Search Results (127)

Shape-stabilized phase change materials (SSPCMs) have been a promising thermal energy storage (TES) solution to combine the high energy density of solid-to-liquid (SL) PCMs and the structural stability of solid–solid PCMs. Although polymeric matrices have been used for their reduced cost and ease of processability, few have evaluated the use of crosslinked natural rubber (NR). In this study, we evaluate by differential scanning calorimetry (DSC) the preparation of room-temperature tailorable SSCPMs by the design of NR matrices with different crosslink density vulcanized by dicumyl peroxide (DCP) or sulphur, with special focus on the quantification of the content of PCM. The results indicate that the amount of PCM stable in the NR matrix is low, with PCM contents between 16 and 24% and enthalpies between 16 and 20 J·g⁻¹. Likewise, it is well-known that thermophysical properties of the PCMs vary upon confinement in a small-scale porous matrix. The confinement of the PCM in the rubber network results in a measured enthalpy below the expected value, and a melting point depression of up to 23.6 °C, dependent on crosslink density. These results highlight the structural complexity of NR-PCM composites and the need for further investigation. Full article

Background and Clinical Significance: Upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, is increasingly prescribed for autoimmune and inflammatory diseases. Although its therapeutic safety profile is well established, fatal intoxications have not been reported to date. Case Presentation: We describe the first fatal case of upadacitinib overdose in a 13-year-old girl. Following ingestion of approximately 600 mg (40 × 15 mg tablets Rinvoq^®), the patient presented with deep coma, profound bradycardia (~40 bpm) with third-degree atrioventricular block, conduction delay, hypotension, hypothermia, and metabolic acidosis. Laboratory tests showed hyperglycemia (17.8 mmol/L) and only minimal elevations in cardiac biomarkers (CK 57.03 U/L, CK-MB 30.64 U/L, troponin 0.003 ng/mL). Despite advanced resuscitation, the patient succumbed within a few hours. Forensic toxicology revealed extremely high concentrations of upadacitinib, 1.84 µg/mL (~1840 ng/mL) in blood and 70.3 µg/mL in gastric contents, far exceeding reported therapeutic plasma levels (Cmax 36.0 ± 8.8 ng/mL). This case establishes the first reported value for a lethal upadacitinib concentration in humans. The combination of conduction abnormalities, refractory shock, and minimal biomarker changes is consistent with an acute electrophysiological and hemodynamic collapse rather than myocardial infarction. Conclusions: The toxicity of upadacitinib in this case is characterized by profound central nervous system depression, severe cardiovascular (electrophysiological and hemodynamic) disturbances, and metabolic abnormalities (acidosis and hyperglycemia). These findings provide essential reference data for clinical and forensic toxicology, highlight the fatal potential of upadacitinib in overdose, and underscore the importance of secure medication storage and pharmacovigilance in households with adolescents. Full article

A central challenge in tight fault-depression reservoirs is understanding how three-dimensional fracture structures control gas storage and flow. This study introduces a data-driven, geologically informed framework that integrates structural-mechanical coupling to decipher fracture networks within the Shahezi Formation. Our model, based on rock failure criteria, achieves quantitative fracture prediction across one-dimensional to three-dimensional scales. This capability overcomes the limitations inherent in single-method approaches for tight, fracture-dominated reservoirs. By synthesizing sedimentary facies-controlled reservoir modeling, sweet-spot inversion, and geo-engineering integration, we establish a predictive system for accurate reservoir assessment. The continental clastic Shahezi Formation is typified by secondary fractures. This study utilizes leverage small-scale data (core, thin section, log) to quantify key parameters (fracture density, aperture), enabling a systematic analysis of fracture typology, heterogeneity, and controls. Building on this foundation, and spatially constrained by large-scale datasets (seismic interpretation, stress-field simulations), we developed a robust fracture development model for deep tight reservoirs. Stress-field modeling delineated fracture-prone zones, where a discrete fracture network (DFN) model was built to characterize 3D fracture geometry and connectivity. Integrating simulated fracture size and aperture-derived permeability allowed us to quantify fracture contribution to total permeability, ultimately mapping favorable targets. The results identify favorable zones primarily in the western sector of the study area, forming an NS-trending, belt-like distribution. They are mainly concentrated around the wells Changshen-4, Changshen-40, and Changshen-41. This distribution is clearly controlled by the Qianshenzijing Fault. Full article

