Abstract: Background: Fibromyalgia is a chronic disease that predominantly affects women and lasts over several months, causing problems both to individuals and society. While several studies have demonstrated the potential of electroacupuncture (EA) to alleviate fibromyalgia pain in mice, further research is needed to investigate its underlying mechanisms. Programmed cell death ligand-1 (PD-L1)/PD-1 was first identified to be involved in cancer immunotherapy, but its application to pain management has not been yet investigated. Methods: This study aimed to explore the mechanism underlying action of PD-L1 on PD-1 pathway in a mouse model of fibromyalgia. Results: We established such a mouse model using intermittent cold stress (ICS) and confirmed mechanical (D4: 2.02 ± 0.13 g, n = 9) and thermal (D4: 4.28 ± 0.21 s, n = 9) hyperalgesia. We found that EA, intracerebral ventricle (ICV) PD-L1 injection, or transient receptor potential vanilloid 1 (Trpv1) knockout effectively counteracted hyperalgesia. We observed low PD-1 expression in the cerebellum of fibromyalgia mice but increased expression of TRPV1 and pain-related kinases. These phenomena could be further reversed by EA, ICV PD-L1 injection, and Trpv1 knockout. To confirm that these effects were caused by PD-L1 release, we added PD-L1 neutralizing antibodies to the EA and PD-L1 treatment. The analgesic effects and EA and PD-L1 mechanisms were inhibited. Conclusions: Our results elucidate the role of the PD-L1/PD-1 pathway in EA treatment of fibromyalgia and reveal its potential value for fibromyalgia.

Abstract: Taiwan faces significant water resource challenges driven by pronounced seasonal variability, regional hydrological contrasts, and growing anthropogenic pressures. To mitigate shortages and uneven distribution, this article emphasizes the urgent need for integrated water resource management that jointly considers surface water and groundwater. Building on principles of sustainability and resilience, we synthesize recent advances in hydrological modeling, sediment transport analysis, and infrastructure optimization—including reservoir desiltation, seawater desalination, rainwater harvesting, and assessments of land subsidence from groundwater extraction. Particular attention is given to spatial sediment dynamics across river reaches and their implications for enhancing storage capacity. We further evaluate the feasibility of single-unit seawater desalination facilities in Taiwan’s coastal zones, analyzing energy demand and unit water costs under varying scenarios. Design guidelines for rainwater harvesting systems are proposed to reflect the distinct hydrological characteristics of northern and southern Taiwan, while integrating ecological resilience and cultural narratives. By bridging technical rigor with socio-cultural perspectives, this article offers a holistic framework for sustainable water resource planning in Taiwan and comparable island contexts. Finally, we outline preliminary guidelines for incorporating artificial intelligence into future management strategies. This research proposes reasonable cost reflection, differentiated water pricing, recycling goals, and a social equity perspective. These measures all have positive indicator benefits for the implementation of carbon budget management, global energy conservation, carbon reduction, and zero-carbon emission goals, and the achievement of carbon reduction targets of 40% reduction by 2030 and 50% reduction by 2050 for Taiwan.

Abstract: Wrist-worn devices enable new paradigms of implicit and continuous user authentication; however, identifying biometric modalities that combine security, robustness, and practical integrability remains challenging. Inner wrist skin texture represents a largely unexplored biometric trait with potential for unobtrusive authentication using commodity hardware. This study evaluates biometric authentication based on inner wrist skin texture using an off-the-shelf capacitive fingerprint sensor and a closed, manufacturer-provided verification algorithm. Two experiments were conducted. Experiment 1 assessed baseline authentication performance under controlled acquisition conditions in a cohort of 33 participants (21 male, 12 female; mean age 30.0 ± 16.9 years, range 10–71 years), yielding 1,768 authentication trials. Experiment 2 evaluated robustness to wrist posture variation under controlled wrist flexion in a separate cohort of 15 participants (11 male, 4 female; mean age 30.9 years, range 18–49 years), with 3,900 authentication trials recorded. Across 86,897 impostor comparisons in Experiment 1, no false acceptances were observed, corresponding to an upper false acceptance rate below 6.7 × 10⁻⁵ at a 99.7% confidence level, while the false rejection rate was approximately 2.93%. In Experiment 2, the overall false rejection rate was 3.52%, with no systematic dependence on wrist angle. These results indicate that inner wrist skin texture is a highly discriminative and geometrically stable biometric trait suitable for practical wrist-worn authentication systems.

