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Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

In this paper, we consider a Thermoelastic system with boundary time-varying delay. Under some appropriate assumptions, the global well-posedness and exponential stability are obtained by using the variable norm technique of Kato and the energy method respectively.

For wind turbine applications, there is a cyclic load-varying process between rolling elements and raceways in pitch bearings. This kind of motion can also lead to radial fretting. However, this is seldom addressed under grease-lubricated conditions in the literature. In this study, grease-lubricated point contact problems have been investigated experimentally under cyclic load-varying conditions. The findings revealed that as the load-varying range diminishes, the variation in grease film distribution becomes more subtle and the rate of discharge of thickener fiber clusters in the stick zone decelerates. This is due to the fact that the rate of change in the Hertz contact radius is reduced and the migration of grease is weakened during the unloading process. Due to the large apparent viscosity of grease with a high soap content, entrapped grease is not easily discharged during loading, and the thickness of the film in the stick zone progressively increases as the soap content of the grease is augmented. This also causes the variable load zone to wear out more easily. As the grease is subjected to repeated loading and unloading, there is a gradual reduction in film thickness, and larger thickener fiber clusters tear, resulting in a flattened form and shear thinning. Grease containing sulphur–phosphorus additives demonstrates a superior effect on reducing fretting wear within the large variable load range but generally proves effective for smaller load-varying ranges. This study may offer insights into the degradation of grease under variable load motion and methods to prevent radial fretting wear.

When dealing with heterogeneous systems, interpreting the mean-square displacement (MSD) data appropriately is crucial. This is due to the limitation that the various interpretations of stochastic differential equations with state-dependent diffusivity may yield the same MSD data, leading to erroneous conclusions. Aided by analytical MSD solutions supported by Langevin simulations, we explore this limitation in diffusion processes exhibiting power-law state-dependent diffusivity, $D_0|x/L|^{-2\mu}$ , with diffusion constant D _0 and scaling index µ . We find that distinct interpretations leading to same MSD data possess different D _0 values. A method is introduced to discern these D _0 -dependent interpretations. When applying the method to subdiffusion MSD data, we observe interpretation transitions depending on the value of the anomalous diffusion coefficient. Furthermore, we demonstrate that these D _0 -dependent interpretations respond diversely to memory effects, which may also be used to decide on the interpretation of MSD data. We believe that these findings offer insights for interpreting MSD data in heterogeneous systems.

BackgroundFlail chest is a common and serious traumatic condition in thoracic surgery. The treatment of flail chest often includes open reduction and internal fixation, which is relatively traumatic, complicated, and expensive. As three-dimensional (3D) printing technology is widely used in the clinical field, the application of 3D-printed products to chest trauma will become a new treatment option. To date, the use of 3D-printed external fixation guides for flail chests has not been reported. Thus, we aimed to assess the short-term efficacy of a new technology that treated flail chests with an individualized 3D-printed external fixation guide combined with video-assisted thoracoscopic surgery (VATS).Patients and methodsA retrospective analysis was performed on patients with flail chest treated with this new technique at our center from January 2020 to December 2022. The following parameters were included: operative time, thoracic tube extraction time, intensive care unit time, thoracic volume recovery rate, visual analog scale score 1 month postoperatively, and postoperative complication rate. All patients were followed up for at least 3 months.ResultsFive patients (mean age: 45.7 years) were enrolled; they successfully underwent surgery without chest wall deformity and quickly returned to daily life. The average number of rib fractures was 8.4; all patients had lung contusion, hemopneumothorax, and anomalous respiration. The abnormal breathing of all patients was completely corrected on postoperative day 1, and the chest wall was stable. One case experienced mild loosening of the 3D-printed guide postoperatively; however, the overall stability was not affected. The other four cases did not experience such loosening because we replaced the ordinary silk wire with a steel wire. All cases were discharged from the hospital 2 weeks postoperatively and returned to normal life 1 month after the removal of the 3D-printed guide on average. Only one case developed a superficial wound infection postoperatively, and no perioperative death occurred.ConclusionsThe 3D-printed external fixation guide combined with video-assisted thoracoscopic surgery is a novel technique in the treatment of flail chest and is safe, effective, feasible, and minimally invasive, with satisfactory clinical efficacy.

