Vitamin K2 (VK2) is an effective compound for anti-ferroptosis and anti-osteoporosis, and Semen sojae praeparatum (Dandouchi in Chinese) is the main source of VK2. Chondrocyte ferroptosis and ...extracellular matrix (ECM) degradation playing a role in the pathogenesis of osteoarthritis (OA). Glutathione peroxidase 4 (GPX4) is the intersection of two mechanisms in regulating OA progression. But no studies have elucidated the therapeutic effects and mechanisms of VK2 on OA. This study utilized an in vivo rat OA model created via anterior cruciate ligament transection (ACLT) and an in vitro chondrocyte oxidative damage model induced by TBHP to investigate the protective effects and mechanisms of action of VK2 in OA. Knee joint pain in mice was evaluated using the Von Frey test. Micro-CT and Safranin O-Fast Green staining were employed to observe the extent of damage to the tibial cartilage and subchondral bone, while immunohistochemistry and PCR were used to examine GPX4 levels in joint cartilage. The effects of VK2 on rat chondrocyte viability were assessed using CCK-8 and flow cytometry assays, and chondrocyte morphology was observed with toluidine blue and alcian blue staining. The impact of VK2 on intracellular ferroptosis-related markers was observed using fluorescent staining and flow cytometry. Protein expression changes were detected by immunofluorescence and Western blot analysis. Furthermore, specific protein inhibitors were applied to confirm the dual-regulatory effects of VK2 on GPX4. VK2 can increase bone mass and cartilage thickness in the subchondral bone of the tibia, and reduce pain and the OARSI score induced by OA. Immunohistochemistry results indicate that VK2 exerts its anti-OA effects by regulating GPX4 to delay ECM degradation. VK2 can inhibit the activation of the MAPK/NFκB signaling pathway caused by reduced expression of intracellular GPX4, thereby decreasing ECM degradation. Additionally, VK2 can reverse the inhibitory effect of RSL3 on GPX4, increase intracellular GSH content and the GSH/GSSG ratio, reduce MDA content, and rescue chondrocyte ferroptosis. The protective mechanism of VK2 may involve its dual-target regulation of GPX4, reducing chondrocyte ferroptosis and inhibiting the MAPK/NFκB signaling pathway to decelerate the degradation of the chondrocyte extracellular matrix.
Dual representations of the Bertrand offset-surfaces are specified and several new results are gained in terms of their integral invariants. A new description of Bertrand offsets of developable ...surfaces is given. Furthermore, several relationships through the striction curves of Bertrand offsets of ruled surfaces and their integral invariants are obtained.
Autophagy is a conserved cellular self-digestion pathway for maintenance of homeostasis under basal and stressed conditions. Autophagy plays pivotal roles in the pathogenesis of many diseases, such ...as aging-related diseases, autoimmune diseases, cardiovascular diseases, and cancers. Of special note is that accumulating data suggest an intimate relationship between autophagy and ovarian carcinoma. Autophagy is well identified to act as either as a tumor-suppressor or as a tumor-promoter in ovarian carcinoma. The exact function of autophagy in ovarian carcinoma is highly dependent on the circumstances of cancer including hypoxic, nutrient-deficient, chemotherapy and so on. However, the mechanism underlying autophagy associated with ovarian carcinoma remains elusive, the precise role of autophagy in ovarian carcinoma also remains undetermined. In this review, we tried to sum up and discuss recent research achievements of autophagy in ovarian cancer. Moreover, waves of novel therapies ways for ovarian carcinoma based on the functions of autophagy were collected.
The metadevice with multiple functions in a fixed nanostructure is highly required. In this paper, we numerically achieved the dual functions of switchable broadband absorption and sensitive ...refractive index (RI) sensing in a fixed fishnet-shaped nanostructure by integrating with the phase change material vanadium dioxide (VO
2
). Exploiting the insulator-to-metal transition of VO
2
, the absorption strength could be dynamically switched from 0.07 to 0.97 in a broad terahertz (THz) band. Meanwhile, the same structure with metallic VO
2
exhibits highly sensitive RI sensing performance. The sensitivity reaches 1.15 THz/RIU, which makes great progress. The proposed metasurface with dual functions will promote the development and applications of THz nanodevices.
Androgen receptor (AR) activation and repression dual-functionality only became known recently and still remains intriguing in prostate cancer (PCa). MYC is a prominent oncogene that functionally ...entangles with AR signaling in PCa. Further exploration of AR regulatory mechanisms on MYC gene transcription bears clinical and translation significance.
Bioinformatics analysis of PCa cell line and clinical RNA-Seq and ChIP-Seq (chromatin immunoprecipitation-sequencing) datasets to anchor interactions of AR and MYC transcriptional networks. ChIP-qPCR and 3C (chromosome conformation capture) analyses to probe MYC distal regulation by AR binding sites (ABSs). CRISPR/Cas9-mediated genome-editing to specify functions of ABS within the 8q24-MYC locus on androgen-mediated MYC transcription. Global FoxA1 and HoxB13 distribution profiling to advance AR transcriptional mechanisms.
