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Atherosclerotic cardiovascular diseases remain the leading causes of morbidity and mortality worldwide. Cholesterol crystals in atherosclerotic plaques play an essential role in atherosclerosis progression. However, no clinical drugs have been used for removing cholesterol crystals from plaque to counter atherosclerosis. Previous studies identified the hydrophobic domain of lipid bilayer in liposomes acted as sinks for solubilizing hydrophobic cholesterol. Moreover, adjusting the composition of the lipid bilayer in liposomes can enhance its hydrophobic molecule loading capacity. Therefore, in this study, ginsenosides Rb1 (Rb1), one of main active components of ginseng which has a similar structure to cholesterol, is anchored into soy phospholipids bilayer with its hydrophobic region to prepare nano-sponge-like liposomes (Rb1-LPs), aiming to amplify the solubilization of cholesterol in lipid bilayer. For targeting delivery to atherosclerotic plaques, Annexin V (AnxV), a protein that can specifically recognize phosphatidylserine upregulated in atherosclerotic plaques, is applied to decorate the surface of Rb1-LPs by click reaction to obtain the final preparation of AnxV-Rb1-LPs. The in vitro studies showed that incorporating Rb1 into lipid bilayer remarkably increased the affinity of the lipid bilayer to free cholesterol and the solubilization of cholesterol crystals. Additionally, nano-sponge-like liposomes could efficiently reduce the accumulation of cholesterol crystals and improve cholesterol efflux, finally inhibiting inflammation and apoptosis in cholesterol-laden cells. Furthermore, AnxV-Rb1-LPs could efficiently accumulate in atherosclerotic plaques after intravenous injection, exert nano-sponge-like functions to remove intra- and extracellular cholesterol crystals, ultimately alleviating inflammation and apoptosis in atherosclerotic plaques for antiatherosclerosis. Therefore, AnxV-Rb1-LPs provide a potential strategy for removing cholesterol crystals in atherosclerotic plaques and can be further utilized in other diseases with excessive cholesterol accumulation.

Cardiovascular disease is responsible for the largest number of deaths worldwide, and atherosclerosis is the primary cause. Apoptotic cell accumulation in atherosclerotic plaques leads to necrotic core formation and plaque rupture. Emerging findings show that the progression of atherosclerosis appears to suppress the elimination of apoptotic cells. Mechanistically, the reduced edibility of apoptotic cells, insufficient phagocytic capacity of phagocytes, downregulation of bridging molecules, and dysfunction in the polarization of macrophages lead to impaired efferocytosis in atherosclerotic plaques. This review focuses on the characteristics of efferocytosis in plaques and the therapeutic strategies aimed at promoting efferocytosis in atherosclerosis, which would provide novel insights for the development of antiatherosclerotic drugs based on efferocytosis.

Chemotherapeutic resistance is a major obstacle in the control of advanced breast cancer (BCa). We have previously shown that small extracellular vesicles (sEVs) can transmit adriamycin resistance between BCa cells. Here, we describe that sEV‐mediated TGF‐β1 intercellular transfer is involved in the drug‐resistant transmission. sEVs were isolated and characterized from both sensitive and resistant cells. sEVs derived from the resistant cells were incubated with the sensitive cells and resulted in transmitting the resistant phenotype to the recipient cells. Cytokine antibody microarray revealed that most metastasis‐associated cytokines present at the high levels in sEVs from the resistant cells compared with their levels in sEVs from the sensitive cells, particularly TGF‐β1 is enriched in sEVs from the resistant cells. The sEV‐mediated TGF‐β1 intercellular transfer led to increasing Smad2 phosphorylation and improving cell survival by suppressing apoptosis and enhancing cell mobility. Furthermore, sEV‐mediated drug‐resistant transmission by delivering TGF‐β1 was validated using a zebrafish xenograft tumor model. These results elaborated that sEV‐mediated TGF‐β1 intercellular transfer contributes to adriamycin resistance in BCa., Here, we show that small extracellular vesicles (sEVs) from adriamycin‐resistant breast cancer cells could confer resistance to adriamycin‐sensitive breast cancer cells. sEVs increased cell proliferation by inhibiting apoptosis and promoted cell mobility by enhancing EMT. sEV‐derived TGF‐β1 activated the TGF‐β1/Smad2 signaling pathway in recipient cells.

