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Methadone (MTD) is a commonly prescribed treatment for opioid use disorder in pregnancy, despite limited information on the effects of passive exposure on fetal brain development. Animal studies suggest a link between perinatal MTD exposure and impaired white matter development. In this study, we characterized the effect of perinatal MTD exposure through the evaluation of oligodendrocyte development and glial cell activation in the neonatal rat brain. Six pregnant Sprague Dawley rat dams were randomized to MTD (0.2 mL/L) or untreated drinking water from embryonic day 7. Pups were terminated at postnatal day 7 and tissue sections were harvested from six randomly selected pups (one male and one female per litter) of each experimental group for immunohistochemistry in areas of corpus callosum (CC), lateral CC, external capsule (EC), and cerebellar white matter. In the MTD-exposed rat pups, myelination was significantly decreased in the CC, lateral CC, EC, and arbor vitae compared with the controls. The increased density and percentage of oligodendrocyte precursor cells (OPCs) were observed in the CC and cerebellar white matter. The highly active proliferation of OPCs as well as decreased density and percentage of differentiated oligodendrocytes were found in the cerebellum but no differences in the cerebrum. Apoptotic activities of both differentiated oligodendrocytes and myelinating oligodendrocytes were significantly increased in all regions of the cerebrum and cerebellum after MTD exposure. There was no quantitative difference in astrocyte, however, cell density and/or morphologic difference consistent with activation were observed in microglia throughout MTD-exposed CC and cerebellum. Taken together, perinatal MTD exposure reveals global attenuation of myelination, accelerated apoptosis of both differentiated and myelinating oligodendrocytes, and microglia activation, supporting an association between antenatal MTD exposure and impaired myelination in the developing brain.

Microneedles offer a convenient transdermal delivery route with potential for long term sustained release of drugs. However current microneedle technologies may not have the mechanical properties for reliable and stable penetration (e.g. hydrogel microneedles). Moreover, it is also challenging to realize microneedle arrays with large size and high flexibility. There is also an inherent upper limit to the amount and kind of drugs that can be loaded in the microneedles. In this paper, we present a new class of polymeric porous microneedles made from biocompatible and photo-curable resin that address these challenges. The microneedles are unique in their ability to load solid drug formulation in concentrated form. We demonstrate the loading and release of solid formulation of anesthetic and non-steroidal anti-inflammatory drugs, namely Lidocaine and Ibuprofen. Paper also demonstrates realization of large area (6 × 20 cm2) flexible and stretchable microneedle patches capable of drug delivery on any body part. Penetration studies were performed in an ex vivo porcine model supplemented through rigorous compression tests to ensure the robustness and rigidity of the microneedles. Detailed release profiles of the microneedle patches were shown in an in vitro skin model. Results show promise for large area transdermal delivery of solid drug formulations using these porous microneedles.

Breathing is a singularly robust behavior, yet this motor pattern is continuously modulated at slow and fast timescales to maintain blood-gas homeostasis, while intercalating orofacial behaviors. This functional multiplexing goes beyond the rhythmogenic function that is typically ascribed to medullary respiration-modulated networks and may explain lack of progress in identifying the mechanism and constituents of the respiratory rhythm generator. By recording optically along the ventral respiratory column in medulla, we found convergent evidence that rhythmogenic function is distributed over a dispersed and heterogeneous network that is synchronized by electrotonic coupling across a neuronal syncytium. First, high-speed recordings revealed that inspiratory onset occurred synchronously along the column and did not emanate from a rhythmogenic core. Second, following synaptic isolation, synchronized stationary rhythmic activity was detected along the column. This activity was attenuated following gap junction blockade and was silenced by tetrodotoxin. The layering of syncytial and synaptic coupling complicates identification of rhythmogenic mechanism, while enabling functional multiplexing.

Monsoon southerlies can be particularly active for days and produce substantial rainfall over East Asia. These multiday episodes of southerly monsoon surge may exhibit distinct diurnal variations due to regional forcings under given large-scale conditions. This study categorizes the southerly surges into two types with different wind diurnal variations to clarify their influence on rainfall over East Asia. In the summers of 1998–2019, there are 63 episodes of southerly surges with large wind diurnal cycles and 55 episodes with small diurnal cycles. The first type of southerly surges usually occurs with anomalous low-level warming over southeastern China related to the westward extension of the western Pacific subtropical high. The second type of southerly surges instead occurs with anomalous cooling due to the deepened midlatitude trough. They thus represent the different mechanisms downscaling from large-scale conditions to regional diurnal forcings. After the onset of the first type, the intensified monsoon southerlies at night lead to the northward displacement of large-scale ascent and northward water vapor transport with warm moist energy. The monsoon rainband tends to move to the north of 35°N with a robust response in precipitation systems, especially in the meso-α-scale rain events from midnight to morning. As a comparison, the rainband stays at 30°–35°N after the onset of the second type when the strengthened large-scale ascent and water vapor convergence are located relatively south. These differences between the two types of southerly monsoon surges highlight that the multiday large-scale conditions interact with subdaily regional forcings and greatly regulate the detailed evolution of summer rainband over East Asia.

