Inhibiting NF-κB-S100A11 signaling and targeting S100A11 for anticancer effects of demethylzeylasteral in human colon cancer.

Colon cancer is a common and deadly malignancy of the gastrointestinal tract. Targeting proteins that inhibit tumor proliferation could lead to innovative treatment strategies for this disease. Demethylzeylasteral, extracted naturally from Tripterygium wilfordii Hook. f., demonstrates incredible anti-colon cancer activity. However, the molecular mechanism behind this requires further investigation. This study aims to identify crucial targets and mechanisms of demethylzeylasteral in treating colon cancer, making it a promising candidate for anti-tumor therapy. Through gene knockout, overexpression techniques, and double Luciferase experiments, we confirmed that demethylzeylasteral reduces S100A11 expression in HT29 cells and in vivo tumor models to anti-colon cancer. By conducting Surface Plasmon Resonance, immunofluorescence staining, and confocal laser microscopy observations, we verified the direct interaction between demethylzeylasteral and S100A11, and explored the impact of S100A11's subcellular localization on cell proliferation. Demethylzeylasteral inhibited S100A11 expression and exhibited anti-cancer activity in both in vitro and in vivo colon cancer models. Conversely, overexpression of S100A11 hindered apoptosis induced by demethylzeylasteral. Additionally, we found that knockdown or overexpression of NF-κB respectively decreased or increased S100A11 expression, subsequently affecting cell proliferation. The dual Luciferase reporting experiment revealed that NF-κB is an upstream transcription factor regulating S100A11 expression. And Surface plasmon resonance confirmed that S100A11 can directly interact with demethylzeylasteral, this interaction limited the transport of S100A11 from the cytoplasm to nucleus, attenuation S100A11 mediated cell proliferation effect.

Intermittent fasting alleviates type 1 diabetes-induced cognitive dysfunction by improving the frontal cortical metabolic disorder.

Intermittent fasting (IF) is an ecological strategy to control various metabolic disorder symptoms, but its protective effect on type 1 diabetes (T1D)-induced cognitive dysfunction and the underlying mechanisms remain poorly defined. Herein, we examined the efficacy of IF in altering the behaviors and brain metabolome in T1D mice and investigated the potential molecular mechanisms. We demonstrated that IF remarkably improved frontal cortical-dependent memory in T1D mice and reduced the loss of neuronal cells. Metabolomics and targeted mass spectrometry assays showed that IF reprogrammed the composition of the frontal cortical metabolome in T1D mice, including activating the aspartate and glutamate pathway and reversing glycerophospholipid and sphingolipid depositions. Mechanistically, IF attenuated the levels of oxidative stress proteins, like NOX2, NOX4, 8-OHdG, and 4-HNE, and inhibited the levels of pro-apoptotic factors Bax and cleaved Caspase-3, ultimately improving the memory ability of T1D mice. In vitro studies confirmed the protective effect of the supplemented N-acetylaspartate, a pivotal metabolite involved in IF-regulated T1D-induced cognitive dysfunction, in high glucose-stimulated SH-SY5Y cells by eliminating toxic lipids accumulation, oxidative stress, and apoptosis. To conclude, the frontal cortical metabolites mediated the protective effects of IF against T1D-induced cognitive dysfunction by attenuating oxidative stress and apoptotic signaling. Thus, IF can be a potential therapeutic strategy for T1D-induced cognitive dysfunction.

Tuning Plasmonic Enhancement of Single Nanocrystal Upconversion Luminescence by Varying Gold Nanorod Diameter.

Plasmonic enhancement induced by metallic nanostructures is an effective strategy to improve the upconversion efficiency of lanthanide-doped nanocrystals. It is demonstrated that plasmonic enhancement of the upconversion luminescence (UCL) of single NaYF4 :Yb3+ /Er3+ /Mn2+ nanocrystal can be tuned by tailoring scattering and absorption cross sections of gold nanorods, which is synthesized wet chemically. The assembly of the single gold nanorod and single upconversion nanocrystal is achieved by the atomic force microscope probe manipulation. By selecting two kinds of gold nanorods with similar longitudinal surface plasmon resonance wavelength but different diameters (27.3 and 46.7 nm), which extinction spectra are separately dominant by the absorption and scattering, the maximum UCL enhancement by a factor of 110 is achieved with the 46.7 nm-diameter gold nanorod, while it is 19 for the nanorod with the diameter of 27.3 nm. Such strong enhancement with the larger gold nanorod is due to stronger scattering ability and greater extent of the near-field enhancement. The enhanced UCL shows a strong dependence on the excitation polarization relative to the nanorod long axis. Time-resolved measurements and finite-difference time-domain simulations unveil that both excitation and emission processes of UCL are accelerated by the nanorod plasmonic effect.

Temporal and spatial multiplexed infrared single-photon counter based on high-speed avalanche photodiode.

We report on a high-speed temporal and spatial multiplexed single-photon counter with photon-number-resolving capability up to four photons. The infrared detector combines a fiber loop to split, delay and recombine optical pulses and a 200 MHz dual-channel single-photon detector based on InGaAs/InP avalanche photodiode. To fully characterize the photon-number-resolving capability, we perform quantum detector tomography and then reconstruct its positive-operator-valued measure and the associated Wigner functions. The result shows that, despite of the afterpulsing noise and limited system detection efficiency, this temporal and spatial multiplexed single-photon counter can already find applications for large repetition rate quantum information schemes.