Potential of damage associated molecular patterns in synergising radiation and the immune response in oesophageal cancer

BACKGROUND There is an intimate crosstalk between cancer formation,dissemination,treatment response and the host immune system,with inducing tumour cell death the ultimate therapeutic goal for most anti-cancer treatments.However,inducing a purposeful synergistic response between conventional therapies and the immune system remains evasive.The release of damage associated molecular patterns(DAMPs)is indicative of immunogenic cell death and propagation of established immune responses.However,there is a gap in the literature regarding the importance of DAMP expression in oesophageal adenocarcinoma(OAC)or by immune cells themselves.AIM To investigate the effects of conventional therapies on DAMP expression and to determine whether OAC is an immunogenic cancer.METHODS We investigated the levels of immunogenic cell death-associated DAMPs,calreticulin(CRT)and HMGB1 using an OAC isogenic model of radioresistance.DAMP expression was also assessed directly using ex vivo cancer patient T cells(n=10)and within tumour biopsies(n=9)both pre and post-treatment with clinically relevant chemo(radio)therapeutics.RESULTS Hypoxia in combination with nutrient deprivation significantly reduces DAMP expression by OAC cells in vitro.Significantly increased frequencies of T cell DAMP expression in OAC patients were observed following chemo-(radio)therapy,which was significantly higher in tumour tissue compared with peripheral blood.Patients with high expression of HMGB1 had a significantly better tumour regression grade(TRG 1-2)compared to low expressors.CONCLUSION In conclusion,OAC expresses an immunogenic phenotype with two distinct subgroups of high and low DAMP expressors,which correlated with tumour regression grade and lymphatic invasion.It also identifies DAMPs namely CRT and HMGB1 as potential promising biomarkers in predicting good pathological responses to conventional chemo(radio)therapies currently used in the multimodal management of locally advanced disease.

Dietary Patterns Associated Metabolic Syndrome in Chinese Adults

Dietary pattern has been revealed to be associated with metabolic syndrome. However, the association was not well documented in Chinese due to the complexity of Chinese foods. We mainly assessed the dietary patterns and examined their effects on metabolic syndrome among Chinese adults. Four dietary patterns including ＇Refined Grains ＆ Vegetables＂ Pattern, ＇Dairy ＆ Eggs＇ Pattern, ＇Organ Meat ＆ Poultry＇ Pattern, and ＇Coarse Grains ＆ Beans＇ Pattern were extracted. ＇Dairy ＆ Eggs＇ Pattern was associated with a decreased odds of metabolic syndrome in women, and ＇Coarse Grains ＆ Beans＇ Pattern was associated with a decreased odds of hypertension in men. These results provided a scientific basis for future research and dietarv euideline Perfection.

Spatial patterns and storage composition of woody debris in a natural secondary forest dominated by Pinus tabulaeformis on Loess Plateau, China

Woody debris(WD) is an important par of natural Pinus tabulaeformis mixed stands, and i affects the forest ecosystem stability and developmen The WD spatial patterns are especially importan structural characteristics that can provide insights into forest dynamics. In this paper, the WD storage WD spatial patterns and WD associations among the main species were examined in the natural secondary forest on Loess Plateau in northwest China. Data were collected in a 1 ha(100 m × 100 m) permanent plot and all the trees with a diameter at breast height o more than 3 cm were measured and stem-mapped Ripley's K functions from the spatial-point-pattern analysis method were used to analyze the spatia distribution and associations. The results showed tha(1) The total storage of WD was 10.73 t/ha, fallen wood was the main source of WD, and the majority diameters were greater than 20 cm, and in intermediate levels of decay;(2) The overall spatia pattern was closely related to the spatial scale, which exhibited an aggregated pattern on a small scale, and a random pattern on a large scale. The spatia patterns of coarse woody debris also gradually transitioned from an aggregated pattern in fine scales to a random pattern in broader spatial scales, which matched the overall spatial pattern. The spatial intensity was gradually decreased with the increasing diameters, and increased with the decomposition classes;(3) The WD of Pinus tabulaeformis species was negatively associated with Betula platyphylla and Populus davidiana on a small scale but positively associated with these species on a large scale. The spatial pattern and interspecies relations were the results of long-term interactions between the natural secondary forest community and the surrounding natural environment. These findings would provide a scientific basis for the sustainable management and protection of natural secondary forest ecosystems on Loess Plateau.

