The case report of AQP4 and MOG IgG double positive NMOSD treated with subcutaneous Ofatumumab.

Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune demyelinating disease with IgG against aquaporin 4 (AQP4) in more than two thirds of patients. Anti-myelin-oligodendrocyte glycoprotein (MOG) antibody is found in some AQP4-negative NMOSD patients and MOG antibody-associated disease (MOGAD) is thought to be distinct from NMOSD. Due to the high disabling nature of NMOSD, treatment strategy on first attack is crucial for good prognosis. Rituximab (RTX), an anti-CD20 monoclonal antibody (mAb), is the first-line treatment for NMOSD. However, RTX can be limited by the relatively high rate of systemic allergic reaction. Herein, we reported a rare case of AQP4 and MOG-IgG double positive NMOSD patient effectively and safely treated with ofatumumab (OFA), a novel fully humanized anti-CD20 mAb.

In vivo Regeneration of Ganglion Cells for Vision Restoration in Mammalian Retinas.

Glaucoma and other optic neuropathies affect millions of people worldwide, ultimately causing progressive and irreversible degeneration of retinal ganglion cells (RGCs) and blindness. Previous research into cell replacement therapy of these neurodegenerative diseases has been stalled due to the incapability for grafted RGCs to integrate into the retina and project properly along the long visual pathway. In vivo RGC regeneration would be a promising alternative approach but mammalian retinas lack regenerative capacity. It therefore has long been a great challenge to regenerate functional and properly projecting RGCs for vision restoration in mammals. Here we show that the transcription factors (TFs) Math5 and Brn3b together are able to reprogram mature mouse Müller glia (MG) into RGCs. The reprogrammed RGCs extend long axons that make appropriate intra-retinal and extra-retinal projections through the entire visual pathway to innervate both image-forming and non-image-forming brain targets. They exhibit typical neuronal electrophysiological properties and improve visual responses in RGC loss mouse models. Together, our data provide evidence that mammalian MG can be reprogrammed by defined TFs to achieve in vivo regeneration of functional RGCs as well as a promising new therapeutic approach to restore vision to patients with glaucoma and other optic neuropathies.

Effects of electrical-hydrothermal aging degradation on dielectric and trap properties of high temperature vulcanized silicone rubber materials.

In this paper, a new aging platform combined the high voltage electric field and the hydrothermal environment was built. To investigate the aging mechanism, physicochemical, dielectric and trap properties of HTV SR before and after electrical-hydrothermal aging for 24 days were discussed. The results indicated that, compared with hydrothermal aging, more cracks and holes appeared on the surface of HTV SR after electrical-hydrothermal aging, and the content of flame retardant decreased significantly. Due to the main chain and side chain scission of PDMS, lots of low weight molecular (LWM) substances and free radicals were produced. And the tensile strength and elongation at break significantly decreased. Various physical and chemical defects appeared in the HTV SR specimen in the process of electrical-hydrothermal degradation, as a result of which, the dielectric constant significantly increased and the peak trap density increased by about 2.5 times compared to the virgin sample. The increase in trap density in turn accelerated the charge accumulation and enhanced the breakdown probability, resulting in the electric field strength decrease from 21.8 kV mm-1 to 16.1 kV mm-1 and severe degradation of HTV SR.

The influence mechanism of nanoparticles on the dielectric properties of epoxy resin.

In order to study the influence mechanism of nanoparticles on the dielectric properties of epoxy resin materials for composite insulators under different nanoparticle filling amounts, the free volume, dielectric relaxation, breakdown strength and trap distribution of the samples were tested by positron annihilation lifetime spectroscopy, breakdown strength, broadband dielectric spectroscopy (BDS) and thermally stimulated current (TSC). The results show that the limiting effect of nanoparticles rapidly reduced the number of traps in the amorphous zone of materials at a low filling amount. As a result, the free path of carriers was increased and the concentration of free volume was decreased, which can limit the injection and transportation of carriers, resulting in the increase of material breakdown strength. At a high filling amount, a large number of interfacial deep traps were introduced into the nanoparticles, and the carrier free volume concentration and size were reduced. The traps inside the material were mainly interfacial deep traps. Under the action of an external electric field, a hetero polar charge was formed on the other end to cause electric field distortion, thus the breakdown field strength of the material was weakened.

