Landscape Of Alterations Research Articles

Anas platyrhynchos (Mallard) has been replacing Anas rubripes (American Black Duck) in human-altered landscapes in Ontario, 1996 to 2019

Abstract Anas rubripes (American Black Duck) has received much attention over the years as a popular game bird species that experienced historical declines on its wintering grounds. Declines may be due to changes in the quality and quantity of breeding habitat, competition with A. platyrhynchos (Mallard), or both. Although the A. rubripes population has stabilized, spatial variation in regional population trends of A. rubripes on their breeding grounds can provide insight into the relative importance of these alternative hypotheses at provincial and local scales. We analyzed indicated breeding pairs count data collected in Ontario between 1996 and 2019 through the Eastern Waterfowl Survey to evaluate the correlation in breeding densities and trends of the 5 most abundant waterfowl species. We also tested whether habitat and anthropogenic disturbance variables could explain the distribution of those species. Overall, A. platyrhynchos breeding pair densities increased across the survey area, whereas A. rubripes breeding pair densities decreased in the southern and northern part of the survey area but remained stable in the central part. Densities of breeding pairs of A. rubripes and A. platyrhynchos were negatively correlated across survey plots but the trends in breeding densities were not correlated. Densities of A. platyrhynchos breeding pairs increased in human altered landscapes, whereas the density of A. rubripes breeding pairs was negatively correlated with agriculture. Our results suggest that A. platyrhynchos did not competitively exclude A. rubripes on the breeding grounds, but instead, A. rubripes were replaced by A. platyrhynchos following encroachment of agriculture into A. rubripes breeding habitat. Habitat management plans focused on breeding A. rubripes should emphasize reduction in the expansion of anthropogenic perturbations and increases in habitat conservation efforts in the central area of the breeding range in Ontario.

The metamorphoses of denationalization of 1993. Report II. The prices of medications as information

In the history of Russian pharmaceutical market, the year of 1993 became the year of both formation of rules of market relations and alteration of market landscape for changed conditions. The significant segment of state centralized purchases moved under responsibility of regional authorities and their health authorities. At that, authorizations of former three state organizations occupied with import purchases were distributed between new state companies of the Ministry of Health Care and commercial organizations and firms that entered pharmaceutical market. Pretty soon, this diversity gave rise both to competition for budget funds and Government experiments with market regulation. The traces of these clashes and attempts to make market manageable are found in the Ministry of Health Care archives and journal publications.The Report II uses informational potential of medications prices to decode rules of play in Russian pharmaceutical market with purpose to analyze distributions of power at playing table.

914P The landscape of somatic copy number alterations of head and neck squamous cell carcinoma across different anatomic sites

914P The landscape of somatic copy number alterations of head and neck squamous cell carcinoma across different anatomic sites

390. CONTINUED IMPLICATIONS OF THE COVID-19 PANDEMIC ENVIRONMENT ON ESOPHAGEAL CANCER CHARACTERISTICS AND TREATMENT IN THE UNITED STATES

Abstract Background The COVID-19 pandemic significantly impacted the stage of presentation and subsequent therapies for patients who were diagnosed with esophageal cancer during the first pandemic year. We aimed to assess for continued implications of the altered healthcare landscape on esophageal cancer presentation and treatment in the second year of the pandemic. Methods This was a retrospective review of the United States National Cancer Database (2019-2021). Demographic, cancer-related and treatment variables were compared between patients diagnosed in the pre-pandemic year (2019), pandemic year one (2020) and pandemic year two (2021). Multivariate logistic regression was performed to control for the impact of demographics on oncologic variables, and then for the impact of oncologic variables on treatment modalities and outcomes. Results Of 42,807 esophageal cancer cases, 15,127 (35.3%) were pre-pandemic, 13,975 (32.7%) were pandemic year 1, and 13,705 (32.0%) were pandemic year two. There were significant differences in the distribution of clinical stage at presentation by year (p=0.0001), see figure, suggesting more advanced stage presentation throughout the pandemic. Compared to the pre-pandemic year, patients diagnosed in pandemic year two had risk-adjusted increases in time to first course treatment (incidence rate ratio 1.057 [95% confidence interval [1.036–1.078]), to radiation (1.029 [1.008–1.050]), and to systemic therapy (1.035 [1.018–1.051]). Additionally, when compared to pandemic year one, patients in pandemic year two continued to experience risk-adjusted increases in time to first course therapy (1.084 [1.063–1.106]), to surgery (1.049 [1.000–1.097]), to radiation (1.046 [1.024–1.068]) and to systemic therapy (1.060 [1.043–1.077]). Conclusions Compared to the pre-pandemic year, patients diagnosed with esophageal cancer in in the U.S. during pandemic year two continued to experience delays to treatment including delays to first course therapy, including delays to surgery, radiation and systemic therapy. The treatment characteristics of esophageal cancer have not returned to pre-pandemic baseline in the United States possibly due to compounding delays to diagnosis and treatment and a growing back log of cases.

