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Abstract Despite limited research on refractory and/or endocrine therapy failure in elderly metastatic breast cancer (MBC) patients, a prior study showed that low-dose oral cyclophosphamide (CY) can improve the overall survival rate of MBC patients, possibly through the immunoregulation of regulatory T cells (Tregs). We preliminarily investigated the combination of endocrine therapy (ET) with oral low-dose CY as salvage therapy in elderly patients via peripheral blood regulatory T-cell analyses. In addition, we evaluated the associations of tumor tertiary lymphoid structures (TLSs) with therapeutic outcomes. HR+/HER2− advanced breast cancer patients who received low-dose CY combined with ET or ET only from April 2015 to August 2021 were enrolled in this retrospective study. The primary outcome was the clinical control rate (CCR), and the secondary outcome was progression-free survival (PFS). Circulating T lymphocyte subpopulations represented by Tregs were monitored during treatment by flow cytometry methods. TLSs wereconfirmed by hematoxylin–eosin staining of pretreatment specimens, and CD3, CD4, and Foxp3 were detected using Opal multicolor immunofluorescence. A total of 85 patients who received CY + ET and 50 patients who received ET only were enrolled, the percentage of patients who received CCR was 73% (62/85) vs. 70% (45/50), and the objective response rate (ORR) was 28% (24/85) vs. 24% (12/50). No deaths occurred during the study period. The mean PFS time was 13 vs. 11 months (P = 0.03). In the CY + ET group, decreases in CD4+/CD25+/Foxp3+ T cells (P

Abstract Plant reproductive ecology is one of the research hotspots in ecology. With the increasing attention paid to the conservation of plant diversity, the research on reproductive characteristics and flowering biological characteristics of more species has attracted more attention. However, plant reproduction is affected by multiple interacting factors such as pollen limitation and resource availability. Vitex negundo var. heterophylla (Franch.) Rehder (Lamiaceae) is a significant species for water and soil conservation. Previous studies have revealed its mating system by the biological characteristics of flowering and SSR markers, but its reproductive strategies remain to be further studied. We evaluated reproductive success through artificial pollination to explore the reproductive characteristics of V. negundo var. heterophylla for the first time. From the results of fruit set, there is a mixed mating system dominated by outcrossing in V. negundo var. heterophylla accompanied by self‐compatibility, and it cannot carry out autonomous selfing. Our data show the pollinator‐mediated interaction in the success of reproduction, whereas the effect of anemophily is very weak. And the seed germination rate of inbred line progenies was lower than that of hybrid progenies, which is suspected to be caused by inbreeding depression. The research will provide scientific information for the protection and conservation of V. negundo var. heterophylla from the point of view of reproduction. In sum, the results are necessary to protect animal vectors in the background of insect decline.

Climate varies along geographic gradients, causing spatial variations in the effects of energy and water on species richness and the explanatory power of different climatic factors. Species of the Quercus genus are important tree species in China with high ecological and socioeconomic value. To detect whether the effects of energy and water on species richness change along climatic gradients, this study built geographically weighted regression models based on species richness and climatic data. Variation partition analysis and hierarchical partitioning analysis were used to further explore the main climatic factors shaping the richness distribution pattern of Quercus in China. The results showed that Quercus species were mainly distributed in mountainous areas of southwestern China. Both energy and water were associated with species richness, with global slopes of 0.17 and 0.14, respectively. The effects of energy and water on species richness gradually increased as energy and water in the environment decreased. The interaction between energy and water altered the effect of energy, and in arid regions, the effects of energy and water were relatively stronger. Moreover, energy explained more variation in species richness in both the entire study area (11.5%) and different climate regions (up to 19.4%). The min temperature of coldest month was the main climatic variable forming the richness distribution pattern of Quercus in China. In conclusion, cold and drought are the critical climatic factors limiting the species richness of Quercus, and climate warming will have a greater impact in arid regions. These findings are important for understanding the biogeographic characteristics of Quercus and conserving biodiversity in China.

