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The excessive inflammatory response mediated by macrophage is one of the key factors for the progress of acute pancreatitis (AP). Paeonol (Pae) was demonstrated to exert multiple anti-inflammatory effects. However, the role of Pae on AP is not clear. In the present study, we aimed to investigate the protective effect and mechanism of Pae on AP in vivo and vitro. In the caerulein-induced mild acute pancreatitis (MAP) model, we found that Pae administration reduced serum levels of amylase, lipase, IL-1β and IL-6 and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. And Pae decrease the ROS generated, restore mitochondrial membrane potential (ΔΨm), inhibit M1 macrophage polarization and NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) in vitro. In addition, specific NLRP3 inhibitor MCC950 eliminated the protective effect of Pae on AP induced by caerulein in mice. Correspondingly, the inhibitory effect of Pae on ROS generated and M1 polarization was not observed in BMDMs with MCC950 in vitro. Taken together, our datas for the first time confirmed the protective effects of Pae on AP via the NLRP3 inflammasomes Pathway.

The inflammatory immune response mediated by neutrophils is closely related to the progression of acute pancreatitis. Previous studies confirmed that CD177 is a neutrophil-specific marker involved in the pathogenesis of conditions such as systemic vasculitis, asthma, and polycythemia vera. Neutrophil extracellular trap (NET) formation is a specific death program by which neutrophils release nuclear DNA covered with histones, granule proteins, etc. It also plays an important role in host defense and various pathological reactions. However, the function of CD177 in regulating the generation of NETs and the development of acute pancreatitis (AP) is unclear. In our manuscript, CD177 was significantly elevated in blood neutrophils in patients and positively correlated with the AP disease severity. Then, recombinant human CD177 protein (rhCD177) could significantly improve pancreatic injury and the inflammatory response in AP mice, and reduce AP-related lung injury. Mechanistically, we found that rhCD177 could inhibit the formation of NETs by reducing reactive oxygen species (ROS) and myeloperoxidase (MPO)/citrullinated histone H3 (CitH3) release. For the first time, we discovered the potential of rhCD177 to protect AP in mice and inhibit the NET formation of AP. CD177 may be a potential treatment strategy for preventing or inhibiting the aggravation of AP.

Emerin (EMD) plays diverse roles in cellular polarity organization, nuclear stability, and cell motility, however, the biological role of EMD relevant to the migration and invasion of hepatocellular carcinoma (HCC) cells has not yet been illustrated. In the present study, we initially found that the upregulation of EMD in HCC tissues, and EMD expression was negatively correlated with the spontaneous metastatic potential of HCC cell lines. Loss of EMD in HCC cells facilitated cell migration and invasion in vitro and metastasis in vivo. Meanwhile, we demonstrated that EMD knockdown induced EMT but enhanced p21 expression in HCC cells. Notably, silencing of EMD in HCC cells increased the cytoplasmic localization of p21 protein, whereas p21 knockdown partially abrogated the migratory and invasive ability, EMT, and the actin cytoskeleton rearrangement induced by EMD knockdown in HCC cells. Our results indicated a significant role of EMD knockdown in the HCC cell motility and metastasis through upregulating the cytoplasmic p21, unveiling a novel mechanism of cell motility regulation induced by EMD.

To investigate the protein expression levels of cyclin-dependent kinase subunit 2 (CKS2) and the cluster of differentiation (CD) 47 in gastric cancer (GC) and their clinical significance. A total of 126 GC patients who underwent radical resection were selected as study subjects. Additionally, 32 patients with benign gastric tumour, 42 patients with low-grade intraepithelial neoplasia (LGIEN), and 49 patients with high-grade intraepithelial neoplasia (HGIEN) who underwent surgery were selected as the control groups. Immunohistochemistry was used to detect the expression of CKS2 and CD47 in surgical specimens. We statistically analysed the clinical significance of the expression of the two factors. (1) The positivity rates for CKS2 in benign gastric tumour tissue, LGIEN tissue, HGIEN tissue, and GC tissue gradually increased, that is, 6.3% (2/32), 30.9% (13/42), 38.8% (19/49), and 60.3% (76/126), respectively, and the positivity rates for CD47 were 18.8% (6/32), 38.1% (16/42), 46.9% (23/49), and 65.9% (83/126), respectively. (2) High expression of CKS2 and CD47 were associated with tumour diameter, Lauren classification, number of lymph node metastases, and TNM stage. In addition, the immunohistochemical scores for CKS2 and CD47 were positively correlated (r = .625, P = .000). (3) The median follow-up time of 126 patients was 46.5 months, and the overall survival (OS) rate was 40.5% (51/126). Survival analysis showed that compared with that in the CKS2 (-) group, the OS rate for patients in the CKS2 (+) group was significantly worse and that compared with the CD47 (-) group, the CD47 (+) group had significantly worse OS (30.1% vs 60.5%, χ

BACKGROUND/AIMS: This retrospective study aimed to evaluate the effect of low-dose aspirin (50–150 mg/d) on the severity of ischemic colitis. MATERIALS AND METHODS: A total of 244 patients admitted to our hospital for ischemic colitis between 2013 and 2018 were included in the study. Patients were divided into two groups—aspirin and non-aspirin groups—based on their recent history of aspirin use before the onset of ischemic colitis. Clinical performance, biochemical indices, and endoscopic findings were compared. RESULTS: The average age and the proportion of underlying disease, including hypertension, cerebral infarction, and coronary heart disease in the aspirin group was significantly higher than those in the non-aspirin group (p

In this study, the addition of chloride ions to silver colloid was proposed as an effective approach to enhance laser-induced breakdown spectroscopy (LIBS) signals. We studied the emission intensity of LIBS as a function of the concentration of chloride ions with an example of Mg I lines at the wavelengths of 383.23 and 383.83 nm. The experimental results showed that the limit of detection with this method was significantly improved, 30.6 ppb for Mg, compared with the order of ppm in the traditional LIBS method. This technique provides an effective method to improve the sensitivity of LIBS.

