A Subpopulation of Luminal Progenitors Secretes Pleiotrophin to Promote Angiogenesis and Metastasis in Inflammatory Breast Cancer.

Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer characterized by rapidly arising diffuse erythema and edema. Genomic studies have not identified consistent alterations and mechanisms that differentiate IBC from non-IBC tumors, suggesting that the microenvironment could be a potential driver of IBC phenotypes. Here, using single-cell RNA sequencing, multiplex staining, and serum analysis in patients with IBC, we identified enrichment of a subgroup of luminal progenitor (LP) cells containing high expression of the neurotropic cytokine pleiotrophin (PTN) in IBC tumors. PTN secreted by the LP cells promoted angiogenesis by directly interacting with the NRP1 receptor on endothelial tip cells located in both IBC tumors and the affected skin. NRP1 activation in tip cells led to recruitment of immature perivascular cells in the affected skin of IBC, which are correlated with increased angiogenesis and IBC metastasis. Together, these findings reveal a role for cross-talk between LPs, endothelial tip cells, and immature perivascular cells via PTN-NRP1 axis in the pathogenesis of IBC, which could lead to improved strategies for treating IBC. SIGNIFICANCE: Nonmalignant luminal progenitor cells expressing pleiotrophin promote angiogenesis by activating NRP1 and induce a prometastatic tumor microenvironment in inflammatory breast cancer, providing potential therapeutic targets for this aggressive breast cancer subtype.

YTHDF1 shapes "cold" tumor and inhibits CD8+ T cells infiltration and function in breast cancer.

While YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) was recognized as a crucial contributor in the development and immune-related regulation of various types of tumors, its function in the immune response of breast cancer has largely remained uninvestigated. Through analysis of public databases, we found YTHDF1 as a highly expressed gene in breast cancers and confirmed this finding in breast cancer cells and clinical specimens from our center. Subsequently, we examined the link between YTHDF1 expression and immune cells and molecules by utilizing immune-related public databases and algorithm. We further validated our findings through cellular and animal experiments, as well as RNA sequencing. YTHDF1 was found highly expressed in tumor tissues of breast cancer, which negatively correlated with patient survival. The downregulation of YTHDF1 promoted the expression of pro-inflammatory markers and improved the anti-cancer ability of immune cells in breast cancer. RNA sequencing analysis revealed that YTHDF1 knockdown resulted in enrichment of differential genes in signal transduction pathways. Additionally, in vitro experiments showed that immune cells had higher cytotoxicity against breast cancer cells with decreased YTHDF1 expression. Moreover, in vivo studies indicated that YTHDF1 promoted breast cancer growth while inhibiting CD8+ T cell infiltration and function. Our study demonstrates that YTHDF1 plays a crucial role in establishing a "cold" tumor microenvironment in breast cancer by inhibiting the release of pro-inflammatory cytokines from cancer cells. As a result, the infiltration and functional differentiation of anti-tumor CD8+ T cells are hindered, ultimately resulting in the immune evasion of breast cancer.

Insights into the coexistence of birds and humans in cropland through meta-analyses of bird exclosure studies, crop loss mitigation experiments, and social surveys.

Birds share lands with humans at a substantial scale and affect crops. Yet, at a global scale, systematic evaluations of human-bird coexistence in croplands are scarce. Here, we compiled and used meta-analysis approaches to synthesize multiple global datasets of ecological and social dimensions to understand this complex coexistence system. Our result shows that birds usually increase woody, but not herbaceous, crop production, implying that crop loss mitigation efforts are critical for a better coexistence. We reveal that many nonlethal technical measures are more effective in reducing crop loss, e.g., using scaring devices and changing sow practices, than other available methods. Besides, we find that stakeholders from low-income countries are more likely to perceive the crop losses caused by birds and are less positive toward birds than those from high-income ones. Based on our evidence, we identified potential regional clusters, particularly in tropical areas, for implementing win-win coexistence strategies. Overall, we provide an evidence-based knowledge flow and solutions for stakeholders to integrate the conservation and management of birds in croplands.

Crystal Structure and Magnetic Properties of HfFe6Ge6-Type ErMn6-xCoxGe6 (x = 0-1.45) Alloys.

