Enzymatic synthesis and functional characterization of site-specific S/O-linked N-glycopeptides: Elucidating the impact of glycosidic linkage patterns on bioactivity.

Glycoengineering of therapeutic peptides/proteins has been hindered by the fact that no cost-effective and scalable strategy is currently available to install a β-N-acetylglucosamine (GlcNAc) residue to a pre-determined Asn site in peptides/proteins, to be further glycosylated by N-glycan. In this study, we developed a two-step enzymatic method to prepare N-glycan-modified peptides with natural β-S/O-glycosylation linkage by sequentially catalyzed by the S/O-HexNAc-transferase from Streptomyces venezuelae ATCC 15439 (SvGT) and the N180H mutant of endoglycosidase from Coprinopsis cinerea (EndoCC). To unravel how glycosylation linkage patterns and glycosylation extent impact the bioactivity of the glycopeptides, cell-based receptor activation potency and in vivo hypoglycemic activity were assayed for β-S/O/N-glycosylated glucagon-like peptide-1 (GLP-1) analogues.

RVG29 and platelet membrane-modified pseudo-mitochondria for cascade targeting of cyclosporin a in traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Cyclosporin A (CsA) is a promising drug for TBI, as it can protect neuronal mitochondria from dysfunction and apoptosis. However, CsA also has serious limitations, such as poor blood-brain barrier (BBB) penetration, non-selective distribution characteristic, and immunosuppressive effects.

Laminarin-mediated oral delivery of miRNA-223 for targeted macrophage polarization in inflammatory bowel disease.

Intestinal inflammatory disorders, such as ulcerative colitis, are driven by excessive pro-inflammatory M1 macrophages, leading to tissue damage and chronic inflammation. MicroRNA-223 (miRNA-223) presents a promising therapeutic approach by shifting macrophage polarization from the M1 to the anti-inflammatory M2 phenotype, thereby reducing inflammation. However, oral delivery of miRNA-223 is hindered by its instability in the harsh gastrointestinal (GI) environment and the challenge of targeting colonic macrophages.

Immunoengineered mitochondria for efficient therapy of acute organ injuries via modulation of inflammation and cell repair.

Acute organ injuries represent a major public health concern, driven by inflammation and mitochondrial dysfunction, leading to cell damage and organ failure. In this study, we engineered neutrophil membrane-fused mitochondria (nMITO), which combine the injury-targeting and anti-inflammatory properties of neutrophil membrane proteins with the cell repairing function of mitochondria. nMITO effectively blocked inflammatory cascades and restored mitochondrial function, targeting both key mechanisms in acute organ injuries.

S100A8/A9 Promotes Dendritic Cell-Mediated Th17 Cell Response in Sjögren's Dry Eye Disease by Regulating the Acod1/STAT3 Pathway.

Purpose: To investigate the role of S100A8/A9 in the pathogenesis of Sjögren's dry eye disease (SjDED) and explore its potential mechanism of action.

Methods: S100A8/A9 expression was determined by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Tear secretion, corneal fluorescein staining, and hematoxylin and eosin staining were used to evaluate the effect of paquinimod, a S100A8/A9 inhibitor, on dry eye disease in nonobese diabetic (NOD) mice.

Machine Learning-Driven Prediction, Preparation, and Evaluation of Functional Nanomedicines Via Drug-Drug Self-Assembly.

Small molecules as nanomedicine carriers offer advantages in drug loading and preparation. Selecting effective small molecules for stable nanomedicines is challenging. This study used artificial intelligence (AI) to screen drug combinations for self-assembling nanomedicines, employing physiochemical parameters to predict formation via machine learning.

Primary roles of soil evaporation and vegetation in driving terrestrial evapotranspiration across global drylands.

Terrestrial evapotranspiration (ET) is a key variable in the global water cycle, notably affected by climate change and vegetation greening. However, its intrinsic driving modes and the ways through which driving factors influence it remain largely unexplored. Here, we quantified the internal and external drivers behind the spatiotemporal variability of ET across global drylands at seasonal and annual temporal scales and component levels based on pixel-by-pixel partial correlation and ridge regression analyses.

Integration of eQTL and multi-omics comprehensive analysis of triacylglycerol synthase 1 (TGS1) as a prognostic and immunotherapeutic biomarker across pan-cancer.

