Search Results (2,857)

Response of large-diameter rock-socketed piles subjected to lateral loads is a critical issue in foundation design for bridges, high-rise buildings, and offshore platforms. Although the p-y curve method is commonly used for pile analysis in soil, its direct application to rock-socketed piles remains challenging due to the significant differences in mechanical properties between rock and soil. This study investigates the initial stiffness and stress distribution around the large-diameter rock-socketed piles under lateral loads. Based on the Serrano method, the Hoek–Brown strength criterion is extended to derive calculation formulas for rock cohesion and internal friction angle considering confining pressure effects. A three-dimensional numerical model was established using FLAC3D to analyze stress distribution, pile displacement, and p-y curves at different depths. Distribution functions for normal stress and shear stress around the pile were developed. Parameter sensitivity analysis reveals that the initial stiffness of p-y curves is primarily influenced by rock deformation modulus and pile diameter, while rock strength parameters and pile length effects are negligible. Empirical formulas for predicting initial stiffness of p-y curves were proposed through regression analysis. These results serve as both a theoretical basis and an engineering reference for the design and analysis of large-diameter rock-socketed piles under lateral loading. Full article

Background/Objectives: Retinoblastoma represents the most common intraocular malignancy in childhood; however, the clinical applicability of mitomycin C (MMC) is restricted by dose-dependent ocular toxicity. Consequently, the development of pharmacological strategies that sensitize tumor cells to MMC while allowing dose reduction remains an unmet therapeutic objective. In this context, quercetin, a bioactive flavonoid with pleiotropic anticancer properties, has emerged as a potential chemosensitizing agent. Methods: Human retinoblastoma cell lines Y79 and WERI-Rb1 were exposed to MMC and quercetin, administered either individually or in fixed-ratio combinations. Cytotoxic responses were quantified through dose–response modeling and IC₅₀ determination following 24 and 48 h of treatment. Drug–drug interactions were quantitatively characterized using the Chou–Talalay combination index (CI) approach and isobologram analysis. Cell cycle distribution was assessed by propidium iodide (PI)-based flow cytometric analysis to evaluate treatment-associated alterations in cell cycle progression. Apoptotic cell death was assessed by Annexin V-FITC/PI flow cytometry, while transcriptional modulation of genes associated with apoptosis, cell cycle regulation, and oxidative stress (BAX, BCL-2, TP53, CASP3, CDKN1A, and HMOX1) was evaluated by qRT-PCR. Modulation of tumor-supportive signaling was examined by measuring VEGF and IL-6 secretion. Translational relevance was further investigated using a three-dimensional (3D) tumor spheroid model, and the functional contribution of reactive oxygen species (ROS) was interrogated through N-acetyl-L-cysteine (NAC) rescue experiments. Results: Quercetin significantly enhanced the cytotoxic activity of MMC in both retinoblastoma cell lines, with CI values below 1 across IC₅₀–IC₉₀ effect levels, indicating a synergistic pharmacological interaction. PI–FACS analysis revealed that combined MMC and quercetin treatment induced a pronounced accumulation of cells in the G2/M phase, consistent with cell cycle arrest, with a more marked effect observed in Y79 cells compared with WERI-Rb1 cells. Combination treatment resulted in a pronounced increase in apoptotic cell populations compared with single-agent exposure and triggered a coordinated pro-apoptotic transcriptional response, characterized by increased expression of BAX, TP53, CASP3, CDKN1A, and HMOX1, alongside suppression of BCL-2 and a marked shift in the BAX/BCL-2 ratio. Concurrently, VEGF and IL-6 secretion were significantly reduced, reflecting attenuation of pro-angiogenic and pro-inflammatory signaling. Notably, synergistic cytotoxicity was maintained in 3D tumor spheroids, where combined treatment induced spheroid shrinkage, architectural disruption, and reduced viability. NAC pretreatment diminished ROS accumulation and partially restored cell viability, indicating that oxidative stress contributes to, but does not solely account for, the observed synergistic cytotoxic effect. Conclusions: Collectively, these findings indicate that quercetin appears to function as an effective chemosensitizing adjuvant to MMC in retinoblastoma models, through transcriptional changes consistent with p53-associated apoptotic signaling at the transcriptional level, G2/M cell cycle arrest, and partial involvement of ROS-related cellular stress responses, along with suppression of tumor-supportive signaling pathways. The preservation of synergistic activity in 3D tumor spheroids supports the potential preclinical relevance of this combination. However, these findings are based on transcriptional and phenotypic analyses and should be interpreted as hypothesis-generating, requiring further validation through protein-level and in vivo studies before translational application. Full article

