Background: We’ve adopted a novel approach that combines cellular barcoding with CRISPR/Cas-9 technology and single-cell RNA sequencing known as continuous lineage tracing to track the development, treatment and inevitable recurrence of glioblastoma. Methods: Patient derived glioma initiating cell lines were engineered with expressed DNA barcodes with CRISPR/Cas-9 targets and engrafted into NOD scid-mice. Clonal and relationships are surmised through identification of expressed barcodes, and cells were characterized by their transcriptional profiles. Phylogenetic lineage trees are created using lineage reconstructive algorithms to define cell fitness and expansion. Results: Our work has revealed a significant amount of intra-clonal cell state heterogeneity, suggesting that tumour cells engage in phenotype switching prior to therapeutic intervention. Phylogenetic lineage trees allowed us to define a gene signature of cell fitness. GBMs exist along a transcriptional gradient between undifferentiated but “high-fit” cells and terminally differentiated, “low-fit” cells, lending further evidence that these tumours consist of pools of cells that are capable of recapitulating the tumour microenvironment after treatment. Conclusions: We have successfully engineered a set of glioma initiating tumours with a novel lineage tracing technique, creating a powerful tool for real-time tracing of tumour growth through the analysis of highly detailed singe-cell RNA sequencing data with associated clonal and phylogenetic relationships.

Objectives/Goals: Cognitive decline is a known sequalae of intracranial radiation in the treatment of brain metastases. In this study, we investigate global structural changes in the brain akin to accelerated aging and compare aging kinetics between patients treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS). Methods/Study Population: This retrospective study consists of patients with brain metastases treated with WBRT and SRS at our institution. Brain MRI images collected prior to radiation therapy and at approximately three and six months following radiation will be analyzed, excluding patients with evidence of worsening disease burden in the brain. Surface morphology of the cerebral cortex and sub-cortical structures will be extracted using Freesurfer and converted to graphs. Data will then be input into a validated graph convolutional neural network model to estimate brain age at each time point. A generalized linear model will be used to estimate the aging pace between baseline and follow-up for each subject within the whole brain as well as the sub-cortical structures, which will be compared between WBRT and SRS treatment groups. Results/Anticipated Results: We anticipate that intracranial radiation will accelerate brain aging to a greater extent following WBRT compared to SRS. Additionally, this accelerated aging will occur globally in the whole brain as well as within individual substructures, including the cerebral cortex, nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Discussion/Significance of Impact: This study will demonstrate structural changes in the brain analogous to accelerated aging, supporting its potential use as an imaging biomarker to monitor cognitive decline after radiation therapy. Future work will explore the relationship between structural brain aging and assessments of neurocognitive function.

The Maz Metasedimentary Series is part of the Maz Complex that crops out in the sierras of Maz and Espinal (Western Sierras Pampeanas) and in the Sierra de Umango (Andean Frontal Cordillera), northwestern Argentina. The Maz Complex is found within a thrust stack of Silurian age, which later underwent open folding. The Maz Metasedimentary Series mainly consists of medium-grade garnet–staurolite–kyanite–sillimanite schists and quartzites, with minor amounts of marble and calc-silicate rocks. Transposed metadacite dykes have been recognized along with amphibolites, metagabbros, metadiorites and orthogneisses. Schist, quartzite and metadacite samples were analysed for SHRIMP U–Pb zircon dating. The Maz Metasedimentary Series is polymetamorphic and records probably three metamorphic events during the Grenvillian orogeny, at c. 1235, 1155 and 1035 Ma, and a younger metamorphism at c. 440–420 Ma resulting from reactivation during the Famatinian orogeny. The sedimentary protoliths were deposited between 1.86 and 1.33–1.26 Ga (the age of the Andean-type Grenvillian magmatism recorded in the Maz Complex), and probably before 1.75 Ga. The main source areas correspond to Palaeoproterozoic and, to a lesser magnitude, Meso-Neoarchaean rocks. The probable depositional age and the detrital zircon age pattern suggest that the Maz Metasedimentary Series was laid down in a basin of the Columbia supercontinent, mainly accreted between 2.1 and 1.8 Ga. The sedimentary sources were diverse, and we hypothesize that deposition took place before Columbia broke up. The Rio Apa block, and the Río de la Plata, Amazonia and proto-Kalahari cratons, which have nearby locations in the palaeogeographic reconstructions, were probably the main blocks that supplied sediments to this basin.

