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Abstract Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver disease worldwide. Si-Wu-Tang (SWT), a traditional Chinese medicine decoction has shown therapeutic effects on various liver diseases. However, the hepatoprotective effects and underlying mechanism of SWT on MAFLD remain unclear. Methods First, a methionine-choline-deficient (MCD) diet-fed mice model was used and lipidomic analysis and transcriptomic analysis were performed. The contents of total iron ions, ferrous ions, and lipid peroxidation were detected and Prussian blue staining was performed to confirm the protective effects of SWT against ferroptosis. Finally, chemical characterization and network pharmacological analysis were employed to identify the potential active ingredients. Results Serological and hepatic histopathological findings indicated SWT's discernible therapeutic impact on MCD diet-induced MAFLD. Lipidomic analysis revealed that SWT improved intrahepatic lipid accumulation by inhibiting TG synthesis and promoting TG transport. Transcriptomic analysis suggested that SWT ameliorated abnormal FA metabolism by inhibiting FA synthesis and promoting FA β-oxidation. Then, ferroptosis phenotype experiments revealed that SWT could effectively impede hepatocyte ferroptosis, which was induced by long-chain acyl-CoA synthetase 4 (ACSL4)-mediated esterification of arachidonic acid (AA). Finally, chemical characterization and network pharmacological analysis identified that paeoniflorin and other active ingredients might be responsible for the regulative effects against ferroptosis and MAFLD. Conclusion In conclusion, our study revealed the intricate mechanism through which SWT improved MCD diet-induced MAFLD by targeting FA metabolism and ferroptosis in hepatocytes, thus offering a novel therapeutic approach for the treatment of MAFLD and its complications. Graphical Abstract

Abstract In this work, a machine learning‐assisted prediction model is proposed to analyze the reliability issues in the 28 nm resistive random access memory (RRAM) chip with raw data measured from RRAM test chip. The neural network of long‐short time memory (LSTM) is trained by the voltages and resistance during the endurance test (input vectors) and generates the output of the dichotomy states with a satisfied testing result >83.08%. According to the prediction results, the “real fail” state or “fake fail” state of the devices can get in the future. By collaborating with a well‐designed resurrection algorithm (RA), the percentage of real and fake failed cells dropped by 35% and 29%, respectively. Besides, the tail bits in retention significantly reduced from 33% to 14.6% due to the reduction of oxygen vacancies in the gaps of conducting filaments by applying ten consecutive cycles of RA. This intelligent prediction and repair module can prolong the lifetime of RRAM chips effectively in practical applications.

Abstract Background Fibrotic liver injury is a progressive scarring event, which may permanently affect liver function and progress into devastating end-stage liver diseases due to the absence of effective therapies. Si-Wu-Tang (SWT), a traditional Chinese medicine formula used in clinic to treat gynecological disorders for centuries, has been investigated in recent preliminary findings for its role in alleviating chronic liver diseases. Here we aim to elucidate the therapeutic effects and possible mechanisms of SWT against fibrotic liver injury. Methods UHPLC-MS/MS was performed to investigate the chemical characterization of SWT. After intragastrically administered with carbon tetrachloride (CCl4) every 3 days for 1-week, C57BL/6 mice were orally administered with SWT (5.2, 10.4 and 20.8 g/kg) once daily for 3 weeks along with CCl4 challenge. Liver function was determined by the measurement of serum biomarkers, hematoxylin and eosin (H&E) and Masson’s trichrome staining. Intestinal inflammatory infiltration and the disruption of intestinal barrier were examined by H&E and E-cadherin immunohistochemical staining. The microbial composition of intestinal content was determined by 16S rRNA sequencing. Serum bile acids (BAs) profiling was analyzed by LC–MS/MS. Simultaneously, the expression of genes of interest was determined by qPCR and western blot. Results SWT exhibited remarkable therapeutic effects on CCl4-induced liver fibrosis, as indicated by improved collagen accumulation in livers, intestinal barrier injury and hepatic and intestinal inflammatory response. Results of 16S rRNA sequencing revealed that SWT treatment strikingly restructured intestinal microbiota in fibrotic mice by increasing the relative abundances of Bacteroides and Lachnoclostridium and decreasing the relative abundances of Alistipes and Rikenellaceae. UHPLC-MS/MS data suggested that SWT altered the composition of BAs in circulation as evidenced by increased unconjugated BAs like cholic acid and chenodeoxycholic acid but decreased conjugated BAs including taurocholic acid and taurodeoxycholic acid, compared to that in CCl4 mice. Notably, SWT efficiently improved the imbalance of BA homeostasis in livers caused by CCl4 via activating farnesoid X receptor (FXR)-fibroblast growth factor 15 enterohepatic and FXR-small heterodimer partner hepatic pathways. Conclusion SWT decreased inflammatory response, reconstructed gut microbiota-mediated BA homeostasis as well as activated FXR pathways, which eventually protected against CCl4-induced fibrotic liver injury.

