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Abstract As CMOS technologies face challenges in dimensional and voltage scaling, the demand for novel logic devices has never been greater, with spin-based devices offering scaling potential, at the cost of significantly high switching energies. Alternatively, magnetoelectric materials are predicted to enable low-power magnetization control, a solution with limited device-level results. Here, we demonstrate voltage-based magnetization switching and reading in nanodevices at room temperature, enabled by exchange coupling between multiferroic BiFeO3 and ferromagnetic CoFe, for writing, and spin-to-charge current conversion between CoFe and Pt, for reading. We show that, upon the electrical switching of the BiFeO3, the magnetization of the CoFe can be reversed, giving rise to different voltage outputs. Through additional microscopy techniques, magnetization reversal is linked with the polarization state and antiferromagnetic cycloid propagation direction in the BiFeO3. This study constitutes the building block for magnetoelectric spin-orbit logic, opening a new avenue for low-power beyond-CMOS technologies.

Dengue fever (DF), which is caused by the dengue virus (DENV) and transmitted through Aedes mosquitoes, is well recognized for its systemic manifestations, with its ocular involvement gaining recent attention. We present a case of a 41-year-old Taiwanese female who developed acute macular neuroretinopathy (AMN) following a DF diagnosis related to DENV-1, emphasizing the need for awareness of this complication. The patient, with a history of completely resolved optic neuritis (ON) and comorbidities, experienced blurred vision on day 10 after the onset of DF. The ophthalmic examination revealed macular edema, ellipsoid zone (EZ) infiltration, and choriocapillaris involvement. Despite pulse therapy with corticosteroids, visual disturbances persisted, highlighting the challenge of managing ocular complications. Ocular manifestations in DF include hemorrhages, inflammation, and vascular complications. DF-associated AMN, a rare presentation, poses challenges in diagnosis and treatment response evaluation. While most patients recover spontaneously, some face persistent visual impairment, especially with AMN. Our case emphasizes the importance of recognizing ocular complications in DF, necessitating a multidisciplinary approach for optimal management and further research to delineate treatment strategies and outcomes.

This study aims to assess the motivational factors influencing the participation of older adults in various exercise interventions during depressive episodes and to identify which types of exercise are most effective in alleviating depressive symptoms in this population. Therefore, randomized controlled trials (RCTs) focusing on exercise interventions and their impact on depression in older adult patients, identified by the terms “exercise” AND “depression” AND “elderly” OR “geriatric”, were selected from primary electronic databases to conduct this network meta-analysis (NMA). The primary outcome was the effect on depressive symptoms, while the secondary outcome was the comparison of dropout rates between the intervention groups and the usual care control groups, as a measure of sustained motivation and engagement. Standardized mean difference (SMD) values and the corresponding 95% confidence intervals (CIs) were computed for effect evaluation. This study protocol has been registered in IPLASY (INPLASY 202460035). The results of 31 RCTs with 3238 participants indicated that qigong (SMD −1.17, −2.28 to −0.06), Otago Exercise (SMD −1.15, −2.29 to −0.01), and yoga (SMD −0.88, −1.55 to −0.21) significantly alleviate depressive symptoms in older adults. Walking (SMD −0.82, −1.34 to −0.31) and strength training (SMD −0.67, −1.05 to −0.30) also showed significant effects. Aerobic, physical training, and tai chi had moderate effects, while multisport showed a weaker impact with no significant improvement. In summary, our research findings demonstrate that exercise can effectively alleviate depressive symptoms in older adults, with low dropout rates likely due to interconnected physiological, psychological, and social mechanisms. This is crucial for enhancing treatment strategies for older adults’ depression.

