Exosomes derived from umbilical cord mesenchymal stem cells promote healing of complex perianal fistulas in rats.

Background: Complex perianal fistulas, challenging to treat and prone to recurrence, often require surgical intervention that may cause fecal incontinence and lower quality of life due to large surgical wounds and potential sphincter damage. Human umbilical cord-derived MSCs (hUC-MSCs) and their exosomes (hUCMSCs-Exo) may promote wound healing.

Methods: This study assessed the efficacy, mechanisms, and safety of these exosomes in treating complex perianal fistulas in SD rats.

A3AR antagonism mitigates metabolic dysfunction-associated steatotic liver disease by exploiting monocyte-derived Kupffer cell necroptosis and inflammation resolution.

Background & Aims: Metabolic dysfunction-associated steatotic liver (MASLD) progression is driven by chronic inflammation and fibrosis, largely influenced by Kupffer cell (KC) dynamics, particularly replenishment of pro-inflammatory monocyte-derived KCs (MoKCs) due to increased death of embryo-derived KCs. Adenosine A3 receptor (A3AR) plays a key role in regulating metabolism and immune responses, making it a promising therapeutic target. This study aimed to investigate the impact of selective A3AR antagonism for regulation of replenished MoKCs, thereby improving MASLD.

LPL-RH suppresses bone loss in ovariectomised rat models.

Background: Evidence has revealed that oestrogen deprivation-induced osteolysis is microbiota-dependent and can be treated by probiotics. However, the underlying mechanism require further investigation. This study aims to provide additional evidence supporting the use of probiotics as an adjuvant treatment and to explore the pathophysiology of oestrogen-deprived osteolysis.

Gas transport mechanisms during high-frequency ventilation.

By virtue of applying small tidal volumes, high-frequency ventilation is advocated as a method of minimizing ventilator-induced lung injury. Lung protective benefits are established in infants, but not in other patient cohorts. Efforts to improve and extend the lung protection potential should consider how fundamental modes of gas transport can be exploited to minimize harmful tidal volumes while maintaining or improving ventilation.

Onco-mNGS facilitates rapid and precise identification of the etiology of fever of unknown origin: a single-centre prospective study in North China.

Objectives: Delayed diagnosis of patients with Fever of Unknown Origin has long been a daunting clinical challenge. Onco-mNGS, which can accurately diagnose infectious agents and identify suspected tumor signatures by analyzing host chromosome copy number changes, has been widely used to assist identifying complex etiologies. However, the application of Onco-mNGS to improve FUO etiological screening has never been studied before.

Deciphering a profiling based on multiple post-translational modifications functionally associated regulatory patterns and therapeutic opportunities in human hepatocellular carcinoma.

Background: Posttranslational modifications (PTMs) play critical roles in hepatocellular carcinoma (HCC). However, the locations of PTM-modified sites across protein secondary structures and regulatory patterns in HCC remain largely uncharacterized.

Methods: Total proteome and nine PTMs (phosphorylation, acetylation, crotonylation, ubiquitination, lactylation, N-glycosylation, succinylation, malonylation, and β-hydroxybutyrylation) in tumor sections and paired normal adjacent tissues derived from 18 HCC patients were systematically profiled by 4D-Label free proteomics analysis combined with PTM-based peptide enrichment.

Predicting lncRNA-protein interactions using a hybrid deep learning model with dinucleotide-codon fusion feature encoding.

Long non-coding RNAs (lncRNAs) play crucial roles in numerous biological processes and are involved in complex human diseases through interactions with proteins. Accurate identification of lncRNA-protein interactions (LPI) can help elucidate the functional mechanisms of lncRNAs and provide scientific insights into the molecular mechanisms underlying related diseases. While many sequence-based methods have been developed to predict LPIs, efficiently extracting and effectively integrating potential feature information that reflects functional attributes from lncRNA and protein sequences remains a significant challenge.

Comorbidities, drug-resistance and length of hospital stay among tuberculosis inpatients in Northeastern China: a retrospective observational study from 2013 to 2021.

