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IntroductionTriazole antifungal agents are widely used to treat and prevent systemic mycoses. With wide clinical use, the number of reported adverse events has gradually increased. The aim of this study was to analyze the cardiac disorders associated with TAAs (fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole) based on data from the US Food and Drug Administration Adverse Event Reporting System FDA Adverse Event Reporting System.MethodsData were extracted from the FAERS database between the first quarter of 2004 and third quarter of 2022. The clinical characteristics in TAA-associated cardiac AE reports were analyzed. Disproportionality analysis was performed to evaluate the potential association between AEs and TAAs using the reporting odds ratio (ROR) and proportional reporting ratio (PRR).ResultsAmong 10,178,522 AE reports, 1719 reports were TAA-associated cardiac AEs as primary suspect drug. Most reports were related to fluconazole (38.34%), voriconazole (28.56%) and itraconazole (26.76%). Itraconazole (N = 195, 42.39%) and isavuconazole (N = 2, 14.29%) had fewer serious outcome events than three other drugs including fluconazole, voriconazole, and posaconazole. 13, 11, 26, 5 and 1 signals were detected for fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole, respectively. The number of new signals unrecorded in the drug label was 9, 2, 13, 2 and 0 for fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole, respectively.ConclusionIsavuconazole might be the safest of the five TAAs for cardiac AEs. TAA-associated cardiac disorders may result in serious adverse outcomes. Therefore, in addition to AEs on the drug label, we should pay attention to new AEs unrecorded on the drug label during the clinical use of TAAs.

Magnesium (Mg) alloys have great potential as biodegradable materials for medical device. However, their susceptibility to corrosion poses a significant challenge for practical applications. In this study, the poly(trimethylene carbonate)-dimethacrylate (PTMC-dMA) was employed as a coating material for ZE21B magnesium alloys. Upon UV irradiation, the PTMC-dMA macromer undergoes cross-linking to form a uniform PTMC coating with a thickness of approximately 5 μm, effectively protecting the magnesium alloy. The corrosion resistance in simulated body fluid (SBF) was evaluated through immersion testing, which showed minimal hydrogen generation (0.16 mL/cm2) during the initial 24-h period and slight corrosion observed on the PTMC-coated magnesium alloy surface after continuous immersion for 21 days. The silane coupling agent significantly enhanced the adhesive performance between the polymer and alloy. Micro-scratch tests revealed adhesion forces of 3.79 N and 5.75 N for coatings without and with the silane agent, respectively. Electrochemical tests also demonstrated the efficacy of silane treatment, showing corrosion currents of 2.100 × 108 A/cm2 for silane-treated samples compared 6.263 × 107 A/cm2 for untreated ones. Given its exceptional tensile and protective properties, this coated material is ideal for intricate bioresorbable applications, like endovascular bioresorbable stents.

Abstract Extracting robust feature representation is one of the key challenges for person re‐identification (ReID) task. Although convolution neural network (CNN)‐based methods have achieved great success, they still cannot handle the part occlusion and misalignment caused by limited receptive field. Recently, pure transformer models have shown its power in the person ReID task. However, current transformer models adopt patches of equal‐scale as input, and cannot solve the problem of cross‐scale interaction properly. To overcome this problem, an adaptive cross‐scale transformer from a perspective of the graph signal, named ACSFormer, is proposed. Specifically, the self‐attention module is first treated as an undirected fully connected graph. And then, “node variation” is introduced as an indicator to adaptively merge neighbourhood tokens. To the best of the authors’ knowledge, their ACSFormer is the first work to attempt to combine pure transformers and graph signal processing in the field of person ReID. Extensive evaluations are conducted on three person ReID datasets to validate the performance of ACSFormer. Experiments demonstrate that this ACSFormer performs on par with state‐of‐the‐art CNN‐based methods and consistently improves transformer‐based baseline, for example, surpassing ViT‐baseline by 2.5%, 2.7% and 4.8% mAP on Market1501, DukeMTMC‐reID and MSMT17, respectively.

Background: The incidence of postoperative acute kidney injury (AKI) is high due to insufficient perfusion in patients with heart failure. Heart failure patients with preserved ejection fraction (HFpEF) have strong heterogeneity, which can obtain more accurate results. There are few studies for predicting AKI after coronary artery bypass grafting (CABG) in HFpEF patients especially using machine learning methodology. Methods: Patients were recruited in this study from 2018 to 2022. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The machine learning methods adopted included logistic regression, random forest (RF), extreme gradient boosting (XGBoost), gaussian naive bayes (GNB), and light gradient boosting machine (LGBM). We used the receiver operating characteristic curve (ROC) to evaluate the performance of these models. The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were utilized to compare the prediction model. Results: In our study, 417 (23.6%) patients developed AKI. Among the five models, random forest was the best predictor of AKI. The area under curve (AUC) value was 0.834 (95% confidence interval (CI) 0.80–0.86). The IDI and NRI was also better than the other models. Ejection fraction (EF), estimated glomerular filtration rate (eGFR), age, albumin (Alb), uric acid (UA), lactate dehydrogenase (LDH) were also significant risk factors in the random forest model. Conclusions: EF, eGFR, age, Alb, UA, LDH are independent risk factors for AKI in HFpEF patients after CABG using the random forest model. EF, eGFR, and Alb positively correlated with age; UA and LDH had a negative correlation. The application of machine learning can better predict the occurrence of AKI after CABG and may help to improve the prognosis of HFpEF patients.

