Compositional Signatures Research Articles

Predicting the presence of tephra layers in lacustrine deposits using spectral gamma ray data: An example from Lake Chalco, Mexico City.

Spectral gamma ray borehole logging data can yield insights into the physical properties of lake sediments, serving as a valuable proxy for assessing climate and environmental changes. The presence of tephra layers resulting from volcanic ash deposition is not related to climate and environmental conditions. As a result, these layers pose challenges when attempting to analyze paleoclimate and environmental time series. Gamma rays are composed of photons, which are elementary particles of electromagnetic radiation. Tephra layers emit photons at specific energy levels that create a distinct pattern in their gamma-ray energy spectrum. The gamma-ray signature of tephra layers varies depending on the stage of the volcanic eruption. Additionally, there is a significant difference between the gamma-ray signature emitted by tephra layers and that of the background lake sediments. A composite signature can be used to predict tephra layers from background sediments by combining several gamma-ray signatures of tephra layers at different depths. We propose five-step protocol for detecting tephra layers within sediments through the utilization of gamma-ray spectroscopy. This protocol is based on a combination of physical aspects of gamma-ray spectroscopy and geological information specific to the lake system being studied. A subset of the training dataset is used, consisting of known tephra and non-tephra layers. The protocol involves identifying similarities between known tephra layers, analyzing differences in gamma-ray signals between tephra and non-tephra layers, and studying the composition of energy channels at various depths within the training dataset. Multiple linear regression models are used to predict the relationship between the composition of tephra layers as a dependent variable and the constituent energy channels of the gamma-ray signal as independent variables. The proposed protocol has the potential to accurately detect and identify thick tephra layers (> 10 cm in thickness) based on the rate of spectral gamma ray measurement in sedimentary sequences. This approach could enhance stratigraphic resolution by enabling finer subdivision of layers in an interior basin.

Hydrochemical Characteristics and Genesis of Sand–Gravel Brine Deposits in the Mahai Basin of the Northern Qinghai–Tibetan Plateau

The sand–gravel brine deposit in the Mahai Basin is a newly discovered large-scale potassium–bearing brine deposit. The potassium–bearing brine is primarily found at depths exceeding 150 m within the porous alluvial and fluvial sand–gravel reservoir of the Middle to Lower Pleistocene. This deposit is characterized by a relatively shallow water table, moderate–to–strong aquifer productivity, high salinity, and a KCl content that meets the conditions for exploitation, with the advantage of reduced salt crystallization during well mining, making it a potential reserve base for potash development. A geochemical analysis of the sand–gravel brine revealed consistent trends for the major ions K+, Na+, Mg2+, Cl−, and SO42− along the east–west axis of the alluvial fan, while Ca2+ showed an opposite trend compared to Mg2+. Along the exploration lines from north to south, the concentrations of the main ions gradually increase. The brine is enriched in Na+ and Cl− ions, while SO42− and HCO3− are depleted. In the K+-Na+-Mg2+/Cl−-H2O (25 °C) quaternary phase diagram, the brine falls within the halite stability field, with the hydrochemical type classified as chloride type. The brine coefficient characteristics indicate a multi-source origin involving residual evaporation, salt rock leaching, and metamorphic sedimentary brine. Comparison studies of the ionic composition and isotopic signatures (δD, δ18O, δ37Cl, and δ7Li) of deep sand–gravel brines in the study area with interstitial and confined brines in the southern depression suggest similar geochemical characteristics between them. The genetic analysis of the deposit proposes that during the basin tectonic evolution, the potassium-rich interstitial and confined brines originally located in the southern depression of the Mahai Basin were displaced under compressional forces and migrated northward as the depositional center shifted, eventually backfilling into the loose alluvial and fluvial sand and gravel reservoirs at the front of the Saishiteng Mountains, forming the deep sand–gravel brine deposits in the foreland.