Microtopography regulates soil erosion by shaping surface heterogeneity, but the mechanism of loess slope soil loss remains insufficiently quantified. This study combined laboratory rainfall simulations and machine learning to investigate how tillage-induced microtopography modulates soil loss through surface heterogeneity and hydrodynamic processes. Simulations used loess soil (silty loam) with a 5° slope, 60 mm/h rainfall intensity, and 5–30 min rainfall durations (RD). Results indicated that the mean weight diameter (MWD) and aggregate stability index (ASI) of structural, transition, and depositional crusts under micro-terrain decreased by 36~65% and 41~60%, respectively, while the fractal dimension (D) increased by 10~19%. Negative relationships were observed between ASI/MWD and D (R² = 0.83~0.98). Horizontal cultivation (T_HC, surface roughness [SR] = 1.76, average depression storage [ADS] = 2.34 × 10⁻² m³) delayed runoff connectivity and reduced cumulative soil loss (LS) by 42–58% compared to hoeing cultivation (T_HE, SR = 1.47, ADS = 3.23 × 10⁻⁴ m³). Abrupt hydrodynamic transitions occurred at 10 min RD (T_HE) and 15 min RD (artificial digging [T_AD]), driven by trench connectivity and depression overflow. LS exhibited a significant positive correlation with D and RD and was inversely correlated with ASI, MWD, and SR. A three-hidden-layer BPNN exhibited high predictive accuracy for LS (mean square error = 0.07), verifying applicability in complex scenarios with significant microtopographic heterogeneity and multi-factor coupling. This study demonstrated that surface roughness and depression storage were the dominant microtopographic controls on loess slope soil loss. BPNN provided a reliable tool for soil loss prediction in heterogeneous microtopographic systems. The findings provide critical insights into optimizing tillage-based soil conservation strategies for sloping loess farmlands. Full article

Karst aquifers, vital freshwater resources, are highly vulnerable to agricultural pollution, yet their hydro-geochemical responses remain poorly understood due to high spatial heterogeneity. This study aimed to unravel these complex responses in a subtropical karst agricultural catchment to provide a basis for its sustainable management. We employed high-frequency monitoring at a headwater spring (background), a depression well (hotspot), and the catchment outlet (integrated) in Southwest China. Using hydrological and geochemical data from 2017, we applied Principal Component Analysis (PCA) to apportion natural and anthropogenic sources. The main findings revealed significant spatial heterogeneity, with the depression well acting as a contamination hotspot characterized by rapid hydrological responses and elevated SO₄²⁻ and Cl⁻ concentrations. PCA successfully decoupled an “anthropogenic factor” (PC1, 40.5%) from a “natural weathering factor” (PC2, 25.2%). Critically, agricultural SO₄²⁻ at the hotspot was counter-intuitively higher during the wet season than the dry season, opposing the typical dilution pattern of background ions and revealing that depressions act as contaminant-concentrating pathways, whose risks are severely underestimated by traditional outlet monitoring. The anomalous sulfate dynamics reveal a cross-seasonal “storage-and-release” mechanism (legacy effect) within the karst Critical Zone, demonstrating that these systems can buffer and “remember” contaminants. Full article

In the northern part of the Songliao Basin, the Aonan Depression is a significant structural feature. It plays a crucial role in the relationship between tectonic evolution and deep natural gas accumulation mechanisms. While previous studies have revealed faulting and sedimentary characteristics in the region, the precise connection between tectonic evolution and hydrocarbon accumulation, particularly for deep natural gas, has not been systematically studied. This research uses structural modeling and stratigraphic restoration to reconstruct the tectonic evolution of the third section of the Shahezi Formation and develops a 3D geological model of the study area. The results show that the tectonic evolution of the Aonan Depression can be divided into three stages: rifting, sagging, and inversion. Each stage significantly controls hydrocarbon distribution. A self-sourced, self-storage gas system formed in the Shahezi Formation, while the Denglouku and Yingcheng formations exhibit a source–reservoir combination. The study reveals how tectonic evolution influences hydrocarbon accumulation and distribution on a regional scale. Based on these findings, a “rift-controlled source, sag-controlled storage, and structure-controlled trapping” accumulation model is proposed, providing new insights into tectonic evolution and hydrocarbon accumulation mechanisms, with important implications for similar basins’ exploration and structural studies. Full article

