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Dysregulated iron metabolism is a hallmark of many cancers, including glioblastoma (GBM). However, its role in tumor progression remains unclear. Herein, we identified coatomer protein complex subunit zeta 1 (COPZ1) as a therapeutic target candidate which significantly dysregulated iron metabolism in GBM cells. Overexpression of COPZ1 was associated with increasing tumor grade and poor prognosis in glioma patients based on analysis of expression data from the publicly available database The Cancer Genome Atlas (P P P

Marine polysaccharides originated from seaweeds, including agar, alginate, carrageenan, and fucoidan, possess various kinds of physiological activities and have been widely used in food, agricultural and medical areas. However, the application has been greatly limited by their poor solubility and low bioavailability. Thus marine oligosaccharides, as the degradation products of those polysaccharides, have drawn increasing attentions due to their obvious biological activities, good solubility and excellent bioavailability. This review will summarize the recent advances on the source, molecular structure and physiological activity of marine oligosaccharides, emphasizing their application as functional food additives. Furthermore, the relationship between the structure and the physiological activity of marine oligosaccharides is also elucidated and highlighted. The review concludes with an outlook toward potential applications for preparing the functional oligosaccharides in food biotechnology and agriculture fields.

KRAS is one of the most frequently mutated oncogenes in human cancers. Despite nearly 40 years of research, KRAS remains largely undruggable, in part due to an incomplete understanding of its biology. Recently, KRAS dimerization was discovered to play an important role in its signalling function. The KRAS D154Q mutant was described as a dimer-deficient variant that can be used to study the effect of dimer- ization in KRAS oncogenicity. However, we show here that KRAS D154Q homo-and heterodimerized with KRAS WT using three separate protein-protein interaction assays, and that oncogenic KRAS dimer- ization was not negatively impacted by the presence of a secondary D154Q mutation. In conclusion, we advise caution in using this variant to study the purpose of dimerization in KRAS oncogenic behaviour.(c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://crea-tivecommons.org/licenses/by-nc- nd/4.0/).

We report the complete mitochondrial genome (mitogenome) sequence of the MacClelland’s Coral Snake Sinomicrurus macclellandi (Reinhardt, 1844). The sequence was determined by shotgun sequencing. Th...

Aim Growing evidence suggests that endothelial-mesenchymal transition (EndMT) play key roles in pulmonary arterial remodeling during pulmonary arterial hypertension (PAH), but the underlying mechanisms have yet to be fully understood. miR-27a has been shown to promote proliferation of pulmonary arterial cells during PAH, but its role in EndMT remains unexplored. This study was designed to investigate the role and underlying mechanism of miR-27a in EndMT during PAH. Main methods Rats were exposed in hypoxia (10% O2) for 3 weeks to induce PAH, and human pulmonary artery endothelial cells (HPAECs) were exposed in hypoxia (1% O2) for 48 h to induce EndMT. Immunohistochemistry, in situ hybridization, immunofluorescence, real-time PCR and Western blot were conducted to detect the expressions of RNAs and proteins, and luciferase assay was used to verify the putative binding site of miR-27a. Key findings We found that hypoxia up-regulated miR-27a in the tunica intima of rat pulmonary arteries and HPAECs, and that inhibition of miR-27a suppressed hypoxia-induced EndMT. Furthermore, elevated expression of miR-27a suppressed bone morphogenetic protein (BMP) signaling by targeting Smad5, thereby lessening Id2-mediated repression of the 2 critical mediators of EndMT (Snail and Twist). Significance Our data unveiled a novel role of miR-27a in EndMT during hypoxia-induced PAH. Thus, targeting of miR-27a-related pathway may be therapeutically harnessed to treat PAH.

In this work, we investigated the functions of structural modules within alginate lyase by truncating an endo-type alginate lyase into two successive catalytic modules. The effects of module deletion on biochemical characteristics and product distributions were further investigated. The N-terminal module (Aly7B-CDI) exhibited no activity toward alginate, polyM or polyG, but the C-terminal module (Aly7B-CDII) retained its activity. The full-length enzyme (Aly7B) and its truncated counterpart (Aly7B-CDII) had similar substrate specificities, but Aly7B-CDII had lower activity. Moreover, the activity of Aly7B was much higher than Aly7B-CDII at 30°C. Aly7B-CDII, however, possessed higher optimal pH and better pH stability than the full-length enzyme. The final degradation products for Aly7B were unsaturated di-, tri- and tetra-oligosaccharides, and those for Aly7B-CDII were unsaturated mono-, di-, tri-, tetra- and penta-oligosaccharides. Therefore, the potential impact of the noncatalytic module Aly7B-CDI on the catalytic module Aly7B-CDII was further elucidated by characterizing Aly7B and its truncations. These data contribute to the functional understanding of these differing modules.

The most commonly applied wood preservatives are based on creosote, pentachlorophenol, and waterborne chromate copper arsenate, which negatively affect the environment. Thus, environmentally friendly wood preservatives are required. This study investigated the antifungal activity and mechanism of several long-chain alkyl gallates (3,4,5-trihydroxybenzoates) against white-rot fungi, Lenzites betulina and Trametes versicolor. The results revealed that octyl gallate (OG) had the best antifungal activity. Additionally, OG may have a mechanism of action similar to surfactants and inhibit ATPase activity, causing mitochondrial dysfunction and endogenous reactive oxygen species (ROS) production. Upon exposure to endogenous ROS, cells rapidly inhibit the synthesis of 60S ribosomal subunits, thus reducing the mycelial growth rate. L. betulina and T. versicolor also remodeled their energy metabolism in response to low ATP levels and endogenous ROS. After OG treatment, ATP citrate synthase activity was downregulated and glycolytic activity was upregulated in L. betulina. However, the activity of aerobic pathways was decreased and the oxidative branch of the pentose phosphate pathway was redirected form nicotinamide adenine dinucleotide phosphate (NADPH) to minimize endogenous ROS-mediated damage in T. versicolor. Taken together, these observations reveal that OG is a potent inhibitor of white-rot fungus. Further structural optimization research and pharmacological investigations are warranted.

Protein-protein interactions (PPIs) play essential roles in Anaplastic Lymphoma Kinase (ALK) signaling. Systematic characterization of ALK interactors helps elucidate novel ALK signaling mechanisms and may aid in the identification of novel therapeutics targeting related diseases. In this study, we used the Mammalian Membrane Two- Hybrid (MaMTH) system to map the phospho-dependent ALK interactome. By screening a library of 86 SH2 domain-containing full length proteins, 30 novel ALK interactors were identified. Many of their interactions are correlated to ALK phosphorylation activity: oncogenic ALK mutations potentiate the interactions and ALK inhibitors attenuate the interactions. Among the novel interactors, NCK2 was further verified in neuroblastoma cells using co-immunoprecipitation. Modulation of ALK activity by addition of inhibitors lead to concomitant changes in the tyrosine phosphorylation status of NCK2 in neuroblastoma cells, strongly supporting the functionality of the ALK/NCK2 interaction. Our study provides a resource list of potential novel ALK signaling components for further study. (C) 2021 The Authors. Published by Elsevier Ltd.

