Prostate cancer (PCa) risk-associated SNPs are enriched in noncoding cis-regulatory elements (rCREs), yet their modi operandi and clinical impact remain elusive. Here, we perform CRISPRi screens of ...260 rCREs in PCa cell lines. We find that rCREs harboring high risk SNPs are more essential for cell proliferation and H3K27ac occupancy is a strong indicator of essentiality. We also show that cell-line-specific essential rCREs are enriched in the 8q24.21 region, with the rs11986220-containing rCRE regulating MYC and PVT1 expression, cell proliferation and tumorigenesis in a cell-line-specific manner, depending on DNA methylation-orchestrated occupancy of a CTCF binding site in between this rCRE and the MYC promoter. We demonstrate that CTCF deposition at this site as measured by DNA methylation level is highly variable in prostate specimens, and observe the MYC eQTL in the 8q24.21 locus in individuals with low CTCF binding. Together our findings highlight a causal mechanism synergistically driven by a risk SNP and DNA methylation-mediated 3D genome architecture, advocating for the integration of genetics and epigenetics in assessing risks conferred by genetic predispositions.
Three-dimensional reconstruction plays a crucial role in capturing plant phenotypes and expediting the process of agricultural informatization. However, the reconstruction of small objects such as ...plant specimens and grains often faces challenges like low two-dimensional image resolution and sparse textures. To enhance the three-dimensional reconstruction of plant specimens like wheat grains for comprehensive phenotypic characterization, this study proposes a novel super-resolution reconstruction network called T-transformer net. The network leverages the self-attention mechanism of Transformers to extract extensive global information from spatial sequences. By employing a hourglass block structure to construct spatial attention units and combining channel attention with window-based self-attention schemes, it effectively harnesses their complementary advantages. This encompasses utilizing global statistical data while capitalizing on potent local fitting capabilities. Evaluation of the model on publicly available datasets Set5, Set14, and Manga109 demonstrates superior overall performance of T-transformer net compared to mainstream super-resolution algorithms at upscaling factors of 2x, 3x, and 4x. In the context of super-resolution tasks involving wheat grain datasets, the peak signal-to-noise ratio reaches 42.89 dB, and the structural similarity index attains 0.9643. Subsequently, we subject the super-resolved wheat grain images to three-dimensional reconstruction. Through comprehensive extraction of high-level semantic information by neural networks, the reconstruction accuracy is improved by 38.96% compared with the unprocessed image, effectively mitigating challenges arising from sparse textures and repetitive patterns in wheat grain structures. This study contributes valuable methodology and insights to the realm of three-dimensional reconstruction in botany, holding significant implications for advancing agricultural informatization.
BeiDou Satellite-based Augmentation System (BDSBAS) has come into the trial operation stage since July, 2020. To evaluate the characteristic of the augmentation message in BDSBAS-B1C signal, the ...effectiveness of the message content was firstly analyzed, and then the validity of the broadcasting strategy was estimated. Finally, the accuracy of the user equivalent ranging error (UERE) and the single frequency positioning error with different correction parameters in BDSBAS-B1C message was evaluated. Based on the above analysis, the effectiveness of the augmentation message was preliminarily verified with the results showing that: (1) the BDSBAS-B1C message type, information content and update interval have basically met the international standard; (2) the accuracy of the UERE obtained with the augmentation message had an obvious improvement in contrast to that of the UERE obtained with the usual navigation message of the GPS satellites, and the ionospheric delay was one of the important factors which affected the accuracy of the UERE; (3) the positioning accuracy obtained with the augmentation message was also improved, and the improvement was more obvious in the service areas with high availability of the ionospheric parameters.
