Analysis of the expression pattern of the BCL11B gene and its relatives in patients with T-cell acute lymphoblastic leukemia

<p>Abstract</p> <p>Background</p> <p>In a human T-cell acute lymphoblastic leukemia (T-ALL) cell line (Molt-4), siRNA-mediated suppression of <it>BCL11B </it>expression was shown to inhibit proliferation and induce apoptosis, functions which may be related to genes involved in apoptosis (such as <it>TNFSF10 </it>and <it>BCL2L1</it>) and TGF-β pathways (such as <it>SPP1</it>and <it>CREBBP</it>).</p> <p>Methods</p> <p>The expression levels of the above mentioned genes and their correlation with the <it>BCL11B </it>gene were analyzed in patients with T-ALL using the TaqMan and SYBR Green I real-time polymerase chain reaction technique.</p> <p>Results</p> <p>Expression levels of <it>BCL11B, BCL2L1</it>, and <it>CREBBP </it>mRNA in T-ALL patients were significantly higher than those from healthy controls (<it>P <</it>0.05). In T-ALL patients, the <it>BCL11B </it>expression level was negatively correlated with the <it>BCL2L1 </it>expression level (<it>r</it>_s= -0.700; <it>P </it><it><</it>0.05), and positively correlated with the <it>SPP1 </it>expression level (<it>r</it>_s= 0.683; <it>P </it><it><</it>0.05). In healthy controls, the <it>BCL11B </it>expression level did not correlate with the <it>TNFSF10</it>, <it>BCL2L1</it>, <it>SPP1</it>, or <it>CREBBP </it>expression levels.</p> <p>Conclusions</p> <p>Over-expression of <it>BCL11B </it>might play a role in anti-apoptosis in T-ALL cells through up-regulation of its downstream genes <it>BCL2L1 </it>and <it>CREBBP</it>.</p

Identification of lactate regulation pattern on tumor immune infiltration, therapy response, and DNA methylation in diffuse large B-cell lymphoma

BackgroundLactate, produced through glycolytic metabolism in the tumor microenvironment (TME), is implicated in tumorigenesis and progression in diverse cancers. However, the impact of lactate on the remodeling of the TME in diffuse large B-cell lymphoma (DLBCL) and its implications for therapy options remain unclear.MethodA lactate-related (LAR) scoring model was constructed in DLBCL patients using bioinformatic methods. CIBERSORT, XCELL, and ssGSEA algorithms were used to determine the correlation between LAR score and immune cell infiltration. Tumor Immune Dysfunction and Exclusion (TIDE), rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) cohorts, and Genomics of Drug Sensitivity in Cancer (GDSC) were utilized to predict the therapeutic response of DLBCL patients. The impact of the hub gene STAT4 on tumor biological behavior and DNA methylation was experimentally validated or accessed by the TSIDE database.ResultsThe LAR scoring model was developed based on 20 prognosis-related lactate genes, which enabled the division of DLBCL patients into high- and low-risk groups based on the median LAR score. Patients with high-risk DLBCL exhibited significantly worse survival outcomes in both the training cohorts (GSE181063) and the validation cohorts (GSE10846, GSE32918, and GSE69053), as indicated by statistically significant differences (all P&lt;0.05) and area under the curve (AUC) values exceeding 0.6. Immune analyses revealed that low-risk DLBCL patients had higher levels of immune cell infiltration and antitumor immune activation compared to high-risk DLBCL patients. Furthermore, DLBCL patients with high LAR scores were associated with a lower TIDE value and poor therapeutic efficacy of the R-CHOP regimen. GDSC analysis identified 18 drugs that exhibited significant response sensitivity in low-risk DLBCL patients. Moreover, in vitro experiments demonstrated that overexpression of the lactate key gene STAT4 could suppress proliferation and migration, induce cell cycle arrest, and promote cell apoptosis in DLBCL cells. Transcriptional expression and methylation of the STAT4 gene were found to be associated with immunomodulators and chemokines.ConclusionThe lactate-based gene signature effectively predicts the prognosis and regulates TME in DLBCL. Our study underscores the role of lactate gene, STAT4, as an important tumor suppressor in DLBCL. Modulating STAT4 could be a promising strategy for DLBCL in clinical practice

Glacial Lake Outburst Flood Monitoring and Modeling through Integrating Multiple Remote Sensing Methods and HEC-RAS

