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Alzheimer’s disease (AD) is a prevalent neurodegenerative disease and the world’s primary cause of dementia among the elderly population. The aggregation of toxic amyloid-beta (Aβ) is one of the main pathological hallmarks of the AD brain. Recently, neuroinflammation has been recognized as one of the major features of AD, which involves a network of interactions between immune cells. The mast cell (MC) is an innate immune cell type known to serve as a first responder to pathological changes and crosstalk with microglia and neurons. Although an increased number of mast cells were found near the sites of Aβ deposition, how mast cells are activated in AD is not clear. We developed a 3D culture system to culture MCs and investigated the activation of MCs by Aβ peptides. Because collagen I is the major component of extracellular matrix (ECM) in the brain, we encapsulated human LADR MCs in gels formed by collagen I. We found that 3D-cultured MCs survived and proliferated at the same level as MCs in suspension. Additionally, they can be induced to secrete inflammatory cytokines as well as MC proteases tryptase and chymase by typical MC activators interleukin 33 (IL-33) and IgE/anti-IgE. Culturing with peptides Aβ1-42, Aβ1-40, and Aβ25-35 caused MCs to secrete inflammatory mediators, with Aβ1-42 inducing the maximum level of activation. These data indicate that MCs respond to amyloid deposition to elicit inflammatory responses and demonstrate the validity of collagen gel as a model system to investigate MCs in a 3D environment to understand neuroinflammation in AD.

With the development of material design theories and synthesis technologies, clay-based composite materials have been controllably prepared and successfully applied in many fields, such as biomedicine, the automotive industry, petrochemical engineering, and wastewater treatment. To date, for the preparation of clay-based composite materials, the physical and chemical properties of clay must be fully considered, including the chemical composition, crystal structure, particle size, morphology, and surface charge. Halloysite, which has a tubular crystal structure, is a curly layered aluminosilicate clay with abundant reserves and a low price for constructing composite materials. The inner and outer surfaces of halloysite nanotubes are composed of Al−OH octahedrons and Si−O tetrahedrons, respectively, which ionize in opposite ways in water, resulting in opposite charges on the inner and outer surfaces. Therefore, the selective modification of halloysite can be achieved by chemical or electrostatic adsorption of the required chemical reagent. Additionally, the modified halloysite nanotubes can be used in catalysis and the loading and release of drug molecules. Moreover, because of its nanotube structure, the halloysite can be used to construct rough structures in micro- or nano-scale. By incorporation with low-surface-energy materials, the hydrophobic halloysite-based composite materials can be prepared for self-cleaning and oil-water separation. In this review, we introduced the rational design and preparation strategies of the hydrophobic halloysite-based composite materials. Then, we summarized the applications of these prepared composite materials in oil-water separation, hydrophobic self-cleaning coating, and the loading and sustained release of drug molecules. In addition, the related mechanisms and strategies for performance improvement were systematically discussed. Finally, the existing challenges and promising future directions in this research field were proposed. The halloysite-based composite materials have enhanced properties that are highly required, including enhanced mechanical and adhesive strength, excellent scratch and wear resistance, self-healing, and higher compatibility with living organisms. We believe fruitful promising results can be achieved in this field with more effort.

Combining chemo-therapeutics with immune checkpoint inhibitors facilitates killing cancer cells and activating the immune system through inhibiting immune escape. However, their treatment effects remain limited due to the compromised accumulation of both drugs and inhibitors in certain tumor tissues. Herein, a new poly (acrylamide-co-acrylonitrile-co-vinylimidazole-co-bis(2-methacryloyl) oxyethyl disulfide) (PAAVB) polymer-based intelligent platform with controllable upper critical solution temperature (UCST) was used for the simultaneous delivery of paclitaxel (PTX) and curcumin (CUR). Additionally, a hyaluronic acid (HA) layer was coated on the surface of PAAVB NPs to target the CD44-overexpressed tumor cells. The proposed nanomedicine demonstrated a gratifying accumulation in tumor tissue and uptake by cancer cells. Then, the acidic microenvironment and high level of glutathione (GSH) in cancer cells could spontaneously decrease the UCST of polymer, leading to the disassembly of the NPs and rapid drug release at body temperature without extra-stimuli. Significantly, the released PTX and CUR could induce the immunogenic cell death (ICD) to promote adaptive anti-tumor immunogenicity and inhibit immunosuppression through suppressing the activity of indoleamine 2,3-dioxygenase 1 (IDO1) enzyme respectively. Therefore, the synergism of this intelligent nanomedicine can suppress primary breast tumor growth and inhibit their lung metastasis.

Abstract Background Nowadays, because of the increasing incidence, the prevention and control of myopia has become an urgent issue. In China, auricular acupressure has been commonly used in the clinical treatment of myopia in children, but the exact effectiveness remains unproven. The purpose of this trial is to observe the efficacy of auricular acupressure in myopia prevention and control, as well as its effect on the choroidal and retinal thickness. Method/design A total of 480 subjects at 8–9 years old will be randomized in a 1:1 ratio to an intervention group versus a control group. The intervention group will receive auricular acupressure for 12 months, while the control group will be taken as a blank control. The primary and secondary outcomes will be measured at baseline, and again at 3, 6, 9, and 12 months after recruitment. The myopia incidence (spherical equivalent ≤ − 0.50 D) and the mean change of spherical equivalent will be taken as the primary variables; the secondary outcome measures include axial length, uncorrected visual acuity, and choroidal and retinal thickness. Discussion This trial aims to evaluate the effectiveness of auricular acupressure for myopia prevention and control with objective evidence and to preliminarily explore the plausible mechanism and provide reference for adopting this approach to retard the onset and control the progression of myopia. Trial registration Chinese Clinical Trial Registry ChiCTR2000038456 . Registered on September 23, 2020.

Abstract Background Idiopathic central precocious puberty (ICPP) reduces patient health-related quality of life (HRQoL). The impacts of disease and treatment on families are also an important concern. This study aimed to assess the association between family impact and HRQoL of children with ICPP. Methods We conducted a case–control study in Chongqing, China. A case group of 134 children with ICPP aged 5–12 years and their caregivers was recruited from a children’s hospital in Chongqing. A total of 210 gender- and age-matched subjects from two primary schools were selected as controls. PedsQLTM4.0 Generic Core Scales (GCS) and PedsQL™ Family Impact Module (FIM) were used in this study. Results Children with ICPP scored lower than controls in all HRQoL domains except physical functioning. In particular, the two groups were significantly different in emotional functioning scores (d = 0.414, P

Background and purposePrevious studies have found that abnormal local spontaneous brain activity in patients with obstructive sleep apnea (OSA) was associated with cognitive impairment, and dynamic functional connections can capture the time changes of functional connections during magnetic resonance imaging acquisition. The purpose of this study was to investigate the dynamic characteristics of regional brain connectivity and its relationship with cognitive function in patients with OSA and to explore whether the dynamic changes can be used to distinguish them from healthy controls (HCs).MethodsSeventy-nine moderate and severe male OSA patients without any treatment and 84 HCs with similar age and education were recruited, and clinical data and resting functional magnetic resonance imaging data were collected. The dynamic regional homogeneity (dReHo) was calculated using a sliding window technique, and a double-sample t-test was used to test the difference in the dReHo map between OSA patients and HCs. We explored the relationship between dReHo and clinical and cognitive function in OSA patients using Pearson correlation analysis. A support vector machine was used to classify the OSA patients and HCs based on abnormal dReHo.ResultCompared with HCs, OSA patients exhibited higher dReHo values in the right medial frontal gyrus and significantly lower dReHo values in the right putamen, right superior temporal gyrus, right cingulate gyrus, left insula and left precuneus. The correlation analysis showed that the abnormal dReHo values in multiple brain regions in patients with OSA were significantly correlated with nadir oxygen saturation, the oxygen depletion index, sleep period time, and Montreal cognitive assessment score. The support vector machine classification accuracy based on the dReHo difference in brain regions was 81.60%, precision was 81.01%, sensitivity was 81.01%, specificity was 82.14%, and area under the curve was 0.89.ConclusionThe results of this study suggested that there was abnormal dynamic regional spontaneous brain activity in patients with OSA, which was related to clinical and cognitive evaluation and can be used to distinguish OSA patients from HCs. The dReHo is a potential objective neuroimaging marker for patients with OSA that can further the understanding of the neuropathological mechanism of patients with OSA.

