High Density Research Articles

(Ag0.80Bi0.04Sr0.04)(Nb1-xTax)O3 ceramics with enhanced energy storage for high-temperature application via synergic optimization

Dielectric capacitors with high power density are essential components in advanced electronic and micro-electronic products. Nevertheless, the limited energy storage density and efficiency, coupled with poor performance at elevated temperatures, severely restrict their usefulness. In this work, Ta was introduced to the (Ag0.80Bi0.04Sr0.04)NbO3 ceramic prepared via the hydrothermal-synthesized powders to improve the room- and high-temperature energy storage performance. A large breakdown strength of 729kV/cm, a high recoverable energy storage density of 8.5J/cm3 and a benign energy efficiency of 75.6% were simultaneously achieved in (Ag0.80Bi0.04Sr0.04)(Nb0.85Ta0.15)O3 ceramics. Moreover, the larger energy storage efficiency (83.5%) at elevated temperatures than room temperature, the benign frequency and cycle stability foreshow great potential in realizing the application of capacitors at high-temperatures.

Equally Split PCB Inductor (ESPI) Design for High Energy Density and Low Near-Field Radiation

Equally Split PCB Inductor (ESPI) Design for High Energy Density and Low Near-Field Radiation

High-Throughput Sequencing Technology Assisted Investigation of the Correlation between Intestinal Flora, Serum Biochemistry, Blood Lipids, and Tumour Markers in Patients with Gastric Cancer and Healthy Plateau Residents.

Aim The goal is to use high-throughput sequencing technology to compare and study the structure and variety of intestinal flora in people with gastric cancer and healthy people in the Qinghai-Tibet Plateau. Background Recent research has connected gut flora structure to numerous disorders. Metabolites, endotoxins, and immunomodulatory modulation might cause gastrointestinal or other systemic diseases and affect gastric cancer treatment and prognosis. We used the correlation study to uncover biomarkers associated with good intestinal flora and gastric cancer groups on the plateau to investigate their involvement in gastric cancer development. Objectives To investigate the possible links between intestinal flora and gastric cancer in the Qinghai Plateau region using a variety of clinical phenotypic data and to investigate the flora that may be linked to gastric cancer. Methods The 22 Qinghai Province tertiary hospital gastric cancer patients and 30 healthy people had their fresh faeces collected. To examine intestinal flora diversity and composition, 52 patients underwent 16S rDNA high-throughput gene sequencing of intestinal bacteria. The correlation between clinical phenotypes and the top 15 dominant intestinal flora at the phylum level was analyzed. Results The difference in total protein TP between the healthy group and the gastric cancer group was statistically significant (P<0.001). Globulin was significantly different (P<0.05), TC of total cholesterol was significantly different (P<0.05). High-density lipoprotein showed statistical significance (P<0.05).The difference in low-density lipoprotein was statistically significant (P<0.001). Alpha-fetoprotein was significantly different (P<0.05). CA72-4 carbohydrate antigen (P<0.05). Conclusion There were significant differences in total protein, globulin, total cholesterol, high density lipoprotein, low-density lipoprotein, alpha-fetoprotein and carbohydrate antigen CA72-4 in patients with gastric cancer in the plateau area compared with the healthy group, and the different clinical variables were correlated with intestinal flora at some phylum and genus levels.

Multiscale modeling of CO2 capture in dicationic ionic liquids: Evaluating the influence of hydroxyl groups using DFT-IR, COSMO-RS, and MD simulation methods.