Tuberculosis (TB) is generally considered a disease that principally afflicts the low-income segments of a population. In the Nanshan District of Shenzhen, China, with the economic transformation and a new Headquarters Economy (HE) emerging, there are now more cases in office workers than in manufacturing workers. To illustrate this trend, we describe a small TB outbreak in an office building located in the centre of the rapidly growing HE district. Two active pulmonary tuberculosis cases were found in workers who shared an office, and whole genome sequencing showed that the genetic distance between the strains of the two cases was just one single nucleotide polymorphism, consistent with intra-office transmission. Investigation of 30 other workers in the same or adjacent offices with interviews, interferon-gamma release assays (IGRAs) and chest X-rays, identified one new TB case and latent tuberculosis infection (LTBI) in 40.0% (12/30) of the contacts. The offices were under-ventilated. None of the IGRA positive, asymptomatic contacts agreed to receive treatment for LTBI, presumably due to TB stigma, and over the next 2 years 69.0% (20/29) of the contacts were lost to follow-up. Treatment for LTBI and stigma of TB remain challenges here. Office workers in the HE of rapidly economic developing areas should be targeted with increased vigilance by TB control programmes.

The fatty acid composition of chicken’s meat is largely influenced by dietary lipids, which are often used as supplements to increase dietary caloric density. The underlying key metabolites and pathways influenced by dietary oils remain poorly known in chickens. The objective of this study was to explore the underlying metabolic mechanisms of how diets supplemented with mixed or a single oil with distinct fatty acid composition influence the fatty acid profile in breast muscle of Qingyuan chickens. Birds were fed a corn-soybean meal diet supplemented with either soybean oil (control, CON) or equal amounts of mixed edible oils (MEO; soybean oil : lard : fish oil : coconut oil = 1 : 1 : 0.5 : 0.5) from 1 to 120 days of age. Growth performance and fatty acid composition of muscle lipids were analysed. LC-MS was applied to investigate the effects of CON v. MEO diets on lipid-related metabolites in the muscle of chickens at day 120. Compared with the CON diet, chickens fed the MEO diet had a lower feed conversion ratio (P < 0.05), higher proportions of lauric acid (C12:0), myristic acid (C14:0), palmitoleic acid (C16:1n-7), oleic acid (C18:1n-9), EPA (C20:5n-3) and DHA (C22:6n-3), and a lower linoleic acid (C18:2n-6) content in breast muscle (P < 0.05). Muscle metabolome profiling showed that the most differentially abundant metabolites are phospholipids, including phosphatidylcholines (PC) and phosphatidylethanolamines (PE), which enriched the glycerophospholipid metabolism (P < 0.05). These key differentially abundant metabolites – PC (14:0/20:4), PC (18:1/14:1), PC (18:0/14:1), PC (18:0/18:4), PC (20:0/18:4), PE (22:0/P-16:0), PE (24:0/20:5), PE (22:2/P-18:1), PE (24:0/18:4) – were closely associated with the contents of C12:0, C14:0, DHA and C18:2n-6 in muscle lipids (P < 0.05). The content of glutathione metabolite was higher with MEO than CON diet (P < 0.05). Based on these results, it can be concluded that the diet supplemented with MEO reduced the feed conversion ratio, enriched the content of n-3 fatty acids and modified the related metabolites (including PC, PE and glutathione) in breast muscle of chickens.

The triplite LiFeSO4F displays both the highest potential ever reported for an Fe-based compound, as well as a comparable specific energy with that of popular LiFePO4. The synthesis is still a challenge because the present approaches are connected with long time, special equipments or organic reagents, etc. In this work, the triplite LiFeSO4F powder was synthesized through an ambient two-step solid-state route. The reaction process and phase purity were analyzed, coupled with structure refinement and electrochemical test.