Background/Objectives: Natural killer (NK) cells are key innate lymphoid cells that restrict tumour progression by secreting proinflammatory cytokines and directly lysing malignant cells, with their activity tightly regulated by a balance of activating and inhibitory surface receptors. The natural cytotoxicity receptor NKp44 is induced on NK cells following stimulation with IL-2 or IL-15 and recognizes platelet-derived growth factor D (PDGF-DD) as a ligand. Mechanistic interpretation of NKp44 signalling upon PDGF-DD engagement is confounded by the existence of three distinct NKp44 isoforms (NKp44-1, -2, and -3), each capable of initiating divergent intracellular signalling cascades. Unlike NKp44-2 and -3, NKp44-1 encodes a cytoplasmic tyrosine residue (Y238) that conforms to a putative immunoreceptor tyrosine-based inhibition motif (ITIM) and has been reported to suppress NK cell effector functions in some contexts. However, it remains unclear whether the NKp44 isoforms are translated and expressed in NK cells, and formal evidence defining NKp44-1 signalling in response to engagement by PDGF-DD is lacking. Methods: In this study, we used C-terminal targeting monoclonal antibodies (mAbs) and a NFAT-GFP reporter system to define the expression and signalling properties of NKp44 isoforms in response to PDGF-DD. Results: We demonstrate protein expression of NKp44-1 and NKp44-2-/3 receptors in IL-2 expanded NK cells. We further show that NKp44-1 transduces activating rather than inhibitory signals when engaged by PDGF-DD ligand, albeit weaker than NKp44-3. Intriguingly, we find that Y238 is dispensable for NKp44-1 activating signalling and instead functions as a YXXΦ internalisation motif. Conclusions: Collectively, these findings provide the first evidence that the NKp44-1 and NKp44-2/3 isoforms are expressed in NK cells and establish that PDGF-DD activates signalling through NKp44-1 independently of Y238. This work lays the foundations for future studies investigating how PDGF-DD sensing by the different NKp44 isoforms shapes immune functions in different physiological and pathological contexts. Full article

Background/Objectives: Salidroside, a bioactive phenylethanol glycoside primarily derived from Rhodiola rosea, and its major in vivo metabolite tyrosol exhibit diverse pharmacological activities. However, their direct molecular targets remain poorly defined. Methods: In the present study, an integrated strategy combining transcriptomic profiling, Connectivity Map (CMap) analysis, and multi-level experimental validation was employed. Transcriptomic signatures derived from A549 cells treated with salidroside or tyrosol were queried against the CMap database. Molecular docking, surface plasmon resonance (SPR), and cellular thermal shift assays (CETSA) were performed to predict and validate binding interactions. Functional validation was performed in SH-SY5Y cells. The phosphorylation level of extracellular signal-regulated kinase (ERK), a downstream signaling event of dopamine D2 receptor (DRD2), was detected after salidroside and tyrosol treatment. DRD2 antagonist sulpiride pre-intervention and small interfering RNA (siRNA)-mediated DRD2 knockdown were conducted to verify the receptor dependence of the compounds’ effects. Results: CMap analysis revealed that the transcriptomic signatures of salidroside and tyrosol showed significant similarity to known DRD2 modulators. Molecular docking predicted potential binding interactions between the two compounds and DRD2, which was confirmed by SPR and CETSA to be direct physical binding. Functional studies showed that both compounds rapidly induced DRD2 downstream ERK phosphorylation in SH-SY5Y cells; this effect was abrogated by sulpiride or DRD2 knockdown, indicating DRD2-dependent signaling activation. Conclusions: These findings identify DRD2 as a direct molecular target of salidroside and tyrosol and provide mechanistic insight into their dopaminergic regulatory effects. This study highlights the utility of CMap-guided target discovery combined with rigorous experimental validation for elucidating the molecular mechanisms of natural products. Full article

