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Abstract Sucrose, xylose, and saccharin are commonly used beverage additives and long-term consumption of these compounds inevitably affects the oral immune system and the composition of oral microbiomes. In this study, we used 24 Sprague Dawley rats divided into four groups, i.e., sucrose, saccharin, xylose, or pure water treated over an eight week period to evaluate any changes in the composition, community structure, and function of the oral microbiomes. At the end of the treatment period, we collected oral microbiome samples from each animal and subjected them to high-throughput sequencing. We also used ELISA to determine the concentration of salivary immunoglobulin in these rats to reveal the effect of sweetener on the oral immune system. Sequencing results demonstrated that Firmicutes and Proteobacteria, remained the predominant phyla, but we found that the oral microbial diversity of rats drinking sucrose water was significantly higher than that of the other groups. Our results indicate that drinking water supplemented with sweeteners may influence oral immunity as well as the composition, metabolic function, and diversity of the oral microbiota, thereby disrupting the oral microbiome.

Abstract The stimulator of interferon genes (STING) connects microbial cytosolic sensing with host cell effector functions. STING signaling plays a central role in cyclic dinucleotides (CDNs) and DNA sensing to induce secretion of interferons and pro-inflammatory mediators. Although activated STING signaling favors antimicrobial progress and facilitates mucosal would healing, its role in mucosal immunity and gut homeostasis is paradoxical, ranging from positive and negative effects within the gut. In our review, we summarize recent advance of STING signaling in gut homeostasis and inflammation, especially focusing on its molecular basis in mucosal immune response. Deep understanding of the regulatory mechanisms of intestinal STING pathway could promote clinical manipulation of this fundamental signaling as a promising immunomodulatory therapy.

Microfibers are key components in construction of fiber-based materials, biomimetic materials, microsensors, and other fiber-based microstructures. Due to the scaling law, the adhesion forces such as van der Waals force or electrostatic force in the micro world play a more dominant role than the gravity, causing difficulties in precise pick-and-place of the micro objects. In this paper, we propose a capillary force-based pick-and-place method for handling microfibers. The method combines the typical robotic transportation technique and capillary gripping method to achieve fast and accurate pick-and-place of microfibers. We quantitatively analyzed the critical conditions for capillary pick-up and placement of microfibers and validated the technique experimentally. The theoretical analysis indicates that both pick-up and the placement of microfibers are largely dependent on the contact length on the fiber or the contact angle of the meniscus on the substrate. The experimental results show that the microfibers can be reliably picked up from and placed on the substrate of different materials including paper tissue, glass, silicon, stainless steel, copper with droplet volume of 0.1 nL and 0.3 nL. We further applied the method to the placement of the microfibers on super hydrophilic-super hydrophobic grooves and studied its placement speed and accuracy. We demonstrated that microfiber can be placed in such grooves in less than 0.1 seconds, with linear placement accuracy of $10~\mu \text{m}$ and angular placement accuracy of 0.5°. The proposed method is fast and simple, and it is especially suitable for handling fragile and flexible micro sized objects and construction of fiber-based materials.

In this article, we investigate intelligent anti-jamming communication method for wireless sensor networks. The stochastic game framework is introduced to model and analyze the multi-user anti-jamming problem, and a joint multi-agent anti-jamming algorithm (JMAA) is proposed to obtain the optimal anti-jamming strategy. In intelligent multi-channel blocking jamming environment, the proposed JMAA adopts multi-agent reinforcement learning to make online channel selection, which can effectively tackle the external malicious jamming and avoid the internal mutual interference among sensor nodes. The simulation results show that, the proposed JMAA is superior to the frequency-hopping method, the sensing-based method and the independent reinforcement learning. Specifically, the proposed JMAA has the higher average packet receive ratio than both the frequency-hopping method and the sensing-based method. Compared with the independent reinforcement learning, JMAA has faster convergence rate when reaching the same performance of average packet receive ratio. In addition, since the JMAA does not need to model the jamming patterns, it can be widely used for combating other malicious jamming such as sweep jamming and probabilistic jamming.

Abstract The cancer drug delivery process involves a series of biological barriers, which require the nanomedicine to exhibit different, even opposite properties for high therapeutic efficacy. The prevailing design philosophy, i.e., integrating these properties within one nanomedicine via on‐demand property transitions such as PEGylation/dePEGylation, complicates nanomedicines’ composition and thus impedes clinical translation. Here, polyzwitterionic micelles of poly(tertiary amine‐oxide)‐block‐poly(ε‐caprolactone) (PTAO‐PCL) amphiphiles that enable all the required functions are presented. The zwitterionic nature and unique cell membrane affinity confer the PTAO micelles long blood circulation, efficient tumor accumulation and penetration, and fast cellular internalization. The mitochondrial targeting capability allows drug delivery into the mitochondria to induce mitochondrial dysfunction and overcome tumor multidrug resistance. As a result, the PTAO/drug micelles exhibit potent anticancer efficacy. This simple yet multipotent carrier system holds great promise as a generic platform for potential clinical translation.

Abstract Osteoarthritis (OA) is a degenerative disease that involves excess reactive oxygen species (ROS) and osteochondral defects. Although multiple approaches have been developed for osteochondral regeneration, how to balance the biochemical and physical microenvironment in OA remains a big challenge. In this study, a bioceramic scaffold by 3D printed akermanite (AKT) integrated with hair‐derived antioxidative nanoparticles (HNPs)/microparticles (HMPs) for ROS scavenging and osteochondral regeneration has been developed. The prepared bioscaffold with multi‐mimetic enzyme effects, which can scavenge a broad spectrum of free radicals in OA, can protect chondrocytes under the ROS microenvironment. Importantly, the bioscaffold can distinctly stimulate the proliferation and maturation of chondrocytes due to the stimulation of the glucose transporter pathway (GLUT) via HNPs/HMPs. Furthermore, it significantly accelerated osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In vivo results showed that the bioscaffold can effectively enhance the osteochondral regeneration compared to the unmodified scaffold. The work shows that integration of antioxidant and mechanical properties via the bioscaffold is a promising strategy for osteochondral regeneration in OA treatment.

BackgroundEnvironmental exposure to toxic elements contributes to the pathogenesis of chronic kidney disease (CKD). Few studies focus on the association of urinary metals and metalloids concentrations with the urinary albumin/creatinine ratio (UACR) among elderly, especially in areas and seasons with severe air pollution.ObjectiveWe aimed to evaluate the associations of urinary metals and metalloids concentration with UACR, which is an early and sensitive indicator of CKD.MethodWe conducted a cross-sectional study among 275 elderly people in Beijing from November to December 2016, which has experienced the most severe air pollution in China. We measured 15 urinary metals and metalloids concentration and estimated their association with UACR using a generalized linear model (GLM). Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) models were also conducted to evaluate the combined effect of metal and metalloid mixtures concentration.ResultsOf the 275 elderly people included in the analysis, we found that higher urinary Cu concentration was positively associated with UACR using GLM (β = 0.36, 95% CI: 0.25, 0.46). Using the BKMR model, we found that the change in UACR was positively associated with a change in urinary Cu concentration from its 25th to 75th percentile value with all other metals and metalloids concentration fixed at their 25th, 50th, or 75th percentile levels. Urinary Cu concentration had the most significant positive contribution (59.15%) in the qgcomp model. Our finding was largely robust in three mixture modeling approaches: GLM, qgcomp, and BKMR.ConclusionThis finding suggests that urinary Cu concentration was strongly positively associated with UACR. Further analyses in cohort studies are required to corroborate this finding.

