Epigenetically associated IGF2BP3 upregulation promotes cell proliferation by regulating E2F1 expression in hepatocellular carcinoma.

RNA-binding proteins (RBPs) are a class of proteins that primarily function by interacting with different types of RNAs and play a critical role in regulating the transcription and translation of cancer-related genes. However, their role in the progression of hepatocellular carcinoma (HCC) remains unclear. In this study, we analyzed RNA sequencing data and the corresponding clinical information of patients with HCC to screen for prognostic RBPs. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was identified as an independent prognostic factor for liver cancer. It is upregulated in HCC and is associated with a poor prognosis. Elevated IGF2BP3 expression was validated via immunohistochemical analysis using a tissue microarray of patients with HCC. IGF2BP3 knockdown inhibited the proliferation of Hep3B and HepG2 cells, whereas IGF2BP3 overexpression promoted the expansion of HuH-7 and MHCC97H cells. Mechanistically, IGF2BP3 modulates cell proliferation by regulating E2F1 expression. DNA hypomethylation of the IGF2BP3 gene may increase the expression of IGF2BP3, thereby enhancing cell proliferation in HCC. Therefore, IGF2BP3 may act as a novel prognostic biomarker and a potential therapeutic target for HCC.

Investigating potential mechanisms of vitamin D against thyroid cancer via network pharmacology and experimental validation.

Thyroid cancer (TC) is one of the most common endocrine malignancies worldwide. Increasing evidence suggests that vitamin D (VD) has potential benefits in the treatment of TC. However, evidence regarding the targets and molecular mechanisms of VD in TC remains limited. In this study, we conducted network pharmacology, molecular docking, and experimental evaluation to explore the target genes, biological functions, and signaling pathways involved in this process. Network analysis revealed 77 potential target genes of VD against TC, and four hub target genes were identified: ESR1, KIT, CCND1, and PGR. Furthermore, we identified the biological processes (BP) and signaling pathways involving these potential target genes, and then determined the possible interaction between the hub targets and VD through molecular docking. Finally, through in vitro experiments, we found that VD effectively inhibits the proliferation of TC cells and downregulates the expression of the ESR1 gene. In conclusion, the effects of VD against TC involve multiple biological targets, BP, and signaling pathways. These findings provide scientific evidence for the application of VD in the treatment of TC.

Unveiling the role of UPF3B in hepatocellular carcinoma: Potential therapeutic target.

RNA-binding proteins can regulate nucleotide metabolism and gene expression. UPF3B regulator of nonsense mediated mRNA decay (UPF3B) exhibits dysfunction in cancers. However, its role in the progression of hepatocellular carcinoma (HCC) is still insufficiently understood. Here, we found that UPF3B was markedly upregulated in HCC samples and associated with adverse prognosis in patients. UPF3B dramatically promoted HCC growth both in vivo and in vitro. Mechanistically, UPF3B was found to bind to PPP2R2C, a regulatory subunit of PP2A, boosting its mRNA degradation and activating the PI3K/AKT/mTOR pathway. E2F transcription factor 6 (E2F6) directly binds to the UPF3B promoter to facilitate its transcription. Together, the E2F6/UPF3B/PPP2R2C axis promotes HCC growth through the PI3K/AKT/mTOR pathway. Hence, it could be a promising therapeutic target for treating HCC.

Lithiation Induced Phases in 1T'-MoTe2 Nanoflakes.

Multiple polytypes of MoTe2 with distinct structures and intriguing electronic properties can be accessed by various physical and chemical approaches. Here, we report electrochemical lithium (Li) intercalation into 1T'-MoTe2 nanoflakes, leading to the discovery of two previously unreported lithiated phases. Distinguished by their structural differences from the pristine 1T' phase, these distinct phases were characterized using in situ polarization Raman spectroscopy and in situ single-crystal X-ray diffraction. The lithiated phases exhibit increasing resistivity with decreasing temperature, and their carrier densities are two to 4 orders of magnitude smaller than the metallic 1T' phase, as probed through in situ Hall measurements. The discovery of these gapped phases in initially metallic 1T'-MoTe2 underscores electrochemical intercalation as a potent tool for tuning the phase stability and electron density in two-dimensional (2D) materials.

