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Li, W. J.

Publications and source records attributed to Li, W. J..

4 recordsLinked to original sources

In vivo Calcium Imaging in the Near-Infrared II Window

Non-invasive deep-tissue calcium imaging of live mammals with high sensitivity and resolution is challenging owing to light scattering experienced by traditional calcium ion (Ca2+) indicators with excitation and emission wavelengths within 400-750 nm. Here, we report near-infrared II (NIR-II) calcium imaging beyond 1000 nm by exploring a natural protein derived from a bacterium (Thermochromatium tepidum) living in a calcium carbonate-rich environment. This highly photostable fluorescent protein enables NIR-II imaging of intracellular Ca2+ responses to stimulant drugs in cultured mammalian cells with sensitivity comparable to that of visible Ca2+ indicators. We achieve in vivo NIR-II imaging of Ca2+ transients in response to two different tumor treatment strategies in intact tumors with high sensitivity, resolution, and contrast, opening the possibility of non-invasive deep-tissue calcium imaging for assessing treatment efficacy longitudinally. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/661443v2_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@149504eorg.highwire.dtl.DTLVardef@37722borg.highwire.dtl.DTLVardef@2878a7org.highwire.dtl.DTLVardef@1091d0c_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

STAT3 restricts prostate cancer metastasis and antiandrogen resistance by controlling LKB1/CREB signaling pathway

Prostate cancer (PCa) lethality is driven by its progression to a metastatic castration-resistant state, yet the signaling mechanisms underlying metastatic spread remain unknown. Here we show that STAT3 converges with the LKB1/mTORC1 and CREB to control metastatic disease in PCa mouse models. Unexpectedly, STAT3 was found to be upregulated in diabetic PCa patients undergoing metformin therapy with a concomitant reduction in mTORC1 expression. In preclinical mouse models of PCa, genetic ablation or activation of STAT3 had opposing effects on LKB1/AMPK/mTORC1- dependent tumorigenesis. Using genetic and pharmacological approaches, we identified LKB1 as a direct STAT3 target while repressing CREB. Furthermore, PCa patients with high CREB expression had inferior clinical outcome with significantly increased risk of disease and metastatic recurrence. We observe that castration state lowers STAT3 abundance and increases AR and CREB levels, leading to castration-resistant PCa (CRPC). Our findings revealed that STAT3 controls mTORC1 and CREB in metastatic disease, suggesting CREB as a promising target for lethal CRPC.

cancer biology↗

Wireless AI-Powered IoT Sensors for Laboratory Mice Behavior Recognition

According to the U.S. Department of Agriculture in 2018, there are more than 100 million animals used in research, education, and testing per year. Of the laboratory animals used for research, 95 percent are mice and rats as reported by the Foundation for Biomedical Research (FBR). We present here our work in developing wireless Artificial Intelligent (AI)-powered IoT Sensors (AIIS) for laboratory mice motion recognition utilizing embedded micro-inertial measurement units (uIMUs). Based on the AIIS, we have demonstrated a small-animal motion tracking and recognition system that could recognize 5 common behaviors of mice in cages with accuracy of ~76.23%. The key advantage of this AIIS-based system is to enable high throughput behavioral monitoring of multiple to a large group of laboratory animals, in contrast to traditional video tracking systems that usually track only single or a few animals at a time. The system collects motion data (i.e., three axes linear accelerations and three axes angular velocities) from the IoT sensors attached to different mice, and classifies these data into different behaviors using machine learning algorithms. One of the challenging problems for data analysis is that the distribution of behavior samples is extremely imbalanced. Behaviors such as sleeping and walking dominate the entire sample set from different mice. However, machine learning algorithms often require a balanced sample set to achieve optimal performance. Thus, several methods are proposed to solve the imbalanced sample problem. Data processing methods for data segmentation, feature extraction, feature selection, imbalanced learning, and machine learning are explored to process motion data including sleeping, walking, rearing, digging, shaking, grooming, drinking and scratching. For example, by tuning the parameters of a machine-learning algorithm (i.e., Support Vector Machine (SVM)), the average accuracy of classifying five behaviors (i.e., sleeping, walking, rearing, digging and shaking) is 48.07% before solving the imbalance sample issue. To address this problem, an iteration of sample and feature selection is applied to improve the SVM performance. A combination of oversampling and undersampling is used to handle imbalanced classes, and feature selection provides the optimal number of features. The accuracy increases from 48.07% to 76.23% when the optimized combination is used. We further obtained an average accuracy of 86.46% by removing shaking, which is proved to have a negative effect on the overall performance, out of these five behaviors. Furthermore, we were able to classify less frequent behaviors including rearing, digging, grooming, drinking and scratching at an average accuracy of 96.35%.

animal behavior and cognition↗

Optical Sectioning of Live Mammal with Near-Infrared Light Sheet

Deep-tissue three-dimensional optical imaging of live mammals in vivo with high spatiotemporal resolution in non-invasive manners has been challenging due to light scattering. Here, we developed near-infrared (NIR) light sheet microscopy (LSM) with optical excitation and emission wavelengths up to ~ 1320 nm and ~ 1700 nm respectively, far into the NIR-II (1000-1700 nm) region for 3D optical sectioning through live tissues. Suppressed scattering of both excitation and emission photons allowed one-photon optical sectioning at ~ 2 mm depth in highly scattering brain tissues. NIR-II LSM enabled non-invasive in vivo imaging of live mice, revealing never-before-seen dynamic processes such as highly abnormal tumor microcirculation, and 3D molecular imaging of an important immune checkpoint protein, programmed-death ligand 1 (PD-L1) receptors at the single cell scale in tumors. In vivo two-color near-infrared light sheet sectioning enabled simultaneous volumetric imaging of tumor vasculatures and PD-L1 proteins in live mammals.

bioengineering↗