Introduction: This researcher focused at the evodiamine and dehydroevodiamine tissue distribution and structure-pharmacokinetics (PK) relationship after intravenous injection in mice.Methods: Using a transmembrane transport experiment, the permeability of evodiamine and dehydroevodiamine on Caco-2 cells was evaluated. The tissue distribution and pharmacokinetics (PK) of evodiamine and dehydroevodiamine in mice were studied. To comprehend the connection between structure and tissue distribution, physicochemical property evaluations and molecular electrostatic potential (MEP) calculations were performed.Results: Dehydroevodiamine’s Papp values in vitro were 10−5 cm/s, whereas evodiamine’s were 10−6 cm/s. At a dose of 5 mg/kg, the brain concentration of dehydroevodiamine was 6.44 times more than that of evodiamine. By MEP or physicochemical measures, the permeability difference between evodiamine and dehydroevodiamine is unaffected. The dihedral angle of the stereo-structure appears to be the main cause of the difference in tissue distribution ability between evodiamine and dehydroevodiamine.Discussion: Dehydroevodiamine has a dihedral angle of 3.71° compared to 82.34° for evodiamine. Dehydroevodiamine can more easily pass through the phospholipid bilayer than evodiamine because it has a more planar stereo-structure. Dehydroevodiamine is therefore more likely to pass cross the blood-brain barrier and enter the brain in a tissue-specific manner.

ObjectivesAims to compare the contemporary and long-term outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in coronary artery disease (CAD) patients with advanced chronic kidney disease (CKD).Methods823 CAD patients with advanced CKD (eGFR

Abstract Background Chronic migraine places a disabling burden on patients, which is extensively modeled by the nitroglycerin (NTG)-treated animal model. Although the NF-κB pathway is involved in an increase in CGRP levels and activation of the trigeminal system in the NTG model, the relationship between NTG and neuroinflammation remains unclear. This study aimed to optimize a chronic NTG rat model with hyperalgesia and the ethological capacity for estimating migraine therapies and to further explore the underlying mechanism of NTG-induced migraine. Methods Rats were administered different doses of NTG s.c. daily or every 2 d; 30 min and 2 h later, the mechanical threshold was tested. After 9 d, the rats were injected with EB or Cy5.5 for the permeability assay. The other animals were sacrificed, and then, brainstem and caudal trigeminal ganglion were removed to test CGRP, c-Fos and NOS activity; Cytokines levels in the tissue and serum were measured by ELISA; and NF-κB pathway and blood–brain barrier (BBB)-related indicators were analyzed using western blotting. Immunohistochemistry was performed to observe microglial polarization and IL-17A+ T cell migration in the medulla oblongata. Results NTG (10 mg/kg, s.c., every 2 d for a total of 5 injections) was the optimal condition, resulting in progressive hyperalgesia and migraine behavior. TNC neuroinflammation with increases in cytokines, CGRP and c-Fos and activation of the NF-κB pathway was observed, and these changes were alleviated by ibuprofen. Furthermore, NTG administration increased BBB permeability by altering the levels functional proteins (RAGE, LRP1, AQP4 and MFSD2A) and structural proteins (ZO-1, Occludin and VE-cadherin-2) to increase peripheral IL-17A permeation into the medulla oblongata, activating microglia and neuroinflammation, and eventually causing hyperalgesia and migraine attack. Conclusions This study confirmed that NTG (10 mg/kg, s.c., every 2 d for a total of 5 injections) was the optimal condition to provoke migraine, resulting in mechanical hyperalgesia and observable migraine-like behavior. Furthermore, IL-17A crossed the blood–brain barrier into the medulla oblongata, triggering TNC activation through microglia-mediated neuroinflammation. This process was a novel mechanism in NTG-induced chronic migraine, suggesting that IL-17A might be a novel target in the treatment of migraine.

