Abstract: Autophagy is an evolutionarily conserved degradation and recycling process through which cells deliver cytoplasmic components such as toxic or defective proteins and organelles to lysosomes for clearance. Unlike dividing cells, neurons depend on degradative pathways to prevent the buildup of cellular waste and to sustain nutrient and energy homeostasis. Emerging evidence indicates that autophagy is particularly critical during early development when neuronal circuits are being established, synaptic connections refined, and activity-dependent mechanisms sculpt overall network architecture. Accordingly, loss of key autophagy-related genes in newly formed neurons disrupts differentiation, synaptic formation and neurotransmission. Despite these insights, the developmental regulation of autophagy genes remains poorly understood, and the composition of the autophagic machinery at synapses is still largely unresolved. To address this, we performed genome-wide transcriptomic analyses of the cortical brain region to characterize the maturation-dependent dynamics of autophagy–lysosomal genes. In parallel, we examined the autophagy-associated proteome within synaptosomes to better understand how autophagic proteins contribute to synaptic processes during critical stages of network formation. Together, these complementary approaches reveal new aspects of autophagy regulation during development and provide a foundation for identifying therapeutic targets for neurological disorders linked to impaired synaptic and cellular homeostasis.

Abstract: The rapid evolution of Large Language Models (LLMs) from static text generators to autonomous agents has revolutionized their ability to perceive, reason, and act within complex environments. However, this transition from single-model inference to System Engineering Security introduces unique structural vulnerabilities—specifically instruction-data conflation, persistent cognitive states, and untrusted coordination—that extend beyond traditional adversarial robustness. To address the fragmented nature of the existing literature, this article presents a comprehensive and systematic survey of the security landscape for LLM-based agents. We propose a novel, structure-aware taxonomy that categorizes threats into three distinct paradigms: (1) External Interaction Attacks, which exploit vulnerabilities in perception interfaces and tool usage; (2) Internal Cognitive Attacks, which compromise the integrity of reasoning chains and memory mechanisms; and (3) Multi-Agent Collaboration Attacks, which manipulate communication protocols and collective decision-making. Adapting to this threat landscape, we systematize existing mitigation strategies into a unified defense framework that includes input sanitization, cognitive fortification, and collaborative consensus. In addition, we provide the first in-depth comparative analysis of agent-specific security evaluation benchmarks. The survey concludes by outlining critical open problems and future research directions, aiming to foster the development of next-generation agents that are not only autonomous but also provably secure and trustworthy.

Abstract: Chronic and hard-to-heal wounds remain a major clinical burden, yet many synthetic nanocarriers used in advanced dressings are constrained by limited biomimicry and concerns over inflammatory risk and off-target toxicity. Here we report porcine skin–derived reconstituted lipid nanoparticles (PS-rLNPs) as a tissue-origin, composition-preserving nanoplatform for wound repair. Total lipids extracted from fresh porcine skin were assembled into nanoparticles via a facile solvent-injection process. Lipidomics revealed a triglyceride- and phosphatidylcholine-dominant composition accompanied by minor membrane-relevant lipid species, suggesting a biocompatible, multi-lipid milieu. PS-rLNPs formed a stable nanoscale dispersion and maintained colloidal stability in physiologically relevant and serum-containing media. In vitro, PS-rLNPs showed no cytotoxicity across the tested dose range and exhibited pronounced intrinsic pro-healing bioactivity, significantly enhancing fibroblast viability and accelerating cell motility in both scratch-closure and Transwell migration assays. Collectively, these results establish PS-rLNPs as a biocompatible, serum-stable, and intrinsically pro-regenerative lipid nanoparticle system, providing a scalable route to tissue-derived nanomedicines that may complement next-generation wound-care strategies.