With the rapid development of internet finance in China, the risk management of internet finance has become an urgent issue. This study analyzes the factors that affect the default risk of Chinese internet finance companies based on measuring the distance to default of companies. This study incorporates ESG rating into the evaluation model to comprehensively reflect the default risk factors. The traditional KMV model is modified with ESG rating, and results are used to construct the panel logit model. Based on internet finance firms listed on China A-Shares data from 2016 to 2020, our results show the following: first, the modified ESG-KMV logit model can effectively analyze the influencing factors of the internet finance default risk. Second, ROE, accounts receivable turnover ratio, asset-liability ratio and z-value are important factors that affect the default risk of internet finance companies. Third, it is also found that COVID-19 has significantly impacted the default risk of internet finance companies. As a policy implication, the regulator can incorporate ESG into the measurement of the default risk to create more awareness among internet finance companies on the importance of the environment and sustainability to human societies.

Ovarian cancer (OvCa) is one of the most widespread malignant tumors, which has the highest morbidity and unsatisfactory clinical outcomes among all gynecological malignancies in the world. Previous studies found that cancer-associated fibroblasts (CAFs) play significant roles in tumor growth, progression, and chemoresistance. In the current research, weighted gene co-expression network analysis (WGCNA), univariable COX regression, and the least absolute shrinkage and selection operator (LASSO) analysis were applied to recognize CAF-specific genes. After multiple bioinformatic analyses, four genes (AXL, GPR176, ITGBL1, and TIMP3) were identified as OvCa-specific CAF markers and used to construct the prognostic signature (CAFRS). Furthermore, the specificity of the four genes' expression was further validated at the single-cell level, which was high-selectively expressed in CAFs. In addition, our results showed that CAFRS is an independent significant risk factor affecting the clinical outcomes of OvCa patients. Meanwhile, patients with higher CAFRS were more likely to establish chemoresistance to platinum. Besides, the CAFRS were notably correlated with well-known signal pathways that were related to tumor progression. In summary, our study identifies four CAF-specific genes and constructs a novel prognostic signature, which may provide more insights into precise prognostic assessment in OvCa.

In this paper, in order to reduce the influence of vibration and noise generated by the motor in rock cotton centrifuges on the quality of the output fiber and the damage to the operator’s hearing, it is meaningful to analyze and optimize the vibration and noise. A high-speed magnetic suspension motor is proposed for the rock cotton centrifuge in the paper. First, the motor model is established in Maxwell, the radial force density wave distributed in the air gap is calculated by the field solver, the main harmonic source is analyzed according to its FFT decomposition graph, and then the optimization scheme of short-range double-layer winding is determined. Second, the optimization scheme is analyzed in modal mode and harmonious response, and the vibration response spectrum of the motor stator is obtained. Finally, the electromagnetic noise characteristics of the motor are obtained through ANSYS acoustics simulation. The results show that the optimized motor noise has a reasonable level under the premise of ensuring electromagnetic performance.

Electrochemical oxidative C–C bond cleavage and functionalization are rarely developed due to the inertness and weak electronic bias of C–C bonds. In this study, the authors report the electrochemical C–C bond cleavage and 1,3-difluorination, 1,3-oxyfluorination and 1,3-dioxygenation of arylcyclopropanes under catalyst-free and external-oxidant-free conditions.

Abstract Background The potential correlation between H2AFY (also known as MacroH2A1) and the clinical characteristics of hepatocellular carcinoma (HCC) patients was analysed through gene expression profiles and clinical data in The Cancer Genome Atlas (TCGA) database, and the diagnostic and prognostic value of H2AFY in HCC was discussed. Methods The gene expression data of HCC and the corresponding clinical characteristics of HCC patients were downloaded from the TCGA database. The differences in H2AFY in normal liver tissues and HCC were analysed. The relationship between H2AFY and clinical characteristics was analysed by Wilcoxon signed-rank test, logistic regression and Kruskal-Wallis test. The Kaplan-Meier method and the Cox regression method were used to analyse the relationship between overall survival and clinical characteristics of the patients. An ROC curve was used to predict the diagnostic value of H2AFY in HCC. Gene set enrichment analysis (GSEA) was used to analyse the pathway enrichment of H2AFY. Result Compared with normal liver tissues, H2AFY was significantly highly expressed in HCC. H2AFY was positively correlated with the age, clinical stage, G stage (grade) and T stage (tumor stage) of liver cancer patients. Higher H2AFY expression predicted a poor prognosis in HCC patients. Cox regression analysis suggested that H2AFY was an independent risk factor for the prognosis of HCC patients. The ROC curve suggested that H2AFY had certain diagnostic value in HCC. GSEA suggested that H2AFY was correlated with lipid metabolism and a variety of tumour pathways. Conclusion Our study showed that H2AFY was significantly overexpressed in HCC. H2AFY may be a potential diagnostic and prognostic marker for HCC, and high expression of H2AFY predicts a poor prognosis in patients with HCC.

Abstract Background Postoperative peritoneal adhesion (PPA) is regarded as fibrous bands connecting both injured abdominal wall and organs or adjacent tissues. It is associated with T helper (Th)1 and Th2 differentiation. However, the critical role of the immunopathogenesis of adhesion formation was precisely unknown. The aim of this study was to investigate the effect of a new agent polylactic acid (PLA) nanoparticles loaded with ligustrazine, that is, ligustrazine nanoparticles (LN) on PPA and identify the potential mechanism. Methods Twenty-four Sprague–Dawley rats were randomly divided into the sham, model, LN, and sodium hyaluronate (SH) groups. The structure of LN, including entrapment efficiency (EE) and loading capacity (LC), and in vitro drug release were calculated. Adhesions were scored and the Masson's trichrome staining was used to determine the collagen deposition. The expressions of TLR4, MyD88, and NF-κB were measured by qRT-PCR, immunohistochemistry, and western blot assay. Moreover, Th1-related cytokines (IFN-γ, IL-12), Th2-related cytokines (IL-4, IL-6) in the cecum tissue and serum were conducted by ELISA. Results LN had good EE, LC, and control-release delivery characters with fairly uniform diameter and spherical morphology. It could effectively prevent adhesion formation after surgery. Besides, it could reduce collagen fibers accumulation, downregulate the expression levels of TLR4, MyD88, and NF-κB, and maintain Th1/Th2 balance. Conclusions Ligustrazine nanoparticles had effective effects on Th1/Th2 balance by regulating TLR4/MyD88/NF-κB pathway in PPA rats. It may be served as a promising therapy on postoperative adhesion formation.