Abstract Schisandra chinensis (S. chinensis) extract powder is an important intermediate for the preparation of many prepared medicines and health products. The physicochemical properties of S. chinensis extract powder have been found to vary tremendously and this has been attributed to the long drying time in the traditional drying method. In this study, S. chinensis specimens were authenticated as the dry fruit of S. chinensis (Turcz.) Baill. S. chinensis were extracted twice with 8 L kg−1 (liquid to solid ratio) distilled water. The extracts were mixed and concentrated under reduced pressure to 1.24 g cm−3. Ultrasound‐assisted vacuum drying (UAVD) was employed as a new approach to improve the efficiency in drying S. chinensis extract powder and produce a higher quality product. The effects of drying temperature (70, 80, 90°C), ultrasonic power (40, 120, 200 W), and ultrasonic application time (4, 12, 20 min every 20 min) on the kinetics and quality of S. chinensis extract were investigated and compared with the conventional vacuum drying (CVD). It was shown that, with the increase in drying temperature, ultrasonic power, and time of UAVD, the drying time for S. chinensis extract to reach the equilibrium moisture decreased. The drying time was reduced by more than 25% when utilizing UAVD compared to the CVD method. The effective moisture diffusivity (Deff) values for CVD and UAVD were 3.48 × 10–9 m2·s–1 and 7.41 × 10–9 m2 s–1, respectively, at the drying temperature of 80°C, indicating an increase of 112.93%. It was also found that a Weibull distribution model was suitable for predicting the moisture content of S. chinensis extract (R2 > 0.95). Furthermore, the content of Schisandrol A in the extracts obtained from UAVD was 12.79% higher than that obtained using CVD at 90°C. This demonstrates that UAVD is an efficient drying technique for S. chinensis extract.

Microglial cell activation and neuroinflammation after intracerebral hemorrhage (ICH) lead to secondary brain damage. Ubiquitin-specific protease 11 (USP11) has been correlated with ICH-induced neuron apoptosis. This study aims to explore the molecular mechanism of USP11 regulating neuroinflammation in ICH. First, an ICH rat model was developed by intracranial administration of collagenase. Silencing USP11 was found to alleviate nerve injury in rats with ICH-like symptoms. Then, through loss- and gain-of-function assays, USP11 knockdown was revealed to alleviate ICH-induced symptoms, corresponding to reduced modified neurological severity scores (mNSS) value, brain water content, blood-brain barrier permeability, neuron apoptosis, microglial cell activation, neutrophil infiltration, and inflammatory factor secretion. It was subsequently shown in microglial cells that USP11 stabilized p53 by deubiquitination and p53 targeted the Kruppel-like factor 2 (KLF2) promoter to repress KLF2 transcription, thereby activating the nuclear factor κB (NF-κB) pathway. Further, rescue experiments were conducted in vivo to validate the function of the USP11/p53/KLF2/NF-κB axis in ICH-induced inflammation, which confirmed that USP11 silencing blocked the release of pro-inflammatory cytokines following ICH by downregulating p53, thus protecting against neurological impairment. Hence silencing USP11 may be a novel anti-inflammatory method for ICH treatment.

ObjectivesTo compare the long-term outcomes of coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) for coronary artery disease (CAD) patients with chronic kidney disease (CKD).MethodsCoronary artery disease patients with decreased kidney function (estimated glomerular filtration rate

There are relatively few articles on the relationship between serum albumin and acute kidney injury (AKI). Therefore, the objective of this research was to study the relationship between serum albumin and AKI in patients who were undergoing surgery for acute type A aortic dissection. Methods: We retrospectively collected data from 624 patients attending a Chinese hospital between January 2015 and June 2017. The target independent variable was serum albumin measured before surgery after hospital admission, and the dependent variable was AKI, defined in accordance with the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Results: The mean age of these 624 selected patients was 48.5 ± 11.1 years, and almost 73.7% were male. A nonlinear association was detected between serum albumin and AKI; the turning point was 32 g/L. The risk of AKI decreased gradually as the serum albumin level increased up to 32 g/L (adjusted OR = 0.87; 95% CI 0.82–0.92; p < 0.001). When the serum albumin level exceeded 32 g/L, the level of serum albumin was not associated with the risk of AKI (OR = 1.01, 95% CI 0.94–1.08; p = 0.769). Conclusions: The findings suggest that preoperative serum albumin below 32 g/L was an independent risk factor for AKI in patients undergoing surgery for acute type A aortic dissection. Trial registration: A retrospective cohort study.

The bar-headed goose (Anser indicus) has two black spots on its head. It is considered an important bird in China. It breeds in plateau lakes, especially saltwater lakes, and swamp areas. However, the intestinal flora of wild bar-headed geese in the Tibet Autonomous Region is currently not known. In this study, 16S rDNA sequencing was performed on the intestinal microbes of wild bar-headed geese. A total of 513,505 reads of raw data were obtained, and the results analyzed the average number of 128,376 ± 2,392 reads per sample. The microbiota of all samples consists of 10 main bacterial phyla, including Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, Cyanobacteria, Patescibacteria, Deferribacteres, Planctomy-cetes, Fusobacteria, and Tenericutes. The results indicated that Firmicutes (67.34%) was the predominant phylum, followed by Proteobacteria (29.03%) and Cyanobacteria (1.97%). In our research, we identified the intestinal flora of the wild bar-headed goose, which provides valuable information for further research on the gene function of the bar-headed goose and the intestinal flora of wild animals. These findings are also useful and valuable for genetic and high-altitude research in the Tibet Autonomous Region.