Sandstorm, as a disastrous weather phenomenon, seriously threatens the ecological environment and human health. In this study, the normalized brightness temperature dust index (NBTDI) data set of sandstorms in Yellow River Basin, China during 2000–2021 was constructed. Based on this, the temporal and spatial distribution pattern of sandstorms in the Yellow River Basin in the 21st century was analyzed. The variation trend of NBTDI in the past 22 years was discussed. The results showed that the interannual variation of sandstorms in the 21st century weakened first and then intensified. From the perspective of seasonal variation, sandstorm events occurred most frequently in spring (92.4%), followed by winter (5.6%), and occasionally in summer and autumn. In space, the distribution of sandstorms in the Yellow River Basin had obvious spatial heterogeneity. The central location of the sandstorm in the Yellow River Basin moved slightly to the north, but all of them were concentrated on desert areas. This was caused by the combination of unique geographical location and meteorological factors. The natural climate was closely related to the occurrence of sandstorms. The variation trend of long time-series NBTDI indicated that there were long memories between 22 years of sandstorms. NBTDI had an increasing trend in the long time series. In the future, sandstorms will become more frequent, in line with past trends. This study provides important data support for comprehensive understanding of extreme sandstorm weather, and has important significance for large-scale and long-term monitoring of sandstorm weather.

ObjectiveAutoantibodies have been reported to be associated with cancers. As a biomarker, autoantibodies have been widely used in the early screening of lung cancer. However, the correlation between autoantibodies and the prognosis of lung cancer patients is poorly understood, especially in the Asian population. This retrospective study investigated the association between the presence of autoantibodies and outcomes in patients with lung cancer.MethodsA total of 264 patients diagnosed with lung cancer were tested for autoantibodies in Henan Provincial People’s Hospital from January 2017 to June 2022. The general clinical data of these patients were collected, and after screening out those who met the exclusion criteria, 151 patients were finally included in the study. The Cox proportional hazards model was used to analyze the effect of autoantibodies on the outcomes of patients with lung cancer. The Kaplan-Meier curve was used to analyze the relationship between autoantibodies and the overall survival of patients with lung cancer.ResultsCompared to lung cancer patients without autoantibodies, those with autoantibodies had an associated reduced risk of death (HRs: 0.45, 95% CIs 0.27~0.77), independent of gender, age, smoking history, pathological type, and pathological stage of lung cancer. Additionally, the association was found to be more significant by subgroup analysis in male patients, younger patients, and patients with small cell lung cancer. Furthermore, lung cancer patients with autoantibodies had significantly longer survival time than those without autoantibodies.ConclusionThe presence of autoantibodies is an independent indicator of good prognosis in patients with lung cancer, providing a new biomarker for prognostic evaluation in patients with lung cancer.

Recent studies have reported the growth of 2D non-centrosymmetric single crystals on substrates with surface steps, but the mechanisms are still unclear. Here, the authors demonstrate a method to grow unidirectionally aligned transition metal dichalcogenide grains on various types of substrates, showing the importance of the simultaneous formation of grain nuclei and substrate steps.

The increase of nitrogen (N) deposition and the diversity of its components lead to significant changes in the structure and function of temperate meadow steppe, which could affect plant nutrient uptake, nutrient resorption and litter decomposition, thus affecting the biogeochemical cycle process. The distribution and metabolism of nitrogen and phosphorus in plants determine the growth process and productivity of plants. Plant nutrient uptake, nutrient resorption and litter decomposition play an important role in the nutrient cycling process of ecosystem. This study closely combined these three processes to carry out experiments with different nitrogen dosages and types, and systematically explored the response of nitrogen and phosphorus nutrient cycling to nitrogen deposition. The results showed that nitrogen deposition can greatly affect ecosystem nutrient cycle of nitrogen and phosphorus. Firstly, Nitrogen deposition has significant effect on plant nutrient uptake. Nitrogen uptake of stems and leaves increased with the increase of nitrogen addition dosage, while phosphorus uptake of stems and leaves showed a downward trend or no significant effect. Besides, nitrogen addition type had a significant effect on nitrogen and phosphorus content of stems. Secondly, Nitrogen addition dosage had a significant effect on plant nutrient resorption, while nitrogen addition type had no significant effect on it. Thirdly, nitrogen deposition has significant effect on litter decomposition. With the increase of nitrogen addition dosage, the initial nitrogen content of litters increased and the decomposition rate of litters accelerated. Nitrogen application type had significant effect on stem litter decomposition. These results indicated that nitrogen deposition significantly affects plant nutrient cycling, and thus affects the structure and function of grassland ecosystem.

