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IntroductionImmunoglobulin A nephropathy (IgAN) presents various clinical manifestations and pathological phenotypes. Approximately 5% of patients with IgAN present with early onset nephrotic syndrome, mild mesangial lesions, and diffuse foot process effacement of podocytes, which resemble minimal change disease (MCD). These patients are defined as MCD-IgAN. Whether MCD-IgAN is a special type of IgAN or simply MCD accompanied by IgA deposition remains controversial.MethodsA total of 51 patients diagnosed with MCD-IgAN at Beijing Anzhen Hospital from January 2010 to September 2022 were recruited. The clinical and pathological characteristics of IgA-MCD were analyzed. Patients with IgAN but without MCD (non-MCD-IgAN) and healthy participants were enrolled as controls. Galactose-deficient immunoglobulin A1 (Gd-IgA1) and complement C3 were detected both in the circulation and in renal tissues.ResultsWe found that the levels of serum Gd-IgA1 were lower in participants with MCD-IgAN than in those with non-MCD-IgAN, but higher than in healthy participants. Gd-IgA1 was rarely deposited in the glomeruli of participants with MCD-IgAN, with a positive rate of only 13.7% (7/51); in contrast, the positive rate in participants with non-MCD-IgAN was 82.4% (42/51). Among renal Gd-IgA1-positive patients, Gd-IgA1 and immunoglobulin A (IgA) colocalized along the glomerular mesangial and capillary areas. Interestingly, we found that the circulating levels of complement C3 were significantly higher in participants with MCD-IgAN than in participants with non-MCD-IgAN. In addition, the intensity of C3c in glomeruli in participants with MCD-IgAN was significantly weaker than in participants with non-MCD-IgAN.ConclusionsOur study suggests that, in MCD-IgAN, most of the IgA that is deposited on glomeruli is not the same pathogenic Gd-IgA1 as found in general IgAN. Complement activation both in the circulation and in the renal locality was much weaker in MCD-IgAN than in non-MCD-IgAN. Our study suggests that IgAN with MCD might be MCD with coincidental IgA deposition.

The frequent variation of influenza virus hemagglutinin (HA) antigen is the main cause of influenza pandemic. Therefore, the study of B cell epitopes of HA is of great significance in the prevention and control of influenza virus. In this study, the cleavage vaccine of 2009 H1N1 influenza virus was used as immunogen, and the monoclonal antibodies (mAbs) were prepared by conventional hybridoma fusion and screening techniques. The characteristics of mAbs were identified by ELISA method, Western-blot test and hemagglutination inhibition test (HI). Using the obtained mAbs as a tool, the B cell epitopes of HA were predicted by ELISA blocking test, sandwich ELISA method and computer simulation method. Finally, four mAbs against HA antigen of H1N1 influenza virus were obtained. The results of ELISA and computer prediction showed that there were at least two types of epitopes on HA of influenza virus. This study provides experimental data for improving the prediction of HA epitopes of influenza viruses and developing potential influenza vaccines, and also provides a new method for the prediction of other pathogenic microorganisms.

IntroductionIgA nephropathy (IgAN) encompasses a wide range of clinical and histology features. Some patients present without hematuria, with or without hypertension, still rapidly progress in renal function. Renal pathology of this part of patients were predominant intrarenal arteriolar lesions, rarely presented glomerular proliferative lesions. We aim to investigate the clinical and pathological characteristics and prognosis of these IgAN patients and initially explore whether the abnormal activation of complement is involved in the intrarenal arteriolar lesions of IgAN.MethodsA total of 866 patients with renal biopsy-proven IgAN diagnosed at Beijing Anzhen Hospital were recruited. IgAN patients without intrarenal arteriolar lesions and proliferative lesions were excluded (n = 115), the rest were divided into arteriolar lesions group (n = 202) and proliferative lesions group (n = 549). Among them, 255 patients were regularly followed up for at least 1 year. Renal biopsy tissues of 104 IgAN patients were stained for complement components by immunohistochemistry and immunofluorescence.ResultsCompared with proliferative lesions group, the arteriolar lesions group experienced high percentage of hypertension (p = 0.004), low percentage of gross hematuria (p = 0.001), microscopic hematuria (p < 0.001) and less initial proteinuria (p = 0.033). Renal survival between the two groups was not significantly different (p = 0.133). MBL, C4d, FH and FHR5, C3c, and MAC deposited on intrarenal arteriole in arteriolar lesions group. Compare with the proliferative lesion group, the arteriolar lesions group exhibited a higher intensity of C3c deposition on the intrarenal arterioles (p = 0.048). C3c and CD31 co-deposited on intrarenal arterioles area in patients with intrarenal arteriolar lesions.ConclusionRenal survival of the IgAN patients in arteriolar lesions group was not better than those in proliferative lesions group. Abnormal activation of complement may be involved in the pathogenesis of arteriolar damage through the injury of endothelial cells in this clinical phenotype of IgAN.

