Search Results (290)

Background/Objectives: IL23R encodes a pivotal component of the IL-23/Th17 signaling axis and represents a validated genetic susceptibility locus for inflammatory bowel disease (IBD), psoriasis, and ankylosing spondylitis. Despite extensive GWAS data, the functional consequences of the full spectrum of IL23R missense single-nucleotide variants (SNVs) have not been systematically characterized. This study aimed to identify high-risk missense SNVs through a multi-tool in silico pipeline. Methods: A total of 723 missense SNVs from NCBI dbSNP were verified against transcript NM_144701.3/Q5VWK5-1 (629 aa) using Ensembl VEP (GRCh38). Sequential filtering was performed using applied SIFT, PolyPhen-2, PROVEAN, E-SNPs&GO, MutPred2, and ConSurf (grade ≥ 7); AlphaMissense and FATHMM-MKL were used as independent annotation layers. Protein stability was assessed with MuPro and DynaMut2 (AlphaFold2 AF-Q5VWK5-F1-v6; pLDDT = 68.19); structural characterization was performed with Project HOPE, and interaction networks were constructed using STRING and GeneMANIA. Results: Sequential filtering identified 37 high-risk missense variants. MuPro predicted destabilizing effects for 36/37 variants, with concordant DynaMut2 results for 35/37. Project HOPE identified disulfide bond disruption in 11 variants, charge-altering substitutions in 8, and glycine/proline backbone conformational changes in 11. STRING analysis identified IL12RB1 (0.999), IL23A (0.999), JAK2 (0.995), IL12B (0.986), and STAT3 (0.980) as the leading IL23R interactors. The protective variant R381Q was appropriately characterized as neutral by PROVEAN (−1.16) and AlphaMissense (likely_benign), supporting the specificity of the pipeline. Conclusions: Comprehensive in silico analysis identified 37 high-risk IL23R missense candidates with convergent computational evidence of predicted deleteriousness, predominantly involving cysteine bridge disruption, charge alteration, and glycine/proline backbone conformational changes. These variants are presented as prioritized candidates for future functional validation and may inform subsequent investigations of IBD susceptibility and IL-23 pathway pharmacogenomics. Full article

Apoptosis maintains tissue homeostasis, and its dysregulation is closely associated with breast cancer progression and therapeutic resistance. We performed an integrative analysis of apoptosis-related signaling in breast cancer tissues across five molecular subtypes and compared these patterns with systemic apoptotic responses following cryoablation of benign fibroadenomas. Gene expression profiling was conducted using mRNA microarrays and validated by qRT-PCR and ELISA. Apoptosis pathway activity was assessed with the MSigDB HALLMARK_APOPTOSIS gene set, including intrinsic and extrinsic pathway scoring and an apoptotic balance index (ABI). MicroRNA profiling combined with in silico analyses identified potential miRNA–mRNA interactions. A progressive shift toward reduced pro-apoptotic and enhanced stress-adaptive signaling was observed with increasing tumor aggressiveness, most pronounced in triple-negative and non-luminal HER2-positive cancers. This pattern included reduced intrinsic pathway activity, decreased ABI, downregulation of pro-apoptotic genes (BIK, BMF, TXNIP), and upregulation of stress-associated or cytoprotective genes (HSPB1, PPT1). Several expression patterns were accompanied by overexpression of miRNAs (miR-582-5p, miR-421, miR-106b-5p, miR-20a-5p, miR-20b-5p, miR-93-5p) predicted to target apoptosis-related genes. In contrast, fibroadenoma cryoablation was associated with transient systemic modulation of apoptosis-related genes and proteins followed by gradual normalization. These findings highlight differences between apoptosis-related dysregulation in malignant tissue and regulated systemic responses following benign tissue injury, supporting pathway-level interpretation and identifying candidate molecular networks warranting further mechanistic and translational investigation. Full article

