4,4′-Dimethyl-1,1′-[ethyl­enedioxy­bis(nitrilo­methyl­idyne)]dibenzene

The Schiff base, C18H20N2O2, which lies about an inversion centre, adopts a linear conformation. The mol­ecules are packed by C—H⋯π inter­actions, forming a two-dimensional supra­molecular network

The cross-reactivity of the enterovirus 71 to human brain tissue and identification of the cross-reactivity related fragments

<p>Abstract</p> <p>Background</p> <p>EV71 occasionally cause a series of severe neurological symptoms, including aseptic meningitis, encephalitis, and poliomyelitis-like paralysis. However, the neurological destruction mechanism was remained to be clarified. This study described the cross reaction between EV71 induced IgG and human brain tissue.</p> <p>Results</p> <p>Cross reaction of the IgG from 30 EV71 infected patients' sera to human tissues of cerebra was observed, which suggested that some EV71 antigens could induce IgG cross-reactivity to human cerebra. To identify the regions of EV71 virus that containing above antigens, the polypeptide of virus was divided into 19 peptides by expression in prokaryotes cell. Mouse anti-sera of these peptides was prepared and applied in immunohistochemical staining with human adult and fetus brain tissue, respectively. The result indicated the 19 peptides can be classified into three groups: strong cross-reactivity, weak cross-reactivity and no cross-reactivity with human brain tissue according the cross reaction activity. Then, the increased Blood Brain Barrier (BBB) permeability and permits IgG entry in neonatal mice after EV71 infection was determined.</p> <p>Conclusion</p> <p>EV71 induced IgG could enter BBB and cross-reacted with brain tissue in EV71 infected neonatal mice, and then the peptides of EV71 that could induce cross-reactivity with brain tissue were identified, which should be avoided in future vaccine designing.</p

Functional connectivity changes are correlated with sleep improvement in chronic insomnia patients after rTMS treatment

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been increasingly used as a treatment modality for chronic insomnia disorder (CID). However, our understanding of the mechanisms underlying the efficacy of rTMS is limited.ObjectiveThis study aimed to investigate rTMS-induced alterations in resting-state functional connectivity and to find potential connectivity biomarkers for predicting and tracking clinical outcomes after rTMS.MethodsThirty-seven patients with CID received a 10-session low frequency rTMS treatment applied to the right dorsolateral prefrontal cortex. Before and after treatment, the patients underwent resting-state electroencephalography recordings and a sleep quality assessment using the Pittsburgh Sleep Quality Index (PSQI).ResultsAfter treatment, rTMS significantly increased the connectivity of 34 connectomes in the lower alpha frequency band (8–10 Hz). Additionally, alterations in functional connectivity between the left insula and the left inferior eye junction, as well as between the left insula and medial prefrontal cortex, were associated with a decrease in PSQI score. Further, the correlation between the functional connectivity and PSQI persisted 1 month after the completion of rTMS as evidenced by subsequent electroencephalography (EEG) recordings and the PSQI assessment.ConclusionBased on these results, we established a link between alterations in functional connectivity and clinical outcomes of rTMS, which suggested that EEG-derived functional connectivity changes were associated with clinical improvement of rTMS in treating CID. These findings provide preliminary evidence that rTMS may improve insomnia symptoms by modifying functional connectivity, which can be used to inform prospective clinical trials and potentially for treatment optimization

Mechanistic aspects of photo-induced formation of peroxide ions on the surface of cubic Ln(2)O(3) (Ln = Nd, Sm, Gd) under oxygen

National Basic Research Program of China [2010CB732303]; National Natural Science Foundation of China [21173173, 21033006, 20923004]; Program for Changjiang Scholars and Innovative Research Team in University [IRT1036]The photo-induced formation of peroxide ions on the surface of cubic Ln(2)O(3) (Ln = Nd, Sm, Gd) was studied by in situ microprobe Raman spectroscopy using a 325 nm laser as excitation source. It was found that the Raman bands of peroxide ions at 833-843 cm(-1) began to grow at the expense of the Ln(3+)-O-2 bands at 333-359 cm(-1) when the Ln(2)O(3) samples under O-2 were continuously irradiated with a focused 325 nm laser beam at temperatures between 25-150 degrees C. The intensity of the peroxide Raman band was found to increase with increasing O-2 partial pressure, whereas no peroxide band was detected on the Ln(2)O(3) under N-2 as well as on the samples first irradiated with laser under Ar or N-2 followed by exposure to O-2 in the dark. The experiments using O-18 as a tracer further confirmed that the peroxide ions are generated by a photo-induced reaction between O-2 and the lattice oxygen (O2-) species in Ln(2)O(3). Under the excitation of 325 nm UV light, the transformation of O-2 to peroxide ions on the surface of the above lanthanide sesquioxides can even take place at room temperature. Basicity of the lattice oxygen species on Ln(2)O(3) also has an impact on the peroxide formation. Higher temperature or laser irradiation power is required to initiate the reaction between O-2 and O2- species of weaker basicity

Inbreeding and Genetic Diversity in Three Imported Swine Breeds in China Using Pedigree Data

