Search Results (2,325)

Electric vehicle (EV) powertrains involve complex interactions between speed regulation, energy consumption, regenerative braking, and battery thermal behavior. Most existing approaches address controller tuning and energy management separately, which may limit the overall system performance. This paper proposes an integrated deep reinforcement learning (DRL) strategy in which a single Twin Delayed Deep Deterministic Policy Gradient (TD3) agent simultaneously adjusts the proportional and integral gains of the speed controller (K_pv, K_iv), the torque modulation coefficient (K_s), and the regenerative braking factor (β_reg). A multi-objective reward formulation is adopted to account for speed tracking performance, energy efficiency, regenerative energy recovery, battery thermal constraints, and driving comfort. The framework is implemented through a MATLAB R2022b/Simulink–Python 3.10 co-simulation environment that enables online interaction between the EV model and the learning agent. Performance is evaluated using the Worldwide Harmonized Light Vehicle Test Procedure (WLTP). Compared with a conventional fixed-gain PI controller, the approach reduces gross energy consumption by 16.2%, decreases speed tracking error by 43.7%, increases regenerative energy recovery by 21.4%, limits battery temperature rise by 30.4%, and lowers RMS jerk by 33.7%. The results indicate that jointly optimizing control and energy management variables can improve both vehicle dynamic performance and energy utilization. The methodology offers a practical framework for the development of adaptive and intelligent control systems in future electric vehicles. Full article

This study evaluates operational decarbonisation options for container vessels operating under the European Union Emissions Trading System (EU ETS) and FuelEU Maritime. This study analyses a 5000 TEU post-Panamax container vessel on the Rotterdam–Limassol route under nine operational scenarios combining three operating speeds (24, 21, and 19 kn) with three fuel configurations (HFO, MGO, and a B30 biofuel blend). The assessment included voyage-level fuel consumption, CO₂ emissions, Energy Efficiency Operational Indicator (EEOI), Tank-to-Wake (TTW) greenhouse-gas intensity, fuel cost, EU ETS exposure, Pareto trade-off analysis, and Monte Carlo uncertainty evaluation. Pareto analysis reduced the nine evaluated scenarios to three representative low-speed operating configurations corresponding to minimum cost (HFO, 19 kn), intermediate emissions reduction (MGO, 19 kn), and minimum emissions (B30, 19 kn). Among these configurations, the B30 case produced the lowest TTW GHG-intensity and EEOI values, whereas the HFO case remained the least-cost option under current market conditions. The break-even assessment indicates that B30 becomes cost-competitive with HFO slow steaming only at carbon prices of approximately 754 EUR/tCO₂ under reference market conditions—substantially above current EU ETS levels (50–80 EUR/tCO₂). Sensitivity analysis shows that reducing the B30 price from 900 USD/t to 720 USD/t lowers this threshold to approximately 406 EUR/tCO₂. The results quantify the current economic gap for transitional biofuels under the EU ETS alone and highlight the complementary role of FuelEU Maritime lifecycle incentives. Key limitations include TTW-based emissions accounting and steady-state operational assumptions. Full article

Rhino-orbital mucormycosis is a rare, life-threatening opportunistic fungal infection, typically affecting immunocompromised patients. During the COVID-19 pandemic, increased cases were mainly linked to SARS-CoV-2 infection, diabetes, and corticosteroid exposure. We report a severe case in a previously healthy 44-year-old immunocompetent man who developed acute left-sided exophthalmos, ophthalmoplegia, severe visual loss, and systemic deterioration 10 days after AZD1222 COVID-19 vaccination. Clinical and radiologic findings suggested invasive rhino-orbital fungal disease, prompting immediate liposomal amphotericin B, broad-spectrum antibiotics, urgent endoscopic sinus surgery, and repeated orbital–sinonasal debridements with amphotericin B irrigation. Histopathological examination demonstrated broad aseptate hyphae with tissue necrosis, consistent with mucormycosis, while fungal culture and ITS sequencing identified Rhizopus arrhizus as the causative species. Therapy was later adjusted to include isavuconazole and antibacterial coverage for persistent inflammation and secondary colonization. Orbital and systemic improvement occurred within the first week, with globe preservation and marked proptosis reduction at 6 months, despite persistent ophthalmoplegia and residual light perception. Isavuconazole was continued for 2 years, with no recurrence during 3 years of follow-up. Although causality with vaccination cannot be established, the temporal association and biological plausibility warrant further investigation. Early suspicion and prompt combined medical–surgical management are essential in rapidly progressive orbital cellulitis. Full article

