Doughertybarr3425

For reversing the treatment failure in P-glycoprotein (P-gp)-associated MDR (multidrug resistance) of breast cancer, a high dose of Lapatinib (Lap), a substrate of breast cancer-resistant protein, was encapsulated into safe and effective acid-cleavable polysaccharide-doxorubicin (Dox) conjugates to form targeted HPP-Dox/Lap nanoparticles with an optimal drug ratio and appropriate nanosize decorated with oligomeric hyaluronic acid (HA) for specially targeting overexpressed CD44 receptors of MCF-7/ADR. The markedly increased cellular uptake and the strongest synergetic cytotoxicity revealed the enhanced reversal efficiency of HPP-Dox/Lap nanoparticles with reversal multiples at 29.83. This was also verified by the enhanced penetrating capacity in multicellular tumor spheroids. The reinforced Dox retention and substantial down-regulation of P-gp expression implied the possible mechanism of MDR reversal. Furthermore, the efficient ex vivo accumulation and distribution of nanoparticles in the tumor site and the high tumor growth inhibition (93%) even at a lower dosage (1 mg/kg) as well as lung metastasis inhibition in vivo with negligible side effects revealed the overwhelming advantages of targeted polysaccharide nanoparticles and Lap-sensitizing effect against drug-resistant tumor. The development of an efficient and nontoxic-targeted polysaccharide delivery system for reversing MDR by synergistic therapy might provide a potential clinical application value.Histidine tautomerism is considered a crucial component that affects the constitutional and accumulation characteristics of the tau267-312 monomer in the neutral condition, which are connected with the pathobiology of Alzheimer's disease (AD). Interpreting the organizational characteristics and accumulation procedure is a challenging task because two tautomeric conformations (the Nε-H or Nδ-H tautomer) can occur in the open neutral condition. In the current work, replica-exchange molecular dynamics (REMD) simulations were performed to investigate the structural properties of the tau267-312 monomer considering the histidine tautomeric effect. Based on the simulation outcomes, the histidine 268 (H268) (δ)-H299 (δ) (δδ) isomer had the highest β-sheet content with a value of 26.2%, which acquires a sheet-governing toxic conformer with the first abundant conformational state of 22.6%. In addition, δδ displayed notable antiparallel β-sheets between lysine 8 (K8)-asparagine 13 (N13) and valine 40 (V40)-tyrosine 44 (Y44) as well as between K32-H33 and V40-Y44 (β-meander supersecondary structure), indicating this tautomeric isomer may exist to stimulate tau oligomerization. Furthermore, H299 was found to play an essential role in the structural stabilization of the δδ isomer compared with H268. The present research will aid in obtaining insight into the organizational and accumulation properties of tau protein in the presence of histidine tautomerism to control AD.The absence of a high-performance p-channel oxide thin-film transistor (TFT) is the major challenge faced in the current oxide semiconductor device technology. Simple solution-based back-channel subgap defect termination using sulfur was developed for p-channel cuprous oxide (Cu2O)-TFTs. We investigated the origin of poor device characteristics in conventional Cu2O-TFTs and clarified that it was mainly because of a back-channel donor-like defect of ∼2.8 ×1013 cm-2 eV-1, which originated from the interstitial Cu defect. see more Sulfur ion treatment using thiourea effectively reduced the back-channel defect down to less then 3 × 1012 cm-2 eV-1 and demonstrated the Cu2O-TFT with a saturation mobility of 1.38 ± 0.7 cm2 V-1 s-1, a s-value of 2.35 ± 1.22 V decade-1, and an on/off current ratio of ∼4.1 × 106. The improvement of device characteristics was attributed to the reduction of back-channel defect by the formation of a thin CuSO4 back-channel passivation layer by the chemical reaction of interstitial Cu with S and O ions. An oxide-based complementary inverter using a p-channel Cu2O-TFT and a n-channel a-In-Ga-Zn-O-TFT was demonstrated with a high voltage gain of ∼230 at VDD = 70 V.With the depletion of nonrenewable resources and the increasingly serious "white pollution" caused by nondegradable plastics, using renewable biomass resources such as chitin to fabricate materials is a green and sustainable pathway. Herein, for the first time, we used N/O-doped carbon nanofibrous microspheres (CNMs) derived from renewable chitin as carriers to successfully construct a highly dispersed platinum nanocatalyst via a facile way. Various physicochemical characterizations provided reliable evidence for the ultrafine and well-dispersed platinum nanoparticles with an average diameter of 2.3 nm. As the supporting framework, the CNM with interconnected nanofibrous networks and a large surface area facilitated the adhesion and dispersion of Pt particles. Meanwhile, the inherent N/O-containing functional groups and the defects in carbonized chitin could anchor the platinum tightly. The CNM/Pt catalyst was further examined for hydrogenation, and it exhibited promising catalytic activity and stability (∼5 runs, 91%) and a broad applicability. This utilization of biomass resources to build catalyst materials would be important for the green and sustainable chemistry.Understanding the recovery of anaerobic ammonium-oxidizing (anammox) bacteria after inhibition by dissolved oxygen (DO) is critical for the successful applications of anammox-based processes. Therefore, the effects of oxygen exposure (2 mg L-1 DO for 90 min) and subsequent recovery treatments [N2 purging or nano zero-valent iron (nZVI) addition] on the activity and gene expression in a Kuenenia stuttgartiensis enrichment culture were examined. Combining the self-organizing map clustering and enrichment analysis, we proposed the oxidative stress response of anammox bacteria based on the existing concepts of oxidative stress in microbes the DO exposure triggered a stringent response in K. stuttgartiensis, which downregulated the transcription levels of genes involved in the central metabolism and diverted energy to a flagellar assembly and metal transport modules; these changes possibly promoted survival during the inhibition of anammox activity. According to the cotranscription with central catabolism genes, putative reactive oxygen species (ROS) scavenger genes (kat and sod) were presumed to detoxify the anammox intermediates rather than ROS.