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Interferon-inducible double-stranded RNA-dependent protein kinase (PKR) is one of the key antiviral arms in the innate immune system. The activated PKR performs its antiviral function by inhibiting protein translation and inducing apoptosis. In our previous study, we identified grass carp TARBP2 as an inhibitor of PKR activity, thereby suppressing cell apoptosis. This study aimed to explore the effects of grass carp TARBP2 on PKR activity and cell apoptosis. Grass carp TARBP2 comprises two N-terminal dsRBDs and a C-terminal C4 domain. Subcellular localization analysis conducted in CIK cells revealed that TARBP2-FL (full-length TARBP2), TARBP2-Δ1 (lack of the first dsRBD), and TARBP2-Δ2 (lack of the second dsRBD) are predominantly located in the cytoplasm, while TARBP2-Δ3 (lack of the two dsRBDs) is distributed both in the nucleus and cytoplasm. Colocalization and immunoprecipitation assays confirmed the interaction of TARBP2-FL, TARBP2-Δ1, and TARBP2-Δ2 with PKR, while TARBP2-Δ3 showed no binding. Furthermore, our findings suggested that the inhibitory effect of TARBP2-Δ1 or TARBP2-Δ2 on the PKR-eIF2α pathway is depressed compared to TARBP2-FL. In cell apoptosis assays, it was observed that TARBP2-FL inhibits PKR-mediated cell apoptosis. TARBP2-Δ1 or TARBP2-Δ2 exhibits decreased inhibition to PKR-mediated cell apoptosis, whereas TARBP2-Δ3 nearly completely loses this inhibitory effect. These findings highlight the critical importance of two dsRBDs of TARBP2 in interaction with PKR, as well as in the inhibition of PKR activity, resulting in the suppression of cell apoptosis triggered by prolonged PKR activation., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Renal failure is one of the most common chronic complications of diabetes. Simultaneous pancreas-kidney transplantation (SPK) is considered the preferred treatment for individuals with diabetes and chronic renal failure. This procedure has demonstrated efficacy in enhancing the quality of life for patients and minimizing the complications associated with diabetes., Objective: In this study, we analyzed the incidence and safety of complications in different thrombosis prevention techniques post simultaneous pancreas-kidney transplantation (SPK)., Methods: Patients who underwent SPK between January 2019 and December 2022 were selectively categorized into two groups: the heparin group and the non-heparin group depending on the utilization of low molecular weight heparin. The occurrence of complications and clinical outcomes were subsequently calculated in each group., Results: In this study, we included a total of 58 recipients who underwent SPK, with 36 in the heparin group and 22 in the non-heparin group. Among the 58 participants, there were 3 cases of pancreatic thrombosis complications, with 2 cases (5.6%) in the heparin group and 1 case (4.6%) in the non-heparin group, and the differences were not statistically significant (P> 0.05). Regarding gastrointestinal bleeding, there were 17 cases out of the total 58 patients, with 14 cases (38.9%) in the heparin group and 3 cases (13.6%) in the non-heparin group, and the difference was statistically significant (P< 0.05)., Conclusion: After surgery, the use of low molecular weight heparin anticoagulation may increase the likelihood of experiencing gastrointestinal bleeding. Prior to the surgery, a comprehensive evaluation of the coagulation status and medical history of the patient should be performed, enabling stratification of risks involved. Based on this assessment, either low-molecular-weight heparin or aspirin should be selected as a preventive measure against thrombosis.

Hippocampal neuronal damage may induce cognitive impairment. Neurotrophic tyrosine kinase receptor 1 (NTRK1) reportedly regulates neuronal damage, although the underlying mechanism remains unclear. The present study aimed to investigate the role of NTRK1 in mouse hippocampal neuronal damage and the specific mechanism. A mouse NTRK1-knockdown model was established and subjected to pre-treatment with BAY-3827, followed by a behavioral test, Nissl staining, and NeuN immunofluorescence (IF) staining to evaluate the cognitive impairment and hippocampal neuronal damage. Next, an in vitro analysis was conducted using the CCK-8 assay, TUNEL assay, NeuN IF staining, DCFH-DA staining, JC-1 staining, ATP content test, mRFP-eGFP-LC3 assay, and LC3-II IF staining to elucidate the effect of NTRK1 on mouse hippocampal neuronal activity, apoptosis, damage, mitochondrial function, and autophagy. Subsequently, rescue experiments were performed by subjecting the NTRK1-knockdown neurons to pre-treatment with O304 and Rapamycin. The AMPK/ULK1/FUNDC1 pathway activity and mitophagy were detected using western blotting (WB) analysis. Resultantly, in vivo analysis revealed that NTRK1 knockdown induced mouse cognitive impairment and hippocampal tissue damage, in addition to inactivating the AMPK/ULK1/FUNDC1 pathway activity and mitophagy in the hippocampal tissues of mice. The treatment with BAY-3827 exacerbated the mouse depressive-like behavior induced by NTRK1 knockdown. The results of in vitro analysis indicated that NTRK1 knockdown attenuated viability, NeuN expression, ATP production, mitochondrial membrane potential, and mitophagy, while enhancing apoptosis and ROS production in mouse hippocampal neurons. Conversely, pre-treatment with O304 and rapamycin abrogated the suppression of mitophagy and the promotion of neuronal damage induced upon NTRK1 silencing. Conclusively, NTRK1 knockdown induces mouse hippocampal neuronal damage through the suppression of mitophagy via inactivating the AMPK/ULK1/FUNDC1 pathway. This finding would provide insight leading to the development of novel strategies for the treatment of cognitive impairment induced due to hippocampal neuronal damage., (© 2023. The Author(s).)

The pathogenesis of ulcerative colitis (UC) is unclear. House dust mite (HDM) is associated with immune inflammation in the body. This study is designed to identify the association between HDM and UC clinical symptoms. UC patients ( n  = 86) and non-UC control (NC) subjects ( n  = 64) were recruited. Colon lavage fluids (CLF) were collected from HDM skin prick test positive patients during colonoscopy, and analyzed by immunological approaches. HDM was detected in fecal samples, which was positively correlated with UC clinical symptoms. HDM-specific eosinophils and Th2 cells were detected in CLF, which could be specifically activated by exposing to HDM in the culture. Direct exposure to HDM induced eosinophil activation in the colon of UC patients. UC patients displayed elevated levels of Th2 cytokines in the serum. UC clinical symptom scores were positively correlated with serum levels of Th2 cytokines. HDM was detected in UC patients' stools, which was positively correlated with UC clinical symptoms. Direct exposure to HDM could trigger eosinophilic activation of the colon.