An increasing number of expression quantitative trait loci (eQTLs) have been linked to tumorigenesis. In this study, we used Mendelian randomization (MR) to identify a novel cancer susceptibility gene, Trimethylguanosine Synthase 1 (TGS1). TGS1-induced hypermethylation at the 5' end of human telomerase RNA (hTR) impedes hTR accumulation, decreasing telomerase assembly factor levels and thus limiting telomere elongation, a crucial factor in tumor progression.

Impact of diabetes mellitus on the risk of Alzheimer's disease: a mendelian randomization study.

Background: The impact of diabetes on the risk of Alzheimer's disease remains uncertain. This study aimed to explore this issue from multiple perspectives by using the Mendelian randomization (MR) approach.

Methods: Instrumental variables for predicting six diabetic traits (including insulin and blood glucose), eight metabolic risk factors for diabetes (including total cholesterol and blood pressure), and seven diabetic genes were extracted from their summary data.

Effects of graphene far-infrared and social network interventions on depression, anxiety and dementia in older adults.

Background: Five-guaranteed elderly individuals are a special group of the elderly Chinese population faced with unique challenges; these individuals lack any financial resources (including support by relatives), and are solely reliant on the government to provide food, clothing, medical care, and housing as well as burials. In this article, we aim to investigate mood problems (depression, anxiety) and cognitive functioning in Five-guaranteed elderly individuals, and to validate the effectiveness of two promising interventions, graphene far-infrared intervention (GFII; an exploratory and noninvasive technique) and social network intervention (SNI), for elderly people to lay the foundation for future social service work.

Methods: To address the emotional and cognitive difficulties experienced by this special group, we designed this study, which is the first to apply GFII in this population.

Do OPEC+ policies help predict the oil price: A novel news-based predictor.

The OPEC+, composed of the Organization of the Petroleum Exporting Countries (OPEC) and non-OPEC oil-producing countries, exerts considerable influence over the global crude oil market. However, existing literature lacks a comprehensive application of this factor in oil price forecasting, primarily due to the complexity of measuring such policy evolutions. To address this research gap, this study develops a news-based OPEC+ policy index based on text mining methods for comprehensive analysis and forecasting of the oil price.

Anti-inflammatory mechanisms of neutrophil membrane-coated nanoparticles without drug loading.

Neutrophil membrane-coated nanoparticles (NM-NPs) are nanomedicines with traits of mimicking the surface properties and functions of neutrophils, which are the most abundant type of white blood cells in the human body. NM-NPs have been widely used as targeted drug delivery systems for various inflammatory diseases, but their intrinsic effects on inflammation are not fully characterized yet. This study found that NM-NPs could modulate inflammation by multiple mechanisms without drug loading.

Paris polyphylla ethanol extract and polyphyllin I ameliorate adenomyosis by inhibiting epithelial-mesenchymal transition.

Background: The active ingredients of the Chinese medical herb Paris polyphylla, P. polyphylla ethanol extract (PPE) and polyphyllin I (PPI), potentially inhibit epithelial-mesenchymal transition (EMT) in tumors. However, the roles of these ingredients in inhibiting EMT in adenomyosis (AM) remain to be explored.

Research progress in intratumoral heterogeneity and clinical significance of ovarian cancer.

Intratumoral heterogeneity has been a hot topic of cancer research in recent years, which has become a part of resolving cancer metastasis, recurrence and drug resistance. Intratumoral heterogeneity shows that cells undergo different division and proliferation during the process of tumor development, and their genomic cells exist in the process of tumor development. Protein and epigenetic changes can lead to differences in proliferation, migration and invasion, sensitivity and pharmacological prognosis of tumor cells, promote sustainable development and development of cancer cells, produce greater adaptability, and lead to metastasis, recurrence and drug resistance of malignant tumors.

Integrated DNA Methylation and Transcriptomics Analyses of Lacrimal Glands Identify the Potential Genes Implicated in the Development of Sjögren's Syndrome-Related Dry Eye.

Purpose: Sjögren's syndrome-related dry eye (SS-related dry eye) is an intractable autoimmune disease characterized by chronic inflammation of lacrimal glands (LGs), where epigenetic factors are proven to play a crucial role in the pathogenesis of this disease. However, the alteration of DNA methylation in LGs and its role in the pathogenesis of SS-related dry eye is still unknown. Here, we performed an integrated analysis of DNA methylation and RNA-Seq data in LGs to identify novel DNA methylation-regulated differentially expressed genes (MeDEGs) in the pathogenesis of SS-related dry eye.

