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Hao Meng - Top 30 Publications

Continuous lumbar cistern drainage before surgical clipping for aneurysmal subarachnoid hemorrhage.

Lumbar drainage (LD) is the choice for the treatment of acute hydrocephalus and increased intracranial pressure in patients with subarachnoid hemorrhage (SAH). It also reduces vasospasm risk and delayed ischemic neurological events. We evaluated the role of LD in the preoperative management of patients with aneurysmal SAH (aSAH).

Swimming training alleviated insulin resistance through Wnt3a/β-catenin signaling in type 2 diabetic rats.

Increasing evidence suggests that regular physical exercise improves type 2 diabetes mellitus (T2DM). However, the potential beneficial effects of swimming on insulin resistance and lipid disorder in T2DM, and its underlying mechanisms remain unclear.

Antidiabetic cataract effects of GbE, rutin and quercetin are mediated by the inhibition of oxidative stress and polyol pathway.

One of the earliest critical secondary complications of diabetes is the opacification of the eye lens - a condition strictly associated with diabetic cataract. The study presented here was designed to investigate the effect of Ginkgo biloba extract (GbE), rutin and quercetin on streptozotocin (STZ) induced diabetic cataract (DC) rats. Ten weeks after administration of GbE, rutin and quercetin, the opacity of diabetic rats' lenseswasgraded under a slit lamp. Then, the levels of malondialdehyde (MDA), reduced glutathione (GSH), advanced glycosylation end products (AGEs), and the activities of aldose reductase (AR) were estimated. The DC-induced rats produced less GSH, higher levels of MDA and AGEs as well as elevated AR activity when compared to the normal group. Administration of GbE, rutin and quercetin remarkably inhibited the AR activity, stimulated the production of glutathione, and decreased the levels of MDA and AGEs in the lenses of DC-induced rats, which eventually delayed the progression of lens opacification in diabetic rats to various degrees. Our results revealed that quercetin had the highest significant (P<0.05) potential to delay the progression of STZ-induced diabetic cataract when compared with rutin and GbE. The mechanism dictating this interesting prowess of quercetin might be attributed to its AR inhibitory strength, anti-lipid peroxidation potential and anti-AGEs activity.

The mTOR promotes oxidative stress-induced apoptosis of mesangial cells in diabetic nephropathy.

Glomerular mesangial cell (MC) apoptosis is one of the important mechanisms of glomerulosclerosis, which induces an increased severity of albuminuria and promotes the development of diabetic nephropathy (DN). However, the mechanism by which high glucose (HG) induces MCs apoptosis is not fully understood. In the present study, we investigated the effects of mTOR signalling on apoptosis in cultured MCs exposed to HG and in type I diabetes, and tried to clarify the specific mechanisms underlying these effects. In vitro, exposure of MCs to HG stimulated ROS production, decreased the antioxidant enzyme superoxide dismutase (SOD) activity and glutathione (GSH) level, increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, upregulated P53 expression and Bax/Bcl-2 ratio and enhanced cleavage of caspase 3, resulting in an increase in programmed cell death. Pretreatment of the cells with rapamycin ameliorated oxidative stress, reduced the number of apoptotic cells induced by HG and caused the downstream effects of mTOR activation. In vivo, compared with control rats, diabetic rats had more apoptotic cells in glomeruli. Induction of diabetes increased the level of MDA and NADPH oxidase activity, decreased the SOD activity and GSH level, elevated the Bax/Bcl ratio and P53 expression and activated caspase 3. mTOR inhibitor rapamycin treatment prevented these changes further alleviated albuminuria and improved renal function. Taken together, our data suggest that mTOR plays a key role in mediating ROS-induced MC apoptosis in diabetic nephropathy, and these effects have been associated with the promotion of ROS production by upregulating the antioxidant enzyme and downregulating the NADPH oxidase activity.

Blueberry Phenolics Reduce Gastrointestinal Infection of Patients with Cerebral Venous Thrombosis by Improving Depressant-Induced Autoimmune Disorder via miR-155-Mediated Brain-Derived Neurotrophic Factor.