Economical sensing and recording of temperature are important in the transportation and management of fragile goods such as medicine, fish/poultry, and other temperature-sensitive items. Existing approaches measure the entire temperature profile using electronic devices running on a continuous power source. This letter presents a simple, intelligent, and battery-free solution for capturing interesting temperature events using the natural thermo-mechanical state of a shape memory alloy (SMA). Our approach utilizes the temperature variation induced irreversible configuration of SMA, which provides a natural ability to capture the temperature history without the need for electronic data logging. In this letter, SMA is used to record the threshold temperature violation event. A prototype antenna is shown to monitor the temperature at 30 $^\circ$ C with a $\pm$ 1 $^\circ$ C error. A difference of 17 dB in frequency response was observed with and without temperature violation. Detailed design and experimental studies have been performed to validate the proposed approach.

BackgroundPrevious studies have established several animal models for experimental autoimmune uveitis (EAU) in rodents without the fovea centralis in the human retina. This study aimed to develop and explore the application of a novel EAU model in tree shrews with a cone-dominated retina resembling the human fovea.MethodsTree shrews were clinically and pathologically evaluated for the development and characteristics of EAU immunized with six inter-photoreceptor retinoid-binding proteins (IRBPs). IRBP-specific T-cell proliferation and serum cytokine of tree shrews were evaluated to determine the immune responses. Differentially expressed genes (DEGs) were identified in the eyes of tree shrews with EAU by RNA-sequencing. The disruptive effects of the DEG RGS4 inhibitor CCG 203769 and dihydroartemisinin on the EAU were investigated to evaluate the potential application of tree shrew EAU.ResultsIRBP1197–1211and R14 successfully induced chronic EAU with subretinal deposits and retinal damage in the tree shrews. The immunological characteristics presented the predominant infiltration of microglia/macrophages, dendritic cells, and CD4-T-cells into the uvea and retina and pathogenic T helper (Th) 1 and Th17 responses. The subretinal deposits positively expressed amyloid β-protein (Aβ), CD8, and P2Y purinoceptor 12 (P2RY12). The crucial DEGs in R14-induced EAU, such asP2RY2andadenylate cyclase 4 (ADCY4), were enriched for several pathways, including inflammatory mediator regulation of transient receptor potential (TRP) channels. The upregulatedRGS4in IRBP-induced EAU was associated with mitogen-activated protein kinase (MAPK) activity. RGS4 inhibition and dihydroartemisinin could significantly alleviate the retinal pathological injuries of IRBP1197-1211-induced EAU by decreasing the expression of CD4 T-cells.ConclusionOur study provides a novel chronic EAU in tree shrews elicited by bovine R14 and tree shrew IRBP1197-1211characterized by retinal degeneration, retinal damage with subretinal Aβ deposits and microglia/macrophage infiltration, and T-cell response, probably by altering important pathways and genes related to bacterial invasion, inflammatory pain, microglial phagocytosis, and lipid and glucose metabolism. The findings advance the knowledge of the pathogenesis and therapeutics of the fovea-involved visual disturbance in human uveitis.

Economical sensing and recording of temperature are important in the transportation and management of sensitive goods such as medicine. Existing approaches measure the entire temperature profile using electronic devices running on a continuous power source. This letter presents a simple, intelligent, and battery-free solution for capturing informative temperature events using the natural thermo-mechanical state of a shape memory alloy (SMA). This approach utilizes the temperature-induced irreversible mechanical deformation of the SMA as a natural way to capture the temperature history without the need for electronic data logging. In this letter, a two-way SMA-based sensor is used to record both high and low temperature peak events. The reading utilizes a smartphone to visualize and quantify temperature-induced deformation for monitoring. Detailed design and experimental studies have been performed to validate the proposed approach.

Multiple sclerosis is an autoimmune disease in which the immune system attacks the myelin sheath in the central nervous system. It is characterized by blood-brain barrier dysfunction throughout the course of multiple sclerosis, followed by the entry of immune cells and activation of local microglia and astrocytes. Glial cells (microglia, astrocytes, and oligodendrocyte lineage cells) are known as the important mediators of neuroinflammation, all of which play major roles in the pathogenesis of multiple sclerosis. Network communications between glial cells affect the activities of oligodendrocyte lineage cells and influence the demyelination-remyelination process. A finely balanced glial response may create a favorable lesion environment for efficient remyelination and neuroregeneration. This review focuses on glial response and neurodegeneration based on the findings from multiple sclerosis and major rodent demyelination models. In particular, glial interaction and molecular crosstalk are discussed to provide insights into the potential cell- and molecule-specific therapeutic targets to improve remyelination and neuroregeneration.

