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Background Increasing evidence has suggested that the cerebellum is associated with pain and migraine. In addition, the descending pain system of the brainstem is the major site of trigeminal pain processing and modulation and has been discussed as a main player in the pathophysiology of migraine. Cerebellar and brainstem structural changes associated with migraineurs remain to be further investigated. Methods Voxel-based morphometry (VBM) (50 controls, 50 migraineurs without aura (MWoAs)) and diffusion tensor imaging (DTI) (46 controls, 46 MWoAs) were used to assess cerebellum and brainstem anatomical alterations associated with MWoAs. We utilized a spatially unbiased infratentorial template toolbox (SUIT) to perform cerebellum and brainstem optimized VBM and DTI analysis. We extracted the average diffusion values from a probabilistic cerebellar white matter atlas to investigate whether MWoAs exhibited microstructure alterations in the cerebellar peduncle tracts. Results MWoAs showed decreased fractional anisotropy (FA) in the vermis VI extending to the bilateral lobules V and VI of the cerebellum. We also found higher axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) in the right inferior cerebellum peduncle tract in MWoAs. MWoAs exhibited both reduced gray matter volume and increased AD, MD and RD in the spinal trigeminal nucleus (SpV). Conclusion MWoAs exhibited microstructural changes in the cerebellum and the local brainstem. These structural differences might contribute to dysfunction of the transmission and modulation of noxious information, trigeminal nociception, and conduction and integration of multimodal information in MWoAs. These findings further suggest involvement of the cerebellum and the brainstem in the pathology of migraine without aura. Electronic supplementary material The online version of this article (10.1186/s10194-019-1045-5) contains supplementary material, which is available to authorized users.

Severe haemorrhagic transformation (HT), a common complication of recombinant tissue plasminogen activator (rtPA) treatment, predicts poor clinical outcomes in acute ischaemic stroke. The search for agents to mitigate this effect includes investigating biomolecules involved in neovascularization. This study examines the role of Cathepsin K (Ctsk) in rtPA-induced HT after focal cerebral ischaemia in mice. After knockout of Ctsk, the gene encoding Ctsk, the outcomes of Ctsk+/+ and Ctsk−/− mice were compared 24 h after rtPA-treated cerebral ischaemia with respect to HT severity, neurological deficits, brain oedema, infarct volume, number of apoptotic neurons and activated microglia/macrophage, blood–brain barrier integrity, vascular endothelial growth factor (VEGF) expression and Akt-mTOR pathway activation. We observed that haemoglobin levels, brain oedema and infarct volume were significantly greater and resulted in more severe neurological deficits in Ctsk−/− than in Ctsk+/+ mice. Consistent with our hypothesis, the number of NeuN-positive neurons was lower and the number of TUNEL-positive apoptotic neurons and activated microglia/macrophage was higher in Ctsk−/− than in Ctsk+/+ mice. Ctsk knockout mice exhibited more severe blood–brain barrier (BBB) disruption, with microvascular endothelial cells exhibiting greater VEGF expression and lower ratios of phospo-Akt/Akt and phospo-mTOR/mTOR than in Ctsk+/+ mice. This study is the first to provide molecular insights into Ctsk-regulated HT after cerebral ischaemia, suggesting that Ctsk deficiency may disrupt the BBB via Akt/mTOR/VEGF signalling, resulting in neurological deficits and neuron apoptosis. Ctsk administration has the potential as a novel modality for improving the safety of rtPA treatment following stroke.

In view of the high toxicity of Cr(VI), simple and rapid on-site analytical approaches are in high demand for environment monitoring. Herein, an innovative chemosensor is developed for on-site sensitive detection of Cr(VI) in minutes by the naked eye. The chemosensor consists of gallic acid-capped gold nanoparticles (GA-Au NPs), methylene blue (MB), and NaBH4. In the presence of Cr(VI) ions, the reduction of MB by NaBH4 is able to greatly accelerate due to the Cr(VI)-stimulated catalytic activity of GA-Au NPs, resulting in a color switching of MB from blue to colorless for the quantitative detection of Cr(VI). The chemosensor in solution exhibits excellent selectivity and ultrahigh sensitivity to Cr(VI), with the detection limits of 0.05 nM by UV-vis spectroscopy and 0.1 nM by the naked eye. Similarly, a paper-based chemosensor is obtained by immobilization of GA-Au NPs and MB onto a piece of filter paper, offering a more convenient approach for rapid on-site detection of Cr(VI). In addition, H2O2 as an oxidizing agent is employed to convert Cr(III) into Cr(VI), thus achieving speciation analysis of Cr. The applicability of a chemosensor is also validated by the detection of Cr speciation in water samples with satisfactory recoveries.

Oesophageal cancer ranks as one of the most common malignancy in China and worldwide. Although genome‐wide association studies and molecular biology studies aim to elucidate the driver molecules in oesophageal cancer progression, the detailed mechanisms remain to be identified. Interestingly, RNF168 (RING finger protein 168) shows a high frequency of gene amplification in oesophageal cancer from TCGA database. Here, we report an important function for RNF168 protein in supporting oesophageal cancer growth and invasion by stabilizing STAT1 protein. RNF168 gene is amplified in oesophageal cancer samples, which tends to correlate with poor prognosis. Depletion RNF168 causes decreased cell proliferation and invasion in oesophageal cancer cells. Through unbiased RNA sequencing in RNF168 depleted oesophageal cancer cell, we identifies JAK‐STAT pathway is dramatically decreased. Depletion RNF168 reduced JAK‐STAT target genes, such as IRF1, IRF9 and IFITM1. Immuno‐precipitation reveals that RNF168 associates with STAT1 in the nucleus, stabilizing STAT1 protein and inhibiting its poly‐ubiquitination and degradation. Our study provides a novel mechanism that RNF168 promoting JAK‐STAT signalling in supporting oesophageal cancer progression. It could be a promising strategy to target RNF168 for oesophageal cancer treatment.

Purpose Identifying previous chronic cerebral hemorrhage (PCH), especially asymptomatic cases in patients with ischemic stroke, is essential for proper antithrombotic management. The study aimed to further clarify the prevalence of PCH and the associated factors in patients with acute ischemic stroke using multi-modal neuroimaging including susceptibility-weighted MR imaging (SWI). Methods This was a retrospective cross-sectional study of 382 patients with acute ischemic stroke. All patients underwent 3.0-T MRI for cranial SWI, 1.5-T or 3.0-T conventional cranial MRI, and cranial CT. Patients found with PCH were matched 1:4 with patients without PCH. Clinical manifestation, computed tomography, conventional cranial MRI, and cranial SWI were used to determine PCH. Clinical and neuroimaging findings between the patients with symptomatic vs. asymptomatic PCH were compared. Results Thirty-six patients (36/382, 9.4%) were determined to have had a PCH. Of these 36 patients, 17 (17/36, 47.2%, or 17/382, 4.5%) had asymptomatic PCH. Multivariable analysis showed that serum total cholesterol (OR = 0.510, 95%CI 0.312–0.832, P = 0.007), cerebral microbleeds (OR = 6.251, 95%CI 2.220–17.601, P = 0.001), and antithrombotic drugs history (OR = 3.213, 95%CI 1.018–10.145, P = 0.047) were independently associated with PCH. Asymptomatic PCH had similar clinical and neuroimaging characteristics with symptomatic PCH. Conclusion PCH is not uncommon in acute ischemic stroke patients. Total serum cholesterol, cerebral microbleeds on SWI, and history of antithrombotic drugs were independently associated with PCH in patients with acute ischemic stroke. Asymptomatic PCH, which is easier to be missed and has similar characteristics with symptomatic PCH, should draw much attention. Electronic supplementary material The online version of this article (10.1007/s00234-018-2141-y) contains supplementary material, which is available to authorized users.

