Search Results (646)

Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated substantial efficacy in improving glycemic control and reducing body weight. However, subcutaneous injection is poorly adherent for patients. To improve treatment compliance, we developed a poly(lactic-co-glycolic acid) (PLGA)-based nanovesicle (PLGA-Lira-NV) system for the oral delivery of Lira using a double-emulsion solvent evaporation technique. The optimized formulation yielded a narrow size distribution and high encapsulation efficiency (>95%). In vitro release studies showed that PLGA-Lira-NVs remained relatively stable under acidic conditions (pH 1.2 to 6.8) and exhibited sustained drug release in a neutral environment (pH 7.4), enabling protection of the fragile peptide in the stomach and controlled release after crossing the intestine. Following oral administration to obese mice (10 mg/kg), PLGA-Lira-NVs achieved prolonged glycemic control for up to 72 h. Notably, body weight decreased to 83% of baseline after 12 days, outperforming the subcutaneous injection (free Lira) group (88%). The consistent trend toward weight reduction confirms the sustained-release properties of PLGA nanocarrier for Lira, highlighting its potential to reduce dosing frequency and improve patient compliance. Collectively, these findings underscore the promising potential of PLGA nanovesicles as an oral delivery platform for peptide therapeutics. Full article

As a leading method for Novel View Synthesis (NVS), 3D Gaussian Splatting (3DGS) faces limitations. Fixed thresholds governing Gaussian scale and opacity lead to over-reconstruction or under-reconstruction, while the linear penalty used for handling outliers during optimization tends to introduce artifacts. Therefore, we propose Adaptive 3DGS featuring a dynamic deletion mechanism. Specifically, our method calculates coverage for each Gaussian based on its scale during removal. Gaussians with high coverage face stricter scale thresholds to reduce over-reconstruction, while those with lower coverage receive lenient thresholds to preserve details. Simultaneously, transparency-based contribution assessment is applied. Gaussians with low contribution meet stricter transparency thresholds to combat over-reconstruction, while high-contribution ones get lenient thresholds to mitigate under-reconstruction. During optimization, introducing Huber loss promotes quadratic growth for small errors, reducing smoothing to alleviate artifacts and better preserve details. Evaluation on standard datasets shows our method improves peak signal-to-noise ratio (PSNR) by 0.3 dB over 3DGS and 0.5 dB over MS-3DGS at 4× resolution, and it achieves a 0.1 dB gain over Mip-Splatting, confirming its effectiveness and robustness. Full article

Hexagonal boron nitride (h-BN) has been widely applied in catalysis. Nevertheless, most research has focused on using h-BN as a substrate to anchor active transition metals, without probing the intrinsic activity of h-BN vacancies. In this work, we investigated the stability and catalytic activity of different h-BN vacancies. We found that B-terminated vacancies are more likely to be exposed under static conditions. The N_v, BN₂, and BN₃ vacancies show intermediate reaction energies for CH₄ activation. Although the B–N pair over the BN₂ vacancy model has the lowest barrier for CH₄ activation, the negative reaction energy could lead to a high potential for surface poisoning. Interestingly, the unsaturated B–B pair over N_v is a promising site for C–H bond activation. Further COHP analysis implies that the high C–H bond homolytic cleavage activity of the B–B pair arises from its relatively weak interaction, which can promote H insertion. Full article

Rydberg-atom electric-field sensors have emerged as an important research direction in quantum precision measurement, owing to their intrinsic SI traceability, noninvasive measurement capability, and wide frequency tunability. However, under free-space conditions, the geometric divergence of microwaves (MWs) limits the practical detection performance of the system. In this work, we propose and experimentally demonstrate a metasurface-assisted Rydberg-atom hybrid sensor. Through introducing wavefront shaping of the incident microwave field with a metasurface (MS), electric-field enhancement in the atomic sensing region is achieved. Without altering the intrinsic sensitivity of the Rydberg-atom sensor, the equivalent sensitivity of the hybrid sensor is improved to $57.3\mathrm{nV}{\mathrm{cm}}^{-1}{\mathrm{Hz}}^{-1/2}$. This scheme provides a new route toward high-sensitivity, integrated quantum sensing of the microwave electric field. Full article