BACKGROUND: Considerable progress of ultrasound simulation on blood has enhanced the characterizing of red blood cell (RBC) aggregation. OBJECTIVE: A novel simulation method aims at modeling the blood with different RBC aggregations and concentrations is proposed. METHODS: The modeling process is as follows: (i) A three-dimensional scatterer model is first built by a mapping with a Hilbert space-filling curve from the one-dimensional scatterer distribution. (ii) To illustrate the relationship between the model parameters and the RBC aggregation level, a variety of blood samples are prepared and scanned to acquire their radiofrequency signals in-vitro. (iii) The model parameters are determined by matching the Nakagami-distribution characteristics of envelope signals simulated from the model with those measured from the blood samples. RESULTS: Nakagami metrics m estimated from 15 kinds of blood samples (hematocrits of 20%, 40%, 60% and plasma concentrations of 15%, 30%, 45%, 60%, 75%) are compared with metrics estimated by their corresponding models (each with different eligible parameters). Results show that for the three hematocrit levels, the mean and standard deviation of the root-mean-squared deviations of m are 0.27 ± 0.0026, 0.16 ± 0.0021, 0.12 ± 0.0018 respectively. CONCLUSION: The proposed simulation model provides a viable data source to evaluate the performance of the ultrasound-based methods for quantifying RBC aggregation.

In this paper, harmonic concise atoms for the mean scatterer spacing (MSS) estimation was proposed to distinguish the normal and the ablated liver tissues. First, the second harmonic RF echo signals are separated with the Butterworth bandpass filter from the ultrasound RF echo signals, and a series of Gabor atoms are found to represent the local components with the concentrated energy. Then, the concise atoms are selected from the found Gabor atoms to optimal match the coherent components in the harmonic signals. Finally, the locations of the adjacent concise atoms are used to estimate the MSSs. In the microwave ablation experiments, the fundamental and second-harmonic RF echo signals were collected from the regions of interest in the normal untreated porcine tissues and thermally coagulated tissues ablated for 300 s, respectively. The MSSs, as well as the means and standard deviations of the MSSs were calculated from the collected signals for further comparation. The experiment results showed that the harmonic-based MSSs had large difference between the normal and the ablated liver tissues. The decrement in the harmonic-based mean MSS, and standard deviation in the ten tissues were 56.33 %, and 8.33 % greater than the fundamental-based results. It indicated that the harmonic-based MSS results with the concise atoms could improve the MSS estimation accuracy to distinguish the normal and the thermal coagulated liver tissues induced by the microwave ablation.

Pulse wave velocity (PWV) is currently the gold standard for quantitatively measuring arterial stiffness, which is of great significance for the early diagnosis and effective prevention of cardio-cerebral vascular diseases. With the development of the ultrafast ultrasound imaging based on the plane wave technique, the ultrasonic transit time-based method with straightforward principle is preferable for the detection of the local PWV of carotid artery. However, the filtering parameter settings in this method are difficult to be flexibly controlled, and the results of pulse wave transit time estimations are not stable. Aiming at these problems, an adaptive local PWV estimation based on the particle swarm optimization algorithm is proposed. First, An improved particle swarm optimization (PSO) with a fitness function evaluated in terms of the Savitzky-Golay (SG) filter length, SG polynomial degree, tracking position and tracking points parameters in regional upstroke tracking (RUT) approach is used to find the most optimum parameter settings for PWV estimation. To quantitatively evaluate the proposed adaptive local PWV estimation method (PSO_RUT), an ultrasound simulation model for three age groups is used. Results show that the mean PWV deviations from theoretical values estimated by the proposed PSO_RUT method are just within 3.8%, and lower than that estimated by RUT method. Therefore, the PSO_RUT approach proposed in this study can provide effective means for the improvement on the accuracy of ultrasound-based carotid PWV estimation.

Complete and accurate separation of harmonic components from the ultrasonic radio frequency (RF) echo signals is essential to improve the quality of harmonic imaging. There are limitations in the existing two commonly used separation methods, that is, the subjectivity for the high-pass filtering (S_HPF) method and motion artifacts for the pulse inversion (S_PI) method. A novel separation method called S_CEEMDAN, based on the complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) algorithm, is proposed to adaptively separate the second harmonic components for ultrasound tissue harmonic imaging. First, the ensemble size of the CEEMDAN algorithm is calculated adaptively according to the standard deviation of the added white noise. A set of intrinsic mode functions (IMFs) is then obtained by the CEEMDAN algorithm from the ultrasonic RF echo signals. According to the IMF spectra, the IMFs that contain both fundamental and harmonic components are further decomposed. The separation process is performed until all the obtained IMFs have been divided into either fundamental or harmonic categories. Finally, the fundamental and harmonic RF echo signals are obtained from the accumulations of signals from these two categories, respectively. In simulation experiments based on CREANUIS, the S_CEEMDAN-based results are similar to the S_HPF-based results, but better than the S_PI-based results. For the dynamic carotid artery measurements, the contrasts, contrast-to-noise ratios (CNRs), and tissue-to-clutter ratios (TCRs) of the harmonic images based on the S_CEEMDAN are averagely increased by 31.43% and 50.82%, 18.96% and 10.83%, as well as 34.23% and 44.18%, respectively, compared with those based on the S_HPF and S_PI methods. In conclusion, the S_CEEMDAN method provides improved harmonic images owing to its good adaptivity and lower motion artifacts, and is thus a potential alternative to the current methods for ultrasonic harmonic imaging.

Human immediate early response 2 (IER2) has been implicated in tumor cell motility and metastasis; however, the underlying mechanisms in hepatocellular carcinoma (HCC) metastasis remain to be clarified. In this study, we demonstrate that dysregulation of IER2 was shown in HCC clinical samples, and IER2 expression resulted in the promotion of cell migration and invasion in vitro, and HCC tumor growth and pulmonary metastasis in vivo. Moreover, we showed that IER2 expression altered assembly of the actin cytoskeleton rearrangement. Furthermore, MAPK and PI3K/Akt signaling pathways induced by IER2 were confirmed to be probably involved in regulating the activity of Rho GTPases, such as RhoA, Rac1 and Cdc42. Collectively, our results indicated a significant role of IER2 in the HCC cell motility and metastasis through MAPK and PI3K/Akt signaling pathways to regulate the activity of Rho GTPases, thereby modulating actin cytoskeleton rearrangement, unveiling a novel mechanism of cell motility regulation induced by IER2.