Common molecular basis of aging and cancer dynamics: complex interactions among age, diseases, external stressors, and environmental factors

There are incremental efforts to understand the multifaceted aspects of aging, particularly focusing on its biological interplay with various environmental stressors and diseases such as cancer. The concept of biological age, which is distinct from chronological age, and its importance in predicting disease onset and mortality patterns are emphasized. Furthermore, exploration of the reversible nature of biological aging under different stress conditions, such as surgery, pregnancy, and diseases such as cancer and coronavirus disease 2019, is intriguing. This narrative review attempts to address the potential impact of viral infections such as severe acute respiratory syndrome coronavirus 2 and the altered landscape of diseases such as cancer on biological aging and their interconnected relationships. Additionally, it also touches upon the influence of emerging technologies, particularly artificial intelligence-driven machines, on aging dynamics, prompting further research in this area. This article may provide insight into a comprehensive framework for interdisciplinary research to better understand the complex interactions among age-related dynamics, diseases, external stressors, and environmental factors, with implications for future interventions and healthcare strategies.

Depiction of the Genetic Alterations and Molecular Landscapes of Thymic Epithelial Tumors: A Systematic Review and Meta-Analysis.

Thymic epithelial tumors (TETs), consisting of thymomas, thymic carcinomas (TCs), and thymic neuroendocrine tumors, are rare diseases. Surgery remains the prime option in resectable and early-stage TETs, while chemotherapy, targeted therapy, and immunotherapy are also potential treatment modalities. However, the inadequate comprehension of the molecular landscape of TETs impedes the exploitation of such therapies. Hence, we conducted a meta-analysis which includes 21 studies reporting on genomic alterations in TETs and 14 studies reporting on PD-L1 expression levels, respectively. The pooled estimated rates of the most frequently mutated genes and PD-L1 expression levels were analyzed using the R software. We uncovered that the pooled estimated overall mutation rate is 0.65 ([0.49; 0.81]), and the top three genes with highest mutation frequency in thymomas and TCs are GTF2I (0.4263 [0.3590; 0.4936]), TP53 (0.1101 [0.0000; 0.2586]), and RAS (0.0341 [0.0104; 0.0710]), and TP53 (0.1797 [0.0732; 0.3203]), CDKN2A (0.0608 [0.0139; 0.1378]), and TET2 (0.0318 [0.0087; 0.0639]), respectively. A uniform GTF2I mutational rate in thymomas and TP53 mutational rate in thymic squamous cell carcinomas (TSCCs) are also observed. The pooled estimated expression level of PD-L1 is 0.71 ([0.59-0.81]). This systematic review provides an overview of the gene alteration landscape and PD-L1 expression levels in TETs, discovers several potential confounding factors that may contribute to the high heterogeneity, and facilitates deeper investigations into the elucidation of the molecular landscape of TETs.

Next-generation sequencing-based evaluation of the actionable landscape of genomic alterations in solid tumors: the "MOZART" prospective observational study.

The identification of the most appropriate targeted therapies for advanced cancers is challenging. We performed a molecular profiling of metastatic solid tumors utilizing a comprehensive next-generation sequencing (NGS) assay to determine genomic alterations' type, frequency, actionability, and potential correlations with PD-L1 expression. A total of 304 adult patients with heavily pretreated metastatic cancers treated between January 2019 and March 2021 were recruited. The CLIA-/UKAS-accredit Oncofocus assay targeting 505 genes was used on newly obtained or archived biopsies. Chi-square, Kruskal-Wallis, and Wilcoxon rank-sum tests were used where appropriate. Results were significant for P < .05. A total of 237 tumors (78%) harbored potentially actionable genomic alterations. Tumors were positive for PD-L1 in 68.9% of cases. The median number of mutant genes/tumor was 2.0 (IQR: 1.0-3.0). Only 34.5% were actionable ESCAT Tier I-II with different prevalence according to cancer type. The DNA damage repair (14%), the PI3K/AKT/mTOR (14%), and the RAS/RAF/MAPK (12%) pathways were the most frequently altered. No association was found among PD-L1, ESCAT, age, sex, and tumor mutational status. Overall, 62 patients underwent targeted treatment, with 37.1% obtaining objective responses. The same molecular-driven treatment for different cancer types could be associated with opposite clinical outcomes. We highlight the clinical value of molecular profiling in metastatic solid tumors using comprehensive NGS-based panels to improve treatment algorithms in situations of uncertainty and facilitate clinical trial recruitment. However, interpreting genomic alterations in a tumor type-specific manner is critical.

