Hotspots of nitrogen losses from anthropogenic sources in the Huang-Huai-Hai Basin, China.

Poor management of nitrogen (N) can lead to serious environmental problems, such as air and water pollution. The accurate identification of priority control areas and emission sources is critical for making effective decisions regarding sustainable N management. This study aimed to identify hotspots for N losses and quantitatively analyze the relative contributions of different emission sources in the Huang-Huai-Hai Basin at the county scale.

Syntaphilin Regulates Neutrophil Migration in Cancer.

Pathologically activated neutrophils (PMN) with immunosuppressive activity, which are termed myeloid-derived suppressor cells (PMN-MDSC), play a critical role in regulating tumor progression. These cells have been implicated in promoting tumor metastases by contributing to premetastatic niche formation. This effect was facilitated by enhanced spontaneous migration of PMN from bone marrow to the premetastatic niches during the early-stage of cancer development.

Ferroptosis of tumour neutrophils causes immune suppression in cancer.

Ferroptosis is a non-apoptotic form of regulated cell death that is triggered by the discoordination of regulatory redox mechanisms culminating in massive peroxidation of polyunsaturated phospholipids. Ferroptosis inducers have shown considerable effectiveness in killing tumour cells in vitro, yet there has been no obvious success in experimental animal models, with the notable exception of immunodeficient mice. This suggests that the effect of ferroptosis on immune cells remains poorly understood.

A Novel Selective Inhibitor JBI-589 Targets PAD4-Mediated Neutrophil Migration to Suppress Tumor Progression.

Unlabelled: Neutrophils are closely involved in the regulation of tumor progression and formation of premetastatic niches. However, the mechanisms of their involvement and therapeutic regulation of these processes remain elusive. Here, we report a critical role of neutrophil peptidylarginine deiminase 4 (PAD4) in neutrophil migration in cancer.

Mechanisms regulating transitory suppressive activity of neutrophils in newborns: PMNs-MDSCs in newborns.

Transitory appearance of immune suppressive polymorphonuclear neutrophils (PMNs) defined as myeloid-derived suppressor cells (PMNs-MDSCs) in newborns is important for their protection from inflammation associated with newly established gut microbiota. Here, we report that inhibition of the type I IFN (IFN1) pathway played a major role in regulation of PMNs-MDSCs-suppressive activity during first weeks of life. Expression of the IFN1 receptor IFNAR1 was markedly lower in PMNs-MDSCs.

Immune suppressive activity of myeloid-derived suppressor cells in cancer requires inactivation of the type I interferon pathway.

Myeloid-derived suppressor cells (MDSC) are pathologically activated neutrophils and monocytes with potent immune suppressive activity. These cells play an important role in accelerating tumor progression and undermining the efficacy of anti-cancer therapies. The natural mechanisms limiting MDSC activity are not well understood.

Lactoferrin-induced myeloid-derived suppressor cell therapy attenuates pathologic inflammatory conditions in newborn mice.

Inflammation plays a critical role in the development of severe neonatal morbidities. Myeloid-derived suppressor cells (MDSCs) were recently implicated in the regulation of immune responses in newborns. Here, we report that the presence of MDSCs and their functional activity in infants are closely associated with the maturity of newborns and the presence of lactoferrin (LF) in serum.

Identification of monocyte-like precursors of granulocytes in cancer as a mechanism for accumulation of PMN-MDSCs.

We have identified a precursor that differentiates into granulocytes in vitro and in vivo yet belongs to the monocytic lineage. We have termed these cells monocyte-like precursors of granulocytes (MLPGs). Under steady state conditions, MLPGs were absent in the spleen and barely detectable in the bone marrow (BM).

Unique pattern of neutrophil migration and function during tumor progression.

Although neutrophils have been linked to the formation of the pre-metastatic niche, the mechanism of their migration to distant, uninvolved tissues has remained elusive. We report that bone marrow neutrophils from mice with early-stage cancer exhibited much more spontaneous migration than that of control neutrophils from tumor-free mice. These cells lacked immunosuppressive activity but had elevated rates of oxidative phosphorylation and glycolysis, and increased production of ATP, relative to that of control neutrophils.

Transitory presence of myeloid-derived suppressor cells in neonates is critical for control of inflammation.

Myeloid-derived suppressor cells (MDSCs) are pathologically activated and relatively immature myeloid cells that have been implicated in the immunological regulation of many pathologic conditions. Phenotypically and morphologically, MDSCs are similar to neutrophils (PMN-MDSCs) and monocytes (M-MDSCs). However, they have potent suppressive activity and distinct gene expression profiles and biochemical characteristics.

Apolipoprotein A-I mimetic peptide 4F suppresses tumor-associated macrophages and pancreatic cancer progression.

Pancreatic cancer is an aggressive malignancy that is unresponsive to conventional radiation and chemotherapy. Therefore, development of novel immune therapeutic strategies is urgently needed. L-4F, an Apolipoprotein A-I (ApoA-I) mimetic peptide, is engineered to mimic the anti-inflammatory and anti-oxidative functionalities of ApoA-I.

tRF/miR-1280 Suppresses Stem Cell-like Cells and Metastasis in Colorectal Cancer.

Several studies have shown that tRNAs can be enzymatically cleaved to generate distinct classes of tRNA-derived fragments (tRF). Here, we report that tRF/miR-1280, a 17-bp fragment derived from tRNA and pre-miRNA, influences Notch signaling pathways that support the function of cancer stem-like cells (CSC) in colorectal cancer progression. tRF/miR-1280 expression was decreased in human specimens of colorectal cancer.

CAR-T cell therapy in gastrointestinal tumors and hepatic carcinoma: From bench to bedside.

The chimeric antigen receptor (CAR) is a genetically engineered receptor that combines a scFv domain, which specifically recognizes the tumor-specific antigen, with T cell activation domains. CAR-T cell therapies have demonstrated tremendous efficacy against hematologic malignancies in many clinical trials. Recent studies have extended these efforts to the treatment of solid tumors.

Parthenolide ameliorates Concanavalin A-induced acute hepatitis in mice and modulates the macrophages to an anti-inflammatory state.

Parthenolide, the principal sesquiterpene lactone present in medicinal plants such as feverfew, has anti-microbial, anti-inflammatory and anticancer activities. In the present study, we investigated the protective role of parthenolide against acute hepatitis in mice. Mice acute hepatitis were induced by Concanavalin A and treated by parthenolide in vivo.

Embelin inhibits pancreatic cancer progression by directly inducing cancer cell apoptosis and indirectly restricting IL-6 associated inflammatory and immune suppressive cells.

Pancreatic cancer is an aggressive malignancy and unresponsive to conventional chemotherapies. Here, the anti-inflammatory and anti-tumor effects of embelin on pancreatic cancer were investigated. Embelin significantly attenuated cells invasion, proliferation and induced apoptosis through inhibition of STAT3 and activation of p53 signaling pathways.

Thermosensitive injectable hydrogel enhances the antitumor effect of embelin in mouse hepatocellular carcinoma.

Embelin, an active ingredient of traditional herbal medicine, is used to treat many diseases such as cancer. However, embelin is hydrophobic and insoluble in water, which makes it unsuitable for in vivo applications. In this study, we constructed an embelin-loaded thermosensitive injectable hydrogel system that we named Embelin/PECT(gel) based on the amphiphilic triblock copolymer of poly (ε-caprolactone-co-1,4,8-trioxa[4.