Canine parvovirus (CPV) is a major pathogen causing severe gastroenteritis in dogs. Since its emergence, CPV has undergone continuous evolution, leading to the predominance of variants such as CPV-2a, CPV-2b, and CPV-2c. To characterize the genetic features and evolutionary trends of CPV-2 at a regional level, 775 fecal samples were collected from domestic and stray dogs with suspected CPV-2 infection in Shanghai between 2016 and 2025. The overall positivity rate was 23.2% (180/775); incidence was substantially higher in stray dogs (30.2%) than in domestic dogs (15.9%). Thirty-one CPV-2 strains were successfully isolated. Temporal analysis revealed a pronounced genotype shift: isolates from 2016 to 2020 were predominantly New CPV-2a, whereas CPV-2c became the dominant genotype from 2021 through 2025. Sequence analysis identified the polymorphism of VP2 gene and characteristic mutations F267Y, Y324I, N426E, Q370R and A440T in CPV-2c strains. A novel I447M mutation was detected in several isolates. Phylogenetic analysis showed that Shanghai isolates formed distinct clusters; CPV-2c strains were closely related to the Asian lineage. Structural modeling indicated that mutations at residues L87M, T101I, Y267F, A297S, G300A, Y305D, I324Y, Q370R, N426E, A440T, and I447M may alter the tertiary structure of the VP2 protein, potentially affecting antigenicity and receptor recognition. Collectively, these results demonstrate the complete genotype replacement of CPV-2 in Shanghai; CPV-2c is now predominant. Identification of the novel I447M mutation and structural analysis of key amino acid substitutions provide insight into CPV molecular evolution. These findings suggest that vaccines primarily based on older CPV-2 or CPV-2b genotypes offer suboptimal protection, highlighting the need for updated vaccine strategies targeting prevalent CPV-2c variants. Full article

The adsorption and activation of CO₂ on Cu_xSc_y nanoclusters with x + y equal to 4 were analyzed using DFT and PDOS and TDOS signatures. The geometries of Cu₃Sc, Cu₂Sc₂, and CuSc₃ were optimized in the gas phase, and the minima were verified by frequencies in ORCA using M06-2X/def2-TZVP. Multiplicities 1, 3, and 5, temperatures between 298 and 400 K, and four CO₂ coordination modes R1 to R4 were evaluated. Naked and complex cluster comparison panels were constructed, and two energy windows, −18 to −10 eV and −8 to 6 eV around the Fermi level, were analyzed, complemented by frontier orbitals and charge maps. Thermodynamics indicated that mode and multiplicity control the adsorption energy, with ANOVA p-values of 0.002 and 0.008, while temperature was not significant (p = 0.682). In Cu₃Sc–C₂v(1), the R1 singlet at 298 K showed E_ads −33.43 kcal·mol⁻¹ with spin contamination, while alternative modes in the singlet were unfavorable. In PDOS and TDOS, the bare cluster exhibits a Cu d band at −11 to −10 eV and a valley around −5 eV. The exergonic complexes show CO₂ signals near the Fermi level, superimposed on Cu and Sc states, with state filling and broadening. Transferable indicators based on CO₂ intensity in the −8 to 6 eV range and metal–adsorbate overlap are proposed as predictors of exergonic adsorption. Full article

Chronic kidney disease (CKD) is a progressively worsening condition that erodes renal function over time, reduces quality of life, and can ultimately culminate in kidney failure with far-reaching systemic complications. In addition to reduced filtration, worsening kidney function disrupts mineral homeostasis and leads to CKD–mineral and bone disorder (CKD-MBD). Dysregulated calcium handling and maladaptive endocrine responses contribute to bone pathology and increase cardiovascular calcification risk; therefore, serial calcium monitoring remains clinically relevant for longitudinal CKD management. Conventional calcium measurements are typically obtained with centralized analyzers or laboratory assays (e.g., colorimetry and electrode/optical readouts). Despite high accuracy, the required instrumentation, controlled operating conditions, and pretreatment steps complicate rapid point-of-care deployment, especially when only microliter-scale biofluids are available. Accordingly, this study develops a finger-actuated microfluidic colorimetric platform capable of determining calcium ion concentrations in human biofluids, such as whole blood, serum, and urine. The platform integrates a three-dimensional PMMA/paper microchip with a compact reader that maintains stable temperature control while enabling CMOS-based optical detection. With just 6 μL of sample, a brief finger press propels the biofluid across an internal filtration layer, generating serum or cleaned urine that subsequently reacts with a pre-deposited murexide reagent. Under optimized conditions (1.6% reagent, 50 °C, 3 min), the signal follows a strong logarithmic relationship with calcium concentration (Y = 47.273 ln X + 28.890; R² = 0.9905), supporting quantification over 1–40 mg/dL and a detection limit of 0.2 mg/dL. Across 80 clinical CKD specimens spanning serum, whole blood, and urine, results aligned closely with the NM-BAPTA reference assay, with R² values exceeding 0.97. Full article

