Tofacitinib uptake by patient-derived intestinal organoids predicts individual clinical responsiveness.

Background & Aims: Despite increasing therapeutic options in the treatment of ulcerative colitis (UC), achieving disease remission remains a major clinical challenge. Nonresponse to therapy is common and clinicians have little guidance in selecting the optimal therapy for an individual patient. This study examined whether patient-derived materials could predict individual clinical responsiveness to the Janus kinase (JAK) inhibitor, tofacitinib, prior to treatment initiation. Method: In 48 patients with UC initiating tofacitinib, we longitudinally collected clinical covariates, stool, and colonic biopsies to analyze the microbiota, transcriptome, and exome variations associated with clinical responsiveness at week 24. We established patient-derived organoids (n = 23) to determine how their viability upon stimulation with proinflammatory cytokines in the presence of tofacitinib related to drug responsiveness in patients. We performed additional biochemical analyses of organoids and primary tissues to identify the mechanism underlying differential tofacitinib sensitivity. Results: The composition of the gut microbiota, rectal transcriptome, inflammatory biomarkers, and exome variations were indistinguishable among UC patients prior to tofacitinib treatment. However, a subset of patient-derived organoids displayed reduced sensitivity to tofacitinib as determined by the ability of the drug to inhibit STAT1 phosphorylation and loss of viability upon cytokine stimulation. Remarkably, sensitivity of organoids to tofacitinib predicted individual clinical patient responsiveness. Reduced responsiveness to tofacitinib was associated with decreased levels of the cationic transporter MATE1, which mediates tofacitinib uptake. Conclusions: Patient-derived intestinal organoids predict and identify mechanisms of individual tofacitinib responsiveness in UC. Specifically, MATE1 expression predicted clinical response to tofacitinib.

Vertical Dipole Dominates Charge Carrier Lifetime in Monolayer Janus MoSSe.

Two-dimensional semiconductor materials with vertical dipoles are promising photocatalysts as vertical dipoles not only promote the electron-hole separation but also enhance the carrier redox ability. However, the influence of vertical dipoles on carrier recombination in such materials, especially the competing relationship between vertical dipoles and band gaps, is not yet clear. Herein, first-principles calculations and nonadiabatic molecular dynamics simulations were combined to clarify the influence of band gap and vertical dipole on the carrier lifetime in Janus MoSSe monolayer. By comparing with the results of MoS2 and MoSe2 as well as exploring the carrier lifetime of MoSSe under strain regulation, it has been demonstrated that the vertical dipole, rather than the band gap, is the dominant factor affecting the carrier lifetime. Strikingly, a linear relationship between the carrier lifetime and vertical dipole is revealed. These findings have important implications for the design of high-performance photocatalysts and optoelectronic devices.

Efficacy and prognostic factors of repeated hepatectomy for postoperative intrahepatic recurrence of hepatocellular carcinoma undergoing initial hepatectomy.