We propose a novel cell structure of spin–orbit torque (SOT) magnetic random-access memory (MRAM), which consists of three transistors and two canted-type x SOT magnetic tunnel junctions (3T2M) with opposite canting angle (+φ/-φ) on a shared heavy-metal, enabling a self-referencing scheme. Owing to the canting-angle-dependent switching polarity, the 3T2M unit keeps switching to complementary states without any complex structure, corroborating an excellent application potential for practical CMOS integration. Moreover, upon tailoring the canting angle and the ratio of field-like over damping-like torque in the free layer, the developed architecture demonstrates efficient and reliable field-free magnetization switching with a significantly improved read sensing margin (230 mV and 160 mV for reading “1” and “0”) and outstanding thermal stability (Δ∼70). The 3T2M cell exhibits 0.25 ns ultra-fast write speed, a 6 × reduced write energy of 35.41 fJ, and 23.65 fJ for “1” and “0” than the state-of-the-art.

Si-Wu-Tang (SWT), a traditional Chinese medicine formula firstly recorded from the Tang dynasty, has been reported to alleviate gynecological and liver diseases. We preliminarily demonstrated that SWT could improve liver fibrosis via modulating intestinal microbiota, but little was known about the mechanisms linking its therapeutic effects to the reshaped immune microenvironment within fibrotic livers. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis murine model to evaluate the hepatoprotective effects and potential mechanisms of SWT. The high-performance liquid chromatography, RNA sequencing and other molecular biological techniques were also performed in our study. Our data demonstrated that SWT significantly improved BDL-induced liver fibrosis and inflammatory responses by inhibiting the expression of genes associated with extracellular matrix synthesis and degradation. Combined with the analysis of immune cell infiltration and gene set enrichment analysis (GSEA), we found that SWT remarkably repaired the unbalanced immune microenvironment by modulating the biological functions of different immune cells, especially for macrophages, neutrophils and CD8+ T cells. In addition, SWT significantly inhibited the activation of M2-like macrophages to reduce the release of profibrotic-cytokines and prevented the activation of neutrophils to suppress neutrophil extracellular trap formation. SWT also efficiently promoted the apoptosis of activated hepatic stellate cells via Fas/FasL signaling pathway, which might be mediated by CD8+ tissue-resident memory T cells. In conclusion, our research not only unraveled the intricate mechanisms underlying the hepatoprotective activities of SWT against liver fibrosis but also provided a novel therapeutic strategy for the treatment of liver fibrosis and its relative complications.