Abstract:

Hepatitis delta (HDV) infection affects 5% of hepatitis B (HBV)-positive patients, is associated with an increased risk of cirrhosis and hepatocellular carcinoma but remains underdiagnosed. The first part of our « Delta Describe » study highlighted insufficient screening of HDV patients in metropolitan France. We report here their real-world management. Patients with at least one positive HDV RNA test performed in 2019 were identified through the main French public and private laboratories. In 2024, informed patients were interviewed and physicians supplemented the collected data. 547 patients were included, median age 44 years, mainly originated from Africa or Eastern Europe. HIV and Hepatitis C coinfections were reported in 15.2% and 4.6% respectively. Liver stiffness was assessed by FibroScan® (75.3%) primarily. Most patients knew the year of diagnosis and 69% their fibrosis stage. Liver related events occurred in 14.3% of patients, mainly cirrhosis decompensation (67.9%) and hepatocellular carcinoma (28.3%). Forty-five patients underwent liver transplantation. In 2024, 47.5% had undetectable HDV RNA. Among treated patients (n=387), 37.4% received bulevirtide with or without pegylated-interferon, and 62.6% nucleos(t)ide analogues (NUCs) only. In metropolitan France, HDV patients had access to specialized follow-up, to innovative therapies (bulevirtide), were mostly on NUCs and demonstrated good disease awareness.

Abstract: The pharmaceutical industry is undergoing a significant transformation driven by digitalization and the adoption of Industry 4.0 principles. Among the most promising innovations is digital twin technology, which creates dynamic virtual replicas of physical manufacturing processes that enable real-time simulation, monitoring, prediction, and optimization. This review article examines the convergence of digital twin technology with established process validation frameworks in pharmaceutical manufacturing, with particular emphasis on the three-stage lifecycle approach outlined in the United States Food and Drug Administration (FDA) Process Validation Guidance and the International Council for Harmonisation (ICH) quality guidelines Q8 (R2), Q9 (R1), Q10, and Q13. The paper explores how digital twins can enhance each stage of process validation, from process design (Stage 1) through process qualification (Stage 2) to continued process verification (Stage 3), by providing mechanistic and data-driven models that improve process understanding, reduce development timelines, and support real-time decision-making. Key enabling technologies, including Process Analytical Technology (PAT), Internet of Things (IoT) sensor networks, machine learning algorithms, and cloud computing platforms, are discussed in the context of their integration with digital twin architectures. Case studies from both small molecule and biologic manufacturing are presented to illustrate practical applications. The article further addresses regulatory considerations, data integrity requirements, model validation challenges, and the ethical implications of adopting AI-augmented digital twins in GMP-regulated environments. Finally, future research directions, including the integration of quantum computing, multi-omics data, and federated learning approaches, are proposed. This review aims to provide pharmaceutical scientists, engineers, and regulatory professionals with a comprehensive roadmap for leveraging digital twin technology to achieve robust, compliant, and efficient manufacturing processes.

Abstract: Background: Splenic marginal zone lymphoma (SMZL) is a rare indolent lymphoma with extremely limited population level evidence on social and treatment correlates of survival. Methods: We conducted a retrospective cohort study using SEER (2000 to 2022) to evaluate OS in primary SMZL (ICD O 3 9689; spleen C42.2). We summarized baseline features and treatments and used Kaplan Meier and Cox regression. Results: The cohort included 3,548 patients (mean age 68.2 years; 53.6% female). Most were White (89.8%) and non Hispanic (92.1%). Ann Arbor stage was missing or blank in 39.4%. Initial therapy included chemotherapy in 26.4%, beam radiation in 0.7%, and primary site surgery in 21.4%. At last follow up, 56.8% were alive; non Hodgkin lymphoma accounted for 15.8% of the full cohort, with substantial competing causes including heart disease (6.1%). In multivariable Cox analysis, OS was independently associated with age (HR 1.073 per year, 95% CI 1.067 to 1.079), male sex (HR 1.337, 95% CI 1.203 to 1.486), Hispanic ethnicity (HR 1.426, 95% CI 1.194 to 1.703), chemotherapy (HR 1.246, 95% CI 1.118 to 1.390), year of diagnosis (HR 0.983 per category, 95% CI 0.973 to 0.993), marital status (married vs divorced HR 0.720, 95% CI 0.600 to 0.863), and race (Asian or Pacific Islander vs White HR 3.210, 95% CI 1.164 to 8.853). Conclusions: In our large population based analysis, OS in SMZL tracks with demographic and social variables and competing risks. Stage missingness and treatment selection limit causal inference for management effects.

