Search Results (36,955)

Retinitis pigmentosa (RP) is a genetically heterogeneous group of inherited retinal degenerations with primary degeneration of rod photoreceptors followed by secondary cone loss. We investigated whether downregulating Nrl (neural retina leucine zipper), a key transcription factor specifying rod fate, can reprogram rods into a more resilient state. In a transgenic Nrl^N/N mouse in which Nrl was markedly downregulated, the rod phenotype became more like a rod precursor, particularly in the inferior retina. Crossing Nrl^N/N mice with two rod degeneration models, rd1 (Pde6b^rd1/rd1) and rhodopsin P23H knock-in (Rho^P23H/P23H) mice, showed significantly improved photoreceptor survival in double-mutant mice. In addition, AAV-mediated delivery of shRNA targeting Nrl mRNA substantially enhanced photoreceptor survival in rd10 (Pde6b^rd10/rd10) mice. These findings demonstrate that downregulation of Nrl reprograms rods and confers broad resistance to degeneration across multiple RP models. AAV-mediated Nrl knockdown represents a promising mutation-independent therapeutic strategy for autosomal recessive and dominant forms of RP. Full article

Latent fingerprint development on rough non-porous substrates using fingerprint powders remains challenging because surface microstructures reduce particle-adhesion selectivity and weaken the contrast between ridges and the background. In this study, Cs${}_2$NaBi${}_{0.6}$Er${}_{0.4}$Cl${}_6$ double-perovskite nanoparticles were prepared by a solvothermal method and investigated as fingerprint-development particles for latent fingerprints on frosted plastic substrates. Structural characterization by X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS) indicated that Er${}^{3+}$ was incorporated into the host matrix and that the product consisted of spherical nanoparticles with smooth surfaces, relatively uniform particle-size distribution, and good dispersibility. Comparative experiments involving 40 categories of latent fingerprint samples showed that the Cs${}_2$NaBi${}_{0.6}$Er${}_{0.4}$Cl${}_6$ nanoparticles outperformed conventional powders in developing fingerprints on frosted plastic substrates. Quantitative grayscale analysis using Image J 1.53K and Origin 2024 further showed that the development contrast, expressed as the D value, reached 51.21 for sebum-rich fingerprints and 35.87 for oil-contaminated model fingerprints, both of which were higher than those obtained with the other three powders. Because the fluorescence of Cs${}_2$NaBi${}_{0.6}$Er${}_{0.4}$Cl${}_6$ under UV excitation was weaker than that of the commercial red fluorescent powder, we attribute the improved development performance mainly to selective adhesion of the particles to fingerprint residues rather than to fluorescence intensity alone. In addition, the material maintained good performance for aged fingerprints within 10 days and for developed fingerprints stored for up to 8 days. These results suggest that selective residue-affinitive adhesion, possibly assisted by the hydrophilic or moisture-affinitive nature of the ionic double-perovskite particles, plays an important role in improving fingerprint development on rough non-porous substrates. This study provides a physical perspective for latent fingerprint development on rough non-porous substrates and broadens the forensic-science application of lead-free double-perovskite nanomaterials. Full article

