CACNA2D3 Enhances the Chemosensitivity of Esophageal Squamous Cell Carcinoma to Cisplatin via Inducing Ca2+-Mediated Apoptosis and Suppressing PI3K/Akt Pathways

Resistance to platinum-based combination chemotherapy is the main cause of poor prognosis in patients with advanced esophageal squamous cell carcinoma (ESCC). Previously, we showed that CACNA2D3 (voltage-dependent subunit alpha 2 delta 3 of a calcium channel complex) was significantly downregulated and functioned as a tumor suppressor in ESCC, but its role in the chemosensitivity of ESCC to cisplatin remained unknown. Here, we found that the expression of CACNA2D3 was significantly associated with poor platinum response in ESCC patients from the Gene Expression Omnibus database. Overexpression of CACNA2D3 increased sensitivity to cisplatin in ESCC in vitro, whereas knockdown of CACNA2D3 increased cisplatin resistance. CACNA2D3 promoted cisplatin-induced apoptosis by modulating intracellular Ca2+ stores. In vivo experiments further showed that overexpression of CACNA2D3 enhanced cisplatin anti-tumor effects in a xenograft mouse model. CACNA2D3 overexpression also resulted in the attenuation of PI3K and Akt phosphorylation. Treatment with the PI3K/Akt inhibitor LY294002 restored the chemosensitivity of CACAN2D3-knockdown cells to cisplatin. In conclusion, the results of the current study indicate that CACAN2D3 enhances the chemosensitivity of ESCC to cisplatin via inducing Ca2+-mediated apoptosis and suppressing PI3K/Akt pathways. Therefore, regulating the expression of CACNA2D3 is a potential new strategy to increase the efficacy of cisplatin in ESCC patients

Neuromorphic Computing-Assisted Triboelectric Capacitive-Coupled Tactile Sensor Array for Wireless Mixed Reality Interaction.

Flexible tactile sensors show promise for artificial intelligence applications due to their biological adaptability and rapid signal perception. Triboelectric sensors enable active dynamic tactile sensing, while integrating static pressure sensing and real-time multichannel signal transmission is key for further development. Here, we propose an integrated structure combining a capacitive sensor for static spatiotemporal mapping and a triboelectric sensor for dynamic tactile recognition. A liquid metal-based flexible dual-mode triboelectric-capacitive-coupled tactile sensor (TCTS) array of 4 × 4 pixels achieves a spatial resolution of 7 mm, exhibiting a pressure detection limit of 0.8 Pa and a fast response of 6 ms. Furthermore, neuromorphic computing using the MXene-based synaptic transistor achieves 100% recognition accuracy of handwritten numbers/letters within 90 epochs based on dynamic triboelectric signals collected by the TCTS array, and cross-spatial information communication from the perceived multichannel tactile data is realized in the mixed reality space. The results illuminate considerable application possibilities of dual-mode tactile sensing technology in human-machine interfaces and advanced robotics

A Flexible and Highly Sensitive Inductive Pressure Sensor Array Based on Ferrite Films

There is a rapid growing demand for highly sensitive, easy adaptive and low-cost pressure sensing solutions in the fields of health monitoring, wearable electronics and home care. Here, we report a novel flexible inductive pressure sensor array with ultrahigh sensitivity and a simple construction, for large-area contact pressure measurements. In general, the device consists of three layers: a planar spiral inductor layer and ferrite film units attached on a polyethylene terephthalate (PET) membrane, which are separated by an array of elastic pillars. Importantly, by introducing the ferrite film with an excellent magnetic permeability, the effective permeability around the inductor is greatly influenced by the separation distance between the inductor and the ferrite film. As a result, the value of the inductance changes largely as the separation distance varies as an external load applies. Our device has achieved an ultrahigh sensitivity of 1.60 kPa−1 with a resolution of 13.61 Pa in the pressure range of 0−0.18 kPa, which is comparable to the current state-of-the-art flexible pressure sensors. More remarkably, our device shows an outstanding stability when exposed to environmental interferences, e.g., electrical noises from skin surfaces (within 0.08% variations) and a constant pressure load for more than 32 h (within 0.3% variations). In addition, the device exhibits a fast response time of 111 ms and a good repeatability under cyclic pressures varying from 38.45 to 177.82 Pa. To demonstrate its practical usage, we have successfully developed a 4 × 4 inductive pressure sensor array into a wearable keyboard for a smart electronic calendar application

Peripheral blood indicators and COVID-19: an observational and bidirectional Mendelian randomization study.

Acknowledgements: Not applicable.Blood is critical for health, supporting key functions like immunity and oxygen transport. While studies have found links between common blood clinical indicators and COVID-19, they cannot provide causal inference due to residual confounding and reverse causality. To identify indicators affecting COVID-19, we analyzed clinical data (n = 2,293, aged 18-65 years) from Guangzhou Medical University's first affiliated hospital (2022-present), identifying 34 significant indicators differentiating COVID-19 patients from healthy controls. Utilizing bidirectional Mendelian randomization analyses, integrating data from over 2.46 million participants from various large-scale studies, we established causal links for six blood indicators with COVID-19 risk, five of which is consistent with our observational findings. Specifically, elevated Troponin I and Platelet Distribution Width levels are linked with increased COVID-19 susceptibility, whereas higher Hematocrit, Hemoglobin, and Neutrophil counts confer a protective effect. Reverse MR analysis confirmed four blood biomarkers influenced by COVID-19, aligning with our observational data for three of them. Notably, COVID-19 exhibited a positive causal relationship with Troponin I (Tnl) and Serum Amyloid Protein A, while a negative association was observed with Plateletcrit. These findings may help identify high-risk individuals and provide further direction on the management of COVID-19

Sensitive Detection of Single-Cell Secreted H₂O₂ by Integrating a Microfluidic Droplet Sensor and Au Nanoclusters

As an important signaling molecule, hydrogen peroxide (H₂O₂) secreted externally by the cells influences cell migration, immunity generation, and cellular communications. Herein, we have developed a microfluidic approach with droplets in combination with Au nanoclusters for the sensitive detection of H₂O₂ secreted by a single cell. Isolated in the ultrasmall volume (4.2 nL) of a microdroplet, single-cell secreted H₂O₂ can initiate dramatic fluorescence changes of horseradish peroxidase–Au nanoclusters. We have demonstrated an ultrahigh sensitivity (200–400 attomole H₂O₂ directly measured from a single cell) with good specificity. It offers a useful research tool to study the cell-to-cell differences of H₂O₂ secretion at the single-cell level