This work employs a combination of density functional theory-infrared (IR), conductor-like screening model for real solvents (COSMO-RS), and molecular dynamic (MD) methods to investigate the impact of hydroxyl functional groups on CO2 capture within dicationic ionic liquids (DILs). The COSMO-RS reveals that hydroxyl groups in DILs reduce the macroscopic solubility of CO2 but improve the selectivity of CO2 over CO, H2, and CH4 gases. Quantum methods in the gas phase and MD simulations in the liquid phase were conducted to delve deeper into the underlying mechanisms. The IR spectrum analysis confirms red shifts in CO2's asymmetric stretching mode and blue shifts in the CR-HR bond of the dication, indicating CO2-DIL interactions and the weakening of the anion-cation interactions caused by the presence of CO2. The results show that the positioning of anions around hydroxyl groups and HR atoms in rings inhibits the proximity of CO2 molecules, causing the hydrogen atoms within methylene groups to accumulate CO2. van der Waals forces were found to dominate the interaction between ions and CO2. The addition of hydroxyl groups strengthens the electrostatic interactions and hydrogen bonds between dications and anions. The stronger interaction energy between ions in [C5(mim)2-(C2)2(OH)2][NTf2]2 limits the displacement of CO2 molecules within this DIL compared to [C5(mim)2-(C4)2][NTf2]2. Compared to [C5(mim)2-(C4)2][NTf2]2, [C5(mim)2-(C2)2(OH)2][NTf2]2 exhibits stronger ion-ion interactions, higher density, and reduced free volume, resulting in a reduction in CO2 capture. These results provide significant insights into the intermolecular interactions and vibrational properties of CO2 in DIL complexes, emphasizing their significance in developing efficient and sustainable strategies for CO2 capture.

Construction of the Ecological Security Pattern in Xishuangbanna Tropical Rainforest Based on Circuit Theory

Urban modernization and economic globalization have led to significant changes in traditional natural landscapes. The unregulated and large-scale expansion of rubber plantations in Xishuangbanna has resulted in water and scenic forests being replaced by rubber forests and the complex rainforest ecosystem being replaced by simple artificial forests. This has resulted in increasingly prominent ecological problems such as soil erosion, regional microclimate changes, and sharp declines in biodiversity. The ecological security pattern is an important way to protect regional ecological sustainability. Taking the tropical rainforest in Xishuangbanna as an example, this study identified ecological sources through the evaluation of the importance of ecosystem services, constructed resistance surfaces through ecological sensitivity evaluation, and used circuit theory to simulate ecological processes in heterogeneous landscapes by calculating “electricity” or “resistance”, thereby identifying ecological corridors and key ecological nodes. The results identified 31 ecological source areas, 65 key ecological corridors, 7 potential ecological corridors, 37 ecological pinch points, and 99 ecological barriers. The overall distribution of ecological sources was scattered, with higher density in the northwest and southeast regions. Ecological corridors were distributed along high mountains, and both ecological sources and corridors were mainly composed of forest land. Based on circuit theory, this study filled the gap in the MCR model’s inability to identify the true width of corridors due to ignoring the randomness of biological migration. It determined the spatial range of ecological corridors and the specific locations of ecological nodes and barriers, providing a reference for solving ecological problems in Xishuangbanna, such as “rainforest fragmentation”.

Floristic composition and biomass estimate of Rubiaceae in Bangi Permanent Forest Reserve, Selangor, Peninsular Malaysia

A study on floristic composition, community structure and biomass of Rubiaceae was carried out in Bangi Permanent Forest Reserve, Selangor. In the 0.45 ha of ecological plots, a total of 17 species from three genera of Rubiaceae was recorded for trees with a diameter ≥ 1.0 cm DBH. Three genera viz. Canthium, Ixora and Urophyllum were represented by two species each, while remaining genera comprised of a single species each. Shrub group represented the largest total number of species with seven species followed by the understorey with four species. The range of tree DBH in the study plot was between 1.0 and 31.3 cm. The genus with highest density was Aidia, viz. 244 trees/ha, represented by Aidia densiflora. Total basal area for Rubiaceae was 1.69 m2/ha, with the genus Aidia, specifically the species Aidia densiflora, contributing the highest basal area of 0.57 m2/ha (33.91%). Total biomass estimate (above ground and below ground) for this family was 16.71 t/ha. At genus level, Timonius contributed the highest total biomass value, viz. 5.82 t/ha (34.85%), represented by the species Timonius wallichianus.

Comparison of Carbon Footprint Differences in Nitrogen Reduction and Density Increase in Double Cropping Rice under Two Evaluation Methods