Hepatotoxicity brought on by acetaminophen (APAP) is significantly impacted by mitochondrial dysfunction. Mitophagy, particularly PINK1-mediated mitophagy, maintains the stability of cell function by eliminating damaged mitochondria. One of the most prevalent dietary polyphenols, chlorogenic acid (CGA), has been shown to have hepatoprotective properties. It is yet unknown, nevertheless, whether its defense against hepatocyte apoptosis involves triggering PINK1-mediated mitophagy. In vitro and in vivo models of APAP-induced hepatotoxicity were established to observe CGA’s effect and mechanism in preventing hepatotoxicity in the present study. Serum aminotransferase levels, mouse liver histology, and the survival rate of HepG2 cells and mice were also assessed. The outcomes showed that CGA could reduce the activities of serum enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH), and alleviate liver injury in mice. It could also significantly increase the cell viability of HepG2 cells and the 24-h survival rate of mice. TUNEL labeling and Western blotting were used to identify the hepatocyte apoptosis level. According to data, CGA could significantly reduce liver cell apoptosis in vivo. Additionally, Tom20 and LC3II colocalization in mitochondria may be facilitated by CGA. CGA considerably increased the levels of genes and proteins associated with mitophagy (PINK1, Parkin, LC3II/LC3I), while considerably decreasing the levels of p62 and Tom20, suggesting that it might activate PINK1/Parkin-mediated mitophagy in APAP-induced liver damage. Additionally, the protection of CGA was reduced when PINK1 was knocked down by siPINK1 in HepG2 cells, and it did not upregulate mitophagy-related proteins (PINK1, Parkin, LC3II/LC3I). In conclusion, our findings revealed that long-term consumption of food-derived CGA could prevent APAP hepatotoxicity via increasing PINK1-dependent mitophagy and inhibiting hepatocyte apoptosis.

Porcine parvovirus (PPV) disease is a worldwide spread animal disease with high infection rate and serious impact on meat economy causing significant losses in livestock production. The purpose of this paper is to investigate and analyze the regional seroprevalence of PPV in Tibetan pigs in Tibet and evaluate risk factors related to the disease. A total of 356 serum samples of Tibetan pigs were collected from four counties and districts in Tibet, and anti-PPV antibodies were detected by using a commercial competitive ELISA. Our results show a seroprevalence of 91.01% (324 serum samples were found to be positive for anti-PPV antibodies). The positive rate among different district was 100%, 96.55%, 93.68% and 72.83%, respectively in the Mainling County, in Bayi district, Nang County and Bomê County. We found significant differences between different age and gender groups; particularly female animals show a seroprevalence of 96.03% while the males only 83.46%. From the perspective of the growth stage, our results indicate that subadults show a seroprevalence significative higher than other age groups (100%). This study describes for the first time the PPV seroprevalence among Tibetan pigs characterizing risk factors involved in its transmission and providing information to be taken into account for eventual surveillance or eradication plans.

Dempster–Shafer (D–S) evidence theory is more and more extensively applied in multi-sensor data fusion. However, it is still an open issue that how to effectively combine highly conflicting evidence in D–S evidence theory. In this article, a novel divergence measure, called pignistic probability transformation divergence, is proposed to measure the difference between evidences. The proposed pignistic probability transformation divergence can reflect the interaction between single-element and multi-element subsets by introducing the pignistic probability transformation, and satisfies the properties of boundedness, non-degeneracy, and symmetry. Moreover, the pignistic probability transformation divergence can degenerate as Jensen–Shannon divergence when mass function and the probability distribution are consistent. Based on the pignistic probability transformation divergence, a new multi-sensor data fusion method is presented. The proposed method takes advantage of pignistic probability transformation divergence to measure the discrepancy between evidences in order to obtain the credibility weights, and belief entropy to measure the uncertainty of the evidences in order to obtain the information volume weights, which can fully mine the potential information between evidences. Then, the credibility weights and the information volume weights are integrated to generate an appropriate weighted average evidence before using Dempster’s combination rule. The results of two application cases illustrate that the proposed method outperforms other related methods for combining highly conflicting evidences.

