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Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

By studying the expression in patients and cell modeling in vitro, antimicrobial peptides for Klebsiella were screened. Killing curve and membrane permeability experiments are used to study the antibacterial effect of antimicrobial peptides in vitro. Cytotoxicity related indicators including lipopolysaccharide (LPS), Capsule polysaccharide (CPS) and outer membrane protein expression were measured. Intranasal inoculation of Pneumoconiosis was used to construct a mouse infection model, and the survival rate and cytokine expression level were tested. Human Neutrophil Peptide 1 (HNP-1) showed significant antibacterial effect, which improved the permeability of the outer membrane of K. pneumoniae. Moreover, HNP-1 decreased LPS, CPS content and outer membrane proteins. K. pneumoniae infection decreased antimicrobial peptide, oxidative stress and autophagy-related genes, while HNP-1 increased these genes. After co-culture with macrophages, the endocytosis of macrophages is enhanced and the bacterial load is greater in K. pneumoniae + peptide group. Besides, higher levels of pp38 and pp65 in K. pneumoniae + peptide group. HNP-1 rescued the cytotoxicity induced by K. pneumoniae. Survival rate is significantly improved after K. pneumoniae treated by HNP-1. All cytokines in the peptide group were significantly higher. HNP-1 promotes immune sterilization by reducing the virulence of multidrug-resistant K. pneumoniae and increasing the ability of macrophages. This article is protected by copyright. All rights reserved.

Despite the increasing number of genes associated with Charcot-Marie-Tooth (CMT) disease, many patients currently still lack appropriate genetic diagnosis for this disease. Autosomal dominant mutations in aminoacyl-tRNA synthetases (ARSs) have been implicated in CMT. Here, we describe causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) for 3 families affected with CMT.Whole-exome sequencing was performed in 16 patients and 14 unaffected members of 3 unrelated families. The functional impact of the genetic variants identified was investigated using bioinformatic prediction tools and confirmed using cellular and biochemical assays.Combined linkage analysis for the 3 families revealed significant linkage (Zmax LOD = 6.9) between the genomic co-ordinates on chromosome 1: 108681600-110300504. Within the linkage region, heterozygous SerRS missense variants segregated with the clinical phenotype in the 3 families. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation.Our findings suggest the heterozygous SerRS variants identified represent a novel cause for autosomal dominant CMT. Mutant SerRS proteins are known to impact various molecular and cellular functions. Our findings provide significant advances on the current understanding of the molecular mechanisms associated with ARS-related CMT. ANN NEUROL 2022.

BACKGROUND Oncocytic adrenocortical tumor (OACT) is rare, with few cases reported in the literature. No more than 20 cases in children have been reported. The clinical characteristics, diagnosis, treatment and prognosis of children with OACT are summarized based on a literature review, in order to improve the understanding of OACT in children. CASE SUMMARY We report a case of a 17-mo-old patient who was admitted to our hospital due to symptoms of odynuria and fever, which are clinical features consistent with a functional adrenocortical tumor. The patient was diagnosed with OACT of uncertain malignant potential. Computed tomography indicated a soft tissue giant tumor in the right adrenal region, approximately 4.3 cm × 5.5 cm in size. Multiple nodular and speckled calcifications were observed in the lesion. The patient received robot-assisted laparoscopic right adrenal tumor resection. Postoperative pathological results were consistent with OACT, and immunohistochemical results showed cytokeratin+/-, chromogranin A+, synaptophysin-, neuron-specific enolase-, S100-, Ki67 about 10%, CD34- and D2-40-. After surgery, urinary tract ultrasonography was reviewed monthly, catecholamine hormone and sex hormone levels were examined every 2 mo and computed tomography was performed every 6 mo. To date, no tumor metastasis or recurrence has been identified in this patient. The levels of sex hormones and catecholamine hormones decreased to normal 1 mo after surgery. CONCLUSION OACT is rare in the pediatric population, with few cases reported in the literature. Although most pediatric OACTs are benign, malignant cases have been reported. Surgical resection is the preferred option in most patients.

sRecent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood–pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