IntroductionIt is of great significance to understand the characteristics and influencing factors of vegetation coverage variation in the warm temperate zone. As a typical region of the warm temperate zone in eastern China, the mountainous and hilly region in central-south Shandong Province has fragile ecological environment and soil erosion problem. Studying on vegetation dynamics and its influencing factors in this region will help to better understand the relationship between climate change and vegetation cover change in the warm temperate zone of eastern China, and the influence of human activities on vegetation cover dynamics.MethodsBased on dendrochronology, a standard tree-ring width chronology was established in the mountainous and hilly region of central-south Shandong Province, and the vegetation coverage from 1905 to 2020 was reconstructed to reveal the dynamic change characteristics of vegetation cover in this region. Secondly, the influence of climate factors and human activities on the dynamic change of vegetation cover was discussed through correlation analysis and residual analysis.Results and discussionIn the reconstructed sequence, 23 years had high vegetation coverage and 15 years had low vegetation coverage. After low-pass filtering, the vegetation coverage of 1911–1913, 1945–1951, 1958–1962, 1994–1996, and 2007–2011 was relatively high, while the vegetation coverage of 1925–1927, 1936–1942, 2001–2003, and 2019–2020 was relatively low. Although precipitation determined the variation of vegetation coverage in this study area, the impacts of human activities on the change of vegetation coverage in the past decades cannot be ignored. With the development of social economy and the acceleration of urbanization, the vegetation coverage declined. Since the beginning of the 21st century, ecological projects such as Grain-for-Green have increased the vegetation coverage.

BackgroundThe tumor immune microenvironment could provide prognostic and predictive information. It is necessary to develop a noninvasive radiomics-based biomarker of a previously validated tumor immune microenvironment signature of gastric cancer (GC) with immunohistochemistry staining.MethodsA total of 230 patients (training (n = 153) or validation (n = 77) cohort) with gastric cancer were subjected to (Positron Emission Tomography-Computed Tomography) radiomics feature extraction (80 features). A radiomics tumor immune microenvironment score (RTIMS) was developed to predict the tumor immune microenvironment signature with LASSO logistic regression. Furthermore, we evaluated its relation with prognosis and chemotherapy benefits.ResultsA 8-feature radiomics signature was established and validated (area under the curve=0.692 and 0.713). The RTIMS signature was significantly associated with disease-free survival and overall survival both in the training and validation cohort (all P

It has widely been documented that nitrogen (N) enrichment stimulates plant growth and modifies plant functional traits in the terrestrial ecosystem. However, it remains unclear whether there are critical transitions or tipping points for the response of plant growth or traits to N enrichment, and how these responses differ to different N forms. We chose the native, perennial clonal grass, Leymus chinensis in Inner Mongolia steppe, and conducted a field experiment, in which six N addition rates (0, 2, 5, 10, 20, and 50 g N m–2 year–1) and five N compound types [NH4NO3, (NH4)2SO4, NH4HCO3, CO(NH2)2, slow-release CO(NH2)2] are considered. Here, we found that the different N compound types had no significant effect on the growth of L. chinensis. N addition rate significantly increased plant aboveground biomass and leaf nitrogen concentration, whereas decreased leaf dry matter content. The tipping point for N-induced aboveground biomass increase was at 10 g N m–2 year–1, and the changes in functional traits were at N addition rates of 20 g N m–2 year–1. Our findings suggested that the responses of aboveground biomass and functional traits to N addition were asymmetric, in which responses in aboveground biomass were more sensitive than that in functional traits. The differential sensitivity of aboveground biomass and functional traits of L. chinensis occurred to N deposition highlights the importance of functional traits in mediating ecosystem functioning in the face of N deposition, regardless of which chemical forms dominate in the deposited N.

