Moracin D suppresses cell growth and induces apoptosis via targeting the XIAP/PARP1 axis in pancreatic cancer.

BACKGROUND: Pancreatic cancer, a tumor with a high metastasis rate and poor prognosis, is among the deadliest human malignancies. Investigating effective drugs for their treatment is imperative. Moracin D, a natural benzofuran compound isolated from Morus alba L., shows anti-inflammation and anti-breast cancer properties and is effective against Alzheimer's disease. However, the effect and mechanism of Moracin D action in pancreatic cancer remain obscure. PURPOSE: To investigate the function and molecular mechanism of Moracin D action in repressing the malignant progression of pancreatic cancer. METHODS: Pancreatic cancer cells were treated with Moracin D, and cell proliferation was evaluated by cell counting kit-8 (CCK-8) and immunofluorescence assays. The clonogenicity of pancreatic cancer cells was assessed based on plate colony formation and soft agar assay. Flow cytometry was used to detect cell apoptosis. The expression of proteins related to the apoptosis pathway was determined by Western blot analysis. Moracin D and XIAP were subjected to docking by auto-dock molecular docking analysis. Ubiquitination levels of XIAP and the interaction of XIAP and PARP1 were assessed by co-immunoprecipitation analysis. Moracin D's effects on tumorigenicity were assessed by a tumor xenograft assay. RESULTS: Moracin D inhibited cell proliferation, induced cell apoptosis, and regulated the protein expression of molecules involved in caspase-dependent apoptosis pathways. Moracin D suppressed clonogenicity and tumorigenesis of pancreatic cancer cells. Mechanistically, XIAP could interact with PARP1 and stabilize PARP1 by controlling its ubiquitination levels. Moracin D diminished the stability of XIAP and decreased the expression of XIAP by promoting proteasome-dependent XIAP degradation, further blocking the XIAP/PARP1 axis and repressing the progression of pancreatic cancer. Moracin D could dramatically improve the chemosensitivity of gemcitabine in pancreatic cancer cells. CONCLUSION: Moracin D repressed cell growth and tumorigenesis, induced cell apoptosis, and enhanced the chemosensitivity of gemcitabine through the XIAP/PARP1 axis in pancreatic cancer. Moracin D is a potential therapeutic agent or adjuvant for pancreatic cancer.

AKIP1 accelerates glioblastoma progression through stabilizing EGFR expression.

A Kinase Interacting Protein 1 (AKIP1) is found to be overexpressed in a variety of human cancers and associated with patients' worse prognosis. Several studies have established AKIP1's malignant functions in tumor metastasis, angiogenesis, and chemoradiotherapy resistance. However, the mechanism of AKIP1 involved in accelerating glioblastoma (GBM) progression remains unknown. Here, we showed that the expression of AKIP1 was positively correlated with the glioma pathological grades. Down-regulating AKIP1 greatly impaired the proliferation, colony formation, and tumorigenicity of GBM cells. In terms of the mechanism, AKIP1 cooperates with transcriptional factor Yin Yang 1 (YY1)-mediated Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1) transcriptional activation, enhancing the stability of Epidermal Growth Factor Receptor (EGFR). YY1 was identified as a potential transcriptional factor of HSP90AA1 and directly interacts with AKIP1. The overexpression of HSP90α significantly reversed AKIP1 depletion incurred EGFR instability and the blocked cell proliferation. Moreover, we further investigated the interacted pattern between EGFR and HSP90α. These findings established that AKIP1 acted as a critical oncogenic factor in GBM and uncovered a novel regulatory mechanism in EGFR aberrant expression.

MicroRNAs reshape the immunity of insects in response to bacterial infection.

The interaction between bacteria and insects can significantly impact a wide range of different areas because bacteria and insects are widely distributed around the globe. The bacterial-insect interactions have the potential to directly affect human health since insects are vectors for disease transmission, and their interactions can also have economic consequences. In addition, they have been linked to high mortality rates in economically important insects, resulting in substantial economic losses. MicroRNAs (miRNAs) are types of non-coding RNAs involved in regulating gene expression post-transcriptionally. The length of miRNAs ranges from 19 to 22 nucleotides. MiRNAs, in addition to their ability to exhibit dynamic expression patterns, have a diverse range of targets. This enables them to govern various physiological activities in insects, like innate immune responses. Increasing evidence suggests that miRNAs have a crucial biological role in bacterial infection by influencing immune responses and other mechanisms for resistance. This review focuses on some of the most recent and exciting discoveries made in recent years, including the correlation between the dysregulation of miRNA expression in the context of bacterial infection and the progression of the infection. Furthermore, it describes how they profoundly impact the immune responses of the host by targeting the Toll, IMD, and JNK signaling pathways. It also emphasizes the biological function of miRNAs in regulating immune responses in insects. Finally, it also discusses current knowledge gaps about the function of miRNAs in insect immunity, in addition to areas that require more research in the future.

Neuromorphic-computing-based adaptive learning using ion dynamics in flexible energy storage devices.

