Bisphenol F (BPF) is a widely used bisphenol A (BPA) substitute plastic additive that has attracted increasing public concerns due to its potential toxic effects on animal and human health. Although previous studies have indicated that BPF might have harmful effects on metabolic homeostasis, the systematic effects of BPF on glucose disorders remain controversial. In this study, mice fed a normal chow diet (ND) and high-fat diet (HFD) were administered BPF at a dose of 100 μg/kg of body weight, and glucose metabolism was monitored after both short- and long-term treatment. Little change in glucose metabolism was observed in BPF-treated ND mice, but improved glucose metabolism was observed in BPF-treated HFD mice. Consistently, BPF treatment led to increased insulin signalling in the skeletal muscle of HFD mice. Additionally, liver metabolite levels also revealed increased carbohydrate digestion and improved TCA cycle progression in BPF-treated HFD mice. Our results demonstrate that sustained BPF exposure at an environmentally relevant dosage may substantially improve glucose metabolism and enhance insulin sensitivity in mice fed a high-fat diet.
Relay of information from the extracellular environment into the cell often results from a peptide growth factor binding to its cognate cell surface receptor; this event is an integral mechanism by which many cellular functions occur, including cell growth, motility, and survival. In recent years, however, this requirement for ligand binding has been shown to be surpassed by several distinct mechanisms, including cell surface receptor cross-talk (e.g., between epidermal growth factor receptor [EGFR] and G-coupled receptors), receptor-extracellular matrix interactions (e.g., EGFR: integrin complexes), and finally by structural mutations within the receptor itself. While all of these pathways result in so-called ligand-independent signaling by the EGF receptor, to date, only structural mutations in the receptor have been shown to result in qualitative changes in downstream targets of the receptor, which specifically result in oncogenic signaling, transformation, and tumorigenicity. In this review, we describe aspects of the known signaling properties of the retroviral oncogene v-ErbB as a model of ligand-independent oncogenic signaling, and compare these properties to results emerging from ongoing studies on structurally related EGF receptor mutants originally identified in human tumors. A better understanding of the signaling pathways used by these uniquely oncogenic receptor tyrosine kinase mutants may ultimately reveal new targets for the development of novel therapeutics selective for the inhibition of tumor cell growth.
We identified an individual who was coinfected with two SARS-CoV-2 variants of concern, the Beta and Delta variants. The ratio of the relative abundance between the two variants was maintained at 1:9 (Beta:Delta) in 14 days. Furthermore, possible evidence of recombinations in the Orf1ab and Spike genes was found.
为了了解境外输入的新型冠状病毒(SARS-CoV-2)变异株的分子特征,本研究对2021年6月深圳市一株从南非输入的SARS-CoV-2毒株进行了全基因组测序和序列分析.Illumina测序技术获得的SARS-CoV-2毒株基因组长度为29567nt.根据"Pango lineages"分型法,本研究测定的毒株属于C.1.2系,该谱系属世界卫生组织定义的监测变异株(Variants Under Monitoring,VUM)成员之一.与参考株 Wuhan-Hu-1(NC_045512.2)比较,本研究 C.1.2系毒株共出现了 58个核苷酸变异位点,其中56个变异位点位于编码区.氨基酸变异位点共有33个,氨基酸变异位点分布于6个开放阅读框,变异数由多到少依次为:S蛋白区12个,ORFlab蛋白区9个,ORF3a蛋白区2个,M区2个,ORF8区2个,E区1个.本研究测定的SARS-CoV-2毒株属我国大陆首例境外输入的C.1.2变异株.开展境外输入的SARS-CoV-2毒株基于基因组测序的分子监测,对防控由境外输入的SARS-CoV-2变异株引起本地新型冠状病毒肺炎(COVID-19)暴发与流行具有重要意义.
