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Targeting ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal overload of lipid peroxides, in cancer therapy is impeded by our limited understanding of the intersection of tumour's metabolic feature and ferroptosis vulnerability. In the present study, arginine is identified as a ferroptotic promoter using a metabolites library. This effect is mainly achieved through arginine's conversion to polyamines, which exerts their potent ferroptosis-promoting property in an H2O2-dependent manner. Notably, the expression of ornithine decarboxylase 1 (ODC1), the critical enzyme catalysing polyamine synthesis, is significantly activated by the ferroptosis signal——iron overload——through WNT/MYC signalling, as well as the subsequent elevated polyamine synthesis, thus forming a ferroptosis-iron overload-WNT/MYC-ODC1-polyamine-H2O2 positive feedback loop that amplifies ferroptosis. Meanwhile, we notice that ferroptotic cells release enhanced polyamine-containing extracellular vesicles into the microenvironment, thereby further sensitizing neighbouring cells to ferroptosis and accelerating the "spread" of ferroptosis in the tumour region. Besides, polyamine supplementation also sensitizes cancer cells or xenograft tumours to radiotherapy or chemotherapy through inducing ferroptosis. Considering that cancer cells are often characterized by elevated intracellular polyamine pools, our results indicate that polyamine metabolism exposes a targetable vulnerability to ferroptosis and represents an exciting opportunity for therapeutic strategies for cancer. Ferroptosis plays an important role in response to radiotherapy and chemotherapy, however, the sensitivity of cancer cell to ferroptosis varies. Here, the authors show that ODC1-mediated polyamine synthesis induces ferroptosis and demonstrate the potential of targeting this axis by combining polyamine supplements with radiotherapy or chemotherapy in preclinical lung cancer models. [ABSTRACT FROM AUTHOR]

Purpose: The tumor immune microenvironment (TME) plays a vital role in tumorigenesis, progression, and treatment. Macrophages, as an important component of the tumor microenvironment, play an essential role in antitumor immunity and TME remodeling. In this study, we aimed to explore the different functions of different origins macrophages in TME and their value as potential predictive markers of prognosis and treatment. Methods: We performed single-cell analysis using 21 lung adenocarcinoma (LUAD), 12 normal, and four peripheral blood samples from our data and public databases. A prognostic prediction model was then constructed using 502 TCGA patients and explored the potential factors affecting prognosis. The model was validated using data from 4 different GEO datasets with 544 patients after integration. Results: According to the source of macrophages, we classified macrophages into alveolar macrophages (AMs) and interstitial macrophages (IMs). AMs mainly infiltrated in normal lung tissue and expressed proliferative, antigen-presenting, scavenger receptors genes, while IMs occupied the majority in TME and expressed anti-inflammatory, lipid metabolism-related genes. Trajectory analysis revealed that AMs rely on self-renew, whereas IMs originated from monocytes in the blood. Cell-to-cell communication showed that AMs interacted mainly with T cells through the MHC I/II signaling pathway, while IMs mostly interacted with tumor-associated fibrocytes and tumor cells. We then constructed a risk model based on macrophage infiltration and showed an excellent predictive power. We further revealed the possible reasons for its potential prognosis prediction by differential genes, immune cell infiltration, and mutational differences. Conclusion: In conclusion, we investigated the composition, expression differences, and phenotypic changes of macrophages from different origins in lung adenocarcinoma. In addition, we developed a prognostic prediction model based on different macrophage subtype infiltration, which can be used as a valid prognostic biomarker. New insights were provided into the role of macrophages in the prognosis and potential treatment of LUAD patients. [ABSTRACT FROM AUTHOR]