Background: The triglyceride glucose index (TyG-i), a biomarker of insulin resistance, has been associated with adverse vascular outcomes and risk stratification in several cardiovascular and cerebrovascular phenotypes. However, data on TyG-i as a prognostic marker in spontaneous intracerebral hemorrhage (ICH) remain limited. Objective: To explore the association between TyG-i and 90-day functional outcome in patients with ICH. Methods: A retrospective analysis of adult patients admitted for non-traumatic small vessel disease-related ICH at three Italian neurological institutions was conducted. TyG-i was calculated on admission as Ln[(fast triglycerides (mg/dL) × fast glucose (mg/dL))]/2. Functional outcome was measured with the modified Rankin Scale (mRS) at 90 days from the index event. TyG-i was analyzed as a continuous variable and categorized in quintiles (Q1 to Q5). Predictors of poor outcome (mRS 4–6) were investigated with multivariable logistic regression. Results: A total of 463 patients were included, of whom 197 (42.5%) had poor outcome at 90 days. TyG-i analyzed as a continuous variable was not associated with unfavorable prognosis. TyG-i analyzed as a categorical variable stratified by quintiles showed a non-linear U-shaped relationship with functional outcome; patients in Q4 had the lowest risk of poor outcome (Q1 reference, OR 0.44, 95% CI 0.22–0.87, p = 0.019). Discussion: We found a potential non-linear relationship between TyG-i and ICH outcome, with higher odds of good prognosis in patients with intermediate values. Conclusions: TyG-i may represent a promising, low-cost and widely available biomarker that might improve prognostication in clinical practice, but further studies are needed. Full article

In this study, we investigate a class of mixed fractional partial integro-differential equations (FrPI-DE) involving symmetric singular kernels. The considered model problem involves Caputo fractional derivatives and integral operators that describe spatial interactions in a bounded domain. For the purpose of analysis, the original problem is reformulated in the form of a nonlinear Volterra–Fredholm integral equation (NV-FIE). The existence and uniqueness of the solution are established by the Banach fixed point theorem. To compute numerical solutions, a modified Toeplitz matrix method (TMM) is proposed to handle the singular kernel efficiently. The method transforms the integral equation to a system of nonlinear algebraic equations, which can be solved numerically. The convergence properties of the resulting numerical scheme are analyzed and illustrate the effectiveness of the method by providing numerical examples involving logarithmic, Cauchy-type, and weakly singular kernels. Numerical results indicate that the proposed method provides highly accurate approximations and exhibits stable convergence behavior for different parameter values. Furthermore, these results confirm the effectiveness and reliability of the proposed method for solving fractional integro-differential equations that include symmetric singular kernels. Full article

Quantum random number generation (QRNG) provides fundamentally unpredictable randomness derived from intrinsic quantum processes. In this work we demonstrate two solid-state, room-temperature QRNG implementations based on nitrogen-vacancy (NV) centers in diamond, i.e., ensemble fluorescence from nanodiamonds and single-photon emission from single NV centers located at the tips of fabricated diamond nanopillars for enhanced light collection efficiency, spatial isolation and minimized crosstalk. We compare entropy rates (above 0.98 bits), statistical performance, and robustness of both approaches in our experimental setup, the results contribute to establishing diamond-based QRNG as a scalable solution for quantum-secure randomness generation. Full article

