Sensitive and Deep Coverage Phosphoproteome Detection Method Reveals Spleen as a More Sensitive Organ than Liver in Early Detection of Liver Fibrosis-Related Signaling Protein Dysregulation.

Although cathepsin S is transported from the spleen to the liver, where it cleaves collagen XVIII to produce endostatin and plays a critical role in the onset of early liver fibrosis, the relationship between liver fibrosis and spleen function remains underexplored. Given the roles of phosphorylation in disease, understanding its regulatory mechanism in early liver fibrosis is crucial. Despite advances in mass spectrometry enhancing phosphoproteomics, its application is limited by small clinical samples and subtle protein changes.

N-glycosylation in the SERPIN domain of C1-Esterase Inhibitor in hereditary angioedema.

Hereditary angioedema is an autosomal dominant disorder caused by defects in C1-esterase inhibitor (C1-INH), resulting in poorly controlled activation of the kallikrein-kinin system and bradykinin overproduction. C1-INH is a heavily glycosylated protein in the serine protease inhibitor (SERPIN) family, yet the role of these glycosylation sites remains unclear. To elucidate the functional impact of N-glycosylation in the SERPIN domain of C1-INH, we engineered four sets consisting of 26 variants at or near the N-linked sequon (NXS/T).

ABCA6 Regulates Chondrogenesis and Inhibits Joint Degeneration via Orchestrated Cholesterol Efflux and Cellular Senescence.

Patellar dysplasia (PD) can cause patellar dislocation and subsequent osteoarthritis (OA) development. Herein, a novel ABCA6 mutation contributing to a four-generation family with familiar patellar dysplasia (FPD) is identified. In this study, whole exome sequencing (WES) and genetic linkage analysis across a four-generation lineage presenting with six cases of FPD are conducted.

Perfluorohexane Sulfonic Acid Disrupts the Immune Microenvironment for Spermatogenesis by Damaging the Structure of the Blood-Testis Barrier in Mice.

Perfluorohexane sulfonic acid (PFHxS) is extensively used in waterproof coatings and fire-fighting foams, and several studies have found it to be a potential health hazard, but there is still unknown about its effects on spermatogenesis. Our results showed that PFHxS-treated mice have significant reproductive toxicity, including a decrease in sperm count and motility, and the levels of sex hormones (P < 0.05).

Youthful Stem Cell Microenvironments: Rejuvenating Aged Bone Repair Through Mitochondrial Homeostasis Remodeling.

Extracellular matrix (ECM) derived from mesenchymal stem cells regulates antioxidant properties and bone metabolism by providing a favorable extracellular microenvironment. However, its functional role and molecular mechanism in mitochondrial function regulation and aged bone regeneration remain insufficiently elucidated. This proteomic analysis has revealed a greater abundance of proteins supporting mitochondrial function in the young ECM (Y-ECM) secreted by young bone marrow-derived mesenchymal stem cells (BMMSCs) compared to the aged ECM (A-ECM).

GABAergic Progenitor Cell Graft Rescues Cognitive Deficits in Fragile X Syndrome Mice.

Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder characterized by a range of clinical manifestations with no effective treatment strategy to date. Here, transplantation of GABAergic precursor cells from the medial ganglionic eminence (MGE) is demonstrated to significantly improve cognitive performance in Fmr1 knockout (KO) mice. Within the hippocampus of Fmr1-KO mice, MGE-derived cells from wild-type donor mice survive, migrate, differentiate into functionally mature interneurons, and form inhibitory synaptic connections with host pyramidal neurons.

Left Insula and Right Middle Temporal Gyrus Dominate Cortical Network Discriminating Arousal-dependent Emotions.

Emotion processing is an integral part of everyone's life. The basic neural circuits involved in emotion perception are becoming clear, though the emotion's cognitive processing remains under investigation. Utilizing the stereo-electroencephalograph with high temporal-spatial resolution, this study aims to decipher the neural pathway responsible for discriminating low-arousal and high-arousal emotions.

Circadian Rhythm Disruption Exacerbates Autoimmune Uveitis: The Essential Role of PER1 in Treg Cell Metabolic Support for Stability and Function.