The accumulation of inbreeding and the loss of genetic diversity is a potential problem in the modern swine breeds in China. Therefore, the purpose of this study was to analyze the pedigrees of Chinese Duroc (CD), Landrace (CL) and Yorkshire (CY) swine to estimate the past and current rates of inbreeding, and to identify the main causes of genetic diversity loss. Pedigree files from CD, CL and CY containing, 4529, 16,776 and 22,600 records, respectively, were analyzed. Pedigree completeness indexes of the three breeds, accounting for one generation back, were 83.72, 93.93 and 93.59%, respectively. The estimated average annual inbreeding rates for CD, CL and CY in recent three years were 0.21, 0.19 and 0.13%, respectively. The estimated average percentage of genetic diversity loss within each breed in recent three years was about 8.92, 2.19, and 3.36%, respectively. The average relative proportion of genetic diversity loss due to unequal contributions of founders in CD, CL and CY was 69.09, 57.95 and 60.57%, and due to random genetic drift was 30.91, 42.05 and 39.43%, respectively. The estimated current effective population size for CD, CL and CY was 76, 117 and 202, respectively. Therefore, CD has been found to have lost considerable genetic diversity, demanding priority for optimizing the selection and mating to control future coancestry and inbreeding. Unequal contribution of founders was a major cause of genetic diversity loss in Chinese swine breeds and random genetic drift also showed substantial impact on the loss of diversity

Iron Regulation of the Major Virulence Factors in the AIDS-Associated Pathogen Cryptococcus neoformans

Iron overload is known to exacerbate many infectious diseases, and conversely, iron withholding is an important defense strategy for mammalian hosts. Iron is a critical cue for Cryptococcus neoformans because the fungus senses iron to regulate elaboration of the polysaccharide capsule that is the major virulence factor during infection. Excess iron exacerbates experimental cryptococcosis and the prevalence of this disease in Sub-Saharan Africa has been associated with nutritional and genetic aspects of iron loading in the background of the HIV/AIDS epidemic. We demonstrate that the iron-responsive transcription factor Cir1 in Cr. neoformans controls the regulon of genes for iron acquisition such that cir1 mutants are “blind” to changes in external iron levels. Cir1 also controls the known major virulence factors of the pathogen including the capsule, the formation of the anti-oxidant melanin in the cell wall, and the ability to grow at host body temperature. Thus, the fungus is remarkably tuned to perceive iron as part of the disease process, as confirmed by the avirulence of the cir1 mutant; this characteristic of the pathogen may provide opportunities for antifungal treatment

Efficacy, Safety, and Immunogenicity of an Escherichia coliProduced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial

HPV是一种常见的生殖道感染病毒，高危型HPV持续性感染能够导致几乎所有的宫颈癌，其中HPV 16型和18型危害最大，可导致约70%的宫颈癌。预防性HPV疫苗有望减少甚至最终消灭由疫苗型别导致的宫颈癌，降低HPV相关的疾病负担。该研究是在全国4个中心5个现场的18-45岁健康女性中进行的多中心、随机、双盲、对照（戊肝疫苗）的三期临床试验，该研究结果证实我校自主研发的双价人乳头瘤病毒疫苗（大肠杆菌）具有良好的安全性、免疫原性和免疫持久性，可有效地预防HPV 16型和/或18型相关的宫颈高度癌前病变及持续性感染。 该论文报告了我校和厦门万泰沧海生物技术有限公司自主研发的双价人乳头瘤病毒疫苗（大肠杆菌）三期临床试验的期中分析结果。这是第一个进入临床试验并提交药品注册申请的国产人乳头瘤病毒疫苗（HPV疫苗），有望成为世界上第四个上市的HPV疫苗，受到世界卫生组织和盖茨基金会等国际组织的高度关注。 中国医学科学院肿瘤医院乔友林教授、我校吴婷教授、广西壮族自治区疾病预防控制中心李荣成主任医师、江苏省疾病预防控制中心胡月梅主任医师、北京大学人民医院魏丽惠教授、中国食品药品检定研究院李长贵研究员、中国医学科学院肿瘤医院陈汶教授为该论文的共同第一作者，我校张军教授、夏宁邵教授和中国医学科学院肿瘤医院乔友林教授为该论文的共同通讯作者。【Abstract】Background The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase 3 clinical trial was conducted to evaluate the efficacy, safety and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multi-centre, randomized, double-blind trial started on November 22, 2012, in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receiving 3 doses of the test or control (hepatitis E) vaccine at months 0, 1 and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received 3 doses of the vaccine. This report presents data from a pre-specified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval [CI] = 55.6% to 100.0%, 0/3306 in the vaccine group vs. 10/3296 in the control group) and 97.8% (95% CI = 87.1% to 99.9%, 1/3240 vs. 45/3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The Escherichia coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18 associated high-grade genital lesions and persistent infection in women.This work was supported by grants from the Chinese National High-tech R&D Program (863 program, 2012AA02A408), the Chinese National Major Scientific and Technological Special Project for “Significant New Drug Development” (2018ZX09308010 and 2012ZX09101316), the National Natural Science Foundation of China (81673240 and U1705283), the Fujian Provincial Major Scientific and Technological Project (2015YZ0002), the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS, 2017-I2M-B&R-03, and 2016-I2M-1-019) and Xiamen Innovax. 该研究获得了国家高技术研究发展计划（863计划）、新药创制国家科技重大专项、国家自然科学基金、福建省科技重大专项、中国医学科学院医学与健康科技创新工程基金以及厦门万泰沧海生物技术有限公司的资助