The solidification microstructure of Mg–Gd–Y–Zr alloy was investigated via an experimental study and cellular automaton (CA) simulation. In this study, step-shaped castings were produced, and the temperature variation inside the casting was recorded using thermocouples during the solidification process. The effects of the cooling rate and Zr content on the grain size of the Mg–Gd–Y–Zr alloy were studied. The results showed that the grain size decreased with an increase in the cooling rate and Zr content. Based on the experimental data, a quantitative model for calculating the heterogeneous nucleation rate was developed, and the model parameters were determined. The evolution of the solidification microstructure was simulated using the CA method, where the quantitative nucleation model was used and a solute partition coefficient was introduced to deal with the solute trapping in front of the solid–liquid (S/L) interface. The simulation results of the grain size were in good agreement with the experimental data. The simulation also showed that the fraction of the eutectics decreased with an increasing cooling rate in the range of 2.6–11.0 °C·s−1, which was verified indirectly by the experimental data.

Purpose The aim of the present study was to investigate the effect of knockdown and knockout of the transcriptional co-activator with PDZ-binding motif (TAZ) on the migration, invasion and autophagy of the hepatocellular carcinoma (HCC) cell lines, as well as the functional connection between the autophagy and cell migratory processes induced by loss of TAZ in HCC cell lines. Methods HCC cell lines SMMC-7721 and SK-HEP1 stably knockdown and knockout of TAZ were established by the lentiviral-mediated TAZ knockdown and knockout approaches. Reverse transcription-quantitative real-time polymerase chain reaction and Western blotting were performed to examine the expression of TAZ and indicated genes in downstream pathways in HCC cell lines. Transwell assay and autophagic flux assay were used to evaluate the effect of TAZ knockdown and knockout on the motility and the autophagy of HCC cell lines. Results We initially found that TAZ exhibited highly abundant and was expressed predominantly in HCC cell lines with different spontaneous metastatic potential. Through performing loss-of-function assays, we demonstrated that both TAZ knockdown and knockout promoted HCC cell autophagy and reduced HCC cell migration, invasion and epithelial-to-mesenchymal transition. In addition, autophagy inhibition in TAZ knockdown and knockout SMMC-7721 and SK-HEP1 cells in the presence of 3-methyladenine or chloroquine partially abrogated the migratory and invasive ability induced by TAZ knockdown and knockout. Conclusion Our findings indicated that loss of TAZ in HCC cells suppressed cell motility probably via altering the autophagy, suggesting that TAZ emerges as an important target in regulating cell motility and autophagy in HCC cells, and blocking TAZ may be a novel therapeutic strategy against HCC.

In this paper, we report experimental observation of the influence of Ag nanoclusters growth on nanoparticle enhanced laser-induced breakdown spectroscopy (NELIBS). In this work, we studied changes in the emission intensity of LIBS, on the example of Si I line at the wavelength of 390.55 nm, as a function of the silver nanoclusters coverage. The emission intensity initially increases before beginning to saturate, and then decreases with increasing Ag nanoclusters coverage. The obtained Ag clusters show a red-shifted plasmon resonance peak with increasing cluster coverage. Atomic force microscopy (AFM) was used to provide information changes in the cluster size and shape. Additionally, a 3D finite-difference-time-domain (FDTD) simulation was performed to estimate the electric field enhancement numerically.

To investigate the occurrence of postoperative complications in and factors influencing the prognosis of patients undergoing radical gastrectomy after neoadjuvant chemotherapy.A total of 238 patients with gastric cancer were enrolled in this study. There were 194 patients who underwent neoadjuvant chemotherapy before surgery and 44 patients who underwent concurrent radiochemotherapy before surgery. The clinical data of patients and the incidence of postoperative complications were collected. Postoperative complications were graded based on the Clavien-Dindo classification. The impact of postoperative complications on the prognosis of patients was analysed.(1) The overall incidence of postoperative complications was 17.2% (41/238) among all patients. A total of 49 patients experienced postoperative complications, including 12 cases of grade I, 15 cases of grade II, seven cases of grade IIIa, three cases of grade IIIb, seven cases of grade IV, and four cases of grade V complications. A total of 21 patients experienced severe complications. Multivariate analysis indicated that age, body mass index (BMI), and scope of gastrectomy were independent risk factors for postoperative complications (The incidence of complications in patients undergoing radical gastrectomy after neoadjuvant chemotherapy is closely correlated with patient age and the scope of surgical resection, and the occurrence of severe complications has a significant adverse effect on patient prognosis.

