A novel design of copper selenide/zinc selenide/Nitrogen-doped carbon derived from MOF for sulfadiazine adsorption: Performance and mechanism.

Herein, a novel copper selenide/zinc selenide/Nitrogen-doped carbon (Cu2Se/ZnSe/NC) sphere was constructed via a combination of cation exchange, selenization and carbonization approaches with zinc-based metal-organic frameworks (ZIF-8) as precursor for sulfadiazine (SDZ) removal. Compared with the ZnSe/NC, the defective Cu2Se/ZnSe interface in the optimizing Cu-ZnSe/NC2 sample caused a remarkably improved adsorption performance. Notably, the adsorption capacity of 129.32 mg/g was better than that of mostly reported adsorbents for SDZ. And the adsorption referred to multiple-layer physical-chemical process that was spontaneous and exothermic. Besides, the Cu-ZnSe/NC2 displayed fast adsorption equilibrium of about 20 min and significant anti-interference ability for inorganic ions. Specially, the adsorbent possessed excellent stability and reusability, which could also be applied for rhodamine B (RhB), methylene blue (MB), and methyl orange (MO) dyes removal. Ultimately, the charge redistribution of Cu2Se/ZnSe interface greatly contributes the superior adsorption performance for SDZ, in which electrostatic attraction occupied extremely crucial status as compared to π-π electron-donor-acceptor (π-π EDA) interaction and hydrogen bonding (H-bonding), as revealed by the density function theory (DFT) calculations and experimental results. This study can provide a guideline for design of high-efficient adsorbent with interfacial charge redistribution.

Insight into the interface engineering between methylammonium lead halide perovskites and gallium oxide: a first-principles approach.

Interface engineering of the organo-lead halide perovskite devices has shown the potential to improve their efficiency and stability. In this study, the atomic, electronic, optical and transport characteristics of MAPbI3/Ga2O3 and MAPbCl3/Ga2O3 interfaces were investigated by using first-principles calculations. Eight different interfacial models were established and the interfacial properties were discussed. The results show that the PbI/O configuration exhibits the largest bonding strength out of all eight interfacial configurations. Owing to the larger interfacial interaction, the charge transfer at the PbI/O interface is significantly more than that at the other interfaces. The analysis of absorption spectra indicates that the Ga-terminated perovskite/Ga2O3 heterostructures are expected to have great potential for efficient optoelectronic applications. The analysis of transmission spectra shows that the MA/O configurations with more transmission peaks near the Fermi level exhibit lower resistance compared to others. The results of our study could help understand the interfacial engineering mechanism between perovskite and Ga2O3.

Nitric oxide-dependent immunosuppressive function of thymus-derived mesenchymal stromal/stem cells.

BACKGROUND: The thymus is required for T cell development and the formation of the adaptive immunity. Stromal cells, which include thymic epithelial cells (TECs) and mesenchymal stromal cells (MSCs), are essential for thymic function. However, the immunomodulatory function of thymus-derived MSCs (T-MSCs) has not been fully explored. METHODS: MSCs were isolated from mouse thymus and their general characteristics including surface markers and multi-differentiation potential were characterized. The immunomodulatory function of T-MSCs stimulated by IFN-γ and TNF-α was evaluated in vitro and in vivo. Furthermore, the spatial distribution of MSCs in the thymus was interrogated by using tdTomato-flox mice corssed to various MSC lineage Cre recombinase lines. RESULTS: A subset of T-MSCs express Nestin, and are mainly distributed in the thymic medulla region and cortical-medulla junction, but not in the capsule. The Nestin-positive T-MSCs exhibit typical immunophenotypic characteristics and differentiation potential. Additionally, when stimulated with IFN-γ and TNF-α, they can inhibit activated T lymphocytes as efficiently as BM-MSCs, and this function is dependent on the production of nitric oxide (NO). Additionally, the T-MSCs exhibit a remarkable therapeutic efficacy in acute liver injury and inflammatory bowel disease (IBD). CONCLUSIONS: Nestin-positive MSCs are mainly distributed in medulla and cortical-medulla junction in thymus and possess immunosuppressive ability upon stimulation by inflammatory cytokines. The findings have implications in understanding the physiological function of MSCs in thymus.