Alginate lyases are essential tools to prepare alginate oligosaccharides with various biological activities. However, alginate lyases with excellent properties such as high activity and good thermal stability are still in shortage. Therefore, it is crucial to exploit new alginate lyases with high activity and polysaccharide-degrading efficiency for alginate oligosaccharide preparation. Herein, we proposed to construct a novel hybrid alginate lyase with improved property by module recombination. The hybrid alginate lyase, designated as Aly7C, was successfully constructed by recombining the carbohydrate binding module (CBM) of Aly7A with the catalytic module of Aly7B. Interestingly, the hybrid enzyme Aly7C exhibited higher activity than the catalytic domain. Moreover, it could degrade sodium alginate, polyM and polyG into oligosaccharides with degrees of polymerization (Dps) 2-5, which exhibit perfect product specificity. This work provides a new insight into well-defined generation of alginate oligosaccharides with associated CBMs and enhances the understanding of functions of the modules.

Background Practitioners of complementary and alternative medicine have suggested that electroacupuncture (EA) could improve post-stroke cognitive impairment, based on the clinical evidence. This study protocol is aimed at showing the effectiveness of theta and gamma EA for post-stroke patients on working memory (WM) and electrophysiology. Methods After assessing their eligibility, 66 patients with stroke will be enrolled from two Chinese medicine hospitals and randomly divided into theta frequency EA group, gamma frequency EA group, and sham-EA group according to the ratio of 1:1:1. All patients will receive 20 sessions of EA procedures for 4 weeks. Patients in three groups will receive EA at two same acupoints in the head: Baihui (GV20) and Shenting (GV24). The frequency of the three groups of EA is set as follows: 6 Hz (theta-EA group), 40 Hz (gamma-EA group), and no current through the electrodes (sham EA). Patients and assessors will be blinded throughout the entire study. The primary outcome is the performance accuracy of 1-back task which is a frequently used measure of WM in cognitive neuroscience research contexts. Secondary outcome measures will include the response time of 1-back task, the Rivermead Behavioral Memory Test, Trail Making Test, Loewenstein Occupational Therapy Cognitive Assessment Scale, modified Barthel Index, and electroencephalogram (EEG) signals during 1-back tasks. A blinding index will be assessed. Data will be statistically analyzed by one-way ANOVA, at 5% of significance level. Discussion We expect this double-center, randomized, patient- and assessor-blinded, sham-controlled, parallel, clinical trial to explore the effectiveness of theta and gamma EA therapy, compared with sham EA, for post-stroke WM. Trial registration Chinese Clinical Trial Registry, ChiCTR2000031995. Registered on 17 April 2020.

Ulvan, a kind of polyanionic heteropolysaccharide consisting of 3-sulfated rhamnose, uronic acids (iduronic acid and glucuronic acid) and xylose, has been widely applied in food and cosmetic industries. In addition, ulvan can be converted into fermentable monosaccharides through the cascade system of carbohydrate-active enzymes. Ulvan lyases can degrade ulvan into ulvan oligosaccharides, which is the first step in the fully degradation of ulvan. Various ulvan lyases have been cloned and characterized from marine bacteria and grouped into five polysaccharide lyase (PL) families, namely: PL24, PL25, PL28, PL37 and PL40 families. The elucidation of the biochemical characterization, action pattern and catalytic mechanism of ulvan lyase would definitely enhance our understanding of the deep utilization of marine bioresource and marine carbon cycling. In this review, we summarized the recent progresses about the source and biochemical characteristics of ulvan lyase. Additionally, the structural characteristics and catalytic mechanisms have been introduced in detail. This comprehensive information should be helpful regarding the application of ulvan lyases.

Objective: To compare the results of surgical repair via median sternotomy, right submammary thoracotomy, and right vertical infra-axillary thoracotomy for atrial septal defect (ASD). Methods: This is a retrospective analysis of the relative perioperative and postoperative data of 136 patients who underwent surgical repair for ASD with the abovementioned three different treatments in our hospital from June 2014 to December 2017. Results: The results of the surgeries were all satisfactory in the three groups. No statistically significant difference was found in operative time, duration of cardiopulmonary bypass, blood transfusion amount, postoperative mechanical ventilation time, duration of intensive care unit, length of hospital stay, and hospital costs. However, the median sternotomy group had the longest incision. Meanwhile, there was no significant difference in postoperative complications. Conclusion: All three types of surgical incisions can be safely and effectively used to repair ASD. The treatments via right submammary thoracotomy and right vertical infra-axillary thoracotomy have advantages over the treatment via median sternotomy in cosmetic results and should be the recommended options.

Ursodeoxycholic acid (UDCA) has demonstrated cancer suppressive potential in several tumors. Here, we investigated the antitumor potential and biochemical mechanism of UDCA on glioblastoma multiforme (GBM), the deadliest form of brain cancer with a median survival of 15 months. Cell viability was assessed using the CCK-8 and colony forming assays. Expression profiles were obtained using RNA sequencing, and PCR and Western blot were used to validate changes in related markers at the RNA and protein levels. Flow cytometry was used to examine cell cycle, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS). UDCA inhibited GBM cell viability in a dose- and time-dependent manner. Flow cytometry demonstrated that cells were arrested in the G1 phase and underwent apoptosis. The RNA sequencing results showed UDCA treatment in part targeted gene expression related to mitochondria and endoplasmic reticulum (ER). UDCA indeed led to decreased MMP, overproduction of ROS, and ER stress. Three critical ER stress sensors ATF6, IRE1α, and PERK were increased in the acute phase. Additionally, combining UDCA with the proteasome inhibitor bortezomib (BTZ) achieved a synergistic effect through enhancing the PERK/ATF4/CHOP pathway and protracting ER stress. UDCA inhibited GBM progression, and the combination with BTZ achieved a synergistic effect via protracted ER stress. Thus, UDCA, alone or with combination of BTZ, shows promise as a possible therapeutic agent for the treatment of GBM. acceptedVersion

Marine polysaccharide-degrading enzymes play an important role in marine algae degradation and carbon cycling, especially the alginate lyases. Although many alginate lyases have been characterized, the enzymes with industrial potential are still rather rare. A gene, encoding a new alginate lyase AlgNJ04, has been cloned from the marine bacterium Vibrio sp. NJ04. The recombinant alginate lyase was characterized followed by purification on Ni-NTA Sepharose. It exhibited an optimum activity (2416 U/mg) at pH 7.0 and 40 °C. Notably, the AlgNJ04 retained more than 80% of its maximum activity at a broad pH range of pH 4.0 and 10.0, which exhibited excellent pH stability. Additionally, it possessed broader substrate specificity, showing activities towards both poly β-D-mannuronate (polyM) and poly α-L-guluronate (polyG). Furthermore, the Km values of AlgNJ04 towards sodium alginate (0.49 mM) and polyG (0.24 mM) were lower than that towards polyM (0.86 mM). Notably, the activity of AlgNJ-04 could be activated by NaCl with certain concentrations, which was partly caused by the removal of bound water from sodium alginate molecules or by the effects of charges in forming the alginate-enzyme complex. The ESI-MS analysis suggested that it mainly released oligosaccharides with DP of 2–5 as end products in an endolytic manner. Therefore, it may be a potent tool to produce alginate oligosaccharides with lower DPs.