Abstract: We introduce a formal and systematic analogy between static mechanical spring networks and electrical resistor networks, establishing a one‑to‑one mathematical correspondence where spring displacements map to electric potentials, spring constants to conductances, and forces to currents. This equivalence transforms the static equilibrium equations of point-mass-spring systems into the nodal equations of resistor networks, enabling the construction of a conductance matrix that is identical in form to a mechanical stiffness matrix and coincides with the weighted graph Laplacian. We demonstrate the versatility of this framework through a series of examples from elementary series and parallel combinations to non-planar networks such as the 3D resistor cube and the Petersen graph. We show that the method provides both an intuitive mechanical interpretation of circuit concepts and a systematic, matrix-based computational algorithm for calculating equivalent resistance. The approach naturally extends to AC networks containing resistors, capacitors, and inductors, offering a unified treatment of linear networks in both DC and AC regimes. We discuss the pedagogical value of the analogy for teaching circuit theory and network analysis, as well as its connections to graph theory and computational implementation. Limitations of the method, including its restriction to linear elements and the numerical considerations of matrix inversion, are briefly discussed.

Abstract:

Context: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by impaired cortisol and aldosterone synthesis. While genotype-phenotype correlations are well-established for common CYP21A2 mutations, the clinical significance of rare missense variants remains a challenge, often leading to their classification as Variants of Uncertain Significance (VUS) and complicating genetic counseling. Objective: To determine the functional impact and pathogenicity of eleven CYP21A2 variants (p.L10del, p.R76K, p.E162G, p.S274Y, p.L308V, p.S373N, p.P387L, p.H393Q, p.R401G, p.R436C, and p.S494N) utilizing a comprehensive approach integrating population genetics, in silico structural modeling, and in vitro functional assays. Methods: Allele frequencies were analyzed using global databases (gnomAD, 1000G). Evolutionary conservation was assessed via ConSurf, and thermodynamic stability was predicted using FoldX and DUET. Structural dynamics were simulated using Molecular Dynamics (MD) (100 ns). Variants were expressed in HEK293T cells, and enzymatic activity was quantified using radiolabeled progesterone and 17-hydroxyprogesterone (17-OHP) as substrates, normalized to protein expression levels determined by Western blot. Results: Population analysis identified p.L10del and p.S494N as common polymorphisms (allele frequencies >5% in specific populations) with near-normal enzymatic activity (~99% and ~67% for 17-OHP, respectively), supporting a Benign classification. Conversely, p.L308V, p.P387L, and p.R436C were ultra-rare and exhibited severe loss of function, retaining <20% of wild-type activity for 17-OHP. Structural modeling revealed that p.L308V causes steric clashes in the conserved I-helix, while p.P387L induces core destabilization and kinetic instability. p.R436C disrupts the surface hydrogen-bond network essential for P450 Oxidoreductase interaction. These variants are reclassified as Pathogenic, likely associated with Simple Virilizing CAH. Variants p.H393Q and p.R401G showed moderate impairment (~40–45% activity), consistent with a Likely Pathogenic status and Non-Classic CAH phenotype. Conclusions: This study resolves the diagnostic status of eleven CYP21A2 variants. We provide definitive evidence that p.L308V is a severe pathogenic missense mutation distinct from frameshift alleles at the same locus, and that surface mutations like p.R436C can be as deleterious as core mutations due to the disruption of redox partner interfaces. These findings refine the genetic classification of CAH, enabling precise diagnosis and personalized management for affected families.

