Glucocorticoid Receptor β Acts As a Co-activator of T-Cell Factor 4 and Enhances Glioma Cell Proliferation

We previously reported that glucocorticoid receptor β (GRβ) regulates injury-mediated astrocyte activation and contributes to glioma pathogenesis via modulation of β-catenin/T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity. The aim of this study was to characterize the mechanism behind cross-talk between GRβ and β-catenin/TCF in the progression of glioma. Here, we reported that GRβ knockdown reduced U118 and Shg44 glioma cell proliferation in vitro and in vivo. Mechanistically, we found that GRβ knockdown decreased TCF/LEF transcriptional activity without affecting β-catenin/TCF complex. Both GRα and GRβ directly interact with TCF-4, while only GRβ is required for sustaining TCF/LEF activity under hormone-free condition. GRβ bound to the N-terminus domain of TCF-4 its influence on Wnt signaling required both ligand- and DNA-binding domains (LBD and DBD, respectively). GRβ and TCF-4 interaction is enough to maintain the TCF/LEF activity at a high level in the absence of β-catenin stabilization. Taken together, these results suggest a novel cross-talk between GRβ and TCF-4 which regulates Wnt signaling and the proliferation in gliomas

374~747 MHz digital tunable microstrip filter

A novel digital microstrip tunable bandpass filter based on digitally tunable capacitor loading microstrip open ring resonators was proposed.The novel non-uniform open ring resonances with mixed coupling structure was used to make the coupling coefficient of the resonators increases with the decreasing of resonance frequency and achieve a con-stant absolute bandwidth tunable filter.Then the proposed digital tunable microstrip filters based on 5 bit digitally tunable capacitance was simulated and manufactured.The measurement shows that the −3 dB absolute bandwidth varies from 44~67 MHz while the central frequency of the passband varying from 374~747 MHz,the OIP3 is greater than 50 dBm

Analyzing Gene Expression Profile in K562 Cells Exposed to Sodium Valproate Using Microarray Combined with the Connectivity Map Database

To explore the mechanism underlying antileukaemia effect of sodium valproate, the growth and survival of the K562 cell line were investigated. Global profiles of gene expression in K562 cells exposed to sodium valproate were assessed and validated. The differentially expressed genes identified were further used to query the connectivity map database to retrieve a ranked list of compounds that act on the same intracellular targets as sodium valproate. A significant increase in cell apoptosis and a change in gene expression profile were observed in valproate-exposed K562 cells. The significant enrichment analysis of gene ontology terms for the differentially expressed genes showed that these genes were involved in many important biological processes. Eight differentially expressed genes involved in apoptosis were verified by quantitative real-time PCR. The connectivity map analysis showed gene expression profile in K562 cells exposed to sodium valproate was most similar to that of HDACi and PI3K inhibitors, suggesting that sodium valproate might exert antileukaemic action by inhibiting HDAC as well as inhibiting PI3K pathway. In conclusion, our data might provide clues to elucidate the molecular and therapeutic potential of VPA in leukaemia treatment, and the connectivity map is a useful tool for exploring the molecular mechanism of drug action

Utjecaj sastava podloge na povećanje biomase micelija i proizvodnje egzopolimera s pomoću gljive Hericium erinaceus CZ-2

In this work, the effects of medium composition and fermentation parameters on the simultaneous production of mycelial biomass and exopolymer by medicinal mushroom Hericium erinaceus CZ-2 were investigated in shake flask cultures using one-factor-at-a-time method and orthogonal array design. Results showed that the most suitable carbon, nitrogen, mineral sources, and cofactors for the mycelial biomass and exopolymer production were: corn flour combined with 1 % glucose, yeast extract, KH2PO4 and corn steep liquor. The intuitive analysis of orthogonal array design results indicated that the effects of nutritional requirement on the mycelial growth of Hericium erinaceus CZ-2 were in regular sequence of corn flour combined with 1 % glucose > yeast extract > corn steep liquor > KH2PO4, and those on exopolymer production were in the order of corn flour combined with glucose > KH2PO4 > yeast extract > corn steep liquor. The maximal yield of mycelial biomass (16.07 g/L) was obtained when the composition of the culture medium was (in g/L): corn flour 30, glucose 10, yeast extract 3, KH2PO4 1, CaCO3 0.5, and 15 mL/L of corn steep liquor; while the maximal exopolymer yield (1.314 g/L) was achieved when the composition of medium was (in g/L): corn flour 30, glucose 10, yeast extract 5, KH2PO4 3, CaCO3 0.5, and 15 mL/L of corn steep liquor. In the 15-litre scale-up fermentation, the maximum mycelial biomass yield of 20.50 g/L was achieved using the optimized medium.U ovom je radu ispitan utjecaj sastava podloge i uvjeta fermentacije na istodobnu proizvodnju biomase micelija i egzopolimera s pomoću ljekovite gljive Hericium erinaceus CZ-2. Pokusi su provedeni na kulturama uzgojenim na tresilici, primjenom jednofaktorske metode i ortogonalnog modela. Rezultati su pokazali da su najbolji izvori dušika, minerala i kofaktora za proizvodnju biomase micelija i egzopolimera kukuruzno brašno s 1 % glukoze, ekstrakt kvasca, KH2PO4 i kukuruzni ekstrakt. Analizom ortogonalnog modela utvrđeno je da na povećanje micelija redom utječu: kukuruzno brašno s 1 % glukoze, zatim ekstrakt kvasca, kukuruzni ekstrakt i KH2PO4, a na proizvodnju egzopolimera kukuruzno brašno s glukozom, zatim KH2PO4, ekstrakt kvasca te kukuruzni ekstrakt. Najveći je prinos biomase micelija (16,07 g/L) postignut s ovim sastavom podloge (u g/L): kukuruzno brašno 30, glukoza 10, ekstrakt kvasca 3, KH2PO4 1, CaCO3 0,5 i 15 mL/L kukuruznog ekstrakta, a najveći je prinos egzopolimera (1,314 g/L) dobiven korištenjem podloge (u g/L) od: kukuruznog brašna 30, glukoze 10, ekstrakta kvasca 5, KH2PO4 3, CaCO3 0,5 i 15 mL/L kukuruznog ekstrakta. Povećanjem obujma fermentacije na 15 L dobiven je najveći prinos biomase micelija od 20,50 g/L pri optimalnim uvjetima