Background: Postoperative recurrence of hepatocellular carcinoma (HCC) is associated with low survival rates. While HCC treatment options have expanded substantially, they are accompanied by several challenges. This study assessed the outcomes of repeated hepatectomy (RH) for postoperative intrahepatic recurrence of HCC among patients undergoing initial hepatectomy (IH) as well as independent risk factors for HCC recurrence among patients undergoing repeated hepatectomy (RH). Methods: Clinical data from 84 patients undergoing both IH and RH and 66 recurrent HCC patients who had received radiofrequency ablation (RFA) from July 2011 to September 2017 were retrospectively reviewed. The following groups were compared: (1) RH Group A (n = 84), (2) IH Group (n = 84, same individuals as RH Group A), (3) RH Group B (n = 45/84 from RH Group A), and (4) RFA Group (n = 66). The clinical pathology and operative characteristics of the patients in RH Group A were compared to those in the IH Group. Meanwhile, the clinical pathology and pre- and post-treatment features of the patients in RH Group B were compared to those in the RFA Group. The tumor-free survival time was compared between patients in RH Group A and the IH Group as well as between patients in RH Group B and the RFA Group. The independent risk factors for the 1-year postoperative tumor-free survival of RH Group A patients were investigated using univariate and multivariate analysis. Results: Measures of clinical pathology, including AFP, Child-Pugh score, HBV-DNA, tumor number, liver cirrhosis, tumor differentiation, surgical approach, and TNM stage differed significantly between patients in RH Group A and the IH Group (all P < 0.05), with the exception of tumor number and tumor size (both P > 0.05). No significant differences were found in these measures between the patients in RH Group B and the RFA Group (all P > 0.05). While patients in the RH Group A had a longer operation time than those in the IH Group (4.35 ± 1.25 h vs. 3.55 ± 0.92 h, P < 0.001), the level of intraoperative bleeding was similar (400.00 ± 199.25 ml vs. 359.40 ± 213.37 ml, P = 0.204). RH Group B patients had a longer hospitalization time than those in the RFA Group (6.5 ± 0.8 d vs. 5.5 ± 1.1 d, P < 0.001), however, the difference in hospitalization costs was not statistically significant (29,009 ± 3,806 CNY vs. 29,944 ± 3,752 CNY, P = 0.202). Five-day post-operative serum biomarker levels, including direct bilirubin (DB) and albumin (ALB), were significantly higher in RH Group B than in the RFA Group (all P < 0.05), with the exception of ALT, AST, and total bilirubin (TB) (all P > 0.05). Patients in RH Group A had a lower tumor-free survival time than those in the IH Group (median: 12 vs. 22 months, P < 0.001), and patients in the RH Group B had a significantly higher tumor-free survival time than those in the RFA group (median: 15 months vs. 8 months, P < 0.001). Age ≥50 y, Child-Pugh class A, and negative HBV-DNA were independent risk factors that positively impacted the 1-year postoperative tumor-free survival rate of postoperative intrahepatic recurrent HCC patients undergoing RH (P < 0.001, respectively). Conclusion: Due to the potential of harm related to relapse of recurrent HCC for cancer patients, RH is a superior option. RH could offer better outcomes for recurrent HCC patients undergoing IH. Compared with lesion pathology, the better target organ of the liver will be key to ameliorating tumor-free survival for recurrent HCC patients undergoing RH.

Formulation of Lipid-Free Polymeric Mesoscale Nanoparticles Encapsulating mRNA.

INTRODUCTION: Nanoparticle-mediated gene therapy has found substantial clinical impact, primarily focused on lipid-based nanoparticles. In comparison with lipid nanoparticles, polymeric particles may have certain advantages such as increased biocompatibility and controlled release. Our prior studies have found that polymeric mesoscale nanoparticles exhibited specific targeting to the renal proximal tubules. Thus, in this study, we sought to identify formulation parameters that allow for development of polymeric mesoscale nanoparticles encapsulating functional mRNA for delivery into tubular epithelial cells. METHODS: We evaluated particle uptake in vitro prior to exploring formulation parameters related to introduction of a primary mixture of polymer in acetonitrile and hydrophilic mRNA in water. Finally, we evaluated their functionality in a renal tubular epithelial cell line. RESULTS: We found that MNPs are endocytosed within 15 min and that the mesoscale nanoparticle formulation procedure was generally robust to introduction of a primary mixture and encapsulation of mRNA. These particles exhibited substantial uptake in renal cells in vitro and rapid (< 1 h) expression of a model mCherry fluorescent protein. CONCLUSION: We anticipate these findings having potential in the delivery of specific gene therapies for renal disorders and cancer.

Effect of Multi-Component on Crack Resistance of High-Performance Concrete on Subway Underground Station Floor.