Due to both of jamming and eavesdropping, active eavesdroppers can induce more serious security threats to unmanned aerial vehicle (UAV)-enabled communications. This paper considers a secure UAV communication system including both the downlink (DL) and uplink (UL) transmissions, where the confidential information is transmitted between a UAV and a ground node in the presence of an active eavesdropper. We aim to maximize the average secrecy rates of the DL and UL communications, respectively, by jointly optimizing the UAV trajectory and the UAV/ground node's transmit power control over a given flight period. Due to the non-convexity of the formulated problems, it is difficult to obtain globally optimal solutions. However, we propose efficient iterative algorithms to obtain high-quality suboptimal solutions by applying the block coordinate descent and successive convex optimization methods. Simulation results show that the joint optimization algorithms can effectively improve the secrecy rate performance for both the DL and UL communications, as compared with other baseline schemes. The proposed schemes can be considered as special cases of UAV-assisted non-orthogonal multiple access (NOMA) networks.

Regular damage detection plays an important role in timely pavement maintenance. However, the existing detection methods struggle to efficiently and accurately identify the category and contour of the damage. Therefore, this paper proposes a Road-Mask R-CNN mobile damage detection model to automatically segment and measure multiple pavement damages. First, the optimized k-means clustering algorithm is used to intelligently determine the size and ratio of the anchor. Subsequently, the traditional nonmaximum suppression (NMS) algorithm is replaced by the distance intersection over union nonmaximum suppression (DIoU-NMS) algorithm, which improves the detection accuracy of multiple damages in the same image with a mean average precision (mAP) value of 0.934. Then, a comparative experiment with U-Net, the unimproved Mask R-CNN, MSNet and the unsupervised domain adaptation network (UDA) is carried out to verify the effectiveness of the proposed model. And combined with the segmentation and measurement results, the damage is quantitatively evaluated. Moreover, a webcam damage detection system combined with a workstation and an automatic damage detection system for smartphones is developed to quickly detect multiple types of pavement damage. In addition, on- site experiments are carried out on real pavements to verify the feasibility and effectiveness of the proposed method.

The propeller wake can cause vibrations on the rudder surface, which worsen the noise and reliability. The vibration monitoring of the rudder operating in the propeller wake with fluid-structure interaction (FSI) method is still challenging. In the present study, the structural response during propeller-rudder interaction is investigated using detached eddy simulation. Three-dimensional distributions of loads, stresses, and deformations are discussed. The leading and trailing edges exhibit the strongest deformations in opposite directions, which are S-shaped. The strongest lateral deformation occurs between the tip vortex and hub vortex regions. In the tip vortex region, the dominant lateral vibrations fluctuate at the blade passing frequency (BPF) and shaft frequency (SF). However, the 75 Hz-fluctuation becomes significant at the trailing edge of the rudder. In the hub vortex region, the lateral deformation fluctuates mainly at 75 Hz except the area near the leading edge. There are weak vibrations occurring at the natural frequencies of the rudder when the natural frequencies of the rudder are much higher than the SF and BPF. However, the plate in the propeller suffers intense vibrations at the frequencies near the natural frequencies, where the natural frequencies of the plate are close to SF and BPF.

The dynamic strain monitoring system is an important means to reflect the deformation and evolution of the structure in the field of traffic and transportation visually. The exact measurement of dynamic strain measurement system is inseparable from the traceability system of high-precision strain gauge. In this paper, the resistance strain monitoring system installed on the web surface of the main girder box of Jiujiang bridge is calibrated online by using the parallel method at a similar location. By means of dynamic strain measurement system calibration sample signal feature extraction, put forward online calibration method based on neural network algorithm for dynamic strain signaler, move the noise of passive nonlinear signal under the circumstance of incentives, set up and designed a calibration method of HOABC-NN for dynamic signal analysis of on-line monitoring system. After verification, it is found that the algorithm is superior to the traditional neural network training method, the calibration precision is improved obviously, and can support the dynamic strain of bridge monitoring system online calibration