Gap junctional intercellular communication (GJIC) composed of connexin proteins is considered vital to cancer onset and progression since 50 years ago based on Lowenstein and Kano's works, however altered expression of connexins is still a lesser known “hallmark” of cancer. Although many studies support the hypothesis that connexins are tumor suppressors, recent evidence indicates that, in some tumor types including glioma, they may play contradictory role in some specific stages of tumor progression. We thus conduct a meta-analysis to evaluate the prognostic role of Cx43 in glioma for the unanswered questions that whether Cx43 is a beneficial or insalubrity factor for glioma. Eight studies with 1,706 patients were included for meta-analysis. The results showed that Cx43 expression was a clearly negative factor with tumor grades (I2 = 34%, P < 0.001) and beneficial for OS (n = 3, HR 2.62, 95%CI 1.47–4.68; P = 0.001). Subgroup analysis also found that Cx43 had different expression in Asian young patients vs. other groups. In conclusion, this article summarize the prognostic value of Cx43 and offer a clinical evidence for the notion that Cx43 is generally a tumor suppressor and beneficial for the patients' survival time.

Patients surviving initial decompressive craniectomy are needed to undergo cranioplasty, which is potentially complicated by postoperative seizures. The definite incidence of post-cranioplasty seizures and application of prophylactic antiepileptic drugs remain controversial.We performed systematic review to clarify these issues. Searching through PubMed, Ovid, Web of Science and Cochrane library databases, we included publications recording the incidence of seizures after cranioplasty and prophylactic treatment. We pooled the respective incidence of seizures and 95% confidence interval (CI). The overall effect was expressed with events per 1,000 person-years calculated by the mean follow-up time. Trim and fill method was used to adjust for publication bias. Subgroup analyses were conducted to examine the differences in incidences of seizures.Two randomized and 14 observational studies were extracted. The pooled incidence of post-cranioplasty seizures was 0.092 (95%CI 0.063, 0.121), which decreased to 0.043 (95%CI 0.010, 0.076) after adjustment. The summarized incidences of early seizures and late seizures were 0.074 (95%CI 0.029, 0.119) and 0.053 (0.027, 0.079) respectively. In the subgroup analyses, randomized studies reported a higher incidence than observational studies, and early cranioplasty (6 months) resulted in an increased incidence compared with late cranioplasty (6 months). The overall effect from two randomized studies showed prophylactic antiepileptic drugs reduced nearly 80% of seizures.The estimated incidence of post-cranioplasty seizures is 43 per 1,000 person-years after adjustment. The incidence of early seizures is obviously higher than that of late seizures. Moreover, early cranioplasty leads to more post-cranioplasty seizures than late cranioplasty does. Based on the present evidences, the application of prophylactic antiepileptic drugs effectively reduces seizures.

Carrageenan, a kind of linear sulfated polysaccharides consisting of D-galactose with alternating α-1,3 and β-1,4 linkages, has been widely applied in the food and cosmetic industries as thickening and gelling agents due to excellent properties, such as gel-forming ability and chemical stability. It can be degraded by carrageenases to produce a series of even-numbered carrageenan oligosaccharides, which exhibit various fascinating functions, such as anti-inflammation, anti-coagulation, anti-tumor, and anti-thrombosis effects. Numerous carrageenases have been isolated and identified from various sources. The enzymes are grouped into three categories, namely κ-carrageenase, ι-carrageenase, and λ-carrageenase based on their substrate specificities and primary sequences, respectively. Elucidating the paradigm of the enzyme at every aspect would definitely enhance our understanding of the marine carbon cycling and natural evolution of glycoside hydrolases (GHs). The structural features of these enzymes have been fully illustrated, which will improve our knowledge of its catalytic mechanisms. In this review, we have summarized the recent progresses of major sources, category, and the enzyme's biochemical characteristics. Additionally, structural characteristics and catalytic mechanisms have been introduced in detail. We conclude with a brief discussion of the potential of the carrageenases in possible future applications in preparing functional oligosaccharides with versatile activities. This comprehensive information should be helpful regarding the application of carrageenases.

Background Spontaneous intracerebral hemorrhage (sICH) is a devastating disease with high mortality and morbidity, and the application of decompressive craniectomy (DC) in sICH is controversial. We conducted a systematic review to verify the effects of DC on improving outcome in sICH. Methods Through searching several electronic databases, we screened eligible publications. Respective risk ratio (RR) and its 95% confidence interval (CI) were calculated, data were synthesized with a fixed-effect model, and sensitivity analyses and subgroup analyses were performed. Publication bias was measured with Begg and Egger tests. Results Overall effect showed that DC significantly reduced the poor outcome compared with the control group (RR, 0.91; 95% CI, 0.84–0.99; P = 0.03). But in the subgroup analyses, only studies published after 2010, studies using hematoma evacuation as control, and studies measuring outcome with Glasgow outcome score showed better outcomes in the DC group than in the control group. The other subgroup analyses and sensitivity analyses achieved inconsistent results. Compared with the control group, DC effectively decreased mortality (RR, 0.67; 95% CI, 0.53–0.85; P = 0.0008). The sensitivity analyses and subgroup analyses achieved consistent results. Conclusions The application of DC effectively reduced mortality in patients with sICH. DC might improve functional outcomes in certain populations and needs further verification. DC is not associated with increased incidences of postoperative rebleeding and hydrocephalus.

Background Tumor-associated macrophages (TAMs) are associated with poor outcomes in multiple solid cancers and play important roles in cancer progression. Epithelial-mesenchymal transition (EMT) may account for metastasis and recurrence. However, the association between TAMs and EMT is not clarified in triple-negative breast cancer (TNBC). The aim of this study was to investigate the effects of TAMs on EMT in TNBC. Material and methods We studied specimens from 278 patients with TNBC. TAMs marker cluster of differentiation 163 and EMT-related marker E-cadherin were detected by immunohistochemistry in TNBC tissues, and their clinical significance was evaluated from the patients' medical records. Results TNBC patients with polarized cluster of differentiation 163+ TAMs infiltration and low level of E-cadherin had a significantly higher risk of aggressive features, including recurrence, histologic differentiation, and lymph node metastasis. Infiltration of TAMs was also negatively correlated with E-cadherin in TNBC tissues. Multivariate analysis indicated that infiltration of TAMs and low expression of E-cadherin were independent prognostic factors of overall survival and disease-free survival in TNBC patients. Conclusions High infiltration of TAMs was associated with low expression of E-cadherin and could be used as an unfavorable prognostic factor for patients with TNBC.

γ-Glutamyltranspeptidase (GGT) is a dimeric protein that specifically catalyzes the transfer of γ-glutamyl in the optimum pH range of 8.5–9.0, but has poor in vitro stability under the alkaline conditions. In the present work, GGT was immobilized on a mesoporoustitania oxide whisker (MTWs) carrier to afford MTWs-GGT that was further modified with Pharmalyte MT (Phar) 8.0–10.5 to yield MTWs-GGT-Phar. Phar absorbed on MTWs-GGT to form a buffering layer with an isoelectric point of ∼9.2 that isolated the immobilized enzyme from the liquid bulk and significantly in proved the pH tolerance and stability of the immobilized GGT. The MTWs-GGT-Phar exhibited a stable enzyme activity in the pH range of 6.0–11.0 and an optimum temperature 10 °C higher than GGT. Its pH stability at pH 11.0 and thermal stability at 50 °C were respectively 23.7 times and 19.4 times higher than those of GGT. In addition, the affinity constant of MTWs-GGT-Phar towards G p NA ( K m ) was 0.597 mM, slightly lower than that of free GGT, indicating that Phar had a protective effect on the structure of GGT.

