Establishment of Biopredictive Dissolution and Bioequivalence Safe Space Using the Physiologically Based Biopharmaceutics Modeling for Tacrolimus Extended-Release Capsules.

A slight variation in in vivo exposure for tacrolimus extended-release (ER) capsules, which have a narrow therapeutic index (NTI), significantly affects the pharmacodynamics of the drug. Generic drug bioequivalence (BE) standards are stricter, necessitating accurate assessment of the rate and extent of drug release. Therefore, an in vitro dissolution method with high in vivo predictive power is crucial for developing generic drugs.

A high-resolution multi-scale industrial water use dataset in China.

Water is crucial for achieving the UN Sustainable Development Goals, particularly SDG 6. As a major source of water use and pollution, industrial sector requires improved water management based on more systematic and refined analysis. Such analysis, however, is compromised by the accuracy, granularity, and coverage of industrial water data.

Clinical Trial Data-Driven Risk Assessment of Drug-Drug Interactions: A Rapid and Accurate Decision-Making Tool.

Background: In clinical practice, the vast array of potential drug combinations necessitates swift and accurate assessments of pharmacokinetic drug-drug interactions (DDIs), along with recommendations for adjustments. Current methodologies for clinical DDI evaluations primarily rely on basic extrapolations from clinical trial data. However, these methods are limited in accuracy owing to their lack of a comprehensive consideration of various critical factors, including the inhibitory potency, dosage, and type of the inhibitor, as well as the metabolic fraction and intestinal availability of the substrate.

A Dual-Targeting, Multi-Faceted Biocompatible Nanodrug Optimizes the Microenvironment to Ameliorate Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is a highly lethal cardiovascular disease that currently lacks effective pharmacological treatment given the complex pathophysiology of the disease. Here, single-cell RNA-sequencing data from patients with AAA and a mouse model are analyzed, which reveals pivotal pathological changes, including the M1-like polarization of macrophages and the loss of contractile function in smooth muscle cells (SMCs). Both cell types express the integrin αvβ3, allowing for their dual targeting with a single rationally designed molecule.

[Normal mouse serum alleviates radiation pneumonitis in mice by inhibiting the focal adhesion signaling pathway].

Objective: To evaluate the therapeutic effect of normal mouse serum on radiation pneumonitis in mice and explore the possible mechanism.

Methods: Mouse models of radiation pneumonitis induced by thoracic radiation exposure were given intravenous injections of 100 μL normal mouse serum or normal saline immediately after the exposure followed by injections once every other day for a total of 8 injections. On the 15th day after irradiation, histopathological changes of the lungs of the mice were examined using HE staining, the levels of TNF-α, TGF-β, IL-1α and IL-6 in the lung tissue and serum were detected using ELISA, and the percentages of lymphocytes in the lung tissue were analyzed with flow cytometry.

Preliminary establishment and validation of the inversion method for growth and remodeling parameters of patient-specific abdominal aortic aneurysm.

Traditional medical imaging and biomechanical studies have challenges in analyzing the long-term evolution process of abdominal aortic aneurysm (AAA). The homogenized constrained mixture theory (HCMT) allows for quantitative analysis of the changes in the multidimensional morphology and composition of AAA. However, the accuracy of HCMT still requires further clinical verification.

Improved adaptive regularization for simulated annealing inversion of transient electromagnetic.

Geophysical inversion usually involves ill-posed problem. Regularization is the most commonly used method to mitigate this problem. There are many regularization parameter selection methods, among which the adaptive regularization method can automatically update parameters during iteration, reducing the difficulty of parameter selection.

Liver resection versus microwave ablation for solitary and small (≤ 3 cm) HCC with early recurrence in different stages of liver cirrhosis: A propensity score matching study.

Background: This study aimed to compare the effectiveness of liver resection (LR) and microwave ablation (MWA) in hepatocellular carcinoma (HCC) patients with early recurrence and varying stages of cirrhosis.

Method: This study analyzed patients with HCC who underwent hepatectomy and experienced early tumor recurrence (≤3 cm) between December 2002 and December 2020 at the Tongji Hospital. Treatment effectiveness was assessed using a propensity score matching (PSM) analysis.