Aiming at the characteristics of non-linearity,uncertainty and susceptibility to disturbance of single-degree-of-freedom magnetic levitation ball system,a back-stepping control method based on extended state observer (ESO-BS) was proposed to improve the control performance of the system.The extended state observer was used to estimate the position,velocity and disturbance information of the levitation ball in real time when the system was disturbed by uncertainty.The estimation was combined with the controller design,then the back-stepping method was used to design the levitation position tracking control law of the magnetic levitation ball,and the Lyapunov method was used to prove the ultimate bounded convergence of the tracking error of the system.The simulation results show that,compared with PID control,the adjusting time of ESO-BS control system is 0.01 s,while that of PID control is 0.08 s,which is obviously longer,so the dynamic characteristic of ESO-BS control is better than that of PID control.When there is uncertainty in the system,the designed control law can realize the stable suspension of the ball,and can realize the position tracking according to the required suspension height position.

Previous studies have shown that the structural and functional impairments of hippocampal subregions in patients with obstructive sleep apnea (OSA) are related to cognitive impairment. Continuous positive airway pressure (CPAP) treatment can improve the clinical symptoms of OSA. Therefore, this study aimed to investigate functional connectivity (FC) changes in hippocampal subregions of patients with OSA after six months of CPAP treatment (post-CPAP) and its relationship with neurocognitive function. We collected and analyzed baseline (pre-CPAP) and post-CPAP data from 20 patients with OSA, including sleep monitoring, clinical evaluation, and resting-state functional magnetic resonance imaging. The results showed that compared with pre-CPAP OSA patients, the FC between the right anterior hippocampal gyrus and multiple brain regions, and between the left anterior hippocampal gyrus and posterior central gyrus were reduced in post-CPAP OSA patients. By contrast, the FC between the left middle hippocampus and the left precentral gyrus was increased. The changes in FC in these brain regions were closely related to cognitive dysfunction. Therefore, our findings suggest that CPAP treatment can effectively change the FC patterns of hippocampal subregions in patients with OSA, facilitating a better understanding of the neural mechanisms of cognitive function improvement, and emphasizing the importance of early diagnosis and timely treatment of OSA.

In the mammalian brain, neurogenesis is maintained throughout adulthood primarily in two typical niches, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) of the lateral ventricles and in other nonclassic neurogenic areas (e.g., the amygdala and striatum). During prenatal and early postnatal development, neural stem cells (NSCs) differentiate into neurons and migrate to appropriate areas such as the olfactory bulb where they integrate into existing neural networks; these phenomena constitute the multistep process of neurogenesis. Alterations in any of these processes impair neurogenesis and may even lead to brain dysfunction, including cognitive impairment and neurodegeneration. Here, we first summarize the main properties of mammalian neurogenic niches to describe the cellular and molecular mechanisms of neurogenesis. Accumulating evidence indicates that neurogenesis plays an integral role in neuronal plasticity in the brain and cognition in the postnatal period. Given that neurogenesis can be highly modulated by a number of extrinsic and intrinsic factors, we discuss the impact of extrinsic (e.g., alcohol) and intrinsic (e.g., hormones) modulators on neurogenesis. Additionally, we provide an overview of the contribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to persistent neurological sequelae such as neurodegeneration, neurogenic defects and accelerated neuronal cell death. Together, our review provides a link between extrinsic/intrinsic factors and neurogenesis and explains the possible mechanisms of abnormal neurogenesis underlying neurological disorders.

In a previous study, we found that long non-coding genes in Alzheimer’s disease (AD) are a result of endogenous gene disorders caused by the recruitment of microRNA (miRNA) and mRNA, and that miR-200a-3p and other representative miRNAs can mediate cognitive impairment and thus serve as new biomarkers for AD. In this study, we investigated the abnormal expression of miRNA and mRNA and the pathogenesis of AD at the epigenetic level. To this aim, we performed RNA sequencing and an integrative analysis of the cerebral cortex of the widely used amyloid precursor protein and presenilin-1 double transgenic mouse model of AD. Overall, 129 mRNAs and 68 miRNAs were aberrantly expressed. Among these, eight down-regulated miRNAs and seven up-regulated miRNAs appeared as promising noninvasive biomarkers and therapeutic targets. The main enriched signaling pathways involved mitogen-activated kinase protein, phosphatidylinositol 3-kinase-protein kinase B, mechanistic target of rapamycin kinase, forkhead box O, and autophagy. An miRNA-mRNA network between dysregulated miRNAs and corresponding target genes connected with AD progression was also constructed. These miRNAs and mRNAs are potential biomarkers and therapeutic targets for new treatment strategies, early diagnosis, and prevention of AD. The present results provide a novel perspective on the role of miRNAs and mRNAs in AD. This study was approved by the Experimental Animal Care and Use Committee of Institute of Medicinal Biotechnology of Beijing, China (approval No. IMB-201909-D6) on September 6, 2019.

Background Kidneys obtained from deceased donors increase the incidence of delayed graft function (DGF) after renal transplantation. Here we investigated the influence of the risk factors of donors with DGF, and developed a donor risk scoring system for DGF prediction. Methods This retrospective study was conducted in 1807 deceased kidney donors and 3599 recipients who received donor kidneys via transplants in 29 centers in China. We quantified DGF associations with donor clinical characteristics. A donor risk scoring system was developed and validated using an independent sample set. Results The incidence of DGF from donors was 19.0%. Six of the donor characteristics analyzed, i.e., age, cause of death, history of hypertension, terminal serum creatinine, persistence of hypotension, and cardiopulmonary resuscitation (CPR) time were risk factors for DGF. A 49-point scoring system of donor risk was established for DGF prediction and exhibited a superior degree of discrimination. External validation of DGF prediction revealed area under the receiver-operating characteristic (AUC) curves of 0.7552. Conclusions Our study determined the deceased donor risk factors related to DGF after renal transplantation pertinent to the Chinese cohort. The scoring system developed here had superior diagnostic significance and consistency and can be used by clinicians to make evidence-based decisions on the quality of kidneys from deceased donors and guide renal transplantation therapy.

Morphological features and physicochemical properties of purple waxy wheat 168 (PWW168) starch were compared with those of normal wheat and maize starches. The morphologies of PWW168 were found to be similar for normal wheat starch. All three crop starches exhibited typical A-type crystallinity. However, PWW168 had lower apparent amylose content and higher degree of crystallinity than normal wheat and maize starches. These differences resulted in a higher light transmittance, swelling power and solution, freeze-thaw stability, peak viscosity, breakdown viscosity, lower retrogradation percentage, and final viscosity and setback viscosity in PWW168 starch. These information suggested that PWW168 should have greater resistance to retrogradation under cooling conditions. Highlighting the differences in physicochemical characteristics of PWW168 starch and normal wheat and maize starches could provide effective application of PWW168 starch in food industry. Abbreviations: AAC, apparent amylose content; SP, swelling power; FTC, freeze-thaw cycles; PV, peak viscosity; TV, trough viscosity; BD, breakdown viscosity; FV, final viscosity; SB, setback viscosity; PT, pasting temperature.

Abstract Vacuolar protein sorting 35 (VPS35) is a major component of the retromer complex that mediates the retrograde transport of cargo proteins from endosomes to the trans-Golgi network. Mutations such as D620N in the VPS35 gene have been identified in patients with autosomal dominant Parkinson’s disease (PD). However, it remains poorly understood whether and how VPS35 deficiency or mutation contributes to PD pathogenesis; specifically, the studies that have examined VPS35 thus far have differed in results and methodologies. We generated a VPS35 D620N mouse model using a Rosa26-based transgene expression platform to allow expression in a spatial manner, so as to better address these discrepancies. Here, aged (20-months-old) mice were first subjected to behavioral tests. Subsequently, DAB staining analysis of substantia nigra (SN) dopaminergic neurons with the marker for tyrosine hydroxylase (TH) was performed. Next, HPLC was used to determine dopamine levels, along with levels of its two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum. Western blotting was also performed to study the levels of key proteins associated with PD. Lastly, autoradiography (ARG) evaluation of [3H]FE-PE2I binding to the striatal dopamine transporter DAT was carried out. We found that VPS35 D620N Tg mice displayed a significantly higher dopamine level than NTg counterparts. All results were then compared with that of current VPS35 studies to shed light on the disease pathogenesis. Our model allows future studies to explicitly control spatial expression of the transgene which would generate a more reliable PD phenotype.

