Deep-learning based flat-fielding quantitative phase contrast microscopy.

Quantitative phase contrast microscopy (QPCM) can realize high-quality imaging of sub-organelles inside live cells without fluorescence labeling, yet it requires at least three phase-shifted intensity images. Herein, we combine a novel convolutional neural network with QPCM to quantitatively obtain the phase distribution of a sample by only using two phase-shifted intensity images. Furthermore, we upgraded the QPCM setup by using a phase-type spatial light modulator (SLM) to record two phase-shifted intensity images in one shot, allowing for real-time quantitative phase imaging of moving samples or dynamic processes. The proposed technique was demonstrated by imaging the fine structures and fast dynamic behaviors of sub-organelles inside live COS7 cells and 3T3 cells, including mitochondria and lipid droplets, with a lateral spatial resolution of 245 nm and an imaging speed of 250 frames per second (FPS). We imagine that the proposed technique can provide an effective way for the high spatiotemporal resolution, high contrast, and label-free dynamic imaging of living cells.

Highly sensitive and wide-range iontronic pressure sensors with a wheat awn-like hierarchical structure.

Flexible pressure sensors with high sensitivity and wide sensing range are highly desired in e-skins and wearable electronics. However, there is always a trade-off between high sensitivity and broad sensing range for most flexible pressure sensors. Herein, an artificial wheat awn-like hierarchical structure is designed onto the dielectric layer of the iontronic pressure sensor, realizing both high sensitivity and broad working range. The sensor is constructed by sandwiching a wheat awn-like polyvinyl alcohol/H3PO4 dielectric layer between two transparent electrodes of silver nanowires/thermoplastic polyurethane/ionic liquid. The obtained sensor exhibits a high precision of 1 Pa, a high sensitivity of 47.65 kPa-1 (1-200 Pa), a wide measurement range from 1 Pa to 238 kPa, short response/recovery time of 13 ms/12 ms, outstanding stability over 6000 cycles, as well as good transparency. Considering these excellent properties, the sensor shows promising potential in health monitoring, human-computer interaction, wearable electronics, etc.

Novel Therapeutic Targeting of CCL3-CCR4 Axis Mediated Apoptotic Intesitnal Injury in Necrotizing Enterocolitis.

Background: Necrotizing enterocolitis (NEC) is the leading cause of neonatal gastrointestinal-related death, while the etiology and pathogenesis are poorly understood. Methods: The levels of CCL3 in intestinal tissue from modeling mice and patients were measured and analyzed. HE staining, TUNEL, Annexin and FCM were used to assess pathological changes and apoptosis in intestinal tissue and epithelial cells. CCL3, CCR4, cytokines, tight junction protein ZO-1, apoptosis-related genes and ERK1/2-NF-κB signaling pathway were detected by ELISA, Q-PCR, Western blotting and immunofluorescence. Results: CCL3 levels in the intestinal tissue significantly elevated in patients with NEC and mouse models. Blockade of CCL3 significantly alleviated NEC-related intestinal tissue damage, while administration of recombinant CCL3 aggravated intestinal injury by exacerbating intestinal epithelial cell apoptosis in NEC mice. Importantly, CCR4 blockade reversed CCL3-mediated damage to intestinal tissue and intestinal epithelial cell apoptosis both in vivo and in vitro. Further mechanistic studies showed that CCL3 regulated apoptosis-related BAX/BCL-2 expression through the activation of the ERK1/2 and NF-κB pathways, which could be reversed by anti-CCR4 treatment. Furthermore, ERK1/2 inhibition reduced CCL3-mediated phosphorylation of NF-κB in IEC-6 cells, while inhibition of NF-κB had no obvious effect on ERK1/2 phosphorylation. As expected, inhibition of NF-κB regulated BAX/BCL-2 expression and alleviated CCL3-induced epithelial cell apoptosis. These results indicate that high expression of CCL3 in NEC lesions promotes intestinal epithelial apoptosis through the CCL3-CCR4-ERK1/2-NFκB-BAX/BCL2 signalling axis, thereby exacerbating NEC-related intestinal injury. Conclusions: Our study represents an important conceptual advance that CCL3 may be one of the key culprits of intestinal tissue damage in NEC patients, and blocking either CCL3, CCR4, or NF-κB may represent a novel effective immunotherapy for NEC.