The tumor suppressor P53 plays critical role in preventing cancer. P53 is rarely mutated and remains functional in luminal-type breast cancer(1). According to current knowledge, wild-type P53 function is tightly controlled by posttranslational modifications, such as ubiquitination. Several ubiquitin ligases have been shown to regulate P53 ubiquitination and protein stability. Here, we report that RNF187, a RING family ubiquitin ligase, facilitates breast cancer growth and inhibits apoptosis by modulating P53 signaling. RNF187 expression was elevated in breast cancer and correlated with breast cancer survival only in the P53 wild-type groups. Bioinformatic analysis showed that the expression of RNF187 was negatively correlated with the expression of P53 target genes, such as IGFBP3 and FAS, in breast cancer. RNF187 depletion inhibited breast cancer growth and facilitated cell death. RNA sequencing analysis indicated that RNF187 could be an important modulator of P53 signaling. Further experiments showed that RNF187 interacts with P53 and promotes its degradation by facilitating its polyubiquitination in breast cancer cells. Interestingly, the in vitro ubiquitin assay showed that RNF187 can directly ubiquitinate P53 in a manner independent of MDM2. These findings reveal a novel direct P53 regulator and a potential therapeutic target for breast cancer.

Breast cancer is one of the most commonly diagnosed malignancies worldwide, while the triple negative breast cancer (TNBC) is the most aggressive and virulent subtype in breast cancers. Compared with luminal type breast cancers, which could be well controlled by endocrine treatment, TNBC is worse in prognosis and lack of effective targeted therapy. Thus, it would be interesting and meaningful to identify novel therapeutic targets for TNBC treatments. Recent genomic data showed the activation of Hippo/YAP signaling in TNBC, indicating its critical roles in TNBC carcinogenesis and cancer progression. Hippo/YAP signaling could subject to several kinds of protein modifications, including ubiquitination and phosphorylation. Quite a few studies have demonstrated these modifications, which controlled YAP protein stability and turnover, played critical role in Hippo signaling activation In our current study, we identified ZNF213 as a negative modifier for Hippo/YAP axis. ZNF213 depletion promoted TNBC cell migration and invasion, which could be rescued by further YAP silencing. ZNF213 knocking down facilitated YAP protein stability and Hippo target gene expression, including CTGF and CYR61. Further mechanism studies demonstrated that ZNF213 associated with YAP and facilitated YAP K48‐linked poly‐ubiquitination at several YAP lysine sites (K252, K254, K321 and K497). Besides, the clinical data showed that ZNF213 negatively correlated with YAP protein level and Hippo target gene expression in TNBC samples. ZNF213 expression correlated with good prognosis in TNBC patients. Our data provided novel insights in YAP proteolytic regulation and TNBC progression., The triple negative breast cancer (TNBC) is the most aggressive and virulent subtype in breast cancers.In our current study, we identified ZNF213 as a negative modifier for Hippo/YAP axis in TNBC. Our data provided novel insights in YAP proteolytic regulation and TNBC progression.

BackgroundBreast cancer is the most common women malignancy worldwide, while estrogen receptor alpha positive type accounts for two third of all breast cancers. Although ER alpha positive breast cancer could be effectively controlled by endocrine therapy, more than half of the cases could develop endocrine resistance, making it an important clinical issue in breast cancer treatment. Thus, decoding the detailed mechanism, which controls ER alpha signaling activation and ER alpha protein stability, is of great importance for the improvement of breast cancer therapy. Several zinc finger proteins were shown to mediate the ubiquitination process and modulate protein stability. Thus, we further explore the function of Zinc finger protein 213 on ER alpha protein stability and tamoxifen resistance.MethodsCCK8 and Edu assay was used to measure cell proliferation. RNA sequence was performed by Ingenuity pathway analysis. The ER alpha signaling activities were measured with luciferase assay, real-time quantitative PCR, and western blotting. Protein stability assay and ubiquitin assay were used to determine ER alpha protein degradation and ubiquitination. The immuno-precipitation was utilized to determine ER alpha and ZNF213 interaction. The ubiquitin-based immuno-precipitation assay was sued to detect specific ubiquitination manner on ER alpha.ResultsWe identified ZNF213 as a novel zinc finger protein, which modulated ER alpha protein. ZNF213 expression correlated with poor outcome in endocrine treated patients. ZNF213 depletion inhibited ER alpha signaling and proliferation in breast cancer cells. Further mechanistic studies showed ZNF213 located in cytosol and nuclear, which modulated ER alpha stability via inhibiting ER alpha K48-linked ubiquitination.ConclusionsOur study reveals an interesting post-translational mechanism between ER alpha and ZNF213 in breast cancer. Targeting ZNF213 could be an appealing strategy for ER alpha positive breast cancer.

Background: Langerhans cell histiocytosis (LCH) is a rare disease that mainly occur in children. The aim of this investigation is to explore the immune microenvironment of LCH and feasibility of immunotherapy for children with LCH. Methods: Tissue samples were collected from 15 children with LCH and their clinical characteristics were recorded. The expressions of PD-1 ligand 1(PD-L1) and the presence of CD8 T lymphocytes were assessed by immunohistochemistry (IHC). Results: Of the total 15 patients, 8 of them were PD-L1 positive and it accounted for 53.33% and 9 of them were CD8 T lymphocytes positive and it accounted for 60%. There were 8 out of the 15 patients that were both PD-L1 positive and CD8 positive and they accounted for 53.33%.Conclusions: Our results showed that the expression of PD-L1 and presence of CD8 T lymphocytes occurred in the microenvironment of LCH. The findings indicated a possible new treatment option for LCH in children.

Accurate, sensitive, and selective analysis of acrylamide generated in thermally processed foods is of great significance for food safety. Herein, a novel acrylamide sensing platform is designed for both sensitive on-site colorimetric analysis and accurate UV–vis spectroscopy quantification, by integrating thiol-ene Michael addition with gold nanoparticles-mediated catalytical oxidation. The Michael addition reaction between acrylamide and glutathione efficiently alleviates glutathione-induced catalytic activity inhibition of gold nanoparticles, evoking the chromogenic reaction of H2O2-mediated 3,3′,5,5′-tetramethylbenzidine. With increasing the concentration of acrylamide, the oxidation of 3,3′,5,5′-tetramethylbenzidine is accelerated, presenting a series of shades from colorless to blue. The sensing platform exhibits excellent detection performance of acrylamide in the range of 0.5–175 μM with a detection limit of 0.16 μM, and is successfully employed in food samples. Especially, a portable assay kit based on the proposed platform is developed for visual determination of acrylamide, opening an avenue for smart sensors of food safety hazards.

