Decreased programmed cell death ligand 2-positive monocytic myeloid-derived suppressor cells and programmed cell death protein 1-positive T-regulatory cells in patients with type 2 diabetes: implications for immunopathogenesis

Objectives: The activation of immune cells plays a significant role in the progression of type 2 diabetes. This study aimed to investigate the potential role of myeloid-derived suppressor cells (MDSCs) and T-regulatory cells (Tregs) in type 2 diabetes. Methods: A total of 61 patients diagnosed with type 2 diabetes were recruited. Clinical characteristics were reviewed and peripheral blood samples were collected. We calculated the percentage of different cells. Frequencies of MDS C subsets refered to the percentage of G-MDSCs (CD15+CD33+CD11b+CD14-HLA-DR-/low) in CD45 positive cells and the percentage of M-MDSCs (CD14+CD15-CD11b+CD33+HLA-DR-/low) in lymphocytes plus monocytes. Results: Frequencies of programmed cell death ligand 1-positive granulo cytic MDSCs (PD-L1+ G-MDSCs), programmed cell death ligand 2-positive monocytic MDSCs (PD-L2+ M-MDSCs), PD-L2+ G-MDSC, and programmed cell death protein 1-positive Tregs (PD-1+Tregs) were decreased in patients with type 2 diabetes. The frequency of PD-1+ Tregs was positively related to PD-L2+ M-MDSCs (r = 0.357, P = 0.009) and negatively related to HbA1c (r = -0.265, P = 0.042), fasting insulin level (r = −0.260, P = 0.047), and waist circumference (r = −0.373, P = 0.005). Conclusions: Decreased PD-L2+ M-MDSCs and PD-1+ Tregs may promote effector T cell activation, leading to chronic low-grade inflammation in type 2 diabetes. These findings highlight the contribution of MDSCs and Tregs to the immunopathogenesis of type 2 diabetes and suggest their potential as targets for new therapeutic approaches

Self-assembly of size-controlled liposomes on DNA nanotemplates

Artificial lipid-bilayer membranes are valuable tools for the study of membrane structure and dynamics. For applications such as studying vesicular transport and drug delivery, there is a pressing need for artificial vesicles with controlled size. However, controlling vesicle size and shape with nanometer precision is challenging and approaches to achieve this can be heavily affected by lipid composition. Here we present a bio-inspired templating method to generate highly monodispersed sub-100nm unilamellar vesicles, where liposome self-assembly was nucleated and confined inside rigid DNA nanotemplates. Using this method we produced homogenous liposomes with four distinct pre-defined sizes. We also show that the method can be used with a variety of lipid compositions and probed the mechanism of the templated liposome formation by capturing key intermediates during membrane self-assembly. The DNA nanotemplating strategy represents a conceptually novel way to guide the lipid bilayer formation, and could be generalized to engineer complex membrane/protein structures with nanoscale precision

Effect of Tanshinone IIA on gut microbiome in diabetes-induced cognitive impairment

Diabetes-induced cognitive impairment (DCI) presents a major public health risk among the aging population. Previous clinical attempts on known therapeutic targets for DCI, such as depleted insulin secretion, insulin resistance, and hyperglycaemia have delivered poor patient outcomes. However, recent evidence has demonstrated that the gut microbiome plays an important role in DCI by modulating cognitive function through the gut–brain crosstalk. The bioactive compound tanshinone IIA (TAN) has shown to improve cognitive and memory function in diabetes mellitus models, though the pharmacological actions are not fully understood. This study aims to investigate the effect and underlying mechanism of TAN in attenuating DCI in relation to regulating the gut microbiome. Metagenomic sequencing analyses were performed on a group of control rats, rats with diabetes induced by a high-fat/high-glucose diet (HFD) and streptozotocin (STZ) (model group) and TAN-treated diabetic rats (TAN group). Cognitive and memory function were assessed by the Morris water maze test, histopathological assessment of brain tissues, and immunoblotting of neurological biomarkers. The fasting blood glucose (FBG) level was monitored throughout the experiments. The levels of serum lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunoassays to reflect the circulatory inflammation level. The morphology of the colon barrier was observed by histopathological staining. Our study confirmed that TAN reduced the FBG level and improved the cognitive and memory function against HFD- and STZ-induced diabetes. TAN protected the endothelial tight junction in the hippocampus and colon, regulated neuronal biomarkers, and lowered the serum levels of LPS and TNF-α. TAN corrected the reduced abundance of Bacteroidetes in diabetic rats. At the species level, TAN regulated the abundance of B. dorei, Lachnoclostridium sp. YL32 and Clostridiodes difficile. TAN modulated the lipid metabolism and biosynthesis of fatty acids in related pathways as the main functional components. TAN significantly restored the reduced levels of isobutyric acid and butyric acid. Our results supported the use of TAN as a promising therapeutic agent for DCI, in which the underlying mechanism may be associated with gut microbiome regulation