Utilizing physical information to improve the performance of the conventional neural networks is becoming a promising research direction in scientific computing recently. For multiphase flows, it would require significant computational resources for neural network training due to the large gradients near the interface between the two fluids. Based on the idea of the physics-informed neural networks (PINNs), a modified deep learning framework BubbleNet is proposed to overcome this difficulty in the present study. The deep neural network (DNN) with separate sub-nets is adopted to predict physics fields, with the semi-physics-informed part encoding the continuity equation and the pressure Poisson equation P for supervision and the time discretized normalizer to normalize field data per time step before training. Two bubbly flows, i.e., single bubble flow and multiple bubble flow in a microchannel, are considered to test the algorithm. The conventional computational fluid dynamics software is applied to obtain the training dataset. The traditional DNN and the BubbleNet(s) are utilized to train the neural network and predict the flow fields for the two bubbly flows. Results indicate the BubbleNet frameworks are able to successfully predict the physics fields, and the inclusion of the continuity equation significantly improves the performance of deep NNs. The introduction of the Poisson equation also has slightly positive effects on the prediction results. The results suggest that constructing semi-PINNs by flexibly considering the physical information into neural networks will be helpful in the learning of complex flow problems.

Background: Researchers have reported that chromium (Cr) exposure may be associated with metabolism of glucose and lipids in residents living in a long-term Cr polluted area. Previous statistical analysis is mainly focused on individual chromium exposure. Furtherly, we aim to investigated the independent, combined, and interaction effects of the co-exposure of urine Cr (UCr) with cadmium (UCd), lead (UPb) and manganese (UMn) on body mass index (BMI), waist circumference, and the risk of overweight and abdominal obesity. Method: We enrolled 1187 participants from annual surveys between 2017 and 2019. Heavy metal concentrations in urine were standardized using covariate-adjusted urine creatinine levels. Multiple linear/logistic regression models were applied to measure the single effect of urine heavy metal concentration on the outcomes. The quantile-based g-computation (g-comp) model was used to evaluate the combined effect of metal mixture on the outcomes and to compare the contribution of each metal. Both additive and multiplicative interactions were measured for UCr with UCd, UPb, UMn on the outcomes. Analysis was performed on the overall population and stratified by smoking habit. Results: For the overall study population, UCr was positively associated with BMI (p trend = 0.023) and waist circumference (p trend = 0.018). For smoking participants, the g-comp model demonstrated that the metal mixture was negatively associated with BMI, with UCr and UCd contributing the most in the positive and negative direction. A negative additive interaction was observed between UCr and UCd on BMI and abdominal obesity. We did not observe a significant interaction effect of UCr with UPb or UMn. Conclusion: Our study indicated that Cr and Cd exposure may be associated with BMI and waist circumference, with combined and interaction effects of the heavy metals noted. Further epidemiological and experimental researches could simultaneously consider single and complex mixed exposure to verify the findings and biological mechanisms.

ObjectiveTo compare the effects of percutaneous kyphoplasty (PKP) with or without posterior pedicle screw fixation (PPSF) on spinal sagittal balance in elderly patients with severe osteoporotic vertebral compression fracture (sOVCF).MethodsFrom January 2016 to December 2018, 102 elderly patients with single-level thoracolumbar sOVCF were enrolled. Among them, 78 cases underwent PKP (Group A), and 24 cases underwent PPSF+KP (Group B). Clinical evaluation included perioperative parameters, Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) for back pain; Radiographic evaluation included anterior vertebral height (AVH) and rate (AVHr), local kyphotic angle (LKA), and spino-pelvic sagittal balance parameters.ResultsPerioperative parameters including operation time, blood loss, fluoroscopic time and hospital stay in Group A were less than those in Group B (p < 0.05). Compared with the pre-operative results, the ODI and VAS scores of both groups decreased significantly in the three follow-ups after surgery (p < 0.05). The post-operative ODI and VAS scores of Group A were significantly better than those of Group B, but the results were opposite at the final follow-up (p < 0.05). Compared with the pre-operative values, except that there was no significant difference in pelvic incidence (PI) (p > 0.05), other radiographic parameters of both groups were improved significantly in the three follow-ups after surgery (p < 0.05). The AVH, AVHr, LKA and lumbar lordosis (LL) in Group B were better than those in Group A in the three follow-ups after surgery (p < 0.05). At the final follow-up, the sacral slope (SS) and pelvic tilt (PT) differed significantly between the two groups (p < 0.05).ConclusionsBoth PPSF+KP and PKP can achieve favorable clinical outcomes and maintain the spinal sagittal balance. Compared with PPSF+KP, PKP showed more significant advantages in the early post-operative period. However, in the long-term follow-up, PPSF+KP showed better clinical outcomes and may be better than PKP in maintaining spinal sagittal balance.

Aims: Prostate cancer is a well-known aggressive malignant tumor in men with a high metastasis rate and poor prognosis. Adapalene (ADA) is a third-generation synthetic retinoid with anticancer properties. We investigated the anti-tumor activity and molecular mechanisms of ADA in the RM-1 prostate cancer cell line in vivo and in vitro.Methods: The effects of ADA on cell proliferation were estimated using the CCK-8 and colony formation assays. The wound-healing assay and the Transwell assay were employed to examine the migratory capacity and invasiveness of the cells. Flow cytometry was utilized to evaluate the cell cycle and apoptosis, and Western blotting analysis was used to assess the expression of the associated proteins. Micro-CT, histomorphological, and immunohistochemical staining were used to assess the effects of ADA on bone tissue structure and tumor growth in a mouse model of prostate cancer bone metastasis.Result: ADA dramatically inhibited cell proliferation, migration, invasiveness, and induced S-phase arrest and apoptosis. ADA also regulated the expression of S-phase associated proteins and elevated the levels of DNA damage markers, p53, and p21 after ADA treatment, suggesting that the anti-tumor effect of ADA manifests through the DNA damage/p53 pathway. Furthermore, we observed that ADA could effectively inhibited tumor growth and bone destruction in mice.Conclusion: ADA inhibited prostate cancer cell proliferation, elicited apoptosis, and arrested the cell cycle in the S-phase. ADA also slowed the rate of tumor growth and bone destruction in vitro. Overall, our results suggest that ADA may be a potential treatment against prostate cancer.

Travel entail change in geography and diet, both of which are known as determinant factors in shaping the human gut microbiome. Additionally, altered gut microbiome modulates immunity, bringing about health implications in humans. To explore the effects of the mid-term travel on the gut microbiome, we generated 16S rRNA gene and metagenomic sequencing data from longitudinal samples collected over six months. We monitored dynamic trajectories of the gut microbiome variation of a Chinese volunteer team (VT) in their whole journey to Trinidad and Tobago (TAT). We found gut microbiome resilience that VT’s gut microbial compositions gradually transformed to the local TAT’s enterotypes during their six-month stay in TAT, and then reverted to their original enterotypes after VT’s return to Beijing in one month. Moreover, we identified driven species in this bi-directional plasticity that could play a role in immunity modulation, as exemplified by Bacteroides dorei that attenuated atherosclerotic lesion formation and effectively suppressed proinflammatory immune response. Another driven species P. copri could play a crucial role in rheumatoid arthritis pathogenesis, a chronic autoimmune disease. Carbohydrate-active enzymes are often implicated in immune and host-pathogen interactions, of which glycoside hydrolases were found decreased but glycosyltransferases and carbohydrate esterases increased during the travel; these functions were then restored after VT’ returning to Beijing. Furthermore, we discovered these microbial changes and restoration were mediated by VT people’s dietary changes. These findings indicate that half-year travel leads to change in enterotype and functional patterns, exerting effects on human health. Microbial intervention by dietary guidance in half-year travel would be conducive to immunity modulation for maintaining health.