Background/Objectives: Virtual surgical planning (VSP) and CAD/CAM technologies have revolutionized complex maxillofacial reconstruction. While high-resolution imaging is critical for these workflows, the specific clinical impact of photon-counting computed tomography (PCCT) remains to be fully established. This prospective pilot study evaluates the feasibility and clinical utility of integrating PCCT into the preoperative planning and surgical workflow of complex maxillofacial reconstructive cases. Methods: This feasibility study included ten patients requiring complex maxillofacial reconstruction with microvascular free flaps. All underwent preoperative imaging with photon-counting CT. Primary endpoints included clinical assessment of osseous invasion, reliability of donor-site vascular mapping from a single acquisition, and compatibility of PCCT datasets with VSP/CAD-CAM platforms. Secondary endpoints included resection margin status, flap survival, and short-term oncologic outcomes. Results: PCCT provided high-resolution visualization of cortical and medullary bone, enabling detailed assessment of tumor-related osseous involvement. In selected cases, findings supported refinement of resection planning when prior imaging had been inconclusive. Spectral reconstructions reduced metal artifacts and facilitated precise segmentation for multi-segment osteotomies. Donor-site vascular anatomy was successfully evaluated within the same scan, supporting operative planning without additional imaging. PCCT datasets were fully compatible with the virtual surgical planning (VSP) software used in this study (CMX Portal, version 2.6.1158, Medartis AG, Basel, Switzerland; or ProPlan CMF, version 5.7.8.025, Materialise NV, Leuven, Belgium) in all cases (100%). Reconstruction was completed successfully in all patients, with 100% flap survival and R0 margins in all malignant cases. No technical failures occurred during imaging transfer or CAD/CAM fabrication. Conclusions: The integration of PCCT into the surgical workflow proved technically feasible and clinically impactful. This pilot data supports its potential to enhance surgical precision and preoperative planning in complex jaw reconstruction. Full article

Bacterial endophytes isolated from medicinal and wild plant species have recently gained significant attention for their medicinal properties, often closely linked to those of their plant hosts. This study identified two endophytic Bacillus isolates using 16S rRNA sequencing-based phylogeny. The impact of sublethal concentrations (0.5 mg/mL) of cadmium and hydrogen peroxide on metabolite production and bioactivity was also investigated. Phytochemical testing and antimicrobial and antioxidant assays revealed shifts in metabolite production under stress conditions. According to the phylogenetic analysis, Bacillus sp. NV35 and NV1 are respectively related to Bacillus cereus and B. mycoides. Phytochemical screening of methanolic crude extracts from both isolates tested positive for alkaloids, flavonoids, and saponins. Notably, tannins were detected only after cadmium treatment, while steroids were present following exposure to both cadmium and H₂O₂. LC-MS fingerprinting confirmed the presence of several tannins and steroids in treated samples. The untreated crude extracts exhibited an IC₅₀ of ~3 mg/mL with the DPPH assay, which decreased to ~1.5 mg/mL after treatment with cadmium or H₂O₂, demonstrating enhanced antioxidant potential under stress conditions. Additionally, extracts from both treated and untreated bacteria displayed antimicrobial activity against selected bacterial pathogens, with MIC values ranging from 62.5 μg/mL to 125 μg/mL. LC-MS analysis identified various antimicrobial and antioxidant metabolites, including phenoxymethylpenicilloyl, maculosin, (S,R,S)-alpha-tocopherol, 3-indoleacrylate, procyanidin A2, cis-11-eicosenamide, 3-hydroxy-3-phenacyloxindole, and 9-octadecenamide. Full article

In this study, frequency locking technology is investigated for high-stability microwave frequency standards based on diamond nitrogen-vacancy (NV) centers. Conventional locking methods typically utilize the side peaks induced via Zeeman splitting; however, this approach renders the frequency output highly susceptible to ambient magnetic field fluctuations. To address this limitation, a robust frequency locking method based on the central peak of the Optically Detected Magnetic Resonance (ODMR) spectrum is proposed. By systematically optimizing the bias magnetic field, the proposed method exploits the central peak’s inherent insensitivity to magnetic field variations and its narrower linewidth in environments with weak magnetic fields, thereby enhancing the quality factor of the frequency discrimination curve. The experimental results demonstrate that the proposed scheme achieves closed-loop locking of the 2.87 GHz microwave frequency, reaching short-term frequency stability (Allan deviation) of 1.73 × 10⁻⁷ at 200 s. Comparative tests under gradient magnetic fields further confirm that central-peak locking significantly suppresses frequency drift compared to side-peak methods. This study provides a vital technical pathway for the development of miniaturized, interference-resistant solid-state quantum frequency standards. Full article