In recent years, PowerShell has become the common tool that helps attackers launch targeted attacks using living-off-the-land tactics and fileless attack techniques. Unfortunately, malware-derived PowerShell Commands (PSCmds) have typically been obfuscated to hide the malicious intent from detection and analysis. Also, malicious PSCmds’ expansive use of multiple obfuscation strategies and encryption methods makes them difficult to be revealed. Despite the advances in malicious PSCmds detection incorporating new approaches such as machine learning and deep learning, there is still no consensus on the solution to de-obfuscating malicious PSCmds and profiling their behavior. To address this challenge, we propose a hybrid framework that combines deep learning and program analysis for automatic PowerShell De-obfuscation and behavioral Profiling (PowerDP) through multi-label classification in a static manner. First, we use character distribution features to forecast obfuscation types of malicious PSCmds. Second, we developed an extensive de-obfuscator utilizing static regular expression replacement to recover the original content of obfuscated PSCmds based on the predicted obfuscation types. Finally, we profile the behavior of PSCmds by features extracted from the abstract syntax tree of PSCmds after de-obfuscation. Our results show that PowerDP achieves a promising 99.82% accuracy and 0.18% hamming loss in obfuscation multi-label classification using deep learning. Furthermore, the successful recovery rate of the de-obfuscator against 15 obfuscation types is 98.11% on average with semantic similarity comparison, and the accuracy of the behavior multi-label classification for identifying 5 behaviors in malicious PSCmds averages 98.53%. The evaluation indicates that PowerDP is able to classify and profile complicated PSCmds.

The stacked and brittle 2D layered structure of molybdenum disulphide limits its practical application in lithium ion batteries. Here, authors report a dewetting-induced manufacture strategy to create the interpenetrating network and induce the pseudocapacity to improve the electrochemical performance.

Abstract Background Genetic mutations underlying familial Alzheimer’s disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression of mutated transgenes have yielded key insights in mechanisms of disease, those models are subject to artifacts, including random genetic integration of the transgene, ectopic expression and non-physiological protein levels. The genetic engineering of novel mouse models using knock-in approaches addresses some of those limitations. With mounting evidence of the role played by microglia in AD, high-dimensional approaches to phenotype microglia in those models are critical to refine our understanding of the immune response in the brain. Methods We engineered a novel App knock-in mouse model (App SAA) using homologous recombination to introduce three disease-causing coding mutations (Swedish, Arctic and Austrian) to the mouse App gene. Amyloid-β pathology, neurodegeneration, glial responses, brain metabolism and behavioral phenotypes were characterized in heterozygous and homozygous App SAA mice at different ages in brain and/ or biofluids. Wild type littermate mice were used as experimental controls. We used in situ imaging technologies to define the whole-brain distribution of amyloid plaques and compare it to other AD mouse models and human brain pathology. To further explore the microglial response to AD relevant pathology, we isolated microglia with fibrillar Aβ content from the brain and performed transcriptomics and metabolomics analyses and in vivo brain imaging to measure energy metabolism and microglial response. Finally, we also characterized the mice in various behavioral assays. Results Leveraging multi-omics approaches, we discovered profound alteration of diverse lipids and metabolites as well as an exacerbated disease-associated transcriptomic response in microglia with high intracellular Aβ content. The App SAA knock-in mouse model recapitulates key pathological features of AD such as a progressive accumulation of parenchymal amyloid plaques and vascular amyloid deposits, altered astroglial and microglial responses and elevation of CSF markers of neurodegeneration. Those observations were associated with increased TSPO and FDG-PET brain signals and a hyperactivity phenotype as the animals aged. Discussion Our findings demonstrate that fibrillar Aβ in microglia is associated with lipid dyshomeostasis consistent with lysosomal dysfunction and foam cell phenotypes as well as profound immuno-metabolic perturbations, opening new avenues to further investigate metabolic pathways at play in microglia responding to AD-relevant pathogenesis. The in-depth characterization of pathological hallmarks of AD in this novel and open-access mouse model should serve as a resource for the scientific community to investigate disease-relevant biology.

