The aim of this study was to investigate the survival effect of palliative surgery in advanced tongue squamous cell carcinoma (TSCC). A retrospective analysis of data in the SEER database for 6151 ...patients with stage III/IV TSCC (American Joint Committee on Cancer (AJCC) staging), diagnosed between 2004 and 2015, was performed. The patients were divided into two groups: palliative surgery and no surgery. Kaplan–Meier and Cox proportional hazards regression analyses were applied to determine risk factors for overall survival (OS) and cancer-specific survival (CSS). A further analysis was performed using 1:1 propensity score matching (PSM) to balance 13 patient variables (sex, age at diagnosis, race, marital status, primary tumour site, SEER stage, AJCC stage, pathological differentiation grade, tumour size, lymph node metastasis, previous lymph node removal, radiotherapy, and chemotherapy). Among the 6151 patients, 706 underwent palliative surgery; the other 5445 did not undergo any kind of surgery. Those who underwent palliative surgery had a higher 5-year survival rate. After PSM, 1274 patients were included in the matched cohort. Multivariate Cox regression analysis showed that patients who underwent palliative surgery had a lower risk of death than those who did not (OS: hazard ratio 0.58, 95% confidence interval 0.49–0.69, P < 0.001; CSS: hazard ratio 0.60, 95% confidence interval 0.49–0.74, P < 0.001). In this comparative study it was found that compared with no surgery, palliative surgery has a positive impact on the survival rate of patients with advanced TSCC.
Developing energy-efficient parallel information processing systems beyond von Neumann architecture is a long-standing goal of modern information technologies. The widely used von Neumann computer ...architecture separates memory and computing units, which leads to energy-hungry data movement when computers work. In order to meet the need of efficient information processing for the data-driven applications such as big data and Internet of Things, an energy-efficient processing architecture beyond von Neumann is critical for the information society. Here we show a non-von Neumann architecture built of resistive switching (RS) devices named "iMemComp", where memory and logic are unified with single-type devices. Leveraging nonvolatile nature and structural parallelism of crossbar RS arrays, we have equipped "iMemComp" with capabilities of computing in parallel and learning user-defined logic functions for large-scale information processing tasks. Such architecture eliminates the energy-hungry data movement in von Neumann computers. Compared with contemporary silicon technology, adder circuits based on "iMemComp" can improve the speed by 76.8% and the power dissipation by 60.3%, together with a 700 times aggressive reduction in the circuit area.
•Impact of different fertilizers on soil microbial characteristics.•The OIO treatment exhibited the highest bacterial and actinomycete levels and AWCD.•The N treatment resulted in the highest fungi ...levels.•Bacillus sp. were the dominant bacteria in the OIO treatment.•Most microbial parameters were correlated with soil organic matter content.
A long-term field experiment was used to evaluate the effects of different fertilizers (OIO, organic inorganic compound fertilizer specially formulated for mulberry; N, N fertilizer only; NPK, N, P and K fertilizer; NF, the control without fertilization) on microbial abundance, community structure and microbial functional diversity. The OIO treatment exhibited the highest bacterial and actinomycete levels, community diversity, Shannon indices and average well color development (AWCD). However, the N treatment resulted in the highest fungi levels. Bacillus sp. were the dominant bacteria in the OIO treatment. The carbohydrate and carboxylic acid utilization by microbes was highest in the OIO treatment, whereas the amino acid utilization was highest in the N treatment. Most microbial parameters were primarily correlated with the soil organic matter content. The principal component analysis of the DGGE profiles suggested that the culture-independent bacterial community was not really affected by the fertilization treatments but was significantly affected by the sampling time. In contrast, the carbon substrate utilization was significantly affected by the fertilization treatments but not by the sampling time. Our findings suggested that the soil microbial activities were significantly changed by long-term fertilization and that more attention should be devoted to seasonal shifts in the microbial community.