Although early life stress (ELS) can increase susceptibility to adulthood psychiatric disorders and produce a greater inflammatory response in a stressful event, targeted preventive and therapeutic drugs still remain scarce. Ganoderma lucidum triterpenoids (GLTs) can exert anti-inflammatory effects in the periphery and central nervous systems. This study employed a combined model of “childhood maternal separation + adulthood sub-stress” to explore whether GLTs may alleviate anxiety- and depression-like behaviors in male and female mice by mitigating inflammation. Male and female pups were separated from their mothers for four hours per day from postnatal day 1 (PND 1) to PND 21; starting from PND 56, GLTs were administered intraperitoneally once daily for three weeks and followed by three days of sub-stress. Results showed that maternal separation increased the anxiety- and depression-like behaviors in both male and female mice, which disappeared after the preemptive GLTs treatment (40 mg/kg) before adulthood sub-stress. Maternal separation up-regulated the pro-inflammatory markers in the periphery and brain, and activated microglia in the prefrontal cortex and hippocampus. All the abnormalities were reversed by GLTs administration, with no adverse effects on immune organ indices, liver, and renal function. Our findings suggest that GLTs can be a promising candidate in treating ELS-induced psychiatric disorders.

Background and purpose The chemokine monocyte chemoattractant protein-1 (MCP-1) is involved in the pathogenesis of Alzheimer's disease (AD). This study aimed to investigate whether urinary MCP-1 can distinguish patients with AD, patients with amnestic mild cognitive impairment (aMCI) and cognitively normal (CN) subjects. Methods A total of 754 participants, including 97 patients with AD, 50 patients with aMCI and 84 age- and sex-matched CN controls as well as a cohort of 523 CN subjects of different ages, were enrolled from five hospitals located in different areas of China. Urinary MCP-1 levels were determined using enzyme-linked immunosorbent assays. The correlations between urinary MCP-1 levels and cognition test scores or age were analysed. The optimal diagnostic sensitivity and specificity were determined using receiver operating characteristic curve analysis. Results In the cohort of CN subjects of different ages, urinary MCP-1 levels increased with ageing and were correlated with age. The urinary MCP-1 levels were higher in females than in males. In the cohort composed of patients with AD, aMCI and age- and sex-matched CN controls, urinary MCP-1 levels were significantly higher in patients with AD and aMCI than in CN controls. There were no differences in urine MCP-1 levels between the AD group and the aMCI group. The urinary MCP-1 levels were correlated with the Mini-Mental State Examination scores and age, and were able to differentiate patients with AD and aMCI from CN subjects. Conclusions Urinary MCP-1 is a potential biomarker for the diagnosis of AD and aMCI.

Background. Klebsiella pneumoniae (K. pneu) is a leading cause of gram-negative pneumonia, which requires effective treatment. Adipose-derived mesenchymal stem cell- (ADSC-) derived exosomal microRNAs (miRNAs) have presented the inhibitory effect of multiple diseases. However, the function of ADSC-derived exosomal miRNAs in K. pneu remains unclear. Aim. In this study, we aimed to explore the effect of ADSC-derived exosomal miR-181-5p on K. pneu infection-induced lung injury. Methods. C57BL/6 mouse model was established by infection of K. pneu. ADSCs and exosomes were extracted and characterized in vitro. The translocation of ADSC-derived exosomes to bone marrow-derived macrophages (BMDMs) was detected. The level of miR-181a-5p was detected by real-time PCR. The secretion of inflammatory factors was determined by ELISA. The interaction between miR-181a-5p with STAT3 was identified. Results. We successfully isolated the ADSCs that express positive markers CD90 and CD105 rather than CD31 and CD45. The exosomal miR-181a-5p secreted by ADSCs were internalized by BMDM and K. pneu infection stimulated the miR-181a-5p level in bronchoalveolar lavage fluid (BALF) and BMDM. ADSC-derived exosomal miR-181a-5p repressed pulmonary outgrowth and dissemination of K. pneu infection in mice, repressed cellular infiltration in lung tissue, and attenuated the inflammasome activity and the levels of IL-1β and IL-18 in the lung. Mechanically, miR-181a-5p was able to inhibit STAT3 expression at posttranscriptional levels and repressed Nlrp3 and Asc expression in BMDM. Conclusion. Consequently, we concluded that ADSC-derived exosomal miR-181a-5p alleviated Klebsiella pneumonia infection-induced lung injury by targeting STAT3 signaling. ADSC-derived exosomal miR-181a-5p may serve as a potential candidate for the treatment of Klebsiella pneumonia infection-induced lung injury.