Spintronic devices provide a promising beyond-complementary metal-oxide-semiconductor (CMOS) device option, thanks to their energy efficiency and compatibility with CMOS. To accurately capture their multiphysics dynamics, a rigorous treatment of both spin and charge and their inter-conversion is required. Here, we present physics-based device models based on $4\times4$ matrices for the spin-orbit coupling (SOC) part of the magneto-electric spin-orbit (MESO) device. Also, a more rigorous physics model of ferroelectric and magnetoelectric (ME) switching of ferromagnets, based on Landau–Lifshitz–Gilbert (LLG) and Landau–Khalatnikov (LK) equations, are presented. With the combined model implemented in a SPICE circuit simulator environment, simulation results were obtained which show feasibility of the MESO implementation and the functional operation of buffers, synchronous oscillators, and majority gates.

Abstract Amantadine hydrochloride (HCl) is commonly prescribed for treating influenza A virus infection and Parkinson’s disease. Recently, several studies have indicated that the use of amantadine HCl is associated with corneal edema; however, the cytotoxic effect of amantadine HCl has not been investigated. In the present study, the effects of amantadine HCl on cell growth, proliferation, and apoptosis in bovine cornea endothelial cells, and in vitro endothelial permeability were examined. Results showed that lower doses of amantadine HCl do not affect cell growth (≤ 20 μΜ), whereas higher doses of amantadine HCl inhibits cell growth (≥ 50 μΜ), induces apoptosis (2000 μΜ), increases sub-G1 phase growth arrest (2000 μΜ), causes DNA damage (≥ 1000 μΜ), and induces endothelial hyperpermeability (≥ 1000 μΜ) in bovine cornea endothelial cells; additionally, we also found that amantadine HCl attenuates the proliferation (≥ 200 μΜ) and arrests cell cycle at G1 phase (≥ 200 μΜ) in bovine cornea endothelial cells. In the present study, we measured the cytotoxic doses of amantadine HCl on cornea endothelial cells, which might be applied in evaluating the association of corneal edema.

Terminal uridyltransferase 7 (TUT7) adds U-tails on diverse RNAs to promote degradation. Here the authors show that TUT7 is induced upon LPS treatment in macrophages and promotes decay of Regnase-1, thereby regulating the expression of a subset of cytokines, including IL-6.

Abstract Background The major barriers to mesenchymal stem cell (MSC) therapy in rheumatoid arthritis (RA) are a low extent of tissue regeneration and insufficient immunomodulation after cell transplantation. In addition, the role of C-X-C chemokine receptor type 7 (CXCR7) and its mechanism of action in MSC-mediated osteogenic or chondrogenic differentiation and immunomodulation are unclear. Methods Gain of CXCR7 function on human MSCs was carried out by lentiviral vector-mediated CXCR7 overexpression or CXCR7 agonist, TC14012. These cells were determined the role and potential mechanisms for CXCR7-regulated MSC differentiation and immunomodulation using cellular and molecular assays. The therapeutic benefits in RA were investigated in rats with collagen-induced arthritis (CIA). Results CXCR7 was upregulated in MSCs during the induction of osteogenic or chondrogenic differentiation. Blockage of CXCR7 function inhibited osteogenic or chondrogenic differentiation of MSCs whereas gain of CXCR7 function had the opposite effects. Besides, MSCs with CXCR7 gain-of-function facilitated macrophage apoptosis and regulatory T cell differentiation in a co-culture system. Gain of CXCR7 function also promoted the production of anti-inflammatory soluble factors. A gene expression profiling assay and signaling reporter assays revealed that CXCR7 could regulate several candidate genes related to the PPAR, WNT, Hedgehog or Notch pathways, and their signaling activities, which are known to control cell differentiation and immunomodulation. Finally, MSCs with CXCR7 gain-of-function significantly reduced the articular index scores, ankle circumference, radiographic scores, histologic scores, and inflammation in rats with CIA compared with control MSCs. Conclusions CXCR7 promotes the osteogenic and chondrogenic differentiation of MSCs and MSC-mediated immunomodulation by regulating several signaling pathways and anti-inflammatory soluble factors. MSCs with CXCR7 gain-of-function significantly ameliorate arthritic symptoms in a CIA model.

