Exogenous Glycinebetaine Regulates the Contrasting Responses in Leaf Physiochemical Attributes and Growth of Maize under Drought and Flooding Stresses.

Flooding and drought are the two most devastating natural hazards limiting maize production. Exogenous glycinebetaine (GB), an osmotic adjustment agent, has been extensively used but there is limited research on its role in mitigating the negative effects of different abiotic stresses. This study aims to identify the different roles of GB in regulating the diverse defense regulation of maize against drought and flooding. Hybrids of Yindieyu 9 and Heyu 397 grown in pots in a ventilated greenhouse were subjected to flooding (2-3 cm standing layer) and drought (40-45% field capacity) at the three-leaf stage for 8 d. The effects of different concentrations of foliar GB (0, 0.5, 1.0, 5.0, and 10.0 mM) on the physiochemical attributes and growth of maize were tested. Greater drought than flooding tolerance in both varieties to combat oxidative stress was associated with higher antioxidant activities and proline content. While flooding decreased superoxide dismutase and guaiacol peroxidase (POD) activities and proline content compared to normal water, they all declined with stress duration, leading to a larger reactive oxygen species compared to drought. It was POD under drought stress and ascorbate peroxidase under flooding stress that played crucial roles in tolerating water stress. Foliar GB further enhanced antioxidant ability and contributed more effects to POD to eliminate more hydrogen peroxide than the superoxide anion, promoting growth, especially for leaves under water stress. Furthermore, exogenous GB made a greater increment in Heyu 397 than Yindieyu 9, as well as flooding compared to drought. Overall, a GB concentration of 5.0 mM, with a non-toxic effect on well-watered maize, was determined to be optimal for the effective mitigation of water-stress damage to the physiochemical characteristics and growth of maize.

Multivariate analysis compares and evaluates drought and flooding tolerances of maize germplasm.

Drought and flooding are the two most important environmental factors limiting maize (Zea mays L.) production globally. This study aimed to investigate the physiological mechanisms and accurate evaluation indicators and methods of maize germplasm involved in drought and flooding stresses. The twice replicated pot experiments with 60 varieties, combined with the field validation experiment with 3 varieties, were conducted under well-watered, drought, and flooding conditions. Most varieties exhibited stronger tolerance to drought than flooding due to higher antioxidant enzyme activities, osmotic adjustment substances, and lower reactive oxygen species. In contrast, flooding stress resulted in higher levels of reactive oxygen species (particularly O2-), ascorbate peroxidase, catalase, peroxidase, and soluble sugars but lower levels of superoxide dismutase, proline, and soluble protein compared with well-watered conditions. Superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, proline, soluble sugars, and protein contents, in addition to plant height, leaf area/plant, and stem diameter, were accurate and representative indicators for evaluating maize tolerance to drought and flooding stresses and could determine a relatively high mean forecast accuracy of 100.0% for the comprehensive evaluation value. A total of 4 principal components were extracted, in which different principal components played a vital role in resisting different water stresses. Finally, the accuracy of the 3 varieties screened by multivariate analysis was verified in the field. This study provides insights into the different physiological mechanisms and accurate evaluation methods of maize germplasm involved in drought and flooding stresses, which could be valuable for further research and breeding.

Microglial AIM2 alleviates antiviral-related neuro-inflammation in mouse models of Parkinson's disease.

Inflammasome involvement in Parkinson's disease (PD) has been intensively investigated. Absent in melanoma 2 (AIM2) is an essential inflammasome protein known to contribute to the development of several neurological diseases. However, a specific role for AIM2 in PD has not been reported. In this study, we investigated the effect of AIM2 in the N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD model by use of various knockout and bone marrow chimeric mice. The mechanism of action for AIM2 in PD was assessed by RNA-sequencing and in vitro primary microglial transfection. Results were validated in the A30P transgenic mouse model of PD. In the MPTP mouse model, AIM2 activation was found to negatively regulate neuro-inflammation independent of the inflammasome. Microglial AIM2 deficiency exacerbated behavioral and pathological features of both MPTP-induced and transgenic PD mouse models. Mechanistically, AIM2 reduced cyclic GMP-AMP synthase (cGAS)-mediated antiviral-related inflammation by inhibition of AKT-interferon regulatory factor 3 (IRF3) phosphorylation. These results demonstrate microglial AIM2 to inhibit the antiviral-related neuro-inflammation associated with PD and provide for a foundation upon which to identify new therapeutic targets for treatment of the disease.