Magnetic resonance imaging (MRI) could be the ideal diagnostic modality for early rheumatoid arthritis (RA). Vascular cell adhesion molecule-1 (VCAM-1) is highly expressed in synovial locations in patients with RA, which could be a potential target protein for RA diagnosis. The peptide VHPKQHR (VHP) has a high affinity to VCAM-1. To make the contrast agent to target RA at an early stage, we used VHP and ultrasmall paramagnetic iron oxide (USPIO) to synthesize UVHP (U stands for USPIO) through a chemical reaction with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide. The size of UVHP was 6.7 nm; the potential was −27.7 mV, and the r2/r1 value was 1.73. Cytotoxicity assay exhibited that the cell survival rate was higher than 80% at even high concentrations of UVHP (Fe concentration 200 µg/mL), which showed the UVHP has low toxicity. Compared with no TNF-α stimulation, VCAM-1 expression was increased nearly 3-fold when mouse aortic endothelial cells (MAECs) were stimulated with 50 ng/mL TNF-α; cellular Fe uptake was increased very significantly with increasing UVHP concentration under TNF-α treatment; cellular Fe content was 17 times higher under UVHP with Fe concentration 200 µg/mL treating MAECs. These results indicate that UVHP can target overexpression of VCAM-1 at the cellular level. RA mice models were constructed with adjuvant-induced arthritis. In vivo MRI and biodistribution results show that the signal intensity of knee joints was increased significantly and Fe accumulation in RA model mice compared with normal wild-type mice after injecting UVHP 24 h. These results suggest that we have synthesized a simple, low-cost, and less toxic contrast agent UVHP, which targeted VCAM-1 for early-stage RA diagnosis and generates high contrast in T1-weighted MRI.

Background Avitinib is one type of the third‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for the treatment of non‐small cell lung cancer (NSCLC) with EGFR mutations. The purpose of this study was to investigate the effect of avitinib on the pharmacokinetics of osimertinib, one FDA approved third‐generation TIKI, both in vitro and in vivo. Methods The in vitro metabolic stability and inhibitory effect of avitinib on osimertinib were assessed with rat liver microsomes (RLM) to determine its IC50 values. For the in vivo study, 18 Sprague‐Dawley rats were randomly divided into three groups: the avitinib multiple dose group (30 mg/kg avitinib once daily for seven days), the avitinib single dose group (PEG200 once daily for six days and a dose of 30 mg/kg avitinib in PEG200 on day 7) and the control group (equal amounts of PEG200 once daily for seven days). Next, all rats were given osimertinib at a dosage of 10 mg/kg. UPLC/MS‐MS was used for the determination of the concentration of osimertinib in plasma. Results In vitro analysis revealed that the IC50 value of osimertinib in rat liver microsomes was 27.6 μM. When rats were pretreated with avitinib, the values of AUC and MRT of the osimertinib were increased, and its Cmax and Tmax were significantly extended, whereas the values of CLz/F were significantly decreased (P

Photodynamic therapy (PDT) has been widely used in cancer treatment. However, hypoxia in most solid tumors seriously restricts the efficacy of PDT. To improve the hypoxic microenvironment, we designed a novel mesoporous platinum (mPt) nanoplatform to catalyze hydrogen peroxide (H2O2) within the tumor cells in situ without an extra enzyme. During the fabrication, the carboxy terminus of the photosensitizer chlorin e6 (Ce6) was connected to the amino terminus of the bifunctional mercaptoaminopolyglycol (SH-PEG-NH2) by a condensation reaction, and then PEG-Ce6 was modified onto the mPt moiety via the mercapto terminal of SH-PEG-NH2. Material, cellular and animal experiments demonstrated that Pt@PEG-Ce6 catalyzed H2O2 to produce oxygen (O2) and that Ce6 transformed O2 to generate reactive oxygen species (ROS) upon laser irradiation. The Pt@PEG-Ce6 nanoplatform with uniform diameter presented good biocompatibility and efficient tumor accumulation. Due to the high atomic number and good near-infrared absorption for Pt, this Pt@PEG-Ce6 nanoplatform showed computed tomography (CT) and photoacoustic (PA) dual-mode imaging ability, thus providing an important tool for monitoring the tumor hypoxic microenvironment. Moreover, the Pt@PEG-Ce6 nanoplatform reduced the expression of hypoxia-inducible factor-1α (HIF-1α) and programmed death-1 (PD-1) in tumors, discussing the relationship between hypoxia, PD-1, and PDT for the first time.

Abstract Background Previous studies have suggested that there is an association between air pollutants and circulatory and respiratory diseases; however, relatively few have analyzed the association between air pollutants and outpatient visits based on the mortality, hospitalization rates, etc., especially in areas with relatively good air quality. Therefore, we conducted this study to research the association between air pollutants and outpatient visits in Fuzhou, China. Methods We used a generalized linear Poisson model to study the association between air pollution and outpatient visits for respiratory and circulatory diseases from 2016 to 2018 in Fuzhou, China. Results In the single pollutant model, nitrogen dioxide (NO2) had a significant effect. For lag day 0 to lag day 5, the effect decreased with every 10 μg/L increase in NO2. The daily maximum 8-h mean ozone (O3-8h) and upper respiratory outpatient visits were positively associated during the cold period [lag2, excess risk (ER) (95% confidence interval (CI)): 1.68% (0.44–2.94%)], while O3-8h and respiratory disease were positively associated during the warm period [lag5, ER (95% CI): 1.10% (0.11–2.10%) and lag4, ER (95% CI): 1.02% (0.032–2.02%)]. Similarly, particulate matter (PM) with an average aerodynamic diameter of less than 10 μm (PM10) and lower respiratory diseases were positively associated during the warm period [lag0, ER (95% CI): 1.68% (0.44–2.94%)]. When the concentration of O3-8h was higher than 100 μg/L, there was a positive effect on circulatory [lag5, ER (95% CI): 2.83% (0.65–5.06%)], respiratory [lag5, ER (95% CI): 2.47% (0.85–4.11%)] and upper respiratory [lag5, ER (95% CI): 3.06% (1.38–4.77%)] outpatient visits. The variation in O3-8h changed slightly when we adjusted for other air pollutants, and after adjusting for O3-8h, the ERs of the other air pollutants changed slightly. After adjusting for PM with an average aerodynamic diameter of less than 2.5 μm (PM2.5), the ERs of the other air pollutants increased, and after adjusting for NO2, the ER of PM decreased. Conclusion Exposure to ambient NO2, O3, PM2.5 and PM10 was associated with an increase in respiratory and circulatory system-related outpatient visits in Fuzhou, China.

Deriving functional pancreatic cell types from human stem cells may have important clinical applications. Building on previous work, here the authors generate stem cell-derived alpha cells via a polyhormonal intermediate, which have a gene expression pattern similar to human islet alpha cells and behave as such when transplanted into mice.