Background: This study aimed to evaluate the predictive potential of contrast-enhanced computed tomography (CT)-based imaging biomarkers (IBMs) for the treatment outcomes of oesophageal squamous cell carcinoma (OSCC) patients after definitive concurrent chemoradiotherapy (CCRT).Methods: A total of 151 ESCC patients who underwent definitive CCRT were included in this retrospective study. All patients were separated randomly to a training cohort (n=97) and the validation cohort (n=54). Pre-treatment contrast-enhanced CT scans were obtained for all patients and used for the extraction of IBMs. An IBM score was constructed by using the least absolute shrinkage and selection operator with logistic regression analysis in training cohort and tested in the validation cohort. IBMsnomograms were built based on IBM score. The concordance index (C-index) was used to assess the performance of the nomograms. Finally, decision curve analysis was performed to estimate the clinical usefulness of the nomograms.Results: A total of 96 IBMs were extracted from each contrast-enhanced CT scan. The IBM score were consisted of 13 CT-based IBMs and were significantly correlated with 3-year overall survival (OS) and 3-year progression-free survival (PFS). Multivariate analysis revealed that IBM score was the independent prognostic factor. In the training cohort, the IBM score yielded an area under the curves (AUCs) of 0.802 (95% CI: 0.713–0.891, pConclusions: TheIBM score based on pre-treatment contrast-enhanced CT could predict the 3-year OS and 3-year PFS for OSCC patients after definitive CCRT. Further multicenter studies with larger sample sizes are warranted.

Background Breast cancer is the most common women malignancy worldwide, while estrogen receptor alpha positive type accounts for two third of all breast cancers. Although ER alpha positive breast cancer could be effectively controlled by endocrine therapy, more than half of the cases could develop endocrine resistance, making it an important clinical issue in breast cancer treatment. Thus, decoding the detailed mechanism, which controls ER alpha signaling activation and ER alpha protein stability, is of great importance for the improvement of breast cancer therapy. Methods ZNF213 and ER alpha protein expression level were measured by western blot, while ER alpha target genes were determined by QPCR. WST-1 assay was used to measure cell proliferation. RNA sequence was performed by Ingenuity pathway analysis. The ER alpha signaling activities were measured with luciferase assay, QPCR and western blotting. Protein stability assay and ubiquitin assay were used to determine ER alpha protein degradation and ubiquitination. The immuno-precipation was utilized to determine ER alpha and ZNF213 interaction. The ubiquitin-based immuno-precipitation assay was sued to detect specific ubiquitination manner on ER alpha. The prognostic data of ZNF213 was derived from public available database. Results Here, we identified ZNF213 as a novel zinc finger protein, which modulates ER alpha protein. ZNF213 expression correlates with poor outcome in endocrine treated patients. ZNF213 depletion inhibits ER alpha signaling and proliferation in breast cancer cells. Further mechanistic studies show that ZNF213 is located in cytosol and nuclear, which modulates ER alpha stability via inhibiting ER alpha K48-linked ubiquitination. Conclusions Our study reveals an interesting post-translational mechanism between ER alpha and ZNF213 in breast cancer. Targeting ZNF213 could be an appealing strategy for ER alpha positive breast cancer.

Background Breast cancer ranks No. 1 in women cancer incidence, while triple negative breast cancer (TNBC) is the most aggressive and the worst prognostic subtype in all breast cancer subtypes. Compared with estrogen receptor alpha positive breast cancer, which could be well controlled by endocrine therapy, TNBC is lack of mature molecular targets for medical therapy. Thus, it is urgent and necessary to discovery the carcinogenic mechanism and potential therapeutic targets for TNBC. Recent studies reveal that Hippo/YAP signaling is an important mediator for TNBC progression. Our current study investigates the role of RING finger protein RNF181 in modulation Hippo/YAP signaling. Methods YAP and RN181 protein level were measured by western blot, while the Hippo classical target genes were measured by real-time PCR. WST1 assay were used to measure cell proliferation, the trans-well and wound healing were used to measure the cell migration and invasion capacity. Protein stability and ubiquitin assay were used to detect the YAP protein ubiquitin and stability. The immuno-precipitation assays were used to detect the protein interactions. Immuno-staining was used to detect the protein localization of YAP and RNF181, while the ubiquitin-based immuno-precipitation assays were used to detect the specific ubiquitination manner of YAP. Results Our current study identified a novel modulator-RNF181 as a positive mediator for Hippo/YAP signaling activation in TNBC. RNF181 depletion significantly inhibited TNBC cell migration, invasion and proliferation, which effect could be rescued by YAP overexpression. RNF181 depletion decreased YAP protein level and Hippo signaling target genes, such as CTGF and CYR61, in TNBC cell lines. Immuno-precipitation assay showed that RNF181 interact with YAP and promoted YAP stability by inhibition K48-linked poly-ubiquitination of YAP in TNBC cells. Besides, public available data showed that RNF181 is elevated in breast cancer and related to poor prognosis in TNBC patients. Conclusion Our study provides evidence to establish a non-proteolytic mechanism in modulating Hippo signaling in breast cancer. RNF181 could be an interesting marker for triple negative breast cancer prognostics and therapeutics.

Oestrogen receptor α (ERα) is overexpressed in two‐thirds of all breast cancer cases and is involved in breast cancer development and progression. Although ERα ‐positive breast cancer can be effectively treated by endocrine therapy, endocrine resistance is an urgent clinical problem. Thus, further understanding of the underlying mechanisms involved in ERα signalling is critical in dealing with endocrine resistance in patients with breast cancer. In the present study, unbiased RNA sequence analysis was conducted between the MCF‐7 and MCF‐7 tamoxifen‐resistant (LCC2) cell lines in order to identify differentially expressed genes. The whole transcriptomic data indicated that the JAK‐STAT pathway is markedly up‐regulated, particularly the ISGF3 complex. As the critical effectors, STAT1 and IRF9 were up‐regulated 5‐ and 20‐fold, respectively, in LCC2 cells. The biological experiments indicated that STAT1 is important for ERα signalling. Depletion of STAT1 or inhibition of STAT1 function significantly decreased levels of ERα protein, ERα ‐target gene expression and cell proliferation in both the MCF‐7 and LCC2 cell lines. Chromatin immunoprecipitation revealed that ERα transcription is associated with STAT1 recruitment to the ERα promoter region, suggesting that transcriptional regulation is one mechanism by which STAT1 regulates ERα mRNA levels and ERα signalling in breast cancer cells. The present study reveals a possible endocrine‐resistant mechanism by which STAT1 modulates ERα signalling and confers tamoxifen resistance. Targeting of STAT1 is a potential treatment strategy for endocrine‐resistant breast cancers.