Background and Purpose: We have previously reported a cardioprotective effect with Xin-Ji-Er-Kang (XJEK) treatment in mice with myocardial infarction (MI)-induced heart failure, but no report about its potential functions in myocardial ischemia-reperfusion (MIR) injury. Here we studied the therapeutic effects of XJEK on MIR injury and investigated the mechanisms involved.Experimental Approach: MIR model of Balb/c mice induced by left anterior descending coronary artery ligation for half an hour, followed by reperfusion, was utilized to study the potential therapeutic effects of XJEK on MIR-induced cardiac injury. Ultra-performance liquid chromatography tandem Orbitrap mass spectrometry platform was used for studying serum lipid metabolic signatures.Key Results: MIR caused cardiac dysfunctions, cardiac injury, myocardial fibrosis, and increased inflammation, and all the observed abnormalities caused by MIR were largely corrected by XJEK treatment. Mechanistically, XJEK exerts its cardioprotective effect in the context of MIR injury by suppressing MIR-induced inflammation and dysregulation of serum lipid metabolism.Conclusion and Implications: We have demonstrated for the first time that XJEK protects heart from MIR injury by restoring dysregulated lipidomics. Our data provide new evidence to support a therapeutic effect for XIEK on MIR-induced cardiac injury, and pave the way for exploring the therapeutic potential of XJEK in large animal study and early clinical trial.

Background. Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. Methods. We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. Results. At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. Conclusions. The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. Trial registration. ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov. Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx

In this work, we report a novel thorium metal–organic framework, [NH2(CH3)][Th2(H2O)2(L)3] (namely, ECUT-36, H3L = 4,4′,4′′-nitrilotribenzoic acid), built on a new Th2 building block, showing a 3,9...

Background: Fast-acting and cognitive-enhancing antidepressants are desperately needed. Activation of translocator protein (18 kDa, TSPO) is a novel strategy for developing potential antidepressants, but there are no data available on the onset time of TSPO ligands. This study aimed to investigate the fast-onset antidepressant actions of AC-5216, a selective TSPO ligand, in TSPO knock-out (KO) mice. Methods: TSPO wild-type (WT) and KO mice were subjected to a six-week chronic unpredicted stress (CUS) paradigm. Then, the mice were treated with AC-5216 and tested with depressive and cognitive behaviours. Results: A single dose of AC-5216 (0.3 mg/kg) exerted anxiolytic- and antidepressant-like actions in TSPO WT mice. Moreover, in chronically stressed WT mice, two to four days of AC-5216 treatment (0.3 mg/kg, once per day) produced fast-onset antidepressant-like effects in the novelty-suppressed feeding and sucrose preference tests, as well as memory-enhancing effects in the novel object recognition test. In addition, a rapid (with five days of treatment) restoration of serum corticosterone levels and prefrontal cortex (PFC) allopregnanolone levels was found. Further studies showed that in these stress-exposed WT mice, AC-5216 significantly increased the levels of mTOR signalling-related proteins (mBDNF, p-mTOR, PSD-95, synapsin-1, GluR1), as well as the total dendritic length and branching points of pyramidal neurons in the PFC. Conclusions: These results suggest that TSPO mediates the fast-onset antidepressant-like and memory-enhancing effects of AC-5216, possibly through the rapid activation of mTOR signalling and restoration of dendritic complexity in the PFC.

Xin-Ji-Er-Kang (XJEK) inhibited cardiovascular remodeling in hypertensive mice in our previous studies. We hypothesized that XJEK may prevent isoproterenol (ISO)-induced myocardial hypertrophy (MH) in mice by ameliorating oxidative stress (OS) through a mechanism that may be related to the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1) pathways. Forty SPF male Kunming mice were randomized into 5 groups (n = 8 mice per group): control group, MH group, MH + different doses of XJEK (7.5 g/kg/day and 10 g/kg/day), and MH + metoprolol (60 mg/kg/day). On the eighth day after drug treatment, electrocardiogram (ECG) and echocardiography were performed, the mice were sacrificed, and blood and heart tissues were collected for further analysis. XJEK administration markedly ameliorated cardiovascular remodeling (CR), as manifested by a decreased HW/BW ratio and CSA and less collagen deposition after MH. XJEK administration also improved MH, as evidenced by decreased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC) levels. XJEK also suppressed the decreased superoxide dismutase (SOD) and catalase (CAT) activities and increased malondialdehyde (MDA) levels in serum of mice with MH. XJEK-induced oxidative stress may be related to potentiating Nrf2 nuclear translocation and HO-1 expression compared with the MH groups. XJEK ameliorates MH by activating the Nrf2/HO-1 signaling pathway, suggesting that XJEK is a potential treatment for MH.

The BCR-associated protein 31 (BAP31), a transmembrane protein in the endoplasmic reticulum, participates in the regulation of immune cells, such as microglia and T cells, and has potential functions in macrophages that remain to be unexplored. In this study, we designed and bred macrophage-specific BAP31 knockdown mice to detect the polarization and functions of macrophages. The results revealed that M2 macrophage-associated genes were suppressed in mouse bone marrow–derived macrophages of Lyz2 Cre-BAP31flox/flox mice. Multiple macrophage-associated transcription factors were demonstrated to be able to be regulated by BAP31. Among these factors, C/EBPβ was the most significantly decreased and was regulated by early growth response 2. BAP31 could also affect C/EBPβ via modulating IL-4Rα ubiquitination and proteasome degradation in IL-4–stimulated macrophages. Furthermore, we found that BAP31 affects macrophages functions, including angiogenesis and skin fibrosis, during the wound healing process through IL-4Rα, as confirmed by infection with adeno-associated virus–short hairpin (sh)-IL-4Rα in Lyz2 Cre-BAP31flox/flox mice. Our findings indicate a novel mechanism of BAP31 in regulating macrophages and provide potential solutions for the prevention and treatment of chronic wounds.

