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Inflammatory bowel disease (IBD) is a persistent and chronic disease that is characterized by destructive gastrointestinal (GI) inflammation. Researchers are trying to identify and develop new and more effective treatments with no side effects. Acute and chronic mouse models of IBD were established using dextran sulfate sodium (DSS) solution. To evaluate the efficacy and mechanism, umbilical cord mesenchymal stem cells (UCMSCs) were obtained from Kunming (KM) mice and humans. In the chronic IBD study, the survival rates of the normal control, model, mouse UCMSC (mUCMSC) and human UCMSC (hUCMSC) groups were 100%, 40%, 86.7%, and 100%, respectively. The histopathological scores of the normal control, intraperitoneal injection, intravenous treatment, and model groups were 0.5 ± 0.30, 5.9 ± 1.10, 8.7 ± 1.39, and 8.8 ± 1.33 (p = 0.021). UCMSCs promoted the expression of the intestinal tight junction protein occludin, downregulated the protein expression of the autophagy marker LC3A/B in colon tissue, and upregulated the expression of VEGF-A and VEGFR-1 at the injured site. This study provides an experimental model for elucidating the therapeutic effects of UCMSCs in IBD. We provide a theoretical basis and method for the clinical treatment of IBD using UCMSCs.

Traditional fluorescent materials used in the anti-counterfeiting field usually exhibit monochromatic luminescence at a single-wavelength excitation, which is easily forged by sophisticated counterfeiters. In this work, Zn

Background: Umbilical cord mesenchymal stem cell transplantation can treat metabolic syndrome, but the tracing of cells in the body after transplantation has always been a problem. Tree shrew umbilical cord mesenchymal stem cells were labeled with the dark red fluorescent dye DIR and a metabolic syndrome model in tree shrew was generated. The migration, distribution, colonization and survival of the cells were observed. Methods: Tree shrew umbilical cord mesenchymal stem cells were labeled with the dark red fluorescent dye DIR. Three days after the tree shrew model was generated, the pancreas, kidney and liver were placed in a small animal live imager to observe the distribution of the labeled cells. Result: The labeled cells showed deep red fluorescence in the live imager. After treatment with the transplanted cells, dark red fluorescent signals were observed in the liver, kidney and pancreas of the tree shrews but not in the untreated group and no dark red fluorescent signal was observed in the cell distribution.

Yindan Xinnaotong soft capsule (YDXNT) is a clinically effective herbal prescription used for the treatment of cardiovascular and cerebrovascular diseases. Since Chinese medicines (CMs) exert their effects via a "multiple-components and multiple-targets" mode, discovery of the active compounds with interactive effects may contribute to reveal their mechanisms of action.This study aimed to establish an image-based fingerprint-efficacy screening strategy to identify active compounds with interaction effects from CM prescription, using YDXNT to inhibit microglia-mediated neuroinflammation as an instance.A multi-component random content-oriented chemical library of YDXNT was constructed by uniform design, and their chemical fingerprint was profiled by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) methods. Then the neuroinflammation activities of chemical library members of YDXNT were determined by image-based dual phenotypic quantification. Subsequently, fingerprint-efficacy correlation and random forest analysis were applied to predict the potentially active compounds with interactive effects. Finally, the interactive effects among the active compounds were confirmed by quantitative polymerase chain reaction (qPCR) and apoptosis analysis, and network pharmacology was applied to explore the possible mechanisms.Image-based fingerprint-efficacy correlation analysis revealed that six tanshinones (TNs) and four flavonoids (FAs) were potential anti-neuroinflammatory compounds. The inter-family of TNs and FAs possessed obvious interactive effects (combination index ≤ 0.825). Moreover, the combination of scutellarein and tanshinone I (2:1, w/w) was discovered as the possible interactive combinatorial components, which, comparing with individual scutellarein or tanshinone I, shown more powerful effects on anti-inflammatory and anti-apoptotic effects in lipopolysaccharide (LPS)-induced BV2 cells. Network pharmacology showed that the active compounds might suppress microglia-mediated neuroinflammation via multiple targets in the T cell receptor, Jak-STAT, and Toll-like receptor signaling pathways.The image-based fingerprint-efficacy strategy simplifies the screening process of efficacious component combinations in CMs for complex diseases, which also offers a promising approach to explore the integrative therapeutic mechanisms of CMs.

Background Cholangiocarcinoma (CCA) is one of the deadliest cancers of the digestive tract. The prognosis of CCA is poor and the 5-year survival rate is low. Bioinformatic analysis showed that early mitotic inhibitor 2 (EMI2) was overexpressed in CCA but the underlying mechanism is not known. Methods The data on bile duct carcinoma from TCGA and GEO databases were used to detect the expression of EMI2. The transcription factors of EMI2 were predicted using JASPAR and PROMO databases. Among the predicted transcription factors, YY1 has been rarely reported in cholangiocarcinoma, and was verified using the luciferase reporter gene assay. RT-PCR was performed to predict the downstream pathway of EMI2, and PI3K/Akt was suspected to be associated with it. Subsequently, in vivo and in vitro experiments were conducted to verify the effects of silencing and overexpressing EMI2 and YY1 on the proliferation, invasion, and metastasis of the bile duct cancer cells. Results EMI2 was highly expressed in CCA. Silencing EMI2 inhibited the proliferation, invasion, and migration of CCA cells, arrested cell cycle in the G1 phase, and promoted of apoptosis. The luciferase reporter gene assay showed that YY1 bound to the promoter region of EMI2, and after silencing YY1, the expression of EMI2 decreased and the progression of CCA was inhibited. Moreover, key proteins in the PI3K/Akt signaling pathway decreased after silencing EMI2. Conclusion EMI2 may be one of the direct targets of YY1 and promotes the progression of CCA through the PI3K/Akt signaling pathway.