Effect of dendrobium mixture in alleviating diabetic cognitive impairment associated with regulating gut microbiota

Dendrobium mixture (DM) is a patent Chinese herbal formulation consisting of Dendrobii Caulis, Astragali Radix, Rehmanniae Radix as the main ingredients. DM has been shown to alleviate diabetic related symptoms attributed to its anti-hyperglycaemic and anti-inflammatory activities. However, the effect on diabetic induced cognitive dysfunction has not been investigated. This study aims to investigate the effect of DM in improving diabetic cognitive impairment and associated mechanisms. Our study confirmed the anti-hyperglycaemic effect of DM and showed its capacity to restore the cognitive and memory function in high fat/high glucose and streptozotocin-induced diabetic rats. The neuroprotective effect was manifested as improved learning and memory behaviours, restored blood-brain barrier tight junction, and enhanced expressions of neuronal survival related biomarkers. DM protected the colon tight junction, and effectively lowered the circulated proinflammatory mediators including tumour necrosis factor-α, interleukin-6 and lipopolysaccharides. In the gut microbiota, DM corrected the increase in the abundance of Firmicutes, the increase in the ratio of Firmicutes/Bacteroidetes, and the decrease in the abundance of Bacteroidetes in diabetic rats. It also reversed the abundance of Lactobacillus, Ruminococcus and Allobaculum genera. Short chain fatty acids, isobutyric acid and ethylmethylacetic acid, were negatively and significantly correlated to Ruminococcus and Allobaculum. Isovaleric acid was positively and significantly correlated with Lactobacillus, which all contributing to the improvement in glucose level, systemic inflammation and cognitive function in diabetic rats. Our results demonstrated the potential of DM as a promising therapeutic agent in treating diabetic cognitive impairment and the underlying mechanism may be associated with regulating gut microbiota

Protective effect of the curcumin-baicalein combination against macrovascular changes in diabetic angiopathy

Endothelial dysfunction is an early pathological event in diabetic angiopathy which is the most common complication of diabetes. This study aims to investigate individual and combined actions of Curcumin (Cur) and Baicalein (Bai) in protecting vascular function. The cellular protective effects of Cur, Bai and Cur+Bai (1:1, w/w) were tested in H2O2 (2.5 mM) impaired EA. hy926 cells. Wistar rats were treated with vehicle control as the control group, Goto-Kakizaki rats (n=5 each group) were treated with vehicle control (model group), Cur (150 mg/kg), Bai (150 mg/kg), or Cur+Bai (75 mg/kg Cur + 75 mg/kg Bai, OG) for 4 weeks after a four-week high-fat diet to investigate the changes on blood vessel against diabetic angiopathy. Our results showed that Cur+Bai synergistically restored the endothelial cell survival and exhibited greater effects on lowering the fasting blood glucose and blood lipids in rats comparing to individual compounds. Cur+Bai repaired the blood vessel structure in the aortic arch and mid thoracic aorta. The network pharmacology analysis showed that Nrf2 and MAPK/JNK kinase were highly relevant to the multi-targeted action of Cur+Bai which has been confirmed in the in vitro and in vivo studies. In conclusion, Cur+Bai demonstrated an enhanced activity in attenuating endothelial dysfunction against oxidative damage and effectively protected vascular function in diabetic angiopathy rats

Search for light dark matter from atmosphere in PandaX-4T

We report a search for light dark matter produced through the cascading decay of $\eta$ mesons, which are created as a result of inelastic collisions between cosmic rays and Earth's atmosphere. We introduce a new and general framework, publicly accessible, designed to address boosted dark matter specifically, with which a full and dedicated simulation including both elastic and quasi-elastic processes of Earth attenuation effect on the dark matter particles arriving at the detector is performed. In the PandaX-4T commissioning data of 0.63 tonne$\cdot$year exposure, no significant excess over background is observed. The first constraints on the interaction between light dark matter generated in the atmosphere and nucleus through a light scalar mediator are obtained. The lowest excluded cross-section is set at $5.9 \times 10^{-37}{\rm cm^2}$ for dark matter mass of $0.1$ MeV$/c^2$ and mediator mass of 300 MeV$/c^2$. The lowest upper limit of $\eta$ to dark matter decay branching ratio is $1.6 \times 10^{-7}$

