The tumour suppressor Fat1 is dispensable for normal murine hematopoiesis.

Loss and overexpression of FAT1 occurs among different cancers with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets that is sustained following transformation, predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout (cKO) mice where Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multi-panel flow cytometry revealed no ostensible differences between Fat1 cKO mice and normal littermates. Further functional comparisons involving colony forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis.

Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Mouse Corneal Epithelial Cells.

Purpose: Corneal epithelial homeostasis is maintained by coordinated gene expression across distinct cell populations, but the gene regulatory programs underlying this cellular diversity remain to be characterized. Here we applied single-cell multi-omics analysis to delineate the gene regulatory profile of mouse corneal epithelial cells under normal homeostasis. Methods: Single cells isolated from the cornea epithelium (with marginal conjunctiva) of adult mice were subjected to scRNA-seq and scATAC-seq using the 10×Genomics platform. Cell types were clustered by the graph-based visualization method uniform manifold approximation and projection and unbiased computational informatics analysis. The scRNA-seq and scATAC-seq datasets were integrated following the integration pipeline described in ArchR and Seurat. Results: We characterized diverse corneal epithelial cell types based on gene expression signatures and chromatin accessibility. We found that cell type-specific accessibility regions were mainly located at distal regions, suggesting essential roles of distal regulatory elements in determining corneal epithelial cell diversity. Trajectory analyses revealed a continuum of cell state transition and higher coordination between transcription factor (TF) motif accessibility and gene expression during corneal epithelial cell differentiation. By integrating transcriptomic and chromatin accessibility analysis, we identified cell type-specific and shared gene regulation programs. We also uncovered critical TFs driving corneal epithelial cell differentiation, such as nuclear factor I (NFI) family members, Rarg, Elf3. We found that nuclear factor-κB (NF-κB) family members were positive TFs in limbal cells and some superficial cells, but they were involved in regulating distinct biological processes. Conclusions: Our study presents a comprehensive gene regulatory landscape of mouse cornea epithelial cells, and provides valuable foundations for future investigation of corneal epithelial homeostasis in the context of cornea pathologies and regenerative medicine.

Encapsulating Organic Dyes in Metal-Organic Frameworks for Color-Tunable and High-Efficiency White-Light-Emitting Properties.

The design of white-light phosphor is highly desirable for practical applications in SSL (solid-state lighting) and its related fields. Dye-loaded metal-organic frameworks (MOFs) have been widely demonstrated as one type of promising down conversion materials for WLEDs (white-light-emitting diodes), but two issues (dye leakage and inadequate quantum efficiency) require to be addressed before possible applications. Here, a series of single-phase dyes@In-MOF phosphors have been prepared in two different ways: the in-situ process and soaking method. The study of these dyes@In-MOF phosphors confirms the importance of this in-situ process that could effectively increase dye loading and quantum efficiency and greatly decrease dye leakage. As a result, a perfect WLED, fabricated using the in-situ-synthesized (AF/RhB@In-MOF)-3 (AF: Acriflavine; RhB: Rhodamine B) and 450 nm blue LED chip, exhibited a very high quantum yield (QY, up to 42.27%), a high luminous efficacy (LE) of 50.75 lm/W, a high color rendering index (CRI) of 91.2, and nearly identical Commission International ed'Eclairage (CIE) coordinates (0.33,0.31), indicating the potential application of the dye-loaded MOFs with good color quality in smart white LEDs.

Characterization of odor-active compounds in moso bamboo (Phyllostachys pubescens Mazel) leaf via gas chromatography-ion mobility spectrometry, one- and two-dimensional gas chromatography-olfactory-mass spectrometry, and electronic nose.

