Safety, efficacy, and immunogenicity of a novel IgG degrading enzyme (KJ103): results from two randomised, blinded, phase 1 clinical trials.

The approved intravenous adeno-associated virus (AAV) therapies are limited by the widespread prevalence of pre-existing anti-AAV antibodies in the general population, which are known to restrict patients' ability to receive gene therapy and limit transfection efficacy in vivo. To address this challenge, we have developed a novel recombinant human immunoglobulin G degrading enzyme KJ103, characterized by low immunogenicity and clinical value for the elimination of anti-AAV antibodies in gene transfer. Herein, we conducted two randomized, blinded, placebo-controlled, single ascending dose Phase I studies in China and New Zealand, to evaluate the pharmacokinetics, pharmacodynamics, safety and immunogenicity of KJ103 in healthy volunteers.

ACC treatment induced alterations in flavonoid accumulation in Toxicodendron vernicifluum.

Lacquer tree (Toxicodendron vernicifluum) is an important economic crop and is rich in flavonoids. ACC (1-aminocyclopropane-1-carboxylic acid) is the precursor to ethylene. ACC treatment can induce physiological and biochemical responses in plants.

ABCA1-Super Enhancer RNA Promotes Cholesterol Efflux, Reduces Macrophage-Mediated Inflammation and Atherosclerosis.

We describe a previously uncharacterized ATP-binding cassette A1 super enhancer RNA (ABCA1-seRNA)-mediated cholesterol efflux. In addition, it promoted macrophage inflammatory cytokine release, and was causally correlated with coronary artery disease severity. Mechanistically, ABCA1-seRNA upregulated cholesterol efflux by interacting with mediator complex subunit 23 and recruiting retinoid X receptor-alpha and liver X receptor-alpha to promote ABCA1 transcription in a manner.

Assessing the Efficacy of ChatGPT Prompting Strategies in Enhancing Thyroid Cancer Patient Education: A Prospective Study.

With the rise of AI platforms, patients increasingly use them for information, relying on advanced language models like ChatGPT for answers and advice. However, the effectiveness of ChatGPT in educating thyroid cancer patients remains unclear. We designed 50 questions covering key areas of thyroid cancer management and generated corresponding responses under four different prompt strategies.

The Hoverfly Attracting Property of a Methyl Salicylate-Containing ()-β-Farnesene Analog (3e) and Potential Mechanism by Mediating the EcorOBP15 and EcorOR3.

Using natural enemies provides a sustainable method to control major agricultural pests. Hoverflies are significant natural enemies of aphids and efficient pollinators. Herbivore-induced plant volatiles (HIPVs), including ()-β-farnesene (EBF) and methyl salicylate (MeSA), are key olfactory cues mediating hoverflies behavior.

Associations of Social, Behavioral, and Clinical Factors With Sex Differences in Stroke Recurrence and Poststroke Mortality.

Background: Few population-based studies have assessed sex differences in stroke recurrence. In addition, contributors to sex differences in recurrence and poststroke mortality, including social factors, are unclear. We investigated sex differences in these outcomes and the contribution of social, clinical, and behavioral factors to the sex differences.

Unraveling the genetic mysteries of spinal muscular atrophy in Chinese families.

Objective: Spinal muscular atrophy (SMA) is a motor neuron disorder encompassing 5q and non-5q forms, causing muscle weakness and atrophy due to spinal cord cell degeneration. Understanding its genetic basis is crucial for genetic counseling and personalized treatment options.

Methods: This study retrospectively analyzed families of patients suspected of SMA at our institution from February 2006 to March 2024.

Mechanistic insights into ferroptosis and apoptosis pathways: Synergistic effects of multi-organ toxicity and transgenerational effects induced by co-exposure of epoxiconazole and aflatoxin B1 in zebrafish.