To overcome the shortcoming of conventional transarterial chemoembolization (cTACE) like high systemic release, a novel droplet-based flow-focusing microfluidic device was fabricated and the biocompatible poly(lactic-co-glycolic acid) (PLGA) magnetic drug-eluting beads transarterial chemoembolization (TACE) microspheres with tunable size and shell thickness were prepared via this device. Paclitaxel, as a model active, was loaded through O/O/W emulsion method with high efficiency. The size and the shell thickness vary when adjusting the flow velocity and/or solution concentration, which caters for different clinical requirements to have different drug loading and release behavior. Under the designed experimental conditions, the average diameter of the microspheres is 60 ± 2 μm and the drug loading efficiency has reached 6%. The drug release behavior of the microspheres shows the combination of delayed release and smoothly sustained release profiles and the release kinetics differ within different shell thickness. The microspheres also own the potential of magnetic resonance imaging (MRI) visuality because of the loaded magnetic nanoparticles. The microsphere preparation method and device we proposed are simple, feasible, and effective, which have a good application prospect.

Although erythropoietin (EPO) has been proven to significantly promote the proliferation of cancer cells, the mechanism for promoting glioma proliferation is poorly understood. Here, we examined the functional role of the AKT/GSK-3β/β-catenin signaling pathway in the EPO-mediated proliferation of glioma. The distribution of EPO and Ki-67 among clinical samples with different WHO grades was plotted by Immunological Histological Chemistry analysis. U87 and U251 glioma cell lines were treated with short hairpin RNA targeting (shEPO), recombinant human erythropoietin (rhEPO) and/or AKT-specific inhibitor (MK-2206). The changes in phosphorylated AKT, nuclear β-catenin, cyclin D1 and p27kip1 expression were detected. Cell cycle distributions and glioma proliferation in vitro and in vivo were analyzed. The expression level of EPO was significantly elevated with the increase of WHO grade and Ki67 in clinical glioma specimens. In vitro, knockdown of endogenous EPO in U87 and U251 cells effectively block the phosphorylation of AKT and GSK-3β and the expression of nuclear β-catenin. shEPO treatment also significantly decreased the expression of cyclin D1 and increased the expression of p27kip1. The cell cycle transition then slowed down and the proliferation of glioma cells or mouse xenograft tumors both decreased. Treatment of cells or tumors with extra rhEPO reversed the above biological effects mediated by shEPO. rhEPO-induced activation of the AKT/GSK-3β/β-catenin pathway and proliferation were abolished by MK-2206. Our study identified the AKT/GSK-3β/β-catenin axis as a critical mediator of EPO-induced glioma proliferation and further provided a clinically significant dimension to the biology of EPO.

Successive mesoscale convective systems may develop for several days during the mei-yu season (June–July) over eastern China. They can yield excessive rainfall in a narrow latitudinal band (called a corridor), causing severe floods. The climatology of rainfall corridors and related environmental factors are examined using 20 yr of satellite rainfall and atmospheric data. A total of 93 corridors are observed over eastern China, with maximum occurrence at 27°–31°N. They typically last 2–3 days, but some persist ≥4 days, with an extreme event lasting 11 days. These multiday convective episodes exhibit primary and secondary peaks in the morning and afternoon, respectively, with a diurnal cycle that is in contrast to other afternoon-peak rain events. On average, the corridors occur in ~23% days of the mei-yu season, but they can contribute ~51% of the total rainfall. They also vary with years and explain ~70% of the interannual variance of mei-yu-season rainfall. Composite analyses show that most corridors develop along zonally oriented quasi-stationary mei-yu fronts over central China where monsoon southwesterlies converge with northerly anomalies from the midlatitudes. The monsoon flow accelerates at ~0200 LST and forms a regional wind maximum or low-level jet over South China, which induces moisture flux convergence in morning-peak corridors. The nocturnal acceleration is less evident for afternoon-peak corridors. The mei-yu front and monsoon southwesterlies also influence the corridor’s duration, which is regulated by a dipole of geopotential anomalies, with positive in the tropics and negative in the midlatitudes. The dipole expresses a joint influence of the blocking patterns in midlatitudes and the El Niño–related anomalous high over the western Pacific Ocean, and the dipole's intensity explains well the interannual variations of the corridors.

Multiscale processes from synoptic disturbances to diurnal cycles during the record-breaking heavy rainfall in summer 2020 were examined in this study. The heavy rainfall consisted of eight episodes, each lasting about 5 days, and were associated with two types of synoptic disturbances. The Type-1 episodes featured a northwestward extending western Pacific subtropical high (WPSH), while the Type-2 episodes had approaching midlatitude troughs with southward retreat in the WPSH. Each heavy rainfall episode had 2–3 occurrences of nocturnal low-level jets (NLLJs), in close association with intense rainfall in the early morning. The NLLJs formed partly due to the geostrophic wind by increased pressure gradients under both types of synoptic disturbances. The NLLJs were also driven by the ageostrophic wind that veered to maximum southerlies at late night due to the boundary-layer inertial oscillation. The diurnal amplitudes of low-level southerlies increased remarkably after the onset of Type-1 episodes, in which the extending WPSH provided strong daytime heating from solar radiation. By contrast, the wind diurnal amplitudes were less changed after the onset of Type-2 episodes. The NLLJs strengthened the mesoscale mean ascent, net moisture flux convergence, and convective instability in elevated warm moist air, which led to the upscale growth of MCSs at the northern terminus of the LLJ after midnight. The MCSs-induced Meiyu rainband was re-established in Central China during the Type-1 episodes with the increased diurnal variations. The findings highlight that the regional diurnal cycles of low-level winds in response to synoptic disturbances can strongly regulate mesoscale convective activities in a downscaling manner, and thus produce heavy rainfall.