Epidemiological data about the prevalence of amblyopia around the world vary widely among regions and periods. This meta-analysis aimed to determine the global prevalence of amblyopia in children. PubMed, Embase, and the Cochrane Library were searched for prevalence studies published up to 5 November 2021. The outcome was the prevalence of amblyopia, analyzed as pooled estimates with 95% confidence intervals (CI). A total of 97 studies were included, including 4,645,274 children and 7,706 patients with amblyopia. The overall worldwide pooled prevalence of amblyopia was 1.36% (95%CI: 1.27–1.46%). The prevalence of amblyopia was higher in males (1.40%, 95%CI: 1.10–1.70%) than in females (1.24%, 95%CI: 0.94–1.54%) (OR = 0.885, 95%CI: 0.795–0.985, P = 0.025). The results of the meta-regression analysis showed that there were no significant associations between the prevalence of amblyopia and geographical area, publication year, age, sample size, and whether it was carried out in a developed or developing country (all P > 0.05). Begg’s test (P = 0.065) and Egger’s test (P < 0.001) showed that there was a significant publication bias in the prevalence of amblyopia. In conclusion, amblyopia is a significant vision problem worldwide, and public health strategies of early screening, treatment, and management are important.

Chlorogenic acid (CGA) is a phenolic compound that is widely distributed in honeysuckle, Eucommia, fruits and vegetables. It has various biological functions, including cardiovascular, nerve, kidney, and liver protection, and it exerts a protective effect on human health, according to clinical research and basic research. The intestine and brain are two important organs that are closely related in the human body. The intestine is even called the “second brain” in humans. However, among the many reports in the literature, an article systematically reporting the regulatory effects and specific mechanisms of CGA on the intestines and brain has not been published. In this context, this review uses the regulatory role and mechanism of CGA in the intestine and brain as the starting point and comprehensively reviews CGA metabolism in the body and the regulatory role and mechanism of CGA in the intestine and brain described in recent years. Additionally, the review speculates on the potential biological actions of CGA in the gut-brain axis. This study provides a scientific theory for CGA research in the brain and intestines and promotes the transformation of basic research and the application of CGA in food nutrition and health care.

In kidney transplantation, the donor kidney inevitably undergoes ischemia-reperfusion injury (IRI). It is of great importance to study the pathogenesis of IRI and find effective measures to attenuate acute injury of renal tubules after ischemia-reperfusion. Our previous study found that Src homology region 2 domain-containing phosphatase-1 (SHP-1) insufficiency aggravates renal IRI. In this study, we systematically analyzed differences in the expression profiles of SHP-1 (encoded by Ptpn6)-insufficient mice and wild-type mice by RNA-seq. We found that a total of 161 genes showed at least a twofold change, with a false discovery rate 2, the most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were the cell division pathway and peroxisome-proliferator activated receptor PPARα signaling pathways. Furthermore, the downregulated genes of the PPARα signaling pathway were mainly related to fatty acid absorption and degradation. Using an agonist of the PPARα signaling pathway, fenofibrate, we found that renal IRI was significantly attenuated in Ptpn6 +/mev mice. In summary, our results show that insufficiency of SHP-1 inhibits the expression of genes in the PPARα signaling pathway, thereby leading to increased reactive oxygen species (ROS) and exacerbating the renal IRI. The PPARα signaling agonist fenofibrate partially attenuates renal IRI induced by SHP-1 insufficiency.

ObjectivesIn this study, we analyzed the metabonomics of intermingled phlegm and blood stasis (IPBS) and its three concurrent syndromes in patients with stable angina pectoris of coronary heart disease.MethodsA total of 164 sera of separated outpatients from 12 national tradition Chinese medicine clinical research centers with IPBS or concurrent syndromes were collected for the study and assessed with LC-ESI-MS/MS (liquid chromatography—electrospray ionization tandem—mass spectrometry)-based metabolomics and multivariate statistical analysis.ResultsNon-differential metabolites between IPBS and its separate syndrome combined with the top 100 most abundant metabolites in four groups were screened to reflect the essence of IPBS. Amino acid and its metabolomics and glycerol phospholipids were screened for common metabolites, and these metabolites were mainly enriched in valine, leucine, and isoleucine metabolism and glycerophospholipid metabolism. Principal component analysis revealed that the difference between IPBS and its separate concurrent syndromes was not distinct. Compared with IPBS, anserine, cytidine 5′-diphosphocholine, and 7,8-dihydro-L-biopterin separately significant increase in phlegm stasis and toxin (PST), phlegm stasis and Qi stagnation (PQS), and phlegm stasis and Qi deficiency (PQD). While these different metabolites were associated with histidine metabolism, beta-alanine metabolism, glycerophospholipid metabolism, and folate biosynthesis. Three accurate identification models were obtained to identify the difference between IPBS and its concurrent syndromes.ConclusionOur study indicated that valine, leucine, and isoleucine metabolism and glycerophospholipid metabolism could represent the essence of IPBS; dysregulated metabolites were valuable in identifying PST from IPBS.

PolyJet 3D printing can be used to fabricate colored physical models of anatomical structures such as skull and heart with realistic appearances. These medical models can be used for surgical simulation and planning of complex operations, as well as anatomy teaching. PolyJet is theoretically capable of producing any color by mixing multiple materials. However, the measured color of a sample printed by PolyJet is often different from the specified color in the printer software. Therefore, it is often difficult to predict the measured color of a sample before printing. This paper reports a study on predictive relationships between measured color and four control factors of PolyJet (i.e., three RGB values of specified color and finish type) by design of experiments and application of multilayer perceptron (MLP) neural network model. Experimental data are collected using a full factorial design of experiments. These data are used to train and test the MLP model using 5-fold cross validation. Then, the prediction performances of the MLP model are compared with a linear regression model and a cubic regression model. The results show that the MLP model is capable of predicting measured color with higher accuracy.

Abstract An amorphous Ni nanoparticles‐loaded ZnO nanowire array is controllably constructed on stainless steel mesh through combined electrodeposition and hydrothermal reaction. Its nano‐arrayed structure not only provides a platform to achieve stable and good dispersion of Ni nanoparticles, but also helps improve their ability to adsorb 4‐nitrophenolate ions and to capture hydrogen radicals, thereby accelerating the hydrogen transfer from metal hydride complex to 4‐nitrophenol. Benefiting from the abovementioned unique features, it outperforms most Ni‐based catalysts. While a 30‐s re‐electrodeposition of Ni can provide it extra 150 min of high catalytic activity towards the reduction of waste 4‐nitrophenol to valuable 4‐aminophenol, further demonstrating its outstanding reusability. The highly general methodology reported here paves the way to economically and effectively synthesize various other metal nanoparticles‐loaded ZnO nanowire arrays on different conductive substrates, which not only enrich the nanowire‐arrayed catalysts, but also significantly promote their practical utilizations in a wide range of environment‐related fields.