Background Studies have suggested that chronic social stress specifically downregulates endothelial tight junction protein expression in the nucleus accumbens (NAc), thus increasing blood-brain barrier (BBB) permeability and promoting depression-like behaviors. However, the molecular mechanism underlying the reduction in tight junction protein, particularly in the NAc, is largely uncharacterized. Methods We performed comparative metabolomic profiling of the nucleus accumbens, prefrontal cortex, and hippocampus of social defeat–stressed mice to identify the molecular events that mediate BBB breakdown. Results We identified the levels of cyclic adenosine monophosphate (cAMP) that were specifically reduced in the NAc and positively correlated with the degree of social avoidance. Replenishing cAMP in the NAc was sufficient to improve BBB integrity and depression-like behaviors. We further found that cAMP levels were markedly decreased in neurons of the NAc, rather than in endothelial cells, astrocytes, or microglia. RNA-sequencing data showed that adenylate cyclase 5 (Adcy5), an enzyme responsible for the synthesis of cAMP from adenosine triphosphate (ATP), was predominantly expressed in the NAc; it also resided exclusively in neurons. Endogenous modulation of cAMP synthesis in neurons through the knockdown of Adcy5 in the NAc regulated the sensitivity to social stress. Moreover, deficient neuronal cAMP production in the NAc decreased the expression of reelin, while supplementary injection of exogenous reelin into the NAc promoted BBB integrity and ameliorated depression-like behaviors. Conclusions Chronic social stress diminished cAMP synthesis in neurons, thus damaging BBB integrity in the NAc and promoting stress vulnerability. These results characterize neuron-produced cAMP in the NAc as a biological mechanism of neurovascular pathology in social stress.

Background Some studies have showed that the reference equations for the walking distance derived mainly from healthy, normal-weight people are not suitable for obese subjects. The main purpose of this study is to establish reference equations for the 6MWD in Chinese obese subjects. Methods In the study, a total of 272 obese subjects underwent American Thoracic Society (ATS) protocolized six-minute walk testing (6MWT), and the longer walking distance was used for further analysis. The reference equations of the 6MWD were developed by stepwise multiple regression analysis. The established equations for the 6MWD were compared to existing prediction equations. Results The mean 6MWD for the cohort was 523±56 m. We found that the reliability of two 6MWTs was good. Age and BMI were identified as independent factors and explained 31% and 27% of the variance in the 6MWD for the male and female groups, respectively. These reference equations reported in previous studies cannot accurately predict the 6MWD in our subjects. Conclusion The study was the first to describe the 6MWD in Chinese obese subjects and to propose predictive equations. These established equations can contribute to improving the assessment of Chinese obese patients with diseases that affect their exercise capacity.

Background Studies have shown that the reference equations for the six-minute walking distance (6MWD), which were mainly derived from healthy, normal-weight people, are not suitable for individuals with obesity. The main purpose of this study was to establish reference equations for the 6MWD in obese Chinese subjects. Methods In our study, a total of 214 individuals with obesity performed the six-minute walking tests (6MWTs) according to the American thoracic society (ATS) guidelines, and the longer 6MWD was used for further analysis. The reference equations for the 6MWD were developed using stepwise multiple regression analysis. The newly established equations for the 6MWD were compared to the existing prediction equations. Results The mean 6MWD for the cohort was 523 ± 56 m. We found that the reliability of two 6MWTs was good. Age and BMI were identified as independent factors, and explained 31% and 27% of the variance in the 6MWD for the male and female participants, respectively. Thus, the reference equations reported in the previous studies did not accurately predict the 6MWD in our subjects. Conclusion Our study was the first to describe the 6MWD in obese Chinese subjects and to propose new predictive equations. These established equations can improve the assessment of the health of obese Chinese patients whose exercise capacity is affected by the disease. Level of evidence III, Cohort study.