Shuangchi Liu,1 Zhiduan Xu,1 Zhuling Fang,2 Dengyong Zhang,1 Zhongqiang Qin,1 Longfei Fan,1 Jiakang Duan,1 Hongxiang Yin,1 Yigang Zhang,1 Qing Pang,1,3 Yi Tan1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, People’s Republic of China; 2Department of Medical Laboratory, Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China; 3Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, People’s Republic of ChinaCorrespondence: Yi Tan; Qing PangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of ChinaEmail doctortanyi2007@126.com; portxiu2@126.comBackground: Advanced liver fibrosis can lead to cirrhosis, portal hypertension and liver failure. Besides, advanced liver fibrosis and cirrhosis are the major risk factors for hepatocellular carcinoma (HCC). Almost all patients with HCC also have liver cirrhosis. This study aims to predict the survival rate of hepatitis B-related hepatocellular carcinoma (HCC) by age, international standardized ratio, albumin and γ-glutamyl transpeptidase (AIAG), an indicator measuring the degree of cirrhosis.Methods: A total of 501 hepatitis B-related HCC patients experiencing radical surgery were analyzed, retrospectively. General data about demographics and labs were collected at the date of diagnosis to calculate AIAG [age, international standardized ratio (INR), albumin and gamma-glutamyl transferase (GGT)]. The Kaplan–Meier curves and Cox analysis were used to evaluate overall survival (OS) and recurrence-free survival (RFS). The C-index was calculated in R software (version 4.0.3) to evaluate the accuracy of the prognostic model.Results: During a median follow-up period of 30 months, 31.1% (156/501) of the patients died, and 34.3% (172/501) experienced the recurrence of HCC. Compared with patients with lower AIAG score, patients with higher AIAG score had higher Child-Pugh grade and were at higher Barcelona Clinic Liver Cancer (BCLC) stage (both P< 0.05). Multivariate analysis suggested that GGT, alpha fetoprotein (AFP), tumor size, BCLC stage and AIAG grade were independent predictors of OS and RFS. Furthermore, the combined use of tumor size, AFP and AIAG stage could predict survival significantly better (C-index=0.710, 95% CI: 0.669– 0.751) than BCLC stage.Conclusion: AIAG is significantly associated with survival of HCC patients, and provides additional prognostic information for patients with HCC. Our findings suggest that the combination of AIAG, tumor size and AFP stage has a better predictive value for the prognosis of patients with hepatitis B-related hepatocellular carcinoma. However, it is necessary for more external evidences to determine clinical utility.Keywords: AIAG, hepatocellular carcinoma, survival, prognosis

Discovering effective combinational components (ECCs) and quality control markers of TCMs is still facing challenges because the holistic healing system comprises hundreds of compounds. Here, taking Yindan Xinnaotong soft capsule (YDXNT), a TCMs preparation composed by 8 herbs, as a case, a strategy that integrated multiple chromatographic analysis and bioactivity assay was proposed for potential ECCs of neuroprotection discovery. Firstly, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF MS) and gas chromatography-mass spectrometry (GC-MS) were applied for comprehensive profiling of the chemical constituents in YDXNT. Given the fact that the complex matrix interference makes it more difficult to identify potentially active compounds, we proposed a structure-diagnostic ions-oriented strategy to remove interference ions from the raw UHPLC-MS data. The proposed strategy consisted of different filtering methods, including diagnostic fragment ions filtering (DFIF), mass defect filtering (MDF) and neutral loss (NL). Using this strategy, a total of 124 compounds were rapidly identified. Among them, 62 non-volatile and 5 volatile constituents in 30 batches of YDXNT were quantified by UHPLC tandem triple quadrupole mass spectrometry (QQQ-MS) and GC-MS methods, respectively. In order to facilitate the quality control of YDXNT, candidate ECCs were selected based on the threshold setting of absolute -contents, and their neuroprotective effects were examined. Finally, a combination of 16 compounds, accounts for 2.80% (w/w) of original YDXNT, was identified as its potential ECCs, which could be considered for the improvement of quality standardization of YDXNT.

The relationship between bone marrow mesenchymal stem cells (BMSCs) and aging, as well as the antiaging effects of BMSCs, was observed. An aging macaque BMSC model was established. We isolated BMSCs from young and aged macaques and used RT-PCR and Western blot to confirm the aging-related mRNAs and their expression, revealing that TERT, SIRT1 and SIRT6 expression was decreased in the aged BMSCs. The morphology, immunophenotype, differentiation potential, proliferation potential, and antiaging effects of aged and young BMSCs on 293T cells were compared. The expression of aging-related genes and the difference between the secreted cytokines in natural aging and induced aging BMSCs were observed. The transcriptome of peripheral blood mononuclear cells from macaques was analyzed by high-throughput sequencing. Finally, the transcriptional characteristics and regulatory mechanisms of gene transcription in aging macaques were investigated.

The objective of this research is to integrate an RFID (Radio Frequency Identification) reader into a Wireless Sensor Network (WSN) to authorize or keep track of people carrying RFID tags. The objective was accomplished by integrating hardware and software. The hardware consisted of two WSN nodes – the RFID node connected to one of the WSN nodes, and a computer connected to the other WSN node. For the RFID equipment, we used the SM130-EK kit, which included the RFID reader and the RFID tags; and for the WSN, we used the Synapse Network Evaluation kit, which included the two sensor nodes. The software consisted of a program module developed in Python to control the microprocessors of the nodes; and a database controlled by a simple program to manage the tag IDs of people wearing them. The WSN and RFID nodes were connected through I2C interfacing. Also, the work of sending commands to the RFID node, to make it read a tag and send it back to the computer, was accomplished by the Python code developed which also controls the data signals. At the computer, the received tag ID is evaluated with other existing tag IDs on the database, to check if that tag has authorization or not to be in the covered area. Our research has the potential of being adapted for use with secure real-time access control applications involving WSN and RFID technologies.