Prussian blue analogue-derived hollow metal oxide heterostructure for high-performance supercapacitors.

Supercapacitors (SCs) have been the subject of considerable interest because of their distinct advantages. The performance of SCs is directly affected by the electrode materials. Metal oxides derived from Prussian blue analogues (PBAs) are often used as electrode materials for SCs. Herein, we developed a multi-step strategy to fabricate ternary hollow metal oxide (CuO/NiO/Co3O4) heterostructures. The core-shell structured PBA (NiHCC@CuHCC) with Ni-based PBA (NiHCC) as the core and Cu-based PBA (CuHCC) as the shell was prepared by a crystal seed method. The ternary metal oxide (CuO/NiO/Co3O4) with a hollow structure was obtained by calcinating NiHCC@CuHCC. The prepared CuO/NiO/Co3O4 demonstrates an excellent specific capacitance of 262.5 F g-1 at 1 A g-1, which is 27.4% and 16.2% higher than those of CuO/Co3O4 and NiO/Co3O4, respectively. In addition, the material showed outstanding cycling stability with a capacitance retention of 107.9% after 3000 cycles. The two-electrode system constructed with CuO/NiO/Co3O4 and nitrogen-doped graphene hydrogel (NDGH) demonstrates a stable and high energy density of 27.1 W h kg-1 at a power density of 1037.5 W kg-1. The capacitance retention rate was 100.7% after 4000 cycles. The reason for the excellent electrochemical properties could be the synergistic effect of the introduced heterojunction of CuO/NiO, the hollow structure, and various metal oxides. This strategy can greatly inspire the construction of SC electrodes.

Structural, Electronic, and Mechanical Properties of Zr2SeB and Zr2SeN from First-Principle Investigations.

MAX phases have exhibited diverse physical properties, inspiring their promising applications in several important research fields. The introduction of a chalcogen atom into a phase of MAX has further facilitated the modulation of their physical properties and the extension of MAX family diversity. The physical characteristics of the novel chalcogen-containing MAX 211 phase Zr2SeB and Zr2SeN have been systematically investigated. The present investigation is conducted from a multi-faceted perspective that encompasses the stability, electronic structure, and mechanical properties of the system, via the employment of the first-principles density functional theory methodology. By replacing C with B/N in the chalcogen-containing MAX phase, it has been shown that their corresponding mechanical properties are appropriately tuned, which may offer a way to design novel MAX phase materials with enriched properties. In order to assess the dynamical and mechanical stability of the systems under investigation, a thorough evaluation has been carried out based on the analysis of phonon dispersions and elastic constants conditions. The predicted results reveal a strong interaction between zirconium and boron or nitrogen within the structures of Zr2SeB and Zr2SeN. The calculated band structures and electronic density of states for Zr2SeB and Zr2SeN demonstrate their metallic nature and anisotropic conductivity. The theoretically estimated Pugh and Poisson ratios imply that these phases are characterized by brittleness.

Theoretical Investigation of Single-Molecule-Magnet Behavior in Mononuclear Dysprosium and Californium Complexes.

Early-actinide-based (U, Np, and Pu) single-molecule magnets (SMMs) have yet to show magnetic properties similar to those of highly anisotropic lanthanide-based ones. However, there are not many studies exploring the late-actinides (more than half-filled f shells) as potential candidates for SMM applications. We computationally explored the electronic structure and magnetic properties of a hypothetical Cf(III) complex isostructural to the experimentally synthesized Dy(dbm)3(bpy) complex (bpy = 2,2'-bipyridine; dbm = dibenzoylmethanoate) via multireference methods and compared them to those of the Dy(III) analogue. This study shows that the Cf(III) complex can behave as a SMM and has a greater magnetic susceptibility compared to other experimentally and computationally studied early-actinide-based (U, Np, and Pu) magnetic complexes. However, Cf spontaneously undergoes α-decay and converts to Cm. Thus, we also explored the isostructural Cm(III)-based complex. The computed magnetic susceptibility and g-tensor values show that the Cm(III) complex has poor SMM behavior in comparison to both the Dy(III) and Cf(III) complexes, suggesting that the performance of Cf(III)-based magnets may be affected by α-decay and can explain the poor performance of experimentally studied Cf(III)-based molecular magnets in the literature. Further, this study suggests that the ligand field is dominant in Cf(III), which helps to increase the magnetization blocking barrier by nearly 3 times that of its 4f congener.