Nonalcoholic fatty liver disease (NAFLD), manifested as the aberrant accumulation of lipids in hepatocytes and inflammation, has become an important cause of advanced liver diseases and hepatic malignancies worldwide. However, no effective therapy has been approved yet. Aurantio-obtusin (AO) is a main bioactive compound isolated from Cassia semen that has been identified with multiple pharmacological activities, including improving adiposity and insulin resistance. However, the ameliorating effects of AO on diet-induced NAFLD and underlying mechanisms remained poorly elucidated. Our results demonstrated that AO significantly alleviated high-fat diet and glucose-fructose water (HFSW)-induced hepatic steatosis in mice and oleic acid and palmitic acid (OAPA)-induced lipid accumulation in hepatocytes. Remarkably, AO was found to distinctly promote autophagy flux and influence the degradation of lipid droplets by inducing AMPK phosphorylation. Additionally, the induction of AMPK triggered TFEB activation and promoted fatty acid oxidation (FAO) by activating PPARα and ACOX1 and decreasing the expression of genes involved in lipid biosynthesis. Meanwhile, the lipid-lowing effect of AO was significantly prevented by the pretreatment with inhibitors of autophagy, PPARα or ACOX1, respectively. Collectively, our study suggests that AO ameliorates hepatic steatosis via AMPK/autophagy- and AMPK/TFEB-mediated suppression of lipid accumulation, which opens new opportunities for pharmacological treatment of NAFLD and associated complications.

In this work, a memristive spike-based computing in memory (CIM) system with adaptive neuron (MSPAN) is proposed to realize energy-efficient remote arrhythmia detection with high accuracy in edge devices by software and hardware co-design. A multi-layer deep integrative spiking neural network (DiSNN) is first designed with an accuracy of 93.6% in 4-class ECG classification tasks. Then a memristor-based CIM architecture and the corresponding mapping method are proposed to deploy the DiSNN. By evaluation, the overall system achieves an accuracy of over 92.25% on the MIT-BIH dataset while the area is 3.438 mm2 and the power consumption is 0.178 μJ per heartbeat at a clock frequency of 500 MHz. These results reveal that the proposed MSPAN system is promising for arrhythmia detection in edge devices.

Chronic inflammation in response to persistent exogenous stimuli or damage results in liver fibrosis, which subsequently progresses into malignant liver diseases with high morbidity and mortality. Ferulic acid (FA) is a phenolic acid widely isolated from abundant plants and exhibits multiple biological activities including anti-oxidant, anti-inflammation and enhancement of immune responses. Adenosine monophosphate-activated protein kinase (AMPK) functions as a critical energy sensor and is regulated through the phosphorylation of liver kinases like LKB1 or dephosphorylation by protein tyrosine phosphatases (PTPs). However, the role of FA in carbon tetrachloride (CCl4)-induced chronic inflammation and liver fibrosis and AMPK activation has not been elucidated. Here we reported that FA ameliorated CCl4-induced inflammation and fibrotic liver damage in mice as indicated by reduced levels of serum liver function enzyme activities and decreased expression of genes and proteins associated with fibrogenesis. Additionally, FA inhibited hepatic oxidative stress, macrophage activation and HSC activation via AMPK phosphorylation in different liver cells. Mechanically, without the participation of LKB1, FA-induced anti-inflammatory and anti-fibrotic effects were abrogated by a specific AMPK inhibitor, compound C. Combining with the results of molecular docking, surface plasmon resonance and co-immunoprecipitation assays, we further demonstrated that FA directly bound to and inhibited PTP1B, an enzyme responsible for dephosphorylating key protein kinases, and eventually leading to the phosphorylation of AMPK. In summary, our results indicated that FA alleviated oxidative stress, hepatic inflammation and fibrotic response in livers through PTP1B-AMPK signaling pathways. Taken together, we provide novel insights into the potential of FA as a natural product-derived therapeutic agent for the treatment of fibrotic liver injury.

Probabilistic computing is an emerging computational paradigm that uses probabilistic circuits to efficiently solve optimization problems such as invertible logic, where traditional digital computations are difficult to solve. This paper proposes a true random number generator (TRNG) based on resistive random-access memory (RRAM), which is combined with an activation function implemented by a piecewise linear function to form a standard p-bit cell, one of the most important parts of a p-circuit. A p-bit multiplexing strategy is also applied to reduce the number of p-bits and improve resource utilization. To verify the superiority of the proposed probabilistic circuit, we implement the invertible p-circuit on a field-programmable gate array (FPGA), including AND gates, full adders, multi-bit adders, and multipliers. The results of the FPGA implementation show that our approach can significantly save the consumption of hardware resources.