In view of the easy cracking of the high-performance concrete (HPC) of the subway underground station floor, the effects of fly ash, basalt fiber, expansive agent, and water reducer on the compressive strength, initial crack time, through-crack time, and crack area of the HPC on a subway underground station floor at different ages by orthogonal experiment are examined. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and mercury intrusion porosimetry (MIP) are used to further analyze the microstructure and product composition of the optimal ratio HPC and reference concrete. The results show that with the increase in the content of fly ash and expander, the 7 d and 28 d compressive strength of the HPC gradually decreased. However, as the content of basalt fiber increased, the 7 d and 28 d compressive strength of the HPC gradually increased. The 7 d and 28 d compressive strength of the HPC increased and then decreased with the increase in water-reducer content. When the content of fly ash, basalt fiber and expander increased, the initial crack and through-crack time of the HPC delayed gradually, and the crack area gradually decreased. When the fly-ash content reached 30%, the cracking area accounted for 65.1% of the concrete with 15% fly-ash content. When the basalt fiber content reached 0.4%, the cracking area accounted for 56.5% of the concrete with 0.1% basalt fiber content. When the expander content reached 10%, the cracking area accounted for 60.5% of the concrete with 4% expander content. With the increase in the content of water reducer, the initial crack and through-crack time of the HPC gradually advanced, and the crack area gradually increased. When the water-reducer content reached 1.3%, the cracking area accounted for 105.7% of the concrete with 1.0% water-reducer content. The addition of fly ash and expander can produce a large number of crystalline products to fill the pores, and the disordered distribution of the added basalt fibers increases the compactness of the structure; moreover, the internal micro-pores increase, and the macro-pores decrease, thus improving the crack resistance.

Electron-Induced Synthesis of Dimethyl Ether in the Liquid-Vapor Interface of Methanol.

Ether synthesis from alcohol is known to be acid-catalyzed. Such a process could happen in the acidified liquid of alcohol, but hitherto lacking the experimental evidence. Here we demonstrate that dimethyl ether is spontaneously synthesized in the liquid-vapor interface of pure methanol after ionizing radiation with electrons. Using time-delayed tandem mass spectrometry measurements in combination with theoretical calculations, we further confirm that the protonated dimethyl ether is produced from the ion-molecule reactions not only in the dense vapor above the interface but also within the molecular clusters of the acidic interface. Our finding provides a convincing piece of evidence about the liquid-vapor interfacial acidification by the electron-impact ionizing radiation, exhibiting a promising way to control the chemical reactions in the liquid surface.

Hyperprogression After Immunotherapy for Primary Small Cell Neuroendocrine Carcinoma of the Ureter: A Case Report.

BACKGROUND: Primary small cell neuroendocrine carcinoma (SCNEC) in the ureter is extremely rare and has been sporadically reported in case reports. Its incidence, diagnosis, treatment, and outcomes have not yet been thoroughly understood. Here we present a patient with advanced SCNEC in the ureter who was treated by multimodal strategies. To the best of our knowledge, this is the first literature report about the clinical outcomes of the combination of programmed death ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) and radiotherapy in patient with primary ureteral SCNEC. CASE PRESENTATION: A 71-year old male presented with right flank pain and gross hematuria. A laparoscopic right nephroureterectomy was performed. He was diagnosed with primary ureteral SCNEC, pT3N0M0. Following the surgery, 4 cycles of adjuvant chemotherapy with carboplatin and etoposide (CE) were administered, with disease-free survival (DFS) of 10.1 months. He was then offered 4 cycles of palliative first-line chemotherapy with nedaplatin and irinotecan. The disease was continuously progressed, with progression-free survival (PFS) of 3.7 months. The patient subsequently received second-line treatment with PD-L1 ICI combined with radiotherapy. Unfortunately, hyperprogressive disease was found at the end of treatment. MRI and CT scan showed bilateral pubic bones, right acetabulum, and liver metastases. Without further intervention, the patient died from extensive metastatic disease 2 months after diagnosis, with overall survival (OS) of 18.2 months. CONCLUSION: Physicians must be aware of this rare and aggressive carcinoma at its initial presentation. Special attention should be paid to the potential likelihood of hyperprogression during the treatment.

A rationally designed two-dimensional MoSe2/Ti2CO2 heterojunction for photocatalytic overall water splitting: simultaneously suppressing electron-hole recombination and photocorrosion.