This paper considers a single-product production-inventory system managed by a base-stock policy where the factory inventory manager with cost concerns over a short time horizon can be modeled with the constant absolute risk aversion (CARA) utility function. We consider both backordering cost and stockout cost scenarios and investigate the roles of capacity utilization level and CARA coefficient on the optimal base-stock level. We derive closed-form solutions for the optimal inventory decisions, present related numerical experiments, and discuss their managerial implications. It is discovered that both scenarios share certain common structure in their optimal inventory decisions. Specifically, in the backordering cost scenario, if the backordering cost is high or the holding cost is low, the optimal base-stock level is high. In the stockout cost scenario, if the stockout cost is high or the holding cost is low, the optimal base-stock level is high. For both scenarios, inventory levels are high with tight capacity, and optimal base-stock level generally increases if the manager becomes more risk averse. [ABSTRACT FROM AUTHOR]

Forkhead box O3 is a protein encoded by the FOXO3 gene expressed throughout the body. FOXO3 could play a crucial role in longevity and many other pathologies, such as Alzheimer's disease, glioblastoma, and stroke. This study is a comprehensive review of the expression of FOXO3 under ischemia and reperfusion (IR) and the molecular mechanisms of its regulation and function. We found that the expression level of FOXO3 under ischemia and IR is tissue-specific. Specifically, the expression level of FOXO3 is increased in the lung and intestinal epithelial cells after IR. However, FOXO3 is downregulated in the kidney after IR and in the skeletal muscles following ischemia. Interestingly, both increased and decreased FOXO3 expression have been reported in the brain, liver, and heart following IR. Nevertheless, these contribute to stimulating ischemia and reperfusion injury via the induction of inflammatory response, apoptosis, autophagy, mitophagy, pyroptosis, and oxidative damage. These results suggest that FOXO3 could play protective effects in some organs and detrimental effects in others against IR injury. Most importantly, these findings indicate that controlling FOXO3 expression, genetically or pharmacologically, could contribute to preventing or treating ischemia and reperfusion damage. [ABSTRACT FROM AUTHOR]

Purpose: Our research investigated predictors of postoperative blood transfusion rate following total joint arthroplasty (TJA) in patients with rheumatoid arthritis (RA) and evaluated the incidence of complications in the transfusion group and non-transfusion group. Methods: The authors retrospectively analyzed risk factors among 320 RA patients who underwent elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) from January 2010 to December 2018. Demographic characteristics, laboratory results, medication history, and surgical protocol were gathered from electronic medical records. Univariable and multivariable logistic regression analyses were conducted to measure the impact of relevant variables on the need for transfusions. In addition, we compared the incidence of complications associated with transfusion. Results: The cohort comprised 320 RA patients, aged 57.4 ± 12.0 years, of whom 137 required postoperative blood transfusions and 183 did not. BMI, type of surgery, duration of surgery, disease activity score 28 (DAS28-CRP), tranexamic acid (TXA) administration, and preoperative hemoglobin (Hb) were all risk factors for transfusion after adjusting for the planned procedure. Conclusion: Previously published predictors, such as BMI, low preoperative hemoglobin, duration of surgery, procedure type (THA), were also identified in our analysis. Moreover, TXA administration and the DAS28-CRP showed the potential to influence risk. The incidence of postoperative complications was increased in patients who received blood transfusions compared to non-transfusion group. Our findings could help to identify RA patient population requiring blood transfusions, to ensure the necessary steps are adopted to limit blood loss and improve blood management strategies. Key Points • The risk factors for blood transfusion in rheumatoid arthritis patients undergoing total joint arthroplasty were BMI, the type of surgery, duration of surgery, TXA administration, DAS28-CRP, and preoperative hemoglobin. • The incidence of postoperative complications was increased in patients who received blood transfusions compared to non-transfusion group. [ABSTRACT FROM AUTHOR]

