OBJECTIVES/GOALS: LSD1 is a histone demethylase important in GBM regulation. Our goal is to design a therapeutic strategy for LSD1 inhibitors to meet clinical needs in GBM. Despite the abundance of LSD1 inhibitors, resistance emerges in GBM mouse models. We aim to understand the relevance of proliferative signaling pathways, such as MAPK, in LSD1 inhibitor resistance. METHODS/STUDY POPULATION: Following LSD1 knockdown in GBM cells, we determined differentially expressed genes using RNA-seq and gene set enrichment analysis (GSEA). Kinase signaling processes enriched for LSD1 expression were identified. Utilizing western blot, we assessed LSD1’s impact on MAPK signaling in patient-derived GBM stem cells (GSCs) and pediatric high-grade glioma cell models. Pharmacological evaluation of LSD1 involved five inhibitor candidates. Additionally, we explored LSD1 inhibition in combination with brain penetrant kinase inhibitors, osimertinib and ulixertinib, directed against the epidermal growth factor receptor (EGFR) and MAPK, respectively. The treatment combinations were assessed at multiple concentrations and analyzed using SynergyFinder. RESULTS/ANTICIPATED RESULTS: Pharmacological LSD1 inhibition after 24 hours induced increased phosphorylated ERK1/2 across multiple glioma cell lines. Concurrent LSD1 and EGFR/MAPK inhibition demonstrated improvedin vitro efficacy compared to individual agents. Notably, the combination of Iadademstat (ORY-1001) and osimertinib demonstrated the highest synergy score of 37.2 using the bliss synergy model in the GSC17s. Furthermore, 11 out of the 12 combination treatments tested had a synergistic relationship, with bliss synergy scores greater than 10. DISCUSSION/SIGNIFICANCE: Our study addresses the pressing need for novel therapeutic strategies in GBM. We leveraged pharmacological tools of LSD1 inhibition to determine how they could be used most effectively, revealing kinase inhibition as a promising strategy with demonstrated in vitro efficacy. Future efforts will focus on validating these findingsin vivo.

Modified kaolinites possess excellent adsorption properties and, therefore, are regarded widely as potential catalytic components. The use of modified kaolinites as a catalytic component for Fischer–Tropsch synthesis (FTS) has remained unexplored, however. In the current study, delaminated and pit-rich nano-kaolinite was prepared via acid treatment of N-methylformamide (NMF)-intercalated kaolinite (intercalation-etching strategy), and was used as a support to prepare a cobalt-based FTS catalyst (denoted as 15%-Co-HNKln). Compared with other FTS catalysts, the supports for which were raw kaolinite or directly acid-treated kaolinite, the 15%-Co-HNKln showed several advantages such as large specific surface area, dispersed Co particles with small particle size, more new active sites, and significant surface acidity. Given the aforementioned advantages, the 15%-Co-HNKln catalyst demonstrated very good FTS performance. Compared with that of the raw kaolinite-supported FTS catalyst, the CO conversion rate and C5–C12 hydrocarbon selectivity of 15%-Co-HNKln increased by 20% and 15%, respectively.

Zearalenone (ZEA), a common contaminant in food and feedstuffs, threatens human and animal health. The present study aimed to investigate the protective effects of modified palygorskite (MPal), a ZEA-targeted adsorbent, on broilers (young chickens) fed a ZEA-contaminated diet. Broilers were subjected to one of three treatments for a period of 42 days: a basal diet (control group), a ZEA- contaminated diet, and a ZEA-contaminated diet supplemented with 1 g/kg of MPal. Blood was collected for serum metabolite assay, and liver and kidney were sampled to determine ZEA residue and antioxidant-related parameters, using commercial spectrophotometric kits. Compared with the basal diet, the ZEA- contaminated diet resulted in compromised growth performance (reduced daily gain and feed intake during finisher period), disordered relative liver weight (decreased at 21 days but increased at 42 days), increased ZEA residue in liver and kidney, abnormal serum metabolites (decreased total protein content but increased alanine aminotransferase activity at 21 and 42 days, reduced albumin content at 21 days, and elevated aspartate aminotransferase activity at 42 days), and disrupted antioxidant capacities of broilers (increased total superoxide dismutase (T-SOD) activity in liver at 21 and 42 days, decreased T-SOD activity in kidney at 21 and 42 days, and in serum at 42 days, greater malondialdehyde accumulation in liver and kidney at 42 days, and lower glutathione content in kidney at 21 days). The adverse consequences resulting from the ZEA-contaminated diet were relieved by the supplementation of MPal (except albumin concentration in serum and T-SOD activity in liver at 21 days), with the values of growth-performance parameters, liver weight, renal ZEA accumulation, total protein content, transaminase activity at 42 days, and antioxidant indexes being similar to those in the control group. These results suggested that MPal supplementation could promote growth performance, attenuate liver damage, and improve the antioxidant abilities of broilers fed ZEA-contaminated diet by reducing ZEA accumulation.