Circular RNA (circRNA) is stable and abundant in exosomes as a potential biomarker for the diagnosis and prognosis of tumor. In this study, cancer specific exosomal circRNAs were identified through circRNA microarray, and 58 circRNAs were significantly upregulated in cancer cells derived exosomes. Then 60 patients with newly diagnosed gastric cancer (GC), 30 chronic gastritis patients and 30 healthy subjects were enrolled for further clinical validation. We detected that hsa_circ_0015286 was remarkably highly expressed in GC tissue, plasma and cancer cells compared with normal controls. Results of ROC curve analysis showed that the area under curve (AUC) of hsa_circ_0015286, CEA and CA 19-9 was 0.778, 0.673, and 0.665, respectively. The combined detection of three indicators had the highest AUC (0.843). Exosomal hsa_circ_0015286 expression was closely associated with tumor size, TNM stage and lymph node metastasis. The expression level of exosomal hsa_circ_0015286 in GC patients decreased significantly after surgery. Overall survival of patients with low hsa_circ_0015286 expression was longer than those with high expression. Our data demonstrated that exosomal hsa_circ_0015286 might be a promising noninvasive biomarker for the diagnosis and prognosis evaluation of GC.

As nitrogen deposition intensifies under global climate change, understanding the responses of arbuscular mycorrhizal (AM) fungi to nitrogen deposition and the associated mechanisms are critical for terrestrial ecosystems. In this study, the effects of nitrogen addition and mowing on AM fungal communities in soil and mixed roots were investigated in an Inner Mongolia grassland. The results showed that nitrogen addition reduced the α-diversity of AM fungi in soil rather than that of root. Besides, nitrogen addition altered the composition of AM fungal community in soil. Soil pH and inorganic nitrogen content were the main causes of changes in AM fungal communities affected by nitrogen addition. Mowing and the interaction of nitrogen addition and mowing had no significant effect on AM fungal community diversity. In contrast, while mowing may reduce the negative effects of nitrogen addition on the richness and diversity of plants by alleviating light limitation, it could not do so with the negative effects on AM fungal communities. Furthermore, AM fungal communities clustered phylogenetically in all treatments in both soil and roots, indicating that environmental filtering was the main driving force for AM fungal community assembly. Our results highlight the different responses of AM fungi in the soil and roots of a grassland ecosystem to nitrogen addition and mowing. The study will improve our understanding of the effects of nitrogen deposition on the function of ecosystem.

Abstract Ziziphus jujuba var. spinosa has been used as a windbreak and for soil conservation and water retention. Previous studies focused on pharmacological effects and extraction of chemical components in this species, and very few explored the breeding system. The present study combined the analysis of floral morphology, behavior of flower visitors, and artificial pollination to reveal reproductive characteristics of the species. Its flowers are characterized by dichogamy, herkogamy, and stamen movement, which are evolutionary adaptations to its breeding system. There were more than 40 species of visiting insects, mainly Hymenoptera and Diptera, and the characteristics of dichogamous and herkogamous flower adapted to the visiting insects. The breeding system is outcrossing, partially self-compatible, and demand for pollinators. The fruit setting rate after natural pollination was 2%. Geitonogamy and xenogamy did not significantly increase the fruit setting rate, indicating that the low fruit setting rate was not due to pollen limitation by likely caused by resource limitation or fruit consumption. The fruit setting rate of zero in emasculated and in naturally and hand self-pollinated individuals suggested the absence of apomixis and spontaneous self-pollination. The above results can be utilized in studies on evolution and cultivation of Z. jujuba var. spinosa.