Purpose: Macrophages (MΦs) play a dual role in the promotion and suppression of lung adenocarcinoma (LUAD), the function of which is influenced by the metabolic status. The role of protein tyrosine phosphatase receptor type F (PTPRF) in cancer has not been elucidated, and its role in MΦs remains to be seen. Methods: The Seahorse XFe 96 Cell Flow Analyzer detected glucose metabolism in tumor cells and macrophages. The expressions of FSCN1, M-CSF, IL4, PTPRF and IGF1 in macrophages were detected by Western blotting and qRT-PCR. Binding of FSCN1 and IGF1R was detected by co-immunoprecipitation. The tumor status in animals was observed using the IVIS Lumina III imaging system. Results: We found that Fascin Actin-Bundling Protein 1 (FSCN1) activates the PI3K-AKT and JAK-STAT signaling pathways in LUAD cells via binding to IGF-1R, thereby promoting the secretion of cytokines such as IL4 and M-CSF. IL4 and M-CSF promote the expression of PTPRF in MΦs, leading to M2 polarization of MΦs by increasing glucose intake and lactate production. In return, M2-type MΦs act on LUAD cells by secreting cytokines such as IGF-1, CCL2, and IL10, which ultimately promote tumor progression. In vivo experiments proved that the knockdown of FSCN1 in A549 cells and PTPRF in MΦs greatly reduced LUAD proliferative and metastatic capacity, which was consistent with the in vitro findings. Conclusions: This study investigated the reprogramming effects of FSCN1 and PTPRF on inflammatory cytokines in the LUAD microenvironment, revealing potential mechanisms by which FSCN1 and PTPRF promote tumor progression and providing a new experimental basis for LUAD treatment. [ABSTRACT FROM AUTHOR]

Metformin has been found to have inhibitory effects on a variety of tumors. However, its effects on non-small cell lung cancer (NSCLC) remain unclear. We demonstrated that metformin could inhibit the proliferation of A549 and H1299 cells. RNA transcriptome sequencing revealed that PDL1 was significantly downregulated in both cell types following treatment with metformin (P < 0.001). Jaspar analysis and chromatin immunoprecipitation showed that CEBPB could directly bind the promoter region of PDL1. Western blotting showed that protein expression of the isoforms CEBPB-LAP*, CEBPB-LAP, and CEBPB-LIP was significantly upregulated and the LIP/LAP ratio was increased. Gene chip analysis showed that PDL1 was significantly upregulated in A549-CEBPB-LAP cells and significantly downregulated in A549-CEBPB-LIP cells (P < 0.05) compared with CEBPB-NC cells. Dual-luciferase reporter gene assay showed that CEBPB-LAP overexpression could promote transcription of PDL1 and CEBPB-LIP overexpression could inhibit the process. Functional assays showed that the changes in CEBPB isoforms affected the function of NSCLC cells. Western blotting showed that metformin could regulate the function of NSCLC cells via AMPK–CEBPB–PDL1 signaling. Animal experiments showed that tumor growth was significantly inhibited by metformin, and atezolizumab and metformin had a synergistic effect on tumor growth. A total of 1247 patients were retrospectively analyzed, including 166 and 1081 patients in metformin and control groups, respectively. The positive rate of PDL1 was lower than that of the control group (HR = 0.338, 95% CI = 0.235–0.487; P < 0.001). In conclusion, metformin inhibited the proliferation of NSCLC cells and played an anti-tumor role in an AMPK–CEBPB–PDL1 signaling-dependent manner. [ABSTRACT FROM AUTHOR]

In this paper, we investigate all coset leaders of primitive BCH codes for δ in the range 1 ≤ δ ≤ q m + 7 2 , which extends Liu and Shi's results. Besides, we also generalize Shi's results by proposing the maximum designed distance of non-narrow-sense( b = k 2 q 2 + k 1 q + k 0 ) primitive BCH codes which can contain their Euclidean dual. At the end, we calculate the dimension of the Euclidean dual containing non-narrow-sense primitive BCH codes and construct some quantum BCH codes. [ABSTRACT FROM AUTHOR]

