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Objective: Stent placement is a feasible approach worldwidely for patients with symptomatic intracranial artery stenosis (sICAS) and hemodynamic impairment (HI) who are at high risk of recurrent stroke after medical treatment. Exploration of factors associated with poor outcomes after stent placement could help develop better individualized therapeutic strategies., Methods: This study conducted a post-hoc analysis of a prospective, multicenter registry study of stent use for sICAS with HI in China. Patient and clinical demographics, and stenotic lesion images were analyzed using univariate and multivariate Cox regression to the time until any endpoints or the end of the follow-up period. The short-term endpoint included any transient ischemic attack (TIA), stroke, or death within 1 month after stent placement. The long-term endpoints included the short-term endpoints and any TIA or stroke in the region of the affected artery that occurred more than 1 month after stent placement., Results: Two hundred and ninety two patients were included, with 13 short-term and 39 long-term endpoints. Multivariate Cox regression analysis revealed that lesions at the arterial origin or bifurcation (Hazard Ratio (HR) = 7.52; 95% CI, 1.89-29.82; p = 0.004) were significantly associated with higher short-term risk. Baseline renal insufficiency reduced the risk (HR = 0.08; 95% CI: 0.01-0.68; p = 0.021). Factors significantly associated with higher long-term risk included irregular or ulcerated plaques at the lesion (HR = 2.15; 95% CI: 1.07-4.33; p = 0.031). Subgroup analyses indicated that higher risk occurred in the older age group (age>59 years, HR = 3.73, 95% CI: 1.27-10.97, p = 0.017), and not in the younger group (age≤59 years, HR = 1.12, 95% CI: 0.42-3.03, p = 0.822)., Conclusion: Irregular or ulcerated plaques in older patients and lesions at the arterial opening or bifurcation were more likely to result in adverse endpoints for stent placement during long or short -term follow-up. Investigation of these factors might facilitate the development of individualized therapeutic strategies for this population., Clinical Trial Registration: http://www.clinicaltrials.gov, identifier: NCT01968122., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gong, Zhang, Meng, Liu, Li, Xiao, Liu, Sun, Liu, Wang, Zhang and Wang.)

The titanium implant surface topography optimization for improving osseointegration has been performed for many years, whereas understanding the mechanisms of topography-induced osteogenic differentiation is still insufficient. In this study, the micro/nano-textured topography was created on titanium implant surface by acid etching and anodization. The MC3T3-E1 cells were incubated with different surfaces and the RNA sequencing technique was performed to obtain the transcriptomic information, which suggested the enrichment at "membrane" and "organelle" (GO) as well as "Calcium signal pathway" (KEGG). Consequently, a special attention was paid to the store-operated calcium entry (SOCE) mediated by Orai1 at ER-PM contact site. By fluorescence staining and western blot, it was confirmed that the Orai1 was upregulated on the micro/nano-textured titanium surface, which was correlated to the enhanced osteogenic differentiation induced by topography. Further experiments indicated that the CaMKII/ERK1/2 pathway was involved in. This research is the first time giving a comprehensive transcriptomic information of osteoblasts on micro/nano-textured topography and may provide deeper insight into the interaction between biomaterials and host., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Recently there has been a great interest in covalent organic frameworks due to their fascinating properties. Current approaches to improve their hydrolytic stability mainly rely on the transformation of the dynamic bonds into strong and irreversible bonds, but these approaches also reduce the versatility of the frameworks. Herein, we would like to demonstrate a solution to this dilemma by forming hierarchical bonds through olefin metathesis to produce highly stable COFs. Our approach allows unprecedented opportunities for post-modification of the inner space through the dynamic imine bonds while maintaining the integrity of the framework. Specifically, we demonstrate an amorphous-to-crystalline transformation. In addition, the porosity can be enhanced by up to 70% after full removal of the amine subunits. Overall, our work provides a new direction for the generation of highly stable while still versatile COFs. Meanwhile, platinum(II) complexes can be supported on BHU-2 (Pt@BHU-2) or BHU-2-Oxidate(Pt@BHU-2-Oxidate) as efficient catalysts for hydrosilylation.