High-accuracy neuromorphic devices with adaptive weight adjustment are crucial for high-performance computing. However, limited studies have been conducted on achieving selective and linear synaptic weight updates without changing electrical pulses. Herein, we propose high-accuracy and self-adaptive artificial synapses based on tunable and flexible MXene energy storage devices. These synapses can be adjusted adaptively depending on the stored weight value to mitigate time and energy loss resulting from recalculation. The resistance can be used to effectively regulate the accumulation and dissipation of ions in single devices, without changing the external pulse stimulation or preprogramming, to ensure selective and linear synaptic weight updates. The feasibility of the proposed neural network based on the synapses of flexible energy devices was investigated through training and machine learning. The results indicated that the device achieved a recognition accuracy of ∼95% for various neural network calculation tasks such as numeric classification.

Dual sensing signal decoupling based on tellurium anisotropy for VR interaction and neuro-reflex system application.

Anisotropy control of the electronic structure in inorganic semiconductors is an important step in developing devices endowed with multi-function. Here, we demonstrate that the intrinsic anisotropy of tellurium nanowires can be used to modulate the electronic structure and piezoelectric polarization and decouple pressure and temperature difference signals, and realize VR interaction and neuro-reflex applications. The architecture design of the device combined with self-locking effect can eliminate dependence on displacement, enabling a single device to determine the hardness and thermal conductivity of materials through a simple touch. We used a bimodal Te-based sensor to develop a wearable glove for endowing real objects to the virtual world, which greatly improves VR somatosensory feedback. In addition, we successfully achieved stimulus recognition and neural-reflex in a rabbit sciatic nerve model by integrating the sensor signals using a deep learning technique. In view of in-/ex-vivo feasibility, the bimodal Te-based sensor would be considered a novel sensing platform for a wide range application of metaverse, AI robot, and electronic medicine.

Integrated polarization-sensitive amplification system for digital information transmission.

Polarized light can provide significant information about objects, and can be used as information carrier in communication systems through artificial modulation. However, traditional polarized light detection systems integrate polarizers and various functional circuits in addition to detectors, and are supplemented by complex encoding and decoding algorithms. Although the in-plane anisotropy of low-dimensional materials can be utilized to manufacture polarization-sensitive photodetectors without polarizers, the low anisotropic photocurrent ratio makes it impossible to realize digital output of polarized information. In this study, we propose an integrated polarization-sensitive amplification system by introducing a nanowire polarized photodetector and organic semiconductor transistors, which can boost the polarization sensitivity from 1.24 to 375. Especially, integrated systems are universal in that the systems can increase the anisotropic photocurrent ratio of any low-dimensional material corresponding to the polarized light. Consequently, a simple digital polarized light communication system can be realized based on this integrated system, which achieves certain information disguising and confidentiality effects.

3D Dielectric Layer Enabled Highly Sensitive Capacitive Pressure Sensors for Wearable Electronics.

Flexible capacitance sensors play a key role in wearable devices, soft robots, and the Internet of things (IoT). To realize these feasible applications, subtle pressure detection under various conditions is required, and it is often limited by low sensitivity. Herein, we demonstrate a capacitive touch sensor with excellent sensing capabilities enabled by a three-dimensional (3D) network dielectric layer, combining a natural viscoelastic property material of thermoplastic polyurethane (TPU) nanofibers wrapped with electrically conductive materials of Ag nanowires (AgNWs). Taking advantage of the large deformation and the increase of effective permittivity under the action of compression force, the device has the characteristics of high sensitivity, fast response time, and low detection limit. The enhanced sensing mechanism of the 3D structures and the conductive filler have been discussed in detail. These superior functions enable us to monitor a variety of subtle pressure changes (pulse, airflow, and Morse code). By detecting the pressure of fingers, a smart piano glove integrated with 10 circuits of finger joints is made, which realizes the real-time performance of the piano and provides the possibility for the application of intelligent wearable electronic products such as virtual reality and human-machine interface in the future.

An Integrated Flexible All-Nanowire Infrared Sensing System with Record Photosensitivity.

Infrared (IR) photodetectors are a key optoelectronic device and have thus attracted considerable research attention in recent years. Photosensitivity is an increasingly important device performance parameter for nanoscale photodetectors and image sensors, as it determines the ultimate imaging quality and contrast. However, photosensitivities of state-of-the-art low-dimensional nanostructure-based IR detectors are considerably low, limiting their practical applications. Herein, a biomimetic IR detection amplification (IRDA) system that boosts photosensitivity by several orders of magnitude by introducting nanowire field effect transistors (FETs), resulting in a peak photosensitivity of 7.6 × 104 under an illumination of 1342 nm, is presented. Consequently, high-contrast imaging of IR light is obtained on the flexible IRDA arrays. The image information can be then trained and recognized by an artificial neural network for higher image-recognition efficiency. This work provides a new perspective for developing high-performance IR imaging systems, and is expected to undoubtedly enlighten future work on artificial intelligence and biorobotic systems.