Search Results (22,863)

The increasing demand for alcohol-free craft beers with functional properties and distinctive sensory attributes has motivated the brewing industry to investigate alternative production strategies, such as the application of non-Saccharomyces yeasts, to obtain sour beers while reducing production time and associated costs. This study explores the combined use of Lachancea thermotolerans L31 and Metschnikowia pulcherrima M29 in the production of beers brewed with blueberries or enriched with grape anthocyanin concentrate. Physicochemical parameters such as pH, color, bitterness, total polyphenols, antioxidant capacity, and anthocyanin and volatile profiles were evaluated, and a sensory analysis was performed. The results showed that both the addition of blueberries and that of anthocyanin concentrate and fermentation with Lachancea and Metschnikowia significantly influenced the chemical and sensory properties of the beer. Mainly, pH values decreased from 4.35 to 3.50 and from 3.69 to 3.26, while antioxidant activity increased from 3 to 10 times, depending on the type of yeast and the addition of fruit. Alcohol content remained constant at approximately 5.0% v/v. This strategy allows for the production of beer with a distinctive profile and functional benefits, representing a step forward in craft beer development and opening new avenues for research and innovation in the sector. Full article

Understanding the coupling mechanisms between vegetation phenology and carbon productivity is essential for assessing ecosystem responses to climate change and guiding sustainable grassland management. This study focuses on stable alpine grasslands on the southern slope of the Qilian Mountains from 2001 to 2020, a climatically sensitive but relatively under-investigated transition zone on the northeastern Tibetan Plateau. We utilized MODIS NDVI time-series (MOD13Q1) and the latest PML V2 gross primary productivity (GPP) product at 500 m resolution to quantify changes in the start (SOS), end (EOS), and length (LOS) of the growing season. A pixel-wise linear regression approach was applied to evaluate the sensitivity of GPP to phenological metrics, explicitly characterizing how much GPP changes in response to unit shifts in SOS, EOS and LOS. Compared with previous studies that mainly described large-scale correlations between phenology and GPP or relied on coarser GPP products, this study provides a pixel-level, sensitivity-based assessment of phenology–carbon coupling in alpine grasslands using a long-term, phenology–GPP dataset tailored to the Qilian alpine region. The results revealed trends of earlier SOS, delayed EOS, and extended LOS, accompanied by a gradual increase in GPP. However, phenology–GPP coupling exhibited notable spatial heterogeneity. In mid- and low-altitude areas, extended growing seasons enhanced GPP, whereas high-altitude zones showed limited or even negative responses, likely due to climatic constraints such as cold stress and thermal–moisture mismatches. To better understand these spatial differences, we constructed a three-dimensional phenology–GPP sensitivity space and applied k-means clustering to delineate three ecological functional zones: (1) high carbon sink potential, (2) ecologically fragile regions, and (3) neutral buffers. This sensitivity-based functional zonation moves beyond traditional correlation analyses and provides a process-oriented and spatially explicit framework for ecosystem service assessment, carbon sink enhancement and adaptive land-use strategies in sensitive mountain environments. Full article

Oxidative stress-induced lipid peroxidation products (LPPs), particularly 4-hydroxy-nonenal (4-HNE) and 4-oxo-nonenal (4-ONE), have recently gained attention for their direct regulation of ion channels essential for pain signaling. In this study, we investigated how these two LPPs affect the electrophysiological properties of neurons, specifically voltage-gated sodium (Na_V) channels, thereby influencing sensory neuron excitability and pain pathways. Using human neuroblastoma (SH-SY5Y) and ND7/23 cells (a fusion cell line exhibiting partial sensory neuron properties), we measured changes in Na_V channel-mediated sodium currents following treatment with 4-HNE or 4-ONE. Whole-cell patch-clamp experiments showed that 4-ONE (10 µM) and 4-HNE (100 µM) did not significantly alter the peak sodium current amplitude in SH-SY5Y cells. However, in ND7/23 cells, both 4-HNE and 4-ONE induced a negative shift in Na_V channel activation voltage dependence, enabling sodium channel activation at lower membrane potentials. Furthermore, current-clamp recordings in primary mouse dorsal root ganglion neurons demonstrated that treatment with 4-ONE and 4-HNE reduced the current threshold required to elicit action potentials and significantly increased action potential firing frequency. These findings indicate that LPPs enhance pain sensitivity by modulating Na_V channels, which play a crucial role in pain transmission. In conclusion, 4-HNE and 4-ONE shift the voltage-dependent activation of sodium channels toward more negative potentials, thereby increasing the excitability of primary sensory neurons and amplifying pain signals. This study provides molecular insights into how oxidative stress-related lipid peroxidation contributes to sensory mechanisms and offers potential avenues for developing new treatments for oxidative stress- or inflammation-associated pain. Full article