A Flexible Carbon Nanotube Sen-Memory Device.

In a modern electronics system, charge-coupled devices and data storage devices are the two most indispensable components. Although there has been rapid and independent progress in their development during the last three decades, a cofunctionality of both sensing and memory at single-unit level is yet premature for flexible electronics. For wearable electronics that work in ultralow power conditions and involve strains, conventional sensing-and-memory systems suffer from low sensitivity and are not able to directly transform sensed information into sufficient memory. Here, a new transformative device is demonstrated, which is called "sen-memory", that exhibits the dual functionality of sensing and memory in a monolithic integrated circuit. The active channel of the device is formed by a carbon nanotube thin film and the floating gate is formed by a controllably oxidized aluminum nanoparticle array for electrical- and optical-programming. The device exhibits a high on-off current ratio of ≈106 , a long-term retention of ≈108 s, and durable flexibility at a bending strain of 0.4%. It is shown that the device senses a photogenerated pattern in seconds at zero bias and memorizes an image for a couple of years.

Flexible 64 × 64 Pixel AMOLED Displays Driven by Uniform Carbon Nanotube Thin-Film Transistors.

Carbon nanotube (CNT) thin-film transistors are expected to be promising for use in flexible electronics including flexible and transparent integrated circuits and in wearable chemical and physical sensors and for driving the circuits of flexible display panels. However, current devices based on CNT channels suffer from poor performance uniformity and low manufacturing yield; therefore, they are still far from being practical. This is usually caused by nonuniform deposition of the semiconducting CNTs and the rough surface of flexible substrates. Here, we report CNT thin-film transistors (TFTs) driving a flexible 64 × 64 pixel active matrix light-emitting diode display (AMOLED) by improving the formation of uniform CNT films and developing a new pretreatment technique for flexible substrates. The achieved AMOLED has uniform brightness and a high yield of 99.93% in its 4096 pixels. More than 8000 TFTs with high-purity semiconducting CNTs as the channel material show an average on-off current ratio of ∼107 and a carrier mobility of 16 cm2 V-1 s-1. The standard deviations of the on-state current and the carrier mobility are 4.1 and 6.5%, respectively. Our result shows that the panel driven by high-purity semiconducting CNTs is a promising strategy for the development of next-generation flexible, large-area displays.

Continuous Fabrication of Meter-Scale Single-Wall Carbon Nanotube Films and their Use in Flexible and Transparent Integrated Circuits.

Single-wall carbon nanotubes (SWCNTs), especially in the form of large-area and high-quality thin films, are a promising material for use in flexible and transparent electronics. Here, a continuous synthesis, deposition, and transfer technique is reported for the fabrication of meter-scale SWCNT thin films, which have an excellent optoelectrical performance including a low sheet resistance of 65 Ω/◽ with a transmittance of 90% at a wavelength of 550 nm. Using these SWCNT thin films, high-performance all-CNT thin-film transistors and integrated circuits are demonstrated, including 101-stage ring oscillators. The results pave the way for the future development of large-scale, flexible, and transparent electronics based on CNT thin films.

High-Throughput Fabrication of Flexible and Transparent All-Carbon Nanotube Electronics.

This study reports a simple and effective technique for the high-throughput fabrication of flexible all-carbon nanotube (CNT) electronics using a photosensitive dry film instead of traditional liquid photoresists. A 10 in. sized photosensitive dry film is laminated onto a flexible substrate by a roll-to-roll technology, and a 5 µm pattern resolution of the resulting CNT films is achieved for the construction of flexible and transparent all-CNT thin-film transistors (TFTs) and integrated circuits. The fabricated TFTs exhibit a desirable electrical performance including an on-off current ratio of more than 105, a carrier mobility of 33 cm2 V-1 s-1, and a small hysteresis. The standard deviations of on-current and mobility are, respectively, 5% and 2% of the average value, demonstrating the excellent reproducibility and uniformity of the devices, which allows constructing a large noise margin inverter circuit with a voltage gain of 30. This study indicates that a photosensitive dry film is very promising for the low-cost, fast, reliable, and scalable fabrication of flexible and transparent CNT-based integrated circuits, and opens up opportunities for future high-throughput CNT-based printed electronics.