Beyond complementary metal–oxide–semiconductor (CMOS) devices have functionalities different from CMOS transistors, and therefore, the development of novel circuits that leverage their properties is necessary for their practical application to computing. The magnetoelectric spin-orbit (MESO) device has been proposed as one of the promising energy-efficient beyond CMOS device candidates, and several basic circuit blocks have been demonstrated with MESO. In this work, we propose a new differential MESO device that enables differential logic circuit design with better interstage isolation. This improves the output voltage of MESO circuits, provides signal common-mode noise rejection, and eliminates any sneak current path. We demonstrate the functionality of multiple essential logic circuit blocks implemented with MESO devices.

BiFeO3 has a wide application but the impact of rare-earth substitution for the evolution of the coupling mechanism is unknown. Here, the authors reveal the correlation between ferroelectricity, antiferromagnetism, a weak ferromagnetic moment, and their switching pathways in La-substituted BiFeO3.

To balance the cost and volume when applying a low output current ripple, the power supply design should be able to eliminate the current ripple under any duty cycle in medium and high switching frequencies, and considerably reduce filter volume to improve power density. A stacked buck converter was eventually selected after reviewing the existing solutions and discussing their advantages and disadvantages. A stacked buck converter is used as a basis to propose the transient response and output current ripple elimination effect, boundary limit control method, and low output ripple dead time modulation method to make individual improvements. The principle, mathematical derivation, small-signal model, and compensator design method of the improvement method are presented in detail. Moreover, simulation results are used to mutually verify the correctness and effectiveness of the improvement method. A stacked buck converter with 330-V input, 50-V output, and 1-kW output power was implemented to verify the effect of the low output current ripple dead time modulation. Experimental results showed that the peak-to-peak value of the output current ripple was reduced from 2.09 A to 559 mA, and the RMS value was reduced from 551 mA to 91 mA, thereby effectively improving the output current ripple.

An ability to understand and predict financial wellbeing for individuals is of interest to economists, policy designers, financial institutions, and the individuals themselves. According to the Nilson reports, there were more than 3 billion credit cards in use in 2013, accounting for purchases exceeding US$ 2.2 trillion, and according to the Federal Reserve report, 39% of American households were carrying credit card debt from month to month. Prior literature has connected individual financial wellbeing with social capital. However, as yet, there is limited empirical evidence connecting social interaction behavior with financial outcomes. This work reports results from one of the largest known studies connecting financial outcomes and phone-based social behavior (180,000 individuals; 2 years' time frame; 82.2 million monthly bills, and 350 million call logs). Our methodology tackles highly imbalanced dataset, which is a pertinent problem with modelling credit risk behavior, and offers a novel hybrid method that yields improvements over, both, a traditional transaction data only approach, and an approach that uses only call data. The results pave way for better financial modelling of billions of unbanked and underbanked customers using non-traditional metrics like phone-based credit scoring.

Proso millet (Panicum miliaceum) is rich in nutritive components and is widely used as a human food, feed and forage for animals, and fuel. This study investigated the effect of a proso millet extract on the inhibition of tyrosinase, a key enzyme in melanogenesis. High performance liquid chromatography analysis indicated that the proso millet extract contained phenolic tyrosinase inhibitors, such as syringic acid, p-coumaric acid, and ferulic acid. The extract had an IC50 for inhibition of tyrosinase activity of 14.02 mg/mL. A Lineweaver-Burk double reciprocal plot showed that the proso millet extract functioned as a mixed competitive and noncompetitive inhibitor. Proso millet has potential as a tyrosinase inhibitor that may have applications in the cosmetics industry.