Cerebral venous thrombosis (CVT) often causes human depression, whereas depression-induced low immunity makes the patients susceptible to gastrointestinal infection. Blueberry possesses antidepressant properties which may improve autoimmunity and reduce gastrointestinal infection. Brain-derived neurotrophic factor (BDNF) performs antidepressant function and can be regulated by miR-155, which may be affected by blueberry. To explore the possible molecular mechanism, blueberry compounds were analyzed by high-performance liquid chromatography. Activity of compounds was tested by using HT22 cells. The present study tested 124 patients with CVT-induced mild-to-moderate depressive symptoms (Center for Epidemiologic Studies-Depression Scale [CES-D] ≥16) and gastrointestinal infection. Patients were randomly assigned to blueberry extract group (BG, received 10 mg blueberry extract daily) and placebo group (PG, received 10 mg placebo daily). After 3 months, depression, gastrointestinal infection and lipid profiles were investigated. Serum miR-155 and BDNF were measured using real-time quantitative polymerase chain reaction and or Western Blot. Blueberry treatment improved depressive symptoms and lipid profiles, and also reduced gastrointestinal infection in the BG group (P < 0.05) but those of the PG group (P = 1). These changes were paralleled by increase in serum levels of BDNF and miR-155 (P < 0.05). HPLC analysis showed that blueberry extracts were the main phenolic acids with 0.18, 0.85, 0.26, 0.72, 0.66, 0.4,1, and 1.92 mg/g of gentisic acid, chlorogenic acid, [2]-epicatechin, p-coumaric acid, benzoic acid, p-anisic acid, and quercetin in blueberry extracts, respectively. Phenolics in blueberry are possible causal agents in improving antidepressant activity and reducing gastrointestinal infection. Administration of blueberry increased BDNF expression and miR-155. Blueberry cannot affect BDNF level when miR-155 is overexpressed or inhibited. Phenolics from blueberry reduced gastrointestinal infection of patients with CVT by improving antidepressant activity via upregulation of miR-155-mediated BDNF.

Associations between Urinary Phthalate Metabolites and Serum Anti-Müller Hormone Levels in U.S. Men Based on National Health and Nutrition Examination Survey 2003-2004.

Anti-Müller hormone (AMH) plays an important role in reproductive development and has a wide potential clinical application value. Phthalates have been widely found in human living environment and have negative effects on human reproduction. This study aimed to explore the relationship between urinary phthalate metabolites and serum AMH level in the general male population. Cross-sectional analyses were performed with a population of 489 men aged more than 12 years who participated in National Health and Nutrition Examination Survey (NHANES) 2003-2004 by Centers for Disease Control and Prevention, the United States. NHANES public data (demographic and socioeconomic information, examinations, and laboratory tests) were analyzed using Kruskal-Wallis test, Wilcoxon test and multivariable regression. Results showed that the urine concentration of mono (3-carboxypropyl) phthalate (MCPP) of 12-20 age group was significantly positively correlated with serum AMH concentration in the model without any covariates (p < 0.05). In the 60-year-old group, the monomethyl phthalate (MEP), mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) concentrations were significantly correlated with serum AMH concentrations in models both with and without covariates (all p < 0.05). It could be concluded that exposure to phthalates might have negative effects on AMH level, especially in seniors. AMH could be used as a marker of exposure to phthalates in aged males. How exposure to phthalates affected AMH level and what the potential long-term health consequences of their relationship are needs more investigation.

The complete phylogeny of pangolins: scaling up resources for the molecular tracing of the most trafficked mammals on Earth.

Pangolins, considered the most-trafficked mammals on Earth, are rapidly heading to extinction. Eight extant species of these African and Asian scale-bodied anteaters are commonly recognized, but their evolutionary relationships remain largely unexplored. Here we present the most comprehensive phylogenetic assessment of pangolins, based on genetic variation of complete mitogenomes and nine nuclear genes. We confirm deep divergence among Asian and African pangolins occurring not later than the Oligocene-Miocene boundary ca. 23 million-years-ago (Ma) (95% HPD=18.7-27.2), limited fossil evidence suggesting dispersals from Europe. We recognize three genera including Manis (Asian pangolins), Smutsia (large African pangolins) and Phataginus (small African pangolins), which first diversified in the Middle-Upper Miocene (9.8-13.3 Ma) through a period of gradual cooling coinciding with a worldwide taxonomic diversification among mammals. Based on large mitogenomic distances among the three genera (18.3-22.8%) and numerous (18) morphological traits unique to Phataginus, we propose the subfamily Phatagininae subfam. nov. to designate small African pangolins. In contrast with the morphological-based literature, our results establish that the thick-tailed pangolin (M.crassicaudata) is sister-species of the Sunda (M. javanica) and Palawan (M. culionensis) pangolins. Mitogenomic phylogenetic delineations supported additional pangolin species subdivisions (n=13), including six African common pangolin (P. tricuspis) lineages, but these patterns were not fully supported by our multi-locus approach. Finally, we identified over 5,000 informative mitogenomic sites and diagnostic variation from five nuclear genes among all species and lineages of pangolins, providing an important resource for further research and for effectively tracing the worldwide pangolin trade.

Treatment of Spontaneous Dissecting Aneurysm in Extracranial Vertebral Artery with Covered Stent.

To treat a 13-year-old boy with a spontaneous vertebrobasilar artery dissecting aneurysm in the extracranial artery, which was only 1 mm away from the initial segment of subclavian artery.