Identification of low abundance proteins interacting with viral proteins can be challenging. Here, Du et al. develop an mRNA display approach with a library of even distribution, identify host proteins interacting with NS1 protein of influenza A virus, and show that one interactor provides a means to regulate cellular fatty acids synthesis.

Magnetic resonance imaging (MRI) is an essential tool for the diagnosis of atherosclerosis, a chronic cardiovascular disease. MRI primarily uses superparamagnetic iron oxide (SPIO) as a contrast agent. However, SPIO integrated with therapeutic drugs has rarely been studied. In this study, we explored biocompatible paramagnetic iron-oxide nanoparticles (NPs) in a complex with low pH-sensitive cyclodextrin for the diagnostic imaging and treatment of atherosclerosis. The NPs were conjugated with profilin-1 antibody (PFN1) to specifically target vascular smooth muscle cells (VSMCs) in the atherosclerotic plaque and integrated with the anti-inflammatory drug, rapamycin. The PFN1-CD-MNPs were easily binded to the VSMCs, indicating their good biocompatibility and low renal toxicity over the long term. Ex vivo near-infrared fluorescence (NIRF) imaging and in vivo MRI indicated the accumulation of PFN1-CD-MNPs in the atherosclerotic plaque. The RAP@PFN1-CD-MNPs alleviated the progression of arteriosclerosis. Thus, PFN1-CD-MNPs served not only as multifunctional imaging probes but also as nanovehicles for the treatment of atherosclerosis.

Dynamic-field acoustic manipulation techniques benefit numerous applications in microsystem assembly, pattern formation, biological research, tissue engineering, and lab-on-a-chip. These techniques generally rely on a theoretical dynamic model of particle motion in the acoustic field. Accordingly, success of the manipulation task highly depends on the accuracy of the employed dynamic model. However, modelling such dynamic behavior is a great challenge in more advanced acoustic manipulation devices and requires significant simplifications. Here, we introduce a model-free control method based on reinforcement learning for highly-dynamic acoustic manipulation devices. In our method, the controller does not need a prior knowledge of the acoustic field and learns the optimal control policy for each manipulation task by merely interacting with the acoustic field. As a proof-of-concept, we apply our method to a classic acoustic manipulation device, a Chladni plate consisting of a centrally-actuated vibrating plate. By employing the controller, we demonstrate successful manipulation of single and multiple particles towards target locations on the plate surface. The model-free control method is not limited to the Chladni plate and can be potentially applied to a broad range of acoustic manipulation devices as well as other forms of field-based micromanipulation systems, where accurate theoretical modelling of the field is challenging.

Temporal consistency analysis is an important problem in Real-Time Database Systems (RTDBSs). Most of existing works on hybrid transaction co-scheduling focus on exploring effective deadline and period assignment methods which can guarantee the temporal consistency of data objects and the schedulability of transactions. To the best of our knowledge, all existing researches have not yet invested sufficient efforts on guaranteeing the Quality of Service (QoS) of control transactions and allow control transactions finish their execution after the data obtained by these control transactions expire. In this paper, we define a new problem of how to schedule a hybrid transaction set under the guarantee on QoS of control transactions. Two deadline and period assignment methods for addressing the defined problem are proposed in this work. Both the proposed methods support the Earliest Deadline First (EDF) scheduling. Extensive experiments are conducted to evaluate the performances of the proposed methods in terms of acceptance ratio, processor workload and efficiency.

Pulse jamming is one of the common malicious jamming patterns that can significantly reduce the of wireless communication's reliability. This paper investigates the problem of anti-jamming communication in a random pulse jamming environment. In order to obtain the countermeasure in time domain, the Markov decision process (MDP) is employed to model and analyze the above problem, and a time-domain anti-pulse jamming algorithm (TDAA) based on reinforcement learning is proposed. The proposed algorithm learns from the dynamic interaction with the jamming environment to gradually approximate the optimal time-domain strategy. The optimal strategy enables the transmitter to switch between two states, i.e. “active” and “silent”, to avoid random pulse jamming. In addition, a state estimation and adjustment method for the random pulse jamming environment is introduced to improve the robustness of the proposed TDAA. Simulation results show that, compared with continuous transmission, the proposed TDAA can effectively reduce the jamming collision ratio and significantly improve the normalized throughput. And compared with transmitting terminal Q-learning algorithm (TTQA), the proposed TDAA has higher time utilization ratio and normalized throughput.

This article presents the influence of thermal aging on space charge accumulation and dissipation of cross-linked polyethylene (XLPE) with different cross-linking agent contents. In this article, dicumyl peroxide (DCP) and low-density polyethylene (LDPE) respectively are used as cross-linking agent and basic experimental material. Additionally, an improved PEA method is used to measure space charge densities during voltage application and removal when thermal aging time respectively is 0, 5, 15, 30 and 80 days due to higher accuracy. And experimental results indicate thermal aging can introduce negative charge traps into pure LDPE and make space charges easier to inject and accumulate in pure LDPE and XLPE, but space charge densities in XLPE increase more rapidly as thermal aging time increases, moreover, thermal aging can simultaneously increase densities of deep and shallow charge traps in pure LDPE and XLPE, etc. And we have also explained the change of space charge accumulation and dissipation of pure LDPE and XLPE after thermal aging from the perspective of micro-structure change of pure LDPE and XLPE through the quantitative analysis of average charge densities. Besides, theoretical model of the average charge decay has also been summed up, and this model can perfectly reflect the dissipation of space charges in pure LDPE and XLPE of different thermal aging time.

During the deceleration phase of a hybrid electric vehicle (HEV), a moment-of-inertia-driven (MoI-driven) engine start-up process can provide a potential economic benefit because it reduces the energy consumption of the starting device. During this start-up process, it is important to maintain drivability by enabling a quick start-up, low driveline vibration, and fast response to torque demand. The wheel rolling distance control should also be considered. This paper proposes electrical motor (EM) participation in an MoI-driven engine start-up process and studies an adaptive model-based predictive optimization method for the drivability control of P2 parallel hybrid vehicles. Based on a new triple mass-spring-system model, an adaptive model predictive controller (MPC) is designed with EM torque set points, clutch friction torque set points, and engine torque set points as manipulated inputs and engine speed, torsion speed, and wheel rolling distance as the measured outputs. A predicted torque demand is introduced to enhance the torque response performance. By considering the constraints of power source components, an optimization algorithm is developed. A simulation is conducted to verify the control strategy on the HEV powertrain and on vehicle dynamics models. The results show that under the same level of start-up, the torsion speed can be reduced by up to 50% with an improved wheel rolling distance and low torque demand error during a certain deceleration.

Context Naringenin and tofacitinib are often used together for treatment of rheumatoid arthritis in Chinese clinics. Objective This experiment investigates the effect of naringenin on the pharmacokinetics of tofacitinib in rats. Materials and methods Twelve Sprague-Dawley rats were randomly divided into two groups (experimental group and control group). The experimental group was pre-treated with naringenin (150 mg/kg/day) for two weeks before dosing tofacitinib, and equal amounts of CMC-Na solution in the control group. After a single oral administration of 5 mg/kg of tofacitinib, 50 μL blood samples were directly collected into 1.5 mL heparinized tubes via the caudal vein at 0.083, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h. The plasma concentration of tofacitinib was quantified by UPLC/MS–MS. Results Results indicated that naringenin could significantly affect the pharmacokinetics of tofacitinib. The AUC0–24 of tofacitinib was increased from 1222.81 ± 222.07 to 2016.27 ± 481.62 ng/mL/h, and the difference was significant (p 0.05). Conclusions This research demonstrated a drug-drug interaction between naringenin and tofacitinib possibly when preadministered with naringenin; thus, we should pay attention to this possibility in the clinic.