A Search for Light Fermionic Dark Matter Absorption on Electrons in PandaX-4T

We report a search on a sub-MeV fermionic dark matter absorbed by electrons with an outgoing active neutrino using the 0.63 tonne-year exposure collected by PandaX-4T liquid xenon experiment. No significant signals are observed over the expected background. The data are interpreted into limits to the effective couplings between such dark matter and electrons. For axial-vector or vector interactions, our sensitivity is competitive in comparison to existing astrophysical bounds on the decay of such dark matter into photon final states. In particular, we present the first direct detection limits for an axial-vector (vector) interaction which are the strongest in the mass range from 25 to 45 (35 to 50) keV/c$^2$

Relating Charge Transport and Exchange Behaviors by Ligand Chemistry of Carbon Dots

The emergence of electrochemical energy storage technologies represents a significant milestone in the pursuit of sustainable energy solutions, offering a viable alternative to fossil fuels. This shift is driven by the urgent need to mitigate environmental impacts and maximize the efficiency of renewable energy systems. Central to this advancement is the development of storage systems with improved energy density (energy stored per unit volume or mass) and power density (rate of energy delivery), crucial for high-capacity applications. Notably, the transition from traditional lithium-ion batteries with organic electrolytes to aqueous battery systems, using water-based electrolytes, brings several advantages. Aqueous batteries are inherently safer, reducing the risk of thermal runaway, vital for large-scale applications like grid storage. They also have a reduced environmental footprint, aligning with sustainability goals, and offer cost-effectiveness due to the use of water-based electrolytes and potential for cheaper materials. Furthermore, aqueous batteries often exhibit superior electrochemical stability and faster ion transport, enhancing cycle life and rapid charging capabilities. Nonetheless, challenges persist, such as the narrow electrochemical stability window of water, which can limit operating voltage and energy density, necessitating innovative electrode and electrolyte design for performance enhancement.The goals of this dissertation have been to investigate some fundamental properties of carbon-based electrodes, specifically carbon nanodots in their chelating chemistry, to tune the electrochemical performance in aqueous energy storage systems. Chapter 2 discusses the role of graphene in enhancing supercapacitors, emphasizing its electrochemical and electrical attributes. Graphene's two-dimensional hexagonal lattice of sp2-hybridized carbon atoms, with exceptional thermal and electrical conductivity, enhances energy storage efficiency. Synthesis methods, including top-down and bottom-up approaches, are reviewed, along with the scalability of graphene production through Graphene Oxide (GO) and reduced Graphene Oxide (rGO). The chapter also explores Carbon Nanodots (CNDs) and Graphene Quantum Dots (GQDs) in energy storage. Chapter 3 focuses on using Carbon Nanodots (CNDs) and derivatives in capacitive energy storage. Strategies to increase their specific surface area and rate capability for high-performance conductive electrodes are discussed, including integrating conductive compounds and polymers. Synthesis methods of CNDs are evaluated, positioning them as components in advanced energy storage systems. Chapter 4 introduces a laser process to enhance sulfonyl compounds' performance in pseudocapacitive charge storage materials. Laser-converted carbon nanodots (CNDs) form conductive scaffolds with high surface areas, enabling efficient Faradaic processes. The resulting electrode exhibits remarkable capacitance and cycling stability, promising for advanced capacitive storage materials. Chapter 5 emphasizes electrode matching for filter electrochemical capacitors (FECs) in green electricity conversion. Effective matching improves capacitance, frequency response, voltage range, and longevity. Analytical methodologies are employed to design a durable filter electrochemical capacitors with exceptional performance metrics. Chapter 6 explores zinc-based batteries for grid-level energy storage. A novel functionalization process using ZnCND and H-ZnCND improves zinc anodes' stability, offering a safer and efficient energy storage solution. Chapter 7 addresses the rechargeability and cycling efficiency of zinc batteries by reengineering the solid-electrolyte interface (SEI) with ZF-rich fluorinated zinc-based SEI, enhancing its mechanical properties and ionic conductivity. This approach leads to dendrite-free zinc metal anodes and promising energy density