In recent years, compute-in-memory (CIM) has been extensively studied to improve the energy efficiency of computing by reducing data movement. At present, CIM is frequently used in data-intensive computing. Data-intensive computing applications, such as all kinds of neural networks (NNs) in machine learning (ML), are regarded as ‘soft’ computing tasks. The ‘soft’ computing tasks are computations that can tolerate low computing precision with little accuracy degradation. However, ‘hard’ tasks aimed at numerical computations require high-precision computing and are also accompanied by energy efficiency problems. Numerical computations exist in lots of applications, including partial differential equations (PDEs) and large-scale matrix multiplication. Therefore, it is necessary to study CIM for numerical computations. This article reviews the recent developments of CIM for numerical computations. The different kinds of numerical methods solving partial differential equations and the transformation of matrixes are deduced in detail. This paper also discusses the iterative computation of a large-scale matrix, which tremendously affects the efficiency of numerical computations. The working procedure of the ReRAM-based partial differential equation solver is emphatically introduced. Moreover, other PDEs solvers, and other research about CIM for numerical computations, are also summarized. Finally, prospects and the future of CIM for numerical computations with high accuracy are discussed.

Two-dimensional van der Waals (2D vdW) ferromagnets possess outstanding scalability, controllable ferromagnetism, and out-of-plane anisotropy, enabling the compact spintronics-based non-volatile in-memory computing (nv-IMC) that promises to tackle the memory wall bottleneck issue. Here, by employing the intriguing room-temperature ferromagnetic characteristics of emerging 2D Fe3GeTe2 with the dissimilar electronic structure of the two spin-conducting channels, we report on a new type of non-volatile spin-orbit torque (SOT) magnetic tunnel junction (MTJ) device based on Fe3GeTe2/MgO/Fe3GeTe2 heterostructure, which demonstrates the uni-polar and high-speed field-free magnetization switching by adjusting the ratio of field-like torque to damping-like torque coefficient in the free layer. Compared to the conventional 2T1M structure, the developed 3-transistor-2-MTJ (3T2M) cell is implemented with the complementary data storage feature and the enhanced sensing margin of 201.4% (from 271.7 mV to 547.2 mV) and 276% (from 188.2 mV to 520 mV) for reading “1” and “0”, respectively. Moreover, superior to the traditional CoFeB-based MTJ memory cell counterpart, the 3T2M crossbar array architecture can be executed for AND/NAND, OR/NOR Boolean logic operation with a fast latency of 24 ps and ultra-low power consumption of 2.47 fJ/bit. Such device to architecture design with elaborated micro-magnetic and circuit-level simulation results shows great potential for realizing high-performance 2D material-based compact SOT magnetic random-access memory, facilitating new applications of highly reliable and energy-efficient nv-IMC.

Blockchain technology is increasingly being used in Internet of things (IoT) devices for information security and data integrity. However, it is challenging to implement complex hash algorithms with limited resources in IoT devices owing to large energy consumption and a long processing time. This paper proposes a RISC-V processor with memristor-based in-memory computing (IMC) for blockchain technology in IoT applications. The IMC-adapted instructions were designed for the Keccak hash algorithm by virtue of the extendibility of the RISC-V instruction set architecture (ISA). Then, a RISC-V processor with area-efficient memristor-based IMC was developed based on an open-source core for IoT applications, Hummingbird E200. The general compiling policy with the data allocation method is also disclosed for the IMC implementation of the Keccak hash algorithm. An evaluation shows that >70% improvements in both performance and energy saving were achieved with limited area overhead after introducing IMC in the RISC-V processor.