To investigate the variation of soil water holding capacity under different land use types can provide scientific basis for evaluating the change characteristics and regulation mechanism of water conservation capacity in alpine ecosystems. We collected soil samples at different depth intervals (0-10, 10-20 and 20-30 cm) under three land use types (farmland, forest, and grassland) in Tibet alpine region to measure the maximum water holding capacity, capillary water holding capacity, field capacity, and basic soil physicochemical properties. The associated environmental factors (mean annual precipitation, normalized difference vegetation index, altitude, slope gradient and surface roughness) were extracted to analyze the change characteristics and influencing factors of soil water holding capacity under different land use types. The results showed that soil water holding capacity (the maximum water holding capacity, capillary water holding capacity, and field capacity) of farmland, forest, and grassland all decreased with increasing soil depth. The mean values of the maximum water holding capacity, capillary water holding capacity, and field capacity in the 0-30 cm soil layer of grassland were 379.79, 329.57 and 194.39 g·kg -1 , respectively, which were significantly higher than that of farmland (301.15, 259.67, and 154.91 g·kg -1 ) and forest (293.09, 251.49, and 117.01 g·kg -1 ). Results of the redundancy analysis showed that soil properties significantly influenced soil water holding capacity, with explanation rate of 44.6%, 42.7%, 37.6% and 35.8% for total porosity, soil organic matter, capillary porosity and soil bulk density, respectively. Results of the principal component analysis showed that mean annual precipitation, normalized difference vegetation index, altitude, slope gradient, and surface roughness were the main environmental factors affecting the spatial variation of soil water holding capacity, with a cumulative contribution of 72.4%. The grassland in the alpine region of Tibet had the highest water holding capacity and could effectively prevent soil erosion. Therefore, the implementation of returning farmland to grassland and the enclosure management of degraded grassland would be conducive to improve soil water conservation capacity in the alpine regions.

Transcriptomics has revealed that cortical inhibitory neurons exhibit a great diversity of fine molecular subtypes 1-6 , but it is not known whether these subtypes have correspondingly diverse patterns of activity in the living brain. Here we show that inhibitory subtypes in primary visual cortex (V1) have diverse correlates with brain state, which are organized by a single factor: position along the main axis of transcriptomic variation. We combined in vivo two-photon calcium imaging of mouse V1 with a transcriptomic method to identify mRNA for 72 selected genes in ex vivo slices. We classified inhibitory neurons imaged in layers 1-3 into a three-level hierarchy of 5 subclasses, 11 types and 35 subtypes using previously defined transcriptomic clusters 3 . Responses to visual stimuli differed significantly only between subclasses, with cells in the Sncg subclass uniformly suppressed, and cells in the other subclasses predominantly excited. Modulation by brain state differed at all hierarchical levels but could be largely predicted from the first transcriptomic principal component, which also predicted correlations with simultaneously recorded cells. Inhibitory subtypes that fired more in resting, oscillatory brain states had a smaller fraction of their axonal projections in layer 1, narrower spikes, lower input resistance and weaker adaptation as determined in vitro 7 , and expressed more inhibitory cholinergic receptors. Subtypes that fired more during arousal had the opposite properties. Thus, a simple principle may largely explain how diverse inhibitory V1 subtypes shape state-dependent cortical processing., (© 2022. The Author(s).)

Functional ultrasound imaging (fUSI) is an appealing method for measuring blood flow and thus infer brain activity, but it relies on the physiology of neurovascular coupling and requires extensive signal processing. To establish to what degree fUSI trial-by-trial signals reflect neural activity, we performed simultaneous fUSI and neural recordings with Neuropixels probes in awake mice. fUSI signals strongly correlated with the slow (<0.3 Hz) fluctuations in the local firing rate and were closely predicted by the smoothed firing rate of local neurons, particularly putative inhibitory neurons. The optimal smoothing filter had a width of ∼3 s, matched the hemodynamic response function of awake mice, was invariant across mice and stimulus conditions, and was similar in the cortex and hippocampus. fUSI signals also matched neural firing spatially: firing rates were as highly correlated across hemispheres as fUSI signals. Thus, blood flow measured by ultrasound bears a simple and accurate relationship to neuronal firing., Competing Interests: Declaration of interests A.U. is the founder and a shareholder of AUTC, a company commercializing neuroimaging solutions for preclinical and clinical research. M.C. is a member of Neuron’s Advisory Board., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Interleukin 10 (IL-10)-producing B cells (B10 cells) are a canonical cell fraction for regulating other activities of immune cells. Posttranscriptional modification of IL-10 in B10 cells is not yet fully understood. Short-chain fatty acids play an important role to regulate the functions of immune cells. This study aims to clarify the role of propionic acid (PA), a short-chain fatty acid, in regulating the expression of IL-10 in B10 cells. Blood samples were collected from patients with food allergy (FA) and healthy subjects. Serum and cellular components were prepared with the samples, and analysed by enzyme-linked immunosorbent assay and flow cytometry, respectively. The results showed that serum PA levels were lower in FA patients. PA concentrations were negatively correlated with serum cytokine Th2 concentrations, specific IgE concentrations in serum and skin prick test results. The peripheral frequency of B10 cells and the production of IL-10 in B cells were also associated with serum PA concentrations. Activation of B cells by CpG induced the production of IL-10 and tristetretrprolin (TTP), in which TTP caused the spontaneous decay of IL-10 mRNA. PA was necessary to stabilize the IL-10 mRNA in B cells by inducing the production of granzyme B, which resulted in the degradation of the IL-10 mRNA. Administration of PA attenuated FA response in mice by maintaining homeostasis of B10 cells. In conclusion, PA is needed to stabilize the expression of IL-10 in B10 cells. PA administration can mitigate experimental FA by maintaining B10 cell functions., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background & Aims: Hepatic fibrosis is characterized by hepatic stellate cell (HSC) activation and transdifferentiation-mediated extracellular matrix (ECM) deposition, which both contribute to cirrhosis. However, no antifibrotic regimen is available in the clinic. microRNA-23b/27b/24-1 cluster inhibition of transforming growth factor-β (TGF-β) signaling during hepatic development prompted us to explore whether this cluster inhibits HSC activation and hepatic fibrosis., Methods: Experimental fibrosis was studied in carbon tetrachloride (CCl 4 )-treated C57BL/6 mice. After administration of miR-23b/27b/24-1 lentivirus or vehicle, animals were euthanized for liver histology. In primary rat HSC and HSC-T6, the anti-fibrotic effect of miR-23b/27b/24-1 cluster was furtherly investigated by RNA-sequencing, luciferase reporter assay, western blotting and bioinformatic means., Results: In this study, we showed that increasing the miR-23b/27b/24-1 level through intravenous delivery of miR-23b/27b/24-1 lentivirus ameliorated mouse hepatic fibrosis. Mechanistically, the miR-23b/27b/24-1 cluster directly targeted messenger RNAs, which reduced the protein expression of 5 secretory profibrotic genes (TGF-β2, Gremlin1, LOX, Itgα2, and Itgα5) in HSCs. Suppression of the TGF-β signaling pathway by down-regulation of TGF-β2, Itgα2, and Itgα5, and activation of the bone morphogenetic protein signaling pathway by inhibition of Gremlin1, decreased extracellular matrix secretion of HSCs. Furthermore, down-regulation of LOX expression softened the ECM. Moreover, a reduction in tissue inhibitors of metalloproteinase 1 expression owing to weakened TGF-β signaling increased ECM degradation., Conclusions: Hepatic overexpression of the miR-23b/27b/24-1 cluster blocked hepatic fibrosis and may be a novel therapeutic regimen for patients with hepatic fibrosis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Enteric anastomotic (EA) bleeding is a potentially life-threatening surgical complication associated with enteric anastomosis during simultaneous pancreas and kidney transplantation (SPKT)., Aim: To investigate whether suture ligation (SL) for submucosal hemostasis during hand-sewn enteric anastomosis could decrease the morbidity of early EA bleeding in SPKT., Methods: We compared the outcomes of 134 patients classified into SL ( n = 44) and no SL (NSL) groups ( n = 90). This study adheres to the declarations of Istanbul and Helsinki and all donors were neither paid nor coerced., Results: During the first postoperative week, the EA bleeding rate in the SL group was lower than that in the NSL group (2.27% vs 15.56%; P = 0.021); no relationship was found between EA bleeding and donor age, mean pancreatic cold ischemia time, platelet count, prothrombin time international normalized rate, activated partial thromboplastin time, and thrombin time. Anastomotic leakage was observed in one case in the SL group at postoperative day (POD) 14 and in one case at POD 16 in the NSL group ( P = 0.754). No significant difference was found between the two groups in the patient survival, pancreas graft survival, or kidney graft survival., Conclusion: SL for submucosal hemostasis during hand-sewn enteric anastomosis in SPKT can decrease the morbidity of early EA bleeding without increasing the anastomotic leakage rate., Competing Interests: Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To investigate clinical efficacy and safety of single and double segmental percutaneous lumbar discectomy for young and middle-aged patients with double-segment disc herniation., Methods: Retrospective analysis was undertaken for 32 young and middle-aged patients with percutaneous endoscopic lumbar discectomy (PELD) in the treatment of double-segment lumbar disc herniation from January 2015 to October 2018 in Peking University First Hospital. In the study, 18 cases were treated with single-segment treatment and 14 cases with double-segment treatment. Visual analogue score (VAS) and oswestry disability index (ODI) assessment were used to compare clinical symptom outcomes before surgery, 3 months after surgery and at the last follow-up. Macnab criteria were used to assess the patients' overall satisfaction after surgery. Imaging parameters included lumbar lordosis, intervertebral height at each segment and endplate angle of lesion segment on the X-ray. And Michigan State University(MSU) rating and Pfirrmann scoring system were used to evaluate the grade of disc herniation and disc degeneration respectively on magnetic resonance imaging (MRI). The perioperative parameters included the surgeon, anesthesia method, operation time, postoperative hospital stay, postoperative bracing time and perioperative complications., Results: The mean follow-up time was (26.78±10.64) months. There was no significant difference in the follow-up time and baseline information between the two groups( P > 0.05). ODI scores 3 months post-operatively and at the last follow-up were lower in the double segment ( P < 0.05). The ODI improvement was also more significant in the double-segment group at the last follow-up ( P < 0.05). There was no significant difference in radiographic parameters at baseline ( P> 0.05). MSU scale for the primary segment was significantly lowered after both operations ( P < 0.05). MSU scale for secondary segment was significantly lowered in double segment group but not in single segment group. Other imaging parameters were similar between the two groups ( P > 0.05). The operation time of the single-segment group was significantly shorter than that of the double-segment group( P < 0.001). No perioperative complications were found in either group, but three patients underwent secondary lumbar surgery during the postoperative follow-up period in the single-segment group., Conclusion: For young and middle-aged patients with double-segment disc herniation, this study suggests double-segment PELD may be more advantageous than single-segment PELD in terms of asuring clinical efficacy without increasing perioperative risks.