BackgroundChronic allograft dysfunction(CAD) is the leading cause of graft loss in kidney transplant recipients (KTRs). Inflammatory process is believed to be one of the major contributors to CAD. The aim of this study is to explore the anti-inflammatory effect of vitamin D (VD) supplementation in KTRs and its role in the graft function improvement(protection).MethodsA retrospective cohort of 39 KTRs with chronic antibody mediated rejection(CAMR)or stable renal function and a prospective cohort of 42 KTRs treated or untreated with VD were enrolled. Serum levels of vitamin D metabolism and serum inflammatory cytokines, renal graft function, and routine blood biomarkers were tested and dynamically tracked within 12 months post-transplant.ResultsCompared with the stable group, the CAMR group exhibited significantly elevated serum levels of inflammatory cytokines IL-1β, IFN-γ, IL-2, IL-10, IP-10, and HMGB1 (P

Abstract Objective Uncertainties remain regarding the relationship between sarcopenic obesity and frailty. This study aimed to explore the association of these two common geriatric syndromes among community-dwelling older adults. Methods Baseline data from the West China Health and Aging Trend (WCHAT) study was used. Sarcopenia was assessed based on the criteria established by the Asian working group for sarcopenia. Body fat percentages above the 60th percentile specified by sex were classified as obesity. Sarcopenic obesity was defined as the concurrence of obesity and sarcopenia. Frailty was assessed by Fried criteria. Multinomial logistic regression was adopted to explore associations of sarcopenic obesity with frailty. Results Overall, 2372 older adults (mean age 67.6 ± 5.9) were involved in this study. The prevalence of frailty and sarcopenic obesity was 6.2 and 6.28%, respectively. After adjusting for covariates, sarcopenic obesity was significantly associated with prefrailty (OR = 1.74, 95% CI = 1.15–2.64, P = 0.009) and frailty (OR = 4.42, 95% CI = 2.19–8.93, P

Abstract The determination of length of time from the last drinking is critical for cases like drunk driving, sexual assault victims, and also postmortem suspected poisoning cases. The study was aimed to established a method of estimating the time of last drinking through the pharmacokinetic study of conjugation metabolites of alcohol in blood after a single oral dose. Twenty-six volunteers (14 males) consumed alcohol with food at a fixed dose of 0.72 g/kg after fasting for 12 h. Five milliliters of blood were collected 120 h after the start of drinking, and all samples were analyzed with headspace-gas chromatography and high-performance liquid chromatography–tandem mass spectrometry. The time point of last drinking was estimated through the relationship between the concentration ratio of ethyl glucuronide to ethyl sulphate and the length of time after drinking. Pharmacokinetic parameters were analyzed by a pharmacokinetic software DAS according to the non-compartment model. A good correlation model was obtained from the relationship between concentration ratio of ethyl glucuronide to ethyl sulphate in blood and the time of alcohol use, and the margin of error was mostly lower than 10%. The time of maximum concentration, maximum concentration, and elimination half-life of ethyl glucuronide in blood were 4.12 ± 1.07 h, 0.31 ± 0.11 mg/L and 2.56 ± 0.89 h; the time of maximum concentration, maximum concentration, and elimination half-life of ethyl sulphate in blood were 3.02 ± 0.70 h, 0.17 ± 0.04 mg/L, and 2.04 ± 0.76 h. The study established a potential method to estimate the length of time after a moderate oral dose, and provided pharmacokinetic parameters of ethyl glucuronide and ethyl sulphate in Chinese population.