Molecular design, construction and analgesic mechanism insights into the novel transdermal fusion peptide ANTP-BgNPB.

Toad venom, a traditional Chinese medicine, exhibits remarkable medicinal properties of significant therapeutic value. The peptides present within toad venom possess a wide range of biological functions, yet the neuropeptide B (NPB) and it modification requires further exploration to comprehensively understand its mechanisms of action and potential applications. In this study, a fusion peptide, ANTP-BgNPB, was designed to possess better analgesic properties through the transdermal modification of BgNPB. After optimizing the conditions, the expression of ANTP-BgNPB was successfully induced. The molecular dynamics simulations suggested that the modified protein exhibited improved stability and receptor binding affinity compared to its unmodified form. The analysis of the active site of ANTP-BgNPB and the verification of mutants revealed that GLN3, SER38, and ARG42 were crucial for the protein's recognition and binding with G protein-coupled receptor 7 (GPR7). Moreover, experiments conducted on mice using the hot plate and acetic acid twist body models demonstrated that ANTP-BgNPB was effective in transdermal analgesia. These findings represent significant progress in the development of transdermal delivery medications and could have a significant impact on pain management.

3D-DESS MRI with CAIPIRINHA two- and fourfold acceleration for quantitatively assessing knee cartilage morphology.

OBJECTIVES: This study aimed to assess the diagnostic image quality and compare the knee cartilage segmentation results using a controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA)-accelerated 3D-dual echo steady-state (DESS) research package sequence in the knee. MATERIALS AND METHODS: A total of 64 subjects underwent both two- and fourfold CAIPIRINHA-accelerated 3D-DESS and DESS without parallel acceleration technique of the knee on a 3.0 T system. Two musculoskeletal radiologists evaluated the images independently for image quality and diagnostic capability following randomization and anonymization. The consistency of automatic segmentation results between sequences was explored using an automatic knee cartilage segmentation research application. The descriptive statistics and inter-observer and inter-method concordance of various acceleration sequences were investigated. P values < .05 were considered significant. RESULTS: For image quality evaluation, the image signal-to-noise ratio and contrast-to-noise ratio decreased with the decrease in scanning time. However, it is accompanied by the reduction of artifacts. Using 3D-DESS without parallel acceleration technique as the standard for cartilage grading diagnosisand the diagnostic agreement of two- and fourfold CAIPIRINHA-accelerated 3D-DESS was good, kappa value was 0.860 (P < .001) and 0.804 (p < 0.001), respectively. Regarding cartilage defects, the sensitivity and specificity of the twofold acceleration 3D-CAIPIRINHA-DESS were 95.56% and 97.70%, and the fourfold CAIPIRINHA-accelerated 3D-DESS were 91.49% and 97.65%, respectively. The intraclass correlation coefficients of various sequences in cartilage segmentation were almost all greater than 0.9. CONCLUSION: The CAIPIRINHA-accelerated 3D-DESS sequence maintained comparable diagnostic and segmentations performance of knee cartilage after a 60% scan time reduction.

Causal effects of body mass index, education, and lifestyle behaviors on intervertebral disc disorders: Mendelian randomization study.