Circadian rhythm plays a critical role in the progression of autoimmune diseases. While our previous study demonstrated the therapeutic effects of melatonin in experimental autoimmune uveitis, the involvement of circadian rhythm remained unclear. Using a light-induced circadian rhythm disruption model, we showed that disrupted circadian rhythms exacerbate autoimmune uveitis by impairing the stability and function of Treg cells.

Nanosize Non-Viral Gene Therapy Reverses Senescence Reprograming Driven by PBRM1 Deficiency to Suppress iCCA Progression.

Polybromo-1 (PBRM1) serves as a crucial regulator of gene transcription in various tumors, including intrahepatic cholangiocarcinoma (iCCA). However, the exact role of PBRM1 in iCCA and the mechanism by which it regulates downstream target genes remain unclear. This research has revealed that PBRM1 is significantly downregulated in iCCA tissues, and this reduced expression is linked to aggressive clinicopathological features and a poor prognosis.

Unveiling the Werner-Type Cluster Chemistry of Heterometallic 4f/Post-Transition Metals: A {DyBi} Complex Exhibiting Quantum Tunneling Steps in the Hysteresis Loops and its 1-D Congener.

A new [DyBiOCl(saph)] () Werner-type cluster has been prepared, which is the first Dy/Bi polynuclear compound with no metal-metal bond and one of the very few Ln-Bi (Ln = lanthanide) heterometallic complexes reported to date. The molecular compound has been deliberately transformed to its 1-D analogue [DyBiO(N)(saph)] () via the replacement of the terminal Cl ions by end-to-end bridging N groups. The overall metallic skeleton of (and ) can be described as consisting of a diamagnetic {Bi} unit with an elongated trigonal bipyramidal topology, surrounded by a magnetic {Dy} equilateral triangle, which does not contain μ-oxo/hydroxo/alkoxo groups.

Polydopamine Nanohydrogel Decorated Adhesive and Responsive Hierarchical Microcarriers for Deafness Protection.

Cisplatin-induced ototoxicity is attributed to the aberrant accumulation of reactive oxygen species (ROS) within the inner ear. Antioxidants represented by α-lipoic acid (ALA) have been demonstrated to scavenge ROS in the cochlea, while effective delivery of these agents in vivo remains a major challenge. Here, a novel polydopamine (PDA) nanogel decorated adhesive and responsive hierarchical microcarriers for controllable is presented ALA delivery and deafness prevention.

KSHV hijacks the antiviral kinase IKKε to initiate lytic replication.

IKKε is a traditional antiviral kinase known for positively regulating the production of type I interferon (IFN) and the expression of IFN-stimulated genes (ISGs) during various virus infections. However, through an inhibitor screen targeting cellular kinases, we found that IKKε plays a crucial role in the lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV). Mechanistically, during KSHV lytic replication, IKKε undergoes significant SUMOylation at both Lys321 and Lys549 by the viral SUMO E3 ligase ORF45.

Exploration and verification of the therapeutic mechanism of shenfu injection in sepsis-induced myocardial injury.

Background: Shenfu injection (SFI), derived from a traditional Chinese medicine (TCM) prescription, is an effective drug for the treatment of sepsis-induced myocardial injury (SIMI) with good efficacy, but its exact therapeutic mechanism remains unclear.

Methods: SwissTargetPrediction and GeneCards database were used to obtain relevant targets for SFI and SIMI. STRING 11.

Development and laboratory evaluation of a novel IoT-based electric-driven metering system for high precision garlic planter.

In order to address many issues, such as the inconsistent and unreliable seeding process in traditional mechanical garlic seed metering systems (SMS), as well as the lack of ability to monitor the effectiveness of the seeding, a highly accurate electric-driven metering system (EDMS) was developed and created specifically for garlic seed planters. This study provided a description of the overall structure and functioning principle, as well as an analysis of the mechanism for smooth transit and delivery. A combination of an infrared (IR) sensor, Arduino Mega board, stepper motor, speed sensor, and a Wi-Fi module was employed to operate the EDMS, as well as monitor and count the quantity of garlic seeds during the planting process and determine the qualified rate (QR) and missing rate (MR).

FBXW7 metabolic reprogramming inhibits the development of colon cancer by down-regulating the activity of arginine/mToR pathways.