Abstract:

Haiti is a Caribbean country of about 11 million people with a high burden of mosquito-transmitted disease and limited vector control, thereby making effective operational mosquito control of high import. Previous studies have examined vector-borne disease burden and insecticide resistance markers in Haitian Aedes and Anopheles mosquitoes but not Culex species. In this study, we examined collections of Culex quinquefasciatus from 12 locations in northern and southern Haiti for the presence of markers of insecticide resistance (using a variety of target site mutations and biochemical assays) and pathogens (using a deep sequencing microbiome workflow). The metagenome analysis identified Wolbachia, Rhabdoviridae and Plasmodium infection in all sample pools at relatively high levels along with less frequent findings of other potential pathogens. Resistance marker examination identified variable frequencies of knockdown resistance and acetylcholinesterase resistance mutations, as well as variation in resistance-associated enzymatic activities in these populations, which indicate that insecticide resistance to the primary pyrethroid and organophosphate insecticides is likely. Though there was variation between Culex mosquito populations and no clear activity pattern, enzymatic activity was significantly higher in the southern sites compared to the northern sites. Similar findings in Cx. quinquefasciatus populations in other locations in the Americas strongly suggest that vector control with pyrethroid and organophosphate adulticides may be of limited efficacy.

Abstract: IoT-Infused Pedagogies Empowering Resilient Digital Societies via Next-Gen Smart Campus Innovations presents a transformative vision for education in an interconnected era. This paper explores how Internet of Things (IoT) technologies revolutionize pedagogical approaches within smart campuses, fostering adaptive learning ecosystems that extend beyond classrooms to cultivate robust digital communities. By integrating real-time data from sensors, wearables, and AI-driven analytics, next-generation innovations enable personalized instruction, predictive resource management, and immersive simulations that mirror real-world challenges. Key contributions include conceptual models for IoT-embedded teaching strategies that enhance student engagement, operational efficiency, and crisis resilience such as automated safety protocols and energy-optimized environments. Drawing from evolving smart campus infrastructures, augmented reality integrations, and gamified platforms, the framework addresses implementation hurdles like data privacy and scalability through ethical guidelines and modular designs. Ultimately, these advancements position universities as prototypes for resilient digital societies, equipping learners with skills in data literacy, collaborative innovation, and sustainable digital governance. This work bridges theory and practice, offering actionable strategies for educators and policymakers to harness IoT for equitable, future-proof education amid rapid technological shifts.

Abstract: Maintaining forest ecosystems is critical for climate regulation, biodiversity conservation, and the socio-economic stability of agrarian societies such as Ethiopia. This study presents a spatiotemporal analysis of deforestation and its biophysical feedbacks across Ethiopia from 2001 to 2022. The methodology integrates the Hansen Global Forest Change dataset, Global Forest Watch carbon flux data, and MODIS/CHIRPS environmental products within the Google Earth Engine platform, validated by a 1,000-point accuracy assessment. Over the 22-year study period, the nation recorded a total reduction of 718,351 hectares of forest cover, peaking in 2014. The Oromia, Southern Nations, Nationalities, and Peoples' (SNNP), and Benishangul-Gumuz regions experienced the greatest extent of forest loss. In these regions, deforestation correlated positively with rapid population growth and the expansion of key agricultural commodities, specifically wheat, maize, and coffee. Topographic analysis indicates an upward altitudinal shift in deforestation, reaching a peak mean altitude of 1,924 meters and expanding onto steeper slopes. These land-cover changes coincide with spatially heterogeneous environmental shifts; in the southeastern highlands, deforestation corresponded with land surface warming, whereas in the western humid lowlands, clearing coincided with substantial increases in evapotranspiration without immediate thermal anomalies. Additionally, forest-related activities contributed approximately 222.38 million Mg of CO₂ emissions, with the Oromia region identified as the primary contributor. These findings indicate that evidence-based conservation strategies, alternative energy adoption, and sustainable land management are necessary to mitigate further forest loss and ensure long-term ecological resilience.

