk factors on clinical outcomes. To explain the mechanism of the risk factors, a core question is how to find the genes/proteins/metabolites that mediate their effects on the clinical outcome.

Tolerogenic dendritic cell-mediated regulatory T cell differentiation by Chinese herbal formulation attenuates colitis progression.

Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by loss of immune tolerance to luminal antigens and progressive intestinal tissue injury. Thus, the re-establishment of immune tolerance is crucial for suppressing aberrant immune responses and UC progression.

Objectives: This study aimed to investigate the mechanisms underlying the action of CDD-2103 and its bioactive compounds in mediating immune regulation in mouse models of colitis.

Challenges and progress in oxygen evolution reaction catalyst development for seawater electrolysis for hydrogen production.

Production of green hydrogen on a large scale can negatively impact freshwater resources. Therefore, using seawater as an electrolyte in electrolysis is a desirable alternative to reduce costs and freshwater reliance. However, there are limitations to this approach, primarily due to the catalyst involved in the oxygen evolution reaction (OER).

Cell mediated ECM-degradation as an emerging tool for anti-fibrotic strategy.

Investigation into the role of cells with respect to extracellular matrix (ECM) remodeling is still in its infancy. Particularly, ECM degradation is an indispensable process during the recovery from fibrosis. Cells with ECM degradation ability due to the secretion of various matrix metalloproteinases (MMPs) have emerged as novel contributors to the treatment of fibrotic diseases.

Effect of Mavacamten on Chinese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy: The EXPLORER-CN Randomized Clinical Trial.

Importance: Mavacamten has shown clinical benefits in global studies for patients with obstructive hypertrophic cardiomyopathy (oHCM), but evidence in the Asian population is lacking.

Objective: To evaluate the safety and efficacy of mavacamten compared with placebo for Chinese patients with symptomatic oHCM.

Design, Setting, And Participants: This phase 3, randomized, double-blind, placebo-controlled clinical trial was conducted at 12 hospitals in China.

Differential Evolution Optimization of Microwave Focused Hyperthermia Phased Array Excitation for Targeted Breast Cancer Heating.

Microwave hyperthermia using the phased array applicator is a non-invasive treatment modality for breast cancer. Hyperthermia treatment planning (HTP) is critical to accurately treating breast cancer and avoiding damage to the patient's healthy tissue. A global optimization algorithm, differential evolution (DE) algorithm, has been applied to optimize HTP for breast cancer and its ability to improve the treatment effect was proved by electromagnetic (EM) and thermal simulation results.

Origin of wiring specificity in an olfactory map revealed by neuron type-specific, time-lapse imaging of dendrite targeting.

How does wiring specificity of neural maps emerge during development? Formation of the adult olfactory glomerular map begins with the patterning of projection neuron (PN) dendrites at the early pupal stage. To better understand the origin of wiring specificity of this map, we created genetic tools to systematically characterize dendrite patterning across development at PN type-specific resolution. We find that PNs use lineage and birth order combinatorially to build the initial dendritic map.

Exploring the Mechanism of Microfracture in the Treatment of Porcine Full-Thickness Cartilage Defect.

Background: Microfracture has the most extensive clinical application because of its advantages of a single operation, unified process, and low operation cost. Because research on the repair mechanism of microfractures in the treatment of cartilage defects is not in-depth, this study aimed to elucidate the mechanism.

Purpose: To identify the characteristic cell subsets at different repair stages after microfracture, systematically analyze the repair process of the defect area after microfracture, and investigate the mechanism of fibrocartilage repair.