"Osteo-Organogenesis Niche" Hyaluronic Acid Engineered Materials Directing Re-Osteo-Organogenesis via Manipulating Macrophage CD44-MAPK/ERK-ETV1/5-MRC1 Axis.

The strategy of re-organogenesis provides an optimal framework for restoring complex organ structures and functions in adult damage. While the focus has often been on restoring organogenesis stem cells, there is limited investigations of reverting the environmental niche to support this approach. The guiding principle of "Nature selects the fittest to survive" drives the intricate dynamic changes in cellular events within the niche environment, especially through immune surveillance.

Hypoxia-Mimicking Mediated Macrophage-Elimination of Erythrocytes Promotes Bone Regeneration via Regulating Integrin αβ/Fe-Glycolysis-Inflammation.

Erythrocytes are the dominant component of a blood clot in terms of volume and number. However, longstanding compacted erythrocytes in blood clots form a physical barrier and make fibrin mesh more anti-fibrinolytic, thus impeding infiltration of mesenchymal stem cells. The necrosis or lysis of erythrocytes that are not removed timely can also lead to the release of pro-inflammatory toxic metabolites, interfering with bone regeneration.

Crosslinking intensity modulates the reliability and sensitivity of chromatin conformation detection at different structural levels.

Formaldehyde (FA) is a chemical that facilitates crosslinking between DNA and proteins. It is widely used in various biochemical assays, such as chromosome conformation capture (3C) and Chromatin Immunoprecipitation (ChIP). While the concentration and temperature of FA treatment are recognized as crucial factors in crosslinking, their quantitative effects have largely remained unexplored.

A digital in situ bone augmentation workflow for reconstructing the alveolar ridge outline using a modified shell technique.

The traditional shell technique is a practical method for augmenting horizontal and vertical alveolar bone defects. However, it has drawbacks, including increased morbidity in the donor site and imprecise harvesting of bone grafts. Instead of using a second surgical site, root areas at the defect site could be the in situ donor site.

Neuroelectrophysiological alteration associated with cognitive flexibility after 24 h sleep deprivation in adolescents.

The cognitive neural mechanisms by which sleep deprivation affects cognitive flexibility are poorly understood. Therefore, the study investigated the neuroelectrophysiological basis of the effect of 24 h sleep deprivation on cognitive flexibility in adolescents. 72 participants (36 females, mean age ± SD=20.

Occupancy Estimation from Blurred Video: A Multifaceted Approach with Privacy Consideration.

Building occupancy information is significant for a variety of reasons, from allocation of resources in smart buildings to responding during emergency situations. As most people spend more than 90% of their time indoors, a comfortable indoor environment is crucial. To ensure comfort, traditional HVAC systems condition rooms assuming maximum occupancy, accounting for more than 50% of buildings' energy budgets in the US.

Huoxue Jiedu Huayu recipe inhibits macrophage-secreted vascular endothelial growth factor-a on angiogenesis and alleviates renal fibrosis in the contralateral kidneys of unilateral ureteral obstruction rats.

Unlabelled: OBJECTIVE：To elucidate the mechanism by which Huoxue Jiedu Huayu recipe (, HJHR) regulates angiogenesis in the contralateral kidney of unilateral ureteral obstruction (UUO) rats and the mechanism by which it reduces of renal fibrosis.

Methods: Male Wistar rats were randomly divided into 4 groups: the sham group, UUO group (180 d of left ureter ligation), UUO plus eplerenone (EPL) group, and UUO plus HJHR group. After 180 d of oral drug administration, blood and contralateral kidneys were collected for analysis.

Esaxerenone Inhibits Interferon-γ Induced Pyroptosis of Macrophages in the Lungs of Aldosterone-treated Mice.

Lung immune cells such as lymphocytes and macrophages can induce an inflammatory response due to the activation of mineralocorticoid receptor (MR), which is manifested by the infiltration of inflammatory cells and the secretion of inflammatory cytokines and subsequent apoptosis, pyroptosis and necrosis of intrinsic lung cells and immune cells. Macrophages are immune cells that are abundant in the lung and act as the first line of defense against pathogens but are also aggravating factors of infection. The activation of the renin-angiotensin-aldosterone system (RAAS), especially aldosterone-stimulated MR activation, can induce macrophage and CD8 T cell aggregation and the secretion of cytokines such as tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ).

Tolerability, safety, and pharmacokinetics of a single intravenous administration of a novel recombinant humanized anti-interleukin-6 receptor monoclonal antibody in healthy Chinese volunteers.

VDJ001 is a novel recombinant humanized monoclonal antibody against the anti-interleukin-6 receptor. As an analog of tocilizumab, it exhibited improved affinity and activity. Based on preclinical studies, a first-in-human clinical study was conducted to evaluate the safety, tolerability, and pharmacokinetics of VDJ001.

Stability Analysis of Fractional Bidirectional Associative Memory Neural Networks With Multiple Proportional Delays and Distributed Delays.

This article investigates the finite-time stability of a class of fractional-order bidirectional associative memory neural networks (FOBAMNNs) with multiple proportional and distributed delays. Different from the existing Gronwall integral inequality with single proportional delay ( N = 1 ), we establish the Gronwall integral inequality with multiple proportional delays for the first time in the case of N ≥ 2 . Since the existing fractional-order single-constant delay Gronwall inequality with two different orders cannot be directly applied to the stability analysis of the aforementioned system, initially, we skillfully develop a novel one with generalized fractional multiproportional delays' Gronwall inequalities of different orders.