Effect of Incorporating Clustered Silica Nanoparticles on the Performance and Biocompatibility of Catechol-Containing PEG-Based Bioadhesive.

A composite adhesive capable of inducing cellular infiltration was prepared by incorporating control clustered silica microparticle (MP) derived from the aggregation of silica nanoparticle (NP) into a catechol-terminated poly(ethylene glycol) bioadhesive (PEG-DA). Incorporation of MP into PEG-DA significantly improved the mechanical and adhesive properties of the bioadhesive. There was no statistical difference between the measured values for NP- and MP-incorporated adhesives, indicating that MP was equally as effective in enhancing the material properties of PEG-DA as NP. Most importantly, MP was significantly less cytotoxic when compared to NP when these particles were directly exposed to L929 fibroblast. When the adhesives were implanted subcutaneously in rats, MP-containing PEG-DA also exhibited reduced inflammatory responses, attracted elevated levels of regenerative M2 macrophage to its interface, and promoted cellular infiltration due to increased porosity within the adhesive network. Control clustered silica microparticle can be used to improve the performance and biocompatibility of PEG-based adhesive while minimizing undesirable cytotoxicity of silica nanoparticle.

Tanshinone IIA attenuates nerve transection injury associated with nerve regeneration promotion in rats.

Tanshinone IIA (Tan IIA) is the major pharmacological constituent of Salvia miltiorrhiza Bunge (Danshen) for the therapeutic purpose of preventing ischemic injury and treating cerebrovascular disease. The aim of the present study was to explore the potential neuroprotective effects of Tan IIA in sciatic nerve transection injury. We investigated the possible beneficial effects of Tan IIA in promoting nerve regeneration after nerve transection injury in rats. Nerve transection injury was induced in male Sprague-Dawley rats by left sciatic nerve transection. After neuroanastomosis, the rats were intraperitoneally (IP) injected with 6mg/kg, 15mg/kg, or 40mg/kg Tan IIA once daily for 12 weeks; the vehicle and positive control groups were injected with normal saline and mecobalamin (MeCbl, 100μg/kg), respectively. Axonal regeneration and functional recovery were evaluated by a range of morphological and functional measures 12 weeks after neuroanastomosis. The administration of 15mg/kg and 40mg/kg Tan IIA and MeCbl achieved better axonal regeneration with significant restoration of motor function as well as a marked decrease in Fluoro-Gold (FG)-labeled neurons and increased nerve regeneration. At 12 weeks post-surgery, 40mg/kg Tan IIA showed a better neuroprotective effect than 15mg/kg Tan IIA and MeCbl. There were no statistical differences between the 15mg/kg Tan IIA and MeCbl groups or the control and 6mg/kg Tan IIA groups. Our findings demonstrate that Tan IIA can alleviate nerve injury and promote nerve regeneration in a sciatic nerve transection model in rats, providing supportive evidence for Tan IIA as an effective potential therapeutic remedy for peripheral nerve injury.

A recombinant type 2 porcine reproductive and respiratory syndrome virus between NADC30-like and a MLV-like: Genetic characterization and pathogenicity for piglets.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen for swine industry worldwide. The recombination occurring among PRRSV strains has been recognized as one of important molecular mechanisms for the evolution of PRRSV. Current prevalence of PRRSV NADC30-like causing clinical disease outbreaks is highly concerned in China. In the present study, the genetic characterization of a recombinant type 2 PRRSV (designated TJnh1501) was analyzed and its pathogenicity for piglets was examined. Our study showed that each region of TJnh1501 genome had 96.67-100% nucleotide and 96.5-100% amino acid identities with a Chinese highly pathogenic PRRSV-derived modified-live virus (MLV)-like except for its nonstructural protein 2 (nsp2)-coding region; while its nsp2-coding region shared higher nucleotide (84.44-85.85%) and amino acid (82.44-84.79%) identities with NADC30 and NADC30-like CHsx1401, and in particular, the highly variable region of nsp2 exhibited characteristic 131-aa deletion identical to NADC30 and NADC30-like CHsx1401. Meanwhile, we identified two recombination breakpoints located in the nt1737 and nt3506 of nsp2-coding region, which had higher nucleotide homology with NADC30 and NADC30-like CHsx1401. Moreover, TJnh1501 infection could cause persistent fever, moderate respiratory clinical signs, higher viremia, and obvious gross and microscopic lung lesions in piglets. The virus was shown to have lower pathogenicity than HP-PRRSV JXwn06, but higher than NADC30-like CHsx1401 for piglets. Our findings reveal that TJnh1501 is a recombinant type 2 PRRSV from the recombinant event between NADC30-like and MLV-like derived from the Chinese highly pathogenic PRRSV, and it exhibits intermediate virulence for pigs. This study adds valuable evidence for understanding the role of genomic recombination in the evolution of PRRSV.