Targeting High-Grade Mineralization via a Synthesis of Compositional Profiles of Alluvial Gold with Structural and Paragenetic Models

Gold compositional studies have been advocated to resolve genetic relationships between alluvial and in situ occurrences based on the assumption that the P-T-X conditions at the sites of mineral deposition are reflected in common compositional signatures of gold. Here, we explore two refinements to a simple ‘same or different’ approach, namely (i) in situ gold sources at different localities may correspond to multiple stages of mineralization and, therefore, different gold grade, and (ii) any duplication of gold signatures between localities requires fluid conduits compatible with the prevailing structural framework. The high-grade gold paragenetic stage at the Cononish Mine, Scotland, is characterized by relatively low Ag alloy associated with Ag-Au and Ag tellurides. This signature is replicated in the inclusion signature of alluvial gold from the adjacent drainage and is also present in two other drainages for which there are no known in situ sources. There is a strong correlation between the spatial extent of this signature and the fault linkage zone, but outside this zone, gold exhibits other compositional signatures. The study shows how structural considerations provide an independent and robust framework to evaluate genetic relationships suggested by compositional studies of alluvial gold in areas where the source location and economic potential are unknown.

Updraft Width Modulates Ambient Atmospheric Controls on Convective Cloud Depth

AbstractThe depth of convective clouds affects vertical transport of atmospheric constituents, influencing downstream weather and climate. Atmospheric controls on the maximum depth reached by moist convection are investigated with radar‐tracked convective cells tagged with sounding‐derived atmospheric parameters from a field campaign in central Argentina. Regression analyses show that narrow (<12‐km diameter) and wide (>16‐km diameter) cell depths respond to disparate factors, where cell areas are defined using composite reflectivity signatures. Undiluted lifted parcel indices including convective available potential energy (CAPE) and level of neutral buoyancy (LNB) are top predictors of wide cell maximum depth while mid‐tropospheric relative humidity is the top predictor of narrow cell maximum depth. Because narrow cells are more numerous than wide cells, the overall outcome of the full cell population does not strongly correlate with CAPE and LNB conditions. Tracked cells and atmospheric conditions in a simulation with 3‐km grid spacing covering the field campaign produce similar results to those observed. Narrow cells that are relatively deep have a cooler and moister mid‐troposphere with weaker free tropospheric subsidence, while relatively deep wide cells have much warmer and moister lower tropospheric conditions. These atmospheric differences are present 1 hr before cell initiation at both a fixed observing site and variable cell initiation locations. Simulated narrow cell maximum equivalent potential temperature decreases with height at a rate similar to the ambient vertical gradient, causing these cells to fall short of their LNB and supporting the view that entrainment‐driven dilution is a dominant control on their depth.

Blockchain-based lightweight trusted data interaction scheme for cross-domain IIoT

To facilitate cross-domain data interaction in the Industrial Internet of Things (IIoT), establishing trust between multiple administrative domains is essential. Although blockchain technology has been proposed as a solution, current techniques still suffer from issues related to efficiency, security, and privacy. Our research aims to address these challenges by proposing a lightweight, trusted data interaction scheme based on blockchain, which reduces redundant interactions among entities. We enhance the traditional Practical Byzantine Fault Tolerance (PBFT) algorithm to support lightweight distributed consensus in large-scale IIoT scenarios. Introducing a composite digital signature algorithm and incorporating veto power minimizes resource consumption and eliminates ineffective consensus operations. The experimental results show that, compared with PBFT, our scheme reduces latency by 27.2%, thereby improving communication efficiency and resource utilization. Furthermore, we develop a lightweight authentication technique specifically for cross-domain IIoT, leveraging blockchain technology to achieve distributed collaborative authentication. The performance comparisons indicate that our method significantly outperforms traditional schemes, with an average authentication latency of approximately 151 milliseconds. Additionally, we introduce a trusted federated learning (FL) algorithm that ensures comprehensive trust assessments for devices across different domains while protecting data privacy. Extensive simulations and experiments validate the reliability of our approach.

Abstract C025: Identification of cell-cell signaling programs across the tumor-tumor microenvironment ecosystem and associated with clinical status in neoadjuvant osimertinib treated patient samples revealed by spatial profiling

