Development of conformation-selective antibodies targeting human SLC15A4.

SLC15A4, an endolysosomal solute carrier family transporter, plays a critical role in TLR7/8/9-induced immune responses through assembling a complex with the downstream adaptor TASL in a conformation-dependent manner. Despite its close functional association and promising therapeutic potential in infections, tumors, and autoimmune diseases, the development of conformation-specific antibodies for human SLC15A4 (hSLC15A4) remains challenging. Here, using a systematic screening and validation approach, we identify a pair of conformation-selective antibodies, clones 107 and 235, targeting the endolysosomal lumen surface of hSLC15A4 with opposite conformation-regulatory activities.

Development and Evaluation of a Multi-Epitope Vaccine Based on P22 Virus-Like Particles Targeting Helicobacter pylori.

Background: The current first-line treatment for Helicobacter pylori (H. pylori) infection is bismuth-based quadruple therapy. However, the widespread use of antibiotics has contributed to the emergence of antibiotic-resistant strains, thereby increasing the likelihood of treatment failure.

Construction and evaluation of a minicell-based dendritic cell-targeted multi-epitope vaccine against .

Background: infection is a global health concern linked to various gastrointestinal diseases, highlighting the urgent need for effective vaccines.

Methods: In this study, we developed two multi-epitope vaccine candidates based on minicells: TA-2m and Apt-TA-2m. Apt-TA-2 is an advanced formulation of TA-2m, coated with dendritic cell-targeting RNA aptamer to enhance antigen delivery and immune activation.

Direct monocular vision algorithm based on deep constraints of point and line features fusion.

Unlabelled: The development of technology and the rapid increase of computing power have enabled the wide application of simultaneous localization and mapping (SLAM) in smart devices. Nevertheless, visual odometry based on the direct method exhibits inaccurate pose estimation in structured environments, because it ignores diverse line segment information, constraints of associated points, and estimated position information.

Objective: This study aimed to address the issue of inaccurate pose estimation in structured environments for direct method-based visual odometry by proposing a direct monocular vision algorithm based on deep constraints of point and line features (DMVA-PLF), with the goal of improving pose estimation accuracy.

DBP degradation and PGPR-mediated enhancement: Mechanisms of Enterobacter sp. X1 revealed by maize (Zea mays L.) transcriptome and rhizosphere microbiome analysis.

Dibutyl phthalate (DBP), a common plasticizer in industrial production, is often detected in agricultural fields and exhibits significant endocrine disrupting effects on humans. Recently, plant growth promoting rhizobacteria (PGPR) have received considerable attention for their application in enhancing phytoremediation of soil organic pollutants. However, few studies have revealed the underlying mechanisms of gene expression changes in the PGPR-assisted phytoremediation process through plant transcriptome and rhizome microbiome analyses.

Molecular basis of SLC19A1-mediated folate and cyclic dinucleotide transport.

The solute carrier protein SLC19A1 is crucial for transporting folate nutrients, antifolate chemotherapeutics, and more recently cyclic dinucleotides (CDNs) immune transmitters, influencing various physiological and pathological processes. While the inward-open state of human SLC19A1 (hSLC19A1) has been previously described, key aspects regarding its conformational dynamics, substrate selectivity, and precise mechanisms underlying CDNs transport remain elusive. Using an antibody-facilitated conformation screening strategy, we present cryo-electron microscopy structures of hSLC19A1 in its outward-open state with and without bound substrates, revealing detailed mechanisms of substrate recognition and conformational changes during transport.

Antioxidants in anti-Alzheimer's disease drug discovery.

Oxidative stress is widely recognized as a key contributor to the pathogenesis of Alzheimer's disease (AD). While not the sole factor, it is closely linked to critical pathological features, such as the formation of senile plaques and neurofibrillary tangles. The development of agents with antioxidant properties has become an area of growing interest in AD research.

Substrate transport and drug interaction of human thiamine transporters SLC19A2/A3.

Thiamine and pyridoxine are essential B vitamins that serve as enzymatic cofactors in energy metabolism, protein and nucleic acid biosynthesis, and neurotransmitter production. In humans, thiamine transporters SLC19A2 and SLC19A3 primarily regulate cellular uptake of both vitamins. Genetic mutations in these transporters, which cause thiamine and pyridoxine deficiency, have been implicated in severe neurometabolic diseases.