Abstract Vitex negundo L. var. heterophylla (Franch.) Rehder (Lamiaceae) is an important tree species for soil and water conservation, yet the reproductive ecology of this species remains to be elucidated. To investigate the reproductive traits of V. negundo var. heterophylla, the phenology, morphological characteristics (a suite of characters was assessed: floral morphology, nectar production, pollen viability, and stigma receptivity) and mating system of this species were systematically revealed for the first time in this study. Phenological observations, morphological measurements, and nectar production analysis were conducted during anthesis. Pollen viability and stigma receptivity at different flowering stages were measured by biochemical methods. Finally, genetic analysis based on SSR markers was used to reveal the mating system; outcrossing index and pollen‐ovule ratio were also calculated to help analysis. V. negundo var. heterophylla showed several obvious characteristics of outcrossing, such as abundant and attractive flowers, secreting nectar, and emitting scent. In addition, mechanisms such as homogamy and a short anther‐stigma distance that can promote self‐fertilization were also identified in this species. The coexistence of selfing and outcrossing characteristics demonstrates a predominantly outcrossed mixed mating system (outcrossing rate, t = 95%). The scientific information provided by this study may contribute to conservation of V. negundo var. heterophylla from a reproductive perspective.

Plasticity of plant functional traits plays an important role in plant growth and survival under changing climate. However, knowledge about how leaf functional traits respond to the multi-level N addition rates, multiple N compound and duration of N application remains lacking. This study investigated the effects of 2-year and 7-year N addition on the leaf functional traits of Leymus chinensis and Thermopsis lanceolata in a meadow grassland. The results showed that the type of N compounds had no significant effect on leaf functional traits regardless of duration of N application. N addition significantly increased the leaf total N content (LN) and specific leaf area (SLA), and decreased the leaf total P content (LP) and leaf dry matter content (LDMC) of the two species. Compared with short-term N addition, long-term N addition increased LN, LP, SLA, and plant height, but decreased the LDMC. In addition, the traits of the two species were differentially responsive to N addition, LN and LP of T. lanceolata were consistently higher than those of L. chinensis. N addition would make L. chinensis and T. lanceolata tend to “quick investment-return” strategy. Our results provide more robust and comprehensive predictions of the effects of N deposition on leaf traits.

Seedlings in regenerating layer are frequently attacked by herbivorous insects, while the combined effects of defoliation and shading are not fully understood. In the present study, two Leguminosae species (Robinia pseudoacacia and Amorpha fruticosa) were selected to study their responses to combined light and defoliation treatments. In a greenhouse experiment, light treatments (L+, 88% vs L−, 8% full sunlight) and defoliation treatments (CK, without defoliation vs DE, defoliation 50% of the upper crown) were applied at the same time. The seedlings’ physiological and growth traits were determined at 1, 10, 30, and 70 days after the combined treatment. Our results showed that the effects of defoliation on growth and carbon allocation under high light treatments in both species were mainly concentrated in the early stage (days 1–10). R. pseudoacacia can achieve growth recovery within 10 days after defoliation, while A. fruticosa needs 30 days. Seedlings increased SLA and total chlorophyll concentration to improve light capture efficiency under low light treatments in both species, at the expense of reduced leaf thickness and leaf lignin concentration. The negative effects of defoliation treatment on plant growth and non-structural carbohydrates (NSCs) concentration in low light treatment were significantly higher than that in high light treatment after recovery for 70 days in R. pseudoacacia, suggesting sufficient production of carbohydrate would be crucial for seedling growth after defoliation. Plant growth was more sensitive to defoliation and low light stress than photosynthesis, resulting in NSCs accumulating during the early period of treatment. These results illustrated that although seedlings could adjust their resource allocation strategy and carbon dynamics in response to combined defoliation and light treatments, individuals grown in low light conditions will be more suppressed by defoliation. Our results indicate that we should pay more attention to understory seedlings’ regeneration under the pressure of herbivorous insects.

Changing precipitation patterns have aggravated the existing uneven water distribution, leading to the alternation of drought and rewatering. Based on this variation, we studied species, namely, Robinia pseudoacacia and Quercus acutissima, with different root forms and water regulation strategy to determine physiological responses to repeated drought-rewatering under different planting methods. Growth, physiological, and hydraulic traits were measured using pure and mixed planting seedlings that were subjected to drought, repeated drought-rewatering (i.e., treatments), and well-irrigated seedlings (i.e., control). Drought had negative effects on plant functional traits, such as significantly decreased xylem water potential (Ψmd), net photosynthetic rate (AP), and then height and basal diameter growth were slowed down, while plant species could form stress imprint and adopt compensatory mechanism after repeated drought-rewatering. Mixed planting of the two tree species prolonged the desiccation time during drought, slowed down Ψmd and AP decreasing, and after rewatering, plant functional traits could recover faster than pure planting. Our results demonstrate that repeated drought-rewatering could make plant species form stress imprint and adopt compensatory mechanism, while mixed planting could weaken the inhibition of drought and finally improve the overall drought resistance; this mechanism may provide a theoretical basis for afforestation and vegetation restoration in the warm temperate zone under rising uneven spatiotemporal water distribution.