Background: Oral delivery of chemotherapeutic agents remains challenging due to gastrointestinal degradation, poor intestinal permeability, and extensive first-pass metabolism, which collectively limit bioavailability. Lipid-based drug delivery systems offer a promising strategy to overcome these barriers. This study aimed to develop a freeze-dried, solid-dispersible self-emulsifying drug delivery system (SEDDS) using a water-in-oil-in-water (w/o/w) double emulsion approach for the co-encapsulation of hydrophilic (doxorubicin) and lipophilic (ellipticine) agents to enhance oral delivery. Methods: Double-emulsion SEDDS were prepared via a two-stage emulsification process to enable compartmentalized drug loading within aqueous and oil phases. The formulations were freeze-dried to improve stability and storage. Physicochemical properties were characterized using dynamic light scattering for droplet size and polydispersity index (PDI), zeta potential analysis for colloidal stability, and differential scanning calorimetry for thermal behavior. Drug encapsulation efficiency was determined, and cellular uptake was evaluated in breast cancer cells using fluorescence microscopy. Results: Optimized SEDDS exhibited droplet sizes of 90–347 nm with low PDI values (0.005–0.336), indicating uniform and stable dispersions. Zeta potential values (−10.64 to 2.38 mV) supported colloidal stability, while freeze-dried formulations retained dispersion characteristics upon reconstitution over extended storage. Both drugs demonstrated high encapsulation efficiency (>97%), and thermal analysis confirmed the formation of stable amorphous systems. Fluorescence imaging revealed enhanced intracellular uptake of both agents. Conclusions: This study demonstrates that freeze-dried double-emulsion SEDDS enable efficient co-delivery of hydrophilic and lipophilic drugs, improving stability and cellular uptake. This platform shows strong potential for overcoming key barriers in oral chemotherapy and provides a promising strategy for combination drug delivery. Full article

Recurrent intrauterine adhesions (IUA) and refractory thin endometrium are associated with impaired endometrial regeneration, reduced implantation, and poor live birth outcomes. Regenerative therapy using mesenchymal stromal cells (MSCs) has shown promising results; however, factors associated with reproductive success remain unclear. In this prospective, single-centre, single-arm uncontrolled observational study, 35 women with recurrent IUA and thin endometrium (<7 mm) unresponsive to standard surgical and hormonal therapy received combined subendometrial and systemic administration of placenta-derived MSCs. The primary endpoint was live birth. Secondary endpoints included clinical pregnancy rate, time to pregnancy, endometrial thickness changes, uterine blood flow (resistance index, RI), and anti-Müllerian hormone (AMH) levels. Univariable logistic regression was performed to identify factors associated with live birth. Clinical pregnancy occurred in 13/35 patients (37.1%), and live birth was achieved in 11/35 (31.4%). Median time to pregnancy was 7 (5–8) months. Shorter duration of infertility or prior pregnancy loss (OR 1.55 per year; 95% CI 1.10–2.57), AFS stage I adhesions (OR 6.8; 95% CI 1.1–42; p = 0.04), lower baseline RI in uterine, arcuate and radial arteries, and higher baseline AMH (OR 2.59 per doubling; 95% CI 1.15–6.89) were significantly associated with live birth. Endometrial thickness increased after therapy but was not significantly associated with live birth. No severe adverse events were observed. Placenta-derived MSC therapy was followed by live birth in 31.4% of women with recurrent IUA and refractory thin endometrium. A shorter duration of reproductive disorders, less severe adhesions, lower baseline RI in uterine, arcuate and radial arteries, and higher AMH levels were associated with live birth after treatment and may help identify patients with a more favourable reproductive prognosis in future controlled studies. Full article

To address the “greenwashing” trust crisis induced by information asymmetry in sustainable supply chains, this study develops a comprehensive game-theoretic model integrating Stackelberg and evolutionary game theories (EGT). We quantitatively investigate the dynamic interactions among multi-dimensional consumer preferences, blockchain implementation costs, and boundedly rational government interventions. Our analysis yields three core contributions. First, we analytically reveal the “double-edged sword effect” of blockchain adoption. While structural transparency unlocks a trust dividend, exorbitant technological costs trigger a “budget crowding-out effect.” Quantitative results demonstrate that breaching the absolute Feasibility Threshold completely cannibalizes the environmental budget, driving substantive green investments strictly to zero. Second, EGT analysis proves that isolated punitive carbon taxes trap supply chains in a suboptimal “shallow greening” equilibrium. A composite tax-subsidy policy is structurally required to expand the feasible cost space and hedge against technological risks. Finally, we formulate a dynamic policy exit mechanism. As blockchain infrastructure matures and the endogenous green premium effectively offsets implementation costs, regulators must systematically phase out subsidies and converge toward a single-taxation regime to prevent corporate policy arbitrage and alleviate long-term public financial burdens. Full article