Objectives The objective of the study was to assess the clinical efficacy of computed tomography (CT)-guided cryoablation as a means to treat adrenal metastasis (AM) secondary to lung cancer. Materials and methods This study was a single-center retrospective study that analyzed 39 consecutive patients with AM secondary to lung cancer who underwent CT-guided cryoablation in our center. The rates of complete ablation, local recurrence, local recurrence-free survival (RFS), and overall survival (OS) were analyzed. Results The rates of primary and secondary complete ablation were 94.9% and 100%, respectively, and none of the patients suffered from a hypertensive crisis associated with the treatment. Over the follow-up period, 20.5% of the patients experienced local recurrence, and the median RFS duration was 26 months. The cumulative 1-, 3-, and 5-year local RFS rates in this study were 84.6%, 51.3%, and 5.9%, respectively. Extra-adrenal gland metastases were detected in five patients. Over the course of follow-up, 26 patients died. The mean OS duration was 34 months with cumulative 1-, 3-, and 5-year OS rates of 89.7%, 53.4%, and 8.3%, respectively. Advanced age (P = 0.001), primary adenocarcinoma (P = 0.006), other primary lung cancers (P = 0.038), and primary Stage III lung cancers (P = 0.007) were all found to be independent predictive factors of poor OS in these patients. Conclusion CT-guided cryoablation can be safely and effectively used to control AM secondary to lung cancer, and patients with AM secondary to lung squamous cell carcinoma may be best suited for this form of treatment.

Copper is a trace element necessary for the normal functioning of organisms, but excessive copper contents may be toxic to the heart. The goal of this study was to investigate the role of excessive copper accumulation in mitochondrial damage and cell apoptosis inhibition. In vivo, the heart copper concentration and cardiac troponin I (c-TnI) and N-terminal forebrain natriuretic peptide (NT-pro-BNP) levels increased in the copper-laden model group compared to those of the control group. Histopathological and ultrastructural observations revealed that the myocardial collagen volume fraction (CVF), perivascular collagen area (PVCA) and cardiomyocyte cross-sectional area (CSA) were markedly elevated in the copper-laden model group compared with the control group. Furthermore, transmission electron microscopy (TEM) showed that the mitochondrial double-layer membrane was incomplete in the copper-laden model groups. Furthermore, cytochrome C (Cyt-C) expression was downregulated in mitochondria but upregulated in the cytoplasm in response to copper accumulation. In addition, Bcl-2 expression decreased, while Bax and cleaved caspase-3 levels increased. These results indicate that copper accumulation in cardiomyocyte mitochondria induces mitochondrial injury, and Cyt-C exposure and induces apoptosis, further resulting in heart damage.

Technologies such as external sensors, data acquisition, trend analysis, and cloud services make remote operation and maintenance of equipment status monitoring more convenient and lower maintenance costs. In this paper, an industrial robot operation and maintenance system is designed. First, the online monitoring of the robot is realized by collecting the control parameters, state parameters, fault information and external sensor monitoring information of the industrial robot. Then, the health baseline of the industrial robot is established based on the historical operation data. The online data is compared with the baseline data to realize the online assessment of the robot’s health status. Finally, a visualization platform for remote operation and maintenance of the robot is built to realize the online display of parameters, health trend tracking and fault status early warning, which is convenient for maintenance personnel to take timely countermeasures.

With the continuous improvement of modern manufacturing automation and process intensification, the complexity of tools and machined parts has greatly increased, and their performance directly affects the quality of workpieces and production efficiency. Accurate prediction of tool life is conducive to improving production efficiency and reducing enterprise costs. In this paper, a tool life prediction method based on multi-source feature PSO-SVR neural network is proposed. By monitoring and collecting the current and vibration signals of the tool during the machining process of CNC machine tools, the time-frequency eigenvalues are extracted. The effective features are extracted by feature selection technology as the input of support vector regression (SVR) neural network, and the parameters of the network are optimized by particle swarm optimization (PSO), so as to improve the accuracy of the predict, and finally predict the remaining useful life(rul) of the tool.

In present study, a novel glutathione functionalized MoS

PURPOSE To evaluate the safety and clinical effectiveness of computed tomography (CT)-guided cryoablation for adrenal pheochromocytoma (AP). MATERIALS AND METHODS From July 2015 to October 2018, we observed 8 patients that underwent CT-guided cryoablation for AP. The blood pressure and pulse before treatment did not exceed 150/90 mm Hg and 90 times/min, respectively. Complete ablation rate, clinical success rate, and long-term outcomes were analyzed. RESULTS A total of 8 patients with 8 APs were treated by CT-guided cryoablation. The mean duration of the procedure was 67.5±4.6 minutes. No patient achieved complete ablation, yet the clinical success rate was 100%. The mean metanephrine decreased from 61.7±11.1 to 2.0±1.1 nmol/L (P

BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important, especially in patients with undetectable hepatitis B virus (HBV) DNA treated with nucleoside analogs. AIM To clarify the monitoring power of hepatitis B core-related antigen (HBcrAg) for hepatic histologic changes in patients with chronic hepatitis B (CHB) treated with entecavir. METHODS This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression, respectively, in 403 CHB patients, including 374 with entecavir for 72 weeks (291 underwent paired liver biopsy) and 29 as controls. RESULTS Level of HBcrAg correlated negatively with liver fibrosis staging (γ = -0.357, P < 0.001) in hepatitis B e antigen (HBeAg)-positive patients, and positively with liver fibrosis staging in HBeAg-negative patients. Higher HBcrAg concentration was associated with younger age, HBeAg positive status, high HBV DNA loads, high level of hepatitis B surface antigen (HBsAg) and higher necroinflammation, but not with HBV genotype. Serum concentration of HBcrAg, basal core promoter/precore (BCP/PC) mutant, quantitation of HBsAg (qHBsAg) and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression. HBV DNA was undetectable in 88.37% of patients treated with entecavir at week 72, while their level of HBcrAg was still detectable. A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement. HBcrAg concentration > 6.33 log IU/mL at baseline and logarithmic reduction > 1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement, respectively. CONCLUSION HBcrAg level is associated with liver fibrosis progression. HBcrAg is an excellent monitor of hepatic histological changes, especially in CHB patients treated with nucleoside analogs.

