Histone Deacetylase Inhibitors Downregulate Calcium Pyrophosphate Crystal Formation in Human Articular Chondrocytes.

Calcium pyrophosphate (CPP) deposition disease (CPPD) is a form of CPP crystal-induced arthritis. A high concentration of extracellular pyrophosphate (ePPi) in synovial fluid is positively correlated with the formation of CPP crystals, and ePPi can be upregulated by ankylosis human (ANKH) and ectonucleotide pyrophosphatase 1 (ENPP1) and downregulated by tissue non-specific alkaline phosphatase (TNAP). However, there is currently no drug that eliminates CPP crystals. We explored the effects of the histone deacetylase (HDAC) inhibitors (HDACis) trichostatin A (TSA) and vorinostat (SAHA) on CPP formation. Transforming growth factor (TGF)-ß1-treated human primary cultured articular chondrocytes (HC-a cells) were used to increase ePPi and CPP formation, which were determined by pyrophosphate assay and CPP crystal staining assay, respectively. Artificial substrates thymidine 5'-monophosphate p-nitrophenyl ester (p-NpTMP) and p-nitrophenyl phosphate (p-NPP) were used to estimate ENPP1 and TNAP activities, respectively. The HDACis TSA and SAHA significantly reduced mRNA and protein expressions of ANKH and ENPP1 but increased TNAP expression in a dose-dependent manner in HC-a cells. Further results demonstrated that TSA and SAHA decreased ENPP1 activity, increased TNAP activity, and limited levels of ePPi and CPP. As expected, both TSA and SAHA significantly increased the acetylation of histones 3 and 4 but failed to block Smad-2 phosphorylation induced by TGF-ß1. These results suggest that HDACis prevented the formation of CPP by regulating ANKH, ENPP1, and TNAP expressions and can possibly be developed as a potential drug to treat or prevent CPPD.

Solution-Processed Flexible Temperature Sensor Array for Highly Resolved Spatial Temperature and Tactile Mapping Using ESN-Based Data Interpolation.

High-performance flexible temperature sensors are crucial in various technological applications, such as monitoring environmental conditions and human healthcare. The ideal characteristics of these sensors for stable temperature monitoring include scalability, mechanical flexibility, and high sensitivity. Moreover, simplicity and low power consumption will be essential for temperature sensor arrays in future integrated systems. This study introduces a solution-based approach for creating a V2O5 nanowire network temperature sensor on a flexible film. Through optimization of the fabrication conditions, the sensor exhibits remarkable performance, sustaining long-term stability (>110 h) with minimal hysteresis and excellent sensitivity (∼-1.5%/°C). In addition, this study employs machine learning techniques for data interpolation among sensors, thereby enhancing the spatial resolution of temperature measurements and adding tactile mapping without increasing the sensor count. Introducing this methodology results in an improved understanding of temperature variations, advancing the capabilities of flexible-sensor arrays for various applications.

A bagging approach for improved predictive accuracy of intradialytic hypotension during hemodialysis treatment.

The primary objective of this study is to enhance the prediction accuracy of intradialytic hypotension in patients undergoing hemodialysis. A significant challenge in this context arises from the nature of the data derived from the monitoring devices and exhibits an extreme class imbalance problem. Traditional predictive models often display a bias towards the majority class, compromising the accuracy of minority class predictions. Therefore, we introduce a method called UnderXGBoost. This novel methodology combines the under-sampling, bagging, and XGBoost techniques to balance the dataset and improve predictive accuracy for the minority class. This method is characterized by its straightforward implementation and training efficiency. Empirical validation in a real-world dataset confirms the superior performance of UnderXGBoost compared to existing models in predicting intradialytic hypotension. Furthermore, our approach demonstrates versatility, allowing XGBoost to be substituted with other classifiers and still producing promising results. Sensitivity analysis was performed to assess the model's robustness, reinforce its reliability, and indicate its applicability to a broader range of medical scenarios facing similar challenges of data imbalance. Our model aims to enable medical professionals to provide preemptive treatments more effectively, thereby improving patient care and prognosis. This study contributes a novel and effective solution to a critical issue in medical prediction, thus broadening the application spectrum of predictive modeling in the healthcare domain.

Enhanced Electrical Transport Properties of Molybdenum Disulfide Field-Effect Transistors by Using Alkali Metal Fluorides as Dielectric Capping Layers.

