Hsa_circ_0005576 promotes osimertinib resistance through the miR-512-5p/IGF1R axis in lung adenocarcinoma cells.

Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for lung adenocarcinoma (LUAD) harboring activating mutations, but patients ultimately develop acquired resistance. Circular RNAs are involved in EGFR-TKI resistance, while the role of hsa_circ_0005576 in the osimertinib resistance of LUAD remains unknown. In this study, we demonstrated that hsa_circ_0005576 could facilitate osimertinib-resistant LUAD cells. Briefly, knockdown of hsa_circ_0005576 not only suppressed the proliferation and promoted the apoptosis of resistant LUAD cells, but also increased their sensitivity to osimertinib. Mechanistically, hsa_circ_0005576, serving as an miRNA sponge, could directly interact with miR-512-5p and subsequently upregulate the miR-512-5p-targeted insulin-like growth factor 1 receptor. Rescue assays indicated that miR-512-5p inhibition could reverse the effects of hsa_circ_0005576 knockdown in LUAD cells resistant to osimertinib. Overall, our study revealed that hsa_circ_0005576 regulates proliferation and apoptosis through miR-512-5p/IGF1R signaling, which contributes further to the resistance of LUAD cells to osimertinib. In addition, this study provides a novel insight into the mechanisms underlying osimertinib resistance of LUAD.

Krüppel-like factor 4 promotes c-Met amplification-mediated gefitinib resistance in non-small-cell lung cancer.

Gefitinib has been widely used in the first-line treatment of advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9-14 months of treatment. This study revealed that Krüppel-like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c-Met-overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib-resistant NSCLC cell lines without c-Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib-resistant NSCLC cells with c-Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib-sensitive NSCLC cells. Furthermore, Western blot analysis revealed that KLF4 contributed to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells by inhibiting the expression of apoptosis-related proteins under gefitinib treatment and activating the c-Met/Akt signaling pathway by decreasing the inhibition of ß-catenin on phosphorylation of c-Met to prevent blockade by gefitinib. In summary, this study's results suggest that KLF4 is a promising candidate molecular target for both prevention and therapy of NSCLC with c-Met overexpression.

Graphene Dynamic Synapse with Modulatable Plasticity.

The synaptic activities in the nervous system is the basis of memory and learning behaviors, and the concept of biological synapse has also spurred the development of neuromorphic engineering. In recent years, the hardware implementation of the biological synapse has been achieved based on CMOS circuits, resistive switching memory, and field effect transistors with ionic dielectrics. However, the artificial synapse with regulatable plasticity has never been realized of the device level. Here, an artificial dynamic synapse based on twisted bilayer graphene is demonstrated with tunable plasticity. Due to the ambipolar conductance of graphene, both behaviors of the excitatory synapse and the inhibitory synapse could be realized in a single device. Moreover, the synaptic plasticity could also be modulated by tuning the carrier density of graphene. Because the artificial synapse here could be regulated and inverted via changing the bottom gate voltage, the whole process of synapse development could be imitated. Hence, this work would offer a broad new vista for the 2D material electronics and guide the innovation of neuro-electronics fundamentally.

Eugenol protects the transplanted heart against ischemia/reperfusion injury in rats by inhibiting the inflammatory response and apoptosis.

The aim of the present study was to investigate the protective effect of eugenol on the transplanted heart and explore its mechanisms of action. Male Sprague-Dawley rats were randomly divided into a sham group (n=10), a eugenol group (n=10 pairs, donors and recipients) and a control group (n=10 pairs, donors and recipients). The recipients in the eugenol group received an intraperitoneal injection of eugenol (20 mg/kg/day). The sham group and the control group received equal volumes of physiological saline by intraperitoneal injection. After 15 days the recipients in the control and eugenol groups underwent abdominal heterotopic heart transplantation, while the sham group received only a coeliotomy. The orthotopic hearts in the sham group and the heterotopic hearts in the eugenol and control groups, as well as the peripheral blood samples from all three groups were taken 3 h post operation for biochemical, histopathological, molecular and apoptosis analyses. Compared with the control group, the eugenol treatment significantly reduced the myocardial malondialdehyde content, serum cardiac troponin I, creatine kinase-MB, tumor necresis factor-α and interleukin-6 levels (P<0.05) and significantly alleviated myocardial injury. Western blot analysis demonstrated that the protein expression of cleaved Poly (ADP-ribose) polymerase 1, BAX and active caspase-3 in the eugenol group were significantly decreased, while B-cell lymphoma 2 expression was significantly increased compared with the control group (P<0.05). The myocardial apoptosis rate of the eugenol group was significantly decreased compared with the control group (P<0.05). In conclusion eugenol treatment significantly reduced myocardial injury and demonstrated protective effects for the transplanted heart.