Introduction: Patients with arteriovenous fistulas are advised to avoid carrying heavy objects draped over the fistula arm. Awareness gradually leads to overprotection and a reduction in the use of the fistula arm. However, restricting motion in the fistula arm leads to decreased quality of life and diminished muscle strength. The current safety recommendations regarding lifting heavy items with the fistula arm are primarily based on experience. Few studies have provided evidence clarifying the scope of safe activity and the influence of load bearing on the continued patency of arteriovenous fistulas. Methods: This prospective observation was based on a long-term follow-up study in which 86 hemodialysis recipients with arteriovenous fistulas were randomized into either a dumbbell group or a handgrip group. The dumbbell group exercised with 6-lb dumbbells, while the handgrip group squeezed rubber balls. Postintervention primary patency and adverse events at the 6-month follow-up were analyzed. Results: No significant difference in postintervention primary patency was observed between the dumbbell group and the handgrip group at 6 months (97.4% vs 95.0%). There were two participants with high-flow fistulas in the dumbbell group and three in the handgrip group, with no significant difference between the two groups (5.3% vs 7.5%). In both groups, there were no other adverse events reported regarding cardiac failure, aneurysm, puncture site hematoma, or hemorrhage. Conclusion: Hemodialysis patients can safely use their fistula arm to lift objects weighing less than 6 lb, which encourages increased motion and helps preserve the functionality of the fistula arm.

Shamir’s polynomial based secret image sharing has been widely adopted to protect an image by splitting it into multiple shadows with G F ( 251 ) calculation. However, mod 251 operation requires pixel values in the secret image to be modified into the range of [ 0 , 250 ] , and leads to image distortion. In this paper, a method for improving recovered image quality in secret image sharing is proposed. To obtain computational efficiency, simple modular arithmetic on a prime number is still adopted. Pixels in the secret image are divided into non-overlapping blocks, and each block contains several N -bit subblocks. Modification strategies for different values of N are given to ensure that each subblock is fit for sharing, as well as theoretical analysis for choosing optimal N . Experimental results by the proposed method are demonstrated, illustrating improved recovered image quality and almost distortion free reconstructed image are achieved.

Objective: The platelet-to-lymphocyte ratio (PLR) is a new marker of atherosclerotic inflammation and has been identified as a predictive factor in cardiovascular diseases, but its significance in patients with acute ischaemic stroke (AIS) who have undergone intravenous thrombolysis (IVT) is still unknown.Methods: Consecutive patients who were treated with IVT using recombinant tissue plasminogen activator (rtPA) for AIS were included from May 2012 to August 2018. The PLR was calculated according to platelet and lymphocyte counts within 24 h after thrombolysis therapy. Functional outcomes were assessed by the modified Rankin Scale (mRS) at 3 months after thrombolysis. Stroke severity was assessed by National Institutes of Health Stroke Scale (NIHSS) scores. The primary endpoint was an unfavorable outcome (mRS > 2), and the secondary endpoint was death at 3 months.Results: A total of 286 patients were included in the study. The median age was 69.5 (59.0–80.0) years, and 59.1% of patients were men. A total of 120 (42.0%) patients had an unfavorable outcome, and 38 (13.2%) died. Patients with an unfavorable outcome had significantly higher PLR values compared with those with a favorable outcome [172.5 (105.3–239.0) vs. 139 (97.0–194.5), P = 0.008], and the PLR values of the patients who died at 3 months were higher than those of the surviving patients [189.5 (127.5–289.0) vs. 142.0 (98.0–215.5), P = 0.006]. After adjustment for other variables, the PLR was independently associated with the two endpoints: unfavorable outcome (OR 2.220, 95% CI 1.245–3.957, P = 0.007) and death (OR 2.825, 95% CI 1.050–7.601, P = 0.040) at 3 months after thrombolysis. In addition, PLR was correlated with the NIHSS score (R = 0.230, P < 0.001).Conclusions: Higher PLR levels were independently associated with an unfavorable outcome and death at 3 months in AIS patients treated with IVT.

Oestrogen receptor ɑ (ERɑ) is overexpressed in two‐thirds of all breast cancers and involves in development and breast cancer progression. Although ERɑ‐positive breast cancer could be effective treated by endocrine therapy, the endocrine resistance is still an urgent clinical problem. Thus, further understanding of the underlying mechanisms ERɑ signalling is critical in dealing with endocrine resistance in breast cancer patients. MCF‐7 and T47D breast cancer cell lines are used to carry out the molecular biological experiments. Western blot is used to assess the relative protein level of ERɑ, RNF168 and actin. Real‐time PCR is used the measure the relative ERɑ‐related gene mRNA level. Luciferase assay is used to measure the relative ERɑ signalling activity. Chromatin immunoprecipitation is used to measure the RNF168 binding affinity to ERɑ promoter regions. WST assay and flow cytometry are used to measure the cell proliferation capacity. We use Student's t test and one‐way ANOVA test for statistical data analysis. Here, we report an important role in ERɑ‐positive breast cancer cells for RNF168 protein in supporting cell proliferation by driving the transcription of ERɑ. RNF168 is highly expressed in breast cancer samples, compared with normal breast tissue. In patients with breast cancer, RNF168 expression level is correlated with poor endocrine treatment outcome. Depletion of RNF168 causes decreased cell proliferation in MCF‐7 and T47D cells. Besides, depletion RNF168 reduced mRNA level of ERɑ and its target genes, such as PS2 and GREB1. Chromatin immunoprecipitation revealed that ERɑ transcription is associated with RNF168 recruitment to ERɑ promoter region, suggesting that transcriptional regulation is one mechanism by which RNF168 regulates ERɑ mRNA level and ERɑ signalling in breast cancer cells. RNF168 is required for ERɑ‐positive breast cancer cell proliferation and facilitate ERɑ signalling activity possibly through promoting transcription of ERɑ.

Increasing evidence has suggested that major depressive disorder (MDD) is highly associated with brain-derived neurotrophic factor (BDNF) levels, dendrites atrophy, and loss of dendritic spines, especially in emotion-associated brain regions including the hippocampus. Paeonol is a kind of polyphenols natural product with a variety of therapeutic effects. Recent studies have reported its antidepressant effects. However, it is unclear what signaling pathways contribute to improve MDD. The present study investigated the effect of Paeonol on hippocampal neuronal morphology and its possible signaling pathways in chronic unpredictable mild stress (CUMS) rat model. Using CUMS rat model, the antidepressant-like effect of Paeonol was validated via depression-related behavioral tests. Neuronal morphology in hippocampal CA1 and DG was assessed using ImageJ’s Sholl plugin and RESCONSTRUCT software. BDNF signaling pathway-related molecules was determined by Western blotting. Paeonol attenuated CUMS-induced depression-like behaviors, which were accompanied by hippocampal neuronal morphological alterations. After Paeonol treatment for 4 weeks, the dendritic length and complexity and the density of dendritic spines markedly increased in the hippocampal CA1 and the dentate gyrus (DG). However, CUMS or Paeonol treatment does not selectively affect dendritic spine types. Simultaneously, administration of Paeonol deterred CUMS-induced cofilin1 activation that is essential for remolding of dendritic spines. The induction of CUMS downregulated BDNF levels and upregulated Rac1/RhoA levels; however, the tendency of these was inhibited by treatment with Paeonol. Our data suggest that BDNF-Rac1/RhoA pathway may be involved in attenuation of CUMS-induced behavioral and neuronal damage by Paeonol that may represent a novel therapeutic agent for depression.