Introduction: Tertiary hyperparathyroidism (THPT) and vitamin D deficiency are commonly seen in kidney transplant recipients, which may result in persistently elevated fibroblast growth factor 23 (FGF23) level after transplantation and decreased graft survival. The aim of this study is to evaluate the effect of vitamin D supplementation on THPT, FGF23-alpha Klotho (KLA) axis and cardiovascular complications after transplantation. Materials and methods: Two hundred nine kidney transplant recipients were included and further divided into treated and untreated groups depending on whether they received vitamin D supplementation. We tracked the state of THPT, bone metabolism and FGF23–KLA axis within 12 months posttransplant and explored the predictors and risk factors for intact FGF23 levels, KLA levels, THPT and cardiovascular complications in recipients. Results: Vitamin D supplementation significantly improved FGF23 resistance, THPT and high bone turnover status, preserved better graft function and prevented coronary calcification in the treated group compared to the untreated group at month 12. The absence of vitamin D supplementation was an independent risk factor for THPT and a predictor for intact FGF23 and KLA levels at month 12. Age and vitamin D deficiency were independent risk factors for coronary calcification in recipients at month 12. Conclusion: Vitamin D supplementation effectively improved THPT, FGF23 resistance and bone metabolism, preserved graft function and prevented coronary calcification after transplantation.

Small molecule kinase inhibitors (SMKIs) are being approved at a fast pace under expedited programs for anticancer treatment. Here, the authors employ a machine-learning model to examine the relationships between kinase targets and adverse events in the trials of 16 FDA-approved SMKIs.

Marine invertebrates are the backbone of marine biodiversity and play a pivotal role in the marine ecosystem. The life cycle of most marine invertebrates includes the settlement and metamorphosis stage, which is induced by marine biofilms, but the mechanism is still enigmatic. In the present study, we constructed the capsular polysaccharide (CPS) synthesis gene capC-deleted mutant of Pseudoalteromonas marina by gene knockout and then compared the phenotype, the biofilm-forming ability, the effect on settlement and metamorphosis of Mytilus coruscus, and the exopolysaccharide and CPS levels between the mutant and the wild-type strains to explicate the relationship between bacteria and mussels. The study presented that the phenotype and biofilm-forming ability between the wild-type and ΔcapC strains had no significant difference, but the inducing activity of ΔcapC biofilms on larval settlement and metamorphosis decreased significantly (p < 0.05). Compared with the wild-type, the CPS content of ΔcapC strain significantly decreased by 38.07%, accompanied by the increase of c-di-GMP. Meanwhile, the biomass of α-polysaccharides and β-polysaccharides on ΔcapC biofilms decreased significantly (p < 0.05). Thus, the CPS synthesis gene could modulate c-di-GMP, which regulates bacterial polysaccharide secretion, and then impact larval settlement and metamorphosis of mussels. This work brings an entry point to deeply understand the interaction between bacterial polysaccharide and larval recruitment.

In order to further explore the influence of evaluation units and non-landslide sample selection methods on landslide susceptibility prediction, a landslide susceptibility evaluation model is established based on self-organizing feature map network and random forest model in this paper. According to the relationship between grid units and slope units, an optimized calculation method of landslide susceptibility index is proposed. Aiming at the deficiencies of grid units and slope units in the evaluation of landslide susceptibility, this model proposes an optimized calculation method for landslide susceptibility index based on the relationship between grid cells and slope cells. On this basis, a landslide susceptibility evaluation model was established based on the random forest Tree Bagger classifier. By comparing and analyzing the influence of self-organizing feature map network and random non-landslide sample selection methods on the evaluation results, the effectiveness of the three evaluation models of self-organizing feature map network, random forest and self-organizing feature map network -random forest were discussed. The evaluation model has been applied to the landslide susceptibility evaluation in Dayu County. The results show that the prediction accuracy of random forest and self-organizing feature map network-random forest is higher, reaching 91.19% and 94.94% respectively, and the AUC of success rate curve was 0.822 and 0.849 respectively. It shows that self-organizing feature map network-random forest has higher prediction rate and success rate，although the prediction accuracy of self-organizing feature map network clustering is limited, it can effectively improve the evaluation accuracy of random forest model as the basis for selecting non landslide samples.