Objectives: Ketamine has demonstrated rapid and sustained antidepressant effects; however, its clinical utility is limited by the risk of addiction and systemic side effects. This study aimed to develop ketamine-loaded nanodroplets (Ket-NDs) with high encapsulation efficiency (EE) and stability for targeted low-dose intravenous (IV) administration in a mice model of depression. Low-intensity focused ultrasound (LIFU) was employed to induce transcranial, region-specific drug release in the lateral habenula (LHb). Methods: Ket-NDs were synthesized using a thin-film hydration method with sonication and emulsification, incorporating perfluoropentane as the core material. Characterization was performed using light microscopy, cryogenic scanning electron microscopy (cryo-SEM), transmission electron microscopy, and dynamic light scattering (DLS). Drug EE and loading efficiency (LE) were quantified by reversed-phase high-performance liquid chromatography. A chronic restraint stress model was established, and Ket-NDs were administered intravenously followed by LIFU targeting the LHb. Antidepressant efficacy and biosafety were systematically evaluated. Results: (1) Ket-NDs exhibited uniform spherical morphology and a narrow size distribution, as confirmed by DLS (particle size: 139.75 ± 9.43 nm; Polydispersity index: 0.225 ± 0.025) and cryo-SEM analysis (number-average diameter: 109.5 ± 10.4 nm). The zeta potential was −15.93 ± 5.906 mV, and the formulation remained stable under 4 °C storage. (2) Ket-NDs demonstrated high EE (78.25 ± 16.13%) and LE (15.55 ± 4.49%). (3) In depressive mice, IV administration of Ket-NDs followed by LIFU targeting the LHb significantly improved behavioral outcomes: increased locomotor activity in the open field test, elevated sucrose preference index, and reduced immobility time in the tail suspension test. (4) Safety assessments revealed no significant organ toxicity or brain tissue damage in ultrasound-exposed regions. Conclusions: In summary, this study developed stable Ket-NDs. When combined with LIFU, they enable precise regional drug delivery to the brain, showcasing a promising treatment strategy for depression with reduced systemic side effects. Full article

Metal oxides are the most widely used material for the resistive switching layer of memristors. Nevertheless, the majority of oxide-based memristors exhibit binary switching, restricting the emulation of neuronal synaptic behaviors. In this paper, the shift from digital-to-analog switching behavior is achieved by inserting an Al₂O₃ layer atop Zr-doped HfO₂. The TiN/Al₂O₃/HZO/W/Si device exhibits long resistance state retention time and consistency. In addition, by applying a varying voltage, the device exhibits up to 20 continuous resistance states, which is highly significant for high-density storage. Upon the application of a programmable pulse signal, the device’s conductance undergoes continual alteration, reflecting long-term potentiation (LTP) and long-term depression (LTD) synaptic characteristics. The conduction mechanism of the device is studied through physical model fitting and schematic diagrams. Full article

Background/Objectives: The intranasal (IN) route of administration is a promising non-invasive approach for brain targeting, bypassing the blood–brain barrier and enhancing bioavailability. Citalopram hydrobromide (CT), a widely prescribed sparingly water-soluble selective serotonin reuptake inhibitor (SSRI), faces challenges with oral and intravenous administration, including delayed onset, adverse effects, and patient compliance issues. Methods: This study aimed to develop a novel thermoresponsive polymeric micelle (PM) system based on Pluronic^® copolymers (Pluronic F127 and Poloxamer 188) improving CT’s solubility, stability, and nasal permeability for enhanced antidepressant efficacy. A preliminary study was conducted to select the optimized formulation. The preparation process involved using the thin-film hydration method, followed by freeze-drying. Comprehensive evaluations of optimized formulation characteristics included Z-average, polydispersity index (PdI), thermal behavior (lower critical solution temperature, LCST), encapsulation efficiency, X-ray powder diffraction (XRPD), thermodynamic solubility, and biological stability. Additionally, in vitro CT release and CT permeability in nasal conditions were studied. Stability under storage was also evaluated. Results: The optimized CT-PM formulation showed nanoscale micelle size (Z-average of 31.41 ± 0.99 nm), narrow size distribution (polydispersity index = 0.241), and a suitable thermal behavior for intranasal delivery (lower critical solution temperature (LCST) ~31 °C). Encapsulation efficiency reached approximately 90%, with an amorphous structure confirmed via XRPD, leading to a 95-fold increase in CT solubility. The formulation demonstrated appropriate biological and physical stability. In vitro studies showed a 25-fold faster CT release from optimized formulation compared to the initial CT, while CT-PM permeability in nasal conditions increased four-fold. Conclusions: This novel nanoscale thermosensitive formulation is a value-added strategy for nasal drug delivery systems, offering enhanced drug solubility, rapid drug release, stability, and improved permeability. This smart nanosystem represents a promising platform to overcome the limitations of conventional CT administration, improving therapeutic outcomes and patient compliance in depression management. Full article