The leaf of moso bamboo (Phyllostachys pubescens Mazel) is rich in odorant compounds, which is important natural materials for the production of flavor. It also contains phenolic acids, amino acids and peptides, which is a potential source of natural bioactive compounds. The study of odor-active compounds in bamboo leaves can provide a basis for the discovery of natural flavor. The leaf, stem, and powder of moso bamboo were analyzed by gas chromatography-ion mobility spectrometry (GC-IMS). Main odor-active compounds in moso bamboo leaf were analyzed and characterized by (1) a gas chromatography olfactory mass spectrometry (GC-O-MS), (2) two-dimensional gas chromatography olfactory mass spectrometry (GC × GC-O-MS) and (3) electronic nose (E-nose). Based on aroma extract dilution analysis (AEDA), 13 key odor-active compounds with high flavor dilution (FD) factor (≥27), including 3-methyl-1-butanol, (E)-2-hexenal, ethyl hexanoate, (Z)-4-heptenenal, 6-methyl-5-hepten-2-one, octanal, ethyl (Z)-3-hexenoate, 1-hexanol, (Z)-3-hexen-1-ol, (E, E)-2,4-heptadienal, (Z)-2-hexen-1-ol, 1-octen-3-ol and benzaldehyde, were further analyzed. The compounds detected by the above four methods were (E)-2-hexenal, 6-methyl-5-hepten-2-one, octanal, (E, E)-2,4-heptadienal, 1-octen-3-ol and benzaldehyde, and all of which were the main and potential odorants of moso bamboo leaf.

Galangin ameliorates severe acute pancreatitis in mice by activating the nuclear factor E2-related factor 2/heme oxygenase 1 pathway.

Acute pancreatitis (AP) is a common serious acute condition of the digestive system that remains a clinical challenge. Severe acute pancreatitis (SAP) in particular is characterized by high morbidity and mortality. The present study was designed to investigate the protective effect of Galangin (Gal), a natural flavonol obtained from lesser galangal, on L-arginine-induced SAP in mice and in AR42J cells. Amylase and lipase activities were measured and the histopathology of the pancreas, lung, and kidney was evaluated. Inflammation and oxidative stress were assessed using ELISA, western blotting, RT-PCR, and immunohistochemistry. Gal was shown to reduce proinflammatory cytokine production and reactive oxygen species (ROS) generation in vivo and in vitro. L-arginine treatment reduced the expression of components of the nuclear factor E2-related factor 2 (Nrf2) signaling pathway and the downstream protein heme oxygenase-1 (HO-1) in mice, whereas Gal increased their expression. Furthermore, the Nrf2/HO-1 pathway inhibitor brusatol prevented the anti-inflammatory and antioxidant effects of Gal in mice with SAP. Taken together, our results imply that Gal has protective effects in L-arginine-induced SAP that are induced by the upregulation of the Nrf2/HO-1 pathway, which has anti-inflammatory and antioxidant effects. Thus, Gal may represent a promising treatment for SAP.

[Optimization of Mouse Model of Aplastic Anemia Induced by Pan T Lymphocytes Combined with Irradiation].

AbstractObjective: To establish an acquired aplastic anemia animal model for investigating the function of T lymphocyte and the pathogenesis and treatment of aplastic anemia(AA). METHODS: To establish the acquired aplastic anemia mouse model through the X-ray irradiation in combination with lymphocytes injection. AA Group: the purified Pan T lymphocytes from the spleen of C57BL/6J mice were enriched and injected to the mice through tail vein(5×106), the CB6F1 mice were exposed to 3,4 and 5 Gy X-ray irradiation; TBI Group: the CB6F1 mice were exposed to 3,4 and 5 Gy X-ray irradiation, and were injected with the same volume of PBS buffer; Control group: the CB6F1 mice were only injected with the same volume of PBS buffer. The peripheral blood routine was examined and the number of nucleated cells in bone marrow were calculated；the hematopoiesis changes in bone marrow was examined；flow cytometry was used to examine the distribution of T lymphocytes in bone marrow, and it also used to examine the apoptosis of bone marrow cells and the differentiation of spleen T lymphocytes. RESULTS: Compared with 4, 5 Gy irradiated mice in AA groups, the survival time of 3 Gy irradiated AA groups was significantly prolonged. 3, 4 and 5 Gy X-ray irradiation combined with Pan T lymphocyte injection could successfully induced severe reduction of red blood cells, blood neutrophils, and platelets, severe reduction of bone marrow nucleated cells, severe bone marrow hematopoietic failure, and the significant expansion of T lymphocytes ratio in the bone marrow. CD4+ and CD8+ T cells were both increased, but mainly on CD8+ T cells, and could promote the differentiation of T cells from naïve T cells to effector memory T cells. CONCLUSION: 3, 4 and 5 Gy X-ray irradiation combined with 5×106 pan-T cell injection could successfully induce acquired aplastic anemia through T lymphocyte hyperfunction. Compared with 4, 5 Gy irradiated AA group, the 3 Gy irradiated AA group shows significantly longer survival time, and the peripheral blood routine profile closely resembles the clinical manifestations of AA patients.