Abstract:

Requirements for robustness and performance in the frequency domain in control theory are usually formulated as constraints on the modulus of complex functions describing the open-loop system, the sensitivity function, and the complementary sensitivity function. These constraints generate circular sets that can be interpreted as admissible or forbidden regions in the complex plane. In engineering practice, they are often treated as method-specific constructions, without clarifying the general geometric mechanism by which they arise. This study develops a geometric approach in which a broad class of frequency domain robustness constraints is represented as level sets of analytic and fractional-linear functions. The resulting circular sets in the Nyquist plane are characterized in a unified manner and transferred to admissible regions in the s-plane through preimage mappings. The approach is formulated entirely using complex transfer functions, without state-space representations, linear matrix inequalities, or optimization methods. Classical robustness measures, including gain margin, phase margin, and constraints on sensitivity and complementary sensitivity, are shown to be special cases of the same geometric structure. This interpretation establishes a direct link between frequency domain constraints and closed-loop pole locations, allowing a qualitative assessment of robustness and dynamic properties of control systems without introducing new stability criteria or design procedures.

Abstract: Over the past decade, Serious Games (SG) and Immersive Virtual Reality (IVR) have gained increasing interest in rehabilitation. However, in IVR the Head-Mounted Displays (HMDs) introduce limitations such as nausea, eye fatigue, and accessibility constraints. As an alternative, low-immersion games using standard monitors can be employed, though they sacrifice spatial correspondence during user interaction with virtual objects. To address it, this paper presents the development of a SG for upper limb (UL) rehabilitation, incorporating a custom wireless wearable device with vibrotactile haptic feedback to restore spatial correspondence. By combining Leap Motion controller (LMC) based on hand tracking, the system enables natural movement interaction in a closed kinematic chain, offering a viable compromise between immersion and usability. Additionally, three virtual scenarios were developed to train pronation/supination, pinch grip, ulnar/radial deviation, as well as wrist, elbow and phalange flexion/extension. User experience (short AttrakDiff), workload (NASA-RTLX), usability (SUS scale), and functionality were evaluated in healthy participants divided into two groups. Group 1 (n=13) used only LMC, while Group 2 (n=9) used LMC and the wearable device. The results shown that the system was perceived as more functional in Group 2, in addition, an increase in usability (from 74.71 to 80.83) and improvements in feedback, movement precision and quick response were observed in this group. These findings indicate that the wearable device signicantly improves spatial correspondence during interaction, making the system a promising option for motor rehabilitation in desktop VR enviroments.

Abstract: We present a self-contained treatment of the dynamic zero principle, the assertion that the element \( 0 \in S = \{-1,0,+1\} \) is not an absorbing terminal state but a compression boundary through which the system transitions without annihilation. Beginning from three pre-numeric modal states and four interaction constraints (closure, totality, boundedness, nontriviality), we derive the unique minimal algebra \( S \), prove that cancellation is forced rather than postulated, and show that Euler’s identity \( e^{i\pi}+1=0 \) emerges as the algebraic termination certificate of the forced completion sequence \( S \to \mathbb{Z} \to \mathbb{Q} \to \mathbb{R} \to \mathbb{C} \). We prove that the primordial states are symmetric under permutation; triadic completion alone admits a symmetric (\( S_3 \)-equivariant) law, but imposing orientation (order sensitivity) forces symmetry breaking. We discuss howthis naturally aligns with the Cayley–Dickson hierarchy through octonions. Modern quantum field theory already rejects the notion of a trivial vacuum: zero-point energy, vacuum polarization, and renormalization reveal that “empty space” is a structured ground state rather than an absence of structure. However, the algebraic status of this structured vacuum is typically introduced through subtraction schemes and regularization procedures that are formally consistent but conceptually layered atop the theory. The dynamic zero principle provides a minimal algebraic model of a non-absorbing ground state in which compression, cancellation, and holonomy arise from closure itself rather than from external adjustment. In this sense, the present work offers a foundational template for thinking about vacuum structure without ad hoc null-state assumptions. We then formalize the dynamic zero as a \( \mathbb{Z}_2 \) holonomy on the spinor cover: the minimal nontrivial loop that returns observables to themselves while inverting the internal state. The paper is organized into three epistemic tiers: Established (results with complete proofs from first principles), Derivable (results contingent on the full Kosmoplex axiom set whose proofs are sketched or referenced), and Open (precisely stated questions whose resolution would strengthen or falsify the framework). No free parameters appear. The dynamic zero is not a number; it is the engine of non-termination.