Innovative utilization of cell membrane-coated nanoparticles in precision cancer therapy.

Cell membrane-coated nanoparticles (CMNPs) have recently emerged as a promising platform for cancer therapy. By encapsulating therapeutic agents within a cell membrane-derived coating, these nanoparticles combine the advantages of synthetic nanoparticles and natural cell membranes. This review provides a comprehensive overview of the recent advancements in utilizing CMNPs as effective drug delivery vehicles for cancer therapy.

Roles of posttranslational modifications in lipid metabolism and cancer progression.

Lipid metabolism reprogramming has emerged as a hallmark of malignant tumors. Lipids represent a complex group of biomolecules that not only compose the essential components of biological membranes and act as an energy source, but also function as messengers to integrate various signaling pathways. In tumor cells, de novo lipogenesis plays a crucial role in acquiring lipids to meet the demands of rapid growth.

The Causal Relationship between Inflammatory Cytokines and Liver Cirrhosis in European Descent: A Bidirectional Two-Sample Mendelian Randomization Study and the First Conclusions.

Background: Observational studies have highlighted the pivotal role of inflammatory cytokines in cirrhosis progression. However, the existence of a causal link between inflammatory cytokines and cirrhosis remains uncertain. In this study, we conducted a bidirectional Mendelian randomization (MR) analysis at a summarized level to illuminate the potential causal relationship between the two variables.

Inhibition of LPCAT3 exacerbates endoplasmic reticulum stress and HBV replication.

Background: Altered phospholipid metabolism plays a key role in changing the immune microenvironment and severely affecting T-cell function. LPCAT3 is one of the vital enzymes regulating phospholipid metabolism. This study aims to verify the effect of LPCAT3 on HBV replication in vitro and the chronic progression of hepatitis B infection based on the results of lipidomic.

Synergistic contributions of plant growth-promoting rhizobacteria and exogenous fulvic acid to enhance phytoremediation efficiency of perfluorooctanoic acid (PFOA)-contaminated soils: Boosting PFOA bioavailability and elevating pak choi tolerance.

Perfluorooctanoic acid (PFOA), a synthetic perfluoroalkyl compound, has caused extensive soil contamination over several decades, posing serious health risks to humans through bioaccumulation in plants and subsequent transfer via the food chain. Due to the durability of PFOA in soil and its propensity to migrate and accumulate in plants, phytoremediation has been recognized as an effective remediation method. However, the phytotoxicity of PFOA and the adsorption of PFOA by soil hindered the efficiency of traditional phytoremediation.

Biomolecule-regulation of fluorescent probe signaling: Homogeneous rapid portable protease sensing in serum.

Background: As is well documented, prostate cancer (PCa) being the second most prevalent cancer in men worldwide, emphasizing the importance of early diagnosis for prognosis. However, conventional prostate-specific antigen (PSA) testing lacks sufficient diagnostic efficiency due to its relatively low sensitivity and limited detection range. Mounting evidence suggests that matrix metalloproteinase 9 (MMP-9) expression increases with the aggressive behavior of PCa, highlighting the significance of detecting the serum level of MMP-9 in patients.

Evaluation of electrokinetic-assisted phytoremediation efficiency of dibutyl phthalate contaminated soil by maize (Zea mays L.) under different electric field intensities.

The excessive accumulation of dibutyl phthalate (DBP) in soil poses a serious threat to soil ecosystems and crop safety production. Electrokinetic-assisted phytoremediation (EKPR) has been considered as a potential technology for remediating organic contaminated soils. In order to investigate the effect of different electric fields on removal efficiency of DBP, three kinds of electric fields were set up in this study (1 V·cm, 2 V·cm and 3 V·cm).

Comparative Bleeding Risk of Brand Vs Generic Rivaroxaban in Elderly Inpatients with Atrial Fibrillation.

Objective: Atrial fibrillation (AF) is the most common abnormal heart rhythm in elderly patients. Rivaroxaban has been widely used for stroke prevention. The anticoagulant response to rivaroxaban increases with age, which may make elderly patients susceptible to adverse outcomes resulting from small differences in bioavailability between generic and brand products.

In silico study of androgen receptor N-terminal domain and exploration of its modulators.