Commercial rolled Mg-3Al-1Zn (AZ31) alloy sheet was used as the experimental material, an Mg-air battery based on its rolling surface (RS) and cross-section surface (CS) were both prepared to study the effect of texture on the performance of Mg-air battery. And the experimental samples had a similar surface roughness to practical application. The impedance spectroscopy (EIS) was used to investigate the electrochemical behavior of the samples. The results show that CS surface has a higher corrosion resistance compared with the RS surface. The battery performance was studied by constant current discharge test, and the results show that the Mg-air battery based on the CS surface anode has higher anode efficiency (71.3%) compared with the Mg-air battery based on the RS surface anode (65.7%). The surface morphologies of the magnesium alloy anodes substrate after discharged for 24 h were observed by scanning electron microscope. The RS anode exhibits a magnesium alloy anode substrate with more holes and gullies, which may contribute to its lower anode efficiency. Thus, the CS anode dominated by (10 1 ¯ 0), (11 2 ¯ 0) and (10 1 ¯ 1) orientated grains is more suitable to use on Mg-air battery.

Chitosan was modified by gamma radiation–induced grafting with maleic acid and then used for the removal of cobalt ions from aqueous solutions. Chitosan-g-maleic acid was characterized by Fourier Transform infrared spectroscopy (FT-IR). The effect of the dose (1–5 kGy) and monomer concentration (0.3–1.3%, m/v) on the grafting ratio was examined. The adsorption kinetics and isotherms were also investigated. The results showed that the optimal dose for grafting was 2 kGy. When monomer concentration was within the range of 0.3–1.3% (m/v), the grafting ratio increased almost linearly. For the adsorption of cobalt ions by chitosan-g-maleic acid beads, the pseudo second-order kinetic model (R2 = 0.99) and Temkin isotherm model (R2 = 0.96) were able to fit the experimental data reasonably well. The equilibrium adsorption capacity of cobalt ions increased from 2.00 mg/g to 2.78 mg/g after chitosan modification.

Background Estrogen receptor alpha (ER alpha) is expressed in the majority of breast cancers and promotes estrogen-dependent cancer progression. ER alpha positive breast cancer can be well controlled by ER alpha modulators, such as tamoxifen. However, tamoxifen resistance is commonly observed by altered ER alpha signaling. Thus, further understanding of the molecular mechanisms, which regulates ER alpha signaling, is important to improve breast cancer therapy. Methods SMURF1 and ER alpha protein expression levels were measured by western blot, while the ER alpha target genes were measured by real-time PCR. WST-1 assay was used to measure cell viability; the xeno-graft tumor model were used for in vivo study. RNA sequencing was analyzed by Ingenuity Pathway Analysis. Identification of ER alpha signaling was accomplished with luciferase assays, real-time RT-PCR and Western blotting. Protein stability assay and ubiquitin assay was used to detect ER alpha protein degradation. Immuno-precipitation based assays were used to detect the interaction domain between ER alpha and SMURF1. The ubiquitin-based Immuno-precipitation based assays were used to detect the specific ubiquitination manner happened on ER alpha. Results Here, we identify the E3 ligase SMURF1 facilitates ER alpha signaling. We show that depletion SMURF1 decreases ER alpha positive cell proliferation in vitro and in vivo. SMURF1 depletion based RNA-sequence data shows SMURF1 is necessary for ER alpha target gene expression in the transcriptomic scale. Immunoprecipitation indicates that SMURF1 associates with the N-terminal of ER alpha in the cytoplasm via its HECT domain. SMURF1 increases ER alpha stability, possibly by inhibiting K48-specific poly-ubiquitination process on ER alpha protein. Interestingly, SMURF1 expression could be induced via estradiol treatment. Conclusions Our study reveals a novel positive feedback between SMURF1 and ER alpha signaling in supporting breast cancer growth. Targeting SMURF1 could be one promising strategy for ER alpha positive breast cancer treatment. Electronic supplementary material The online version of this article (10.1186/s13046-018-0672-z) contains supplementary material, which is available to authorized users.

Herein, monolayer self-assembly of polyhedral oligomeric silsesquioxane (POSS) onto graphene oxide (GO) is facilely achieved by taking advantage of their electrostatic and hydrogen-bonding interaction. Attributed by the rigid nanocage and donor/acceptor effect of POSS, the as-prepared POSS-GO monolayer nanostructure (denoted as PG) shows an ultrathin thickness of 1.6 nm and significantly suppressed stacking. Followed by post-functionalization of Cu 2+, the POSS-GO-Cu2+ nanostructure (shortly termed as PGCu) exhibits outstanding performances including hemoglobin specificity, salt tolerance and ultrahigh adsorption capacity (up to 1657.2 mg g−1). Moreover, PGCu is successfully utilized for the separation of hemoglobin from human whole blood with the maintenance of protein activity. The present study furnishes a simple, rapid and cost-efficient route for the fabrication of ultrathin two-dimensional materials with considerable application potentialities for bio-separation and analysis.