Exercise Protects Against Cognitive Injury and Inflammation in Alzheimer's Disease Through Elevating miR-148a-3p.

Alzheimer's disease (AD) is a chronic neurological disorder with high morbidity. Exercise is one of the effective ways to ameliorate AD. In this study, we assessed the effects of exercise on cognition and inflammation and studied the role of miR-148a-3p in AD. In 88 patients with AD, the expression of miR-148a-3p was studied using qRT-PCR. ROC curve and Pearson analysis were utilized to evaluate the roles of miR-148a-3p in AD. MWM test was conducted to investigate the effects of miR-148a-3p and exercise on cognition and memory. Moreover, inflammatory indicators were identified using an enzyme-linked immunosorbent assay. Relative luciferase levels reflected whether miR-148a-3p targeted SYNJ1. miR-148a-3p levels declined in patients with AD, indicating its potential as a biomarker. Interestingly, miR-148a-3p levels were elevated in patients with AD after exercise. MiR-148a-3p levels correlated with cognitive scores and proinflammatory levels. The cognitive situation and pro-inflammatory state were partly recovered in the mice after exercise. MiR-148a-3p silencing reversed these abovementioned tendencies. Patients with AD exhibited a low level of miR-148a-3p, which was increased after exercise. Therefore, exercise might improve the cognitive function and memory of mice with AD by upregulating miR-148a-3p.

Mesenchymal stem/stromal cells primed by inflammatory cytokines alleviate psoriasis-like inflammation via the TSG-6-neutrophil axis.

Psoriasis is currently an incurable skin disorder mainly driven by a chronic inflammatory response. We found that subcutaneous application of umbilical cord- derived mesenchymal stem/stromal cells (MSCs) primed by IFN-γ and TNF-α, referred to as MSCs-IT, exhibited remarkable therapeutic efficacy on imiquimod (IMQ)-induced psoriasis-like inflammation in mice. Neutrophil infiltration, a hallmark of psoriasis, was significantly reduced after treatment with MSCs-IT. We further demonstrated that the effects of MSCs-IT were mediated by tumor necrosis factor (TNF) stimulating gene-6 (TSG-6), which was greatly upregulated in MSCs upon IFN-γ and TNF-α stimulation. MSCs transduced with TSG-6 siRNA lost their therapeutic efficacy while recombinant TSG-6 applied alone could also reduce neutrophil infiltration and alleviate the psoriatic lesions. Furthermore, we demonstrated that TSG-6 could inhibit neutrophil recruitment by decreasing the expression of CXCL1, which may be related to the reduced level of STAT1 phosphorylation in the keratinocytes. Thus, blocking neutrophil recruitment by MSCs-IT or TSG-6 has potential for therapeutic application in human psoriasis.

Two-Dimensional Half-Metallic and Semiconducting Lanthanide-Based MXenes.

As a large family of two-dimensional materials, MXenes have attracted intensive attention in recent years. For more functional applications, it is of great significance to determine new MXene members. Here, we theoretically expand the M elements of MXenes to the lanthanide series. Based on density functional theory calculations, the bare lanthanide-based carbides M2C (M = Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, and Yb) and the corresponding fluorine- and hydroxyl-terminated configurations are investigated. Most of the fluorine- and hydroxyl-terminated MXenes investigated are half-metals. Specifically, in the half-metallic Eu2CF2, the spin-down states show a band gap larger than 2 eV, implying this configuration's potential applications in spin generation and injection. Both Gd2CT2 (T = F and OH) are magnetic semiconductors. The former shows an indirect band gap of 1.38 eV, while the latter presents a direct one of 0.882 eV. These two configurations also show large magnetic moments higher than 13.7 µB per unit cell. All the hydroxyl-terminated MXene members show relatively low work functions, with the lowest value of 1.46 eV determined in Tm2C(OH)2. These predicted electronic properties imply that the lanthanide-based MXenes could have potential applications in spintronics, information storage, near-infrared detectors, field effect transistors, and field emitter cathodes.