We evaluated the variations of bacterial communities in six heavy metal contaminated soils sampled from Yanzi Bian (YZB) and Shanping Cun (SPC) tailings located in northwestern China. Statistical analysis showed that both the heavy metals and soil chemical properties could affect the structure and diversity of the bacterial communities in the tailing soils. Cd, Cu, Zn, Cr, Pb, pH, SOM (soil organic matters), TP (total phosphorus) and TN (total nitrogen) were the main driving factors of the bacterial community variations. As a consequence, the relative abundances of certain bacterial phyla including Proteobacteria, Chloroflexi, Firmicutes, Nitrospirota and Bacteroidota were significantly increased in the tailing soils. Further, we found that the abundance increasement of these phyla were mainly contributed by certain species, such as s__unclassified_g__Thiobacillus (Proteobacteria), s__unclassified_g__Sulfobacillus (Firmicutes) and Leptospirillum ferriphilum (Nitrospirota). Thus, these species were considered to be strongly heavy metal tolerant. Together, our findings will provide a useful insight for further bioremediations of these contaminated areas., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The objective of this study was to assess the safety, feasibility, and outcomes of endovascular recanalization for symptomatic intracranial internal carotid and middle cerebral artery occlusion lasting longer than 72 h., Methods: Thirty-nine consecutive patients with symptomatic occlusion of the anterior circulation and failure of medical therapy underwent endovascular recanalization and were included in this retrospective study. Patient characteristics, atherosclerotic risk factors, successful recanalization rates, and angiographic data were collected., Results: Recanalization was successful in 37 cases (94.9%). The average residual stenosis immediately after intervention was 11.6 ± 4.3%. The patients who underwent balloon angioplasty alone had similar residual stenosis to those who also underwent stent placement (15.6 ± 7.3% vs. 9.0 ± 6.4%, P = 0.184). Intra- and perioperative complications occurred in three cases (7.69%). One patient (2.7%) developed severe in-stent restenosis with transient ischemic attack symptoms at 1-year follow-up., Conclusions: Endovascular recanalization is feasible for symptomatic occlusion of the anterior circulation lasting longer than 72 h. Recanalization provides a higher success rate when performed within 6 months of the qualifying event., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Brain Circulation.)

20MnTiB steel is the most widely used high-strength bolt material for steel structure bridges in China, and its performance is of great significance to the safe operation of bridges. Based on the investigation of the atmospheric environment in Chongqing in recent years, the corrosion solution to simulate the humid climate of Chongqing was designed in this study, and the stress corrosion experiment of high-strength bolts in the simulated humid climate of Chongqing was carried out. The effects of temperature, pH and concentration of simulated corrosion solution on the stress corrosion behavior of 20MnTiB high-strength bolts were studied., (© 2021. The Author(s).)