To evaluate the effects of noise, bright light and mechanical stimulation on sleep, blood-brain barrier and cognitive function in septic rats.Forty male Sprague-Dawley (SD) rats were selected and intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS) was used to establish sepsis model. 0, 30, 45, 60, 75 dB noise stimulation or 0, 50, 100, 200, 400 Lux light stimulation were given to rats (all n = 4). The serum levels of cortisol and melatonin, and the cerebral content of Evans blue (EB) were measured 96 hours after the stimulation to determine the optimal intensity of intervention. The other 40 SD rats were randomly divided into control group (Con group), LPS group, noise intervention group (LPS+60 dB group), 200 Lux light intervention group (LPS+200 Lux group) and mechanical stimulation group (LPS+MS group), with 8 rats in each group. The open fields test and fear conditioning test were used to evaluate the exploratory behavior and cognitive function 96 hours after corresponding stimulation. The enzyme linked immunosorbent assay (ELISA) was used to detect cerebral level of interleukin-6 (IL-6) and serum levels of cortisol and melatonin. The blood-brain barrier integrity was assessed by EB staining. The protein levels of ZO-1, Claudin-5 and caspase-3 in the hippocampus were detected by Western blotting to assess the blood-brain barrier integrity and neuronal apoptosis.Compared with 0 dB group or 0 Lux group, the serum melatonin concentration in 60 dB group and 200 Lux group were significantly reduced, while the serum cortisol concentration and cerebral EB content were significantly increased. Therefore, 60 dB noise and 200 Lux light were selected in the subsequent experiments. Compared with Con group, the horizontal score and vertical score in the open field test in LPS group were significantly decreased. There were no significant differences in the proportion of freezing time, the cerebral contents of EB and IL-6, the serum levels of melatonin and cortisol, and the hippocampal expressions of ZO-1, Claudin-5 and caspase-3. Compared with LPS group, the horizontal score, vertical score and the percentage of freezing time in LPS+60 dB group, LPS+200 Lux group and LPS+MS group were significantly reduced [horizontal score: 73.8±9.7, 80.3±9.4, 64.5±8.3 vs. 103.6±15.5; vertical score: 9.4±1.7, 11.2±1.9, 6.8±0.9 vs. 15.9±2.8; the percentage of freezing time: (45.3±4.7)%, (53.3±5.8)%, (42.1±5.1)% vs. (66.1±6.3)%], the serum level of melatonin was significantly decreased (ng/L: 53.62±6.20, 44.25±6.41, 45.33±5.84 vs. 74.39±7.54), the serum level of cortisol was significantly increased (nmol/L: 818.34±95.53, 710.04±65.41, 989.73±91.63 vs. 398.82±72.59), the levels of EB, IL-6 in the brain tissue were significantly increased [EB (μg/g): 2.80±0.35, 2.38±0.31, 3.24±0.42 vs. 1.59±0.26; IL-6 (ng/g): 31.56±4.11, 26.69±3.75, 37.47±4.56 vs. 16.28±2.69], the expressions of ZO-1 and Claudin-5 were significantly decreased (ZO-1/β-actin: 0.37±0.04, 0.32±0.05, 0.24±0.04 vs. 0.80±0.09; Claudin-5/β-actin: 0.62±0.08, 0.47±0.06, 0.35±0.05 vs. 0.97±0.20), and the expression of cleaved caspase-3 was significantly increased (caspase-3/β-actin: 0.56±0.06, 0.39±0.04, 0.72±0.12 vs. 0.20±0.03), with statistically significant differences (all P0.05).60 dB noise, 200 Lux light or mechanical stimulation for 96 hours could inhibit the secretion of serum melatonin, promote the secretion of cortisol, and activate neuroinflammation in septic rats, and lead to neuronal apoptosis in hippocampus and hyper-permeability of blood-brain barrier, which in turn could cause sleep disturbance and cognitive impairment.

Objective: Wogonin has been reported to exhibit pharmacological effects against cancer by regulating cell proliferation, metastasis and apoptosis, however, the role of wogonin in hepatocellular carcinoma (HCC) remains poorly elucidated. Objective: The current study aimed to illustrate whether wogonin influences HCC cell cycle progression and apoptosis by regulating Hippo signaling. Methods: The effects of wogonin on HCC cell viability, cell cycle progression and apoptosis were analyzed by utilizing CCK-8 and flow cytometry. RNA-seq was employed to analyze the expression profiles between wogonin-treated and control HCC cells, and the selected RNA-seq transcripts were validated by Reverse Transcription-quantitative realtime Polymerase Chain Reaction (RT-qPCR). Immunofluorescence staining was performed to detect the distribution of YAP/TAZ in the nucleus and cytoplasm in HCC cells. Western blotting and human apoptosis array were performed to examine the expression of the indicated genes. Results: We demonstrated that wogonin induced cell cycle arrest and apoptosis of HCC cell lines SMMC7721 and HCCLM3. RNA-seq analysis showed enrichment in genes associated with cell cycle progression and apoptosis following incubation with wogonin in HCC cells, and the pathways analysis further identified that Hippo signaling pathways highly altered in wogonin-treated cells. Specifically, wogonin increased the phosphorylation of MOB1 and LATS1, promoted translocation of endogenous YAP and TAZ from the nucleus to the cytoplasm, and facilitated phosphorylation of YAP and TAZ. Notably, overexpression of YAP or TAZ partially abrogated the wogonin-mediated HCC cell cycle arrest and apoptosis, and reversed wogonin-mediated suppression of Claspin. Conclusion: Wogonin induced HCC cell cycle arrest and apoptosis probably by activating MOB1-LATS1 signaling to inhibit the activation of YAP and TAZ, and then decrease the expression of Claspin, suggesting that the understanding of the molecular mechanisms underlying wogonin-induced cell cycle arrest and apoptosis may be useful in HCC therapeutics.

Objectives Astilbin exerts immunoregulatory activities and plays anti-inflammatory effects in inflammation-associated diseases. IL-10-producing B cells are the major subset of regulatory B cells (Bregs) and inhibit inflammation and autoimmune diseases. This study aimed to analyse the inducing effect of astilbin on Bregs and investigate the involved molecular mechanisms. Methods The frequencies and activities of IL-10-producing Bregs were observed using the co-treatment of astilbin and lipopolysaccharide (LPS) ex vivo. The protective effect of astilbin/LPS-induced Bregs on dextran sulphate sodium (DSS)-induced colitis was confirmed in vivo. The molecular signalling events of Breg induction were checked via Western blot. CD40−/− and toll-like receptor (TLR) 4−/− B cells were treated with astilbin/LPS to determine the modulatory role of CD40 or TLR4 on astilbin/LPS-induced Bregs. Results Although astilbin alone could not affect Bregs, the co-treatment of astilbin and LPS remarkably induced CD19+ CD1dhi and CD19+ TIM-1+ cells which produced IL-10 ex vivo. Colonic CD19+ CD1dhi and CD19+ TIM-1+ cells were also increased in astilbin-treated mice with DSS-induced colitis. The adoptive transfer of CD19+ TIM-1+ cells pre-induced by astilbin/LPS directly suppressed the progression of DSS-induced colitis. Combined astilbin and LPS stimulated the STAT3 activation of CD19+ TIM-1+ cells but had no effects on SOCS3, AKT, NF-κB, Erk, JNK nor P38. Inhibiting the STAT3 phosphorylation of CD19+ TIM-1+ cells abolished Breg induction by astilbin/LPS. Furthermore, Breg induction was weakened in CD40−/− B cells with the decrease in STAT3 activation, but had disappeared in TLR4−/− B cells with no STAT3 activation, thereby confirming the indispensable role of TLR4 signalling in the induction of IL-10-producing Bregs. Conclusions This study reports the new immunoregulatory role of astilbin for promoting IL-10-producing B cells and suggests the possible use of astilbin in the therapy of inflammatory diseases.

