Search Results (301,314)

The Internet of Things increasingly relies on EDHOC (Ephemeral Diffie–Hellman Over COSE, RFC 9528) and OSCORE (Object Security for Constrained RESTful Environments, RFC 8613) for lightweight authenticated key exchange and application-layer security. On resource-constrained devices, however, the computational cost of these protocols remains prohibitive in software: a complete EDHOC handshake requires hundreds of milliseconds to several seconds on typical embedded processors. Prior evaluations of EDHOC and OSCORE focus almost exclusively on ARM Cortex-M platforms; to the best of our knowledge, no dedicated evaluation or hardware acceleration study exists for RISC-V. This paper presents the first performance characterization of EDHOC and OSCORE on a RISC-V platform. It introduces a hardware accelerator integrated as a memory-mapped peripheral within a Rocket RV32IMAC SoC. The accelerator offloads the complete EDHOC Method 3 handshake, encompassing X25519 scalar multiplication, HMAC-SHA-256 key derivation, AES-CCM-16-64-128 authenticated encryption, and all protocol state management and message construction within a single hardware boundary; OSCORE per-packet AEAD is accelerated through a dedicated post-handshake interface using the same core. By moving the entire handshake execution to dedicated hardware, the accelerator eliminates the residual overhead that remains in software, regardless of whether individual cryptographic primitives are offloaded. Implemented on a Xilinx Arty A7-100T FPGA, the design consumes 10,597 Slice LUTs, 10,421 Slice Registers, and 15 DSP slices. The accelerator completes the EDHOC handshake in 6.64 ms and 4.52 ms for the Initiator and Responder, respectively, achieving 58× and 85× speedups over the optimized Monocypher software baseline on the same platform, and delivers 37× to 56× speedups for OSCORE per-packet AEAD acceleration across payload sizes from 10 to 1000 bytes. The host firmware footprint is reduced from over 25 KB to 3.6 KB for EDHOC-only and to 5.2 KB for the combined EDHOC and OSCORE stack. Full article

Semaglutide represents a unique therapeutic option for patients with type 2 diabetes mellitus (T2DM), being the first and currently only glucagon-like peptide-1 receptor agonist (GLP-1RA) available in both subcutaneous and oral formulations. This study aimed to compare the effectiveness of oral versus subcutaneous (sc) semaglutide on metabolic parameters and cardiovascular risk factors in T2DM patients. This is a retrospective real-world study including adult patients with T2DM taking oral or sc semaglutide followed at the ASUGI Diabetes Center. We analyzed data from 434 patients (median age 70 years, diabetes duration 13 years), treated with oral (n = 232) or sc (n = 202) semaglutide. The oral formulation had a higher discontinuation rate. Among these patients, 130 patients in the oral group and 145 in the sc group had an 18-month follow-up. When comparing these groups, patients taking sc semaglutide had a significantly higher baseline BMI. However, multivariate linear regression models suggested that both formulations were comparably effective in reducing HbA1c and BMI, with baseline values being the primary predictors of response. To address BMI imbalances, propensity score matching was performed, identifying 55 matched pairs. Both oral and sc semaglutide reduced HbA1c and BMI and there were no significant differences in the median change in HbA1c and BMI between groups. Interestingly, oral semaglutide was associated with a significantly greater reduction in diastolic blood pressure compared to the sc formulation. Furthermore, concomitant therapy with SGLT2 inhibitors significantly enhanced the reduction in total and LDL cholesterol. Oral and subcutaneous semaglutide show comparable effectiveness in lowering HbA1c and BMI in a real-world setting. Full article