The Shishapangma region, situated in the middle of the Himalayas, is rich in glacial lakes and glaciers. Hence, glacial lake outburst floods (GLOFs) have become a top priority because of the severe threat posed by GLOFs to the downstream settlements. This study presents a comprehensive analysis of GLOF hazards using multi-source remote sensing datasets and designs a flood model considering the different breaching depths and release volumes for the Galong Co region. Based on high-resolution optical images, we derived the expanding lake area and volume of glacial lakes. We monitored deformation velocity and long-term deformation time series around the lake dam with Small BAseline Subset Interferometric Synthetic Aperture Radar (SBAS-InSAR). The glacier thinning trend was obtained from the difference in the Digital Elevation Model (DEM). We identified potential avalanche sources by combining topographic slope and measurable deformation. We then carried out flood modeling under three different scenarios using the hydrodynamic model HEC-RAS for Galong Co, which is formed upstream of Nyalam. The results show that the Nyalam region is exposed to high-intensity GLOFs in all scenarios. The larger breaching depth and release volumes caused a greater flow depth and peak discharge. Overall, the multiple remote sensing approaches can be applied to other glacial lakes, and the modeling can be used as a basis for GLOF mitigation

Extending Ag Nanoparticles as Colorimetric Sensor to Industrial Zinc Electrolyte for Cobalt Ion Detection

The direct and rapid determination of trace cobalt ion (Co2+) in the electrolyte of zinc smelting plants is urgently needed but is impeded by the severe interference of extremely high-concentration zinc ions in the solution. Herein, colorimetric detection of Co2+ by the polyvinylpyrrolidone functionalized silver nanoparticles (PVP-AgNPs) is realized in solutions with the Zn/Co ratio being high, up to (0.8–5) × 104, which is located within the ratio range in industrial solution. The high concentration of Zn2+ induces a strong attenuation of Co2+-related signals in ultraviolet-visible (UV-vis) extinction spectra; nevertheless, a good linear range for detecting 1–6 mg/L Co2+ in 50 g/L Zn2+ solution is still acquired. The strong anti-interference toward other metal ions and the mechanism understanding for trace Co2+ detection in such a high-concentration Zn2+ solution are also revealed by systematic analysis techniques. The results extend the AgNPs as colorimetric sensors to industrial solutions, providing a new strategy for detecting trace-metal ions in industrial plants

Conceptions of Adulthood Among Chinese Emerging Adults

With the influence of globalization, Chinese young adults’ transition to adulthood today are cultivated by both traditional Chinese values (e.g., collectivism, Confucian philosophy), as well as Western values (e.g., individualism, independence). The present study aimed to characterize emerging adults’ perception of adulthood in China today in terms of (1) the criteria for adulthood Chinese emerging adults considered important; (2) the relationships between subjective importance of adulthood status and status as a student or non-student; (3) gender; and (4) hukou status (rural vs urban). Chinese emerging adults aged 17–30 (N = 7099; 69% college students; 54% female; 57% with rural hukou status) completed a cross-sectional survey between October and November 2021. We found that most Chinese emerging adults felt ambivalent about their adulthood status. The findings suggest that cultural and geographical differences exist between emerging Chinese and Western young adults in their perceptions of entering adulthood. Concerning the self-perceived adulthood status and the subjective importance of criteria, several differences were found among Chinese emerging adults based on gender (male vs female), hukou status (rural vs urban), and educational status (student vs non-student). With increasing age, being men or having rural hukou, Chinese emerging adults may be more likely to adhering to traditional markers of adulthood. Overall, this study not only sheds light on conceptions of adulthood among Chinese emerging adults, but also provides implication for understanding emerging adults’ lived experience and subjective perception of this life stage. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature

Enhancer Reprogramming within Pre-existing Topologically Associated Domains Promotes TGF-β-Induced EMT and Cancer Metastasis.