Abstract:

While industrial scale dairy fermentations often employ pasteurized milk as the substrate, many farmhouse and traditional production practices apply raw milk derived from a variety of mammals. Certain artisanal production systems rely on the autochthonous microbiota of the milk, fermentation vessels, equipment and/or environment to initiate milk coagulation. While the technological properties of lactic acid bacteria associated with dairy fermentations are well described, their interactions with other organisms during fermentation and cheese ripening are poorly investigated. This study presents an overview of the microbial ecology of raw and pasteurized milk used in the production of cheeses. Furthermore, we report on the motility phenotype, lactose utilization ability and metabolic products of isolates of Hafnia paralvei and Hafnia alvei, and determine that these strains could grow in a non-antagonistic manner on plates with strains of Lactococcus lactis and Streptococcus thermophilus. As artisanal and farmhouse production systems are often associated with protected or regionally significant products, it is essential to develop a clear understanding of the microbial communities within and the complex relationships between the community members.

Abstract: Penicillium expansum inflicts significant economic damage in the fruit and vegetable industry due to its wide distribution and ability to infect a diverse range of hosts. Therefore, developing safe and environmentally sustainable strategies to suppress the growth of this pathogen is of critical importance. Bacillus subtilis, recognized for its broad antimicrobial activity and widespread occurrence, has been widely utilized in the biological management of plant diseases. This research seeks to assess the inhibitory potential of B. subtilis against P. expansum. The cell-free supernatant (CFS) derived from B. subtilis significantly suppresses the germination spores, germ tube extension, and hyphal development of P. expansum. It also reduces disease incidence in grapes and citrus and suppresses the expansion of lesions. Further investigate had shown that it can induced mycelium reactive oxygen species (ROS) accumulation, destroyed the cell membrane integrity, led to leakage of cytoplasmic contents and induced membrane lipid peroxidation. Moreover, exposure to high concentrations of CFS results in mycelial contraction and morphological abnormalities, triggering the disintegration of intracellular organelles and markedly upregulating the expression of apoptosis-associated genes. The self-protective response elicited by 5% CFS is insufficient to counteract the extent of cellular damage, ultimately driving cells toward a dynamic, multistage, and disintegrative form of cell death. The findings of this study offer a theoretical foundation for managing P. expansum after harvest.

Abstract: This paper presents modified Lagrange-Jacobi functions derived from the sine, exponential, and hyperbolic tangent coordinate transformations. The resulting Lagrange-Jacobi functions and their respective matrix elements for observables can be reduced to their respective Lagrange-Legendre, Lagrange-Chebyshev, and Lagrange-Gegenbauer functions. Furthermore, this paper postulates that the Lagrange-mesh functions form approximate complete set of basis, a property implied by their approximate orthogonality.

Abstract: This perspective article proposes and systematically develops a phenomenological framework centered on the correlation between dark energy dynamics and cosmic structure growth. Building upon the foundational linear relation w(a) = -1 + η(γ(a) - 0.55), where w is the dark energy equation of state and γ is the structure growth index, we extend it to allow for redshift-dependent couplings and provide a complete roadmap for empirical testing. We establish its theoretical basis as an interacting dark energy-dark matter model that respects energy-momentum conservation. A key advancement is our complete parameterization w(z)=−1+η(z)[γ(z)− 0.55]+Δw_bg(z), which separates structure-dependent coupling from possible background evolution and allows for redshift-dependent interactions. This work introduces a novel, phenomenologically motivated piecewise parameterization for the coupling strength η(z), designed to capture potential variations across distinct cosmic epochs (z < 0.5, 0.5 ≤ z ≤ 1.5, z > 1.5) based on the history of structure formation.​ We provide a comprehensive testing roadmap using hierarchical Bayesian model comparison, detailing the specific observational data, analysis methods, and systematic error treatments required. Using Fisher matrix forecasts based on detailed survey specifications, we demonstrate that upcoming surveys (DESI, Euclid, Roman Space Telescope) will provide decisive tests, capable of detecting coupling strengths |η| ≳0.05 with strong evidence. This framework offers a unified approach to addressing both the Hubble and S8​ tensions while making distinctive, testable predictions that differentiate it from other proposed solutions. We conclude with specific recommendations for observational teams and theoretical directions for further development.

