Dynamic properties of transcriptional condensates modulate CRISPRa-mediated gene activation.

CRISPR activation (CRISPRa) is a powerful tool for endogenous gene activation, yet the mechanisms underlying its optimal transcriptional activation remain unclear. By monitoring real-time transcriptional bursts, we find that CRISPRa modulates both burst duration and amplitude. Our quantitative imaging reveals that CRISPR-SunTag activators, with three tandem VP64-p65-Rta (VPR), form liquid-like transcriptional condensates and exhibit high activation potency.

Multifunctional Liposome Delivery System Based on Ursodeoxycholic Acid Sodium for the Encapsulation of Silibinin and Combined Treatment of Alcoholic Liver Injury.

Alcohol liver disease (ALD) is a chronic liver disorder resulting from long-term heavy alcohol consumption. The pathogenesis of ALD is multifactorial, and existing therapeutic agents primarily target specific aspects of the disease while presenting significant side effects, including drug-induced liver injury and hepatobiliary disease. Silibinin (SLB) has attracted widespread attention for its hepatoprotective effects and favorable safety profile.

The shared mechanism of barrier dysfunction in ulcerative colitis and Alzheimer's disease: DDIT4/IL1β neutrophil extracellular traps drive macrophages-mediated phagocytosis.

Ulcerative colitis (UC) and Alzheimer's disease (AD) share a common etiology as inflammatory diseases characterized by barrier deterioration. The aim of this study is to elucidate how neutrophil extracellular traps (NETs), serving as a comorbid etiological factor, can trigger the dysfunction in both the intestinal barrier and blood-brain barrier (BBB). Integrated bioinformatics analysis revealed 14 overlapped NETs-related differential expressed genes in UC and AD, which strongly featured barrier dysfunction.

Correction: Phosphatidylserine-functionalized liposomes-in-microgels for delivering genistein to effectively treat ulcerative colitis.

Correction for 'Phosphatidylserine-functionalized liposomes-in-microgels for delivering genistein to effectively treat ulcerative colitis' by Huijia Yan , , 2023, , 10404-10417, https://doi.org/10.1039/D3TB00812F.

Synergistic therapy with celastrol-curcumin multifunctional nanomedicine: Anti-hepatocellular carcinoma and reduced hepatotoxicity.

Hepatocellular carcinoma is one of the leading causes of cancer deaths globally and a key hindrance to extending life expectancy. Celastrol (CEL) demonstrates excellent antitumor activity, but faces challenges like low solubility and a narrow therapeutic window, limiting its clinical application. To address these limitations, drug combinations and nano-delivery systems have emerged as effective solutions.

Disulfidptosis and Its Hub Gene Slc3a2 Involved in Ulcerative Colitis Pathogenesis, Disease Progression, and Patient Responses to Biologic Therapies.

To analyze the role of disulfidptosis in ulcerative colitis (UC), large-scale datasets combined with weighted gene co-expression network analysis (WGCNA) and machine learning were utilized and analyzed. When the hub genes that are associated with UC disease phenotypes and have predictive performance were identified, immune cell infiltration and the CeRNA network were constructed, the role of hub genes in UC pathogenies and biotherapy were investigated, and molecular docking studies and mice-verified tests were carried out to further explore the potential core genes and potential target. Finally, we found 21 DRGs involved in UC pathogenesis, including SLC3A2, FLNA, CAPZB, TLN1, RPN1, etc.

Ursodeoxycholic acid grafted chitosan oligosaccharide self-assembled micelles with enhanced oral absorption and antidiabetic effect of oleanolic acid.

Oleanolic acid (OA) is a food-derived bioactive component with antidiabetic activity, but its water solubility and oral bioavailability are notably restricted. In this study, to overcome these limitations, ursodeoxycholic acid-modified chitosan oligosaccharide (UCOS) was synthesized to encapsulate OA in self-assembled nanomicelles (UCOS-OA). The encapsulation efficiency and drug loading of UCOS-OA were 86 % and 11 %, respectively.