DHCR24 Knockdown Induces Tau Hyperphosphorylation at Thr181, Ser199, Ser262, and Ser396 Sites via Activation of the Lipid Raft-Dependent Ras/MEK/ERK Signaling Pathway in C8D1A Astrocytes.

The synthetase 3ß-hydroxysterol-Δ24 reductase (DHCR24) is a key regulator involved in cholesterol synthesis and homeostasis. A growing body of evidence indicates that DHCR24 is downregulated in the brain of various models of Alzheimer's disease (AD), such as astrocytes isolated from AD mice. For the past decades, astrocytic tau pathology has been found in AD patients, while the origin of phosphorylated tau in astrocytes remains unknown. A previous study suggests that downregulation of DHCR24 is associated with neuronal tau hyperphosphorylation. Herein, the present study is to explore whether DHCR24 deficiency can also affect tau phosphorylation in astrocytes. Here, we showed that DHCR24 knockdown could induce tau hyperphosphorylation at Thr181, Ser199, Thr231, Ser262, and Ser396 sites in C8D1A astrocytes. Meanwhile, we found that DHCR24-silencing cells had reduced the level of free cholesterol in the plasma membrane and intracellular organelles, as well as cholesterol esters. Furthermore, reduced cellular cholesterol level caused a decreased level of the caveolae-associated protein, cavin1, which disrupted lipid rafts/caveolae and activated rafts/caveolae-dependent Ras/MEK/ERK signaling pathway. In contrast, overexpression of DHCR24 prevented the overactivation of Ras/MEK/ERK signaling by increasing cellular cholesterol content, therefore decreasing tau hyperphosphorylation in C8D1A astrocytes. Herein, we firstly found that DHCR24 knockdown can lead to tau hyperphosphorylation in the astrocyte itself by activating lipid raft-dependent Ras/MEK/ERK signaling, which might contribute to the pathogenesis of AD and other degenerative tauopathies.

Water-Induced Self-Assembly and In Situ Mineralization within Plant Phenolic Glycol-Gel toward Ultrastrong and Multifunctional Thermal Insulating Aerogels.

Biopolymer/silica nanocomposite aerogels are highly attractive as thermally insulating materials for prevailing energy-saving engineering but are usually plagued by their lack of mechanical strength and environmental stability. Lignin is an appealing plant phenolic biopolymer due to its natural abundance, high stiffness, water repellency, and thermostability. However, integrating lignin and silica into high-performance 3D hybrid aerogels remains a substantial challenge due to the unstable co-sol process. In diatoms, the silicic acid stabilization prior to the condensation reaction is enhanced by the intervention of biomolecules in noncovalent interactions. Inspired by this mechanism, we herein rationally design an ultrastrong silica-mineralized lignin nanocomposite aerogel (LigSi) with an adjustable multilevel micro/nanostructure and arbitrary machinability through an unusual water-induced self-assembly and in situ mineralization based on ethylene glycol-stabilized lignin/siloxane colloid. The optimized LigSi exhibits an ultrahigh stiffness (a specific modulus of ∼376.3 kN m kg-1) and can support over 5000 times its own weight without obvious deformation. Moreover, the aerogel demonstrates a combination of outstanding properties, including superior and humidity-tolerant thermal insulation (maintained at ∼0.04 W m-1 K-1 under a relative humidity of 33-94%), excellent fire resistance withstanding an ∼1200 °C flame without disintegration, low near-infrared absorption (∼9%), and intrinsic self-cleaning/superhydrophobic performance (158° WCA). These advanced properties make it an ideal thermally insulating material for diversified applications in harsh environments. As a proof of concept, a dual-mode LigSi thermal device was designed to demonstrate the application prospect of combining passive heat-trapping and active heating in the building.

