We report a generation of energetic protons by the interaction of a high-energy electron driving beam with an underdense plasma slab. After an interaction period of approximately 4000 fs, a proton beam with maximum energy greater than 250 MeV can be achieved by applying a driving beam with energy 1.0 GeV to a 200 $\mathrm {\mu }$m plasma slab. Our two-dimensional particle-in-cell simulations also show that the proton acceleration process can be divided into two stages. In the first stage, a strong positive longitudinal electric field appears near the rear boundary of the plasma slab after the driving beam has passed through it. This acceleration process is similar to the target normal sheath acceleration scheme by the interaction between intense pulsed laser with overdense plasma targets. In the second stage, the accelerated protons experience a long-range acceleration process with a two-stream instability between the high-energy driving beam and the proton beam. Further analyses show that this accelerated proton beam is equipped with the property of good collimation and high energy. This scheme presents a new way for proton or ion acceleration on some special occasions.

Widely distributed Mid-Neoproterozoic mafic rocks of the Qilian – Qaidam – East Kunlun region record the tectonic evolution of the northeastern Tibetan Plateau. This study presents whole-rock geochemistry, zircon U–Pb geochronology and Hf isotopes for the Xialanuoer gabbros of the central South Qilian Belt (SQB). Zircon laser ablation – inductively coupled plasma – mass spectrometry (LA-ICP-MS) U–Pb dating indicates that the gabbros were emplaced at ca. 738 Ma, indicating they are contemporaneous with mafic magmatism elsewhere in the northeastern Tibetan Plateau. The gabbros have low SiO2, Cr and Ni contents and Mg# values, are relatively enriched in light rare-earth elements (LREEs) and depleted in high-field-strength elements (HFSEs; e.g. Nb and Ta), have no positive Zr or Hf anomalies and have relatively high Nb/Ta but low Nb/La ratios. These data indicate that the Xialanuoer gabbros formed from calc-alkaline basaltic magmas that were originally generated by the partial melting of an enriched mantle of type-I (EMI-type) enriched region of the lithospheric mantle, underwent little to no crustal contamination prior to their emplacement, and have within-plate basalt geochemical affinities. Combining these data with the presence of widespread contemporaneous continental rift-related magmatism and sedimentation in the North Qilian, Central Qilian, South Qilian, Quanji, North Qaidam and East Kunlun regions suggests that the northeastern Tibetan Plateau underwent Mid-Neoproterozoic continental rifting, which also affected other Rodinian blocks (e.g. Tarim, South China, Australia, North America and Southern Africa).

Tumors have posed a serious threat to human life and health. Researchers can determine whether or not cells are cancerous, whether the cancer cells are invasive or metastatic, and what the effects of drugs are on cancer cells by the physical properties such as hardness, adhesion, and Young's modulus. The atomic force microscope (AFM) has emerged as a key important tool for biomechanics research on tumor cells due to its ability to image and collect force spectroscopy information of biological samples with nano-level spatial resolution and under near-physiological conditions. This article reviews the existing results of the study of cancer cells with AFM. The main foci are the operating principle of AFM and research advances in mechanical property measurement, ultra-microtopography, and molecular recognition of tumor cells, which allows us to outline what we do know it in a systematic way and to summarize and to discuss future directions.