Multifunctional carboxymethyl chitosan/oxidized carboxymethyl cellulose hydrogel loaded with ginsenoside Rg1 and polydopamine nanoparticles for infected diabetic wound healing.

Besides bacterial infection, diabetic wounds are often accompanied by local inflammatory response, oxidative stress imbalances, and vascular formation disorders, which are the main reasons for long-term non-healing of diabetic wounds. In order to solve this problem, Ch-OCMC-PDA NPs-Rg1 self-healing hydrogel was constructed by Schiff base reaction. With the addition of PDA NPs and Rg1, Ch-OCMC-PDA NPs-Rg1 hydrogel showed excellent physical properties, like compressive strength of 142 kPa, swelling ratio of 148.

Novel sodium tauroursodeoxycholate-based multifunctional liposomal delivery system for encapsulation of oleanolic acid and combination therapy of type 2 diabetes mellitus.

Liposomes have demonstrated great potential for drug delivery and diabetes treatment. However, hydrolysis by enzymes and emulsification by endogenous bile salts make liposomes unstable in the gastrointestinal tract. In this study, sodium tauroursodeoxycholate (TUDCNa)-based multifunctional bilosomes were designed to address the deficiencies of conventional liposomes.

Efficacy of immediate loading compared to conventional loading in implant-supported removable prostheses: a systematic review and meta-analysis.

Purpose: This systematic review and meta-analysis aimed to evaluate the efficacy of two different loading methods in implant-supported removable prostheses (partial dentures and full-maxillary dentures).

Methods: As of August 2023, three electronic databases and nine oral implant-related journals had been searched. Only randomised controlled trials (RCTs) that compare immediate loading with conventional loading in implant-supported removable prostheses were included.

SPECT/CT imaging of poor sleep quality in people with epilepsy.

Purpose: To analyze the characteristics of cerebral blood flow changes of poor sleep quality in people with epilepsy(PWE).

Methods: 90 PWE treated in The General Hospital of Ningxia Medical University from December 2021 to September 2023 were divided into poor sleep quality group (PSQG) and good sleep quality group (GSQG) according to the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI), to compare the differences in cerebral perfusion between the two groups of patients, so as to summarize the characteristics of cerebral blood flow changes of poor sleep quality in PWE.

Results: The positive rate of interictal single-photon emission computed tomography/computed tomography (SPECT/CT) was 76.

SOS1 gene family in mangrove (Kandelia obovata): Genome-wide identification, characterization, and expression analyses under salt and copper stress.

Background: Salt Overly Sensitive 1 (SOS1), a plasma membrane Na/H exchanger, is essential for plant salt tolerance. Salt damage is a significant abiotic stress that impacts plant species globally. All living organisms require copper (Cu), a necessary micronutrient and a protein cofactor for many biological and physiological processes.

Functional properties and molecular docking of different nanoparticles with ROS-sensitive phenylboronylated chitosan as the carrier.

Objective: To prepare chitosan-loaded nanoparticles (NPs) that enhance the oral bioavailability of puerarin (Pur) and render it responsive to reactive oxygen species (ROS).

Significance: This research makes substantial progress towards the theory of intelligent drug delivery, offering a new reference for combining Pur with other natural medicinal active ingredients.

Methods: The acylation reaction between chitosan and ROS-sensitive 3-carboxyphenylboronic acid (PBA) was used to synthesise ROS-sensitive phenylboronylated chitosan (PBACS).

Hyperaccumulators' Diversity Enhances Cd-Contaminated Soil Restoration and Reduces Rice Cd Uptake under an Intercropping System.

Cd accumulation in rice-cultivated soils across China is a major problem that needs to be tackled. A plot experiment was carried out using heavy metal (HM) hyperaccumulators L. and (L.