Developing noble-metal-based catalysts with ultralow loading to achieve excellent performance for selective hydrogenation of alkynes under mild reaction conditions is highly desirable but still faces huge challenges. To this end, a SO3H-anchored covalent organic framework (COF-SO3H) as the support was deliberately designed, and then ultralow-content Pd (0.38 wt %) was loaded by a wet-chemistry immersion dispersion method. The resulting Pd0.38/COF-SO3H composite exhibits outstanding performance for the selective hydrogenation of phenylacetylene with 97.06% conversion and 93.15% selectivity to styrene under mild reaction conditions (1 bar of H2, 25 °C). Noticeably, the turnover frequency value reaches as high as 3888 h-1, which outperforms most of reported catalysts for such use. Moreover, such a catalyst also exhibits excellent activity for a series of other alkynes and high stability without obvious loss of catalytic performance after five consecutive cycles.

In this study, cysteamine-functionalized molybdenum disulfide quantum dots (MoS2 QDs) were synthesized by a one-pot hydrothermal method. A range of techniques including of Thioflavin T and 8-Anilino-1-naphthalenesulfonic acid fluorescence assays, circular dichroism, and transmission electron microscope have been employed to determination the efficacy of MoS2 QDs on the inhibition/reversion of fibrillation and hindering cytotoxicity induced by protofibrils and amyloid fibrils of bovine serum albumin (BSA). Results demonstrated that MoS2 QDs could effectively inhibit the fibrillogenesis and destabilize preformed fibrils of BSA in a concentration-dependent manner. Cytotoxicity protection and imagine on Hela cells was investigated using the methyl thiazolyl tetrazolium (MTT) assay. It was found that MoS2 QDs not only has good biocompatibility, low toxicity and good cell penetration, but also could effectively decrease the cytotoxicity caused by the formed fibrils of BSA. The results obtained in this work suggested the potential biological application of MoS2 QDs in therapeutics and provided new insight into the design of multifunctional nanomaterials for amyloid-related diseases.

Low-intensity pulsed ultrasound (LIPUS) has been proved to promote the proliferation of myoblast C2C12. However, whether LIPUS can effectively prevent muscle atrophy has not been clarified, and if so, what is the possible mechanism. Myostatin (MSTN) is a negtive regulator of skeletal muscle, and inhibition of its expression has a positive effect on the growth and development of skeletal muscle.The aim of this study is to evaluate the effects of LIPUS on muscle atrophyin hind limb unloading rats, and explored the mechanisms. The rats were randomly divided into four groups: normal control group (NC), hind limb unloading group (UL), hind limb unloading plus 30 mW/cm2 irradiation group (UL + 30 mW/cm2), hind limb suspension plus 80 mW/cm2 irradiation group (UL + 80 mW/cm2). The rats were suspended or/and treated with LIPUS for 20 min/d for 28 days. C2C12 cells were exposed to LIPUS at 30 or 80 mW/cm2 for 5 days. After 28 days, LIPUS significantly prevented the decrease of cross-sectional area of muscle fiber and promoted the quality of gastrocnemius muscle. In addition, LIPUS significantly inhibited the content of MSTN in the serum and gastrocnemius muscle of hind limb rats, and its receptor, and promoted myoblast C2C12 proliferation, promoted the stability of alanine, aspartate and glutamate metabolism pathway. These results suggest that the key mechanism of LIPUS in preventing muscle atrophy induced by hind limb unloading may be through inhibiting MSTN and stabilizing alanine, aspartate and glutamate metabolism.

In this paper, the effects of three isoflavones including daidzein, genistein, and puerarin on fibrillation of hen egg-white lysozyme were investigated by various analytical methods. The results demonstrated that all isoflavones could effectively inhibit the fibrillogenesis of hen egg-white lysozyme and destabilized the preformed fibrils of hen egg-white lysozyme in a dose-dependent manner. To further understand the inhibition mechanism, molecular modeling was carried out. The docking results demonstrated that the isoflavones could bind to two key fibrogenic sites in hen egg-white lysozyme through van der Waals force, electrostatic forces, and hydrogen bonding, as well as σ-π stacking. By these means, isoflavones could not only obviously enhance the hydrophobicity of the binding sites, but also greatly stabilize the native state of HEWL, which was able to postpone the fibrosis process of hen egg-white lysozyme.

The functions carried out by macrophages are essential in the processes of repairing skin injury. However, the mechanism of the M2 macrophage and its role in cutaneous wound healing remain elusive. B cell receptor associated protein 31 (BAP31) plays an important role in the immune system, and its function in connection with macrophages has yet to be determined. The present study demonstrates that the process of cutaneous wound healing slowed down in bone marrow-specific BAP31 knock down Lyz2-cre-BAP31flox/flox mice. In addition, further studies show that various kinds of macrophage M2 polarization related factors were regulated by BAP31. Among these molecules C/EBP β was significantly affected. However, IL-4 but not IFN-γ, is able to recover the expression levels of C/EBP β and its downstream transcript factors induced by BAP31. Then, we demonstrated that BAP31 regulated macrophage M2 polarization by negative regulation of IL-4Rα and positive influence on Egr-2 to affect C/EBP β. Our findings reveal a novel mechanism of BAP31 in regulating M2 macrophage, and provide novel targets for the prevention and treatment of chronic wounds.

