BACKGROUND: Leukemias driven by activated, chimeric FGFR1 kinases typically progress to AML which have poor prognosis. Mouse models of this syndrome allow detailed analysis of cellular and molecular changes occurring during leukemogenesis. We have used these models to determine the effects of leukemia development on the immune cell composition in the leukemia microenvironment during leukemia development and progression.
METHODS: Single cell RNA sequencing (scRNA-Seq) was used to characterize leukemia associated neutrophils and define gene expression changes in these cells during leukemia progression.
RESULTS: scRNA-Seq revealed six distinct subgroups of neutrophils based on their specific differential gene expression. In response to leukemia development, there is a dramatic increase in only two of the neutrophil subgroups. These two subgroups show specific gene expression signatures consistent with neutrophil precursors which give rise to immature polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Analysis of gene expression in these precursor cells identified pathways that were specifically upregulated, the most pronounced of which involved matrix metalloproteinases Mmp8 and Mmp9, during leukemia progression. Pharmacological inhibition of MMPs using Ilomastat preferentially restricted in vitro migration of neutrophils from leukemic mice and led to a significantly improved survival in vivo, accompanied by impaired PMN-MDSC recruitment. As a result, levels of T-cells were proportionally increased. In clinically annotated TCGA databases, MMP8 was shown to act as an independent indicator for poor prognosis and correlated with higher neutrophil infiltration and poor pan-cancer prognosis.
CONCLUSIONS: We have defined specific leukemia responsive neutrophil subgroups based on their unique gene expression profile, which appear to be the precursors of neutrophils specifically associated with leukemia progression. An important event during development of these neutrophils is upregulation MMP genes which facilitated mobilization of these precursors from the BM in response to cancer progression, suggesting a possible therapeutic approach to suppress the development of immune tolerance.

BACKGROUND: Indoor tanning is a preventable risk factor for skin cancer. Statewide shutdowns during the COVID-19 pandemic resulted in temporary closures of tanning businesses. Little is known about how tanners reacted to losing access to tanning businesses.
OBJECTIVE: This study aimed to analyze Twitter (subsequently rebranded as X) chatter about indoor tanning during the statewide pandemic shutdowns.
METHODS: We collected tweets from March 15 to April 30, 2020, and performed a directed content analysis of a random sample of 20% (1165/5811) of tweets from each week. The 2 coders independently rated themes (κ=0.67-1.0; 94%-100% agreement).
RESULTS: About half (589/1165, 50.6%) of tweets were by people unlikely to indoor tan, and most of these mocked tanners or the act of tanning (562/589, 94.9%). A total of 34% (402/1165) of tweets were posted by users likely to indoor tan, and most of these (260/402, 64.7%) mentioned missing tanning beds, often citing appearance- or mood-related reasons or withdrawal. Some tweets by tanners expressed a desire to purchase or use home tanning beds (90/402, 22%), while only 3.9% (16/402) mentioned tanning alternatives (eg, self-tanner). Very few tweets (29/1165, 2.5%) were public health messages about the dangers of indoor tanning.
CONCLUSIONS: Findings revealed that during statewide shutdowns, half of the tweets about indoor tanning were mocking tanning bed users and the tanned look, while about one-third were indoor tanners reacting to their inability to access tanning beds. Future work is needed to understand emerging trends in tanning post pandemic.

Traditional aquaculture systems appear challenged by the high levels of total ammoniacal nitrogen (TAN) produced, which can harm aquatic life. As demand for global fish production continues to increase, farmers should adopt recirculating aquaculture systems (RAS) equipped with biofilters to improve the water quality of the culture. The biofilter plays a crucial role in ammonia removal. Therefore, a biofilter such as a moving bed biofilm reactor (MBBR) biofilter is usually used in the RAS to reduce ammonia. However, the disadvantage of biofilter operation is that it requires an automatic system with a water quality monitoring and control system to ensure optimal performance. Therefore, this study focuses on developing an Internet of Things (IoT) system to monitor and control water quality to achieve optimal biofilm performance in laboratory-scale MBBR. From 35 days into the experiment, water quality was maintained by an aerator\'s on/off control to provide oxygen levels suitable for the aquatic environment while monitoring the pH, temperature, and total dissolved solids (TDS). When the amount of dissolved oxygen (DO) in the MBBR was optimal, the highest TAN removal efficiency was 50%, with the biofilm thickness reaching 119.88 μm. The forthcoming applications of the IoT water quality monitoring and control system in MBBR enable farmers to set up a system in RAS that can perform real-time measurements, alerts, and adjustments of critical water quality parameters such as TAN levels.

The autoimmune regulator (AIRE) is a transcriptional regulator expressed in the thymus and is necessary for maintaining immunological self-tolerance. Extrathymic AIRE expression is rare, and a role for AIRE in tumor-associated innate immune cells has not yet been established. In this study, we show that AIRE is expressed in human pro-tumor neutrophils. In breast cancer, AIRE was primarily located to tumor-associated neutrophils (TANs), and to a lesser extent to tumor-associated macrophages (TAMs) and tumor cells. Expression of AIRE in TAN/TAMs, but not in cancer cells, was associated with an adverse prognosis. We show that the functional role for AIRE in neutrophils and macrophages is to regulate expression of immune mediators and the extrinsic apoptotic pathway involving the Fas/TNFR death receptors and cathepsin G. Here, we propose that the role for AIRE in TAN/TAMs in breast tumors is to regulate cell death and inflammation, thus promoting tumor progression.

