Design and biochemical evaluation of 2-cyclopropyl-thioureidobenzamide (CP-TBA) derivatives as potent HBV capsid assembly modulators targeting a novel binding site.

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a promising therapeutic approach in the treatment of chronic HBV infection. In the quest for effective therapeutics against chronic Hepatitis B virus (HBV) infection, we employed a novel binding site occupancy strategy to develop novel 2-cyclopropyl-thioureidobenzamide (CP-TBA) derivatives as potent HBV CAMs. Our diversity modification approach led to the identification of compound 17e, which demonstrated remarkable anti-HBV activity with an EC of 0.

Mapping simulated visual field defects with movie-viewing pupil perimetry.

Purpose: Assessing the quality of the visual field is important for the diagnosis of ophthalmic and neurological diseases and, consequently, for rehabilitation. Visual field defects (VFDs) are typically assessed using standard automated perimetry (SAP). However, SAP requires participants to understand instructions, maintain fixation and sustained attention, and provide overt responses.

Transcriptomic Analysis Reveals the Opposite Regulatory Effects of WRKY and CAMTA Transcription Factors on Total Tannin Production in Fruit.

Tannins are prevalent compounds found in plant fruits, contributing to the bitter taste often associated with these fruits and nuts, thereby influencing their overall taste quality. Numerous studies have been conducted to investigate the regulatory factors involved in tannin synthesis. Among these factors, transcription factors exhibit the most significant capacity to regulate tannin production as they can modulate the expression of several key enzyme genes within the tannin synthesis pathway.

Highly Efficient Chiral Separation Based on Alkali-proof Protein Immobilization by Covalent Organic Frameworks.

Chiral separation plays a pivotal role in both practical applications and industrial productions. However, traditional chiral stationary phases (CSPs) exhibit inherent instability in alkaline environments, presenting a significant challenge despite their importance. Herein, basophilic alcalase is creatively developed to fabricate ultrastable protein-based CSPs that can efficiently work under alkaline conditions.

MyD88 deficiency in mammary epithelial cells attenuates lipopolysaccharide (LPS)-induced mastitis in mice.

Lactation mastitis is a debilitating inflammatory mammary disease in postpartum animals. Myeloid differentiation primary response protein MyD88 is the key downstream adapter for innate pattern recognition receptor toll-like receptor 4 (TLR4), which plays an important role in inflammation. However, the specific role of MyD88 in mammary epithelial cells in the progression of mastitis has not been investigated.

Design, synthesis and anti-HBV activity study of novel HBV capsid assembly modulators.

Capsid assembly modulators (CAMs) have the potential to cure chronic hepatitis B, as demonstrated in clinical trials. Lead compounds NVR3-778 and 5a were found to exist in normal and flipped conformations through induced fit docking. Therefore, we designed and synthesized series I and II compounds by interchanging the amide and sulfonamide bonds of 5a to modify both the tolerance region and solvent-opening region.

Triglyceride-glucose index and combined indicators: effective indicators for screening NAFLD in snoring patients.

Aims: Nonalcoholic fatty liver disease (NAFLD) is a common complication in snoring patients, especially in patients with obstructive sleep apnea syndrome (OSA). Triglyceride-glucose (TyG) index was a simple indicator of metabolic status and a surrogate marker of insulin resistance. This study aimed to explore the relationship between NAFLD and TyG index in snoring patients.

The Structure Characteristics of Laminar Premixed Flames of Gasoline-like Fuel Under CI Engine-Relevant Conditions.

Gasoline compression ignition characterized by partially premixed and long ignition delays typically features complex flame structures such as deflagration or spontaneous ignition fronts. In this study, the flame structure and propagation characteristics of PRF90/air mixtures under compression ignition engine-relevant conditions are investigated numerically. Similar to other types of fuels, under such conditions, the propagation speed of PRF90 laminar premixed flames depends not only on the unburnt mixture properties but also on the residence time, and the transition of the flame regime depends only on the residence time.

general psychopathology factor in Chinese adolescents and its correlation with trans-diagnostic protective psycho-social factors.

Background: Comorbidity in mental disorders is prevalent among adolescents, with evidence suggesting a general psychopathology factor ("p" factor) that reflects shared mechanisms across different disorders. However, the association between the "p" factor and protective factors remains understudied. The current study aimed to explore the "p" factor, and its associations with psycho-social functioning, in Chinese adolescents.

Crossroads of assembling a moss genome: navigating contaminants and horizontal gene transfer in the moss Physcomitrellopsis africana.

The first chromosome-scale reference genome of the rare narrow-endemic African moss Physcomitrellopsis africana (P. africana) is presented here. Assembled from 73 × Oxford Nanopore Technologies (ONT) long reads and 163 × Beijing Genomics Institute (BGI)-seq short reads, the 414 Mb reference comprises 26 chromosomes and 22,925 protein-coding genes [Benchmarking Universal Single-Copy Ortholog (BUSCO) scores: C:94.

Investigating the effects of rare ginsenosides on hyperuricemia and associated sperm damage via nontargeted metabolomics and gut microbiota.

