Pathologically Activated Neuroprotection via Uncompetitive Blockade of \u3cem\u3eN\u3c/em\u3e-Methyl-d-aspartate Receptors with Fast Off-rate by Novel Multifunctional Dimer Bis(propyl)-cognitin

Uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists with fast off-rate (UFO) may represent promising drug candidates for various neurodegenerative disorders. In this study, we report that bis(propyl)-cognitin, a novel dimeric acetylcholinesterase inhibitor and γ-aminobutyric acid subtype A receptor antagonist, is such an antagonist of NMDA receptors. In cultured rat hippocampal neurons, we demonstrated that bis(propyl)-cognitin voltage-dependently, selectively, and moderately inhibited NMDA-activated currents. The inhibitory effects of bis(propyl)-cognitin increased with the rise in NMDA and glycine concentrations. Kinetics analysis showed that the inhibition was of fast onset and offset with an off-rate time constant of 1.9 s. Molecular docking simulations showed moderate hydrophobic interaction between bis(propyl)-cognitin and the MK-801 binding region in the ion channel pore of the NMDA receptor. Bis(propyl)-cognitin was further found to compete with [3H]MK-801 with a Ki value of 0.27 μm, and the mutation of NR1(N616R) significantly reduced its inhibitory potency. Under glutamate-mediated pathological conditions, bis(propyl)-cognitin, in contrast to bis(heptyl)-cognitin, prevented excitotoxicity with increasing effectiveness against escalating levels of glutamate and much more effectively protected against middle cerebral artery occlusion-induced brain damage than did memantine. More interestingly, under NMDA receptor-mediated physiological conditions, bis(propyl)-cognitin enhanced long-term potentiation in hippocampal slices, whereas MK-801 reduced and memantine did not alter this process. These results suggest that bis(propyl)-cognitin is a UFO antagonist of NMDA receptors with moderate affinity, which may provide a pathologically activated therapy for various neurodegenerative disorders associated with NMDA receptor dysregulation

The impact of subclinical hypothyroidism on growth and development in infants and young children aged 0 to 5 years

Introduction: The objective was to investigate the growth and development of infants and young children with mild subclinical hypothyroidism aged 0 to 5 years, especially those aged 0 to 2 years. Material and methods: The study was a retrospective analysis of the birth status, physical growth, and neuromotor development of patients aged 0 to 5 years, who were diagnosed with subclinical hypothyroidism during newborn screening (NBS) in Zhongshan between 2016 and 2019. Based on preliminary results, we compared 3 groups: with thyroid-stimulating factor (TSH) value of 5–10 mIU/L (442 cases), TSH value of 10–20 mIU/L (208 cases), and TSH above 20 mIU/L (77 cases). Patients with TSH value above 5 mIU/L were called back for repeat testing and were divided into 4 groups as follows: mild subclinical hypothyroidism group 1 with a TSH value of 5–10 mIU/L in both initial screening and repeat testing; mild subclinical hypothyroidism group 2 with TSH value above 10 mIU/L in initial screening; and TSH value of 5–10 mIU/L in repeat testing; the severe subclinical hypothyroidism group with TSH value of 10–20 mIU/L in both the initial screening and repeat testing and the congenital hypothyroidism group. Results: There were no significant differences in the maternal age, type of delivery, gender, length, and weight at birth between the preliminary groups; however, the gestational age at birth was significantly different (F = 5.268, p = 0.005). The z-score for length at birth was lower in the congenital hypothyroidism group compared to the other 3 groups but showed no difference at 6 months of age. The z-score for length in mild subclinical hypothyroidism group 2 was lower compared to the other 3 groups but showed no difference at 2–5 years of age. At 2 years of age there was no significant difference in the developmental quotient (DQ) of the Gesell Developmental Scale between the groups. Conclusion: The gestational age at birth affected the neonatal TSH level. Intrauterine growth in infants with congenital hypothyroidism was retarded compared to that of infants with subclinical hypothyroidism. Neonates with a TSH value of 10–20 mIU/L in the initial screening and a TSH value of 5–10 mIU/L in the repeat testing showed developmental delay at 18 months but caught up at age 2 years. There was no difference in neuromotor development between the groups. Levothyroxine in patients with mild subclinical hypothyroidism is not required, but we recommend that the growth and development of such infants and young children continues to be monitored

The Large Sky Area Multi-object Fiber Spectroscopic Telescope (LAMOST) Quasar Survey: Quasar Properties from Data Release Six to Nine

We report the fourth installment in the series of the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) Quasar Survey, which includes quasars observed between September, 2017 and June, 2021. There are in total 13,066 quasars reliably identified, of which 6,685 are newly discovered that are not reported in the SDSS DR14 quasar catalog or Million Quasars catalog. Because LAMOST does not provide accurate absolute flux calibration, we re-calibrate the spectra with the SDSS/Pan-STARRS1 multi-band photometric data. The emission line properties of H$\alpha$, H$\beta$, Mg\,{\sc ii} and C\,{\sc iv}, and the continuum luminosities are measured by fitting the re-calibrated spectra. We also estimate the single-epoch virial black hole masses ($\rm M_{BH}$) using the derived emission line and continuum parameters. This is the first time that the emission line and continuum fluxes were estimated based on LAMOST re-calibrated quasar spectra. The catalog and spectra for these quasars are available online. After the nine-year LAMOST quasar survey, there are in total 56,175 identified quasars, of which 24,127 are newly discovered. The LAMOST quasar survey not only discovers a great number of new quasars, but also provides a database for investigating the spectral variability of the quasars observed by both LAMOST and SDSS, and finding rare quasars including changing-look quasars and broad absorption line quasars.Comment: arXiv admin note: text overlap with arXiv:1811.01570, Accepted by ApJ

