RGS5+ lymphatic endothelial cells facilitate metastasis and acquired drug resistance of breast cancer through oxidative stress-sensing mechanism.

AIMS: Oxidative stress reflected by elevated reactive oxygen species (ROS) in the tumor ecosystem, is a hallmark of human cancers. The mechanisms by which oxidative stress regulate the metastatic ecosystem and resistance remain elusive. This study aimed to dissect the oxidative stress-sensing machinery during the evolvement of early dissemination and acquired drug resistance in breast cancer. METHODS: Here, we constructed single-cell landscape of primary breast tumors and metastatic lymph nodes, and focused on RGS5+ endothelial cell subpopulation in breast cancer metastasis and resistance. RESULTS: We reported on RGS5 as a master in endothelial cells sensing oxidative stress. RGS5+ endothelial cells facilitated tumor-endothelial adhesion and transendothelial migration of breast cancer cells. Antioxidant suppressed oxidative stress-induced RGS5 expression in endothelial cells, and prevented adhesion and transendothelial migration of cancer cells. RGS5-overexpressed HLECs displayed attenuated glycolysis and oxidative phosphorylation. Drug-resistant HLECs with RGS5 overexpression conferred acquired drug resistance of breast cancer cells. Importantly, genetic knockdown of RGS5 prevented tumor growth and lymph node metastasis. CONCLUSIONS: Our work demonstrates that RGS5 in lymphatic endothelial cells senses oxidative stress to promote breast cancer lymph node metastasis and resistance, providing a novel insight into a potentially targetable oxidative stress-sensing machinery in breast cancer treatment.

Exploring the biological behavior and underlying mechanism of KITLG in triple-negative breast cancer.

The tyrosine-kinase receptor that is specified by the KIT locus is demarcated by KITLG. This multifaceted factor is instrumental during in-utero germ and neural cell maturation and hematopoiesis, ostensibly reflecting its role in facilitating cell migration. Concurrently, KITLG is prone to a mutation in germ cell tumors, entailing a presumed connection to tumorigenesis. Despite this, the intricacies of its function in breast cancer and the relevant mechanisms remain elusive. Multiple independent databases depict a consistently low expression of KITLG within tissues affected by triple-negative breast cancers (TNBC), a trend strongly coupled with reduced survival rates. Interestingly, non-triple-negative breast cancers exhibit a markedly high expression of KITLG compared to the norm. An initial analysis of the GEO database speculates that KITLG may serve as an oncogene suppressor in TNBC, hinting at varied roles for KITLG isoforms within this disease context. In conclusion, our preliminary analysis offers valuable insights into the role and expression pattern of KITLG in TNBC. We provide evidence supporting its consideration as a promising new prognostic marker, thereby potentially enriching therapeutic strategies for TNBC. Indeed, given the limited advances in molecularly targeted therapy for TNBC, a significant need exists for a more precise therapeutic approach and a comprehensive understanding of its inherent mechanisms of action.

A novel anoikis-related gene signature predicts prognosis in patients with breast cancer and reveals immune infiltration.

Breast cancer (BRCA) is a common malignancy worldwide that is associated with a high mortality rate. Despite recent improvements in diagnosis and treatment, there is an urgent need to investigate the processes underlying cancer progression and identify novel prognostic indicators. Anoikis, which plays a role in the development of human malignant tumors, has been gaining increasing interest from researchers. However, the potential role of anoikis-related genes (ANRGs) in the advancement of BRCA remains unknown. In this study, we aimed to assess the predictive value of ANRGs in BRCA, construct a prognostic model based on ANRGs, and explore the tumor microenvironment in different prognostic score groups. This study utilized data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to collect clinical information and RNA sequencing data from patients with BRCA. Information on ANRGs was gathered from GeneCards and Harmonizome portals. A risk score model based on ANRGs was created using least absolute shrinkage and selection operator Cox (LASSO) regression analysis. Additionally, the study explored the tumor microenvironment and enriched pathways in different risk groups. Finally, a novel ANRG-based nomogram is developed. A total of 142 differentially expressed genes associated with survival were identified, of which 5 genes were selected to create the ANRG signature. The risk score based on this signature proved to be an independent prognostic factor. Further analysis revealed that different risk subgroups exhibited variations in the tumor microenvironment and drug sensitivities. Subsequently, a nomogram was developed using risk scores and clinicopathological factors. The decision curve analysis results suggest that patients with BRCA might derive clinical treatment benefits from utilizing this prognostic model. Based on the results of this study, the ANRG signature and nomograph established can be used for clinical decision-making in patients with BRCA.

Predicting changes in molluscan spatial distributions in mangrove forests in response to sea level rise.

Mollusks are an important component of the mangrove ecosystem, and the vertical distributions of molluscan species in this ecosystem are primarily dictated by tidal inundation. Thus, sea level rise (SLR) may have profound effects on mangrove mollusk communities. Here, we used dynamic empirical models, based on measurements of surface elevation change, sediment accretion, and molluscan zonation patterns, to predict changes in molluscan spatial distributions in response to different sea level rise rates in the mangrove forests of Zhenzhu Bay (Guangxi, China). The change in surface elevation was 4.76-9.61 mm year-1 during the study period (2016-2020), and the magnitude of surface-elevation change decreased exponentially as original surface elevation increased. Based on our model results, we predicted that mangrove mollusks might successfully adapt to a low rate of SLR (2.00-4.57 mm year-1) by 2100, with mollusks moving seaward and those in the lower intertidal zones expanding into newly available zones. However, as SLR rate increased (4.57-8.14 mm year-1), our models predicted that surface elevations would decrease beginning in the high intertidal zones and gradually spread to the low intertidal zones. Finally, at high rates of SLR (8.14-16.00 mm year-1), surface elevations were predicted to decrease across the elevation gradient, with mollusks moving landward and species in higher intertidal zones blocked by landward barriers. Tidal inundation and the consequent increases in interspecific competition and predation pressure were predicted to threaten the survival of many molluscan groups in higher intertidal zones, especially arboreal and infaunal mollusks at the landward edge of the mangroves, resulting in a substantial reduction in the abundance of original species on the landward edge. Thus, future efforts to conserve mangrove floral and faunal diversity should prioritize species restricted to landward mangrove areas and protect potential species habitats.