The findings regarding the associations between red meat, fish and poultry consumption, and the metabolic syndrome (Mets) have been inconclusive, and evidence from Chinese populations is scarce. A cross-sectional study was performed to investigate the associations between red meat, fish and poultry consumption, and the prevalence of the Mets and its components among the residents of Suzhou Industrial Park, Suzhou, China. A total of 4424 participants were eligible for the analysis. A logistic regression model was used to estimate the OR and 95 % CI for the prevalence of the Mets and its components according to red meat, fish and poultry consumption. In addition, the data of our cross-sectional study were meta-analysed under a random effects model along with those of published observational studies to generate the summary relative risks (RR) of the associations between the highest v. lowest categories of red meat, fish and poultry consumption and the Mets and its components. In the cross-sectional study, the multivariable-adjusted OR for the highest v. lowest quartiles of consumption was 1·23 (95 % CI 1·02, 1·48) for red meat, 0·83 (95 % CI 0·72, 0·97) for fish and 0·93 (95 % CI 0·74, 1·18) for poultry. In the meta-analysis, the pooled RR for the highest v. lowest categories of consumption was 1·20 (95 % CI 1·06, 1·35) for red meat, 0·88 (95 % CI 0·81, 0·96) for fish and 0·97 (95 % CI 0·85, 1·10) for poultry. The findings of both cross-sectional studies and meta-analyses indicated that the association between fish consumption and the Mets may be partly driven by the inverse association of fish consumption with elevated TAG and reduced HDL-cholesterol and, to a lesser extent, fasting plasma glucose. No clear pattern of associations was observed between red meat or poultry consumption and the components of the Mets. The current findings add weight to the evidence that the Mets may be positively associated with red meat consumption, inversely associated with fish consumption and neutrally associated with poultry consumption.

ABSTRACT IMPACT: We are developing the 3D perfusion system for use with patient-derived bacteria to further characterize the mechanism behind bacterial-induced inflammation and cancer. OBJECTIVES/GOALS: We previously reported the adherent invasive E. coli NC101 promote colorectal cancer (CRC) in mice. FimH, a mannose-specific adhesin on type 1 fimbriae, is involved in bacterial surface adhesion. Herein, we investigated the role of FimH in E. coli NC101-induced adherence and carcinogenesis in a novel 3D perfusion culture imaging plate. METHODS/STUDY POPULATION: E. coli NC101 gene fimH was deleted byï ŲRed Recombinase System. Biofilm formation was assessed by crystal violet and congo red staining. 5 dpf (wild-type strain) zebrafish embryos were infected in 6x107 cfu/ml wild type (WT) or fimH-deleted (ï ,,fimH) E. coli NC101 for 24hr and gut dissected for bacterial culture. A 2D/3D infection culture system for IEC-6 and HT-29 cells was infected for 4 hr and imaged and then DNA damage examined by comet assay, cell cycle andÎ3H2AX accumulation. Germ-free (GF) Il10-/- (colitis) mice were orally gavaged with 108 cfu WT orï ,,fimH E. coli NC101 for 16 weeks. E. coli colonization were quantified by plate culture and qPCR. Lipocalin2 was quantified by ELISA. PCNA and β-catenin were evaluated by immunohistochemistry (IHC). RESULTS/ANTICIPATED RESULTS: Biofilm formation was reduced by more than 40% (p<0.05) in E. coli NC101ï ,,fimH compared to WT strain. Zebrafish larvae showed a 41% decrease in intestinal colonization ofï ,,fimH compared to WT (p<0.05). E. coli NC101-induced DNA damage was reduced by 67% (p<0.0001) in HT-29 cells infected withï ,,fimH compared to WT strain. Using the 3D infection system, a 46% decrease in yH2AX (p<0.05) and 42% decrease in G2 cell cycle arrest (p<0.05) was observed inï ,,fimH infected IEC-6 cells compared to WT strain. Furthermore, ï ,,fimH infected Il10-/- mice showed decreased colonization (p<0.01), decreased intestinal inflammation (p<0.05), decreased stool lipocalin2 level (p<0.01), and reduction of PCNA positive cells in the intestine (p<0.05) compared to mice infected with WT strain. DISCUSSION/SIGNIFICANCE OF FINDINGS: Adhesin protein FimH is required by E. coli NC101 to colonize and promote colitis and carcinogenesis both in a 3D perfusion culture and in mice and may serve as potential therapeutic target.