A Flexible 360-Degree Thermal Sound Source Based on Laser Induced Graphene.

A flexible sound source is essential in a whole flexible system. It's hard to integrate a conventional sound source based on a piezoelectric part into a whole flexible system. Moreover, the sound pressure from the back side of a sound source is usually weaker than that from the front side. With the help of direct laser writing (DLW) technology, the fabrication of a flexible 360-degree thermal sound source becomes possible. A 650-nm low-power laser was used to reduce the graphene oxide (GO). The stripped laser induced graphene thermal sound source was then attached to the surface of a cylindrical bottle so that it could emit sound in a 360-degree direction. The sound pressure level and directivity of the sound source were tested, and the results were in good agreement with the theoretical results. Because of its 360-degree sound field, high flexibility, high efficiency, low cost, and good reliability, the 360-degree thermal acoustic sound source will be widely applied in consumer electronics, multi-media systems, and ultrasonic detection and imaging.

A point acoustic device based on aluminum nanowires.

A point Electrical Thermal Acoustic (ETA) device based on aluminum nanowire contacts is designed and fabricated. Interdigitated structural aluminum nanowires are released from the substrate by Inductively Coupled Plasma Reactive Ion Etching (ICP-RIE). By releasing the interdigitated structure, the nanowires contact each other at approximately 1 mm above the wafer, forming a Point Contact Structure (PCS). It is found that the PCS acoustic device realizes high efficiency when a biased AC signal is applied. The PCS acoustic device reaches a sound pressure level as high as 67 dB at a distance of 1 cm with 74 mW AC input. The power spectrum is flat, ranging from 2 kHz to 20 kHz with a less than ±3 dB fluctuation. The highest normalized Sound Pressure Level (SPL) of the point contact structure acoustic device is 18 dB higher than the suspended aluminum wire acoustic device. Comparisons between the PCS acoustic device and the Suspended Aluminum Nanowire (SAN) acoustic device illustrate that the PCS acoustic device has a flatter power spectrum within the 20 kHz range, and enhances the SPL at a lower frequency. Enhancing the response at lower frequencies is extremely useful, which may enable earphone and loudspeaker applications within the frequency range of the human ear with the help of pulse density modulation.

A graphene-based resistive pressure sensor with record-high sensitivity in a wide pressure range.

Pressure sensors are a key component in electronic skin (e-skin) sensing systems. Most reported resistive pressure sensors have a high sensitivity at low pressures (<5 kPa) to enable ultra-sensitive detection. However, the sensitivity drops significantly at high pressures (>5 kPa), which is inadequate for practical applications. For example, actions like a gentle touch and object manipulation have pressures below 10 kPa, and 10-100 kPa, respectively. Maintaining a high sensitivity in a wide pressure range is in great demand. Here, a flexible, wide range and ultra-sensitive resistive pressure sensor with a foam-like structure based on laser-scribed graphene (LSG) is demonstrated. Benefitting from the large spacing between graphene layers and the unique v-shaped microstructure of the LSG, the sensitivity of the pressure sensor is as high as 0.96 kPa(-1) in a wide pressure range (0 ~ 50 kPa). Considering both sensitivity and pressure sensing range, the pressure sensor developed in this work is the best among all reported pressure sensors to date. A model of the LSG pressure sensor is also established, which agrees well with the experimental results. This work indicates that laser scribed flexible graphene pressure sensors could be widely used for artificial e-skin, medical-sensing, bio-sensing and many other areas.

In Situ Tuning of Switching Window in a Gate-Controlled Bilayer Graphene-Electrode Resistive Memory Device.

A resistive random access memory (RRAM) device with a tunable switching window is demonstrated for the first time. The SET voltage can be continuously tuned from 0.27 to 4.5 V by electrical gating from -10 to +35 V. The gate-controlled bilayer graphene-electrode RRAM can function as 1D1R and potentially increase the RRAM density.

The construction of a hospital disease tracking and control system with a disease infection probability model.

With relatively short latency and rapid propagation, viral diseases could be transmitted through the air to medical personnel or the public during the incubation period. To reduce the possibilities of spread, this research creates an infection probability model based on the settling velocity and concentration distribution of infectious droplets. Then, radio frequency identification (RFID) technology is employed to track the travel history (time, date and place) of the infected patients. A tree structure algorithm and an infection probability model are applied to trace the transmission routes, discover the correlations between carriers and suspected cases, and finally calculate the infection probability on the basis of time interval. In case of an epidemic outbreak or once an infected case is confirmed, the disease tracking and control system could be initiated by accessing RFID logs to plot the carriers' time of onset and to trace possible routes of transmission via tree diagrams. The disease tracking and control system developed in this research can assist hospitals in assessing the risk of infection among medical personnel, as well as in prompt implementation of infection prevention and control measures, in order to reduce hospital acquired infections and provide a safe health care setting.