Zonation of mangrove flora and fauna in a subtropical estuarine wetland based on surface elevation.

In the context of sea-level rise (SLR), an understanding of the spatial distributions of mangrove flora and fauna is required for effective ecosystem management and conservation. These distributions are greatly affected by tidal inundation, and surface elevation is a reliable quantitative indicator of the effects of tidal inundation. Most recent studies have focused exclusively on the quantitative relationships between mangrove-plant zonation and surface elevation, neglecting mangrove fauna. Here, we measured surface elevation along six transects through the mangrove forests of a subtropical estuarine wetland in Zhenzhu Bay (Guangxi, China), using a real-time kinematic global positioning system. We identified the mangrove plants along each transect and investigated the spatial distributions of arboreal, epifaunal, and infaunal molluscs, as well as infaunal crabs, using traditional quadrats. Our results indicated that almost all mangrove forests in the bay were distributed within the 400-750 m intertidal zone, between the local mean sea level and mean high water (119 cm above mean sea level). Mangrove plants exhibited obvious zonation patterns, and different species tended to inhabit different niches along the elevation gradient: Aegiceras corniculatum dominated in seaward locations while Lumnitzera racemosa dominated in landward areas. Mangrove molluscs also showed distinct patterns of spatial zonation related to surface elevation, independent of life-form and season. The spatial distributions of some molluscs were correlated to the relative abundances of certain mangrove plants. In contrast, the spatial distributions of crabs were not related to surface elevation. To the best of our knowledge, this is the first study to explicitly quantify the influences of surface elevation on the spatial distributions of mangrove fauna. This characterization of the vertical ranges of various flora and fauna in mangrove forests provides a basic framework for future studies aimed at predicting changes in the structure and functions of mangrove forests in response to SLR.

Prevalence of Human Noroviruses in Commercial Food Establishment Bathrooms.

Although transmission of human norovirus in food establishments is commonly attributed to consumption of contaminated food, transmission via contaminated environmental surfaces, such as those in bathrooms, may also play a role. Our aim was to determine the prevalence of human norovirus on bathroom surfaces in commercial food establishments in New Jersey, Ohio, and South Carolina under nonoutbreak conditions and to determine characteristics associated with the presence of human norovirus. Food establishments (751) were randomly selected from nine counties in each state. Four surfaces (underside of toilet seat, flush handle of toilet, inner door handle of stall or outer door, and sink faucet handle) were swabbed in male and female bathrooms using premoistened macrofoam swabs. A checklist was used to collect information about the characteristics, materials, and mechanisms of objects in bathrooms. In total, 61 (1.5%) of 4,163 swabs tested were presumptively positive for human norovirus, 9 of which were confirmed by sequencing. Some factors associated with the presence of human norovirus included being from South Carolina (odd ratio [OR], 2.4; 95% confidence interval [CI], 1.2 to 4.9; P < 0.05) or New Jersey (OR, 1.7; 95% CI, 0.9 to 3.3; 0.05 < P < 0.10), being a chain establishment (OR, 1.9; 95% CI, 1.1 to 3.3; P < 0.05), being a unisex bathroom (versus male: OR, 2.0; 95% CI, 0.9 to 4.1; 0.05 < P < 0.10; versus female: OR, 2.6; 95% CI, 1.2 to 5.7; P < 0.05), having a touchless outer door handle (OR, 3.3; 95% CI, 0.79 to 13.63; 0.05 < P < 0.10), and having an automatic flush toilet (OR, 2.5, 95% CI, 1.1 to 5.3; 0.05 < P < 0.10). Our findings confirm that the presence of human norovirus on bathroom surfaces in commercial food establishments under nonoutbreak conditions is a rare event. Therefore, routine environmental monitoring for human norovirus contamination during nonoutbreak periods is not an efficient method of monitoring norovirus infection risk.

Presence of human noroviruses on bathroom surfaces: a review of the literature.

Enteric viruses are the most common cause of acute gastroenteritis worldwide with most cases of illness attributed to caliciviruses, such as human noroviruses (HuNoV). While environmental transmission of HuNoV is reported to be low, environmental surfaces could be a source of secondary transmission. As many vomiting/fecal episodes occur in bathrooms, bathroom surfaces could be an important vehicle for transmitting HuNoV. We systematically reviewed the literature to determine the presence of HuNoV on bathroom surfaces. Our review included 22 eligible studies conducted in commercial and institutional settings. Under outbreak conditions, 11 studies reported detection rates of 20-100 %. Six studies implicated bathroom surfaces as primary sources of HuNoV infection while three reported HuNoV present on bathroom surfaces but indicated different primary sources. Under non-outbreak conditions, five studies reported detection rates of 2-17 %. Factors associated with HuNoV presence in bathrooms included population density, setting type, employee numbers, food handler knowledge, awareness, and behaviours, and cleaning/disinfecting procedures. Our review suggests bathrooms could be vehicles that transmit HuNoV under both outbreak and non-outbreak conditions.