Background and Aim: The management of patients with chronic Hepatitis B Virus (HBV) HBeAg-negative infection in the indeterminate-grey zone (GZ) remains debatable. We conducted a systematic review and meta-analysis to compare these patients with those with chronic HBV HBeAg-negative infection (inactive carriers; IC/HBeAg-negative), regarding the severity of liver inflammation and fibrosis and the risk of developing hepatocellular carcinoma (HCC). Methods: A literature search was conducted to identify all published studies comparing GZ/HBeAg-negative patients with IC/HBeAg-negative patients. Data on the severity of liver inflammation and fibrosis were extracted, and pooled relative risks (RR) and 95% confidence intervals (CI) were calculated. The risk of HCC was estimated by pooled hazard ratios (HR). A random-effects meta-analysis model was performed using R v4.1.2. Results: Eleven studies were finally included. GZ/HBeAg-negative patients had significantly higher mean HBV-DNA and alanine transferase (ALT) levels, compared to their IC/HBeAg-negative counterparts (4089.9 ± 4840.5 vs. 215.9 ± 318.1 IU/mL; p = 0.0004, and 39.6 ± 26.9 IU/L and 20.1 ± 7.6 IU/L/; p < 0.0001, respectively). GZ/HBeAg-negative patients showed a trend towards a higher risk of significant liver inflammation (RR: 5.11; 95%CI: 0.68–38.33; p = 0.1), F2/F3 fibrosis (RR: 2.13; 95%CI: 0.89–5.1; p = 0.09), and cirrhosis (RR: 14.39; 95%CI: 0.5–417.08; p = 0.12), respectively, compared to IC/HBeAg-negative patients. After a median follow-up of 6.2 years, the former group demonstrated a significantly higher risk of developing HCC (HR: 4.7; 95% CI: 1.4–15.6; p < 0.0001). Conclusions: GZ/HBeAg-negative patients have a higher risk of developing HCC compared to IC/HBeAg-negative patients, which raises concerns about the potential need to initiate treatment in this patient group. Full article

We investigate the multi-layer atmospheric impacts of Typhoon Hagibis (2019), which formed on 6 October, tracked across 12–35${}^{\circ }$ N and 135–155${}^{\circ }$ E, and made landfall on 12 October over the Izu Peninsula, central Honshu, Japan. We present a multi-layer study that involves the troposphere, stratosphere and upper ionosphere to examine the thermodynamic and electromagnetic coupling between these layers due to such extreme weather conditions. Using ERA5 reanalysis, we identify pronounced stratospheric temperature perturbations, elevated atmospheric gravity wave (AGW) potential energy, substantial spatiotemporal variability in the zonal (U) and meridional (V) wind components, relative humidity, and specific rainwater content throughout the cyclone’s evolution. Quantitatively, AGW potential energy increased from background levels of <5 J kg${}^{-1}$ to >40 J kg${}^{-1}$ near the cyclone core, while tropospheric wind anomalies reached $\pm 30$–40 m s${}^{-1}$, accompanied by relative humidity values exceeding 90% and specific rainwater content up to $1.5\times {10}^{-3}$ kg kg${}^{-1}$, indicative of vigorous moist convection and strong vertical energy transport. The ionospheric response, derived from GPS-based Total Electron Content (TEC) at 10 Japanese IGS stations, reveals vertical TEC (VTEC) perturbations whose amplitudes and temporal evolution vary systematically with GPS-station-to-typhoon-eye distance, including clear enhancements and reductions around the closest-approach day. These signatures indicate a measurable ionospheric response to cyclone-driven atmospheric forcing under geomagnetically quiet conditions, confirming that Hagibis produced vertically coupled disturbances linking stratospheric AGW activity with ionospheric electron density variability. Full article

Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options and poor survival outcomes. This study evaluated the anticancer potential of seco-duocarmycin SA (seco-DSA), a potent DNA-alkylating agent, alone and in combination with proton radiation in human GBM cell lines. Human glioblastoma cell lines T98G and LN18 were treated with varying concentrations of seco-DSA, proton radiation doses (2, 4, or 8 Gy), or both. Proton irradiation was delivered with a 250-MeV beam. Clonogenic survival, cell proliferation, and cell cycle distribution were analyzed using colony formation and flow cytometry assays. Proteomic analysis of LN18 cells was performed by LC-MS/MS followed by bioinformatic pathway analysis. Statistical significance was determined using a two-tailed unpaired t-test (p ≤ 0.05), and Bliss synergy scores were calculated to assess treatment interactions. Combination therapy produced additive and synergistic inhibition of colony formation and enhanced G2/M phase arrest compared with either treatment alone. Apoptosis and necrosis increased modestly but did not fully account for observed cytotoxicity. Proteomic profiling revealed differential expression of proteins involved in DNA repair, apoptosis, and senescence, indicating that seco-DSA broadened radiation-induced stress responses. Seco-DSA potentiates the cytotoxic effects of proton radiation in GBM cells through enhanced clonogenic inhibition and modulation of cell cycle and DNA repair pathways. These findings support seco-DSA as a promising radiosensitizer for further preclinical evaluation. Full article

The relatively poor cycle stability of zinc–air batteries (ZABs) hinders their widespread application, while self-supporting electrode materials have shown great potential in enhancing the cycling stability of ZABs. To construct a self-supporting electrode, bamboo was employed as a sustainable precursor, and a two-step pyrolysis strategy was implemented to integrate ZIF-67-derived catalysts onto a hierarchically porous carbon framework, yielding the composite material Co-N@CB. Benefiting from its structural and electronic advantages, Co-N@CB exhibits outstanding electrocatalytic performance. The overpotential for the oxygen evolution reaction (OER) in alkaline electrolyte is 1.5 V at 10 mA cm⁻², with a potential gap (ΔE) of 0.69 V. This material is directly used as the air cathode in ZABs, delivering over 10,000 stable cycles. This excellent cycling stability arises from the strong carbon framework provided by bamboo and the enhanced electrical conductivity achieved through the pyrolytic graphitization of ZIF-67. This study paves the way for further exploration of biomass-based self-supporting electrodes toward high-performance ZABs and emerging micro/nanoscale sensing technologies. Full article

Myocardial and vascular injury secondary to SARS-CoV-2 infection and vaccination has emerged as a clinically relevant phenomenon, with distinct but overlapping mechanisms. Myocardial injury in COVID-19 results from a complex interplay between direct viral effects and immune-mediated inflammation, supported by histopathological studies revealing macrophage-rich infiltrates, microthrombosis, and supporting fibrosis in isolated areas. In contrast, vaccine-associated myocarditis—reported predominantly following mRNA vaccines—has a self-limiting clinical course, with mechanisms likely involving molecular mimicry, aberrant immune activation, or hypersensitivity reactions, although these pathways require further validation. Although mRNA vaccines have been associated with a small increase in myocarditis, particularly in young men, the risk is significantly lower than that associated with COVID-19 infection, and the cardiovascular benefits of vaccination far outweigh these rare adverse events in most populations. After the end of the pandemic, the number of patients with severe forms of COVID-19 has decreased significantly, but we consider that cardiac involvement remains an important issue for the acute and long-term prognosis of patients with SARS-CoV-2 infection. Our paper synthesizes the latest epidemiological and mechanistic evidence on the link between COVID-19, vaccination, and myocardial and/or vascular injuries, highlighting the clinical implications and providing practical recommendations for management, as well as future perspectives on risk assessment, targeted immunotherapy, advanced diagnostic tools, and long-term monitoring. Full article

