In vivo self-assembled siRNAs within small extracellular vesicles attenuate LRRK2-induced neurodegeneration in Parkinson's disease models.

Rationale: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene play an important role in Parkinson's disease (PD) pathogenesis, and downregulation of LRRK2 has become a promising therapy for PD. Here, we developed a synthetic biology strategy for the self-assembly and delivery of small interfering RNAs (siRNAs) of LRRK2 into the substantia nigra via small extracellular vesicles (sEVs) using a genetic circuit (in the form of naked DNA plasmid) to attenuate PD-like phenotypes in mouse model.

Methods: We generated the genetic circuit encoding both a neuron-targeting rabies virus glycoprotein (RVG) tag and a LRRK2 siRNA under the control of a cytomegalovirus (CMV) promoter, and assessed its therapeutic effects using LRRK2 mouse models of PD.

A combined association of alanine aminotransferase, aspartate transaminase and bilirubin with sleep duration in aged 16-85 years (2005-2010).

Sleep is a vital restorative process that plays a pivotal role in maintaining the delicate equilibrium of mental and physical well-being. Both short and long sleep duration are associated with a range of adverse health outcomes. Numerous studies have consistently demonstrated a robust association between sleep duration and liver disease.

High-resolution mass spectrometry-based suspect and nontarget screening of natural toxins in foodstuffs and risk assessment of dietary exposure.

Daily dietary intake inevitably exposes individuals to various natural toxins, which may pose potential health threats. Focusing only on specific toxins could underestimate dietary risks. Therefore, we have developed a suspect and nontarget method based on ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) to screen both known and unknown natural toxins in various foodstuffs.

Decision-making of autonomous vehicles in interactions with jaywalkers: A risk-aware deep reinforcement learning approach.

Jaywalking, as a hazardous crossing behavior, leaves little time for drivers to anticipate and respond promptly, resulting in high crossing risks. The prevalence of Autonomous Vehicle (AV) technologies has offered new solutions for mitigating jaywalking risks. In this study, we propose a risk-aware deep reinforcement learning (DRL) approach for AVs to make decisions safely and efficiently in jaywalker-vehicle interactions.

Spraying KHPO Alleviates the Damage of Spring Low-Temperature Stress by Improving the Physiological Characteristics of Wheat Flag Leaves.

The low-temperature stress (LTS) in spring results in tremendous yield loss in wheat production, and the application of potassium dihydrogen phosphate (KHPO) can alleviate stress-induced damage. However, the underlying effect of spraying KHPO on the physiological characteristics of wheat flag leaves under spring LTS remains unclear. In this study, we investigated the effect of spraying KHPO on flag leaf physiological traits and yield under spring LTS, including treatments at 15 °C and spraying HO (CK), treatment at -4 °C and spraying HO (LT1), and treatment at -4 °C and spraying KHPO (LT2).

Suspect and nontarget screening of pesticides and their transformation products in agricultural products using liquid chromatography-high-resolution mass spectrometry.

Intensive agricultural production involves the extensive use of chemicals, leading to the presence of pesticides and their transformation products (TPs) in agricultural products. Our study developed a high-coverage method to map the occurrence of pesticides and their transformation products in agricultural products using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Initially, a suspect list of 1265 pesticides was compiled based on in-house standards and online databases to identify potential parent pesticides.

Five-Component [2 + 2 + 1 + 1] Tandem Benzannulation Leading to Multifunctionalized Aromatic Amines.

An unprecedented five-component [2 + 2 + 1 + 1] benzannulation strategy for regioselective assembly of densely functionalized aromatic amines from two ynals, two malononitriles, and sodium sulfinates is established. The benzannulation protocol enables the efficient installation of five substituents on a benzene ring via the formation of multiple chemical bonds in a single operation, providing various multifunctionalized aromatic primary amines in moderate to good yields. Additionally, three-component [3 + 2 + 1] cycloaddition of malononitriles, ynals, and NHSCN was also achieved to produce 2-amnopyridine derivatives with NHSCN serving as an ammonia surrogate.

Inulin alleviates atherosclerosis through improving lipid metabolism, inflammation, and gut microbiota in ApoE-knockout mice: the short-chain is more efficacious.