Elderly individuals in rural China are highly vulnerable to extreme weather events and temperature fluctuations due to inadequate infrastructure in the built environment and constrained economic conditions, thereby increasing their health risks. Outdoor spaces represent one of the primary daily activity settings for rural older adults. However, existing research rarely links spatiotemporal patterns of outdoor activities to evidence-based thermal environment optimization, leaving a critical knowledge gap for age-friendly and sustainable rural design. This study focuses on the spatiotemporal differentiation patterns of daily outdoor activities among elderly people aged 60 years and above in rural Xi’an, as well as the optimization of spatial variations in thermal environments. Using on-site interviews, thermal environment measurements, thermal comfort questionnaires, continuous thermal environment monitoring, and machine learning based on random forest, this study drew the following conclusions: (1) outdoor activities in winter were concentrated between 9:00–11:00 and 13:00–17:00, while in summer, they shifted to the morning and evening periods, namely 6:00–9:00 and 17:00–21:00. (2) Models for outdoor clothing adjustment, thermal sensation, and thermal acceptability among elderly residents were established. The calculated neutral temperature was 10.19 °C, with a 90% outdoor thermal acceptability range of 9.6–27.2 °C and an 80% outdoor thermal acceptability range of 6.2–30.6 °C. These findings differ from those documented in regions with distinct climate zones and geographical settings. This discrepancy stems from regional climatic features, lifestyle variations between urban and rural older adults, and differences in the thermal environment quality of elderly-oriented outdoor activity spaces. (3) In winter, the acceptable period of the Universal Thermal Climate Index (UTCI) at south-facing entrances (10:30–16:30) was significantly longer than that in the courtyard (13:30–14:00). In summer, the comfortable period in the courtyard (before 10:00 and after 20:00) was longer than that at north-facing entrances (before 09:00). A random forest model for thermal sensation was established, and the relative importance of each parameter influencing thermal sensation was analyzed. On this basis, priority improvement pathways and strategies for the thermal environment, as well as suggestions for the subjective adaptive behaviors of elderly residents, were proposed. The research results of this study can provide technical solutions for age-friendly thermal environment design in rural areas, thereby safeguarding the comfort, health, and social well-being of the elderly population in rural areas. Full article

Primula nutans Georgi, a medicinal herb used in Mongolian and Tibetan medicine for treating respiratory ailments, is a natural agent with antiobesity potential. We investigated the antiobesity and insulin-sensitizing effects of P. nutans Georgi extract (PGE) using in vitro and in vivo models. In 3T3-L1 preadipocytes, PGE inhibited adipocyte differentiation and lipid accumulation without cytotoxicity, accompanied by the reduced expression of adipogenic transcription factors (PPARG, C/EBPA, and adiponectin) and lipogenic genes (FASN, SCD1, and ACC), particularly during the early stages of adipogenesis. Similar effects were observed in primary stromal vascular cells derived from mouse inguinal white adipose tissue. PGE upregulated C/EBP homologous protein and C/EBPB and was associated with altered cell cycle progression, increased G2/M phase distribution, and the potential disruption of mitotic clonal expansion during early adipogenesis. In HFD-induced obese mice, intraperitoneal administration of PGE (10 or 30 mg/kg) significantly reduced body weight gain, white adipose tissue mass, and hepatic steatosis, independent of food intake. PGE downregulated lipogenic and proinflammatory gene expression in adipose and hepatic tissues and increased AMPK phosphorylation in white adipose tissue. PGE improved glucose tolerance and was associated with enhanced insulin sensitivity, as evidenced by reduced areas under the curve in the glucose tolerance and insulin tolerance tests and increased circulating adiponectin levels. Feature-based molecular networking identified 61 compounds from PGE. Network pharmacology analysis revealed several antiobesity targets, including PPARG and AKT1. Molecular docking analyses suggested favorable binding affinities between major compounds and metabolic regulators. Collectively, these findings suggest that PGE may suppress adipogenesis and improve metabolic parameters in obese mice, supporting its potential as a natural candidate for obesity and related metabolic disorders. Full article

Off-grid electric vehicle (EV) charging infrastructure powered by hybrid solar–wind systems address critical adoption barriers in developing countries, where grid unreliability and sparse charging networks constrain transportation electrification. Despite growing research interest, no comprehensive review has systematically synthesized the interplay between hybrid renewable architectures, intelligent energy management strategies, and techno-economic viability specifically for off-grid EV charging in resource-constrained settings. This systematic review applies the PRISMA methodology to analyze 94 peer-reviewed publications (2013–2026), examining system architectures, intelligent control strategies, power electronics, battery storage, and deployment frameworks for standalone hybrid solar–wind EV charging stations. Key findings indicate that hybrid solar–wind configurations achieve 30–50% reductions in battery storage requirements and 15–25% lower levelized cost of energy (LCOE) (USD 0.08–0.15/kWh) compared with single-source systems, driven by diurnal and seasonal resource complementarity. Among intelligent control methods, the two-stage distributionally robust optimization (TSDRO) framework emerges as the most promising for data-scarce environments, outperforming conventional deterministic and stochastic approaches by 10–20% in managing renewable intermittency without requiring precise probability distributions. Wide-bandgap power semiconductors (SiC, GaN) enable 96–98% conversion efficiency, while lithium iron phosphate batteries provide 3000–5000 cycle lifetimes suited to tropical operating conditions. Critical gaps remain with field validation still predominantly simulation based, long-term operational data exceeding 24 months on equipment degradation and climate resilience are scarce, and scalable financing models for developing country contexts require further development. Nigeria is presented as an exemplar deployment context, with transferable insights for sub-Saharan Africa, South Asia, and Southeast Asia. Full article