On June 14, 2021, a customs officer (Case A) went to the infirmary at Baoan International Airport in Shenzhen due to a runny nose and fever.He was admitted to the Central Hospital of Baoan immediately.This patient preliminarily tested positive for coronavirus disease 2019 (COVID-19) infection, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using a quantitative realtime reverse transcription polymerase chain reaction (qRT-PCR) method in this hospital.Then, a mixed specimen of nasopharyngeal swab, oropharyngeal swab, and anal swab was sent to the virology laboratory of Shenzhen Center for Disease Control and Prevention (Shenzhen CDC) and was confirmed positive for SARS-CoV-2 by a qRT-PCR method simultaneously implemented in two commercial kits (Daan, Guangzhou, China and Bojie, Shanghai, China) (Supplementary Table S1, available in http://weekly.chinacdc.cn/).This patient tested negative for SARS-CoV-2 on June 8, 2021 and participated in an epidemiological investigation and sampling in a flight from South Africa that arrived at Baoan International Airport on June 10, 2021.Between June 10, 2021 and June 25, 2021, a total of 39 passengers (Case 1 to 39) from this flight were confirmed to be infected with SARS-CoV-2 in the virology laboratory of Shenzhen CDC.On June 17, 2021, a third-party laboratory detected SARS-CoV-2 in a mixed specimen of 10 swabs from ten individuals by qRT-PCR method, and the preliminary result was positive.This mixed specimen and one (Case B) of ten nasopharyngeal swabs from ten individuals were confirmed positive for SARS-CoV-2 in the virology laboratory of Shenzhen CDC.Case B was a 22-year-old female who worked in a restaurant at Baoan International Airport.The third case (Case C) lived in Dongguan City and worked in
Screening for coronavirus disease 2019 (COVID-19) virus, also known as SARS-CoV-2, infection every seven days was performed for high-risk populations who worked at the Yantian Port in Yantian District, Shenzhen City, Guangdong Province. On May 20, 2021, an oropharyngeal swab from a 44-year-old male (Case A) tested preliminarily positive for COVID-19 by a quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) method in a third-party laboratory. On May 21, 2021, 3 types of specimens (nasopharyngeal swab, oropharyngeal swab, and anal swab) from this case were collected by Yantian CDC and were confirmed positive for COVID-19 virus by a RT-qPCR method simultaneously implemented in two commercial kits (Daan, Guangzhou, China and Bojie, Shanghai, China) in the virology laboratory of Shenzhen CDC (Table 1). Then, screening was initiated for employees from the Yantian Port and close contacts. A total of 5 cases were confirmed with COVID-19 infections between May 22, 2021 and May 24, 2021 (Table 1). These cases were transported immediately to the Shenzhen Third People’s Hospital for isolated treatment by ambulance after COVID-19 virus infection was confirmed. Specimens from the cases above collected by the Shenzhen Third People’s Hospital were sent to the virology laboratory of Shenzhen CDC for discharge assessment. High-throughput sequencing was performed for six COVID-19 virus strains from this study. First, viral RNA was extracted directly from 200-μL swab samples with the lowest Ct value in RT-qPCR tests using a High Pure Viral RNA Kit (Roche, Germany). Second, libraries were prepared using a Nextera® XT Library Prep Kit (Illumina, USA), and the resulting DNA libraries were sequenced on a MiSeq platform (Illumina) using a 300-cycle reagent kit (1). Last, mapped assemblies were generated using the COVID-19 virus/SARS-CoV-2 reference sequence Wuhan-Hu-1 (GenBank no. NC_045512.2). Nucleotide (nt) and amino acid (AA) differences between the six virus genome sequences from this study and the reference sequence Wuhan-Hu-1 were analyzed using the programs BioEdit 7.19 and MEGA version7 (2). The 6 strains from Case A, Case B, Case C, Case D, Case E, and Case F were designated as hCoV-19/Guangdong/IVDC-05-01-2/2021, hCoV-19/Guangdong/IVDC-05-02-2/2021, hCoV-19/Guangdong/IVDC-05-03/2021, hCoV-19/Guangdong/IVDC-05-04/2021, hCoV19/Guangdong/IVDC-05-05/2021, and