Objective: Glucagon-like peptide-1 receptor (GLP1R) specifically expressed on the surface of pancreatic β-cells and insulinoma, is a potential biomarker for imaging β-cell mass (BCM). In this study, two new 68 Ga-labelled GLP1R targeting agents were prepared and their biological properties for imaging BCM and insulinoma were evaluated., Methods: [ 68 Ga]Ga-HBED-CC-MAL-Cys 39 -exendin-4 ([ 68 Ga]Ga-4) and its dimer ([ 68 Ga]Ga-5) were synthesized from corresponding precursors. Cell uptake studies were evaluated in INS-1 cells. Biodistribution and microPET studies were performed in male normal Sprague-Dawley rats, diabetic rats and insulinoma xenograft NOD/SCID mice., Results: [ 68 Ga]Ga-4 and [ 68 Ga]Ga-5 were efficiently radiolabelled by a simple one-step reaction without purification leading to high radiochemical yields and radiochemical purities (both >95%, decay corrected, n = 6, molar activity 15 GBq/μmol). They both showed excellent stability (~95%) in phosphate-buffered saline, pH 7.4, and in rat serum (~90%) for 2 h. Biodistribution studies and small animal PET/CT imaging showed that [ 68 Ga]Ga-4 displayed specific uptake in rat pancreas and mouse insulinoma, and a reduced uptake in the pancreas of diabetic rat was observed (~62% reduction). Notably, it exhibited a rapid time-to-peak pancreatic uptake (0.96 ± 0.19%ID/g in 15 min) and fast clearance from the kidney (42% clearance in 30 min). Results suggested a favorable in vivo kinetics for human imaging studies., Conclusions: [ 68 Ga]Ga-4 targeting GLP1R of pancreatic β-cells may be a potentially useful PET agent and a suitable candidate for further structural modification studies. This agent has demonstrated several advantages, rapid time-to-peak pancreatic uptake and faster clearance from the kidney, factors may enhance diagnosis of diabetes and insulinoma., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The outbreak of Coronavirus Disease 2019 (COVID-19) has become a severe global acute respiratory pandemic around the world in just a few months with an increasing number of infections and deaths. COVID-19 is a highly contagious and fatal disease. Almost everyone in the population is susceptible, and the incubation period is 1-14 days, mostly 3-7 days. The clinical symptoms of the COVID-19 are fever, dry cough and fatigue. Some patients are accompanied by symptoms such as nasal congestion, runny nose, sore throat, myalgia and diarrhea. Severe patients could even develop acute respiratory distress syndrome, septic shocks, metabolic acidosis and multifunctional organ failure, etc. Due to the relatively closed environment of dental clinics and the unique nature of dental procedures, both dental personnel and patients are easy to get infection through currently known respiratory droplet transmission, aerosol transmission, close contact transmission and other ways, inducing mutual cross-infection. Dental practitioners are facing unprecedented challenges due to the high risk of exposure to droplets and aerosols from saliva and other body fluids during dental procedures. Based on our experience and relevant research, this article introduces the basic knowledge about COVID-19 and the corresponding protective measures for dental practitioners, includes the risk of infection during dental procedures, the precautions related to the patients, infection control measures during dental treatment in clinics, protection measures at different levels for dental practitioners, and emergency dental treatment for confirmed COVID-19. It is the responsibility of every dental practitioner to fully understand the characteristics of the new coronavirus and strictly implement the most appropriate protective measures to reduce and control the risk of cross infection in dental procedures., (Copyright © 2020. Published by Elsevier Ltd.)

Aneurysms located in the posterior inferior cerebellar artery (PICA) are not a majority of the intracranial aneurysms cases. Many challenges were addressed in the endovascular procedure to treat the disease. The authors have successfully diagnosed and treated a ruptured proximal PICA aneurysm. However, digital subtraction angiography showed acute thrombosis in the vertebral artery in the procedure, which probably could be an acute in-stent thrombosis. The tirofiban hydrochloride injection was subjected through a microcatheter, and then, the second Neuroform EZ stent was planted. In the 6-month follow-up, no recurrence of the aneurysm and complete patency of the right PICA at the site of aneurysm formation were found. We believe that the treatment of PICA aneurysms with Neuroform EZ stents could get a favorable result. Combination of tirofiban hydrochloride and Neuroform EZ stent could be an effective approach in treating acute thrombotic complications., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Brain Circulation.)