// Ting Zhuang 1, 2, * , Sifan Yu 1, 2, 3 * , Lichen Zhang 1, 2, 4 * , Huijie Yang 1, 2 , Xin Li 1, 2 , Yingxiang Hou 1, 2 , Zhenhua Liu 1, 2, 5 , Yuanyuan Shi 1, 2 , Weilong Wang 6, 7 , Na Yu 6, 7 , Anqi Li 1, 2, 8 , Xuefeng Li 9 , Xiumin Li 6, 7 , Gang Niu 10, 11, 12 , Juntao Xu 10, 11, 12 , Muhammad Sharif Hasni 12, 13 , Kun Mu 14 , Hui Wang 1, 2 and Jian Zhu 1, 2, 15 1 Research Center for Immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan, China 2 Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan, China 3 Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Renal Cancer and Melanoma, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China 4 Laboratory of Genetic Regulators in the Immune System, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan, China 5 Synthetic Biology Remaking Engineering and Application Laboratory, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan, China 6 Department of Gastroenterology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China 7 Center for Cancer Research, Xinxiang Medical University, Xinxiang, Henan, China 8 School of International Education, Xinxiang Medical University, Xinxiang, Henan, China 9 Department of Medical Oncology, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China 10 Department of Cancer genomics, LemonData biotech (Shenzhen) Ltd, Shenzhen, Guangdong, China 11 Phil Rivers Technology (Beijing) Ltd. Beijing, China 12 Institute of Biochemistry University of Balochistan, Quetta, Pakistan 13 Department of Hematology and Transfusion Medicine, Lund University, Lund, Sweden 14 Department of Pathology, School of Medicine, Shandong University, Jinan, Shandong, China 15 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA * Ting Zhuang, Sifan Yu and Lichen Zhang contribute equally to this study Correspondence to: Jian Zhu, email: jian.zhu@utsouthwestern.edu Ting Zhuang, email: zhuangting_83@qq.com Hui Wang, email: wanghui@xxmu.edu.cn Kun Mu, email: mukun@sdu.edu.cn Keywords: SHARPIN, ER alpha, breast cancer, ubiquitination, protein stability Received: May 17, 2017 Accepted: June 29, 2017 Published: August 19, 2017 ABSTRACT Estrogen receptor α is expressed in the majority of breast cancers and promotes estrogen-dependent cancer progression. In our study, we identified the novel E3 ubiquitin ligase SHARPIN function to facilitate ERα signaling. SHARPIN is highly expressed in human breast cancer and correlates with ERα protein level by immunohistochemistry. SHARPIN expression level correlates with poor prognosis in ERα positive breast cancer patients. SHARPIN depletion based RNA-sequence data shows that ERα signaling is a potential SHARPIN target. SHARPIN depletion significantly decreases ERα protein level, ERα target genes expression and estrogen response element activity in breast cancer cells, while SHARPIN overexpression could reverse these effects. SHARPIN depletion significantly decreases estrogen stimulated cell proliferation in breast cancer cells, which effect could be further rescued by ERα overexpression. Further mechanistic study reveals that SHARPIN mainly localizes in the cytosol and interacts with ERα both in the cytosol and the nuclear. SHARPIN regulates ERα signaling through protein stability, not through gene expression. SHARPIN stabilizes ERα protein via prohibiting ERα protein poly-ubiquitination. Further study shows that SHARPIN could facilitate the mono-ubiquitinaiton of ERα at K302/303 sites and facilitate ERE luciferase activity. Together, our findings propose a novel ERα modulation mechanism in supporting breast cancer cell growth, in which SHARPIN could be one suitable target for development of novel therapy for ERα positive breast cancer.

Constitutive depletion of p21-activated kinase 4 (PAK4) in the mouse causes embryonic lethality associated with heart and brain defects. Given that conventional gene depletion of PAK1 or PAK3 caused functional deficits in the mouse pancreas, while gene depletion of PAK5 or PAK6 did not, we asked if PAK4 might have a functional role in pancreas development. We therefore introduced conditional, Pdx1-Cre-mediated, pancreatic PAK4 gene depletion in the mouse, verified by loss of PAK4 protein expression in the pancreas. PAK4 knock-out (KO) mice were born at Mendelian ratios in both genders. Further, morphological and immunohistochemical examinations and quantifications indicated that exocrine, endocrine and ductal compartments retained the normal proportions and distributions upon PAK4 gene depletion. In addition, body weight records and a glucose tolerance test revealed no differences between WT and PAK4 KO mice. Together, this suggests that PAK4 is dispensable for mouse pancreas development. This will facilitate future use of our Pdx1-Cre-driven conditional PAK4 KO mouse model for testing in vivo potential functions of PAK4 in pancreatic disease models such as for pancreatitis and different pancreatic cancer forms.

Purpose The association between intracranial internal carotid artery (IICA) calcification and lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMBs) has been well researched. However, enlarged cerebral perivascular space (PVS) has not yet been reported to correlate with intracranial internal carotid artery calcification. Therefore, the primary aim of this study was to investigate the relationship between IICA calcification and enlarged PVS. Methods A total of 189 patients with ischemic stroke in the middle cerebral artery territory who presented within 7 days of ictus from 2012 to 2015 were enrolled respectively. All patients were required to have undergone head computed tomography, magnetic resonance imaging, susceptibility-weighted magnetic resonance imaging, magnetic resonance angiography, or computed tomography angiography. Clinical characteristics were recorded. IICA calcification and enlarged PVS were semi-quantitatively evaluated, and the presence of lacunes, WMH, and CMBs was recorded. Results Of the 189 patients, 63.5% were male. Mean age of the patients was 68.6 ± 12.2 years. There were 104 patients with IICA calcification. Age, diabetes mellitus, lacunes, and white matter hyperintensity were significantly associated with IICA calcification (P

Esophageal cancer is among the most deadly malignant diseases. However, the genetic factors contributing to its occurrence are poorly understood. Multiple studies with large clinic-based cohorts revealed that variations of the phospholipase C epsilon (PLCE1) gene were associated with esophageal cancer susceptibility. However, the causative role of PLCE1 in esophageal cancer is not clear. We inactivated the functional alleles of PLCE1 by CRISPR/Cas9 genome editing technology. The resultant PLCE1 inactivated cells were analyzed both in vitro and in vivo. Our results showed that loss of PLCE1 dramatically decreased the invasion and proliferation capacity of esophageal carcinoma cells in vitro. Moreover, such PLCE1 inactivated tumor grafts exhibited significantly decreased tumor size in mice. We found that PLCE1 was required to maintain protein level of snail a key transcription factor responsible for invasion. Our further transcriptomic data revealed that deficient cells were significantly decreased in expression of genes enriched as targets of Snail. Strikingly, recovery of Snail protein at least partially rescued the invasion and proliferation capacity in PLCE1 inactivated cells. In ESCC clinical specimens, PLCE1 was correlated with tumor stage (P

The authors have prepared a super-hydrophilic polymer consisting of a poly-polyhedral oligomeric silsesquioxane (POSS)-formaldehyde (PPF) composite. The polymerization process does not require a catalyst and results in a material with excellent hydrophilic properties and abundant functional groups. The PFF composite, even if not chemically modified, can selectively bind glycoproteins due to strong hydrophilic interactions. It is shown that glycoproteins can be selectively captured by the composite that has a binding capacity as large as 542 mg g−1 for the model protein ovalbumin. The PPF was applied to the selective capture and isolation of ovalbumin from complex biological samples.

The ubiquitin binding protein SHAPRIN is highly expressed in human breast cancer, one of the most frequent female malignancies worldwide. Here, we perform SHARPIN depletion in breast cancer cells together with RNA sequencing. The global expression profiling showed p53 signaling as a potential SHARPIN target. SHARPIN depletion decreased cell proliferation, which effect could be rescue by p53 knocking down. Depletion SHARPIN significantly increases p53 protein level and its target genes in multiple breast cancer cell lines. Further experiment revealed that SHARPIN could facilitate p53 poly-ubiquitination and degradation in MDM2 dependent manner. Immuno-precipitation assay showed that SHARPIN associated with MDM2 and prolonged MDM2 protein stability. Analysis of public available database showed SHARPIN correlated with poor prognosis specifically in p53 wild-type breast cancer patients. Together, our finding revealed a novel modifier for p53/MDM2 complex and suggested SHARPIN as a promising target to restore p53 function in breast cancer.