Here we recognize AR bi-directional transcription mechanisms by exploiting the prominent 8q24-MYC locus conferring androgen hyper-sensitivity. At ~ 25 Kb downstream of the MYC gene, we identified an undefined ABS, P10. By chromatin analyses, we validated androgen-dependent spatial interaction between P10 and MYC-Promoter (MYC-Pro) and temporal epigenetic repression of these MYC-proximal elements. We next designed a CRISPR/Cas9-mediated double genomic knock-out (KO) strategy to show that P10-KO slightly lessened androgen-elicited MYC transrepression in LNCaP-AR cells. In similar genomic editing assays, androgen-mediated MYC repression became slightly deepened upon KO of P11, an ABS in the PVT1 gene locus highly enriched in AR-binding motifs and peaks. We also investigated multiple ABSs in the established PCAT1 super-enhancer that distally interacts with MYC-Pro for transactivation, with each KO pool consistently shown to relieve androgen-elicited MYC repression. In the end, we systemically assessed androgen effects in the 8q24-MYC locus and along PCa genome to generalize H3K27ac and BRD4 re-distribution from pioneer factors (FoxA1 and HoxB13) to AR sites.
Together, we reconciled these observations by unifying AR dual-functions that are mechanistically coupled to and equilibrated by co-factor redistribution.
The indeterminacy of computation Fresco, Nir; Copeland, B. Jack; Wolf, Marty J.
Synthese (Dordrecht),
12/2021, Letnik:
199, Številka:
5-6
Journal Article
Recenzirano
Odprti dostop
Do the dynamics of a physical system determine what function the system computes? Except in special cases, the answer is no: it is often
indeterminate
what function a given physical system computes. ...Accordingly, care should be taken when the question ‘What does a particular neuronal system do?’ is answered by hypothesising that the system computes a
particular
function. The phenomenon of the indeterminacy of computation has important implications for the development of computational explanations of biological systems. Additionally, the phenomenon lends some support to the idea that a single neuronal structure may perform multiple cognitive functions, each subserved by a different computation. We provide an overarching conceptual framework in order to further the philosophical debate on the nature of computational indeterminacy and computational explanation.
In this paper we present a complete iteration complexity analysis of inexact first-order Lagrangian and penalty methods for solving cone-constrained convex problems that have or may not have optimal ...Lagrange multipliers that close the duality gap. We first assume the existence of optimal Lagrange multipliers and study primal-dual first-order methods based on inexact information and augmented Lagrangian smoothing or Nesterov-type smoothing. For inexact (fast) gradient augmented Lagrangian methods, we derive an overall computational complexity of
projections onto a simple primal set in order to attain an ε-optimal solution of the conic convex problem. For the inexact fast gradient method combined with Nesterov-type smoothing, we derive computational complexity
projections onto the same set. Then, we assume that optimal Lagrange multipliers might not exist for the cone-constrained convex problem, and analyse the fast gradient method for solving penalty reformulations of the problem. For the fast gradient method combined with penalty framework, we also derive an overall computational complexity of
projections onto a simple primal set to attain an ε-optimal solution for the original problem.
This paper derives the expressions for kinematic-geometry of lines with special trajectories in spatial kinematics by means of the E. Study map. A particular assurance goes to the 2nd order movement ...characteristics for extracting a new proof of the Disteli formulae of the axodes. Meanwhile, a new height dual function is defined and utilized to investigate the geometrical properties of the Disteli-axis. Consequently, as an implementation, the spatial equivalent of the cubic of stationary curvature is established and researched. Finally, Disteli formulae of a line-trajectory are extracted and inspected in detail.
● Dolomite-doped biochar/bentonite was synthesized for phosphate removal. ● DO/BB exhibited a high phosphate adsorption capacity in complex water environments. ● PVC membrane incorporated with DO/BB ...can capture low concentration phosphate. ● Electrostatic interaction, complexation and precipitation are main mechanisms.
The removal of phosphate from wastewater using traditional biological or precipitation methods is a huge challenge. The use of high-performance adsorbents has been shown to address this problem. In this study, a novel composite adsorbent, composed of dolomite-doped biochar and bentonite (DO/BB), was first synthesized via co-pyrolysis. The combination of initial phosphate concentration of 100 mg/L and 1.6 g/L of DO/BB exhibited a high phosphate-adsorption capacity of 62 mg/g with a removal efficiency of 99.8%. It was also stable in complex water environments with various levels of solution pH, coexisting anions, high salinity, and humic acid. With this new composite, the phosphate concentration of the actual domestic sewage decreased from 9 mg/L to less than 1 mg/L, and the total nitrogen and chemical oxygen demand also decreased effectively. Further, the cross-flow treatment using a PVC membrane loaded with DO/BB (PVC-DO/BB), decreased the phosphate concentration from 1 to 0.08 mg/L, suggesting outstanding separation of phosphate pollutants via a combination of adsorption and separation. In addition, the removal of phosphate by the PVC-DO/BB membrane using NaOH solution as an eluent was almost 90% after 5 cycles. The kinetic, isotherm and XPS analysis before and after adsorption suggested that adsorption via a combination of electrostatic interaction, complexation and precipitation contributed to the excellent separation by the as-obtained membranes.
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