1,25(OH)2D3 inhibits pancreatic stellate cells activation and promotes insulin secretion in T2DM.

PURPOSE: To evaluate the effect and mechanism of 1,25(OH)2D3 on pancreatic stellate cells (PSCs) in type 2 diabetes mellitus (T2DM). METHODS: A mouse model of T2DM was successfully established by high-fat diet (HFD) /streptozotocin (STZ) and administered 1,25(OH)2D3 for 3 weeks. Fasting blood glucose (FBG), glycated hemoglobin A1c (GHbA1c), insulin (INS) and glucose tolerance were measured. Histopathology changes and fibrosis of pancreas were examined by hematoxylin and eosin staining and Masson staining. Mouse PSCs were extracted, co-cultured with mouse insulinoma ß cells (MIN6 cells) and treated with 1,25(OH)2D3. ELISA detection of inflammatory factor expression. Tissue reactive oxygen species (ROS) levels were also measured. Immunofluorescence or Western blotting were used to measure fibrosis and inflammation-related protein expression. RESULTS: PSCs activation and islets fibrosis in T2DM mice. Elevated blood glucose was accompanied by significant increases in serum inflammatory cytokines and tissue ROS levels. 1,25(OH)2D3 attenuated islet fibrosis by reducing hyperglycemia, ROS levels, and inflammatory factors expression. Additionally, the co-culture system confirmed that 1,25(OH)2D3 inhibited PSCs activation, reduced the secretion of pro-inflammatory cytokines, down-regulated the expression of fibrosis and inflammation-related proteins, and promoted insulin secretion. CONCLUSION: Our findings identify that PSCs activation contributes to islet fibrosis and ß-cell dysfunction. 1,25(OH)2D3 exerts beneficial effects on T2DM potentially by inhibiting PSCs activation and inflammatory response, highlighting promising control strategies of T2DM by vitamin D.

A dual-gas sensor for simultaneous detection of methane and acetylene based on time-sharing scanning assisted wavelength modulation spectroscopy.

Methane (CH4) and acetylene (C2H2) are important bioscience and chemical gases. The real-time monitoring and analysis of them have important research value in industrial process control. The time-sharing scanning assisted wavelength modulation spectroscopy (WMS) technique is developed for real-time and simultaneous detection of CH4 and C2H2. This system involves two near-infrared distributed feedback (DFB) lasers and a compact multipass cavity with an effective optical path of 52.2 m. The selected strong absorption lines of methane and acetylene are located at 6046.96 cm-1 and 6531.7 cm-1, respectively. The experiment environment is conducted at room temperature 23 °C and pressure 760 Torr. The sensor performance, including the minimum detection limit (MDL) and the stability, was improved by eliminating the influence of light intensity fluctuation using the WMS-2f/SAW technique. Allan deviation analysis indicates that a MDL of 0.1 ppm for CH4 and 0.2 ppm for C2H2 are achieved with 1-s integration time. And the instrument response time is about 44 s through the continuous analysis of standard gases. This sensitive, simple, reliable, and lowcost dual-gas sensor is very suitable for applications in the field environment, chemical process, and many other gas-phase analysis areas.

Manganese-Based Nanoactivator Optimizes Cancer Immunotherapy via Enhancing Innate Immunity.

Cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) are essential components of the innate immune sensors to cytosolic DNA and elicit type I interferon (IFN). Recent studies have revealed that manganese (Mn) can enhance cGAS and STING activation to viral infection. However, the role of Mn in antitumor immunity has not been explored. Here, we designed a nanoactivator, which can induce the presence of DNA in cytoplasm and simultaneously elevate Mn2+ accumulation within tumor cells. In detail, amorphous porous manganese phosphate (APMP) NPs that are highly responsive to tumor microenvironment were employed to construct doxorubicin (DOX)-loaded and phospholipid (PL)-coated hybrid nanoparticles (PL/APMP-DOX NPs). PL/APMP-DOX NPs were stably maintained during systemic circulation, but triggered to release DOX for inducing DNA damage and Mn2+ to augment cGAS/STING activity. We found that PL/APMP-DOX NPs with superior tumor-targeting capacity boosted dendritic cell maturation and increased cytotoxic T lymphocyte infiltration as well as natural killer cell recruitment into the tumor site. Furthermore, the NPs increased production of type I IFN and secretion of pro-inflammatory cytokines (for example, TNF-α and IL-6). Consequently, PL/APMP-DOX NPs exhibited excellent antitumor efficacy and prolonged the lifespan of the tumor-bearing mice. Collectively, we developed a PL-decorated Mn-based hybrid nanoactivator to intensify immune activation and that might provide therapeutic potential for caner immunotherapy.