The upsurge in the number of people affected by the COVID-19 is likely to lead to increased rates of emotional trauma and mental illnesses. This article systematically reviewed the available data on the benefits of interventions to reduce adverse mental health sequelae of infectious disease outbreaks, and to offer guidance for mental health service responses to infectious disease pandemic. PubMed, Web of Science, Embase, PsycINFO, WHO Global Research Database on infectious disease, and the preprint server medRxiv were searched. Of 4278 reports identified, 32 were included in this review. Most articles of psychological interventions were implemented to address the impact of COVID-19 pandemic, followed by Ebola, SARS, and MERS for multiple vulnerable populations. Increasing mental health literacy of the public is vital to prevent the mental health crisis under the COVID-19 pandemic. Group-based cognitive behavioral therapy, psychological first aid, community-based psychosocial arts program, and other culturally adapted interventions were reported as being effective against the mental health impacts of COVID-19, Ebola, and SARS. Culturally-adapted, cost-effective, and accessible strategies integrated into the public health emergency response and established medical systems at the local and national levels are likely to be an effective option to enhance mental health response capacity for the current and for future infectious disease outbreaks. Tele-mental healthcare services were key central components of stepped care for both infectious disease outbreak management and routine support; however, the usefulness and limitations of remote health delivery should also be recognized.

The reliability of the plasma etched copper lines with the self-aligned copper oxide passivation layer has been studied with the electromigration stress method. The oxide passivation layer was prepared by plasma oxidation, which covers the entire exposed copper line to prevent the surface oxidation under the ambient condition. The void formation and growth process reflect the line broken mechanism. Voids formed from grain boundary depletion and grain thinning were monitored by optical microscopes. The line failure times with respect to line width and current density were measured. The addition of the oxide passivation layer shortened the lifetime due to the poor heat transfer and copper diffusion, which accelerated the formation and growth of the voids. The narrow line has a longer lifetime than the wide line because of the fewer grain boundaries for flux divergence to form voids. The copper oxide passivation layer was formed self-aligned to the copper line. It also gettered copper atoms diffused from the bulk copper film.

In 2018, the Alliance for Open Media (AOMedia) finalized its first video compression format AV1, which is jointly developed by the industry consortium of leading video technology companies. The main goal of AV1 is to provide an open source and royalty-free video coding format that substantially outperforms state-of-the-art codecs available on the market in compression efficiency while remaining practical decoding complexity as well as being optimized for hardware feasibility and scalability on modern devices. To give detailed insights into how the targeted performance and feasibility is realized, this paper provides a technical overview of key coding techniques in AV1. Besides, the coding performance gains are validated by video compression tests performed with the libaom AV1 encoder against the libvpx VP9 encoder. Preliminary comparison with two leading HEVC encoders, x265 and HM, and the reference software of VVC is also conducted on AOM's common test set and an open 4k set.

Resistant starch (RS) was recently approved to exert a powerful influence on gut health, but the effect of RS on the caecal barrier function in meat ducks has not been well defined. Thus, the effect of raw potato starch (RPS), a widely adopted RS material, on microbial composition and barrier function of caecum for meat ducks was determined. A total of 360 Cherry Valley male ducks of 1-d-old were randomly divided and fed diets with 0 (control), 12, or 24 % RPS for 35 d. Diets supplemented with RPS significantly elevated villus height and villus height:crypt depth ratio in the caecum. The 16S rRNA sequence analysis indicated that the diet with 12 % RPS had a higher relative abundance of Firmicutes and the butyrate-producing bacteria Faecalibacterium, Subdoligranulum, and Erysipelatoclostridium were enriched in all diets. Lactobacillus and Bifidobacterium were significantly increased in the 24 % RPS diet v. the control diet. When compared with the control diet, the diet with 12 % RPS was also found to notably increase acetate, propionate and butyrate contents and up-regulated barrier-related genes including claudin-1, zonula occludens-1, mucin-2 and proglucagon in the caecum. Furthermore, the addition of 12 % RPS significantly reduced plasma TNF-α, IL-1β and endotoxin concentrations. These data revealed that diets supplemented with 12 % RPS partially improved caecal barrier function in meat ducks by enhancing intestinal morphology and barrier markers expression, modulating the microbiota composition and attenuating inflammatory markers.

