A first-in-human, randomized study of the safety, pharmacokinetics and pharmacodynamics of povetacicept, an enhanced dual BAFF/APRIL antagonist, in healthy adults.

Therapeutic agents targeting the tumor necrosis factor (TNF) superfamily cytokines B-cell activating factor (BAFF, BLyS) and/or A PRoliferation Inducing Ligand (APRIL) have demonstrated clinical effectiveness in multiple autoimmune diseases, such as systemic lupus erythematosus, lupus nephritis, and immunoglobulin A nephropathy (IgAN). However, their clinical utility can often be limited by incomplete and/or prolonged times to clinical response and inconvenient dosing regimens, which may be improved by more potent dual inhibition of both cytokines. Povetacicept (ALPN-303; TACI vTD-Fc) is a crystallizable fragment (Fc) fusion protein of an engineered transmembrane activator and CAML interactor (TACI) domain which mediates more potent inhibitory activity than wild-type TACI-Fc or BAFF- or APRIL-specific antibodies and demonstrates superior pharmacokinetic and pharmacodynamic activity in multiple preclinical disease models.

Association between glioma and neurodegenerative diseases risk: a two-sample bi-directional Mendelian randomization analysis.

Background: Earlier observational studies have demonstrated a correlation between glioma and the risk of neurodegenerative diseases (NDs), but the causality and direction of their associations remain unclear. The objective of this study was to ascertain the causal link between glioma and NDs using Mendelian randomization (MR) methodology.

Methods: Genome-wide association study (GWAS) data were used in a two-sample bi-directional MR analysis.

Event-related prefrontal activations during online video game playing are modulated by game mechanics, physiological arousal and the amount of daily playing.

There is a trend to study human brain functions in ecological contexts and in relation to human factors. In this study, functional near-infrared spectroscopy (fNIRS) was used to record real-time prefrontal activities in 42 male university student habitual video game players when they played a round of multiplayer online battle arena game, League of Legends. A content-based event coding approach was used to analyze regional activations in relation to event type, physiological arousal indexed by heart rate (HR) change, and individual characteristics of the player.

Effects of abamectin nanocapsules on bees through host physiology, immune function, and gut microbiome.

Pesticide usage is a common practice to increase crop yields. Nevertheless, the existence of pesticide residues in the surrounding environment presents a significant hazard to pollinators, specifically the potential undisclosed dangers related to emerging nanopesticides. This study examines the impact of abamectin nanocapsules (AbaNCs), created through electrostatic self-assembly, as an insecticide on honey bees.

Predictors and Outcomes of Help-Seeking Behaviors: A Longitudinal Investigation in Mental Illness.

Millions of people around the world are affected by mental illness, yet a substantive portion of individuals with mental illness do not regularly seek help from medical professionals or utilize mental health services. Help-seeking involves an individual's communicative intention and behaviors to solicit advice and/or treatment and thus is essentially a communicative process. This manuscript reports a longitudinal study that examined predictors and outcomes of help-seeking in mental illness contexts.

Transcriptional regulation in the development and dysfunction of neocortical projection neurons.

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas, and between the neocortex and other regions of the brain and spinal cord. Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination, proliferation, specification, differentiation, migration, survival, axonogenesis, and synaptogenesis. These processes are precisely regulated in a tempo-spatial manner by intrinsic factors, extrinsic signals, and neural activities.

Povetacicept, an Enhanced Dual APRIL/BAFF Antagonist That Modulates B Lymphocytes and Pathogenic Autoantibodies for the Treatment of Lupus and Other B Cell-Related Autoimmune Diseases.

Objective: Dysregulated APRIL/BAFF signaling is implicated in the pathogenesis of multiple autoimmune diseases, including systemic lupus erythematosus and lupus nephritis. We undertook this study to develop and evaluate a high-affinity APRIL/BAFF antagonist to overcome the clinical limitations of existing B cell inhibitors.

Methods: A variant of TACI-Fc generated by directed evolution showed enhanced binding for both APRIL and BAFF and was designated povetacicept (ALPN-303).

Proper irrigation amount for eggplant cultivation in a solar greenhouse improved plant growth, fruit quality and yield by influencing the soil microbial community and rhizosphere environment.

Water scarcity is a worldwide problem, and in order to obtain plenty of production, agricultural irrigation water accounts for a large portion. Many studies have shown that the interaction of root microorganisms and soil can promote crop growth. Developing ways to reduce irrigation to maintain soil fertility and ensure crop yield by regulating the root microenvironment is an important research goal.

Identifying the roles of imine and alkyne linkages in determining the photocatalytic hydrogen evolution over thiadiazole-based covalent organic frameworks.

Covalent organic frameworks (COFs) have emerged as an extremely promising material for photocatalytic water splitting for hydrogen production. However, their photocatalytic performance is seriously affected by the properties of their donors, acceptors and linkages. So far, few studies have been reported on the key roles of the linkages of a specific COF in improving its photocatalytic hydrogen production performance.

Intestinal Bacterial Diversity and Functional Analysis of Three Lepidopteran Corn Ear Worm Larvae.