Chronic skin wounds are difficult to heal or nonhealing. These wounds may become infected and progress to tissue necrosis, potentially leading to limb amputation, sepsis, reduced quality of life, depression, economic burden on the healthcare system, and social isolation. Several clinical strategies, including negative pressure wound therapy, antibiotic-based infection control, and wound debridement, have been developed to treat skin wounds. However, these approaches primarily target local wound conditions and offer only short-term relief, not achieving sustained functional regeneration. Stem cell-based therapy has emerged as an alternative therapeutic method for skin wound treatment owing to its ability to suppress inflammation, stimulate angiogenesis, and promote cellular proliferation. However, the low post-transplantation survival rate of stem cells remains a major limitation. Exosomes, nanosized extracellular vesicles, transport proteins, lipids, mRNAs, and miRNAs and mediate regenerative functions, including anti-inflammatory effects, angiogenesis promotion, and extracellular matrix remodeling. Stem cell-derived exosomes (SC-Exos) offer several advantages over their parent cells, including greater stability, lower immunogenicity, absence of tumorigenic risks, and ease of storage and distribution. These attributes render SC-Exos particularly attractive for cell-free regenerative therapies. In this review, we introduce exosomes derived from various types of stem cells and explore their therapeutic applications in skin wound regeneration. Full article

In the context of the evolving global energy landscape, tight gas fields have gained in-creasing significance due to their low-porosity and low-permeability reservoirs, where natural fractures play a critical role in improving permeability and enhancing storage capacity. Foreland basins, such as the Dibei area in the northern Kuqa Depression of the Tarim Basin, are typical hosts for tight gas reservoirs, but the complex fracture development induced by multiple tectonic movements restricts natural gas exploration. This study employs core observation, imaging logging analysis, and thin-section microscopy to characterize the genetic types and development features of natural fractures in the Ahe Formation. Results show that 54% of natural fractures in the Dibei area are structurally originated, predominantly high-angle and open. The highest fracture density (0.351 fractures/m), six times that of other regions, occurs in the upper horst zones. Three fracture patterns are identified, namely fault–fold, fault-related, and monocline types. Fault–fold fractures are most developed due to folding and thrusting, while monocline zones are poorly fractured. Structural fractures are best developed in horst crests with fault–fold patterns. Fracture development is jointly controlled by folds, faults, stress, and lithology, with distinct characteristics across different structural positions and lithological combinations. Clarifying the development characteristics and distribution patterns of natural fractures in the Ahe Formation of the Dibei area facilitates accurate evaluation of high-quality reservoirs, providing crucial geological basis for optimizing hydrocarbon sweet spots and refining accumulation models in the region. Full article

Background/Objectives: Niemann-Pick disease Type C (NPC) represents an autosomal recessive disorder with an incidence rate of 1 in 100,000 live births that belongs to the lysosomal storage diseases (LSDs). NPC is characterized by the abnormal accumulation of unesterified cholesterol, in addition to being an autosomal recessive inherited pathology, which belongs to LSDs. It occurs in 95% of cases due to mutations in the NPC1 gene, while 5% of cases are due to mutations in the NPC2 gene. In the cerebral cortex (CC), the disease shows lipid inclusions, increased cholesterol and multiple sphingolipids in neuronal membranes, and protein aggregates such as hyperphosphorylated tau, α-Synuclein, TDP-43, and β-amyloid peptide. Mitochondrial damage and oxidative stress are some alterations at the cellular level in NPC. Therefore, the aim of this work was to determine the gene expression profile in the CC of NPC1 mice in order to identify altered molecular pathways that may be related to the pathophysiology of the disease. Methods: In this study, we performed a microarray analysis of a 22,000-gene chip from the cerebral cortex of an NPC mutant mouse compared to a WT mouse. Subsequently, we performed a bioinformatic analysis in which we found groups of dysregulated genes, and their expression was corroborated by qPCR. Finally, we performed Western blotting to determine the expression of proteins probably dysregulated. Results: We found groups of dysregulated genes in the cerebral cortex of the NPC mouse involved in the ubiquitination, fatty acid metabolism, differentiation and development, and underexpression in genes with mitochondrial functions, which could be involved in intrinsic apoptosis reported in NPC, in addition, we found a generalized deregulation in the cortical circadian rhythm pathway, which could be related to the depressive behavior that has even been reported in NPC patients. Conclusions: Recognizing that there are changes in the expression of genes related to ubiquitination, mitochondrial functions, and cortical circadian rhythm in the NPC mutant mouse lays the basis for targeting treatments to new potential therapeutic targets. Full article