The electronic properties of 2D materials are highly influenced by the molecular activity at their interfaces. A method was proposed to address this issue by employing passivation techniques using monolayer MoS2 field-effect transistors (FETs) while preserving high performance. Herein, we have used alkali metal fluorides as dielectric capping layers, including lithium fluoride (LiF), sodium fluoride (NaF), and potassium fluoride (KF) dielectric capping layers, to mitigate the environmental impact of oxygen and water exposure. Among them, the LiF dielectric capping layer significantly improved the transistor performance, specifically in terms of enhanced field effect mobility from 74 to 137 cm2/V·s, increased current density from 17 µA/µm to 32.13 µA/µm at a drain voltage of Vd of 1 V, and decreased subthreshold swing to 0.8 V/dec The results have been analytically verified by X-ray photoelectron spectroscopy (XPS) and Raman, and photoluminescence (PL) spectroscopy, and the demonstrated technique can be extended to other transition metal dichalcogenide (TMD)-based FETs, which can become a prospect for cutting-edge electronic applications. These findings highlight certain important trade-offs and provide insight into the significance of interface control and passivation material choice on the electrical stability, performance, and enhancement of the MoS2 FET.

Phase/Interfacial-Engineered Two-Dimensional-Layered WSe2 Films by a Plasma-Assisted Selenization Process: Modulation of Oxygen Vacancies in Resistive Random-Access Memory.

Here, we propose phase and interfacial engineering by inserting a functional WO3 layer and selenized it to achieve a 2D-layered WSe2/WO3 heterolayer structure by a plasma-assisted selenization process. The 2D-layered WSe2/WO3 heterolayer was coupled with an Al2O3 film as a resistive switching (RS) layer to form a hybrid structure, with which Pt and W films were used as the top and bottom electrodes, respectively. The device with good uniformity in SET/RESET voltage and high low-/high-resistance window can be obtained by controlling a conversion ratio from a WO3 film to a 2D-layered WSe2 thin film. The Pt/Al2O3/(2D-layered WSe2/WO3)/W structure shows remarkable improvement to the pristine Pt/Al2O3/W and Pt/Al2O3/2D-layered WO3/W in terms of low SET/RESET voltage variability (-20/20)%, multilevel characteristics (uniform LRS/HRS distribution), high on/off ratio (104-105), and retention (∼105 s). The thickness of the obtained WSe2 was tuned at different gas ratios to optimize different 2D-layered WSe2/WO3 (%) ratios, showing a distinctive trend of reduced and uniform SET/RESET voltage variability as 2D-layered WSe2/WO3 (%) changes from 90/10 (%) to 45/55 (%), respectively. The electrical measurements confirm the superior ability of the metallic 1T phase of the 2D-layered WSe2 over the semiconducting 2H phase. Through systemic studies of RS behaviors on the effect of 1T/2H phases and 2D-layered WSe2/WO3 ratios, the low-temperature plasma-assisted selenization offers compatibility with the temperature-limited 3D integration process and also provides much better thickness control over a large area.

Hierarchically Hybrid Porous Co3O4@NiMoO4/CoMoO4 Heterostructures for High-Performance Electrochemical Energy Storage.

Hierarchical, ultrathin, and porous NiMoO4@CoMoO4 on Co3O4 hollow bones were successfully designed and synthesized by a hydrothermal route from the Co-precursor, followed by a KOH (potassium hydroxide) activation process. The hydrothermally synthesized Co3O4 nanowires act as the scaffold for anchoring the NiMoO4@CoMoO4 units but also show more compatibility with NiMoO4, leading to high conductivity in the heterojunction. The intriguing morphological features endow the hierarchical Co3O4@NiMoO4@CoMoO4 better electrochemical performance where the capacity of the Co3O4@NiMoO4@CoMoO4 heterojunction being 272 mA·h·g-1 at 1 A·g-1 can be achieved with a superior retention of 84.5% over 1000 cycles. The enhanced utilization of single/few NiMoO4@CoMoO4 shell layers on the Co3O4 core make it easy to accept extra electrons, enhancing the adsorption of OH- at the shell surface, which contribute to the high capacity. In our work, an asymmetric supercapacitor utilizing the optimized Co3O4@NiMoO4@CoMoO4 activated carbon (AC) as electrode materials was assembled, namely, Co3O4@NiMoO4@CoMoO4//AC device, yielding a maximum high energy density of 53.9 W·h·kg-1 at 1000 W·kg-1. It can retain 25.92 W·h·kg-1 even at 8100 W·kg-1, revealing its potential and viability for applications. The good power densities are ascribed to the porous feature from the robust architecture with recreated abundant mesopores on the composite, which assure improved conductivity and enhanced diffusion of OH- and also the electron transport. The work demonstrated here holds great promise for synthesizing other heterojunction materials M3O4@MMoO4@MMoO4 (M = Fe, Ni, Sn, etc).