This paper presents an all-digital fractional-N phase-locked loop (ADPLL) operating in the 2.86–3.2 GHz range, optimized for IoT and high-frequency RF transceiver applications demanding stringent phase noise performance, fast settling time, and high integration capability. The key innovation lies in the introduction of a bandpass delta-sigma time-to-digital converter (BPDSTDC) that achieves high-resolution phase detection, an extended detection range of ±2$\pi$, and superior noise-shaping characteristics, completely eliminating the complex calibration procedures typically required in conventional TDC designs. The proposed architecture synergistically combines the BPDSTDC with digital down-conversion blocks to extract phase error at baseband, a divider chain integrated with phase interpolators achieving 1/4 fractional resolution to suppress in-band quantization noise, and a wide-bandwidth digital loop filter (>1 MHz) ensuring fast dynamic response and robust stability. The bandpass delta-sigma modulator is implemented with compact resonator structures and a flash quantizer, achieving an optimal balance among resolution, power consumption, and silicon area. The incorporation of highly linear phase interpolators extends fractional frequency synthesis capability without requiring complex digital-to-time converters (DTCs), significantly reducing design complexity and calibration overhead. Fabricated in a 180-nm CMOS technology, the proposed chip demonstrates robust measured performance. The band-pass delta-sigma TDC achieves a low integrated rms timing noise of 183 fs within a 1-MHz bandwidth. Leveraging this low TDC noise, the complete ADPLL exhibits a measured in-band phase noise of −120 dBc/Hz at a 1-MHz offset for a 3.2-GHz output frequency while operating with a loop bandwidth exceeding 1 MHz. This corresponds to a normalized phase noise of −216 dBc/Hz. The system operates from a 1.8-V supply and consumes 10 mW, achieving competitive performance compared with prior noise-shaping TDC-based all-digital PLLs. Full article

Endurance running exposure alone may not be sufficient to slow the age-related decline in plantarflexor function, which is also thought to contribute to the decline in running economy. Strength training has been shown to improve running performance, but specific programs have not been evaluated for their assistance in maintaining plantarflexor function and “youthful” metabolic costs in aging runners. The purpose of this study was to assess the relative influence of three types of resistance training interventions on running economy (RE), plantarflexor function, and Achilles tendon (AT) stiffness in middle-aged runners. Methods: Twenty-six middle-aged runners (51 ± 5 yrs) participated in one of three 10-week resistance training interventions: (1) heavy resistance training, (2) heavy resistance training + plyometrics, and (3) endurance resistance training + plyometrics. Laboratory testing for RE, biomechanical variables, peak plantarflexor torque, and AT stiffness during isometric contractions occurred before and after the interventions. A mixed-design repeated measures ANOVA was used to address our research question, while paired and independent t-tests were used to compare time and group effects, respectively. Results: Relative (to $\dot{V}{O}_{2max}$) RE (−2.4%, p = 0.016), AT stiffness (+26.1%, p = 0.002), and peak isometric plantarflexor torque (+26.4%, p = 0.001) improved with resistance training, with no interaction or group effects. No significant interaction, time, or group effects were observed for $\dot{V}{O}_{2max}$ and peak plantarflexor torque, peak positive ankle power, or positive and negative ankle work while running. Conclusions: We present novel but exploratory findings that resistance training, regardless of modality, may moderately improve RE and Achilles tendon stiffness in middle-aged recreational runners. However, sagittal plane lower joint kinematics, extensor torques, powers, and work were unaffected by resistance training in middle-aged runners. Full article