The root-associated actinobacteria play important roles in plant growth, nutrient use, and disease resistance due to their functional diversity. Salvia miltiorrhiza is a critical medicinal plant in China. The root actinobacterial community structure has been studied; however, the functions of root-associated actinobacteria of S. miltiorrhiza have not been elucidated. This study aimed to decipher the diversity and function of the culturable root-associated actinobacteria in plant growth using culture-dependent technology and culturable microbe metagenomes. We isolated 369 strains from the root-associated actinobacteria, belonging to four genera, among which Streptomyces was dominant. Besides, the functional prediction revealed some pathways related to plant growth, nitrogen and phosphorus metabolism, and antagonistic pathogens. We systematically described the diversity and functions of the culturable root-associated actinobacteria community. Our results demonstrated that the culturable root-associated actinobacteria of S. miltiorrhiza have rich functionalities, explaining the possible contribution of culturable root-associated actinobacteria to S. miltiorrhiza 's growth and development. This study provides new insights into understanding the function of the culturable root-associated actinobacteria and can be used as a knowledge base for plant growth promoters and biological control agent development in agriculture., Competing Interests: The authors declare there are no competing interests., (©2021 Wu et al.)

A new fluorescent probe LXY based on the rhodamine 6G platforms has been designed, synthesized, and characterized, which could recognize Fe 3+ effectively in HEPES buffer (10 mM, pH = 7.4)/CH 3 CN (2:3, v/v). And the distinct color change and the rapid emergence of fluorescence emission at 550 nm achieved "naked eye" detection of Fe 3+ . The interaction mode between them was achieved by Job's plot, MS, SEM, and X-ray single-crystal diffraction. Importantly, the crystal structures proved that Fe 3+ could induce the rhodamine moiety transform the closed-cycle form to the open-cycle form. But it is interesting that Fe 3+ did not appear in the crystal structures. Meanwhile, the limit of detection (LOD) of LXY to Fe 3+ was calculated to be 3.47 × 10 -9 . In addition, the RGB experiment, test papers, and silica gel plates all indicated that the probe LXY could be used to distinguish Fe 3+ quantitatively and qualitatively on-site. Moreover, the probe LXY has also been successfully applied to Fe 3+ image in Caenorhabditis elegans , adult mice, and plant tissues. Thus, LXY was considered to have some potential for application in bioimaging., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

During navigation, the visual responses of neurons in mouse primary visual cortex (V1) are modulated by the animal's spatial position. Here we show that this spatial modulation is similarly present across multiple higher visual areas but negligible in the main thalamic pathway into V1. Similar to hippocampus, spatial modulation in visual cortex strengthens with experience and with active behavior. Active navigation in a familiar environment, therefore, enhances the spatial modulation of visual signals starting in the cortex., Competing Interests: ED, CR, SS, TM, KH, AS, MC No competing interests declared, (© 2021, Diamanti et al.)

With the increasing incidence of hepatobiliary diseases, it is particularly important to understand the role of molecular, cellular and physiological factors in the clinical diagnosis and treatment with traditional Chinese medicine(TCM) in the development of liver disease. Appropriate animal models can help us identify the possible mechanisms of relevant diseases. Danio rerio(zebrafish) model was traditionally used to study embryonic development, and has been gradually used in screening and evaluation of liver diseases and relevant drug in recent years. Zebrafish embryos develop rapidly and the digestive organs of 5-day-old juvenile fish are all mature. At this stage, they may develop hepatobiliary diseases induced by developmental defects or compounds. Zebrafish liver is similar to human liver in cell composition, function, signal transduction, response to injury and cell process mediating liver disease. Furthermore, due to the high conservation of genes and proteins between humans and zebrafish, zebrafish becomes an alternative system for studying basic mechanisms of liver disease. Therefore, genetic screening could be performed to identify new genes involving specific disease processes, and chemical screening could be made for drugs in specific processes. This paper briefly introduced the experimental properties of zebrafish as model system, emphasized the study progress of zebrafish models for pathological mechanism of liver diseases, especially fatty liver, and drug screening and evaluation, so as to provide ideas and techniques for the future liver toxicity assessment of TCM.