Memristors with resistive switching capabilities are vital for information storage and brain-inspired computing, making them a key focus in current research. This study demonstrates non-volatile analog resistive switching behavior in Al/TiO_x/TiN/Si(n⁺⁺)/Al memristive devices. Analog resistive switching offers gradual, controllable conductance changes, which are essential for mimicking brain-like synaptic behavior, unlike digital/abrupt switching. The amorphous titanium oxide (TiO_x) active layer was deposited using the pulsed-DC reactive magnetron sputtering technique. The impact of increasing the oxide thickness on the electrical performance of the memristors was investigated. Electrical characterizations revealed stable, forming-free analog resistive switching, achieving endurance beyond 300 DC cycles. The charge conduction mechanisms underlying the current–voltage (I–V) characteristics are analyzed in detail, revealing the presence of ohmic behavior, Schottky emission, and space-charge-limited conduction (SCLC). Experimental results indicate that increasing the TiO_x film thickness from 31 to 44 nm leads to a notable change in the current conduction mechanism. The results confirm that the memristors have good stability (>1500 s) and are capable of exhibiting excellent long-term potentiation (LTP) and long-term depression (LTD) properties. The analog switching driven by oxygen vacancy-induced barrier modulation in the TiO_x/TiN interface is explained in detail, supported by a proposed model. The remarkable switching characteristics exhibited by the TiO_x-based memristive devices make them highly suitable for artificial synapse applications in neuromorphic computing systems. Full article

Nanoparticle floating gate (NPFG) transistors have gained attention as synaptic devices due to their discrete charge storage capability, which minimizes leakage currents and enhances the memory window. In this study, we propose and evaluate a mesh-type floating gate transistor (Mesh-FGT) designed to emulate the characteristics of NPFG transistors. Individual floating gates with dimensions of 3 µm × 3 µm are arranged in an array configuration to form the floating gate structure. The Mesh-FGT is composed of an Al/Pt/Cr/HfO₂/Pt/Cr/HfO₂/SiO₂/SOI (silicon-on-insulator) stack. Threshold voltages (Vth) extracted from the transfer and output curves followed Gaussian distributions with means of 0.063 V (σ = 0.100 V) and 1.810 V (σ = 0.190 V) for the erase (ERS) and program (PGM) states, respectively. Synaptic potentiation and depression were successfully demonstrated in a multi-level implementation by varying the drain current (I_ds) and Vth. The Mesh-FGT exhibited high immunity to leakage current, excellent repeatability and retention, and a stable memory window that initially measured 2.4 V. These findings underscore the potential of the Mesh-FGT as a high-performance neuromorphic device, with promising applications in array device architectures and neuromorphic neural network implementations. Full article

Based on a detailed investigation of the geological setting of coalbed methane by previous work in the Xiangzhong Depression, Hunan Province, numerical simulation methods were used to simulate the geological storage of carbon dioxide and displacement gas production in this area. In this simulation, a 400 m × 400 m square well group was constructed for coalbed methane production, and a carbon dioxide injection well was arranged in the center of the well group. Injection storage and displacement gas production simulations were carried out under the conditions of original permeability and 1 mD permeability. At the initial permeability (0.01 mD), carbon dioxide is difficult to inject, and the production of displaced and non-displaced coalbed methane is low. During the 25-year injection process, the reservoir pressure only increased by 7 MPa, and it is difficult to reach the formation fracture pressure. When the permeability reaches 1 mD, the carbon dioxide injection displacement rate can reach 4000 m³/d; the cumulative production of displaced and non-displaced coalbed methane is 7.83 × 10⁶ m³ and 9.56 × 10⁵ m³, respectively, and the average daily production is 1430 m³/d and 175 m³/d. The displacement effect is significantly improved compared to the original permeability. In the later storage stage, the carbon dioxide injection rate can reach 8000 m³/d, reaching the formation rupture pressure after 3 years, and the cumulative carbon dioxide injection volume is 1.17 × 10⁷ m³. This research indicates that permeability has a great impact on carbon dioxide geological storage. During the carbon dioxide injection process, selecting areas with high permeability and choosing appropriate reservoir transformation measures to enhance permeability are key factors in increasing the amount of carbon dioxide injected into the area. Full article