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Further, invitro experiments showed that NaPs-induced reproductive toxicity associated with reducing PGC-1α. Meanwhile, NaPs-induced higher expression PGC-1α was further enhanced by NaHS co-treatment. Together, this study highlight that exogenous H2S should be an essential therapeutic approach to alleviate NaPs-induced reproductive toxicity via regulating Nrf2/PGC-1α signal.Because of scaling issues, passive muscle and joint forces become increasingly important as limb size decreases.1-3 In some small limbs, passive forces can drive swing in locomotion,4,5 and antagonist passive torques help control limb swing velocity.6 In stance, minimizing antagonist muscle and joint passive forces could save energy. These considerations predict that, for small limbs, evolution would result in the angle range over which passive forces are too small to cause limb movement (called "resting-state range" in prior insect work4 and "area of neutral equilibrium" in physics and engineering) correlating with the limb's typical working range, usually that in locomotion. We measured the most protracted and retracted thorax-femur (ThF) angles of the pro- (front), meso- (middle), and metathoracic (hind) leg during stick insect (Carausius morosus) walks. This ThF working range differed in the three leg types, being more posterior in more posterior legs. In other experiments, we manually protracted or retracted the denervated front, middle, and hind legs. Upon release, passive forces moved the leg in the opposite direction (retraction or protraction) until it reached the most protracted or most retracted edge of the ThF resting-state range. The ThF resting-state angle ranges correlated with the leg-type working range, being more posterior in more posterior legs. The most protracted ThF walking angles were more retracted than the post-protraction ThF angles, and the most retracted ThF walking angles were similar to the post-retraction ThF angles. These correlations of ThF working- and resting-state ranges could simplify motor control and save energy. These data also provide an example of evolution altering behavior by changing passive muscle and joint properties.7.Osteosarcoma is one of the most common malignant bone tumors. click here However, the treatment and clinical outcomes of osteosarcoma have hardly changed over the past three decades due to the comprehensive heterogeneity and higher rate of mutation of osteosarcoma. Recent studies have shown that STAT3 has the potential to suppress the proliferation and metastasis of osteosarcoma. In this study, a novel class of 2-amino-3-cyanothiophene derivatives were designed and synthesized to inhibit osteosarcoma by targeting STAT3. Representative compound 6f showed potent antiproliferative effects against osteosarcoma cells, directly bound to the STAT3 SH2 domain with a KD of 0.46 μM, and inhibited the phosphorylation of STAT3 Y705 in a dose-dependent manner. Furthermore, compound 6f promoted osteosarcoma cell apoptosis in vitro and significantly suppressed the growth and metastasis of osteosarcoma in vivo. These findings demonstrate that targeting STAT3 may be a feasible therapeutic strategy for the treatment of metastatic osteosarcoma.Hierarchically porous metal-organic frameworks (HP-MOFs) are a class of promising functional material with micropores, mesopores, and/or macropores, which can address the issue of slow mass transfer and less exposed active sites for primitive microporous MOFs. Despite many attempts that have been achieved through a variety of techniques to date, there is still a myriad of spaces that urgently need to be exploited. In this work, we report the novel synthesis of HP-MOFs via slow chemical steam etching. The preparation process can be subtly achieved using water vapor as an etchant; meanwhile, the addition of ethanol into the vapor atmosphere is carried out because it can stabilize the MOF framework well with its hydrophobic alkane tails, thereby slowing the etching rate toward MOFs, successfully realizing the controllable etching manner of MOF components. Furthermore, the joint influence of the water content and etching temperature on the MOF backbone structure etched has thus been investigated in detail. Impressively, we can harvest desired HP-MOFs with the retained crystalline structure at a water content of 50% and an etching temperature of 120 °C. The resulting HK-120/50 product etched exhibits excellent catalytic activity and stability in [2 + 3] cycloaddition of CO2 than pristine MOF, which can be attributed to the more exposure of active sites and the acceleration of mass transportation across the entire MOF skeleton. Noteworthy, the strategy proposed in this study may be extended to other HP-MOF construction systems due to the lability of most MOFs toward the chemical water vapor.

To assess the performance of two point (2-pt) Dixon-based chemical exchange saturation transfer (CEST) imaging for fat suppression in renal transplant patients.

The 2-pt Dixon-based CEST MRI was validated in an egg-phantom and in fourteen renal transplant recipients (5 females and 9 males; age range 23-78years; mean age 51±16.8). All CEST experiments were performed on a 3T clinical MRI scanner using a dual-echo CEST sequence. The 2-pt Dixon technique was applied to generate water-only CEST images at different frequency offsets, which were further used to calculate the z-spectra. The magnetization transfer ratio asymmetry (MTR

) values in the frequency ranges of hydroxyl, amine and amide protons were estimated in the renal cortex and medulla.

Results of the in vitro experiments suggest that the 2-pt Dixon technique enables effective fat peak removal and does not introduce additional asymmetries to the z-spectrum. Accordingly, our results in vivo show that the fat-corrected amide proton transfer (APT) effect in the kidney is significantly higher compared to that obtained from the CEST data acquired close to the in-phase condition both in the renal cortex (-0.1 [0.7] vs. -0.7 [1.2], P=0.029) and medulla (0.3 [0.8] vs. 0.01 [1.3], P=0.049), indicating that the 2-pt Dixon-based CEST method increases the specificity of the APT contrast by correcting the fat-induced artifacts.