Background: Tuberculosis (TB) remains a significant global health issue. Drug-resistant TB and comorbidities exacerbate its burden, influencing treatment outcomes and healthcare utilization. Despite the growing prevalence of TB comorbidities, research often focuses on single comorbidities rather than comorbidity patterns.

Efficacy of corneal squamous cell carcinoma antigen-1 in early infancy in predicting atopic dermatitis and food allergy: A prospective study.

Background: Identification of predictive biomarkers is crucial for formulating preventive interventions and halting the progression of atopic march. Although controversial, the use of accessible markers to predict or detect early onset of atopic diseases is highly desirable. Therefore, this study aimed to investigate whether corneal squamous cell carcinoma antigen-1 (SCCA1) collected from infants can predict the development of atopic dermatitis and food allergy.

Choroid plexus cysts on 7T MRI: Relationship to aging and neurodegenerative diseases.

Introduction: The choroid plexus (CP) may play a crucial role in brain degeneration. We aim to assess whether CP cysts (CPCs), defined using ultra-high field magnetic resonance imaging (MRI), relate to aging and neurodegeneration.

Methods: We used multi-sequence 7T MRI to observe CPCs, characterizing their presence and characteristics in healthy younger controls, healthy older controls (OCs), patients with Alzheimer's disease (AD), patients with Parkinson's disease (PD), and patients with uremic encephalopathy.

Highly Sensitive LC-MS/MS Method for Determination of Dexamethasone in Rat Plasma and Brain Tissue: An Application to Pharmacokinetic Study in Rats.

A highly sensitive and rapid LC-MS/MS method was developed and validated for the quantification of dexamethasone in rat plasma and brain tissue. Protein precipitation method was used for sample preparation. The separation of dexamethasone and the IS (labetalol) was achieved on an Atlantis dC column using an isocratic mobile phase (10 mM ammonium formate and acetonitrile, 25/75, v/v) delivered at 0.

Simultaneous Determination of Vitamins A and E and Their Generated Metabolites in Human Serum by LC-MS/MS.

In the context of personalized and precision medicine, simultaneous monitoring of different forms of vitamins A and E and their metabolites could help us better understand the status of vitamins A and E in the body. The aim of this study was to establish a method for simultaneous determination of 13 kinds of vitamins A and E and their metabolites in human serum. Serum samples were directly detected by LC-MS/MS after deproteinization.

Temperature effects on nitrogen removal and NO emissions in anammox reactors.

Mainstream anammox faces challenges in adapting to non-optimal temperatures and managing greenhouse gas emissions. This study investigates nitrogen removal and NO emissions in attached-growth anammox reactors subjected to rapid temperature shifts (15 - 55 °C). Temperature reductions to 15 - 25 °C had minimal impact on the anammox bacterial populations, with nitrogen removal rates of 0.

Comparison of Population Pharmacokinetic Modeling and Machine Learning Approaches for Predicting Voriconazole Trough Concentrations in Critically Ill Patients.

Despite the widespread use of voriconazole in antifungal treatment, its high pharmacokinetic and pharmacodynamic variability may lead to suboptimal efficacy, especially in intensive care unit (ICU) patients. Machine learning (ML), an artificial intelligence modeling approach, is increasingly being applied to personalized medicine. The effectiveness of ML models for predicting voriconazole blood concentrations in ICU patients, compared to traditional population pharmacokinetics (popPK) models, has been uncertain until now.

Interfacial functionalization and capillary force welding of enhanced silver nanowire-cellulose nanofiber composite electrodes for electroluminescent devices.

The development of flexible, intelligent, and lightweight optoelectronic devices based on flexible transparent conductive electrodes (FTCEs) utilizing silver nanowires (AgNWs) has garnered increasing attention. However, achieving low surface resistance, strong adhesion to the flexible substrate, low surface roughness, and green degradability remains a challenge. Here, a composite electrode combining natural polymer cellulose nanofibers (TCNFs) with AgNWs was prepared.