Wearables have garnered significant attention in recent years not only as consumer electronics for entertainment, communications, and commerce but also for real-time continuous health monitoring. This has been spurred by advances in flexible sensors, transistors, energy storage, and harvesting devices to replace the traditional, bulky, and rigid electronic devices. However, engineering smart wearables that can seamlessly integrate with the human body is a daunting task. Some of the key material attributes that are challenging to meet are skin conformability, breathability, and biocompatibility while providing tunability of its mechanical, electrical, and chemical properties. Electrospinning has emerged as a versatile platform that can potentially address these challenges by fabricating nanofibers with tunable properties from a polymer base. In this article, we review advances in wearable electronic devices and systems that are developed using electrospinning. We cover various applications in multiple fields including healthcare, biomedicine, and energy. We review the ability to tune the electrical, physiochemical, and mechanical properties of the nanofibers underlying these applications and illustrate strategies that enable integration of these nanofibers with human skin.

Background: Previous studies have established several animal models for experimental autoimmune uveitis (EAU) in rodents without the human fovea. This study aimed to develop and disrupt the application of a novel EAU model in tree shrews with a cone-dominated retina resembling the human fovea.Methods: Tree shrews were immunized with six inter-photoreceptor retinoid-binding proteins (IRBPs) in Freund’s adjuvant. Immunized tree shrews were clinically and pathologically evaluated for the development and characteristics of EAU. IRBP-specific T-cell proliferation and serum cytokine production of tree shrews were evaluated to determine immune responses. Gene-expression profiles were analyzed in the eyes of tree shrews under EAU immunization with screened IRBP to identify differentially expressed genes (DEGs). The disruptive effects of the DEG RGS4 inhibitor CCG 203769 and dihydroartemisinin on the EAU were investigated to evaluate the potential application of tree shrew EAU.Results: Tree shrew IRBP1197–1211 and bovine R14 successfully induced chronic EAU with predominate features of mild vasculitis, diffuse inflammatory infiltration, and retinal damage in the tree shrews. Immunohistological results showed that ionized calcium–binding adaptor molecule-1 (Iba-1)+ macrophages, purinergic receptor P2Y, G-protein–coupled 12 (P2RY12)+ microglia, and CD11c+ dendritic cells, CD4+ and CD8+ T-cells were the main infiltrating cells in the ciliary body, retina, and choroid during the development of disease. IRBP-specific lymphocyte proliferation and pathogenic T helper (Th) 1 and Th17 responses were observed in tree shrew EAU. DEGs in the R14 group were involved in regulation of cell-substrate adhesion, adenylate cyclase activity, and ruffle, and DEGs in the IRBP1197–1211 group were enriched in the supramolecular complex and the microtubule. In particular, the pathways of bacterial invasion of epithelial cells and inflammatory mediator regulation of TRP channels were significantly enriched in the R14 group. RGS4 inhibition and dihydroartemisinin can significantly alleviate the inflammatory severity of EAU by reducing the retinal pathological injuries after treatment.Conclusions: Our study first established a novel chronic EAU in tree shrews elicited by R14 and IRBP1197-1211, probably by altering important pathways and genes related to microglia infiltration, photoreceptor damages, and T-cell responses, thereby allowing the pathogenesis and therapeutics study of the fovea-involved visual disturbance in human uveitis.

Economical sensing and recording of temperatures are important for monitoring the supply chain. Existing approaches measure the entire temperature profile over time using electronic devices running on a battery. This paper presents a simple, intelligent, battery-free solution for capturing key temperature events using the natural thermo-mechanical state of a Shape Memory Alloy (SMA). This approach utilizes the temperature-induced irreversible mechanical deformation of the SMA as a natural way to capture the temperature history without the need for electronic data logging. In this article, two-way SMA is used to record both high-temperature and low-temperature peak events. Precise thermo-mechanically trained SMA are employed as arms of the dipole antenna for Radio Frequency (RF) readout. The fabricated antenna sensor works at 1 GHz and achieves a sensitivity of 0.24 dB/°C and −0.16 dB/°C for recording temperature maxima and minima, respectively.

