Single-Pore Nanofluidic Logic Memristor with Reconfigurable Synaptic Functions and Designable Combinations.

The biological neural network is a highly efficient in-memory computing system that integrates memory and logical computing functions within synapses. Moreover, reconfiguration by environmental chemical signals endows biological neural networks with dynamic multifunctions and enhanced efficiency. Nanofluidic memristors have emerged as promising candidates for mimicking synaptic functions, owing to their similarity to synapses in the underlying mechanisms of ion signaling in ion channels. However, realizing chemical signal-modulated logic functions in nanofluidic memristors, which is the basis for brain-like computing applications, remains unachieved. Here, we report a single-pore nanofluidic logic memristor with reconfigurable logic functions. Based on the different degrees of protonation and deprotonation of functional groups on the inner surface of the single pore, the modulation of the memristors and the reconfiguration of logic functions are realized. More noteworthy, this single-pore nanofluidic memristor can not only avoid the average effects in multipore but also act as a fundamental component in constructing complex neural networks through series and parallel circuits, which lays the groundwork for future artificial nanofluidic neural networks. The implementation of dynamic synaptic functions, modulation of logic gates by chemical signals, and diverse combinations in single-pore nanofluidic memristors opens up new possibilities for their applications in brain-inspired computing.

Matrine induces autophagic cell death by triggering ROS/AMPK/mTOR axis and apoptosis in multiple myeloma.

Despite significant advancements in multiple myeloma (MM) treatment in recent years, most patients will eventually develop resistance or experience relapse. Matrine, a primary active compound of traditional Chinese medicinal herb Sophora flavescens Ait, has been found to have anti-tumor properties in various types of malignant tumors. Whether autophagy plays a crucial role in the anti-MM effect of matrine remain unknown. Herein, we found that matrine could trigger apoptosis and cell cycle arrest, and meanwhile induce autophagy in MM cells in vitro. We further ascertained the role of autophagy by using ATG5 siRNA or the autophagy inhibitor spautin-1, which partially reversed matrine's inhibitory effect on MM cells. Conversely, the combination of matrine with the autophagy inducer rapamycin enhanced their anti-tumor activity. These findings suggest that autophagy induced by matrine can lead to cell death in MM cells. Further mechanism investigation revealed that matrine treatment increased the levels of reactive oxygen species (ROS) and AMPKα1 phosphorylation and decreased the phosphorylation of mTOR in MM cells. Additionally, co-treatment with AMPKα1 siRNA or the ROS scavenger N-acetyl-1-cysteine weakened the increase in autophagy that was induced by matrine. Finally, we demonstrated a synergistic inhibitory effect of matrine and rapamycin against MM in a xenograft mouse model. Collectively, our findings provided novel insights into the anti-MM efficacy of matrine and suggest that matrine induces autophagy by triggering ROS/AMPK/mTOR axis in MM cells, and combinatorial treatment of matrine and rapamycin may be a promising therapeutic strategy against MM.

miR-1246-overexpressing exosomes improve UVB-induced photoaging by activating autophagy via suppressing GSK3ß.

Stem cell paracrine has shown potential application in skin wound repair and photoaging treatment. Our previous study demonstrated that miR-1246-overexpressing Exosomes (OE-EXs) isolated from adipose-derived stem cells (ADSCs) showed superior photo-protecting effects on UVB-induced photoaging than that of the vector, however, the underlying mechanism was unclear. The simultaneous bioinformatics analysis indicated that miR-1246 showed potential binding sites with GSK3ß which acted as a negative regulator for autophagy. This study was aimed to explore whether OE-EXs ameliorate skin photoaging by activating autophagy via targeting GSK3ß. The results demonstrated that OE-EXs significantly decreased GSK3ß expression, enhanced autophagy flux and autophagy-related proteins like LC3II, while suppressed p62 expression. Meanwhile, OE-EXs markedly reversed the levels of intracellular ROS, MMP-1, procollagen type I and DNA damage in human skin fibroblasts caused by UVB irradiation, but the ameliorating effects were significantly inhibited when 3-Methyladenine (3-MA) was introduced to block the autophagy pathway. Further, OE-EXs could reverse UVB-induced wrinkles, epidermal hyperplasia, and collagen fibers reduction in Kunming mice, nevertheless, the therapeutical effects of OE-EXs were attenuated when it was combinative treated with 3-MA. In conclusion, OE-EXs could cure UVB induced skin photoaging by activating autophagy via targeting GSK3ß.

Learning from the Brain: Bioinspired Nanofluidics.