Genome-wide association studies have identified 270 loci conferring risk for prostate cancer (PCa), yet the underlying biology and clinical impact remain to be investigated. Here we observe an ...enrichment of transcription factor genes including HNF1B within PCa risk-associated regions. While focused on the 17q12/HNF1B locus, we find a strong eQTL for HNF1B and multiple potential causal variants involved in the regulation of HNF1B expression in PCa. An unbiased genome-wide co-expression analysis reveals PCa-specific somatic TMPRSS2-ERG fusion as a transcriptional mediator of this locus and the HNF1B eQTL signal is ERG fusion status dependent. We investigate the role of HNF1B and find its involvement in several pathways related to cell cycle progression and PCa severity. Furthermore, HNF1B interacts with TMPRSS2-ERG to co-occupy large proportion of genomic regions with a remarkable enrichment of additional PCa risk alleles. We finally show that HNF1B co-opts ERG fusion to mediate mechanistic and biological effects of the PCa risk-associated locus 17p13.3/VPS53/FAM57A/GEMIN4. Taken together, we report an extensive germline-somatic interaction between TMPRSS2-ERG fusion and genetic variations underpinning PCa risk association and progression.
How to efficiently treat municipal solid waste (MSW) has become one of the critical solutions in response to the call for "carbon neutrality". Here, the waste polypropylene nonwoven fabric of waste ...diapers was converted into hierarchical nanoporous biochar (HPBC) through pre-carbonization and activation processes as an ideal precursor for supercapacitors (SCs) with excellent performance. The prepared HPBC-750-4 with an ultrahigh specific surface area (3838.04 m
2
g
−1
) and abundant heteroatomic oxygen (13.25%) and nitrogen (1.16%) codoped porous biochar structure. Given its structural advantages, HPBC-750-4 achieved a specific capacitance of 340.9 F g
−1
at a current density of 1 A g
−1
in a three-electrode system. Its capacitance retention rate was above 99.2% after 10 000 cycles at a current density of 10 A g
−1
, which indicated an excellent rate capability and long-term cycling stability. Furthermore, the HPBC-750-4//HPBC-750-4 symmetric SC exhibited a superb energy density of 10.02 W h kg
−1
with a power density of 96.15 W kg
−1
in a 6 M KOH electrolyte. This work not only demonstrates the enormous potential of waste polypropylene nonwoven fabric in the SC industry but also provides an economically feasible means of managing MSW.
How to efficiently treat municipal solid waste (MSW) has become one of the critical solutions in response to the call for "carbon neutrality".
Non-small cell lung cancer (NSCLC) causes considerable mortality in the world. Owing to molecular biological progress, treatments in adenocarcinoma have evolved revolutionarily while those in ...squamous lung cancer remain unsatisfied. Recent studies revealed high-frequency alteration of Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-like factor 2 (Keap1/Nrf2) pathway within squamous lung cancer, attracting researchers to focus on this particular pathway. In NSCLC patients, deregulated Nrf2 signal is recognized as a common feature at both DNA and protein level. Emerging associations between Nrf2 and other pathways have been elucidated. MicroRNA was also implicated in the regulation of Nrf2. Agents activating or antagonizing Nrf2 showed an effect in preclinical researches, reflecting different effects of Nrf2 during tumor initiation and progression. Prognostic evaluation demonstrated a negative impact of Nrf2 signal on NSCLC patients' survival. Considering the importance of Nrf2 signal in NSCLC, further studies are required in the future.
The conversion of nitrogen–oxygen-rich biomass wastes into heteroatomic co-doped nanostructured carbons used as energy storage materials has received widespread attention. In this study, an in situ ...nitrogen–oxygen co-doped porous carbon was prepared for supercapacitor applications via a two-step method of pre-carbonization and pyrolytic activation using mixed egg yolk/white and rice waste. The optimal sample (YPAC-1) was found to have a 3D honeycomb structure composed of abundant micropores and mesopores with a high specific surface area of 1572.1 m2 g−1, which provided abundant storage space and a wide transport path for electrolyte ions. Notably, the specific capacitance of the constructed three-electrode system was as high as 446.22 F g−1 at a current density of 1 A g−1 and remained above 50% at 10 A g−1. The capacitance retention was 82.26% after up to 10,000 cycles. The symmetrical capacitor based on YPAC-1 with a two-electrode structure exhibited an energy density of 8.3 Wh kg−1 when the power density was 136 W kg−1. These results indicate that porous carbon materials prepared from mixed protein and carbohydrate waste have promising applications in the field of supercapacitors.