Eco-friendly and low-cost composite, amidoxime-functionalized microcrystalline cellulose/mesoporous silica (MCC/MS-AO), were synthesized by co-condensation method. The obtained materials were characterized by scanning electron microscope (SEM), energy dispersive spectrometer (EDS), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and N2 adsorption–desorption analysis. Batch experiments were carried out to study the adsorption capacity of U(VI) on MCC/MS-AO. The results show that the material has good adsorption capabilities for U(VI) including high capacity, good selectivity, and reusability. The adsorption process conforms to pseudo-second-order kinetic model and Langmuir model, and it is spontaneous and endothermic. Finally, the possible adsorption mechanism was further studied by X-ray photoelectron spectroscopy (XPS) techniques. [ABSTRACT FROM AUTHOR]

Two series of novel NLRP3 inflammasome inhibitors are designed, synthesized, and evaluated in an effort to develop diversified analogs based on the N-(phenylcarbamoyl)benzenesulfonamide scaffold. SAR studies reveal that the sulfonylurea linker can tolerate chemical modifications with either simply changing over the position of carbonyl and sulfonyl group or structurally flexibly inserting a cyclopropyl group, leading to identification of several more potent and diversified NLRP3 antagonists (e.g., 9) with low nanomolar inhibitory activities. Further studies indicate that these two series of compounds with low cytotoxicity exhibited weak effects on the generation of NO and TNF-a. The findings may serve as good starting points for the development of more potent NLRP3 inflammasome inhibitors as valuable pharmacological probes or potential drug candidates. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) plays an essential role in the occurrence and progression of malignancy. The potential prognostic TME-related biomarkers of lung adenocarcinoma (LUAD) remained unclear, which were investigated in this research. The RNA-sequencing profiles and corresponding clinical parameters were extracted from TCGA and GEO databases, based on which the stromal and immune scores were calculated through the ESTIMATE algorithm. Overlapping differentially expressed genes between stromal and immune score group were analyzed by the LASSO and Random Forrest algorithms and validated in cases from our center. And a prognostic 8-gene signature was constructed using Cox regression. The infiltration of 22 hematopoietic cell phenotypes was assessed by the CIBERSORT algorithms. We found that female, elder patients, and solid predominant subtype had obviously higher stromal and immune scores. And patients with early stage LUAD received a prominently higher immune score. A high stromal or immune score meant a good prognosis. Subsequently, eight TME-related prognostic genes (ATAD5, CYP4F3, CYP4F12, ESPNL, FXYD2, GPX2, NLGN4Y, and SERPINC1) were identified by both LASSO regression and Radom Forest algorithms. High 8-gene signature group exhibited worse overall survival. Furthermore, B cell naïve, plasma cells, T cell follicular helper, and macrophages M1 were prominently more in high signature group. Nevertheless, fewer T cells CD4 memory resting, monocytes, and dendritic cell resting were identified in the high signature group. The composition of the tumor microenvironment significantly affected the prognosis of LUAD patients. We provided a new strategy for the exploration of prognostic TME-related biomarkers and immunotherapy. [ABSTRACT FROM AUTHOR]

The amidoxime-functionalized biopolymer/graphene oxide gels were prepared and their performance in the application of the adsorption separation of uranium (VI) in aqueous solution has been studied. The prepared gels were characterized by using scanning electron microscopy, energy dispersive spectroscopy, Fourier transformed infrared spectra, and X-ray diffraction to determine the microscopic morphology, chemical composition and crystal structure. The adsorption performance of the gels including the effects of solution pH and contact time on the adsorption capacity has been evaluated by a batch adsorption technology. The adsorption isotherms and kinetics were measured, and the experimental data were analyzed and shown to be agreed with the Langmuir isotherm and the pseudo-second-order kinetic model. The results demonstrated that the adsorption process was the rate-limiting step in the separation process. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) has a high worldwide incidence with a tendency to metastasize to the lungs. We aimed to identify clinical factors related to lung metastasis (LM) and analyze the prognosis of patients after LM. Methods: Multivariate logistic regression analysis was used to identify risk factors for LM from CRC. Univariate and multivariate Cox proportional hazard models were performed to identify potentially important prognostic factors for patients with LM. Results: Age (p = 0.010), tumor size (p < 0.001), T stage (p < 0.001), N stage (p < 0.001), race (p < 0.001), tumor site (p < 0.001), liver metastasis (p < 0.001), brain metastasis (p < 0.001), bone metastasis (p < 0.001), serum levels of carcinoembryonic antigen (CEA) (p < 0.001), and circumferential resection margin (CRM) (p < 0.001) were associated with a risk of LM from CRC. All factors (all, p < 0.001) except tumor size (p = 0.095) and race (p = 0.650) were related to the overall survival of patients. Two nomograms were formulated to visually predict lung metastasis risk and 1-, 3-, and 5- year overall survivals for patients with LM. The concordance indices were 0.754 and 0.749, respectively. Conclusions: Age, tumor size, histological grade, serum levels of CEA, tumor site, surgery modalities of CRC, CRM, number of positive lymph nodes, and chemotherapy were independent risk factors for LM from CRC. The nomograms we developed can be effectively used to forecast the risk of LM and predict the survival for LM from CRC. [ABSTRACT FROM AUTHOR]

