Enhanced Interstitial Fluid Extraction and Rapid Analysis via Vacuum Tube-Integrated Microneedle Array Device.

Advancing the development of point-of-care testing (POCT) sensors that utilize interstitial fluid (ISF) presents considerable obstacles in terms of rapid sampling and analysis. Herein, an innovative strategy is introduced that involves the use of a 3D-printed, hollow microneedle array patch (MAP), in tandem with a vacuum tube (VT) connected through a hose, to improve ISF extraction efficiency and facilitate expedited analysis. The employment of negative pressure by the VT allows the MAP device to effectively gather ≈18 µL of ISF from the dermis of a live rabbit ear within a concise period of 5 min. This methodology enables the immediate and minimally invasive measurement of glucose levels within the body, employing personal healthcare meters for quantification. The fusion of the VT and MAP technologies provides for their effortless integration into a comprehensive and mobile system for ISF analysis, accomplished by preloading the hose with custom sensing papers designed to detect specific analytes. Moreover, the design and functionality of this integrated VT-MAP system are intuitively user-friendly, eliminating the requirement for specialized medical expertise. This feature enhances its potential to make a significant impact on the field of decentralized personal healthcare.

Cholinergic anti-inflammatory pathway mediates diesel exhaust PM2.5-induced pulmonary and systemic inflammation.

Previous research has indicated that the cholinergic anti-inflammatory pathway (CAP) can regulate the duration and intensity of inflammatory responses. A wide range of research has demonstrated that PM2.5 exposure may induce various negative health effects via pulmonary and systemic inflammations. To study the potential role of the CAP in mediating PM2.5-induced effects, mice were treated with vagus nerve electrical stimulation (VNS) to activate the CAP before diesel exhaust PM2.5 (DEP) instillation. Analysis of pulmonary and systemic inflammations in mice demonstrated that VNS significantly reduced the inflammatory responses triggered by DEP. Meanwhile, inhibition of the CAP by vagotomy aggravated DEP-induced pulmonary inflammation. The flow cytometry results showed that DEP influenced the CAP by altering the Th cell balance and macrophage polarization in spleen, and in vitro cell co-culture experiments indicated that this DEP-induced change on macrophage polarization may act via the splenic CD4+ T cells. To further confirm the effect of alpha7 nicotinic acetylcholine receptor (α7nAChR) in this pathway, mice were then treated with α7nAChR inhibitor (α-BGT) or agonist (PNU282987). Our results demonstrated that specific activation of α7nAChR with PNU282987 effectively alleviated DEP-induced pulmonary inflammation, while specific inhibition of α7nAChR with α-BGT exacerbated the inflammatory markers. The present study suggests that PM2.5 have an impact on the CAP, and CAP may play a critical function in mediating PM2.5 exposure-induced inflammatory response. AVAILABILITY OF DATA AND MATERIALS: The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

Impacts of physical activity and particulate air pollution on the onset, progression and mortality for the comorbidity of type 2 diabetes and mood disorders.

OBJECTIVE: The co-occurrence of type 2 diabetes (T2D) and mood disorders (depression or anxiety) is an exceedingly common comorbidity with poor prognosis. We aimed to explore the effects of physical activity (PA), fine particulate matter (PM2.5) air pollution or their interactions on the initiation, progression and subsequent mortality of this comorbidity. METHODS: The prospective analysis was based on 336,545 participants in UK Biobank. Multi-state models were applied to capture potential impacts in all transition phases simultaneously along the natural history of the comorbidity. RESULTS: PA [walking (4th vs 1st quantile), moderate (4th vs 1st quantile) and vigorous activities (yes vs no)] protected against incident T2D and comorbid mood disorders afterwards, incident mood disorders, and all-cause mortality from baseline health and T2D, with the risk reductions ranging from 9 % to 23 %. Moderate and vigorous activities further prevented T2D development or mortality among depressive/anxious population. PM2.5 was associated with higher risks of developing incident mood disorders [Hazard ratio (HR) per interquartile range increase = 1.03], as well as of developing incident T2D (HR = 1.04) and further transition to comorbid mood disorders (HR = 1.10). The impacts of PA and PM2.5 were stronger during transitions to comorbidities than the occurrence of first diseases. The benefits of PA remained across all PM2.5 levels. CONCLUSIONS: Physical inactivity and PM2.5 could accelerate the initiation and progression of the comorbidity of T2D and mood disorders. PA and reducing pollution exposure may be included in health promotion strategies to decrease the comorbidity burden.