Objectives: Symptomatic atherosclerotic disease of the basilar artery (BA) portends a poor prognosis, and BA seemed to be the most dangerous site for stenting. The authors review their interventional results and mid-term results with or without predilation in BA stenting to find a safer interventional approach., Patients and Method: A database review identified 94 patients with severe symptomatic BA stenosis were treated with stenting. According to with balloon predilation or not, they were divided into two groups: direct stenting group and angioplasty before stenting group. Baseline data, lesion characteristics, complications and follow-up data from the two groups were compared and analyzed., Results: The length of lesion in angioplasty before stenting group was longer than that in the direct stenting group (8.12 ± 2.76 mm versus 6.83 ± 2.27 mm, p = 0.015). The proportions of Mori C type lesion was higher in angioplasty before stenting group (31.3 % versus 8.7 %, p = 0.006). The residual stenosis was higher in angioplasty before stenting group (12.66 ± 9.24 % versus 7.67 ± 8.01 %, p = 0.006). There were no significant differences in TIA, stroke, and death between the two groups in the perioperative and postoperative > 1 year follow-up (p > 0.05)., Conclusion: BA stenting is relatively safe and has a good results for experienced operators. Angioplasty before stenting is a good way for BA stenting, it makes the operations on difficult lesions as safe as normal one. More optimized stents and safer interventional approach need to be further explored and verified., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

HDAC3 is an essential negative regulator of neuronal plasticity and memory formation. Although a chemical inhibitor has been invented, little is known about its endogenous modulators. We explored whether miR-494 affects HDAC3-mediated neuronal injury following acute ischemic stroke. A substantial increase in plasma miR-494 was detected in AIS patients and was positively associated with the mRS at one year after symptom onset. The miR-494 levels were transiently increased in the infarcted brain tissue of mice. In contrast, miR-494 levels were reduced in neurons but increased in the medium after OGD. Intracerebroventricular injection of miR-494 agomir reduced neuronal apoptosis and infarct volume at the acute stage of MCAO, promoted axonal plasticity and long-term outcomes at the recovery stage, suppressed neuronal ataxin-3 and HDAC3 expression and increased acetyl-H3K9 levels in the ipsilateral hemisphere. In vitro studies confirmed that miR-494 posttranslationally inhibited HDAC3 in neurons and prevented OGD-induced neuronal axonal injury. The HDAC3 inhibitor increased acetyl-H3K9 levels and reversed miR-494 antagomir-aggravated acute cerebral ischemic injury, as well as brain atrophy and long-term functional recovery. These results suggest that miR-494 may serve as a predictive biomarker of functional outcomes in AIS patients and a potential therapeutic target for the treatment of ischemic stroke.

The present study evaluated the diagnostic and predictive potential of microRNA-93 in acute ischemic stroke (AIS) patients within 6 h of stroke onset and its regulation on microglial inflammation in vitro. Our results showed that the miR-93 levels in plasma and neutrophil detected by real-time PCR were evidently reduced in AIS patients, and Pearson's correlation analysis showed that miR-93 levels in plasma and neutrophils had a significant positive linear correlation. Moreover, miR-93 levels in plasma and neutrophils of stroke patients at time of admission were not correlated with infarct volume and NIHSS (National Institute of Health stroke scale) scores at admission, but neutrophil miR-93 levels were positively correlated with the Barthel Index 7 days after stroke. Importantly, miR-93 levels in plasma and neutrophil of AIS patients were negatively correlated with the expression of TNF-α and IL-10. Furthermore, in vitro treatment with miR-93 agomir decreased the OGD (Oxygen and glucose deprivation)-induced proliferation of BV2 microglial cells tested by Flow cytometry. We demonstrated that miR-93 in blood has a potential to facilitate the diagnosis and prediction of neurological outcomes of acute ischemic stroke, and is involved in inflammation possibly through targeting the proliferation of microglia., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To compare the technical and 1-year clinical outcome in balloon-mounted versus self-expanding stenting for symptomatic severe stenosis of the middle cerebral artery combined with poor collaterals in China., Methods: Ninety-one patients with severe middle cerebral artery atherosclerotic stenosis combined with poor collaterals were recruited in the study. Balloon-mounted stent or self-expanding stent were selected to treat patients following a guideline. The baseline characteristics, cerebral angiography, and outcomes were compared between the patients treated with balloon-mounted stent and self-expanding stent., Results: The mean degree of stenosis was 85.5% ± 6.37% in the balloon-mounted stenting group and 85.4% ± 7.73% in the self-expanding stenting group before treatment (P = 0.930). A longer operative time occurred in patients treated with self-expanding stent than in those treated with balloon-mounted stent (96.7 vs. 68.6 minutes, respectively; P = 0.002). Patients with self-expanding stent had a higher rate of residual stenosis than those with balloon-mounted stent (67.3% vs. 38.9%, respectively; P = 0.014). The patients in balloon-mounted stenting group was less likely to have restenosis (6.1% vs. 26.5%, P = 0.019) and had a lower degree of stenosis (5.0% ± 0.0% vs. 26.9% ± 29.2%, P = 0.019) compared with patients in the self-expanding stenting group. During the 1-year follow-up, the recurrence rate of ischemic stroke, transient ischemic attack, hemorrhage stroke, and death was not significantly different between the 2 groups (1/33 vs. 2/49, P = 0.804; 1/33 vs. 1/49, P = 0.776; 0/33 vs. 2/49, P = 0.240; 1/33 vs. 0/49, P = 0.220, respectively)., Conclusions: Balloon-mounted stents may have a shorter operative time and lower restenosis occurrence than self-expanding stents. No significant difference in 1-year outcome was observed between the 2 groups., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The exchange proteins activated by cAMP (Epacs) have been shown to play important roles in producing inflammation-induced nociception. Transient receptor potential vanilloid type 1 (TRPV1) is a major receptor processing thermal and chemosensitive nociceptive information. The role of Epacs in modulating the activity of TRPV1 has yet to be determined. Studying the effect of complete Freund adjuvant (CFA)-induced inflammation on capsaicin-activated TRPV1 nociceptive responses in dorsal root ganglia (DRG), we found that CFA produced a large increase in capsaicin-induced responses. The increase was inhibited by Epac1 and Epac2 antagonists. Thus, activation of Epacs is critical in producing enhancement in TRPV1-mediated responses under inflammatory conditions. In addition, the inflammation-induced enhancement of TRPV1 responses was blocked by PKCα and PKCε inhibitors, suggesting the essential roles of these PKCs in enhancing TRPV1 responses. To determine the mechanism underlying the Epac actions on TRPV1, we studied the effects of the Epac activator, 8-(4-chlorophenylthio)-2-O-methyl-cAMP (CPT), on capsaicin-induced nociceptive behavioral responses, capsaicin-activated currents, expression and membrane trafficking of PKC and TRPV1 in DRG. CPT was found to enhance capsaicin-induced nociception and ionic currents. The enhancement was inhibited by PKCα and PKCε inhibitors. In addition, CPT increased the expression of phosphorylated PKCα (pPKCα) and membrane TRPV1 expression in DRG. Studying the colocalization of TRPV1 and pPKCα or pPKCε in DRG slices prepared from CFA-treated rats, we found that pPKCα or pPKCε expressed with TRPV1 in different-sized neurons to exert differential influences on TRPV1 activity. Thus, Epac-PKC signaling is critically important in producing inflammation-induced potentiation of TRPV1 functions.

Stroke is the number one cause of neurological dysfunction in adults and has a heavy socioeconomic burden worldwide. The etiological origins of ischemic stroke and resulting pathological processes are mediated by a multifaceted cascade of molecular mechanisms that are in part modulated by posttranscriptional activity. Accumulating evidence has revealed a role for microRNAs (miRNAs) as essential mediators of posttranscriptional gene silencing in both the physiology of brain development and pathology of ischemic stroke. In this review, we compile miRNAs that have been reported to regulate various stroke risk factors and pre-disease mechanisms, including hypertension, atherosclerosis, and diabetes, followed by an in-depth analysis of miRNAs in ischemic stroke pathogenesis, such as excitotoxicity, oxidative stress, inflammation, apoptosis, angiogenesis and neurogenesis. Since promoting or suppressing expression of miRNAs by specific pharmaceutical and non-pharmaceutical therapies may be beneficial to post-stroke recovery, we also highlight the potential therapeutic value of