Ternary intermetallic compounds RMn6Ge6 with complex magnetic phase transitions are expected to be developed and applied in spintronic storage and computing devices in the future. The relationship between the crystal structure and physical properties (electrical conductivity, thermal analysis, and complex magnetic transformation) of ErMn6-xCoxGe6 (x = 0-1.45) alloys was studied in the range of 80-600 K. The result shows that the polycrystalline alloys crystallize in the hexagonal HfFe6Ge6 type (P6/mmm). Co doping causes orbital hybridization between Co 2p, Mn 2p, and Er 4d and leads to the presence of mixed valence states of Mn3+ and Mn4+, leading to complex magnetic behaviors: the alloys display a Néel point at a high temperature TN (∼500 K), magnetization increases again at TC (∼250 K), and a second peak in the temperature dependence of magnetization at about Tt (∼150 K), which is spin reorientation. We discuss these phenomena in terms of Mn-Mn, Er-Mn, and Mn3+/Mn4+ and the prospect for potential applications of the studied alloy in magneto memory and new topological kagome magnet fields.

Pollution, ecological risk, and source identification of potentially toxic elements in sediments of a landscape urban lagoon, China.

Given the great importance of Yundang lagoon (China), a detailed evaluation and source identification of multiple potentially toxic elements (PTEs) is required. Low concentrations of the PTEs were found in the Diversion canal, while high in the Main canal, Inner lagoon, and Outer lagoon. Evaluation results indicated that the pollution of PTEs was widespread, and that the extremely high eco-risks and evident toxicity were owing to the great contributions of Hg and Cd. Positive matrix factorization model demonstrated that the PTEs were from both natural and different types of anthropogenic sources. TOC played a critical role in the PTEs. It was also found that the limited environmental carrying capacity and the poor hydrological condition of the lagoon may still accumulate the pollution in a progressive fashion. These findings provide a detailed information on making effective strategies of new directions for long-term prevention of PTEs pollution in the landscape urban lagoon.

Targeting tumor-associated macrophages in the tumor microenvironment.

Tumor-associated macrophages (TAMs) are the most abundant population type of tumor-infiltrating immune cells found in the tumor microenvironment (TME), and are evolutionarily associated with microvessel density in tumor tissues. TAMs can be broadly divided into M1-like and M2-like TAMs, which demonstrate antitumor and pro-tumor activity in the TME, respectively. Studies have indicated that: i) The predominate presence of M2-like TAMs in the TME can result in tumor immunosuppression and chemoresistance; ii) the ratio of M1-like to M2-like TAMs in the TME is positively correlated with better long-term prognosis of patients with cancer; iii) epigenetic silencing, preventing the secretion of M1-like TAM-associated molecules, is an important immune evasion mechanism during tumor progression; and iv) the transformation from M2-like to M1-like TAMs following exposure to specific conditions can result in tumor regression. The present study discusses the molecular events underlying the recruitment of macrophages and their polarization into M1-like or M2-like TAMs, and their differential roles in angiogenesis, angiostasis, invasion, metastasis and immune activity in the TME. This insight may inform the improved design of TAM-targeted cancer immunotherapy. Some of these therapeutic strategies show promising effects; however, challenges remain.

Riverine microplastic pollution matters: A case study in the Zhangjiang River of Southeastern China.

Microplastics have pulled the alarm for its far-reaching impacts in the environment and potential risks to human health. Here, we first investigated the microplastic pollution in the Zhangjiang River of southeastern China. Water samples were collected across a river catchment using bulk sampling method. The abundance, distribution, and characteristics of microplastics were analyzed using stereomicroscopy and micro-Raman spectroscopy. The results indicated that microplastic abundance ranged from 50 to 725 items m-3 with an average of 246 items m-3. PP and PE were the major polymers and accounted for ~75%. The dominant shape, color, and size of microplastics are fragment, white, and 0.5-1 mm, respectively. The findings established the baseline information on the microplastic pollution in the Zhangjiang River, which may improve the knowledge of sources of microplastic debris to the local watershed and future evaluation on the role of river catchments in transporting microplastics to the estuary and beyond into the ocean.

Anti-Oxidant and Anti-Endothelial Dysfunctional Properties of Nano-Selenium in vitro and in vivo of Hyperhomocysteinemic Rats.

PURPOSE: Elevation of blood homocysteine (Hcy) level (hyperhomocysteinemia) is a risk factor for cardiovascular disorders and is closely associated with endothelial dysfunction. The present study aims to investigate the protective effect and underlying mechanism of nanoscale selenium (Nano-Se) in Hcy-mediated vascular endothelial cell dysfunction in vitro and in vivo. MATERIALS AND METHODS: By incubating vascular endothelial cells with exogenous Hcy and generating hyperhomocysteinemic rat model, the effects of Nano-Se on hyperhomocysteinemia-mediated endothelial dysfunction and its essential mechanisms were investigated. RESULTS: Nano-Se inhibited Hcy-induced mitochondrial oxidative damage and apoptosis by preventing the downregulation of glutathione peroxidase enzyme 1 and 4 (GPX1, GPX4) in the vascular endothelial cells, thus effectively prevented the vascular damage in vitro and in vivo in the hyperhomocysteinemic rats. Nano-Se possessed similar protective effects but lower toxicity against Hcy in vascular endothelial cells when compared with other forms of Se. CONCLUSION: The application of Nano-Se could serve as a novel promising strategy against Hcy-mediated vascular dysfunction with reduced risk of Se toxicity.