Seasonality and causes of the Yellow Sea Warm Current

To study the seasonality and causes of the Yellow Sea Warm Current (YSWC) in detail, rotated empirical orthogonal function (REOF) and extended associate pattern analysis are adopted with daily sea surface salinity (SSS), sea surface temperature (SST) and sea surface height (SSH) datasets covering 1126 days from American Navy Experimental Real-Time East Asian Seas Ocean Nowcast System in the present paper. Results show that in the Yellow and East China Seas, the YSWC is a mean barotropic flow as compensation of winter-monsoon-driven surface currents, which has been directly observed. When East Asia winter monsoon weakens, so do the meridional pressure gradient of the surface seawater and the YSWC, while the transversal pressure gradient changes rather slowly that results in the YSWC left turning. In addition, there is southward mean flow compensation of summer-monsoon-driven surface currents, which actually was also directly observed.

An Association Pattern of Constituent Factors of the Elder Care Community in China

With the development of the aging society in China,the contradiction between the growing old people and the shortage of the elder care community has been increasingly sharp.How to reasonably and effectively establish the elder care community becomes a problem that demanding prompt solution in China.This paper,starting from the most basic constituent factors of the elder care community,namely the concept,the configuration and the service,analyzes 6 types of the concept,redefines the type of the building configuration of the elder care community,and explains the types and levels of the service,which aims to guide the elder care community to deal with the relationship between the 3 factors with a view to providing a reference for the architectural design and standard preparation in the elder care community.

Effects of microtopography on spatial point pattern of forest stands on the semi-arid Loess Plateau,China

Microtopography may affect the distribution of forests through its effect on rain redistribution and soil water distribution on the semi-arid Loess Plateau,China.In this study,we investigated the characteristics of microtopography on two shady slopes（slope A,5 hm2,uniform slope;slope B,5 hm2,microtopography slope） and surveyed the height,the diameter at breast height and the location（x,y coordinates） of all selected individual trees（Robinia pseudoacacia Linn.,Pyrus betulifolia Bunge,Populus hopeiensis Hu ＆ Chow,Armeniaca sibirica Lam.,Populus simonii Carr.and Ulmus pumila Linn.） on slope A and slope B in the watersheds of Wuqi county,Shaanxi province.Subsequently,the effects of microtopography on the spatial pattern of forest stands were analyzed using Ripley＇s K（r） function.The results showed that：（1） The maximal aggregation radiuses of the tree species on the uniform slope（slope A） were larger than 40 m,whereas those of the tree species on the microtopography slope（slope B） were smaller than 30 m.（2） On slope B,the spatial association of R.pseudoacacia with P.betulifolia,A.sibirica,P.simonii and U.pumila varied from being strongly negative to positive at microtopography scales.The spatial association of Populus hopeiensis Hu ＆ Chow with U.pumila also varied from being strongly negative to positive at microtopography scales.However,there was no spatial association between P.betulifolia and P.hopeiensis,P.betulifolia and A.sibirica,P.betulifolia and P.simonii,P.betulifolia and U.pumila,P.hopeiensis and A.sibirica,P.hopeiensis and P.simonii,A.sibirica and P.simonii,A.sibirica and U.pumila,and P.simonii and U.pumila.On slope A,the spatial association between tree species were strongly negative.The results suggest that microtopography may shape tree distribution patterns on the semi-arid Loess Plateau.

Spatial pattern analysis and associations of different growth stages of populations of Abies georgei var.smithii in Southeast Tibet,China

Abies georgei var.smithii is an important plant species in Southeast Tibet,China.It has high ecological value in terms of biodiversity protection,as well as soil and water conservation.We analyzed the spatial pattern and associations of A.georgei var.smithii populations at different growth stages by using Ripley's L function for point pattern analysis.The diameter structure was a nearly reverse 'J' shape.The amount of saplings and medium-sized trees accounts for a large part of the entire population,suggesting a high regeneration rate and an expanding population.In the transition from saplings to medium trees or to large trees,saplings show a significant aggregation distribution at small scales,while medium trees and large trees show a random distribution.There are significant inverse associations between saplings and medium trees and large trees at small scales,while there are no obvious associations between medium trees and large trees.The natural regeneration was affected by interspecific competition,and it was also affected by intraspecific competition.The joint effects of biological characteristics and environmental factors contribute to the spatial distribution pattern and associations of this A.georgei var.sm ithii population.

E1 Nio phenomenon in simple ocean data assimilation data

To study how the air and sea interact with each other during El Nifio/La Nifia onsets, extended associate pattern analysis （EAPA） is adopted with the simple ocean data assimilation （SODA） data. The results show that as El Niйo/La Niйa＇s parents their behaviors are quite different, there does not exist a relatively independent tropical atmosphere but does exist a relatively independent tropical Pacific Ocean because the air is heated from the bottom surface instead of the top surface and of much stronger baroclinic instability than the sea and has a very large inter-tropical convergence zone covering the most tropical Pacific Ocean. The idea that it is the wester burst and wind convergence, coming from middle latitudes directly that produce the seawater eastward movement and meridional convergence in the upper levels and result in the typical E1 Nifio sea surface temperature warm signal is confirmed again.