Quercetin inhibited epithelial mesenchymal transition in diabetic rats, high-glucose-cultured lens, and SRA01/04 cells through transforming growth factor-β2/phosphoinositide 3-kinase/Akt pathway.

Diabetic cataract (DC), an identified life-threatening secondary complication of diabetes mellitus, has proven to be a dilemma because of its multifactorial caused and progression. An increasing number of studies have shown that in addition to the maillard reaction, enhanced polyol pathway, and oxidative insults, epithelial mesenchymal transition (EMT) is related to the prevalence of DC. Quercetin, a classic flavonoid with multiple pharmacological effects has been reported to possess therapeutic efficacy in the management and treatment of this disease. However, the mechanism underlying its therapeutic efficacy in EMT of lens epithelial cells (SRA01/04) and contribution to resolving DC remains a mystery. Therefore, in this study, we investigated the effects of quercetin on EMT of SRA01/04 and high-glucose (HG)-induced lens opacity accompanied by lens fibrosis induced by type-1 diabetes. Furthermore, we sought to clarify the specific mechanisms underlying these effects. At week 14 after streptozotocin (STZ) intraperitoneal administration, diabetic rats showed lens opacity accompanied with diminished antioxidant function, enhanced polyol pathway activity, and non-enzymatic glycation. Western blotting confirmed EMT in rat SRA01/04 cells with significantly increased α-smooth muscle actin (α-SMA) and decreased E-cadherin expressions. Treatment of the lens with quercetin ameliorated the oxidative stress, inhibited aldose reductase (AR) activation, reduced advanced glycation end product (AGE) production, and finally suppressed EMT in the early stages. Our in vitro results showed that high-glucose activated the transforming growth factor-β2/phosphoinositide 3-kinase/protein kinase B (TGF-β2/PI3K/Akt) signalling and EMT in SRA01/04 cells. Further, induced oxidative stress, activation of aldose reductase, and accumulation of advanced glycation end products were also involved in this process. Quercetin was potent enough to effectively ameliorate the high glucose (HG)-induced EMT of SRA01/04 cells by inhibiting the activation of TGF-β2/PI3K/Akt, enhancing the antioxidant capacity, inhibiting AR activity, and reducing AGE production. From the whole animal to tissues, and finally the cellular level, our results provide considerable evidence of the therapeutic potential of quercetin for DC. This might be due to its inhibition of EMT mediated through inhibition of the TGF-β/PI3K/Akt pathway.

A Smart Nano-Prodrug Platform with Reactive Drug Loading, Superb Stability, and Fast Responsive Drug Release for Targeted Cancer Therapy.

Nano-prodrugs usually involve a multistep synthesis which largely compromises their benefits. Here, a smart nano-prodrug platform with reactive drug loading, superb stability, and triggered drug release is reported for targeted melanoma therapy. cRGD-decorated polymersomal mertansine prodrug (cRGD-PS-DM1) is readily fabricated from cRGD-functionalized poly(ethylene glycol)-b-poly(trimethylene carbonate-co-dithiolane trimethylene carbonate) with simultaneous loading of mertansine (DM1) via thiol-disulfide exchange reaction and disulfide cross-linking of polymersomal membrane. cRGD-PS-DM1 exhibits a size of ≈100 nm, little drug leakage, and fast DM1 release in the presence of 2 × 10-3 -10 × 10-3 m glutathione. Tetrazolium-based colorimetric assay (MTT) and confocal microscopy studies confirm effective homing of cRGD-PS-DM1 to αv β3 overexpressing B16F10 melanoma cells. Notably, the in vivo studies show that cRGD-PS-DM1 has a greatly improved toleration as compared with free DM1 and effectively inhibits tumor growth and extends the survival time of B16F10 melanoma-bearing mice. cRGD-PS-DM1 nano-prodrug with reactive drug loading and multifunction provides an advanced nanomedicine for cancer therapy.

Feasibility study: Effect of hand resistance exercise on handwriting in Parkinson's disease and essential tremor.

A single group, repeated measures design was used.

A Moldable Nanocomposite Hydrogel Composed of a Mussel-Inspired Polymer and a Nanosilicate as a Fit-to-Shape Tissue Sealant.

The engineering of bioadhesives to bind and conform to the complex contour of tissue surfaces remains a challenge. We have developed a novel moldable nanocomposite hydrogel by combining dopamine-modified poly(ethylene glycol) and the nanosilicate Laponite, without the use of cytotoxic oxidants. The hydrogel transitioned from a reversibly cross-linked network formed by dopamine-Laponite interfacial interactions to a covalently cross-linked network through the slow autoxidation and cross-linking of catechol moieties. Initially, the hydrogel could be remolded to different shapes, could recover from large strain deformation, and could be injected through a syringe to adhere to the convex contour of a tissue surface. With time, the hydrogel solidified to adopt the new shape and sealed defects on the tissue. This fit-to-shape sealant has potential in sealing tissues with non-flat geometries, such as a sutured anastomosis.