Context Rivaroxaban and ticagrelor are two common drugs for the treatment of atrial fibrillation and acute coronary syndrome. However, the drug–drug interaction between them is still unknown. Objective To investigate the effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats both in vivo and in vitro. Materials and methods A sensitive and reliable UPLC-MS/MS method was developed for the determination of rivaroxaban in rat plasma. Ten Sprague-Dawley rats were randomly divided into ticagrelor pre-treated group (10 mg/kg/day for 14 days) and control group. The pharmacokinetics of orally administered rivaroxaban (10 mg/kg, single dose) with or without ticagrelor pre-treatment was investigated with developed UPLC-MS/MS method. Additionally, Sprague-Dawley rat liver microsomes were also used to investigate the drug–drug interaction between these two drugs in vitro. Results The Cmax (221.34 ± 53.33 vs. 691.18 ± 238.31 ng/mL) and the AUC(0–t) (1060.97 ± 291.21 vs. 3483.03 ± 753.83 μg·h/L) of rivaroxaban increased significantly (p

Abstract Objective Approximately 300 mg of calcium a day is provided into infants to maintain the physical development of infants, and 5 to 10% bone loss occurs in women during breastfeeding. Hip fractures are considered the most serious type of osteoporotic fracture. We performed this meta-analysis to investigate the association between breastfeeding and osteoporotic hip fractures. Material and methods PubMed and Embase were searched until May 1, 2019, for studies evaluating the relationship between breastfeeding and osteoporotic hip fracture in women. The quality of the included studies was evaluated by the methodological index for non-randomized studies (MINORS). For the dose-response meta-analysis, we used the “generalized least squares for trend estimation” method proposed by Greenland and Longnecker to take into account the correlation with the log RR estimates across the duration of breastfeeding. Results Seven studies were moderate or high quality, enrolling a total of 103,898 subjects. The pooled outcomes suggested that breastfeeding can decrease the incidence of osteoporotic hip fracture (RR = 0.64 (95% CI 0.43, 0.95), P = 0.027). Dose-response analysis demonstrated that the incidence of osteoporotic hip fracture decreased with the increase of breastfeeding time. The RR and 95% CI for 3 months, 6 months, 12 months, and 24 months were RR = 0.93, 95% CI 0.88, 0.98; RR = 0.87, 95% CI 0.79, 0.96; RR = 0.79, 95% CI 0.67, 0.92; and RR = 0.76, 95% CI 0.59, 0.98, respectively, whereas no significant relationship was found between them when the duration of breastfeeding time was more than 25 months. Conclusions Our meta-analysis demonstrated that the incidence of osteoporotic hip fracture decreased with the extension of breastfeeding time. However, there is no significant relationship between them when the duration of breastfeeding time was more than 25 months.

This article investigates circular formation control problems for a group of anonymous mobile robots in the plane, where all robots can converge asymptotically to a predefined circular orbit around a fixed target point without collision, and maintain any desired relative distances from their neighbors. Given the limited resources for communication and computation of robots, a distributed event-triggered method is firstly designed to reduce dependence on resources in multi-robot systems, where the controller’s action is determined by whether the norm of the event-trigger function exceeds zero through continuous sampling. And then, to further minimize communications costs, a self-triggered strategy is proposed, which only uses discrete states sampled and sent by neighboring robots at their event instants. Furthermore, for the two proposed control laws, a Lyapunov functional is constructed, which allows sufficient stability conditions to be obtained on the circular formation for multi-robot systems. And at the same time, the controllers are proved to exclude Zeno behavior. At last, numerical simulation of controlling uniform and non-uniform circular formations by two control methods are conducted. Simulation results show that the designed controller can control all mobile robots to form either a uniform circular formation or a non-uniform circular formation while maintaining any desired relative distances between robots and guaranteeing that there is no collision during the whole evolution. One of the essential features of the proposed control methods is that they reduce the update rates of controllers and the communication frequency between robots. And also, the spatial order of robots is also preserved throughout the evaluation of the system without collision.

Purpose. Previous studies have shown that the peripheral red blood cell distribution width (RDW) and human serum albumin (ALB) were both predictors of the risk and mortality of cerebrovascular diseases, and the ratio of RDW to ALB (RAR) was a combined new index that can predict the prognosis of the cardiovascular and respiration systemic diseases, but its role in cerebrovascular diseases had not been effectively evaluated. This study is aimed at exploring whether RAR can effectively predict the 30-day all-cause mortality of acute ischemic stroke (AIS) patients. Methods. This retrospective cohort study was conducted on AIS patients (age>18 years) in the intensive care database MIMIC-IV. The RAR was measured based on the red blood cell distribution width and albumin. The main result was 30-day all-cause mortality, and the secondary results were ICU mortality and hospital mortality. Obtain the odds ratio (OR) estimate from the logistic regression model of log-transformed RAR values and mortality. We had used another database for external validation. Results. A total of 1412 patients were enrolled, with an average age of 68.8±15.9, including 708 (50.1%) males. When log-transformed RAR values were used as a continuous variable, as the values increases, the risk of death increases (30-day all-cause mortality OR=4.02 (2.21, 7.32) P

Rheumatoid arthritis (RA) is a systemic chronic autoinflammatory disease, and the synovial hyperplasia, pannus formation, articular cartilage damage and bone matrix destruction caused by immune system abnormalities are the main features of RA. The use of Disease Modifying Anti-Rheumatic Drugs (DMARDs) has achieved great advances in the therapy of RA. Yet there are still patients facing the problem of poor response to drug therapy or drug intolerance. Current therapy methods can only moderate RA progress, but cannot stop or reverse the damage it has caused. Recent studies have reported that there are a variety of long non-coding RNAs (LncRNAs) that have been implicated in mediating many aspects of RA. Understanding the mechanism of LncRNAs in RA is therefore critical for the development of new therapy strategies and prevention strategies. In this review, we systematically elucidate the biological roles and mechanisms of action of LncRNAs and their mechanisms of action in RA. Additionally, we also highlight the potential value of LncRNAs in the clinical diagnosis and therapy of RA.

Clinically used intervertebral cages have several bottleneck problems, such as lack of osteogenic properties and high subsidence rate. This research aims to design a novel biomimetic titanium alloy cage through three improvements: cross-sectional shape mimics, Young's modulus matches and osteogenic property enhances. Two inner porous structures (1450–200 μm and 800–200 μm) were selected, and the Young's modulus were 540.7 MPa (similar to cancellous bone) and 1139.2 MPa, respectively. Shape of the cages was designed by radiographic images and assistant softwares to make the dense border contact the peripheral cortical bone of the vertebrae. Hydroxyapatite (HA) biocoating was performed through the slurry foaming and impregnation method, and the average thickness was approximately 40 μm. The biocoated and nonbiocoated cages were then implanted in goats’ intervertebral space. During the 6-month follow-up, the lordosis angle and disc space height maintained well in all groups. Histological results showed a significant increase in bone ingrowth area between the nonbiocoating and biocoating groups, meaning a great enhancement of osteogenic properties by HA biocoating. The osseointegration also improved greatly. Additionally, the fusion condition of Young's modulus matching cages, before or after biocoating, was superior to that of unmatched cages. The results demonstrated that biomimetic designs could help avoid subsidence and promote fusion.