Optimized fertilizer use improves crop yield and mitigates environmental pollution associated with crop production. Fertilizer and plant density are core strategies to ensure food security and cope with climate change. However, little is known about the long-term interactive effect of reduced nitrogen (N) and increased density on yield and C (Carbon) balance. In this study, field experiments were conducted in a double-cropping rice region to evaluate long-term effects on yield and carbon footprint (CF) by crop-based and soil-based methods. Treatments were set for 10% reduction in N coupling with conventional density (N1D1), 20% higher density (N1D2), 40% higher density (N1D3), and 20% reduction in N coupling with conventional density (N2D1), 20% higher density (N2D2), and 40% higher density (N2D3), with the prevailing practices as control, conventional plant density, and fertilizer dose. Results showed that the yield continued to increase with increasing density; under the same density, reducing N by 10% is more beneficial for yield improvement and for CH4 emission reduction. Compared with CK, reducing N application by 10% generally increased the annual yields by 7.34–23.25% on average, and reduced CH4 emissions by 16.19–22.11%, resulting in a reduced crop-based carbon footprint of 22.24–26.82%, and a reduced soil-based carbon footprint of 22.08–32.85%. While reducing N application by 20% increased the annual yields by 5.00–20.19% and reduced the CH4 emission by 1.66–4.93%, it reduced crop-based carbon footprints by 1.81–10.05% and reduced soil-based carbon footprints by 7.22–19.86%. As density increased, the crop-based CF decreased, whereas the soil-based CF increased. Overall, the highest yield and the lowest soil-based CF and unit yield CF (CFy) were observed in N1D3. Regarding sustainability, a 10% reduction in N, along with an increase in density to 40%, can be recommended for double-cropping rice production.

Natural genetic variation in dynamic photosynthesis is correlated with stomatal anatomical traits in diverse tomato species across geographical habitats.

Plants grown under field conditions experience fluctuating light. Understanding the natural genetic variations for a similarly dynamic photosynthetic response among untapped germplasm resources, as well as the underlying mechanisms, may offer breeding strategies to improve production using molecular approaches. Here, we measured gas exchange under fluctuating light, along with stomatal density and size, in eight wild tomato species and two tomato cultivars. The photosynthetic induction response showed significant diversity, with some wild species having faster induction rates than the two cultivars. Species with faster photosynthetic induction rates had higher daily integrated photosynthesis, but lower average water use efficiency because of high stomatal conductance under natural fluctuating light. The variation in photosynthetic induction was closely associated with the speed of stomatal responses, highlighting its critical role in maximizing photosynthesis under fluctuating light conditions. Moreover, stomatal size was negatively correlated with stomatal density within a species, and plants with smaller stomata at a higher density had a quicker photosynthetic response than those with larger stomata at lower density. Our findings show that the response of stomatal conductance plays a pivotal role in photosynthetic induction, with smaller stomata at higher density proving advantageous for photosynthesis under fluctuating light in tomato species. The interspecific variation in the rate of stomatal responses could offer an untapped resource for optimizing dynamic photosynthetic responses under field conditions.

Yields, growth and water use under chemical topping in relations to row configuration and plant density in drip-irrigated cotton

BackgroundWater deficit is an important problem in agricultural production in arid regions. With the advent of wholly mechanized technology for cotton planting in Xinjiang, it is important to determine which planting mode could achieve high yield, fiber quality and water use efficiency (WUE). This study aimed to explore if chemical topping affected cotton yield, quality and water use in relation to row configuration and plant densities.ResultsExperiments were carried out in Xinjiang China, in 2020 and 2021 with two topping method, manual topping and chemical topping, two plant densities, low and high, and two row configurations, i.e., 76 cm equal rows and 10+66 cm  narrow-wide rows, which were commonly applied in matching harvest machine. Chemical topping increased seed cotton yield, but did not affect cotton fiber quality comparing to traditional manual topping. Under equal row spacing, the WUE in higher density was 62.4% higher than in the lower one. However, under narrow-wide row spacing, the WUE in lower density was 53.3% higher than in higher one (farmers’ practice). For machine-harvest cotton in Xinjiang, the optimal row configuration and plant density for chemical topping was narrow-wide rows with 15 plants m-2 or equal rows with 18 plants m-2.ConclusionThe plant density recommended in narrow-wide rows was less than farmers’ practice and the density in equal rows was moderate with local practice. Our results provide new knowledge on optimizing agronomic managements of machine-harvested cotton for both high yield and water efficient.

Recruitment dynamics of juvenile salmonids: Comparisons among populations and with classic case studies.