Endovascular therapy has been used as an alternative treatment for vasospasm following subarachnoid hemorrhage. The effectiveness and safety of endovascular therapy are still controversial. We performed a systematic review and meta-analysis to identify any advantage of endovascular therapy over traditional medical treatment. We systematically reviewed related English publications by searching PubMed, Ovid, Cochrane library, and Web of Science up to May 2017.The risk ratios (RR) and 95% confidence intervals (CI) were synthesized with fixed effect model. Subgroup analyses and sensitivity analyses were conducted to check the robustness the result. Publication bias was measured with funnel plot. Eight cohort studies were included, receiving a mean score of 7 on the Newcastle-Ottawa Scale. The overall effect (RR 1.01, [95% CI 0.80–1.26]) found no significant difference in the outcome between the endovascular treatment and control groups but with heterogeneity (Chi2 = 18.07, p = 0.01, I2 = 61%). Subgroup analyses stratified by country, year of publication, treatment modality, follow-up time, and sensitivity analysis by excluding the most biased study yielded the same result (RR 1.19, [95% CI 0.94–1.52]), with rare heterogeneity (Chi2 = 4.21, p = 0.65, I2 = 0). Funnel plot was visually symmetric in sensitivity analysis. Despite good performance in reversing vasospasm in previous studies, endovascular therapy did not show superiority to traditional medical treatment in improving patient outcomes. Further randomized controlled studies are needed to elucidate this issue.

The timing of surgery for aneurysmal subarachnoid hemorrhage influences the outcome, but the optimal timing remains controversial. We conducted a systematic review to clarify whether early surgery was better than late surgery for improving outcome.We systematically searched several databases to screen eligible studies. After synthesizing data, an overall effect was shown using a risk ratio (RR) and 95% confidence interval (CI). Subgroup analyses were stratified by multiple variables to control the confounding factors. Sensitivity analyses were applied to check the robustness of the results. Publication bias was measured with Egger's and Begg's tests.A total of 14 studies were included in the analysis. Compared with late surgery, early surgery significantly decreased the incidence of poor outcome, regardless of whether patients were in good condition (RR, 0.65 [95%CI, 0.50 0.84]; p = 0.001) or in poor condition on admission (RR, 0.71 [95%CI, 0.61 0.83]; p 0.0001). Moreover, when patients were in good condition on admission, early surgery also effectively reduced the death rate (RR, 0.61 [95%CI, 0.46 0.82]; p = 0.001). Additionally, early surgery reduced the death rate compared with late surgery in patients older than 50 years (RR, 0.49 [95%CI, 0.27 0.89]; p 0.002).Early surgery was superior to late surgery in reducing a poor outcome and death rate when patients were in good condition on admission, and decreased the incidence of poor outcome when patients were in poor condition on admission. Age was a potential confounding factor, influencing the effect of early surgery. Further study is required on this issue.

It is designed to discuss the relationship between the expression of chemokine receptor 7 (chemokine receptor 7, CXCR7) and nuclear transcription factor-κB (nuclear factor kappa B, NF-κB) and the occurrence of the breast cancer and lymphatic metastasis. Method: 80 samples were excised and confirmed as breast cancer through our hospital pathology from January 2014 to December 2016 and tumor tissues and normal mammary tissues 2 cm from the tumor edges were taken as an experimental group and a control group, respectively. The method of immunohistochemical is utilized to test the expression of CXCR7 and NF-κB in the breast cancer tissue, compared with the para-carcinoma tissue, and analyze its relevance with the clinicopathologic features of the breast cancer tissue, such as tumor size, TNM staging, lymphatic metastasis and other conditions. Results: both CXCR7 and NF-κB were highly expressed in the breast cancer tissue, the positive rate was significantly higher that that of paracancerous normal tissues, and the difference was statistically significant. And the expressions of CXCR7 and NF-κB were related to TNM staging of the breast cancer and lymphatic metastasis and unrelated to the tumor size, age, and expressions of ER, PR and HER2. Conclusion: both CXCR7 and NF-κB are related to the malignant grade of the breast cancer and lymphatic metastasis, which may be regarded as in important indicator to judge the prognosis of the breast cancer and be expected to be the new target of curing part of the breast cancer.

Alginate lyases play an essential role in the production of oligosaccharides by degrading alginate polysaccharide. Although many alginate lyases from various microorganisms have been characterized, reports on alginate lyases with special characteristics and commercial potential are still rather rare. In this study, a new alginate lyase, FsAlgA, was cloned from the deep-sea marine bacterium Flammeovirga sp. NJ-04. The recombinant enzyme was purified on Ni-NTA sepharose and then characterized in detail. It exhibited the highest activity (3343.7 U/mg) at pH 7.0 and 50 °C. Notably, the FsAlgA retained more than 80% of its maximum activity after incubation at 50 °C for 30 min, suggesting that FsAlgA was a heat-stable alginate lyase. Additionally, FsAlgA possessed broad substrate specificity, showing high activities toward both poly β-d-mannuronate (polyM) and poly α-l-guluronate (polyG). Furthermore, the K m values of FsAlgA toward sodium alginate (0.48 mM) and polyG (0.94 mM) were lower than that toward polyM (1.42 mM). The TLC and ESI–MS analyses indicated that FsAlgA endolytically degraded alginate polysaccharide and released oligosaccharides with degree of polymerization (DP) of 2–5. Therefore, it may be a potent tool to produce alginate oligosaccharides with low DPs.

Receptor tyrosine kinases (RTKs) and protein phosphatases comprise protein families that play crucial roles in cell signaling. We used two protein-protein interaction (PPI) approaches, the Membrane Yeast Two-Hybrid (MYTH) and the Mammalian Membrane Two-Hybrid (MaMTH), to map the PPIs between human RTKs and phosphatases. The resulting RTK-phosphatase interactome reveals a considerable number of previously unidentified interactions and suggests specific roles for different phosphatase families. Additionally, the differential PPIs of some protein tyrosine phosphatases (PTPs) and their mutants suggest diverse mechanisms of these PTPs in the regulation of RTK signaling. We further found that PTPRH and PTPRB directly dephosphorylate EGFR and repress its downstream signaling. By contrast, PTPRA plays a dual role in EGFR signaling: besides facilitating EGFR dephosphorylation, it enhances downstream ERK signaling by activating SRC. This comprehensive RTK-phosphatase interactome study provides a broad and deep view of RTK signaling.

Protein-protein interactions (PPIs) play an integral role in numerous cellular processes. Membrane protein interactions, in particular, are critical in cellular responses to stresses and stimuli, with dysfunction of these PPIs (e.g., due to aberrant expression and/or mutation of interaction partners) leading to a diverse array of pathological states. Exploration of the interaction space and dynamics of membrane proteins is difficult due to the limitations of current techniques used to study proteins in the biochemically complex environment of biological membranes. In the protocols below, we describe a newly developed membrane protein interaction assay called the Mammalian-Membrane Two-Hybrid (MaMTH), designed specifically for the detection of integral membrane PPIs in the context of living mammalian cells. Prior to using MaMTH, cell lines of interest are genetically modified to encode a reporter of choice. MaMTH "bait" and "prey" constructs of interest are also generated using Gateway cloning technology. The assay is then performed by co-transfection of baits and preys, with bait-prey interaction quantifiably assessed by way of a reporter signal (e.g., light (luciferase), fluorescence (GFP). © 2017 by John Wiley & Sons, Inc.