Abstract
Likelihood estimates of extreme winds, including those from tropical cyclones (TCs) at certain locations are used to inform wind load standards for structural design. Here, wind speed ...average recurrence intervals (ARIs) determined from TC climate data dating back to the 1970s in two quantile–quantile adjusted reanalysis datasets (ERA5 and BARRA 1990), and best-track observations for context, were compared with Standardized ARIs (AS/NZS) across seven tropical and two subtropical Australian inland coastal regions. The novelty of this work lies in determining TC-wind speed ARIs from a range of datasets that are not typically used to evaluate this metric. Inherent differences between the data used to determine the Standard ARIs (large sample size allow for larger extrapolations; GEV function) and TC data ARIs (smaller sample size and less certain data; the more asymptotic Lognormal/Weibull functions are used) led to the use of different extreme value functions. Results indicated that although these are two distinct ways of determining design wind speeds, when they are considered equivalent, there was a moderate reproduction of the ARI curves with respect to the Standard in both reanalysis datasets, suggesting that similar analyses using climate model products can provide useful information on these types of metrics with some caveats. Trends in TC wind strength affecting coastal Australia were also analyzed, indicating a potential slight downtrend in tropical West coast TC wind strength and slight uptrend for tropical East coast TC wind strength, noting considerable uncertainty given the short time period and limitations of data quality including over longer time periods. Such trends are not only limited to the relationship between TC intensity and anthropogenic warming, but also to regional changes in TC frequency and track direction. This could lead to significant trends emerging in regional Australian TC wind gust strength before several decades of warming have occurred. It is hoped that climate models can provide both longer-term and a more homogenous base for these types of evaluations and subsequent projections with respect to climate change simulations.
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•Intrahepatic Vδ2neg γδ T cells are clonally focussed and feature private TCR rearrangements.•Effector CD27lo/neg Vδ1+ T cells are enriched in liver, but naïve CD27hi cells are ...absent.•A subset of Vδ1+ T cells is distinct from those in blood and may be liver tissue resident.•Liver Vδ1+ γδ T cells are polyfunctional and respond to both TCR and innate stimuli.
γδ T cells comprise a substantial proportion of tissue-associated lymphocytes. However, our current understanding of human γδ T cells is primarily based on peripheral blood subsets, while the immunobiology of tissue-associated subsets remains largely unclear. Therefore, we aimed to elucidate the T cell receptor (TCR) diversity, immunophenotype and function of γδ T cells in the human liver.
We characterised the TCR repertoire, immunophenotype and function of human liver infiltrating γδ T cells, by TCR sequencing analysis, flow cytometry, in situ hybridisation and immunohistochemistry. We focussed on the predominant tissue-associated Vδ2− γδ subset, which is implicated in liver immunopathology.
Intrahepatic Vδ2− γδ T cells were highly clonally focussed, with single expanded clonotypes featuring complex, private TCR rearrangements frequently dominating the compartment. Such T cells were predominantly CD27lo/− effector lymphocytes, whereas naïve CD27hi, TCR-diverse populations present in matched blood were generally absent in the liver. Furthermore, while a CD45RAhi Vδ2− γδ effector subset present in both liver and peripheral blood contained overlapping TCR clonotypes, the liver Vδ2− γδ T cell pool also included a phenotypically distinct CD45RAlo effector compartment that was enriched for expression of the tissue tropism marker CD69, the hepatic homing chemokine receptors CXCR3 and CXCR6, and liver-restricted TCR clonotypes, suggestive of intrahepatic tissue residency. Liver infiltrating Vδ2− γδ cells were capable of polyfunctional cytokine secretion, and unlike peripheral blood subsets, were responsive to both TCR and innate stimuli.
These findings suggest that the ability of Vδ2− γδ T cells to undergo clonotypic expansion and differentiation is crucial in permitting access to solid tissues, such as the liver, which results in functionally distinct peripheral and liver-resident memory γδ T cell subsets. They also highlight the inherent functional plasticity within the Vδ2− γδ T cell compartment and provide information that could be used for the design of cellular therapies that suppress liver inflammation or combat liver cancer.