Objectives: This study evaluated auditory performance and quality of life in cochlear implant recipients aged 60 years and older, and identified factors associated with postoperative outcomes. Methods: This cross-sectional descriptive study included 34 patients aged 60 years and older who underwent unilateral cochlear implantation between 2002 and 2020 at the Department of Otolaryngology, Çukurova University Faculty of Medicine. Preoperative WHOQOL-BREF data were not available; postoperative outcomes were therefore assessed against demographic and clinical predictors rather than within-patient change. The patients were grouped by preoperative hearing loss duration (1–3, 4–6, or ≥7 years), daily device use (<11 vs. ≥11 h), and age (60–70 vs. >70 years). Auditory gain was assessed by pure-tone audiometry, quality of life by the WHOQOL-BREF, and cognitive status by the Montreal Cognitive Assessment (MoCA). Cohen’s d, η² and 95% CIs were reported, multiple comparisons were Benjamini–Hochberg-corrected, and multivariable linear regression was applied per domain. Results: The cohort comprised 19 women (55.9%) and 15 men (44.1%), with a mean age of 66.06 ± 5.8 years; eight patients (23.5%) were older than 70. Mean audiological gain was 45.5 ± 13.1 dB and varied with preoperative duration (η² = 0.50, p < 0.001; 1–3 vs. ≥7 years Δ 20.9 dB, 95% CI 12.2–29.6; d = 2.04). Daily device use was a consistent predictor of well-being: those using their implant for more than 11 h daily scored higher across all WHOQOL-BREF subscales (all q ≤ 0.011; d −1.45 to −2.50). Comorbidity was associated with lower scores in four of five domains (q ≤ 0.048; d −0.85 to −1.26), and a higher MoCA score independently predicted the psychological subscale (β = +1.0 per point; p = 0.014). Apparent sex and education effects did not survive correction. Mean preoperative hearing thresholds were 84.3 ± 7.9 dB and 76.1 ± 16.2 dB in patients under and over 70, respectively; postoperative thresholds were 37.8 ± 10.4 dB and 33.9 ± 6.8 dB, with no significant between-group difference in gain (d = 0.32). Conclusions: In this cross-sectional cohort, cochlear implantation was associated with substantial audiological gain and favourable quality-of-life scores in patients aged 60 and older, with an acceptable safety profile. Age alone did not constrain outcomes; the absence of preoperative QoL data precludes direct quantification of within-patient change. Full article

This paper presents a 140 GHz two-channel transmitter in 40 nm bulk CMOS technology for D-band wireless communication systems. The transmitter employs a direct upconversion architecture with IQ Gilbert cell mixers and a shared ×9 frequency multiplier for local oscillator (LO) generation. The Lange coupler generates quadrature LO signals for I and Q paths, while the two-way four-stage differential power amplifier with cascade topology provides high output power. On-wafer measurement at 140 GHz LO frequency demonstrates a 9.9 dB conversion gain with a 5.5–6.1 GHz 3 dB bandwidth. The measured saturated output power is 10.1 dBm with an output 1 dB compression point of 6.5 dBm. The IQ imbalance remains within 2 dB across the 3 dB bandwidth. The fabricated transmitter occupies a chip area of 1.68 mm² and consumes 435 mW from a 1 V supply. The power density of 6.09 mW/mm² is the highest among reported CMOS-based D-band transmitters. The dual-channel architecture with shared LO generation enables MIMO transmission, spatial multiplexing, and diversity techniques while maintaining compact size and competitive power efficiency for high data rate wireless applications in the D-band frequency range. Full article

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder in which presymptomatic treatment substantially improves survival and motor outcomes, yet newborn screening for SMA remains unevenly implemented across Europe, and evidence from lower-resource health systems is needed to guide scale-up. In this study, we assessed the feasibility, diagnostic performance, and public health implications of implementing neonatal SMA screening in the Republic of Moldova within an established national newborn screening framework. A pilot genetic screening program was conducted using dried blood spot (DBS) samples collected through routine newborn screening workflows; SMN1 exon 7 deletion testing was performed by real-time polymerase chain reaction (qPCR), and positive findings were confirmed by multiplex ligation-dependent probe amplification (MLPA), alongside the evaluation of operational integration and system-level requirements. Screening was operationally feasible within existing DBS processes and demonstrated high analytical performance, consistent with published international experience, although performance results should be interpreted cautiously due to the limited sample size. Two SMA cases were confirmed in a small cohort, enabling early diagnosis and timely referral for disease-modifying therapy, and integration into the existing program was practical and resource-efficient. These findings support the incorporation of SMA into national newborn screening panels using DBS-based molecular methods, highlighting an implementable model for introducing advanced genetic testing within routine public health services. Full article