Ethnopharmacological Relevance: In ancient times, ginseng was used for hyperuricemia treatment as described in the classic traditional Chinese medical text Shang Han Lun. Recent studies have shown that common ginsenosides and rare ginsenosides (RGS) are the main active compounds in ginseng. RGS have higher activity and are less studied in the treatment of hyperuricemia.

The Role of Heat-Induced Stress Granules in the Blood-Testis Barrier of Mice.

Stress granules (SGs) are membraneless ribonucleoprotein (RNP)-based cellular foci formed in response to stress, facilitating cell survival by protecting against damage. Mammalian spermatogenesis should be maintained below body temperature for proper development, indicating its vulnerability to heat stress (HS). In this study, biotin tracer permeability assays showed that the inhibition of heat-induced SG assembly in the testis by 4-8 mg/kg cycloheximide significantly increased the percentage of seminiferous tubules with a damaged blood-testis barrier (BTB).

Vascular Endothelial Cell-Derived Exosomal Sphingosylphosphorylcholine Attenuates Myocardial Ischemia-Reperfusion Injury through NR4A2-Mediated Mitophagy.

Cardiomyocyte survival is a critical contributing process of host adaptive responses to cardiovascular diseases (CVD). Cells of the cardiovascular endothelium have recently been reported to promote cardiomyocyte survival through exosome-loading cargos. Sphingosylphosphorylcholine (SPC), an intermediate metabolite of sphingolipids, mediates protection against myocardial infarction (MI).

Inhibition of p38 MAPK/NF-κB p65 signaling pathway activity by rare ginsenosides ameliorates cyclophosphamide-induced premature ovarian failure and KGN cell injury.

Ethnopharmacological Relevance: Panax ginseng C. A. Mey.

Artificial intelligence in the risk prediction models of cardiovascular disease and development of an independent validation screening tool: a systematic review.

Background: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation.

Methods: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021.

Open-DPSM: An open-source toolkit for modeling pupil size changes to dynamic visual inputs.

Pupil size change is a widely adopted, sensitive indicator for sensory and cognitive processes. However, the interpretation of these changes is complicated by the influence of multiple low-level effects, such as brightness or contrast changes, posing challenges to applying pupillometry outside of extremely controlled settings. Building on and extending previous models, we here introduce Open Dynamic Pupil Size Modeling (Open-DPSM), an open-source toolkit to model pupil size changes to dynamically changing visual inputs using a convolution approach.

Chromosome-level genome assembly of provides new insights into heat stress responses in mosses.

With a diversity of approximately 22,000 species, bryophytes (hornworts, liverworts, and mosses) represent a major and diverse lineage of land plants. Bryophytes can thrive in many extreme environments as they can endure the stresses of drought, heat, and cold. The moss (Grimmiaceae, Grimmiales) can subsist for extended periods under heat and drought conditions, providing a good candidate for studying the genetic basis underlying such high resilience.

Subcutaneous Rapid Dissolution Microneedle Patch Integrated with CuO and Disulfiram for Augmented Antimelanoma Efficacy through Multimodal Synergy of Photothermal Therapy, Chemodynamic Therapy, and Chemotherapy.

Melanoma is a malignancy of the skin that is resistant to conventional treatment, necessitating the development of effective and safe new therapies. The percutaneous microneedle (MN) system has garnered increasing interest as a viable treatment option due to its high efficacy, minimal invasiveness, painlessness, and secure benefits. In this investigation, a sensitive MN system with multiple functions was created to combat melanoma effectively.

Optimization of green deep eutectic solvent (DES) extraction of Willd. husks saponins by response surface methodology and their antioxidant activities.

Quinoa saponins have outstanding activity, and there are an increasing number of extraction methods, but there are few research programs on green preparation technology. The extraction conditions of quinoa saponins with deep eutectic solvents (DESs) were optimized by single-factor experiments combined with response surface methodology. The antioxidant capacity of saponins extracted by DESs and traditional methods was evaluated by the DPPH clearance rate, iron ion chelation rate and potassium ferricyanide reducing power.

Entropy-Stabilized Layered KNiFeMgTiMnO as a High-Rate and Stable Cathode for Potassium-Ion Batteries.

Mn-based layered oxides have been considered the most promising cathode candidates for cost-effective potassium-ion batteries (PIBs). Herein, equiatomic constituents of Ni, Fe, Mg, and Ti have been introduced into the transition metal layers of Mn-based layered oxide to design a high-entropy KNiFeMgTiMnO (HE-KMO, = 1.17R).

SUMOylation of Rho-associated protein kinase 2 induces goblet cell metaplasia in allergic airways.

Allergic asthma is characterized by goblet cell metaplasia and subsequent mucus hypersecretion that contribute to the morbidity and mortality of this disease. Here, we explore the potential role and underlying mechanism of protein SUMOylation-mediated goblet cell metaplasia. The components of SUMOylaion machinery are specifically expressed in healthy human bronchial epithelia and robustly upregulated in bronchial epithelia of patients or mouse models with allergic asthma.