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Abstract H3K27ac has been widely recognized as a representative epigenetic marker of active enhancer, while its regulatory mechanisms in pathogenesis of metabolic dysfunction‐associated steatotic liver disease (MASLD) remain elusive. Here, a genome‐wide comparative study on H3K27ac activities and transcriptome profiling in high fat diet (HFD)‐induced MASLD model is performed. A significantly enhanced H3K27ac density with abundant alterations of regulatory transcriptome is observed in MASLD rats. Based on integrative analysis of ChIP‐Seq and RNA‐Seq, TDO2 is identified as a critical contributor for abnormal lipid accumulation, transcriptionally activated by YY1‐promoted H3K27ac. Furthermore, TDO2 depletion effectively protects against hepatic steatosis. In terms of mechanisms, TDO2 activates NF‐κB pathway to promote macrophages M1 polarization, representing a crucial event in MASLD progression. A bovine serum albumin nanoparticle is fabricated to provide sustained release of Allopurinol (NPs‐Allo) for TDO2 inhibition, possessing excellent biocompatibility and desired targeting capacity. Venous injection of NPs‐Allo robustly alleviates HFD‐induced metabolic disorders. This study reveals the pivotal role of TDO2 and its underlying mechanisms in pathogenesis of MASLD epigenetically and genetically. Targeting H3K27ac‐TDO2‐NF‐κB axis may provide new insights into the pathogenesis of abnormal lipid accumulation and pave the way for developing novel strategies for MASLD prevention and treatment.

Background: Hepatocellular carcinoma (HCC) is the most prevalent malignant tumor, ranking fifth in terms of fatality with poor prognosis and a low survival rate. Rhoifolin (ROF), a flavonoid constituent, has previously been shown to suppress the proliferation of breast and pancreatic cancer cells. However, its inhibitory effect on HCC has remained unexplored. Objectives: Exploring the potent inhibitory activities and underlying mechanisms of ROF on HCC cells. Methods: The suppressive effect of ROF on HCC cells were assessed via CCK8 assay, apoptosis assay, cell cycle analysis and xenograft tumor mouse model. Furthermore, quantitative real-time PCR and western blot were applied to analyze the underlying mechanisms of ROF on HCC cells. Results: Firstly, the IC50 values of ROF in HepG2 and HuH7 cells were 373.9 and 288.7 µg/mL at 24 h and 208.9 and 218.0 µg/mL at 48 h, respectively. Moreover, the apoptosis rates of HepG2 and HuH7 cells increased from 6.63% and 6.59% to 17.61% and 21.83% at 24 h and increased from 6.63% and 6.59% to 30.04% and 37.90% at 48 h, respectively. Additionally, ROF induced cell cycle arrest at the S phase in HCC cells. Furthermore, ROF suppressed the tumor growth of HCC cells in vivo without obvious toxicity. Mechanically, ROF facilitated apoptosis by upregulating the expression of PIDD1, CASP8, CASP9, BID, BAX, BIM, and BAK1 in HCC cells. Conclusions: ROF significantly restrains the growth of HCC cells in vitro and in vivo, which could be an effective supplement for HCC therapy.

It is essential to recognize efficient heterogeneous catalysts for environmental remediation that can eliminate organic contaminants or transform them into beneficial byproducts. Herein, we have designed and developed a gold nanoparticle based green nanocomposite material templated over the Curcuma longa extract. The Au NPs/C. longa nanomaterial was thoroughly characterized by FT-IR and UV–Vis spectroscopy followed by FE-SEM, EDX, TEM and XRD analysis. Subsequently, towards the wastewater treatment, it demonstrated excellent potential in the reduction of water contaminant toxic organic dyes like methylene blue (MB), methyl orange (MO), and 4-nitrophenol (4-NP) following excellent kinetics, as monitored by UV–Vis spectrophotometer. The reaction followed a pseudo-first order kinetics. The robustness of the nanocatalyst was justified by reusability studies, and hot filtration test and the catalytic activity did not substantially decline over the course of seven cycles. Towards the assessment of biological activity of Au NPs/C. longa nanocomposite antioxidant capacity was evaluated first using the DPPH radical scavenging method. Further, the study was extended in the investigation of anti-lung cancer properties against a number of standard lung cancer cell lines, viz., NCI-H661, NCI-H1975, NCI-H1573, and NCI-H1563 following MTT colorimetric in vitro studies. Curcuma longa-modified Au NPs are thought to have potential biological activities because of their exceptional capacity to produce reactive oxygen species (ROS).

Abstract Comprehensive investigation of tumor-infiltrating lymphocytes in cancer is crucial to explore the effective immunotherapies, but the composition of infiltrating T cells in urothelial bladder carcinoma (UBC) remains elusive. Here, single-cell RNA sequencing (scRNA-seq) were performed on total 30,905 T cells derived from peripheral blood, adjacent normal and tumor tissues from two UBC patients. We identified 18 distinct T cell subsets based on molecular profiles and functional properties. Specifically, exhausted T (TEx) cells, exhausted NKT (NKTEx) cells, Ki67+ T cells and B cell-like T (B-T) cells were exclusively enriched in UBC. Additionally, the gene signatures of TEx, NKTEx, Ki67+ T and B-T cells were significantly associated with poor survival in patients with BC and various tumor types. Finally, IKZF3 and TRGC2 are the potential biomarkers of TEx cells. Overall, our study demonstrated an exhausted context of T cells in UBC, which layed a theoretical foundation for the development of effective tumor immunotherapies.

Abstract Background Community-acquired infections of Pseudomonas aeruginosa (P. aeruginosa) occur very rarely. Case presentation P. aeruginos was detected in cultures of venous blood and peritoneal exudate of a newborn with 58 perforations in the small intestine. Intravenous administration of imipenem cilastratin sodium and emergency abdominal surgery were performed. The patient fully recovered and was discharged 17 days after the operation. Conclusions Mild symptoms of systemic infections in newborns may delay the diagnosis. Early detection and timely treatment are the key to improved prognosis.