A Schizophrenia-Related Deletion Leads to KCNQ2-Dependent Abnormal Dopaminergic Modulation of Prefrontal Cortical Interneuron Activity.

Altered prefrontal cortex function is implicated in schizophrenia (SCZ) pathophysiology and could arise from imbalance between excitation and inhibition (E/I) in local circuits. It remains unclear whether and how such imbalances relate to genetic etiologies. We used a mouse model of the SCZ-predisposing 22q11.2 deletion (Df(16)A+/- mice) to evaluate how this genetic lesion affects the excitability of layer V prefrontal pyramidal neurons and its modulation by dopamine (DA). Df(16)A+/- mice have normal balance between E/I at baseline but are unable to maintain it upon dopaminergic challenge. Specifically, in wild-type mice, D1 receptor (D1R) activation enhances excitability of layer V prefrontal pyramidal neurons and D2 receptor (D2R) activation reduces it. Whereas the excitatory effect upon D1R activation is enhanced in Df(16)A+/- mice, the inhibitory effect upon D2R activation is reduced. The latter is partly due to the inability of mutant mice to activate GABAergic parvalbumin (PV)+ interneurons through D2Rs. We further demonstrate that reduced KCNQ2 channel function in PV+ interneurons in Df(16)A+/- mice renders them less capable of inhibiting pyramidal neurons upon D2 modulation. Thus, DA modulation of PV+ interneurons and control of E/I are altered in Df(16)A+/- mice with a higher excitation and lower inhibition during dopaminergic modulation.

H2O2-Sensitive Isoforms of Drosophila melanogaster TRPA1 Act in Bitter-Sensing Gustatory Neurons to Promote Avoidance of UV During Egg-Laying.

The evolutionarily conserved TRPA1 channel can sense various stimuli including temperatures and chemical irritants. Recent results have suggested that specific isoforms of Drosophila TRPA1 (dTRPA1) are UV-sensitive and that their UV sensitivity is due to H2O2 sensitivity. However, whether such UV sensitivity served any physiological purposes in animal behavior was unclear. Here, we demonstrate that H2O2-sensitive dTRPA1 isoforms promote avoidance of UV when adult Drosophila females are selecting sites for egg-laying. First, we show that blind/visionless females are still capable of sensing and avoiding UV during egg-laying when intensity of UV is high yet within the range of natural sunlight. Second, we show that such vision-independent UV avoidance is mediated by a group of bitter-sensing neurons on the proboscis that express H2O2-sensitive dTRPA1 isoforms. We show that these bitter-sensing neurons exhibit dTRPA1-dependent UV sensitivity. Importantly, inhibiting activities of these bitter-sensing neurons, reducing their dTRPA1 expression, or reducing their H2O2-sensitivity all significantly reduced blind females' UV avoidance, whereas selectively restoring a H2O2-sensitive isoform of dTRPA1 in these neurons restored UV avoidance. Lastly, we show that specifically expressing the red-shifted channelrhodopsin CsChrimson in these bitter-sensing neurons promotes egg-laying avoidance of red light, an otherwise neutral cue for egg-laying females. Together, these results demonstrate a physiological role of the UV-sensitive dTRPA1 isoforms, reveal that adult Drosophila possess at least two sensory systems for detecting UV, and uncover an unexpected role of bitter-sensing taste neurons in UV sensing.

High Throughput Assay to Examine Egg-Laying Preferences of Individual Drosophila melanogaster.

Recently, egg-laying preference of Drosophila has emerged as a genetically tractable model to study the neural basis of simple decision-making processes. When selecting sites to deposit their eggs, female flies are capable of ranking the relative attractiveness of their options and choosing the "greater of two goods." However, most egg-laying preference assays are not practical if one wants to take a systematic genetic screening approach to search for the circuit basis underlying this simple decision-making process, as they are population-based and laborious to set up. To increase the throughput of studying of egg-laying preferences of single females, we developed custom chambers that each can simultaneously assay egg-laying preferences of up to thirty individual flies as well as a protocol that ensures each female has a high egg-laying rate (so that their preference is readily discernable and more convincing). Our approach is simple to execute and produces very consistent results. Additionally, these chambers can be equipped with different attachments to allow video recording the egg-laying animals and to deliver light for optogenetics studies. This article provides the blueprints for fabricating these chambers and the procedure for preparing the flies to be assayed in these chambers.

[Process-based Emission Characteristics of Volatile Organic Compounds (VOCs) from Paint Industry in the Yangtze River Delta, China].