Statistical analysis of surface hydrography and circulation variations in northern South China Sea

To study the variations in surface hydrography and circulation in northern South China Sea (NSCS), rotated empirical orthogonal function (REOF) and extended associate pattern analysis (EAPA) are used with daily sea surface salinity (SSS), sea surface temperature (SST) and sea surface height (SSH) datasets cover- ing 1 126 days from American Navy Experimental Real-Time East Asian Seas Ocean Nowcast System in this paper. Results show that in summer, the SCS Diluted Water Expansion (SDWE) is the most dominant factor con- trolling SSS variations in the NSCS. The remarkable SDWE usually begins in early July, reaches its maximum in middle August and weakens in late September. In summer flourishing period, its low saline core is just limited between 21°N and 22°N because of strong surface anomalous anticyclonic circulation in the NSCS. In early or late stage, the anomalous anticyclonic circulation becomes weak or turns into cyclonic one, thus the weak SCS diluted water can disperse. And its influence on the SSS variations has obviously decreased. The Kuroshio intrusion is the second controlling factor, and it has the almost opposite seasonal or intraseasonal oscillations and spatial charac- teristics to the SDWE. Winter Kuroshio Intrusion (WKI) begins in early November and lasts about three months. Intraseasonal Kuroshio Intrusion (IKI) takes place at any seasons. The westward Ekman transport produced by the north anomaly of East Asia Monsoon (EAM) pushes warmer and more saline seawater into the NSCS through the Bashi Strait and seems to decide the intensity of seasonal and intraseasonal Kuroshio intrusions.

Immunological aspects of age-related diseases

The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of na?ve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging. Many effector functions including phagocytosis of myeloid cells are down regulated by aging. The studies of aging of myeloid cells have some controversial results. Although M1 macrophages have been shown to be replaced by antiinflammatory(M2) macrophages by advanced age, many human studies showed that pro-inflammatory cytokines are elevated in older human. To solve this discrepancy here we divide age-related pathological changes into two categories. One is an aging of immune cell itself. Second is involvement of immune cells to age-related pathological changes. Cellular senescence and damaged cells in aged tissue recruit pro-inflammatory M1 macrophages, which produce pro-inflammatory cytokines and proceed to agerelated diseases. Underlying biochemical and metabolic studies will open nutritional treatment.

Phylotype resolved spatial variation and association patterns of planktonic Thaumarchaeota in eastern Chinese marginal seas

The majority of marine ammonia oxidizers belong to Thaumarchaeota,a phylum of Archaea,which is distributed throughout the water column.Marine surface waters contain distinct thaumarchaeotal phylotypes compared to the deeper ocean,but spatial dynamics of the surface-associated lineages are largely unsolved.This study of 120 seawater samples from the eastern Chinese marginal seas identifed contrasting distribution and association patterns among thaumarchaeotal phylotypes across diferent dimensions.Horizontally,Nitrosopumilus-like and Nitrosopelagicus-like phylotypes dominated the surface water(3 m)of the Yellow Sea(YS)and East China Sea(ECS),respectively,along with increased abundance of total free-living Thaumarchaeota in ECS.Similar compositional changes were observed in the surface microlayer.The spatial heterogeneity of particle-attached Thaumarchaeota was less clear in surface microlayers than in surface waters.Vertically,the Nitrosopelagicus-like phylotype increased in abundance from surface to 90 m in ECS,which led to an increase in the proportion of Thaumarchaeota relative to total prokaryotes.This occurred mainly in the free-living fraction.These results indicate a clear size-fractionated niche partitioning,which is more pronounced at lower depths than in the surface water/surface microlayer.In addition,associations of Thaumarchaeota with other microbial taxa varied between phylotypes and size fractions.Our results show that a phylotype-resolved and size-fractionated spatial heterogeneity of the thaumarchaeotal community is present in surface oceanic waters and a vertical variation of the Nitrosopelagicus-like phylotype is present in shallow shelf waters.

Old and new damage‐associated molecular patterns (DAMPs) in autoimmune diseases

All organisms living in complex environments have evolved effective mechanisms of dynamic responses to extracellular stimuli.The immune system activates when damaged or injured cells release damage‐associated molecular patterns(DAMPs).In addition to well‐characterized DAMPs such as high‐mobility group box 1 and adenosine triphosphate,studies on new classes of DAMPs have emerged.Here,we review recent reports of a new class of isoprenoid‐derived DAMPs,including farnesyl pyrophosphate and geranylgeranyl pyrophosphate,both of which are pivotal metabolic inter-mediates of the mevalonate pathway.We also explore the roles of old and new DAMPs in autoimmune diseases that result from dysregulated inflammation.The findings highlight that understanding the functional mechanisms of DAMPs is important to enrich the DAMP family and decipher their immunoregulatory mechanisms to provide new therapeutics for the prevention and treatment of autoimmune diseases.