γδ T cells are frequently enriched in many solid tissues, however the immunobiology of such tissue-associated subsets in humans has remained unclear. We show that intrahepatic γδ T cells are enriched for clonally expanded effector T cells, whereas naïve γδ T cells are largely excluded. Moreover, whereas a distinct proportion of circulating T cell clonotypes was present in both the liver tissue and peripheral blood, a functionally and clonotypically distinct population of liver-resident γδ T cells was also evident. Our findings suggest that factors triggering γδ T cell clonal selection and differentiation, such as infection, can drive enrichment of γδ T cells into liver tissue, allowing the development of functionally distinct tissue-restricted memory populations specialised in local hepatic immunosurveillance.
CD8⁺ T lymphocytes play a key role in host defense, in particular against important persistent viruses, although the critical functional properties of such cells in tissue are not fully defined. We ...have previously observed that CD8⁺ T cells specific for tissue-localized viruses such as hepatitis C virus express high levels of the C-type lectin CD161. To explore the significance of this, we examined CD8⁺CD161⁺ T cells in healthy donors and those with hepatitis C virus and defined a population of CD8⁺ T cells with distinct homing and functional properties. These cells express high levels of CD161 and a pattern of molecules consistent with type 17 differentiation, including cytokines (e.g., IL-17, IL-22), transcription factors (e.g., retinoic acid-related orphan receptor γ-t, P = 6 x 10⁻⁹; RUNX2, P = 0.004), cytokine receptors (e.g., IL-23R, P = 2 x 10⁻⁷; IL-18 receptor, P = 4 x 10⁻⁶), and chemokine receptors (e.g., CCR6, P = 3 x 10⁻⁸; CXCR6, P = 3 x 10⁻⁷; CCR2, P = 4 x 10⁻⁷). CD161⁺CD8⁺ T cells were markedly enriched in tissue samples and coexpressed IL-17 with high levels of IFN-γ and/or IL-22. The levels of polyfunctional cells in tissue was most marked in those with mild disease (P = 0.0006). These data define a T cell lineage that is present already in cord blood and represents as many as one in six circulating CD8⁺ T cells in normal humans and a substantial fraction of tissue-infiltrating CD8⁺ T cells in chronic inflammation. Such cells play a role in the pathogenesis of chronic hepatitis and arthritis and potentially in other infectious and inflammatory diseases of man.
The Eastern Qinling region, located in the southern margin of the North China Craton, is characterised by widespread granitoid intrusions. Precise geochronological constraints on the age and timing ...of these intrusions are lacking. In this paper, we report SHRIMP zircon U-Pb ages of 12 representative granitoid plutons, together with one syenite stock, dolerite, diorite and granitic dykes in Eastern Qinling. The results revealed two main magmatic events, which occurred in the Late Jurassic-Early Cretaceous (158 ± 3 to 136 ± 2 Ma) and the Early Cretaceous (134 ± 1 to 108 ± 2 Ma), respectively. The granitoids formed in the early magmatic event are similar in composition and are characterised by a mantle source mixed with variable amounts of crustal components, whereas those resulting from the late-stage magmatism show characters of I-, S- and A-types granite and coexist with coeval dolerite dykes and syenite stocks. A similar magmatic age distribution is also recognised in other belts or regions in East China, and even in other parts of the East Eurasian continental margin. This suggests that the Jurassic-Early Cretaceous magmatism was associated with the subduction of the Izanagi plate at a shallow angle or flat-slab subduction beneath the eastern China continent, whereas the Early Cretaceous magmatism was related to lithospheric thinning, asthenospheric upwelling and partial melting of the lower crust, induced by a change in Izanagi plate motion parallel to the continent margin.