Acinar cell necrosis is one of the most prominent pathophysiological changes of acute pancreatitis (AP). Asiaticoside (AS) is a triterpene compound with confirmed apoptosis-and necrosis-related activities. However, the specific effects of AS on AP have not been determined. In this study, we aimed to investigate the protective effect of AS on AP using two mouse models. In the caerulein-induced mild acute pancreatitis (MAP) model, We found that AS administration reduced serum amylase levels and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. And the levels of toll-like receptor 4 (TLR4) and necrotic related proteins (RIP3 and p-MLKL) of pancreatic tissue were reduced after AS administration. In addition, TLR4 deficiency eliminated the protective effect of AS on AP induced by caerulein in mice. Correspondingly, we elucidated the effect of AS in vitro and found that AS protected against pancreatic acinar cells necrosis and TAK-242 counteracted this protective effect. Meanwhile, we found that AS ameliorated the severity of pancreatic tissue injury and pancreatitis-associated lung injury in a severe acute pancreatitis model induced by l-arginine. Furthermore, Molecular docking results revealed interaction between AS and TLR4. Taken together, our data for the first time confirmed the protective effects of AS on AP in mice via TLR4 pathway.

This article presents a novel peroxidase mimetic by doping S atoms into reduced graphene oxide (rGO), which was synthesized through a facile hydrothermal reaction without any templates or surfactants. The peroxidase-like activity of S-doped rGO (S-rGO) is greatly boosted compared with the pristine rGO, demonstrating the peroxidase-like active sites are dominantly originated in sulfur-containing groups. The steady-state kinetic studies further indicate that S-rGO obeys the typical Michaelis-Menten curves and has a much smaller Michaelis constant (Km) for hydrogen peroxide (H2O2) and 3, 3′, 5, 5′-tetramethylbenzidine (TMB). In view of the outstanding performance of S-rGO as a peroxidase mimetic, an efficient and sensitive colorimetric detection platform for H2O2 and glucose has been successfully established. The linear detection for H2O2 is obtained in a range of 0.1–1 μM with an extremely lower detection limit of 0.042 μM, and glucose can be measured in a linear range of 1–100 μM, giving a detection limit of 0.38 μM. This study not only provides a new avenue for the reasonable design of heteroatom-doped carbon-based nanomaterials but also offers meaningful reference for detecting the important biomolecules in biotechnology.

In this paper, an experimental evidence of enhanced laser-induced breakdown spectroscopy (LIBS) emission using nanoparticles and amphiphiles was reported. The measurement showed an enhanced emissio...

Introduction Acute pancreatitis (AP) is a common clinical pancreatic disease. Patients with different severity levels have different clinical outcomes. With the advantages of algorithms, machine learning (ML) has gradually emerged in the field of disease prediction, assisting doctors in decision-making. Methods A systematic review was conducted using the PubMed, Web of Science, Scopus, and Embase databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Publication time was limited from inception to 29 May 2021. Studies that have used ML to establish predictive tools for AP were eligible for inclusion. Quality assessment of the included studies was conducted in accordance with the IJMEDI checklist. Results In this systematic review, 24 of 2,913 articles, with a total of 8,327 patients and 47 models, were included. The studies could be divided into five categories: 10 studies (42%) reported severity prediction; 10 studies (42%), complication prediction; 3 studies (13%), mortality prediction; 2 studies (8%), recurrence prediction; and 2 studies (8%), surgery timing prediction. ML showed great accuracy in several prediction tasks. However, most of the included studies were retrospective in nature, conducted at a single centre, based on database data, and lacked external validation. According to the IJMEDI checklist and our scoring criteria, two studies were considered to be of high quality. Most studies had an obvious bias in the quality of data preparation, validation, and deployment dimensions. Conclusion In the prediction tasks for AP, ML has shown great potential in assisting decision-making. However, the existing studies still have some deficiencies in the process of model construction. Future studies need to optimize the deficiencies and further evaluate the comparability of the ML systems and model performance, so as to consequently develop high-quality ML-based models that can be used in clinical practice.

// Dongling Teng 1, 2, * , Keyan Wu 1, 2, * , Yunyun Sun 1, 2, * , Min Zhang 1, 2 , Dan Wang 1, 2 , Jian Wu 1, 2 , Tao Yin 2 , Weijuan Gong 1, 2 , Yanbing Ding 1, 2 , Weiming Xiao 1, 2 , Guotao Lu 1, 2 and Weiqin Li 3 1 Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225000, Jiangsu, China 2 Laboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225000, Jiangsu, China 3 Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu, China * These authors contributed equally to this work Correspondence to: Guotao Lu, email: Gtlu@yzu.edu.cn Weiming Xiao, email: wmxiao@yzu.edu.cn Keywords: acute pancreatitis; CA199; pancreatic cancer; retrospective study Received: October 13, 2017 Accepted: November 13, 2017 Published: January 04, 2018 ABSTRACT Background and study aims: Carbohydrate antigen 19-9 (CA199) has been identified as a tumor marker for pancreatic cancer but also increases in benign lesions of the digestive system. However, literature associated with the relationship between CA199 and acute pancreatitis (AP) is limited. This study aimed to focus on serum CA199 level measurements in AP patients and the associated clinical significance. Materials and methods: From January 2006 to December 2015, 1,609 consecutive patients with AP were admitted to our department and included in the study. The relationships among the etiology of AP, the disease severity, the incidence of pancreatic cancer during hospitalization and CA199 levels were analyzed. Results: Serum CA199 levels were measured for 693 of 1,609 AP patients. Of those patients, 186 (26.8%) had elevated CA199 levels (> 37 U/ml). Patients with high CA199 levels were older and had predominantly biliary causes in comparison with patients with normal CA199 levels. There were no definite specific correlations between CA199 levels and disease severity in AP. In addition, serum levels of CA199 positively correlated with serum alanine aminotransferase, aspartate transaminase, glutamyl transpeptidase, alkaline phosphatase and creatinine levels. After stratification, the incidence of pancreatic cancer increased proportionally to CA199 levels in AP patients. Conclusions: Serum CA199 levels was elevated in patients with AP, especially in patients with biliary pancreatitis. AP patients with significantly increased CA199 levels may have a higher risk for the presence of pancreatic cancer. We recommended routinely monitoring CA199 levels during hospitalization for AP patients.

