163559 research outputs found
Sort by
Impaired chaperone-mediated autophagy leads to abnormal SORT1 (sortilin 1) turnover and CES1-dependent triglyceride hydrolysis
No full textSORT1 (sortilin 1), a member of the the Vps10 (vacuolar protein sorting 10) family, is involved in hepatic lipid metabolism by regulating very low-density lipoprotein (VLDL) secretion and facilitating the lysosomal degradation of CES1 (carboxylesterase 1), crucial for triglyceride (TG) breakdown in the liver. This study explores whether SORT1 is targeted for degradation by chaperone-mediated autophagy (CMA), a selective protein degradation pathway that directs proteins containing KFERQ-like motifs to lysosomes via LAMP2A (lysosomal-associated membrane protein 2A). Silencing LAMP2A or HSPA8/Hsc70 with siRNA increased cytosolic SORT1 protein levels. Leupeptin treatment induced lysosomal accumulation of SORT1, unaffected by siLAMP2A co-treatment, indicating CMA-dependent degradation. Human SORT1 contains five KFERQ-like motifs (658VVTKQ662, 730VREVK734, 733VKDLK737, 734KDLKK738, and 735DLKKK739), crucial for HSPA8 recognition; mutating any single amino acid within these motifs decreased HSPA8 binding. Furthermore, compromised CMA activity resulted in elevated SORT1-mediated degradation of CES1, contributing to increased lipid accumulation in hepatocytes. Consistent with in vitro findings, LAMP2A knockdown in mice exacerbated high-fructose diet-induced fatty liver, marked by increased SORT1 and decreased CES1 levels. Conversely, LAMP2A overexpression promoted SORT1 degradation and CES1D accumulation, counteracting fasting-induced CES1D suppression through CMA activation. Our findings reveal that SORT1 is a substrate of CMA, highlighting its crucial role in directing CES1 to lysosomes. Consequently, disrupting CMA-mediated SORT1 degradation significantly affects CES1-dependent TG hydrolysis, thereby affecting hepatic lipid homeostasis.Abbreviations: APOB: apolipoprotein B; CES1: carboxylesterase 1; CMA: chaperone-mediated autophagy; HSPA8/Hsc70: heat shock protein family A (Hsp70) member 8; LAMP2A: lysosomal associated membrane protein 2A; LDL-C: low-density lipoprotein-cholesterol; PLIN: perilipin; SORT1: sortilin 1; TG: triglyceride; VLDL: very low-density lipoprotein; Vps10: vacuolar protein sorting 10.N
Van der Waals epitaxy and beyond for monolithic 3D integration
No full textAs the limitations of silicon-based technologies approach their physical boundaries, monolithic three-dimensional integration (M3D) and two-dimensional (2D) materials, such as transition metal dichalcogenides (TMDs), have emerged as promising solutions for continuous scaling in semiconductor devices. This perspective explores the evolution of van der Waals (vdW) epitaxy and its potential to integrate TMDs into M3D structures. By circumventing lattice mismatch issues, vdW epitaxy allows the formation of high-quality single-crystal heterostructures across diverse material systems. However, the challenge of achieving films with uniform thickness control remains unresolved. Herein, advanced epitaxial growth techniques for TMDs are reviewed, including quasi-vdW epitaxy, vdW recrystallization, and remote epitaxy, whilst also introducing emerging approaches, such as hypotaxy and interfacial epitaxy. These emerging techniques have the potential to produce large-area defect-free films with controllable thicknesses. Ultimately, the development of new epitaxial methods specifically designed for TMDs is essential for the future integration of 2D materials into industrial applications.N
Enhanced prediction of cadmium partitioning in oxidized sediments: The role of Fe hydroxides and ferrihydrite
No full textThis study enhances the prediction of cadmium (Cd) partition coefficients (Kd) in sediments by integrating the roles of total organic carbon (TOC), amorphous iron oxides (ferrihydrite), and iron hydroxides (Fe(OH)3). Using the Windermere Humic Aqueous Model (WHAM 7) alongside experimental data, Kd values were predicted across a wide pH range and compared to measured values from 21 sediment samples. The results show that while traditional models primarily focusing on TOC provide reasonable Kd estimates under certain conditions, they may fail in samples with significant contributions from other binding phases, particularly Fe oxides. The study revealed that at pH levels above the point of zero charge (PZC) of ferrihydrite (∼7.5), Cd binding is dominated by amorphous Fe oxides, surpassing TOC in importance. This highlights the need for models to incorporate the significant role of Fe oxides in Cd partitioning, especially in oxic environments. Sensitivity analysis further emphasized the influence of pH, showing a shift in the dominant binding phase from TOC at lower pH levels to amorphous Fe oxides at higher pH levels. The comparison between predicted and measured Kd values demonstrated that most predictions were within an order of magnitude of the measured values. However, discrepancies in samples with low TOC and Fe oxide content suggest the need to account for additional binding phases, such as Mn oxides, in future models. In conclusion, this study provides a more robust framework for predicting Cd partitioning in sediments, emphasizing the need to consider multiple binding phases to improve accuracy in environmental risk assessments.N