This study aimed to investigate the causal risk factors for intervertebral disc disorders (IVDD) to help establish prevention strategies for IVDD-related diseases. We performed two-sample Mendelian randomization analyses to investigate the causal effects of body mass index (BMI), education, and lifestyle behaviors (sedentary behavior, smoking, and sleeping) on thoracic/thoracolumbar/lumbosacral IVDD (TTL-IVDD) and cervical IVDD. The inverse-variance weighted (IVW) method was conducted as the primary model to pool effect sizes using odds ratio and 95% confidence interval. The strength of causal evidence was evaluated from the effect size and different Mendelian randomization methods (MR-Egger/weighted median/weighted mode method, Cochran's Q test, leave-one-out analysis, MR Steiger, MR-PRESSO and radial IVW analyses). We found strong evidence for the causal associations between IVDD and BMI (TTL-IVDD, 1.27 [1.18, 1.37], p = 2.40 × 10-10 ; cervical IVDD, 1.24 [1.12, 1.37, p = 6.58 × 10-5 ), educational attainment (TTL-IVDD, 0.57 [0.51, 0.64], p = 9.64 × 10-21 ; cervical IVDD, 0.58 [0.49, 0.68], p = 1.78 × 10-10 ), leisure television watching (TTL-IVDD, 1.54 [1.29, 1.84], p = 7.80 × 10-6 ; cervical IVDD, 1.65 [1.29, 2.11], p = 0.0001), smoking initiation (TTL-IVDD, 1.37 [1.25, 1.50], p = 1.78 × 10-10 ; cervical IVDD, 1.32 [1.16, 1.51], p = 6.49 × 10-5 ), short sleep (TTL-IVDD, 1.28 [1.09, 1.49], p = 0.0027; cervical IVDD, 1.53 [1.21, 1.94], p = 0.0008), or frequent insomnia (TTL-IVDD, 1.20 [1.11, 1.30], p = 1.54 × 10-5 ; cervical IVDD, 1.37 [1.20, 1.57], p = 7.80 × 10-6 ). This study provided genetic evidence that increased BMI, low educational attainment, sedentary behavior by leisure television watching, smoking initiation, short sleep, and frequent insomnia were causal risk factors for IVDD. More efforts should be directed toward increasing public awareness of these modifiable risk factors and mobilizing individuals to adopt healthy lifestyles.

SHP-1 Regulates CD8+ T Cell Effector Function but Plays a Subtle Role with SHP-2 in T Cell Exhaustion Due to a Stage-Specific Nonredundant Functional Relay.

SHP-1 (Src homology region 2 domain-containing phosphatase 1) is a well-known negative regulator of T cells, whereas its close homolog SHP-2 is the long-recognized main signaling mediator of the PD-1 inhibitory pathway. However, recent studies have challenged the requirement of SHP-2 in PD-1 signaling, and follow-up studies further questioned the alternative idea that SHP-1 may replace SHP-2 in its absence. In this study, we systematically investigate the role of SHP-1 alone or jointly with SHP-2 in CD8+ T cells in a series of gene knockout mice. We show that although SHP-1 negatively regulates CD8+ T cell effector function during acute lymphocytic choriomeningitis virus (LCMV) infection, it is dispensable for CD8+ T cell exhaustion during chronic LCMV infection. Moreover, in contrast to the mortality of PD-1 knockout mice upon chronic LCMV infection, mice double deficient for SHP-1 and SHP-2 in CD8+ T cells survived without immunopathology. Importantly, CD8+ T cells lacking both phosphatases still differentiate into exhausted cells and respond to PD-1 blockade. Finally, we found that SHP-1 and SHP-2 suppressed effector CD8+ T cell expansion at the early and late stages, respectively, during chronic LCMV infection.

Spin-Stabilization by Coulomb Blockade in a Vanadium Dimer in WSe2.

Charged dopants in 2D transition metal dichalcogenides (TMDs) have been associated with the formation of hydrogenic bound states, defect-bound trions, and gate-controlled magnetism. Charge-transfer at the TMD-substrate interface and the proximity to other charged defects can be used to regulate the occupation of the dopant's energy levels. In this study, we examine vanadium-doped WSe2 monolayers on quasi-freestanding epitaxial graphene, by high-resolution scanning probe microscopy and ab initio calculations. Vanadium atoms substitute W atoms and adopt a negative charge state through charge donation from the graphene substrate. VW-1 dopants exhibit a series of occupied p-type defect states, accompanied by an intriguing electronic fine-structure that we attribute to hydrogenic states bound to the charged impurity. We systematically studied the hybridization in V dimers with different separations. For large dimer separations, the 2e- charge state prevails, and the magnetic moment is quenched. However, the Coulomb blockade in the nearest-neighbor dimer configuration stabilizes a 1e- charge state. The nearest-neighbor V-dimer exhibits an open-shell character for the frontier defect orbital, giving rise to a paramagnetic ground state. Our findings provide microscopic insights into the charge stabilization and many-body effects of single dopants and dopant pairs in a TMD host material.