Remote sensing semantic segmentation encounters several challenges, including scale variation, the coexistence of class similarity and intra-class diversity, difficulties in modeling long-range dependencies, and shadow occlusions. Slender structures and complex boundaries present particular segmentation difficulties, especially in high-resolution imagery acquired by satellite and aerial cameras, UAV-borne optical sensors, and other imaging payloads. These sensing systems deliver large-area coverage with fine ground sampling distance, which magnifies domain shifts between different sensors and acquisition conditions. This work builds upon DeepLabV3+ and proposes complementary improvements at three stages: input, context, and decoder fusion. First, to mitigate the interference of complex and heterogeneous data distributions on network optimization, a feature-mapping network is introduced to project raw images into a simpler distribution before they are fed into the segmentation backbone. This approach facilitates training and enhances feature separability. Second, although the Atrous Spatial Pyramid Pooling (ASPP) aggregates multi-scale context, it remains insufficient for modeling long-range dependencies. Therefore, a routing-style global modeling module is incorporated after ASPP to strengthen global relation modeling and ensure cross-region semantic consistency. Third, considering that the fusion between shallow details and deep semantics in the decoder is limited and prone to boundary blurring, a fusion module is designed to facilitate deep interaction and joint learning through cross-layer feature alignment and coupling. The proposed model improves the mean Intersection over Union (mIoU) by 8.83% on the LoveDA dataset and by 6.72% on the ISPRS Potsdam dataset compared to the baseline. Qualitative results further demonstrate clearer boundaries and more stable region annotations, while the proposed modules are plug-and-play and easy to integrate into camera-based remote sensing pipelines and other imaging-sensor systems, providing a practical accuracy–efficiency trade-off. Full article

High-quality spectral filters with versatile tuning mechanisms are essential for applications in photonic integrated circuits, including sensing, laser stabilization, and spectral signal processing. We report the implementation of thermo-optic (TO) and electro-optic (EO) spectral tuning in silicon nitride Mach–Zehnder interferometers (MZIs) and micro-ring resonators (MRRs) by functionalizing the devices with a PMMA:JRD1 polymer cladding and integrating titanium tracks as heaters and electrodes. The fabricated MZIs and MRRs exhibit narrow linewidths of 25–30 pm and achieved TO tuning efficiencies of 1.7 and 13 pm/mW and EO tuning efficiencies of 0.33 and 1.6 pm/V, respectively. Closed-loop regulation using TO and EO effects enables stable half-fringe locking under environmental perturbations. This simple, broadly compatible hybrid platform demonstrates a practical approach to dual-mode spectral tuning and modulation in integrated photonic filters, providing a flexible route toward compact, reconfigurable, and environmentally robust photonic circuits. Full article

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can develop as post-vaccination syndrome (PVS) or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). In our prior retrospective study, most patients with PVS who developed ME/CFS had vitamin D insufficiency or deficiency. We evaluated the efficacy of vitamin D replacement therapy guidance for ME/CFS symptom improvement in patients with vitamin D insufficiency or deficiency. Methods: This open-label randomized controlled trial enrolled 91 participants with ME/CFS as PVS or PASC and serum 25(OH) vitamin D < 30 ng/mL across five clinical sites. Participants were randomized 1:1 to intervention (active vitamin D preparation plus vitamin D replacement therapy guidance: 25 μg daily supplementation, dietary counseling, sun exposure, and exercise) or control (active vitamin D preparation alone) for 12 weeks. The primary endpoint was the change in ME/CFS symptom count from screening to Week 12. Results: Mean symptom change was −6.7 in the intervention group versus −1.2 in the control group (between-group difference −5.6; 95% CI: −7.2, −3.9; p < 0.001). Serum 25(OH) vitamin D improved from 18.6 to 27.1 ng/mL in the intervention group, while the control group showed a decreasing trend (between-group difference 10.2 ng/mL; 95% CI: 7.9, 12.5). Achievement of <8 symptoms (i.e., no longer meeting ME/CFS diagnostic criteria) was significantly higher in the intervention group, with 16 participants achieving this threshold compared to 1 in the control group (p < 0.001). Subgroup analyses showed consistent benefit in both PVS (n = 56) and PASC (n = 29) cohorts. Conclusions: Vitamin D replacement therapy guidance significantly reduced ME/CFS symptoms along with improvement of serum 25(OH) vitamin D levels in patients with vitamin D insufficiency or deficiency who developed ME/CFS as PVS or PASC. Full article