Introduction: In the environment, mycotoxins and fungicides frequently coexist, potentially causing synergistic risks to organisms. Epoxiconazole (EPO) and aflatoxin B1 (AFB1) are a common fungicide and mycotoxins, respectively, which are widely present in the environment and have toxic effects on multiple organs once entering the organism, but it is still unclear whether the co-exposure has a synergistic toxic effect.

Objectives: This study delves into the molecular mechanisms underlying the co-exposure to EPO and AFB1, emphasizing multi-organ toxicity in female zebrafish (F0 generation) and potential transgenerational impacts on the offspring embryos (F1 generation) through multi-omics approaches.

Ganoderic Acid A Alleviates Severe Acute Pancreatitis by Modulating Gut Homeostasis and Inhibiting TLR4-NLRP3 Signaling.

Background Severe acute pancreatitis (SAP) manifests as a critical state marked by acute abdominal symptoms, often associated with intestinal barrier dysfunction, exacerbating SAP retroactively. Ganoderic acid A (GAA) demonstrates anti-inflammatory properties in various inflammatory disorders. Nonetheless, its potential therapeutic impact on SAP and the underlying mechanisms remain unexplored.

The crosstalk between senescence, tumor, and immunity: molecular mechanism and therapeutic opportunities.

Cellular senescence is characterized by a stable cell cycle arrest and a hypersecretory, proinflammatory phenotype in response to various stress stimuli. Traditionally, this state has been viewed as a tumor-suppressing mechanism that prevents the proliferation of damaged cells while activating the immune response for their clearance. However, senescence is increasingly recognized as a contributing factor to tumor progression.

Ultrafast Synthesis of Nanoscale Metal Borides for Efficient Hydrogen Evolution.

Nanoscale metal borides, with exceptional physicochemical properties, have been attracted widespread attention. However, traditional synthesis methods of metal borides often lead to surface coking and large particle sizes. Herein, we have employed a flash Joule heating (FJH) technique to enable the ultrafast synthesis of metal boride nanomaterials.

Aesthetic Unit Preservation in Emergency Facial Lacerations: A Prospective Evaluation of Landmark-Based Nerve Blocks.

Background: Facial trauma repair requires precise reconstruction while preserving aesthetic units. Traditional local anesthesia can distort tissue planes and compromise surgical precision.

Methods: This prospective study evaluated landmark-based nerve blocks versus local infiltration for complex facial laceration repair in emergency settings from January 2022 through February 2023.

Genome-wide CRISPR-Cas9 screening identifies ITGA8 responsible for abivertinib sensitivity in lung adenocarcinoma.

The emergence of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has improved the prognosis for lung cancer patients with EGFR-driven mutations. However, acquired resistance to EGFR-TKIs poses a significant challenge to the treatment. Overcoming the resistance has primarily focused on developing next-generation targeted therapies based on the molecular mechanisms of resistance or inhibiting the activation of bypass pathways to suppress or reverse the resistance.

The global, regional, and national patterns of change in the burden of bacterial pyoderma from 1990 to 2019 and the forecast for the next decade.

Pyoderma, commonly known as impetigo, is a bacterial skin infection causing pus formation, prevalent globally, especially in resource-poor areas. It affects both children and adults, including those with conditions like diabetes. Despite its significant impact and economic burden, research on its global epidemiology is limited.

A One Stone Three Birds Paradigm of Photon-Driven Pyroptosis Dye for Amplifying Tumor Immunotherapy.

Activating the pyroptosis pathway of tumor cells by photodynamic therapy (PDT) for immunogenic cell death (ICD) is considered a valid strategy in pursuit of antitumor immunotherapy, but it remains a huge challenge due to the lack of reliable design guidelines. Moreover, it is often overlooked that conventional PDT can exacerbate the development of tumor immunosuppressive microenvironment, which is apparently unfavorable to clinical immunotherapy. The endoplasmic reticulum's (ER) pivotal role in cellular homeostasis and its emerging link to pyroptosis have galvanized interest in ER-centric imaging and therapeutics.