A succession of MCSs developed during the last week of October 2016 and produced extreme heavy rainfall in central China. The event underwent an evident shift from a mei-yu-like warm scenario to an autumn cold scenario. Diurnal cycles of rainfall and low-level winds may be modulated by the shifting of large-scale atmospheric conditions. We conducted observational analyses and numerical experiments to examine how large-scale circulations influenced rainfall systems through diurnally varying processes. The results show that, in the first half (warm) period of the event, intense rainfall mostly occurred in eastern-central China with an early morning peak. It was closely related to a nocturnal southwesterly low-level jet (NLLJ) on the flank of the western Pacific subtropical high. The NLLJ formed near midnight in southern China where ageostrophic wind rotated clockwise due to Blackadar’s inertial oscillation. The NLLJ extended downstream to central China during the predawn hours due to the horizontal advection of momentum. Both the formation and extension of the NLLJ were supported by an enhanced subtropical high that provided relatively warm conditions with surface heating for boundary layer inertial oscillation and strong background southwesterly winds for momentum transport. The NLLJ induced MCSs at its northern terminus where the low-level ascent, moisture flux convergence, and convective instability were enhanced during the predawn hours. In the second half period with an intrusion of cold air, the diurnal amplitude of low-level winds became small under relatively cold and cloudy conditions. Moderate rainfall tended to occur in western-central China with a peak after midnight, most likely due to frontogenetic processes, upslope lifting, and nighttime cloud-top cooling.

Background Silk fibroin hydrogel, derived from Bombyx mori cocoons, has been shown to have potential effects on wound healing due to its excellent biocompatibility and less immunogenic and biodegradable properties. Many studies suggest silk fibroin as a promising material of wound dressing and it can support the adhesion and proliferation of a variety of human cells in vitro. However, lack of translational evidence has hampered its clinical applications for skin repair. Herein, a heparin-immobilized fibroin hydrogel was fabricated to deliver FGF1 (human acidic fibroblast growth factor 1) on top of wound in rats with full-thickness skin excision by performing comprehensive preclinical studies to fully evaluate its safety and effectiveness. The wound-healing efficiency of developed fibroin hydrogels was evaluated in full-thickness wound model of rats, compared with the chitosan used clinically. Results The water absorption, swelling ratio, accumulative FGF1 releasing rate and biodegradation ratio of fabricated hydrogels were measured. The regenerated fibroin hydrogels with good water uptake properties rapidly swelled to a 17.3-fold maximum swelling behavior over 12 h and a total amount of 40.48 ± 1.28% hydrogels was lost within 15 days. Furthermore, accumulative releasing data suggested that heparinized hydrogels possessed effective release behavior of FGF1. Then full-thickness skin excision was created in rats and left untreated or covered with heparinized fibroin hydrogels-immobilized recombinant human FGF1. The histological evaluation using hematoxylin and eosin (HE) and Masson’s trichrome (MT) staining was performed to observe the dermic formation and collagen deposition on the wound-healing site. To evaluate the wound-healing mechanisms induced by fibroin hydrogel treatment, wound-healing scratch and cell proliferation assay were performed. it was found that both fibroin hydrogels and FGF1 can facilitate the migration of fibroblast L929 cells proliferation and migration. Conclusion This study provides systematic preclinical evidence that the silk fibroin promotes wound healing as a wound-healing dressing, thereby establishing a foundation toward its further application for new treatment options of wound repair and regeneration.

Devices that can morph their functions on demand provide a rich yet unexplored paradigm for the next generation of electronic devices and sensors. For example, an antenna that can morph its shape can be used to adapt communication to different wireless standards or improve wireless signal reception. We utilize temperature-sensitive shape memory alloys (SMA) to realize a shape morphing antenna (ShMoA). In the designed architecture, multiple conjoined shape memory alloy sections form the antenna. The shape morphing of this antenna is achieved through temperature control. Different temperature threshold levels are used for programming the shape. Besides its conventional use for RF applications, ShMoA can serve as a multi-level temperature sensor, analogous to thermoreceptors in an insect antenna. ShMoA essentially combines the function of temperature sensing, embedded computing for detection of threshold crossings, and radio frequency readout, all in the single construct of a shape-morphing antenna (ShMoA) without the need for any battery or peripheral electronics. The ShMoA can be employed as bio-inspired wireless temperature sensing antennae on mobile robotic flies, insects, drones and other robots. It can also be deployed as programmable antennas for multi-standard wireless communication.

The study hopes to define the most obvious consumption habits of Generation Z people. The research aims to describe a typical customer pattern of Generation Z people where their shopping behavior can be clearly displayed. This research seeks to conclude the difference between Generation Z people from United States and China in terms of consumption habit reflected by related data. According to the data analysis method, this research uses a quantitative data analysis method based on source data from social media platforms. The research seeks to provide a deep understanding of Generation Z people in the aspect of consumption, which may help to design products, advertisements and delivery methods. Machine learning models include regression models and classification models are built to help user behavior prediction and the construction of consumer recommendation systems.