Evidence from an Avian Embryo Model that Zinc-Inducible MT4 Expression Protects Mitochondrial Function Against Oxidative Stress.

Background: Metallothioneins (MTs) have a strong affinity for zinc (Zn) and remain at a sufficiently high level in mitochondria. As the avian embryo is highly susceptible to oxidative damage and relatively easy to manipulate in a naturally closed chamber, it is an ideal model of the effects of oxidative stress on mitochondrial function. However, the protective roles and molecular mechanisms of Zn-inducible protein expression on mitochondrial function in response to various stressors are poorly understood.

Intelectin-1 is a novel prognostic biomarker for hepatocellular carcinoma.

The molecular mechanisms of hepatocellular carcinoma (HCC) are still not well understood. Gene microarray analysis showed that the expression of Intelectin-1 (ITLN-1) in tumor-adjacent normal liver tissue was 454.8 times higher than in the corresponding cancer tissue.

Portal vein velocity predicts portal vein system thrombosis after splenectomy with esophagogastric devascularization.

Background: Portal vein system thrombosis (PVST) is a potentially fatal complication after splenectomy with esophagogastric devascularization (SED) in cirrhotic patients with portal hypertension. However, the impact of portal vein velocity (PVV) on PVST after SED remains unclear. Therefore, this study aims to explore this issue.

CENPA functions as a transcriptional regulator to promote hepatocellular carcinoma progression via cooperating with YY1.

The centromere proteins (CENPs), a critical mitosis-related protein complexes, are involved in the kinetochore assembly and chromosome segregation. In this study, we identified that CENPA was significantly up-regulated in HCC and highly expressed CENPA correlated with poor prognosis for HCC patients. Knockdown of CENPA inhibited HCC cell proliferation and tumor growth and .

Single-cell RNA sequencing of intestinal crypts reveals vital events in damage repair and the double-edged sword effect of the Wnt3/β-catenin pathway in irradiated mice.

In this study, we executed single-cell RNA sequencing of intestinal crypts. We analyzed the differentially expressed genes (DEGs) at different time points (the first, third, and fifth days) after 13 Gy and 15 Gy abdominal body radiation (ABR) exposure and then executed gene ontology (GO) enrichment analysis, RNA velocity analysis, cell communication analysis, and ligand‒receptor interaction analysis to explore the vital events in damage repair and the multiple effects of the Wnt3/β-catenin pathway on irradiated mice. Results from bioinformatics analysis were confirmed by a series of biological experiments.

Effects of square spatial periodic forcing on oscillatory hexagon patterns in coupled reaction-diffusion systems.

One of the central issues in pattern formation is understanding the response of pattern-forming systems to an external stimulus. While significant progress has been made in systems with only one instability, much less is known about the response of complex patterns arising from the interaction of two or more instabilities. In this paper, we consider the effects of square spatial periodic forcing on oscillatory hexagon patterns in a two-layer coupled reaction diffusion system which undergoes both Turing and Hopf instabilities.

How to understand high global food price? Using SHAP to interpret machine learning algorithm.

The global food prices have surged to historical highs, and there is no consensus on the reasons behind this round of price increases in academia. Based on theoretical analysis, this study uses monthly data from January 2000 to May 2022 and machine learning models to examine the root causes of that period's global food price surge and global food security situation. The results show that: Firstly, the increase in the supply of US dollars and the rise in oil prices during pandemic are the two most important variables affecting food prices.

High-fat diet alters the radiation tolerance of female mice and the modulatory effect of melatonin.

High-fat diet (HFD) increases the risk of developing malignant tumors. Ionizing radiation (IR) is used as an adjuvant treatment in oncology. In this study, we investigated the effects of an 8-week 35% fat HFD on the tolerance to IR and the modulatory effect of melatonin (MLT).

A Molecular Switch-Integrated Nanoplatform Enables Photo-Unlocked Antibacterial Drug Delivery for Synergistic Abscess Therapy.