Understanding recruitment, the process by which individuals are added to a population or to a fishery, is critical for understanding population dynamics and facilitating sustainable fisheries management. Important variation in recruitment dynamics is observed among populations, wherein some populations exhibit asymptotic productivity and others exhibit overcompensation (i.e., compensatory density-dependence in recruitment). Our ability to understand this interpopulation variability in recruitment patterns is limited by a poor understanding of the underlying mechanisms, such as the complex interactions between density dependence, recruitment, and environment. Furthermore, most studies on recruitment are conducted using an observational design with long time series that are seldom replicated across populations in an experimentally controlled fashion. Without proper replication, extrapolations between populations are tenuous, and the underlying environmental trends are challenging to quantify. To address these issues, we conducted a field experiment manipulating stocking densities of juvenile brook trout Salvelinus fontinalis in three wild populations to show that these neighboring populations-which exhibit divergent patterns of density dependence due to environmental conditions-also have important differences in recruitment dynamics. Testing against four stock-recruitment models (density independent, linear, Beverton-Holt, and Ricker), populations exhibited ~twofold variation in asymptotic productivity, with no overcompensation following a Beverton-Holt model. Although environmental variables (e.g., temperature, pH, depth, substrate) correlated with population differences in recruitment, they did not improve the predictive power in individual populations. Comparing our patterns of recruitment with classic salmonid case studies revealed that despite differences in the shape and parameters of the curves (i.e., Ricker vs. Beverton-Holt), a maximum stocking density of about five YOY fish/m2 emerged. Higher densities resulted in very marginal increases in recruitment (Beverton-Holt) or reduced recruitment due to overcompensation (Ricker).

Histologic and Genomic Analysis of Conjunctival SCC in African and American Cohorts Reveal UV Light and HPV Signatures and High Tumor Mutation Burden.

Conjunctival squamous cell carcinoma (conjSCC) is more prevalent and aggressive in sub-Saharan African countries compared with the rest of the world. This study aims to compare the genomic, immunophenotypic, and histologic features between patients from the United States and Ethiopia, to identify etiopathogenic mechanisms and unveil potential treatment strategies. We compared histologic features and mutational profiles using whole exome sequencing, high-risk human papillomavirus (HPV) status, PD-L1 expression, and tumor-infiltrating lymphocytes in conjSCC tumors of patients from Ethiopia (ETH; n = 25) and the United States (from MD Anderson [the MDA cohort]; n = 29). Genomic alterations were compared with SCCs from other anatomic sites using data from The Cancer Genome Atlas. Solar elastosis was seen in 78% of ETH and 10% of MDA samples. Thicker tumors had higher density of CD8+ and CD3+ cells. HPV status was similar between the cohorts (ETH = 21% and MDA = 28%). The mean tumor mutation burden (TMB) was significantly higher in conjSCC (3.01/Mb, log10) and cutaneous SCC compared other SCC subtypes. ETH samples had higher TMB compared to the MDA cohort (3.34 vs. 2.73). Mutations in genes associated with ultraviolet light (UV) signature were most frequently encountered (SBS7b = 74% and SBS7a = 72%), with higher prevalence in the ETH cohort, whereas SBS2 and SBS13 signatures were more common among MDA HPV+ conjSCCs. Our findings suggest that UV exposure may play a major role in conjSCC, with a higher prevalence in the ETH cohort compared with the MDA cohort, where HPV also contributes.

Biological and functional responses of the benthic surf zone community to different beach types

In this study, we analyzed the biological descriptors and functional traits of the benthic community inhabiting the water/bottom layer in the surf zones of three sandy beaches: a tide-dominated flat, and two intermediate beaches, from tide-modified to wave-dominated. Samples were collected seasonally in the inner surf zone by hand-towing a benthic sledge equipped with two nets, one above the other, across transects parallel to the shore, capturing the benthic community in two levels, close to the seafloor. A total of 116 species were collected, with a total of 327,678 specimens. Arthropods were 99.63% of all individuals caught across the three beaches, mainly represented by peracarid crustaceans. An important species turnover was detected along the shore, with a significant change in community composition. The biological descriptors and some functional traits vary among beaches: the total density, the density of individuals of small (5–10 mm length) and very small sizes (<5 mm length), the density of larval forms, and the presence of colonial species were higher in the tide-dominated flat (sometimes also in the tide-modified beach). More arthropods and more mobile individuals were found in those beaches, while mollusks and sedentary individuals were found in high number in the wave-dominated beach. Stratification was present across the three studied beaches, with higher densities in the near-bottom layer. In the tide-dominated beach, there was also a higher richness in this layer, with a nested community between levels. In the wave-dominated beach, similar richness was registered between levels, with a different community composition (and some differences in functional traits), indicating that some species can maintain their position close to the bottom despite the turbulent conditions experienced on this beach. Differences in wave conditions among beach types could be an important factor driving the biological descriptors and functional traits of the benthic community in surf zone ecosystems. Therefore, acknowledging their role is crucial in deciphering global patterns in surf zone biodiversity.