The study investigated whether different dietary energy and protein sources affect laying performance, antioxidant status, fresh yolk fatty acid profile and quality of salted yolks in laying ducks. In all, 360 19-week-old Longyan ducks were randomly assigned to four diets in a factorial arrangement (2×2). The four diets consisted of two energy sources, corn (CO) or sorghum (SO) and two protein sources, soybean meal (SM) and rapeseed meal with corn distillers dried grains with solubles (RMD), and each treatment contained six replicates of 15 birds each. The experimental diets were isocaloric (metabolizable energy, 10.84 MJ/kg) and isonitrogenous (CP, 17%). The results showed that egg production, average egg weight, egg mass and feed conversion ratio were not affected by diets (P>0.05). Plasma contents of reduced glutathione (GSH), GSH/oxidized glutathione and total antioxidant capacity were lower (P<0.05) in ducks fed the RMD diets compared with those fed SM diets with a substantial increase (P=0.006) in plasma content of malondialdehyde (MDA). Egg yolks from ducks fed SO diets had higher proportions of polyunsaturated fatty acids (PUFA) and lower saturated and monounsaturated fatty acids compared with CO diets (P<0.001). Similarly, ducks fed RMD diets had a higher content of PUFA and n-6/n-3 ratio in fresh yolks (P<0.001), and increased salted yolk MDA, carbonylated proteins content and incidence of hard salted yolks (P<0.05) compared with SM diets. Scanning electron microscopy showed that salted yolks contained rougher polyhedral granules and fewer fat droplets, and were surrounded with a layer of bunchy fibers in ducks fed SO+RMD than those fed CO+SM diet. In conclusion, the current study showed that feeding laying ducks with diets containing SO or RMD reduced antioxidant capacity and increased egg yolk concentrations of PUFA. It appeared that egg yolks from ducks fed these diets were more sensitive to lipid peroxidation and protein oxidation during salting, and reduced the quality of salted yolks.

The mammalian target of rapamycin (mTOR) has been shown to be involved in lipopolysaccharide (LPS)-induced immune responses in many mammal cells. Here, we suggest that the mTOR pathway is involved in the intestinal inflammatory responses evoked by LPS treatment in chicken embryos. The intestinal tissue from Specific pathogen free chick embryos was cultured in the presence of LPS for 2 h. Secretory immunoglobulin A (sIgA) concentrations, messenger RNA (mRNA) expression of cytokines, and protein levels of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), mTOR and p70 ribosomal S6 kinase (p70S6K) were determined. The results showed that LPS treatment increased sIgA concentrations in a dose-dependent manner. The mRNA levels of interleukine (IL)-6, IL-8, IL-10, tumor necrosis factor-α and Toll-like receptor (TLR) 4 were upregulated by LPS treatment (P<0.05). Lipopolysaccharide increased the phosphorylation of Jun N-terminal kinase (JNK), p38 MAPK and NF-κB (P<0.05) while decreasing the phosphorylation level of mTOR (P<0.05). Supplementation of leucine at doses of 10, 20 and 40 mM dose-dependently decreased sIgA production. Leucine supplementation at 40 mM restored the phosphorylation level of mTOR and p70S6K while suppressing the phosphorylation levels of NF-κB (P<0.05) and partially down-regulating the phosphorylation of p38 MAPK and JNK. The transcription of IL-6 was significantly decreased by leucine supplementation. These results suggested that leucine could alleviate LPS-induced inflammatory responses by down-regulating NF-κB signaling pathway and evoking mTOR/p70S6K signaling pathway, which may involve in the regulation of the intestinal immune system in chicken embryos.

Soluble starch synthase II (SSII) plays an important role in the biosynthesis of starch and in rice it consists of three isoforms encoded by SSII-1, SSII-2 and SSII-3. However, the genetic effects of various SSII alleles on grain quality have not been systematically characterized. In the present study, the japonica alleles on SSII-1, SSII-2 and SSII-3 (SSIIa) loci from a japonica cultivar, Suyunuo, were respectively introgressed by molecular marker-assisted selection into a typical indica cultivar, Guichao2, through successive backcrossing, generating three sets of near-isogenic lines (NILs). Grain quality and starch property analysis showed that NIL-SSII-3j exhibited significant decreases in the following parameters: amylose content, average granule size, and setback viscosity and consistency; but increases in peak viscosity, hot paste viscosity, gelatinization temperature and relative crystallinity. Moreover, the proportion of short amylopectin chains and branching degree also increased when compared with those of NIL-SSII-3i (Guochao2). Similar effects were observed in NIL-SSII-1j , and certain alterations in the fine structure of starch (granule size) were revealed. However, NIL-SSII-2j did not exert significant effect on grain quality and starch properties. In brief, among the SSII gene family, the functional diversity occurred on SSII-1 and SSII-3, and not on SSII-2. Therefore, it appears that more attention should be directed to SSII-1 and SSII-3 loci for improving the eating and cooking quality of rice.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by a novel bunyavirus, SFTSV. The study aimed to disclose the epidemiological and clinical characteristics of SFTSV infection in China so far. An integrated clinical database comprising 1920 SFTS patients was constructed by combining first-hand clinical information collected from SFTS sentinel hospitals (n = 1159) and extracted data (n = 761) from published literature. The considered variables comprised clinical manifestations, routine laboratory tests of acute infection, hospitalization duration and disease outcome. SFTSV-IgG data from 19 119 healthy subjects were extracted from the published papers. The key clinical variables, case-fatality rate (CFR) and seroprevalence were estimated by meta-analysis. The most commonly seen clinical manifestations of SFTSV infection were fever, anorexia, myalgia, chill and lymphadenopathy. The major laboratory findings were elevated lactate dehydrogenase, aminotransferase, followed by thrombocytopenia, lymphocytopenia, elevated alanine transaminase and creatine kinase. A CFR of 12·2% was estimated, significantly higher than that obtained from national reporting data, but showing no geographical difference. In our paper, the mortality rate was about 1·9 parts per million. Older age and longer delay to hospitalization were significantly associated with fatal outcome. A pooled seroprevalence of 3·0% was obtained, which increased with age, while comparable for gender. This study represents a clinical characterization on the largest group of SFTS patients up to now. A higher than expected CFR was obtained. A wider spectrum of clinical index was suggested to be used to identify SFTSV infection, while the useful predictor for fatal outcome was found to be restricted.