Introduction: Atherosclerosis (AS) is considered the underlying cause of many diseases, particularly cardiovascular and cerebrovascular diseases. Inulin, a type of fructan, has shown potential in improving atherosclerosis, although there are conflicting findings. It is hypothesized that the polymerization degree of inulin may largely influence its therapeutic effectiveness.

Multifunctional Bioactivity Electrospinning Nanofibers Encapsulating Emodin Provide a Potential Postoperative Management Strategy for Skin Cancer.

Skin cancer is threatening more and more people's health; its postoperative recurrence and wound infection are still critical challenges. Therefore, specialty wound dressings with multifunctional bioactivity are urgently desired. Emodin is a natural anthraquinone compound that has anti-cancer and anti-bacterial properties.

Physiological and transcriptomic analyses to determine the responses of the harmful algae Akashiwo sanguinea to phosphorus utilization.

Phosphorus (P) is an essential nutrient driving algal growth in aquatic ecosystems. Dissolved inorganic and organic P (DIP and DOP) are the main components in the marine P pools and are closely related to harmful algal blooms. The dinoflagellate Akashiwo sanguinea is a cosmopolitan species which frequently causes dense blooms in estuaries and coasts worldwide, while the availability of P to A.

A hybrid approach for modeling bicycle crash frequencies: Integrating random forest based SHAP model with random parameter negative binomial regression model.

To effectively capture and explain complex, nonlinear relationships within bicycle crash frequency data and account for unobserved heterogeneity simultaneously, this study proposes a new hybrid framework that combines the Random Forest-based SHapley Additive exPlanations (RF-SHAP) method with a random parameter negative binomial regression model (RPNB). First, four machine learning algorithms, including random forest (RF), support vector machine (SVM), gradient boosting machine (GBM), and Extreme Gradient Boosting (XGBoost), were compared for variable importance calculation. The RF algorithm, demonstrating the best performance, was selected and integrated into an interpretable machine learning-based method (i.

Profiling of phenolic composition in camellia oil and its correlative antioxidant properties analysis.

Less research has been conducted on the association between camellia oil's (CO) phenolic composition and antioxidant capability. In this study, the phenolic profile of CO and its connection to antioxidant capacity were examined utilizing a combination of widely-targeted phenolic metabolomics and multivariate statistical analysis. A total of 751 phenolics were discovered.

A molecular ferroelectric thin film of imidazolium perchlorate on silicon.

Molecular ferroelectrics have garnered significant attention due to their structural tunability, low synthesis temperature, and high flexibility. Herein, we successfully synthesized imidazole perchlorate (ImClO) single crystals and high-quality, highly-oriented thin films on Si substrates. These films demonstrated a high inverse piezoelectric coefficient of 55.

3D chitosan scaffolds loaded with ZnO nanoparticles for bone tissue engineering.

Bone defect has always been a difficult problem in clinical work. According to the current research results, tissue engineered scaffolds with a single function, structure, and composition are not sufficient to repair complex bone defects. In this work, a three-dimensional (3D) chitosan degradable composite scaffold loaded with zinc oxide (ZnO) was constructed, and the effect of ZnO content on scaffold performance and osteogenesis was explored.

Barrier Membrane with Janus Function and Structure for Guided Bone Regeneration.

Guided bone regeneration (GBR) technology has been demonstrated to be an effective method for reconstructing bone defects. A membrane is used to cover the bone defect to stop soft tissue from growing into it. The biosurface design of the barrier membrane is key to the technology.

High-coverage identification of hydroxyl compounds based on pyridine derivatization-assisted liquid chromatography mass spectrometry.

Hydroxyl compounds are widely present in plants and play essential roles in plant growth and development. High-coverage detection of hydroxyl compounds is crucial for understanding the physiological processes of plants. Despite the prevalence of chemical derivatization-assisted liquid chromatography-high resolution mass spectrometry (CD-LC-HRMS) in high-coverage detection of compounds with diverse functional groups, the confident identification of these compounds after derivatization remains a significant challenge.

Short time-series expression transcriptome data reveal the gene expression patterns and potential biomarkers of blood infection with LPS and poly (I:C) in Mandarin fish (Siniperca chuatsi).