Electron-hole recombination and photocorrosion are two challenges that seriously limit the application of two-dimensional (2D) transition metal dichalcogenides (TMDs) for photocatalytic water splitting. In this work, we propose a 2D van der Waals MoSe2/Ti2CO2 heterojunction that features promising resistance to both electron-hole recombination and photocorrosion existing in TMDs. By means of first-principles calculations, the MoSe2/Ti2CO2 heterojunction is demonstrated to be a direct Z-scheme photocatalyst for overall water splitting with MoSe2 and Ti2CO2 serving as photocatalysts for hydrogen and oxygen evolution reactions, respectively, which is beneficial to electron-hole separation. The ultrafast migration of photo-generated holes from MoSe2 to Ti2CO2 as well as the anti-photocorrosion ability of Ti2CO2 are responsible for photocatalytic stability. This heterojunction is experimentally reachable and exhibits a high solar-to-hydrogen efficiency of 12%. The strategy proposed here paves the way for developing 2D photocatalysts for water splitting with high performance and stability in experiments.

2D Heterostructured Nanofluidic Channels for Enhanced Desalination Performance of Graphene Oxide Membranes.

The two-dimensional (2D) lamellar membrane assembly technique shows substantial potential for sustainable desalination applications. However, the relatively wide and size-variable channels of 2D membranes in aqueous solution result in inferior salt rejections. Here we show the establishment of nanofluidic heterostructured channels in graphene oxide (GO) membranes by adding g-C3N4 sheets into GO interlamination. Benefiting from the presence of stable and sub-nanometer wide (0.42 nm) GO/g-C3N4 channels, the GO/g-C3N4 membrane exhibits salt rejections of ∼90% with water permeances of above 30 L h-1 m-2 bar-1, while the pure GO membrane only has salt rejections of below 30% accompanied by water permeances of below 4 L h-1 m-2 bar-1. Combining experimental and theoretical investigations, size exclusion has proved to be the dominating mechanism for high rejections, and the ultralow friction water flow along g-C3N4 sheets is responsible for permeation enhancements. Importantly, the GO/g-C3N4 membrane shows promising long-term, antioxidation, and antipressure stability.

Research on the accuracy of dynamic real-time navigation and digital guide navigation implanting techniques / 口腔疾病防治

Objective @#To compare the accuracies of implants with dynamic real-time navigation versus digital guide navigation to provide a reference for clinical precision dental implants. @*Methods@#Forty-six cases (seventy teeth) with missing teeth admitted to the Department of Stomatology, Wuzhou Red Cross Hospital from April 2018 to December 2019 were randomly divided into two groups (thirty-five teeth in each group) for dynamic real-time navigation and digital guide navigation implantation techniques. To compare the entry point, apex point, depth and angle deviation of the preoperative and postoperative position of implants in the two groups. SPSS 21.0 software was used for statistical analysis.@*Results @#Dental implants were successfully placed in both groups. The deviations of apex point, depth and angle in the dynamic real-time navigation group were all smaller than those in the digital guide navigation group, and the differences were statistically significant (P < 0.05). There was no statistically significant deviation in the entry point between the two groups (P > 0.05). @*Conclusion@#In this study, both techniques had good clinical effects. The accuracy of dynamic real-time navigation was higher than that of digital guidance.

Identifying the Molecular Orientation and Clusters in the Liquid-Vapor Interface of 1-Propanol by Time-Delayed Mass Spectrometry.

Structural inhomogeneity of the liquid-vapor interface, such as the spatial orientation of molecular specific groups and the non-uniform distribution of hydrogen-bonded (HB) clusters, is crucial for understanding the physicochemical processes therein. Although the molecular orientation at the outermost layer was authenticated, to date, direct experimental evidence of the in situ existence of different-sized HB clusters, as a long-standing theoretical argument, is still lacking. Here we report time-delayed electron-impact tandem mass spectrometry, and its powerful ability to identify the local structures of the liquid-vapor interface of 1-propanol is demonstrated not only by mapping the molecular orientations both in the outermost layer and in the subsurface but also by validating the existence of the HB molecular dimers in the subsurface by detecting their protonated ions. We further distinguish two different sources of the protonated dimer: the gas-phase protonation of the neutral dimer that evaporates in advance and the time-lag evaporation of the protonated dimer produced in the subsurface. This methodology is a brand-new way to explore the microstructures and the electron-driven chemical reactions in different local regions of the liquid-vapor interface.