Variation in Water-Holding Capacity in Sphagnum Species Depends on Both Plant and Colony Structure

Peatlands have become a focal point in climate mitigation strategies as these ecosystems have significant carbon sequestration capacities when healthy but release CO2 and other greenhouse gases when damaged. However, as drought episodes become more frequent and prolonged, organisms key to the functioning of some peatlands are increasingly under pressure from desiccation. The Sphagnum mosses, which tend to keep their ecosystem waterlogged and many of whom promote peat formation, are only mildly desiccation-tolerant in comparison to other mosses. The role of Sphagnum anatomy and colony structure is poorly understood in the context of desiccation resilience. Using four different Sphagnum species belonging to four different subgenera and positions along the gradient of the water table, we show that plant morphological traits and colony density are important determinants of water storage capacity. Our results show that, as previously postulated, the majority of the water is stored in an easily exchangeable form, probably extracellularly, and that plant morphological traits, specifically the type and presence of branches, are major contributors to water storage and can explain some of the interspecies variation. We also show that plant density is another important determinant for water storage capacity as higher densities hold larger quantities of water per unit of biomass for all four species, which increases resilience to desiccation. The results presented here suggest that species choice and planting density should receive more attention when considering peatland restoration strategies.

Low-severity fires in the boreal region: reproductive implications for black spruce stands in between stand-replacing fire events.

Stand-replacing crown fires are the most prevalent type of fire regime in boreal forests in North America. However, a substantial proportion of low-severity fires are found within fire perimeters. Here we aimed to investigate the effects of low-severity fires on the reproductive potential and seedling recruitment in boreal forests stands in between stand-replacing fire events. We recorded site and tree characteristics from 149 trees within twelve sites dominated by mature black spruce [Picea mariana (Mill.) B.S.P.] trees in the Northwest Territories, Canada. The presence of fire-scarred trees supported classification of sites as unburned or affected by low-severity fires in recent history. We used non-parametric tests to evaluate differences in site conditions between unburned and low-severity sites, and mixed effect models to evaluate differences in tree age, size, and reproductive traits among unburned trees and trees from low-severity sites. Results showed significantly higher density of dead black spruce trees in low-severity sites, and marginally significant higher presence of permafrost. Trees from low-severity fire sites were significantly older, exhibited significantly lower tree growth, and showed a tendency towards a higher probability of cone presence and percentage of open cones compared to trees from unburned sites. Surviving fire-scarred trees affected by more recent low-severity fires showed a tendency towards higher probability of cone presence and cone production. Density of black spruce seedlings significantly increased with recent low-severity fires. Trees in low-severity sites appeared to have escaped mortality from up to three fires, as indicated by fire scar records and their older ages. Shallow permafrost at low-severity sites may cause lower flammability, allowing areas to act as fire refugia. Low-severity surface fires temporarily enhanced the reproductive capacity of surviving trees and the density of seedlings, likely as a stress response to the fire event.

Enhancing electrochemical corrosion resistance in Al–6Ni alloys through trace Sc additions

Al–Ni-Sc alloys exhibit superior mechanical properties at both room and elevated temperatures, owing to the high thermal and chemical stability of Al3Ni microfibers, and Al3Sc nanoprecipitates. This study explores the impact of scandium additions (0.2 and 0.4 wt%) in eutectic Al–6Ni casting alloys and the influence of aging treatment on electrochemical corrosion behavior in a 0.05 M NaCl solution. Scandium addition did not alter the polarization curve direction but reduced the anodic current density, slowing corrosion. Scandium strengthened the passive film, evident in Electrochemical Impedance Spectroscopy (EIS) with higher Rp values. Sc addition influences the susceptibility to localized corrosion in Al–Ni alloys by promoting the coherence of passive films through the formation of Al3Sc nanoprecipitates and affecting the distribution of Al3Ni. XPS results show that as-aged Sc-containing increases the density of coherent Al3Sc nanoprecipitates, which could result in the formation of Sc2O3 film along with films like Ni2O3 and Al2O3. These synergistic effects contribute to improving the overall corrosion resistance with Sc additions subjected to aging treatment. The microgalvanic effects between the matrix and reinforcement phases, as a result of the formation of nobler Al3Ni and Al3Sc that serve as cathodes within anode Al matrix, cause severe pitting. Nevertheless, after aged treatment, the corrosion resistance dramatically drops for alloys with 0.2 wt% Sc and remains unchanged for 0.4 wt% Sc, due to higher density of nobler Al3Sc nanoprecipitates phase that can counteract the microgalvanic effects and lead to less extensive pitting than as-aged Al–6Ni-0.2Sc.