The androgen receptor (AR, Uniprot: P10275) signaling plays a key role in the progression of prostate cancer, various AR-related ligands have been reported to treat prostate cancer. However, some resistance mechanisms limited the treating effect of these ligands. Since DBD binding or the allosteric binding sites in LBD of AR may allow the circumvention of some drug resistance mechanisms, anti-resistance is expected especially through the NTD (N-terminal domain) targeting.

[Development of a Catalytic Hairpin Assembly-Based Fluorescent Assay for the Rapid Detection of SARS-CoV-2 Target RNA].

Objective: To develop a catalytic hairpin assembly (CHA)-based fluorescent assay for the detection of the target RNA of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), so as to realize the rapid nucleic acid testing of SARS-CoV-2.

Methods: A 24-nt segment of the SARS-CoV-2 nucleocapsid protein gene (N gene, NC_045512.2) was chosen as the target RNA and the hairpin motif 1 (H1) and hairpin motif 2 (H2) were designed based on the principle of CHA reaction.

Platelet-derived drug delivery systems: Pioneering treatment for cancer, cardiovascular diseases, infectious diseases, and beyond.

Platelets play a critical role as circulating cells in the human body and contribute to essential physiological processes such as blood clotting, hemostasis, vascular repair, and thrombus formation. Currently, platelets are extensively employed in the development of innovative biomimetic drug delivery systems, offering significant enhancements in circulation time, biocompatibility, and targeted delivery efficiency compared to conventional drug delivery approaches. Leveraging the unique physiological functions of platelets, these platelet-derived drug delivery systems (DDSs) hold great promise for the treatment of diverse diseases, including cancer, cardiovascular diseases, infectious diseases, wound healing and other diseases.

The survival of murine hepatitis virus (a surrogate of SARS-CoV-2) on conventional packaging materials under cold chain conditions.

Introduction: The cold chain conditions have been suggested to facilitate long-distance transmission of SARS-CoV-2, but it is unclear how viable the virus is on cold chain packaging materials.

Methods: This study used the MHV-JHM strain of murine hepatitis virus as a model organism to investigate the viability of SARS-CoV-2 on foam, plastic, cardboard, and wood sheets at different temperatures (-40°C, -20°C, and 4°C). In addition, the ability of peracetic acid and sodium hypochlorite to eliminate the MHV-JHM on plastic and cardboard sheets were also evaluated.

Laccase as a useful assistant for maize to accelerate the phenanthrene degradation in soil.

Polycyclic aromatic hydrocarbon (PAH) pollution has attracted much attention due to their wide distribution in soil environment and serious harm to human health. In order to establish an efficient and eco-friendly technology for remediation of PAH-contaminated soil, phytoremediation utilizing maize assisted with enzyme remediation was explored in this study. The results showed that the participation of laccase could promote the degradation of phenanthrene (PHE) from soil and significantly reduce the accumulation of PHE in maize.

The role of microplastics in the process of laccase-assisted phytoremediation of phenanthrene-contaminated soil.

Polycyclic aromatic hydrocarbons (PAHs) are highly toxic organic pollutants widely distributed in terrestrial environments and laccase was considered as an effective enzyme in PAHs bioremediation. However, laccase-assisted phytoremediation of PAHs-contaminated soil has not been reported. Moreover, the overuse of plastic films in agriculture greatly increased the risk of co-existence of PAHs and microplastics in soil.

Genetically Engineered-Cell-Membrane Nanovesicles for Cancer Immunotherapy.

The advent of immunotherapy has marked a new era in cancer treatment, offering significant clinical benefits. Cell membrane as drug delivery materials has played a crucial role in enhancing cancer therapy because of their inherent biocompatibility and negligible immunogenicity. Different cell membranes are prepared into cell membrane nanovesicles (CMNs), but CMNs have limitations such as inefficient targeting ability, low efficacy, and unpredictable side effects.

Transcriptional and Epigenetic Alterations in the Progression of Non-Alcoholic Fatty Liver Disease and Biomarkers Helping to Diagnose Non-Alcoholic Steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of conditions from simple steatosis (non-alcoholic fatty liver (NAFL)) to non-alcoholic steatohepatitis (NASH), and its global prevalence continues to rise. NASH, the progressive form of NAFLD, has higher risks of liver and non-liver related adverse outcomes compared with those patients with NAFL alone. Therefore, the present study aimed to explore the mechanisms in the progression of NAFLD and to develop a model to diagnose NASH based on the transcriptome and epigenome.