MS-FRAN: A Novel Multi-Source Domain Adaptation Method for EEG-Based Emotion Recognition.

Electroencephalogram (EEG)-based emotion recognition has gradually become a research hotspot. However, the large distribution differences of EEG signals across subjects make the current research stuck in a dilemma. To resolve this problem, in this article, we propose a novel and effective method, Multi-Source Feature Representation and Alignment Network (MS-FRAN). The effectiveness of proposed method mainly comes from three new modules: Wide Feature Extractor (WFE) for feature learning, Random Matching Operation (RMO) for model training, and Top- h ranked domain classifier selection (TOP) for emotion classification. MS-FRAN is not only effective in aligning the distributions of each pair of source and target domains, but also capable of reducing the distributional differences among the multiple source domains. Experimental results on the public benchmark datasets SEED and DEAP have demonstrated the advantage of our method over the related competitive approaches for cross-subject EEG-based emotion recognition.

Ecological differentiation and assembly processes of abundant and rare bacterial subcommunities in karst groundwater.

The ecological health of karst groundwater has been of global concern due to increasing anthropogenic activities. Bacteria comprising a few abundant taxa (AT) and plentiful rare taxa (RT) play essential roles in maintaining ecosystem stability, yet limited information is known about their ecological differentiation and assembly processes in karst groundwater. Based on a metabarcoding analysis of 64 groundwater samples from typical karst regions in southwest China, we revealed the environmental drivers, ecological roles, and assembly mechanisms of abundant and rare bacterial communities. We found a relatively high abundance of potential functional groups associated with parasites and pathogens in karst groundwater, which might be linked to the frequent regional anthropogenic activities. Our study confirmed that AT was dominated by Proteobacteria and Campilobacterota, while Patescibacteria and Chloroflexi flourished more in the RT subcommunity. The node-level topological features of the co-occurrence network indicated that AT might share similar niches and play more important roles in maintaining bacterial community stability. RT in karst groundwater was less environmentally constrained and showed a wider environmental threshold response to various environmental factors than AT. Deterministic processes, especially homogeneous selection, tended to be more important in the community assembly of AT, whereas the community assembly of RT was mainly controlled by stochastic processes. This study expanded our knowledge of the karst groundwater microbiome and was of great significance to the assessment of ecological stability and drinking water safety in karst regions.

KCNQ2 channels regulate the population activity of neonatal GABAergic neurons ex vivo.

Over the last decade KCNQ2 channels have arisen as fundamental and indispensable regulators of neonatal brain excitability, with KCNQ2 loss-of-function pathogenic variants being increasingly identified in patients with developmental and epileptic encephalopathy. However, the mechanisms by which KCNQ2 loss-of-function variants lead to network dysfunction are not fully known. An important remaining knowledge gap is whether loss of KCNQ2 function alters GABAergic interneuron activity early in development. To address this question, we applied mesoscale calcium imaging ex vivo in postnatal day 4-7 mice lacking KCNQ2 channels in interneurons (Vgat-ires-cre;Kcnq2f/f;GCamp5). In the presence of elevated extracellular potassium concentrations, ablation of KCNQ2 channels from GABAergic cells increased the interneuron population activity in the hippocampal formation and regions of the neocortex. We found that this increased population activity depends on fast synaptic transmission, with excitatory transmission promoting the activity and GABAergic transmission curtailing it. Together, our data show that loss of function of KCNQ2 channels from interneurons increases the network excitability of the immature GABAergic circuits, revealing a new function of KCNQ2 channels in interneuron physiology in the developing brain.

Exchange-Driven Intermixing of Bulk and Topological Surface States by Chiral Excitons in Bi_{2}Se_{3}.

Topological surface states (TSS) in the prototypical topological insulator (TI) Bi_{2}Se_{3} are frequently characterized using optical probes, but electron-hole interactions and their effect on surface localization and optical response of the TSS remain unexplored. Here, we use ab initio calculations to understand excitonic effects in the bulk and surface of Bi_{2}Se_{3}. We identify multiple series of chiral excitons that exhibit both bulk and TSS character, due to exchange-driven mixing. Our results address fundamental questions about the degree to which electron-hole interactions can relax the topological protection of surface states and dipole selection rules for circularly polarized light in TIs by elucidating the complex intermixture of bulk and surface states excited in optical measurements and their coupling to light.