FBXW7 is a tumor suppressor gene that regulates metabolism and is associated with the onset and progression of colorectal cancer (CRC)), however, the precise mechanism whereby FBXW7 participates in the metabolic reprogramming of CRC remains unclear. Here, the research aims to reveal the association between the expression of FBXW7 and clinical variables and to investigate the molecular mechanism by which FBXW7 plays a critical role in the development of CRC. The clinical importance of FBXW7 in CRC was determined by immunohistochemistry.

Bimodal In Situ Analyzer for Circular RNA in Extracellular Vesicles Combined with Machine Learning for Accurate Gastric Cancer Detection.

Circular RNAs in extracellular vesicles (EV-circRNAs) are gaining recognition as potential biomarkers for the diagnosis of gastric cancer (GC). Most current research is focused on identifying new biomarkers and their functional significance in disease regulation. However, the practical application of EV-circRNAs in the early diagnosis of GC is yet to be thoroughly explored due to the low accuracy of EV-circRNAs analysis.

Does financial asset allocation term structure affect audit fees? Evidence from China.

The financialization of real enterprises presents a dilemma for China's economic development. This study examines the impact of the financial asset allocation term structure on audit fees using a sample of Chinese A-share listed companies from 2009 to 2019. It also investigates the mediating role of financial risk and the moderating role of independent director characteristics.

Used economy market insight: Sailboat industry pricing mechanism and regional effects.

With the popularity of circular economy around the world, transactions in the second-hand sailboat market are extremely active. Determining pricing strategies and exploring their regional effects is a blank area of existing research and has important practical and statistical significance. Therefore, this article uses the random forest model and XGBoost algorithm to identify core price indicators, and uses an innovative rolling NAR dynamic neural network model to simulate and predict second-hand sailboat price data.

Inverse association of oxidative balance score with depression and specific depressive symptoms among cancer population: Insights from the NHANES (2005-2020).

Background: The rising prevalence of depression among cancer patients is alarming. This study examines the relationship between the Oxidative Balance Score (OBS)-a composite measure of dietary and lifestyle factors-and depression, including specific depressive symptoms in this population.

Methods: Data were analyzed from 3,280 adult cancer patients collected in NHANES from 2005-2020.

Composition and functional diversity of soil and water microbial communities in the rice-crab symbiosis system.

Rice-crab co-culture is an environmentally friendly agricultural and aquaculture technology with high economic and ecological value. In order to clarify the structure and function of soil and water microbial communities in the rice-crab symbiosis system, the standard rice-crab field with a ring groove was used as the research object. High-throughput sequencing was performed with rice field water samples to analyze the species and abundance differences of soil bacteria and fungi.

Bonding Features of Period 3 and Period 1 Two-Dimensional Superatoms.

Despite being studied for almost two centuries, aromaticity has always been a controversial concept. We previously proposed a unified aromatic rule for π-conjugated systems by two-dimensional (2D) superatomic-molecule theory, where benzenoid rings are treated as period 2 2D superatoms (3π-N, 4π-O, 5π-F, 6π-Ne) and, further, bond to form 2D superatomic molecules. Herein, to build a 2D periodic table, we further extend the theory to period 3 (7π-P, 8π-S, 9π-Cl, 10π-Ar) and period 1 (1π-H, 2π-He) elements.

Is reflux hypersensitivity truly a functional gastrointestinal disorder? A retrospective cross-sectional study.

Background: According to Rome IV, reflux hypersensitivity (RH) represents a novel form of functional esophageal disorder. This study was designed to compare the clinical features of three types of endoscopic-negative heartburn: RH, nonerosive reflux disease (NERD), and functional heartburn (FH).

Methods: Patients with heartburn in a medical center from 01/01/2017 to 10/31/2021 were included.

Exploring potential drug targets for SLE through Mendelian randomization and network pharmacology.

Background: Systemic lupus erythematosus (SLE) is a complex and incurable autoimmune disease, so several drug remission for SLE symptoms have been developed and used at present. However, treatment varies by patient and disease activity, and existing medications for SLE were far from satisfactory. Novel drug targets to be found for SLE therapy are still needed.

CircDNA2-Educated YTHDF2 Phase Separation Promotes PM-Induced Malignant Transformation Through the Blunting of GADD45A Expression.

Substantial epidemiological evidence suggests a significant correlation between particulate matter 2.5 (PM) and lung cancer. However, the mechanism underlying this association needs to be further elucidated.