Background: Ureteric stricture is a common and salvaging complications after renal transplantation. Two treatment methods are usually used, retrograde ureteral stent placement and percutaneous nephrostomy. The former has a higher failure rate, the latter has a great risk. Therefore, a safe and reliable treatment is needed., Case Presentation: A technique of retrograde insertion of ureteral stent was established, which was applicable in three transplant recipients with post-transplant ureteral stenosis, and the data was retrospectively recorded. The patients are 2 men and 1 woman, ages 44, 27 and 32 years. These patients underwent a total of five times of retrograde insertion of ureteral stent between 2018 and 2019. None of these patients had any postoperative complication, but all patients had complete recovery from oliguric status within two weeks., Conclusions: The retrograde ureteric stent insertion by percutaneous suprapubic access to the bladder (RUS-PSAB) was demonstrated feasibility and safety in a case series with short-term follow-up. However, larger prospective studies are needed.

The fluorescent probe L , based on naphthalimide-modified coumarin, was designed, synthesized, and characterized, which could recognize Cu 2+ from other cations selectively and sensitively in HEPES buffer (10 mM, Ph = 7. 4)/CH 3 CN (1:4, V/V). When the probe L interacted with Cu 2+ , the color and the fluorescent intensity changed obviously and it provided the naked-eye detection for Cu 2+ . The recognition mode between them was achieved by Job's plot, IR, MS, SEM, and 1 HNMR. In addition, test strips made from L could still interact with Cu 2+ in tap water effectively. The limit of detection (LOD) of L was 3.5 × 10 -6 M. Additionally, the density functional theory (DFT) calculation method was used to analyze the action mechanism of L toward Cu 2+ . Importantly, the fluorescent probe L could demonstrate favorable selectivity toward Cu 2+ in Caenorhabditis elegans . Thus, L was considered to have some potential for application in bioimaging., (Copyright © 2020 Zhang, Chen, Bai, Qiao, Wei, Zhang, Li and Qu.)

A two-dimensional model MIKE21 coupled with a modified EcoLab module was applied to model the water quality of surface flow wetlands. In the model, vegetation effects, oxygen production, nutrient consumption by microorganisms and vegetation were set in the solutions of hydrodynamic, chemical, and biological processes. Based on the field investigation and measurements in the Guishui River wetland, the model was established for the downstream reaches of the Guishui River and the Sanli River. The model calculated the hydrodynamics and water quality changes by vegetation type and distribution. The model parameters were calibrated and results were validated using the measurements. The concentrations of ammonia nitrogen, phosphate, and total nitrogen at outflow decreased by 14.29%, 33.33%, and 20.00% in the presence of wetland vegetation compared to no wetland vegetation. During water circulation, the flow rate increased by 0.4 m 3 ·s -1 at the inlet of Guishui and Sanli rivers, increasing the water level and velocity in some parts of the rivers. The water areas with vegetation in Sanli and Guishui rivers increased by 144.44% and 13.16%, respectively. The concentrations of ammonia nitrogen, phosphate, and total nitrogen at outflow decreased by 35.71%, 50.00%, and 46.67% compared to no wetlands and no circulation. The circulation strengthened the wetland purification function. The wetland vegetation distribution was organically integrated into the model for water quality calculation, which provides the technical support for the water quality response research under comprehensive measures such as river and lake wetland ecological restoration and water conservancy regulation.

A fluorescent and colorimetric chemosensor L based on rhodamine 6G was designed, synthesized, and characterized. Based on a two-step reaction, the chemosensor L effectively recognized Hg 2+ . The interaction between the chemosensor and Hg 2+ was confirmed by ultraviolet-visible spectrophotometry, fluorescence spectroscopy, electrospray ionization-mass spectrometry, Fourier-transform infrared spectroscopy, and frontier molecular orbital calculations. The chemosensor L was also incorporated into test strips and silica gel plates, which demonstrated good selectivity and high sensitivity for Hg 2+ ., (Copyright © 2020 Bai, Wang, Zhang, Wang, Qiao, Wei, Zhang, Chen and Yang.)

Deciding between stimuli requires combining their learned value with one's sensory confidence. We trained mice in a visual task that probes this combination. Mouse choices reflected not only present confidence and past rewards but also past confidence. Their behavior conformed to a model that combines signal detection with reinforcement learning. In the model, the predicted value of the chosen option is the product of sensory confidence and learned value. We found precise correlates of this variable in the pre-outcome activity of midbrain dopamine neurons and of medial prefrontal cortical neurons. However, only the latter played a causal role: inactivating medial prefrontal cortex before outcome strengthened learning from the outcome. Dopamine neurons played a causal role only after outcome, when they encoded reward prediction errors graded by confidence, influencing subsequent choices. These results reveal neural signals that combine reward value with sensory confidence and guide subsequent learning., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

A naked-eye colorimetric chemosensor DK based on benzothiazole could recognize CN - effectively. When DK interacted with CN - in the aqueous solution, the obvious color change of the solution was directly observed by the naked eye. Other anions did not cause any interference. It is interesting that DK could also discriminate Ni 2+ from other cations, and the possible interaction mode between them was verified based on the Job's plot, 1 H nuclear magnetic resonance titration, infrared , electrospray ionization mass spectrometry, scanning electron microscopy analysis, and density functional theory calculation methods. As a result, it is clear that the mode of action between DK and CN - was different from that between DK and Ni 2+ . Meanwhile, the limit of detection of DK toward CN - and Ni 2+ was calculated to be 1.7 × 10 -8 or 7.4 × 10 -9 M, respectively. In addition, CN - was recognized qualitatively by a test paper and silica gel plates made from DK . DK was able to detect CN - in tap water quantitatively, rapidly, and on-site by the use of a smartphone APP. All results implied that DK has certain prospects for practical application to identify CN - in water., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

The aim of the present study was to investigate whether class C1 decoy oligodeoxynucleotides (ODNs) can inhibit the expression of pro‑fibrotic genes associated with rat hepatic stellate cell (HSC) activation and hepatic fibrosis. Luciferase reporter assays were performed to test the promoter activities of transforming growth factor (TGF)‑β and its downstream target genes following transfection of decoy ODNs and plasmids into HSC‑T6 cells, and western blot assays were performed to measure the protein expression of those genes following decoy ODN transfection. Class C1 decoy ODNs were confirmed to inhibit the promoter activity of TGF‑β and its downstream target genes, such as type 1 collagen (COLI)α1, tissue inhibitor of metalloproteinases (TIMP)1 and α‑smooth muscle actin by Gaussia luciferase reporter assay, and to further downregulate the expression of TGF‑β, SMAD3, COLIα1 and TIMP1 by western blotting in activated HSC‑T6 cells. In conclusion, class C1 decoy ODNs inhibited pro‑fibrotic gene expression in rat HSCS by downregulating TGF‑β signaling.

A novel long-wavelength turn-on fluorescent chemosensor CS based on pyrene was synthesized to detect Hg 2+ . In the presence of other metal ions, CS could effectively recognize Hg 2+ and produce the turn-on fluorescent emission at 607 nm. Also, the absorption spectrum exhibited red-shift. Meanwhile, the change of the solution color from yellow to orange was directly observed by the naked eye. The interaction between CS and Hg 2+ was confirmed by the Job's plot, electrospray ionization mass spectrometry, scanning electron microscopy, and density functional theory calculations. It was found that the fluorescence of CS could be reversible when I - was added into the solution of CS and Hg 2+ . CS illustrated high selectivity and good sensitivity for Hg 2+ with the limit of detection of 36 nm. Moreover, CS could be utilized as test strips and silica gel plates to identify Hg 2+ ., Competing Interests: The authors declare no competing financial interest.