Multi-echo in steady-state acquisition improves MRI image quality and lumbosacral radiculopathy diagnosis efficacy compared with T2 fast spin-echo sequence.

PURPOSE: This study compares the performance of a 4-min multi-echo in steady-state acquisition (MENSA) with a 6-min fast spin echo with variable flip angle (CUBE) protocol for the assessment of lumbosacral plexus nerve root lesions. METHODS: Seventy-two subjects underwent MENSA and CUBE sequences on a 3.0-T MRI scanner. Two musculoskeletal radiologists independently assessed the images for quality and diagnostic capability. A qualitative assessment scoring system for image quality and quantitative nerve signal-to-noise ratio (SNR) and iliac vein and muscle contrast-to-noise ratios (CNR) was applied. Using surgical reports as the reference, sensitivity, specificity, accuracy, and area under the receiver operating characteristic curves (AUC) were evaluated. Intraclass correlation coefficients (ICC) and weighted kappa were used to calculate reliability. RESULTS: MENSA image quality rating (3.679 ± 0.47) was higher than for CUBE images (3.038 ± 0.68), and MENSA showed higher mean nerve root SNR (36.935 ± 8.33 vs. 27.777 ± 7.41), iliac vein CNR (24.678 ± 6.63 vs. 5.210 ± 3.93), and muscle CNR (19.414 ± 6.07 vs. 13.531 ± 0.65) than CUBE (P < 0.05). Weighted kappa and ICC values indicated good reliability. Sensitivity, specificity, and accuracy of diagnosis based on MENSA images were 96.23%, 89.47%, and 94.44%, respectively, and AUC was 0.929, compared with 92.45%, 84.21%, 90.28%, and 0.883 for CUBE images. The two correlated ROC curves were not significantly different. Weighted kappa values for intraobserver (0.758) and interobserver (0.768-0.818) reliability were substantial to perfect. CONCLUSION: A time-efficient 4-min MENSA protocol exhibits superior image quality and high vascular contrast with the potential to produce high-resolution lumbosacral nerve root images.

Structure, stability, and potential function of groundwater microbial community responses to permafrost degradation on varying permafrost of the Qinghai-Tibet Plateau.

The ongoing permafrost degradation under climate warming has modified aboveground biogeochemical processes mediated by microbes, yet groundwater microbial structure and function as well as their response to permafrost degradation remain poorly understood. We separately collect 20 and 22 sub-permafrost groundwater samples from Qilian Mountain (alpine and seasonal permafrost) and Southern Tibet Valley (plateau isolated permafrost) on the Qinghai-Tibet Plateau (QTP) to investigate the effects of permafrost groundwater characteristics on the diversity, structure, stability, and potential function of bacterial and fungal communities. Regional discrepancy of groundwater microbes between two permafrost regions reveals that permafrost degradation might reshape microbial community structure, increase community stability and potential functions relevant to carbon metabolism. Bacterial community assembly in permafrost groundwater is governed by deterministic processes, whereas fungal communities are mainly controlled by stochastic processes, suggesting that bacterial biomarkers might provide the better 'early warning signals' to permafrost degradation in deeper layers. Our study highlights the importance of groundwater microbes in ecological stability and carbon emission on the QTP.

Themis suppresses the effector function of CD8+ T cells in acute viral infection.

