Drug Development.

Background: Alzheimer's disease neuropathology involves the deposition in brain of aggregates enriched with microtubule-binding-region (MTBR) of tau adopting an abnormal conformation between residues 306-378 in the core of aggregates. Anti-tau drugs targeting around this domain have the potential to interfere with the cell-to-cell propagation of pathological tau. Bepranemab is a humanized monoclonal Ig4 antibody binding to tau residues 235-250.

Drug Development.

Background: A traditional method for validating a surrogate endpoint typically involves assessing the correlation between changes in biomarkers and changes in clinical endpoints using Pearson's and/or Spearman's correlation. However, this approach may not provide an accurate representation of the true correlation due to several reasons: (i) it only considers the change from baseline to the last visit and does not use all post-baseline longitudinal data; (ii) the raw change has large variability; (iii) it does remove the within-subject variability. The objective of this presentation is to propose two alternative approaches that overcome these limitations and allow for a more accurate estimation of the true correlation using all available longitudinal data.

Unveiling the nexus between irradiation and phase reconstruction in tin-lead perovskite solar cells.

Tin-lead perovskites provide an ideal bandgap for narrow-bandgap perovskites in all-perovskite tandem solar cells, fundamentally improving power conversion efficiency. However, light-induced degradation in ambient air is a major issue that can hinder the long-term operational stability of these devices. Understanding the specifics of what occurs during this pathway provides the direction for improving device stability.

Understanding Awareness, Utilization, and the Awareness-Utilization Gap of HIV PrEP and nPEP Among Young MSM in China.

HIV/AIDS remains a significant public health challenge in China, particularly among men who have sex with men (MSM). Pre-Exposure Prophylaxis (PrEP) and non-occupational post-exposure Prophylaxis (nPEP) are effective interventions to reduce HIV transmission in high-risk populations. This study assessed awareness and utilization levels of PrEP and nPEP among young MSM (YMSM) aged 18-29 in China and examined associated factors.

[Discussion on the commonalities of scalp acupuncture schools and the feasibility of a unified scalp acupuncture protocol].

The data of 44 scalp acupuncture schools are collected to analyze their commonalities in theoretical foundations, needling sites, techniques, and indications. The integration of these characteristics into an optimized, unified scalp acupuncture protocol has become an inevitable trend. The paper discusses the potential for a unified scalp acupuncture protocol from aspects such as theoretical unification, the relationships between point areas, lines, and sites, and needle numbers.

Structural equation modeling of dietary patterns and association with vitamin D levels in children aged 9-16 years in Guangzhou, China.

Background: Vitamin D deficiency and insufficiency represent critical public health concerns on a global scale. Due to the increase in indoor activities, the role of dietary intake of vitamin D has become increasingly prominent. However, previous studies have focused solely on a single food item.

Visualization of Hg Stress on Plant Health at the Subcellular Level Revealed by a Highly Sensitive Fluorescent Sensor.

The presence of Hg causes substantial stress to plants, adversely affecting growth and health by disrupting cell cycle divisions, photosynthesis, and ionic homeostasis. Accurate visualization of the spatiotemporal distribution of Hg in plant tissues is crucial for the management of Hg pollution; however, the related research is still at its early stage. Herein, a small-molecule amphiphilic fluorescent probe (termed ) was developed for the specific detection of Hg with a high sensitivity (~16 nM).

Integrating multi-omics features enables non-invasive early diagnosis and treatment response prediction of diffuse large B-cell lymphoma.

Background: Multi-omics features of cell-free DNA (cfDNA) can effectively improve the performance of non-invasive early diagnosis and prognosis of cancer. However, multimodal characterization of cfDNA remains technically challenging.

Methods: We developed a comprehensive multi-omics solution (COMOS) to specifically obtain an extensive fragmentomics landscape, presented by breakpoint characteristics of nucleosomes, CpG islands, DNase clusters and enhancers, besides typical methylation, copy number alteration of cfDNA.

Accurate localization of indoor high similarity scenes using visual slam combined with loop closure detection algorithm.

Accurate localization is a critical technology for the application of intelligent robots and automation systems in complex indoor environments. Traditional visual SLAM (Simultaneous Localization and Mapping) techniques often face challenges with localization accuracy in high similarity scenes. To address this issue, this paper proposes an improved visual SLAM loop closure detection algorithm that integrates deep learning techniques.

A nomogram for predicting prognostic risk factors in individuals with poor grade aneurysmal subarachnoid hemorrhage: a retrospective study.

Poor-grade aneurysmal subarachnoid hemorrhage (PGASAH) is associated with high mortality and morbidity despite advanced treatments. Accurate prediction of prognosis remains a clinical challenge. This study aimed to identify independent risk factors and develop a predictive nomogram for unfavorable outcomes in PGASAH patients.

Disruption of tumor-intrinsic PGAM5 increases anti-PD-1 efficacy through the CCL2 signaling pathway.

Background: Immunosuppressive phenotype compromised immunotherapy efficacy of hepatocellular carcinoma. Tumor cells intrinsic mitochondria dynamics could pass effects on the extracellular microenvironment through mtDNA stress. PGAM5 anchors at mitochondria and regulates mitochondria functions.

Research Progress in Blastic Plasmacytoid Dendritic Cell Neoplasm.

Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is an extremely rare invasive tumor with poor prognosis.The common clinical manifestations of BPDCN include skin injury,bone marrow involvement,and tumor cell spread.BPDCN is often misdiagnosed as other diseases and its diagnosis often requires a combination of clinical manifestations,imaging,histology,and immunophenotyping.