Insects, as the most abundant animal group on earth, and their symbionts help their hosts to adapt to various environments. , and are three main pests co-occurring in the ear stage of corn, which significantly affect the yield and quality of corn. The purpose of this study was to compare the diversity and function of the intestinal bacteria of the three co-occurring lepidopteran pests, , and , and to explore the reason of their prevalence from the microbiota's view.

Arsenic bioaccumulation and biotransformation in aquatic organisms.

Arsenic exists universally in freshwater and marine environments, threatening the survival of aquatic organisms and human health. To elucidate arsenic bioaccumulation and biotransformation processes in aquatic organisms, this review evaluates the dissolved uptake, dietary assimilation, biotransformation, and elimination of arsenic in aquatic organisms and discusses the major factors influencing these processes. Environmental factors such as phosphorus concentration, pH, salinity, and dissolved organic matter influence arsenic absorption from aquatic systems, whereas ingestion rate, gut passage time, and gut environment affect the assimilation of arsenic from foodstuffs.

Acazicolcept (ALPN-101), a dual ICOS/CD28 antagonist, demonstrates efficacy in systemic sclerosis preclinical mouse models.

Background: Uncontrolled immune response with T cell activation has a key role in the pathogenesis of systemic sclerosis (SSc), a disorder that is characterized by generalized fibrosis affecting particularly the lungs and skin. Costimulatory molecules are key players during immune activation, and recent evidence supports a role of CD28 and ICOS in the development of fibrosis. We herein investigated the efficacy of acazicolcept (ALPN-101), a dual ICOS/CD28 antagonist, in two complementary SSc-related mouse models recapitulating skin fibrosis, interstitial lung disease, and pulmonary hypertension.

A novel lamellar structural biomaterial and its effect on bone regeneration.

To evaluate a novel lamellar structural biomaterial as a potential biomaterial for guided bone regeneration, we describe the preparation of a collagen membrane with high mechanical strength and anti-enzyme degradation ability by using the multi-level structure of scales. The physical and chemical properties, degradation, biocompatibility, and osteogenic activity were preliminarily evaluated. In conclusion, it was shown that the multi-layered collagen structure material had sufficient mechanical properties, biocompatibility, and osteogenic ability.

The toxicity of virgin and UV-aged PVC microplastics on the growth of freshwater algae Chlamydomonas reinhardtii.

Although more attention has been paid to plastic pollution in marine ecosystems, research on the influence of plastic in freshwater ecosystems remains limited. To help fill this information gap, this article represents an investigation of the effects of virgin polyvinyl chloride (v-PVC) microplastics (MPs) and UV-aged polyvinyl chloride (a-PVC) MPs on the growth and chlorophyll content of the freshwater algae, Chlamydomonas reinhardtii (C. reinhardtii) at different periods (0, 24, 48, 72 and 96 h).

Preparation of gelatin/poly (γ-glutamic acid) hydrogels with stimulated response by hot-pressing preassembly and radiation crosslinking.

The conventional preparation method of natural polymers is low in strength, which limits the application of multi stimuli responsive hydrogels as intelligent wound dressings. In this work, interpenetrating gelatin and γ-polyglutamic acid (γ-PGA) hydrogels with good biocompatibility, biodegradability and mechanical properties were prepared by hot-pressing pre-gelation of gelatin/γ-PGA and synergistic with gamma irradiation. The effects of radiation crosslinking dosage on gel fraction, swelling ratio, tensile strength and surface morphology were investigated.

Effects of Different Hosts on Bacterial Communities of Parasitic Wasp .

Parasitism is a special interspecific relationship in insects. Unlike most other ectoparasites, spend most of its life cycle (egg, larvae, pupae, and early adult stage) inside the pupae of flies, which is covered with hard puparium. Microbes play important roles in host development and help insect hosts to adapt to various environments.

Diesel Soot and Amine-Containing Organic Sulfate Aerosols in an Arctic Oil Field.

The rapid decrease in Arctic sea ice is motivating development and increasing oil and gas extraction activities. However, few observations of these local Arctic emissions exist, limiting the understanding of impacts on atmospheric composition and climate. To address this knowledge gap, the chemical composition of atmospheric aerosols was measured within the North Slope of Alaska oil fields during August and September 2016 using an aerosol time-of-flight mass spectrometer (ATOFMS) and a time-of-flight aerosol chemical speciation monitor (ToF-ACSM).

Effects of Opinion Climate, Efficacy Messages, and Publicness of Social Media on Intentions to Retransmit Anti-Binge Drinking Messages on Facebook.

Reducing the rate of college binge drinking is a major public health goal. Social media sites such as Facebook serve as platforms for young adults' online communication, so they could potentially extend the reach of health campaign messages via retransmission. Thus, it is important to identify the factors that predict intentions to share health-related messages on social media.

Waterborne and Dietborne Toxicity of Inorganic Arsenic to the Freshwater Zooplankton Daphnia magna.

Waterborne and dietborne exposure are both important sources for the accumulation of inorganic arsenic (iAs) in aquatic organisms. Although the waterborne toxicity of iAs has been extensively investigated, its dietborne toxicity has received little attention. The present study examined the acute and chronic toxicity of arsenate (iAs) and arsenite (iAs) to the freshwater zooplankton species Daphnia magna under both waterborne and dietborne exposure scenarios.