Posthepatectomy liver failure (PHLF) is a life-threatening complication after liver resection, resulting in an increased morbidity and mortality. Epidemiological evidence of the association between preoperative albumin-bilirubin (ALBI) score, a newly established model for assessing liver functional reserve, and the risk of PHLF and mortality remains controversial. A systematical search for relevant literature was performed in PubMed, Embase, and Web of Science databases from December 2014 to September 2020. Odds ratio (OR) value and 95% confidence interval (CI) were extracted or calculated to synthetically estimate the association of preoperative ALBI score with PHLF and mortality. Meta-analyses were performed using a random-effects model. Twelve studies with a total of 21,348 patients were included in this meta-analysis. It was indicated that, compared to patients with a lower preoperative ALBI grade, patients with a higher grade had a significantly elevated risk of PHLF (6 studies, 18,291 patients; OR = 2.48, 95%CI: 2.00–3.07) and mortality (4 studies15, 139 patients; OR = 2.35, 95% CI: 1.38–4.00). In addition, when it was expressed as a continuous variable, ALBI was also a significant predictor of PHLF (6 studies, 3,833 patients; OR = 3.16, 95% CI: 2.07–4.81, per 1-point increase in ALBI score). No significant publication biases were detected as suggested by funnel plots inspection and Begg’s tests. The current meta-analysis demonstrates that preoperative elevated ALBI is associated with higher risk of PHLF and mortality after hepatectomy.

Background There is increasing evidence supporting coronavirus disease 2019 (COVID-19)-related coagulopathy. In the available literature, only 2 cases of superior mesenteric vein thrombosis have been described. Methods We present a peculiar case of high-grade small bowel obstruction in a patient with COVID-19 infection. Results Exploratory laparotomy revealed a congenital adhesion band with associated focal bowel ischemia contributed by superior mesenteric vein thrombosis and positive lupus anticoagulant. Conclusions It is important to consider the rare differential of mesenteric vein thrombosis and its related sequelae of mesenteric ischemia in a patient with COVID-19 who presents with abdominal pain.

A rapid ultra-high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-QqQ MS/MS) approach with high sensitivity and selectivity was developed for the quantification of twenty compounds, including 9 saponins, 8 flavonoids, 2 oligosaccharide esters and 1 phenolic acid, in rat plasma and brain, which was administrated intragastrically with Jia-Wei-Qi-Fu-Yin (JWQFY), Mass spectrometric detection was operated under multiple reaction monitoring (MRM) mode. All calibration curves possessed good linearity with correlation coefficients ( r2) higher than 0.9916 in their respective linear ranges. For intra- and inter-day precision, all the relative standard deviations (RSDs) at different levels were less than 14.68 %. Based on the UHPLC-QqQ MS/MS quantitative results, pharmacokinetic study and brain distribution of multiple components in JWQFY was then successfully performed. As a result, constituents with discrepancy structures showed diverse pharmacokinetic and distribution characteristics. For instance, ferulic acid (phenolic acid), 3, 6′-disinapoyl sucrose and tenuifoliside A (oligosaccharide esters) showed short Tmax ( 4 h). Besides, ferulic acid, epimedin C, icariin, glycyrrhizin, ginsenoside Rb1 and ginsenoside Rg1 were considered as the potential effective ingredients of JWQFY because of their relatively high exposure to blood and brain. Our study would provide relevant information for discovery of pharmacodynamic ingredients, as well as further action mechanisms investigations of JWQFY.

Aim: To explore the prognostic significance of Syt-7 in hepatocellular carcinoma (HCC) and the potential mechanisms. Methods: Immunohistochemistry was used to examine the expression of Syt-7. Overall survival and disease-free survival were compared between Syt-7 positive and negative groups. The effects of Syt-7 knockdown on BEL-7404 cells were further evaluated. Results: Syt-7 expression was significantly higher in HCC tumorous tissues compared with paracancerous tissues. Syt-7 was closely associated with α-fetoprotein tumor size, vascular invasion, tumor node metastasis stage and tumor differentiation. Syt-7 was an independent risk factor for overall survival and disease-free survival. Additionally, Syt-7 knockdown inhibited proliferation and colony formation and induced cell cycle arrest in HCC cells. Conclusion: Syt-7 overexpression forecasts unfavorable prognosis and promotes cell proliferation in HCC.

To compare the efficacy and outcomes of self-expandable metallic stent combined with catheter-loaded iodine-125 seeds (SEMS-CL-125I) brachytherapy versus conventional palliative surgery (PS) in advanced extrahepatic cholangiocarcinoma (EHCC). The retrospective analysis consisted of 101 advanced EHCC patients who received SEMS-CL-125I (n = 67) or underwent PS (n = 34). The clinical characteristics, postoperative complications and overall survival (OS) were compared between the two groups. Serum levels of bilirubin, transaminase, and albumin (ALB) were significantly improved at 1 month, 3 months, and 6 months postoperatively in both groups (all P

As highly conserved non-coding RNAs of approximately 18–24 nucleotides, microRNAs (miRNAs) regulate the expression of target genes. Multiple studies have demonstrated that miRNAs participate in the regulation of human cancer. MircoRNA-217 (miR-217) participates in the regulation of various tumors by specifically binding target genes and post-transcriptional regulation. In recent years, there have been numerous reports about miR-217 in tumor progression. MiR-217 is known mainly as a tumor suppressor, although some studies have shown that it functions as an oncomiR. Here, we review the current research related to miR-217, including its role in tumor progression and the molecular mechanisms.