AC microgrids with high penetration of inverter-based distributed energy resources (IBDERs) introduce major protection challenges due to reduced fault current levels, bidirectional power flows, and control-dependent fault behavior. Under these conditions, short-circuit current calculation and relay protection coordination become tightly coupled, since inaccurate fault modeling directly degrades relay sensitivity and selectivity. This review presents a protection-oriented assessment of state-of-the-art short-circuit calculation and relay protection strategies for AC microgrids. The analysis shows that conventional IEC-based fault models and static overcurrent protection schemes are insufficient for inverter-dominated networks. Generalized Δ-circuit–based modeling framework is identified as the most suitable foundation for microgrid fault analysis, as they enable inverter-aware phasor-domain representation and support both grid-connected and islanded operation. In addition, adaptive relay coordination approaches that incorporate time-varying IBDER participation and fault ride-through behavior demonstrate improved coordination robustness compared to conventional fixed settings, although their practical deployment remains constrained by network topology and communication requirements. Simulation results obtained on a representative microgrid case study confirm that the combined application of protection-oriented short-circuit modeling and adaptive relay coordination significantly improves fault detection reliability and coordination performance. The findings highlight the necessity of jointly addressing fault modeling and protection design to ensure reliable operation of inverter-dominated AC microgrids. Full article

Reactive astrocytes are a hallmark of several neurological diseases in multiple sclerosis and experimental demyelination models. Their morphological alterations are commonly assessed by qualitative histopathology, yet quantitative tools are required to better capture astrocytic heterogeneity and to allow correlations with imaging-derived biomarkers. Here, we present a workflow for the quantitative analysis of Glial Fibrillary Acidic Protein (GFAP) network remodeling in astrocytes in the cuprizone model of demyelination. C57BL/6 mice were intoxicated with cuprizone for 3 or 5 weeks to induce progressive demyelination, microglial activation, and reactive astrogliosis. Brain sections were processed for anti-GFAP immunohistochemistry, and individual astrocytes from the stratum oriens of the hippocampus were digitally reconstructed. Diverse parameters of GFAP topology, including soma size, process length, branching order, convex hull area, and ramification index, were extracted using either the commercial Neurolucida^® 360 software or the open-source Simple Neurite Tracer (SNT) plugin in ImageJ. Principal component analysis revealed clear differences between control astrocytes and astrocytes in cuprizone-intoxicated animals, with reactive astrocytes displaying increased numbers of primary processes, enhanced bifurcation, and process complexity. Comparative evaluation of Neurolucida^® 360 and SNT demonstrated that both tools are suitable for astrocyte reconstruction, although Neurolucida^® 360 enabled faster and more detailed tracing. This protocol provides a reproducible pipeline for the quantitative assessment of astrocyte morphology under control and pathological conditions, thereby supporting future efforts to link cellular remodeling to functional outcomes in neuroinflammatory disease models. Full article

To address the urgent need for electronics operable in extremely high-temperature environments, this paper presents a novel three-terminal, dual-gate, lateral 4H-SiC n-channel depletion-mode junction field effect transistor (JFET) without a backside electrode. Featuring a fully planar electrode layout, the device eliminates the back-gate effect and significantly improves integration compatibility. Experimental results demonstrate stable DC operation up to 500 °C, with an intrinsic gain of 9.79 at room temperature and 6.01 at 500 °C. Comparison with TCAD simulations confirms excellent agreement in the key physical trends of threshold voltage drift and mobility degradation, though quantitative discrepancies are observed and attributed to process-induced parasitic effects such as non-ideal ohmic contacts and interface states. Analysis shows that the new structure broadens the channel depletion layer by optimizing the depletion profile, thereby suppressing channel-length modulation and improving both output resistance and gate control. This work not only provides an effective device platform for high-temperature 4H-SiC analog integrated circuits (ICs) but also deepens the understanding of process-performance correlations, offering clear guidance for process-oriented device optimization. The proposed structure serves as a foundation for developing fully planar, high-temperature 4H-SiC analog ICs with promising potential in aerospace, automotive, and energy exploration systems. Full article