Understanding the volatile organic compounds (VOCs) emission characteristics from solvent usage industry is essential to reduce PM2.5 and O3 in Yangtze River Delta region. In this work, VOCs source characteristics of ship container, shipbuilding, wood, and automobile painting industry were measured using canister-GC-MS/FID analysis system. The results showed that VOCs emitted from these industrial sectors were mainly aromatics, such as toluene, xylene, and ethylbenzene, accounting for 79%-99% of total VOCs. The VOCs treatment facilities of activated carbon adsorption had little impact on changing the composition patterns of VOCs, while catalytic combustion treatments produced more alkenes. The combustion treatment of VOCs changed the maximum increment reactivity (MIR) of the VOCs emissions, and was thus very likely to change the ozone formation potentials.

Process-specific emission characteristics of volatile organic compounds (VOCs) from petrochemical facilities in the Yangtze River Delta, China.

Process-specific emission characteristics of volatile organic compounds (VOCs) from petrochemical facilities were investigated in the Yangtze River Delta, China. Source samples were collected from various process units in the petrochemical, basic chemical, and chlorinated chemical plants, and were measured using gas chromatography-mass spectrometry/flame ionization detection. The results showed that propane (19.9%), propene (11.7%), ethane (9.5%) and i-butane (9.2%) were the most abundant species in the petrochemical plant, with propene at much higher levels than in petrochemical profiles measured in other regions. Styrene (15.3%), toluene (10.3%) and 1,3-butadiene (7.5%) were the major species in the basic chemical industry, while halocarbons, especially dichloromethane (15.2%) and chloromethane (7.5%), were substantial in the chlorinated chemical plant. Composite profiles were calculated using a weight-average approach based on the VOC emission strength of various process units. Emission profiles for an entire petrochemical-related industry were found to be process-oriented and should be established considering the differences in VOC emissions from various manufacturing facilities. The VOC source reactivity and carcinogenic risk potential of each process unit were also calculated in this study, suggesting that process operations mainly producing alkenes should be targeted for possible controls with respect to reducing the ozone formation potential, while process units emitting 1,3-butadiene should be under priority control in terms of toxicity. This provides a basis for further measurements of process-specific VOC emissions from the entire petrochemical industry. Meanwhile, more representative samples should be collected to reduce the large uncertainties.

Mechanosensitive neurons on the internal reproductive tract contribute to egg-laying-induced acetic acid attraction in Drosophila.

Selecting a suitable site to deposit their eggs is an important reproductive need of Drosophila females. Although their choosiness toward egg-laying sites is well documented, the specific neural mechanism that activates females' search for attractive egg-laying sites is not known. Here, we show that distention and contraction of females' internal reproductive tract triggered by egg delivery through the tract plays a critical role in activating such search. We found that females start to exhibit acetic acid (AA) attraction prior to depositing each egg but no attraction when they are not laying eggs. Artificially distending the reproductive tract triggers AA attraction in non-egg-laying females, whereas silencing the mechanosensitive neurons we identified that can sense the contractile status of the tract eliminates such attraction. Our work uncovers the circuit basis of an important reproductive need of Drosophila females and provides a simple model for dissecting the neural mechanism that underlies a reproductive need-induced behavioral modification.

Visual responses to contrast-defined contours with equally spatial-scaled carrier in cat area 18.

Contrast-defined contours are one type of second-order contours, across which there are no differences in luminance. Although they can be always perceived, their responses have been only investigated when the spatial frequency of carrier, the background texture whose contrast is modulated to form contours, is much higher than that of contrast-defined contours, due to the interference of responses to luminance contours in other cases. In the present study, we examined visual responses in cat area 18 to the contrast-defined contours with carrier at same spatial frequency equal to neuron's preferred value for luminance contours, by establishing a control stimulus including all the luminance components but lack of the contrast contour information. Using single unit recording and intrinsic optical imaging, we demonstrated that contrast gratings with equally spatial-scaled carrier induced responses in a proportion of cat area 18 neurons with the preferred orientation similar to that for luminance contours, and the responses generated orientation maps similar to those for luminance contours. Our finding suggests that early visual cortex can process second-order contours regardless of the spatial frequency of carriers, in a way similar to the processing of luminance contours. This uniform manner of early visual processing might underlie the visual detection of both luminance contours and non-luminance second-order contours.