An 8 week feeding trial was carried out to investigate the effects of dietary nucleotides on growth performance, intestinal morphology, immune response and disease resistance of juvenile largemouth bass, Micropterus salmoides. Five grades of dietary nucleotide levels were designed as 0, 0.2, 0.4, 0.8 and 1.2 g kg

In this study, we aimed to explore the effect of ADSC-derived exosomal miR-181-5p onC57BL/6 mouse model was established by infection ofWe successfully isolated the ADSCs that express positive markers CD90 and CD105 rather than CD31 and CD45. The exosomal miR-181a-5p secreted by ADSCs were internalized by BMDM andConsequently, we concluded that ADSC-derived exosomal miR-181a-5p alleviated

Background: For extremely low-birth-weight infants (ELBWIs), mechanical ventilation and total parenteral nutrition are generally required in the early stages and lose the protective effect of early gastrointestinal nutrition of colostrum. We conducted a prospective randomized controlled trial to explore the effectiveness of early colostrum oropharyngeal administration on the feeding status of ELBWIs on mechanical ventilation. Materials and Methods: We randomly divided mechanically ventilated ELBWIs into an intervention group and a control group. In the intervention group, we provided oropharyngeal administration of colostrum during mechanical ventilation. The first colostrum oropharyngeal administration ended within 24 hours of birth. In the control group, we gave colostrum only for gastrointestinal nutrition, and other interventions were the same as for the intervention group. We collected the 1st and 6th day of life airway secretions and urine specimens from both groups. We recorded feeding status, including corrected gestational age at onset of enteral nutrition, corrected gestational age of no gastric retention during feeding, corrected gestational age of full enteral nutrition, corrected gestational age of sucking began, and corrected gestational age of per oral feeding. We also recorded growth of body mass, the incidence of feeding intolerance, and necrotizing enterocolitis (NEC). Results: On the 6th day of life, concentrations of secretory immunoglobulin A, and lactoferrin in airway secretions and urine of the intervention group were significantly higher than those of the control group (p < 0.05). The intervention group showed younger corrected gestational age of no gastric retention during feeding, corrected gestational age of full enteral nutrition, the corrected gestational age of sucking began and per oral feeding than those in the control group (p < 0.05). The day of recovery to birth weight was earlier than those in the control group (p < 0.05). The rate of feeding intolerance and NEC incidence in the intervention group was significantly lower than in the control group (p < 0.05). Conclusions: Early oropharyngeal administration of colostrum improves immune function of the gastrointestinal tract and the systemic anti-infective capability in ELBWI on mechanical ventilation, promoting the maturity of gastrointestinal function, improving feeding condition, and reducing the risk of feeding intolerance and NEC.

No studies have examined endogenous insulin secretion in pediatric patients with type 1 diabetes in China using the gold-standard mixed-meal tolerance test. Because the latter is labor-intensive, we examined simpler surrogate markers of endogenous insulin secretion in Chinese youth, as previously reported for a European population.Participants were 57 children and adolescents with type 1 diabetes aged 4.4-16.8 years (56% females). We performed 120-minute mixed-meal tolerance tests with serum C-peptide (CP) measurements every 30 minutes. Severe insulin deficiency (SID) was defined as CP peak 0.2 nmol/L. Urine CP and creatinine levels were measured at 0 and 120 minutes.Twenty-five (44%) patients had SID. Fasting CP levels missed one case (96% sensitivity) with no false positives (100% specificity). While the 120-minute urine CP/creatinine had 100% sensitivity, it yielded markedly lower specificity (63%). Every 1-year increase in diabetes duration and 1-year decrease in age at diagnosis were associated with 37% (P 0.001) and 20% (P = 0.005) reductions in serum CP area-under-the-curve, respectively. Thus, 86% of children aged 5 years had SID compared to none among patients aged ≥ 11 years.Simple fasting CP measurements could be used to detect most SID cases in Chinese youth with type 1 diabetes. Fasting CP is a far more reliable measure of endogenous insulin secretion than the more commonly used insulin dose. Therefore, it could more precisely determine insulin secretory capacity to target those who could benefit, if treatments to preserve residual insulin secretion are developed.