The role of DHCR24 in the pathogenesis of AD: re-cognition of the relationship between cholesterol and AD pathogenesis.

Previous studies show that 3ß-hydroxysterol-Δ24 reductase (DHCR24) has a remarked decline in the brain of AD patients. In brain cholesterol synthetic metabolism, DHCR24 is known as the heavily key synthetase in cholesterol synthesis. Moreover, mutations of DHCR24 gene result in inhibition of the enzymatic activity of DHCR24, causing brain cholesterol deficiency and desmosterol accumulation. Furthermore, in vitro studies also demonstrated that DHCR24 knockdown lead to the inhibition of cholesterol synthesis, and the decrease of plasma membrane cholesterol and intracellular cholesterol level. Obviously, DHCR24 could play a crucial role in maintaining cholesterol homeostasis via the control of cholesterol synthesis. Over the past two decades, accumulating data suggests that DHCR24 activity is downregulated by major risk factors for AD, suggesting a potential link between DHCR24 downregulation and AD pathogenesis. Thus, the brain cholesterol loss seems to be induced by the major risk factors for AD, suggesting a possible causative link between brain cholesterol loss and AD. According to previous data and our study, we further found that the reduced cholesterol level in plasma membrane and intracellular compartments by the deficiency of DHCR24 activity obviously was involved in ß-amyloid generation, tau hyperphosphorylation, apoptosis. Importantly, increasing evidences reveal that the brain cholesterol loss and lipid raft disorganization are obviously linked to neuropathological impairments which are associated with AD pathogenesis. Therefore, based on previous data and research on DHCR24, we suppose that the brain cholesterol deficiency/loss might be involved in the pathogenesis of AD.

Ruthenium-nickel-cobalt alloy nanoparticles embedded in hollow carbon microtubes as a bifunctional mosaic catalyst for overall water splitting.

The development of efficient bifunctional catalysts for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is essential for reducing the cost of hydrogen production by water splitting. Herein, hollow microtubes composed of RuNi1Co1 alloy nanoparticles uniformly embedded in the carbon matrix (RuNi1Co1@CMT) are prepared through a simple impregnation followed by reduction. Benefiting from the unique mosaic structure and the synergistic effect between Ru and NiCo, RuNi1Co1@CMT achieves more exposed active sites and improved reaction kinetics. As a consequence, RuNi1Co1@CMT exhibits considerable catalytic activities with the overpotentials of 78 mV for HER and 299 mV for OER at 10 mA cm-2 in 1 M KOH. In addition, RuNi1Co1@CMT exhibits excellent stability for up to 30 h in both HER and OER processes at 20 mA cm-2, which is attributed to the protection of the RuNi1Co1 alloy particles by the carbon layer. Furthermore, the assembled RuNi1Co1@CMT || RuNi1Co1@CMT overall water splitting system shows a cell voltage of 1.58 V at 10 mA cm-2. The density functional theory (DFT) calculations indicate that the addition of Ru can optimize the hydrogen adsorption free energy of Ni and Co sites. Finally, a solar panel-driven water splitting device is built, which can realize green and sustainable hydrogen production. The fabrication of RuNi1Co1@CMT provides a new way for the preparation of effective alloy nanomaterials for energy storage and conversion.

Construction of reduced graphene oxide coupled with CoSe2-MoSe2 heterostructure for enhanced electrocatalytic hydrogen production.