The direct sintering process of coal fly ash for the preparation of glass-ceramics is the liquid-phase sintering process, from non-densification to densification. When the temperature exceeds the densification temperature point, the porosity of glass-ceramics on the contrary increases and the pore diameter increases. This provides a basis to prepare porous glass-ceramics by direct overfiring. Adding borax to coal fly ash can reduce the temperature of liquid phase formation, reduce the preparing temperature of porous glass-ceramics, achieve the purpose of energy saving. The effects of borax on the structure, properties and sintering kinetics of porous glass-ceramics prepared from coal fly ash by overfiring were investigated. It is found that the introduction of B-O bond can change the network structure of non-crystalline vitreous in coal fly ash, reduce the melting temperature, promote the formation of liquid phase, and thus increase the porosity of porous glass-ceramics. This paper provides a certain experimental basis for the preparation of porous glass-ceramics by direct overfiring of coal fly ash at low temperature without adding pore-forming agent, and provides a new possibility for the high-value resource utilization of coal fly ash.

Abstract Aim To explore an effective personalized training model for nurses working in emergency isolation wards of COVID‐19 in a short period. Design This study is a longitudinal study from 24 January 2020 to 28 February 2020. Methods There are 71 nursing staff working in the emergency isolation wards of Sichuan Provincial People's Hospital that participated in this study. The questionnaires were conducted with Likert scale. The operation assessment teachers have received standardized training. The self‐rating anxiety scale (SAS) and self‐rating depression Scale (SDS) were applied to assess the mental state of nurses. Results After short‐term training, these nurses can handle the emergency tasks in a timely manner. The pass rate of nurse theory and operation assessment is 100%. The 111 suspected patients admitted to the emergency isolation ward have been scientifically diagnosed and treated, the three confirmed patients have received appropriate treatment. No nurses have been infected. Conclusions In this study, the personalized emergency training mode was feasible in the emergency isolation ward during the COVID‐19 epidemic, which rapidly improved the rescue ability of nurses and effectively avoid the occurrence of cross‐infection. This mode can provide a valuable reference for the emergency training of nurses in the future.

Abstract Background and Aim While adenoma detection rate (ADR) is an important quality metric for screening colonoscopy, it remains difficult to be accessed due to the lack of integrated endoscopy and pathology databases. Hence, the use of an adenoma‐to‐polyp detection rate quotient and polyp detection rate (PDR) has been proposed to predict ADR. This study aimed to examine the usefulness of estimated ADR across different colonic segments in two age groups for Shenzhen people in China. Methods We retrospectively analyzed 7329 colonoscopy procedures performed by 12 endoscopists between January 2012 and February 2014. The PDR, actual ADR, and estimated ADR of the entire, proximal, and distal colon, and within each colonic segment, in two patient age groups:

Abstract Background Significant developments in stem cell therapy for Parkinson’s disease (PD) have already been achieved; however, methods for reliable assessment of dopamine neuron maturation in vivo are lacking. Establishing the efficacy of new cellular therapies using non-invasive methodologies will be critical for future regulatory approval and application. The current study examines the utility of neuroimaging to characterise the in vivo maturation, innervation and functional dopamine release of transplanted human embryonic stem cell-derived midbrain dopaminergic neurons (hESC-mDAs) in a preclinical model of PD. Methods Female NIH RNu rats received a unilateral stereotaxic injection of 6-OHDA into the left medial forebrain bundle to create the PD lesion. hESC-mDA cell and sham transplantations were carried out 1 month post-lesion, with treated animals receiving approximately 4 × 105 cells per transplantation. Behavioural analysis, [18F]FBCTT and [18F]fallypride microPET/CT, was conducted at 1, 3 and 6 months post-transplantation and compared with histological characterisation at 6 months. Results PET imaging revealed transplant survival and maturation into functional dopaminergic neurons. [18F]FBCTT-PET/CT dopamine transporter (DAT) imaging demonstrated pre-synaptic restoration and [18F]fallypride-PET/CT indicated functional dopamine release, whilst amphetamine-induced rotation showed significant behavioural recovery. Moreover, histology revealed that the grafted cells matured differently in vivo producing high- and low-tyrosine hydroxylase (TH) expressing cohorts, and only [18F]FBCTT uptake was well correlated with differentiation. Conclusions This study provides further evidence for the value of in vivo functional imaging for the assessment of cell therapies and highlights the utility of DAT imaging for the determination of early post-transplant cell maturation and differentiation of hESC-mDAs.

The welding of 8-mm thick Q235 low-carbon steel plates by keyhole tungsten inter gas welding (K-TIG), a deep penetration argon arc welding technique with tungsten electrode, is associated with many problems, including an unstable welding process and a small welding current window. To solve these prominent problems, the method of adding shielding flux on the back of the welding workpieces was proposed for the first time in this paper. This method can improve the stability of the welding process. The butt welding method was used to achieve the result of single-sided welding and double-sided forming without adding welding wire or prefabricating groove during the welding process. The results show that direct current (DC) in the range of 430–480 A is successfully used to weld the 8-mm thick Q235 low-carbon steel. The welding current window is expanded to 50 A, and the welding process stability is significantly improved. After expanding the welding current window, the microstructures and properties of welded joints obtained under different welding currents were systematically studied. The results show that the distribution of microstructures and the mechanical properties of the welded joints under different welding currents present the same states. The microstructures of the weld zone are composed of ferrite + pearlite + widmanstatten structure; the microstructures of the fusion zone are composed of Widmanstatten structure; the structures of the heat-affected zones are composed of ferrite + a small amount of pearlite. In addition, with the increase in the welding current, the fusion width of the back of the workpiece increased slightly. In the welding joint, the hardness value of the fusion zone is the highest, followed by the weld zone, and the heat-affected zone. The base material has the least hardness, and the final tensile fracture position of the welded joint is in the heat affected zone.

Abstract Understanding and improving the robustness of networks has significant applications in various areas, such as bioinformatics, transportation, critical infrastructures, and social networks. Recently, there has been a large amount of work on network dismantling, which focuses on removing an optimal set of nodes to break the network into small components with sub-extensive sizes. However, in our experiments, we found these state-of-the-art methods, although seemingly different, utilize the same refinement technique, namely reinsertion, to improve the performance. Despite being mentioned with understatement, the technique essentially plays the key role in the final performance. Without reinsertion, the current best method would deteriorate worse than the simplest heuristic ones; while with reinsertion, even the random removal strategy achieves on par with the best results. As a consequence, we, for the first time, systematically revisit the power of reinsertion in network dismantling problems. We re-implemented and compared 10 heuristic and approximate competing methods on both synthetic networks generated by four classical network models, and 18 real-world networks which cover seven different domains with varying scales. The comprehensive ablation results show that: i) HBA (High Betweenness Adaption, no reinsertion) is the most effective network dismantling strategy, however, it can only be applicable in small scale networks; ii) HDA (High Degree Adaption, with reinsertion) achieves the best balance between effectiveness and efficiency; iii) The reinsertion techniques help improve the performance for most current methods; iv) The one, which adds back the node based on that it joins the clusters minimizing the multiply of both numbers and sizes, is the most effective reinsertion strategy for most methods. Our results can be a survey reference to help further understand the current methods and thereafter design the better ones.

Abstract Background This study aimed to compare long-term postoperative quality of life and satisfaction differences between SMILE and FS-LASIK for myopia correction. Methods This cross-sectional study enrolled patients under the age of 39 years, who chose to undergo SMILE or FS-LASIK surgery to both eyes 3 years previously. Patients completed a common vision test and Quality of Life Impact of Refractive Correction (QIRC) questionnaire, together with the surgical satisfaction, adverse symptoms subjective survey. Patients with preoperative corrected distance visual acuity and postoperative uncorrected distance visual acuity of 20/20 or greater were included. Propensity score matching (PSM) was used to match the preoperative and postoperative spherical equivalent, age, and designed optical zones of the left and right eyes between the two groups. Results Forty-nine patients were included in each group after PSM from 188 patients. No significant difference in the total QIRC score was found between the SMILE and FS-LASIK groups (45.89 ± 5.91 vs 45.09 ± 5.65, p = 0.492). There were no differences in surgical satisfaction between the groups (p = 0.178). Compared to the SMILE group, the FS-LASIK group had more glare (2.12 ± 2.25 vs 3.22 ± 2.54, p = 0.026) and severe dryness (1.80 ± 1.98 vs 2.79 ± 2.19, p = 0.021). Conclusion Postoperative quality of life is similar after SMILE or FS-LASIK. Dry eye symptoms and glare were milder in the SMILE group than in the FS-LASIK group.