Human viral entry receptor mouse models exist to overcome a fundamental experimental barrier: many clinically important viruses bind their human entry factors far more efficiently than the corresponding murine orthologs, leaving conventional mice unable to support authentic infection, physiological tissue tropism, or meaningful countermeasure evaluation. This review is organized around the receptor-humanization concept rather than around a single coronavirus model. Engineering strategies compared here include random transgenesis, endogenous-locus knock-in, minimal receptor-interface humanization, conditional and inducible expression, and transient vector-mediated delivery. Receptor systems covered span human angiotensin-converting enzyme 2 (hACE2)-dependent sarbecoviruses, human dipeptidyl peptidase 4 (hDPP4)-dependent Middle East respiratory syndrome coronavirus (MERS-CoV), human cluster of differentiation 4/human C-C chemokine receptor type 5 (hCD4/hCCR5)-dependentt human immunodeficiency virus type 1 (HIV-1), adenovirus receptor models, human intercellular adhesion molecule 1 (hICAM-1) rhinovirus systems, hepatitis C virus (HCV), hepatitis B virus (HBV), and hepatitis D virus (HDV) entry-factor models, measles receptor models, poliovirus receptor/CD155 (PVR/CD155) models, human scavenger receptor class B member 2 (hSCARB2) enterovirus systems, and human transferrin receptor 1 (hTfR1) arenavirus models. We then discuss how these platforms support antibody evaluation, Fc-effector analysis, vaccine protection, variant benchmarking, and safety assessment. These models yield the most reliable data when the experimental question is explicitly entry-dependent and when receptor expression level, anatomical distribution, pathology window, and immune context have all been independently validated. They are least informative when receptor expression is non-physiological, when disease readouts are driven by promoter artifacts, or when post-entry species barriers remain the dominant bottleneck. A validation-centered framework is therefore proposed to guide the selection of each model for the specific antiviral antibody or vaccine question it can legitimately answer. Full article

Density Functional Theory (DFT) calculations were applied at the B3LYP/6-311G+(d,p) level to examine how nitrogen (N) and boron (B) and combined nitrogen/boron doping (N/B) affected the electronic properties and chemical behavior of graphene oxide (GrO). The work aimed to measure how global reactivity descriptors, including ionization potential, chemical hardness, and electrophilicity, changed when dopants entered the system while evaluating their prediction accuracy for gas sensing performance against NH₃ and H₂O and CO₂. The results show that undoped GrO exhibits a HOMO/LUMO gap value of 2.9059 eV while the introduction of dopants increases reactivity through gap reduction because N-doping decreased the gap to 1.3622 eV, B-doping reduced it to 1.3388 eV, and co-doping (GrO-NB) led to a gap of 1.9897 eV. The TDM analysis and the gas interaction energy gap results show that GrO-NB-H₂O exhibits the strongest interaction which results in chemical reactivity through its lowest ΔE of 1.9565 eV, establishing itself as a highly sensitive water vapor sensor when compared with NH₃ and CO₂. With adsorption energies of −0.1986, −0.1742, and −0.0735 eV for NH₃, H₂O, and CO₂, respectively, the N/B co-doped graphene oxide demonstrated favorable and reversible physisorption, underscoring its potential for gas sensing applications. The results offer an essential understanding of how N/B co-doping influences the electronic and adsorption characteristics of graphene oxide, thereby supporting its potential use in graphene-based sensing technologies. Full article