Fruit coloration is a key determinant of tomato quality, yet how light and temperature interact to regulate pigmentation during ripening remains unclear. Using a semi-in-fruit experimental system, we demonstrate that while high light accelerates chlorophyll degradation and lycopene accumulation at 25 °C, supra-optimal temperature (40 °C) completely abolishes lycopene biosynthesis irrespective of light conditions, primarily through transcriptional suppression of SlPSY1 and SlGGPS2. Elevated postharvest temperatures (≥30 °C) not only change the carotenoid composition but also reduce the antioxidant capacity and vitamin C content in fruit. Temperature-switch experiments revealed a critical developmental window, days 2–4 after ethylene treatment, during which temperature exerts dominant control over carotenoid metabolism. Exposure to high temperature within this window irreversibly shifts pigment accumulation from lycopene to yellow/orange carotenoids. These findings identify a temporally precise regulatory nexus integrating environmental signals with the ripening program, offering a framework for targeted temperature management to optimize tomato color and nutritional quality. Full article

Resistance to 5-fluorouracil (5-FU) and oxaliplatin (OXA) remains an obstacle in colorectal cancer (CRC) therapy, but the upstream mechanisms enabling adaptive survival remain unclear. Angiomotin (AMOT), a Hippo-YAP regulator, is expressed as two major isoforms, p130 and p80, but the contribution of isoform-specific AMOT regulation to chemoresistance is unknown. RNA-seq of OXA-resistant cells identified AMOT as a candidate determinant, and its isoform-specific regulation and functional relevance were then examined in OXA- and 5-FU-resistant CRC sublines. AMOT-p80 was preferentially upregulated, whereas AMOT-p130 remained largely unchanged. Common AMOT pre-mRNA was elevated, whereas p130-specific pre-mRNA was unchanged, consistent with preferential transcriptional activation favoring the p80 isoform. Functionally, AMOT depletion minimally affected basal viability but significantly sensitized resistant cells to 5-FU or OXA, with increased apoptotic responses. AMOT silencing reduced nuclear YAP and lowered c-Myc and Cyclin D1 protein levels, whereas AMOT-p80 re-expression restored nuclear YAP, with recovery of c-Myc/Cyclin D1 levels and drug tolerance. YAP knockdown attenuated these outputs and blunted the additional effect of AMOT depletion. AMOT-p80 overexpression in parental cells increased c-Myc/Cyclin D1 protein levels and enhanced tolerance to 5-FU and OXA. These findings suggest that preferential AMOT-p80 upregulation is linked to YAP-associated chemoresistant phenotypes in CRC cells. Full article

The aim of the study was to investigate the effect of enriching carrot slices by NFC (not from concentrate) juices from chokeberry (CH), sea buckthorn (SB), cherry (CHE) and carrot (CA) before microwave-vacuum (MVD) and freeze-drying (FD) carrot on the physicochemical and thermal properties. While water activity (AW) was not dependent on enrichment treatment but only on drying method, NFC juices significantly enriched carrot slices with biocomponents. Freeze-dried samples, as a reference, had significantly lower AW than those dried by the MVD method. Both FD and MVD-dried samples had comparable polyphenol content and DPPH antioxidant activity (AA), but the MVD-dried samples exhibited higher ABTS antioxidant activity. Carrot enrichment in chokeberry and cherry juices resulted in up to six and 10 times higher TPC than in the raw material. In addition, samples enriched in these juices and dried with FD proved to be the most stable in terms of water state and glass transition temperature (61.4 and 69.6 °C) and water activity (approx. 0.10). In FTIR analysis, all samples exhibited similar spectral shapes, indicating similar chemical composition and functional group composition. Only in the spectral region below 900 cm⁻¹ were unique molecular vibrations induced by various organic compounds present. Enriching carrot in juices and MVD can lead to increased hardness (Fmax and breaking work), although this is associated with increased crispness, resulting from the microstructure with a large number of small pores, especially in MVD samples enriched with cherry, chokeberry, and carrot juices, with scores of 8.0–8.4 In this respect, the average crispness rating of the MVD samples (7.2) exceeded that of the FD samples (6.8). If there is a requirement for crunchiness in the future production of dried vegetables as snacks, changes in hardness should be prioritized, along with color and biocomponent content. Full article

This article settles a new multi-fault-tolerant control problem of an Euler–Bernoulli beam system (EBBS) in the existence of multiplicative faults, additive faults, and control-matched disturbances simultaneously, using the direct adaptive learning control technique. Such an EBBS can be employed to model the vibration of flexible vehicles and flexible manipulators in the actual engineering control. An original hierarchical adaptive boundary control strategy is developed to compensate for multiplicative and additive faults and to reject control-matched disturbances. The classical Lyapunov direct method, together with the variation of Wirtinger’s inequality is utilized to demonstrate the closed-loop system performance. The modified ${\mathcal{C}}_0$-semigroup frame is exploited to certify the well-posedness of its solution under the designed controller. Simulation study on a simply supported beam is demonstrated to verify the validity of the evolved multi-fault-tolerant boundary control algorithm. Full article