Major depressive disorder (MDD) is a common and complex mental disorder, that adversely impacts an individual’s quality of life, but its diagnosis and treatment are not accurately executed and a symptom-based approach is utilized in most cases, due to the lack of precise knowledge regarding the pathophysiology. So far, the first-line treatments are still based on monoamine neurotransmitters. Even though there is a lot of progress in this field, the mechanisms seem to get more and more confusing, and the treatment is also getting more and more controversial. In this study, we try to review the broad advances of monoamine neurotransmitters in the field of MDD, and update its effects in many advanced neuroscience studies. We still propose the monoamine hypothesis but paid special attention to their effects on the new pathways for MDD, such as inflammation, oxidative stress, neurotrophins, and neurogenesis, especially in the glial cells, which have recently been found to play an important role in many neurodegenerative disorders, including MDD. In addition, we will extend the monoamine hypothesis to basic emotions; as suggested in our previous reports, the three monoamine neurotransmitters play different roles in emotions: dopamine—joy, norepinephrine—fear (anger), serotonins—disgust (sadness). Above all, this paper tries to give a full picture of the relationship between the MDD and the monoamine neurotransmitters such as DA, NE, and 5-HT, as well as their contributions to the Three Primary Color Model of Basic Emotions (joy, fear, and disgust). This is done by explaining the contribution of the monoamine from many sides for MDD, such the digestive tract, astrocytes, microglial, and others, and very briefly addressing the potential of monoamine neurotransmitters as a therapeutic approach for MDD patients and also the reasons for its limited clinical efficacy, side effects, and delayed onset of action. We hope this review might offer new pharmacological management of MDD.

The negation of probability distribution is a new perspective from which to obtain information. Dempster–Shafer (D–S) evidence theory, as an extension of possibility theory, is widely used in decision-making-level fusion. However, how to reasonably construct the negation of basic probability assignment (BPA) in D–S evidence theory is an open issue. This paper proposes a new negation of BPA, logarithmic negation. It solves the shortcoming of Yin’s negation that maximal entropy cannot be obtained when there are only two focal elements in the BPA. At the same time, the logarithmic negation of BPA inherits the good properties of the negation of probability, such as order reversal, involution, convergence, degeneration, and maximal entropy. Logarithmic negation degenerates into Gao’s negation when the values of the elements all approach 0. In addition, the data fusion method based on logarithmic negation has a higher belief value of the correct target in target recognition application.

Styrax, one of the most famous folk medicines, is a necessary medicine in formulas to help other drugs reach the focal zone and maximize the effectiveness, the mechanism that promotes absorption is not clear yet. This study was carried out to investigate the absorption-promoting effects and the mechanism of benzaldehyde, a key active compound of styrax, on the diffusion rates of drugs with different oral bioavailability. Caco-2 transport experiments were used to investigate the transport rate. Molecular Dynamics Simulation analysis and fluorescence-anisotropy measurements were used to explore the underlying mechanism of absorption-promoting. Validation test in vivo was carried out to reveal the absorption-promoting effects of benzaldehyde on high hydrophilicity drugs. Our data indicated that benzaldehyde(50 μM) elevated the cumulative quantity of passively diffusion drugs with high hydrophilicity such as acyclovir and hydrochlorothiazide. MD and membrane fluidity data explained that benzaldehyde can loosen the structure of the lipid bilayer. The validation tests showed that benzaldehyde (140 mg/kg) remarkably increased the Cmax and AUC0-6 of acyclovir and hydrochlorothiazide in vivo. These present studies suggested that benzaldehyde can promote the absorption of drugs with a lower oral bioavailability through disturbing the integrity of lipid bilayer enhanced membrane permeability.

Abstract Background Thoracic aortic surgery and cardiopulmonary bypass are both associated with development of postoperative acute kidney injury. In this study, we undertook to investigate the relationship between cardiopulmonary bypass time and postoperative acute kidney injury in patients undergoing thoracic aortic surgery for acute DeBakey Type I aortic dissection. Methods All patients receiving thoracic aortic surgery for acute DeBakey Type I aortic dissection in Beijing Anzhen hospital from December 2015 to April 2017 were included. Cardiopulmonary bypass time was recorded during surgery. Acute kidney injury was defined based on the Kidney Disease Improving Global Outcomes criteria. A total of 115 consecutive patients were eventually analyzed. Results The overall incidence of acute kidney injury was 53.0% (n = 61). The average age was 47.8 ± 10.7 years; 74.8% were male. Mean cardiopulmonary bypass time was 211 ± 56 min. In-hospital mortality was 7.8%. Multivariate logistic regression revealed that cardiopulmonary bypass time was independently associated with the occurrence of postoperative acute kidney injury after adjust confounding factors (odds ratio = 1.171; 95% confidence interval: 1.002–1.368; P = 0.047). Conclusions Cardiopulmonary bypass time is independently associated with an increased hazard of acute kidney injury after thoracic aortic surgery for acute DeBakey Type I aortic dissection. Further understanding of the mechanism of this association is crucial to the design of preventative strategies.