A methionine methyl ester-modified coumarin derivative was designed and synthesized, which could discriminate Cu 2+ from other metal ions in HEPES buffer (10 mM, pH 7.4)/CH 3 CN (40:60, V/V). The detection limit of WM toward Cu 2+ was 1.84 × 10 -7  M, which was lower than the concentration of Cu 2+ in drinking water suggested by WHO and EPA. And the proposed coordination mode exhibiting the interaction between WM and Cu 2+ was studied by UV-Vis, fluorescence spectrum, ESI-MS and FT-IR. Based on the fluorescent reversibility of WM, WM was considered as a molecular logic gate and molecular keypad lock. In addition, the test strips and the silica gel plates prepared from the solution of WM also demonstrate the favorable selectivity toward Cu 2+ ., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: The objective of this study was to evaluate cerebral venous recanalization with magnetic resonance black-blood thrombus imaging (MRBTI) in patients with cerebral venous thrombosis (CVT) who underwent batroxobin treatment in combination with anticoagulation., Methods: A total of 31 CVT patients were enrolled in this real-world registry study. The patients were divided into batroxobin (n = 21) and control groups (n = 10). In addition to the same standard anticoagulation as in the control group, patients in the batroxobin group underwent intravenous batroxobin for a total of three times., Results: In the batroxobin group compared with the control group, we found better odds of recanalization degree [adjusted OR (95%CI) of 8.10 (1.61-40.7)] and segment-stenosis attenuation [adjusted OR (95%CI) of 4.48 (1.69-11.9)] with batroxobin treatment. We further noted a higher ratio of patients with the attenuation of stenosis [adjusted OR (95%CI) of 26.4 (1.10-635)]; as well as a higher ratio of segments with stenosis reversion [adjusted OR (95%CI) of 4.52 (1.48-13.8)]. However, neurological deficits between the two groups showed no statistical difference at 90-day follow-up (P > 0.05)., Conclusions: Batroxobin may promote venous sinus recanalization and attenuate CVT-induced stenosis. Further randomized study of this promising drug may be warranted to better delineate the amount of benefit., (© 2018 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Neuronal populations in sensory cortex produce variable responses to sensory stimuli and exhibit intricate spontaneous activity even without external sensory input. Cortical variability and spontaneous activity have been variously proposed to represent random noise, recall of prior experience, or encoding of ongoing behavioral and cognitive variables. Recording more than 10,000 neurons in mouse visual cortex, we observed that spontaneous activity reliably encoded a high-dimensional latent state, which was partially related to the mouse's ongoing behavior and was represented not just in visual cortex but also across the forebrain. Sensory inputs did not interrupt this ongoing signal but added onto it a representation of external stimuli in orthogonal dimensions. Thus, visual cortical population activity, despite its apparently noisy structure, reliably encodes an orthogonal fusion of sensory and multidimensional behavioral information., (Copyright © 2019, American Association for the Advancement of Science.)

Introduction: Mitochondria are promising targeting organelles for anticancer strategies; however, mitochondria are difficult for antineoplastic drugs to recognize and bind. Mitochondria-penetrating peptides (MPPs) are unique tools to gain access to the cell interior and deliver a bioactive cargo into mitochondria. MPPs have combined or delivered a variety of antitumor cargoes and obviously inhibited the tumor growth in vivo and in vitro. MPPs create new opportunities to develop new treatments for cancer., Areas Covered: We review the target sites of mitochondria and the target-penetration mechanism of MPPs, different strategies, and various additional strategies decorated MPPs for tumor cell mitochondria targeting, the decorating mattes including metabolism molecules, RNA, DNA, and protein, which exploited considered as therapeutic combined with MPPs and target in human cancer treatment., Expert Opinion/commentary: Therapeutic selectivity that preferentially targets the mitochondrial abnormalities in cancer cells without toxic impact on normal cells still need to be deepen. Moreover, it needs appropriate study designs for a correct evaluation of the target delivery outcome and the degradation rate of the drug in the cell. Generally, it is optimistic that the advances in mitochondrial targeting drug delivery by MPPs plasticity outlined here will ultimately help to the discovery of new approaches for the prevention and treatment of cancers.

A new rhodamine-6G-based chemosensor X was designed and synthesized for the colorimetric and fluorometric detection of Hg 2+ . The chemosensor X responsed to Hg 2+ had good sensitivity, high selectivity and excellent reversibility in HEPES buffer (10 mM, pH 7.4)/CH 3 CN (40:60, V/V). The recognition mechanism of X toward Hg 2+ was evaluated by Job's plot, IR and MS. Meanwhile, X-Hg 2+ fluorescence lifetime was also measured. It was interesting that X displayed favorable reversibility to form an "off-on-off" type signaling behavior with the Hg 2+ -induced emission spectra being quenched by I - . Furthermore, it could be applied as a molecular logic gate and test strips based on X exhibited a good reversibility selectivity to Hg 2+ ., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: The aim of this study is to prepare medical staff in order to prevent medical malpractice litigation through analysis of litigation cases related to the department of surgery in Korea., Methods: A total of 94 litigation cases related to the department of surgery, where a certain amount of payment was ordered to the defendant between 2005 through 2010, were analyzed. We examined time of occurrence, amount claimed and awarded in damages, plaintiff claims, and court opinion., Results: An average of 3.2 years was spent from the date of the incident occurring to the end of the litigation procedures. The average amount awarded in judgments for damages was 59,708,983 ± 67,307,264 (range, 1,700,000-365,201,482) Korean won. Cases were found involving the following opinion of the court: violation of duty of care (49 cases), violation of informed consent (7 cases), violation of duty of care and informed consent (5 cases), and settlement, reconciliation, and others (32 cases). By analyzing defendants' negligence in court opinions, diagnosis (30.8%) was the most common, followed by post-operation management (27.7%)., Conclusion: Physicians have to conduct treatment and surgery based on exact diagnosis and be careful to observe patients' conditions and symptoms after surgery. It is essential to identify the current status and characteristics of medical litigation for reducing further litigation and improving patient safety. In order to create a safe medical environment, national efforts should be made not only by individuals but also at the national level., Competing Interests: CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported.

Cell-penetrating peptides (CPPs) have a great potential for intracellular delivery of cell-impermeable biological macromolecules in clinical therapy. However, their lack of cell and tissue specificity remains the primary limitation for their clinical development as drug delivery vehicles. In this study, based on phage display and an in silico approach, we found a novel CPP-MT23 with mouse melanoma cell specificity, it can only enter B16 melanoma cancer cells and without any cytotoxicity, Moreover, MT23 showed higher penetration efficiency based on fluorescence microcopy and quantitative assay, and it has capability for mediating functional Apoptin into cells in vitro or in vivo. Moreover, MT23-Apoptin can significantly inhibit tumor growth and induce the cell apoptosis in B16 tumor bearing mice. To sum up, all the results implicated that MT23 has the potential to deliver exogenous therapeutic proteins for further use and it also expected to lay the foundation for developing human melanoma cancer cell specific CPP., (Copyright © 2017 Elsevier B.V. All rights reserved.)