Hepatic stellate cell interferes with NK cell regulation of fibrogenesis via curcumin induced senescence of hepatic stellate cell.

Hepatic fibrosis, a common scarring response to various forms of chronic liver injury, is a precursor to cirrhosis and liver cancer. During liver fibrosis, hepatic stellate cells (HSCs) initially activate and proliferate, which are responsible for the secretion of extracellular matrix components. However, these cells eventually senesce and are cleared by natural killer (NK) cells. Our previous researches have shown that the natural product curcumin could promote the senescence of activated HSC. In this study, we investigated how NK cells target senescent HSC and assessed the effect of this process on liver fibrosis. We found that senescent HSC induced by curcumin are susceptible to NK cells killing, due to the increased expression of NK cell activating ligand major histocompatibility complex class I chain-related genes A (MICA) and UL16-binding proteins 2 (ULBP2), but not Poliovirus Receptor (PVR). Further studies displayed that the interaction between NK cells and senescent LX2 cells stimulated granule exocytosis. Moreover, the inhibition of granule exocytosis weakened the cytotoxicity of NK cells and promoted the accumulation of senescent LX2 cells. Therefore, these aggregated data indicated that NK cells mediated clearance of senescent LX2 cells and granule exocytosis could play a protective role in the improvement of liver fibrosis.

Alterations in over-ground walking patterns in obese and overweight adults.

Obesity has been associated with negative effects on postural control, including falls. Previous studies revealed different outcomes regarding the effects of obesity on gait features, and the use of BMI may lead to bias in assessing the true effects of obesity on gait. To better understand the effects of obesity on gait, it is important to examine gait features and associated body composition measures. The purpose of this study was: (1) to assess gait features of normal weight, overweight and obese adults, and (2) to assess the relationship between body composition measures and gait features. Thirty participants were assigned to one of three groups based upon their BMI at the onset of the study: healthy weight (BMI: 18.5-24.9kg/m2), overweight (BMI: 25-29.9kg/m2), or obese (BMI: 30-40kg/m2). Participants performed straight-line over-ground walking through a 200m hallway at their natural preferred speed while wearing their own shoes. The angular displacements, range of motion (ROM), and approximate entropy of kinematic data of the bilateral hips, knees, and ankles in the sagittal plane were computed. Walking speed, step length, stride length, single leg support phase, double leg support phase, swing phase and bilateral stance phase times were extracted from the GaitRite data. Overall, body mass and BMI were associated with peak flexion and ROM in the knees as well as single support, double support, stance, and swing phases. Body fat percentage did not exhibit correlations with measured gait features. Gait variables were more highly correlated with BMI and body mass instead of percent body fat, suggesting that absolute mass is more influential on gait features rather than amount of fat tissue.

Immobilization of lysozyme proteins on a hierarchical zeolitic imidazolate framework (ZIF-8).

A hierarchical zeolitic imidazolate framework-8 (micro/meso-ZIF-8) was fabricated by using cetyltrimethylammonium bromide as a structure-controlling agent and l-histidine as co-templates. Compared to the conventional microporous ZIF-8 (micro-ZIF-8), the hierarchical porous structure of micro/meso-ZIF-8 contains micropores and maximum mesopores of around 35.6 nm. The as-prepared hierarchical micro/meso-ZIF-8 featured a large surface area and superior spontaneous adsorption activity than micro-ZIF-8 towards lysozyme (LZM), bovine hemoglobin (BHb) and bovine serum albumin (BSA), and the adsorption capacity increased with the decreasing of the protein size due to the molecule cutoff effects. The maximum adsorption capacity of LZM on micro/meso-ZIF-8 was higher than most of the reported results under similar adsorption conditions. The analyses of adsorption kinetics and thermodynamics implied that the adsorption mechanism mainly involved physical adsorption. Moreover, the micro/meso-ZIF-8 showed good thermal stability against temperature and excellent regeneration ability in the recycling adsorption experiments. This work proposed herein opens a broad application prospect of hierarchical MOFs in biological molecule separation, immobilization and enrichment.

Canonical hedgehog signalling regulates hepatic stellate cell-mediated angiogenesis in liver fibrosis.

Hepatic stellate cells (HSCs) are liver-specific pericytes regulating angiogenesis during liver fibrosis. We aimed to elucidate the mechanisms by which hedgehog signalling regulated HSC angiogenic properties and to validate the therapeutic implications.