Targeted Degradation of HCV Polymerase by GalNAc-Conjugated ApTACs for Pan-Genotypic Antiviral Therapy with High Resistance Barriers.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Although interferon-free direct-acting antivirals have led to significant advancements in the treatment of HCV infection, the high genetic variability of the virus and the emergence of acquired drug resistance pose potential threats to their effectiveness. In this study, we develop a broad-spectrum aptamer-based proteolysis targeting chimera, designated dNS5B, which effectively degrades both pan-genotypic NS5B polymerase and drug-resistant mutants through ubiquitin proteasome system.

Polystyrene Nanomicroplastics Aggravate Ammonia-Induced Neurotoxic Effects in Zebrafish Embryos.

The highly hazardous chemical ammonia has been proven to be absorbed by nanoparticles, thereby exerting highly toxic effects on aquatic organisms. As a ubiquitous pollutant in aquatic environments, polystyrene nanomicroplastics (PSNPs) have shown strong adsorption capacity due to their large surface area. Therefore, the potential joint effects of ammonia and PSNPs need to be clarified.

Factors and Mechanisms Affecting Arsenic Migration in Cultivated Soils Irrigated with Contained Arsenic Brackish Groundwater.

Contained arsenic (As) and unsafe brackish groundwater irrigation can lead to serious As pollution and increase the ecological risk in cultivated soils. However, little is known about how Fe oxides and microbes affect As migration during soil irrigation processes involving arsenic-contaminated brackish groundwater. In this study, the samples (porewater and soil) were collected through the dynamic soil column experiments to explore the As migration process and its effect factors during soil irrigation.

Observed Shyness-Related Behavioral Responses to a Self-Presentation Speech Task: A Study Comparing Chinese and Canadian Children.

Past research suggests that expressions of shyness are associated with several distinct behaviors that may differ between Eastern and Western cultures. However, this evidence has largely been derived from subjective ratings, such self-, teacher-, and parent-report measures. In this study, we examined between-country differences on measures of directly observed shyness-related behaviors during a speech task in children.

Effect of Different Probiotic Fermentations on the Quality of Plant-Based Hempseed Fermented Milk.

This study investigated the effects of three different single-strain probiotics XD117, LC-37, and LGG, on the quality of hempseed fermented milk. The main findings were that adding probiotics increased the inhibition rate of α-glucosidase and pancreatic lipase in hempseed fermented milk significantly. Non-targeted metabolomic correlation analysis results confirmed that 14 substances, including three flavonoids, six amino acids and their derivatives, and five short peptides, were positively correlated with the hypoglycemic and hypolipidemic activities of hempseed fermented milk.

Parallel Bayesian Optimization of Thermophysical Properties of Low Thermal Conductivity Materials Using the Transient Plane Source Method in the Body-Fitted Coordinate.

The transient plane source (TPS) method heat transfer model was established. A body-fitted coordinate system is proposed to transform the unstructured grid structure to improve the speed of solving the heat transfer direct problem of the winding probe. A parallel Bayesian optimization algorithm based on a multi-objective hybrid strategy (MHS) is proposed based on an inverse problem.

Insights into the Donkey Hindgut Microbiome Using Metagenome-Assembled Genomes.

The gut microbiota plays an important role in the digestion, absorption, and metabolism of nutrients, as well as in the immunity, health, and behavior of donkeys. While reference genomes and gut microbial gene catalogs have been helpful in understanding the composition of the donkey, there is still a significant gap in sequencing and understanding the functional aspects of donkey gut microbial genomes. In this study, we analyzed metagenomic sequencing data from 26 donkeys' gut samples and successfully assembled 844 microbial metagenome-assembled genomes (MAGs).

Effect of conjugative transfer of antibiotic resistance genes mediated by plasmids on the microecology of different intestinal segments.

Introduction: The conjugative transfer of antibiotic resistance genes (ARGs) mediated by plasmids occurred in different intestinal segments of mice was explored.

Methods: The location of ARG donor bacteria and ARGs was investigated by qPCR, flow cytometry, and small animal imaging. The resistant microbiota was analyzed by gene amplification sequencing.

Mitochondria: a crucial factor in the progression and drug resistance of colorectal cancer.

Colorectal cancer (CRC), as one of the malignant tumors with the highest incidence and mortality rates worldwide in recent years, originating primarily from the mucosal tissues of the colon or rectum, and has the potential to rapidly develop into invasive cancer. Its pathogenesis is complex, involving a multitude of factors including genetic background, lifestyle, and dietary habits. Early detection and treatment are key to improving survival rates for patients with CRC.

Evaluating the prognostic relevance of neutrophil-to-lymphocyte ratio in cervical cancer: a systematic review and meta-analysis.

Background: Recently, the neutrophil-to-lymphocyte ratio (NLR) has emerged as a promising prognostic marker for survival outcomes in individuals affected cervical cancer. However, research specifically focusing on the prognostic relevance of NLR across different cancer stages and in cases of recurrent metastases remains scant.

Methods: We executed a systematic review of the literature from databases including PubMed, Embase, the Cochrane Library, and Web of Science, covering publications up to March 3, 2024.

PLK1 inhibition impairs erythroid differentiation.

Polo-like kinase 1 (PLK1), a key regulator of the G2/M phase in mitosis, is frequently overexpressed in numerous tumors. Although PLK1 inhibitors have emerged as promising therapeutic agents for cancer, their use has been linked to significant anemia in a subset of patients, yet the underlying mechanisms remain poorly understood. In this study, we utilized an human umbilical cord blood-derived CD34 cell-based erythroid differentiation system, alongside a murine model, to investigate the impact of PLK1 inhibitors on erythropoiesis.