CD8+ T cells play a central role in antiviral immune responses. Upon infection, naive CD8+ T cells differentiate into effector cells to eliminate virus-infected cells, and some of these effector cells further differentiate into memory cells to provide long-term protection after infection is resolved. Although extensively investigated, the underlying mechanisms of CD8+ T-cell differentiation remain incompletely understood. Themis is a T-cell-specific protein that plays critical roles in T-cell development. Recent studies using Themis T-cell conditional knockout mice also demonstrated that Themis is required to promote mature CD8+ T-cell homeostasis, cytokine responsiveness, and antibacterial responses. In this study, we used LCMV Armstrong infection as a probe to explore the role of Themis in viral infection. We found that preexisting CD8+ T-cell homeostasis defects and cytokine hyporesponsiveness do not impair viral clearance in Themis T-cell conditional knockout mice. Further analyses showed that in the primary immune response, Themis deficiency promoted the differentiation of CD8+ effector cells and increased their TNF and IFNγ production. Moreover, Themis deficiency impaired memory precursor cell (MPEC) differentiation but promoted short-lived effector cell (SLEC) differentiation. Themis deficiency also enhanced effector cytokine production in memory CD8+ T cells while impairing central memory CD8+ T-cell formation. Mechanistically, we found that Themis mediates PD-1 expression and its signaling in effector CD8+ T cells, which explains the elevated cytokine production in these cells when Themis is disrupted.

Determinants of diurnal variation in lumbar intervertebral discs and paraspinal muscles: A prospective quantitative magnetic resonance imaging study.

PURPOSE: To prospectively investigate the determinants of diurnal variations in lumbar intervertebral discs and paraspinal muscles. METHOD: 71 females aged 19 âˆ¼ 31 years were examined by morning-evening T2 mapping/diffusion kurtosis imaging (DKI), with weight and lifestyle information (time in night bed-rest [TIB], bed-napping, activity time, and sitting time) assessed by standardized questionnaires. Diurnal shifts in T2, mean diffusivity and mean kurtosis (T2-DS, MD-DS and MK-DS; morning-value minus evening-value) were evaluated for L4-S1 discs (normal, Pfirrmann grade Ⅰ/Ⅱ; degenerative, III/IV). T2 and T2-DS were assessed for L4/5 multifidus and erector spinalis. RESULTS: For normal discs, bed-napping correlated with MD-DS and MK-DS in disc entirety (p = 0.001 and 0.004); increased activity time suggested higher T2-DS in nucleus pulposus (p = 0.004); prolonged sitting time predicted greater T2-DS in disc entirety and posterior inner annulus fibrosus (PI-AF, p ≤ 0.011); decreased TIB and weight suggested lower T2-DS and higher MK-DS in PI-AF (p = 0.001 âˆ¼ 0.035). For degenerative discs, bed-napping predicted lower T2-DS in nucleus pulposus and PI-AF (p = 0.019); increased TIBsuggested higher T2-DS and lower MK-DS in PI-AF (p = 0.006 and 0.034); longer sitting time predicted higher MK-DS in PI-AF (p = 0.020). Paraspinal muscles exhibited diurnal T2 variation (p < 0.001) which did not correlate with lifestyle factors (p > 0.050). CONCLUSIONS: Lifestyle and weight have causal effects on the diurnal variation of lumbar discs. Bed-rest may correlate with disc hydration and microstructural stability reserves for subsequent daytime activities. Sitting behavior could induce greater dehydration in normal discs and may alleviate diurnal microstructural rearrangement in degenerative discs. T2 mapping and DKI are promising tools to evaluate disc biomechanics in clinics.

Detection of erosions and fat metaplasia of the sacroiliac joints in patients with suspected sacroiliitis using a chemical shift-encoded sequence (IDEAL-IQ).

PURPOSE: To evaluate the performance of a chemical shift-encoded sequence called IDEAL-IQ for detecting sacroiliac joint (SIJ) erosions and fat metaplasia compared to T1-weighted fast spin echo (T1 FSE) using qualitative and quantitative analysis. METHOD: Thirty-four patients with suspicion of sacroiliitis who underwent both MRI and CT were included. Each SIJ was divided into four quadrants for analysis. For qualitative analysis, the diagnostic performance of IDEAL-IQ and T1 FSE for erosions were compared by the McNemar test, using CT as the gold standard. Cochran's Q and McNemar tests were used to determine differences in structural changes detected by different imaging methods. For quantitative analysis, two-sample t test and receiver operating characteristic (ROC) analysis were used for the analysis of histogram parameters of proton density fat fraction (PDFF). RESULTS: Diagnostic sensitivity and accuracy of IDEAL-IQ were greater than T1 FSE for erosions (all P < 0.05). IDEAL-IQ and CT detected more erosions than T1 FSE (all P < 0.05). IDEAL-IQ did not statistically significantly differ from T1 FSE for the detection of fat metaplasia (P = 0.678). All histogram parameters were different between groups with and without fat metaplasia (all P < 0.05) and could distinguish the two groups (all P < 0.05). PDFF75th was the most effective histogram parameter. CONCLUSION: IDEAL-IQ detects SIJ erosions with better accuracy than T1 FSE and is similar to T1 FSE for detection of fat metaplasia, enabling further quantitative analysis of the latter via histogram analysis.