αvβ3 Integrin-targeted reduction-sensitive micellar mertansine prodrug: Superb drug loading, enhanced stability, and effective inhibition of melanoma growth in vivo.

Antibody-maytansinoid conjugates (AMCs) have emerged as one of the most promising active targeting cancer therapeutics. Their clinical use is, however, challenged by their low drug content, poor stability, high cost and potential immune response. Here, we designed and developed robust, cRGD-functionalized, reduction-sensitive polymeric micellar mertansine (DM1) prodrug (cRGD-MMP) that showed targeted treatment of B16F10 melanoma-bearing C57BL/6 mice. cRGD-MMP was obtained with a superb drug content of ~40wt.% and a small size of ~45nm from poly(ethylene glycol)-b-(poly(trimethylene carbonate)-graft-SSDM1) (PEG-P(TMC-g-SSDM1)) and cRGD-functionalized PEG-P(TMC-g-SSDM1) copolymers. cRGD-MMP exhibited excellent stability in 10% fetal bovine serum and cell culture medium while fast swelling and markedly accelerated drug release under a reductive environment. Confocal microscopy, flow cytometry and MTT assays indicated receptor-mediated uptake and high antitumor effect of cRGD-MMP in αvβ3 integrin over-expressing B16F10 melanoma cells. Notably, cRGD-MMP displayed a long elimination half-life of 5.25h and 4-fold better maximum-tolerated dose than free DM1. The in vivo studies demonstrated that cRGD-MMP effectively inhibited B16F10 melanoma growth and greatly improved mice survival rate as compared to free DM1 and non-targeted MMP control. cRGD-MMP with superior stability, drug loading, and αvβ3 targetability offers an attractive alternative to AMCs for malignant tumor therapy.

Cognitive dysfunction in adult patients with neuromyelitis optica: a systematic review and meta-analysis.

The objective of this study was to investigate cognitive dysfunction in 24-60-year-old neuromyelitis optica (NMO) patients, demographically matched healthy subjects, and MS patients. We conducted a comprehensive literature review of the PubMed, Medline, EMBASE, CNKI, Wan Fang Date, Web of Science, and Cochrane Library databases from inception to May 2016 for case-control studies that reported cognitive test scores in NMO patients, healthy subjects, and MS patients. Outcome measures were cognitive function evaluations, including performance on attention, language, memory, information processing speed, and executive function tests. The meta-analysis included eight studies. NMO patients performed significantly worse on attention (P < 0.00001), language (P = 0.00008), memory (P = 0.00004), information processing speed (P < 0.00001), and executive function tests (P = 0.00009) than healthy subjects. There were no significant differences in performance between NMO patients and MS patients on these tests. This meta-analysis indicates that NMO patients aged 24-60 years have significantly worse cognitive performance than demographically matched healthy subjects. However, this was comparable to the performance of demographically matched MS patients. There is a need for further rigorous randomized controlled trials with focus on elucidating the underlying mechanism of cognitive dysfunction in NMO patients.

Inhibition of YAP signaling contributes to senescence of hepatic stellate cells induced by tetramethylpyrazine.

Accumulating evidence indicates that hepatic stellate cells (HSCs) are the central mediators and major effectors in the development of hepatic fibrosis. It is well-known that regulation of cell proliferation and apoptosis are potential strategies to block the activation of HSCs. Recently, several studies have revealed that induction of HSC senescence could prevent and cure the liver fibrosis. In our previous work, we have demonstrated that the natural product tetramethylpyrazine (TMP) could inhibit the activation of HSCs and ameliorate hepatic fibrosis. The aim of this study was to identify a new role of TMP in the regulation of activated HSC senescence and to elucidate the underlying mechanisms. In this study, our data showed that TMP could promote HSC senescence in vivo and in vitro. Moreover, TMP affected the cell cycle and telomerase activity. We further demonstrated that P53 siRNA or P53 pharmacological inhibitor PFT-α abrogated the TMP-induced HSC senescence in vitro. Meanwhile, similar results were obtained in vivo. Further studies indicated that TMP promoted the expression of P53 through a YAP inhibition-dependent mechanism. Moreover, silencing YAP enhanced TMP induction of activated HSC senescence. Collectively, our results suggested that TMP inhibited the activation of HSCs by inducing senescence and had therapeutic implication for the treatment of liver fibrosis.

Model polymer system for investigating the generation of hydrogen peroxide and its biological responses during the crosslinking of mussel adhesive moiety.