Microplastic abundance, distribution and composition in the mid-west Pacific Ocean.

Microplastic pollution is widespread across most ocean basins around the world. Microplastics (MPs) are small plastic particles that have a significant impact on the marine environment. Various research on plastic pollution have been conducted in several regions. However, currently, there is limited data on the distribution and concentration of MPs in the mid-west Pacific Ocean. Therefore, this study we investigated the abundance, distribution, characteristics, and compositions of MPs in this region. Sea surface water samples collected from 18 stations showed a microplastic concentration range of 6028-95,335 pieces/km2 and a mean concentration of 34,039 ± 25,101 pieces/km2. Highest microplastic concentrations were observed in the seamount region of western Pacific. We observed a significant positive correlation between microplastic abundance and latitude across the study region. It was observed that microplastic concentrations decreased with increasing offshore distance at sites located on a 154° W transect. Fibres/filaments were the dominant microparticles observed in this study (57.4%), followed by fragments (18.3%). The dominant particle size range was 1-2.5 mm (35.1%), followed by 0.5-1 mm (28.5%), and the dominant particle colour was white (33.8%), followed by transparent (31.0%) and green (24.6%). The most common polymer identified by µ-Raman was polypropylene (39.1%), followed by polymethyl methacrylate (16.2%), polyethylene (14.1%) and polyethylene terephthalate (14.2%). The possible sources and pathways of microplastics in the study area were proposed based on the morphological and compositional characteristics of particles, their spatial distribution patterns, and shipboard current profiling (ADCP). Our study contributes to the further understanding of MPs in remote ocean areas.

A bibliometric analysis of long non-coding RNA and chemotherapeutic resistance research.

The global outputs of annual publication in long non-coding RNAs (lncRNAs) and chemotherapeutic resistance research exponentially increased from 2 in 2008 to 176 in 2017. Using Java application CiteSpace V and VOSviewer, this study assessed the publication model of lncRNAs and chemoresistance by bibliometric analysis. Totally, 2883 authors contributed 528 publications of lncRNAs and chemoresistance in 215 academic journals in the recent decade (2008-2018). Oncotarget in the 215 academic journals published the highest number of publications (60). China had the highest number of publication outputs (358). The leading institute was Nanjing Medical University. Wang Y was the most influential author (13 counts). Gupta RA had the most cited documents (87 counts). "Gene expression" and "poor prognosis" were identified as the hotspots. "Cancer stem cell", "HOTAIR" and "UCA1" were the frontiers of the fields in recent years. The increase of publications on lncRNAs and chemotherapeutic resistance will continue in the next years. HOTAIR and UCA1 with multiple roles in drug resistance may offer big opportunities for targeted chemoresistance in cancer therapy. These results may help us discover and explain the possible underlying laws of the subject.

Association between lipoproteins and telomere length in US adults: data from the NHANES 1999-2002.

BACKGROUND: Evidence regarding the correlation between lipoproteins and telomere length in US adults is limited. We aimed to investigate whether lipoproteins was associated with telomere length using US National Health and Nutrition Examination Survey (NHANES) database. METHODS: A total of 6468 selected participants were identified in the NHANES Data Base (1999-2002). The independent and dependent variables were lipoproteins and telomere length, respectively. The covariates included demographic data, dietary data, physical examination data, and comorbidities. RESULTS: In fully-adjusted model, we found that 0.1 differences of telomere length were positively associated with HDL-C [0.19 (95% CI 0.07, 0.31)], while the associations between LDL-C [0.19 (95% CI -0.27, 0.65)], TG [- 1.00 (95% CI -2.09, 0.07) and telomere length were not detected. By nonlinearity test, only the relationship between HDL-C and telomere length was nonlinear. The inflection point we got was 1.25. On the left side of the inflection point (telomere length ≤ 1.25), a difference in 0.1 of telomere length was associated with 0.50 difference in HDL-C. CONCLUSION: After adjusting for demographic data, dietary data, physical examination data, and comorbidities, telomere length is not associated with LDL-C and TG, but is positively associated with HDL-C when telomere length is less than 1.25.

Targeting the autophagy in bone marrow stromal cells overcomes resistance to vorinostat in chronic lymphocytic leukemia.