In engineering product design, modeling and drawing design, and in the study of the law of numerical changes in real life, people often encounter the unknown geometric curve processing problems, that is, to extract the geometric curve functions contained in some discrete points by mathematical methods. This paper mainly introduces the Lagrange interpolation method and the Newton interpolation method, calculation method and the basic idea of its convergence, verified by the use of discrete point interpolation method for the feasibility of curve fitting, and combined with the practical problems of mathematics modeling method, using interpolation method in car door design, the application of curve compared the advantages and disadvantages of the two methods, make us more profound and comprehensive understanding of the interpolation method, for its future in social production, modelling design provides important application basis.

Objective Hepatocellular carcinoma (HCC) is one of the most lethal human malignancies in China, and the genetic link of hepatocarcinogenesis remains to be defined. Thus, we explored the role of SET and myeloid translocation protein 8, Nervy, and DEAF1 (MYND) domain containing protein 3 (SMYD3) gene polymorphism on risk and prognosis of HCC. Methods A total of 236 patients with HCC who received treatment in Affiliated Hospital of Jining Medical University for the first time and 230 healthy individuals were enrolled in the study. After DNA extraction for all the subjects, polymerase chain reaction (PCR) was used to amplify and sequence variable numbers of tandem repeat (VNTR) loci of SMYD3 gene. SMYD3 gene was genotyped and its frequency distribution was calculated. Age, education level, income, smoking and drinking history, HCC family history, tumor node metastasis (TNM) staging, maximum tumor diameter, lymph node metastasis (LNM) etc. were investigated. Correlation of SMYD3 gene polymorphism and other risk factors with the occurrence and prognosis of HCC was analyzed. Results The family history of HCC, drinking history, cirrhosis, and HBV or/and HCV infection, SMYD3 VNTR 3/3 were more frequently observed in subjects with HCC. Patients with SMYD3 VNTR 3/3 genotype, drinking-history, family history of HCC, cirrhosis and hepatitis B virus (HBV), TNM staging, maximum tumor diameter, LNM were more vulnerable to HCC. Besides, patients with SMYD3 VNTR 3/3 genotype had lower 2- and 3-year survival rate. The COX regression analysis revealed that drinking history, family history of HCC, SMYD3 VNTR 3/3 genotype, TNM staging, and LNM were all related to the prognosis of HCC. Conclusion This study indicates that drinking history, family history of HCC and SMYD3 VNTR 3/3, TNM staging, maximum tumor diameter, LNM might be risk factors for HCC, and SMYD3 VNTR 3/3 might contribute to a lower 2- and 3-year survival rate of patients with HCC.

Background Kinase inhibitor sorafenib is the most widely used drug for advanced HCC clinical treatment nowadays. However, sorafenib administration is only effective for a small portion of HCC patients, and the majority develop sorafenib-resistance during treatment. Thus, it is urgent to discover the endogenous mechanism and identify new pharmaceutical targets of sorafenib-resistance. Methods Pregnane X receptor (PXR) was detected by immunohistochemistry and quantitative PCR. GST-pull down and LC-MS/MS was used to detect the interaction of PXR and Sorafenib. To test the properties of HCC tumor growth and metastasis, in vivo tumor explant model, FACS, trans-well assay, cell-survival inhibitory assay and Western blot were performed. In terms of mechanistic study, additional assays such as ChIP and luciferase reporter gene assay were applied. Results In the present work, we found high PXR level in clinical specimens is related to the poor prognosis of Sorafenib treated patients. By the mechanistic studies, we show that sorafenib binds to PXR and activates PXR pathway, and by which HCC cells develop sorafenib-resistance via activating. Moreover, PXR overexpression helps HCC cells to persist to sorafenib treatment. Conclusion This study reports the endogenous sorafenib-resistance mechanism in HCC cells, which offers an opportunity to design new therapeutic approaches for HCC treatment. General significance PXR mediates sorafenib-resistance in HCC cells and targeting PXR can be a useful approach to facilitate HCC treatment.

The fabrication of ultrathin MOFs nanosheets (just single- or few-layer) is highly desired but seriously restricted by the relatively strong interactions between layers in layered MOFs precursors. Herein, for the first time, we employ a proof-of-concept weak supramolecular-interactions strategy to construct ultrathin uranyl-organic framework nanosheets. Impressively, the thickness of the resulting nanosheets is extremely thin down to only 1 nm, just equal to two layers, and also shows high dependence on the stacking mode of 2D uranyl MOFs precursors, for example, two layers in the eclipsed stacking mode vs. eight layers in the staggered stacking mode. Most importantly, this would significantly tailor their optical and electronic properties. As a result, the ultrathin nanosheet samples (two layers) present significantly enhanced photocatalytic oxidation activity compared to their pristine counterpart (4.5 times) and another nanosheet sample (eight layers, 2.2-fold). This work may open up a gate toward ultrathin uranyl-organic nanosheet for advanced functions.