miRNAs in clinical settings., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The topography of biomaterials can significantly influence the osteogenic differentiation of cells. Understanding topographical signal transduction is critical for developing biofunctional surfaces, but the current knowledge is insufficient. Recently, numerous reports have suggested that the unfolded protein response (UPR) and osteogenic differentiation are inter-linked. Therefore, we hypothesize that the UPR pathway may be involved in the topography-induced osteogenesis. In the present study, different surface topographies were fabricated on pure titanium foils and the endoplasmic reticulum (ER) stress and UPR pathway were systematically investigated. We found that ER stress and the PERK-eIF2α-ATF4 pathway were activated in a time- and topography-dependent manner. Additionally, the activation of the PERK-eIF2α-ATF4 pathway by different topographies was in line with their osteogenic induction capability. More specifically, the osteogenic differentiation could be enhanced or weakened when the PERK-eIF2α-ATF4 pathway was promoted or inhibited, respectively. Furthermore, tuning of the degree of ER stress with different concentrations of thapsigargin revealed that mild ER stress promotes osteogenic differentiation, whereas excessive ER stress inhibits osteogenic differentiation and causes apoptosis. Taken together, our findings suggest that the UPR may play a critical role in topography-induced osteogenic differentiation, which may help to provide new insights into topographical signal transduction., Statement of Significance: Suitable implant surface topography can effectively improve bioactivity and eventual bone affinity. However, the mechanism of topographical signaling transduction is unclear and criteria for designation of an appropriate implant surface topography is lacking. This study shows that the ER stress and PERK-eIF2α-ATF4 pathway were activated by micro- and micro/nano-topographies, which is corresponding to the osteogenic induction abilities of these topographies. Furthermore, we have found that mild ER stress improves osteogenic differentiation, whereas excessive ER stress inhibits osteogenic differentiation and causes apoptosis. Our findings demonstrate that the UPR plays a critical role in the topography induced osteogenic differentiation, which may help to provide new insights into the topographical signaling transduction., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Micro/nano-textured titanium surface topography promotes osteoblast differentiation and the Wnt/β-catenin signaling pathway. However, the response of rat bone mesenchymal stem cells (MSCs) to micro/nano-textured topography, and the underlying mechanisms of its effects, are not well understood. We hypothesized that cell division cycle 42 protein (Cdc42), a key member of the Rho GTPases family, may regulate rat MSCs morphology and osteogenic differentiation by micro/nano-textured topography, and that crosstalk between Cdc42 and Wnt/β-catenin is the underlying mechanism. To confirm the hypothesis, we first tested rat MSCs' morphology, cytoskeleton, and osteogenic differentiation on micro/nano-textured topography. We then examined the cells' Wnt pathway and Cdc42 signaling activity. The results show that micro/nano-textured topography enhances MSCs' osteogenic differentiation. In addition, the cells' morphology and cytoskeletal reorganization were dramatically different on smooth surfaces and micropitted/nanotubular topography. Ligands of the canonical Wnt pathway, as well as accumulation of β-catenin in the nucleus, were up-regulated by micro/nano-textured topography. Cdc42 protein expression was markedly increased under these conditions; conversely, Cdc42 silencing significantly depressed the enhancement of MSCs osteogenic differentiation by micro/nano-textured topography. Moreover, Cdc42si attenuated p-GSK3β activation and resulted in β-catenin cytoplasmic degradation on the micro/nano-textured topography. Our results indicate that Cdc42 is a key modulator of rat MSCs morphology and cytoskeletal reorganization, and that crosstalk between Cdc42 and Wnt/β-catenin signaling though GSK3β regulates MSCs osteogenic differentiation by implant topographical cues., Statement of Significance: Topographical modification at micro- and nanoscale is widely applied to enhance the tissue integration properties of biomaterials. However, the response of bone mesenchymal stem cells (MSCs) to the micro/nano-textured topography and the underlying mechanisms are not well understood. This study shows that the micropitted/nanotubular