Ultrahigh-performance transparent conductive films of carbon-welded isolated single-wall carbon nanotubes.

Single-wall carbon nanotubes (SWCNTs) are ideal for fabricating transparent conductive films because of their small diameter, good optical and electrical properties, and excellent flexibility. However, a high intertube Schottky junction resistance, together with the existence of aggregated bundles of SWCNTs, leads to a degraded optoelectronic performance of the films. We report a network of isolated SWCNTs prepared by an injection floating catalyst chemical vapor deposition method, in which crossed SWCNTs are welded together by graphitic carbon. Pristine SWCNT films show a record low sheet resistance of 41 ohm □-1 at 90% transmittance for 550-nm light. After HNO3 treatment, the sheet resistance further decreases to 25 ohm □-1. Organic light-emitting diodes using this SWCNT film as anodes demonstrate a low turn-on voltage of 2.5 V, a high current efficiency of 75 cd A-1, and excellent flexibility. Investigation of isolated SWCNT-based field-effect transistors shows that the carbon-welded joints convert the Schottky contacts between metallic and semiconducting SWCNTs into near-ohmic ones, which significantly improves the conductivity of the transparent SWCNT network. Our work provides a new avenue of assembling individual SWCNTs into macroscopic thin films, which demonstrate great potential for use as transparent electrodes in various flexible electronics.

Growth of semiconducting single-wall carbon nanotubes with a narrow band-gap distribution.

The growth of high-quality semiconducting single-wall carbon nanotubes with a narrow band-gap distribution is crucial for the fabrication of high-performance electronic devices. However, the single-wall carbon nanotubes grown from traditional metal catalysts usually have diversified structures and properties. Here we design and prepare an acorn-like, partially carbon-coated cobalt nanoparticle catalyst with a uniform size and structure by the thermal reduction of a [Co(CN)6](3-) precursor adsorbed on a self-assembled block copolymer nanodomain. The inner cobalt nanoparticle functions as active catalytic phase for carbon nanotube growth, whereas the outer carbon layer prevents the aggregation of cobalt nanoparticles and ensures a perpendicular growth mode. The grown single-wall carbon nanotubes have a very narrow diameter distribution centred at 1.7 nm and a high semiconducting content of >95%. These semiconducting single-wall carbon nanotubes have a very small band-gap difference of ∼0.08 eV and show excellent thin-film transistor performance.

Periventricular hyperintensities are associated with elevated cerebral amyloid.

OBJECTIVE: To investigate the association between periventricular white mater hyperintensities (PVWMH) and biomarkers of elevated cerebral ß-amyloid (Aß) in the Alzheimer's Disease Neuroimaging Initiative, a large prospective multicenter observational study. METHODS: The burden of frontal, parietal, and occipital PVWMH on 3T fluid-attenuated inversion recovery MRI was evaluated in 698 cognitively normal participants and participants with mild cognitive impairment (MCI) using a novel semiquantitative visual rating scale. Results were correlated with CSF-Aß, florbetapir-PET, and fluorodeoxyglucose (FDG)-PET. RESULTS: Increased burden of parietal, occipital, and frontal PVWMH was associated with elevated cerebral amyloid evidenced by high florbetapir-PET signal (p < 0.01) and low CSF-Aß (p < 0.01). In logistic regression models, including PVWMH, age, sex, APOE status, vascular risk factors, pulse pressure, vascular secondary prevention medications, education, ethnicity, and race, parietal, occipital, and frontal PVWMH burden was independently associated with high florbetapir-PET uptake (p < 0.05). In a similar logistic regression model, parietal and occipital (p < 0.05) but not frontal (p = 0.05) PVWMH were independently associated with CSF-Aß. Weaker associations were found between parieto-occipital PVWMH and elevated CSF-tau (p < 0.05) and occipital PVWMH and elevated CSF-phospho-tau (p < 0.05). PVWMH were associated with cerebral hypometabolism on FDG-PET independent of CSF-Aß levels (p < 0.05). Absolute and consistency of agreement intraclass correlation coefficients were, respectively, 0.83 and 0.83 for frontal, 0.78 and 0.8 for parietal, and 0.45 and 0.75 for occipital PVWMH measurements. CONCLUSIONS: Increased PVWMH were associated with elevated cerebral amyloid independent of potential confounders such as age, APOE genotype, and vascular risk factors. The mechanisms underlying the association between PVWMH and cerebral amyloid remain to be clarified.