Abstract Background The purpose of this study is to identify the risk factors for postoperative severe hypoxemia after surgery for acute type A aortic dissection. Methods This was a single-center retrospective study including 112 consecutive patients undergoing urgent aortic arch surgery for acute type A aortic dissection between December 2016 and April 2017 at Beijing Anzhen Hospital. Results Multivariate logistic regression analysis identified female (OR, 12.978; 95% CI, 3.332 to 50.546; p

Abstract Background Mesenchymal stem cells (MSCs) have been extensively explored as a promising therapeutic agent in the field of bone tissue engineering due to their osteogenic differentiation ability. In this study, the osteogenic differential ability and the effect of fibronectin and laminin on the osteogenic differentiation in four types of MSCs derived from placental tissue are compared to determine the ideal source for bone reconstruction tissue engineering. Results The present study examines the osteogenic differentiation levels of four types of MSCs using alizarin red staining and quantifies the calcium levels and alkaline phosphatase (ALP) activity. In addition, this study examines the osteoblast differentiation protein markers osterix, collagen I, osteopontin, and osteocalcin using a Western blot assay. qPCR and EdU labeling assays were employed to identify the kinetics of osteogenic differentiation. Calcium deposit levels, ALP activity, and osteopontin and osteocalcin concentrations were determined to confirm the role of Extracellular matrix (ECM) components role on the osteogenic differentiation of MSCs. The data demonstrated that MSCs isolated from different layers of placenta had different potentials to differentiate into osteogenic cells. Importantly, AM-MSCs and UC-MSCs differentiated into the osteoblast stage more efficiently and quickly than CM-MSCs and DC-MSCs, which was associated with a decrease in their proliferation ability. Among the different types of MSCs, AM-MSCs and UC-MSCs had a higher osteogenic differentiation potential induced by fibronectin due to enhanced phosphorylation during the Akt and ERK pathways. Conclusions Taken together, these results indicate that AM-MSCs and UC-MSCs possess a higher osteogenic potential, and fibronectin can robustly enhance the osteogenic potential of the Akt and ERK pathways.

The wide diffusion of information in social networks can be exploited to solve searching-for-a-target (SFT) problems including those of missing individuals. Incentive mechanisms that promote active individual participation can be designed to favor a clear propagation direction to help efficiently find a target. However, the existing incentive research rarely focuses on a clear propagation direction based on a specific goal. Thus, we propose an effective contribution-driven information propagation incentive mechanism (IPIM) that exploits ego networks to solve the SFT problem. First, we use an all-pay auction-inspired model to determine the propagation of alters in each ego network. We then propose a novel algorithm, the node propagation utility, based on effective contributions, to focus the propagation toward the target rather than searching indiscriminately and inefficiently. The theoretical analyses and simulation results indicate that IPIM guarantees the truthfulness, individual rationality, and budget feasibility. The simulations are conducted based on real and public social datasets. The IPIM shows increased efficiencies of 951.18 % of success rate, of 215.65 % in propagation hops, and of 514.41 % in participation scale, compared with a typical incentive mechanism. In conclusion, the IPIM shows significant value in the potential application in SFT.

Background and Aims: Epicardial adipose tissue, exosomes, and miRNAs have important activities in atherosclerosis. The purpose of this study was to establish miRNA expression profiles of epicardial adipose tissue-derived exosomes in patients with coronary atherosclerosis. Methods: Biopsies of epicardial adipose tissue were obtained from patients with and without coronary artery disease (CAD, n = 12 and NCAD, n = 12) during elective open-heart surgeries. Tissue was incubated with DMEM-F12 for 24 hours. Exosomes were isolated, then nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting were performed to confirm the existence of exosomes. Total RNA in exosomes was subjected to high-throughput sequencing to identify differentially expressed miRNAs. MicroRNA target gene prediction was performed, and target genes were analyzed by Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and mirPath to identify function. Reverse transcription quantitative PCR was performed to confirm the differentially expressed miRNAs. Results: Fifty-three unique miRNAs were identified (adjusted p < 0.05, fold of change >2), among which 32 miRNAs were upregulated and 21 miRNAs were downregulated in coronary artery disease patients. Reverse transcription quantitative PCR validated the results for seven miRNAs including miR-141-3p, miR-183-5p, miR-200a-5p, miR-205-5p, miR-429, miR-382-5p and miR-485-3p, with the last two downregulated. GO and KEGG analysis by mirPath indicated that these differentially expressed miRNAs were enriched in cell survival, apoptosis, proliferation, and differentiation. Conclusions: Coronary artery disease patients showed differential epicardial adipose tissue exosomal miRNA expression compared with patients without coronary artery disease. The results provide clues for further studies of mechanisms of atherosclerosis.

Functional neurologic disorders (FNDs), also called conversion disorder (previously called hysteria), can show almost all the symptoms of other neurological diseases, including both physical (for example, seizure, weakness, fatigue) and psychological (for instance, depression, anxiety) symptoms. In spite of our general knowledge about emotional processes and developmental defects in the formation of these somatic symptoms, there is still no systemic and comprehensive research on the effects of emotional developmental variables in FND. Recently, both experimental and theoretical emotion studies have been greatly increased, such as prediction error, conceptual act model, basic emotional theory, and monoamine neuromodulator based three primary emotions. In addition, a large amount of evidence has confirmed the role of psychosocial adversity (such as stressful life events, interpersonal difficulties) as an important risk factor for FND. Here, we review recent advances about emotional stress on FND, and pay special attention to the effects of monoamine neuromodulators, such as how norepinephrine and serotonin affect behaviors. Then, we discuss the significance of these changes for FND, which may contribute to clarifying the pathogenesis of FND, and thus provide potential therapeutic drug targets or psychological intervention methods in the future.