Transcription growth factor β (TGF-β) signaling-triggered epithelial-to-mesenchymal transition (EMT) process is associated with tumor stemness, metastasis, and chemotherapy resistance. However, the epigenomic basis for TGF-β-induced EMT remains largely unknown. Here we reveal that HDAC1-mediated global histone deacetylation and the gain of specific histone H3 lysine 27 acetylation (H3K27ac)-marked enhancers are essential for the TGF-β-induced EMT process. Enhancers gained upon TGF-β treatment are linked to gene activation of EMT markers and cancer metastasis. Notably, dynamic enhancer gain or loss mainly occurs within pre-existing topologically associated domains (TADs) in epithelial cells, with minimal three-dimensional (3D) genome architecture reorganization. Through motif enrichment analysis of enhancers that are lost or gained upon TGF-β stimulation, we identify FOXA2 as a key factor to activate epithelial-specific enhancer activity, and we also find that TEAD4 forms a complex with SMAD2/3 to mediate TGF-β signaling-triggered mesenchymal enhancer reprogramming. Together, our results implicate that key transcription-factor (TF)-mediated enhancer reprogramming modulates the developmental transition in TGF-β signaling-associated cancer metastasis

Enhancer Reprogramming within Pre-existing Topologically Associated Domains Promotes TGF-β-Induced EMT and Cancer Metastasis.

Transcription growth factor β (TGF-β) signaling-triggered epithelial-to-mesenchymal transition (EMT) process is associated with tumor stemness, metastasis, and chemotherapy resistance. However, the epigenomic basis for TGF-β-induced EMT remains largely unknown. Here we reveal that HDAC1-mediated global histone deacetylation and the gain of specific histone H3 lysine 27 acetylation (H3K27ac)-marked enhancers are essential for the TGF-β-induced EMT process. Enhancers gained upon TGF-β treatment are linked to gene activation of EMT markers and cancer metastasis. Notably, dynamic enhancer gain or loss mainly occurs within pre-existing topologically associated domains (TADs) in epithelial cells, with minimal three-dimensional (3D) genome architecture reorganization. Through motif enrichment analysis of enhancers that are lost or gained upon TGF-β stimulation, we identify FOXA2 as a key factor to activate epithelial-specific enhancer activity, and we also find that TEAD4 forms a complex with SMAD2/3 to mediate TGF-β signaling-triggered mesenchymal enhancer reprogramming. Together, our results implicate that key transcription-factor (TF)-mediated enhancer reprogramming modulates the developmental transition in TGF-β signaling-associated cancer metastasis

Psychometric evaluation of the inventory of dimensions of emerging adulthood (IDEA) in China

Background/Objective: Emerging adulthood (EA, age range between 18 to 29 years) is an important developmental stage that is characterized by marked social and psychological changes. Currently, its developmental features are quantified by the Inventory of the Dimensions of Emerging Adulthood (IDEA) but a validated Chinese version of this questionnaire (IDEA-C) is lacking. Thus, this research, which consists of two consecutive studies, aimed to investigate the psychometric properties of the translated IDEA in a Chinese sample of emerging adults. Method: Firstly, a forward-backward translation of the IDEA-C scale was conducted. Item analysis and exploratory factor analysis were performed in Sample 1a (n = 2438), followed by structural validity test in Sample 1b (n = 2461). Concurrent validity and internal consistency were evaluated in Sample 1(n = 4899). Finally, test-retest reliability was tested in Sample 2 (n = 185). Then, the second study aimed to test the factor structure proposed by study 1 in the non-student sample (n = 2200) by confirmatory factor analysis. In addition, the second study also investigated whether the attainment of college education influenced the EA experience of non-student emerging adults in China. And the association was examined between the socioeconomic status of emerging adults and the subscales of IDEA. Results: In the college sample, the IDEA-C scale presented a four-factor structure different from the original five-factor structure (χ2(190)=1116.84, p \u3c 0.001; CFI = 0.97; TLI = 0.96; SRMR = 0.039; RMSEA = 0.050 [90%CI=0.047-0.052]). In addition, IDEA-C exhibited good internal consistency reliability (Cronbach\u27s alpha \u3e0.77), test-retest reliability (r\u3e0.49, p \u3c 0.01) and concurrent validity. And the CFA in non-student sample also showed an adequate fit indices (χ2(158) =710.10, p \u3c 0.001, TLI=0.93, CFI=0.94, SRMR=0.038, RMSEA=0.04 [90%CI=0.037-0.040]) and an adequate internal consistency (Cronbach\u27s alpha \u3e0.64) and test-retest reliability (r\u3e0.43, p \u3c 0.01). Conclusion: The results of the present study confirmed that the Chinese version of the IDEA is found to be valid for measuring psychological characteristics of EA in Chinese-speaking samples of emerging adults