The Asian citrus psyllid Diaphorina citri Kuwayama (Hemiptera: Liviidae) is the vector of the devastating citrus disease Huanglongbing, posing a significant threat to the global citrus industry and necessitating environmentally sound management strategies. This study aimed to evaluate Australian tea tree oil (TTO) and its primary constituents as potential botanical insecticides. Gas chromatography-mass spectrometry (GC-MS) was performed to analyze the chemical profile of commercial TTO, and behavioral effects on D. citri adults were assessed using a Y-tube olfactometer. Direct spray bioassays were conducted to determine contact toxicity. A total of 12 compounds were identified, with TTO being a Terpinen-4-ol chemotype, dominated by Terpinen-4-ol (40.62%), γ-Terpinene (21.46%), and α-Terpinene (10.45%). TTO demonstrated potent, concentration-dependent repellency, achieving 100% repellency at 10 g/L. In contrast, Terpinen-4-ol alone was attractive to psyllids at low concentrations, suggesting synergistic or masking effects within the complex oil blend. TTO and its major constituents also exhibited significant dose- and time-dependent contact toxicity. Although the 72 h LC₅₀ of TTO (19.18 g/L) indicates lower potency compared to conventional insecticides (0.59–1.23 g/L), its combined repellent and toxic properties make it a promising candidate for integrated pest management (IPM) programs aimed at controlling D. citri and mitigating insecticide resistance. Full article

Pegmatites with miarolitic cavities have not previously been reported from the Larsemann Hills, East Antarctica, and their age and origin remain poorly constrained. We report the first geochemical and geochronological data for fluorapatite from a newly discovered pegmatite with miarolitic cavities in the Larsemann Hills. Large Fe-rich fluorapatite crystals (up to 5 cm) contain abundant oriented monazite-(Ce) inclusions and display elevated REE (1397–7966 ppm), relatively high Y (945–4192 ppm), and low Sr (52.2–83.5 ppm). Their trace-element signatures plot within the fields of partial melts, high-grade metamorphic rocks, and evolved fluid-rich magmatic systems. U–Pb dating of fluorapatite yields concordant ages of 519 ± 4 Ma (ID-TIMS) and 521 ± 31 Ma (LA-ICP-MS), indicating crystallization during the D₄ stage of the Pan-African orogeny. The isotopic equilibrium between apatite and monazite inclusions suggests synchronous formation and late-stage fluid overprinting. Combined geological, geochemical, and isotopic evidence shows that the pegmatite formed in situ as a product of anatexis of the Broknes paragneisses and evolved within a volatile-rich magmatic–hydrothermal system. These results provide the first direct age constraints on pegmatites with miarolitic cavities in Antarctica and shed new light on the final stages of East Gondwana assembly. Full article

Objectives: This study aimed to analyze the three-dimensional displacement of maxillary first molars using a finite element model with two headgear configurations, namely cervical and horizontal pull headgears, as well as pendulum, infrazygomatic miniscrews, Bollard miniplates, Advanced Molar Distalization Appliance (AMDA), and Beneslider. The goal was to clarify how variations in anchorage design and force direction influence molar movement across the sagittal, vertical, and transverse planes. Methods: A three-dimensional finite element model of the maxillary dentition and supporting structures was constructed using reference anatomical data and standardized material properties. Each appliance was virtually simulated under its clinically recommended force magnitude and direction to ensure realistic biomechanical conditions. The orientation of each force vector relative to the molar’s center of resistance (CR) was analyzed, and resulting tooth displacements were quantified along the sagittal (Z), vertical (Y), and transverse (X) axes using 49-node reference paths connecting key anatomical landmarks. Results: Appliances applying forces through or above the molar CR, such as the AMDA, infrazygomatic miniscrews, and Bollard miniplates, produced nearly bodily distalization with minimal tipping (<0.6° (range 0.3–0.6°)) and slight intrusion (−0.12 to −0.18 mm). Conversely, systems delivering forces below the CR, such as the cervical headgear and pendulum, resulted in greater crown tipping and extrusion. The Beneslider exhibited an intermediate displacement pattern with moderate vertical control. Conclusions: Force vector height and direction relative to the molar CR critically determine 3D displacement behavior. Skeletal anchorage and adjustable systems, particularly the AMDA, demonstrated the most controlled distalization pattern with minimal tipping, whereas conventional tooth-borne designs induced more tipping and extrusion. Full article