hierarchical topography produced by etching and anodic oxidation treatment drives fusiform cell morphology, cytoskeletal reorganization as well as better MSCs osteogenic differentiation. The cross-talk between Cdc42 pathway and Wnt/β-catenin pathway though GSK3β modulates the osteoinductive effect of the micro/nano-textured topography on MSCs. This finding sheds light on a novel mechanism involved in micro/nano-textured surface-mediated MSCs osteogenic differentiation and is a major step in the development of new surface modifications aiming to accelerate and enhance the process of osseointegration., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objectives: We have previously shown the neuroprotective function of microRNA-99a-5p in experimental stroke. Here, we explore its diagnostic potential for acute stroke patients., Materials and Methods: MiR-99a-5p levels in circulating from acute stroke patients and control were measured by real-time polymerase chain reaction. Pearson's correlation and receiver operator characteristic (ROC) curves were used to analyze clinical significance of miR-99a-5p and its sensitivity and specificity for stroke diagnosis., Results: We demonstrated that miR-99a-5p expression was upregulated in neutrophils of both ischemic stroke and hemorrhage patients, while was only increased in the lymphocytes of hemorrhage patients. ROC analysis revealed that the miR-99a-5p level in neutrophils and lymphocytes had a moderate diagnostic value for stroke. Moreover, a positive correlation existed between plasma miR-99a-5p levels and neutrophil numbers or neutrophil/lymphocyte ratio. Meanwhile, miR-99a-5p levels in neutrophils were negatively correlated with thrombin time, while positively correlated with D-dimer and urea levels. Lymphocytic miR-99a-5p levels were positively correlated with platelet mean volume and distribution width., Conclusion: This study demonstrated that miR-99a-5p levels in circulating immune cells might facilitate the diagnosis of ischemic stroke., Competing Interests: There are no conflicts of interest.

A novel label-free electrochemical biosensor for the detection of Hg 2+ based on ligase mediated creation of G-quadruplex-hemin DNAzyme has been developed. Firstly, Cp probe was immobilized on the gold electrode surface through Au-SH bond. In the presence of Hg 2+ , Cp and Ap probes were partly hybridized with the LJ probe respectively through the specific T-Hg 2+ -T interaction. Then, the adjacent 3'-OH terminal of Cp will link with the 5'-PO 4 terminal of Ap to form a G-rich DNA at the function of T4-ligase. After interaction with hemin, the G-rich DNA can form a G-quadruplex-hemin HRP-mimicking DNAzyme. Through measuring the current change caused by DNAzyme-catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine(TMB), sensitive detection of Hg 2+ can be achieved. The proposed sensor is simple, sensitive and selective, without the need of complicated labeling process, thus holds great potential for routine analysis of Hg 2+ in environmental and biological samples., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Patients with cerebral sinus and cortical venous thrombosis develop venous infarcts in approximately 50% of cases, resulting in serious clinical symptoms. An animal model is needed to further clarify the underlying mechanisms and consequences surrounding cerebral venous sinus thrombosis, particularly for severe ones., Methods: Adult male Sprague-Dawley rats were used to develop a new superior sagittal sinus thrombosis model involving cortical veins. The superior sagittal sinus was exposed and ligated. A microcatheter was inserted into the sinus, then both common carotid arteries were temporary occluded to reduce cerebral blood flow, and thrombin was injected into the sinus. Twenty-four hours later, after evaluating neurological function and obtaining a magnetic resonance imaging, animals were sacrificed and data pertaining to brain water content, infarct volume, and tissue histology was collected., Results: Superior sagittal sinus thrombosis and brain infarction were detected in all rats (100%). Hemorrhagic infarction, when present, and brain edema were observed in the brain parenchyma of the parietal lobe. The rate of hemorrhage was 59%, which is similar to that seen clinically in patients with superior sagittal sinus thrombosis. Brain edema, as measured by brain water content percentage, was significantly increased in thrombosed animals compared with sham-operated animals (80.8% ± 0.55% vs. 78.8% ± 0.14%, P < 0.05). Infarct volumes were 53.02 ± 7.91 mm(3)., Conclusions: We suggest that our modified model of