It is necessary to investigate the wavelength-dependent variation rules of the refractive index of edible oils so as to explore the specificity of the dispersion in light propagation, imaging, and interference processes among different types of edible oil products. In this study, by deriving the refractive index equations of the double glass sheet holding device and oil, the reflectance spectra of three different types of oil samples, namely, peanut oil, colza oil, and kitchen waste oil, were measured via a spectrometer. Furthermore, the refractive index model of these different types of oil samples was investigated. Additionally, based on the oil dispersion characteristics, the dispersion of oil in optical coherence tomography (OCT) was compensated via deconvolution. In the wavelength range of λ∈ (380, 1500)nm, the analytical expressions of the double glass sheet holding device and oils are featured by practical reliability. The refractive indexes of three different types of oils n∈ (1.38, 1.52) show normal dispersion characteristics. The Cauchy coefficient matrix of the oil refractive index can be used for oil identification; in particular, the healthy oil and waste oil differ significantly in terms of the Cauchy coefficient matrix in the infrared band. Oil dispersion has almost no influence on the phase spectra of oils but can enhance their amplitude spectra. The dispersion mismatch can be eliminated by calculating the convolution kernel. The envelope broadening factors of OCT interference signals of oil products are 0.84, 0.64, and 0.91, respectively. According to the present research results, the refractive index model of oil can effectively remove the influence of the holding device. The refractive indexes of three different types of oil samples show similar wavelength-dependent variation characteristics, which confirms the existence of many correlated components in these oil samples. The established refractive index model of oil in a wide spectral range, from the ultraviolet to the infrared band, can be adequately employed for identifying different types of oils. The numerical dispersion compensation based on the established refractive index model can enhance the axial resolution in OCT imaging.

Endoplasmic reticulum stress (ERS) plays a vital and pathogenic role in the onset and progression of Alzheimer’s disease (AD). Phosphorylation of PKR-like endoplasmic reticulum kinase (PERK) induced by ERS depresses the interaction between actin-binding protein filamin-A (FLNA) and PERK, which promotes F-actin accumulation and reduces ER-plasma membrane (PM) communication. Echinacoside (ECH), a pharmacologically active component purified from Cistanche tubulosa, exhibits multiple neuroprotective activities, but the effects of ECH on ERS and F-actin remodeling remain elusive. Here, we found ECH could inhibit the phosphorylation of PERK. Firstly ECH can promote PERK-FLNA combination and modulate F-actin remodeling. Secondly, ECH dramatically decreased cerebral Aβ production and accumulation by inhibiting the translation of BACE1, and significantly ameliorated memory impairment in 2 × Tg-AD mice. Furthermore, ECH exhibited high affinity to either mouse PERK or human PERK. These findings provide novel insights into the neuroprotective actions of ECH against AD, indicating that ECH is a potential therapeutic agent for halting and preventing the progression of AD.

Peppers have been used in clinics for a long time and its major component, piperine (PPR), has been proven to be effective in the treatment of seizures. The purpose of this study was to investigate the effects of piperine on early seizures in mice after a traumatic brain injury (TBI) and to explore the mechanism of the drug against the development on TBI. Specific-pathogen-free-grade mice were randomly divided into six dietary groups for a week: control group, TBI group, three piperine groups (low PPR group with 10 mg/kg PPR, medium PPR group with 20 mg/kg PPR, and high PPR group with 40 mg/kg PPR), and a positive control group (200 mg/kg valproate). Except for the control group, all the other groups used Feeney free weight falling method to establish the TBI of closed brain injury in mice, and the corresponding drugs were continuously injected intraperitoneally for 7 days after the brain injury. The results from behavior and electroencephalogram showed that piperine attenuated the subthreshold dose of pentylenetetrazole-induced seizures compared with the TBI group. The western blot results showed that the expression levels of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were reduced by piperine. The immunostaining results showed that the brain-derived neurotrophic factor (BDNF) was also reduced by piperine. In addition, positive cell counts of astrocytic fibrillary acidic protein (GFAP) in immuno-fluorescence showed that they were also reduced. Our data show that piperine treatment can reduce the degree of cerebral edema, down-regulate TNF-α, IL-1β, and BDNF, decrease the reactivity of GFAP in the hippocampus, and inhibit TBI-induced seizures.