Fog and rain was collected during an 18-day period in January 2011 at Mt. Bamboo, northern Taiwan. Almost 300 hourly fog samples and 16 daily rain samples were taken. One single fog sample (pH 3.17) was influenced by local volcanic activity, otherwise the pH ranged from 3.23 to 6.41 in fog and from 3.59 to 6.31 in rain. All the respective air masses arrived from the northeast, but exhibited two distinct groups: Group_1 had high concentrations of all ions (median interquartile range of total ion concentrations 3200–6200 µeq.·L−1) and low pHs (median 3.52), the respective air masses had travelled over densely populated and industrialized regions of mainland China. Group_2 was from air masses with long travel times over the ocean and relatively low total ion concentrations (80–570 µeq.·L−1) and higher pHs (median 4.80). The cleanest samples are among the cleanest reported in the literature of worldwide fog and rain. In both groups, the pH was governed by the balance of sulfate, nitrate, ammonium, and, in some cases, calcium. The variability of these ions was higher than the variability of 10−pH, which shows that the pH is a rather robust parameter in contrast to its drivers such as non-sea-salt sulfate.

The Franz diffusion cell is one of the most widely used devices to evaluate transdermal drug delivery. However, this static and nonflowing system has some limitations, such as a relatively large solution volume and skin area and the development of gas bubbles during sampling. To overcome these disadvantages, this study provides a proof of concept for miniaturizing models of transdermal delivery by using a microfluidic chip combined with a diffusion cell. The proposed diffusion microchip system requires only 80 μL of sample solution and provides flow circulation. Two model compounds, Coomassie Brilliant Blue G-250 and potassium ferricyanide, were successfully tested for transdermal delivery experiments. The diffusion rate is high for a high sample concentration or a large membrane pore size. The developed diffusion microchip system, which is feasible, can be applied for transdermal measurement in the future.

Stimulating naïve CD8+ T cells with specific antigens and costimulatory signals is insufficient to induce optimal clonal expansion and effector functions. In this study, we show that the activation and differentiation of CD8+ T cells require IL-2 provided by activated CD4+ T cells at the initial priming stage within 0-2.5 hours after stimulation. This critical IL-2 signal from CD4+ cells is mediated through the IL-2Rbetagamma of CD8+ cells, which is independent of IL-2Ralpha. The activation of IL-2 signaling advances the restriction point of the cell cycle, and thereby expedites the entry of antigen-stimulated CD8+ T-cell into the S phase. Besides promoting cell proliferation, IL-2 stimulation increases the amount of IFNgamma and granzyme B produced by CD8+ T cells. Furthermore, IL-2 at priming enhances the ability of P14 effector cells generated by antigen activation to eradicate B16.gp33 tumors in vivo. Therefore, our studies demonstrate that a full CD8+ T-cell response is elicited by a critical temporal function of IL-2 released from CD4+ T cells, providing mechanistic insights into the regulation of CD8+ T cell activation and differentiation.

As CMOS technologies face challenges in dimensional and voltage scaling, the demand for novel logic devices has never been greater, with spin-based devices offering scaling potential, at the cost of significantly high switching energies. Alternatively, magnetoelectric materials are predicted to enable lowpower magnetization control, a solution with limited device-level results. Here, we demonstrate voltage-based magnetization switching and reading in nanodevices at room temperature, enabled by exchange coupling between multiferroic BiFeO3 and ferromagnetic CoFe, for writing, and spin-to-charge current conversion between CoFe and Pt, for reading. We show that, upon the electrical switching of the BiFeO3, the magnetization of the CoFe can be reversed, giving rise to different voltage outputs. Through additional microscopy techniques, magnetization reversal is linked with the polarization state and antiferromagnetic cycloid propagation direction in the BiFeO3. This study constitutes the building block for magnetoelectric spin-orbit logic, opening a new avenue for low-power beyond-CMOS technologies. [ABSTRACT FROM AUTHOR]