A novel three-dimensional (3D) magnetic carbon framework (MCF) is developed and applied as an efficient absorbent for the removal of lead from aqueous medium. The MCF adsorbent was designed with Prussian blue (PB), amylopectin and polyurethane (PU) sponge serving as iron and carbon precursors at a calcination temperature of 450 °C. The framework is characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and surface charge analysis to elucidate the mechanism for the formation of the framework structure and its performance in Pb (II) removal. The 3D network structure of PU sponge provides an ideal support for the magnetic PB. Meanwhile, a better porous network structure obtained by the introduction of amylopectin endows MCF with a high specific surface area and a large number of active adsorption sites. An adsorption capacity of up to 386 mg g−1 for Pb (II) is achieved in aqueous medium at pH 7. MCF provides excellent features of regeneration and ease of magnetic separation, thus it shows a vast potential for water remediation.

Background: Arteriovenous fistulas (AVF) have been the main vascular accesses for haemodialysis patients, but the maintenance after maturation poses serious challenges. Arm exercises promote the maturation of AVFs. However, few studies have evaluated the effect of arm exercise on matured AVF and addressed the intervention for late fistula failure. Objectives: The study was conducted to explore the effect of dumbbell exercise on mature AVF. Methods: 86 participants undergoing haemodialysis with AVFs were randomized into the control group and experimental group. The experimental group held 6-pound dumbbells on non-dialysis days for 3 months, while the control group squeezed rubber balls. Results: For blood flow of draining vein (DV; primary outcome), the between-group effects, interaction effect and time effect showed significant differences. A significant increase in blood flow of DV was observed in the dumbbell group at the 3rd month (mean difference, 359.50 [111.90–829.05] mL/min; p = 0.001). The difference in blood flow of AVF proximal artery, blood flow of brachial artery, the diameter of DV and the incidence of adverse events at 3 months (secondary outcomes) between the 2 groups was insignificant. Conclusion: Prolonged training with arm exercises is essential for patients with AVFs though the fistula has matured. The designed dumbbell exercise is an economical, effective intervention to maintain the function of AVF, especially for patients with potential reduction of access blood flow and no percutaneous transluminal angioplasty indication.

p21-activated kinases (PAKs) are serine/threonine kinases functioning as downstream effectors of the small GTPases Rac1 and Cdc42. Members of the PAK family are overexpressed in human breast cancer, but their role in mammary gland development is not fully explored. Here we examined the functional role of PAK4 in mammary gland development by creating a mouse model of MMTV-Cre driven conditional PAK4 gene depletion in the mammary gland. The PAK4 conditional knock-out mice were born healthy, with no observed developmental deficits. Mammary gland whole-mounts revealed no defects in ductal formation or elongation of the mammary tree through the fat pad. PAK4 gene depletion also did not alter proliferation and invasion of the mammary epithelium in young virgin mice. Moreover, adult mice gave birth to healthy pups with normal body weight upon weaning. This implies that MMTV-Cre induced gene depletion of PAK4 in mice does not impair normal mammary gland development and thereby provides an in vivo model that can be explored for examination of the potential function of PAK4 in breast cancer.

Overcoming cellular growth restriction, including the evasion of cellular senescence, is a hallmark of cancer. We report that PAK4 is overexpressed in all human breast cancer subtypes and associated with poor patient outcome. In mice, MMTV-PAK4 overexpression promotes spontaneous mammary cancer, while PAK4 gene depletion delays MMTV-PyMT driven tumors. Importantly, PAK4 prevents senescence-like growth arrest in breast cancer cells in vitro, in vivo and ex vivo, but is not needed in non-immortalized cells, while PAK4 overexpression in untransformed human mammary epithelial cells abrogates H-RAS-V12-induced senescence. Mechanistically, a PAK4 – RELB - C/EBPβ axis controls the senescence-like growth arrest and a PAK4 phosphorylation residue (RELB-Ser151) is critical for RELB-DNA interaction, transcriptional activity and expression of the senescence regulator C/EBPβ. These findings establish PAK4 as a promoter of breast cancer that can overcome oncogene-induced senescence and reveal a selective vulnerability of cancer to PAK4 inhibition., Oncogene induced senescence protects cells from unrestricted growth and cancer. Here, the authors show that PAK4 overrides this senescence in breast cancer cells through phosphorylation of RELB, thereby inhibiting transcription of the senescence regulator C/EBPβ.

It remains a real challenge to treat the industrial wastewater containing hardly-decomposed dyes and heavy metal ions. Herein, an environment-friendly hybrid hydrogel is prepared by a simple mixing of selenocarrageenan (SeCA) and graphene oxide (GO) under heating and stirring for 5 min without any other reagent. Such a selenocarrageenan hybrid graphene hydrogel (SeCA-GH) without volume shrinkage exhibits excellent adsorption capacity and selective binding to dyes and Hg

The brainstem has been discussed as the main player in the pathogenesis of migraine. Dysfunctional brainstem nuclei and their abnormal connections to other key brain centers may contribute to headache and other symptoms of migraine. In the present study, 32 patients with migraine without aura (MWoA) and 32 age- and sex-matched healthy controls (HCs) underwent resting-state fMRI scans. We used masked independent analysis (mICA) to investigate whether patients with MWoA exhibited abnormal brainstem nuclei-cortical functional connectivity (FC). The mICA can suppress adjacent physiological noise and prevent results from being driven by the much stronger signals of the surrounding structures. Regional homogeneity (ReHo) was used to investigate whether the brainstem regions with abnormal FC to other brain areas exhibited abnormal regional neuronal activity. Patients with MWoA showed significantly weaker FC between the posterior pons and the left superior parietal lobule, the left middle temporal gyrus, and the left middle frontal gyrus. Furthermore, patients with MWoA exhibited significantly decreased ReHo values in the posterior pons compared with HCs, and the posterior pons ReHo value was significantly negatively correlated with HIT-6 scores in the MWoA group. Patients with MWoA exhibited functional abnormalities in the posterior pons and weakened connections between the posterior pons and several key cortical brain areas involved in pain processing during the resting state. PERSPECTIVE: This study provided increased evidence that the pons is involved in the pathophysiological mechanism of migraine, and weakened connections suggest that the touch and pain sensation of migraine sufferers may not be properly relayed to cortical processing areas, which may be associated with the pathogenesis of MWoA.

Parkinson’s disease (PD) is a progressive neurological degenerative disorder characterized by impaired motor function and non-motor dysfunctions. While recent studies have highlighted the role of the cerebellum in PD, our understanding of its role in PD remains limited. In the present study, we used resting-state fMRI to evaluate dysfunctions within the cerebellum in PD patients treated with medication and drug-naive PD patients. We applied amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) analysis methods. Thirty-one patients with early stage PD (22 drug-naive and 9 medicated patients) and 31 gender- and age-matched healthy controls were recruited in this study. ALFFs increased in the left cerebellar areas (lobules VI/VIIb/CruI/CruII and the dentate gyrus) and right cerebellar areas (lobules VI/VIIb/VIIIa/CruI/CruII and the dentate gyrus) of all PD patients and in the left and right cerebellar areas (lobules VI/VIIb/CruI and the dentate gyrus) of drug-naive PD patients but were not significantly changed in medicated PD patients. DC increased in the right cerebellar areas of all PD patients and medicated PD patients. All PD patients and all drug-naive PD patients showed significantly weaker functional connectivity (FC) between the left cerebellum and the left medial frontal gyrus. However, FC was significantly stronger between the right cerebellum and the left precentral and right middle occipital gyri in the medicated PD patients than in controls. Furthermore, a correlation analyses revealed that ALFF z scores in the left cerebellum (lobule VI) and right cerebellum (lobule VI/CruI and dentate gyrus) were negatively correlated with Mini-Mental State Examination (MMSE) scores in all PD patients and drug-naive patients. These results indicate that the cerebellum plays an important role in PD, mainly by exerting a compensatory effect in early stage PD. Additionally, antiparkinsonian medication would modified PD-induced changes in local neural activity and FC in PD patients. The results of this study offer novel insights into the roles of the cerebellum in early stage drug-naive PD.