A fluorescent DNA based probe for Hg(II) based on thymine-Hg(II)-thymine interaction and enrichment via magnetized graphene oxide.

The authors describe a fluorometric assay for the determination of Hg(II). A naphthalimide derivative is used as a label for a thymine (T) rich ssDNA, and graphene oxide magnetized with Fe3O4 nanoparticles acts as a quencher and preconcentrators. In the absence of Hg(II), the labeled ssDNA does not separate from the magnetized graphene oxide. As a result, fluorescence is fully quenched. In the presence of Hg(II), a T-Hg(II)-T link is formed dues to the highly affinity between T and Hg(II). Hence, fluorescence is restored. The assay has a linear response in the 1.0 to 10.0 nM Hg(II) concentration range, and a 0.65 nM detection limit. The method is selective and sensitive. It was applied to the analysis of spiked environmental water samples, and data agreed well with those obtained by atomic fluorescence spectrometry. Graphical abstract Strategy of a fluorescent probe for detecting Hg(II). The method has a 0.65 nM detection limit and is selective. MGO: magnetized graphene oxide, AHN: a fluorescent derivative of naphthalimide.

The Effect of Silibinin on the Pharmacokinetics of Ivabradine and N-Desmethylivabradine in Rats.

The objective of this work was to investigate the effect of orally administered silibinin on the pharmacokinetics of ivabradine and its active metabolite N-desmethylivabradine in rats. Twelve healthy male Sprague-Dawley rats were randomly divided into 2 groups: the control group (received oral 1.0 mg/kg ivabradine alone) and the combination group (1.0 mg/kg ivabradine orally coadministered with 30 mg/kg silibinin). The plasma concentration of ivabradine and N-desmethylivabradine were estimated by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) and different pharmacokinetic parameters were calculated using the DAS 2.0 software. The pharmacokinetic parameters of t1/2, Cmax, AUC(0-t) and AUC(0-∞) of ivabradine in the combination group were significantly higher than those in the control group (p < 0.01). However, silibinin has no effect on the pharmacokinetics of N-desmethylivabradine. This study demonstrates that silibinin increase plasma concentration of ivabradine. Henceforth, the pharmacodynamic influence of this interaction should be taken into consideration while prescribing ivabradine to patients already taking silibinin.

Chronic bronchitis with fungal infection presenting with marked elevation of serum carbohydrate antigen 19-9: a case report.

Carbohydrate antigen 19-9 (CA19-9) is the most frequently applied serum tumor marker for diagnosis of cancers in the digestive organs. However, some patients with benign diseases can have elevated serum levels of CA19-9 as well. The current study presents a 55-year-old female who was admitted to our hospital for further evaluation of a nodular cavity shadow in the right lower lobe and clarification of the cause of the marked elevation of serum CA19-9 levels. Abdominal MRI and gastrointestinal endoscopy did not find any malignancy. As lung cancer cannot be excluded in this patient, a video-assisted thoracoscopic surgery was carried, intraoperative and postoperative biopsy analysis both suggested chronic bronchitis with fungal infection (due to Histoplasma capsulatum or Penicillium marneffei) and organization. Immunohistochemistry showed marked positive staining for CA19-9 in the damaged lung tissue. The CA19-9 levels quickly returned to the normal range following lobe resection. Therefore, the marked elevation of serum CA19-9 levels, in this case, may have resulted from the chronic bronchitis with fungal infection.