Mussel adhesive moiety, catechol, has been utilized to design a wide variety of biomaterials. However, the biocompatibility and biological responses associated with the byproducts generated during the curing process of catechol has never been characterized. An in situ curable polymer model system, 4-armed polyethylene glycol polymer end-capped with dopamine (PEG-D4), was used to characterize the production of hydrogen peroxide (H2O2) during the oxidative crosslinking of catechol. Although PEG-D4 cured rapidly (under 30s), catechol continues to polymerize over several hours to form a more densely crosslinked network over time. PEG-D4 hydrogels were examined at two different time points; 5min and 16h after initiation of crosslinking. Catechol in the 5min-cured PEG-D4 retained the ability to continue to crosslink and generated an order of magnitude higher H2O2 (40μM) over 6h when compared to 16h-cured samples that ceased to crosslink. H2O2 generated during catechol crosslinking exhibited localized cytotoxicity in culture and upregulated the expression of an antioxidant enzyme, peroxiredoxin 2, in primary dermal and tendon fibroblasts. Subcutaneous implantation study indicated that H2O2 released during oxidative crosslinking of PEG-D4 hydrogel promoted superoxide generation, macrophage recruitment, and M2 macrophage polarization in tissues surrounding the implant. Given the multitude of biological responses associated with H2O2, it is important to monitor and tailor the production of H2O2 generated from catechol-containing biomaterials for a given application.

Whole Genome Sequencing Identifies a Missense Mutation in HES7 Associated with Short Tails in Asian Domestic Cats.

Domestic cats exhibit abundant variations in tail morphology and serve as an excellent model to study the development and evolution of vertebrate tails. Cats with shortened and kinked tails were first recorded in the Malayan archipelago by Charles Darwin in 1868 and remain quite common today in Southeast and East Asia. To elucidate the genetic basis of short tails in Asian cats, we built a pedigree of 13 cats segregating at the trait with a founder from southern China and performed linkage mapping based on whole genome sequencing data from the pedigree. The short-tailed trait was mapped to a 5.6 Mb region of Chr E1, within which the substitution c. 5T > C in the somite segmentation-related gene HES7 was identified as the causal mutation resulting in a missense change (p.V2A). Validation in 245 unrelated cats confirmed the correlation between HES7-c. 5T > C and Chinese short-tailed feral cats as well as the Japanese Bobtail breed, indicating a common genetic basis of the two. In addition, some of our sampled kinked-tailed cats could not be explained by either HES7 or the Manx-related T-box, suggesting at least three independent events in the evolution of domestic cats giving rise to short-tailed traits.

Rapid magnetic solid-phase extraction of Congo Red and Basic Red 2 from aqueous solution by [email protected] O4 hybrid composites.

Core-shell metal-organic framework materials have attracted considerable attention mainly due to their enhanced or new physicochemical properties compared with their single-component counterparts. In this work, a core-shell heterostructure of CoFe2 O4 -Zeolitic Imidazolate Framework-8 ([email protected] O4 ) is successfully fabricated and used as an solid-phase extraction adsorbent to efficiently extract Congo Red and Basic Red 2 dyes from contaminated aqueous solution. Vibrating sample magnetometry indicates that the saturated magnetization of [email protected] O4 is 3.3 emu/g, which is large enough for magnetic separation. The obtained hybrid magnetic metal-organic framework based material [email protected] O4 can remove the investigated dyes very fast within 1 min of the contact time. The adsorbent [email protected] O4 also shows a good reusability. After regeneration, the adsorbent can still exhibit high removal efficiency (∼97%) toward Congo Red for five cycles of desorption-adsorption. This work reveals the great potential of core-shell [email protected] O4 sorbents for the fast separation and preconcentration of organic pollutants in aqueous solution before high-performance liquid chromatography analysis.

Use of electrospinning to construct biomaterials for peripheral nerve regeneration.

A number of limitations associated with the use of hollow nerve guidance conduits (NGCs) require further discussion. Most importantly, the functional recovery outcomes after the placement of hollow NGCs are poor even after the successful bridging of peripheral nerve injuries. However, nerve regeneration scaffolds built using electric spinning have several advantages that may improve functional recovery. Thus, the present study summarizes recent developments in this area, including the key cells that are combined with the scaffold and associated with nerve regeneration, the structure and configuration of the electrospinning design (which determines the performance of the electrospinning scaffold), the materials the electrospinning fibers are composed of, and the methods used to control the morphology of a single fiber. Additionally, this study also discusses the processes underlying peripheral nerve regeneration. The primary goals of the present review were to evaluate and consolidate the findings of studies that used scaffolding biomaterials built by electrospinning used for peripheral nerve regeneration support. It is amazing that the field of peripheral nerve regeneration continues to consistently produce such a wide variety of innovative techniques and novel types of equipment, because the introduction of every new process creates an opportunity for advances in materials for nerve repair.

Course Control of Underactuated Ship Based on Nonlinear Robust Neural Network Backstepping Method.