As a key molecule involved in cell recognition, calreticulin (CRT) may be expressed on the surface of (pre-) apoptotic cells and provide the signal that is recognized by dendritic cells (DCs) or other antigen presenting cells (APCs), which results in phagocytosis. Within the APCs, tumor-associated antigens (TAAs) may be subsequently presented to T lymphocytes, which triggers a specific antitumor immune response. It has been hypothesized that CRT is able to act as the immunologic adjuvant and translocate itself and TAAs to the cell surface and induce a specific antitumor immune response. In the present study, CRT was demonstrated to translocate itself and mucin 1 (MUC1), a breast cancer antigen, to the surface of 4T1 cells and the MUC1-CRT-coated cells were able to induce apoptosis in a time-dependent manner. When DCs were infected with adenovirus containing MUC1-CRT, an increase in T cell proliferation and cytokine production was exhibited. These results suggest that CRT may act as an immunologic adjuvant with MUC1 and induce a strong immune response.

Aim: To analyse and summarise clinical and radiological features among patients with posterior reversible encephalopathy syndrome (PRES), to assess related factors with eclampsia and pre-eclampsia, and to compare the different factors between cytotoxic and vasogenic oedema among PRES patients., Materials and Methods: The clinical and radiological findings of 237 pre-eclamptic or eclamptic patients with neurological symptoms were evaluated retrospectively. Multiple logistic regression analyses were performed to compare the differences among these parameters., Results: Seventy-six patients (32.07%) were diagnosed with PRES. Multiple logistic regression indicated that seizure (odds ratio [OR], 2.760; 95% confidence interval [CI]: 1.087-7.011; p=0.033), visual disturbances (OR=2.062 95%CI, 1.033-4.115; p=0.004), multiple production history (OR=3.637; 95% CI: 1.068-8.228; p=0.002) were independent risk factors for PRES. PRES+ (OR=3.217; 95%CI, 1.346-7.686; p=0.009), Visual disturbances (OR=4.283; 95% CI: 1.843-9.953; p=0.001) had strong association with eclampsia. Visual disturbances (OR=7.200; 95% CI: 2.116-24.496; p=0.002) had strong correlation with eclampsia among PRES+ patients. Visual disturbances (OR=2.947; 95% CI: 1.135-7.648; p=0.026) were independently related to cytotoxic oedema., Conclusions: Nearly one-third of pre-eclampsia or eclampsia patients with neurological symptoms have PRES. Visual disturbances, seizure, multiple production history are independent risk factors for PRES. Visual disturbances have a strong association with eclampsia whether patients have PRES or not. Visual disturbances are independently related to cytotoxic oedema among PRES+ patients., (Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Gremlin1, the antagonist of bone morphogenetic protein-7 and one of the target genes of transforming growth factor (TGF)-β signal pathway, plays an important role in embryonic development and its expression decreases along with aging. To explore the expression of gremlin1 in liver fibrosis and the causal link between gremlin1 and hepatic stellate cell (HSC) activation, we detected the expression of gremlin1 in mice with hepatic fibrosis induced by porcine serum using real time quantitative PCR (RT-qPCR) and immunohistochemical staining. The hepatic fibrosis mice were evaluated by the external feature of the liver, histology, hepatic function, collagen deposition, and the expression of fibrosis-related genes (genes COLIα2 and COLIVα2) in the liver. In the HSC-T6, western blotting was used to analyze the expression of α-smooth muscle actin (α-SMA), COL1α, and TGF-β1 in conditions of overexpression of gremlin1 or gremlin1 being knocked down by specific siRNA, respectively. The results showed that the mRNA expression of the gremlin1 gene was significantly increased consistent with increased expression of COLIα2 and COLIVα2 in the liver tissue of the hepatic fibrosis mice. Increased expression of gremlin1 coincided with the same area of the collagen deposition. Furthermore, the results also showed that the expression of α-SMA, COLIα1, and TGF-β1 was consistent with the expression of gremlin1 not only in the HSC-T6 overexpressing gremlin1 but also in the HSC-T6 that gremlin1 is knocked down by specific siRNA. The findings suggest that gremlin1 might play an important role in the progression of hepatic fibrosis and that it modulates HSC activation.

Carbon nitride is a novel nonmetal semiconductor photocatalyst, which has developed into an ideal environmental treatment material in recent years. Graphite carbon nitride(g-C 3 N 4 ) was prepared through pyrolysis melamine, and the structure, morphology and optical properties of samples were characterized by X-ray diffraction(XRD), transmission electron microscopy(TEM) and UV-Vis diffuse reflectance spectra(UV-Vis DRS). The potential application of g-C 3 N 4 in the simultaneous photocatalysis reduction of Cr(Ⅵ) and oxidation of sulfosalicylic acid(SSA) was further explored. And the effects of different conditions such as catalyst dosage, pH and initial concentration ratio of Cr(Ⅵ) with SSA on the simultaneous photocatalysis were also investigated. The results showed that when the catalyst dosage was 0.5 g·L -1 , pH=2, the initial concentration ratio of Cr (VI) and SSA was 1:4(10 mg·L -1 :40 mg·L -1 ), optimal simultaneous photocatalysis efficiency was achieved, which was more than 3 times higher than that of the separated photoreduction or photooxidation reactions. Within 3 hours, the reduction ratio of Cr(Ⅵ) and oxidation ratio of SSA could reach 98.9% and 93.4%, respectively. The mechanism of simultaneous photocatalysis was discussed. Cr(Ⅵ) was reduced by electrons and SSA was oxidized by the combined function of hole, O 2 ·- and·OH under visible light.

Glycogen synthase kinase3 (GSK3α and GSK3β) are serine/threonine protein kinases acting on numerous substrates and involved in the regulation of various cellular functions such as their proliferation, survival, glycogen metabolism, and autophagy. Accumulating evidence indicates that the expression of GSK3α is increased mainly in androgendependent while that of GSK3β in androgenindependent prostate cancer, and that GSK3β is also involved in the regulation of the transactivation of the androgen receptor (AR) and growth of prostate cancer. Animal experiments have proved that some GSK3 inhibitors, such as lithium, can significantly suppress tumor growth in different animal models of prostate cancer. The GSK3 inhibitor is promising to be an important agent for the clinical management of prostate cancer.

The imbalance between transforming growth factor β and bone morphogenetic protein 7 signaling pathways is a critical step in promoting hepatic stellate cell activation during hepatic fibrogenesis. Gremlin1 may impair the balance. Something remains unclear about the regulatory mechanisms of gremlin1 action on hepatic stellate cell activation and hepatic fibrosis. In the current study, gremlin1 overexpression promotes activation of hepatic stellate cells. Knockdown of gremlin1 with siRNAs suppresses hepatic stellate cell activation and attenuates hepatic fibrosis in rat model. Our results also show that miR-23b/27b cluster members bind to 3'-untranslated region of gremlin1 resulting in reduction of transforming growth factor β, α-smooth muscle actin and collagenI α1/2 gene expression. Our findings suggest that gremlin1 promotes hepatic stellate cell activation and hepatic fibrogenesis through impairment of the balance between transforming growth factor β and bone morphogenetic protein 7 signaling pathways. The miR-23b/27b cluster suppresses activation of hepatic stellate cells through binding gremlin1 to rectify the imbalance.