Abstract Background The chronic unpredictable mild stress (CUMS) model has long been considered the best model for exploring the pathophysiological mechanisms underlying depression. However, there are no widely recognised standards for strategies for modeling and for behavioral testing. The present study aimed to optimize the protocols for food deprivation and the sucrose preference test (SPT) for the CUMS model. Methods We first evaluated the effects of different long periods of food deprivation on the body weight of Sprague Dawley (SD) rats by testing food deprivation for 24 hours (8:00‐8:00+), food deprivation for 12 hours during the daytime (8:00‐20:00) and food deprivation for 12 hours at night (20:00‐8:00+). Next, we established a SD rat CUMS model with 15 different stimulations, and used body weight measurement, SPT, forced swim test (FST), open field test (OFT) and Morris water maze (MWM) test to verify the success of the modeling. In the SPT, consumption of sucrose and pure water within 1 and 12 hours was measured. Results Twelve hours of food deprivation during the daytime (8:00‐20:00) had no effect on body weight, while 12 hours of food deprivation at night (20:00‐8:00+) and 24 hours of food deprivation (8:00‐8:00+) significantly reduced the mean body weight of the SD rats. When SPT was used to verify the successful establishment of the CUMS rat model, sucrose consumption measured within 12 hours was less variable than that measured within 1 hour. Conclusions Twelve hours of food deprivation in the daytime (8:00‐20:00) may be considered a mild stimulus for the establishment of a CUMS rat model. Measuring sucrose consumption over 12 hours is recommended for SPT.

Objective The Yip1 domain family (YIPF) proteins were proposed to function in endoplasmic reticulum (ER) to Golgi transport and maintenance of the morphology of the Golgi, which were homologues of yeast Yip1p and Yif1p. YIPF3, the member 3 of YIPF family was a homolog of Yif1p. The aim of present study was to investigate the expression and regulation mechanism of porcine YIPF3. Methods Quantitative realtime polymerase chain reaction (qPCR) was used to analyze porcine YIPF3 mRNA expression pattern in different tissues and pig kidney epithelial (PK15) cells stimulated by polyinosine-polycytidylic acid (poly [I:C]). Site-directed mutations combined with dual luciferase reporter assays and electrophoretic mobility shift assay (EMSA) were employed to reveal transcription regulation mechanism of porcine YIPF3. Results Results showed that the mRNA of porcine YIPF3 (pYIPF3) was widely expressed with the highest levels in lymph and lung followed by spleen and liver, while weak in heart and skeletal muscle. Subcellular localization results indicated that it expressed in Golgi apparatus and plasma membranes. Upon stimulation with poly (I:C), the level of this gene was dramatically up-regulated in a time- and concentration-dependent manner. pYIPF3 core promoter region harbored three cis-acting elements which were bound by ETS proto-oncogene 2 (ETS2), zinc finger and BTB domain containing 4 (ZBTB4), and zinc finger and BTB domain containing 14 (ZBTB14), respectively. In which, ETS2 and ZBTB4 both promoted pYIPF3 transcription activity while ZBTB14 inhibited it, and these three transcription factors all played important regulation roles in tumorigenesis and apoptosis. Conclusion The pYIPF3 mRNA expression was regulated by ETS2, ZBTB4, and ZBTB14, and its higher expression in immune organs might contribute to enhancing ER to Golgi transport of proteins, thus adapting to the immune response.

Background: The role of Epstein–Barr virus (EBV) in inflammatory bowel disease (IBD) remains to be elucidated. The aim of this study was to investigate the presence of EBV in the blood and intestinal mucosa of patients with IBD and evaluate the association between EBV positivity and IBD. Methods: Patients with IBD, hospitalized between January 2015 and April 2018, were enrolled. The EBV-DNA load in blood samples from each subject was analyzed by quantitative real-time polymerase chain reaction. EBV-encoded small-RNA 1 (EBER-1) was detected by in-situ hybridization in intestinal mucosa tissue sections of patients with IBD. Result: EBV-DNA was detected in 48 out of 568 patients with IBD (8.4%), and EBER-1 positivity was detected in 27 of these patients (56.3%). Refractory IBD and severe mucosal inflammation were more common in patients with detectable levels of EBER-1 than in those without; the number of EBER-1-positive cells positively correlated with mucosal inflammation (P value < 0.05). Age (≥60 years old) and use of azathioprine were risk factors for EBV infection. There was no significant difference in clinical remission rate and surgical rate between the EBER-1 positive group and EBER-1 negative group, antiviral group and the non-antiviral group, among IBD patients who tested positive for EBV-DNA. Conclusion: Elderly patients with IBD, treated with azathioprine, are more susceptible to EBV positivity. Further, EBV mucosal detection correlated with the severity of mucosal damage and refractoriness, but not prognosis.

In some computed tomography (CT) applications, limited-angle projections are used for image reconstruction, and traditional reconstruction methods, such as filtered back-projection (FBP) or simultaneous algebraic reconstruction technique (SART), cannot reconstruct high-quality CT images without prior knowledge assistance. For limited-angle CT reconstruction, total variation minimization (TVM) method is not conductive to recovering image structures. Image reconstruction methods based on anisotropic total variation (ATV) and reweighted anisotropic total variation (RwATV) can significantly reduce the shading artifacts using prior knowledge of the scanning angular range and image sparsity. However, using the knowledge of image sparsity does not further improve image quality in some applications. In this paper, we propose a new reconstruction method based on anisotropic relative total variation (ARTV) for limited-angle CT reconstruction. In ARTV, the windowed inherent variation (WIV) indicates the strength of structure information and WIV values are adaptively determined by local structure information. In limited-angle CT, particular scanning angular range urges us into exerting different strengths on different directions of ARTV. Experiments on FORBILD HEAD phantom, a thoracic image and real projections of a walnut are performed to test the new method. Experimental results show that the destroyed structures are recovered to some extent, and we acquire higher image quality compared to some existing limited-angle CT reconstruction methods.

With the increasing expectations of electromagnetic devices, the defects of monofunctional devices that are susceptibly limited by external constraints are becoming more and more obvious and the integration of multiple functions has gradually become the pursuit of researchers. In this paper, a novel multifunctional metamaterial tailored by the solid state plasma (SSP) is proposed. By inspiring the particular SSP resonators, such a metamaterial can be handily switched back and forth among two functions and form three working states. When the proposed SSP metamaterial is served in State I, its function embodies as an energy absorber and the absorption which is over 90% for TE and TM modes are 5.84-7.30 GHz and 5.41-6.34 GHz whose relative bandwidths (RBs) are 22.22% and 15.83%, respectively. States II and III keep the same functionality of cross-polarization conversion but a distinct operating band. The polarization conversion rate (PCR) of State II which is higher than 90% is 7.40-12.20 GHz (the RB is 48.98%) and this operational range will be shifted to 5.71-8.47 GHz (the RB is 38.92%) after switching to State III. Compared with the conventional tunable devices, this SSP metamaterial has the advantage of functional diversity and it provides a new design idea of absorber and polarization converter to promote potential applications of multifunctional devices.