As the “fifth major factor of production,” data plays a crucial role in fostering China’s tourism industry, advancing high-quality economic development, and gaining competitive market advantages. Serving as institutional infrastructure for data factor rights confirmation, pricing, trading, and value conversion, data trading platforms are central to the market-based allocation of data factors. The efficient flow and value realization of data elements have paved the way for the rapid development of digital tourism; new forms of digital tourism represent a profound transformation of the industry resulting from integration and innovation with other sectors. Based on the platform ecosystem theory, we select the panel data of 297 Chinese cities from 2012 to 2024 and innovatively use the Double/Debiased Machine Learning (DDML) model to empirically test the impact of data trading platforms on the new forms of digital tourism and its mechanisms. It is found that the construction of data trading platforms effectively empowers the development of new forms of digital tourism, and this conclusion still holds after a series of robustness tests, such as changing the sample split ratio, replacing the machine learning algorithm, and the instrumental variables method. Mechanism analysis indicates that data trading platforms significantly promote new forms of digital tourism through dual pathways of talent agglomeration and technological innovation, an effect further strengthened by increased government support. Heterogeneity analysis found that the empowerment effect is more significant in cities with lower resource endowment and common administrative level and historical cities, which can be effectively transformed into an employment support effect. Spatial effect analysis reveals that the establishment of data trading platforms exerts a positive pull effect on new forms of tourism in surrounding cities within a 30 km core zone. However, this effect gradually weakens with increasing distance, turning into a significant negative siphon effect beyond 60 km. The findings provide theoretical basis and empirical support for regionally differentiated digital tourism development policies. Full article

Background/Objectives: Efficient patient flow in urgent urology services is critical to timely care delivery, yet workflow bottlenecks in specialty clinics remain underexplored. This study aimed to identify workflow bottlenecks, evaluate patient flow and staff attitudes, and explore clinician readiness for digital decision-support in a high-volume NHS emergency urology walk-in clinic. Methods: A two-week observational study was conducted at an emergency urology service in London. Time-stamped pathway data were collected for 80 patient journeys to identify total clinic duration. Differences associated with investigation ordering and senior escalation were analyzed using t-tests. Clinicians (n = 34) completed a questionnaire assessing perceptions of AI, and nursing staff provided qualitative feedback on operational pressures. Results: Mean total clinic journey time was 2 h 42 min, with the post-assessment phase accounting for 64% of total duration. Investigation ordering was the principal source of delay: patients undergoing investigations remained significantly longer in clinic than those who did not (3 h 17 min vs. 2 h 15 min, p < 0.05), and doctor-to-discharge time more than doubled (2 h 20 min vs. 1 h 2 min, p < 0.005). Senior escalation did not significantly prolong patient flow. Staff surveys demonstrated moderate trust in and comfort with AI as a decision-support tool. Nursing feedback highlighted inappropriate attendances, limited staffing, and workspace constraints as key stressors. Discussion: Delays were primarily driven by investigation ordering rather than senior review, identifying investigation timing as a potential target for future pathway optimisation. Conclusions: Investigation-related delays were the dominant workflow bottleneck. While no AI system was deployed in this study, these findings provide empirical groundwork to inform the design and prospective evaluation of AI-supported triage in specialty acute care settings. Full article