A Generalizable Prioritization Protocol for Climate-Sensitive Zoonotic Diseases.

Emerging and re-emerging zoonotic diseases pose a significant threat to global health and economic security. This threat is further aggravated by amplifying drivers of change, including climate hazards and landscape alterations induced by climate change. Given the complex relationships between climate change and zoonotic disease health outcomes, a structured decision-making process is required to effectively identify pathogens of greatest concern to prioritize prevention and surveillance efforts. Here, we describe a workshop-based expert elicitation process in six steps to prioritize climate-sensitive zoonoses based on a structured approach to defining criteria for climate sensitivity. Fuzzy analytical hierarchy process methodology is used to analyze data provided by experts across human, animal, and environmental health sectors accounting for uncertainties at different stages of the prioritization process. We also present a new interactive expert elicitation interface that facilitates data collection and real-time visualization of prioritization results. The novel approach presented in this paper offers a generalized platform for prioritizing climate-sensitive zoonoses at a national or regional level. This allows for a structured decision-making support process when allocating limited financial and personnel resources to enhance preparedness and response to zoonotic diseases amplified by climate change.

Single-cell RNA sequencing reveals the effects of high-fat diet on oocyte and early embryo development in female mice

BackgroundObesity is a global health issue with detrimental effects on various human organs, including the reproductive system. Observational human data and several lines of animal experimental data suggest that maternal obesity impairs ovarian function and early embryo development, but the precise pathogenesis remains unclear.MethodsWe established a high-fat diet (HFD)-induced obese female mouse model to assess systemic metabolism, ovarian morphology, and oocyte function in mice. For the first time, this study employed single-cell RNA sequencing to explore the altered transcriptomic landscape of preimplantation embryos at different stages in HFD-induced obese mice. Differential gene expression analysis, enrichment analysis and protein-protein interactions network analysis were performed.ResultsHFD-induced obese female mice exhibited impaired glucolipid metabolism and insulin resistance. The ovaries of HFD mice had a reduced total follicle number, an increased proportion of atretic follicles, and irregular granulosa cell arrangement. Furthermore, the maturation rate of embryonic development by in vitro fertilization of oocytes was significantly decreased in HFD mice. Additionally, the transcriptional landscapes of preimplantation embryos at different stages in mice induced by different diets were significantly distinguished. The maternal-to-zygotic transition was also affected by the failure to remove maternal RNAs and to turn off zygotic genome expression.ConclusionsHFD-induced obesity impaired ovarian morphology and oocyte function in female mice and further led to alterations in the transcriptional landscape of preimplantation embryos at different stages of HFD mice.

XOL-1 regulates developmental timing by modulating the H3K9 landscape in C. elegans early embryos.

Sex determination in the nematode C. elegans is controlled by the master regulator XOL-1 during embryogenesis. Expression of xol-1 is dependent on the ratio of X chromosomes and autosomes, which differs between XX hermaphrodites and XO males. In males, xol-1 is highly expressed and in hermaphrodites, xol-1 is expressed at very low levels. XOL-1 activity is known to be critical for the proper development of C. elegans males, but its low expression was considered to be of minimal importance in the development of hermaphrodite embryos. Our study reveals that XOL-1 plays an important role as a regulator of developmental timing during hermaphrodite embryogenesis. Using a combination of imaging and bioinformatics techniques, we found that hermaphrodite embryos have an accelerated rate of cell division, as well as a more developmentally advanced transcriptional program when xol-1 is lost. Further analyses reveal that XOL-1 is responsible for regulating the timing of initiation of dosage compensation on the X chromosomes, and the appropriate expression of sex-biased transcriptional programs in hermaphrodites. We found that xol-1 mutant embryos overexpress the H3K9 methyltransferase MET-2 and have an altered H3K9me landscape. Some of these effects of the loss of xol-1 gene were reversed by the loss of met-2. These findings demonstrate that XOL-1 plays an important role as a developmental regulator in embryos of both sexes, and that MET-2 acts as a downstream effector of XOL-1 activity in hermaphrodites.