Impact of irradiance and inorganic carbon availability on heterologous sucrose production in Synechococcus elongatus PCC 7942

Cyanobacteria have been proposed as a potential alternative carbohydrate feedstock and multiple species have been successfully engineered to secrete fermentable sugars. To date, the most productive cyanobacterial strains are those designed to secrete sucrose, yet there exist considerable differences in reported productivities across different model species and laboratories. In this study, we investigate how cultivation conditions (specifically, irradiance, CO2, and cultivator type) affect the productivity of sucrose-secreting Synechococcus elongatus PCC 7942. We find that S. elongatus produces the highest sucrose yield in irradiances far greater than what is often experimentally utilized, and that high light intensities are tolerated by S. elongatus, especially under higher density cultivation where turbidity may attenuate the effective light experienced in the culture. By increasing light and inorganic carbon availability, S. elongatus cscB/sps produced a total of 3.8 g L-1 of sucrose and the highest productivity within that period being 47.8 mg L-1 h-1. This study provides quantitative description of the impact of culture conditions on cyanobacteria-derived sucrose that may assist to standardize cross-laboratory comparisons and demonstrates a significant capacity to improve productivity via optimizing cultivation conditions.

In Vitro Investigation of the Antimicrobial Potential and Cell Viability of Different Dosages of Ozone Therapy

ABSTRACT The aim of the study was to evaluate and compare, in vitro, the cytotoxicity of different applied ozone dosages in keratinocyte (NOK) and fibroblast (L929) cell lines, as well as the antimicrobial potential for Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). NOK and L929 cells and strains of gram-positive bacteria S. aureus and gram-negative bacteria E. coli were divided into seven experimental groups: ozone at doses from 0, 0.005, 0.01, 0.02, 0.03, 0.04 and 0.05 mg/L. The effect of ozone on cell viability/cytotoxicity was determined using the alamarBlue® assay, the Live/Dead® assay and the morphometric analysis of the percentage of live and dead cells. The results show that applied ozone dosages of 0.005, 0.01 and 0.02 mg/L showed the highest viability values of NOK and L929 cells, as well as a higher density and percentage of live cells in the 72-hour experimental. However, no difference was observed in the percentage of dead cells between the experimental groups. Furthermore, ozone promoted a reduction in CFUs at all tested dosages. With the results obtained in the present study, it is possible to confirm the restorative potential of ozone therapy in a dose-dependent response, as well as its antimicrobial potential.

Abstract NG07: Association between somatic microsatellite instability, hypermutation status, and specific T cell subsets in colorectal cancer tumors