Based on the characteristics of modern weapon injury, a repetitive model of traumatic systemic inflammatory response syndrome (SIRS) and an evaluation system were established. The models were treated with GFP-labeled tree shrew umbilical cord mesenchymal stem cells (UCMSCs). Forty out of 50 tree shrews were used to make a unilateral femoral comminuted fracture. LPS was injected intravenously to create a traumatic SIRS model. The other 10 shrews were used as normal controls. After the model was established for 10 days, 20 tree shrews were injected in the veins with GFP-labeled UCMSCs, and 18 tree shrews were not injected as the model control group. The distribution of GFP-labeled cells in vivo was measured at 2 and 10 days after injection. Twenty days after treatment, the model group, the normal control group, and the treatment group were taken to observe the pathological changes in each tissue, and blood samples were taken for the changes in liver function, renal function and heart function. Distribution of GFP-positive cells was observed in all tissues at 2 and 10 days after injection. After treatment, the HE staining results of the treatment group were close to those of the normal group, and the model group had a certain degree of lesions. The results of liver function, renal function and heart function tests in the treatment group were returned to normal, and the results in the model group were abnormally increased. UCMSCs have a certain effect on the treatment of traumatic SIRS and provide a new technical solution for modern weapon trauma treatment.

Rail tankers are the main tools of transport for liquid goods and represent a measuring instrument for trade settlement. The cylinder diameter of rail tankers must be measured for process quality control and to calculate the volume. In this paper, an automated system for non-tactile diameter measurements is presented. This study aims to improve the working efficiency and reduce the artificial labor intensity of such measurements. Therefore, a 3D laser scanner is selected and combined with a computing system. The scanner collects many points along with the coordinate information, and these points constitute the point cloud and accurately reflect the tanker shape. Then, the computing system processes the point cloud by establishing a digital model, calculating the fitting initial values, fitting the curved surface, etc., and it then displays the diameter value in a 3D diagram. To verify the performance of this method, the results are compared with those of the artificial method.

A model of allergic rhinitis (AR) in BALB/c mice was established and evaluated to provide experimental subjects for further research. Preparation of human umbilical cord mesenchymal stem cells (hUCMSCs), including isolation, expansion culture, passaging, cryopreservation, and preparation of cell suspensions, provided materials for experimental research and clinical treatment. The mouse AR model was established by ovalbumin (OVA) intraperitoneal injection and the nasal stimulation induction method, and the model had a good effect and high repeatability. GFP-labeled hUCMSCs had good effects and were stable cells that could be used for tracking in animals. Transplantation of hUCMSCs by intraperitoneal and tail vein injections had a specific effect on the AR model of mice, and tail vein injection had a better effect. Tracking of hUCMSCs in vivo showed that the three groups of mice had the greatest number of hUCMSCs in the nose at week 2. The mouse AR model was used to evaluate the efficacy of hUCMSC transplantation via multiple methods for AR. The distribution of hUCMSCs in vivo was tracked by detecting green fluorescent protein (GFP), and the treatment mechanism of hUCMSCs was elucidated. This study provides technical methods and a theoretical basis for the clinical application of hUCMSCs.

The design on synthesizing a sturdy, low-cost, clean, and sustainable electrocatalyst, as well as achieving high performance with low overpotential and good durability toward water splitting, is fairly vital in environmental and energy-related subject. Herein, for the first time the growth of sulfur (S) defect engineered self-supporting array electrode composed of metallic Re and ReS

Jia-Wei-Qi-Fu-Yin (JWQFY) is a newly developed anti-Alzheimer's disease (AD) prescription modified from a classical traditional Chinese medicine formula, Qi-Fu-Yin (QFY). However, a systematic understanding of its chemical constituents and molecular mechanisms is still elusive. To address this problem, comprehensive chemical profiling followed by network pharmacology-based analysis of JWQFY was performed. Firstly, a total of 136 compounds were characterized by high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF MS), 17 of them were specifically identified in JWQFY comparing with QFY. Seventy compounds were further quantified via a validated HPLC coupled with triple quadrupole tandem mass spectrometry (QQQ MS) method. Then the protein targets of the seventy compounds were gathered from public databases for network construction. As a result, fifty-seven compounds were filtered, which interacted with 655 targets. Thirty-four of them were mapped into the KEGG pathway of AD, indicating JWQFY might exert anti-AD effects by anti-inflammation, neuronal apoptosis intervening, Aβ production inhibition and phosphorylating tau protein moderating. Furthermore, in the compound-target-AD network, a list of hub compounds and hub targets was identified based on their topological features, including the degree, node betweenness and closeness. Four of the hub compounds were specifically originated from JWQFY, supporting the modification rationality of this formula. This study provided a scientific basis for understanding the bioactive compounds and the multi-target mechanism of JWQFY.