Berberine Protects against Hepatocellular Carcinoma Progression by Regulating Intrahepatic T Cell Heterogeneity.

Accumulating evidence suggests that berberine (BBR) exhibits anti-cancer effects in hepatocellular carcinoma (HCC). However, the mechanisms by which BBR regulates the immunological microenvironment in HCC has not been fully elucidated. In this study, a mouse model of orthotopic HCC is established and treated with varying doses of BBR. BBR showed effectiveness in reducing tumor burden in mice with HCC. Cytometry by time-of-flight depicted the alterations in the tumor immune landscape following BBR treatment, revealing the enhancement in the T lymphocytes effector function. In particular, BBR decreased the proportion of TCRbhiPD-1hiCD69+CD27+ effector CD8+ T lymphocytes and increased the proportion of Ly6ChiTCRb+CD69+CD27+CD62L+ central memory CD8+ T lymphocytes. Single-cell RNA sequencing further elucidates the effects of BBR on transcriptional profiles of liver immune cells and confirms the phenotypical heterogeneity of T lymphocytes in HCC immune microenvironment. Additionally, it is found that BBR potentially regulated the antitumor immunity in HCC by modulating the receptor-ligand interaction among immune cells mediated by cytokines. In summary, the findings improve the understanding of BBR's impact on protecting against HCC, emphasizing BBR's role in regulating intrahepatic T cell heterogeneity. BBR has the potential to be a promising therapeutic strategy to hinder the advancement of HCC.

Comprehensive single-cell analysis deciphered microenvironmental dynamics and immune regulator olfactomedin 4 in pathogenesis of gallbladder cancer

ObjectiveElucidating complex ecosystems and molecular features of gallbladder cancer (GBC) and benign gallbladder diseases is pivotal to proactive cancer prevention and optimal therapeutic intervention.DesignWe performed single-cell transcriptome analysis on 230...

Inheriting the royals: royal chartered bodies in Ireland after 1922

The establishment of the Irish Free State (Saorstát Éireann) in 1922 did not occur on a blank canvas. A slew of administrative bodies and agencies with pre-1922 origins now found themselves under a new jurisdiction, still familiar in some respects but alien in others. The Irish State Administration Database indicates that the functions performed by these pre-1922 bodies included the delivery of public services and regulatory oversight. The resilience of pre-1922 bodies arguably ensured a greater degree of day-to-day administrative continuity and stability after 1922 than may otherwise have been the case.This article focuses on a particular subset of these pre-1922 entities – royal chartered bodies – carried into Saorstát Éireann and beyond. Of special interest are the peculiar legal mechanisms through which these bodies were sustained in an altered constitutional landscape. The discontinuation of a pre-1922 royal prerogative to grant and amend royal charters presented legal conundrums for royal chartered bodies and the state. This was mitigated through a mixture of tailored public and private legislation of the Oireachtas. These dynamics are interrogated through the lenses of temporality and legal pluralism.

Identification of differentially expressed tumour-related genes regulated by UHRF1-driven DNA methylation

Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an epigenetic regulator that plays critical roles in tumours. However, the DNA methylation alteration patterns driven by UHRF1 and the related differentially expressed tumour-related genes remain unclear. In this study, a UHRF1-shRNA MCF-7 cell line was constructed, and whole-genome bisulfite sequencing and RNA sequencing were performed. The DNA methylation alteration landscape was elucidated, and DNA methylation-altered regions (DMRs) were found to be distributed in both gene bodies and adjacent regions. The DMRs were annotated and categorized into 488 hypermethylated/1696 hypomethylated promoters and 1149 hypermethylated/5501 hypomethylated gene bodies. Through an integrated analysis with the RNA sequencing data, 217 methylation-regulated upregulated genes and 288 downregulated genes were identified, and these genes were primarily enriched in nervous system development and cancer signalling pathways. Further analysis revealed 21 downregulated oncogenes and 15 upregulated TSGs. We also showed that UHRF1 silencing inhibited cell proliferation and migration and suppressed tumour growth in vivo. Our study suggested that UHRF1 and the oncogenes or TSGs it regulates might serve as biomarkers and targets for breast cancer treatment.

The Proteomic Landscape of Monocytes in Response to Colorectal Cancer Cells.