Background Sleep disorder-associated cognitive impairments are often accompanied by impaired synaptic plasticity. In the pathological process of sleep deprivation, microglia, as an important innate immune cell in central nervous system, are involved and mediate the synaptic pruning, in which the CX3C-chemokine receptor 1 receptor (CX3CR1) plays an indispensable role. In this study, the potential role of CX3CR1 in modulating the cognition decline during sleep deprivation was evaluated in terms of microglial neuroinflammation and synaptic pruning. Methods Middle-aged wild type C57BL/6 mice (WT) (13 months) and age-matched CX3CR1 -/- mice were either subjected to sleep deprivation (SD) or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night in real life. The hippocampus-dependent cognition was assessed by fear conditioning test. Mice brains were extracted for neuroinflammation and synaptic pruning studies. Data were analyzed by Student’s t-test and one-way analysis of variance (one-way ANOVA). Results The CX3CR1 deficiency mice differed from WT mice in many measures. CX3CR1 deficiency prevented SD-induced cognitive impairments, in which the levels of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP-responsive element binding protein (p-CREB) were markedly increased in the hippocampus. Compared with the CX3CR1 -/- -S group, the CX3CR1 -/- -SD mice reported a markedly decreased microglial density in the dentate gyrus, notably-decreased levels of cellular oncogene fos (c-fos), and pro-inflammatory cytokines and increased levels of anti-inflammatory cytokines in the hippocampus, and a significant increase in the density of spines of the dentate gyrus area. Furthermore, the CX3CR1 -/- -SD group also showed a decreasing expression of microglial phagocytosis-related factors. Conclusion These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to sleep deprivation. CX3CR1 deletion can alleviate the sleep deprivation-induced cognitive impairment. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.

Background Circulating exosomal microRNAs are reflective of the characteristics of the tumor, are valuable biomarkers in different types of tumors, and play important roles in tumor progression and metastasis. The purpose of this study was to investigate the circulating exosomal microRNAs miRNA-21 and miRNA-210 as novel biomarkers for patients with pancreatic cancer (PC).Methods Serum exosomal microRNAs were extracted from the serum of PC and chronic pancreatitis (CP) patients using an RNA Isolation kit. To identify the exosomes in the serum, we used transmission electron micrographs for the crystalline structure, western blotting, and NanoSight for exosomal markers and nanoparticle characterization. The relative expression levels of exosomal microRNAs were quantified using quantitative PCR and compared between PC and CP patients.Results A total of 40 serum samples (30 PC and 10 CP) were collected. The expression levels of both exosomal miRNA-21 and miRNA-210 were obviously higher in PC patients compared with those in CP patients (both P0.05). Exosomal miRNA-21 and miRNA-210 were related to tumor stage, as well as other factors. The diagnostic of exosomal miRNA-21 and miRNA-210 levels was 83% and 85%, respectively. Furthermore, when combining the expression of exosomal miRNA with serum CA19-9, the accuracy increased to 90%.Conclusions We herein identified that the serum exosomal miRNAs miRNA-21 and miRNA-210 may be of value as potential biomarkers and therapeutic targets for the diagnosis and treatment of PC.

Objective: To study the relationship of PDCD5 expression with apoptosis, inflammatory factors and MMPs/TIMPs expression in degenerated intervertebral disc tissue. Methods: Patients with lumbar disc herniation who were treated in the Seventh People's Hospital of Shanghai between March 2015 and February 2017 were selected as the LDH group and patients with violent thoracolumbar vertebral fracture were selected as the control group. The intervertebral disc tissue was collected to determine the mRNA expression of PDCD5 as well as the protein levels of apoptosis molecules, inflammatory factors and MMPs/TIMPs molecules. Results: PDCD5 mRNA expression in intervertebral disc tissue of LDH group was significantly higher than that of control group; Caspase-3, Caspase-8, Fas, Caspase-9, Bax, SDF-1, CXCR-4, TNF-α, PGE2, MMP1, MMP2, MMP8 and MMP9 protein levels in intervertebral disc tissue of LDH group were significantly higher than those of control group and positively correlated with PDCD5 mRNA expression while TIMP1 and TIMP2 protein levels were significantly lower than those of control group and negatively correlated with PDCD5 mRNA expression. Conclusion: The high expression of PDCD5 in degenerated intervertebral disc tissue can activate apoptosis and inflammatory response and cause MMPs/ TIMPs imbalance.