As an advanced near-net shape technology, squeeze casting is an excellent method for producing high integrity castings. Numerical simulation is a very effective method to optimize squeeze casting process, and the interfacial heat transfer coefficient (IHTC) is an important boundary condition in numerical simulation. Therefore, the study of the IHTC is of great significance. In the present study, experiments were conducted and a “plate shape” aluminum alloy casting was cast in H13 steel die. In order to obtain accurate temperature readings inside the die, a special temperature sensor units (TSU) was designed. Six 1 mm wide and 1 mm deep grooves were machined in the sensor unit for the placement of the thermocouples whose tips were welded to the end wall. Each groove was machined to terminate at a particular distance (1, 3, and 6 mm) from the front end of the sensor unit. Based on the temperature measurements inside the die, the interfacial heat transfer coefficient (IHTC) at the metal-die interface was determined by applying an inverse approach. The acquired data were processed by a low pass filtering method based on Fast Fourier Transform (FFT). The feature of the IHTC at the metal-die interface was discussed.

In this paper, red blood cell aggregation classification based on hyper spectral analysis of ultrasonic radiofrequency (RF) echo signals is proposed. Firstly, Morlet wavelet is applied to the sub-band decomposition of ultrasonic RF echo signals. Then, five statistical features including mean, variance, median, kurtosis and root mean square of each sub-band are calculated to form the feature vectors. 18 kinds of blood with different red blood cell concentration-aggregation are taken as samples, then multi-frame ultrasonic RF echo signals are collected using ultrasonic linear array probe. The region of interest (ROI) is selected from the B-mode image of a certain frame. 20 subbands are obtained by the hyper spectral analysis of each line of ultrasonic RF echo signals in the ROI. Five statistical features of each sub-band are calculated, and then the feature vectors are obtained after local normalization. Finally, support vector machine (SVM) and random forest classifiers are used to classify the feature vectors respectively. The overall average classification accuracy of SVM is $91.43\pm 6.17\%$ , and the overall average classification accuracy of random forest classifier is 96.19 ± 4.28 %.

Astilbin is a potential agent for autoimmune and inflammatory diseases and has a protective effect in mice with DSS-induced colitis. NK1.1

Wogonin exerts anti‐tumour activities via multiple mechanisms. We have identified that high‐dose wogonin (50 or 100 mg/kg) could inhibit the growth of transplanted tumours by directly inducing tumour apoptosis and promoting DC, T and NK cell recruitment into tumour tissues to enhance immune surveillance. However, wogonin (20–50 μM) ex vivo prevents inflammation by inhibiting NF‐κB and Erk signalling of macrophages and epithelial cells. It is elusive whether high‐dose wogonin promotes or prevents inflammation. To investigate the effects of high‐dose wogonin on murine colitis induced by dextran sodium sulphate (DSS), mice were co‐treated with DSS and various doses of wogonin. Intraperitoneal administration of wogonin (100 mg/kg) exacerbated DSS‐induced murine colitis. More CD4+ CD44+ and CD8+ CD44+ cells were located in the inflamed colons in the wogonin (100 mg/kg) treatment group than in the other groups. Frequencies of CD4+ CD25+ CD127− and CD4+ CD25+ Foxp3+ cells in the colons and spleen respectively, were reduced by wogonin treatment. Ex vivo stimulations with high‐dose wogonin (50–100 μg/ml equivalent to 176–352 μM) could synergize with IL‐2 to promote the functions of CD4+ and CD8+ cells. However, regulatory T cell induction was inhibited. Wogonin stimulated the activation of NF‐κB and Erk but down‐regulated STAT3 phosphorylation in the CD4+ T cells. Wogonin down‐regulated Erk and STAT3‐Y705 phosphorylation in the regulatory T cells but promoted NF‐κB and STAT3‐S727 activation. Our study demonstrated that high‐dose wogonin treatments would enhance immune activity by stimulating the effector T cells and by down‐regulating regulatory T cells.

Selective detection of toxic Hg2+ is of great significance in the control of the environmental and industrial pollution because it poses serious threat to human health. Herein, we present a differential pulse anodic stripping voltammetric (DPASV) method for Hg2+ detection by using hollow and porous three-dimensional nano-structured NiCo2O4 with cage-like morphology as an electrode modifier. The NiCo2O4 nanocages (NiCo2O4 NCs) derived from ZIF-67 (a cobaltic zeolite imidazole framework) possess large specific surface areas that can provide a large number of adsorption sites for Hg2+. The NiCo2O4 NCs modified glassy carbon electrode (NiCo2O4 NCs/GCE) was demonstrated to be an advantageous and high-performance platform for the electrochemical detection of Hg2+ with a wide linear range (0.1 nmol/L–3.5 µmol/L) and low detection limit (0.09 nmol/L). Additionally, the NiCo2O4 NCs/GCE was proved to be highly stable, representing it was benign to environment and could be well applied to detect Hg2+ in real water samples.

Due to the obstacle of sluggish kinetics on cathode of fuel cells and metal–air batteries, developing low-cost and durable electrocatalysts to replace the platinum-based catalysts still remains a grand challenge. Here, we describe a simple self-template approach to synthesize N-doped mesoporous carbon nanocages (FeCo@NC) embedded with FeCo alloy nanoparticles as oxygen reduction reaction (ORR) electrocatalyst. The resulting heterostructure is derived from corresponding PBA@PPy composites, which are pre-prepared by polymerization of polypyrrole (PPy) layer on Prussian blue analogue (PBA) nanocubes. The FeCo alloy nanoparticles with an average particle size of ∼10 nm are well dispersed and confined within the shell of carbon nanocages. Benefiting from the mesoporous structure and the synergetic interaction of binary metals, the optimized FeCo@NC-3-800 electrocatalyst exhibits comparable ORR performances (0.83 V for half-wave potential (E1/2), 5.323 mA cm−2 for limiting current density (Jk)), superior durability and excellent methanol tolerance to the commercial Pt/C (20 wt%). This work provides an appropriate strategy for general, efficient and practical synthesis of more promising non-precious metal electrocatalyst with high ORR activity.