Colorectal cancer (CRC) involves a complex interaction between tumor cells and immune cells, notably monocytes, leading to immunosuppression. This study explored these interactions using in vitro coculture systems of THP-1 cells and CRC cell lines, employing quantitative proteomics to analyze protein changes in monocytes. Multiple analytical methods were utilized to delineate the altered proteomic landscape, identify key proteins, and their associated functional pathways for comprehensive data analysis. Differentially expressed proteins (DEPs) were selected and validated by cross-referencing them with publicly available TCGA and GEO data sets to explore their potential clinical significance. Our analysis identified 161 up-regulated and 130 down-regulated DEPs. The enrichment results revealed impairments in adhesion and innate immune functions in monocytes, potentially facilitating cancer progression. The down-regulation of FN1, THSB1, and JUN may contribute to these impairments. Furthermore, the overexpression of ADAMTSL4, PRAM1, GPNMB, and NPC2 on monocytes was associated with unfavorable prognostic outcomes in CRC patients, suggesting potential biomarkers or therapeutic targets. This study illustrated the proteomic landscape of monocytes in response to CRC cells, providing clues for future investigations of the crosstalk between cancer cells and monocytes within the tumor microenvironment.

Sequences within and upstream of the mouse Ets1 gene drive high level expression in B cells, but are not sufficient for consistent expression in T cells.

The levels of transcription factor Ets1 are high in resting B and T cells, but are downregulated by signaling through antigen receptors and Toll-like receptors (TLRs). Loss of Ets1 in mice leads to excessive immune cell activation and development of an autoimmune syndrome and reduced Ets1 expression has been observed in human PBMCs in the context of autoimmune diseases. In B cells, Ets1 serves to prevent premature activation and differentiation to antibody-secreting cells. Given these important roles for Ets1 in the immune response, stringent control of Ets1 gene expression levels is required for homeostasis. However, the genetic regulatory elements that control expression of the Ets1 gene remain relatively unknown. Here we identify a topologically-associating domain (TAD) in the chromatin of B cells that includes the mouse Ets1 gene locus and describe an interaction hub that extends over 100 kb upstream and into the gene body. Additionally, we compile epigenetic datasets to find several putative regulatory elements within the interaction hub by identifying regions of high DNA accessibility and enrichment of active enhancer histone marks. Using reporter constructs, we determine that DNA sequences within this interaction hub are sufficient to direct reporter gene expression in lymphoid tissues of transgenic mice. Further analysis indicates that the reporter construct drives faithful expression of the reporter gene in mouse B cells, but variegated expression in T cells, suggesting the existence of T cell regulatory elements outside this region. To investigate how the downregulation of Ets1 transcription is associated with alterations in the epigenetic landscape of stimulated B cells, we performed ATAC-seq in resting and BCR-stimulated primary B cells and identified four regions within and upstream of the Ets1 locus that undergo changes in chromatin accessibility that correlate to Ets1 gene expression. Interestingly, functional analysis of several putative Ets1 regulatory elements using luciferase constructs suggested a high level of functional redundancy. Taken together our studies reveal a complex network of regulatory elements and transcription factors that coordinate the B cell-specific expression of Ets1.

Landscape of Concomitant Driver Alterations in Classical EGFR-Mutated Non-Small Cell Lung Cancer.

Next-generation sequencing (NGS) has enabled the detection of concomitant driver alterations in non-small cell lung cancer (NSCLC). However, the magnitude and clinical relevance of concomitant drivers remain to be explored. We profiled concomitant driver alterations of EGFR+ NSCLC by using targeted NGS. The associated genomic and clinical features were analyzed and validated in an independent The Cancer Genome Atlas cohort of patients with EGFR+ NSCLC. Out of the total patient population, 334 patients had EGFR mutations along with concomitant driver mutations, comprising 3.09% of the entire cohort. The most frequent co-occurring mutations with sensitizing EGFR mutations include KRAS at 53.9%, followed by ERBB2 at 24.3%, MET at 16.5%, and BRAF at 3.3%. KRAS mutations in concomitant drivers were frequently hyperexchange mutations (25.6% v 8.2%, P < .001), compared with KRAS single drivers. EGFR/ERBB2 drivers exhibited a higher incidence of ERBB2 amplification (40.7% v 16.5%, P < .001) and p.S310F/Y mutations (44.4% v 4.3%, P < .001) compared with ERBB2 alone. EGFR/MET drivers had a higher frequency of MET amplification (71.4% v 43.3%) than MET single drivers. At the genomic level, the median number of additional concurrent mutations was four, with TSC2 (4%), CD274 (1%), and TP53 (63%) being the most frequently coaltered genes in concomitant driver tumors. Interestingly, clonality analysis indicated that EGFR mutations were more likely to occur as clonal events, whereas the codrivers were more often subclonal. Patients with concomitant drivers or with concomitant MET amplification exhibited worse prognosis. These findings might aid in the selection of effective therapeutic regimens and facilitate the development of combination therapies.