Circulating exosomal microRNAs (ex-miRNAs) are reflective of the characteristics of the tumor and are valuable biomarkers in different types of tumor. In addition, miRNAs serve important roles in tumor progression and metastasis. The present study aimed to investigate the circulating ex-miRNA-21 and miRNA-210 as novel biomarkers for patients with pancreatic cancer (PC). For this purpose, serum ex-miRNAs were extracted from the serum of patients with PC (n=30) and chronic pancreatitis (CP) (n=10) using an RNA isolation kit. For exosome identification in serum, transmission electron micrographs were used to determine crystalline structure, western blotting was used to identify exosomal markers, and NanoSight was used for nanoparticle characterization. The relative expression levels of ex-miRNAs were quantified using quantitative PCR and compared between patients with PC and CP. The expression levels of both ex-miRNA-21 and miRNA-210 were significantly higher in patients with PC compared with patients with CP (both P0.05). ex-miRNA-21 and miRNA-210 were associated with tumor stage, as well as other factors. The diagnostic potential of ex-miRNA-21 and miRNA-210 levels was 83 and 85%, respectively. In addition, when ex-miRNA and serum carbohydrate antigen 19-9 expression levels were combined, the accuracy increased to 90%. The present study identified that serum ex-miRNAs, miRNA-21 and miRNA-210 may be of value as potential biomarkers and therapeutic targets for the diagnosis and treatment of PC.

// Xiang Tang 1,* , Di Wu 1,* , Li-Hua Gu 1 , Bin-Bin Nie 2 , Xin-Yang Qi 1 , Yan-Juan Wang 1 , Fang-Fang Wu 1 , Xiao-Li Li 1 , Feng Bai 1 , Xiao-Chun Chen 3 , Lin Xu 4,5 , Qing-Guo Ren 1 and Zhi-Jun Zhang 1 1 Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute, School of Medicine, Southeast University, Nanjing, Jiangsu, China 2 Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China 3 Department of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian, China 4 Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China 5 Graduate School of Chinese Academy of Sciences, Beijing, China * These authors have contributed equally to this work Correspondence to: Zhi-Jun Zhang, email: // Qing-Guo Ren, email: // Keywords : Alzheimer’s disease, 5XFAD mice, cognition, neuroimaging, manganese enhanced MRI, Pathology Section Received : March 25, 2016 Accepted : July 19, 2016 Published : August 17, 2016 Abstract Dysfunction of neuronal activity is a major and early contributor to cognitive impairment in Alzheimer’s disease (AD). To investigate neuronal activity alterations at early stage of AD, we encompassed behavioral testing and in vivo manganese-enhanced magnetic resonance imaging (MEMRI) in 5XFAD mice at early ages (1-, 2-, 3- and 5-month). The 5XFAD model over-express human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations, which have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-β. In the Morris water maze, 5XFAD mice showed longer escape latency and poorer memory retention. In the MEMRI, 5XFAD mice showed increased signal intensity in the brain regions involved in spatial cognition, including the entorhinal cortex, the hippocampus, the retrosplenial cortex and the caudate putamen. Of note, the observed alterations in spatial cognition were associated with increased MEMRI signal intensity. These findings indicate that aberrant increased basal neuronal activity may contribute to the spatial cognitive function impairment at early stage of AD, and may further suggest the potential use of MEMRI to predict cognitive impairments. Early intervention that targets aberrant neuronal activity may be crucial to prevent cognitive impairment.