BACKGROUND: The bone marrow microenvironment constitutes a sanctuary for leukemia cells. Recent evidence indicates that environment-mediated drug resistance arises from a reciprocal influence between tumor cells and the surrounding stroma. The present study aimed to investigate the effect of chronic lymphocytic leukemia (CLL) cells on the metabolism of bone marrow stroma, to determine the role of this metabolic change in the stroma in vorinostat resistance of CLL cells, and thus to assess a novel strategy to target stroma and achieve the maximum therapeutic effect of vorinostat. METHODS: To evaluate this issue, we used freshly isolated CLL cells from peripheral blood samples of patients with CLL, and co-cultured them with bone marrow stromal cell lines to examine autophagy activity and metabolic changes in both CLL cells and stromal cells after vorinostat treatment. RESULTS: The results demonstrated that CLL cells were under intrinsic oxidative stress which was further enhanced by vorinostat treatment, and released H2O2 outside the cells. The adjacent stromal cells took up H2O2 and drove autophagy, mitophagy and glycolysis, resulting in the local production of high-energy mitochondrial fuels, which were then taken up by CLL cells to be effectively utilized through mitochondrial oxidative phosphorylation to enable more ATP production. Notably, targeting autophagic stromal cells with autophagy inhibitor remarkably decreased stromal protection against vorinostat treatment in CLL cells. CONCLUSION: This study demonstrated that the stroma in the CLL microenvironment is abnormal and undergoes autophagy, and manipulation of autophagic stromal cells could serve as a novel promising strategy to circumvent stroma-mediated drug resistance in CLL cells.

Graphene oxide-sensitized molecularly imprinted opto-polymers for charge-transfer fluorescent sensing of cyanoguanidine.

The hierarchical structuring of materials offers exciting opportunities to construct functional sensors. Multiple processes were combined to create complex materials for the selective detection of cyanoguanidine (CYA) using graphene oxide-sensitized molecularly imprinted opto-polymers (MIOP). Molecular imprinting was used to construct molecular-scale analyte-selective cavities, graphene oxide was introduced to provide a platform for the polymerization, and increase the stability and binding kinetic properties, and 3-methacryloxy propyl trimethoxy silane-modified quantum dots were combined with a functional monomer to increase the fluorescence quantum yield. Polymer cross-linking and fluorescence intensity were optimized for molecular recognition and opto-sensing detection. Selective and sensitive, fluorescence sensing of CYA was possible at concentrations as low as to 1.6µM. It could be applied to the rapid and cost-effective monitoring of CYA in infant formula. The approach is generic and applicable to many molecules and conventional opto-sensors, based on molecularly imprinted polymer formulations, individually or in multiplexed arrays.

Development and applications of molecularly imprinted polymers based on hydrophobic CdSe/ZnS quantum dots for optosensing of N(ε)-carboxymethyllysine in foods.

A novel molecularly imprinted polymer (MIP) based on hydrophobic CdSe/ZnS quantum dots (HBQDs) was synthesized via an approach that combines MIPs for the selectivity and sensitivity with semiconductor HBQDs as optosensing material (HBQDs@MIP). Here, using a one-pot water-in-oil reverse microemulsion polymerization, the HBQDs@MIP was used as a molecular recognition element to construct an N(ε)-carboxymethyllysine (CML) optosensor. The HBQDs were coated with silica to endow the nanoparticles with high dispersibility and broad compatibility with hydrophilic analytes. Under optima conditions, the relative fluorescence intensity of the HBQDs@MIP decreased linearly with increasing CML concentration in the range 5-400µgL(-1). The proposed method enables, detection procedures to be completed within 90min, with good recoveries, ranging from 85% to 106%. It can be applied to the rapid and cost-effective monitoring of CML in food samples.

A novel quantum dots-labeled on the surface of molecularly imprinted polymer for turn-off optosensing of dicyandiamide in dairy products.

A novel optosensing system based on quantum dots (QDs)-labeled on the surface of a molecularly imprinted polymer (MIP) was developed for turn-off fluorescence sensing of dicyandiamide (DCD). The QDs were modified with silica to covalently adhere to the MIP surface, which resulted in a higher fluorescence quantum yield than MIP-coated QDs. Under optimal conditions, there was a linear relationship, with a correlation coefficient of 0.9950, between the fluorescence intensity and the DCD concentration over the range 5-1600 µmolL(-1). The detection limit of this system was 2.7 µmolL(-1). The proposed method exhibited with good recoveries ranging from 95% to 106%. Most importantly, the optosensing approach can be successfully applied for the determination of DCD in dairy products. With excellent sensitivity and selectivity, such simple and cheap materials are potentially suitable for monitoring of DCD in other food, in agriculture and for environmental applications.