PDMS SlipChips are vital for precision medicine, but their performance often degrades when solutions leak or air pockets become trapped between layers. These failures stem from the inherent stickiness of PDMS and uneven surface contact, as the sliding nature of the device prevents permanent sealing. This work addresses these technical hurdles by integrating magnetic clamping with oil-infused lubrication and refined microwell geometries. A 3D-printed magnetic fixture maintains steady contact pressure during operation, while custom-made microstages provide the precise control needed to align microwells across the x–y plane. By allowing the porous PDMS to absorb silicone oil, we created a stable lubricating interface that prevents leakage and reduces friction without sacrificing mobility. We found that a microwell-to-channel width ratio of five substantially suppresses bubble formation compared with narrower designs. These enhancements ensure the generation of consistent, discrete concentration gradients and establish a reliable platform for high-throughput assays using minute sample volumes. Full article

Traditional concert-hall evaluations primarily rely on ISO 3382-1 scalar parameters (e.g., C₅₀ and C₈₀), which summarize temporal energy behavior but provide limited insight into the directional composition of early reflections, particularly in geometrically shadowed seating zones. This paper presents a first-order Ambisonics (FOA)-based 3D acoustic sensing framework to diagnose under-balcony directional imbalance, with emphasis on early vertical-reflection deficiency. Scene-based FOA impulse responses (WXYZ) were measured at 11 audience positions (P1–P11) in the National Concert Hall (Taipei) and analyzed using intensity-based direction-of-arrival (DoA) proxies, axis-resolved directional energy build-up, and a distributional descriptor based on directional spatial entropy. Results are presented at three representative frequencies (125 Hz, 1 kHz, and 4 kHz) and analyzed within full (0–200 ms), early (0–80 ms), and late (80–200 ms) windows. While the magnitude proxy $\mid p^{meas}\left(f\right)\mid$ exhibits strong seat-to-seat variability and does not support a uniform attenuation assumption under the balcony, direction-resolved metrics reveal a consistent under-balcony signature. Specifically, the early–late vertical energy discrepancy $\Delta R_z={\displaystyle R_z^{early}}-{\displaystyle R_z^{late}}$ is persistently negative at under-balcony positions (P7–P11) across all three frequencies, indicating a selective reduction in early vertical contribution relative to the late field. Directional entropy analysis further shows predominantly negative $\Delta H_n={\displaystyle H_n^{early}}-{\displaystyle H_n^{late}}$, with more negative values in the under-balcony group, consistent with stronger early directional constraint in shadowed seats. Spatial trend maps are provided via Gaussian RBF interpolation within the audience domain for visualization only. The proposed FOA-based diagnostic framework provides a practical and physically interpretable approach to identify direction-specific early-reflection deficits that remain masked in conventional scalar evaluations, supporting mechanism-oriented assessment and targeted intervention in geometrically constrained listening areas. Full article

