Design, synthesis, and biological evaluation of a potent and orally bioavailable FGFRs inhibitor for fibrotic treatment.

Organ fibrosis, such as lung fibrosis and liver fibrosis, is a progressive and fatal disease. Fibroblast growth factor receptors (FGFRs) play an important role in the development and progression of fibrosis. Through scaffold hopping, bioisosteric replacement design, and structure-activity relationship optimization, we developed a series of highly potent FGFRs inhibitors, and the indazole-containing candidate compound A16 showed potent kinase activity comparable to that of AZD4547.

Regulation of T Cell Glycosylation by MXene/β-TCP Nanocomposite for Enhanced Mandibular Bone Regeneration.

Immune-mediated bone regeneration driven by bone biomaterials offers a therapeutic strategy for repairing bone defects. Among 2D nanomaterials, TiCT MXenes have garnered substantial attention for their potential in tissue regeneration. This investigation concentrates on the role of MXene nanocomposites in modulating the immune microenvironment within bone defects to facilitate bone tissue restoration.

[Research Advances in Strategies to Enhance the Therapeutic Effects of Mesenchymal Stem Cells on Graft-Versus-Host Disease Post Hematopoietic Stem Cell Transplantation --Review].

Mesenchymal stem cells (MSC) possess unique immunomodulatory properties and have enormous potential in the treatment of graft-versus-host disease (GVHD). However, the low implantation and survival rates of MSC in vivo, coupled with their weak immunosuppressive functions, have resulted in unstable clinical efficacy in the treatment of GVHD. Preconditioning of MSC with hypoxia, active molecules and gene modification can enhance the function of MSC and improve the implantation rate, survival rate and therapeutic effect of MSC.

Endoscopic resection of a giant irregular leiomyoma in fundus and cardia: A case report.

Background: Endoscopic resection of giant gastric leiomyomas, particularly in the fundus and cardia regions, is infrequently documented and presents a significant challenge for endoscopic surgery.

Case Summary: Herein, a case of a 59-year-old woman with a giant gastric leiomyoma was reported. The patient presented to the department of hepatological surgery with a complaint of right upper abdominal pain for one month and worsening for one week.

Exploring the molecular mechanisms by which secretory phospholipase a2 regulates lymphatic endothelial cell dysfunction by activating macrophages.

This study offers new insights into the dual role of secretory phospholipase A2 (sPLA2) in lymphedema, highlighting its impact on lymphatic endothelial cell (LEC) functionality. Through transcriptomic analyses and co-culture experiments, we observed that sPLA2 has both protective and detrimental effects on human LECs (HLECs), mediated by macrophage activation. Our findings reveal that while low levels of sPLA2 promote LEC health, excessive sPLA2 leads to dysfunction, emphasizing the significance of the sPLA2/PLA2R axis and arachidonic acid metabolism (AA) in lymphedema pathology.

Behaviors and attitudes towards mobile learning during course work and scientific research among dental, medical and non-medical undergraduates: a cross-sectional study.

Background: Mobile learning is a valuable supplement to traditional education methods, but the current research on mobile learning is still insufficient. This study aimed to assess dental undergraduates' behaviors and attitudes towards mobile learning during course work and scientific research and to compare these findings to those of medical and non-medical students.

Methods: A cross-sectional survey was conducted among undergraduates at Sichuan University, China.

Mitigation of polystyrene microplastic-induced hepatotoxicity in human hepatobiliary organoids through bile extraction.

Background & Aims: Polystyrene microplastics (PS-MPs) are pervasive in our daily life and can be ingested by the human body through bioaccumulation, causing organ damage, especially liver damage. However, the effect of PS-MPs bioaccumulation on human hepatotoxicity and their metabolism remains unclear. Recent studies have demonstrated that PS-MPs cause lipid and bile acid metabolism disorders.

Altered mammary gland development and pro-tumorigenic changes in young female mice following prenatal BPAF exposure.

Bisphenol A (BPA) is being phased out owing to its endocrine-disrupting effects and is increasingly being replaced by its substitute compounds such as bisphenol AF (BPAF). This study aims to explore the potential adverse outcomes of prenatal BPAF exposure combined with postnatal cross-fostering on the development and long-term health effects of the mammary gland in offspring. The results suggested that prenatal BPAF exposure accelerates the puberty, and induces duct dilatations, angiogenesis, lobular hyperplasia, and enhanced inflammatory cell infiltration in the mammary gland of female offspring.

Chylous Reflux in Pediatric Primary Lymphedema of the Lower Limbs and Genitalia: A Retrospective Study of 167 Patients.

Chylous reflux (CR) in primary lymphedema (PL) of the lower extremities is rare and requires particular diagnostic procedures. This study aimed to determine clinical and lymphoscintigraphic traits for efficient screening. Pediatric patients with PL of lower extremities treated in our institution between January 2020 and December 2023 were reviewed.

Polyphyllin VI Ameliorates Pulmonary Fibrosis by Suppressing the MAPK/ERK and PI3K/AKT Signaling Pathways via Upregulating DUSP6.