Transurethral front-firing Greenlight bladder autoaugmentation for bladder contracture: technique and clinical outcomes.

OBJECTIVE: To describe a novel transurethral front-firing Greenlight bladder autoaugmentation for the treatment of bladder contracture and report initial clinical outcomes. METHODS: Between April 2014 and August 2015, five patients diagnosed with contracted bladder were all refractory to conservative treatment and received novel transurethral autoaugmentation. CT scan and urodynamics examination were conducted before operation for disease assessment. Mucosal and muscular layers of bladder wall in fundus were incised vertically and horizontally with front-firing Greenlight laser to enlarge bladder capacity in the operation. Imaging examination and periodical urodynamics study were performed to evaluate the clinical outcomes of the procedure in postoperative follow-up. RESULTS: Transurethral front-firing Greenlight bladder autoaugmentation was performed successfully on all the patients. The mean operative time was 59 min (range 52-65 min) with no significant blood loss. Urodynamic parameters of these patients after operation improved significantly compared with those before operation. Average maximum cystometric capacity (Vmax) increased from 91.2 to 333 ml (p < 0.01), average maximum flow rate (Qmax) ascended from 12.6 to 18.62 ml/min (p < 0.01), and average flow rate (Q(ave)) also increased from 5.74 to 13.18 ml/min (p < 0.01). At the last follow-up, all the patients could void spontaneously with good bladder emptying and their symptoms improved significantly. CONCLUSION: Our novel transurethral front-firing Greenlight bladder autoaugmentation is a safe and effective treatment for contracted bladders. Future studies with larger sample size and long-term follow-up are needed to confirm our findings.

[Movement Control of Striatum Neural Pathway].

Striatum is the central structure controlling movement. It plays a pivotal role in the regulation of voluntary movement, unconscious movement, muscle tone, posture adjustment and fine movement. Dysfunction of striatum causes a variety of movement disorders ranging from the hypokinetic disorders with increased muscle tone, such as Parkinson's disease, to the hyperkinetic disorders with decreased muscle tone, such as Huntington's disease. It is generally recognized that striatum receives the neural movement signals from the motor cortex, and then processes and modifies these signals and subsequently transfers the signals back to the motor cortex via thalamus for execution of the movement through pyramidal system. The movement control function of striatum depends on a complex neural circuit system. In this review, the studies on the movement control function of striatum as well as the striatal neural circuit system are summarized with an emphasis on the progress made during recent years for better understanding the mechanism underlying the movement control function as well as the disease association of striatum.

[Protein Kinase A and Lipid Metabolism].

Protein kinase A(PKA),as a pivotal factor in the cellular signal transduction,plays an es-sential role in the regulation of lipid metabolism.PKA activates the key lipases including hormone sensi-tive lipase (HSL)and adipose triglyceride lipase (ATGL)to promote the fat mobilization.PKA signaling up-regulates the mitochondrial thermogenesis by enhancing the expression of uncoupling protein-1 (UCP-1),which critically contributes to the body heat production.PKA is closely involved in the regulation of lipogenesis in the liver.Notably,the dysregulation of PKA signaling is associated with the pathogenic mechanisms underlying the obesity,cardiovascular diseases and diabetes mellitus.The pharmacological studies show that PKA is linked to the pharmacological effects of the major lipid regulating agents.In this review,the studies on roles of PKA in the regulation of lipid metabolism are summarized with an emphasis on progress made during the last five years for providing insights into the mechanism by which PKA regu-lates the lipid metabolism as well as the novel therapeutic strategy for lipid-metabolic diseases.