superior sagittal sinus thrombosis, involving cortical veins, is suitable for the study of its underlying mechanisms, as well as therapeutic approaches directed at the disease., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A novel supramolecular gel has been prepared via host-guest interaction between cucurbit[8]uril (Q[8]) and N-(4-diethylaminobenzyl)chitosan (EBCS). The structure of supramolecular gel has been characterized. The spectrum of (1)H NMR demonstrated the benzene ring of EBCS is reside inside the hydrophobic cavity of Q[8] and the host-guest interaction between Q[8] and EBCS was the main driving force for the formation of the supramolecular gel. The network structure of the xerogel of Q[8]/EBCS gel was observed by SEM. The Q[8]/EBCS gel system showed thermosensitive and pH-sensitive properties. The physical characterization by SEM, DSC, TG demonstrated the distinguished characters, which proved the formation of supramolecular gel instead of physical blending. The in vitro release study of the 5-fluorouracil-loaded supramolecular gel showed that sustained release profile in acidic condition, suggesting that Q[8]/EBCS gel could be a potential carrier for pH-sensitive drug controlled release system., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Evaluation of analgesics in large animals is a necessary step in the development of better pain medications or gene therapy prior to clinical trials. However, chronic neuropathic pain models in large animals are limited. To address this deficiency, we developed a neuropathic pain model in sheep, which shares many anatomical similarities in spine dimensions and cerebrospinal fluid volume as humans., Methods: A neuropathic pain state was induced in sheep by tight ligation and axotomy of the common peroneal nerve. The analgesic effect of intrathecal (IT) morphine was investigated. Interspecies comparison was conducted by analyzing the ceiling doses of IT morphine for humans, sheep, and rats., Results: Peroneal nerve injury (PNI) produced an 86% decrease in von-Frey filament-evoked withdrawal threshold on postsurgery day 3 and the decrease lasted for the 8-week test period. Compared to the pre-injury, sham, and contralateral hindlimb, the IT morphine dose that produces 50% of maximum analgesia (ED(50)) for injured PNI hindlimb was 1.8-fold larger and E(max), the dose that produces maximal analgesia, was 6.1-fold lower. The sheep model closely predicts human IT morphine ceiling dose by allometric scaling. This is in contrast to the approximately 10-fold lower morphine ceiling dose predicted by the rat spinal nerve ligated or spared nerve injury models., Conclusion: PNI sheep model has a fast onset and shows stable and long-lasting pain behavioral characteristics. Since the antinociceptive properties of IT morphine are similar to those observed in humans, the PNI sheep model will be a useful tool for the development of analgesics. Its large size and consistent chronic pain behavior will facilitate the development and evaluation of surgical intervention and gene therapy. The PNI sheep pain model provides us with the opportunity for multi-species testing, which will improve the success of clinical trials.

Scutellaria barbata D. Don is widely used as a folk antitumor and anti-inflammatory agent in Asia. However, a simple and global quality control method for S. barbata was lacking. In this study, six phenolic compounds, including P-coumaric acid, scutellarin, apigenin 5-O-β-glucopyranoside, luteolin, apigenin and 4'-hydroxywogonin were obtained from S. barbata by phytochemical investigations. The six compounds plus baicalein show cytotoxcities to the nine human cancer cells, K562, MGC-803, HL60, SH-SY5Y, SW1116, SMMC-7221, SW480, HepG2 and KB. Subsequently, a high-performance liquid chromatography with photodiode array detector (HPLC-DAD) was developed for both fingerprint analysis of S. barbata and quantitative determination of the seven anticancer active compounds in S. barbata. The chromatographic separation was accomplished on an Ultimate™ XB-C18 column (4.6 x 250 mm, 5 µm) in 65 min. For fingerprinting, 26 common peaks were found and selected as characteristic peaks to assess the consistency of S. barbata samples. For quantitative analysis, the seven bioactive compounds showed good regression relationship ( R² > 0.999) within test ranges and the recovery of the method was in the range of 90-105 %. In brief, the present study provides the fingerprint analysis and quantitative methods for global and systematical quality control of S. barbata for its anticancer usage., (© Georg Thieme Verlag KG Stuttgart · New York.)