The rapid growth of prosumer photovoltaic installations has introduced significant supply–demand imbalances in modern power grids, motivating the development of energy management systems that can coordinate distributed resources without sacrificing local control responsiveness. This paper presents qToggleEMS, a distributed architecture that combines cloud-resident receding-horizon planning with edge-resident bounded-override control for prosumer sites equipped with photovoltaic generation, battery storage, and grid interconnection. The contribution is positioned at the systems-engineering level: a documented partitioning of responsibilities between a cloud planner (forecasting, price-aware scheduling) and an edge controller (sub-second actuation, autonomous fallback) that preserves planning quality while remaining operational under cloud–edge disconnection. The cloud component, powerHub, is implemented as a set of microservices communicating via MQTT and TimescaleDB; the edge component runs qToggleOS on an ARM single-board computer and accesses inverters directly via Modbus RTU, bypassing manufacturer-provided cloud APIs. The system was deployed at a commercial prosumer site for approximately two months using the prosumer-oriented optimization strategy. Compared with a within-period counterfactual baseline (the cost the site would have incurred under its previous flat-tariff contract), monthly energy costs decreased by 14–15%. An analytical projection of the producer-oriented strategy using historical day-ahead prices from OPCOM PZU suggests a revenue uplift of approximately 23%, pending field validation. Full article

Background: Age-related macular degeneration (AMD) is a common retinal degenerative disease linked to adaptive immune response dysregulation. This study aimed to identify shared immune-related biomarkers and explore their underlying mechanisms. Methods: GSE29801 and GSE135092 served as training and validation sets. Adaptive immune response-related genes (AIR-RGs) from MSigDB were intersected with AMD-related differentially expressed genes (DEGs) to identify candidate genes. Machine learning algorithms were applied to screen biomarkers, validated in datasets and a mouse model of choroidal neovascularization by qPCR. A nomogram was constructed and assessed. GSEA and immune infiltration analyses explored mechanisms and immune microenvironment associations. Results: A total of 148 DEGs were identified, yielding 15 candidate genes after intersection with AIR-RGs. Machine learning identified C3 and HLA-DOA as potential biomarkers, with their differential expression validated across datasets. A nomogram based on these biomarkers demonstrated good predictive performance for AMD pathology (AUC = 0.795). Biomarkers were associated with some immune-inflammatory pathways. Significant differences in immune cell infiltration were observed between AMD and control groups, with biomarkers positively correlated with differentially infiltrated immune cells, such as natural killer cells. Conclusions: The identification of the established biomarker C3 serves as a proof-of-principle for the analytical approach, rather than a novel discovery, thereby validating the model’s capacity to uncover other critical immune targets. Consequently, C3 and HLA-DOA serve as potential biomarkers for AMD, significantly correlated with disease progression via immune pathways and offering insights for immune-based therapeutic strategies. Full article

Background: Dragon’s blood (dried resin of Dracaena cochinchinensis (Lour.) S.C.Chen) is a classic traditional medicine for treating ischemic stroke, yet its bioactive components capable of penetrating the blood–brain barrier (BBB) remain ill-defined. This study aims to elucidate its material basis and the synergistic mechanism of Borneol as a “guide drug.” Methods: A systematic strategy integrating UHPLC-Q-TOF-MS/MS and metabolomics was employed to map the chemical profile of dragon’s blood and identify its migrating constituents in rats. Results: A total of 96 compounds were characterized in vitro. In vivo analysis of the cerebrospinal fluid (CSF) revealed a brain-penetrating profile that was significantly enriched by Borneol, with the number of detected constituents increasing from 11 in the DB group to 16 in the DB + B group. The results demonstrated that demethylation, glycoside hydrolysis, and oxidation are primary metabolic pathways, validating a “pro-drug” mechanism where aglycones and hydroxylated derivatives act as the central effectors. Notably, Borneol not only enhanced the BBB permeability of lipophilic flavonoids but also facilitated unique metabolic transformations, such as the cyclization of berberrubine to coptisine. Conclusions: This study elucidates the brain-penetrating material basis of dragon’s blood and reveals the dual synergistic mechanism of Borneol involving both physical permeation enhancement and metabolic modulation, offering scientific evidence for its clinical application in central nervous system diseases. Full article