The PhoP–PhoR two-component system (TCS) controls transcription of the Pho regulon in response to inorganic phosphate limitation in Bacillus subtilis. In addition to its role in phosphate homeostasis, increasing evidence suggests that central metabolic pathways influence Pho regulon activity. Here, we investigated the mechanism underlying phosphate-independent activation of the Pho regulon in a ccpA mutant lacking the global regulator of CCR. Gene expression analyses demonstrated strong glucose-dependent induction of Pho regulon genes in the absence of both CcpA and the cognate histidine kinase PhoR. Using PhosTag gel electrophoresis analysis and a phoasphoablative mutation in phoP (D53A), we detected early PhoP phosphorylation and determined that Pho regulon activation requires a phosphorylatable form of PhoP, even when the cognate histidine kinase phoR gene was deleted. Because PhoR can phosphorylate non-cognate response regulator YycF, we examined whether the essential YycFG signaling system contributes to PhoP activation. Co-immunoprecipitation and in vitro phosphorylation assays confirmed a direct interaction between PhoP and YycG and demonstrated in vitro PhoP phosphorylation by YycG. Taken together, we propose a model in which CcpA limits excessive PhoP accumulation to preserve signaling specificity and prevent aberrant activation through non-cognate kinases. Furthermore, our study reveals a previously unrecognized link between carbon catabolite repression and phosphate starvation signaling and demonstrates another crosstalk between two-component signal transduction systems in the Gram-positive bacterium, B. subtilis. Full article

The increasing discharge of pharmaceutical contaminants, particularly antibiotics like metronidazole (MNZ), into water systems poses significant ecological and public health risks due to their high solubility and low biodegradability. This study developed and characterized a highly porous activated carbon derived from maize cob (MC-AC). The synthesized material was characterized using FTIR, FESEM, PXRD, HRTEM, and BET analysis. Batch adsorption experiments were conducted, and the removal efficiency of MC-AC for MNZ was 98.6%. Optimization and modeling of the process variables of pH (3–11), contact time (0–75 min), concentration (0–70 mg/L), temperature (25–35 °C), and adsorbent dosage (0.5–1.5 g/L) were investigated using the Box–Behnken design (BBD) of response surface methodology, and 29 runs were obtained. The BBD model determined an optimal removal efficiency of 94.6 for metronidazole. Furthermore, non-linearized kinetic and isotherm models were used to determine the adsorption mechanism and mode of metronidazole from water. From the investigation, it was observed that both the Freundlich and pseudo-second-order models exhibited high correlation coefficients. The models with the best performance and low error metrics were determined by R², MSE, RMSE, SAE, and SSE. Therefore, the adsorption mode was multilayer heterogeneous, and the mechanism was chemisorption. Therefore, this study provides a unique alternative for using the Box–Behnken design, kinetic, and isotherm models to understand the removal of metronidazole from water using maize cob-activated carbon. Full article

Diabetic retinopathy (DR) reflects retinal microvascular injury and systemic immune-metabolic stress, and most public DR transcriptomic datasets lack paired microbiome/metabolomic profiles. We used gutMGene v2.0 as a curated microbe/metabolite–host gene prior and integrated it with peripheral blood transcriptomics from GSE221521. Candidate genes were refined by weighted gene co-expression network analysis (WGCNA), repeated resampling, cross-dataset assessment, mechanism scoring, peripheral blood mononuclear cell (PBMC) single-cell localization and filamin A (FLNA)-centered single-cell gene regulatory network (GRN) virtual knockout. The gutMGene prior contained 238 host genes; 15 DR-associated genes overlapped this prior, and WGCNA retained ten candidate gut microbe and microbial metabolite-related genes (GMMRGs): FLNA, AKT1, IRAK1, BCL10, CDK6, CTSD, JUP, CXCL1, CXCR2 and IL4R. Resampling prioritized FLNA as the most consistent candidate. Cross-dataset assessment localized the strongest signal to type 2 diabetes (T2D) PBMCs, retinal endothelial cells and advanced proliferative diabetic retinopathy with diabetic macular edema (PDR + DME) retinal tissue, with weaker separation in whole blood, broad retinal tissue and six-donor type 1 diabetes (T1D) PBMCs. FLNA virtual knockout predicted cell-context-dependent perturbation of immune-related transcriptional programs, including IL4R in DR B cells and CTSD in DR monocytes/NK cells. This prior-guided study identifies FLNA within a ten-gene GMMRG set as a circulating host-response signal that links curated microbe/metabolite–host records to immune-vascular and cytoskeletal remodeling in DR. Full article

