T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

BACKGROUND: Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV). METHODS: We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development. RESULTS: We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron. CONCLUSION Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Child ; Humans ; Neurodevelopmental Disorders/epidemiology* ; Genetic Testing ; Phenotype ; Brain/pathology* ; Genetic Background ; SOX Transcription Factors/genetics*

Aim To observe the effect of total flavonoid from Mori folium(TFMF) on renal interstitial fibrosis in type 1 diabetic mice and its possible mechanism.Methods Diabetic mice were induced by intraperitoneal injection of streptozotocin(STZ) dissolved in 0.01 mol·L-1 citrate buffer(pH 4.5) at 150 mg·kg-1 body weight after 12 h of food deprivation.Forty model mice were divided randomly into four groups: model group, and low-(0.25 g·kg-1), moderate-(0.5 g·kg-1), high-dose groups(1 g·kg-1) fed with TFMF once daily.In addition, eight normal mice were used as normal group.After 12 weeks, the fasting blood glucose(FBG), serum creatinine(Cr), blood urea nitrogen(BUN) and microalbuminuria(mAlb) were measured.Masson staining, Sirius red staining and collagen type Ⅳ immunohistochemical staining were used to detect the expression of collagen protein in the cortex, while laminin staining to assess the degree of glomerular and renal tubular basement membrane thickening.The protein expressions related to epithelial-mesenchymal transition and PI3K/Akt/mTOR in the renal cortex of mice were detected by Western blot.Results The moderate and high dose of TFMF could significantly decrease the levels of FBG, Cr, BUN and mAlb in diabetic mice, meanwhile decreasing the expression of α-SMA protein by inhibiting the activation of PI3K/Akt/mTOR signaling pathway, which led to the amelioration of the pathological alterations of renal tissue.Conclusions The moderate and high dose of TFMF can reduce the level of renal interstitial fibrosis in type 1 diabetic mice, and its mechanism may be related to the inhibition of activation of PI3K/Akt/mTOR signaling pathway.

Objective To construct a recombinant lentivirus containing human beta defensins -3 ( hBD3 ) , connective tissue growth factor gene (CTGF) and enhanced green fluorescent protein (EGFP), and to detect its translation in rabbit bone marrow mesenchymal stem cells (BMSC).Methods The lentivirus containing hBD3, CTGF and EGFP genes was constructed in vitro.The titer of lentivirus was tested with end-paint dilution assay .Rabbit BMSCs were transfected with recombinant virus.The best value of multiplicity of infection (MOI) was tested.The expression condition, transfection efficacy and genetic stability of the target genes were evaluated by using fluorescence microscopy and flow cytometry . Western blotting was used to detect the expression of the target protein .Results Recombinant lentivirus vectors: Lenti-CTGF-hBD3-EGFP, Lenti-hBD3-EGFP, and Lenti-EGFP, were successfully obtained . The titer of the recombinant lentiviruses was 3.21 ×108, 5.80 ×108, and 1.16 ×109, respectively.The best MOI value to transfect BMSCs was 150. The transfection efficacy of these lentivirus vectors was high , reaching 79.72%as assessed by flow cytometry , and it could be stably inherited .Western blotting displayed that target protein expression was successful .Conclusion The construction of recombinant lentiviruses carrying hBD3 and CTGF genes is successful and can be effectively transfected into BMSCs .

Intravascular ultrasound (IVUS) is widely used in coronary artery examination. Ultrasonic elastography combined with IVUS is very conspicuous in identifying plaque component and in detecting plaque vulnerability degree. In this study, a simulation model of the blood vessel based on finite element analysis (FEA) was established. The vessel walls generally have radial changes caused by different intravascular pressure. The signals at lower pressures were used as the pre-deformation data and the signals at higher pressure were used as the post-deformation data. Displacement distribution was constructed using the time-domain cross-correlation method, and then strain images. By comparison of elastograms under different pressures, we obtained the optimal pressure step. Furthermore, on the basis of the obtained optimize pressure step, the simulation results showed that this method could effectively distinguish characteristics between different component plaques, and could guide the later experiments and clinical applications.
Angiography ; Arteries ; diagnostic imaging ; pathology ; Elasticity Imaging Techniques ; Finite Element Analysis ; Humans ; Plaque, Atherosclerotic ; diagnostic imaging ; Pressure

Objective To explore the relationship of depth of trophoblastic invasion with trophoblast cell activity and serum β-hCG according to the expression of proliferation antigen Ki-67 which viewed as an indicator of cell proliferation activity.Methods Fallopian tube specimens collected from 108 patients who underwent operation treatment for fallopian tubal pregnancy in our hospital were investigated by light microscopic examination.They were divided into three groups according to the depth of trophoblastic infiltration: Ⅰ group (stage): trophoblastic invasion of tubal mucosa,Ⅱ group(stage): trophoblastic invasion of the muscularis,Ⅲ group(stage): trophoblast invasion of serosa layer(muscularis penetration).The expression of Ki-67 was detected by SP method and blood β-hCG was detected within 2 hours of preoperative.The level of β-hCG,the expression of Ki-67 and the depth of trophoblast invasion were analyzed.Results Mean level of serumβ-hCG in Group Ⅰ,Ⅱ and Ⅲ were(1416.64 ± 859.94)U/L,(3380.33 ± 2392.36)U/L and(6999.33 ± 4949.90)U/L respectively.Positive expression rate of cell proliferation antigen Ki-67 in Group Ⅰ,Ⅱ and Ⅲ were 21.95％,53.66％ and 6.40％ respectively.There were significant difference on the expression of Ki-67 between group Ⅰ and group Ⅱ,group Ⅱ and Ⅲ group,group Ⅰ and group Ⅲ(x2 =3.94,4.07,4.35,respectively,P ＜ 0.05).The serumβ-hCG level also displayed statistics difference in the three groups(F =9.914,P ＜ 0.01).The positive expression of Ki-67 and serum β-hCG level were positively correlated with each other(r =0.678,P ＜ 0.05)Conclusion The high level of the serum β-hCG indicates high expression of Ki-67 and deeper trophoblast invasion of tubal wall.

0.05), so they were called the non-Dampness-Stagnation type. After adjusting age, sex, blood pressure, blood fat and blood glucose, Logistic regression analysis demonstrated that insulin sensitivity was closely correlated with SDT (P

0.05),were remarkably higher than those of the control group(P