Ionomic and metabolomic analyses reveal association between nutritional value and aleurone layer thickness in rice.

The fortification of aleurone cells represents a promising avenue for enhancing the nutritional quality of cereal. This study investigated dorsal aleurone thickness (DAT) in a rice diversity panel comprising 180 varieties, revealing that DAT of the Geng subspecies is typically greater than that of the Xian subspecies. The minerals and primary metabolites accumulated in the brown grains of ten rice varieties exhibiting distinct DAT were subjected to analysis using spectrometry-based technologies.

A Game Model and Fault Recovery Algorithm for SDN Multi-Domain.

Software-defined networking (SDN) offers an effective solution for flexible management of Wireless Sensor Networks (WSNs) by separating control logic from sensor nodes. This paper tackles the challenge of timely recovery from SDN controller failures and proposes a game theoretic model for multi-domain controllers. A game-enhanced autonomous fault recovery algorithm for SDN controllers is proposed, which boasts fast fault recovery and low migration costs.

Preparation of Novel Slow-Release Acid Materials for Oilfield Development via Encapsulation.

Acid-fracturing technology has been applied to form pathways between deep oil/gas resources and oil production pipelines. The acid fracturing fluid is required to have special slow-release performance, with no acidity at low temperatures, while steadily generating acid at high temperatures underground. At present, commercial acid systems in oilfields present problems such as the uncontrollable release effect, high costs, and significant pollution.

Evaluating the Accumulation of Grain Mercury in Engineered Rice Lines Containing and Genes Under an Organic Mercury-Enriched Condition.

Rice is a critical crop for human sustenance worldwide. Food security has increasingly attracted public concerns, particularly due to heavy metal pollution, which adversely impacts crop yield and quality, with cadmium and mercury being the primary culprits. Excessive soil mercury not only hampers rice's growth and development but also leads to a substantial accumulation in grains, posing a significant threat to human health.

Mapping the chromothripsis landscape in urothelial carcinoma unravels great intratumoral and intertumoral heterogeneity.

Chromothripsis, a hallmark of cancer, is characterized by extensive and localized DNA rearrangements involving one or a few chromosomes. However, its genome-wide frequency and characteristics in urothelial carcinoma (UC) remain largely unknown. Here, by analyzing single-regional and multi-regional whole-genome sequencing (WGS), we present the chromothripsis blueprint in 488 UC patients.

The predictive value of anti-IFI16 antibodies for the development or persistence of digital ulcers in systemic sclerosis.

To evaluate the association of anti-IFI16 antibodies with peripheral vasculopathy and the predictive value of anti-IFI16 antibodies for the development or persistence of digital ulcers (DPDU) in SSc. A total of 42 SSc patients and 42 age- and sex-matched healthy controls were enrolled. Anti-IFI16 antibodies were examined by ELISA.

Integrated healthy lifestyle even in late-life mitigates cognitive decline risk across varied genetic susceptibility.

It remains unclear whether the benefits of adhering to a healthy lifestyle outweigh the effects of high genetic risk on cognitive decline. We examined the association of combined lifestyle factors and genetic risk with changes in cognitive function and six specific dimensions of cognition among older adults from the Chinese Longitudinal Healthy Longevity Survey (1998-2018, n = 18,811, a subset of 6301 participants with genetic information). Compared to participants with an unfavorable lifestyle, those with a favorable lifestyle showed a 46.

Antimicrobial Silicon Rubber Crosslinked with Bornyl-Siloxane.

Silicone rubber (SiR) has a wide range of medical applications, but it lacks antimicrobial properties, leading to potential infection issues with related implants or medical devices. Most studies focus on adding anti-bacterial agents or surface modification, which usually result in composites with anti-bacterial properties, rather than synthesizing SiR with intrinsically antimicrobial performances. To tackle this issue, a double substituted bornyl-siloxane crosslinker (BC) is designed.