BackgroundBotulinum toxin type A (BoNT-A) is generally considered safe and is widely used to treat a variety of clinical conditions involving muscle hyperactivity and for cosmetic purposes. However, the effects of BoNT-A poisoning (botulism) on brain function are poorly understood.Methodology/principal findingsHerein, we investigated brain functions in 9 patients who received illegal cosmetic injections of botulinum and 18 matched controls by combining the analysis methods of regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) based on resting-state fMRI. Compared with the controls, the patients with botulism exhibited significantly reduced ReHo values in the left posterior lobe of the cerebellum extending to the right anterior lobe of the cerebellum, as well as in the right anterior lobe of the cerebellum extending to the parahippocampal gyrus and right posterior lobe of the cerebellum. The patients with botulism also showed weakened ALFF values in the right anterior lobe of the cerebellum extending to the left anterior lobe of the cerebellum and right posterior lobe of the cerebellum, as well as in the right anterior lobe of the cerebellum.Conclusions/significanceThe results indicate that BoNT-A may modulate cerebral activation in specific areas, which may play roles in both the adverse effects of botulism and the mechanism underlying clinical treatment with BoNT-A.

Objective To investigate the epidemiology and clinical characteristics of autoimmune hepatitis (AIH). Methods Hospitalization data of 62 consenting patients with autoimmune hepatitis admitted to the First Affiliated Hospital of Ji'nan University from November 2002 to March 2014 were collected. Clinical characteristics, epidemiology, serum IgG or γ-globulin levels, liver function indices, and liver fibrosis indices in these patients were analyzed. Results ①62 patients participated in this research, including 9 males and 53 females. The male-female ratio of AIH patients was 1:5.89. The patients, age ranged from 15 to 79 years (median age 56 years), and middle aged patients accounted for 40.3% (25 patients). Fatigue (61.3%), hepatomegaly (54.8%) and loss of appetite (53.2%) were the most common clinical symptoms. Type ⅠAIH accounted for 77.42%, type Ⅱfor 3.23%, type Ⅲfor 3.23% and type Ⅳfor 16.13%. ②Different types of AIH patients showed no statistically significant difference in the gender, age, clinical manifestations and incidence of complications, serum IgG or γ-globulin levels and liver function. ③Due to the limited size of type Ⅱ, type Ⅲand type ⅣAIH patients, only type ⅠAIH patients were enrolled in a further analysis. In type ⅠAIH patients, the incidences of abdominal distension, palmar erythema, spider nevi, edema of lower extremities, upper gastrointestinal hemorrhage and spontaneous peritonitis were higher in males. Females had a higher concentration of gamma glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP), and a lower concentration of hyaluronic acid and laminin. Type ⅠAIH patients in all age groups showed no statistical ly significant difference in clinical manifestations and incidence of complications, serum IgG or γ-globulin levels and liver function. Conclusions AIH predominantly affects middle-aged women. Fatigue, hepatomegaly and reduction of appetite are the most common clinical symptoms. Type Ⅰis the most common type among the three types. Females has a higher concentration of GGT and ALP and a lower concentration of hyaluronic acid and laminin. DOI: 10.11855/j.issn.0577-7402.2016.08.13

Objective To evaluate the association between modest alcohol consumption and the risk of fatty liver disease (FLD) or nonalcoholic fatty liver disease (NAFLD). Methods PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Digital Journal Full-text Database, and database for Chinese Technical Periodicals (VIP) till Nov. 2015 were searched for the studies in evaluating the effect of alcohol consumption on FLD or NAFLD. The quality assessment of included studies was performed according to the combined evaluation for cross-sectional studies and Newcastle-Ottawa scale (NOS) for cohort studies. A meta-analysis was performed using Stata12.0 software. Results A total of 16 studies including 13 cross-sectional studies, 2 cross-sectional following longitudinal studies, and 1 cohort study with 76 967 participants were selected finally. The results of Meta-analysis were as follows. Minimal and light alcohol consumptions reduced the risk for FLD or NAFLD by 17% and 27%, respectively, and moderate alcohol consumption was marginally associated with decreased risk for FLD or NAFLD. The results of subgroup analysis by gender showed that (1) Minimal and light alcohol consumptions reduced the risk of FLD or NAFLD by 29% and 33%, respectively, but moderate alcohol consumption was not statistically significant in reducing the risk of FLD or NAFLD in females compared with controls; (2) Light alcohol consumption reduced the risk of FLD or NAFLD by 23%, but minimal and moderate alcohol consumptions were not statistically significant in reducing the risk of FLD or NAFLD in male compared with controls; (3) Light and moderate alcohol consumptions in Asian males reduced the risk of FLD or NAFLD by 29.7% and 30.3%, respectively. Conclusions Modest alcohol consumptions may not increase the risk of FLD or NAFLD. Inversely, minimal and light alcohol consumptions in female reduce the risk of FLD or NAFLD remarkably, and light to moderate alcohol consumption in males, especially in Asian males, can also significantly reduce the risk of FLD or NAFLD. DOI: 10.11855/j.issn.0577-7402.2016.07.15

A rare 3-D Mn–organic framework, [(CH3)2NH2]3[Mn5(btc)4(Ac)(H2O)4]·5H2O (1), based on pentanuclear manganese clusters as building blocks has been prepared and structurally characterized by EA, IR, TGA, PXRD, and single-crystal X-ray diffraction. Structural analysis indicates the pentanuclear manganese cluster in 1 has a bow-like configuration, which is the first found to act as secondary building unit in the field of metal–organic framework. Gas adsorption measurements reveal that 1 can absorb a considerable amount of N2 and CO2.

In this study, an Mg-air battery based on air cathode with different content of Na2SO4 was prepared to study the effect of Na2SO4 on the performance of Mg-air battery. The electrochemical performance of the air cathode was studied by potentiodynamic polarization and electrochemical impedance spectroscopy. The results indicated that the electrochemical activity of the electrode enhanced with the increasing Na2SO4. The discharge performance of the battery was investigated by constant-current discharge test, and the results showed that the discharge potential of the battery also improved with the increasing of Na2SO4. However, the forming of air cathode became difficult gradually with the increasing content of Na2SO4. What is worse, the oversize pore produced in the moisture barrier when the content of Na2SO4 was too high and the moisture barrier would lose resistance to water. So the content of Na2SO4 should not be too high.