Fusarium head blight monitoring in wheat ears using machine learning and multimodal data from asymptomatic to symptomatic periods

The growth of the fusarium head blight (FHB) pathogen at the grain formation stage is a deadly threat to wheat production through disruption of the photosynthetic processes of wheat spikes. Real-time nondestructive and frequent proxy detection approaches are necessary to control pathogen propagation and targeted fungicide application. Therefore, this study examined the ch\lorophyll-related phenotypes or features from spectral and chlorophyll fluorescence for FHB monitoring. A methodology is developed using features extracted from hyperspectral reflectance (HR), chlorophyll fluorescence imaging (CFI), and high-throughput phenotyping (HTP) for asymptomatic to symptomatic disease detection from two consecutive years of experiments. The disease-sensitive features were selected using the Boruta feature-selection algorithm, and subjected to machine learning-sequential floating forward selection (ML-SFFS) for optimum feature combination. The results demonstrated that the biochemical parameters, HR, CFI, and HTP showed consistent alterations during the spike–pathogen interaction. Among the selected disease sensitive features, reciprocal reflectance (RR=1/700) demonstrated the highest coefficient of determination (R2) of 0.81, with root mean square error (RMSE) of 11.1. The multivariate k-nearest neighbor model outperformed the competing multivariate and univariate models with an overall accuracy of R2 = 0.92 and RMSE = 10.21. A combination of two to three kinds of features was found optimum for asymptomatic disease detection using ML-SFFS with an average classification accuracy of 87.04% that gradually improved to 95% for a disease severity level of 20%. The study demonstrated the fusion of chlorophyll-related phenotypes with the ML-SFFS might be a good choice for crop disease detection

Solar Ring Mission: Building a Panorama of the Sun and Inner-heliosphere

Solar Ring (SOR) is a proposed space science mission to monitor and study the Sun and inner heliosphere from a full 360{\deg} perspective in the ecliptic plane. It will deploy three 120{\deg}-separated spacecraft on the 1-AU orbit. The first spacecraft, S1, locates 30{\deg} upstream of the Earth, the second, S2, 90{\deg} downstream, and the third, S3, completes the configuration. This design with necessary science instruments, e.g., the Doppler-velocity and vector magnetic field imager, wide-angle coronagraph, and in-situ instruments, will allow us to establish many unprecedented capabilities: (1) provide simultaneous Doppler-velocity observations of the whole solar surface to understand the deep interior, (2) provide vector magnetograms of the whole photosphere - the inner boundary of the solar atmosphere and heliosphere, (3) provide the information of the whole lifetime evolution of solar featured structures, and (4) provide the whole view of solar transients and space weather in the inner heliosphere. With these capabilities, Solar Ring mission aims to address outstanding questions about the origin of solar cycle, the origin of solar eruptions and the origin of extreme space weather events. The successful accomplishment of the mission will construct a panorama of the Sun and inner-heliosphere, and therefore advance our understanding of the star and the space environment that holds our life.Comment: 41 pages, 6 figures, 1 table, to be published in Advances in Space Researc

Human CIK Cells Loaded with Au Nanorods as a Theranostic Platform for Targeted Photoacoustic Imaging and Enhanced Immunotherapy and Photothermal Therapy

How to realize targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy of gastric cancer has become a great challenge. Herein, we reported for the first time that human cytokine-induced killer cells (CIK) loaded with gold nanorods were used for targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy of gastric cancer. Silica-modified gold nanorods were prepared; then incubated with human cytokine-induced killer cells (CIK), resultant human CIK cells loaded with Au nanorods were evaluated for their cytotoxicity, targeted ability of gastric cancer in vitro and in vivo, immunotherapy, and photothermal therapy efficacy. In vitro cell experiment shows that human CIK cells labeled with gold nanorods actively target gastric cancer MGC803 cells, inhibit growth of MGC803 cells by inducing cell apoptosis, and kill MGC803 cells under low power density near-infrared (NIR) laser treatment (808-nm continuous wave laser, 1.5 W/cm2, 3 min). In vivo experiment results showed that human CIK cells labeled with gold nanorods could target actively and image subcutaneous gastric cancer vessels via photoacoustic imaging at 4 h post-injection, could enhance immunotherapy efficacy by up-regulating cytokines such as IL-1, IL-12, IL-2, IL-4, IL-17, and IFN-γ, and kill gastric cancer tissues by photothermal therapy via direct injection into tumor site under near-infrared (NIR) laser irradiation. High-performance human CIK cells labeled with Au nanorods are a good novel theranostic platform to exhibit great potential in applications such as tumor-targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy in the near future