The first example of a metal-free unactivated C(sp 3 )-H bond functionalization of alkyl nitriles with terminal vinylarenes to provide γ-ketonitrile derivatives is described. This protocol features simple operations, a broad substrate scope, and atom and step economy. In addition, Cu-catalyzed C(sp 3 )-H bond functionalization of azodiisobutyronitrile (AIBN) and analogues with terminal vinylarenes to generate γ-ketonitriles was also studied. A preliminary free-radical pathway was confirmed by capturing an alkyl radical, and a conjugate system was found that can stabilize radical intermediates and be in favor of this transformation. Density functional theory (DFT) calculations also provide important evidence of the free-radical pathway.

Hepatic fibrosis is a reversible process involving plenty of transcription factors and pathways. Vitamin D receptor (VDR) as a member of ligand-induced transcription factors can interact with 9-cis retinoid X receptor (RXR) and VDR-interacting repressor (VDIR) to mediate transactivation or transrepression in the absence or in the presence of VDR ligand to regulate the expression of VDR target genes. The active form of vitamin D [1α,25(OH)2D3] can downregulate the expression of type I collagen both α1 and α2 (COLIα1 and COLIα2) in hepatic stellate cells (HSC-T6) in a time-dependent fashion, which provides a new direction for hepatic fibrosis therapy. As one of VDR target genes, rat COLIα1 gene contains 1αnVDRE (E-box1 and E-box2) in its promoter, and unliganded VDR/RXR may bind to 1αnVDRE through VDIR to mediate transactivation, whereas liganded VDR/RXR may bind to 1αnVDRE through VDIR for transrepression. The results suggested a sort of relying on each other relationship between VDR/RXR and VDIR in regulating the expression of COLIα1 gene in HSC-T6 cells, which established VDR as a potential target for blocking and even reversing hepatic fibrosis.

Used in combination with immunomodulatory therapies, remyelinating therapies are a viable therapeutic approach for treating individuals with multiple sclerosis. Studies of postmortem MS brains identified greater remyelination in demyelinated cerebral cortex than in demyelinated brain white matter and implicated reactive astrocytes as an inhibitor of white matter remyelination. An animal model that recapitulates these phenotypes would benefit the development of remyelination therapeutics. We have used a modified cuprizone protocol that causes a consistent and robust demyelination of mouse white matter and cerebral cortex. Spontaneous remyelination occurred significantly faster in the cerebral cortex than in white matter and reactive astrocytes were more abundant in white matter lesions. Remyelination of white matter and cerebral cortex was therapeutically enhanced by daily injections of thyroid hormone triiodothyronine (T3). In summary, we describe an in vivo demyelination/remyelination paradigm that can be powered to determine efficacy of therapies that enhance white matter and cortical remyelination., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cell-penetrating peptide (CPP) based delivery have provided immense potential for the therapeutic applications, however, most of nonhuman originated CPPs carry the risk of possible cytotoxicity and immunogenicity, thus may restricting to be used. Here, we describe a novel human-derived CPP, denoted hPP10, and hPP10 has cell-penetrating properties evaluated by CellPPD web server, as well as In-Vitro and In-Vivo analysis. In vitro studies showed that hPP10-FITC was able to penetrate into various cells including primary cultured cells, likely through an endocytosis pathway. And functionalized macromolecules, such as green fluorescent protein (GFP), tumor-specific apoptosis inducer Apoptin as well as biological active enzyme GCLC (Glutamate-cysteine ligase, catalytic subunit) can be delivered by hPP10 in vitro and in vivo. Collectively, our results suggest that hPP10 provide a novel and versatile tool to deliver exogenous proteins or drugs for clinical applications as well as reprogrammed cell-based therapy., Competing Interests: None to disclose.

Background: Many studies have reported that depression and anxiety have bidirectional relationship with headache. However, few researches investigated the roles of depression or anxiety in patients with headache. We surveyed the prevalence of depression and anxiety as a complication or cause of headache among outpatients with a chief complaint of headache at neurology clinics in general hospitals. Additional risk factors for depression and anxiety were also analyzed., Methods: A cross-sectional study was conducted at 11 general neurological clinics. All consecutive patients with a chief complaint of headache were enrolled. Diagnoses of depression and anxiety were made using the Chinese version of the Mini International Neuropsychiatric Interview, and those for headache were made according to the International Classification of Headache Disorders, 2nd Edition. The headache impact test and an 11-point verbal rating scale were applied to assess headache severity and intensity. Logistic regression was used to analyze risk factors of patients with headache for depression or anxiety., Results: A total of 749 outpatients with headache were included. Among them, 148 (19.7%) were diagnosed with depression and 103 (13.7%) with anxiety. Further analysis showed that 114 (15.2%) patients complaining headache due to somatic symptoms of psychiatric disorders and 82 (10.9%) had a depression or anxiety comorbidity with headache. Most patients with depression or anxiety manifested mild to moderate headaches. Poor sleep and severe headache-related disabilities were predictors for either depression or anxiety., Conclusion: Clinicians must identify the etiology of headache and recognize the effects of depression or anxiety on headache to develop specific treatments.

Background: The excessive accumulation of extracellular matrix of hepatic fibrosis is positively correlated with tissue inhibitors of metalloproteinase 1 (TIMP1). Here we aimed to investigate whether TIMP1 may be down-regulated by Decoy ODNs strategy to capture transcriptional factor upstream TIMP1 element 1 (UTE1) and specificity protein 1(SP1)., Results: By luciferase reporter assays, we confirmed that these Decoy ODNs could influence the promoter activation of TIMP-1, α-SMA and Collagen Iα2 (COLΙα2) genes as well as the enhancer activation of TRE in HSC-T6 cells, and the combination tended to be more effective than SP1 or UTE1 Decoy ODN alone. Western blot analysis also demonstrated down-regulation of the expression of those target genes except for TGF-β. Furthermore, we observed that the viability of HSC-T6 cells at 72 h was significantly in decline in combination group., Conclusion: The combination of SP1 and UTE1 Decoy ODNs treatments inhibit the activation and proliferation of HSCs more effectively than one of the Decoy ODNs through co-regulation of TIMP1 and TGF-β signal pathway but not the expression of TGF-β itself.

To evaluate the predictive and prognostic significance of the prognostic nutritional index (PNI) in a large cohort of gastric cancer patients who underwent gastrectomy.Assessing a patient's immune and nutritional status, PNI has been reported as a predictive marker for surgical outcomes in various types of cancer.We retrospectively reviewed data from a prospectively maintained database of 7781 gastric cancer patients who underwent gastrectomy from January 2001 to December 2010 at a single center. From this data, we analyzed clinicopathologic characteristics, PNI, and short- and long-term surgical outcomes for each patient. We used the PNI value for the 10th percentile (46.70) of the study cohort as a cut-off for dividing patients into low and high PNI groups.Regarding short-term outcomes, multivariate analysis showed a low PNI (odds ratio [OR] = 1.505, 95% CI = 1.212-1.869, P <0.001), old age, male sex, high body mass index, medical comorbidity, total gastrectomy, and combined resection to be independent predictors of postoperative complications. Among these, only low PNI (OR = 4.279, 95% CI = 1.760-10.404, P = 0.001) and medical comorbidity were independent predictors of postoperative mortality. For long-term outcomes, low PNI was a poor prognostic factor for overall survival, but not recurrence (overall survival: hazard ratio [HR] = 1.383, 95% CI = 1.221-1.568, P < 0.001; recurrence-free survival: HR = 1.142, 95% CI = 0.985-1.325, P = 0.078).PNI can be used to predict patients at increased risk of postoperative morbidity and mortality. Although PNI was an independent prognostic factor for overall survival, the index was not associated with cancer recurrence.