Abstract Background: Colorectal cancer (CRC) is a critical public health concern as the third most commonly diagnosed cancer and second leading cause of cancer death globally. CRC is a heterogeneous disease with many different mechanisms and molecular subtypes. Around 15% of sporadic CRCs are classified as exhibiting high microsatellite instability (MSI-high) due to deficient DNA mismatch repair (dMMR). In the presence of MSI-high, colorectal tumors accumulate somatic mutations, resulting in high neoantigen burden, which, in turn, elicits a strong T cell response. Several previous studies have shown that MSI-high status is associated with overall levels of T cell infiltration in CRC and, specifically, with CD45RO+ T cell density. However, many studies have measured T cell densities using single-plex immunohistochemistry assays of individual T cell markers, which fail to capture the complexity of the T cell response in tumors, and the contributions of different T cell subsets. Using a multiplex immunofluorescence panel, we aimed to characterize the composition of the T cell response in CRC tumors in relation to MSI-high and hypermutation status in CRC. Methods: This study was conducted within a subset of participants from three well-characterized epidemiologic studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO): the Ontario Family Colon Cancer Registry (OFCCR), the Nurses’ Health Study (NHS), the Health Professionals Follow-up Study (HPFS). In a total of N=637 participants with CRC, we profiled the in-situ T cell landscape of CRC using digital imaging, machine learning, and a multiplexed immunofluorescence panel. Our customized 9-plex panel included antibodies directed against CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, and MKI67, as well as a pan-cytokeratin antibody to identify tumor/epithelial cells and nuclear DAPI (4’, 6-diamidino-2-phenylindole) stain. Assays were conducted using tissue microarrays (TMAs) where all slides were sent to Dana Farber Cancer Institute for analysis. In brief, core selection from donor FFPE blocks was guided by pathologist review of H&amp;E-stained slides. For each CRC case, TMA blocks have 2-4 cores (0.6 mm) from tumor areas. T cell immune microenvironment is assessed for each tumor histologically using a multispectral imaging platform (PerkinElmer Vectra 3.0) for multiplexed immunofluorescence (mIF), where TMAs are stained with all markers concurrently and imaged. With pathologist supervision, a machine learning algorithm segmented tissue into epithelial and stromal area regions as well as phenotyped individual cells. The mIF panel has been validated against traditional chromogenic IHC. Based on these markers, we quantified counts and densities of naive, memory, and regulatory subsets of helper (CD3+CD4+) and cytotoxic (CD3+CD8+) T cells, and looked separately at these subsets within epithelial and stromal tissue, resulting in 12 unique subsets. Microsatellite instability and hypermutation status were determined from one of two targeted sequencing panels that included either 205 or 298 genes. MSI status was called using mSINGS. Hypermutation status was defined by plotting point mutations for all samples and observing different peaks, separately by panel. The minimum value between the two peaks was 23 and 26 point mutations per sample, respectively, which were used as cut-points. We used multivariable ordinal logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between MSI/hypermutation status with quantiles of specific T cell densities in CRC. As an alternative approach where counts were modeled directly, we used negative binomial count models with an offset term for area. Ordinal logistic regression either used quartiles or tertiles of T cell densities as the outcome, where different subsets were assessed for zero-inflation considering both epithelial and stromal tissue, so the same subset used the same categorization in each tissue. Subsets with less than 25% zero counts were divided into quartiles, subsets with greater than 25% zero counts into tertiles. Study-specific quantile cut points were used to limit potential batch effects across TMAs. Models were adjusted for age, sex, and study, and p-values were adjusted for multiple testing using the false discovery rate method for 12 independent tests. Results: Among 637 CRC tumors with targeted tumor sequencing and T cell immune profile available, 107 were classified as MSI-high, and 106 were classified as hypermutated. 98 tumors were both MSI-high and hypermutated. Compared to tumors with low microsatellite instability (MSI-low) or microsatellite stable (MSS) tumors, MSI-high tumors were strongly associated (ORs around 2 or higher) with higher T cell densities for all epithelial area CD3+CD4+, epithelial area CD3+CD8+, and stromal area CD3+CD8+ T cells (adjusted p-values &amp;lt;0.001). Compared to MSI-low/MSS tumors, MSI-high tumors had 3 times the odds of greater quantile of epithelial area CD3+CD8+ subsets defined as naive, memory, and regulatory [OR= 3.2 95% CI (2.14, 4.79), OR=3.19 (2.15, 4.72), OR=3.31 (2.20, 4.97), respectively]. MSI-high tumors were not associated with higher densities of stromal area CD3+CD4+ naive, memory, or regulatory cells. Effect estimates for hypermutation status showed consistent results and the same conclusions as MSI. Effect estimates from negative binomial models showed consistent findings with the ordinal logistic results presented. Conclusions: While it is well known that T cells overall are strongly associated with MSI status in CRC, the present study improves our understanding of what specific T cell subsets in what location in the tumor are associated with MSI and hypermutation status. Additionally, given the high level of T cell infiltration in MSI-high/dMMR tumors, these tumors are more likely to respond favorably to immune checkpoint inhibitors (ICIs). A more granular understanding of specific T cell subsets that are associated with these tumor phenotypes may improve our understanding of underlying biology and help inform targeted immunotherapy treatment decision-making for the MSI-high/dMMR CRC subtype. In future work we aim to examine increasing mutation frequency as a continuous variable and with more specific categorization of mutation frequency than binary cut-points in association with T cell profile. Citation Format: Claire Elizabeth Thomas, Yasutoshi Takashima, Tomotaka Ugai, Daniel D. Buchanan, Conghui Qu, Li Hsu, Andressa Dias Costa, Stephen Gallinger, Robert C. Grant, Jeroen R. Huyghe, Sushma S. Thomas, Robert S. Steinfelder, Shuji Ogino, Amanda I. Phipps, Jonathan A. Nowak, Ulrike Peters. Association between somatic microsatellite instability, hypermutation status, and specific T cell subsets in colorectal cancer tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr NG07.