For limited-angle computed tomography (CT) image reconstruction, the classical total variation (TV) based algorithms suffer from the limited-angle artifacts, because TV only used the gradient information of the image. The priori image constrained compressed sensing (PICCS) based reconstruction algorithms can reduce the limited-angle artifacts by using a priori image consistent with the target image. However, it is difficult to ensure the consistency of priori image and target image in practice. In order to reconstruct high quality image when the prior image is inconsistent with the target image, we proposed a guided image filter reconstruction based on TV and prior image (TVPI-G). In each iteration phase, our algorithm first performs a TV step (include simultaneous algebra reconstruction technique (SART) and TV) to get initiatory reconstruction image; Then, the results of TV iteration are combined with prior images to form an intermediate result; Finally, we use the guided image filter to modify the intermediate results with the TV result as the guide image. Numerical reconstruction results on simulation phantom with different intensities Poisson noise illustrates that our proposed TVPI-G algorithm is better than other comparison algorithms in both qualitative and quantitative aspects, including TV, PICCS, and SART guided image filtering.

Neuromarketing is an emerging research field for prospective businesses on consumer’s preference. Consumer’s preference prediction based on electroencephalography (EEG) can reliably predict likes or dislikes of a product. However, the current EEG prediction and classification accuracy have yet to reach ideal level. In addition, it is still unclear how different brain region information and different features such as power spectral density, brain asymmetry, differential entropy, and Hjorth parameters affect the prediction accuracy. Our study shows that by taking footwear products as an example, the recognition accuracy of product likes or dislikes reaches 94.22%. Compared with other brain regions, the features of the frontal and occipital brain region obtained a higher prediction accuracy, but the fusion of the features of the whole brain region could improve the prediction accuracy of likes or dislikes even further. Future work would be done to correlate the EEG-based like or dislike prediction results with product sales and self-reports.

BackgroundDeep venous thrombosis (DVT) of the lower extremities is one of the common complications for neurointensive care unit patients, which leads to increased morbidity and mortality. The purpose of our study was to explore risk factors and develop a prognostic nomogram for lower extremity DVT in neurointensive care unit patients.MethodsWe prospectively collected and analyzed the clinical data of 420 neurointensive care unit patients who received treatment in our institution between January 2018 and September 2019. Stepwise logistic regression was used to select predictors. R software was used to develop the prognostic nomogram. The performance of the nomogram was validated using a validation cohort of patients with data collected between October 2019 and March 2020.ResultsAmong 420 patients, 153 (36.4%) had lower extremity DVT and five (1.2%) had both DVT and pulmonary embolism (PE) in our study. Logistic regression analysis indicated that age [odds ratio (OR): 1.050; 95% confidence interval (CI): 1.029–1.071; P < 0.001], Glasgow Coma Scale (GCS) score (OR: 0.889; 95% CI: 0.825–0.959; P = 0.002), D-dimer level (OR: 1.040; 95% CI: 1.008–1.074; P = 0.014), muscle strength (OR: 2.424; 95% CI: 1.346–4.366; P = 0.003), and infection (OR: 1.778; 95% CI: 1.034–3.055; P = 0.037) were independent predictors for lower extremity DVT. These predictors were selected to be included in the nomogram model. The area under the curve values in the primary cohort and validation cohort were 0.817 (95% CI: 0.776–0.858) and 0.778 (95% CI: 0.688–0.868), respectively, and respective Brier scores were 0.167 and 0.183.ConclusionAge, GCS score, D-dimer level, muscle strength, and infection are independent predictors for lower extremity DVT. The nomogram is a reliable and convenient model to predict the development of lower extremity DVT in neurointensive care unit patients.

A steel-wire wound reinforced thermoplastic pipe (SWW-RTP) has been widely utilized in many industrial areas, and a soil landslide is an inevitable hazardous extreme condition for the SWW-RTP as it is usually buried underground. It is imperative to study the mechanical failure behavior and the failure criterion of the SWW-RTP under the combination of internal pressure and soil landslide conditions, and this paper is the first study to investigate the topic. In this paper, groups of stress–strain curves of high-density polyethylene (HDPE) and steel wires were obtained by uniaxial tensile tests at different strain rates, with the help of a Digital Image Correlation device (DIC). A rate-dependent constitutive model was employed to represent the mechanical behavior of the HDPE and to help deduce the stress–strain curve of the HDPE under the required strain rate, estimated from the static simplification of the dynamic soil landslide. Afterwards, a finite element model of the SWW-RTP, embedded in a cubic of soil, was established with the software ABAQUS. The SWW-RTP model was composed of HDPE solid elements, embedded with steel-wire truss elements, and the soil was characterized with the extended Drucker–Prager model. A quartic polynomial displacement distribution was applied to the soil model to represent the soil landslide. Then, the mechanical response of the SWW-RTP was analyzed. It was found that the failure criterion of the HDPE yield was more suitable for the pipe subjected to internal pressure and soil landslide conditions, instead of the steel-wire strength failure criterion always used in traditional research on the SWW-RTP. Further, the influence of landslide width, internal pressure and steel-wire number were discussed. The larger the width of the landslide area, the gentler the deformation of the pipeline; this resulted in an increase in the maximum landslide and a decrease in the maximum curvature with the width of the landslide area. The relatively high internal pressure was beneficial to the safety of the SWW-RTP under landslide, because the internal pressure could increase the stiffness of the pipeline. The number of steel wires had a limited influence on the maximum landslide required for the SWW-RTP’s failure. This work can be useful for the design and safe assessment of the SWW-RTP under internal pressure and soil landslide conditions.

A graph containing some edges with probability measures and other edges with uncertain measures is referred to as an uncertain random graph. Numerous real-world problems in social networks and transportation networks can be boiled down to optimization problems in uncertain random graphs. Actually, information in optimization problems in uncertain random graphs is always asymmetric. Regularization is a common optimization problem in graph theory, and the regularity index is a fundamentally measurable indicator of graphs. Therefore, this paper investigates the regularity index of an uncertain random graph within the framework of chance theory and information asymmetry theory. The concepts of k-regularity index and regularity index of the uncertain random graph are first presented on the basis of the chance theory. Then, in order to compute the k-regularity index and the regularity index of the uncertain random graph, a simple and straightforward calculating approach is presented and discussed. Furthermore, we discuss the relationship between the regularity index and the k-regularity index of the uncertain random graph. Additionally, an adjacency matrix-based algorithm that can compute the k-regularity index of the uncertain random graph is provided. Some specific examples are given to illustrate the proposed method and algorithm. Finally, we conclude by highlighting some potential applications of uncertain random graphs in social networks and transportation networks, as well as the future vision of its combination with symmetry.

This study investigated the anti-hepatoma molecular mechanism of Alisol G, which is an effective component of the Chinese medicine Alisma orientalis, in the presence of metal ions Cu2+ and Fe3+ based on c-myc DNA. Here, a combination of Alisol G and metal ions (Cu2+, Fe3+) to augment anti-hepatoma efficiencies of Alisol G has been identified by methyl thiazolyl tetrazolium (MTT) assay. Network pharmacology revealed that c-myc DNA was the potential target of Alisol G with respect to its anti-hepatoma effects. By performing multi-spectroscopic analyses, we showed that the interaction of Alisol G with c-myc DNA was a process of static quenching. The binding constants and thermodynamic constants indicated that a 1:1 complex was formed between Alisol G and c-myc DNA. Moreover, metal ions strengthened the interaction between Alisol G and c-myc DNA. Molecular docking and molecular dynamics simulation further unveiled that the higher binding affinity between Alisol G-Fe3+ complex and c-myc DNA as compared to Alisol G-Cu2+ complex. This probably resulted from the polarization of metal ions and the structural flexion of Alisol G. The C22-O31-H76 and C18-O32-H77 of Alisol G were key groups in the interaction with c-myc DNA. Addition of metal ion, had greatly changed the c-myc DNA-binding domain of Alisol G while didn’t affect the kinetic stability of the interaction, thus facilitating the insertion of Alisol G into c-myc DNA A-T base pair. Importantly, the DG113 of c-myc DNA was important for its binding to metal ions. Together, our findings suggested that Alisol G in combination with metal ions may be an efficient and promising option for the treatment of liver cancer.