The Hong Kong Dwarf Snake Calamaria septentrionalis Boulenger, 1890 is widely distributed in south of China and North of Vietnam. The complete mitochondrial genome (mitogenome) sequence of C. septe...

The paper studies the industrial energy transferring paths among the industries of China by distinguishing direct causality from the indirect. With complementary graphs, we propose that industrial causal relationship can be heterogeneous, and provide insights for refining robust industrial causality framework. First, by analyzing the in-weight and out-weight of the industries in Granger causality networks we find that public utilities have significant causality with other industries, and the industries with higher degree value tend to have stronger causality with others. Further, we eliminate the exogenous links by partial Granger causality model and find both Granger and partial Granger networks have consistent hub industries while some outliers emerge in partial Granger causality networks. Besides, compared with GX, GZ, HN and YN, the correlation between the volume of electricity consumption and the weight of each industry is more significant in the networks of GD and NF. By studying the characteristics of complementary graphs, we show that the industrial energy transferring paths in GD are more multidimensional, and the corresponding interdependent relationship among industries is more robust. Finally, using bootstrap method we verify the reliability of each industrial relationship network. Results exhibit that GD, GX and NF have more reliable causal relationship networks than other provinces, revealing their industrial structure to be more stable.

Alginate lyases are important enzymes to prepare alginate oligosaccharides for industrial applications and elucidating the degradation pattern of alginate lyases is essential for expanding their applications. Herein, we cloned and expressed AlyPL6, a novel member of polysaccharide lyase family-6 (PL6) with high activity from Pedobacter hainanensis NJ-02. It was found that AlyPL6 could recognize tetrasaccharide as the minimal substrate to release oligosaccharides with low degrees of polymerization (DPs). As a result, it could be speculated that the cleavage site of substrate is located between −1 and +1 subsites. For further application, AlyPL6 was then immobilized onto mesoporous titanium oxide particles (MTOPs) with >55.4% of maximal activity retained at 45 °C after it was reused for 10 times. The research provided extended insights into the substrate recognition and degradation pattern of PL 6 alginate lyases, which may benefit the further application of alginate lyases a lot.

Alginate lyases have been widely used to prepare alginate oligosaccharides in food, agricultural, and medical industries. Therefore, discovering and characterizing novel alginate lyases with excellent properties has drawn increasing attention. Herein, a novel alginate lyase FsAlyPL6 of Polysaccharide Lyase (PL) 6 family is identified and biochemically characterized from Flammeovirga sp. NJ-04. It shows highest activity at 45 &deg, C and could retain 50% of activity after being incubated at 45 &deg, C for 1 h. The Thin-Layer Chromatography (TLC) and Electrospray Ionization Mass Spectrometry (ESI-MS) analysis indicates that FsAlyPL6 endolytically degrades alginate polysaccharide into oligosaccharides ranging from monosaccharides to pentasaccharides. In addition, the action pattern of the enzyme is also elucidated and the result suggests that FsAlyPL6 could recognize tetrasaccharide as the minimal substrate and cleave the glycosidic bonds between the subsites of &minus, 1 and +3. The research provides extended insights into the substrate recognition and degradation pattern of PL6 alginate lyases, which may further expand the application of alginate lyases.

It has well been demonstrated that E3 ubiquitin ligase cullin7 plays important roles in cancer cell growth control via down-regulating p53 expression. The noncanonical function or the pathogenic role of p53 has more recently been implicated in pulmonary vascular remodeling. Therefore, whether cullin7 participates in hypoxia-induced pulmonary vascular remodeling deserves to be elucidated. The present study found that hypoxia up-regulated the expression of cullin7 mRNA and protein in pulmonary arteries and pulmonary artery smooth muscle cells, and knockdown of cullin7 inhibited hypoxia-induced proliferation and migration of pulmonary artery smooth muscle cells and reversed hypoxia-induced inhibition of p53 expression. Notably, administration of proteasome inhibitor MG132 significantly inhibited the expression of cullin7 and up-regulated the expression of p53 in pulmonary arteries concomitantly with improvement of hypoxia-induced pulmonary vascular remodeling. Our study demonstrated that hypoxia induced up-regulation of cullin7 expression resulting to the proliferation and migration of pulmonary artery smooth muscle cells via down-regulating p53 expression, which contributed to pulmonary vascular remodeling.

Pulmonary arterial remodeling is a crucial cause of increased pulmonary artery pressure during pulmonary hypertension (PH). Recently, growing evidence has upheld the contribution of endothelial-mesenchymal transition (EndMT) to pulmonary arterial remodeling, but the underlying mechanisms remain largely unaddressed. miR-204 has been implicated in PH, being anti-proliferative and pro-apoptotic in pulmonary artery smooth muscles cells (PASMCs), but its role in EndMT is still unknown. Here we found that miR-204 was down-regulated by hypoxia in rat pulmonary arterial intima and human pulmonary artery endothelial cells (HPAECs), and its further down-regulation by using miR-204 inhibitor suppressed hypoxia-induced EndMT. Moreover, autophagy, evoked by hypoxia in rat pulmonary arterial intima and HPAECs, suppressed hypoxia-induced EndMT via p62-dependent degradation of Snail and Twist. Additionally, autophagy was regulated by miR-204 targeting ATG7. While down-regulation of miR-204 in PASMCs reportedly promoted monocrotaline-induced pulmonary arterial hypertension via increased cell proliferation, our data suggested an important, albeit dichotomous, role of miR-204 down-regulation in endothelial cells in the process of EndMT that it attenuated EndMT by enhancing autophagy, thereby ameliorating hypoxia-induced PH to some extent.

IMPORTANCE: There is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors. OBJECTIVE: To evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer. DESIGN, SETTING, AND PARTICIPANTS: After radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018. INTERVENTIONS: Patients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m(2)), or SCRT (cisplatin, 60-75 mg/m(2), plus paclitaxel, 135-175 mg/m(2)) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of disease-free survival (DFS) at 3 years. RESULTS: A total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00806117

Social media greatly facilitate online social interaction among friends, and user behavior in social interaction may be influenced by interpersonal relationships. While individuals sometimes do enjoy the content shared by friends, they may also feel that they have a moral obligation to like what their friends share. Drawing on the stimulus-organism-response model, this paper examines whether the characteristics of interpersonal relationships are associated with moral obligation as well as whether moral obligation is associated with “like” intention. By using data from 348 users of WeChat Moments, we provide empirical evidence that the stimuli of interpersonal relationships (perceived authority, perceived closeness, and peer referent) are positively associated with the sense of moral obligation, which in turn, is positively associated with user intention to click the Like button on their friends’ postings on social media. Theoretical and practical implications of the findings are discussed.

In this study, we evaluated the photodynamic efficacy of a new photosensitizer, benzochloroporphyrin derivative 18 (BCPD-18), in Ewing sarcoma. We found that BCPD-18 decreased the viability of TC-71 cells irradiated by 670 nm laser in a concentration dependent manner. We also observed cells undergoing apoptosis as well as cell cycle arrest at the G2M phase after BCPD–18-mediated photodynamic therapy (BCPD-PDT). In addition, in vivo study (subcutaneous and orthotopic models) showed that BCPD-PDT reduced tumor size, tumor weight and tumor-bearing leg weight. After PDT, apoptosis was shown in vivo. Bax expression was increased, and Bcl-2 expression was decreased. This study provides evidence that BCPD-18 could probably be a useful photosensitizer in PDT for Ewing sarcoma.