Oxidative stress plays an important role in the progression of Alzheimer's disease (AD) and other neurodegenerative conditions. Glutathione (GSH), the major antioxidant in the central nervous system, is primarily synthesized and released by astrocytes. We determined if β-amyloid (Aβ42), crucially involved in Alzheimer's disease, affected GSH release. Monomeric Aβ (mAβ) stimulated GSH release from cultured cortical astrocytes more effectively than oligomeric Aβ (oAβ) or fibrillary Aβ (fAβ). Monomeric Aβ increased the expression of the transporter ABCC1 (also referred to as MRP1) that is the main pathway for GSH release. GSH release from astrocytes, with or without mAβ stimulation, was reduced by pharmacological inhibition of ABCC1. Astrocytes robustly express connexin proteins, especially connexin43 (Cx43), and mAβ also stimulated Cx43 hemichannel-mediated glutamate and GSH release. Aβ-stimulation facilitated hemichannel opening in the presence of normal extracellular calcium by reducing astrocyte cholesterol level. Aβ treatment did not alter the intracellular concentration of reduced or oxidized glutathione. Using a mouse model of AD with early onset Aβ deposition (5xFAD), we found that cortical ABCC1 was significantly increased in temporal register with the surge of Aβ levels in these mice. ABCC1 levels remained elevated from 1.5 to 3.5 months of age in 5xFAD mice, before plunging to subcontrol levels when amyloid plaques appeared. Similarly, in cultured astrocytes, prolonged incubation with aggregated Aβ, but not mAβ, reduced induction of ABCC1 expression. These results support the hypothesis that in the early stage of AD pathogenesis, less aggregated Aβ increases GSH release from astrocytes (via ABCC1 transporters and Cx43 hemichannels) providing temporary protection from oxidative stress which promotes AD development. GLIA 2015;63:2208–2219

The accelerated aging tests under salt fog conditions were carried out on two types of composite insulators in order to evaluate their anti-aging properties. FTIR spectroscopy, hydrophobicity, and hardness measurements were taken to characterize insulator housings' physical and chemical properties before and after aging. It was found that the aging characteristics were highly dependent on housing profile, aging time, and filling materials.

Single-crystal structures of the best high-temperature trichromatic blue azo dye C.I. Disperse Blue 148 and its diazonium component 3-amino-5-nitro-[2,1]- benzisothiazole are described herein. C.I. Disperse Blue 148 exhibits an essentially coplanar molecular structure and a dimeric packing mode between adjacent phenyl and benzisothiazole rings. Particularly, PXRD measurement reveals the existence of a new crystalline form of C.I. Disperse Blue 148 having the highest melting point and the best thermal stability, which is obviously different from all the known α, β, and γ forms. A one-phase recrystallization method, which can guarantee the complete transformation, is used to prepare the new crystalline form instead of the conventional heating of an aqueous suspension of α form. Furthermore, TGA–DSC and pH titration experiments have been carried out to reveal the thermal and pH stabilities of this heterocyclic dye. To our knowledge, this is the first structural example on benzisothiazole involved azo dyes.

Using the Minifilter framework and AES group encryption algorithm, the paper develops a filter driver for encrypting the file of particular types under the security directory. The principle of the file system filter driver is discussed here, and makes a special research about the file operation process especially for word format. This paper also makes a deep analysis of transformation mechanism between the plaintext and ciphertext, and the implementation algorithms of encryption and decryption. Finally, the paper describes the method of path filtering in detail.

In the current wireless network technology, the most important research is Ad-hoc, and the most promising is the WSN. Ad-hoc which develops on the basis of packet radio network is a wireless mobile network with self-organizing, peer to peer and multi-hop. WSN combines Ad-hoc and sensor technology to collaboratively perceive, collect and process the message of sensing objects in the coverage area of network, and send to the viewer.

Mucolipidosis II alpha/beta (ML II alpha/beta; I-cell disease) is a rare, inherited, metabolic disease and has often been clinically misdiagnosed. ML II alpha/beta results from a deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-PT), which causes the lysosomal enzymes to accumulate in plasma. We identified two new Chinese patients with ML II alpha/beta by lysosomal enzyme assay. Using targeted next-generation sequencing genetic analysis, we located two homozygous nonsense mutations in the GNPTAB gene, c.1071G>A (p.W357X) and c.1090C>T (p.R364X). These results were confirmed by Sanger sequencing. To our knowledge, the c.1071G>A mutation has not been previously reported. Our findings add to the number of reported cases of this rare illness and to the GNPTAB pathogenic mutation database. This work also demonstrates the application of lysosomal enzyme assay and targeted next-generation sequencing for the genetic screening analysis and diagnosis of ML II alpha/beta.