Objectives: Esophageal perforation is associated with multiple serious complications and high mortality. Herein, we identify some predictors for postoperative outcomes, compare the outcomes of various surgical approaches, and summarize our experience with esophageal perforation over the past 13 years. Methods: We retrospectively analyzed 38 patients diagnosed with esophageal perforation caused by foreign body between November 2004 and May 2018. Univariate analysis and multivariate logistic regression analysis were performed to identify potential risk factors related to prognosis. Effects of different surgery were compared based on postoperative outcomes. Results: Of the 38 patients, the number of females was equal to males with a mean age of 55.6 ± 14.9 (range 23–93) years; 22 had thoracic perforations and 16 had cervical perforations. The overall mortality rate was 5.3%. Univariate analysis revealed that sex (p = 0.049), type of foreign body (p = 0.042), abscess (p = 0.049), and site of perforation (p = 0.031) were associated with prognosis. The interval between perforation and surgery did not significantly influence prognosis (p = 0.929). No significant difference was found in postoperative outcomes among various surgeries. Conclusions: The interval between perforation and treatment was not as important as previously reported. Surgical management should be performed early when feasible, even if the interval between perforation and surgery is 24 h or longer. [ABSTRACT FROM AUTHOR]

Human influenza viruses preferentially bind to sialic acid-α2,6-galactose (SAα2,6Gal) receptors, which are predominant in human upper respiratory epithelia, whereas avian influenza viruses preferentially bind to SAα2,3Gal receptors. However, variants with amino acid substitutions around the receptor-binding sites of the hemagglutinin (HA) protein can be selected after several passages of human influenza viruses from patients’ respiratory samples in the allantoic cavities of embryonated chicken eggs. In this study, we detected an egg-adapted HA S190R mutation in the pandemic H1N1 virus 2009 (pdmH1N1), and evaluated the effects of this mutation on receptor binding affinity and pathogenicity in mice. Our results revealed that residue 190 is located within the pocket structure of the receptor binding site. The single mutation to arginine at position 190 slightly increased the binding affinity of the virus to the avian receptor and decreased its binding to the long human α2,6-linked sialic acid receptor. Our study demonstrated that the S190R mutation resulted in earlier death and higher weight loss in mice compared with the wild-type virus. Higher viral titers at 1 dpi (days post infection) and diffuse damage at 4 dpi were observed in the lung tissues of mice infected with the mutant virus. [ABSTRACT FROM AUTHOR]