It is important to develop novel energy to solve energy shortage and environmental problems. Hydrogen evolution reaction (HER) is envisaged as a viable technology that can be used to develop sustainable clean energy. Herein, we report a catalyst with CoSe2-MoSe2 heterostructure grown on reduced graphene oxide with an optimum Co/Mo proportion of 1:1 (CoSe2-MoSe2(1-1)/rGO). It exhibits good HER activities in both acidic and alkaline conditions. The CoSe2-MoSe2(1-1)/rGO shows an overpotential of 107 mV at 10 mA cm-2 with a Tafel slope of 56 mV dec-1 under acidic condition. Meanwhile, CoSe2-MoSe2(1-1)/rGO also presents an overpotential of 182 mV at 10 mA cm-2 and with a Tafel slope of 89 mV dec-1 under alkaline condition. These impressive performances of the catalyst are mainly due to the excellent electronic transmission capability of rGO and the abundant active sites of CoSe2-MoSe2 heterostructure as well as the optimized hydrogen adsorption energy of CoSe2-MoSe2 interface. The design of CoSe2-MoSe2(1-1)/rGO provides a meaningful guide for manufacturing electrode in energy storage and conversion.

Iron molybdenum selenide supported on reduced graphene oxide as an efficient hydrogen electrocatalyst in acidic and alkaline media.

It is of great significance to develop inexpensive and high-efficiency electrocatalysts for the hydrogen evolution reaction (HER). In this work, we synthesized iron molybdenum selenide (FeSe2-MoSe2) loaded on reduced graphene oxide (FeSe2-MoSe2/rGO) by a one-step hydrothermal method. We further optimized the Fe/Mo ratio and determined the best ratio to be 1-1. In acidic (or alkaline) solution, the optimized FeSe2-MoSe2(1-1)/rGO has a small Tafel slope of 55 (or 80) mV dec-1 and needs an overpotential of 101 (or 178) mV to achieve 10 mA cm-2. These good properties are mainly due to the structure of bimetallic selenides combining rGO. Moreover, rGO enhances the electrical conductivity. Furthermore, the synergistic effect between FeSe2-MoSe2(1-1) and rGO results in better HER performance. Density functional theory (DFT) calculation proves that FeSe2-MoSe2(1-1)/rGO has a small work function. Based on our reasonable design and analysis, FeSe2-MoSe2(1-1)/rGO is expected to be an efficient and robust catalyst for large-scale applications.

DHCR24 Knock-Down Induced Tau Hyperphosphorylation at Thr181, Ser199, Thr231, Ser262, Ser396 Epitopes and Inhibition of Autophagy by Overactivation of GSK3ß/mTOR Signaling.

Accumulating evidences supported that knock-down of DHCR24 is linked to the pathological risk factors of AD, suggesting a potential role of DHCR24 in AD pathogenesis. However, the molecular mechanism link between DHCR24 and tauopathy remains unknown. Here, in order to elucidate the relationship between DHCR24 and tauopathy, we will focus on the effect of DHCR24 on the tau hyperphosphorylation at some toxic sites. In present study, we found that DHCR24 knock-down significantly lead to the hyperphosphorylation of tau sites at Thr181, Ser199, Thr231, Ser262, Ser396. Moreover, DHCR24 knock-down also increase the accumulation of p62 protein, simultaneously decreased the ratio of LC3-II/LC3-I and the number of autophagosome compared to the control groups, suggesting the inhibition of autophagy activity. In contrast, DHCR24 knock-in obviously abolished the effect of DHCR24 knock-down on tau hyperphosphrylation and autophagy. In addition, to elucidate the association between DHCR24 and tauopathy, we further showed that the level of plasma membrane cholesterol, lipid raft-anchored protein caveolin-1, and concomitantly total I class PI3-K (p110α), phospho-Akt (Thr308 and Ser473) were significantly decreased, resulting in the disruption of lipid raft/caveola and inhibition of PI3-K/Akt signaling in silencing DHCR24 SH-SY5Y cells compared to control groups. At the same time, DHCR24 knock-down simultaneously decreased the level of phosphorylated GSK3ß at Ser9 (inactive form) and increased the level of phosphorylated mTOR at Ser2448 (active form), leading to overactivation of GSK3ß and mTOR signaling. On the contrary, DHCR24 knock-in largely increased the level of membrane cholesterol and caveolin-1, suggesting the enhancement of lipid raft/caveola. And synchronously DHCR24 knock-in also abolished the effect of DHCR24 knock-down on the inhibition of PI3-K/Akt signaling as well as the overactivation of GSK3ß and mTOR signaling. Collectively, our data strongly supported DHCR24 knock-down lead to tau hyperphosphorylation and the inhibition of autophagy by a lipid raft-dependent PI3-K/Akt-mediated GSK3ß and mTOR signaling. Taking together, our results firstly demonstrated that the decrease of plasma membrane cholesterol mediated by DHCR24 deficiency might contribute to the tauopathy in AD and other tauopathies.