Maternal exposure to ambient PM2.5 perturbs the metabolic homeostasis of maternal serum and placenta in mice.

Epidemiological and animal studies have shown that maternal fine particulate matters (PM2.5) exposure correlates with various adverse pregnancy outcomes such as low birth weight (LBW) of offspring. However, the underlying biological mechanisms have not been fully understood. In this study, female C57Bl/6 J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during pregestational and gestational periods, and metabolomics was performed to analyze the metabolic features in maternal serum and placenta by liquid chromatography-mass spectrometry (LC-MS). The partial least squares discriminate analysis (PLS-DA) displayed evident clustering of FA- and CAP-exposed samples for both maternal serum and placenta. In addition, pathway analysis identified that vitamin digestion and absorption was perturbed in maternal serum, while metabolic pathways including arachidonic acid metabolism, serotonergic synapse, 2-oxocarboxylic acid metabolism and cAMP signaling pathway were perturbed in placenta. Further analysis indicated that CAP exposure influenced the nutrient transportation capacity of placenta, by not only changing the ratios of some critical metabolites in placenta to maternal serum but also significantly altering the expressions of nutrition transporters in placenta. These findings reaffirm the importance of protecting women from PM2.5 exposure, and also advance our understanding of the toxic actions of ambient PM2.5.

Visual cortex encodes timing information in humans and mice.

Despite the importance of timing in our daily lives, our understanding of how the human brain mediates second-scale time perception is limited. Here, we combined intracranial stereoelectroencephalography (SEEG) recordings in epileptic patients and circuit dissection in mice to show that visual cortex (VC) encodes timing information. We first asked human participants to perform an interval-timing task and found VC to be a key timing brain area. We then conducted optogenetic experiments in mice and showed that VC plays an important role in the interval-timing behavior. We further found that VC neurons fired in a time-keeping sequential manner and exhibited increased excitability in a timed manner. Finally, we used a computational model to illustrate a self-correcting learning process that generates interval-timed activities with scalar-timing property. Our work reveals how localized oscillations in VC occurring in the seconds to deca-seconds range relate timing information from the external world to guide behavior.

Behavioral mimicry of eating in mice.

Nonconscious behavioral mimicry is prevalent in humans and highly social animals who imitate the behaviors of others without awareness. Previous studies indicated people tended to match their amount of eating to that of their eating companions due to behavioral mimicry, however whether such phenomena were existed in rodents is still unknown. Developing a behavioral paradigm would be helpful to better understand the molecular and circuit mechanisms underlying behavioral mimicry. In this study, we examined behavioral mimicry of eating in C57BL/6J mice which had strong sociality and were widely used as animal model in researches. We set up an eating monitoring platform, and this platform could record the data of mice eating behavior in real time. We further examined the behavioral mimicry of eating in mice, and found that the mice observing eating behavior of food-restricted mice would consume more food than control mice, and visual cue with eating behavior was sufficient to increased food consumption in mice. Our study indicated behavioral mimicry of eating was existed in mice and provided a mouse model for future studies on the mechanism of behavioral mimicry of eating.

A shape-memory and spiral light-emitting device for precise multisite stimulation of nerve bundles.

We previously demonstrated that for long-term spastic limb paralysis, transferring the seventh cervical nerve (C7) from the nonparalyzed side to the paralyzed side results in increase of 17.7 in Fugl-Meyer score. One strategy for further improvement in voluntary arm movement is selective activation of five target muscles innervated by C7 during recovery process. In this study, we develop an implantable multisite optogenetic stimulation device (MOSD) based on shape-memory polymer. Two-site stimulation of sciatic nerve bundles by MOSD induces precise extension or flexion movements of the ankle joint, while eight-site stimulation of C7 nerve bundles induce selective limb movement. Long-term implant of MOSD to mice with severed and anastomosed C7 nerve is proven to be both safe and effective. Our work opens up the possibility for multisite nerve bundle stimulation to induce highly-selective activations of limb muscles, which could inspire further applications in neurosurgery and neuroscience research.