Protein kinase G type II (PKG II) is a serine/threonine-protein kinase that was originally isolated from the small intestinal mucosa with primary functions in the secretion of small intestinal mucosal cells, secretion of renin and aldosterone, and chondrocyte activities. Recent studies have shown that PKG II exerts anti-tumor effects, while a previous study by our group confirmed that PKG II inhibited the proliferation and migration of cancer cells. Interestingly, PKG II, which was typically bound to the intracellular side of the membrane, was detected in the serum and cell culture medium as a diagnostic biomarker of tumor growth. Thus, the aim of the present study was to elucidate the function and the targets of PKG II, and the mechanism underlying the secretion of this kinase.Construction of peptides and plasmids, RNA interference, Immunoelectron microscopy, Co-immunoprecipitation, N-glycosylation assay and Isolation of the Golgi apparatus were applied to investigate the secretory mechanism, and the targets and function of PKG II.PKG II was secreted by enterochromaffin (EC) cells, which were components of the endocrine system in the gastrointestinal tract. Myristoylation of glycine 2 and the N-terminal sequence, especially the amino acids 3-30, acted as a signal peptide to induce the secretion of PKG II via the conventional protein secretory pathway. Moreover, recombinant PKG II inhibited the epidermal growth factor (EGF)-induced activation of the EGF receptor via phosphorylating the T406 of the extracellular domain and blocked EGF-triggered proliferation of various cancer cells.These results revealed a correlation between the endocrine system and the secretion of protein kinase, suggesting a novel protein secretory pathway. The resuls also indicated that secreted PKG II was a potential diagnostic biomarker and an inhibitor of tumor.

Background The aim of this study is to explore whether or to what extent the metabolic syndrome (METs) and its components was associated with poor outcome in acute type A aortic dissection patients (ATAAD) after surgery. Methods This study involved 353 ATAAD patients undergo surgery. Data on demographic and clinical characteristics were collected. Subgroup analysis, mixed models regression analysis, score systems and receiver-operating characteristic curves (ROC) analysis were done. Results Overall, 353 inpatients were assigned to the poor outcome group (n = 69) and control group (n = 284) with or without METs. Compared to control group, the incidence of METs was higher in poor outcome group. Poor outcome were present in 0%, 4.4%, 12.3%, 47.6%, 71.4% and 100% of the six groups, who met the diagnostic criteria of MetS 0, 1, 2, 3, 4 and 5 times. For multivariable logistic regression, quartiles of BMI remained the risk factors of poor outcome after adjustment other risk factors. After adjustment for potential confounding factors, METs was an independent risk factors in several models. Assigning a score of one for each components, the AUC were 0.877 (95%CI: 0.823-0.923) in all patients, 0.864 (95%CI: 0.7945-0.935) in METs and 0.700 (95%CI: 0.567-0.833) in non-METs by Receiver-operating characteristic. Conclusions METs, especially for BMI, confers greater risk for poor outcome in ATAAD after surgery during 3-year follow up.

Background and objective While the six-minute walk test (6MWT) is often used to assess exercise capacity, the less well-known two-minute walk test (2MWT) is more feasible for some patients. In previous studies, we developed reference equations for the two-minute walk distance (2MWD) for healthy Chinese adults. However, our study did not recruit people with obesity, and the reference equations did not apply to participants with a body mass index (BMI) > 30 kg/m2. The main objective of this study was to establish reference equations for the 2MWD among middle-aged and elderly Chinese individuals with obesity. Methods A total of 295 individuals were recruited. The participants underwent two 2MWTs, with the longer of the two 2MWDs used for further analyses. The reference equations for the 2MWD were developed using stepwise multiple regression analysis. The newly established equations for the 2MWD were then compared with the existing equations. Results The mean 2MWD of the participants was 176±20 m. Age and BMI were identified as independent factors that influenced the 2MWD and explained 28% and 32% of the variance in walking distance for the male and female groups, respectively. The reference equations for the 2MWD were as follows: Male:2MWD(m)=443.058−[age(yr)x6.782]+[BMI(kg/m2)x0.847];r2=0.283Female:2MWD(m)=300.160−[age(yr)x0.841]−[BMI(kg/m2)x2.541];r2=0.315 Conclusion This study resulted in the development of reference equations for predicting 2MWD among middle-aged and elderly Chinese people with obesity. These equations will be a clinically valuable tool for evaluating functional capacity, determining prognoses and monitoring treatment in middle-aged and elderly Chinese people with obesity.