Green-light laser en bloc resection versus conventional transurethral resection for initial non-muscle-invasive bladder cancer: A randomized controlled trial.

OBJECTIVE: To compare the safety and outcomes between green-light laser en bloc resection and transurethral resection of bladder tumor. METHODS: A single-center, randomized controlled trial was carried out from August 2014 to September 2018. Patients with initial non-muscle-invasive bladder cancer were randomized to green-light laser en bloc resection or transurethral resection of bladder tumor. The primary outcomes were pathological findings and perioperative events. The secondary outcome was tumor recurrence. RESULTS: A total of 233 patients were randomized to the transurethral resection of bladder tumor group (117 patients) and the green-light laser en bloc resection group (116 patients). The resection time was longer in the green-light laser en bloc resection group (P = 0.022); however, no differences were identified in overall operative time (P = 0.255). Nine patients (7.7%) had an obturator nerve reflex during transurethral resection of bladder tumor. The estimated volume of blood loss was significantly lower in the green-light laser en bloc resection group (P = 0.012). The green-light laser en bloc resection group had a higher rate of T1 bladder cancer (P = 0.031). A total of 104 patients (89.7%) treated with green-light laser en bloc resection had detrusor muscle presence in the specimen, whereas 37 (31.9%) patients had the presence of muscularis mucosae, which was significantly higher than the corresponding number of transurethral resection of bladder tumor patients (P = 0.005 and 0.002, respectively). After a median follow-up period of 48 months, just five patients had tumor recurrence (three in the transurethral resection of bladder tumor group and two in the green-light laser en bloc resection group), and there was no difference between these two groups. CONCLUSIONS: Compared with transurethral resection of bladder tumor, green-light laser en bloc resection is more effective due to less obturator nerve reflex and the same recurrence rate. Most importantly, green-light laser en bloc resection can provide better tumor specimens for pathological examinations.

DHCR24 Knockdown Lead to Hyperphosphorylation of Tau at Thr181, Thr231, Ser262, Ser396, and Ser422 Sites by Membrane Lipid-Raft Dependent PP2A Signaling in SH-SY5Y Cells.

Accumulating data suggest that the downregulation of DHCR24 is linked to the pathological risk factors of AD, denoting a potential role of DHCR24 in AD pathogenesis. However, it remains unclear whether the downregulation of DHCR24 affects the abnormal heper-phosphorylation of tau protein, which is involved in tauopathy. In present papers, immunofluorescence and Filipin III fluorescence results showed that DHCR24 knockdown significantly lowered the level of plasma membrane cholesterol and expression level of membrane lipid-raft structural protein caveolin-1; and overexpression of DHCR24 could increase the plasma membrane cholesterol levels and facilitating caveolae structure through increase the expression of caveolin-1. PP2A is the key phosphatase involving in tau phosphorylation, which is localized in cholesterol-dependent caveola/raft lipid domains. Here, the PP2A activity was detected by western blot assay. Interestingly, the level of p-PP2Ac at Y307 (inactive) and p-GSK3ß at Y216 (active) in the downstream of the PP2A signal pathway were both significantly increased in silencing DHCR24 SH-SY5Y cells, which denoted an inhibition of the PP2A and activation of GSK3ß signaling. Conversely, overexpression of DHCR24 blunted the inhibition effect of PP2A and activation of GSK3ß. Besides, in the SH-SY5Y cell lines we demonstrated that DHCR24 knockdown obviously induced hyperphosphorylation of tau at Thr181, Thr231, Ser262, Ser396, and Ser422 Sites. In contrast, DHCR24 overexpression protects neuronal SH-SY5Y cells against the hyperphosphorylation of tau at Thr181, Thr231, Ser262, Ser396, and Ser422 Sites. Furthermore, PP2A activator D-erythro-Sphingosine (DES) also obviously inhibited the hyperphosphorylation of tau induced by DHCR24 knockdown. Collectively, our findings firstly confirmed that DHCR24 knockdown obviously induced abnormal hyperphosphorylation of tau by a novel lipid raft-dependent PP2A signaling. We propose that DHCR24 downregulation led to altered cholesterol synthesis as a potential mechanism in the progression of tau hyperphosphorylation involving in AD and other tauopathies.