This paper presents a comprehensive investigation of the impact of I/Q (In-phase/Quadrature) imbalance on the performance of a six-port receiver operating in the millimeter-wave band, specifically in the 60–65 GHz frequency range. Unlike traditional heterodyne architectures, the six-port junction offers a low-cost and low-power alternative for direct conversion; however, it is highly sensitive to hardware imperfections. This study demonstrates that manufacturing tolerances in passive components, such as 90° hybrid couplers and power dividers, introduce significant amplitude and phase disparities. These imbalances geometrically distort the ideal QPSK constellation, transforming the circular decision boundaries into an elliptical profile. The research methodology employs a robust co-simulation approach in Advanced Design System (ADS), integrating measured S-parameters with mathematical analysis to quantify signal degradation. Performance is evaluated using the Error Vector Magnitude (EVM) metric. The experimental findings reveal that even at the higher end of the spectrum (65 GHz), where the amplitude imbalance reaches 0.7 dB and the phase error is approximately 5°, the six-port QPSK receiver maintains an EVM of 8.7%. This result is comfortably below the 17.5% limit mandated by modern wireless communication standards, such as LTE and 5G. These results confirm the architectural resilience of the six-port receiver, validating its effectiveness as a reliable solution for high-speed, short-range data transmission in future ultra-wideband telecommunication infrastructures. Full article

Q-matrix construction is a foundational yet challenging step in cognitive diagnostic assessment (CDA), which is traditionally reliant on labor-intensive and subjective methods like expert judgment and verbal report analysis. This study explores the potential of generative artificial intelligence (GenAI) to optimize this critical process within the domain of EFL reading. By applying three GenAI models (DeepSeek-V3.2, Kimi 2.5, and Doubao 2.0), three purely GenAI-informed Q-matrices (Qmat-DS, Qmat-K, and Qmat-DB) were generated, and through expert revision, a human–AI collaborative Q-matrix (Qmat-DS-H) was obtained. These were compared with an expert-constructed Q-matrix (Qmat-E) and a student-derived Q-matrix (Qmat-S). Using a simulated dataset (N = 1000) and empirical response data from 1083 EFL learners on a diagnostic reading test, the psychometric performance of the six Q-matrices was estimated via the G-DINA model, ACDM model, and RRUM model. Results demonstrated that the human–AI collaborative Q-matrix consistently outperformed the other five Q-matrices, achieving the best absolute model-data fit, the highest classification accuracy, the most stable item parameters, and the most balanced attribute correlation structure. The purely GenAI-informed Q-matrices showed mixed results: there were some improvements in relative fit and slip stability compared to manually constructed Q-matrices, but variable absolute fit and attribute correlation patterns. The findings substantiate GenAI as a feasible pathway for enhancing the efficiency, consistency, and psychometric quality of Q-matrix construction. This study offers a preliminary framework for advancing CDA development, addressing a key methodological bottleneck in language assessment. Full article

This study investigates trellis shaping (TS) for mitigating nonlinear impairments in photonic terahertz (THz) communication systems. A parallel shaping architecture integrating hierarchical modulation (HM) with adjustable power allocation is proposed. The scheme applies TS to structure the data stream hierarchically and employs superposition coding (SC) to generate non-uniformly distributed TS-16QAM signals, enhancing transmission performance. Experimental validation over a 5-m link at 320 GHz demonstrates that the proposed scheme achieves a 1.65 dB improvement in input power sensitivity and a 1.39 dB gain in Q-factor compared to the Maxwell–Boltzmann (MB) distribution. Furthermore, the system provides enhanced power allocation flexibility, expanding the tunable range of the hierarchical power ratio by a factor of 1.37. Full article

Accurate permittivity characterization at terahertz frequencies is important for material analysis and device design, yet it remains challenging for small-volume samples and compact test structures. In this work, a terahertz permittivity sensor based on a spoof surface plasmon polariton (SSPPs) transmission line coupled to a backside split-ring resonator (SRR) is proposed and numerically studied. The SSPPs line is patterned on the top side of the substrate, while the SRR is etched on the backside, with the sample loaded into the SRR gap. The SSPPs mode penetrates through the substrate and excites the SRR, producing a pronounced transmission notch. Changes in the sample permittivity modulate the effective capacitance of the resonator, resulting in a monotonic shift in the notch center frequency. For relative permittivities from 1 to 8, the notch center frequency decreases from 152.1 GHz to 117.8 GHz, corresponding to a total shift of 34.3 GHz and an average sensitivity of about 4.90 GHz/ε_r. The minimum S₂₁ remains within approximately −23.80 to −21.56 dB, while the Q-factor stays in the range of 94.33–108.23, indicating good spectral readability. Tolerance analysis further shows that the resonance frequency is sensitive to critical structural dimensions and layer alignment, and practical implementation is therefore more suitable for single-device calibrated frequency-shift sensing. These results demonstrate the feasibility of the proposed dual-layer SSPPs–SRR configuration for compact permittivity sensing in the terahertz regime. Full article