Underground Nuclear Astrophysics in China (JUNA) will take the advantage of the ultra-low background in Jinping underground lab. High current accelerator with an ECR source and detectors were commissioned. JUNA plans to study directly a number of nuclear reactions important to hydrostatic stellar evolution at their relevant stellar energies. At the first period, JUNA aims at the direct measurements of 25Mg(p,γ)26 Al, 19F(p,α) 16 O, 13C(α, n) 16O and 12C(α,γ) 16O near the Gamow window. The current progress of JUNA will be given.

A recently developed symmetry-based theory is extended to derive an algebraic model for compressible turbulent boundary layers (CTBL) – predicting mean profiles of velocity, temperature and density – valid from incompressible to hypersonic flow regimes, thus achieving a Mach number ($Ma$) invariant description. The theory leads to a multi-layer analytic form of a stress length function which yields a closure of the mean momentum equation. A generalized Reynolds analogy is then employed to predict the turbulent heat transfer. The mean profiles and the friction coefficient are compared with direct numerical simulations of CTBL for a range of $Ma$ from 0 (e.g. incompressible) to 6.0 (e.g. hypersonic), with an accuracy notably superior to popular current models such as Baldwin–Lomax and Spalart–Allmaras models. Further analysis shows that the modification is due to an improved eddy viscosity function compared to competing models. The results confirm the validity of our $Ma$-invariant stress length function and suggest the path for developing turbulent boundary layer models which incorporate the multi-layer structure.

Both genetic selection and increasing nutrient density for improving growth performance had inadvertently increased leg problems of meat ducks, which adversely affects animal welfare. We hypothesised that slowing weight gain with improving tibia quality probably enhanced tibial mechanical properties and alleviated leg deformities. Therefore, the present study aimed to evaluate the effect of graded Ca supplementation in a low-nutrient density (LND) diet on tibia composition and bone turnover in meat ducks. A total of 720 15-d-old male meat ducks were randomly assigned and fed a standard nutrient density positive control (PC) diet containing 0·9 % Ca, and four LND diets with 0·5, 0·7, 0·9 and 1·1 % Ca, respectively. Ducks fed the 0·5 % Ca LND diet and the PC diet had higher incidence of tibial dyschondroplasia (TD). When compared with the 0·5 % Ca LND diet, LND diets with ≥0·7 % Ca significantly improved tibia composition, microarchitecture and mechanical properties, and consequently decreased the incidence of TD. Furthermore, LND diets with ≥0·7 % Ca increased osteocyte-specific gene mRNA expression, blocked the expression of osteoblast differentiation marker genes including osteocalcin, collagenase-1 and alkaline phosphatase (ALP), and also decreased the expression of osteoclast differentiation genes, such as vacuolar-type H+-ATPase, cathepsin K and receptor activator of NF-κB. Meanwhile bone markers such as serum ALP, osteocalcin (both osteoblast markers) and tartrate-resistant acid phosphatase (an osteoclast marker) were significantly decreased in at least 0·7 % Ca treated groups. These findings indicated that LND diets with ≥0·7 % Ca decreased bone turnover, which subsequently increased tibia quality for 35-d-old meat ducks.

Water deficit is an environmental factor that constrains crops to express their ecophysiological potential and causes crop yield reduction. Eruca vesicaria has been reported to be one of the most drought-tolerant species in Cruciferae. In this study, polyethylene glycol-simulated drought tolerance was evaluated in one line of Brassica carinata, one line of Brassica napus and 249 Eruca lines based on the principal component analysis (PCA) and unweighted pair-group arithmetic average (UPGMA) cluster analysis. The PCA based on eight drought tolerance indices indicated that the first three components accounted for 85.46% of the total variation, with principal component (PC) 1 accounting for 43.89%, PC2 for 27.85% and PC3 for 13.73% of the total variation. The UPGMA cluster analysis indicated that B. napus cultivar Zhongshuang 9 and Eruca lines could be clustered into five major groups, with group 1 being, in general, drought sensitive, group 2 being slightly–medium drought tolerant, group 3 being drought tolerant, group 4 being highly drought sensitive and group 5 being highly drought tolerant. B. carinata cultivar XB1, as an outstander, showed high drought sensitivity. The UPGMA cluster dendrogram provides a good representation of the similarity matrix (r= 0.68). The drought-tolerant Eruca materials obtained in this study will be valuable for genetic improvement not only in Eruca itself, but also in Brassica crops since they are drought-tolerant lines from a drought-tolerant species.