Boosting Occluded Image Classification via Subspace Decomposition-Based Estimation of Deep Features.

Classification of partially occluded images is a highly challenging computer vision problem even for the cutting-edge deep learning technologies. To achieve a robust image classification for occluded images, this article proposes a novel scheme using the subspace decomposition-based estimation (SDBE). The proposed SDBE-based classification scheme first employs a base convolutional neural network to extract the deep feature vector (DFV) and then utilizes the SDBE to compute the DFV of the original occlusion-free image for classification. The SDBE is performed by projecting the DFV of the occluded image onto the linear span of a class dictionary (CD) along the linear span of an occlusion error dictionary (OED). The CD and OED are constructed, respectively, by concatenating the DFVs of a training set and the occlusion error vectors of an extra set of image pairs. Two implementations of the SDBE are studied in this article: 1) the l1 -norm and 2) the squared l2 -norm regularized least-squares estimates. By employing the ResNet-152, pretrained on the ImageNet Large-Scale Visual Recognition Challenge 2012 (ILSVRC2012) training set, as the base network, the proposed SBDE-based classification scheme is extensively evaluated on the Caltech-101 and ILSVRC2012 datasets. Extensive experimental results demonstrate that the proposed SDBE-based scheme dramatically boosts the classification accuracy for occluded images, and achieves around 22.25% increase in classification accuracy under 20% occlusion on the ILSVRC2012 dataset.

Mechanism of miR-210 involved in epithelial-mesenchymal transition of pancreatic cancer cells under hypoxia.

Purpose: To investigate the possible mechanism of miR-210 involved in epithelial-mesenchymal transition (EMT) of pancreatic cancer cells under hypoxia. Methods: In this study, we used the following approaches. Hypoxic microenvironment was stimulated in vitro, and the CCK-8 assay was used to analyze cell viability. The MiRNA expression level was measured by qRT-PCR. HOXA9, EMT-related proteins, and NF-κB activities were examined by immunoblotting assay. Dual luciferase reporter assay was used to assess whether HOXA9 was a target of miR-210.Results: Under hypoxia condition, miR-210, HIF-1α and NF-κB were increased, and the HOXA9 was reduced in PANC-1 cells. When miR-210 was overexpressed in normoxic PANC-1 cells, EMT epithelial markers of E-cadherin and ß-catenin were down-regulated, and mesenchymal markers of vimentin and N-cadherin were up-regulated to promote cell migration/invasive ability, and the HOXA9 level was decreased. After HOXA9 level decreased, the sensitivity to chemotherapeutic drug of gemcitabine was reduced, NF-κB expression level and cell migration/invasive ability was enhanced. Whereas, miR-210 antagonist into hypoxic PANC-1 cells, which up-regulated E-cadherin, ß-catenin level, and down-regulated vimentin and N-cadherin levels to decrease cell migration/invasive ability, and increase the HOXA9. Furthermore, increasing HOXA9 level decreased NF-κB expression level and cell migration/invasive ability, enhanced the sensitivity to gemcitabine. At last, miRDB and TargetScan predicted that HOXA9 was a target of miR-210, and dual luciferase reporter assay verified this hypothesis.Conclusion: MiR-210 inhibited the expression of HOXA9 to activate the NF-κB signaling pathway and mediated the occurrence of EMT of pancreatic cancer cells induced by HIF-1α under hypoxia.