Background: There is insufficient data in the literature regarding the relationship between bidirectional conduction block (BCB) parameters and right atrial dimension (RAd). In our study, we aimed to evaluate the relationship between RAd and BCB parameters in typical atrial flutter (AFL) patients. Methods: This prospective study included 197 patients who underwent successful RFA with a diagnosis of typical AFL between 2020 and 2025. We performed RAd and BCB measurements in addition to routine assessments in all patients. The presence of BCB was confirmed by measurement of the CTI double-potential peak-to-peak interval (DPPPI) during CSp pacing, as well as by the difference between the conduction times from isthmus lateral-to-medial pacing to the CSp stimulus (ΔI-CS = LI-to-CSp − MI-to-CSp) and the difference between the conduction times from CSp pacing to the lateral and medial isthmus sites (ΔCS-I = CSp-to-LI − CSp-to-MI). Patients were divided into 3 groups according to RAd: Group-I: <2.2 cm/m², Group-II: 2.2–2.4 cm/m², and Group-III: >2.4 cm/m². Results: The number of patients in Groups I, II, and III was determined to be 99, 55, and 43, respectively. RA-volume, LVEF, RAd, and LAd values, as well as LI-to-CSp, ΔI-CS, CSp-to-LI, ΔCS-I, and DPPPI durations, significantly increased from Group I to Group III. MI-to-CSp and CSp-to-MI durations also increased from Group I to Group III; being Group I was significantly lower than Groups II and III. When DPPPI durations were categorized as ≤110 ms, 110–119 ms, 120–129 ms, and ≥130 ms, a significant difference was observed among the groups, and all Group II–III cases were found to have a DPPPI duration of ≥120 ms. In Groups II and III, the proportions of patients with DPPPI ≥ 130 ms were 46% and 84%, respectively. Conclusions: Our study showed that cavotricuspid-isthmus BCB parameters, which are indicators of successful AFL ablation, are closely and significantly related to RAd. Full article

Background: Periprosthetic joint infections (PJIs), a significant complication of total knee replacement surgery, are influenced by patient, surgeon, and healthcare system factors. Natural disasters can disrupt healthcare services and alter microbiological factors in the hospital environment. The impact of natural disasters on pathogen distribution in periprosthetic joint infection (PJI) is unclear. Therefore, this study investigated the association between the 2023 Kahramanmaraş-centered earthquakes in Türkiye and changes in microbiological patterns of PJI after knee arthroplasty. Methods: This retrospective cohort study included patients who developed PJI following total knee arthroplasty at the study center. The patients were divided into two groups based on the timing of their PJI diagnosis: pre-earthquake and post-earthquake. The demographic characteristics, comorbid diseases, and perioperative characteristics of each patient were recorded, and their microbiological profiles were analyzed. Logistic regression analysis examined the relationships between patient-related factors and causative agents. Results: 56 patients were studied and divided into two groups: 26 patients in the pre-earthquake group and 30 in the post-earthquake group. Furthermore, 79 bacterial isolates were obtained from these patients. Demographic, metabolic, and preoperative characteristics were similar between the two groups. No significant difference was found in the overall distribution of bacterial isolates. However, Gram-negative organisms, primarily Acinetobacter baumannii and Pseudomonas aeruginosa, increased in the isolate distribution after the earthquake. Patient analysis revealed that polymicrobial PJIs were significantly more frequent after the earthquake (56.7% vs. 23.1%; p = 0.011). Diabetes mellitus (DM) and smoking were associated with an increased risk of polymicrobial infection; the association was not statistically significant. Conclusions: In the post-earthquake period, patients who had undergone total knee arthroplasty and developed PJI showed a higher proportion of polymicrobial infections and a numerical increase in Gram-negative pathogens, along with more complex infection patterns compared to the pre-earthquake period. Although both patient groups demonstrated similar characteristics regarding patient-related and surgical factors, the observed changes indicate that the pressure on the healthcare system after a natural disaster can affect a hospital’s microbiological ecology. Identifying these indirect effects is crucial for guiding microbiological surveillance and infection control during post-disaster recovery periods, even for elective patients. Full article

When poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is employed as the hole transport layer in visible/near-infrared photodetectors, the extraction and transport of holes are hindered by the accumulation of the PSS insulating phase at the interface. This accumulation results in an increase in contact resistance and creates a potential barrier for hole injection. This study introduces a self-assembled monolayer, (2-(9H-carbazol-9-yl)ethyl)phosphonic acid (2PACz), to modify PEDOT:PSS, effectively optimizing the interface of the hole transport layer. Such improvements lead to a reduction in recombination losses during charge transfer, a lower dark current, and improved energy level alignment in the device, thereby boosting the performance of visible/near-infrared photodetectors. The fabricated double hole layer photodetector exhibits a low dark current of (1.4 ± 0.6) × 10⁻⁵ A at −1 V bias and a switching ratio of up to 7.62 × 10⁵ at 0 V bias. The device achieves a responsivity of 0.31 A/W and a high specific detection rate of 3.23 × 10¹² Jones at a wavelength of 780 nm, which corresponds to the peak responsivity, showcasing enhanced detection capabilities. In comparison to a reference device based on PEDOT:PSS, the response speed, cutoff frequency, and linear dynamic range of the double hole layer device have been enhanced by 400%, 213%, and 81%, respectively, thereby better aligning with practical application requirements. This research presents a novel approach for the development of high-performance organic visible/near-infrared photodetectors. Full article

Handwritten signatures retain their legal validity and play a central role in the forensic examination of documents. While it is recognized that signatures can be influenced by contextual and human factors, research on the systematic evaluation of signature stability within a structured and quantitative framework under prolonged professional shift conditions remains limited. The aim of this study is to identify the temporal pattern of signature variability over a 24-h shift and to systematically quantify this variability using a structured ordinal rating system. This prospective observational study included 25 emergency department resident physicians working on a 24-h shift system. Handwriting samples were collected from the participants at the 0th, 8th, 16th, and 24th h of their shift. The signatures were evaluated using the Signature Change Scale, which assigns an ordinal score on a 0–5 scale, with each participant’s baseline (0-h) signature serving as the reference. The evaluations were conducted under double-blind conditions by two independent experts, each with over 10 years of experience in forensic document examination. In order to assess reliability, the inter- and intra-observer reliability were calculated. Inter-observer reliability was assessed by comparing the scores assigned by two independent raters for the same signatures. Intra-observer reliability was determined by re-evaluating the same anonymized dataset under the same conditions. Statistical analysis was performed using descriptive statistics, Wilcoxon signed-rank test, and intraclass correlation coefficient (ICC) analysis for reliability assessment. It was observed that signature deviation scores varied across time points. At the 8-h mark, mild deviation was detected in 84% of participants. By the 16th h, the frequency of higher deviation categories had increased; by the 24th h, mild deviation was observed in 60% of participants, mild-to-moderate in 32%, and moderate in 8%. It was noted that average deviation scores increased up to the 16th h, with no further significant increase observed between the 16th and 24th h. The inter- and intra-observer reliability ranged from 0.89 to 0.97 and 0.85 to 0.93, respectively. These ICC values indicate that inter- and intra-observer reliability was at a good to excellent level. A 24-h shift duration was observed to be associated with intra-individual variability in signature characteristics under controlled professional conditions. High inter- and intra-observer reliability observed under blind and repeated evaluations suggests good scoring consistency within the controlled conditions of the present study. The findings suggest that signature characteristics may exhibit context-sensitive variability influenced by individual and environmental factors. The Signature Change Scale should be regarded as an exploratory methodological framework only, and further studies with larger samples and comprehensive content, construct, criterion, and external validity analyses are required before any forensic or practical application. Full article

Plastics are indispensable to modern life, yet pose a double-edged sword as their escalating production threatens human health and ecosystems. This urgent reality drives intensive efforts to develop recycling technologies that convert waste plastics into valuable feedstocks. Herein, we develop an efficient organocatalytic strategy for the depolymerization and closed-loop chemical recycling of poly(butylene succinate) (PBS). The strong organic base TBD demonstrated the highest catalytic activity for the methanolysis depolymerization of PBS, achieving a yield of 93.1% under mild conditions (100 °C, 2 h). GC and MS analyses identified dimethyl succinate (DMS) and 1,4-butanediol (1,4-BDO) as the major products. Investigation into the depolymerization behavior and mechanism revealed that the process proceeds via random chain scission, facilitated by a dual hydrogen-bonding activation mechanism mediated by TBD. Closed-loop chemical recycling was achieved by repolymerizing the recovered monomers into PBS. The reproduced polymer exhibited properties comparable to commercial virgin PBS. Moreover, this strategy could be extended to other commercial polyester systems, establishing an eco-friendly and viable pathway for sustainable polymer recycling. Full article

