Model-Based Feedback Control for an Automated Micro Liquid Dispensing System Based on Contacting Droplet Generation through Image Sensing.

Over the past few decades, micro liquid dispensing technology has been widely used in biology, chemistry, material and environmental sciences due to its efficacy in processing multiple samples. For practical applications, precise and effective droplet generation is very important. Despite numerous droplet generation methods, the implementation of droplet-on-demand still faces challenges concerning system complexity, precision, cost, and robustness. In this work, a novel on-demand contacting droplet generation method incorporated with model-based feedback control with an image processing unit as a sensor was proposed. By studying droplet identification using image processing techniques, the model of droplet formation was simplified. Then model-based feedback control was implemented using volumes of dispensed samples as sensing signals by tuning related parameters adaptively to resist disturbances. The proposed method was integrated and applied to a homebuilt automated micro liquid dispensing system with droplets ranging from 20 nanoliter to 200 nanoliter. The experimental results demonstrated a high degree of accuracy and precision. Additionally, the proposed system's practical utility was evaluated by analyzing mutations in genes associated with sensorineural hearing loss, verifying its effectiveness.

Nerve Injury-Induced γH2AX Reduction in Primary Sensory Neurons Is Involved in Neuropathic Pain Processing.

Phosphorylation of the serine 139 of the histone variant H2AX (γH2AX) is a DNA damage marker that regulates DNA damage response and various diseases. However, whether γH2AX is involved in neuropathic pain is still unclear. We found the expression of γH2AX and H2AX decreased in mice dorsal root ganglion (DRG) after spared nerve injury (SNI). Ataxia telangiectasia mutated (ATM), which promotes γH2AX, was also down-regulated in DRG after peripheral nerve injury. ATM inhibitor KU55933 decreased the level of γH2AX in ND7/23 cells. The intrathecal injection of KU55933 down-regulated DRG γH2AX expression and significantly induced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner. The inhibition of ATM by siRNA could also decrease the pain threshold. The inhibition of dephosphorylation of γH2AX by protein phosphatase 2A (PP2A) siRNA partially suppressed the down-regulation of γH2AX after SNI and relieved pain behavior. Further exploration of the mechanism revealed that inhibiting ATM by KU55933 up-regulated extracellular-signal regulated kinase (ERK) phosphorylation and down-regulated potassium ion channel genes, such as potassium voltage-gated channel subfamily Q member 2 (Kcnq2) and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in vivo, and KU559333 enhanced sensory neuron excitability in vitro. These preliminary findings imply that the down-regulation of γH2AX may contribute to neuropathic pain.

Intestinal microbiota in the treatment of metabolically associated fatty liver disease.

Metabolically associated fatty liver disease (MAFLD) is a common cause of chronic liver disease, the hepatic manifestation of metabolic syndrome. Despite the increasing incidence of MAFLD, no effective treatment is available. Recent research indicates a link between the intestinal microbiota and liver diseases such as MAFLD. The composition and characteristics of the intestinal microbiota and therapeutic perspectives of MAFLD are reviewed in the current study. An imbalance in the intestinal microbiota increases intestinal permeability and exposure of the liver to adipokines. Furthermore, we focused on reviewing the latest "gut-liver axis" targeted therapy.

Target Area Extraction Algorithm for the In Vivo Fluorescence Imaging of Small Animals.

Bio-optical imaging can noninvasively describe specific biochemical reaction events in small animals using endogenous or exogenous imaging reagents to label cells, proteins, or DNA. The fluorescence optical bio-imaging system excites the fluorescent group to a high energy state by excitation light and then generates emission light. However, many substances in the organism will also emit fluorescence after being excited by the excitation light, and the nonspecific fluorescence generated will affect the detection sensitivity. This paper designs and develops a set of high-level biosafety in vivo fluorescence imaging system for small animals suitable for virology research and proposes a target area extraction algorithm for fluorescence images. The fluorescence image target extraction algorithm first maps the nonlinear separation data in the low-dimensional space to the high-dimensional space. Then, based on the analysis of the characteristics of the fluorescent region, a method for discriminating the target fluorescent region based on the two-step entropy function is proposed, and the real target fluorescent region is obtained according to the set connected region. Based on the experiment of collecting and analyzing the in vivo fluorescent images of mice, it is verified that the proposed algorithm can automatically extract the target fluorescent region better than the classical linear model. It shows that the proposed algorithm is less affected by background fluorescence, and the estimated separated spectrum based on this method is closer to the real target spectrum.

pH-Triggered Drug Release of Monodispersed P(St-co-DMAEMA) Nanoparticles: Effects of Swelling, Polymer Chain Flexibility and Drug-Polymer Interactions.

Monodispersed pH-sensitive poly(styrene-co-N,N'-dimethylaminoethyl methacrylate) (P(St-co- DMAEMA)) nanoparticles (NPs) were synthesized by emulsion polymerization for use in potential applications in targeted drug delivery to the tumor microenvironment. pH-Sensitive volume swelling and drug release of the NPs with varied St/DMAEMA molar ratios, crosslinking degrees and model drug coumarin-6 loading were explored in vitro to elucidate the pH-sensitive drug release mechanisms. The swelling of the NPs, which accounts for the electrostatic repulsion of protonated tertiary amine groups under acidic conditions, reaches maximum at low pH, low crosslinking density and high DMAEMA content. The NPs undergo a pH-triggered drug release, and under the condition of pH 5 and pH 2, the average release rate during 24 h is 1.5-fold and 3-fold higher than that at physiological pH, respectively. The pH-triggered drug release is related to pH-sensitive swelling, polymer chain flexibility and drug-polymer interaction, and is significantly impacted by the St/DMAEMA molar ratio, degree of crosslinking and drug loading.

Synthesis and characterization of monodispersed P(St-co-DMAEMA) nanoparticles as pH-sensitive drug delivery system.

Monodispersed poly(styrene-co-N,N'-dimethylaminoethyl methacrylate) nanoparticles (P(St-co-DMAEMA) NPs) were synthesized by emulsion polymerization. Zeta potential, volume swelling ratio and in vitro release of fluorescer coumarin-6 from the NPs were determined in buffer of various pH. With an optimized formulation, the diameter of NPs is 100 nm approximately and the polydispersity index (PI) is less than 0.1. The NPs have a hydrophilic surface and alterable surface charge which is almost neutral at normal physiological pH, but becomes much more positive under acidic conditions. The volume swelling ratios and in vitro release of coumarin-6 are highly dependent on pH, which are significantly increased at the lower pH and higher DMAEMA/St molar ratio. More than 70% of the loaded coumarin-6 could be released in 24 h at pH2, which is 2.3-folds higher than that at normal physiological pH. The P(St-co-DMAEMA) NPs show promising applications to targeted drug delivery to tumors.