Glancing angle deposition of large-scale helical Si@Cu3Si nanorod arrays for high-performance anodes in rechargeable Li-ion batteries.

Silicon (Si) anode materials have attracted substantial interest due to their high theoretical capacity. Here, the growth of helical Si@Cu3Si nanorod arrays via glancing angle deposition (GLAD) followed by an annealing process is reported. Pre-deposited Cu atoms were driven into Si-nanorods and successfully reacted with Si to form a Si-Cu alloy at a high temperature. By varying the rotation rate and annealing temperature, the resultant Si@Cu3Si nanorod arrays showed a reasonably accessible surface area with precise control spacing behavior in favor of accommodating Si volume expansion. Meanwhile, the Si@Cu3Si anode materials showed higher electrical conductivity, facilitating Li+ ion diffusion and electron transfer. The Si@Cu3Si nanorod arrays in half cells exhibited a volumetric capacity as high as 3350.1 mA h cm-3 at a rate of 0.25 C and could maintain 1706.7 mA h cm-3 after 100 cycles, which are superior to those of pristine Si materials. This facile and innovative technology provided new insights into the development of Si-based electrode materials.

MCPIP1 Enhances TNF-α-Mediated Apoptosis through Downregulation of the NF-κB/cFLIP Axis.

Monocyte chemoattractant protein-1-induced protein 1 (MCPIP1) is rapidly produced under proinflammatory stimuli, thereby feeding back to downregulate excessive inflammation. In this study, we used the stable, inducible expressions of wild-type (WT) MCPIP1 and an MCPIP1-D141N mutant in T-REx-293 cells by means of a tetracycline on (Tet-on) system. We found that WT MCPIP1 but not MCPIP1-D141N mutant expression dramatically increased apoptosis, caspase-3, -7, -8, and -9 activation, and c-Jun N-terminal kinase (JNK) phosphorylation in TNF-α-treated cells. The pan-caspase inhibitor, z-VAD-fmk, and the caspase-1 inhibitor, z-YVAD-fmk, but not the JNK inhibitor, SP600125, significantly reversed apoptosis and caspase activation in TNF-α/MCPIP1-treated cells. Surprisingly, MCPIP1 itself was also cleaved, and the cleavage was suppressed by treatment with the pan-caspase inhibitor and caspase-1 inhibitor. Moreover, MCPIP1 was found to contain a caspase-1/-4 consensus recognition sequence located in residues 234~238. As expected, the WT MCPIP1 but not the MCPIP1-D141N mutant suppressed NF-κB activation, as evidenced by inhibition of IκB kinase (IKK) phosphorylation and IκB degradation using Western blotting, IKK activity using in vitro kinase activity, and NF-κB translocation to nuclei using an immunofluorescence assay. Interestingly, MCPIP1 also significantly inhibited importin α3 and importin α4 expressions, which are major nuclear transporter receptors for NF-κB. Inhibition of NF-κB activation further downregulated expression of the caspase-8 inhibitor, cFLIP. In summary, the results suggest that MCPIP1 could enhance the TNF-α-induced apoptotic pathway through decreasing NF-κB activation and cFLIP expression.

The Antihistamine Deptropine Induces Hepatoma Cell Death through Blocking Autophagosome-Lysosome Fusion.

Some antihistamines have exhibited significant antitumor activity alone or in combination with other therapies in in vitro and clinical studies. However, the underlying mechanisms of how antihistamines inhibit hepatocellular carcinoma proliferation are still unknown. We first screened the antiproliferation activity of 12 benzocycloheptene structural-analogue drugs, and results showed that deptropine was the most potent inhibitor of both Hep3B and HepG2 human hepatoma cells. Deptropine significantly increased light chain 3B-II (LC3B-II) expression but did not induce sequestosome 1 (SQSTM1/p62) degradation in either cell line. Interestingly, other autophagy-related proteins, such as autophagy-related 7 (ATG7), vacuolar protein sorting 34 (VPS34), phosphorylated adenosine 5'-monophosphate-activated protein kinase (AMPK), and phosphorylated protein kinase B (PKB, also known as Akt), exhibited no significant change in either deptropine-treated cell line. Deptropine also inhibited the processing of cathepsin L from its precursor form to its mature form. Immunofluorescence microscopy showed an increase of autophagosomes in deptropine-treated cells, but deptropine blocked the fusion between autophagosomes and lysosomes. In a xenograft nude mice model, 2.5 mg/kg deptropine showed a great inhibitory effect on Hep3B tumor growth. These results suggest that deptropine can induce in vitro and in vivo hepatoma cell death, and the underlying mechanisms might be mediated through inhibiting autophagy by blocking autophagosome-lysosome fusion.