Specific Emitter Identification (SEI) distinguishes individual emitters by extracting subtle features from intercepted radio frequency signals. This process relies on the design and extraction of specific features. Current methods for selecting and characterizing radio frequency fingerprints vary by individual, and the extraction process is closely coupled with environmental conditions. As a result, the generality of such identification algorithms is often limited, particularly when the application environment does not match the premise of feature design, leading to rapid degradation or even failure of individual identification performance. This paper proposes a deep clustering model based on polarization feature learning for identifying individual communication emitters. The approach involves constructing a guided network to extract datasets of polarization features from communication signals and utilizing a contrastive representation learning network to extract dual-polarization features from I/Q data samples. Subsequently, a Bayesian nonparametric (BNP) class mixture model algorithm, capable of inferring an unknown number of clusters, is employed to build a multi-level clustering network for clustering analysis of the extracted features. Under 5 dB conditions, the method described in this paper achieves an average recognition accuracy of 87.5%. Full article

This article presents a novel compact high-Q bandpass filter (BPF) utilizing a 3-D stacked stripline configuration. T-shaped stepped impedance resonators (SIRs) are employed to achieve miniaturization. By folding the filter geometry from an inline arrangement into a U-shape along the broadside direction, both broadside and edge coupling structures are realized, enabling various cross-coupling schemes for flexible placement of transmission zeros (TZs). A comprehensive analysis of both electric and magnetic coupling structures is conducted to support the overall filter design. To validate the concept, a tenth-order general Chebyshev BPF prototype centered at 3.485 GHz with a 1 dB bandwidth of 380 MHz is designed, fabricated, and measured. The filter is constructed by vertically soldering two patterned sheet metal layers together with three stacked cavities. Despite having an electrical size of only 0.58 × 0.23 × 0.19 λ_g³, the filter exhibits a high unloaded Q-factor (Q_u) of 1200, along with up to six TZs and a spurious-free frequency range extending to 12 GHz. Measured results show an insertion loss of 0.58 dB at the center frequency and a return loss of better than 20 dB within the passband, demonstrating favorable agreement with simulations. Featuring solid electrical performance, the proposed filter is ideally suited for 5G and 5G-Advanced (5G-A) communication base stations. Full article

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. The Shen-Kang Recipe (SKR) is a traditional Chinese medicine formula used clinically to slow DKD progression, but its bioactive constituents and molecular targets remain unclear. Solute carrier family 15 member 2 (SLC15A2/PEPT2), a high-affinity peptide transporter expressed in renal proximal tubules, has been implicated in kidney pathophysiology, yet its potential role in mediating the therapeutic effects of the SKR has not been explored. Here, we evaluated the effects of the SKR in db/db mice and found that SKR treatment significantly improved renal function, attenuated glomerulosclerosis, and reduced interstitial collagen deposition. Wide-target metabolomics and quantitative proteomics revealed that the SKR broadly reversed DKD-associated metabolic and proteomic disturbances, particularly in pathways related to energy and amino acid metabolism. Proteomic analysis identified SLC15A2 as a key proximal tubule protein downregulated in DKD and selectively restored by the SKR. UPLC-Q-TOF/MS-based serum pharmacochemistry and network pharmacology highlighted quercetin as a principal bioactive component of the SKR. Molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) confirmed direct, high-affinity binding between quercetin and SLC15A2 (KD = 7.5 µM). In TGF-β1-stimulated HK-2 cells, quercetin suppressed epithelial-mesenchymal transition (EMT), as evidenced by restored E-cadherin and reduced N-cadherin, vimentin, and α-SMA expression; this effect was abrogated by siRNA-mediated SLC15A2 knockdown, demonstrating the functional necessity of this axis. Collectively, these findings identify a quercetin-SLC15A2 axis through which the SKR inhibits EMT and alleviates renal fibrosis in DKD, providing a mechanistic basis for its clinical application and nominating SLC15A2 as a potential therapeutic target. Full article