Mesenchymal stem cells ameliorate inflammation and pyroptosis in diabetic cardiomyopathy via the miRNA-223-3p/NLRP3 pathway.

Background: Diabetic cardiomyopathy (DCM) stands as the primary cause of heart failure and mortality among patients with diabetes. Nevertheless, conventional treatment approaches are limited in their ability to effectively prevent myocardial tissue damage itself. Mesenchymal stem cell (MSC) therapy exhibits immense potential for treating DCM; however, the precise mechanisms involved in regulating inflammatory responses and pyroptosis processes, an emerging form of cellular death, within myocardial cells remain elusive.

Tryptophan Metabolism in Alzheimer's Disease with the Involvement of Microglia and Astrocyte Crosstalk and Gut-Brain Axis.

Alzheimer's disease (AD) is an age-dependent neurodegenerative disease characterized by extracellular Amyloid Aβ peptide (Aβ) deposition and intracellular Tau protein aggregation. Glia, especially microglia and astrocytes are core participants during the progression of AD and these cells are the mediators of Aβ clearance and degradation. The microbiota-gut-brain axis (MGBA) is a complex interactive network between the gut and brain involved in neurodegeneration.

Inhibition of miR-199b-5p reduces pathological alterations in osteoarthritis by potentially targeting and .

Osteoarthritis (OA) is a degenerative disease with a high prevalence in the elderly population, but our understanding of its mechanisms remains incomplete. Analysis of serum exosomal small RNA sequencing data from clinical patients and gene expression data from OA patient serum and cartilage obtained from the GEO database revealed a common dysregulated miRNA, miR-199b-5p. In vitro cell experiments demonstrated that miR-199b-5p inhibits chondrocyte vitality and promotes extracellular matrix degradation.

Myositis Autoantibody Profiles and Clinical Significance in Patients with Inflammatory Myopathies in Southwest China.

Background: The purpose of this study is to analyze the distribution of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) in patients with idiopathic inflammatory myopathies (IIMs) in southwest China and to explore the relevance between each subtype, each clinical feature, and to explore the relevance between the laboratory indexes.

Methods: For this study, 200 patients with IIMs were tested for myositis autoantibodies. Clinical manifestations and laboratory metrics were collected and the correlations between autoantibodies and clinical phenotypes were analyzed.

The role of extracellular glutamate homeostasis dysregulated by astrocyte in epileptic discharges: a model evidence.

Glutamate (Glu) is a predominant excitatory neurotransmitter that acts on glutamate receptors to transfer signals in the central nervous system. Abnormally elevated extracellular glutamate levels is closely related to the generation and transition of epileptic seizures. However, there lacks of investigation regarding the role of extracellular glutamate homeostasis dysregulated by astrocyte in neuronal epileptic discharges.

Ultrasound-assisted complex enzyme extraction, structural characterization, and biological activity of polysaccharides from Ligustrum robustum.

Ligustrum robustum is one of the traditional teas in China with a long history of drinking and medicinal use. Through Response surface optimization, the yield of polysaccharides extracted by ultrasonic-assisted complex enzyme (UAE-EN) method was increased to 14.10 ± 0.

A novel interactive deep cascade spectral graph convolutional network with multi-relational graphs for disease prediction.

Graph neural networks (GNNs) have recently grown in popularity for disease prediction. Existing GNN-based methods primarily build the graph topological structure around a single modality and combine it with other modalities to acquire feature representations of acquisitions. The complicated relationship in each modality, however, may not be well highlighted due to its specificity.

gene family in : genome-wide identification, expression analysis, and response to five different copper stress conditions.

Natural resistance-associated macrophage proteins (NRAMPs) are a class of metal transporters found in plants that exhibit diverse functions across different species. Transporter proteins facilitate the absorption, distribution, and sequestration of metallic elements within various plant tissues. Despite the extensive identification of family genes in various species, a full analysis of these genes in tree species is still necessary.