The effective hydrogen production in single-chamber microbial electrolysis cells (MECs) has been seriously challenged by various hydrogen consumers resulting in substantial hydrogen loss. In previous studies, the total ammonia nitrogen (TAN) has been used to inhibit certain hydrogen-consuming microorganisms to enhance hydrogen production in fermentation. In this study, we explored the feasibility of using source-separated urine to overcome hydrogen loss in the MEC, with the primary component responsible being TAN generated via urea hydrolysis. Experimental results revealed that the optimal TAN concentration ranged from 1.17 g N/L to 1.75 g N/L. Within this range, the hydrogen production rate substantially improved from less than 100 L/(m3·d) up to 520 L/(m3·d), and cathode recovery efficiency and energy recovery efficiency were greatly enhanced, with the hydrogen percentage achieved over 95 % of the total gas volume, while maintaining uninterrupted electroactivity in the anode. Compared to using chemically added TAN, using source separated urine as the source of ammonia also showed the effect of overcoming hydrogen loss but with lower Coulombic efficiency due to the complex organic components. Pre-adaptation of the reactor with urea enhanced hydrogen production by nearly 60 %. This study demonstrated the effectiveness of TAN and urine in suppressing hydrogen loss, and the results are highly relevant to MECs treating real wastewater with high TAN concentrations, particularly human fecal and urine wastewater.

Here, retrotransposon-like 1 (RTL1) is introduced as a marker for circulating and tissue neutrophils, tissue macrophages, and tumor-associated macrophages (TAM) and neutrophils (TAN). Anti-RTL1 polyclonal and monoclonal antibodies were produced, and their reactivity was examined by Western blotting (WB), ELISA, and immunostaining of human normal and cancer tissues. The reactivity of the anti-RTL1 antibodies with peripheral blood leukocytes and a panel of hematopoietic cell lines was examined. The generated antibodies specifically detected RTL1 in the WB of the placenta and U937 cells. The polyclonal antibody showed excellent reactivity with tissue-resident macrophages, Hofbauer cells, alveolar and splenic macrophages, Kupffer cells, and inflammatory cells in the tonsil, appendix, and gallbladder. In vitro GM-CSF-differentiated macrophages also showed a high level of intracellular RTL1 expression. TAM and TAN also showed excellent reactivity with this antibody. Almost all circulating granulocytes but not lymphocytes or monocytes expressed RTL1 at their surface. Serial sections of the appendix stained with CD15 and RTL1 and placenta stained with CD68 and RTL1 showed a considerable overlap in RTL1 expression in CD15+ granulocytes and CD68+ macrophages. A small percentage of myelomonocytic cell lines was positive for surface RTL1, while promyelocytic, monocytic, megaloblastic, and lymphoblastic cell lines were negative. Endothelial cells of normal and cancer tissues highly expressed RTL1. RTL1 could be considered a new marker for different normal tissue macrophages, TAM, circulating and tissue neutrophils, and TAN.

Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent human malignancies, leading to poor prognosis due to its high recurrence and metastasis rates. In recent years it has become increasingly evident that the tumor microenvironment (TME) plays an important role in tumor progression and metastasis. Tumor microenvironment (TME) refers to the complex tissue environment of tumor occurrence and development. Here, we summarize the development of HCC and the role of cellular and non-cellular components of the TME in the metastasis HCC, with particular reference to tumor-infiltrating immune cells. We also discuss some of the possible therapeutic targets for the TME and the future prospectives of this evolving field. SIGNIFICANCE: This review provides a comprehensive analysis of the role of the infiltrating immune cells in TME in the metastasis of HCC and highlights the future outlook for targeted therapy of the TME in the context of recent experiments revealing a number of therapeutic targets targeting the TME.

The notion that neutrophils only perform a specific set of single functions in the body has changed with the advancement of research methods. As the most abundant myeloid cells in human blood, neutrophils are currently emerging as important regulators of cancer. Given the duality of neutrophils, neutrophil-based tumor therapy has been clinically carried out in recent years and has made some progress. But due to the complexity of the tumor microenvironment, the therapeutic effect is still not satisfactory. Therefore, in this review, we discuss the direct interaction of neutrophils with the five most common cancer cells and other immune cells in the tumor microenvironment. Also, this review covered current limitations, potential future possibilities, and therapeutic approaches targeting neutrophil function in cancer therapy.

How complex morphological patterns form is an intriguing question in developmental biology. However, the mechanisms that generate complex patterns remain largely unknown. Here, we sought to identify the genetic mechanisms that regulate the tan (t) gene in a multi-spotted pigmentation pattern on the abdomen and wings of Drosophila guttifera. Previously, we showed that yellow (y) gene expression completely prefigures the abdominal and wing pigment patterns of this species. In the current study, we demonstrate that the t gene is co-expressed with the y gene in nearly identical patterns, both transcripts foreshadowing the adult abdominal and wing melanin spot patterns. We identified cis-regulatory modules (CRMs) of t, one of which drives reporter expression in six longitudinal rows of spots on the developing pupal abdomen, while the second CRM activates the reporter gene in a spotted wing pattern. Comparing the abdominal spot CRMs of y and t, we found a similar composition of putative transcription factor binding sites that are thought to regulate the complex expression patterns of both terminal pigmentation genes y and t. In contrast, the y and t wing spots appear to be regulated by distinct upstream factors. Our results suggest that the D. guttifera abdominal and wing melanin spot patterns have been established through the co-regulation of y and t, shedding light on how complex morphological traits may be regulated through the parallel coordination of downstream target genes.

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