In this article, the electron trapping and acceleration in the wake field driven by an ultrarelativistic hollow electron beam is studied. When the hollow driver injects into plasma, there is a doughnut-shaped electron bubble formed because of the existence of a special ‘backflow’ beam in the centre of the electron bubble. At the same time, there is a transverse convergence of the hollow driver, which leads to the weakening of the backflow beam. This results in a local electron density transition at the rear of the bubble. During this process, there is an expansion of the longitudinal electron bubble size, and a bunch of background electrons is trapped by the wake field at the rear of the bubble. The tracks for the trapped electrons show that there are two sources: one is from the bubble sheath and the other is from the unique backflow beam. In the particle-in-cell simulation where the driving beam has initial energy of $1.0$ GeV per particle, the trapped beam can be accelerated to energy of more than $1.5$ GeV per particle and the corresponding transformer ratio is $1.5$. With the increase of driving beam energy up to $40.0$ GeV, a transformer ratio of $1.4$ still can be achieved. By adjusting the hollow beam density, it is possible to control the trapped beam charge value and beam quality, such as its energy spread and transverse emittance.

Given the possibility of cultural differences in the meaning and levels of gratitude among children, we evaluated the measurement invariance of the Gratitude Questionnaire–5 (GQ–5) and differences in latent means across adolescents from two distinct cultures, China and America. Data were obtained from 1,991 Chinese and 1,685 American adolescents. Confirmatory factor analysis and multigroup confirmatory factor analysis were performed to examine the factor structure and the measurement equivalence across Chinese and American adolescents. The Cronbach’s alpha and Item-total Correlations of the GQ–5 were also evaluated. Results of confirmatory factor analyses provided support for the expected one-factor structure. Also, a series of multi-group confirmatory factor analyses supported full configural invariance, full metric invariance, and partial scalar invariance between the two groups. Furthermore, the findings suggested that the GQ–5 is suitable for conducting mean level comparisons. The subsequent comparison of latent means revealed that the Chinese adolescents reported significantly lower gratitude than American adolescents.

We study the axisymmetric evolution of a liquid film on a solid sphere governed by gravity, capillarity and viscous forces. The lubrication equations established in spherical coordinates are numerically solved using finite elements and local similarity solutions are obtained. Results show that the evolution behaves differently at early and late stages. At the early stage, the interface evolves in such a way that the capillary effect can be ignored. At the late stage, there emerge four zones from top to bottom: a thin film, a ridge ring, a dimple ring and a pendant drop. Each zone is governed by the balance of different forces, and hence is characterized by an individual physical mechanism. Consequently, the pendant drop is quasi-static, and the film thicknesses of other regions follow different scaling laws. The position of the dimple remains unchanged at the late stage.

Shifts in the maternal gut microbiota have been implicated in the development of gestational diabetes mellitus (GDM). Understanding the interaction between gut microbiota and host glucose metabolism will provide a new target of prediction and treatment. In this nested case-control study, we aimed to investigate the causal effects of gut microbiota from GDM patients on the glucose metabolism of germ-free (GF) mice. Stool and peripheral blood samples, as well as clinical information, were collected from 45 GDM patients and 45 healthy controls (matched by age and prepregnancy body mass index (BMI)) in the first and second trimester. Gut microbiota profiles were explored by next-generation sequencing of the 16S rRNA gene, and inflammatory factors in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Fecal samples from GDM and non-GDM donors were transferred to GF mice. The gut microbiota of women with GDM showed reduced richness, specifically decreased Bacteroides and Akkermansia, as well as increased Faecalibacterium. The relative abundance of Akkermansia was negatively associated with blood glucose levels, and the relative abundance of Faecalibacterium was positively related to inflammatory factor concentrations. The transfer of fecal microbiota from GDM and non-GDM donors to GF mice resulted in different gut microbiota colonization patterns, and hyperglycemia was induced in mice that received GDM donor microbiota. These results suggested that the shifting pattern of gut microbiota in GDM patients contributed to disease pathogenesis.