Birds are frequently vocal. Monitoring their songs and calls has provided much useful information about their ecology and behavior. Recording bird songs and locations can be resource intensive, frequently requiring two or more observers, causing considerable disturbance and possible only for short times. Passive arrays of acoustic sensors offer the possibility of greatly increasing our ability to monitor bird activity. The desirability of such arrays is obvious: they are less intrusive, can monitor continuously over long periods, permit collaboration which enables better localization, provide fault tolerance, and facilitate sharing to optimize scarce resources. That the interest has been increasing so much lately is in large part, because we are now at the point, where the promise of such arrays is realizable with current or reasonably anticipated technologies. Controlling collaborative arrays can be difficult. Engineered solutions are sometimes available, but they are often brittle and appropriate only for ideal environments. We would like our systems to be: robust, in that they can handle changing environments or agents and are untroubled by occasionally wrong or noisy messages; adaptive in that they can learn to deal with unanticipated source or events, form new concepts, and communicate in languages that are specialized for particular agents; and finally, they should be self-configuring, to deal with changing situations and goals. After reviewing research employing sensor arrays by others to monitor bird behavior, we will describe research in our laboratory. Our focus will be on the construction of such systems, especially how such arrays can extract information from the environment and communicate to arrive at a collective understanding of their region and events occurring there. [ABSTRACT FROM AUTHOR]

Codebooks are widely applied in code-division multiple-access systems. Recently, several authors constructed codebooks meeting or nearly meeting the Welch bound (i.e. nearly optimal codebooks) using difference set, almost difference set, relative difference set, and so on. In this paper, we will give two families of nearly optimal codebooks. First, we give a class of new almost difference sets and use them to construct nearly optimal codebooks. Second, we present a general construction of codebooks from partial difference sets and obtain several classes of nearly optimal codebooks. [ABSTRACT FROM AUTHOR]

As an early type of lung adenocarcinoma, ground glass nodule (GGN) has been detected increasingly and now accounts for most lung cancer outpatients. GGN has a satisfactory prognosis and its characteristics are quite different from solid adenocarcinoma (SADC). We compared the GGN adenocarcinoma (GGN-ADC) with SADC using the single-cell RNA sequencing (scRNA-seq) to fully understand GGNs. The tumor samples of five patients with lung GGN-ADCs and five with SADCs underwent surgery were digested to a single-cell suspension and analyzed using 10× Genomic scRNA-seq techniques. We obtained 60,459 cells and then classified them as eight cell types, including cancer cells, endothelial cells, fibroblasts, T cells, B cells, Nature killer cells, mast cells, and myeloid cells. We provided a comprehensive description of the cancer cells and stromal cells. We found that the signaling pathways related to cell proliferation were downregulated in GGN-ADC cancer cells, and stromal cells had different effects in GGN-ADC and SADC based on the analyses of scRNA-seq results. In GGN-ADC, the signaling pathways of angiogenesis were downregulated, fibroblasts expressed low levels of some collagens, and immune cells were more activated. Furthermore, we used flow cytometry to isolate the cancer cells and T cells in 12 GGN-ADC samples and in an equal number of SADC samples, including CD4+ T and CD8+ T cells, and validated the expression of key molecules by quantitative real-time polymerase chain reaction analyses. Through comprehensive analyses of cell phenotypes in GGNs, we provide deep insights into lung carcinogenesis that will be beneficial in lung cancer prevention and therapy. [ABSTRACT FROM AUTHOR]

Background: The computed tomography (CT) characteristic of ground glass opacity (GGO) were shown to be associated with clinical significance in lung adenocarcinoma. We evaluated the prognostic value of the solid component ratio of GGO IA invasive lung adenocarcinoma., Methods: We retrospectively analyzed the records of GGO IA patients who received surgical resection from April 2012 to December 2015. The solid component ratio was calculated based on thin-slice CT scans. Baseline features were compared stratified by the ratio. Cox proportional hazard models and survival analyses were adopted to explore potential prognostic value regarding overall survival (OS) and disease-free survival (DFS)., Results: Four hundred fifteen patients were included. The higher ratio was significantly associated with larger tumor diameter, pathological subtypes and choice of surgical type. There was a significantly worse DFS with a > 50% ratio. The subgroups of 0% and ≤ 50% ratio showed close survival curves of DFS. Similar trends were observed in OS. Multivariate analyses revealed that the ratio was a significant predictor for DFS, but not for OS. No significant prognostic difference was observed between lobectomy and limited resections., Conclusion: A higher solid component ratio may help to predict a significantly worse prognosis of GGO IA lung adenocarcinoma.