In recent decades, great changes have taken place in residents’ lifestyle and consumption structure. Urban household consumption plays an increasingly significant role in promoting energy use and related carbon emissions. Communities are regarded as the basic part of city, and also units and cases where management methods and policies are most likely to be operated and implemented. In this paper, questionnaire surveys were administered to investigate the consumption characteristics of urban households at the community scale in Zengcheng. Based on statistical analysis, we assessed the consumption differences among the five selected communities. Meanwhile, the carbon emissions caused by household energy consumption (CEs-HE) were evaluated and the influencing factors were studied. The results showed that respondents from different communities had significant differences in their residential consumption, housing conditions, daily travel distance, public transport charge, household durable goods service life, monthly staple food consumption, and monthly energy consumption, respectively. The average CEs-HE of each household were 410.6 ​kg CO2 per month. The Household demographic information, main expenditure items, housing conditions, daily travelling, family life habits and residents’ environmental awareness all had significant impacts on CEs-HE. The results supplied in this study could provide some valuable information for decision-makers to explore the road of urban sustainable development.

BackgroundWe evaluated the ability of radiomics based on intratumoral and peritumoral regions on preoperative gastric cancer (GC) contrast-enhanced CT imaging to predict disease-free survival (DFS) and chemotherapy response in stage II/III GC.MethodsThis study enrolled of 739 consecutive stage II/III GC patients. Within the intratumoral and peritumoral regions of CT images, 584 total radiomic features were computed at the portal venous-phase. A radiomics signature (RS) was generated by using support vector machine (SVM) based methods. Univariate and multivariate Cox proportional hazards models and Kaplan-Meier analysis were used to determine the association of the RS and clinicopathological variables with DFS. A radiomics nomogram combining the radiomics signature and clinicopathological findings was constructed for individualized DFS estimation.ResultsThe radiomics signature consisted of 26 features and was significantly associated with DFS in both the training and validation sets (both P

Understanding the vegetation greenness dynamics in the forest–steppe transition zone is essential for ecosystem management, and in order to study ecological changes in the region. This study provides a valuable record of the vegetation greenness dynamics in the western Greater Khingan Range over the past 193 years (1826–2018) based on tree-ring data represented by the normalized difference vegetation index (NDVI). The reconstructed vegetation greenness dynamics record contains a total of 32 years of high vegetation greenness and 37 years of low vegetation greenness, together occupying 35.8% of the entire reconstructed period (193 years). Climate (precipitation) is the main influence on the vegetation greenness dynamics at this site, but human activities have also had a significant impact over the last few decades. The magnitude, frequency, and duration of extreme changes in vegetation greenness dynamics have increased significantly, with progressively shorter intervals. Analyses targeting human behavior have shown that the density of livestock, agricultural land area, and total population have gradually increased, encroaching on forests and grasslands and reducing the inter-annual variability. After 2002, the government implemented projects to return farmland to its original ecosystems, and for the implementation of new land management practices (which are more ecologically related); as such, the vegetation conditions began to improve. These findings will help us to understand the relationship between climate change and inter- and intra- annual dynamics in northeastern China, and to better understand the impact of human activities on vegetation greenness dynamics.

Abstract In many flowering plants, floral scents are a significant trait for visitors, playing an important role in attracting pollinators and/or detracting herbivores. The evolution of flowering plants from hermaphroditism to dioecy is often accompanied by sexual dimorphism in floral scent. In this study, floral scents emitted by different sexual morphs of the subdioecious shrub Eurya japonica Thunb. were collected using a dynamic headspace method, and sexual and temporal variations were evaluated by gas chromatography–mass spectrometry (GC–MS). Two volatiles, α‐pinene and linalool, were identified as the major components of floral scents in females, hermaphrodites, and males. The males emit higher amounts of floral scents, particularly α‐pinene, compared to females or hermaphrodites. Floral scents emitted by males generally decrease as flowers enter senescence, whereas those from females or hermaphrodites do not significantly differ. Intraspecific variations in floral scents of subdioecious species provided by this study would contribute to better understanding of sexual dimorphism in floral scent.