Selective and sensitive monitoring of toxic heavy metals is prerequisite to the curb of water contamination. Herein, we present a differential pulse anodic stripping voltammetric (DPASV) method for the determination of mercury in water samples with a glassy carbon electrode (GCE) modified with nitrogen-doped reduced graphene (NRGO). Through thermal treatment of graphene oxide (GO) in NH3 atmosphere, nitrogen atoms can be facilely doped into the hexagonal lattice of graphene to produce NRGO. The NRGO modified GCE (abbreviated as NRGO/GCE) shows an impressively favorable electron transfer activity and a high stripping voltammetric response for mercury compared to that of reduced graphene oxide (RGO) modified electrode. Not only does the NRGO/GCE show an extraordinary low detection limit of 0.58 nM, it also demonstrates a wide linear concentration range from 1 nM to 800 nM and a high sensitivity of 2.69 μA/μM. Due to the excellent selectivity of the NRGO/GCE to mercury, the interference from other heavy metals such as Fe(III), Co(II), Ni(II), Cu(II), Mn(II), Cd(II), Al(III), Ca(II), and Pb(II) were almost negligible. Those outstanding features guarantee the proposed anodic stripping voltammetric method highly applicable to the assay of mercury ions in real water samples, which is validated by the conventional atomic fluorescence spectrometry.

Figure S1. After admission, the AP patient underwent CT scan to assess the disease. The waist circumference was regarded as an ellipse in the mathematical model. From the above diagram we can see that the long axis was 311.5 mm and the short one was 208.7 mm on the L4 plane, and the coefficient was × (short axis + long axis) ÷2 according to the ellipse formula. It is concluded that the Waist circumference of the patient is 82 cm. (DOCX 1308 kb)

Background and Aim. The incidence of nonalcoholic fatty liver disease (NAFLD) as a metabolic disease is increasing annually. In the present study, we aimed to explore the influence of NAFLD on the severity of acute pancreatitis (AP). Methods. The severity of AP was diagnosed and analyzed according to the 2012 revised Atlanta Classification. Outcome variables, including the severity of AP, organ failure (all types of organ failure), and systemic inflammatory response syndrome (SIRS), were compared for patients with and without NAFLD. Results. Six hundred and fifty-six patients were enrolled in the study and were divided into two groups according to the presence or absence of NAFLD. The non-NAFLD group contained 278 patients and the main etiology in this group was gallstone. The NAFLD group consisted of 378 patients and the main etiology was hyperlipidemia. The incidence of mild AP, moderately severe AP, and severe AP was 77.30%, 18.3%, and 4.3% in the non-NAFLD group and 58.2%, 33.9%, and 7.9% in the NAFLD group, respectively. There were significant differences between the two groups according to the severity of AP (P ≤ 0.001). In addition, the Ranson and BISAP scores as well as the incidence of SIRS and organ failure in the NAFLD group were higher than those in the non-NAFLD group (all P < 0.05). The patients were further divided into non-NAFLD, mild-NAFLD, and moderate-severe NAFLD (M+S-NAFLD) groups. The results showed that the severity of AP increased gradually from the non-NAFLD group to the M+S-NAFLD group. In addition, the incidence rates of SIRS and organ failure showed an upward trend with the aggravation of fatty liver severity. Multivariate logistic analysis showed that patients with NAFLD, especially those with M+S-NAFLD, had higher risks of SIRS and organ failure. Conclusions. Compared with non-NAFLD, NAFLD has a clinically relevant impact on the severity of AP and may be an early prognostic parameter for patients with AP.

Astilbin is a potential agent for autoimmune and inflammatory diseases and has a protective effect in mice with DSS-induced colitis. NK1.1- CD4+ NKG2D+ T cells are a subpopulation of regulatory T cells that produce TGF-β1 and IL-10. Whether astilbin directly promotes the induction of NK1.1- CD4+ NKG2D+ T cells and whether these astilbin-stimulated T cells exert an immune-regulatory role remain unclear. Here, we show that astilbin efficiently induces the production of NK1.1- CD4+ NKG2D+ T cells with high expressions of TGF-β1, IL-10, CCR6, and CCR9 in a dose-dependent manner ex vivo. These regulatory T cells also substantially inhibit the activities of CD8+ T cells and macrophages. Intraperitoneal injection of astilbin ameliorates the severity of colitis with an increase in the frequency of NK1.1- CD4+ NKG2D+ T cells in the colon tissue of DSS-treated mice. Moreover, adoptive transfer of NK1.1- CD4+ NKG2D+ T cells induced by astilbin remarkably protects against the onset of DSS-induced colitis. Finally, the PI3K, STAT3, and MAPK signaling pathways are involved in the induction of NK1.1- CD4+ NKG2D+ T cells by astilbin. Taken together, our study elucidates a new immune-regulatory mechanism of astilbin by inducing the regulatory NK1.1- CD4+ NKG2D+ T cells and indicates a potential clinical use of astilbin for patients with inflammatory bowel diseases.

Background: Transcribed ultraconserved regions (T-UCRs) are a subset of long noncoding RNAs. It has been reported that T-UCRs are dysregulated in cancers and play an important role in the development and progression of malignancies. uc.160 was found to be a suppressive factor of cancer development, but its role has not been fully elucidated. Methods: The uc.160 expression was examined in gastric cancer tissues and established cell lines by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The biological function of gastric cancer cells with uc.160 over-expression were investigated, and the interaction between uc.160 and microRNA miR-155 was examined by dual-luciferase reporter assay. PTEN levels were detected by Western blotting. Anti-tumor effects of uc.160 were further explored in tumor transplantation models. Results: uc.160 expression was significantly down-regulated in gastric cancer tissues and gastric cell lines as compared to adjacent normal tissues and immortalized gastric epithelial cell line (GES-1), respectively. Over-expression of uc.160 in SGC-7901 and AGS gastric cancer cells significantly suppressed their proliferation in vitro and in vivo. Moreover, uc.160 positively regulated the tumor suppressor protein PTEN. Interestingly, uc.160 was inhibited by microRNA miR-155 that is also a negative regulator of gastric cancer. Conclusion: uc.160 is significantly down-regulated in gastric carcinomas and can inhibit the tumor growth both in vitro and in vivo, suggesting that uc.160 may be used as a diagnostic marker and therapeutic target of gastric malignancies.

A series of phenyl derivatives were systematically investigated as carbon source to prepare carbon nanotubes. The phenyl derivatives with electron-donating groups are ideal carbon sources for the m...