EI NIO PHENOMENON AND EXTENDED ASSOCIATE PATTERN ANALYSIS

To study the causes of El Nino Phenomenon the Extended Associate PatternAnalysis (EAPA) is set up with monthly sea surface wind stress and precipitation besides Sea LevelPressure (SLP) and Sea Surface Temperature (SST) in or over the Pacific and related seas since 1979in present paper. The results show that El Nino Phenomenon means a SST redistribution, coveringalmost the whole Pacific that needs a huge amount of energy provided by air-sea interaction in themost Pacific regions; It is the wester burst and wind convergence, coming from meddle latitudesdirectly, instead of Kelvin waves that produce the strong SST warm signal in Nino regions; Twonegative SLP anomalies in middle of the North and South Pacific, most likely produced by the averageair pressure decreasing effect of explosive cyclones through precipitation, and the positive SLPanomaly o-ver the Asia-Australia land bridge, coming mainly from the south hemisphere with a littleinfluence from the Asian continent, are the three major causes for El Nino onset, they work togetherto produce anomalous wind convergence in Nino regions and wester burst in middle of the North andSouth Pacific that result in a warm tongue and cold pincers gearing together; Basically, during itsearly stage the ocean is forced by the atmosphere, while during its late stage the atmosphere isforced by the ocean.

Fission-fusion dynamics of a pelagic delphinid in the arctic:the white-beaked dolphin(Lagenorhynchus albirostris)

Delphinids exhibit great variability in their social structures.It is therefore important to document lesser known species,in extreme changing habitats,to compare and contrast mechanisms driving sociality.Here,we describe the first long-term assessment of social structure of white-beaked dolphins(Lagenorhynchus albirostris)using a compiled version of SOCPROG 2.8 and an 11-year photo-identification dataset(2002–2013)collected from whalewatching vessels at 2 sites(Faxaflói and Skjálfandi bays)off Iceland.We identified a total of 487 dolphins which are suggested to be part of an open population as shown by the discovery curve obtained analyzing photo-id data.The social analyses were restricted to 35 adults which were sighted on≥5 different days.The mean residency time of white-beaked dolphins in our 2 study areas was of 95 days(SE=35.63;95%CI:23-171),with the“migration-full interchange”model best describing movements of dolphins in and out of our 2 study sites.Social differentiation in this population was high(Likelihood:S=0.87,SE=0.04;r=0.31,SE=0.03)indicating diverse,non-random social relationships.Temporal associations best fit the model of“casual acquaintances”against the standardized lagged association rates with the majority of white-beaked dolphin associations being short-term,but with a few long-term across years.Testing for preferred companionship,long-term associations are favored over short-term.In this study,associations among white-beaked dolphins are short-term but with desirably long-term associations fitting into a society with fission-fusion dynamics.This information expands the latitudinal range for which social structure has been described for oceanic dolphin species.

Antepenultimate residue at the C-terminus of NADPH oxidase RBOHD is critical for its function in the production of reactive oxygen species in Arabidopsis

Production of reactive oxygen species(ROS)is a conserved immune response primarily mediated by NADPH oxidases(NOXs),also known in plants as respiratory burst oxidase homologs(RBOHs).Most microbe-associated molecular patterns(MAMPs)trigger a very fast and transient ROS burst in plants.However,recently,we found that lipopolysaccharides(LPS),a typical bacterial MAMP,triggered a biphasic ROS burst.In this study,we isolated mutants defective in LPS-triggered biphasic ROS burst(delt)in Arabidopsis,and cloned the DELT1 gene that was shown to encode RBOHD.In the delt1-2 allele,the antepenultimate residue,glutamic acid(E919),at the C-terminus of RBOHD was mutated to lysine(K).E919 is a highly conserved residue in NADPH oxidases,and a mutation of the corresponding residue E568 in human NOX2 has been reported to be one of the causes of chronic granulomatous disease.Consistently,we found that residue E919 was indispensable for RBOHD function in the MAMP-induced ROS burst and stomatal closure.It has been suggested that the mutation of this residue in other NADPH oxidases impairs the protein’s stability and complex assembly.However,we found that the E919K mutation did not affect RBOHD protein abundance or the ability of protein association,suggesting that the residue E919 in RBOHD might have a regulatory mechanism different from that of other NOXs.Taken together,our results confirm that the antepenultimate residue E is critical for NADPH oxidases and provide a new insight into the regulatory mechanisms of RBOHD.