Mangrove ecosystems play a critical role in sequestering heavy metals pollutants, yet the dynamics of heavy metals accumulation during mixed litter decomposition remain poorly understood. This study investigated the seasonal and species-specific variations in heavy metals accumulation during the decomposition of Kandelia obovata (KO) and Avicennia marina (AM) leaf litter mixtures in a subtropical mangrove forest in the Jiulong River Estuary, Fujian, China. Using the litterbag technique, we monitored eight heavy metals (V, Cr, Ni, Cu, Zn, As, Se, Cd) across three mixing ratios (KO:AM = 1:2, 1:1, 2:1) in summer and winter. Results revealed that V concentrations were influenced by both season and litter ratio, with higher KO proportions enhancing V accumulation in summer but reducing it in winter. In contrast, Cr, Ni, Cu, As, Se, and Cd were primarily regulated by litter ratios: KO-dominated mixtures promoted Cr and Ni accumulation, while AM-dominated mixtures favored Cu, As, Se, and Cd. Zn exhibited the highest variability and was unaffected by season or ratio. Total organic carbon (TOC) and carbon/metal (C/M) ratios significantly correlated with reduced bioavailability of most heavy metals, whereas total nitrogen (TN) and C/N ratios showed no consistent relationship. The heavy metals accumulation index (MAI) indicated higher accumulation in summer than in winter, with the highest MAI observed in the KO:AM = 2:1 treatment group during summer (MAI = 1.36), whereas winter decomposition slowed accumulation rates. These findings highlight the dual regulatory roles of species composition and environmental factors in mangrove heavy metals cycling, offering critical insights for ecological risk assessment and contaminated soil remediation strategies in coastal ecosystems. Full article

Coronaviruses are worldwide-distributed RNA viruses with zoonotic potential and the ability to jump from one host species to another, including humans. Even after the COVID-19 pandemic, the search for new, biologically active substances with anti-coronavirus activity continues to be a critical milestone for human health protection. In the framework of a complex engineering strategy, we cultivated the microalgal species Scenedesmus acutus in two different innovative types of flat-plate photobioreactors (PBR1 and K1) for CO₂ utilization and biomass production with special features. Isolated extracts from the microalgal biomass of each one were compared for their anti-coronavirus potential. The design of both PBRs allows a hydrodynamic regime to achieve best fluid flow distribution in their sections, therefore providing the optimal so-called flashing light effect. Of course, this is achieved under well-controlled operational conditions. A strain of beta coronavirus 1 (BCoV, bovine coronavirus) replicated in MDBK cells was used as an in vitro model for the evaluation of the antiviral activity of both extracts. The cell viability, number of survived BCoV particles, and cytopathic effect were evaluated after pre-incubation of the virus with the extracts or direct treatment. The extracts’ samples exhibited evident antiviral activity—extract 1 (from PBR1) in concentrations ≥ 200 µg/mL and extract 2 (from K1) in concentrations ≥150 µg/mL. The ddPCR result revealed significant diminishment of the BCoV particles in samples treated with higher concentrations of the extracts. The phytochemical analysis for certain main groups of compounds (flavonoids, polyphenols, carotenoids, and lipids) showed some differences for both extracts, which could be a possible reason for the observed difference in the antiviral activity. In conclusion, the innovative PBRs are a good platform for studying microalgal growth kinetics by applying different stress conditions from hydrodynamics and mass transfer subsystems. Both extracts showed promising potential for the isolation of metabolites with antiviral activity against BCoV and could be an object for future pharmacological investigations. Full article