The heat transfer enhancement achieved by the additional electric field in Rayleigh–Bénard convection (RBC) of a dielectric fluid is numerically studied beyond the Rayleigh number Ra = 105. We carried out direct numerical simulations of RBC in a rectangular enclosure under the strong injection condition with a fixed non-dimensional injection parameter C = 10, a fixed mobility number M = 10, two Rayleigh numbers Ra = 105 and Ra = 106, and two Prandtl numbers Pr = 1 and Pr = 10 to investigate the characteristics of flow structure and heat transfer and evaluate the dependence on these parameters. It is observed that the flow structure exhibits multiple states with various steady or unsteady flow patterns such as four cells, three cells, and two cells (up/down). It is found that the introduction of an electric field is an effective way to achieve heat transfer enhancement. The heat flux is augmented more efficiently for a large Prandtl number and a low Rayleigh number, where the electric field has a strong effect relative to buoyancy. It is also found that heat transfer is most efficient when the flow pattern is in a three cells flow state.

Na-ion batteries (NIBs) have received significant interest as potential candidates for large-scale energy storage owing to the widespread distribution of sodium and superior low-temperature performance. However, their commercial application is usually hindered by the high production cost and inadequate performance for electrode materials, particularly for cathodes. Na3(VOPO4)2F (NVOPF) has been recognized as one of the most promising cathodes for high-energy NIBs owing to the high working voltage and energy density. Here, we report a facile highly efficient room-temperature solution protocol for large-scale synthesis of NVOPF cathode for NIBs. By simply regulating pH, NVOPF can be obtained, which delivered a discharge capacity of 120.2 mAh g-1 at 0.1 C and 72% capacity retention over 8000 cycles at 25 C. Besides, the kilogram-level NVOPF products have been synthesized, and 26650 cylindrical cells were fabricated, which exhibit excellent cycling stabilities, remarkable low-temperature performance with comparable safety features. We hope our findings could provide insights on the industrial application of NVOPF in NIBs.

Purpose. Acute ischemic stroke (AIS) is a devastating disease and remains the leading cause of death and disability. This retrospective study aims to investigate associations between systemic immune-inflammation index (SII) and all-cause mortality in patients with AIS. Patients and Methods. We used the data from Medical Information Mart for Intensive Care IV. A total of 1,181 patients with acute ischemic stroke (AIS) were included. Systemic immune-inflammation index (SII) was calculated as platelet count (/L) × neutrophil count (/L)/lymphocyte count (/L). The main outcomes were 30-day all-cause mortality. The association between SII with mortality was evaluated using the Cox proportional hazards regression model. Results. After adjusting for potential covariates, the highest quartiles of SII versus the lowest quartiles of SII, the HR was 2.74 (CI 1.79–4.19, P

Objective The effect of the serum chloride (Cl) level on mortality in critically ill patients with acute kidney injury (AKI) remains unknown. We sought an association between mortality and serum Cl. Methods We identified AKI patients in the eICU Collaborative Research Database from 2014 to 2015 at 208 US hospitals. The outcomes included in-hospital and intensive care unit (ICU) mortality. Time-varying covariates Cox regression models and the Kaplan-Meier (K-M) curves were used to assess the association between serum Cl levels and mortality. Multivariable adjusted restricted cubic spline models were used to analyze the potential nonlinear relationship between mortality and serum Cl. Results In total, 4,234 AKI patients were included in the study. Compared with normochloremia (98≤chlorideConclusions Lower serum Cl levels after ICU admission was associated with increased in-hospital and ICU mortality in critically ill patients with AKI. The results should be verified in well-designed prospective studies.

The pathogenesis of intervertebral disc degeneration (IDD) is still unclear. It has been shown that the pathological process of IDD is most closely related to inflammation of nucleus pulposus cells (NPCs), in which inflammatory factors play an important role. Exosomes are the main paracrine mediators and are microvesicles with biological functions similar to those of the cells from which they are derived. Studies have shown that bone mesenchymal stem cells (BMSCs) can inhibit apoptosis of NPCs by sending exosomes as anti-inflammatory and antioxidant, which has been proved to be effective on IDD. However, the specific mechanism of inhibiting apoptosis of NPCs is still unclear. In our study, BMSC-derived exosomes (BMSC-Exo) were isolated from the BMSC culture medium, and their antiapoptotic effects were evaluated in cells and rat models to explore the possible mechanisms. We observed that BMSC-Exo promotes autophagy in NPCs and inhibits the release of inflammatory factors such as IL-1β and TNF-α in LPS-treated NPCs and inhibits apoptosis in NPCs. Further studies showed that BMSC-Exo inhibited the Akt-mTOR pathway. Intramuscular injection of BMSC-Exo alleviates disc degeneration in rat IDD models. In conclusion, our results suggest that BMSC-Exo can reduce NPC apoptosis and alleviate IDD by promoting autophagy by inhibiting the Akt-mTOR pathway. Our study confers a promising therapeutic strategy for IDD.

Introduction: Abnormal inter arm systolic blood pressure, inter leg systolic blood pressure and ankle brachial index (ABI) are related to vascular diseases. Our aim was to evaluate the correlation of inter arm systolic blood pressure difference (IASBPD), inter leg systolic blood pressure difference (ILSBPD), and ABI with acute aortic dissection (AAD) and their role in predicting AAD. Methods: In this prospective case-control study, 180 patients with AAD admitted to the emergency department were prospectively and consecutively collected in Tongji Hospital from October 2019 to December 2020. 180 healthy people matched by sex, age and BMI served as control group. All participants were adults over 18 years of age who underwent four-limb blood pressure measurements. IASBPD, ILSBPD and ABI were compared between the two groups and their associations with AAD were analyzed. Results: A total of 360 patients (180 cases and 180 controls) were analyzed. In case group IASBPD was larger [(15.23 ± 16.15) mm Hg vs. (4.19 ± 3.63) mm Hg] and ILSBPD was larger (13.00 mm Hg vs. 5.70 mm Hg). ABI was smaller [(0.98 ± 0.24) vs. (1.12 ± 0.09)], and the difference was statistically significant (all p < 0.05). According to the receiver operating characteristic curve (ROC), IASBPD ≥10 mm Hg (Sen 61.7%, Spe 88.9%), ILSBPD ≥13 mm Hg (Sen 50.6%, Spe 80.6%) and ABI ≤0.9 (Sen 53.3%, Spe 87.2%), showed significant correlation with AAD (all p < 0.001). Conclusions: Compared with healthy people, IASBPD and ILSBPD levels were higher and ABI levels were lower in patients with AAD. IASBPD ≥10 mm Hg and ILSBPD ≥13 mm Hg can be used as indicators for early screening of AAD, and IASBPD ≥10 mm Hg has better predictive value for the occurrence of AAD. In patients with typical chest pain, attention needs to be paid to measuring blood pressure in the extremities.