The effect of die coating thickness on the heat transfer at the metal-die interface in squeeze casting process was studied, where the interfacial heat transfer coefficient (IHTC) was determined by applying an inverse approach based on the temperature measurements inside the mold. The acquired data were processed by a low pass filtering method based on Fast Fourier Transform (FFT). The die coating used in these experiments was water-based graphite which was sprayed onto the surface of the die cavity. The die coating thickness was measured by using TT260B coating thickness gauge. The results showed that the peak and average value of the IHTC increased with the increasing of the die coating thickness when the die coating thickness was less than 32 μm. When it was more than 32 μm, the peak and average value of the IHTC decreased with the increasing of the die coating thickness. Besides, the effect of the applied pressure on the IHTC was getting smaller as the die coating thickness increased.

A custom experimental apparatus was designed to realize the in-situ observation of dendritic growth under pressure in directional solidification of model material, succinonitrile. The evolution of dendritic growth under ambient pressure \((P_{0} )\) and pressure of 3.0 MPa (P) was captured by a high-speed microscope and compared by analyzing qualitative distinctions in morphology and the quantitative ones in tip velocity and SDAS. Qualitatively, increased pressure promotes dendrite growth in directional solidification, elevating growth velocity and facilitating the burgeoning and growth of secondary arms, resulting in longer and more developed dendrites and much smaller SDAS. Quantitatively, the average tip velocities under \(P_{0}\) and P are 14.5 μm/s and 29.8 μm/s, respectively, with 100% rise when growing under pressure P . Moreover, the SDAS is 50.3 μm and 30.2 μm, respectively, declining by 40% when solidified under pressure P . This phenomenon can be attributed to the effect of pressure on melting point and its destabilizing effect on S/L interface.

UNLABELLED PHII-7, a derivative of indirubin, showed significant anti-cancer activities in vivo and in vitro. We asked whether treating human metastatic cancers and multidrug resistant cancer with PHII-7 would inhibit their invasion and migration. Cell growth was tested by MTT assay and colony formation assay. Apoptosis was examined by flow cytometry. Transwell-based assay and wound healing assay were used to examine cell invasion and migration. Real-time PCR assay and western blot assay were performed to test gene expression on mRNA and protein level, respectively. Firstly, we confirmed that MCF-7/ADR cells showed more invasive and migratory properties compared with MCF-7 cells which were associated with several EMT markers, such as E-cadherin, Slug and vimentin. Secondly, we found that slightly toxic doses of PHII-7 decreased the number of cells that invaded a model epithelial basement membrane and that migrated by switching the molecular signature of the cells from mesenchymal to epithelial. And PHII-7 significantly regulated expression of several epithelial-mesenchymal transition (EMT)-related genes, including E-cadherin, Slug, β-catenin and vimentin. Thirdly, compared with control, PHII-7 inhibited cell proliferation in a time- and dose-dependent manner. Higher doses of PHII-7 also induced apoptosis through activating PARP, caspase-9 and caspase-3. PHII-7 significantly inhibited invasion and migration in both metastatic cancers and multidrug resistant cancer. Our results may provide several data for future application of PHII-7 on drug design and patients treatment. KEYWORDS PHII-7, invasion, migration, multidrug resistance, epithelial-mesenchymal transition.

The aim of this study was to investigate the prevalence and risk factors of fatty pancreas in Yangzhou, China.This was a cross-sectional study. Initially, 2093 subjects were included in the study. After the exclusion of 865 subjects based on incomplete information, a total of 1228 subjects were selected for further analysis. The subjects were stratified into two groups (the fatty pancreas group and the non-fatty pancreas group) based on the results. Anthropometric and biochemical findings were compared between the groups.Among the 2093 study subjects, 56 (2.7%) had fatty pancreas. Overall, 53 out of 1228 subjects were diagnosed with fatty pancreas and included into the fatty pancreas group. Univariate analysis showed significant differences in age and the prevalence of general obesity, central obesity, alcohol consumption, metabolic syndrome and fatty liver between the two groups (all p 0.01). The fatty pancreas group had higher levels of aspartate aminotransferase, alanine aminotransferase, serum uric acid, fasting blood glucose, total cholesterol, triglycerides and low-density lipoprotein, and lower levels of high-density lipoprotein than did the non-fatty pancreas group (all p0.05). Multivariate logistic regression analysis showed that age (p = 0.007), central obesity (p = 0.002) and fatty liver (p = 0.006) were independent risk factors for fatty pancreas, with odds ratios (ORs) of 1.034 (95% confidence interval (CI): 1.009-1.059), 5.364 (95% CI: 1.890-15.227), and 2.666 (95% CI: 1.332-5.338), respectively.The prevalence of fatty pancreas in the examined population is approximately 2.7%. Increased age, central obesity and fatty liver disease are independent risk factors for fatty pancreas.

The integrin α6 subunit is part of the integrin α6β1 and α6β4 complexes, which are known to mediate the invasion of carcinoma cells. However, the precise role of integrin α6 in intrahepatic cholangiocarcinoma (ICC) has not yet been addressed. Twenty cases of ICCs and matched nontumor samples were used to analyze integrin α6 expression by immunohistochemistry. After the expression of integrin α6 was determined by RT-PCR and Western blot in ICC cells, we regulated the expression of integrin α6 in ICC cells with specific vshRNA-integrin α6, and assessed the role of integrin α6 in the proliferation and metastasis/invasion of ICC cells. Finally, the involved mechanisms and clinical significance were further investigated. The expression of integrin α6 in ICC tissues was much higher than that in nontumor samples, and the high level of integrin α6 was detected in ICC cells compared with normal liver cells and HepG2 cells. After the down-regulation of integrin α6 in HCCC-9810 cells, we showed that the ability of ICC cells to metastasize and invade was much decreased in vitro, and cell proliferation was inhibited significantly. Further study indicated high expression of integrin α6 enhanced the activation of ERK1/2 and AKT signals in ICC cells and the inhibition of ERK1/2 down-regulated ICC cell proliferation, while the inhibition of AKT markedly impaired ICC cell metastasis and invasion. Integrin α6 overexpression was significantly correlated with larger tumors, multiple nodular, microvascular/bile duct invasion, and lymphatic metastasis (p