Endowing g-C3 N4 Membranes with Superior Permeability and Stability by Using Acid Spacers.

g-C3 N4 membranes were modulated by intercalating molecules with SO3 H and benzene moieties between layers. The intercalation molecules break up the tightly stacking structure of g-C3 N4 laminates successfully and accordingly the modified g-C3 N4 membranes give rise to two orders magnitude higher water permeances without sacrificing the separation efficiency. The sulfonated poly(2,6-dimethyl-1,4-phenylene oxide) (SPPO)/g-C3 N4 with a thickness of 350 nm presents an exceptionally high water permeance of 8867 L h-1 m-2 bar-1 and 100 % rejection towards methyl blue, while the original g-C3 N4 membrane with a thickness of 226 nm only exhibits a permeance of 60 L h-1 m-2 bar-1 . Simultaneously, SO3 H sites firmly anchor nitrogen with base functionality distributing onto g-C3 N4 through acid-base interactions. This enables the nanochannels of g-C3 N4 based membranes to be stabilized in acid, basic, and also high-pressure environments for long periods.

Construction of direct Z-Scheme photocatalysts for overall water splitting using two-dimensional van der waals heterojunctions of metal dichalcogenides.

The direct Z-scheme system constructed by two-dimensional (2D) materials is an efficient route for hydrogen production from photocatalytic water splitting. In the present work, the 2D van der Waals (vdW) heterojunctions of MoSe2 /SnS2 , MoSe2 /SnSe2 , MoSe2 /CrS2 , MoTe2 /SnS2 , MoTe2 /SnSe2 , and MoTe2 /CrS2 are proposed to be promising candidates for direct Z-scheme photocatalysts and verified by first principles calculations. Perpendicular electric field is induced in these 2D vdW heterojunctions, which enhances the efficiency of solar energy utilization. Replacing MoSe2 with MoTe2 not only facilitates the interlayer carrier migration, but also improves the optical absorption properties for these heterojunctions. Excitingly, the 2D vdW MoTe2 /CrS2 heterojunction is demonstrated, for the first time, to be 2D near-infrared-light driven photocatalyst for direct Z-scheme water splitting. © 2018 Wiley Periodicals, Inc.

Material Design for Photocatalytic Water Splitting from a Theoretical Perspective.

Currently, problems associated with energy and environment have become increasingly serious. Producing hydrogen, a clean and renewable resource, through photocatalytic water splitting using solar energy is a feasible and efficient route for resolving these problems, and great efforts have been devoted to improve the solar-to-hydrogen efficiency. Light harvesting and electron-hole separation are key in enhancing the efficiency of solar energy utilization, which stimulates the development of new photocatalytic materials. Here, recent advances in material design for photocatalytic water splitting are presented from a theoretical perspective. Specifically, aiming to enhance the photocatalytic performance, general strategies of materials design are discussed, including codoping and introducing a built-in electric field to improve the light harvesting of materials, reducing the dimension of materials to shorten the migration pathway of carriers to inhibit electron-hole recombination, and constructing heterojunctions to enhance light harvesting and electron-hole separation. Future opportunities and challenges in the theoretical design of photocatalytic materials toward water splitting are also included.

Intrinsic Electric Fields in Two-dimensional Materials Boost the Solar-to-Hydrogen Efficiency for Photocatalytic Water Splitting.

Two-dimensional (2D) materials with the vertical intrinsic electric fields show great promise in inhibiting the recombination of photogenerated carriers and widening light absorption region for the photocatalytic applications. For the first time, we investigated the potential feasibility of the experimentally attainable 2D M2X3 (M = Al, Ga, In; X = S, Se, Te) family featuring out-of-plane ferroelectricity used in photocatalytic water splitting. By using first-principles calculations, all the nine members of 2D M2X3 are verified to be available photocatalysts for overall water splitting. The predicted solar-to-hydrogen efficiency of Al2Te3, Ga2Se3, Ga2Te3, In2S3, In2Se3, and In2Te3 are larger than 10%. Excitingly, In2Te3 is manifested to be an infrared-light driven photocatalyst, and its solar-to-hydrogen efficiency limit using the full solar spectrum even reaches up to 32.1%, which breaks the conventional theoretical efficiency limit.

