Preceding human metapneumovirus infection increases adherence of Streptococcus pneumoniae and severity of murine pneumococcal pneumonia

BackgroundCoinfection with respiratory virus and Streptococcus pneumoniae has been frequently reported in several epidemiologic studies. The aim of this study was to explore the effect of preceding human metapneumovirus (hMPV) inoculation on subsequent pneumococcal infection.MethodsHep-2 and A549 cells were infected with hMPV then inoculated with S. pneumoniae. Bacterial adhesion was measured using colony forming unit and cytometric-fluorescence assays. In vivo bacterial adhesion was examined in hMPV-infected mice after inoculation of fluorescence-conjugated S. pneumoniae. Pulmonary inflammation (bacterial titers, cytokine levels, and histopathology) of hMPV-infected mice was investigated after inoculation with S. pneumoniae.ResultsIn vitro results of bacterial infection with S. pneumoniae on A549 and Hep-2 monolayer cells showed that even though cellular adherence was variable among different serotypes, there was significantly enhanced bacterial adherence in A549 cells with preceding hMPV infection. In addition, in vivo study of hMPV-infected mice showed increased adhesion of S. pneumoniae on the bronchial epithelium with delayed bacterial clearance and exacerbated histopathology. Furthermore, mice with preceding hMPV infection showed repressed recruitment of airway neutrophils with decreased expression of neutrophil chemoattractants during pneumococcal infection.ConclusionThese results suggest that hMPV-infected airway cells, especially the lower airway epithelium, express increased adherence with S. pneumoniae. Furthermore, hMPV-infected mice showed impaired recruitment of airway neutrophils, possibly leading to delayed bacterial clearance and exacerbated pulmonary inflammation, after secondary infection with pneumococcal isolates

Single-nucleotide polymorphisms and haplotype of CYP2E1 gene associated with systemic lupus erythematosus in Chinese population

Introduction: Cytochrome P-450 2E1 (CYP2E1) is an important member of the CYP superfamily, which is involved in the metabolism and activation of many low molecular weight toxic compounds. We tried to investigate the possible association of CYP2E1 tag single nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese Han population. Methods: The coding and flanking regions of the CYP2E1 gene were scanned for polymorphisms and tag SNPs were selected. A two-stage case-control study was performed to genotype a total of 876 SLE patients and 680 geographically matched healthy controls (265 cases and 288 controls in stage I and 611 cases and 392 controls in stage II). SLE associations of alleles, genotypes and haplotypes were tested by age and sex adjusted logistic regression. The gene transcription quantitation was carried out for peripheral blood mononuclear cell (PBMC) samples from 120 healthy controls. Results: Tag SNP rs2480256 was found significantly associated with SLE in both stages of the study. The "A" allele was associated with slightly higher risk (odds ratio (OR) = 1.165, 95% confidence interval (CI) 1.073 to 1.265, P = 2.75E-4) and "A/A" genotype carriers were with even higher SLE risk (OR = 1.464 95% CI 1.259 to 1.702, P = 7.48E-7). When combined with another tag SNP rs8192772, we identified haplotype "rs8192772-rs2480256/TA" over presented in SLE patients (OR 1.407, 95% CI 1.182 to 1.675, P = 0.0001) and haplotype "TG" over presented in the controls (OR 0.771, 95% CI 0.667 to 0.890, P = 0.0004). The gene transcription quantitation analysis further proved the dominant effect of rs2480256 as the "A/A" genotype showed highest transcription. Conclusions: Our results suggest the involvement of CYP2E1 as a susceptibility gene for SLE in the Chinese population

Study of behavior of plastic modified bitumen by incorporating carbon black

In recent years, the performance of polymer modified bitumen has been widely studied. This study reports a research carried out to investigate the properties of polymer modified bitumen (PMB) by using polypropylene as modifier, carbon black as additives, to examine the optimum ratio of polypropylene to carbon black. With this objective, sample preparation using wet mixing method combining high shear mix was firstly performed. Subsequently, 18 samples were developed for the study, of which the polypropylene (PP) contents 10%, 12%, 14%, 16%, 18% and 20% with 2%, 3%, 4% of carbon black content. Afterwards, samples were characterized by standard tests (Dynamic Shear Rheometer and Viscosity), and all the test results showed improved performance. Finally, the results concluded that the optimum binder-PP ratio PMB for applying is 14% PP with 3% carbon black

What Is the Impact of Early and Subsequent Epidemic Characteristics on the Pre-delta COVID-19 Epidemic Size in the United States?

It is still uncertain how the epidemic characteristics of COVID-19 in its early phase and subsequent waves contributed to the pre-delta epidemic size in the United States. We identified the early and subsequent characteristics of the COVID-19 epidemic and the correlation between these characteristics and the pre-delta epidemic size. Most (96.1% (49/51)) of the states entered a fast-growing phase before the accumulative number of cases reached (30). The days required for the number of confirmed cases to increase from 30 to 100 was 5.6 (5.1–6.1) days. As of 31 March 2021, all 51 states experienced at least 2 waves of COVID-19 outbreaks, 23.5% (12/51) experienced 3 waves, and 15.7% (8/51) experienced 4 waves, the epidemic size of COVID-19 was 19,275–3,669,048 cases across the states. The pre-delta epidemic size was significantly correlated with the duration from 30 to 100 cases (p = 0.003, r = −0.405), the growth rate of the fast-growing phase (p = 0.012, r = 0.351), and the peak cases in the subsequent waves (K1 (p < 0.001, r = 0.794), K2 (p < 0.001, r = 0.595), K3 (p < 0.001, r = 0.977), and K4 (p = 0.002, r = 0.905)). We observed that both early and subsequent epidemic characteristics contribute to the pre-delta epidemic size of COVID-19. This identification is important to the prediction of the emerging viral infectious diseases in the primary stage