The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern. The current study aims to explore whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with the development of death in patients with COVID-19. A total of 131 patients diagnosed with COVID-19 from 13 February 2020 to 14 March 2020 in a hospital in Wuhan designated for treating COVID-19 were enrolled in the current study. These 131 patients had a median age of 64 years old (interquartile range: 56–71 years old). Furthermore, among these patients, 111 (91.8%) patients were discharged and 12 (9.2%) patients died in the hospital. The pooled analysis revealed that the NLR at admission was significantly elevated for non-survivors, when compared to survivors (P < 0.001). The NLR of 3.338 was associated with all-cause mortality, with a sensitivity of 100.0% and a specificity of 84.0% (area under the curve (AUC): 0.963, 95% confidence interval (CI) 0.911–1.000; P < 0.001). In view of the small number of deaths (n = 12) in the current study, NLR of 2.306 might have potential value for helping clinicians to identify patients with severe COVID-19, with a sensitivity of 100.0% and a specificity of 56.7% (AUC: 0.729, 95% CI 0.563–0.892; P = 0.063). The NLR was significantly associated with the development of death in patients with COVID-19. Hence, NLR is a useful biomarker to predict the all-cause mortality of COVID-19.

Non-communicable diseases (NCDs) including obesity, diabetes, and allergy are chronic, multi-factorial conditions that are affected by both genetic and environmental factors. Over the last decade, the microbiome has emerged as a possible contributor to the pathogenesis of NCDs. Microbiome profiles were altered in patients with NCDs, and shift in microbial communities was associated with improvement in these health conditions. Since the genetic component of these diseases cannot be altered, the ability to manipulate the microbiome holds great promise for design of novel therapies in the prevention and treatment of NCDs. Together, the Developmental Origins of Health and Disease concept and the microbial hypothesis propose that early life exposure to environmental stimuli will alter the development and composition of the human microbiome, resulting in health consequences. Recent studies indicated that the environment we are exposed to in early life is instrumental in shaping robust immune development, possibly through modulation of the human microbiome (skin, airway, and gut). Despite much research into human microbiome, the origin of their constituent microbiota remains unclear. Dust (also known as particulate matter) is a key determinant of poor air quality in the modern urban environment. It is ubiquitous and serves as a major source and reservoir of microbial communities that modulates the human microbiome, contributing to health and disease. There are evidence that reported significant associations between environmental dust and NCDs. In this review, we will focus on the impact of dust exposure in shaping the human microbiome and its possible contribution to the development of NCDs.

OBJECTIVES/GOALS: We seek to develop a 3D perfusion culture imaging plate for human fecal bacteria co-culture with epithelial cells in a structure that mimics the gut epithelium. We will develop this system for use with patient fecal samples to characterize patient risk of developing cancer. METHODS/STUDY POPULATION: E. coli NC101, a strain that harbors the pks gene island, produces the genotoxin colibactin which causes DNA damage that can lead to colorectal cancer development. The genotoxic ability of this bacterium is dependent upon cell-to-cell contact. Here, we present 3D printed E. coli NC101 and intestinal epithelial cells (IEC-6) in a perfusion imaging plate, enabling visualization of the cytotoxic effects of the bacteria in real time using confocal microscopy, in combination with flow cytometry analysis for cell cycle arrest (a surrogate marker of DNA damage). RESULTS/ANTICIPATED RESULTS: 40,000 IEC-6 cells were 3D printed in a cylindrical layer in our triple well imaging plate. The cells were infected at an MOI of 100 for 18 hours and time lapse images of the infection were recorded by confocal microscopy. The cells were then harvested for analysis by flow cytometry for cell cycle arrest as a measure of DNA damage. Our images and flow cytometry data show that E. coli NC101 co-localizes with IEC-6 cells and causes cell cycle arrest in phase G2 (infected %G2 = 40.1), compared to uninfected cells (%G2 = 24.7, P = 0.034). Mutant strains lacking adhesion protein FimH or the ability to produce colibactin do not cause G2 cell cycle arrest (P = 0.844 and P = 0.644, respectively). DISCUSSION/SIGNIFICANCE OF IMPACT: We are able to recapitulate the DNA damage phenotype of E. coli NC101 in our 3D culture system. We show here that host-microbe interactions leading to cancer can be modeled in our 3D perfusion system, and we will next use patient fecal samples in our culture system.