Abstract Lung cancer is the leading cause of cancer mortality, and despite improvements in treatment, tumors typically respond incompletely and resume growth after acquisition of drug resistance. Recent completion of a neoadjuvant osimertinib Phase II trial treating patients with surgically resectable stage I-IIIA EGFR-mutated non-small cell lung cancer (EGFRm NSCLC) (NCT03433469) (Blakely et. Al, JCO 2024) has highlighted the importance of further identifying non-genomic mechanisms of persistence and resistance to targeted therapy. Here we analyzed these patient samples to identify transcriptionally regulated signaling patterns enriched at Residual Disease (RD) after neoadjuvant osimertinib treatment compared to treatment naïve samples (TN), as well as signaling patterns enriched at RD in patients who ultimately develop disease recurrence after surgical resection compared to those who remain disease-free. Spatially resolved transcriptomic sequencing was performed, using the 10X Genomics Visium platform, on 36 tissue sections (n=9 TN, n=19 RD, n=4 Progressive Disease (PD), n=4 Tumor Adjacent Normal), from 25 patients. TN and PD samples were from standard-of-care surgical resections. 18 of 19 RD samples were from NCT03433469. The Visium array spots that tile the sequencing capture area are 55 µm in diameter, and thus can contain an estimated 1-10 cells within each array spot. After quality control, 91,582 array spots remained for downstream analysis. We identified high confidence tumor array spots annotated both as “Cancer” by a board-certified pathologist and with tumor characteristic copy number variations. Through dimensionality reduction clustering, we identified 10 major array spot clusters, including the high confidence tumor array spot cluster. These clusters were further subset into 44 high resolution clusters of array spot niches, 32 of which were shared across at least nine patients. Because array spots are not single-cell resolution, these niches represent spots with similar mixed cell type composition and transcriptional signatures. We identified significant increases in the CCL14+ Endothelial Cell Niche, CXCL2+ Endothelial Cell Niche, Lymphocytes + Endothelial Niche, and CXCL12+ Fibroblast Niche in RD samples compared to TN. We identified a cell signaling program defined by spatially co-expressed ligand-receptor pairs associated with focal adhesion, enriched in PD samples. This same pattern was enriched in RD samples from patients who had recurrent disease after surgical resection compared to RD samples from patients who remained disease free. These data describe an increase in immune trafficking in RD samples, as well as identify an EGFR- alternative signaling pathway correlating with osimertinib resistance. Identification of spatially resolved, differential architectural organization and signaling patterns in RD and PD states will expand our understanding of targeted therapy resistance in EGFRm NSCLC, with the potential to identify additional clinically actionable targets. Citation Format: Whitney Tamaki, Daniel L. Kerr, Wei Wu, Grant Eilers, Anatoly Urisman, Yu-Ting Chou, Philippe Gui, Shigeki Nanjo, Johannes R. Kratz, David M. Jablons, Trever G. Bivona, Collin M. Blakely. Identification of cell-cell signaling programs across the tumor-tumor microenvironment ecosystem and associated with clinical status in neoadjuvant osimertinib treated patient samples revealed by spatial profiling [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C025.

Bone marrow microenvironment signatures associate with patient survival after guadecitabine and atezolizumab therapy in HMA-resistant MDS.

Almost 50% of patients with myelodysplastic syndrome (MDS) are refractory to first-line hypomethylating agents (HMAs), which presents a significant clinical challenge considering the lack of options for salvage. Past work revealed that immune checkpoint molecules on peripheral myeloblasts and immune cells are up-regulated after HMA treatment. Therefore, we conducted a Phase I/II clinical trial combining guadecitabine (an HMA) and atezolizumab (an immune checkpoint inhibitor) to treat HMA-relapsed or refractory (HMA-R/R) MDS patients. This combination therapy showed median overall survival of 15.1 months relative to historical controls (4-6 months). Here, we profiled the cell composition and gene expression signatures of cells from bone marrow aspirates from trial participants with short-term (<15 months) or long-term (>15 months) survival at single-cell resolution. Long-term survivors showed a significant reduction of immunosuppressive monocytes, and an expansion of effector lymphocytes after combination therapy. Further immune profiling suggests that gamma delta T cell activation through primed dendritic cells was associated with global interferon activation in the bone marrow microenvironment of long-term survivors. Short-term survivors exhibited elevated inflammation and senescence-like gene signatures that were not resolved by combination therapy. We propose that distinct bone marrow microenvironment features, such as senescence-associated inflammation or immunosuppressive monocyte presence, could improve patient stratification for HMA and immunotherapy combinations in HMA-R/R MDS patients.

Fecal and Sputum Microbiota and Treatment Response in Patients with Mycobacterium abscessus Pulmonary Disease.