Autophagic Flux Unleashes GATA4-NF-κB Axis to Promote Antioxidant Defense-Dependent Survival of Colorectal Cancer Cells under Chronic Acidosis.

Solid tumors are usually associated with extracellular acidosis due to their increased dependence on glycolysis and poor vascularization. Cancer cells gradually become adapted to acidic microenvironment and even acquire increased aggressiveness. They are resistant to apoptosis but exhibit increased autophagy that is essential for their survival. We here show that NF-κB, a master regulator of cellular responses to stress, is upregulated in colorectal cancer cells adapted to acidosis (CRC-AA). NF-κB is more relied upon for survival in CRC-AA than in their parental cells and drives a robust antioxidant response. Supplementation of antioxidant abolishes the increased sensitivity of CRC-AA to NF-κB inhibition or depletion, suggesting that NF-κB supports the survival of CRC-AA by maintaining redox homeostasis. Because SQSTM1/p62 is known to mediate the selective autophagy of GATA4 that augments NF-κB function, we tested whether the enhanced autophagic flux and consequently the reduction of SQSTM1/p62 in CRC-AA cells could activate the GATA4-NF-κB axis. Indeed, GATA4 is upregulated in CRC-AA cells and augments the NF-κB activity that underlies the increased expression of cytokines, inhibition of apoptosis, and reduction of reactive oxygen species. Interestingly, secretory factors derived from HCT15-AA cells, the soluble ICAM-1 in particular, also possess antioxidant cytoprotective effect against acidic stress. Together, our results demonstrate a prosurvival role of the p62-restricted GATA4-NF-κB axis in cancer cells adapted to acidic microenvironment.

FOXM1-Dependent Transcriptional Regulation of EZH2 Induces Proliferation and Progression in Prostate Cancer.

BACKGROUND: Prostate cancer is one of the most commonly diagnosed cancers and one of the most common causes of cancer-related deaths among men worldwide. Patients who are diagnosed with localized prostate cancer and treated with radical prostatectomy often respond well to therapy. The current standard therapy for prostate cancer involves maximal surgical resection, followed by radiotherapy and chemotherapy. Clarifying the molecular mechanism of tumor proliferation and recurrence becomes more and more important for clinical therapies of prostate cancer. METHODS: Quantitative Real-Time PCR and Western-blot were used in the detection of mRNA and protein expression. Lentivirus infection was used to overexpress or knockdown the target gene. Flow cytometry analysis was performed to test protein expression and apoptosis level. Immunohistochemistry was used to identify protein expression in tissue. Statistical differences between the two groups are evaluated by two-tailed t-tests. The comparison among multiple groups is performed by one-way Analysis of Variance (ANOVA) followed by Dunnett's posttest. The statistical significance of the Kaplan-Meier survival plot is determined by log-rank analysis. RESULTS: In this study, we identified that FOXM1 expression was significantly enriched in prostate cancer compared with normal tissue. Additionally, FOXM1 was functionally required for tumor proliferation and its expression was associated with poor prognosis in prostate cancer patients. Mechanically, FOXM1-dependent regulation of EZH2 is essential for proliferation and progression in prostate cancer. CONCLUSION: Taken together, our data suggest that oncogenic transcription factor FoxM1 is up-regulated in prostate cancer, suggesting that the growth of cancer cells may depend on FOXM1 activity. FOXM1 may serve as a clinical prognostic factor and a therapeutic target for prostate cancer.