To overcome the physical constraints during the miniaturization of conventional semiconductor devices, spintronics is playing an increasingly prominent role. The Rashba effect, characterized by spin–momentum locking, has emerged as a promising solution to address challenges. Two-dimensional (2D) Janus transition metal dichalcogenides (TMDCs) break spatial inversion symmetry, creating favorable conditions for the Rashba effect. Based on first-principles calculations, 2D Janus materials XMoYZ₂ (X = S/Se/Te; Y = Si/Ge; Z = N/P) were investigated, with strain, external electric field and charge doping employed to modulate the Rashba effect. The strain results reveal that the Rashba constants of XMoYZ₂ increase significantly with compressive strain. Specifically, after applying uniaxial strain, the Rashba constant of TeMoSiP₂ is enhanced to ~2.2 times its initial value. Compressive strain reduces atomic spacing, enhances orbital overlap, and increases spin–orbit coupling (SOC) strength. All the TeMoYZ₂ materials exhibit significant anisotropy under uniaxial strain, which is favorable for spin-oriented transport. SeMoGeP₂ shows an almost linear Rashba constant–electric field correlation, while TeMoGeP₂ and TeMoSiP₂ show non-monotonic variation. The Rashba constant of TeMoSiP₂ can be enhanced to ~2.7 times its intrinsic value under either positive or negative applied electric fields. Charge doping induces negligible changes in the SOC effect. Finally, the optical absorption properties of TeMoGeP₂, TeMoSiN₂, and TeMoSiP₂ were investigated. This study clarifies the mechanism underlying the enhancement of Rashba constants in XMoYZ₂ materials, enriching the research landscape of spintronics. Full article

Desmodium styracifolium (Osb.) Merr., a member of the Leguminosae family, is an important medicinal plant widely used in traditional Chinese medicine. In September 2024, D. styracifolium plants exhibiting symptoms of little leaf and stunted growth were observed in a field of Zhanjiang, Guangdong province, China. Since the symptoms resembled those associated with phytoplasma infections, total DNA was extracted from the leaves of four symptomatic plants and one healthy plant for molecular identification. Universal primer pairs (P1/P7, R16mF2/mR1) for phytoplasma detection were used to amplify the 16S rDNA fragments (~1.8 kb and ~1.4 kb), while a specific primer pair secY-F/secY-R was employed to amplify a ~1.4 kb segment of the secY gene. Target fragments were successfully amplified from all symptomatic samples but not from the healthy control. These amplicons were cloned and sequenced. The obtained 16S rDNA sequence of D. styracifolium little leaf phytoplasma (DsLFP-GDZJ) showed the highest identity (99.67–100%) with strains of ‘Ca. Phytoplasma australasiaticum’ (subgroup 16SrII-A and 16SrII-D). Phylogenetic analysis also indicated that DsLFP-GDZJ formed a small evolutionary branch with strains of ‘Ca. Phytoplasma australasiaticum’ (subgroup 16SrII-A and 16SrII-D). Virtual RFLP (restriction fragment length polymorphism) analysis of the 16S rDNA sequence demonstrated DsLFP-GDZJ belongs to the 16SrII-A subgroup (GenBank accession number L33765). The secY gene sequence of DsLFP-GDZJ also showed the highest similarity and the closest relationship with those of the 16SrII-A subgroup phytoplasma strains. These results showed that DsLFP-GDZJ is a strain of ‘Ca. Phytoplasma australasiaticum’ (16SrII-A subgroup). To our knowledge, this is the first report of ‘Ca. Phytoplasma australasiaticum’—related phytoplasma associated with D. styracifolium little leaf disease in China, thereby establishing D. styracifolium (Osb.) Merr. as a new host plant of phytoplasma. Full article

Background/Objectives: Transfusion-dependent β-thalassaemia (TDT) is a lifelong condition requiring coordinated multidisciplinary care. In France, where the disease is rare, transition from pediatric to adult care remains poorly structured, potentially compromising adherence and long-term outcomes. Methods: This national retrospective study evaluated current transition practices and their clinical impact among young adults with TDT. Patients aged 20–25 years in December 2022 were identified from the national NaThalY registry. Those diagnosed and managed in France before age 15 were included. Clinical data were collected for the two years preceding and following transition. Transition practices were assessed using a standardized questionnaire sent to pediatric centers. Results: Thirty-four patients were included (mean transition age: 19 years). The rate of response to the questionnaire was 90.5%, with feedback from 19 centers. Only one-third of centers offered joint pediatric–adult consultations, and one-quarter provided transition-focused education. No written transition protocols were reported. Mean pre-transfusion hemoglobin levels were significantly lower after the transition (8.5 vs. 8.0 g/dL; p = 0.01). Ferritin levels showed a non-significant increase, with no statistically significant changes observed in hepatic or cardiac iron concentrations. Conclusions: This study demonstrates marked heterogeneity and limited formalization of transition practices in France. Development of structured, standardized transition pathways is urgently needed to ensure continuity of care and optimal disease management in adults with TDT. Full article