Esaxerenone Inhibits Renal Angiogenesis and Endothelial-Mesenchymal Transition via the VEGFA and TGF-β1 Pathways in Aldosterone-Infused Mice.

Renal fibrosis is an inevitable process in the progression of chronic kidney disease (CKD). Angiogenesis plays an important role in this process. Vascular endothelial cells are involved in renal fibrosis by phenotypic transformation and secretion of extracellular matrix.

Effects of liraglutide on astrocyte polarization and neuroinflammation in db/db mice: focus on iron overload and oxidative stress.

Neuroinflammation plays a crucial role in the occurrence and development of cognitive impairment in type 2 diabetes mellitus (T2DM), but the specific injury mechanism is not fully understood. Astrocyte polarization has attracted new attention and has been shown to be directly and indirectly involved in neuroinflammation. Liraglutide has been shown to have beneficial effects on neurons and astrocytes.

Pharmacokinetics and bioequivalence of Ezetimibe tablet versus Ezetrol®:an open-label, randomized, two-sequence crossover study in healthy Chinese subjects.

Background: Ezetimibe is a new class of antihyperlipidemic agent indicated for the prevention of atherosclerosis disease and for the treatment of hypercholesterolemia. Information on the pharmacokinetic profiles of ezetimibe tablet in healthy Chinese volunteers are lacking, and regulatory requirements necessitate a bioequivalence study of ezetimibe tablet versus Ezetrol® in China.

Methods: A single-dose randomized, open-label, two-group, two-period crossover study was conducted in 59 healthy Chinese volunteers under fasting or fed conditions to assess the bioequivalence between two preparations.

A novel solvent-free co-grinding preparation improves curcumin bioavailability in healthy volunteers: A single-center crossover study.

Curcumin, from the rhizome of turmeric ( L.), has a wide variety of biological activities. Unfortunately, its poor water-solubility greatly limits its bioavailability.

The Achilles heel of TNBCs: Ferroptosis heterogeneity.

Resistance to ferroptosis, a form of programmed cell death, is associated with the development of some refractory cancers. In this issue, Yang et al. systematically illustrate the ferroptosis heterogeneity in triple-negative breast cancers (TNBCs) and reveal an innovative immunotherapy combination strategy for the luminal androgen receptor (LAR) subtype of TNBC.

Canagliflozin primes antitumor immunity by triggering PD-L1 degradation in endocytic recycling.

Understanding the regulatory mechanisms of PD-L1 expression in tumors provides key clues for improving immune checkpoint blockade efficacy or developing novel oncoimmunotherapy. Here, we showed that the FDA-approved sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin dramatically suppressed PD-L1 expression and enhanced T cell-mediated cytotoxicity. Mechanistic study revealed that SGLT2 colocalized with PD-L1 at the plasma membrane and recycling endosomes and thereby prevented PD-L1 from proteasome-mediated degradation.

Eplerenone inhibits the macrophage-to-myofibroblast transition in rats with UUO-induced type 4 cardiorenal syndrome through the MR/CTGF pathway.

Cardiovascular complications are the leading causes of death in patients with chronic kidney disease (CKD), accounting for approximately 50% of deaths. Despite significant advances in the understanding of cardiac disease due to CKD, the underlying mechanisms involved in many pathological changes have not been fully elucidated. In our previous study, we observed severe fibrosis in the contralateral kidney of a 6-month-old rat UUO model.

Eplerenone Prevents Cardiac Fibrosis by Inhibiting Angiogenesis in Unilateral Urinary Obstruction Rats.

Introduction: Cardiovascular disease constitutes the leading cause of mortality in patients with chronic kidney disease (CKD), which is termed cardiorenal syndrome type 4 (CRS-4). Here, we report the development of pathological cardiac remodeling and fibrosis in unilateral urinary obstruction (UUO) rats.

Methods: Hematoxylin and eosin (H&E) staining was performed to observe the pathology of myocardial tissue.

Esaxerenone inhibits the macrophage-to-myofibroblast transition through mineralocorticoid receptor/TGF-β1 pathway in mice induced with aldosterone.

Renal fibrosis is the inevitable pathway of the progression of chronic kidney disease to end-stage renal disease, which manifests as progressive glomerulosclerosis and renal interstitial fibrosis. In a previous study, we observed severe interstitial fibrosis in the contralateral kidneys of 6-month unilateral ureteral obstruction (UUO) rats, which was accompanied by increased macrophage infiltration and phenotypic transformation; after eplerenone administration, these effects were reduced. Therefore, we hypothesized that this effect was closely related to mineralocorticoid receptor (MR) activation induced by the increased aldosterone (ALD) level.

The effect of rifampin on the pharmacokinetics of famitinib in healthy subjects.

Background: Famitinib is an oral, small-molecule, multi-targeted tyrosine kinase inhibitor under clinical investigation for the treatment of solid tumors. As famitinib is metabolized mainly by cytochrome P450 3A4 (CYP3A4), the study was conducted to investigate the effect of potent CYP3A4 inducer rifampin on the pharmacokinetics of famitinb.

Methods: This single-center, single-arm and fixed-sequence drug-drug interaction study enrolled 21healthy Chinese male subjects.