Phosphoglucomutase (PGM) is a key enzyme in glycolysis and gluconeogenesis, regulating both glycogen and trehalose metabolism in insects. In this study, we explored the potential function of phosphoglucomutase (PGM) using RNA interference technology in Nilaparvata lugens, the brown planthopper. PGM1 and PGM2 were found highly expressed in the midgut of brown planthoppers, with different expression levels in different instar nymphs. The glycogen, glucose, and trehalose levels were also significantly increased after brown planthoppers were injected with dsRNA targeting PGM1 (dsPGM1) or PGM2 (dsPGM2). In addition, injection of dsPGM1 or dsPGM2 resulted in increased membrane-bound trehalase activity but not soluble trehalase activity. Furthermore, the expression of genes related to trehalose and glycogen metabolism decreased significantly after injection with dsPGM1 and dsPGM2. The expression levels of genes involved in chitin metabolism in the brown planthopper were also significantly decreased and the insects showed wing deformities and difficulty molting following RNAi. We suggest that silencing of PGM1 and PGM2 expression directly inhibits trehalose metabolism, leading to impaired chitin synthesis. Electronic supplementary material The online version of this article (10.1007/s13205-020-2053-5) contains supplementary material, which is available to authorized users.

Ischemia-reperfusion injury is an important contributor to acute kidney injury and a major factor affecting early functional recovery after kidney transplantation. We conducted this experiment to investigate the protective effect of induced multipotent stem cell transplantation on renal ischemia-reperfusion injury. Forty rabbits were divided into four groups of 10 rabbits each. Thirty rabbits were used to establish the renal ischemia-reperfusion injury model, and ten rabbits served as the model group and were not treated. Among the 30 rabbits with renal ischemia-reperfusion injury, 10 rabbits were treated with induced peripheral blood mononuclear cells (PBMCs), and 10 other rabbits were treated with noninduced PBMCs. After three weekly treatments, the serum creatinine levels, urea nitrogen levels and urine protein concentrations were quantified. The kidneys were stained with hematoxylin-eosin (HE), periodic acid-Schiff (PAS) and Masson’s trichrome and then sent for commercial metabolomic testing. The kidneys of the rabbits in the model group showed different degrees of pathological changes, and the recovery of renal function was observed in the group treated with induced cells. The results indicate that PBMCs differentiate into multipotent stem cells after induction and exert a therapeutic effect on renal ischemia-reperfusion injury.

Serotonin is involved in the pathological processes of several liver diseases via the regulation of inflammatory response and oxidative stress. We aimed to investigate the role of serotonin in Concanavalin A- (Con A-) induced acute liver injury (ALI). ALI was induced in C57B/6 wild-type (WT) mice and tryptophan hydroxylase 1 (TPH1) knockout mice through tail vein injection of Con A (15 mg/kg body weight). Another group of TPH1 knockout ALI mice was supplied with 5-hydroxytryptophan (5-HTP) in advance to recover serotonin. The blood and liver tissues of mice were collected in all groups. Markedly increased serum levels of serotonin were identified after the injection of Con A. Increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and stronger hepatic tissue pathology were detected, suggesting that serotonin could mediate Con A-induced liver damage. Serotonin significantly facilitated the release of serum and intrahepatic inflammatory cytokines, including interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-17A (IL-17A), interferon-gamma (IFN-γ), and tumor necrosis-alpha (TNF-α), after the administration of Con A. In addition, serotonin significantly increased the intrahepatic levels of oxidative stress markers malonaldehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) and decreased antioxidant stress indicator glutathione (GSH) in Con A-treated mice. Additionally, serotonin promoted hepatocyte apoptosis and autophagy based on B-cell lymphoma-2 (Bcl-2), Bcl-2-asociated X protein (Bax), and Beclin-1 levels and TUNEL staining. More importantly, serotonin activated nuclear factor kappa B (NF-κB) and upregulated the hepatic expressions of high mobility group protein B1 (HMGB1), toll-like receptor-4 (TLR4), and downstream molecules in Con A-mediated liver injury. Serotonin 2A receptor was upregulated in liver tissue after Con A injection, and serotonin 2A receptor antagonist Ketanserin protected against Con A-induced hepatitis. These results indicated that serotonin has the potential to aggravate Con A-induced ALI via the promotion of inflammatory response, oxidative stress injury, and hepatocyte apoptosis and the activation of hepatic HMGB1-TLR signaling pathway and serotonin 2A receptor.

The present study aims to investigate the roles of herb pairs containing Angelicae Sinensis Radix (Danggui) in Xin-Sheng-Hua Granule (XSHG) on hemolytic and aplastic anemia (HAA) mice. HAA model mice were induced by acetyl phenylhydrazine and cyclophosphamide; then the samples of XSHG and its decomposed recipes (DY, DC, DT, DH, DJ, and DZ) were orally administrated to these mice. Indicators of peripheral blood routine, organ index, and ATPase activities were tested. Moreover, the main effective components in these samples were also analyzed by UHPLC-TQ-MS/MS. Clear separation between the control and model groups from score plot of principal component analysis (PCA) was easily seen, indicating that HAA model was successfully conducted. Afterwards, relative distance calculation method between dose groups and control group from PCA score plot was adopted to evaluate the integrated effects of hematinic function of different samples. And the orders of hematinic effects were as follows: XHSG > DJ > DT > DZ > DH > DC > DY. Further analysis of these samples by UHPLC-TQ-MS/MS revealed that XSHG underwent complicated changes when herb pairs containing Danggui were excluded from XSHG, respectively. Compared with XSHG, the vast majority of active compounds in sample DY (formula minus herb pair Danggui-Yimucao) decreased significantly, which could partly explain why herb pair Danggui-Yimucao made great contribution to XSHG. These findings showed that withdrawal analysis method is a valuable tool to analyze the impacts of herb pairs containing Danggui on XSHG, which could lay foundation to reveal the compatibility rules of this formula.