Colorectal cancer (CRC) exhibits a highly heterogeneous tumor immune microenvironment (TME), ranging from “immune-inflamed” to “immune-desert” or “immune-excluded” phenotypes. Understanding how immune cell composition, cytolytic activity (CYT) and genomic alternations shape tumor-immune interactions is critical for improving immunotherapy outcomes. We analyzed TCGA-COAD and TCGA-READ datasets to evaluate immune competency, CYT, immune subtypes, microsatellite instability (MSI), and genomic instability, including somatic mutations, copy number aberrations (CNAs), and chromothriptic events. Immune cell infiltration was correlated with CYT levels, immune checkpoint expression, and immune-related gene signatures. Immune-competent (IC) tumors were predominantly CYT-high, enriched in stromal and immune scores, and exhibited distinct TME characteristics compared with immune-deficient (ID) tumors. IC/CYT-high tumors expressed higher levels of immune checkpoints (PD-1, PD-L1, CTLA-4, IDO1/2, LAG-3) and cytokines/chemokines (C1QA/B/C, CXCL9/10/11, CXCL13). Differences in immune infiltration were observed across tumors with significant mutations and copy number alterations. No prognostic difference was observed between CYT-high and CYT-low patients, indicating that CYT reflects immune activation rather than clinical outcome. Functionally, stimulated CD8⁺ T cells exhibited cytotoxicity activity against MSI-high (HCT-116) and microsatellite-stable (HT-29) CRC cells, with MSI-H cells showing higher sensitivity. Dynamic 3D co-culture demonstrated tumor-guided T cell infiltration and retention of CD8 expression, and co-culture was associated with moderate upregulation of cytotoxicity-related genes GZMA and PRF1 within the system. Cytotoxic activity decreased at lower effector-to-target ratios, highlighting the importance of effector dose. Overall, these findings link CYT, immune competency, MSI status, and genomic instability to T cell cytotoxic responses, providing insights into tumor-immune interactions, and suggest potential associations relevant for immunotherapy research in CRC. Full article

Messenger RNA (mRNA) vaccines represent a transformative platform in vaccinology, with applications extending beyond SARS-CoV-2 to other infectious diseases and cancer immunotherapy. However, patients with solid tumors receiving active anticancer treatment were largely underrepresented in pivotal vaccination trials, limiting understanding of vaccine-induced immunity in this population. In this prospective exploratory study, we assessed humoral and cellular immune responses after two doses of SARS-CoV-2 mRNA vaccines in 39 patients with solid tumors undergoing active treatment. Blood samples were collected before vaccination and approximately two months after the second vaccine dose, prior to the next treatment cycle. Anti-spike IgG, neutralizing antibodies, receptor-binding domain (RBD) levels, interleukin-6 (IL-6), hematological parameters, immune cell subsets, T-cell differentiation, and early apoptosis in αβ and γδ T-cell subsets were analyzed. Vaccination induced a robust humoral response, with high post-vaccination anti-spike IgG levels (median 988.69 BAU/mL), 97.44% seropositivity, 96.88% true seroconversion among baseline IgG−/NAb− patients, and strong neutralizing antibody activity (median 85.73%). Hematological parameters and IL-6 levels remained broadly stable, suggesting no detectable increase in systemic inflammation during the study period. Cellular analyses identified a reduction in peripheral CD19+ B-cell frequencies and decreased early apoptosis, particularly in CD8+ T cells and CD3+CD56+ NKT-like cells. Although changes in T-cell frequencies and differentiation profiles were also observed, these findings were attenuated after exclusion of participants with possible prior SARS-CoV-2 exposure and should be interpreted as exploratory. Overall, these results show that patients with solid tumors receiving active treatment can mount robust humoral responses to SARS-CoV-2 mRNA vaccination and suggest measurable post-vaccination changes in lymphocyte dynamics, including reduced early T-cell apoptosis. Full article