Three combinations of molecular chaperones from Escherichia coli (i.e., DnaK-DnaJ-GrpEGroEL- GroES, GroEL-GroES, and DnaK-DnaJ-GrpE) were overproduced in E. coli BL21, and their in vitro stabilizing effects on a nitrile hydratase (NHase) were assessed. The optimal gene combination, E. coli groEL-groES (ecgroEL-ES), was introduced into Rhodococcus ruber TH3. A novel engineered strain, R. ruber TH3G was constructed with the native NHase gene on its chromosome and the heterologous ecgroEL-ES genes in a shuttle plasmid. In R. ruber TH3G, NHase activity was enhanced 37.3% compared with the control, TH3. The in vivo stabilizing effect of ecGroEL-ES on the NHase was assessed using both acrylamide immersion and heat shock experiments. The inactivation behavior of the in vivo NHase after immersion in a solution of dynamically increased concentrations of acrylamide was particularly evident. When the acrylamide concentration was increased to 500 g/l (50%), the remaining NHase activity in TH3G was 38%, but in TH3, activity was reduced to 10%. Reactivation of the in vivo NHases after varying degrees of inactivation was further assessed. The activity of the reactivated NHase was more than 2-fold greater in TH3G than in TH3. The hydration synthesis of acrylamide catalyzed by the in vivo NHase was performed with continuous acrylonitrile feeding. The final concentration of acrylamide was 640 g/l when catalyzed by TH3G, compared with 490 g/l acrylamide by TH3. This study is the first to show that the chaperones ecGroEL-ES work well in Rhodococcus and simultaneously possess protein-folding assistance functions and the ability to stabilize and reactivate the native NHases.

The aim of the present study was to summarize the clinical characteristics, diagnosis, treatment and prognosis of carcinoma showing thymus-like differentiation of the thyroid (CASTLE). A search of the relevant literature was conducted, which identified 82 cases of CASTLE reported to date. A review of the clinical and auxiliary examination data, treatment, pathological findings and follow-up of these cases was performed. The clinical manifestations of CASTLE varied and did not demonstrate specificity. During ultrasound examination, CASTLE was described as a solid and hypoechoic mass, and the echo was typically observed to be heterogeneous. In computed tomography (CT), CASTLE was demonstrated to be a well-defined, soft tissue density mass without calcification, which appeared enhanced following administration of contrast medium. In emission CT, CASTLE was revealed as a 'cold nodule'. A total of 78 patients underwent radical surgery, and 12 patients experienced recurrence. Lymph node metastasis did not promote recurrence, and postoperative radiation was not able to reduce the recurrence rate (P=0.144 and 1.000, respectively). The median follow-up time was 14 months (range, 1-312 months). Typical immunohistochemical examinations demonstrated the specimens to be positive for cluster of differentiation (CD)5, CD117, cytokeratin 19, epithelial membrane antigen and tumor protein 63, and negative for calcitonin, thyroglobulin and thyroid transcription factor-1. Thyroid CASTLE is a rare malignancy whose exact diagnosis relies on pathological examination, particularly immunohistochemistry, since preoperative examinations are usually unable to provide an exact diagnosis. Radical resection is the primary treatment for CASTLE, which presents favorable prognosis.

Aim Proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) are regarded as the primary factors resulting in pulmonary arterial remodeling in pulmonary hypertension (PH). Myeloid ecotropic viral integration site 1 (MEIS1) has been positioned as a negative cardiomyocyte cell cycle regulator and regulates proliferation of multiple kinds of cancer cells. Whether MESI1 is involved in the proliferation and migration of PASMCs deserves to be identified. Main methods Sprague Dawley rats were exposed to hypoxia condition (10% O2) for 4 weeks to induce PH and primary rat PASMCs were cultured in hypoxia condition (3% O2) for 48 h to induce proliferation and migration. Immunohistochemistry, immunofluorescence, reverse transcription PCR and Western blot analysis were performed to detect the expressions of target mRNAs and proteins. EDU, CCK8 and wound healing assays were conducted to measure the proliferation and migration of PASMCs. Key findings Hypoxia down-regulated the expression of MEIS1 (both mRNA and protein) in pulmonary arteries and PASMCs. Over-expression of MEIS1 inhibited the proliferation and migration of PASMCs afforded by hypoxia. In contrast, knockdown of MEIS1 under normoxia condition like hypoxia induced the proliferation and migration of PASMCs. MEIS1 mediated hypoxia-induced the proliferation and migration of PASMCs via METTL14/MEIS1/p21 signaling. Significance The present study revealed that MEIS1 regulated the proliferation and migration of PASMCs during hypoxia-induced PH. Thus, MEIS1 may be a potential target for PH therapy.

6007 Background: There are limited data from previous studies regarding whether the addition of chemotherapy to adjuvant radiation after radical surgery improves outcomes among patients with early-stage cervical cancer and adverse pathological factors. Methods: This was a prospective randomized trial including patients with FIGO 2009 stage IB1-IIA2 cervical cancer and squamous-cell, adenocarcinoma, or adenosquamous carcinoma with at least one adverse factor after radical hysterectomy. Patients were randomized 1:1:1 to receive adjuvant radiation alone, concurrent chemoradiation with weekly cisplatin (30-40 mg/m2), or sequential chemoradiation with cisplatin (60-75 mg/m2) plus paclitaxel (135-175 mg/m2) in 21 day cycles, given 2 cycles before and 2 cycles after radiotherapy respectively. The primary outcome was the rate of disease-free survival at 3 years. Results: A total of 1,048 patients were included in the study (350, radiation alone; 345, concurrent chemoradiation; and 353, sequential chemoradiation). Overall, the median follow-up was 56 months and the median age of patients was 48 years. Most patients (75%) had stage IB1 or IIA1 disease. The three groups were similar with respect to histologic subtypes, the rate of lymphovascular invasion, parametrial, surgical margin and deep stromal involvement, tumor grade, rate of use of minimally invasive surgery, and neoadjuvant chemotherapy, except for lymph-node involvement that was lowest in radiation alone arm. In the intention-to-treat population, sequential chemoradiation was associated with a higher rate of disease-free survival than radiation alone (3-year rate, 90·0% vs. 82·0%; HR 0·52; 95% CI, 0·35 to 0·76) and concurrent chemoradiation (90·0% vs. 85·0%; HR 0·65; 95% CI, 0·44 to 0·96), differences remained after adjustment for lymph-node involvement. Sequential chemoradiation was also associated with a higher rate of overall survival than radiation alone (5-year rate, 92·0% vs. 88·0%; HR for death from cancer, 0·58; 95% CI, 0·35 to 0·95). However, neither disease-free survival nor cancer death risk was different between patients treated with concurrent chemoradiation or radiation alone. Conclusions: In this trial, sequential chemoradiation, rather than concurrent chemoradiation, resulted in a higher disease-free survival and lower risk of cancer death than radiation alone among women with early-stage cervical cancer after radical surgery. Clinical trial information: NCT00806117.