Abstract The purpose of the present study is to clarify the diffusion of non-volatile substances into cell walls during the conditioning procedure under varying relative humidities (RH). In this paper, wood blocks were impregnated using an aqueous solution of melamine formaldehyde (MF), and they were subsequently conditioned under RHs of 11, 43, and 75%. The solute that diffused into the cell walls was visualized using time-of-flight secondary ion mass spectrometry (TOF-SIMS). The volumetric relative swelling of the samples during the conditioning procedure was calculated. The results showed increased cell wall swelling at higher RH, which may have been caused by higher MF diffusion into the cell walls and/or higher moisture content. Cryo-TOF-SIMS measurements showed that more cell cavities were unfilled with MF at higher RH, indicating that most of the MF diffused from the cell cavities into the cell walls. The relative intensity of MF in the cell walls of the cured samples was evaluated from dry-TOF-SIMS images, which showed a higher relative intensity of MF in the cell walls at higher RH. With the ability to visualize and semi-quantitatively evaluate the solute in cell walls, TOF-SIMS will serve as a powerful tool for future studies of solute diffusion mechanisms in solution-impregnated wood.

Abstract Background ICG-001, a small molecule, binds CREB-binding protein (CBP) to disrupt its interaction with β-catenin and inhibits CBP function as a co-activator of Wnt/β-catenin-mediated transcription. Given its ability to inhibit Wnt/β-catenin signaling pathway, ICG-001 has been used in some tumor types to exert its anticarcinogenic effect. Here, we examined ICG-001 and its potential role as a therapeutic in gastric cancer (GC). Methods The gastric cancer cell lines SGC-7901, MGC-803, BGC-823 and MKN-45 were used in vitro and in vivo. The abilities of cell proliferation, tumor sphere formation, metastasis, tumorgenesis and chemoresistance to chemotherapy drugs in vitro were evaluated by MTT assay, colony formation assay, flow cytometry, migration and invasion assay, and tumor spheres culture. The in vivo experiments were performed using a subcutaneous transplantation tumor model in athymic nude mice. Alterations at RNA and protein levels were followed by qRT-PCR, western blot, coimmunoprecipitations and immunofluorescence assay. Results In this study, we showed that ICG-001 significantly inhibited growth and metastasis of multiple GC cell lines, induced cell apoptosis, and augmented in vitro tumor spheres suppression when used in combination with chemotherapy drugs probably through robustly blocking association of β-catenin with CBP and N-cadherin, but promoting association of β-catenin with P300 and E-cadherin, instead of altering the distribution and expression of β-catenin. Conclusions Our findings suggest that ICG-001 suppresses GC cell line growth, metastasis and reduces its stem cell-like properties and chemoresistance, indicating that ICG-001 is a potentially useful small molecule therapeutic for GC.