Lentiviral Vector-Mediated SHC3 Silencing Exacerbates Oxidative Stress Injury in Nigral Dopamine Neurons by Regulating the PI3K-AKT-FoxO Signaling Pathway in Rats with Parkinson’s Disease

Background/Aims: Parkinson’s disease (PD) is a prevalent disease that leads to motor and cognitive disabilities, and oxidative stress (OS) injury was found to be related to the etiology of PD. Increasing evidence has shown that SHC3 is aberrantly expressed in neurons. The current study examines the involvement of SHC3 silencing in OS injury in the nigral dopamine neurons in rats with PD via the PI3K-AKT-FoxO signaling pathway. Methods: To study the mechanisms and functions of SHC3 silencing in PD at the tissue level, 170 rats were selected, and a lentivirus-based packaging system was designed to silence SHC3 expression in rats. Furthermore, PC12 cells were selected for in vitro experimentation. To evaluate the effect of SHC3 silencing in nigral dopamine neuronal growth, an MTT assay, propidium iodide (PI) single staining and Annexin V-PI double staining were performed to detect cell viability, cell cycle progression and cell apoptosis, respectively. Results: SHC3 shRNA led to decreased SOD and MDA levels and enhanced GSH activity, indicating that SHC3 silencing leads to motor retardation. SHC3 silencing repressed the extent of Akt and FoxO phosphorylation, thereby inhibiting the PI3K-AKT-FoxO signaling pathway. Furthermore, in cell experiments, SHC3 silencing suppressed PC12 cell proliferation and cell cycle progression, whereas it enhanced cell apoptosis. Conclusion: The current study provides evidence suggesting that SHC3 silencing may aggravate OS injury in nigral dopamine neurons via downregulation of the PI3K-AKT-FoxO signaling pathway in PD rats

Mega-TTS: Zero-Shot Text-to-Speech at Scale with Intrinsic Inductive Bias

Scaling text-to-speech to a large and wild dataset has been proven to be highly effective in achieving timbre and speech style generalization, particularly in zero-shot TTS. However, previous works usually encode speech into latent using audio codec and use autoregressive language models or diffusion models to generate it, which ignores the intrinsic nature of speech and may lead to inferior or uncontrollable results. We argue that speech can be decomposed into several attributes (e.g., content, timbre, prosody, and phase) and each of them should be modeled using a module with appropriate inductive biases. From this perspective, we carefully design a novel and large zero-shot TTS system called Mega-TTS, which is trained with large-scale wild data and models different attributes in different ways: 1) Instead of using latent encoded by audio codec as the intermediate feature, we still choose spectrogram as it separates the phase and other attributes very well. Phase can be appropriately constructed by the GAN-based vocoder and does not need to be modeled by the language model. 2) We model the timbre using global vectors since timbre is a global attribute that changes slowly over time. 3) We further use a VQGAN-based acoustic model to generate the spectrogram and a latent code language model to fit the distribution of prosody, since prosody changes quickly over time in a sentence, and language models can capture both local and long-range dependencies. We scale Mega-TTS to multi-domain datasets with 20K hours of speech and evaluate its performance on unseen speakers. Experimental results demonstrate that Mega-TTS surpasses state-of-the-art TTS systems on zero-shot TTS, speech editing, and cross-lingual TTS tasks, with superior naturalness, robustness, and speaker similarity due to the proper inductive bias of each module. Audio samples are available at https://mega-tts.github.io/demo-page

Reducing PM2.5 Exposure Lowers Dyslipidemia Risk:A Longitudinal Quasi-Experimental Study

Evidence demonstrating the beneficial effects of improved air quality on lipid health is scarce. This study addresses this gap by examining whether reducing PM2.5 exposure can decrease the risk of dyslipidemia. We conducted a longitudinal quasi-experimental study using the Taiwan MJ and Hong Kong MJ cohorts from 2000 to 2018. A total of 8,808 adults with consistently high PM2.5 exposure (≥ 25 μg/m3) were paired with 4,612 adults whose PM2.5 exposure decreased from high to low levels (< 25 μg/m3) using propensity score matching. Cox regression models with time-dependent covariates were used to analyze the associations between PM2.5 reduction and the risk of dyslipidemia, as well as individual lipid abnormalities. We found that participants with reducing PM2.5 exposure had a significantly lower risk of dyslipidemia compared to their counterparts (HR = 0.75, 95% CI: 0.68, 0.84). Non-linear concentration-response relationships were observed. Similar associations were found for elevated TC (HR = 0.61, 95% CI: 0.51, 0.74) and LDL-C (HR = 0.69, 95% CI: 0.57, 0.84), and decreased HDL-C (HR = 0.59, 95% CI: 0.47, 0.75). Reducing PM2.5 exposure significantly lowers the risk of dyslipidemia and improves lipid profiles, providing direct evidence of the health benefits associated with air quality improvement