In view of the advantage of cross-polarized inspection (CrPI) in microwave nondestructive testing (MNT), in this paper a dual-polarized narrow-beam antenna as the pivotal reflectometric sensor is systematically designed and realized particularly for enhancement of detection and imaging of subsurface defects in dielectric structures. The antenna is equipped with a compact asymmetric waveguide orthomode transducer, with Teflon used as the internal filling material, in an effort to reduce its size and narrow the beamwidth. The internal dimensions of the realized dual-polarized narrow-beam antenna are optimized via numerical simulations. Based on the optimal design parameters, the antenna is fabricated and assessed through experiments. The experimental results reveal that the fabricated antenna has better metric indicators in terms of a return loss better than 10 dB, isolation better than 40 dB in 30.0 GHz~36.0 GHz and half-power beamwidths below 36.9° at 36.0 GHz. In order to further affirm the applicability of the fabricated antenna for CrPI, an MNT system is established to perform two-dimensional scanning and imaging of back-surface volumetric defects in polyethylene specimens. Based on the image characteristics of CrPI, a flaw-recovery algorithm is proposed to retrieve the defect opening profile. The averaged contrast-to-noise ratio of the processed CrPI-based image is found to be approximately five times larger than that of the raw CrPI-based image and fourteen times bigger than that of the raw CoPI-based image. Experimental results have further indicated that the fabricated antenna is feasible for not only co-polarized inspection (CoPI) but for CrPI, which exhibits higher testing sensitivity and defect-image contrast than CoPI. In conjunction with the flaw-recovery algorithm, by utilizing the dual-polarized narrow-beam antenna with the better metric indicators for CrPI, the image quality of the back-surface flaws in polyethylene slabs can be effectively improved. Full article

Background: Despite the circulation of evolutionarily related cold-causing coronaviruses (CCCs) in the pre-COVID era, most individuals lacked pre-existing serum IgG and/or class-switched memory B cell (B_mem) reactivity for the SARS-CoV-2 Spike (S) glycoprotein expressed by the ancestral Wuhan-Hu-1 (WH1) strain. Subsequent priming of the immune system through natural infection or prophylactic COVID-19 mRNA vaccination successfully generated robust B_mem responses against the WH1-S antigen, along with eliciting cross-reactivity for the future Omicron (BA.1) variant responsible for breakthrough infections (BTIs). However, to what extent immunological imprinting of B_mem towards the WH1-S antigen detrimentally constrains the elicitation of variant-specific antibody responses following subsequent booster vaccinations or BTIs—a phenomena referred to as “original antigenic sin”—remains an unresolved and open question. Methods: Using ImmunoSpot^®, we evaluated peripheral blood mononuclear cells (PBMCs) from defined human cohorts for IgG⁺ ASC reactivity against Spike proteins representing CCCs and SARS-CoV-2. Additionally, we developed a novel dual-label inverted FluoroSpot assay to distinguish between strain-specific and cross-reactive IgG⁺ ASCs recognizing epitopes in the receptor binding domain (RBD) of SARS-CoV-2 Omicron variants. Results: Our data demonstrate a lack of appreciable back-boosting of IgG⁺ B_mem recognizing structurally conserved epitopes shared between CCCs and SARS-CoV-2. Moreover, we found evidence for immunological imprinting and the preferential expansion of B_mem recognizing cross-reactive epitopes in the RBD following BTI. Nevertheless, Omicron strain-specific B_mem were detected in PBMC donors collected in 2025. Conclusions: Our novel inverted dual-label FluoroSpot methodology evidenced preferential expansion of cross-reactive B_mem following breakthrough SARS-CoV-2 infection and supports the influence of original antigenic sin shaping the recall response. Moreover, the inverted dual-label assay provides a highly flexible and easily implementable technique for distinguishing between strain-specific and cross-reactive B cell responses and has broad applications in translational vaccine research against pathogens that undergo antigenic drift. Full article

Following the integrated optical assembly and single printed circuit board co-layout design concept for electrical circuits, this paper develops a field-programmable gate array (FPGA) based, miniaturized, eight-channel microwave photonic transceiver stabilization system for the joint regulation of lasers and Mach–Zehnder modulators (MZMs). The integrated single-board hardware enables high-precision, high-reliability automatic temperature control (ATC), automatic power control (APC), and arbitrary closed-loop control of the MZMs bias point, overcoming the drawbacks of discrete single-channel, independent control schemes reported in previous works, which lack expandability for large radar arrays. The laser sub-module supports continuously adjustable drive current and multi-level protection, achieving wavelength stability of 0.01 nm and an output optical power fluctuation of less than 0.02%. The MZM control unit delivers wide-range, high-stability bias drift suppression with arbitrary bias point stability up to 0.05 dB. All static and dynamic performance indicators of the proposed module are characterized using a dedicated experimental setup comprising optical power meters, optical spectrum analyzers, temperature cycling chambers, and vector signal analyzers. Leveraging FPGA-based parallel hardware logic, the system features low latency, low jitter, cross-channel mismatch compensation, and excellent timing synchronization, with a compact overall footprint of 180 mm × 120 mm that matches the size of radar antenna panels and supports flexible array scaling. The proposed integrated module meets the low-noise, high-reliability, and high-integration requirements of radio-over-fiber links in microwave photonic radars. It effectively advances the practical engineering deployment of microwave photonic radar systems. Full article

