M6A-mediated upregulation of lncRNA TUG1 in liver cancer cells regulates the antitumor response of CD8+ T cells and phagocytosis of macrophages.

Tumor immune evasion relies on the crosstalk between tumor cells and adaptive/innate immune cells. Immune checkpoints play critical roles in the crosstalk, and immune checkpoint inhibitors have achieved promising clinical effects. The long non-coding RNA taurine-upregulated gene 1 (TUG1) is upregulated in hepatocellular carcinoma (HCC). However, how TUG1 is upregulated and the effects on tumor immune evasion are incompletely understood. Here, METTL3-mediated m6A modification led to TUG1 upregulation is demonstrated. Knockdown of TUG1 inhibited tumor growth and metastasis, increased the infiltration of CD8+ T cells and M1-like macrophages in tumors, promoted the activation of CD8+ T cells through PD-L1, and improved the phagocytosis of macrophages through CD47. Mechanistically, TUG1 regulated PD-L1 and CD47 expressions by acting as a sponge of miR-141 and miR-340, respectively. Meanwhile, TUG1 interacted with YBX1 to facilitate the upregulation of PD-L1 and CD47 transcriptionally, which ultimately regulated tumor immune evasion. Clinically, TUG1 positively correlated with PD-L1 and CD47 in HCC tissues. Moreover, the combination of Tug1-siRNA therapy with a Pdl1 antibody effectively suppressed tumor growth. Therefore, the mechanism of TUG1 in regulating tumor immune evasion is revealed and can inform existing strategies targeting TUG1 for enhancing HCC immune therapy and drug development.

A bioinspired configurable cochlea based on memristors.

Cochleas are the basis for biology to process and recognize speech information, emulating which with electronic devices helps us construct high-efficient intelligent voice systems. Memristor provides novel physics for performing neuromorphic engineering beyond complementary metal-oxide-semiconductor technology. This work presents an artificial cochlea based on the shallen-key filter model configured with memristors, in which one filter emulates one channel. We first fabricate a memristor with the TiN/HfOx/TaOx/TiN structure to implement such a cochlea and demonstrate the non-volatile multilevel states through electrical operations. Then, we build the shallen-key filter circuit and experimentally demonstrate the frequency-selection function of cochlea's five channels, whose central frequency is determined by the memristor's resistance. To further demonstrate the feasibility of the cochlea for system applications, we use it to extract the speech signal features and then combine it with a convolutional neural network to recognize the Free Spoken Digit Dataset. The recognition accuracy reaches 92% with 64 channels, compatible with the traditional 64 Fourier transform transformation points of mel-frequency cepstral coefficients method with 95% recognition accuracy. This work provides a novel strategy for building cochleas, which has a great potential to conduct configurable, high-parallel, and high-efficient auditory systems for neuromorphic robots.

Ultra-High Performance Amorphous Ga2 O3 Photodetector Arrays for Solar-Blind Imaging.

The growing demand for scalable solar-blind image sensors with remarkable photosensitive properties has stimulated the research on more advanced solar-blind photodetector (SBPD) arrays. In this work, the authors demonstrate ultrahigh-performance metal-semiconductor-metal (MSM) SBPDs based on amorphous (a-) Ga2 O3 via a post-annealing process. The post-annealed MSM a-Ga2 O3 SBPDs exhibit superhigh sensitivity of 733 A/W and high response speed of 18 ms, giving a high gain-bandwidth product over 104 at 5 V. The SBPDs also show ultrahigh photo-to-dark current ratio of 3.9 × 107 . Additionally, the PDs demonstrate super-high specific detectivity of 3.9 × 1016 Jones owing to the extremely low noise down to 3.5 fW Hz-1/2 , suggesting high signal-to-noise ratio. Underlying mechanism for such superior photoelectric properties is revealed by Kelvin probe force microscopy and first principles calculation. Furthermore, for the first time, a large-scale, high-uniformity 32 × 32 image sensor array based on the post-annealed a-Ga2 O3 SBPDs is fabricated. Clear image of target object with high contrast can be obtained thanks to the high sensitivity and uniformity of the array. These results demonstrate the feasibility and practicality of the Ga2 O3 PDs for applications in solar-blind imaging, environmental monitoring, artificial intelligence and machine vision.

