Biochemotaxis-Oriented Engineering Bacteria Expressing GLP-1 Enhance Diabetes Therapy by Regulating the Balance of Immune.

Glucagon like peptide-1 (GLP-1) is an effective hypoglycemic drug that can repair the pancreas ß cells and promote insulin secretion. However, GLP-1 has poor stability and lacks of target ability, which makes it difficult to reach the site of action to exert its efficacy. Here, GLP-1-expressing plasmids are introduced into the Escherichia coli Nissle 1917 (EcN) and a lipid membrane is formed through simple self-assembly on its surface, resulting in an oral delivery system (LEG) capable of resisting the harsh environment of the gastrointestinal tract. The system utilizes the chemotactic properties of probiotics to achieve efficient enrichment at the pancreatic site, and protects islet ß cells from destruction by regulating the balance of immune cells. More interestingly, LEG not only continuously produces GLP-1 to restore pancreatic islet ß cell function and secrete insulin to control blood sugar levels, but also regulates the intestinal flora and increases the richness and diversity of probiotics. In mice diabetes models, oral administration of LEG only once every other day has good biosafety and compliance, and achieves long-term control of blood glucose. Therefore, this strategy not only provides an oral delivery platform for pancreatic targeting, but also opens up new avenues for reversing diabetes.

Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment.

Type 2 diabetes mellitus (T2DM) therapy is facing the challenges of long-term medication and gradual destruction of pancreatic islet ß-cells. Therefore, it is timely to develop oral prolonged action formulations to improve compliance, while restoring ß-cells survival and function. Herein, we designed a simple nanoparticle with enhanced oral absorption and pancreas accumulation property, which combined apical sodium-dependent bile acid transporter-mediated intestinal uptake and lymphatic transportation. In this system, taurocholic acid (TCA) modified poly(lactic-co-glycolic acid) (PLGA) was employed to achieve pancreas location, hydroxychloroquine (HCQ) was loaded to execute therapeutic efficacy, and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) was introduced as stabilizer together with synergist (PLGA-TCA/DLPC/HCQ). In vitro and in vivo results have proven that PLGA-TCA/DLPC/HCQ reversed the pancreatic islets damage and dysfunction, thus impeding hyperglycemia progression and restoring systemic glucose homeostasis via only once administration every day. In terms of mechanism PLGA-TCA/DLPC/HCQ ameliorated oxidative stress, remodeled the inflammatory pancreas microenvironment, and activated PI3K/AKT signaling pathway without obvious toxicity. This strategy not only provides an oral delivery platform for increasing absorption and pancreas targetability but also opens a new avenue for thorough T2DM treatment.

Phosphorescent Carbon-Nanodots-Assisted Förster Resonant Energy Transfer for Achieving Red Afterglow in an Aqueous Solution.

Water-soluble red afterglow imaging agents based on ecofriendly nanomaterials have potential application in time-gated afterglow bioimaging due to their larger penetration depth and nondurable excitation. Herein, red afterglow imaging agents consisted of Rhodamine B (RhB) and carbon nanodots (CNDs) have been designed and demonstrated. In these agents, CNDs act as energy donors, and RhB acts as an energy acceptor. Both of them are confined into a hydrophilic silica shell to form a CNDs-RhB@silica nanocomposite. The phosphorescence emission spectrum of the CNDs and the absorption spectrum of the RhB match well, and efficient energy transfer from the CNDs to the RhB via Förster resonant energy transfer process can be achieved, with a transfer efficiency can reach 99.2%. Thus, the as-prepared nanocomposite can emit a red afterglow in aqueous solution, and the afterglow spectrum of CNDs-RhB@silica nanocomposite can extend to the first near-infrared window (NIR-I). The luminescence lifetime and afterglow quantum yield (QY) of the CNDs-RhB@silica can reach 0.91 s and 3.56%, respectively, which are the best results in red afterglow region. Time-gated in vivo afterglow imaging has been demonstrated by using the CNDs-RhB@silica as afterglow agents.

Application of a Fluid-Structure Interaction Model for Analysis of the Thermodynamic Process and Performance of Boil-Off Gas Compressors.

Boil-off gas (BOG) compressors are among the most critical devices in transportation and receiving systems for liquid natural gas (LNG) because they are used to pump out excess BOG from LNG storage tanks to ensure safety. Because of the ultralow suction temperature, the influence of heat transfer between the cold gas and the compressor parts on the in-cylinder thermodynamic process cannot be ignored. This paper reports the effects of suction temperature on the thermodynamic process and performance of a BOG compressor with consideration of gas pulsation. A computational fluid dynamics (CFD) model with dynamic and sliding meshes was established, in which user-defined functions (UDFs) were used to calculate the real-time valve lift to realize coupling between the thermodynamic process and the gas pulsation, and a performance test rig was constructed to verify the proposed numerical model. The simulated results agreed well with the experimental ones. The results show that as the suction temperature decreased from 30 °C to -150 °C, the first-stage volumetric efficiency decreased to 0.69, and the preheating increased to 45.8 °C. These results should provide academic guidance and an experimental basis for the design and optimization of BOG compressors.

Adenoviral vectors with E1A regulated by tumor-specific promoters are selectively cytolytic for breast cancer and melanoma.

We have previously demonstrated that a truncated form of the L-plastin promoter can confer tumor-specific patterns of expression on replication-incompetent adenoviral vector reporter and therapeutic transcription units. In this report, a 2.5-kb truncated version of the L-plastin promoter was placed 5' to the E1A gene of a wild-type adenovirus. The vector generated (Ad-Lp-E1A) was directly cytotoxic to established breast and ovarian cancer cell lines and to primary explant cultures derived from ovarian cancer, but was not cytotoxic to explant cultures of normal mammary epithelial cells. This vector was not cytotoxic to cell lines in which the L-plastin E1A transcription unit was not expressed, whereas the same cell lines were sensitive to the cytotoxic effect of a replication-competent adenoviral vector in which the cytomegalovirus (CMV) promoter drove E1A expression. When the tyrosinase promoter/enhancer was placed 5' to the E1A gene in the adenoviral backbone, the resulting vector (Ad-Tyr-E1A) was selectively toxic to melanoma cells and one percent as toxic to explants of ovarian cancer cells as the Ad-Lp-E1A vector. Injection of these vectors (Ad-Lp-E1A and Ad-Tyr-E1A) into nodules derived from the MCF-7 and MDA-MB-468 human breast cancer cell lines and the TF-2 human melanoma cell line, respectively, which were growing subcutaneously in severe combined immunodeficiency (SCID) mice, induced regression of these tumors. Such vectors may therefore be useful in cancer treatment.