Background. Banxia Xiexin Decoction (BXXD) reportedly regulates glycolipid metabolism and inhibits pancreatic β-cell apoptosis. This study is aimed at investigating the protective effect of BXXD on tert-butyl hydroperoxide- (t-BHP-) induced apoptosis in MIN6 cells and the underlying mechanisms. Methods. MIN6 cells were preincubated with BXXD or liraglutide (Li) with or without PI3K inhibitor LY294002 (LY) for 12 h, following which t-BHP was added to induce MIN6 cell apoptosis. The protective effects of BXXD on MIN6 cells were evaluated by detecting cell viability and proliferation and glucose-stimulated insulin secretion (GSIS). The antiapoptotic effects were evaluated by Hoechst 33342 staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL). Malondialdehyde and glutathione peroxidase content and superoxide dismutase activity were measured using commercial kits. The expression of PI3K/AKT/FOXO1 signaling pathway-related signal molecules, and that of apoptotic indicators Bax, P27, and Caspase-3, was quantified using western blotting. Results. Preincubation with BXXD significantly improved t-BHP-induced proliferation inhibition and apoptosis and enhanced GSIS. t-BHP induced the generation of reactive oxygen species and inhibited the activities of antioxidant enzymes, which could be neutralized by pretreatment with BXXD. BXXD promoted the phosphorylation of AKT and FOXO1 in t-BHP-induced MIN6 cells. Moreover, BXXD attenuated the expression of related apoptotic indicators Bax, P27, and Caspase-3. LY abolished these effects of BXXD. Conclusion. BXXD protected MIN6 cells against t-BHP-induced apoptosis and improved insulin secretory function through modulation of the PI3K/AKT pathway and the downstream FOXO1, thus suggesting a novel therapeutic approach for type 2 diabetes mellitus (T2DM).

This study aimed at investigating the efficacy of percutaneous transhepatic biliary stenting (PTBS) combined with 125I seeds intracavitary irradiation in the treatment of extrahepatic cholangiocarcinoma (EHC) and to preliminarily explore the prognostic values of inflammation-based scores in these patients. A total of 113 clinically/pathologically diagnosed cases of EHC who received PTBS combined with 125I seeds implantation were retrospectively analyzed. The postoperative changes of clinical symptoms and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total serum bilirubin (TBIL), direct bilirubin (DBIL), and albumin (ALB) were observed. Preoperative clinical data were extracted to calculate inflammation-based scores, including systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelets-to-lymphocyte ratio (PLR). Kaplan–Meier survival curves and Cox regression analyses were used to evaluate the prognostic significance of inflammation-based scores. After operation, clinical symptoms such as jaundice and fever significantly improved in all patients. At 1 month and 3 months postoperatively, serum levels of ALT, AST, ALP, TBIL, and DBIL significantly reduced, and ALB significantly increased, compared with preoperative values. The median survival time of the patients was 12 months and the 1-year survival rate was 56.8%. Univariate analysis revealed that factors related to overall survival were CA19-9, TBIL, ALB, SII, and NLR. Multivariate analysis further identified SII and NLR as independent prognostic models. The combination of PTBS and 125I seeds intracavitary irradiation is an effective palliative treatment for advanced EHC. Elevated SII and NLR can be used to predict poor survival.

Background To date, epidemiological evidence of the association between preoperative prognostic nutritional index (PNI) and the prognosis of hepatocellular carcinoma (HCC) remains controversial. Methods A literature search was performed in the databases of PubMed, Embase, and Web of Science. Hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI) were extracted to estimate the association of preoperative PNI with overall survival (OS), disease-free survival (DFS), and postoperative recurrence of HCC, respectively. A random-effects model was used to calculate the pooled effect size. Results Thirteen studies with a total of 3,738 patients with HCC met inclusion criteria for this meta-analysis. It indicated that a lower level of preoperative PNI was a significant predictor of worse OS (HR = 1.82, 95%CI: 1.44-2.31) and DFS (HR = 1.49, 95% CI: 1.06-2.07). In addition, risk of postoperative recurrence was significantly higher in patients with a lower preoperative PNI (OR = 1.92, 95% CI: 1.33-2.76). Subgroup analysis based on therapeutic intent demonstrated a significant positive association between preoperative low PNI and worse OS for those patients undergoing surgical resection and for those undergoing TACE or non-surgical treatment. Conclusion The current meta-analysis demonstrates that preoperative PNI is a prognostic marker in HCC.

Umbilical cord mesenchymal stem cells (UC-MSCs) exert strong immunomodulatory effects and can repair organs. However, their roles in radiation injury remain unclear. We show that in tree shrews with acute radiation injury, injected UC-MSCs significantly improved survival rates, reduced lung inflammation and apoptosis, prevented pulmonary fibrotic processes, recovered hematopoiesis, and increased blood counts. A protein microarray analysis showed that serum levels of the anti-inflammatory cytokines IL-10 and IL-13 and the growth factors BMP-5, BMP-7, HGF, insulin, NT-4, VEGFR3, and SCF were significantly higher, while those of the inflammatory cytokines IL-2, TIMP-2, TNF-α, IFN-γ, IL-1ra, and IL-8 and the fibrosis-related factors PDGF-BB, PDGF-AA, TGF-β1, IGFBP-2, and IGFBP-4 were significantly lower in UC-MSC-injected animals. A transcriptome analysis of PBMCs showed that the mRNA expression of C1q was upregulated, while that of HLA-DP was downregulated after UC-MSC injection. These results confirm the immunohistochemistry results. eGFP-labeled UC-MSCs were traced in vivo and found in the heart, liver, spleen, lungs, kidneys, thymus, small intestine and bone marrow. Our findings suggest that UC-MSC transplantation may be a novel therapeutic approach for treating acute radiation injury.