Abstract Background Cisplatin-based chemotherapy is frequently used to treat advanced gastric cancer (GC). However, the resistance often occurs with the mechanisms being not well understood. Recently, emerging evidence indicates that tumor-associated macrophages (TAMs) play an important role in chemoresistance of cancer. As the important mediators in intercellular communications, exosomes secreted by host cells mediate the exchange of genetic materials and proteins to be involved in tumor aggressiveness. The aim of the study was to investigate whether exosomes derived from TAMs mediate cisplatin resistance in gastric cancer. Methods M2 polarized macrophages were obtained from mouse bone marrow or human PBMCs stimulated with IL-4 and IL-13. Exosomes isolated from M2 macrophages culture medium were characterized, and miRNA expression profiles of M2 derived exosomes (M2-exos) were analyzed using miRNA microarray. In vitro cell coculture was further conducted to investigate M2-exos mediated crosstalk between TAMs and tumor cells. Moreover, the in vivo experiments were performed using a subcutaneous transplantation tumor model in athymic nude mice. Results In this study, we showed that M2 polarized macrophages promoted cisplatin (DDP) resistance in gastric cancer cells and exosomes derived from M2 macrophages (M2-exos) are involved in mediating the resistance to DDP. Using miRNA profiles assay, we identify significantly higher levels of microRNA-21 (miR21) isomiRNAs in exosomes and cell lysate isolated from M2 polarized macrophage. Functional studies revealed that exosomal miR-21 can be directly transferred from macrophages to the gastric cancer cells, where it suppresses cell apoptosis and enhances activation of PI3K/AKT signaling pathway by down-regulation of PTEN. Conclusions Our findings suggest that exosomal transfer of tumor-associated macrophages derived miR-21 confer DDP resistance in gastric cancer, and targeting exosome communication may be a promising new therapeutic strategy for gastric cancer patients.

Aedes albopictus, a vector of Dengue and Chikungunya viruses, is a robust invasive species in both tropical and temperate environments. MicroRNAs (miRNAs) regulate gene expression and biological processes including embryonic development, innate immunity and infection. While a number of miRNAs have been discovered in some mosquitoes, no comprehensive effort has been made to characterize them from different developmental stages from a single species. Systematic analysis of miRNAs in Ae. albopictus will improve our understanding of its basic biology and inform novel strategies to prevent virus transmission. Between 10-14 million Illumina sequencing reads per sample were obtained from embryos, larvae, pupae, adult males, sugar-fed and blood-fed adult females. A total of 119 miRNA genes represented by 215 miRNA or miRNA star (miRNA*) sequences were identified, 15 of which are novel. Eleven, two, and two of the newly-discovered miRNA genes appear specific to Aedes, Culicinae, and Culicidae, respectively. A number of miRNAs accumulate predominantly in one or two developmental stages and the large number that showed differences in abundance following a blood meal likely are important in blood-induced mosquito biology. Gene Ontology (GO) analysis of the targets of all Ae. albopictus miRNAs provides a useful starting point for the study of their functions in mosquitoes. This study is the first systematic analysis of miRNAs based on deep-sequencing of small RNA samples of all developmental stages of a mosquito species. A number of miRNAs are related to specific physiological states, most notably, pre- and post-blood feeding. The distribution of lineage-specific miRNAs is consistent with mosquito phylogeny and the presence of a number of Aedes-specific miRNAs likely reflects the divergence between the Aedes and Culex genera.

Background: The tumor immune microenvironment could provide prognostic and predictive information. It is necessary to develop a noninvasive radiomicsbased biomarker of a previously validated tumor immune microenvironment signature of gastric cancer (GC) with immunohistochemistry staining. Methods: A total of 230 patients (training (n = 153) or validation (n = 77) cohort) with gastric cancer were subjected to (Positron Emission Tomography-Computed Tomography) radiomics feature extraction (80 features). A radiomics tumor immune microenvironment score (RTIMS) was developed to predict the tumor immune microenvironment signature with LASSO logistic regression. Furthermore, we evaluated its relation with prognosis and chemotherapy benefits. Results: A 8-feature radiomics signature was established and validated (area under the curve=0.692 and 0.713). The RTIMS signature was significantly associated with disease-free survival and overall survival both in the training and validation cohort (all P<0.001). RTIMS was an independent prognostic factor in the Multivariate analysis. Further analysis revealed that high RTIMS patients benefitted from adjuvant chemotherapy (for DFS, stage II: HR 0.208 (95% CI 0.061-0.711), p=0.012; stage III: HR 0.321(0.180-0.570), p<0.001, respectively); while there were no benefits from chemotherapy in a low RTIMS patients. Conclusion: This PET/CT radiomics model provided a promising way to assess the tumor immune microenvironment and to predict clinical outcomes and chemotherapy response. The RTIMS signature could be useful in estimating tumor immune microenvironment and predicting survival and chemotherapy benefit for patients with gastric cancer, when validated by further prospective randomized trials. [ABSTRACT FROM AUTHOR]