Matrix effects are a major concern in liquid chromatography coupled to tandem mass spectrometry for the determination of pesticide residues. In this work, a novel and efficient lipophilicity-matched chromatographic separation strategy was developed to improve the separation efficiency on an alkyl bonded phase chromatographic column and reduce matrix effects. An ultra-high performance liquid chromatography-tandem mass spectrometry method based on this strategy was established to minimize matrix effects for the determination of triazole fungicides. The samples were cleaned-up with dispersive solid phase extraction and separated on a chromatographic column with similar lipophilicity to the fungicides. The results showed that the proposed method effectively minimized the matrix effects and improved the separation. The matrix effects of 21 fungicides ranged from −8.3% to 4.7%. Moreover, the average recoveries were between 91.4% and 108.1% using solvent calibration for quantification, and the limits of quantitation were between 0.5 and 3.5 μg/kg. These results demonstrate the effectiveness of the proposed strategy in improving the chromatographic efficiency. This work provides a practical strategy and reference for the liquid chromatography-tandem mass spectrometry determination of pesticide residues. [ABSTRACT FROM AUTHOR]

AbstractThe evolution of digital technology offers virtual reality environment to escape and redefines visitor engagement in exhibitions. This study proposed a theoretical model that delineates the influence of perceived escapism on visitor engagement, encompassing various digital experience variables. Moreover, it categorizes digital exhibition engagement into two dimensions: breadth and depth of engagement. Focusing on the experience of viewing the Sanxingdui digital exhibition, an online survey was conducted and analyzed, with a sample of 464 participants in China. The findings of this investigation unveil several key insights: (a) Perceived escapism exhibits a positive correlation with visitor engagement; (b) Mediating effects of entertainment, immersion, and flow experience exist between perceived escapism and visitor engagement, with flow experience emerging as the most significant mediator; (c) Digital literacy negatively moderates the mediating effect of perceived escapism and immersion experience. Consequently, enhancing visitor engagement in digital exhibitions can be achieved by exhibition designers considering the diverse patterns of social interaction among visitors and creating a personalized and interactive escape environment. [ABSTRACT FROM AUTHOR]

In this study, experimental research, a numerical simulation, and a theoretical analysis were performed on the bearing capacity of an aluminum alloy circular tube filled with a lightweight filler (ATLF). Bearing capacity tests were conducted for six ATLF columns and two aluminum alloy hollow tubes (AAHTs), and their local buckling failure modes and mechanical properties were obtained. A finite element model was developed using ABAQUS software (ABAQUS 2016, ABAQUS Inc., Palo Alto, CA, USA) for numerical calculations. Furthermore, a large-scale numerical analysis was performed to investigate the effect of structural parameters, such as the tube thickness, diameter, column length, and initial geometric imperfections, as well as the aluminum alloy’s properties and the lightweight filler’s properties, on the bearing capacity of the ATLF columns and AAHTs under axial compression. Based on the test and numerical analysis results, a formula for calculating the local buckling stress of AAHTs under axial compression is proposed. An improved coefficient of bearing capacity for the ATLF columns caused by the internal lightweight filler was obtained by fitting, and based on the results, a formula for computing the bearing capacity of ATLF columns under axial compression is proposed in this study.

Abstract Heterogeneous treatment effect (HTE) analysis focuses on examining varying treatment effects for individuals or subgroups in a population. For example, an HTE‐informed understanding can critically guide physicians to individualize the medical treatment for a certain disease. However, HTE analysis has not been widely recognized and used, even given the explosive increase of data availability attributed to the arrival of the Big Data era. Part of the reason behind its underuse is that data are often of high dimension and high complexity, which pose significant challenges for applying conventional HTE analysis methods. To meet these challenges, a newly developed causal forest HTE method has been derived from the random forest machine‐learning algorithm. We conducted a systematic performance evaluation for the causal forest method against the conventional two‐step method by simulating scenarios with different levels of complexity for the analysis. Our results show that causal forest outperforms the conventional HTE method in assessing treatment effect, especially when data are complex (e.g., nonlinear) and high dimensional, suggesting that causal forest is a promising tool for real‐world applications of HTE analysis.