Impact of program/erase operation on the performances of oxide-based resistive switching memory.

Further performance improvement is necessary for resistive random access memory (RRAM) to realize its commercialization. In this work, a novel pulse operation method is proposed to improve the performance of RRAM based on Ti/HfO2/Pt structure. In the DC voltage sweep of the RRAM device, the SET transition is abrupt under positive bias. If current sweep with positive bias is utilized in SET process, the SET switching will become gradual, so SET is current controlled. In the negative voltage sweep for RESET process, the change of current with applied voltage is gradual, so RESET is voltage controlled. Current sweep SET and voltage sweep RESET shows better controllability on the parameter variation. Considering the SET/RESET characteristics in DC sweep, in the corresponding pulse operation, the width and height of the pulse series can be adjusted to control the SET and RESET process, respectively. Our new method is different from the traditional pulse operation in which both the width and height of program/erase pulse are simply kept constant which would lead to unnecessary damage to the device. In our new method, in each program or erase operation, a series of pulses with the width/height gradually increased are made use of to fully finish the SET/RESET switching but no excessive stress is generated at the same time, so width/height-controlled accurate SET/RESET can be achieved. Through the operation, the uniformity and endurance of the RRAM device has been significantly improved.

[Theoretical study of corresponding points for pain].

The theoretical basis of "corresponding points" originates from opposing needling, contralateral needling and distal needling in acupuncture. It is to select points in corresponding area that is distant from diseased re gion to balance yin and yang and to activate meridians. Acupuncture at corresponding points, through reflex regu- lation of nervous system. could activate protective inhibition of cerebral cortex and cutoff of local malignant stimu lation, leading to quick elimination of pain. In clinic, it is mostly used for pain-related diseases.

[Clinical observation of compound xiatianwu tablets in treatment of 120 cases with active rheumatoid arthritis].

OBJECTIVE: To observe the clinical efficacy of Compound Xiatianwu tablets in the treatment of active rheumatoid arthritis. METHOD: One hundred and eighty cases with active rheumatoid arthritis were randomly divided into the control group (60 cases) with leflunomide, sulfasalazine, and celecoxib; the treatment group (120 cases) given compound Xiatianwu tablets on the basis of the control group, 2 tablets each time, 3 times/day, with the course of treatment of 3 month. Patients of the two groups were observed for clinical symptoms, erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and immunoglobulin changes before and after the treatment. RESULT: The treatment group showed an overall efficiency of 94. 2% , the Xiatianwu group showed an overall efficiency of 80. 0%, while the control group showed an overall efficiency of 81.7%. The difference among the three groups was statistically significant (P <0. 05 or P <0. 01) , indicating that the treatment group was superior to the Xiatianwu group, while the Xiatianwu group was superior to the control group. CONCLUSION: Compound Xiatianwu tablets has remarkable effect in the treatment of active rheumatoid arthritis.

A study of cycling induced degradation mechanisms in Si nanocrystal memory devices.

The endurance of Si nanocrystal memory devices under Fowler-Nordheim program and erase (P/E) cycling is investigated. Both threshold voltage (V(th)) and subthreshold swing (SS) degradation are observed when using a high program or erase voltage. The change of SS is found to be proportional to the shift of V(th), indicating that the generation of interface traps plays a dominant role. The charge pumping and the mid-gap voltage methods have been used to analyze endurance degradation both qualitatively and quantitatively. It is concluded that high erase voltage causes severe threshold voltage degradation by generating more interface traps and trapped oxide charges.