Synchronous rectification for two-transformer active-clamp forward-flyback converters to remove voltage spikes on secondary-side field-effect transistors
No full textThe paper proposes a new synchronous rectification (SR) technique for two-transformer active-clamp forward-flyback converters (ACFFs). The proposed technique overlaps the gate signals of two secondary-side field-effect transistors (SR FETs) to remove the voltage spikes on the SR FETs in the discontinuous conduction mode or in the low-power condition. The overlap duration is fixed regardless of operation conditions of the ACFF, and no additional voltage or current sensors are required. The performance of the proposed SR is verified by an experimental 800 V-13.5 V ACFF prototype.N
Comparison of clinical characteristics and outcomes in hospitalized adult patients infected with respiratory syncytial virus and influenza virus
No full textBackground Because patients infected with respiratory syncytial virus (RSV) have been reported to be older than patients infected with influenza virus, the more frequent incidence of complications in RSV-infected patients may be age-related. This study compared clinical characteristics and outcomes in hospitalized adults infected with RSV with findings in age- and sex-matched adults infected with influenza virus. Methods The medical records of hospitalized adult patients infected with RSV or influenza virus at two university hospitals from 2013 to 2022 were retrospectively analyzed. Virus infection was confirmed by real-time polymerase chain reaction. Each RSV-infected patient was matched by age and sex with two influenza virus-infected patients, and their clinical symptoms, laboratory parameters and hospital courses were compared. Results The study cohort consisted of 552 patients, 184 infected with RSV and 368 infected with influenza virus. Fever (71.2% vs. 79.9%, p = .022) and cough (70.1% vs. 80.4%, p = .007) were significantly less frequent in the RSV than in the influenza group, whereas white blood cell counts (9132/mm(3) vs. 7616/mm(3), p < .001) and C-reactive protein concentrations (10.25 vs. 8.88 mg/dL, p = .029) were significantly higher in the RSV group. The frequency of oxygen therapy was higher (60.3% vs. 48.6%, p = .010) and hospital stay was longer (8 vs. 6 days, p = .003) in RSV than in influenza virus-infected patients. Conclusions Clinical symptoms were less frequent, but disease was more severe, in hospitalized adult patients infected with RSV than in age- and sex-matched patients infected with influenza. Greater attention should be paid to diagnosing and preventing RSV infection in adults.N
Evaluation of spatial and temporal variability in Sentinel-2 surface reflectance on a rice paddy landscape
No full textHigh spatial resolution spaceborne remote sensing systems provide a new data source for agricultural applications. As a key deliverable, surface reflectance (SR) enables immediate and non-destructive estimation of crop status, thus the demand for reliable pixelwise SR is increasing. However, the evaluations are typically conducted on pseudo-invariant areas and the reliability of pixelwise SR has not been thoroughly examined over heterogenous, dynamic surfaces. In this study, we evaluated pixelwise Sentinel-2 (S2) SR on a rice paddy landscape across seasons using drone-based hyperspectral images and tower-based continuous hyperspectral observations as the ground references. We also examined the impact of spatial and atmospheric properties on S2 SR. Overall, S2 SR showed strong linear relationships with the ground references (the overall R2 > 0.8). The residual errors were influenced by sub-pixel geolocation errors (0.01–0.017 (2.1–11.8 %)), a widen PSF (0.007 (7.6 %) for red) and underestimated AOT retrievals (0.027 (40.7 %) for blue). Notably, atmospheric adjacency effects broadened the PSF, causing the consistency of S2 with the ground reference image to depend on the landscape's heterogeneity. Our findings outlined the key factors contributing to uncertainties in S2 SR, which could affect downstream products like vegetation indices and leaf area index. Considering these factors would enhance remote sensing of landscapes with high contrast in reflectance and elevated aerosol loadings, such as urban, savanna, wetland and dry agricultural land.Y
Signaling long-term information using short-term forecasts