Abstract: This study aimed to develop a recycling process for reintegrating dental zirconia waste into CAD/CAM systems and to demonstrate the feasibility of producing functional products from the recycled material. The process began with the purification of zirco-nia, followed by the fabrication of pre sintered blocks compatible with these systems. Subsequently, sintered commercial and recycled zirconia were characterized and compared through density measurements, Vickers hardness, flexural strength, X ray diffraction, hydrothermal degradation analysis, and scanning electron microscopy. The results showed that recycled zirconia exhibits structural properties suitable for practi-cal applications, enabling the fabrication of several industrial prototypes. Overall, this work demonstrates that high value materials such as zirconia can be successfully recy-cled and reintegrated into manufacturing workflows, thereby reducing harmful waste while contributing to environmental sustainability and cost reduction.

Abstract: Mealybugs (Hemiptera: Pseudococcidae) are one of the prevalent pests infesting wine grapes in the eastern United States. Their close association with ants (Hymenoptera: Formicidae) provides them with protection against natural enemies. The study examines mealybug species identification, dominant ant genera present in vineyards, and the impact of sugar dispensers on ant and mealybug populations, as well as fruit cluster infestations. Field trials were conducted in two commercial vineyards in Virginia, USA, both with a history of mealybug infestations. Sampling plots with or without sugar dispensers were compared to assess differences in mealybug and ant population densities and fruit cluster infestation levels. Two mealybug species, Pseudococcus maritimus (Ehrhorn) and Ferrisia gilli Gullan were recorded from both sites. Some dominant ant genera, including Tetramorium Mayr, Lasius Fabricius, Solenopsis molesta (Say), Crematogaster Lund, and Pheidole Westwood were found in close association with mealybugs. Ant populations remained consistently low in the untreated plots throughout the sampling season. While sugar dispensers containing insecticide initially attracted a higher number of ants, the population subsequently declined. Fruit cluster infestation was also highest in the untreated plots lacking sugar dispensers.

Abstract: CdSe-coated electrodes, formed by electrodeposition of CdSe barrier layers on metallic Ti or porous TiO2 substrates were characterized by electrochemical impedance spectroscopy in a (photo)cell with aqueous redox electrolytes based on the sulfide/polysulfide and ferro/ferricyanide couples. Common to the metallic and oxide substrate electrodes, the shape and features of Mott–Schottky plots were found to be influenced by the electrode material properties, the electrolyte contact, and measurement conditions (illumination, frequency, potential-scan speed). The information obtained from capacitance measurements are evaluated on the basis of the ideal Schottky-diode model and photocurrent voltammetry data. The rationale behind the observed non-idealities is inquired, and peculiarities of the measuring procedure connected to the non-stationary character of the interface are discussed.

Abstract: We develop a general framework for quantum field theory in curved spacetime based on Local Minkowski Coordinates (LMC), which incorporates curvature effects into local Feynman diagrammatics. Gravitational influence enters through a curvature-dependent normalization function $B(x)$, derived from covariant current conservation, and a gravitational phase $S(x)$, obtained via the WKB approximation. These quantities enter through local phase accumulation and observer-dependent normalization of external states, without affecting global observables. As a first application, we analyze the local redshift normalization and phase structure of quantum amplitudes in the vicinity of a Schwarzschild black hole. Within their range of validity, the curvature-dependent factors $B(x)$ and $S(x)$ reproduce the expected gravitational redshift of field amplitudes in general relativity. When amplitudes are propagated to asymptotic infinity and evaluated in a standard global quantum state (such as the Unruh state), the resulting flux is consistent with the standard Hawking result. The framework refines the local WKB structure and clarifies the separation between local normalization effects and globally conserved fluxes.

Abstract: Background: Parkinson's disease (PD) has become the fastest-growing neurodegenerative disorder worldwide. A valuable approach for unraveling the disease's mechanisms and new therapeutic targets involves investigating the PD-causing genes identified in families exhibiting the Mendelian inheritance of Parkinsonism. Methods: In this article, we review how genetically modified mouse models can be employed to decipher the genetic architecture of PD. Results: We first discuss how well the human motor and non-motor symptoms of PD are currently evaluated in these PD mouse models, highlighting limitations. The pathogenic roles of five inherited PARK genes in PD are then extensively examined through their respective genetic mouse models in terms of phenotypic and cellular im-pacts. Furthermore, we discuss the strengths and weaknesses of existing transgenic mouse models and highlight significant accomplishments and advancements in this field from 2018 to the present. Conclusions: Building upon the newfound understanding of PD, we propose potential directions for enhancing genetic mouse models to further unveil the underlying mechanisms of PD and advance therapeutic research.