To explore a novel strategy in suppressing tumor metastasis, we took the advantage of a recent RNA activation (RNAa) theory and used small double-strand RNA molecules, termed as small activating RNAs (saRNA) that are complimentary to target gene promoter, to enhance transcription of metastasis suppressor gene. The target gene in this study is Dihydro-pyrimidinase-like 3 (DPYSL3, protein name CRMP4), which was identified as a metastatic suppressor in prostate cancers. There are two transcriptional variants of DPYSL3 gene in human genome, of which the variant 2 is the dominant transcript (DPYSL3v2, CRMP4a) but is also significantly down-regulated in primary prostate cancers. A total of 8 saRNAs for DPYSL3v1 and 14 saRNAs for DPYSL3v2 were tested in multiple prostate cancer cell lines. While none of the saRNAs significantly altered DPYSL3v1 expression, 4 saRNAs showed a strong enhancing effect on DPYSL3v2 expression, resulting in reduced cell mobility in vitro. To achieve a prostate cancer-specific delivery for in vivo testing, we conjugated the most potent saV2-9 RNA molecule with the prostate-specific membrane antigen (PSMA)-targeting aptamer A10-3.2. The conjugates successful increased DPYSL3v2 gene expression in PSMA-positive but not PSMA-negative prostate cancer cells. In nude mice bearing orthotopic xenograft of prostate cancer, a 10-day consecutive treatment with the saV2-9 conjugates significantly suppress distal metastasis compared to the control saRNAs. Analysis of xenograft tissues revealed that DPYSL3v2 expression was largely increased in saV2-9 conjugate-treated group compared to the control group. In conclusion, DPYSL3v2 promoter-targeted saRNA molecules might be used as an adjunctive therapy to suppress prostate cancer metastasis., Competing Interests: The authors declare no conflicts of interest.

Superficial spreading early gastric cancer (EGC) is a rare disease that is treated mainly by surgery. There are few studies on the safety of endoscopic treatment for patients with superficial spreading EGC. The aims of this study were to (1) investigate the risk of lymph node metastasis of superficial spreading EGC and (2) investigate the potential criteria for endoscopic treatment of superficial spreading EGC using surgical specimens.Between 2000 and 2010, patients who received curative surgery of R0 resection at Severance Hospital (Seoul, Korea) for early gastric cancer were enrolled. The superficial spreading EGC was defined as cancer in which the longest tumor length was ≥6 cm. The medical records of the patients were reviewed retrospectively.Of the 3813 patients with EGC, 140 (3.7%) had lesions ≥ 6 cm, whereas 3673 (96.3%) had lesions < 6 cm. Patients with superficial spreading EGC had higher rates of submucosal cancer (59.3% vs 45.7%, P = 0.002), lymphovascular invasion (18.6% vs 9.8%, P < 0.001), and lymph node metastasis (15.7% vs 10.1%, P = 0.033) compared with patients with common EGC (< 6 cm). Multivariate analysis revealed that a tumor ≥ 6 cm was not strongly associated with lymph node metastasis in EGC, as compared with a tumor < 6 cm, but submucosal invasion and lymphovascular invasion were strongly associated with lymph node metastasis in EGC. In mucosal cancer without ulcers, tumors ≥ 6 cm had a higher rate of lymph node metastasis than tumors ≤ 2 cm; however, this trend was not significant (7.7% vs 5.3%, P = 0.455).Superficial spreading EGC was not associated with an increased risk of lymph node metastasis compared with common EGC. We suggest that differentiated intramucosal superficial spreading EGC without ulceration can be treated by endoscopic submucosal dissection., Competing Interests: The authors have no funding and conflicts of interest to disclose.

The patient-derived xenograft (PDX) model is emerging as a promising translational platform to duplicate the characteristics of tumours. However, few studies have reported detailed histological and genomic analyses for model fidelity and for factors affecting successful model establishment of gastric cancer. Here, we generated PDX tumours surgically-derived from 62 gastric cancer patients. Fifteen PDX models were successfully established (24.2%, 15/62) and passaged to maintain tumours in immune-compromised mice. Diffuse type and low tumour cell percentage were negatively correlated with success rates (p = 0.005 and p = 0.025, respectively), while reducing ex vivo and overall procedure times were positively correlated with success rates (p = 0.003 and p = 0.01, respectively). The histology and genetic characteristics of PDX tumour models were stable over subsequent passages. Lymphoma transformation occurred in five cases (33.3%, 5/15), and all were in the NOG mouse, with none in the nude mouse. Together, the present study identified Lauren classification, tumour cell percentages, and ex vivo times along with overall procedure times, as key determinants for successful PDX engraftment. Furthermore, genetic and histological characteristics were highly consistent between primary and PDX tumours, which provide realistic paraclinical models, enabling personalised development of treatment options for gastric cancer.

A controlled new oxidant sulfate radical anion (SO4(·-)) was found and it can be easily prepared by mixing Na2S2O4 and TBHP with stirring. In this new metal-free oxidation system (Na2S2O4/TBHP), SO4(·-) can be used as a controllable oxidant to oxidize various aromatic alcohols to the corresponding aldehydes in good yields without any acid formation at room temperature. SO4(·-) was determined by a DMPO (5,5-dimethyl-1-pyrroline-N-oxide) spin-trapping EPR method at room temperature on a Bruker E500 spectrometer and the results suggested that SO4(·-) was generated in this transformation.

Objectives: To investigate the value of diffusion tensor imaging (DTI) and tractography in renal allografts at the early stage after kidney transplantation., Methods: This study was approved by the institutional ethical review committee, and written informed consent was obtained. A total of 54 renal allograft recipients 2-3 weeks after transplantation and 26 age-matched healthy volunteers underwent renal DTI with a 3.0-T magnetic resonance imaging (MRI) system. Recipients were divided into three groups according to the estimated glomerular filtration rate (eGFR). Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the cortex and medulla were measured and compared among the groups. Whole-kidney tractography was performed. Correlation of eGFR with diffusion parameters was evaluated., Results: In allografts with stable function, the medullary ADC was higher and the cortical FA was lower (p < 0.001) than in healthy kidneys. The cortical ADC, medullary ADC and FA decreased as the allograft function declined, and with a positive correlation with eGFR (p < 0.001); cortical FA did not. Tractography demonstrated a decrease of tract density in impaired functional allografts., Conclusions: Renal DTI produces reliable results to assess renal allograft function at the early stage after transplantation., Key Points: • DTI and tractography can evaluate renal allograft function at an early stage • Medullary FA, cortical and medullary ADC can effectively evaluate allograft function • Medullary FA, cortical and medullary ADC are correlated with eGFR in renal allografts • Medullary ADC increased and cortical FA decreased in stable allografts compared to control subjects • Medullary FA, cortical and medullary ADC decreased and allograft function declined.