The microbiota is a potential source of biomarkers for clinical outcomes in chronic respiratory conditions, but its role in Mycobacterium abscessus pulmonary disease (PD) remains unexplored. We aimed to identify microbial signatures in fecal and sputum microbiotas associated with treatment response in patients with M. abscessus PD. We conducted a cohort study prospectively enrolling patients undergoing antibiotic treatment for M. abscessus PD. Fecal and sputum samples were collected before, and 2 weeks and 6 months after, treatment initiation. 16S rRNA amplicon sequencing approach was used to characterize the microbiotas. After categorizing patients as early treatment responders and non-responders based on sputum culture results at 2 weeks, we elucidated the differences in their diversity and composition of microbiotas. Among 32 patients enrolled, 27 patients (median 66 years, 85.2% women, 48.1% with subspecies abscessus) were included for microbiota analysis. Fifteen patients (55.6%) achieved negative conversion at 2 weeks, which was maintained in 14 (93.3%) after 6 months. Alpha-diversity of the fecal microbiota after 2 weeks of treatment decreased significantly in responders, but not in non-responders (P=0.029). Increased abundance of Eubacterium hallii group in baseline fecal microbiota was indicative of unresponsiveness to antibiotics, whereas an increase in Enterococcus in fecal microbiota at week 2 was linked with favorable response. Increased abundance of Burkholderia-Caballeronia-Paraburkholderia and Porphyromonas in baseline, and decreased abundance of Rothia in week 2 sputum microbiota were also associated with good treatment response. In M. abscessus PD, changes in microbial diversity and compositional signatures vary with treatment response.

Combining array-assisted SERS microfluidic chips and machine learning algorithms for clinical leukemia phenotyping

The disease progression and treatment options of leukemia between different subtypes vary considerably, emphasizing the importance of phenotyping. However, early typing of leukemia remains challenging due to the lack of highly sensitive and specific analytical tools. Herein, we propose a SERS-based platform for the classification of acute lymphoblastic T-cell leukemia (T-ALL) and chronic myeloid leukemia (CML) through the combination of machine learning and microfluidic chips. The ordered arrays in microfluidic channels reshape the microscopic flow field and contacting interfaces, facilitating the uniform and efficient capture of tumor cells. To enable phenotypic analysis, spectrally orthogonal SERS aptamer nanoprobes were applied, providing composite spectral signatures of individual cells in accordance with surface protein expression. Further, machine learning algorithms were employed to analyze the SERS signatures automatically, resulting in an accuracy of 98.6 % for 73 clinical blood samples. The results demonstrate that this platform holds promising potential for clinical leukemia diagnosis and precision medicine.

Single-cell analysis of nasal epithelial cell development in domestic pigs

The nasal mucosa forms a critical barrier against the invasion of respiratory pathogens. Composed of a heterogeneous assortment of cell types, the nasal mucosa relies on the unique characteristics and complex intercellular dynamics of these cells to maintain their structural integrity and functional efficacy. In this study, single-cell RNA sequencing (scRNA-seq) of porcine nasal mucosa was performed, and nineteen distinct nasal cell types, including nine epithelial cell types, five stromal cell types, and five immune cell types, were identified. The distribution patterns of three representative types of epithelial cells (basal cells, goblet cells, and ciliated cells) were subsequently detected by immunofluorescence. We conducted a comparative analysis of these data with published human single-cell data, revealing consistent differentiation trajectories among porcine and human nasal epithelial cells. Specifically, basal cells serve as the initial stage in the differentiation process of nasal epithelial cells, which then epithelial cells. This research not only enhances our understanding of the composition and transcriptional signature of porcine nasal mucosal cells but also offers a theoretical foundation for developing alternative models for human respiratory diseases.

Distant Metastases of Breast Cancer Resemble Primary Tumors in Cancer Cell Composition but Differ in Immune Cell Phenotypes.

Breast cancer is the most commonly diagnosed cancer in women, with distant metastasis being the main cause of breast cancer-related deaths. Elucidating the changes in the tumor and immune ecosystems that are associated with metastatic disease is essential to improve understanding and ultimately treatment of metastasis. Here, we developed an in-depth, spatially resolved single-cell atlas of the phenotypic diversity of tumor and immune cells in primary human breast tumors and matched distant metastases, using imaging mass cytometry to analyze a total of 75 unique antibody targets. While the same tumor cell phenotypes were typically present in primary tumors and metastatic sites, suggesting a strong founder effect of the primary tumor, their proportions varied between matched samples. Notably, the metastatic site did not influence tumor phenotype composition, except for the brain. Metastatic sites exhibited a lower number of immune cells overall, but had a higher proportion of myeloid cells as well as exhausted and cytotoxic T cells. Myeloid cells showed distinct tissue-specific compositional signatures and increased presence of potentially matrix remodeling phenotypes in metastatic sites. This analysis of tumor and immune cell phenotypic composition of metastatic breast cancer highlights the heterogeneity of the disease within patients and across distant metastatic sites, indicating myeloid cells as the predominant immune modulators that could potentially be targeted at these sites.