Abstract: This study examines the determinants of liquidity in blockchain-based Voluntary Carbon Markets (VCMs) using three tokenized carbon assets: $KLIMA, BCT, and MCO2. Liquidity is measured by dollar volume, bid-ask spread, and return volatility. Using 1,075 daily on-chain observations from 20 November 2021 to 29 October 2024, we analyze the effects of total supply, transaction activity, market capitalization, transaction frequency, and active wallets. The empirical results reveal substantial heterogeneity across tokens. Dollar volume is jointly driven by token supply, on-chain trading activity, and network participation, particularly for BCT, while $KLIMA and MCO2 liquidity are more sensitive to token supply. Transfer amount and supply dispersion are found to widen bid-ask spreads for BCT. While market capitalization is the main determinant for $KLIMA and MCO2, indicating elevated transaction costs under fragmented and speculative trading conditions. Return volatility is primarily influenced by transfer amount for $KLIMA and market capitalization for BCT and MCO2, highlighting distinct volatility transmission mechanisms. The variables of shared volume, transaction value, and market capitalization on firm value could be moderated by the regulation index, which is referred to as pure moderation. For the variables of total supply, transfer amount, and active wallet, none of them could be moderated by the regulation index. This study contributes a unique integrative approach to measuring liquidity and market microstructure in VCMs, as no standardized global model or index currently captures both dimensions in tokenized carbon markets while incorporating regulatory conditions.

Abstract: Renal cell carcinomas (RCCs) driven by TFE3 rearrangement or TFEB alteration (MiT-RCC) account for up to 40% of pediatric RCC but are rare in adults. MiT-RCC includes fusion-driven tumors with TFE3 or TFEB rearrangements (translocation RCC, tRCC) and TFEB-amplified RCC. Morphologic heterogeneity and historical exclusion from trials have limited evidence-based management. We reviewed literature through January 2026 to summarize molecular biology, pathology, clinical behavior, and systemic therapy. MiT-RCC comprises biologically distinct entities: TFEB-rearranged tumors are often indolent in younger patients, whereas TFEB-amplified RCC, frequently co-amplifying VEGFA, behaves aggressively in older adults. In TFE3-rearranged RCC, fusion partner influences prognosis. Paradoxically, ASPSCR1–TFE3 fusions have the poorest natural history, yet fusion-annotated cohorts suggest these tumors may derive particular benefit from immune checkpoint inhibitor (ICI) plus VEGF receptor tyrosine kinase inhibitor (VEGFR-TKI) combinations. Diagnostic advances including GPNMB immunohistochemistry, TRIM63 RNA in situ hybridization, and sequencing-based fusion panels improve detection of cryptic alterations. First-line ICI + VEGFR-TKI combinations are increasingly favored for metastatic tRCC in eligible patients, while optimal management of TFEB-amplified RCC remains uncertain.

Abstract: Urban renewal, driven by investments in urban space, has transformed the urban landscape and significantly impacted changes in land use and the physical appearance of the urban environment. Incorporating GOS to change the appearance of cities is an important strategy for urban development, by utilizing them as central points of building orientation. Changes in the land use of GOS into other functions that have a negative impact on the urban environment have been widely studied by researchers, but not much research has been done on changes in land use around GOS which function as the central point of urban orientation. This research will examine changes in land use patterns around the Karebosi Field Complex GOS on a building plot unit scale using a survey research approach with descriptive analysis. The research was conducted in Makassar City, and data analysis was carried out in 2023. The GOS sample was selected through purposive sampling, the Karebosi Field Complex GOS was deliberately chosen as the research subject because of its area and optimal and dynamic activities, as a leading landmark that contributes to Makassar city branding. It was found that changes in land use based on building plot units, some of which have taken place three times, 89 percent of the land plots around GOS have changed function, all land function changes have become land with commercial functions, the two land plot units that have not changed function are Makassar District Court Office and Church Building. Centrifugal force occurs when government building land is pushed away from the city core and replaced by commercial building land as a manifestation of centripetal force which is attracted to enter the city core area and function as a central business district.