Pulmonary fibrosis (PF) is a lethal disease caused by inordinate repair of damaged lungs, for which limited strategies are available. Polyphyllin VI (PPVI), extracted and isolated from Paris polyphylla Smith var. chinensis (Franch.

Generation of human hepatobiliary organoids with a functional bile duct from chemically induced liver progenitor cells.

Background: Liver disease imposes a significant medical burden that persists due to a shortage of liver donors and an incomplete understanding of liver disease progression. Hepatobiliary organoids (HBOs) could provide an in vitro mini-organ model to increase the understanding of the liver and may benefit the development of regenerative medicine.

Methods: In this study, we aimed to establish HBOs with bile duct (BD) structures and mature hepatocytes (MHs) using human chemically induced liver progenitor cells (hCLiPs).

Integrative single-cell and bulk transcriptome analyses identify a distinct pro-tumor macrophage signature that has a major prognostic impact on glioblastomas.

Glioblastoma (GBM) is a highly heterogeneous disease with poor clinical outcomes. To comprehensively dissect the molecular landscape of GBM and heterogeneous macrophage clusters in the progression of GBM, this study integrates single-cell and bulk transcriptome data to recognize a distinct pro-tumor macrophage cluster significantly associated with the prognosis of GBM and develop a GBM prognostic signature to facilitate prior subtypes. Leveraging glioma single-cell sequencing data, we identified a novel pro-tumor macrophage subgroup, marked by S100A9, which might interact with endothelial cells to facilitate tumor progression via angiogenesis.

Solution Synthesis and Light-Emitting Applications of One-Dimensional Lead-Free Cerium(III) Metal Halides.

Combining rare earth elements with the halide perovskite structure offers valuable insights into designing nonlead (Pb) luminescent materials. However, most of these compositions tend to form zero-dimensional (0D) networks of metal-halide polyhedra, with higher-dimensional (1D, 2D, and 3D) structures receiving relatively less exploration. Herein, we present synthesis and optical properties of CsCeCl·3HO, characterized by its unique 1D crystal structure.

Ultrasonographic Predictors for Post-operative Ischemic Events After Indirect Revascularization Surgeries in Patients with Moyamoya Disease.

Objective: Recurrent stroke after revascularization surgeries predicts poor outcome in patients with moyamoya disease (MMD). Early identification of patients with stroke risk paves the way for rescue intervention. This study aimed to investigate the role of ultrasound in identifying patients at risk of post-operative ischemic events (PIEs).

New insight into the spatiotemporal distribution and ecological risk assessment of endocrine-disrupting chemicals in the Minjiang and Tuojiang rivers: perspective of watershed landscape patterns.

This study evaluated the pollution characteristics, spatiotemporal distribution, and ecological risks of eight endocrine-disrupting chemicals (EDCs) in the Minjiang and Tuojiang rivers. Utilizing 3S technology (ArcGIS, remote sensing, GPS) and Fragstats, the research calculated eight landscape pattern indices related to land use types along the Minjiang river and established correlations between landscape factors and EDC distribution through stepwise multiple regression. The results indicated that bisphenol A (BPA) and nonylphenol (NP) were the most concerning EDCs, with detection frequencies of 97-100% and peak concentrations up to 63.

Amelioration of gait and balance disorders by rosuvastatin is associated with changes in cerebrovascular reactivity in older patients with hypertensive treatment.

To investigate the effect of rosuvastatin on gait and balance disorder progression and elucidate the role of cerebrovascular reactivity (CVR) on this effect. From April 2008 to November 2010, 943 hypertensive patients aged ≥60 years were enrolled from the Shandong area of China. Patients were randomized into rosuvastatin and placebo groups.

Molecular mechanism of the metal-independent production of hydroxyl radicals by thiourea dioxide and HO.

It is well-known that highly reactive hydroxyl radicals (HO) can be produced by the classic Fenton system and our recently discovered haloquinone/HO system, but rarely from thiol-derivatives. Here, we found, unexpectedly, that HO can be generated from HO and thiourea dioxide (TUO), a widely used and environmentally friendly bleaching agent. A carbon-centered radical and sulfite were detected and identified as the transient intermediates, and urea and sulfate as the final products, with the complementary application of electron spin-trapping, oxygen-18 isotope labeling coupled with HPLC/MS analysis.

miRNome targeting NF-κB signaling orchestrates macrophage-triggered cancer metastasis and recurrence.

Whether and how tumor intrinsic signature determines macrophage-elicited metastasis remain elusive. Here, we show, in detailed studies of data regarding 7,477 patients of 20 types of human cancers, that only 13.8% ± 2.

Microgel-based carriers enhance skeletal stem cell reprogramming towards immunomodulatory phenotype in osteoarthritic therapy.

Skeletal stem cells (SSC) have gained attentions as candidates for the treatment of osteoarthritis due to their osteochondrogenic capacity. However, the immunomodulatory properties of SSC, especially under delivery operations, have been largely ignored. In the study, we found that Pdpn and Grem1 SSC subpopulations owned immunoregulatory potential, and the single-cell RNA sequencing (scRNA-seq) data suggested that the mechanical activation of microgel carriers on SSC induced the generation of PdpnGrem1Ptgs2 SSC subpopulation, which was potent at suppressing macrophage inflammation.