Anionic polysaccharides as delivery carriers for cancer therapy and theranostics: An overview of significance.

Recently, cancer therapy has witnessed remarkable advancements with a growing focus on precision medicine and targeted drug delivery strategies. The application of anionic polysaccharides has gained traction in various drug delivery systems. Anionic polysaccharides have emerged as promising delivery carriers in cancer therapy and theranostics, offering numerous advantages such as biocompatibility, low toxicity, and the ability to encapsulate and deliver therapeutic agents to tumor sites with high specificity.

Enhancing the stability of krill oil through microencapsulation with endogenous krill protein and chitosan and application in senior milk powder.

Krill oil (KO) exhibits several biological actions, particularly providing distinct advantages for cognitive health in the aged. Nonetheless, its inadequate water solubility, pronounced flavor, and vulnerability to oxidative degradation restrict its utilization in the food sector. Encapsulation provides a solution, and the study of natural, suitable wall materials is crucial.

A cross-species assessment of in silico prediction methods of steady-state volume of distribution using Simcyp Simulators.

Predicting steady-state volume of distribution (V) is a key component of pharmacokinetic predictions and often guided using preclinical data. However, when bottom-up prediction from physiologically-based pharmacokinetic (PBPK) models and observed V misalign in preclinical species, or predicted V from different models varies significantly, no consensus exists for selecting models or preclinical species to improve the prediction. Through systematic analysis of V prediction across rat, dog, monkey, and human, using common methods, a practical strategy for predicting human V, with or without integration of preclinical PK information is warranted.

Converting multiple hydrophobic aromatic plastic monomers into a single water-soluble substrate to increase bioavailability for the synthesis of polyhydroxyalkanoates by bacteria using batch, fed batch and continuous cultivation.

We demonstrate the proof of concept of increasing the bioavailability of carbon substrates, derived from plastic waste, for their conversion to the biodegradable polymer polyhydroxyalkanoate [PHA] by bacteria and test various approaches to PHA accumulation through batch, fed batch and continuous culture. Styrene, ethylbenzene, and toluene are produced from the pyrolysis of mixed plastic waste (Kaminsky, 2021; Miandad et al., 2017), but they are volatile and poorly soluble in water making them difficult to work with in aqueous fermentation systems.

An MRI-Based Radiomics Model for Preoperative Prediction of Microvascular Invasion and Outcome in Intrahepatic Cholangiocarcinoma.

Purpose: Microvascular invasion (MVI) serves as a significant predictor of poor prognosis in intrahepatic cholangiocarcinoma (ICC). This study aims to establish a comprehensive model utilizing MR radiomics for preoperative MVI status stratification and outcome prediction in ICC patients.

Materials And Methods: A total of 249 ICC patients were randomly assigned to training and validation cohorts (174:75), along with a time-independent test cohort consisting of 47 ICC patients.

Discovery of a novel CDK4/6 and HDAC dual-targeting agent for the treatment of hepatocellular carcinoma.

The down-regulation of p21 after long-term CDK4/6 inhibition represents a key mechanism causing resistance to CDK4/6 inhibitors in some tumor cells, while the HDAC inhibitor could upregulate the level of p21. Herein, a series of novel CDK4/6 and HDAC dual-targeting inhibitors based on the moiety of palbociclib were designed and synthesized. Among them, compound N14 potently inhibited CDK4/6 and HDAC1/6 at nanomolar levels and induced cell apoptosis and G/G phase arrest through HDAC-p21-CDK signaling pathway in HuH-7 cell line.

Effects of transglutaminase on the gelation properties and digestibility of pea protein isolate with resonance acoustic mixing pretreatment.

Our previous research confirmed that resonance acoustic mixing (RAM) pretreatment effectively improved the emulsification and water retention of commercial pea protein isolate (PPI), but significantly reduced its gel performance. This study aimed to investigate the effect of transglutaminase (TGase, 0.1 %, 0.