Blood transcriptomics has emerged as a vital tool for tracking the immune system and supporting disease diagnosis, prognosis, treatment, and research. The present study was conducted to analyze the gene expression profile and potential biomarker candidates using the whole blood of mandarin fish (Siniperca chuatsi) infected with LPS or poly (I:C) at 0 h, 3 h, 6 h, and 12 h. Our data suggest that 310 shared differentially expressed genes (DEGs) were identified among each comparison group after LPS infection, and 137 shared DEGs were identified after poly (I:C) infection.

Valence-Change MnO-Coated Arsenene Nanosheets as a Pin1 Inhibitor for Hepatocellular Carcinoma Treatment.

The heterogeneity of hepatocellular carcinoma (HCC) can prevent effective treatment, emphasizing the need for more effective therapies. Herein, we employed arsenene nanosheets coated with manganese dioxide and polyethylene glycol (AMPNs) for the degradation of Pin1, which is universally overexpressed in HCC. By employing an "AND gate", AMPNs exhibited responsiveness toward excessive glutathione and hydrogen peroxide within the tumor microenvironment, thereby selectively releasing AsO to mitigate potential side effects of AsO.

Metal ion-complexed DNA probe coupled with CRISPR/Cas12a amplification and AuNPs for sensitive colorimetric assay of metallothionein in fish.

The accurate and sensitive detection of metallothionein (MT) is of great significance in the fields of biomedical, toxicological and environmental sciences. In this work, based on the high affinity interaction between MT and the heavy metal ions of Hg and the significant signal amplification capability of Cas12a/crRNA enzyme as well, we report a simple and highly sensitive method for visual detection of MT, a biomarker in fish for heavy metal ion-induced water bio-pollution. The target MT molecules bind Hg in the Hg- complexed hairpin DNA probes to unfold the hairpin structure into ssDNAs, which hybridize with the partial dsDNA duplexes via strand displacement to yield specific sequence-containing dsDNAs.

Target-responsive triplex aptamer nanoswitch enables label-free and ultrasensitive detection of antibody in human serum via lighting-up RNA aptamer transcriptions.

Accurate and sensitive monitoring of the concentration change of anti-digoxigenin (Anti-Dig) antibody is of great importance for diagnosing infectious and immunological diseases. Combining a novel triplex aptamer nanoswitch and the high signal-to-noise ratio of lighting-up RNA aptamer signal amplification, a label-free and ultrasensitive fluorescent sensing approach for detecting Anti-Dig antibodies is described. The target Anti-Dig antibodies recognize and bind with the nanoswitch to open its triplex helix stem structure to release Taq DNA polymerase and short ssDNA primer simultaneously, which activates the Taq DNA polymerase to initiate downstream strand extension of ssDNA primer to yield specific dsDNA containing RNA promoter sequence.

SOX9 functionalized scaffolds as a barrier to against cartilage fibrosis.

Hyaline cartilage regeneration will bring evangel to millions of people suffered from cartilage diseases. However, uncontrollable cartilage fibrosis and matrix mineralization are the primary causes of cartilage regeneration failure in many tissue engineering scaffolds. This study presents a new attempt to avoid endochondral ossification or fibrosis in cartilage regeneration therapy by establishing biochemical regulatory area.

Toxin production and transcriptomic response to nitrate concentrations in the toxic dinoflagellate Alexandrium tamarense.

The bloom-forming dinoflagellate Alexandrium tamarense is one of the most important producers of paralytic shellfish poisoning toxins. Annually recurrent blooms of this dinoflagellate species is associated with the incremental nitrogen influx, especially excessive nitrate input. However, limited studies have been conducted on the toxin production and underlying molecular regulation mechanisms of A.

The Role of Microglia with Mitochondrial Dysfunction and Its Therapeutic Prospects in Alzheimer's Disease.

Alzheimer's disease (AD), a primary cause of dementia, is rapidly emerging as one of the most financially taxing, lethal, and burdensome diseases of the 21st century. Increasing evidence suggests that microglia-mediated neuroinflammation plays a key role in both the initiation and progression of AD. Recently, emerging evidence has demonstrated mitochondrial dysfunction, particular in microglia where precedes neuroinflammation in AD.