Similar sources but distinct δ13C signatures in adjacent low-temperature travertines from Laguna Amarga (Southern Patagonian Andes)

This study examined the waters and carbonates from two cold spring travertines (ca. 13 °C) located on the sun-exposed (north-facing travertine) and sun-shaded (south-facing travertine) margins of Laguna Amarga, an alkaline lake from the semiarid region of the eastern Patagonian Andes (51°S).The travertines are composed of calcite + low-Mg calcite ± aragonite. Both exhibit similar sedimentological transitions along their longitudinal profiles. In the proximal zones, biologically-influenced carbonates form in wetland-like environments. Spherulitic calcite precipitates in association with extracellular polymeric substances in microbial biofilms containing cyanobacteria-like molds at the vent of the south-facing travertine, while aragonite spherulite formation at the north-facing travertine vent also involves sulfate-reducing bacteria, as indicated by their close association with framboidal pyrite. Downstream, in the intermediate and distal zones, crystalline dendrites predominantly precipitate due to increased turbulence-induced CO2 degassing.Both travertines share a similar range of carbonate 87Sr/86Sr composition (0.70720–0.70740) and isotopic signatures of the spring waters, including δ2H (ca. −110 ‰ VSMOW), δ18Owater (ca. −14 ‰ VSMOW) and δ13C-DIC (ca. −5 ‰ VPDB), suggesting common sources and processes influencing fluid composition. This points to the dissolution of carbonates from mudstone-rich marine units of the Lower Cretaceous (δ13C ca. −1 ‰ VPDB) and Upper Cretaceous (δ13C ca. −10 ‰ VPDB) during shallow subsurface circulation of meteoric waters through the bedrock. The carbon isotopic composition of the deposits resembles those of endogenic travertines (δ13Ctrav −1.2 to 5.3 ‰ VPDB), with the highest δ13Ctrav values associated with carbonates from the vents. However, the involvement of deep CO2 sources is unclear and epigenic processes capable of producing the observed 13C enrichments are discussed.Despite their common sources, similar sedimentological features and δ18Otrav compositional range (−12.4 to −10.1 ‰ VPDB), the δ13Ctrav values are lower in the south-facing travertine (−1.2 to 1.9 ‰ VPDB) compared to the north-facing travertine (1.8 to 5.3 ‰ VPDB). This disparity is inferred to result from variations in local environmental conditions due to different levels of insolation, which favored the incorporation of soil-derived CO2 in the south-facing travertine and likely increased photosynthetic productivity in the north-facing travertine, thereby shifting their δ13Ctrav signatures to lower and higher values, respectively. These relationships highlight the sensitivity of low-temperature spring carbonates to subtle environmental changes at basin scales.

A Conceptual Site Model for Per‐ and Polyfluoroalkyl Substance Water Supply Impacts in a Residential Community

ABSTRACTAt a Class 4 State Superfund site located in a densely developed residential/commercial area in a suburb of New York City, emerging contaminant sampling for PFAS was performed as part of a statewide data‐gathering project. Two per‐ and polyfluoroalkyl substances (PFAS), perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), were detected at concentrations in excess of drinking water standards in bedrock and overburden monitoring wells at the State Superfund site. A bedrock private water supply well sampling program and a PFAS source investigation, consisting of overburden investigations near potential sources (i.e., sites with a history of known or suspected use, storage, or discharge of PFAS), were undertaken to assess exposures and identify and potentially eliminate sources of PFAS contaminants in the bedrock drinking water supply.Relative ratios of PFAS (i.e., PFAS signatures) were plotted geospatially to facilitate comparison of the characteristics of overburden groundwater sampling results to that of nearby bedrock private water supply sampling results. In addition, total PFAS concentrations in overburden groundwater and bedrock private water supply samples were compared to identify potential sources of bedrock groundwater impacts. The PFAS signature analysis revealed that (1) PFAS signatures of overburden groundwater samples were generally consistent with nearby bedrock private water supply samples; (2) total PFAS concentrations detected in overburden groundwater samples were marginally higher than concentrations detected in nearby bedrock private water supplies; (3) there was generally low variability in PFAS signatures throughout the study area (Assessment Area); and (4) overburden groundwater and bedrock private water supply PFAS signatures were similar to that of the nearby wastewater treatment plant effluent discharge, which represents a composite average PFAS signature for domestic wastewater from the area. Finally, septic system tracers were also detected in bedrock private water supply and overburden groundwater samples. Based on the results of the investigation, multiple lines of evidence support the Conceptual Site Model, which is likely applicable to many PFAS‐contaminated drinking water supplies with conditions similar to the Assessment Area: consumer product use and discharge to domestic septic systems in a densely developed residential area, lacking area‐wide municipal water and sewer, with shallow groundwater and bedrock, and a vertical downward groundwater gradient, have resulted in the widespread presence of PFAS in private water supply wells.