Asparaginyl endopeptidase enhances pancreatic ductal adenocarcinoma cell invasion in an exosome-dependent manner and correlates with poor prognosis.

Pancreatic cancer is one of the most lethal types of cancer; owing to low early detection rates and high metastasis rates, it is associated with an extremely poor prognosis. Therefore, a better understanding of the molecular mechanisms that underlie its metastasis and the identification of potential prognostic biomarkers are urgently required. Although high expression levels of asparaginyl endopeptidase (AEP) have been detected in various types of solid tumor, the expression and functions of AEP in pancreatic carcinomas have yet to be determined. The present study aimed to examine the putative functions of AEP in pancreatic carcinoma. Immunohistochemical analysis revealed that AEP was highly expressed in pancreatic cancer tissues compared with adjacent normal tissues. Patients with high AEP expression exhibited a significantly shorter overall survival time. Results from multivariate Cox regression analysis revealed that AEP was an independent prognostic factor for overall survival. Gain- and loss-of-function experiments demonstrated that knockdown of AEP expression significantly reduced the invasive ability of pancreatic cancer cells, whereas overexpression of AEP increased the invasive ability. In addition, AEP was detected in exosomes that were derived from cultured pancreatic ductal adenocarcinoma cells (PDACs) and in the serum from patients with PDAC. The Matrigel-Transwell invasion assay revealed that exosomes enriched with AEP were able to enhance the invasive ability of PDAC cells, whereas exosomes lacking AEP decreased the invasive ability. Furthermore, results from the present study suggested that AEP may be crucial for activation of the phosphoinositide 3-kinase/RAC­α serine/threonine-protein kinase signaling pathway in PDAC cells. The present study data indicated that high AEP expression may be important for pancreatic carcinoma progression in an exosome-dependent manner, and that AEP may be an independent indicator of poor prognosis in patients with PDAC and may be a novel prognostic biomarker or therapeutic target in pancreatic carcinoma.

Role of BET Bromodomain in Hematopoietic Differentiation from hESCs / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the role of bromodomain and extra terminal (BET) bromodomain in hematopoietic differentiation from human enbryonic stem cells (hESC).</p><p><b>METHODS</b>The effect of BET hematopoietic inhibitor I-BET151 on hematopoietic differentiation from hESC was detected by using a monolayer hematopoietic defferentiation model, immunofluorescence, flow cytometry and real-time PCR; moreover the role of I-BET151 in process of hematopoietic differentiation was explored by adding I-BET151 in different differentiation stages.</p><p><b>RESULTS</b>The analysis results of immunofluorescence, flow cytometry and real-time PCR showed that I-BET 151 significantly inhibited the generation of CD43 positive hematopoietic stem and progenitor cells (HSPCs). It was found that the addition of I-BET 151 in different stages, including APLNR lateral plate mesoderm production, CD34CD31 hemogenic endothelium (HEP) generation and endothelial-to-hematopoietic transition, significantly suppressed the generation of CD43 positive hematopoietic progenitor cells.</p><p><b>CONCLUSION</b>I-BET 151 inhibites hematopoietic differentiation from hESCs at several stages, suggesting that the BET bromodomain plays important roles in multiple stages of hematopoietic differentiation from hESCs.</p>

Different aggregation dynamics of benzene-water mixtures.

All-atom molecular dynamics simulations for benzene-water mixtures are performed, aiming to explore the relationship between the microscopic structures and the thermodynamic properties, in particular, the transformation dynamics from the mutually soluble state to the phase-separated state. We find that the molecular aggregation of benzene in the water-rich mixture is distinctly different from that of water in the benzene-rich mixture. This aggregation difference is attributed to the different intermolecular interactions: the clustering of benzene molecules in the water-rich mixture is primarily driven by weak short-distance π-π interactions; while the formation of water clusters in the benzene-rich solution is triggered by long-range dipole-dipole electrostatic interactions. Moreover, the molecular aggregations show double-scaled features: firstly assembling in a quasi-plane at a low concentration, then bulking in three dimensions with an increase in concentration.