Adenovirus-delivered CIAPIN1 small interfering RNA inhibits HCC growth in vitro and in vivo

Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. The specific cellular gene alterations responsible for hepatocarcinogenesis are not well known. Cytokine-induced antiapoptotic molecule (CIAPIN1), a recently reported antiapoptotic molecule which plays an essential role in mouse definitive hematopoiesis, is considered a downstream effecter of the receptor tyrosine kinase–Ras signaling pathway. However, the exact function of this gene in tumors is not clear. In this study, we reported that CIAPIN1 is highly expressed in HCC as compared with non-tumor hepatic tissue (P < 0.05). We employed adenovirus-mediated RNA interference technique to knock down CIAPIN1 expression in HCC cells and observed its effects on HCC cell growth in vitro and in vivo. Among the four HCC and one normal human liver cell lines we analyzed, CIAPIN1 was highly expressed in HCC cells. Knock down of CIAPIN1 could inhibit HCC cell proliferation by inhibiting the cell cycle S-phase entry. Soft agar colony formation assay indicated that the colony-forming ability of SMMC-7721 cells decreased by ∼70% after adenovirus AdH1-small interfering RNA (siRNA)/CIAPIN1 infection. In vivo experiments showed that adenovirus AdH1-siRNA/CIAPIN1 inhibited the tumorigenicity of SMMC-7721 cells and significantly suppressed tumor growth when injected directly into tumors. These results suggest that knock down of CIAPIN1 by adenovirus-delivered siRNA may be a potential therapeutic strategy for treatment of HCC in which CIAPIN1 is overexpressed

Identification and characterization of a novel fumarase gene by metagenome expression cloning from marine microorganisms

<p>Abstract</p> <p>Background</p> <p>Fumarase catalyzes the reversible hydration of fumarate to <smcaps>L</smcaps>-malate and is a key enzyme in the tricarboxylic acid (TCA) cycle and in amino acid metabolism. Fumarase is also used for the industrial production of <smcaps>L</smcaps>-malate from the substrate fumarate. Thermostable and high-activity fumarases from organisms that inhabit extreme environments may have great potential in industry, biotechnology, and basic research. The marine environment is highly complex and considered one of the main reservoirs of microbial diversity on the planet. However, most of the microorganisms are inaccessible in nature and are not easily cultivated in the laboratory. Metagenomic approaches provide a powerful tool to isolate and identify enzymes with novel biocatalytic activities for various biotechnological applications.</p> <p>Results</p> <p>A plasmid metagenomic library was constructed from uncultivated marine microorganisms within marine water samples. Through sequence-based screening of the DNA library, a gene encoding a novel fumarase (named FumF) was isolated. Amino acid sequence analysis revealed that the FumF protein shared the greatest homology with Class II fumarate hydratases from <it>Bacteroides </it>sp. 2_1_33B and <it>Parabacteroides distasonis </it>ATCC 8503 (26% identical and 43% similar). The putative fumarase gene was subcloned into pETBlue-2 vector and expressed in <it>E. coli </it>BL21(DE3)pLysS. The recombinant protein was purified to homogeneity. Functional characterization by high performance liquid chromatography confirmed that the recombinant FumF protein catalyzed the hydration of fumarate to form <smcaps>L</smcaps>-malate. The maximum activity for FumF protein occurred at pH 8.5 and 55°C in 5 mM Mg²⁺. The enzyme showed higher affinity and catalytic efficiency under optimal reaction conditions: <it>K</it>_m= 0.48 mM, <it>V</it>_max= 827 μM/min/mg, and <it>k</it>_cat/<it>K</it>_m= 1900 mM/s.</p> <p>Conclusions</p> <p>We isolated a novel fumarase gene, <it>fumF</it>, from a sequence-based screen of a plasmid metagenomic library from uncultivated marine microorganisms. The properties of FumF protein may be ideal for the industrial production of <smcaps>L</smcaps>-malate under higher temperature conditions. The identification of FumF underscores the potential of marine metagenome screening for novel biomolecules.</p

AgentBench: Evaluating LLMs as Agents

Large Language Models (LLMs) are becoming increasingly smart and autonomous, targeting real-world pragmatic missions beyond traditional NLP tasks. As a result, there has been an urgent need to evaluate LLMs as agents on challenging tasks in interactive environments. We present AgentBench, a multi-dimensional evolving benchmark that currently consists of 8 distinct environments to assess LLM-as-Agent's reasoning and decision-making abilities in a multi-turn open-ended generation setting. Our extensive test over 27 API-based and open-sourced (OSS) LLMs shows that, while top commercial LLMs present a strong ability of acting as agents in complex environments, there is a significant disparity in performance between them and OSS competitors. We identify the typical reasons of failures in environments and LLMs, showing that poor long-term reasoning, decision-making, and instruction following abilities are the main obstacles for developing usable LLM agents. Training on code and high quality multi-turn alignment data could improve agent performance. Datasets, environments, and an integrated evaluation package for AgentBench are released at \url{https://github.com/THUDM/AgentBench}.Comment: 55 page