In response to growing concerns over global warming and energy sustainability, transitioning from fossil-fuel-based heating systems to renewable alternatives is essential. This study evaluates the economic and environmental performance of geothermal heat pumps for building heating and compares it with conventional coal-fired boilers, natural-gas boilers, and diesel furnaces. Using the heating degree-day (HDD) method, heating energy demand was analyzed for four U.S. cities—Anchorage (AK), San Francisco (CA), Salt Lake City (UT), and Las Vegas (NV)—representing diverse climatic zones. The analysis integrates thermodynamic and economic parameters, including the coefficient of performance (COP = 2–5) and annual fuel-utilization efficiency (AFUE = 80–97%), to evaluate heating-system performance and operational cost across different climatic regions. Sensitivity analysis with ±10% variations in fuel and electricity prices and system efficiencies demonstrates that geothermal heating remains the most stable and emission-efficient option under all scenarios. Results indicate that geothermal systems, despite higher reported initial investment, achieve lower operational and emissions-related costs and offer a robust and sustainable solution for decarbonizing building-heating systems. For example, the estimated seasonal geothermal heating cost is $370.59 in Anchorage compared with $646.48 for coal heating and $3375.65 for diesel systems. Furthermore, policy evaluation indicates that federal and state incentives, such as investment tax credit under the Inflation Reduction Act and rebate programs, can reduce installation costs by 25–40%, improving economic feasibility, particularly in colder regions. The analysis focuses exclusively on energy and emissions-related costs and does not explicitly model capital investment or levelized cost metrics. Full article

Parkinson’s disease (PD) and associated synucleinopathies are preceded by a prolonged prodromal phase during which neurodegenerative processes evolve years before the onset of motor or cognitive symptoms. Identifying biologically specific and accessible biomarkers during this window is critical for early diagnosis, risk stratification, and the development of disease-modifying therapies. Increasing evidence supports the skin as a key peripheral tissue involved in synucleinopathy, offering a minimally invasive source for in vivo detection of pathological α-synuclein. This review summarizes current evidence on skin-derived biomarkers across the prodromal continuum of PD, with particular emphasis on skin biopsy-based detection of phosphorylated α-synuclein and α-synuclein seed amplification assays (SAAs). Findings in high-risk prodromal phenotypes, including idiopathic REM sleep behavior disorder (iRBD) and pure autonomic failure (PAF), are critically reviewed. Emerging data suggest that cutaneous α-synuclein pathology may precede nigrostriatal dopaminergic degeneration and may predict phenoconversion to overt synucleinopathies. Important knowledge gaps are highlighted, including the lack of data in other prodromal phenotypes such as hyposmia. Overall, skin-based biomarkers appear to represent promising, scalable tools for biological diagnosis, prognostication, and enrichment of prodromal PD cohorts in clinical trials. Full article