We study the structural, electronic and magnetic properties of 3d transition metal (TM) atoms (Cr, Mn, Fe, Co, Ni and Cu) adsorbed GaN monolayer (GaN-ML) using first-principles calculations. The results show that, for 6 different TM adatoms, the most stable adsorption sites are the same. The adsorption of TM atoms results in significant lattice distortions. A covalent chemical bonding character between TM adatom and GaN-ML is found in TM adsorbed systems. Except for Ni adsorbed system, all TM adsorbed systems show spin polarization implying that the adsorption of TM induces magnetization. The magnetic moments of the adsorbed systems are concentrated on the TM adatoms and the nearest-neighbor N atoms of the adsorption site contributed slightly. Our analysis shows that the GaN-ML properties can be effectively modulated by TM adsorption, and exhibit various electronic and magnetic properties, such as magnetic metals (Fe adsorption), half-metal (Co adsorption), and spin gapless semiconductor (Cu adsorption). These present properties of TM adsorbed GaN-ML may be of value in electronics and spintronics applications.

Optical hysteresis behavior (OHB) is of great importance for technological applications including optical data switching and manipulation. In this study, the power-dependent luminescent property of a single one-dimensional NaYbF4:X3+ (X = Er, Ho, and Tm) microcrystal was systematically investigated. We observed the interesting OHB that a system exhibits two different optical responses for the same laser input. A series of real colour luminescence patterns with information-rich upconversion cryptography were also obtained, which offers great opportunities for optical barcoding at the single particle level. The intrinsic OHB strongly depends on excitation approach, excitation power density range, Yb3+ concentration and sample crystallinity rather than active center. The underlying mechanisms of the intrinsic OHB and luminescence loss were explored, and a mechanism based on permanent local structural changes and intrinsic defect induced luminescence quenching is proposed. The laser thermal effect was confirmed by decreased luminescence intensity ratio of 2H11/2 → 4I15/2 to 4S3/2 → 4I15/2 transitions of Er3+ as the excitation power increased. The luminescent loss includes both irreversible and reversible processes, and these two processes can be distinguished via excitation power cycling experiments. Reversible luminescence loss contributed to defect quenching due to energy migration from Yb3+ to the native defects, and irreversible luminescence quenching originated from the thermally induced permanent local structural changes of microcrystals. This work not only enables a deeper understanding of power-dependent OHB in related systems, but also provides the new dimensions for special applications such as multilevel anti-counterfeiting and intelligent memory storage.

BACKGROUND AND OBJECTIVE The objective of this study was to investigate the prognostic significance of several inflammation-based models in hepatitis B-associated hepatocellular carcinoma (HCC). PATIENTS AND METHODS We retrospectively reviewed 470 cases of hepatitis B-associated HCC. Preoperative data were collected to calculate the inflammation-based markers, including systemic immune-inflammation index (neutrophil×platelets/lymphocyte), platelets-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio (NLR). Overall survival and recurrence-free survival were estimated by the Kaplan-Meier method and Cox analysis. RESULTS During a median follow-up time of 29 months, 34.0% (160/470) of patients died and 36.0% (169/470) experienced recurrence. Compared with patients with lower scores of inflammation models, patients in the higher group had larger tumor diameter and higher risk of vascular invasion (both P

Efficient metal-free catalysts for oxygen evolution reaction (OER) are challenged for enhancing the efficiency of water electrolysis. Here, an extremely simple one-step calcination route is put forward to synthesize free-standing N-doped C electrocatalyst for the OER. The incorporation of N into carbon cloth (CC) can tune the electronic structure around the C sites for enhancing the reaction active sites and electrical conductivity, and optimizing adsorption energies for intermediates. As expected, the as-prepared CC-9NH3-3h electrode demonstrates remarkable OER performance in alkaline medium, affording an extremely low overpotential of 298 mV (@10 mA cm−2) and Tafel slope of 62 mV dec−1, which is comparable to that of a commercial RuO2 and other promising metal-based OER catalysts. Our findings provide opportunities to explore CC as a new class of self-supporting OER electrocatalyst, and to improve its performance by modulating their intrinsic structure.

The preparation of alloy nanoparticles for hydrogen evolution reaction (HER) is a feasible strategy to optimize the inherent electronic structure of bimetallic catalysts, affording high catalytic activity. However, most of the metal alloys prepared currently exist in the form of bimetals, so it is urgent to find a facile method for preparing alloys. Herein, we developed a facile process by desulfurization from bimetallic sulfide solid solution for effectively constructing an electrocatalyst of RuNi alloy implanted with S-doped defective carbon (RuNi-alloy@SC), which performs outstanding HER performance in both acidic and alkaline solutions. As expected, the optimized catalyst displayed quite a low overpotential of 34 mV at current density of 10 mA cm−2, small Tafel slope of 55 mV dec−1, and long-term durability over 120 h for HER operation in acidic solution. In alkaline medium, the low overpotential and Tafel slope of 93 mV and 96 mV dec−1 were further achieved. Density functional theory (DFT) simulations reveal the hydrogen adsorption free energy (ΔGH*) of RuNi alloy with different crystal faces, in which RuNi (1 0 3) face enables the lowest ΔGH* for HER, whose value equals to that of the Pt. This work provides an advanced method and novel insights into the design of alloy electrocatalyst for HER.