Vascular dementia (VaD) is a general term used to describe difficulties in memory, reasoning, judgment, and planning caused by a reduced blood flow to the brain and consequent brain damage, in which microRNAs (miRNAs) are involved. Dracocephalum moldavica L. (D. moldavica) is traditionally used in the treatment of cardiovascular diseases as well as VaD, but the biomolecular mechanisms underlying its therapeutic effect are obscure. In the present study, the molecular mechanisms involved in the treatment of VaD by the total flavonoids from Dracocephalum moldavica L. (TFDM) were explored by the identification of miRNA profiling using bioinformatics analysis and experimental verification. A total of 2,562 differentially expressed miRNAs (DEMs) and 3,522 differentially expressed genes (DEGs) were obtained from the GSE120584 and GSE122063 datasets, in which the gene functional enrichment and protein-protein interaction network of 93 core targets, originated from the intersection of the top DEM target genes and DEGs, were established for VaD gene profiling. One hundred and eighty-five targets interacting with 42 flavonoids in the TFDM were included in a compound-target network, subsequently found that they overlapped with potential targets for VaD. These 43 targets could be considered in the treatment of VaD by TFDM, and included CaMKII, MAPK, MAPT, PI3K, and KDR, closely associated with the vascular protective effect of TFDM, as well as anti-oxidative, anti-inflammatory, and anti-apoptotic properties. The subsequent analysis of the compound-target gene-miRNA network indicated that eight miRNAs that mediated 43 targets had a close interaction with TFDM, suggesting that the neuroprotective effects were principally due to kaempferol, apigenin, luteolin, and quercetin, which were mostly associated with the miR-3184-3p/ESR1, miR-6762-3p/CDK1, miR-6777-3p/ESRRA, and other related axes. Furthermore, the in vitro oxygen-glucose deprivation (OGD) model demonstrated that the dysregulation of miR-3184-3p and miR-6875-5p found by qRT-PCR was consistent with the changes in the bioinformatics analysis. TFDM and its active compounds involving tilianin, luteolin, and apigenin showed significant effects on the upregulation of miR-3184-3p and downregulation of miR-6875-5p in OGD-injured cells, in line with the improved cell viability. In conclusion, our findings revealed the underlying miRNA-target gene network and potential targets of TFDM in the treatment of VaD.

Utilizing microinjection to introduce biological molecules such as DNA, mRNA, siRNA, and proteins into the cell is well established to study oocyte maturation and early embryo development in vitro. However, microinjection is an empirical technology. The cellular survival after microinjection is mainly dependent on the operator, and an experienced operator should be trained for a long time, from several months to years. Optimizing the microinjection to be highly efficient and quickly learned should be helpful for new operators and some newly established laboratories. Here, we combined the tip pipette and piezo-assisted micromanipulator to microinject the oocyte and early embryos at different stages of mouse. The results showed that the survival rate after microinjection was more than 85% for cumulus–oocyte complex, germinal vesicle oocyte, two-cell, and four-cell embryos, and close to 100% for MII oocyte and zygotes. The high-rate survival of microinjection can save many experimental samples. Thus, it should be helpful in studying some rare animal models such as aging and conditional gene knockout mice. Furthermore, our protocol is much easier to learn for new operators, who can usually master the method proficiently after several training times. Therefore, we would like to publicly share this experience, which will help some novices master microinjection skillfully and save many laboratory animals.

Destination loyalty is a key indicator of the competitiveness of tourist destinations. Rural summer health leisure vacations for urban elderly (RSHLVUE) tourists span a wide range of ages. Destination operators need to understand the loyalty formation mechanisms of different aged tourists. RSHLVUE tourists were divided into a low-aged group (LA) and a high-aged group (HA) to examine and modify the hypothesis of the relationship between perceived value, tourist well-being, place attachment, and destination loyalty based on affect, behavior, and cognition (ABC) theory. The test results of the measurement model indicate that the HA showed stronger responses in terms of cost value, sense of meaning, and place dependency. The formation mechanism of destination loyalty for the LA is tourist well-being → perceived value → place attachment → destination loyalty, and for the HA is perceived value → tourist well-being → place attachment → destination loyalty. The findings deepen the understanding of destination loyalty among elderly leisure vacation tourists and can guide RSHLVUE destination managers to enhance destination competitiveness.

Glutamate is an excitatory neurotransmitter in the nervous system. Excessive glutamate transmission can lead to increased calcium ion expression, related to increased neurotoxicity. Memantine is used for treating patients with Alzheimer’s disease (AD) due to its protective action on the neurons against toxicity caused by over activation of N-methyl-D-aspartate receptors. Nootropics, also called “smart drugs”, are used for the treatment of cognitive deficits. In this work, we evaluate the neuroprotective action of four memantine analogues of glycine derivatives, including glycyl-glycine, glycyl-glycyl-glycine, sarcosine, dimethylglycine and three conjugates with nootropics, modafinil, piracetam and picamilon. The new structural memantine derivatives improved cell viability against copper-induced neurotoxicity in APPswe cells and glutamate-induced neurotoxicity in SH-SY5Y cells. Among these novel compounds, modafinil-memantine, piracetam-memantine, sarcosine-memantine, dimethylglycine-memantine, and glycyl-glycine-memantine were demonstrated with good EC50 values of the protective effects on APPswe cells, accompanied with moderate amelioration from glutamate-induced neurotoxicity. In conclusion, our study demonstrated that novel structural derivatives of memantine might have the potential to develop promising lead compounds for the treatment of AD. The solubility of memantine analogues with nootropics and memantine analogues with glycine derivatives in buffer solutions at pH 2.0 and pH 7.4 simulating the biological media at 298.15 K was determined and the mutual influence of the structural fragments in the molecules on the solubility behavior was analyzed. The significative correlation equations relating the solubility and biological properties with the structural HYBOT (Hydrogen Bond Thermodynamics) descriptors were derived. These equations would greatly simplify the task of the directed design of the memantine analogues with improved solubility and enhanced bioavailability.

Cancer progression and metastases are the leading causes of poor outcomes in patients with colon cancer. Colon cancer metastasis is a multigene, multistep, multistage complex process in which target genes, microRNAs, epithelial-stromal transformation, tumour stem cells, the tumour microenvironment, and various cell signalling pathways are implicated in the progression and metastasis of colon cancer. Although conventional therapies have made significant advances in treating the progression and metastasis of colorectal cancer, they have failed to improve survival outcomes. Natural compounds may have more significant potential in preventing and treating colon cancer. Active natural compounds exert their antitumor effects by inducing tumour cell differentiation, promoting tumour cell apoptosis, inhibiting tumour vascular growth, and regulating immunity. Natural compounds, combined with conventional therapies, can target mutant genes and various cellular signalling pathways, inhibit epithelial-stromal transformation, and improve the tumour microenvironment to inhibit tumour progression and metastasis. The synergism of natural compounds and conventional therapeutics has the potential to become a promising therapy for treating colorectal cancer progression and metastases.