Mixed Source Region Signatures inside Magnetic Switchback Patches Inferred by Heavy Ion Diagnostics

Since Parker Solar Probe’s (Parker’s) first perihelion pass at the Sun, large-amplitude Alfvén waves grouped in patches have been observed near the Sun throughout the mission. Several formation processes for these magnetic switchback patches have been suggested with no definitive consensus. To provide insight into their formation, we examine the heavy ion properties of several adjacent magnetic switchback patches around Parker’s 11th perihelion pass, capitalizing on a spacecraft lineup with Solar Orbiter where each samples the same solar wind streams over a large range of longitudes. Heavy ion properties (Fe/O, C6+/C5+, O7+/O6+) related to the wind’s coronal origin, measured with Solar Orbiter, can be linked to switchback patch structures identified near the Sun with Parker. We find that switchback patches do not contain distinctive ion and elemental compositional signatures different from the surrounding nonswitchback solar wind. Both the patches and ambient wind exhibit a range of fast and slow wind qualities, indicating coronal sources with open and closed field lines in close proximity. These observations and modeling indicate switchback patches form in coronal hole boundary wind and with a range of source region magnetic and thermal properties. Furthermore, the heavy ion signatures suggest interchange reconnection and/or shear-driven processes may play a role in their creation.

Transcripts with high distal heritability mediate genetic effects on complex metabolic traits.

Although many genes are subject to local regulation, recent evidence suggests that complex distal regulation may be more important in mediating phenotypic variability. To assess the role of distal gene regulation in complex traits, we combined multi-tissue transcriptomes with physiological outcomes to model diet-induced obesity and metabolic disease in a population of Diversity Outbred mice. Using a novel high-dimensional mediation analysis, we identified a composite transcriptome signature that summarized genetic effects on gene expression and explained 30% of the variation across all metabolic traits. The signature was heritable, interpretable in biological terms, and predicted obesity status from gene expression in an independently derived mouse cohort and multiple human studies. Transcripts contributing most strongly to this composite mediator frequently had complex, distal regulation distributed throughout the genome. These results suggest that trait-relevant variation in transcription is largely distally regulated, but is nonetheless identifiable, interpretable, and translatable across species.

Single-Cell RNA-Sequencing: Opening New Horizons for Breast Cancer Research.

Breast cancer is the most prevalent malignant tumor among women with high heterogeneity. Traditional techniques frequently struggle to comprehensively capture the intricacy and variety of cellular states and interactions within breast cancer. As global precision medicine rapidly advances, single-cell RNA sequencing (scRNA-seq) has become a highly effective technique, revolutionizing breast cancer research by offering unprecedented insights into the cellular heterogeneity and complexity of breast cancer. This cutting-edge technology facilitates the analysis of gene expression profiles at the single-cell level, uncovering diverse cell types and states within the tumor microenvironment. By dissecting the cellular composition and transcriptional signatures of breast cancer cells, scRNA-seq provides new perspectives for understanding the mechanisms behind tumor therapy, drug resistance and metastasis in breast cancer. In this review, we summarized the working principle and workflow of scRNA-seq and emphasized the major applications and discoveries of scRNA-seq in breast cancer research, highlighting its impact on our comprehension of breast cancer biology and its potential for guiding personalized treatment strategies.

Advances in understanding the cellular composition and molecular signatures of the adult Drosophila eye through single-cell RNA sequencing

Advances in understanding the cellular composition and molecular signatures of the adult Drosophila eye through single-cell RNA sequencing

A comparative study of dietary amino acid patterns: unveiling growth, composition, and molecular signatures in juvenile Onychostoma macrolepis.

