We designed and fabricated a novel microfluidic device that can be operated through simple finger squeezing. On-chip microfluidic flow control is enabled through an optimized network of check-valves and squeeze-pumps. The sophisticated flow system can be easily constructed by combining a few key elements. We implemented this device to perform quantitative biochemical assays with no requirement for precision instruments.

Microglia are the major cell type expressing complement C3a receptor (C3aR) in the brain. Using a knockin mouse line in which a Td-tomato reporter is incorporated into the endogenous C3ar1 locus, we identified 2 major subpopulations of microglia with differential C3aR expression. Expressing the Td-tomato reporter on the APP^NL-G-F–knockin (APP-KI) background revealed a significant shift of microglia to a high-C3aR-expressing subpopulation and they were enriched around amyloid β (Aβ) plaques. Transcriptomic analysis of C3aR-positive microglia documented dysfunctional metabolic signatures, including upregulation of hypoxia-inducible factor 1 (HIF-1) signaling and abnormal lipid metabolism in APP-KI mice compared with wild-type controls. Using primary microglial cultures, we found that C3ar1-null microglia had lower HIF-1α expression and were resistant to hypoxia mimetic–induced metabolic changes and lipid droplet accumulation. These were associated with improved receptor recycling and Aβ phagocytosis. Crossing C3ar1-knockout mice with the APP-KI mice showed that C3aR ablation rescued the dysregulated lipid profiles and improved microglial phagocytic and clustering abilities. These were associated with ameliorated Aβ pathology and restored synaptic and cognitive function. Our studies identify a heightened C3aR/HIF-1α signaling axis that influences microglial metabolic and lipid homeostasis in Alzheimer disease, suggesting that targeting this pathway may offer therapeutic benefit.

We report a novel method to fabricate high zoom-ratio optofluidic compound microlenses using poly(dimethylsiloxane) with multi-layer architecture. The layered structure of deformable lenses, biconvex and plano-concave, are self-aligned as a group. The refractive index contrast of each lens, which is controlled by filling the chambers with a specific medium, is the key factor for determining the device's numerical aperture. The chip has multiple independent pneumatic valves that can be digitally switched on and off, pushing the liquid into the lens chambers with great accuracy and consistency. This quickly and precisely tunes the focal length of the microlens device from centimetres to sub-millimetre. The system has great potential for applications in portable microscopic imaging, bio-sensing, and laser beam configuration.

Objective: This study aimed to investigate the feasibility of blood oxygen level‐dependent magnetic resonance imaging (BOLD‐MRI) to evaluate visceral adipose tissue (VAT) oxygenation in Zucker diabetic fatty (ZDF) rats and its associations with systemic metaflammation.Methods: Five‐week‐old ZDF rats and Zucker lean (ZL) rats were fed a high‐fat diet (HFD) for 18 weeks. A baseline BOLD‐MRI scan of perirenal adipose tissue was performed after 8 weeks of HFD feeding, and then the rats were randomized to receive pioglitazone or a vehicle for the following 10 weeks. At sacrifice, BOLD‐MRI scan, Hypoxyprobe‐1 injection, and circulating T helper 17 (Th17), regulatory T (Treg) cells, and monocyte subtype flow cytometry analysis were performed.Results: HFD feeding led to a significant increase in VAT BOLD‐MRI R2* signals (20.14 ± 0.23 per second vs. 21.53 ± 0.20 per second; P = 0.012), an indicator for decreased oxygenation. R2* signal was significantly correlated with VAT pimonidazole adduct‐positive area, insulin resistance, Th17 and Treg cells, CD43 + and CD43+ + monocyte subtypes, and VAT macrophage infiltration. Pioglitazone treatment improved the insulin resistance and was associated with a delayed progression of VAT oxygenation.Conclusions: This work demonstrated the feasibility of BOLD‐MRI for detecting the VAT oxygenation status in ZDF rats, and the BOLD‐MRI signals were associated with insulin resistance and systemic metaflammation in ZDF rats during the development of obesity.