The human brain completes intelligent behaviors such as the generation, transmission, and storage of neural signals by regulating the ionic conductivity of ion channels in neuron cells, which provides new inspiration for the development of ion-based brain-like intelligence. Against the backdrop of the gradual maturity of neuroscience, computer science, and micronano materials science, bioinspired nanofluidic iontronics, as an emerging interdisciplinary subject that focuses on the regulation of ionic conductivity of nanofluidic systems to realize brain-like functionalities, has attracted the attention of many researchers. This Perspective provides brief background information and the state-of-the-art progress of nanofluidic intelligent systems. Two main categories are included: nanofluidic transistors and nanofluidic memristors. The prospects of nanofluidic iontronics' interdisciplinary progress in future artificial intelligence fields such as neuromorphic computing or brain-computer interfaces are discussed. This Perspective aims to give readers a clear understanding of the concepts and prospects of this emerging interdisciplinary field.

Increase of CD3+CD7- T cells in bone marrow predicts invasion in patients with T-cell non-Hodgkin's lymphoma.

Background: The T-cell non-Hodgkin's lymphoma (T-NHL) patients with bone marrow (BM) invasion have a poor prognosis. Although BM biopsy is still a confirmed diagnosis method, the low sensitivity restricts its use to detect the minimal BM invasion. It is of great clinical significance to establish a rapid and highly sensitive method to evaluate BM invasion. Methods: We conducted a retrospective study of 85 patients with new diagnosed T-NHL patients enrolled in our institute. The bone marrow mononuclear cells (BMMNCs) cells were isolated, stained with different combinations of antibody and subjected to flow cytometry analysis. Results: We found that CD3+CD7- T cells increased significantly in the BM in T-NHL patients with BM invasion. The patients were divided into the low and high groups according to the cutoff value of 1.035% obtained by analyzing the receiver operating characteristic (ROC) curve of the percentage of CD3+CD7- T cells of nucleated cells at diagnosis. The ratio of invasion in high group was markedly higher than that in low group. Furthermore, CD3+CD7- T cells presented significantly higher level of programmed cell death-1 (PD-1), lymphocyte-activation-gene-3 (LAG3) and CD4/CD8 ratio. Conclusions: Our study revealed the percentage of CD3+CD7- T cells of nucleated cells in BM was a potential diagnostic predictor of BM invasion with T-NHL.

A Web of Science-based scientometric analysis about mammalian target of rapamycin signaling pathway in kidney disease from 1986 to 2020.

BACKGROUND: The mammalian target of rapamycin (mTOR) signaling pathway is vital for the regulation of cell metabolism, growth and proliferation in the kidney. This study aims to show current research focuses and predict future trends about mTOR pathway in kidney disease by the methods of scientometric analysis. METHODS: We referred to publications from the Web of ScienceTM Core Collection (WoSCC) Database. Carrot2, VOSviewer and CiteSpace programs were applied to evaluate the distribution and contribution of authors, institutes and countries/regions of extensive bibliographic metadata, show current research focuses and predict future trends in kidney disease's area. RESULTS: Until July 10, 2020, there are 2,585 manuscripts about mTOR signaling pathway in kidney disease in total and every manuscript is cited 27.39 times on average. The big name of course is the United States. Research hot spots include "diabetic nephropathy", "kidney transplantation", "autosomal dominant polycystic kidney disease", "tuberous sclerosis complex", "renal cell carcinoma" and "autophagy". Seven key clusters are detected, including "kidney transplantation", "autosomal dominant polycystic kidney disease", "renal transplantation", "renal cell carcinoma", "hamartin", "autophagy" and "tuberous sclerosis complex". CONCLUSIONS: Diabetic nephropathy, kidney transplantation, autosomal dominant polycystic kidney disease, tuberous sclerosis complex, renal cell carcinoma and autophagy are future research hot spots by utilizing scientometric analysis. In the future, it is necessary to research these fields.

A Review of the Current Practice of Diagnosis and Treatment of Idiopathic Membranous Nephropathy in China.

Idiopathic membranous nephropathy (IMN), a common pathological type of nephrotic syndrome, is one of the main causes of kidney failure. With an increasing prevalence, IMN has received considerable attention in China. Based on recent studies, we discuss advances in the diagnosis of IMN and the understanding of its genetic background. Although the pathogenesis of IMN remains unclear, our understanding has been substantially enhanced by the discovery of new antigens such as phospholipase A2 receptor, thrombospondin type-1 domain-containing 7A, exostosin1/exostosin2, neural epidermal growth factor-like 1 protein, neural cell adhesion molecule 1, semaphorin 3B, and factor H autoantibody. However, due to ethnic, environmental, economic, and lifestyle differences and other factors, a consensus has not yet been reached regarding IMN treatment. In view of the differences between Eastern and Western populations, in-depth clinical evaluations of biomarkers for IMN diagnosis are necessary. This review details the current treatment strategies for IMN in China, including renin-angiotensin system inhibitors, corticosteroid monotherapy, cyclophosphamide, calcineurin inhibitors, mycophenolate mofetil, adrenocorticotropic hormone, and traditional Chinese medicine, as well as biological preparations such as rituximab. In terms of management, the 2012 Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines do not fully consider the characteristics of the Chinese population. Therefore, this review aims to present the current status of IMN diagnosis and treatment in Chinese patients, and includes a discussion of new approaches and remaining clinical challenges.