Summary: Carbon is one of the most versatile atoms and fosters a wealth of carbon allotropes with superior mechanical and electronic properties. A three-dimensional covalent carbon nanotube, named CCN, with a hexagonal honeycomb-like crystalline structure is proposed theoretically. CCN consists of sp3 bonded coaxially teamed (6,0) carbon nanotubes, and the tube walls possess intrinsic wrinkles, which trigger miraculous physical properties. The mechanical and thermal dynamic stabilities are confirmed, and molecular dynamics simulations indicate high temperature thermal stability up to 1500 K. CCN has an unusual cork-like zero Poisson’s ratio along the axial direction of the nanotubes, and the axial/radial stretching or compression rarely effects the radial/axial dimensions of the nanotubes. CCN is superhard with Vickers hardness of 82.8 GPa, matching that of cubic boron nitride. Substitution B and N atoms for C atoms result in superhard CCN-B12N8 and CCN-C8N12 with quasi-zero Poisson’s radio along both axial and radial directions.

ABSTRACT Solid‐state nuclear magnetic resonance (SSNMR), a technique capable of studying solid or semisolid biological samples, was first applied to study the cell differentiation and mineralization using the whole‐cell sample. Mesenchymal stromal cells (MSCs) with multipotent differentiation capacity were induced to differentiate into osteoblasts. The whole differentiation process, osteoblast mineralization and the mineral maturation, was investigated using SSNMR, providing intact, atomic level information on the cellular mineral structural transformation. Our research indicated the extent of osteoblast mineralization could vary significantly for different cell populations whereas the difference was not easily shown by other means of characterization. The SSNMR spectra revealed hydroxylapatite (or hydroxyapatite [HAP]) formation around 2 to 4 weeks after osteogenic induction for MSCs with a high differentiation potency. The early mineral phase deposit before HAP formation contained a high amount of HPO42−. The structures of minerals in the extracellular matrix (ECM) of osteoblasts could evolve for a period of time, even after the incubation of cells has been stopped. This observation was only possible by studying the sample in an intact state, where ECM was not disturbed. These findings improved our understanding of MSCs, which had wide applications in bone regeneration and tissue engineering. Meanwhile, this work demonstrated the advantage of studying these cellular systems as a whole without any mineral extraction, which had been largely overlooked. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Objective To study the short-term outcomes of laparoscopic right hemicolectomy with transvaginal specimen extraction without abdominal incisions(CRC-NOSES Ⅷ A) for radical resection of colon cancer comparing with laparoscopic right hemicolectomy with transabdominal specimen extraction. Methods Clinical data of the patients with complete laparoscopic right hemicolectomy including 29 cases in transvaginal group and 29 cases in transabdominal group were collected. Comparision between two groups was done for preoperative clinical features, intraoperative indexes, post-operative complications, female sexual function score to charify the impact of the two methods of specimen removal on patients. Results There were no significant differences in intraoperative blood loss, fever and bleeding after operation, intestinal obstruction, anastomotic leakage and other postoperative complications between two groups. Compared with transabdominal group, operative time prolonged [(151.52±33.73) min vs. (179.59±47.02) min, P=0.012 0] and postoperative hospital stay decreased (7.14 d vs. 6.07 d, P=0.013 0) in transvaginal group. The female sexual activity recovered more quickly with less discomfort caused by the scar in transvaginal group and there was no statistical difference in postoperative female sexual function score between two groups. Conclusions CRC-NOSES Ⅷ A could be safe and feasible when compared with conventional laparoscopic hemicolectomy with transabdominal specimen extraction for radical resection of colon cancer. The patients in transvaginal group had less sensation of scars and faster recovery of sexual activity.