Pine wilt disease (PWD) has caused huge economic and environmental losses since it invaded China. Although early monitoring is an effective way to control this hazard, the monitoring window for the early stage is hard to identify, and varies in different hosts and environments. We used UAV-based multispectral images of Pinus thunbergii forest in East China to identify the change in the number of infected trees in each month of the growing season. We built classification models to detect different PWD infection stages by testing three machine learning algorithms—random forest, support vector machine, and linear discriminant analysis—and identified the best monitoring period for each infection stage (namely, green attack, early, middle, and late). From the obtained results, the early monitoring window period was determined to be in late July, whereas the monitoring window for middle and late PWD stages ranged from mid-August to early September. We also identified four important vegetation indices to monitor each infection stage. In conclusion, this study demonstrated the effectiveness of using machine learning algorithms to analyze multitemporal multispectral data to establish a window for early monitoring of pine wilt disease infestation. The results could provide a reference for future research and guidance for the control of pine wilt disease.

Mortality attributable to atherosclerosis can be reduced significantly with timely diagnosis and treatment. It is meaningful to find a proper way to diagnose and prevent the progression of atherosclerosis. Vascular cell adhesion molecule-1 (VCAM-1) expressed by endothelial cells is a prominent marker of atherosclerotic plaques. There are a number of researches on VCAM-1 based probes for targeted imaging, but rarely on a system with both targeting and drug delivery. Here, we report a novel magnetic mesoporous silicon nanoparticle that is capable of drug delivery and targeting at atherosclerosis plaque. The nanoparticles were constructed using incorporated FITC (fluorescein isothiocyanate) and VHPKQHR peptide into Fe3O4@SiO2 (FITC-VHP-Fe3O4@SiO2). The FITC-VHP-Fe3O4@SiO2 nanoparticles showed great morphological characteristics, superior targeting ability, low toxicity and good biocompatibility in vitro and in vivo. The in vivo experiments showed that FITC-VHP-Fe3O4@SiO2 is a superior contrast agent of magnetic resonance imaging (MRI) for diagnosis of atherosclerosis plaques.

Background: Recurrent implantation failure (RIF) remains a critical and challenging problem in assisted reproductive technology mainly due to impaired decidualization. The endocytic and transcytotic activity in the endometrium are crucial for decidualization. The most representative endocytic gene is the C-terminal Eps15 homology domain-containing 1 (EHD1), but whether EHD1-mediated endocytic function is responsible for embryo implantation during decidualization remains unclear. Methods: A transcriptomic analysis was performed to evaluate the differentially expressed genes between the fertile control and RIF group. The expression and location of EHD1 in endometrial tissues were further examined by IHC, qRT-PCR and Western blotting. The transduction of an EHD1 recombinant adenovirus into human endometrial stromal cells was performed to investigate relevant decidualization marker genes. Additionally, a microarray analysis following the adenovirus-mediated overexpression of EHD1 was conducted to identify EHD1-related changes in HESCs, and the potential molecular mechanisms were further confirmed through immunofluorescence and coimmunoprecipitation analyses. Findings: An RNA-seq analysis demonstrated that EHD1 expression was significantly higher in the mid-secretory endometrium of the RIF group than in that of the fertile control group. The analysis of the menstrual cycle showed that expression of EHD1 increased in the mid-proliferative phase and showed a gradual decrease in the mid-secretory and decidual phases. Furthermore, EHD1 overexpression impaired decidualization by suppressing the expression of prolactin and insulin-like growth factor binding protein-1 and the formation of the cytoskeleton. The mechanistic analysis revealed the EHD1 regulated LRP5/6 protein function through the endocytic pathway, and subsequently suppressed the Wnt4/β-catenin pathway during decidualization. In addition, a Wnt4 agonist improved an impaired decidualization process. Interpretation: Regulation of the EHD1-Wnt4 pathway might serve as a promising therapeutic strategy for improving endometrial receptivity in RIF women. Keywords: EHD1, Decidualization, RIF, Wnt4

Background: Emerging pieces of evidence demonstrated that the solute carrier family 39 (SLC39A) members are critical for the oncogenic and immune infiltrating targets in multiple types of tumors. However, the precise relationship between the SLC39A family genes and clinical prognosis as well as the pan-cancer tumor cell infiltration has not been fully elucidated.Methods: In this study, the pan-cancer expression profile, genetic mutation, prognostic effect, functional enrichment, immune infiltrating, and potential therapeutic targets of the SLC39A family members were investigated by analyzing multiple public databases such as the Oncomine, TIMER, GEPIA, cBioPortal, KM-plotter, PrognoScan, GeneMANIA, STRING, DAVID, TIMER 2.0, and CellMiner databases.Results: The expression levels of most SLC39 family genes in the tumor tissues were found to be significantly upregulated compared to the normal group. In mutation analysis, the mutation frequencies of SLC39A4 and SLC39A1 were found to be higher among all the members (6 and 4%, respectively). Moreover, the overall mutation frequency of the SLC39A family genes ranged from 0.8 to 6% pan-cancer. Also, the function of the SLC39A highly related genes was found to be enriched in functions such as zinc II ion transport across the membrane, steroid hormone biosynthesis, and chemical carcinogenesis. In immune infiltration analysis, the expression level of the SLC39A family genes was found to be notably related to the immune infiltration levels of six types of immune cells in specific types of tumors. In addition, the SLC39A family genes were significantly related to the sensitivity or resistance of 63 antitumor drugs in a variety of tumor cell lines.Conclusion: These results indicate that the SLC39 family genes are significant for determining cancer progression, immune infiltration, and drug sensitivity in multiple cancers. This study, therefore, provides novel insights into the pan-cancer potential targets of the SLC39 family genes.

The developmental pattern of the amygdala throughout childhood and adolescence has been inconsistently reported in previous neuroimaging studies. Given the relatively small size of the amygdala on full brain MRI scans, discrepancies may be partly due to methodological differences in amygdalar segmentation. To investigate the impact of volume extraction methods on amygdala volume, we compared FreeSurfer, FSL and volBrain segmentation measurements with those obtained by manual tracing. The manual tracing method, which we used as the ‘gold standard’, exhibited almost perfect intra- and inter-rater reliability. We observed systematic differences in amygdala volumes between automatic (FreeSurfer and volBrain) and manual methods. Specifically, compared with the manual tracing, FreeSurfer estimated larger amygdalae, and volBrain produced smaller amygdalae while FSL demonstrated a mixed pattern. The tracing bias was not uniform, but higher for smaller amygdalae. We further modeled amygdalar growth curves using accelerated longitudinal cohort data from the Chinese Color Nest Project (http://deepneuro.bnu.edu.cn/?p=163). Trajectory modeling and statistical assessments of the manually traced amygdalae revealed linearly increasing and parallel developmental patterns for both girls and boys, although the amygdalae of boys were larger than those of girls. Compared to these trajectories, the shapes of developmental curves were similar when using the volBrain derived volumes. FreeSurfer derived trajectories had more nonlinearities and appeared flatter. FSL derived trajectories demonstrated an inverted U shape and were significantly different from those derived from manual tracing method. The use of amygdala volumes adjusted for total gray-matter volumes, but not intracranial volumes, resolved the shape discrepancies and led to reproducible growth curves between manual tracing and the automatic methods (except FSL). Our findings revealed steady growth of the human amygdala, mirroring its functional development across the school age. Methodological improvements are warranted for current automatic tools to achieve more accurate amygdala structure at school age, calling for next generation tools.