Qing Pang,1,* Hao Jin,1,* Kai Qu,2,* Zhongran Man,1 Yong Wang,1 Song Yang,1 Lei Zhou,1 Huichun Liu1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China *These authors contributed equally tothis work Background: Recent studies have showed that nonsteroidal anti-inflammatory drugs (NSAIDs) could reduce the risk of several types of cancer. However, epidemiological evidence of the association between NSAIDs intake and the risk of hepatocellular carcinoma (HCC) remains controversial. Methods: To assess the preventive benefit of NSAIDs in HCC, we simultaneously searched the databases of PubMed, EmBase, Web of Science, and Scopus and screened eligible publications. Results: A total of twelve articles (published from 2000 to 2017) from five countries were identified by retrieval. We observed a significantly lower risk of HCC incidence among users of NSAIDs than among those who did not use NSAIDs (pooled hazard ratio [HR] value =0.81, 95% confidence interval [CI]: 0.69–0.94). No evidence of publication bias was observed (Begg’s test, P=0.755; Egger’s test, P=0.564). However, when stratified according to the categories of NSAIDs, users of non-aspirin NSAIDs (HR =0.81, 95% CI: 0.70–0.94), but not aspirin (HR=0.77, 95% CI: 0.58–1.02), showed a statistically significant reduced HCC incidence. We also found that NSAIDs use significantly reduced the recurrent risk of HCC, with a HR value of 0.79 (95% CI: 0.75–0.84), whereas there was no statistically significant association between NSAIDs use and HCC mortality, with a HR value 0.65 (95% CI: 0.40–1.06). Conclusion: Taken together, our meta-analysis demonstrates that NSAIDs significantly reduce the incident and recurrent risk of HCC. Keywords: NSAIDs, aspirin, hepatocellular carcinoma, incidence, recurrence

Hao Jin,1–3 Geliang Xu,2 Qiang Zhang,3 Qing Pang,3 Meifang Fang3 1School of Medicine, Shandong University, Jinan, 2Department of Hepatic Surgery, Anhui Provincial Hospital, Hefei, 3Department of Hepatobiliary Surgery, The First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui, People’s Republic of China Background: Synaptotagmin-7 (Syt-7) is a member of the synaptotagmin (Syt) family, which plays an important role in many physiological and pathological processes. However, to the best of our knowledge, there is no study describing its function in tumors, particularly in hepatocellular carcinoma (HCC). Therefore, in this study, we examined the role of Syt-7 in HCC and attempted to elucidate its underlying mechanism. Materials and methods: We examined the expression levels of Syt-7 in HCC cell lines and normal hepatocytes by real-time quantitative polymerase chain reaction analysis. The effects of Syt-7 knockdown on in vitro cell growth were assessed by Celigo image cytometry, MTT assay, colony formation assay, and cell cy cle analysis. In vivo tumorigenesis was evaluated using a nude mouse model. The underlying molecular mechanism was evaluated using a PathScan Stress Signaling Antibody Array. Results: Syt-7 mRNA levels were highly expressed in Huh-7 and Hep3B cells; moderately expressed in SMMC-7721, HepG2, and BEL-7402 cells; and lowly expressed in normal hepatocytes L-O2. Functional experiments demonstrated that Syt-7 knockdown significantly suppressed cell proliferation and induced cell cycle arrest by increasing phosphorylation of Chk1 and p53. Furthermore, Syt-7 knockdown remarkably reduced the growth of xenograft tumors in mice. Conclusion: The results of this study suggest that Syt-7 plays a vital role in tumorigenesis and in the development of HCC. Syt-7 can be used as a new diagnostic and therapeutic target in HCC. Keywords: hepatocellular carcinoma, Syt-7, Chk1, p53, cell cycle

The structural, energetic and electronic properties of germanene adsorbed with small nitrogen-based molecules, including N 2 , NH 3 , NO 2 and NO, have been investigated by using first-principles calculations. The results show that all nitrogen-based molecules considered bind much stronger to germanene than to graphene due to the hybridized sp 2 -sp 3 bonding of Ge atoms. The N 2 , NO and NO 2 molecules all act as an acceptor, while the NH 3 molecule donates electrons to germanene. We also found sizable band gaps (2–158 meV) are opened at the Dirac point of germanene through N 2 , NH 3 , and NO 2 adsorptions, but with only slightly destroying its Dirac cone shape. The NO 2 molecule also shows a heavy p-type doping character and makes germanene to be metallic. Moreover, when adsorbed by NO molecule, the germanene can change to be a ferromagnetic half-metal with 100% spin-polarization at the Fermi level. Overall, the different adsorption behaviors of small nitrogen-based gas molecules on germanene provide a feasible way to exploit chemically modified germanene for a wide range of practical applications, such as field-effect transistors, gas sensors and spintronic devices.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality. 5-Hydroxytryptamine (5-HT) is an important regulatory factor in inflammation. The aim of this study is to investigate the role of 5-HT on cecal ligation and puncture- (CLP-) induced sepsis in the mouse model. CLP was performed on C57B/6 wild-type (WT) mice and tryptophan hydroxylase 1 (TPH1) knockout (KO) mice. The results showed that the 5-HT-sufficient group mice had a significantly lower survival rate than the 5-HT-deficient group in CLP-induced sepsis and septic shock. The KO-CLP sepsis group received a lower clinical score than the WT-CLP sepsis group. Meanwhile, the body temperature of mice in the KO-CLP sepsis group was higher than that in the WT-CLP sepsis group and was much closer to the normal body temperature 24 hours after CLP. The tissue histopathology analysis revealed that 5-HT markedly exacerbated histological damages in the peritoneum, lung, liver, kidney, intestinal tissue, and heart in sepsis. Moreover, significant lower levels of TNF-α, IL-6, bacterial loads, MPO, and ROS were discovered in the KO-CLP sepsis group in contrast to the WT-CLP sepsis group. In conclusion, 5-HT drives mortality and exacerbates organ dysfunction by promoting serum cytokines and bacterial loads as well as facilitating oxidative stress in the process of sepsis.