SERINC5 is a host restriction factor that impairs infectivity of HIV-1 and other primate lentiviruses and is counteracted by the viral accessory protein Nef. However, the importance of SERINC5 antagonism for viral replication and cytopathicity remained unclear. Here, we show that the Nef protein of the highly divergent SIVcol lineage infecting mantled guerezas (Colobus guereza) is a potent antagonist of SERINC5, although it lacks the CD4, CD3 and CD28 down-modulation activities exerted by other primate lentiviral Nefs. In addition, SIVcol Nefs decrease CXCR4 cell surface expression, suppress TCR-induced actin remodeling, and counteract Colobus but not human tetherin. Unlike HIV-1 Nef proteins, SIVcol Nef induces efficient proteasomal degradation of SERINC5 and counteracts orthologs from highly divergent vertebrate species, such as Xenopus frogs and zebrafish. A single Y86F mutation disrupts SERINC5 and tetherin antagonism but not CXCR4 down-modulation by SIVcol Nef, while mutation of a C-proximal di-leucine motif has the opposite effect. Unexpectedly, the Y86F change in SIVcol Nef had little if any effect on viral replication and CD4+ T cell depletion in preactivated human CD4+ T cells and in ex vivo infected lymphoid tissue. However, SIVcol Nef increased virion infectivity up to 10-fold and moderately increased viral replication in resting peripheral blood mononuclear cells (PBMCs) that were first infected with HIV-1 and activated three or six days later. In conclusion, SIVcol Nef lacks several activities that are conserved in other primate lentiviruses and utilizes a distinct proteasome-dependent mechanism to counteract SERINC5. Our finding that evolutionarily distinct SIVcol Nefs show potent anti-SERINC5 activity supports a relevant role of SERINC5 antagonism for viral fitness in vivo. Our results further suggest this Nef function is particularly important for virion infectivity under conditions of limited CD4+ T cell activation., Author summary The accessory protein Nef promotes primate lentiviral replication and enhances the pathogenicity of HIV-1 by mechanisms of immune evasion and enhancing viral infectivity and replication. Here, we show that the evolutionarily most isolated primate lentivirus SIVcol lacks several otherwise conserved Nef functions. Nevertheless, SIVcol Nef potently antagonizes SERINC5, a recently discovered inhibitor of viral infectivity, by down-modulating it from the cell surface and inducing its proteasomal degradation. We identified Y86 in SIVcol Nef as a key determinant of SERINC5 antagonism. Efficient counteraction of SERINC5 did not increase HIV-1 replication in preactivated CD4+ T cells and in ex vivo infected lymphoid tissue but had modest enhancing effects when resting PBMCs were first infected and activated six days later. Evolution of high anti-SERINC5 activity by SIVcol Nef supports a relevant role of this antagonism in vivo, for instance by enhancing virion infectivity under conditions of limited T cell activation.

The aim of the present study was to improve the conventional wire-guided localization biopsy (WGLB) of breast microcalcifications to overcome disadvantages associated with the procedure, including inaccurate localization and large specimen volume. The novel approach described in the present study was termed double wire-guided localization and rotary cutting biopsy (DWGLB). Prior to surgery, the precise localization of the lesions was assessed using two wires under the assistance of mammography X-ray and ultrasound, followed by complete excision of the lesions using a novel rotary cutting tool. The cylindrical specimen was placed on a scaled specimen holder for pathological examination. DWGLB was performed in 108 patients with the classification of as Breast Imaging Reporting and Data System score 4A. Percutaneous localization of the lesions guided by a mammography X-ray and ultrasound were successful in all 108 lesions (100%) with one puncture attempt. The lesions were precisely excised in all of 108 patients, and included 13 malignant lesions (DCIS of breast in 7 cases, DCIS with focal invasive carcinoma in 3 cases and invasive ductal carcinoma in 3 cases). The average distance of the BARD Dualok to the lesion was 4.1 mm; the average weight of specimens was 8.5 g. Compared with WGLB, DWGLB offers several advantages, including more accurate localization of lesions, a more standardized biopsy method and a smaller specimen volume. DWGLB can also provide the precise position of lesions in the specimen for further pathological examination.

Aim To summarize and calculate the accurate rate of good outcome and the prognosis, using a uniform definition of good outcome, evaluating the long-term effect of surgery. Material and methods Through searching the relevant databases, we included eligible studies measuring outcomes with the modified Rankin Scale (mRS), Glasgow Outcome Scale (GOS) and Kim's category. Single group rates were transformed and synthesized to yield the mean weighted probability. Sensitivity analyses were conducted to check the robustness of overall effect. Subgroup analyses were stratified by study type, population, age phase, presentation, surgical procedure and outcome measurement. Results The overall estimated rate of good outcome was 0.87 (95%CI, 0.84 0.90), with substantial heterogeneity. In the subgroup analyses, the outcome measured with GOS led to the highest rate of 91%, while Kim's category had the lowest rate of 82%. The combined bypass surgery group resulted in a higher good outcome rate of 0.92 (95%CI, 0.89 0.96) than the indirect bypass group of 0.83% (95%CI, 0.78 0.88). Conclusion Moyamoya disease after surgical treatment could achieve a good outcome rate of 87%. Kim's category reflected the functional outcome better, resulting in a good outcome rate of 82%. The combined bypass surgery led to better outcomes than indirect bypass.

Background/Aims: Gq protein-coupled receptors (GqPCRs) regulate various cellular processes including mainly proliferation and differentiation. In a previous study, we found that in prostate cancer cells, the GqPCR of GnRH induces apoptosis by reducing the PKC-dependent AKT activity and elevating JNK phosphorylation. Since it was thought that GqPCR induces mainly activation of AKT, we undertook to examine how general is this phenomenon and understand its signaling. Methods: We used various cells to follow the phosphorylation of signaling components using western blotting. Results: In a screen of 21 cell lines, we found that PKC activation results in the reduction of AKT activity, which correlates nicely to JNK activation and in some cases to apoptosis. To further understand the signaling pathways involved in this stimulation, we studied in detail the SVOG-4O and αT3-1 cells. We found that PGF2α and GnRH agonist (GnRH-a) indeed induce significant Gq- and PKC- dependent apoptosis in these cells. This is mediated by two signaling branches downstream of PKC, which converge at the level of MLK3 upstream of JNK. One branch consists on c-Src activation of the JNK cascade and the second involves reduction of AKT activity that alleviates its inhibitory effect on MLK3, to allow the flow of the c-Src signal to JNK. At the MAPKK level, we found that the signal is transmitted by MKK7 and not MKK4. Conclusion: Our results present a general mechanism that mediates a GqPCR-induced, death receptors-independent, apoptosis in physiological, as well as cancer-related systems.

Spontaneous intracerebral hemorrhage remains a major cause of death and dependence. Endoscopic surgery (ES) is potential to improve outcomes, but a consensus on the superiority of ES has not been achieved. We conducted a systematic review to clarify the effect of ES in spontaneous intracerebral hemorrhage and compare it with other treatment options (craniotomy, conservation, and stereotactic aspiration [SA]).We performed this review based on the Preferred Reporting Items for Systematic review and Meta-Analysis. The subgroup analyses were stratified by study type, location, hematoma volume, interval to treatment, follow-up time, and stereotactic frame assistance.A total of 18 studies were included containing 1213 patients, most of whom harbored a hematoma greater than 50 mL. Compared with craniotomy and conservation, ES significantly reduced the mortality (P0.0001), poor outcomes (P0.00001), rebleeding (P = 0.0009), and pneumonia (P0.00001). In the subgroup analyses, late surgery (48 hours) benefited more from ES than early surgery (24 hours). The study location, hematoma volume, and stereotactic frame assistance insignificantly influenced the therapeutic effect of ES. Comparing ES and SA, we found that differences in mortality, poor outcomes, and rebleeding were insignificant, but ES had a greater evacuation rate and SA had shorter operative times.ES achieves a better performance than craniotomy and conservation in terms of reducing mortality, dependence, and specific complications. Despite being similarly effective in improving functional outcomes, ES and SA have respective advantages. ES is a feasible alternation to craniotomy and conservation, and the comparison between ES and SA warrants further study.