Three pairs of heterocyclic azo dyes and their corresponding Schiff bases were prepared by diazotization and Schiff-base condensation reactions between substituted 2-aminobenzothiazoles and either 3-(diethylamino)phenol or 3,5-dichloro-2-hydroxybenzaldehyde in order to obtain some high performance Disperse Red dyes and compare the structural and spectral differences between the azo dyes and Schiff bases. All azo dyes and Schiff bases in this work have the same benzothiazole/phenol skeleton but different substituent group in the phenyl ring. X-ray single-crystal diffraction analyses of selected compounds reveal that they have a similar planar conformation between the benzothiazole and phenol units but dissimilar dimeric crystal packing. Electronic spectra of the dyes demonstrate that the presence of N N and C N double bond chromophore units as well as substituent effects of different auxochrome groups in the benzothiazole backbone leads to significant alterations of bathochromic and hypsochromic shifts despite only slight differences in their molecular structures.

Top management support (TMS) is one of critical success factors of information systems. However, prior research had no agreement on the contents, forms and roles of TMS. Especially, studies conducted in Chinese manufacturing industry context were scarce. This paper constructed a model to describe the effects of TMS on information systems success and the reactions. Following multi-case study approach, it collected the qualitative data from eleven manufacturing enterprises, and nine of which were got together through interviewing the CIOs. As result, the conceptual model was supported. The findings have significant meanings for practice.

Magnetic Cu2+-chelated silica particles using polyacrylamide as a metal-chelating ligand was developed and used for the immobilization of laccase by coordination. The effect of pH and temperature on the enzymatic property of immobilized laccase and its catalytic capacity for pentachlorophenol (PCP) degradation were evaluated systemically. Compared with free laccase, the immobilized laccase showed improved acid adaptability and thermal stability. The immobilized laccase prepared in this work exhibited a good catalytic capacity for PCP removal from aqueous solutions.

The insulin-like growth factor-1 (IGF-1) plays an important role in the regulation of reproductive function. In the present study, we examined the effects of caloric restriction (CR) on the reproductive lifespan in rats and investigated the potential role of IGF-1. After 10 weeks of treatment, we determined the distribution of the ovarian follicles at various stages and measured the plasma level of IGF-1, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrogen (ESG). Our results show that IGF-1 level was decreased after CR and correlated with the decrease in the levels of LH, FSH and ESG. Moreover, a higher percentage of primordial follicles and surviving follicles was observed in CR rats than in control rats (P

The method of chemical mechanical polishing (CMP) using slurry which was ultrasonic subtle atomized was researched, and the system of Ultrasonic Subtle Atomization—Chemical Mechanical Polishing was established. The effects of polish parameters on polishing were also investigated. The results show that the experimental system can fully realize the expected function of polishing, the use of slurry is about one-tenth of the amount of traditional CMP, material removal rate can reach 113.734nm/min and the surface roughness is similar to the surface roughness in the traditional way.

The transport properties of C14 monocyclic ring sandwiched between two Al(1 0 0) electrodes are investigated by first-principle calculations. The variation of the equilibrium conductance as the function of the separation distance between the molecule and the electrodes is studied. C14 monocyclic ring shows metallic behavior according to the calculated equilibrium conductance. Electron transmission occurs through the lowest unoccupied molecular orbital (LUMO). With gate-voltage applied, it is found that the positive and negative gate-voltages can bring very different effect on the variation of equilibrium conductance. We also calculate the effects of adsorbing other atoms on the carbon ring such as oxygen and sulfur atoms. The results indicate that adsorption of this kind of electron-accepting impurity will decrease the conductance of the system.

ABE-KONDOH-NAGANO, ABID, YANG-SHIH and LAUNDER-SHARMA low-Reynolds number turbulence models were applied to simulating unsteady turbulence flow around a square cylinder in different phases flow field and time-averaged unsteady flow field. Meanwhile, drag and lift coefficients of the four different low-Reynolds number turbulence models were analyzed. The simulated results of YANG-SHIH model are close to the large eddy simulation results and experimental results, and they are significantly better than those of ABE-KONDOH-NAGANO, ABID and LAUNDER-SHARMR models. The modification of the generation of turbulence kinetic energy is the key factor to a successful simulation for YANG-SHIH model, while the correction of the turbulence near the wall has minor influence on the simulation results. For ABE-KONDOH-NAGANO, ABID and LAUNDER-SHARMA models satisfactory simulation results cannot be obtained due to lack of the modification of the generation of turbulence kinetic energy. With the joint force of wall function and the turbulence models with the adoption of corrected swirl stream, flow around a square cylinder can be fully simulated with less grids by the near-wall.