The 18 kDa translocator protein (TSPO) is a five transmembrane domain protein that plays a crucial role in neurosteroid (e.g., allopregnanolone) synthesis by promoting the transport of cholesterol to the inner mitochondrial membrane. This protein is predominantly expressed in steroid-synthesizing tissues, including the central and peripheral nervous system, affecting stress-related disorders such as anxiety and depression. Recent studies have focused on the hippocampal dentate gyrus, which is very important for involvement of anxiety and depression. However, the exact role that TSPO plays in the pathophysiology of anxiety and depression and the involvement of the hippocampal dentate gyrus in regulating these behavioural effects remain elusive. This study used the lentiviral vectors mediating TPSO overexpression to assess the effects of TPSO overexpression in the hippocampal dentate gyrus on anxiolytic and antidepressant-like behavioural effects in mice. The expression of TSPO and the concentration of allopregnanolone in hippocampus tissues (3 mm in diameter around the injection site on both sides) were measured by Western blot and ELISA, respectively. The results indicated that microinjection of the LV-TSPO resulted in a significant increase in TSPO expression and allopregnanolone concentration in the hippocampus. Moreover, TSPO overexpression of the mouse hippocampal dentate gyrus generated significant anxiolytic and antidepressant-like behavioural effects in a series of behavioural models. These effects were completely blocked by the TSPO antagonist PK11195 (3 mg/kg, intraperitoneally) and the 5α-reductase inhibitor finasteride (5 mg/kg,intraperitoneally). Meanwhile, the increased allopregnanolone was also reversed by PK11195 and finasteride. In addition, neither PK11195 nor finasteride had an effect on the expression of TSPO. Overall, our results are the first to suggest that the overexpression of TSPO in the hippocampal dentate gyrus produced anxiolytic and antidepressant-like behavioural effects that are partially mediated by downstream allopregnanolone biosynthesis. Our results suggest that TSPO would be a potential anxiolytic and antidepressant therapeutic target.

To minimize the assembly stress and thermal stress introduced by the support structure, and ensure the high surface accuracy and high thermal stability of space mirror. An ultra-lightweight design of secondary mirror was carried out for some space remote sensor, and three tangential bipods were used for quasi-kinematic support. Firstly, the design principle of quasi-kinematic support structure was investigated, and advantages of bipod kinematic support were analyzed from the angle of degree of freedom decoupling. Based on structure designed above, the finite element model was established. Taking surface accuracy of the mirror as optimization objectives, the integrated optimization method was adopted to extract the structural parameters with high sensitivity on the surface accuracy in the flexible support structure, and parameters optimization design was carried out. Finally, the static and dynamic characteristics of the optimized mirror assembly were analyzed. The analysis results showed that the surface shape accuracy (RMS) of the mirror assembly is better than 1 nm under a load case of 1g gravity when the optical axis is level. Surface accuracy (RMS) is better than 2 nm under the load case of 4℃ uniform temperature rise. The first-order natural frequency of the secondary mirror assembly is 587 Hz. The optimized mirror support structure can well unload the additional deformation caused by the support structure, and has good dynamic stiffness, which verifies that the designed mirror and its support structure are reasonable, and the optimization design method is reliable. This paper provides a reference and idea for the design of flexible support structure of space mirror.

The separation of C2H2/C2H4 mixtures is of industrial importance in the production of high-purity C2H2 and C2H4. The primary objective of this work is to enhance the selectivity of C2H2/C2H4 separation by developing a method for appropriate modification of porous adsorbents. Toward this end, directly doping low-content Na+ ions into covalent organic frameworks (COFs) via cation exchange is proposed in this work. Relative to the pristine COF, COF-ECUT-1, with C2H2 and C2H4 adsorption capacities of 55.39 cm3 g−1 and 28.63 cm3 g−1, the Na+-anchored phase with just 4.0 wt% sodium content, Na@COF-ECUT-1, enables largely enhanced adsorption ability with the corresponding values of 89.70 cm3 g−1 and 49.26 cm3 g−1, respectively. As a result, the adsorption selectivity of C2H2 over that of C2H4 is enhanced from 6.33 to 9.41, and the separation potential estimated by the simulated transient breakthrough is largely improved about three-fold. The density functional theory (DFT) calculation reveals that the trap of Na+ within the COF channel affords strong affinity towards C2H2 or C2H4 through Na–π interactions and relatively stronger contact for C2H2 than for C2H4 is observed. This result is in line with the experimental results of both enhanced C2H2 and C2H4 adsorption capacity and C2H2/C2H4 separation performance. This work outlines a general and simple method to enhance the gas separation performance upon COF materials.

To investigate multilineage-differentiating stress-enduring (Muse) by immunomagnetic bead screening from Wharton's jelly mesenchymal stromal cells(WJ-MSCs), and explore transplantation of Muse cell for safety and effectivensess of sub acute cord injury in rats.Donated Wharton's Jelly-mesenchymal stromal cells (WJ-MSCs) were successfully derived from a human umbilical cord by a series of procedures namely physical isolation of Wharton's Jelly from cord membrane, collagenase and trypsin treatment and density gradient centrifugation. Magnetic activated cell sorting was performed to specifically select SSEA3+ Muse cells, and flow cytometry and immunocytochemistry were used to identify further. In vivo, spinal cord contusion injury model in rats was induced by NYU-III impactor, and were randomly divided and equally into four groups, namely group A (sham), group B (control), group C (Non-Muse cells transplantation) and group D (Muse cells transplantation). Laminectomy was conducted in group A but no spinal cord contusion injury. Laminectomy and cord injury were performed in group B, C and D, 10 g trip rod was freely falling down from 12.5 mm. Two weeks later, group B, C and D were received PBS injection, Non-Muse cells transplantation and Muse cells transplantation respectively, four-point injection were performed in each cord with totally 4×10⁵ cells. BBB scores were evaluated on 1 day, 1, 2, 3, 4, 5 and 6 week after injury. Four weeks after cell transplantation, the rats were sacrificed, and immunohistochemistry were carried out to observe survival, migration and differentiation of the injected cells.The expression of CD105, CD90 and CD73 were over 99.5% in the derived WJ-MSCs population, but CD45 and CD14 were lower than 0.5%, positive rate of SSEA3+ was 1.46% under flow cytometer, However, after MACS sorting, the percentage of 92.0% Muse cells expressed SSEA3 and CD105, and immunohistochemistry results of SSEA3 showed typically membrane morphology with special processes. In vivo, BBB scores was 21 in group A at different time points. One-way ANOVA and LSD analysis showed that BBB scores in group C and D were significantly higher than that in group B (Immunomagnetic bead screening is efficient to select large number of purified SSEA3+ Muse cells. Muse cells could survive and target-migrate in injured cord to improve BBB scores continuously. Muse cells are a novel kind of seed cells in the spinal cord injury treatment.