Receptor tyrosine kinases (RTKs) are transmembrane receptors of great clinical interest due to their role in disease. Historically, therapeutics targeting RTKs have been identified using in vitro kinase assays. Due to frequent development of drug resistance, however, there is a need to identify more diverse compounds that inhibit mutated but not wild-type RTKs. Here, we describe MaMTH-DS (mammalian membrane two-hybrid drug screening), a live-cell platform for high-throughput identification of small molecules targeting functional protein-protein interactions of RTKs. We applied MaMTH-DS to an oncogenic epidermal growth factor receptor (EGFR) mutant resistant to the latest generation of clinically approved tyrosine kinase inhibitors (TKIs). We identified four mutant-specific compounds, including two that would not have been detected by conventional in vitro kinase assays. One of these targets mutant EGFR via a new mechanism of action, distinct from classical TKI inhibition. Our results demonstrate how MaMTH-DS is a powerful complement to traditional drug screening approaches.

Enzymatic preparation of carrageenan oligosaccharides has drawn increasing attention due to its advantages of mild reaction conditions and excellent product-specificity. A novel gene (CgkA) encoding a new κ-carrageenase was cloned, heterogeneously expressed and characterized from a newly isolated marine bacterium Pedobacter hainanensis NJ-02. It consisted of 1539bp and encoded 512 amino acid residues with a molecular weight of 57.12kDa. Multiple alignment analysis indicated that CgkA belongs to glycoside hydrolase (GH) family 16 and was most homologous to κ-carrageenase of Zobellia sp. M-2 with identity of 50%. The recombinant enzyme showed maximal activity of 3659.72U/mg at 40°C and pH 7.0. Additionally, it could retain more than 80% of its maximal activity after being incubated at pH of 5.0-9.0 below 40°C.K+ and Na+ with a wide range of concentration can activate the enzyme, while other divalent ions such as Cu2+, Zn2+ showed inhibitory effect on the enzyme. The ESI-MS analysis of hydrolysates indicated that the enzyme can endolytically depolymerize the carrageenan into tetrasaccharides and hexasaccharides. The results suggest that it is an endo-type carrageenase and could be a valuable enzyme tool to produce carrageenan oligosaccharides with higher Dps.

A novel κ-carrageenase gene (CgkB) has been cloned from Pedobacter hainanensis NJ-02 and expressed heterologously in Escherichia coli BL21 (DE3). It consisted of 1935 bp and encoded 644 amino acid residues with a molecular weight of 71·61 kDa. The recombinant enzyme showed maximal activity of 2458 U mg-1 at 40°C and pH 8·0. Additionally, it could retain more than 70% of its maximal activity after being incubated at pH of 5·5-10·0 below 40°C. K+ and a broad range of NaCl can activate the enzyme. The Km and Vmax of CgkB was 2·4 mg ml-1 and 126 mmol mg-1 min-1 . The ESI-MS analysis of hydrolysates indicated that the enzyme can endolytically depolymerize the carrageenan into tetrasaccharides and hexasaccharides. The results indicated that the enzyme with high activity could be a valuable enzyme tool to produce carrageenan oligosaccharides with various activities. SIGNIFICANCE AND IMPACT OF THE STUDY Enzymatic preparation of carrageenan oligosaccharides has drawn increased attention due to their various physiological activities. It is urgent to explore enzyme tools with higher activity and better stability. In this work, a novel κ-carrageenase was identified and characterized from marine bacterium Pedobacter hainanensis NJ-02. The enzyme with high activity could be a valuable tool to produce carrageenan oligosaccharides with various activities.

Chronic subdural haematoma is a common but retractable neurological disease in the elderly with a high rate of recurrence. Dexamethasone (DX) either as monotherapy or adjuvant therapy has been applied clinically, but its effectiveness and feasibility remain controversial. We conducted this review to clarify this issue. With a systematic review through multiple databases, we retrieved eligible English language publications and extracted relevant data to perform meta-analyses. The respective risk ratio (RR) and its 95% confidence interval (CI) were pooled to evaluate the overall effect. Our meta-analysis showed overall that DX (alone or adjuvant) resulted in a lower recurrence rate when compared with non-DX therapy (RR, 0.54; 95% CI, 0.33-0.88; p = 0.01), but sensitivity analysis by excluding the most influential study achieved inconsistent results. The pooled effect revealed no statistical difference on recurrence rate between DX alone and non-DX therapy or surgical therapy (RR, 0.86; 95% CI, 0.43-1.71; p = 0.66) (RR, 0.89; 95% CI, 0.43-1.85; p = 0.76). Comparison between DX alone with the surgical therapy demonstrated no difference on the poor outcome (RR, 0.40; 95% CI, 0.15-1.04; p = 0.06). We had no enough evidence to support DX use as an effective alternation to surgical therapy. But adjuvant DX use may facilitate the surgical therapy by reducing recurrence. Further study focusing on adjuvant DX was required.

Background Intracranial aneurysm in patients with sickle cell disease is rare, but with an increased incidence in the recent years. This type of intracranial aneurysm possesses distinctive characteristics, and it has been the subject of case reports and series. Material and Methods We systematically searched relevant publications through PubMed, EMBASE, Web of Science, and Google Scholar up to December 21, 2016. We extracted data about clinical features and outcomes and then conducted a descriptive analysis. Results We identified 46 related publications, comprising 111 patients and 218 aneurysms. The mean age was 27 years (range, 5–54 years), and the male:female ratio was 0.96 (52:54). A male predominance existed in children, whereas a female predominance in adults. Age distribution approximated normal distribution, with peak phase between 21 and 30 years. In the child cohort, 13 of 31 (41.9%) aneurysms ruptured, whereas 62 of 79 (78.5%) aneurysms rupturing in the adult cohort. Aneurysms tended to be multiple (45.0%), small (85.6%), and saccular type (90.8%) and they exhibited a preference for posterior circulation (31.7%). Conservation and clipping became the main treatment in children and adults, respectively, but children had more good outcomes (80%) than adults did (67.1%). Conclusions Intracranial aneurysms related to sickle cell disease mainly affected patients in their 20s, with a contradictory sex ratio in children and adults. Aneurysms manifested predisposition for multiplicity and posterior circulation. There was no difference between children and adults regarding shape and location of aneurysms. However, children with lower aneurysm rupturing rates had better outcomes than their adult counterparts did.

To obtain a global picture of how protein phosphatases are involved in receptor tyrosine kinase (RTK) signaling, we mapped the RTK-phosphatase interactome. Analyses of selected interactions revealed detailed mechanisms of their actions. This study provides new knowledge to better understand cancer development and to identify novel therapeutic targets.