Limited information is available on the prevalence of hepatitis C virus (HCV) in the general population in China. A community-based epidemiological study was conducted in three counties in eastern China. A total of 149 175 individuals were investigated in 60 communities in three counties in Jiangsu province, eastern China, of whom 1175 subjects [0·79%, 95% confidence interval (CI) 0·74–0·83] were HCV antibody positive. The prevalence was low in children (0·09%, 95% CI 0·04–0·17), but increased progressively from adolescents (0·20%, 95% CI 0·15–0·28) to adults aged ⩾21 years (95% CI 0·15–1·64). Women had a higher prevalence of HCV infection than men in most age groups. In a multilevel regression analysis, age, sex, education, occupation, blood transfusion [odds ratio (OR) 2·91, 95% CI 1·09–5·37], invasive testing (OR 1·28, 95% CI 1·14–1·61), and dental therapy (OR 2·27, 95% CI 1·41–3·42) were associated with HCV infection. In conclusion, although the prevalence of HCV in this population was lower than reported from national levels, the total reservoir of infection is significant and warrants public health measures, such as health education to limit the magnitude of the problem.

The Chinese Astronomical Data Center (CAsDC) is a member of World Data System, hosted at National Astronomical Observatories, Chinese Academy of Sciences(NAOC). The CAsDC keeps close collaboration with IVOA, WDS and CODATA. The whole set of LAMOST data, including raw data and data products, are hosted at the CAsDC. Data resources and services of the CAsDC are introduced.

We report the results of using n-type hydrogenated nanocrystalline silicon oxide alloy (nc-SiOx:H) in hydrogenated nanocrystalline silicon (nc-Si:H) and amorphous silicon germanium alloy (a-SiGe:H) single-junction solar cells. We used VHF glow discharge to deposit nc-SiOx:H layers on various substrates for material characterizations. We also used VHF glow discharge to deposit the intrinsic layer in nc-Si:H solar cells. RF glow discharge was used for the deposition of the doped layers and the intrinsic layer in a-SiGe:H solar cells. Various substrates such as stainless steel (SS), Ag coated SS, and ZnO/Ag coated SS were used for different cell structures. We found that by using nc-SiOx:H to replace the ZnO and the a-Si:H n-layer in nc-Si:H solar cells, the cell structure is greatly simplified, while the cell performances remain nearly identical to those made using the conventional n-i-p structure on standard ZnO/Ag BR’s. Solar cells with nc-SiOx:H as the n layer directly deposited on textured Ag show similar quantum efficiency (QE) as the n-i-p cells on ZnO/Ag BRs. In both cases, QE is higher than that in the n-i-p cells made directly on Ag coated SS. This effect is probably caused by the shift of surface plasmon-polariton resonance frequency due to the difference in index of refraction of ZnO, nc-SiOx:H, and Si.

Multi-junction solar cells incorporating hydrogenated nanocrystalline silicon (nc-Si:H) exhibit a high current capability and low light-induced degradation. In this paper, we report our recent progress in developing nc-Si:H solar cells using a modified very-high-frequency glow discharge technique. We achieved a short-circuit current density >30 mA/cm2and 10.6% conversion efficiency from single-junction solar cells. Using the improved nc-Si:H cells in an a-Si:H/nc-Si:H/nc-Si:H triple-junction structure, we attained initial and stabilized efficiencies of 13.9% and 13.6%, respectively. Issues related to improving material properties and device structures are addressed. Besides using the conventional techniques, such as hydrogen dilution profiling, optimized Ag/ZnO back reflector, and buffer layers, we found that compensation from Boron and Oxygen micro-doping is also critical in obtaining the above achievements.

We report on the investigation of large area a-Si:H/a-SiGe:H double-junction and a-Si:H/a-SiGe:H/a-SiGe:H triple-junction solar cells prepared by our proprietary High Frequency (HF) glow discharge technique. For investigative purposes, we initially used the simpler double-junction structure. We studied the effect of: (1) Ge content, (2) cell thickness, and (3) SiH4 and GeH4 gas flow on the light-induced degradation of the solar cells. Our results show that the double-junction cells with different Ge concentration have open-circuit voltage (Voc) in the range of 1.62-1.75 V. Voc exhibits a flat plateau in the range of 1.65-1.72 V for both initial and stabilized states. The light-induced degradation for cells in this range of Voc is insensitive to the Ge content. In terms of thickness dependence of the intrinsic layers, we found that the initial efficiency increases with cell thickness in the thickness range 2000-4000 Å. However, light-induced degradation increases with increasing thickness. Consequently, the stabilized efficiency is invariant with cell thickness in the thickness range studied. The results of SiH4 and GeH4 gas flow on cell characteristics demonstrate that the deposition rate decreases by only 20% when the active gas flow is reduced to 0.25 times standard flow. The initial and stabilized efficiencies are similar. The information gleaned from the study was used to fabricate high efficiency, large area (~464 cm2) double- and triple-junction solar cells. The highest stable efficiency, as measured by NREL, was 9.8% and 11.0% for the double- and triple-junction structures, respectively.