Esophageal squamous-cell carcinoma (ESCC), one of the most prevalent and lethal malignant disease, has a complex but unknown tumor ecosystem. Here, we investigate the composition of ESCC tumors based on 208,659 single-cell transcriptomes derived from 60 individuals. We identify 8 common expression programs from malignant epithelial cells and discover 42 cell types, including 26 immune cell and 16 nonimmune stromal cell subtypes in the tumor microenvironment (TME), and analyse the interactions between cancer cells and other cells and the interactions among different cell types in the TME. Moreover, we link the cancer cell transcriptomes to the somatic mutations and identify several markers significantly associated with patients’ survival, which may be relevant to precision care of ESCC patients. These results reveal the immunosuppressive status in the ESCC TME and further our understanding of ESCC.

B lymphocytes are activated upon Ag sensing by BCRs. The substrate presenting the Ag can show different degrees of stiffness. It is not clear whether B cells can respond to changes in substrate stiffness. In this study we use high-resolution, high-speed live cell imaging techniques to capture the molecular events in B cell activation after the recognition of Ags tethered to polyacrylamide gel substrates with variable degrees of stiffness as quantified by Young’s modulus (2.6–22.1 kPa). We show that the initiation of B cell activation is extremely sensitive to substrate stiffness. B cells exhibit much stronger activation responses when encountering Ags tethered to substrates with a high degree of stiffness as measured by the accumulation of BCR, phospho-spleen tyrosine kinase, and phosphotyrosine molecules into the B cell immunological synapse. Ags tethered to stiff substrates induce the formation of more prominent BCR and phospho-spleen tyrosine kinase microclusters with significantly enhanced colocalization as compared with Ags tethered to soft substrates. Moreover, the expression of the B cell activation marker CD69 is enhanced in B cells encountering Ags on stiffer substrates. Through time-lapse live cell imaging, we find that the different responses of B cells to substrate stiffness are only demonstrated 5 min after BCR and Ag recognition. Using a series of cytoskeleton inhibitors, we determine that the mechanosensing ability of B cells is dependent on microtubules, and only mildly linked to the actin cytoskeleton. These results suggest the importance of the mechanical properties mediated by substrate stiffness in B cell activation.

BackgroundThe China’s 1-3-7 strategy was initiated and extensively adopted in different types of counties (geographic regions) for reporting of malaria cases within 1 day, their confirmation and investigation within 3 days, and the appropriate public health response to prevent further transmission within 7 days. Assessing the level of compliance to the 1-3-7 strategy at the county level is a first step towards determining whether the surveillance and response strategy is happening according to plan. This study assessed if the time-bound targets of the 1-3-7 strategy were being sustained over time. Such information would be useful to improve implementation of the 1-3-7 strategy in China.MethodsThis cross-sectional study involved country-wide programmatic data for the period January 1st 2013 to June 30th 2014. Data variables were extracted from the national malaria information system and included socio-demographic information, type of county, date of diagnosis, date of reporting, date of case investigation, case classification (indigenous, or imported, or unknown), focus investigation, date of reactive case detection (RACD), and date of indoor residual spraying (IRS). Summary statistics and proportions were used and comparisons between groups were assessed using the chi-square test. Level of significance was set at a P-value ≤ 0.05.ResultsOf a total of 5,688 malaria cases from 731 counties, there were 55 (1 %) indigenous cases (only in Type 1 and Type 2 counties) and 5,633 (99 %) imported cases from all types of counties. There was no delay in reporting malaria cases by type of county. In terms of case investigation, 97.5 % cases were investigated within 3 days with the proportion of delays (1.5 %) in type 2 counties, being significantly lower than type 1 counties (4.1 %). Regarding active foci, 96.4 % were treated by RACD and/or IRS.ConclusionsThe performance of 1-3-7 strategy was encouraging but identified some challenges that if addressed can further improve implementation.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-015-0089-2) contains supplementary material, which is available to authorized users.

BackgroundRemarkable progress has been made towards the elimination of malaria in China since the National Malaria Elimination Programme (NMEP) was launched in 2010. The incidence of locally-acquired malaria cases has declined rapidly and endemic areas have also dramatically shrunk. In total, 3 078 malaria cases were reported in 2014, but only 56 cases were indigenous. In order to further promote the elimination programme, we reviewed the progress of and experiences associated with malaria elimination in China, and identified the challenges and priorities for the next stage of the programme.MethodsData were collected from the web-based China Information System for Disease Control and Prevention, and the China Annual Report of Malaria Elimination. The progress towards the elimination of malaria from 2010 to 2014 was measured.ResultsDuring the implementation of the NMEP from 2010 to 2014, local malaria incidence has declined continuously, only remaining in the Yunnan Province and Tibet Autonomous Region in 2014. By the end of 2015, 75.6 % (1 636/2 163) of the malaria-endemic counties passed the sub-national elimination assessment. The main challenges are cases of border malaria and imported malaria from other countries. Sustainable support and investment from the government, the establishment of an effective surveillance and response system, and risk assessments for the potential reintroduction of malaria are priorities for the next stage of the elimination programme.ConclusionsThe NMEP in China has been successfully implemented thus far and the malaria map has shrunk dramatically. The priorities for malaria elimination are interventions to block transmission at border areas, management of imported malaria cases, preventing malaria reintroduction, capacity building, and sustainability of malaria surveillance and response.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-016-0146-5) contains supplementary material, which is available to authorized users.