The wild Onychostoma macrolepis, a species under national class II protection in China, lacks a specific compound feed for captive rearing. Understanding the dietary amino acid pattern is crucial for optimal feed formulation. This study aimed to investigate the effects of the four different dietary amino acid patterns, i.e., anchovy fishmeal protein (FMP, control group) and muscle protein (MP), whole-body protein (WBP), fish egg protein (FEP) of juvenile Onychostoma macrolepis, on the growth performance, body composition, intestinal morphology, enzyme activities, and the expression levels of gh, igf, mtor genes in juveniles. In a 12-week feeding trial with 240 juveniles (3.46±0.04g), the MP group demonstrated superior outcomes in growth performance (FBW, WGR, SGR), feed utilization efficiency (PER, PRE, FCR). Notably, it exhibited higher crude protein content in whole-body fish, enhanced amino acid composition in the liver, and favorable fatty acid health indices (AI, TI, h/H) in muscle compared to other groups (P < 0.05). Morphologically, the MP and FMP groups exhibited healthy features. Additionally, the MP group displayed significantly higher activities of TPS, ALP, and SOD, along with elevated expression levels of gh, igf, mtor genes, distinguishing it from the other groups (P < 0.05). This study illustrated that the amino acid pattern of MP emerged as a suitable dietary amino acid pattern for juvenile Onychostoma macrolepis. Furthermore, the findings provide valuable insights for formulating effective feeds in conserving and sustainably farming protected species, enhancing the research's broader ecological and aquacultural significance.

One-to-Nine Single Spectroscopic Intelligent Probe for Risk Assessment of Multiple Metals in Drinking Water.

26% of the world's population lacks access to clean drinking water; clean water and sanitation are major global challenges highlighted by the UN Sustainable Development Goals, indicating water security in public water systems is at stake today. Water monitoring using precise instruments by skilled operators is one of the most promising solutions. Despite decades of research, the professionalism-convenience trade-off when monitoring ubiquitous metal ions remains the major challenge for public water safety. Thus, to overcome these disadvantages, an easy-to-use and highly sensitive visual method is desirable. Herein, an innovative strategy for one-to-nine metal detection is proposed, in which a novel thiourea spectroscopic probe with high 9-metal affinity is synthesized, acting as "one", and is detected based on the 9 metal-thiourea complexes within portable spectrometers in the public water field; this is accomplished by nonspecialized personnel as is also required. During the processing of multimetal analysis, issues arise due to signal overlap and reproducibility problems, leading to constrained sensitivity. In this innovative endeavor, machine learning (ML) algorithms were employed to extract key features from the composite spectral signature, addressing multipeak overlap, and completing the detection within 30-300 s, thus achieving a detection limit of 0.01 mg/L and meeting established conventional water quality standards. This method provides a convenient approach for public drinking water safety testing.

Evaluation of the Immune Response within the Tumor Microenvironment in African American and Non-Hispanic White Patients with Non-Small Cell Lung Cancer.

African Americans have higher incidence and mortality from lung cancer than non-Hispanic Whites, but investigations into differences in immune response have been minimal. Therefore, we compared components of the tumor microenvironment among African Americans and non-Hispanic Whites diagnosed with non-small cell lung cancer based on PDL1 or tertiary lymphoid structure (TLS) status to identify differences of translational relevance. Using a cohort of 280 patients with non-small cell lung cancer from the Inflammation, Health, Ancestry, and Lung Epidemiology study (non-Hispanic White: n = 155; African American: n = 125), we evaluated PDL1 tumor proportion score (<1% vs. ≥1%) and TLS status (presence/absence), comparing differences within the tumor microenvironment based on immune cell distribution and differential expression of genes. Tumors from African Americans had a higher proportion of plasma cell signatures within the tumor microenvironment than non-Hispanic Whites. In addition, gene expression patterns in African American PDL1-positive samples suggest that these tumors contained greater numbers of γδ T cells and resting dendritic cells, along with fewer CD8+ T cells after adjusting for age, sex, pack-years, stage, and histology. Investigation of differential expression of B cell/plasma cell-related genes between the two patient populations revealed that two immunoglobulin genes (IGKV2-29 and IGLL5) were associated with decreased mortality risk in African Americans. In the first known race-stratified analysis of tumor microenvironment components in lung cancer based on PDL1 expression or TLS status, differences within the immune cell composition and transcriptomic signature were identified that may have therapeutic implications. Future investigation of racial variation within the tumor microenvironment may help direct the use of immunotherapy.