Drug delivery systems (DDSs) capable of sequential multistage drug release are urgently needed for antibacterial applications. Herein, a molecular switch-integrated, photo-responsive nanoplatform is reported based on hollow mesoporous silica nanospheres (HMSN) loaded with silver nanoparticles (Ag NPs), vancomycin (Van), and hemin (HAVH) for bacteria elimination and abscess therapy. Upon near-infrared (NIR) light irradiation, the molecular switch, hemin, can effuse from the mesopores of HMSN, triggering the release of pre-loaded Ag and Van, which enables photothermal-modulated drug release and synergistic photothermal-chemo therapy (PTT-CHT).

Molecular vasculogenic mimicry-Related signatures predict clinical outcomes and therapeutic responses in bladder cancer: Results from real-world cohorts.

Bladder cancer (BLCA) is a heterogeneous disease, and there are many classical molecular subtypes that reflect tumor immune microenvironment (TME) heterogeneity but their clinical utility is limited and correct individual treatment and prognosis cannot be predicted based on them. To find reliable and effective biomarkers and tools for predicting patients' clinical responses to several therapies, we developed a new systemic indicator of molecular vasculogenic mimicry (VM)-related genes mediated by molecular subtypes based on the Xiangya cohort and additional external BLCA cohorts using a random forest algorithm. A correlation was then done between the VM_Score and classical molecular subtypes, clinical outcomes, immunophenotypes, and treatment options for BLCA.

Unveiling the Nature of Ultrastable Potassium Storage in BiSbSe Composite.

The conversion and alloying-type anodes for potassium-ion batteries (PIBs) have drawn attention. However, it is still a challenge to relieve the huge volume expansion/electrode pulverization. Herein, we synthesized a composite material comprising BiSbSe nanoparticles uniformly dispersed in carbon nanofibers (BiSbSe@C).

Adipose-derived stem cell/FGF19-loaded microfluidic hydrogel microspheres for synergistic restoration of critical ischemic limb.

The efficacy of stem cell therapy is substantially compromised due to low cell survival rate and poor local retention post-delivery. These issues drastically limit the application of stem cells for ischemic limb therapy, which requires effective blood perfusion and skeletal muscle regeneration. Herein, based on microfluidic technology, an integrated stem cell and cytokine co-delivery system designed for functional ischemic limb salvage was constructed by first incorporating the myogenic cytokine, fibroblast growth factor 19 (FGF19), into microspheres composed of methacrylate gelatin (GelMA).

The study on the impact of AAA wall motion on the hemodynamics based on 4D CT image data.

To analyze the effect of the physiological deformation of the vessel wall on the hemodynamics in the abdominal aortic aneurysm (AAA), this paper compared the hemodynamics in AAA based on the moving boundary (MB) simulation and the rigid wall (RW) simulation. Patient-specific models were reconstructed to generate mesh based on four-dimensional computed tomography angiography (4D CT) data. The dynamic mesh technique was used to achieve deformation of the vessel wall, surface mesh and volume mesh of the fluid domain were successively remeshed at each time step.

Oncogenic lncRNA BBOX1-AS1 promotes PHF8-mediated autophagy and elicits sorafenib resistance in hepatocellular carcinoma.

Some long non-coding RNAs (lncRNAs) have been documented to be involved in cancer progression and anticancer drug resistance in hepatocellular carcinoma (HCC). Thus, approaches designed to target these genes may facilitate the development of promising strategies for treating HCC. Previously, we showed that lncRNA BBOX1-AS1 was highly expressed and played an oncogenic role in HCC.

Sex Differences of Radiation Damage in High-Fat-Diet-Fed Mice and the Regulatory Effect of Melatonin.

The consumption of a high-fat diet (HFD) and exposure to ionizing radiation (IR) are closely associated with many diseases. To evaluate the interaction between HFDs and IR-induced injury, we gave mice whole abdominal irradiation (WAI) to examine the extent of intestinal injury under different dietary conditions. Melatonin (MLT) is a free radical scavenger that effectively prevents hematopoietic, immune, and gastrointestinal damage induced by IR.