hCoV-19/Guangdong/IVDC-05-06/2021, respectively, in this study. The genome sequences of these 6 strains were 29,844 nt, 29,867nt, 29,808 nt, 29,846 nt, 29,760 nt, and 29,832nt in length, respectively. Based on the “Pango lineages” rule (3), the 6 virus strains from this study were assigned to lineage B.1.1.7, which was also known as Variant of Concern 202012/01 (VOC-202012/01) or 20B/501Y.V1. The lineage B.1.1.7 was first identified in the UK in September 2020 and had 24 characteristic mutations (ORF1a: T1001I, A1708D, I2230T, del3675-3677;ORF1b: P314L;S: del69/70, del144, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H;ORF8:Q27stop, R52I, Y73C;N: D3L, R203K, G204R, S235F). Compared with the reference genome sequence Wuhan-Hu-1, 5 strains (hCoV-19/Guangdong/IVDC-05-01-2/2021, hCoV-19/Guangdong/IVDC-05-02-2/2021, hCoV-19/Guangdong/IVDC-05-03/2021, hCoV-19/Guangdong/IVDC-05-04/2021, and hCoV-19/Guangdong/IVDC-05-06/2021) displayed 38 nucleotide variation sites (C241T, C643T, C913T, C2536T, A2784G, C3037T, C3267T, C5388A, C5986T, T6954C, C7851T, G13975T, C14408T, C14676T, T15096C, C15279T, T16176C, C17430T, G17944T, G21578T, A23063T, C23271A, A23403G, C23604A, C23709T, T24506G, G24914C, C27972T, G28048T, A28111G, G28280C, A28281T, T28282A, G28739T, G28881A, G28882A, G28883C, and C28977T) and 18 deletion mutations (ORF1a: del11288-11296/TCTGGTTTT;S: del21766-21771/ACATGT, del21994-21996/TTA). Except for the mutations above, other two variation sites (ORF1a: C884T and S: A23898T) were observed in genome of the strain hCoV-19/Guangdong/IVDC-05-05/2021 (Case E). By comparing deduced amino acid sequences, the 5 SARS-CoV-2 strains (hCoV-19/Guangdong/IVDC-05-01-2/2021, hCoV-19/Guangdong/IVDC-05-02-2/2021, hCoV-19/Guangdong/IVDC-05-03/2021, hCoV-19/Guangdong/IVDC-05-04/2021, and hCoV-19/Guangdong/IVDC-05-06/2021) displayed 24 AA variation sites (ORF1a: N840S, T1001I, A1708D, I2230T, A2529V;ORF1b: G170C, P314L, V1493L;S: V6F, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H;ORF8: Q27stop, R52I, Y73C;N: D3L, A156S, R203K, G204R, and S235F) and 6 deletion mutations (ORF1a: S3675del, G3675del, and F3677 del;S: H69del, V70del, and Y144del). Except for the mutations above, 2 other variation sites (ORF1a: R207C;S: Q779L) were observed in amino acid sequence of the strain hCoV-19/Guangdong/IVDC-05-05/2021 (Case E). All of the characteristic mutations belonging to SARS-CoV-2 variant B.1.1.7 were found in genomes of the 6 SARS-CoV-2 strains from this study. Whole-genome sequencing (WGS) confirmed that all SARS-CoV-2 strains from this study were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure at the Yantian Port. SARS-CoV-2 lineage B.1.1.7 is of growing concern because it has shown to be significantly more transmissible than other variants (4-7). As of now, the 4 SARS-CoV-2 VOCs (B.1.1.7, B.1.351, P.1, and B.1.617.2) have been imported into mainland China (8-11). There is a high risk that imported SARS-CoV-2 VOCs may cause local outbreaks and epidemics. In this study, we focused on laboratory testing and genome characterization of the pathogen. Detailed epidemiological investigation is essential in a follow-up report. Data availability: The six SARS-CoV-2 genome sequences determined in this study has been deposited in GISAID (www.gisaid.org) under the accession number EPI_ISL_2405168, EPI_ISL_2405169, EPI_ISL_2432955, EPI_ISL_2405170, EPI_ISL_2405171, and EPI_ISL_2405172.
为了解深圳境外输入的新型冠状病毒(SARS-CoV-2)的遗传特征,本研究对2021年2月六株境外输入的SARS-CoV-2毒株进行了高通量测序与基因组序列分析.测序获得的六株SARS-CoV-2毒株基因组长度分别为29 450 nt、28 936 nt﹑28 875 nt、29 855 nt、29 146 nt 和29 528 nt.根据"Pango lineages"分型法,三个来自肯尼亚、南非和柬埔寨的毒株属于B.1.1.7系(VOC-202012/01),一个来自美国的毒株属于B.1.2系(美国谱系),两个来自南非和肯尼亚的毒株属于B.1.351系(20H/501Y.V2).与武汉毒株Wuhan-Hu-1(NC_045512.2)比较,B.1.1.7系毒株的刺突蛋白(S)中发现了多达10个氨基酸的变异,B.1.2系毒株的S蛋白仅发现一个氨基酸的变异,B.1.351系毒株的S蛋白中发现了多达11个氨基酸的变异.来自柬埔寨的一株B.1.1.7系毒株的S蛋白中发现了三个变异(H69S,V70I与Y144V)与另外两个B.1.1.7系毒株中的变异(H69del,V70del与Y144del)不同.六个毒株在ORF1b上都表现出了 P314L的变异,在S蛋白上都表现出了 D614G的变异.2021年2月深圳输入了传染性更强的B.1.1.7英国变异株和B.1.351南非变异株.境外输入的SARS-CoV-2变异株存在引起本地暴发与流行的风险,需持续对境外输入的SARS-CoV-2毒株进行分子监测.