Precise control of structural parameters through nanoscale engineering to continuously tailor optical and electronic properties of functional nanomaterials remains an outstanding challenge. Previous work focused largely on chemical or physical interactions that occur under ambient pressures. In this article, we introduce a new pressure-directed assembly and fabrication method that uses a mechanical compressive force applied to nanoparticles (NPs) to induce structural phase transitions and consolidate new nanomaterials with precisely controlled structures and tunable properties. By manipulating NP coupling through external pressure instead of through chemistry, a reversible change in assembly structure and properties can be demonstrated. In addition, over a certain threshold, the external pressure forces these NPs into contact, allowing the formation and consolidation of one- to three-dimensional nanostructures. Through stress-induced NP assembly, unusual materials engineering and synthesis, in which morphology and architecture can be readily tuned to produce desired optical and electrical properties, appear feasible.

Hand, foot and mouth disease (HFMD) is an acute contagious condition caused by a spectrum of human enteroviruses. HFMD reinfection is common in the absence of cross-protection from other virus subtypes. This study focused on reinfection in children in Anhui province, China between 2008 and 2013 using surveillance system data. We classified 8960 cases as reinfected, corresponding to a rate of 2·02%. The reinfection rate was higher in boys than in girls [odds ratio (OR) 1·27, 95% confidence interval (CI) 1·21–1·32, P < 0·001], children aged < 3 years (OR 3·82, 95% CI 3·58–4·07, P < 0·001), and children living in rural areas (OR 1·09, 95% CI 1·04–1·14, P = 0·001). The reinfection rate in children who were originally infected with non-enterovirus A71 (non-EVA71) enteroviruses was higher than those infected with EVA71 (OR 1·36, 95% CI 1·02–1·80, P = 0·034). Influential factors of reinfection rate included annual incidence (β coefficient = 0·715, P = 0·002) and the proportion of EVA71 in patients with mild HFMD (β coefficient = −0·509, P = 0·018). These results demonstrate that boys aged <3 years, especially those in rural areas or regions with a lower EVA71 proportion are more prone to reinfection, and specific health education programmes should be developed to protect these susceptible populations.

Ag–reduced graphene oxide (Ag/rGO) nanoparticle composites were synthesized through a facile one-step hydrothermal reaction using GO and silver carbonate (Ag2CO3) as raw materials. The homogeneous silver nanospheres with an average size of 50 nm well dispersed on the surface of rGO were obtained without other additives. During the formation process, GO both promotes the dispersion of Ag2CO3 in aqueous solution and acts as the substrate of silver cations, and the hydrolysis of Ag2CO3 provides silver cations and alkaline condition. Moreover, GO further serves as reducing agent to generate elemental silver in the alkaline condition. The as-prepared materials exhibit excellent surface-enhanced Raman scattering activities when used to detect the Raman signals of R6G absorbed on the Ag/rGO substrate.

High-redshift quasars are unique probes of the evolution of supermassive black holes and the intergalactic medium at the end of the epoch of reionization. We present the optical spectra of eight new z ~ 6 quasars selected from the Panoramic Survey Telescope & Rapid Response System 1 (Pan-STARRS1). Details of the selection strategy can be found in Bañados et al. (2014). With this work we increase the number of known quasars at z < 5.7 by more than 10%. The quasars discovered here span a large range of luminosities (19.6 ≤ zP1 ≤ 21.2) and are remarkably heterogeneous in their spectral features: half of them show bright emission lines whereas the other half show weak or no Lyα emission line. We find a larger fraction of weak–line emission quasars than in lower redshift studies, although still based on low number statistics, this may imply that the quasar population could be more diverse than previously thought.