Wolbachia infections confer protection for their insect hosts against a range of pathogens including bacteria, viruses, nematodes and the malaria parasite. A single mechanism that might explain this ...broad-based pathogen protection is immune priming, in which the presence of the symbiont upregulates the basal immune response, preparing the insect to defend against subsequent pathogen infection. A study that compared natural Wolbachia infections in Drosophila melanogaster with the mosquito vector Aedes aegypti artificially transinfected with the same strains has suggested that innate immune priming may only occur in recent host-Wolbachia associations. This same study also revealed that while immune priming may play a role in viral protection it cannot explain the entirety of the effect.
Here we assess whether the level of innate immune priming induced by different Wolbachia strains in A. aegypti is correlated with the degree of protection conferred against bacterial pathogens. We show that Wolbachia strains wMel and wMelPop, currently being tested for field release for dengue biocontrol, differ in their protective abilities. The wMelPop strain provides stronger, more broad-based protection than wMel, and this is likely explained by both the higher induction of immune gene expression and the strain-specific activation of particular genes. We also show that Wolbachia densities themselves decline during pathogen infection, likely as a result of the immune induction.
This work shows a correlation between innate immune priming and bacterial protection phenotypes. The ability of the Toll pathway, melanisation and antimicrobial peptides to enhance viral protection or to provide the basis of malaria protection should be further explored in the context of this two-strain comparison. This work raises the questions of whether Wolbachia may improve the ability of wild mosquitoes to survive pathogen infection or alter the natural composition of gut flora, and thus have broader consequences for host fitness.
ABSTRACT
H9N2 subtype avian influenza virus (AIV) was the highly contagious pathogen which has caused severe losses in the poultry industry throughout China in recent years. Using current epidemic ...viruses as vaccine was an effective way to prevent infection of H9N2 subtype AIV. In this study, a total of 23 H9N2 subtype AIV strains were isolated in 200 samples from 13 provinces of China during 2012-2016. The sequencing and phylogenetic analysis of the hemagglutinin gene sequence of the isolation strains showed that 22 isolation strains were clustered to h9.4.2.5 lineage, while only 1 belonged to h9.4.2.6. The data of cross-HI, neutralization and cross-immune protection shown that the A/chicken/Hunan/HN/2015 (HN) and A/chicken/Shandong/SD/2014 (SD) strains as vaccine could effectively protect present viruses infection compared with other strains. These results indicated that current epidemic viruses were mainly belong to h9.4.2.5 lineage and HN and SD strains as candidate vaccine strains were potentiality for the protection of present H9N2 subtype AIV infection.
Abstract Chemokines direct leukocyte trafficking and positioning within tissues. They thus play critical roles in regulating immune responses and inflammation. The chemokine system is complex ...involving interactions between multiple chemokines and their receptors that operate in combinatorial cascades with adhesion molecules. The involvement of multiple chemokines and chemokine receptors in these processes brings flexibility and specificity to recruitment. The hepatic vascular bed is a unique low flow environment through which leukocyte are recruited to the liver during homeostatic immune surveillance and in response to infection or injury. The rate of leukocyte recruitment and the nature of cells recruited through the sinusoids in response to inflammatory signals will shape the severity of disease. At one end of the spectrum fulminant liver failure results from a rapid recruitment of leukocytes that leads to hepatocyte destruction and liver failure at the other diseases such as chronic hepatitis C infection may progress over many years from hepatitis to fibrosis and cirrhosis. Chronic hepatitis is charactezised by a T lymphocyte rich infiltrate and the nature and outcome of hepatitis will depend on the T cell subsets recruited, their activation and function within the liver. Different subsets of effector T cells have been described based on their secretion of cytokines and specific functions. These include Th1 and Th2 cells and more recently Th17 and Th9 cells which are associated with different types of immune response and which express distinct patterns of chemokine receptors that promote their recruitment under particular conditions. The effector function of these cells is balanced by the recruitment of regulatory T cells that are able to suppress antigen-specific effectors to allow resolution of immune responses and restoration of immune homeostasis. Understanding the signals that are responsible for recruiting different lymphocyte subsets to the liver will elucidate disease pathogenesis and open up new therapeutic approaches to modulate recruitment in favour of resolution rather than injury.
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