Morphogenic characteristics of black oat and vetch under different densities

The objective of this study was to assess the morphogenic characteristics Avena strigosa and Vicia sativa plants cultivated in different sowing densities. The experiment was conducted in vases with farming soil. The experimental design involved randomized units, with four repetitions, consisting of a single vetch plant placed in the centre of each experimental unit and a variable number of oat plants (0, 1, 2, 3, 4, and 5) planted around the borders. The same procedure was also conducted with a single oat plant placed in the centre of the vase and a variable number of vetch plants (0, 1, 2, 3, 4, and 5) planted around the borders. The plants were grown for a total of 35 days. Morphogenic characteristics of the central plant were assessed at the time of transplantation as well as every 7 days. It was observed that the density increase in vetch plants did not significantly influence stem elongation, plant elongation, and leaf senescence rates of oat plants. However, higher densities did reduce the tiller appearance rate in oat plants. Increases in oat density caused significant impacts on the elongation rate and linear growth in the leaf senescence rate and reduced the number of ramifications in vetch plants. Higher density caused reduced leaf appearance and tiller rates while increasing phyllochron values. The results of this study indicate that increases in plant density trigger competition responses in both oat and vetch, which in turn negatively affect many of the assessed morphogenic characteristics for both species.

Nail Telocytes: Identification, Potential Physiological Function, and Role in Pathology: A Reappraisal of the So-Called Onychofibroblasts/Onychodermis.

Some authors have suggested that the fibroblasts of the nail mesenchyme (onychofibroblasts) can be distinguished from skin fibroblasts by their high expression of CD10. My 2015 study documented the presence of a relatively sparse CD34+/CD10+ dendritic subpopulation in the dermis and hypodermis of the matrix. For some time now, my hypothesis has been that these interstitial dendritic mesenchymal cells of the matrix correspond to telocytes. Telocytes have been described as peculiar interstitial dendritic cells present in the mesenchymal tissue of numerous organs, including the skin, but their presence and characteristics in the nail unit have not been explored. This study was undertaken to more comprehensively investigate the existence and characteristics of nail telocytes. A series of 20 normal adult nail units were examined with a combination of morphological and immunohistochemical analyses. The matrix dermis contained a sparse subpopulation of CD34+/CD10+ elongated telocytes with a higher density in the lunular region and, at this distal level, a change in their immunohistochemical profile, resulting in a progressive loss of CD34 expression. The matrix hypodermis showed CD34+/CD10+ telocytes in their classical elongated aspect, which acquired, especially in the distal fibromyxoid area of the thumb, an oval to round morphology with multiple intracytoplasmic vacuoles. The characteristic dynamic immunophenotypic profile of the dermal telocytes with a progressive distal loss of the defining molecule CD34 was equally observed in the distal hypodermis. The nail bed dermis was thick with a dense fibrous connective tissue. A reticular network of CD34-/CD10+ telocytes was present in the superficial dermis of the proximal nail bed. The mesenchymal cells of the deep part of the proximal nail bed dermis and the entire distal nail bed dermis were CD34-/CD10-. The adult nail mesenchyme is composed of 3 microanatomically distinct regions. Only the thumb has a distal hypodermis rich in mucinous material. The population of telocytes is relatively sparse compared with the fibroblastic population of the entire nail mesenchyme. The concept of onychodermis/onychofibroblasts is not valid. Nail telocytes have a dynamic immunohistochemical profile depending on whether they are located proximally or distally. The CD34+/CD10+ profile correlates with the onychogenic epithelial region, while the CD34-/CD10+ profile correlates with a spatial rearrangement of the nail epidermal bed.