YY1 transcription factor induces proliferation and aerobic glycolysis of neuroblastoma cells via LDHA regulation.

The present study investigated the effect of transcription factor yin yang 1 (YY1) on aerobic glycolysis and cell proliferation in neuroblastoma and its mechanism. Neuroblastoma cell lines were used to investigate the association between YY1 and lactate dehydrogenase A (LDHA) expression. Cell Counting Kit (CCK)-8 and clone formation experiments were used to detect the cell viability. The interaction of YY1 and LDHA was detected using chromatin immunoprecipitation assay. Glucose uptake, intra/extracellular lactate and pyruvate and LDHA expression were evaluated using standard methods. Reverse transcription quantitative PCR, western blotting and gene overexpression or silencing were undertaken to explore the biological effects and underlying mechanisms of transcriptional regulators in NB cells. The results demonstrated that YY1 was significantly upregulated in neuroblastoma cell lines. The results of aerobic glycolysis and CCK-8 indicated that YY1 significantly promoted the proliferation and aerobic glycolysis of neuroblastoma cells. In addition, chromatin immunoprecipitation-PCR results demonstrated that YY1 was directly bound to the promoter LDHA. Overexpression of LDHA could reverse the inhibitory effect of sh-YY1 on aerobic glycolysis and proliferation of neuroblastoma cells. In conclusion, YY1 could induce aerobic glycolysis and proliferation of neuroblastoma cell lines, and may directly mediate the regulation of LDHA. These findings may provide novel insight for the treatment of neuroblastoma.

Diurnal Variation in Hydration of the Cervical Intervertebral Disc Assessed Using T2 Mapping of Magnetic Resonance Imaging.

OBJECTIVE: The study aimed to investigate the diurnal variation in cervical disc hydration and its relationship with cervical degeneration. MATERIALS AND METHODS: C3-C7 discs of 86 prospectively enrolled participants (37 males, 49 females; mean age ± standard deviation, 23.5 ± 2.5 years) were assessed using T2 mapping in the morning and evening. All discs were stratified by Miyazaki grade or C2-C7 Cobb angle and T2 values (T2). The degree of diurnal T2 variation (T2-DDV), defined as (morning T2 - evening T2)/morning T2 × 100%, was measured for the entire disc, annulus fibrosus (AF), nucleus pulposus (NP), and endplate zones. RESULTS: T2 of the entire disc decreased significantly after the daytime load (p < 0.001), with a T2-DDV of 13.3% for all discs and 16.0%, 12.2%, and 13.0% for healthy (grade I), mild degenerative (grade II), and advanced degenerative (grade III/IV) discs, respectively. T2 of regional NPs and AFs decreased significantly from morning to evening (p ≤ 0.049) except in the healthy anterior inner AF (p = 0.092). Compared with healthy discs, mild degenerative discs displayed lower T2 and T2-DDV in regional NPs (p < 0.001). Advanced degenerative discs showed higher T2-DDV in the anterior inner AF compared with healthy discs (p = 0.050). Significant diurnal T2 changes in the endplate zones were observed only in healthy discs (p = 0.013). Cervical discs in the low Cobb angle group showed higher T2-DDV in the anterior AFs and anterior NP and lower T2-DDV in the posterior AF than those in the high Cobb angle group (p ≤ 0.041). CONCLUSION: This study characterized the diurnal variation in hydration of the cervical discs as assessed using T2 mapping and revealed early chemo-mechanical coupling dysfunction in degenerating discs. Cervical sagittal alignment on MRI can affect the diurnal stress patterns of the cervical discs. T2 mapping is sensitive to disc biomechanical dysfunction and offers translational potential from biomechanical research to clinical application.