A review of safety-related pregnancy data surrounding the oral disease-modifying drugs for multiple sclerosis.

The recent approval of several oral disease-modifying drugs (DMDs) for multiple sclerosis (MS) brings promise of improved clinical effectiveness as well as greater drug compliance compared to the existing non-oral DMDs, and substantially increases patient choice and therapeutic options in the effective management of MS. However, for men and women with MS of childbearing age, concerns about the effect of oral DMDs on pregnancy and the fetus may arise. Some limited data from animal reproductive studies of oral DMDs suggest a potential increased risk of early pregnancy loss, impaired growth and birth defects. Although active surveillance mechanisms exist, there is limited data to inform clinical practice. Using existing information from published clinical trials and drug monographs, as well as recent conference proceedings, this review summarizes the mechanism of action (in relation to embryogenesis and pregnancy) and existing animal or human pregnancy-related data for approved (fingolimod, teriflunomide and dimethyl fumarate) and investigational (laquinimod and firategrast) oral DMDs for MS.

Safety of disease-modifying drugs for multiple sclerosis in pregnancy: current challenges and future considerations for effective pharmacovigilance.

When contemplating a pregnancy, women treated for multiple sclerosis (MS) with a disease-modifying drug must decide to discontinue their medication before conception or risk exposing their unborn child to potential drug toxicity. Few studies exist as reference for patients and physicians, and of those available, the majority are less than ideal due to real-world constraints, ethical issues and methodological shortcomings. The authors provide a brief summary of existing animal and human data with current recommendations regarding the safety of IFN-ß, glatiramer acetate, natalizumab, mitoxantrone, fingolimod and teriflunomide during pregnancy and lactation in women with MS. We also assess the quality, strengths and limitations of the existing studies including challenges with study design. The investigation of outcomes such as spontaneous abortion and congenital anomalies are highlighted with potential methodological improvements for future studies on drug safety in pregnancy suggested. The authors explore the pharmacokinetics and pharmacodynamics of the MS disease-modifying drugs for their possible mechanistic role in fetal harm and discuss the potential role of clinical trials. Future pharmacovigilance studies should continue to pursue multicenter collaboration with an emphasis on appropriate study design.

Disease-modifying drugs for multiple sclerosis in pregnancy: a systematic review.

OBJECTIVE: To systematically review the literature regarding safety of disease-modifying drug (DMD) use during pregnancy on perinatal and developmental outcomes in offspring of patients with multiple sclerosis (MS). METHODS: A PubMed and EMBASE search up to February 2012 was conducted with a manual search of references from relevant articles. Selected studies were evaluated using internationally accepted criteria. RESULTS: Fifteen studies identified 761 interferon ß-, 97 glatiramer acetate-, and 35 natalizumab-exposed pregnancies. Study quality ranged from poor to good; no study was rated excellent. Small sample sizes limited most studies. Compared with data for unexposed pregnancies, fair- to good-quality prospective cohort studies reported that interferon ß exposure was associated with lower mean birth weight, shorter mean birth length, and preterm birth (<37 weeks), but not low birth weight (<2,500 g), cesarean delivery, congenital anomaly (including malformation), or spontaneous abortion. Fewer studies of fair quality were available for glatiramer acetate and natalizumab. Glatiramer acetate exposure was not associated with lower mean birth weight, congenital anomaly, preterm birth, or spontaneous abortion. Natalizumab exposure did not appear to be associated with shorter mean birth length, lower mean birth weight, or lower mean gestational age. No studies examined mitoxantrone or fingolimod exposure. One study of paternal DMD use during conception found no effect on gestational age or birth weight. Few studies examined longer-term developmental outcomes. CONCLUSION: Further studies are needed to determine the potential risks associated with preconceptional and in utero DMD exposure in patients with MS. Discontinuation of DMDs before conception is still recommended.