Background: Achilles tendon re-rupture following operative repair remains a challenging complication, and biomechanical evidence guiding revision strategies is limited. The mechanical behavior of commonly used revision constructs has not been well characterized. The objective of this exploratory study was to provide a descriptive biomechanical characterization of commonly used Achilles tendon revision constructs, focusing on viscoelastic behavior, load-to-failure properties, and failure mechanisms under standardized loading conditions. Although limited by the absence of construct replication, this study provides hypothesis-generating biomechanical insight into the failure mechanisms of revision constructs, which may inform future comparative studies and surgical strategy selection. Methods: Four fresh-frozen human cadaveric lower limbs underwent standardized Achilles tendon transection with segmental excision to simulate revision conditions. Five revision techniques were evaluated: tensioned cross-lock Bunnell, Krakow, posterior tibial tendon (PTT) augmentation with Bunnell repair, double Kessler with circumferential running suture, and V–Y advancement combined with three simple sutures and double Kessler. All repairs were performed using No. 2 high-strength suturing by a single surgeon. Constructs underwent stress relaxation testing under a constant 100 N load followed by uniaxial load-to-failure testing. Mechanical parameters and failure modes were recorded. Results: All constructs demonstrated time-dependent stress relaxation. The tensioned cross-lock Bunnell repair retained the highest residual force during sustained loading. The PTT-augmented construct exhibited the highest load to failure among the constructs tested and failed at the tendon substance, whereas non-augmented repairs failed predominantly at the suture–tendon interface. The V–Y advancement construct failed at relatively low applied loads under the applied testing protocol. Conclusions: Achilles tendon revision constructs demonstrate distinct biomechanical behaviors. Augmented constructs exhibited higher resistance to tensile loading in this experimental setting and shifted failure away from the repair site, while non-augmented repairs were limited by suture–tendon interface strength. Given that each construct was tested only once and that one specimen was used sequentially for two repairs, the findings should be interpreted strictly as descriptive and hypothesis-generating, without any basis for comparative or inferential conclusions. Full article

Background and clinical significance: Catheter knotting is a rare but potentially serious complication of urethral catheterization in neonates and infants, particularly when feeding tubes are used due to small urethral caliber. Case Presentation: We report the case of a 6-month-old male infant with Crouzon syndrome who underwent cranioplasty. Intraoperatively, a 6 Fr feeding tube was inserted for bladder drainage. On postoperative day 6, resistance was encountered during catheter removal. Radiography revealed a double knot in the distal urethra and a single knot in the proximal urethra. The catheter was successfully removed surgically via cystotomy, and the infant recovered uneventfully with normal voiding function. Conclusions: This case demonstrates the exceptional occurrence of simultaneous double and single knots in a urinary catheter. Awareness of this rare complication, careful control of insertion length, and prompt intervention upon resistance are essential to prevent urethral trauma and ensure patient safety. Full article

This paper presents a temperature field analysis and a new water-cooling channel design for a 1000 kW, 72-slot/8-pole permanent magnet synchronous motor used in mining applications. To capture temperature rise data related to electromagnetic losses and fluid heat transfer, a multiphysics coupling model was established, and its accuracy was verified through temperature rise experiments on a prototype. To address the issues of poor temperature uniformity and excessive head loss in the original structure, a double-helix return cooling water channel structure was designed, effectively compensating for the heat exchange capacity at the motor ends and reducing fluid resistance. Comparative analysis shows that this structure significantly outperforms traditional cooling water channels in terms of heat dissipation efficiency, temperature uniformity, and pressure loss. Under optimal geometric parameters—10 spiral turns and a flow velocity of 1 m/s—the maximum winding temperature was suppressed to 67.7 °C, with a winding temperature difference of only 2.6 °C, while the pressure drop was maintained at a low level of 9580 Pa. This study provides a theoretical basis and an efficient engineering solution for the design of water-cooling structures in large mining motors. Full article