Establishment and application of multiplex droplet digital polymerase chain reaction assay for bovine enterovirus, bovine coronavirus, and bovine rotavirus.

Bovine enterovirus (BEV), bovine coronavirus (BCoV), and bovine rotavirus (BRV) are still the major worldwide concerns in the health care of cattle, causing serious economic losses in the livestock industry. It is urgent to establish specific and sensitive methods to detect viruses for the early control of diseases. Droplet digital PCR (ddPCR) has been proposed to effectively detect viral particles, and it does not involve Ct values or standard curves.

An innovative predictive model for cervical cancer constructed around a gene profile associated with cholesterol metabolism.

Cholesterol metabolism is crucial for cell survival and cancer progression. The prognostic patterns of genes linked to cholesterol metabolism (CMAGs) in CESC, however, have received very little attention in research. From public databases, TCGA-CESC cohorts with mRNA expression patterns and the accompanying clinical information of patients were gathered.

The long non-coding RNA maternally expressed 3-micorRNA-15a-5p axis is modulated by melatonin and prevents nucleus pulposus cell inflammation and apoptosis.

Nucleus pulposus (NP) cell apoptosis is regarded as a critical risk factor for intervertebral disc degeneration (IVDD). Melatonin exerts a protective role on NP cells. The study concentrates on the role and mechanism of lncRNA MEG3 in melatonin-mediated effects on NP cells.

Effect of Norepinephrine on Peripheral Perfusion Index and Its Association With the Prognosis of Patients With Sepsis.

To evaluate whether the use of norepinephrine during the management of patients with sepsis affects the perfusion index (PI) and patient outcomes. We retrospectively studied patients with septic shock between January 2014 and December 2018 who had undergone Pulse index Continuous Cardiac Output-Plus cardiac output monitoring and received norepinephrine during the management. We collected data regarding basic clinical characteristics.

An anticoagulant/procoagulant self-converting and bleeding site-targeting systemic nanotherapy for rapidly controlling noncompressible bleeding without risk of thrombosis.

Background: Hemorrhage, in particular noncompressible hemorrhage, is the leading cause of casualties in combat trauma and civilian trauma. Although systemic agents can stop bleeding at both inaccessible and accessible injury sites, the application of systemic hemostats in clinics is strictly limited by the nontargeting ability of hemostats and their subsequent potential for thromboembolic complications.

Objectives: To engineer an anticoagulant/procoagulant self-converting and bleeding site-targeting systemic nanohemostat to rapidly control noncompressible bleeding without thrombosis risk.

Accurate based global adiabatic potential energy surfaces for the 1A'', 1A' and 2A' states of SiH.

Three accurate global adiabatic potential energy surfaces for the 1A'', 1A' and 2A' states of SiH are constructed by fitting numerous energies calculated at the aug-cc-pV(+d)Z and aug-cc-pV(5+d)Z basis sets based on the multi-reference configuration interaction level with Davidson correction. It is worth noting that the potential energy surface of the 1A'' state is established for the first time. The topographic features of these novel potential energy surfaces are investigated in detail and are very consistent with those obtained in the available literature.

Mechanical stress-caused chondrocyte dysfunction and cartilage injury can be attenuated by dioscin via activating sirtuin1/forkhead box O1.

Sirtuin1 (Sirt1)/forkhead box O1 (FoxO1) axis has been reported as a crucial regulator involved in chondral homeostasis of healthy or osteoarthritis (OA) cartilage. In our study, the aim is to investigate whether dioscin functions as an activator of Sirt1/FoxO1 to protect against mechanical stress-induced chondrocyte dysfunction in vitro and in vivo models. HERB and PubChem databases were implemented to predict dioscin-related gene targets.

Analysis of the Mechanism of GuizhiFuling Wan in Treating Adenomyosis Based on Network Pharmacology Combined with Molecular Docking and Experimental Verification.

Background: The effect of GuizhiFuling Wan (GFW) on adenomyosis (AM) is definite. This study aimed to explore the mechanism and key therapeutic targets of GFW in treating AM through network pharmacology combined with molecular docking and experimental verification.

Materials And Methods: In network pharmacology, firstly, the active components of GFW, its drug, and disease targets were screened through several related public databases, and GFW-AM common targets were obtained after the intersection.