Datacenter is an important product of information society and an important supporting part for the development of new Internet businesses. With the emergence of a large number of new Internet technologies, the network demand and data traffic of users are growing rapidly. Datacenter needs larger data capacity and better system performance. High-speed optical interconnection technology has attracted more and more attention and become the main solution to the problem of traffic growth in datacenter, with its characteristics of high bandwidth, low loss and low cost. In this paper, several mainstream signal modulation formats, digital signal processing (DSP) compensation algorithms and signal damage compensation algorithms are investigated for intra datacenter optical interconnection and inter/extended datacenter optical interconnection, respectively. Their principles, performance, advantages and disadvantages are analyzed and compared in detail, and the future development of datacenter optical transmission is prospected.

Purpose: Previous studies have shown that parental abnormal physiological conditions such as inflammation, stress, and obesity can be transferred to offspring. The purpose of this study was to investigate the impact of parental uveitis on the development and susceptibility to experimental autoimmune uveitis (EAU) in offspring. Methods: Parental male and female B10RIII mice were immunized with interphotoreceptor retinoid binding protein (IRBP) 161–180 in complete Freund's adjuvant and were immediately allowed to mate. Gross examination of the offspring gestated with EAU was performed to determine the influence of parental uveitis on offspring development after birth. Gene expression profiles were analyzed in the affected eyes of offspring under EAU to identify differentially expressed genes (DEGs). Adult offspring were given 5, 25, and 50 μg IRBP161−180 to compare their susceptibility to EAU. Immunized mice were clinically and pathologically evaluated for the development of EAU. Ag-specific T-cell proliferation and IL-17 production from spleens and lymph nodes were evaluated on day 14 or 35 after immunization. Results: Hair loss, delay of eye opening, and swollen spleens in the offspring from parents with uveitis were observed from day 14 to 39 after birth. DEGs were involved in the immune system process, muscle system process, and cell development. The altered antigen processing and presentation, cell adhesion molecules, and phagosome in the eyes of the offspring from uveitis-affected parents were enriched. Offspring gestated with EAU showed a susceptibility to EAU and an earlier onset and higher severity of EAU compared to the control group mice. IRBP-specific lymphocyte proliferation and IL-17 production were observed in the EAU offspring with exposure to parental uveitis. Conclusions: The results suggest that mouse parents with uveitis can increase their offspring's susceptibility to EAU, probably through altering cell adhesion molecules and antigen processing and presentation related to the T-cell proliferation and Th17 response.

The complex features of rainfall diurnal cycles at the south China coast are examined using hourly rain gauge data and satellite products (CMORPH and TRMM 3B42) during 1998–2014. It is shown that morning rainfall is pronounced near the coasts and windward mountains, with high rainfall in the summer monsoon season, while afternoon rainfall is dominant on land, and nocturnal rainfall occurs at northern inland sites. Both satellite products report less morning rainfall and more afternoon rainfall than the rain gauge data, and they also miss the midnight rainfall minimum. These errors are mainly attributable to an underestimation of morning moderate and intense rains at coasts and an overestimation of afternoon–evening light rains on land. With a correction of the systematic bias, satellite products faithfully resolve the spatial patterns of normalized rainfall diurnal cycles related to land–sea contrast and terrains, suggesting an improved data application for regional climate studies. In particular, they are comparable to the rain gauge data in showing the linear reduction of morning rainfall from coasts to inland regions. TRMM is marginally better than CMORPH in revealing the overall features of diurnal cycles, while higher-resolution CMORPH captures more local details. All three datasets also present that morning rainfall decreases from May–June to July–August, especially on land; it exhibits pronounced interannual variations and a decadal increase in 1998–2008 at coasts. Such long-term variations of morning rainfall are induced by the coastal convergence and mountain liftings of monsoon shear flow interacting with land breeze, which is mainly regulated by monsoon southwesterly winds in the northern part of the South China Sea.

Background Gliomas account for the major part of primary brain tumors. Based on their histology and molecular alternations, adult gliomas have been classified into four grades, each with distinct biology and outcome. Previous studies have focused on cell-line-based models and patient-derived xenografts (PDXs) from patient-derived glioma cultures for grade IV glioblastoma. However, the PDX of lower grade diffuse gliomas, particularly those harboring the endogenous IDH mutation, are scarce due to the difficulty growing glioma cells in vitro and in vivo. The purpose of this study was to develop a panel of patient-derived subcutaneous xenografts of different grade gliomas that represented the heterogeneous histopathologic and genetic features of human gliomas. Methods Tumor pieces from surgical specimens were subcutaneously implanted into flanks of NOD-Prkdcscid ll2rgnull mice. Then, we analyzed the association between the success rate of implantation with clinical parameters using the Chi square test and resemblance to the patient’s original tumor using immunohistochemistry, immunofluorescence, short tandem repeat analysis, quantitative real-time polymerase chain reaction, and whole-exome sequencing. Results A total of 11 subcutaneous xenografts were successfully established from 16 surgical specimens. An increased success rate of implantation in gliomas with wild type isocitrate dehydrogenase (IDH) and high Ki67 expression was observed compared to gliomas with mutant IDH and low Ki67 expression. Recurrent and distant aggressive xenografts were present near the primary implanted tumor fragments from WHO grades II to IV. The xenografts histologically represented the corresponding patient tumor and reconstituted the heterogeneity of different grade gliomas. However, increased Ki67 expression was found in propagated xenografts. Endothelial cells from mice in patient-derived xenografts over several generations replaced the corresponding human tumor blood vessels. Short tandem repeat and whole-exome sequencing analyses indicated that the glioma PDX tumors maintained their genomic features during engraftments over several generations. Conclusions The panel of patient-derived glioma xenografts in this study reproduced the diverse heterogeneity of different grade gliomas, thereby allowing the study of the growth characteristics of various glioma types and the identification of tumor-specific molecular markers, which has applications in drug discovery and patient-tailored therapy.