The problem of course control for underactuated surface ship is addressed in this paper. Firstly, neural networks are adopted to determine the parameters of the unknown part of ideal virtual backstepping control, even the weight values of neural network are updated by adaptive technique. Then uniform stability for the convergence of course tracking errors has been proven through Lyapunov stability theory. Finally, simulation experiments are carried out to illustrate the effectiveness of proposed control method.

Self-crosslinkable and intracellularly decrosslinkable biodegradable micellar nanoparticles: A robust, simple and multifunctional nanoplatform for high-efficiency targeted cancer chemotherapy.

Nanomedicines based on biodegradable micelles offer a most promising treatment for malignant tumors. Their clinical effectiveness, however, remains to be improved. Here, we report that self-crosslinkable and intracellularly decrosslinkable micellar nanoparticles (SCID-Ms) self-assembled from novel amphiphilic biodegradable poly(ethylene glycol)-b-poly(dithiolane trimethylene carbonate) block copolymer achieve high-efficiency targeted cancer chemotherapy in vivo. Interestingly, doxorubicin (DOX)-loaded SCID-Ms showed favorable features of superb stability, minimal drug leakage, long circulation time, triggered drug release inside the tumor cells, and an unprecedented maximum-tolerated dose (MTD) of over 100mg DOX equiv./kg in mice, which was at least 10 times higher than free drug. The in vivo studies in malignant B16 melanoma-bearing C57BL/6 mice revealed that DOX-SCID-Ms at a dosage of 30mg DOX equiv./kg could effectively suppress tumor growth and prolong mice survival time without causing obvious systemic toxicity. Moreover, DOX-SCID-Ms could be readily decorated with a targeting ligand like cRGD peptide. The biodistribution studies showed that cRGD20/DOX-SCID-Ms had a high tumor accumulation of 6.13% ID/g at 6h post injection, which was ca. 3-fold higher than that for clinically used pegylated liposomal doxorubicin (DOX-LPs). Accordingly, cRGD20/DOX-SCID-Ms exhibited significantly better therapeutic efficacy and lower side effects than DOX-LPs in B16 melanoma-bearing mice. These self-regulating biodegradable micellar nanoparticles offer a robust, multifunctional and viable nanoplatform for targeted cancer chemotherapy.

Gelatin Microgel Incorporated Poly(ethylene glycol)-Based Bioadhesive with Enhanced Adhesive Property and Bioactivity.

Up to 7.5 wt % of chemically cross-linked gelatin microgel was incorporated into dopamine-modified poly(ethylene glycol) (PEGDM) adhesive to simultaneously improve the material property and bioactivity of the PEG-based bioadhesive. Incorporation of gelatin microgel reduced cure time while it increased the elastic modulus and cross-linking density of the adhesive network. Most notably, the loss modulus values for microgel-containing adhesive were an order of magnitude higher when compared to microgel-free control. This drastic increase in the viscous dissipation ability of the adhesive is attributed to the introduction of reversible physical bonds into the adhesive network with the incorporation of the gelatin microgel. Additionally, incorporation of the microgel increased the adhesive properties of PEGDM by 1.5- to 2-fold. From in vitro cell culture studies, the composite adhesive is noncytotoxic and the incorporation of microgels provided binding site for promoting fibroblast attachment and viability. The subcutaneous implantation study indicated that the microgel-containing PEGDM adhesive is biocompatible and the incorporated microgels provided pockets for rapid cellular infiltration. Gelatin microgel incorporation was demonstrated to be a facile method to simultaneously enhance the adhesive property and the bioactivity of PEG-based adhesive.

Nitro-Group Functionalization of Dopamine and its Contribution to the Viscoelastic Properties of Catechol-Containing Nanocomposite Hydrogels.

Linear polyacrylamide (PAAm) is modified with dopamine or nitrodopamine (PAAm-D and PAAm-ND, respectively) to evaluate the effect of nitro-group modification on the interfacial binding properties of polymer-bound catechol. Nanocomposite hydrogels are prepared by mixing PAAm-based polymers with Laponite and the viscoelastic properties of these materials are determined using oscillatory rheometry. The incorporation of a small amount of catechol (≈0.1 wt% in swollen hydrogel) drastically increases the shear moduli by 1-2 orders of magnitude over those of the catechol-free control. Additionally, PAAm-ND exhibits higher shear moduli values than PAAm-D across the whole pH range tested (pH 3.0-9.0). Based on the calculated effective crosslinking density, effective functionality, and molecular weight between crosslinks, nitro-group functionalization of dopamine results in a polymer network with increased crosslinking density and crosslinking points with higher functionality. Nitro-functionalization enhances the interfacial binding property of dopamine and increases its resistant to oxidation, which results in nanocomposite hydrogels with enhanced stiffness and a viscous dissipation property.