Hypidone hydrochloride (YL-0919), is a novel structural antidepressant candidate as a triple selective serotonin re-uptake inhibitor (SSRI), 5-HT1A partial agonist and 5-HT6 agonist. Here, we investigated the rapid onset antidepressant-like effects of YL-0919 and the possible mechanism in rats exposed to a chronic unpredictable stress (CUS) paradigm. In the CUS rats, it was found that fluoxetine (FLX, 10 mg/kg) treatment exerted antidepressant actions on 20-22d, while YL-0919 or vilazodone (VLZ, a dual 5-HT1A partial agonist and SSRI) administrated once daily exerted faster antidepressant-like behaviors [4 days in the sucrose preference test (SPT) and 6 days in the novelty suppressed feeding test (NSF)]. Thereafter, the serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels were reversed by treatment with YL-0919 for 7 days. Furthermore, YL-0919 treatment for 5 days reversed the brain derived neurotrophic factor (BDNF)-mammalian target of rapamycin (mTOR) signaling and the key synaptic proteins, such as post-synaptic density (PSD95), GluR1 and presynaptic protein synapsin1. Meanwhile, the dendritic complexity of pyramidal neurons in prefrontal cortex (PFC) were also increased in the CUS rats. These data suggest that YL-0919 exerts a faster antidepressant-like effect on behaviors and this effect maybe at least partially mediated by the BDNF-mTOR signaling related dendritic complexity increase in the PFC.

We examined the therapeutic effects of argon-helium cryoablation guided by computed tomography (CT) in the treatment of sacral chordoma. This is a retrospective study. CT-guided argon-helium cryoablation was used to treat 9 sacral chordoma patients at our centers between January 2016 and June 2019. We collected data on treatment response and success. Data from long-term follow-up of treatment outcomes were also assessed. All patients were treated successfully according to the indicated technical parameters. There were no reports of procedure-related complications from any of the patients. Complete response (CR) was also achieved in all patients. Six patients (66.7%) achieved initial CR after 1 treatment session and 3 patients (33.3%) achieved secondary CR after 2 treatment sessions. The chordoma-related symptoms improved significantly in all patients after treatment. The mean visual analogue scale score improved from 7.3 before treatment to 4.2 after treatment (P

Thorium, as a nuclear-power replacement for the uranium-based nuclear reactors and an effective avenue to produce uranium source, has become a key element for the increasing energy demand. However, we now are seriously restricted to gain thorium from mineral, due to co-existence of thorium, uranium, and rare earth elements. Accordingly, there is an urgent need to develop solid extraction technique with both large thorium adsorption capacity and high adsorption selectivity. In this work, a COF (covalent organic framework) adsorbent, namely [NH4]+[COF-SO3−] was prepared for selective extraction of thorium from uranium, and rare earth elements. The selective adsorption towards Th(IV) is reflected on the large distribution coefficient (Kd) of 1.34 × 105 mL/g, the big difference up to two orders of magnitude in the adsorption capacity, and the high selectivity (more than nine). This ultrahigh Th(IV) capture up to 395 mg/g presents the largest value for Th(IV) adsorption by porous absorbents. Furthermore, the practical separation of Th(IV) from U(VI) and rare earth elements (Eu3+ and Ce3+) was for the first time executed by both the breakthrough experiment and membrane-based separation experiment. Most importantly, upon this breakthrough separation a Th(VI) solution with high purity up to 93.5% was obtained.

There is a serious need for fast-acting drugs to treat post-traumatic stress disorder (PTSD). Our previous studies revealed that YL-IPA08, a novel small-molecule TSPO agonist, exerted significant anti-PTSD effects in various animal models. However, the onset time of YL-IPA08 and its underlying mechanisms remain unclear. In the present study, we first investigated the time course of YL-IPA08 compared to selective serotonin reuptake inhibitors (SSRIs) in the well-known time-dependent sensitization model of PTSD. YL-IPA08 required only 2-4 days of treatment to take effect in behavioural models of PTSD, whereas sertraline required 7-8 days. Furthermore, the mechanism study revealed that YL-IPA08 elicited anti-PTSD-like effects associated with increased GABA levels and allopregnanolone efflux in the hippocampus and prefrontal cortex and increased corticosterone levels in the serum after only 5 days of treatment, whereas sertraline required 9 days. Our results demonstrate that YL-IPA08 can exert fast-onset anti-PTSD-like effects, and its mechanisms may be related to the increased GABA levels, allopregnanolone efflux and the hypothalamic-pituitary-adrenal (HPA) axis function.