The objective of this study was to evaluate the effect of platinum-based drugs on nuclear-factor erythroid2 like 2 (NRF2) signaling in non-small cell lung cancer cell lines with or without Kelch-like ...ECH-associated protein 1 (KEAP1) mutations and to determine the role of NRF2 and KEAP1 on platinum-based drug treatment.
We used real-time PCR to assess relative mRNA expression and used western blotting and immunofluorescence assays to assess protein expression. Small interfering RNA and shuttle plasmids were used to modulate the expression of NRF2, wild-type KEAP1, and mutant KEAP1. Drug sensitivity to platinum-based drugs was evaluated with Cell Count Kit-8.
We found that platinum-based therapies modified the NRF2 signaling pathway differently in KEAP1-mutated non-small cell lung cancer (NSCLC) cell lines compared with wild-type KEAP1 cell lines. The reactive degree of NRF2 signaling also varies between nedaplatin and cisplatin. The modification of NRF2 or KEAP1 expression in NSCLC cell lines disrupted downstream gene expression and cell sensitivity to platinum-based drugs. Finally, gene expression data retrieved from The Cancer Genome Atlas (TCGA) consortium indicated that KEAP1 mutation significantly affects NRF2 signaling activity in patients with NSCLC.
Our findings suggest that NRF2 signaling plays an indispensable role in NSCLC cell sensitivity to platinum-based treatments and provides a rationale for using NRF2 as a specific biomarker for predicting which patients will be most likely to benefit from platinum-based treatment.
The SIX family homeobox genes have been demonstrated to be involved in the tumor initiation and progression, but their clinicopathological features and prognostic values in non-small cell lung cancer ...(NSCLC) have not been well defined. We analyzed relevant datasets and performed a systemic review and a meta-analysis to assess the profile of SIX family members in NSCLC and evaluate their importance as biomarkers for diagnosis and prediction of NSCLC.
This meta-analysis included 17 studies with 2358 patients. Hazard ratio (HR) and 95 % confidence interval (CI) were calculated to represent the prognosis of NSCLC with expression of the SIX family genes. Heterogeneity of the ORs and HRs was assessed and quantified using the Cochrane Q and I
test. Begg's rank correlation method and Egger's weighted regression method were used to screen for potential publication bias. Bar graphs of representative datasets were plotted to show the correlation between the SIX expression and clinicopathological features of NSCLC. Kaplan-Meier survival curves were used to validate our prognostic analysis by pooled HR.
The systematic meta-analysis unveiled that the higher expressions of SIX1-5 were associated with the greater possibility of the tumorigenesis. SIX4 and SIX6 were linked to the lymph node metastasis (LNM). SIX2, SIX3, and SIX4 were correlated with higher TNM stages. Furthermore, the elevated expressions of SIX2, SIX4, and SIX6 predicted poor overall survival (OS) in NSCLC (SIX2: HR = 1.14, 95 % CI, 1.00-1.31; SIX4: HR = 1.39, 95 % CI, 1.16-1.66; SIX6: HR = 1.18, 95 % CI, 1.00-1.38) and poor relapse-free survival (RFS) in lung adenocarcinoma (ADC) (SIX2: HR = 1.42, 95 % CI, 1.14-1.77; SIX4: HR = 1.52, 95 % CI, 1.09-2.11; SIX6: HR = 1.25, 95 % CI, 1.01-1.56).
Our report demonstrated that the SIX family members play distinct roles in the tumorigenesis of NSCLC and can be potential biomarkers in predicting prognosis of NSCLC patients.
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