Diffusion probabilistic models are powerful generative tools but are purely data-driven, limiting their ability to incorporate domain knowledge—such as physical laws, degradation trends, or engineering priors—in scientific and engineering applications. We introduce Prior-Guided Diffusion Processes (PGDPs), a unified mathematical framework that integrates arbitrary differentiable prior knowledge into the reverse diffusion dynamics by augmenting the score function with a guidance term derived from a prior potential V(x,t) and weighted by a time-dependent strength γ_t. This formulation subsumes existing mechanisms (classifier guidance, model-based diffusion, physics-informed corrections) as special cases. We analyze the guided path measures, providing an upper bound on the Kullback–Leibler divergence between guided and unguided marginals (Theorem 1), quantifying the inherent trade-off between data fidelity and prior satisfaction. Experiments on synthetic data confirm the predicted dependence on γ_t. On the NASA C-MAPSS turbofan benchmark, we enforce compressor-oriented physical constraints (e.g., speed–pressure consistency, monotonicity) within PGDP; remaining useful life scores are reported only as reference metrics under transparent protocols. A cross-domain study on the NASA IGBT accelerated aging dataset, using the same backbone with a replaced physics module, achieves a 99.98% reduction in monotonicity loss, demonstrating generality across distinct degradation mechanisms. PGDP provides a principled, extensible template for knowledge-informed generative modeling with theoretical guarantees and verifiable physical consistency. Full article

Fraxinus chinensis Roxb. (Qinpi), a traditional Chinese medicinal plant, accumulates abundant coumarins that contribute to its anti-inflammatory and other bioactivities. However, the enzymatic basis for coumarin structural diversification in this species remains largely unexplored. Here, through transcriptome-wide identification of the 2-oxoglutarate-dependent dioxygenase (2OGD) family in F. chinensis, followed by phylogenetic analysis, heterologous expression, and in vitro enzyme assays, we identified FcDOH2, a member of the DOXC31 subfamily, which exhibits substrate-dependent bifunctionality, catalyzing the C6-O-demethylation of scopoletin (3) to esculetin (2) and the C8-hydroxylation of umbelliferone (1) to daphnetin (6). Using AlphaFold3-based structural modeling, molecular docking, and alanine scanning mutagenesis, we revealed that residues R155 and R221 are essential for both activities through stabilizing hydrogen bonds, whereas residue F312 acts as a functional switch, being critical for demethylation but negatively regulating hydroxylation. These findings uncover a rare bifunctional 2OGD with substrate-dependent catalytic plasticity, providing mechanistic insights into coumarin diversification in medicinal plants and a structural basis for future enzyme engineering. Full article

The tumor suppressor protein phosphatase 2A (PP2A) plays a crucial role in regulating oncogenic signaling. Its inactivation, specifically through inhibitory phosphorylation at Tyr307 mediated by SET and CIP2A, contributes to breast cancer (BC) progression. Modulation of these interactions represents a promising pharmacological strategy to restore PP2A function. We integrated computational approaches with experimental validation to analyse SET/CIP2A mechanisms and explore how PP2A reactivation suppresses tumor progression. Molecular docking and dynamics simulations showed that the SET inhibitor/FTY-720 forms stable hydrogen bond networks with SET, disrupting its interaction with PP2A. In contrast, CIP2A suppressor/erlotinib interacts with CIP2A through weaker hydrophobic and π-interactions. Protein–protein interaction analyses indicate reduced SET/CIP2A binding to PP2A upon treatment, supporting a structural basis for PP2A reactivation. Gene expression analyses revealed upregulation of PP2A, SET, CIP2A, and cytoskeletal markers in tumor and metastatic tissues. Studies on Triple Negative Breast Cancer (TNBC) cells showed that FTY-720 and erlotinib significantly reduce PP2A-Tyr307 phosphorylation, restoring its activity. Additionally, both compounds decreased c-Myc levels and inhibited Src/FAK/paxillin/PAK1 and ERK signaling, attenuating migratory and proliferative pathways. Our findings identify the SET/CIP2A–PP2A axis as a pharmacological target for the design of next-generation PP2A activators, highlighting the potential of inhibition as a therapeutic strategy to counteract TNBC progression. Full article