Background/Objectives: The retina is enriched in polyunsaturated fatty acids (PUFAs) which are indispensable for normal vision, and recent clinical studies have shown that dietary supplementation of ω-6-and ω-3-polyunsaturated fatty acids (PUFAs) can provide a protective role against retinopathy of prematurity (ROP). Our study aims to understand the mechanisms by which altering ω-6-and ω-3-polyunsaturated fatty acids (PUFAs) in the eye can protect against pathologic retinal neovascularization (NV). Methods: We interrogated the effects of endogenous ω-3-PUFA enrichment using transgenic fat-1 mice which convert ω-6-PUFAs to ω-3-PUFAs in the oxygen-induced retinopathy (OIR) murine model. In the OIR model, mice are exposed to 75% oxygen from postnatal day 7 (P7) to P12, then returned to room air (RA). We used a combination of immunofluorescence, bulk retinal RNA sequencing, and lipid mediator profiling by UHPLC-MS/MS in P17 mouse retinas to identify mechanisms underlying the protective effect against NV seen in fat-1 mice exposed to OIR. Results:Fat-1 OIR mice were protected against the development of retinopathy, demonstrating 15.1% less vaso-obliteration (75.5% relative reduction) after OIR and a 6.1% reduction in neovascularization (71.8% relative reduction) at P17 (p < 0.0001 for both). We found a dampened transcriptional response to OIR in the retina of fat-1 mice as compared to WT mouse retinas (198 vs. 782 genes, adjusted p-value < 0.01). Pathway analyses confirmed these findings, with significant OIR-induced transcriptional shifts in angiogenesis (adjusted p-value < 10⁻²⁷), inflammation (adjusted p-value < 10⁻²⁵), and microglial activation pathways (adjusted p-value < 10⁻⁹) in WT mouse retina that were not observed in fat-1 mice. Enrichment scores obtained through the integration of our bulk transcriptomics data with cell-resolved retina data indicate that the protective phenotype observed in fat-1 mice could be associated with intrinsic differences in microglia cell subtypes between WT and fat-1 mice. In situ, WT OIR mice demonstrated an increase in Iba1+ microglia compared to WT RA mice, whereas fat-1 OIR mice showed no difference when compared to fat-1 RA mice. Three ARA-derived oxylipins, 12-hydroxyeicosatetraenoic acid (12-HETE), prostaglandin D2 (PGD2), and thromboxane B2 (TXB2) demonstrated a pattern of upregulation in WT OIR compared to WT RA, but no upregulation in fat-1 OIR mice compared to fat-1 RA. Two EPA-derived specialized pro-resolving mediators and two LA-derived oxylipins were also differentially expressed. Conclusions: These findings show that a lower ω-6:ω-3 protects against neovascularization and is associated with attenuation of hyperoxia-induced microglial recruitment and activation, as well as inflammation and angiogenic signaling. Full article

To address complex noise in nitrogen-vacancy center fluorescence signal acquisition, a hybrid denoising framework combining marine predators algorithm-optimized variational mode decomposition (VMD) and wavelet thresholding is proposed. MPA adaptively selects VMD parameters, enhancing decomposition reliability. Wavelet thresholding then suppresses noise-dominant intrinsic mode functions while preserving signal components. Results show significant SNR improvement to 57.12 dB (14.6% higher than standalone VMD), RMSE reduction by 56.7%, and 7.9% SNR enhancement over wavelet thresholding alone, with the correlation coefficient reaching 0.97. More importantly, the proposed method substantially improves the accuracy of ODMR resonance parameter estimation. Compared to wavelet denoising, RMSE of the center frequency is reduced by 29.8% and RMSE of the FWHM is reduced by 44.5%; compared to VMD denoising, the FWHM RMSE is reduced by 20.7% while maintaining comparable center frequency accuracy. This approach validates the synergistic effect of VMD’s global decomposition and wavelet’s local denoising, offering an effective method for high-precision ODMR inversion with substantial application potential in quantum sensing and precision measurement. Full article

(1) Theoretical studies have shown that large-scale vorticity generates a divergent-type helicity flux associated with small-scale magnetic fluctuations. Similar to the $\alpha$-effect, this mechanism breaks the equatorial reflection symmetry of magnetic fluctuations in stellar convection zones. This contribution has been termed the new Vishniac flux (hereafter NV flux). (2) Methods: We employ a mean-field dynamo model to investigate the influence of the NV flux on solar-type dynamos. (3) Results: We find that the NV flux leads to an enhancement of the dynamo efficiency for the turbulent generation of the large-scale poloidal magnetic field in the Sun. The dynamical impact of the NV flux on the evolution of the magnetic field results in a concentration of dynamo waves toward the equatorial region. Using numerical simulations of the mean-field dynamo, we compare the helicity production rates arising from different turbulent dynamo mechanisms, namely the $\alpha$-effect and the NV flux. The model demonstrates that the new dynamo source associated with large-scale vorticity and small-scale dynamo action leads to an amplification of poloidal field generation in the polar regions near the top of the dynamo domain. (4) Conclusions: Any fluctuating magnetic activity arising within the differentially rotating stellar convection zone can serve as an additional source for the generation of the large-scale poloidal magnetic field of a star. Full article