Abstract: Docosahexaenoic acid (DHA), an omega-3 fatty acid essential for human health, is highly prone to oxidation in nanoemulsions due to their large interfacial area and presence of transition metal ions. This study investigated macroalgal chelators for stabilizing DHA-rich nanoemulsions. Sequential enzymatic–alkaline extraction using Alcalase® produced an extract with the strongest Fe2+-chelating activity (IC50 = 1.22 mg/mL), protein content of 10.11 ± 0.15%, and total phenolics ≈17 µg GAE/mL. This extract was incorporated into nanoemulsions (5 wt% DHA oil, 1 wt% Tween® 20) at 0.61, 1.22, and 2.44 mg/mL and compared with controls containing EDTA (0.025 mg/mL) or no antioxidant. Droplet size remained stable (D3,2 ≈ 77-80 nm; D4,3 ≈ 199-215 nm) and zeta potential averaged -17 to -19 mV, confirming physical stability. Confocal microscopy revealed concentration-dependent interfacial adsorption of extract components. During iron-accelerated storage, extract-treated nanoemulsions slowed hydroperoxide formation and delayed tocopherol depletion compared to the control, while reducing volatile oxidation markers such as 1-penten-3-ol by up to 40%. However, EDTA consistently provided superior protection against oxidation. These findings highlight the potential of macroalgal extracts as clean-label, natural chelators for mitigating metal-driven oxidation in DHA nanoemulsions, though synthetic chelators remain more effective under severe prooxidant conditions.

Abstract: Terahertz waves are located in the "transition zone" between millimeter waves and infrared light. Terahertz video synthetic aperture radar utilizes the high operating frequency, strong radar cross-section intensity, and high azimuth repetition frequency of terahertz waves to detect and track ground moving targets. The conventional methods for detecting moving targets do not take into account the imaging characteristics of moving targets in terahertz video synthetic aperture radar. The Constant False Alarm Rate (CFAR) detection method is used together with other methods to detect moving targets, resulting in unsatisfactory detection performance. This article proposes a new detection method for single channel slow-moving targets in terahertz video SAR based on shadows and light spots, which extracts the features of the shadow and spot areas of the moving target, and determines the position and direction of the moving target through the identification of the shadow and spot areas. The progressiveness of this method is verified by simulation and experimental tests.

Abstract: Mutations in leucine-rich repeat kinase 2 (LRRK2) are among the most common genetic causes of Parkinson’s disease (PD), yet substantial heterogeneity exists among pathogenic variants. How mutations in distinct functional domains of LRRK2 differentially perturb cellular homeostasis remains incompletely understood. Here, we compared two pathogenic LRRK2 mutations—G2019S in the kinase domain and I1371V in the GTPase domain—across multiple cellular models, including SH-SY5Y and U87 cells, and healthy human iPSC-derived floor plate cells. We demonstrate that the I1371V mutation induces markedly more severe cellular dysfunction than G2019S. I1371V-expressing cells exhibited elevated LRRK2 autophosphorylation at S1292 and robust hyperphosphorylation of Rab8A and Rab10, indicating enhanced downstream signaling. These alterations impaired sterol trafficking, leading to selective depletion of plasma membrane cholesterol without changes in total cellular cholesterol. Consequently, I1371V cells displayed increased membrane fluidity, disrupted microdomain organization, altered membrane topology, reduced Caveolin-1 expression, and impaired dopamine transporter surface expression and dopamine uptake. Lipidomic profiling further revealed broad disruption of lipid homeostasis, including reductions in cholesteryl esters, sterols, sphingolipids, and glycerophospholipids, whereas G2019S cells showed comparatively modest changes. Pharmacological intervention revealed mutation-specific responses, with the non-selective LRRK2 modulator GW5074 outperforming the kinase-selective inhibitor MLi-2 in restoring Rab8A phosphorylation, membrane integrity, and dopaminergic function. Collectively, these findings identify membrane lipid dysregulation as a central cell-biological mechanism in LRRK2-associated PD and underscore the importance of variant-specific therapeutic strategies.

Abstract: This study quantified the analytical performance of an automated videotopography system for dry eye disease (DED) and evaluated a novel multivariate composite score to improve diagnostic accuracy. In a prospective, repeated-measures study, 35 adults completed three visits involving automated (Keratograph 5M) and manual (fluorescein break-up time; slit-lamp meniscus height) assessments. Data were analysed using linear mixed-effects models and Bland–Altman plots, while a logistic regression-based Objective Symptom Risk Score (Objective-SRS) was derived to predict symptom status. Results showed that automated meniscus height (NIKTMH) had excellent precision (CV 8.8%) and reliability (ICC 0.727), whereas non-invasive break-up times were highly variable (CV &gt; 40%). Automated and manual measures demonstrated wide limits of agreement and systematic bias, precluding interchangeability. While individual objective tests failed to differentiate symptom groups, the composite Objective-SRS achieved good accuracy (AUC 0.768) and superior net clinical benefit. The study concludes that diagnostically useful information is distributed across multiple signals; thus, automated and manual measures should be used complementarily, with multivariate models offering superior discrimination of DED symptom burden.