Zanthoxylum bungeanum Maxim (Rutaceae), a popular condiment and dietetic herbal medicine, has been used traditionally in the treatment of forgetfulness, as recorded in Shen Nong's Herbal Medicine, an old Chinese medicine book. To explore effects and potential mechanisms of it, extracts of Z. bungeanum through water (WEZ), volatile oil (VOZ), petroleum ether (PEZ), and methylene chloride (MCZ) were used to treat the memory loss induced in D-galactose-induced aging mice. The impaired memory was significantly alleviated after WEZ and VOZ extract treatment. WEZ and VOZ extracts also prevented D-galactose-induced hippocampal neuron damage. In addition, WEZ and VOZ extracts upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), which suggests that the effects of WEZ and VOZ extracts on oxidative stress and apoptosis might be involved in the cognitive dysfunctions. Furthermore, WEZ and VOZ extracts enhanced the activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), which suggests that Z. bungeanum has an appreciable therapeutic effect on learning and memory disabilities, and its mechanism may be related to activate PI3K/Akt signaling pathway. Collectively, our study suggested that Z. bungeanum extracts are promising agents for prevention of aging-related cognitive dysfunction and neurological deficits.

Abstract Background Marfan syndrome (MFS) is an inherited connective tissue disease that mainly involves Fibrillin‐1 (FBN1) mutations and aortic manifestations. In this study, we investigated the correlations between the FBN1 genotype–phenotype and aortic events (aortic dissection and aortic aneurysm) in patients with Marfan syndrome. Methods Genotype and phenotype information was evaluated in 180 patients with MFS. DNA sequencing was performed on each patient. According to the clinical manifestation, these patients were split into two groups: the aortic dissection group and the aortic aneurysm group. Aortic wall tissue was obtained from Marfan patients who underwent surgery and was used for staining. Results A total of 180 patients with FBN1 mutations were grouped into four categories: 90 with missense mutations, 32 with splicing mutations, 29 with frameshift mutations, and 29 with nonsense mutations. There was a significantly higher frequency of frameshift and nonsense mutations observed in aortic dissection than in aortic aneurysm (25.58% vs. 4.35%, p = .005; 25.58% vs. 8.70%, p = .033, respectively;), while missense mutations showed a higher frequency in aortic aneurysm than in aortic dissection (69.57% vs. 32.56%, respectively; p

Abstract Background Hyperlipidemia characterized of elevated serum lipid levels is a prevalent disease frequently resulting in cardiovascular disease (CVD). Berberine and evodiamine are herbal products of traditional Chinese herb Coptis chinensis and Evodia rutaecarpa, which are indicated to exert regulation of lipid metabolism. Therefore, the objective of this study was to investigate the lipid-lowering effect of berberine and evodiamine combination in hyperlipidemic rats. Method The rat model of hyperlipidemia was established by providing high-fat-diet (HFD) for 4 weeks. Berberine (BB), evodiamine (EV), and their combination (BB + EV) were orally administered to HFD induced rats for 4 weeks. Body weight, food utilization, histopathology of liver tissues, lipid profiles of serum and liver were measured. Gas chromatography (GC) analysis was applied to examine the level of plasma total cholesterol and ß- Sitosterol (BS) to estimate cholesterol absorption activity. Furthermore, intestinal NPC1L1, ACAT2, and ApoB48 protein expressions were evaluated by immunohistochemical assay. Result According to the results, decreased levels of serum cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), as well as hepatic TC were showed in hyperlipidemic rats treated by combination of berberine and evodiamine. GC analysis indicated that the elevated plasma BS was significantly ameliorated by BB, EV, and BB + EV. In addition, immunohistochemical analysis revealed that BB + EV treatment down-regulated the expressions of intestinal NPC1L1 and ACAT2, and ApoB48 in HFD induced rats. Conclusion Based on the above results, combination of berberine and evodiamine exerted a promising preventive effect on hyperlipidemia, partially through inhibiting intestinal absorption of cholesterol.

Conflicting evidence affects the final target recognition results. Thus, managing conflicting evidence efficiently can help to improve the belief degree of the true target. In current research, the existing approaches based on belief entropy use belief entropy itself to measure evidence conflict. However, it is not convincing to characterize the evidence conflict only through belief entropy itself. To solve this problem, we comprehensively consider the influences of the belief entropy itself and mutual belief entropy on conflict measurement, and propose a novel approach based on an improved belief entropy and entropy distance. The improved belief entropy based on pignistic probability transformation function is named pignistic probability transformation (PPT) entropy that measures the conflict between evidences from the perspective of self-belief entropy. Compared with the state-of-the-art belief entropy, it can measure the uncertainty of evidence more accurately, and make full use of the intersection information of evidence to estimate the degree of evidence conflict more reasonably. Entropy distance is a new distance measurement method and is used to measure the conflict between evidences from the perspective of mutual belief entropy. Two measures are mutually complementary in a sense. The results of numerical examples and target recognition applications demonstrate that our proposed approach has a faster convergence speed, and a higher belief degree of the true target compared with the existing methods.