Additional file 2: Figure S1. Proliferation activity and vessels of the patient’s primary tumor and xenografts. Proliferation index was analyzed by immunohistochemistry against anti-human Ki-67 and then calculated the positive cell rate of patient gliomas and corresponding xenografts. Compared with patients, a significant increase was observed in xenografts (P = 0.035).

Additional file 1: Table S1. Semi-quantitative analysis of immunehistochemistry of primary tumors and xenograft tumors.

BACKGROUND: Acute type A aortic dissection (TAAD) is cardiovascular emergency and requires surgical interventions. In-hospital mortality rate of surgical-treated TAAD patients remains high. We aim to examine the prognostic implications of peri-operative parameters to identify high-risk patient for in-hospital mortality. METHODS: A total of 264 surgically treated TAAD patients were included in this study. The association between in-hospital mortality and peri-operative parameters were examined. RESULTS: Thirty patients (11.36%) died during hospitalization. Patients with higher Apache II score had a significantly higher rate of in-hospital mortality when compared with patients scored ≤20 in unadjusted model [Score 21–25: HR =12.9 (1.7–100.8), P=0.0148; Score >25: HR =94.5 (12.6–707.6), P120 mmHg, Cr >200 mmol/L (both at admission and after surgery), BUN >8.2 mmol/L (both at admission and after surgery), AST >80 µ/L, aortic cross-clamping time >120 min and cardiopulmonary bypass time (CPBT) >230 min were also significantly related to higher rate of in-hospital mortality in univariate analysis. In multivariable analysis, APACHE II score [Score 21–25: HR =9.5 (1.2–74.4), P=0.032; Score >25: HR =51.0 (6.7–387.7), P=0.0001], AST >80 µmol/L [HR =2.3 (1.1–4.8), P=0.0251], aortic cross-clamping time >120 min (HR =2.9 (1.1–7.7), P=0.0315) remained significant in predicting TAAD in-hospital mortality. CONCLUSIONS: APACHE II score could be a useful tool to predict TAAD in-hospital mortality. AST >80 µ/L and aortic cross-clamping time >120 min were also independent predictors.

The aim of the present study was to explore the possible mechanisms by which hypertonic saline (HS) effectively ameliorates cerebral oedema via the vascular endothelial growth factor receptor 2 (VEGFR2)-mediated endothelial nitric oxide synthase (eNOS) pathway of endothelial cells in rats. A middle cerebral artery occlusion (MCAO) model in Sprague-Dawley rats and an oxygen-glucose deprivation (OGD) model in cells were used in the present study. Evans blue (EB) staining and a horseradish peroxidase flux assay were performed to evaluate the protective effect of 10% HS on the blood-brain barrier (BBB). The expression levels of vascular endothelial growth factor (VEGF), VEGFR2, zonula occludens 1 (ZO1) and occludin were quantified. The results demonstrated that 10% HS effectively reduced EB extravasation in the peri-ischaemic brain tissue. At 24 h after MCAO, the protein expression levels of VEGF and VEGFR2 in the peri-ischaemic brain tissue were downregulated following treatment with 10% HS. In vitro experiments demonstrated that the permeability of a monolayer endothelial cell barrier was decreased significantly following HS treatment. In addition, VEGF and VEGFR2 protein expression levels were increased in endothelial cells under hypoxic conditions, but that effect was suppressed by HS treatment. Furthermore, HS inhibited the downregulation of ZO1 and occludin effectively, possibly through the VEGFR2/phospholipase C γ1 (PLCγ1)/eNOS signalling pathway. In conclusion, 10% HS may alleviate cerebral oedema through reducing ischaemia-induced BBB permeability, as a consequence of inhibiting VEGFR2/PLCγ1/eNOS-mediated downregulation of ZO1 and occludin.

This paper proposes a low-noise readout circuit with a noise floor of 11 fArms/sq(Hz) and a bandwidth of 1.3 MHz. The novel electrostatic discharge (ESD) leakage current cancellation stage allows the circuit to detect sub-pA range current input. A total trans-impedance gain of 160 dB is obtained by a current preamplification stage with a 100 × current gain followed by a transimpedance amplifier (TIA) with a 1 Mohm feedback resistive gain. The reader is designed in a 0.18 μm CMOS process and consumes 5.6 mW from a 1.8 V supply.