Abstract: Optical precision measurement is fundamental to space technology and physics. For over a century, the “ray-of-light” paradigm and the Equivalence Principle have underpinned both theoretical and applied optics. However, recent theoretical and experimental work demonstrates that these paradigms are fundamentally flawed when applied to photon-level phenomena. This manuscript synthesizes a trilogy of research—spanning theoretical falsification, experimental confirmation, and practical application—to show that photons do not inherit the velocity vector of their source, and that the Equivalence Principle does not hold for photon propagation. We introduce the Real Velocity Measuring Device (RVMD), a novel instrument enabling direct measurement of real velocity vectors in real space. The potential implications for spacecraft navigation and metrology (including our planet) are profound, necessitating a paradigm shift in optical science.

Abstract: This pilot study evaluates whether Wi-Fi Channel State Information (CSI)-derived micro-movements can reflect autonomic patterns associated with Heart Rate Variability (HRV). CSI-estimated inter-beat intervals were compared with smartwatch-derived HRV metrics during relaxation and mild stress tasks involving 14 volunteers. While absolute HRV values differed, CSI-derived LF/HF variations showed directional alignment with physiological state changes (r = 0.84, p < 0.001), with mean absolute error of 5.8 ms for SDNN and 4.1 ms for RMSSD. Results underscore potential for contactless autonomic monitoring and motivate further clinical investigation, avoiding any claim of diagnostic utility. The findings suggest CSI-based passive wireless analytics may complement existing wearable methods for stress monitoring and autonomic assessment in ecologically valid settings.

Abstract: Topography plays a crucial role in shaping local urban microclimates and can drive the formation of cold-air pools in valley bottoms. This study examines the Eiras Valley (Coimbra, Portugal), a rapidly growing peri-urban area, to identify the conditions under which cold-air pools form and to characterize their spatial and vertical dynamics. Field measurements were carried out using Tinytag Plus 2 data loggers at the surface (≈1.5 m above ground) and mounted on an unmanned aerial vehicle (UAV) for vertical profiles, complemented by high-resolution thermal mapping through Empirical Bayesian Kriging. The results show that a nocturnal cold-air pool develops within the valley under clear, anticyclonic winter conditions, persisting into the early morning hours and dissipating after sunrise due to solar heating. In contrast, under overcast or summer conditions, no cold-air pooling was observed. The temperature inversion capping the cold-air pool was found at approximately 275 m altitude, inhibiting vertical mixing and trapping pollutants near the ground. These findings underscore the importance of topoclimatology in urban and regional planning, with implications for thermal comfort, air quality, and public health. The study contributes to urban climate research by highlighting how local topography and seasonal atmospheric stability govern cold-air pool formation in valley environments, supporting the development of mitigation strategies aligned with urban sustainability goals.

Abstract: People in mid-life interact with several different environments during their daily life in-cluding employment, leisure, commuting, and various family responsibilities, a concept defined as activity space. However, little is known about how these activity spaces contrib-ute to individuals’ daily health behavior choices. The Everyday Environments and Expe-riences (E3) study was conducted to explore these relationships. In this paper, we provide a reproducible GPS processing workflow to generate time-weighted exposure measures (activity spaces) inferred from 21 days of continuous GPS monitoring among 340 mid-life adults in Cook County, Illinois (N=340) from the E3 study. Data from waist-mounted GPS devices that recorded one-minute location epochs were aggregated after excluding time spent within an 800-meter buffer around the home. For each epoch, we derived proximity and kernel density measures for eleven food and physical-activity-related location types (e.g., supermarkets, fitness facilities), along with twenty-six environmental context varia-bles (e.g., land use, crime, population density). Time-weighted averages characterized each participant’s typical non-home environmental exposure. After adjustment for envi-ronmental context, age and gender were generally unrelated to activity-space measures. However, Black and Hispanic participants (as compared to White participants) spent less time near both food and physical-activity resources, suggesting systemic inequities in ac-cess beyond neighborhood composition.