To evaluate the feasibility, local control, and survival after computed tomography (CT)-guided cryoablation for adrenal metastases. This study included 31 consecutive patients with adrenal metastases who were treated by CT-guided cryoablation in our center from July 2011 to October 2017. The technical success rate, local progression rate, local progression-free survival (LPFS), systemic progression-free survival (SPFS), and overall survival were assessed. The predictors of survival were determined using univariate and multivariate Cox regression analyses. The primary and secondary technical success rates were 90.3% and 100%, respectively. None of the patients experienced a hypertensive crisis. The local progression rate during follow-up was 19.4%. Systemic progression was found in 9 patients. The cumulative 1-, 3-, and 5-year LPFS rates were 80.6%, 37.8%, and 18.4%, respectively. The cumulative 1-, 3-, and 5-year SPFS rates were 77.4%, 31.9%, and 14.6%, respectively. The cumulative 1-, 3-, and 5-year overall survival rates were 83.9%, 45.0%, and 30.0%, respectively. The existence of an extra-adrenal tumor was a significant independent predictor of worse overall survival (P = .012). The mean overall survival durations were significantly different between patients with and without an extra-adrenal tumor (16.6 ± 2.4 vs 50.9 ± 4.5 months, P

In this study, cysteamine-functionalized molybdenum disulfide quantum dots (MoS

Similar to other major electrical apparatuses, the reliability and stability of the dc network is becoming the most important issue when using the voltage-source-converter-based multiterminal dc (VSC-MTDC) system for offshore wind power integration. A coordinated control strategy of VSC-MTDC named master–auxiliary is proposed by combining the advantages of the voltage margin and voltage droop control. This strategy has three advantages. First, the master converter station with the constant dc voltage control can provide reference to the system dc voltage and is helpful for the stabilization of dc voltage. Second, the integrated control of the dc voltage in both master and auxiliary converter stations are helpful for providing adequate active power control (APC) and restraining large power variation. Third, the APC converter station can serve as a backup for the dc voltage control in abnormal conditions. In order to guarantee the reliability and stability of the system under various operating conditions, this paper introduces the priority of dc voltage control to the coordination control strategy. Moreover, a parameter optimizing method of controllers for this strategy is also proposed. Finally, the effectiveness of the master–auxiliary control is verified by simulations under normal and abnormal conditions.

A systematic theoretical study is reported on the mechanisms of reductive elimination from arylPd(II) trifluoromethyl complexes, an important elementary reaction for Pd-catalyzed trifluoromethylation reactions. Various mechanisms leading to the formation of trifluoromethylated products and also competing side pathways have been evaluated. Furthermore, ligand effects are systematically evaluated which provide valuable information about the favourable properties of the ancillary ligands for promoting reductive elimination of trifluoromethylated products from Pd(II) centers.

Fog-based VANETs (Vehicular ad hoc networks) is a new paradigm of vehicular ad hoc networks with the advantages of both vehicular cloud and fog computing. Real-time navigation schemes based on fog-based VANETs can promote the scheme performance efficiently. In this paper, we propose a secure and privacy-preserving navigation scheme by using vehicular spatial crowdsourcing based on fog-based VANETs. Fog nodes are used to generate and release the crowdsourcing tasks, and cooperatively find the optimal route according to the real-time traffic information collected by vehicles in their coverage areas. Meanwhile, the vehicle performing the crowdsourcing task can get a reasonable reward. The querying vehicle can retrieve the navigation results from each fog node successively when entering its coverage area, and follow the optimal route to the next fog node until it reaches the desired destination. Our scheme fulfills the security and privacy requirements of authentication, confidentiality and conditional privacy preservation. Some cryptographic primitives, including the Elgamal encryption algorithm, AES, randomized anonymous credentials and group signatures, are adopted to achieve this goal. Finally, we analyze the security and the efficiency of the proposed scheme.

In this paper, pavement performance index PCI, road surface deflection and pavement rutting are proposed as the design indexes of pavement structure by analyzing the desert region of bad natural environment under heavy load traffic asphalt pavement condition and using finite element analysis. The stress distribution of durable asphalt pavement structure in desert area was obtained. The results showed that it is an approximate linear relationship between maximum vertical deformation of road surface and wheel load under different wheel load. With the increase of axial load, the maximum vertical deformation increases gradually. The maximum tensile stress of the road surface is symmetrical distribution with the wheel axis. The shear stress in the pavement structure increases with the increase of depth, and the shear stress reaches the peak value in the distance from the road surface 5cm. The results of the research can be a scientific theoretical support and a technical guidance for the selection and structural design of the asphalt pavement in the desert region.

The hydrophosphorylation of aldehydes with a P-stereogenic H-phosphinate was realized by heating two compounds in a neat state or catalyzed by a base, to afford P-retention α-hydroxyl phosphinates. The (SP,SC) and other diastereomers were isolated, and their structures were confirmed by NMR spectroscopy and crystallography.

The microscopic characteristics of solid particles have important influence on the formation of fluid slag, coarse slag and fine slag during entrained-flow gasification process. Based on the bench-scale opposed multi-burner (OMB) gasifier, solid particles were sampled at different axial distances along the gasifier chamber under typical operating conditions (oxygen and carbon atomic ratio at 1.0). The microscopic characteristics of solid particles were studied by using N2 adsorption-desorption and scanning electron microscopy (SEM) methods. The results show that the solid particles are comprised mainly of porous irregular particle and spherical particle, and few solid particles generated at burner plane perform as dense irregular and hollow shape. As the gasification reaction proceeds along the axis of gasifier, the surface structure of particles becomes rougher, and the pore structure increases. The isotherms of particle samples are all type II, and the particle samples consist of continuous and complete system of pores. The hysteresis loops are H3-type, and there are a large amount of fractured pores. BET surface area and pore volume increase with increasing distance from the burner plane, and average pore diameter gradually reduces, and larger changes occur in the vicinity of the burner plane. The mesopores less than 10 nm vary apparently and increase with increasing distances from the burner plane, while the pores larger than 10 nm are almost unchanged.