Quantitative detection for nanomolar analytes is a challenge for surface-enhanced Raman scattering (SERS). In this report, a SERS method which combined with an internal standard method and a two-step centrifugation method was established for trace analysis of two drugs using a portable Raman spectrometer. Metformin hydrochloride was used as an internal standard for phenformin hydrochloride to increase the linearity of SERS detection, while, streptomycin sulfate was used for tigecycline. The two-step centrifugation method for sample preparation increased the density of hot spots and the concentration of analyte by accumulating silver nanoparticles. Therefore, the detection sensitivity was significantly improved. Furthermore, the repeatability of SERS signals was increased by adding 200 µL of the sample solution into a slit-type quartz cuvette to make the excitation light transmit through a heavy thickness sample solution. The RSDs of SERS signal intensity ratio of phenformin hydrochloride and tigecycline to internal standard were 1% and 1.6%, respectively. Finally, phenformin hydrochloride and tigecycline exhibited a good linearity in the range of 1–500 nM (R2 = 0.9976) and 10–750 nM (R2 = 0.9926), respectively. In a word, this method greatly improved the lower limit of quantitation of SERS, and laid foundation for rapid and convenient quantitative detection of low concentration drug in biological samples.

Word Sense Disambiguation (WSD), as a tough task in Natural Language Processing (NLP), aims to identify the correct sense of an ambiguous word in a given context. There are two mainstreams in WSD. Supervised methods mainly utilize labeled context to train a classifier which generates the right probability distribution of word senses. Meanwhile knowledge-based (unsupervised) methods which focus on glosses (word sense definitions) always calculate the similarity of context-gloss pair as score to find out the right word sense. In this paper, we propose a generative adversarial framework WSD-GAN which combines two mainstream methods in WSD. The generative model, based on supervised methods, tries to generate a probability distribution over the word senses. Meanwhile the discriminative model, based on knowledge-based methods, focuses on predicting the relevancy of the context-gloss pairs and identifies the correct pairs over the others. Furthermore, in order to optimize both two models, we leverage policy gradient to enhance the performances of the two models mutually. Our experimental results show that WSD-GAN achieves competitive results on several English all-words WSD datasets.

To overcome the shortcoming of drug-loaded nanoparticles, such as high initial burst release and wide size distribution, a novel manufacturing technique for core-shell structure nanoparticle was developed by combining microfluidic chip and electrohydrodynamic atomization. In this study, the mixture solution of the surfactant 1, 2- dipalmitoyl-sn-glycero-3-phosphoglycerol and the polymeric coating material polylactic-glycolic-acid was introduced into the outer microchannel of the microfluidic chip as the particle's shell. And the encapsulated drug paclitaxel was pumped into the inner microchannel as the core. Then, the particles with a nanoscale-size core-shell structure were generated by applying an electric field on the laminar flow which was formed in the microfluidic chip. Operation parameters, including working voltage, carrier material and surfactant concentration as well as liquid flow rates were optimized for nanoparticles generation. The properties of drug-loaded nanoparticles in terms of their particle size, zeta potential and encapsulation efficiency were investigated. Under the optimal experimental conditions, the particle size was approximately 145 nm and encapsulation efficiency reached 92%. Moreover, the drug release of these nanoparticles could be prolonged over a significant period for more than ten days. It can be expected that this innovative approach could provide a useful platform for drug-loaded core-shell nanoparticles developing.

Background Ischemic stroke is a major disease that threatens human health in ageing population. Increasing evidence has shown that neuroinflammatory mediators play crucial roles in the pathophysiology of cerebral ischemia injury. Notch signaling is recognized as the cell fate signaling but recent evidence indicates that it may be involved in the inflammatory response in activated microglia in cerebral ischemia. Previous report in our group demonstrated hypertonic saline (HS) could reduce the release of interleukin-1 beta and tumor necrosis factor-alpha in activated microglia, but the underlying molecular and cellular mechanisms have remained uncertain. This study was aimed to explore whether HS would partake in regulating production of proinflammatory mediators through Notch signaling. Results HS markedly attenuated the expression of Notch-1, NICD, RBP-JK and Hes-1 in activated microglia both in vivo and in vitro. Remarkably, HS also reduced the expression of iNOS in vivo, while the in vitro levels of inflammatory mediators Phos-NF-κB, iNOS and ROS were reduced by HS as well. Conclusion Our results suggest that HS may suppress of inflammatory mediators following ischemia/hypoxic through the Notch signaling which operates synergistically with NF-κB pathway in activated microglia. Our study has provided the morphological and biochemical evidence that HS can attenuate inflammation reaction and can be neuroprotective in cerebral ischemia, thus supporting the use of hypertonic saline by clinicians in patients with an ischemia stroke. Electronic supplementary material The online version of this article (doi:10.1186/s12868-017-0351-6) contains supplementary material, which is available to authorized users.