Abstract: Physical activity (PA) improves health and well-being, and helps prevent long-term conditions. Yet opportunities to be active are not evenly distributed, with social, economic, and environmental disadvantages constraining access to PA among populations who may benefit most. Since the extent to which PA interventions incorporate equity considerations remains insufficiently characterised, risking exacerbation of health inequity, this scoping review aims to synthesise trial evidence on interventions of PA to improve health outcomes in populations at risk of health inequity as defined by the PROGRESS-Plus and CORE20PLUS5 frameworks. PubMed, Web of Science, and Scopus were searched for randomised controlled trials of PA interventions with at-risk populations published between 2020 and 2025. Study characteristics, intervention design, and equity-relevant factors were extracted. Two reviewers independently screened and synthesised findings narratively. Results indicate that of 2,480 articles identified, 23 trials met eligibility criteria. Most reported positive effect of PA on health outcomes amongst at-risk populations, including weight loss, improved motor skills and gait speed, reduced anxiety and PTSD, and fewer fractures or hospital visits. Interventions commonly included strength and balance training, group exercise, stretching, and aerobic fitness. UK-based studies and subgroup analyses by e.g. sex or age were largely absent, and many populations at risk of health inequity were underrepresented. Explicit equity considerations throughout design, implementation, or evaluation were rare across trials and few assessed differential effects between social or economic groups. Integrating equity frameworks and engaging with at-risk populations is recommended in future physical activity interventions to mitigate exacerbation of health inequity.

Abstract: Head-mounted (“virtual reality”) perimeters (HMPs), based on standard consumer electronic hardware, are a cheaper alternative to standard automated perimetry. They have not been validated in patients with inherited retinal disease (IRDs), yet. We evaluated the Iowa-HMP in a first pilot study. It consists of a legacy smartphone, a headset, and freely available, open-source software. We used the 10-2 grid, the ZEST algorithm, and a background of 10 cd/m^2 to measure central visual fields in one normal subject, and in patients with occult macular dystrophy (n = 2), Stargardt’s disease (n=3) and retinitis pigmentosa (n = 6). Results were compared with those from an Octopus 900 perimeter. The typical patterns of visual field loss were clearly discernible, but head-mounted perimeters generally have a limited dynamic range. Within the dynamic range of the Iowa-HMP (14 to 30 dB Octopus sensitivity), the Limits of Agreement (Bland-Altman) were ±7.5 dB. The Iowa-HMP had a diagnostic sensitivity of 0.67 for detecting locations with low perimetric sensitivity (< 14 dB in the Octopus perimetry) with a diagnostic specificity of 0.95. Although the Iowa-HMP cannot be directly compared to standard perimetry in IRDs, open software greatly facilitates research in this area.

Abstract:

This population-based study aimed to analyze the annual incidence and case fatality trends, and the clinical-epidemiological profile of gastroschisis in the state of Paraná, Brazil, between 2013 and 2024. Specifically, temporal trends in annual incidence and mortality rates related to gastroschisis were examined. Maternal, gestational, and neonatal characteristics were analyzed. Data from the Live Birth Information System and the Mortality Information System were analyzed using polynomial regression modeling. During the study period, 1,798,727 live births were recorded, including 491 cases of gastroschisis and 179 related deaths. The mean incidence was 2.73 per 10,000 live births. A significant 39.5% decrease over the study period was observed (p < 0.001). The case fatality rate was 36.5%. The predominant profile included young mothers (< 25 years; 77%), low educational attainment (87.7%), and no partner (59.1%). High frequencies of cesarean deliveries (84.3%), prematurity (57.3%), low birth weight (63.7%), and low Apgar scores were also observed. Gastroschisis incidence in Paraná declined significantly from 2013 to 2024. While the annual incidence showed a decreasing trend, mortality fluctuated. The persistently high case fatality rate underscores the need for public policies focused on prenatal care and specialized neonatal management.