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SARS-CoV-2 has been spreading around the world for the past year. Recently, several variants such as B.1.1.7 (alpha), B.1.351 (beta), and P.1 (gamma), which share a key mutation N501Y on the receptor-binding domain (RBD), appear to be more infectious to humans. To understand the underlying mechanism, we used a cell surface-binding assay, a kinetics study, a single-molecule technique, and a computational method to investigate the interaction between these RBD (mutations) and ACE2. Remarkably, RBD with the N501Y mutation exhibited a considerably stronger interaction, with a faster association rate and a slower dissociation rate. Atomic force microscopy (AFM)-based single-molecule force microscopy (SMFS) consistently quantified the interaction strength of RBD with the mutation as having increased binding probability and requiring increased unbinding force. Molecular dynamics simulations of RBD–ACE2 complexes indicated that the N501Y mutation introduced additional π-π and π-cation interactions that could explain the changes observed by force microscopy. Taken together, these results suggest that the reinforced RBD–ACE2 interaction that results from the N501Y mutation in the RBD should play an essential role in the higher rate of transmission of SARS-CoV-2 variants, and that future mutations in the RBD of the virus should be under surveillance.

During sperm cryopreservation, the most significant phenotype of cryodamage is the decrease in sperm motility. Several proteomics studies have already been performed to search for key regulators at the protein level. However, sperm functions are known to be highly regulated by phosphorylation signaling. Here, we constructed a quantitative phosphoproteome to investigate the expression change of phosphorylated sites during sperm cryopreservation. A total of 3107 phosphorylated sites are identified and 848 of them are found to be significantly differentially expressed (DE). Bioinformatics analysis showed that the corresponding genes of these regulated sites are highly associated with sperm motility, providing a connection between the molecular basis and the phenotype of cryodamage. We then performed kinase enrichment analysis and successfully identified glycogen synthase kinase-3α (GSK3A) as the key kinase that may play an important role in the regulation of sperm motility. We further constructed a GSK3A centric network that could help us better understand the molecular mechanism of cryodamage in sperm motility. Finally, we also verified that GSK3A was abnormally activated during this process. The presented phosphoproteome and functional associations provide abundant research resources for us to learn the regulation of sperm functions, as well as to optimize the cryoprotectant for sperm cryopreservation.

Purpose Electrospun scaffolds have been studied extensively for their potential use in bone tissue engineering. However, their hydrophobicity and relatively low matrix stiffness constrain their osteoinduction capacities. In the present study, we studied polymer electrospun scaffolds coated with hydrophilic hematite nanoparticles (αFeNPs) constructed using layer-by-layer (LbL) assembly to construct a bioactive interface between the scaffolds and cells, to improve the osteoinduction capacities of the scaffolds. Materials and methods The morphology of the αFeNPs was assessed. Surface properties of the scaffolds were tested by X-ray photoelectron spectroscopy (XPS), surface water contact angle, and in vitro protein adsorption test. The stiffness of the coating was tested using an atomic force microscope (AFM). In vitro cell assays were performed using rat adipose-derived stem cells (ADSCs). Results Morphology characterizations showed that αFeNPs assembled on the surface of the scaffold, where the nano assemblies improved hydrophilicity and increased surface roughness, with increased surface stiffness. Enhanced initial ADSC cell spread was found in the nano assembled groups. Significant enhancements in osteogenic differentiation, represented by enhanced alkaline phosphatase (ALP) activities, elevated expression of osteogenic marker genes, and increased mineral synthesis by the seeded ADSCs, were detected. The influencing factors were attributed to the better hydrophilicity, rougher surface topography, and harder interface stiffness. In addition, the presence of nanoparticles was believed to provide better cell adhesion sites. Conclusion The results suggested that the construction of a bioactive interface by LbL assembly using αFeNPs on traditional scaffolds should be a promising method for bone tissue engineering.