Skeletal muscle is increasingly recognized as a dynamic secretory organ capable of translating contractile, metabolic, mechanical and inflammatory stimuli into systemic biological signals. Among these signals, myokines and myokine-associated exerkines mediate communication between skeletal muscle and distant organs, influencing glucose and lipid metabolism, immune regulation, bone remodeling, neuroplasticity, vascular function and tissue regeneration. Representative mediators considered include IL-6, IL-15, myostatin, follistatin, decorin, FNDC5/irisin, FGF21, myonectin/CTRP15, BDNF, cathepsin B, SPARC, apelin and extracellular-vesicle cargo. However, current evidence remains fragmented across individual molecules, exercise modalities, sampling windows, assay platforms and disease contexts. This narrative mechanistic review proposes the concept of the “myokine adaptome” as an integrated, context-dependent signaling network through which skeletal muscle contributes to systemic homeostasis in health and disease. We synthesize evidence on cellular triggers of myokine release, including AMPK-PGC-1α signaling, mTORC1-dependent mechanical sensing, calcium flux, redox signaling, inflammatory pathways and extracellular-vesicle-mediated communication. We further examine how exercise modality, aging, obesity, type 2 diabetes, sarcopenia, osteoporosis, cardiovascular disease, COPD, cancer/cachexia and chronic inflammation reshape myokine production and target-organ responsiveness. The central argument is that myokine biology should be interpreted not as a catalog of isolated mediators, but as a dynamic adaptive code defined by signal amplitude, temporal pattern, molecular composition, delivery route and recipient-tissue sensitivity. Its novelty is operational rather than nominal: it requires source confidence, temporal kinetics, co-signal context, delivery route and functional decoding to be evaluated together. This framework may improve biomarker design, disease-specific exercise prescription and therapeutic strategies aimed at restoring adaptive muscle–organ communication. The framework is further strengthened by testable predictions concerning adaptive pulsatility, modality-specific signatures, source attribution, recovery quality, disease-specific decoding and the superiority of multi-marker panels over single-molecule readouts. Full article

Background: Wastewater systems provide an integrated One Health perspective on antimicrobial resistance but remain uneven globally, with limited data from rapidly urbanizing and highly connected regions such as the Arabian Gulf. Methods: An eight-month prospective study was conducted in Dubai, United Arab Emirates, with monthly sampling from nine community and two hospital nodes and two wastewater treatment plants (WWTP). Samples were analysed using high-throughput quantitative PCR (HT-qPCR; Resistomap, Finland) with a 72-target One Health gene panel. Results: Across the 120 samples analyzed, the number of detected gene targets ranged from 26 to 68 genes, with the highest diversity in hospital wastewater and the lowest in WWTP effluent. Pathogen-associated markers were detected in all sources, with enterococci, Escherichia coli, and Klebsiella pneumoniae predominant. Hospital wastewater showed broader pathogen-associated gene markers, including those linked to Acinetobacter baumannii and Pseudomonas aeruginosa. Antibiotic resistance genes (ARGs) associated with macrolide–lincosamide–streptogramin B, tetracycline, and aminoglycoside resistance were widespread. Community and influent samples were dominated by msrE, tet(M), and aminoglycoside resistance genes, whereas hospital wastewater showed the highest ARG burden, including enrichment of aac(6′)-Ib, qnrS2, bla_GES, bla_TEM, bla_KPC-2, and bla_IMP-1. Several ARGs, including mcr-1, persisted in WWTP effluent. Mobile genetic elements (MGEs) were ubiquitous, with integron-associated markers prominent in WWTP effluent. ARG–MGE network analysis demonstrated extensive co-occurrence, with MGEs as central hubs linking multiple ARGs. Conclusions: Wastewater captures distinct resistome profiles across urban compartments, supporting its role for AMR surveillance. The persistence of ARGs and MGEs in WWTP effluent highlights the potential for environmental dissemination, through reuse of treated wastewater. Full article