Movement behavior in a dominant ungulate underlies successful adjustment to a rapidly changing landscape following megafire

BackgroundMovement plays a key role in allowing animal species to adapt to sudden environmental shifts. Anthropogenic climate and land use change have accelerated the frequency of some of these extreme disturbances, including megafire. These megafires dramatically alter ecosystems and challenge the capacity of several species to adjust to a rapidly changing landscape. Ungulates and their movement behaviors play a central role in the ecosystem functions of fire-prone ecosystems around the world. Previous work has shown behavioral plasticity is an important mechanism underlying whether large ungulates are able to adjust to recent changes in their environments effectively. Ungulates may respond to the immediate effects of megafire by adjusting their movement and behavior, but how these responses persist or change over time following disturbance is poorly understood.MethodsWe examined how an ecologically dominant ungulate with strong site fidelity, Columbian black-tailed deer (Odocoileus hemionus columbianus), adjusted its movement and behavior in response to an altered landscape following a megafire. To do so, we collected GPS data from 21 individual female deer over the course of a year to compare changes in home range size over time and used resource selection functions (RSFs) and hidden Markov movement models (HMMs) to assess changes in behavior and habitat selection.ResultsWe found compelling evidence of adaptive capacity across individual deer in response to megafire. Deer avoided exposed and severely burned areas that lack forage and could be riskier for predation immediately following megafire, but they later altered these behaviors to select areas that burned at higher severities, potentially to take advantage of enhanced forage.ConclusionsThese results suggest that despite their high site fidelity, deer can navigate altered landscapes to track rapid shifts in encounter risk with predators and resource availability. This successful adjustment of movement and behavior following extreme disturbance could help facilitate resilience at broader ecological scales.

Development of a Rhizobium Seed Coating to Establish Lupine Species on Degraded Rangelands.

Restoring native plant species on degraded landscapes is challenging. Symbiotic partners in the plant rhizosphere can aid in nutrient acquisition, pathogen protection, stress tolerance, and many other processes. However, these microbes are often absent in altered landscapes and need to be re-integrated to improve restoration efforts. We evaluated, within a laboratory setting, the ability of commercial and indigenous rhizobia strains to form nodules on lupine species used for rangeland seedings in the Great Basin region of the Western United States and ascertained if these strains could be applied through a seed coating. We also evaluated if a compost amendment applied via seed coating could further enhance the performance of the rhizobia strains. Our analysis showed that successful nodulation could occur using commercial and wildland-collected indigenous strains through either a liquid culture applied to seedlings or as a dry seed coating. However, the number of root nodules and the presence of a pink color (indicating nitrogen fixation) were typically higher in the commercial product than in the indigenous strains. Compost did not improve nodulation or the performance of the nodules; however, this treatment alone improved shoot growth. Overall, these results suggest that commercial rhizobium may be more effective in improving plant growth, and future research with native rhizobia may want to consider identifying strains compatible with seed-coating delivery. Longer-term studies are now merited for assessing how the rhizobia strains evaluated in this study influence plant growth, particularly in a field setting.

Single-cell profiling reveals altered immune landscape and impaired NK cell function in gastric cancer liver metastasis.

Gastric cancer (GC) is a substantial global health concern, and the development of liver metastasis (LM) in GC represents a critical stage linked to unfavorable patient prognoses. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the immune landscape of GC liver metastasis, revealing several immuno-suppressive components within the tumor immune microenvironment (TIM). Our findings unveiled an increased presence of cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cell (MDSC)-like macrophages, tumor-associated macrophage (TAM)-like macrophages, and naive T cells, while conventional dendritic cells (cDCs) and effector CD8 T cells declined in LM. Additionally, we identified two distinct natural killer (NK) cell clusters exhibiting differential cytotoxicity-related gene expression, with cytotoxic NK cells notably reduced in LM. Strikingly, TGFβ was identified as an inducer of NK cell dysfunction, potentially contributing to immune evasion and tumor metastasis. In preclinical LM models, the combined approach of inhibiting TGFβ and transferring NK cells exhibited a synergistic impact, resulting in a significant reduction in liver metastasis. This work highlights the importance of understanding the complex immune dynamics within GC liver metastasis and presents a promising strategy combining TGFβ inhibition and NK-based immunotherapy to improve patient outcomes.