Combination of the dual-echo CEST acquisition with Dixon post-processing provides effective water-fat separation, allowing more accurate quantification of the APT CEST effect in the transplanted kidney.

Combination of the dual-echo CEST acquisition with Dixon post-processing provides effective water-fat separation, allowing more accurate quantification of the APT CEST effect in the transplanted kidney.

Cannabis sativa L. is among numerous medicinal plants widely used in traditional medicine in treating various ailments including kidney diseases.

The protective effect of C. sativa on oxidative stress, cholinergic and purinergic dysfunctions, and dysregulated glucogenic activities were investigated in oxidative injured kidney (Vero) cell lines.

Fixed Vero cells were treated with sequential extracts (hexane, dichloromethane [DCM] and ethanol) of C. sativa leaves for 48h before subjecting to MTT assay. Vero cells were further incubated with FeSO

for 30min, following pretreatment with C. sativa extracts for 25min. Normal control consisted of Vero cells not treated with the extracts and/or FeSO

, while untreated (negative) control consisted of cells treated with only FeSO

.

MTT assay revealed the extracts were slightly cytotoxic at the highest concentrations (250μg/mL). There was a significant depletion in glutathione level and catalase activity on induction of oxidative stress, with significant elevation in malondialdehyde level, acetylcholinesterase, ATPase, ENTPDase, fructose-1,6-biphosphatase, glucose 6-phosphatase and glycogen phosphorylase activities. These activities and levels were significantly reversed following pretreatment with C. sativa extracts.

These results portray the protective potentials of C. sativa against iron-mediated oxidative renal injury as depicted by the ability of its extracts to mitigate redox imbalance and suppress acetylcholinestererase activity, while concomitantly modulating purinergic and glucogenic enzymes activities in Vero cells.

These results portray the protective potentials of C. sativa against iron-mediated oxidative renal injury as depicted by the ability of its extracts to mitigate redox imbalance and suppress acetylcholinestererase activity, while concomitantly modulating purinergic and glucogenic enzymes activities in Vero cells.Photocatalytic water splitting sustainably offers clean hydrogen energy, but it is challenging to produce low-cost photocatalysts that split water stoichiometrically into H2 and O2 without sacrificial agents under visible light. Here, we designed 17 two-dimensional (2D) covalent heptazine frameworks (CHFs) by topologically assembling heptazine and benzene-containing molecular units that provide active sites for hydrogen and oxygen evolution reactions, respectively. Among them, 12 CHFs have band gap values of less then 3.0 eV with band margins straddling the chemical reaction potential of H2/H+ and O2/H2O. In particular, a 2D H@DBTD CHF based on heptazine and 4,7-diphenyl-2,1,3-benzothiadiazole is a potential photocatalyst with a band gap of 2.47 eV for overall water splitting, which was confirmed with the calculated Gibbs free energy, non-adiabatic molecular dynamics, and preliminary experiment. This study presents an experimentally feasible molecular design of 2D CHFs as metal-free photocatalysts for overall water splitting under visible light.A new rhodamine-based probe 3,5-di-tert-butylsalicylaldehyde rhodamine hydrazone (RHTB) has been synthesized and well characterized using spectroscopic techniques and single-crystal X-ray crystallography. Among several metal ions, it selectively detects Cu2+ ions as monitored by UV-Vis and emission spectral titrations. It displays "turn on" behavior owing to the opening of a spirolactum ring and the presence of 3,5-di-tert-butyl as an electron releasing group. Further, Cu2+ ions play a pivotal role in extracellular aggregation of Aβ42 peptides. So far, we know probably that there are no promising drugs available in this regard. Hence, countering the Cu2+ ions by RHTB chelation against orally administered Cu2+ ion-induced neurotoxicity in the eye tissue of Drosophila expressing human Aβ42 (amyloid-β42) has been tested. The present study involves in vivo and in silico approaches. They reveal the therapeutic potential of RHTB against Cu2+ ion-induced Aβ42 toxicity in Alzheimer's disease (AD) model of Drosophila.Radiotherapy is an important treatment modality for glioblastoma (GBM), yet the initial effectiveness of radiotherapy is eventually lost due to the development of adaptive radioresistance during fractionated radiation therapy. Defining the molecular mechanism(s) responsible for the adaptive radioresistance in GBM is necessary for the development of effective treatment options. The cellular labile iron pool (LIP) is very important for determining the cellular response to radiation, as it contributes to radiation-induced production of reactive oxygen species (ROS) such as lipid radicals through Fenton reactions. Recently, cytochrome c oxidase (CcO), a mitochondrial heme-containing enzyme also involved in regulating ROS production, was found to be involved in GBM chemoresistance. However, the role of LIP and CcO in GBM radioresistance is not known. Herein, we tested the hypothesis that CcO-mediated alterations in the level of labile iron contribute to adaptive radioresistance. Using an in vitro model of GBM adaptive radioresistance, we found an increase in CcO activity in radioresistant cells that associated with a decrease in the cellular LIP, decrease in lipid peroxidation, and a switch in the CcO subunit 4 (COX4) isoform expressed, from COX4-2 to COX4-1.