No full textThis paper shows theoretically and empirically that the decision to disclose a short-term earnings forecast can reveal managers private information about long-term performance. Consistent with the predictions of our model, we find that the decision to disclose a short-term earnings forecast predicts long-term performance for up to three years. The relation strengthens when current period performance is poor, when managers have longer horizons, and when competitive threats are lower. Endogenizing the proprietary costs of disclosure, our analysis suggests that––despite the short horizon––the decision to provide an earnings forecast contains significant information about long-term performance and thus can entail proprietary costs.Y
Tunable Mechanical Properties in Biodegradable Cellulosic Bioplastics Achieved via Ring-Opening Polymerization
No full textThe development of bioplastics is advancing globally to promote a sustainable society. In this study, we designed cellulosic dual-network bioplastics to address the need for sustainable materials with balanced mechanical properties and biodegradability. Cellulose was used as the first network, and the second network was functionalized to enhance mechanical strength while preserving biodegradability. The dynamic covalent moieties within the second network were generated through dithiolane ring-opening polymerization. The ultimate tensile strength and flexural elongation were controlled within 8.8-193 MPa and 3.3-32.5%, respectively, depending on the degree of dynamic bonds. Moreover, the bioplastics exhibited gradual biodegradability, achieving approximately 30% degradation within 2 weeks. Interestingly, our bioplastics demonstrated the ability to coexist with plants, as their degradation did not negatively affect cell viability or plant growth. This study provides a promising approach to developing advanced bioplastics that reach sustainability goals while offering tunable mechanical properties.N
Transparent Temperature Sensors for Photothermal Neuromodulation: Advances, Challenges, and Future Directions
No full textPhotothermal neuromodulation, a rapidly advancing technique in neuroscience, has been introduced as an incredibly versatile platform for the in-depth study of neural electrophysiological signals and the development of treatments for various neurological disorders. Particularly, nanomaterial-based photothermal neuromodulation technologies have advantages compared to optogenetic stimulation methods, such as non-genetic modification, minimally invasive, and reduced immune response. Photothermal neuromodulation research has introduced various nanomaterials and stimulation methods to regulate thermosensitive ion channels or modify cell membrane capacitance, enabling excitation and inhibition of neural activity. Recent advances in nanomaterials have significantly improved the precision and efficiency of photothermal neuromodulation, expanding its potential applications in neuroscience research. In the photothermal neuromodulation studies, different temperature measurement methods have been used but do not satisfy all the requirements necessary to analyze this phenomenon. An ideal temperature sensor for a photothermal neuromodulation study must have high transparency, high thermal sensitivity, and high spatial and temporal resolution. This review aims to cover the current status of thermally induced neuromodulation studies and the transparent temperature sensing methodologies that can be used for photothermal neuromodulation.Y
Potential of X-ray irradiation for pathogen inactivation in semi-moist pet food and changes in nutritional and physicochemical qualities
No full textThe aim of the study was to investigate the effect of X-ray irradiation at different dose levels on semi-moist pet foods. Samples were subjected to X-ray irradiation at 0, 2.5, 5, and 10 kGy, and their microbial, nutritional and physicochemical properties were evaluated for 60 days at 20-day intervals. Among these, samples irradiated at 10 kGy completely sterilized bacterial pathogens and inhibited their growth throughout the storage period. Following this, a dose of 5 kGy showed a better bacterial pathogen reduction. Above 5 kGy irradiated samples exhibited a significant effect on moisture and protein contents. Samples treated with above 5 kGy tended to exhibit a significant decline in water activity, pH, and a* values during the storage period while continuing to exert microbial stability and quality attributes. However, lipid oxidation and protein degradation were observed in samples irradiated with above 5 kGy of X-ray during storage. Considering all results, we conclude that about 5 kGy X-ray irradiation could prevent microbial activity while maintaining the maximum losses of nutritional and physicochemical properties of semi-moist pet foods.N