The ongoing Chinese Color Nest Project (CCNP) was established to create normative charts for brain structure and function across the human lifespan, and link age-related changes in brain imaging measures to psychological assessments of behavior, cognition, and emotion using an accelerated longitudinal design. In the initial stage, CCNP aims to recruit 1520 healthy individuals (6–90 years), which comprises three phases: developing (devCCNP: 6–18 years, N = 480), maturing (matCCNP: 20–60 years, N = 560) and aging (ageCCNP: 60–84 years, N = 480). In this paper, we present an overview of the devCCNP, including study design, participants, data collection and preliminary findings. The devCCNP has acquired data with three repeated measurements from 2013 to 2017 in Southwest University, Chongqing, China (CCNP-SWU, N = 201). It has been accumulating baseline data since July 2018 and the second wave data since September 2020 in Chinese Academy of Sciences, Beijing, China (CCNP-CAS, N = 168). Each participant in devCCNP was followed up for 2.5 years at 1.25-year intervals. The devCCNP obtained longitudinal neuroimaging, biophysical, social, behavioral and cognitive data via MRI, parent- and self-reported questionnaires, behavioral assessments, and computer tasks. Additionally, data were collected on children’s learning, daily life and emotional states during the COVID-19 pandemic in 2020. We address data harmonization across the two sites and demonstrated its promise of characterizing the growth curves for the overall brain morphometry using multi-center longitudinal data. CCNP data will be shared via the National Science Data Bank and requests for further information on collaboration and data sharing are encouraged.

Cu(II)-modified nitrogen-rich covalent organic polymer (Cu/N-COP-1) was fabricated and employed to catalyze the cross-dehydrogenative ortho-aminomethylation of phenols. The Cu/N-COP-1 catalyst displayed excellent catalytic activity under mild conditions without any ligand. Various substituted phenols and N,N-dimethylanilines were successfully converted to the corresponding products. Moreover, the catalyst can be readily reused for at least five consecutive runs without obvious loss of catalytic activity. This can be attributed to the interaction between the nitrogen-containing group of the covalent organic polymer and Cu species, which makes Cu species steadily immobilized on the surface of polymer.

BackgroundTo predict the treatment response for axial spondyloarthritis (axSpA) with hip involvement in 1 year based on MRI and clinical indicators.MethodsA total of 77 axSpA patients with hip involvement (60 males; median age, 25 years; interquartile, 22–31 years old) were treated with a drug recommended by the Assessment of SpondyloArthritis international Society and the European League Against Rheumatism (ASAS-EULAR) management. They were prospectively enrolled according to Assessment in SpondyloArthritis international Society (ASAS) criteria. Clinical indicators, including age, gender, disease duration, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were collected at baseline and in 3 months to 1-year follow-up. Treatment response was evaluated according to ASAS response criteria. MRI indicators consisting of bone marrow edema (BME) in acetabulum and femoral head, hip effusion, fat deposition, thickened synovium, bone erosion, bone proliferation, muscle involvement, enthesitis and bony ankylosis were assessed at baseline. Spearman’s correlation analysis was utilized for indicator selection. The selected clinical and MRI indicators were integrated with previous clinical knowledge to develop multivariable logistic regression models. Receiver operator characteristic curve and area under the curve (AUC) were used to assess the performance of the constructed models.ResultsThe model combining MR indicators comprising hip effusion, BME in acetabulum and femoral head and clinical indicators consisting of disease duration, ESR and CRP yielded AUC values of 0.811 and 0.753 for the training and validation cohorts, respectively.ConclusionThe model combining MRI and clinical indicators could predict treatment response for axSpA with hip involvement in 1 year.

Performing location-based services in a secure and efficient manner that remains a huge challenge for the Internet of Vehicles with numerous privacy and security risks. However, most of the existing privacy protection schemes are based on centralized location servers, which makes them all have a common drawback of a single point of failure and leaking user privacy. The employment of anonymity and cryptography is a well-known solution to the above problem, but its expensive resource consumption and complex cryptographic operations are difficult problems to solve. Based on this, designing a distributed and privacy-secure privacy protection scheme for the Internet of Vehicles is an urgent issue for the smart city. In this paper, we propose a privacy protection scheme for the Internet of Vehicles based on privacy set intersection. Specially, using privacy set intersection and blockchain techniques, we propose two protocols, that is, a dual authentication protocol and a service recommendation protocol. The double authentication protocol not only ensures that both communicating parties are trusted users, but also ensures the reliability of their session keys; while the service recommendation protocol based on pseudorandom function and one-way hash function can well protect the location privacy of users from being leaked. Finally, we theoretically analyze the security that this scheme has, i.e., privacy security, non-repudiation, and anti-man-in-the-middle attack.

T-complex protein-1 ring complex (TRiC), also known as Chaperonin Containing T-complex protein-1 (CCT), is a multisubunit chaperonin required for the folding of nascent proteins. Mounting evidence suggests that TRiC also contributes to the development and progression of tumors, but there are limited studies on pathogenic functions in hepatocellular carcinoma (HCC). We comprehensively evaluated the expression pattern and biological functions of TRiC subunits using The Cancer Genome Atlas and The Human Protein Atlas. Expression levels of TRiC subunits TCP1, CCT2/3/4/5/6A/7/8 were significantly upregulated in HCC tissues at both transcript and protein levels, which predicted shorter overall survival (OS). Moreover, high mutation rates were found in several CCT subunits, and patients with altered CCT genes exhibited poorer clinical outcomes. Functional enrichment analysis showed that co-regulated genes were preferentially involved in ‘protein folding’ and ‘microtubule-based process’, while genes co-expressed with CCT subunits were primarily involved in ‘ribosome’ and ‘spliceosome’. Knockout of CCT5 in a HCC cell line reduced while overexpression enhanced proliferation rate, cycle transition, migration, and invasion. In conclusion, these findings suggest that subunits of the TRiC may be potential biomarkers for the diagnosis of HCC and play an important role in the occurrence and development of HCC.

Background: Coronavirus disease 2019 (COVID-19) has outbroken in China and subsequently spread worldwide since the end of 2019. Chest computed tomography (CT) plays an important role in the diagnosis of lung diseases, but its value in the diagnosis of cardiac injury remains unknown.Methods: We enrolled 241 consecutive hospitalized patients (aged 61 ± 16 years, 115 males) with laboratory-confirmed COVID-19 at Renmin Hospital of Wuhan University from January 11 to March 2, 2020. They were divided into two groups according to whether major adverse cardiovascular events (MACEs) occurred during the follow-up. The anteroposterior diameter of the left atrium (LAD), the length of the left ventricle (LV), and cardiothoracic ratio (CTR) were measured. The values of myocardial CT were also recorded.Results: Of 241 patients, 115 patients (47.7%) had adverse cardiovascular events. Compared with no MACEs, patients with MACEs were more likely to have bilateral lesions (95.7% vs. 86.5%, p = 0.01). In multivariable analysis, bronchial wall thickening would increase the odds of MACEs by 13.42 (p = 0.01). LAD + LV and CTR was the best predictor for MACEs (area under the curve = 0.88, p < 0.001) with a sensitivity of 82.6% and a specificity of 80.2%. Plasma high-sensitivity troponin I levels in patients with cardiac injury showed a moderate negative correlation with minimum CT value (R2 = −0.636, p < 0.001).Conclusions: Non-contrast chest CT can be a useful modality for detection cardiac injury and provide additional value to predict MACEs in COVID-19 patients.