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Background: Gastroesophageal reflux disease (GERD) is a common condition characterized by the reflux of stomach contents into the esophagus. Despite its widespread prevalence worldwide, the causal link between GERD and various cancer risks has not been fully established, and past medical research has often underestimated or overlooked this relationship. Methods: This study performed Mendelian randomization (MR) to investigate the causal relationship between GERD and 19 different cancers. We leveraged data from 129,080 GERD patients and 473,524 controls, along with cancer-related data, obtained from the UK Biobank and various Genome-Wide Association Studies (GWAS) consortia. Single nucleotide polymorphisms (SNPs) associated with GERD were used as instrumental variables, utilizing methods such as inverse variance weighting, weighted median, and MR-Egger to address potential pleiotropy and confounding factors. Results: GERD was significantly associated with higher risks of nine types of cancer. Even after adjusting for all known risk factors—including smoking, alcohol consumption, major depression, and body mass index (BMI)—these associations remained significant, with higher risks for most cancers. For example, the adjusted risk for overall lung cancer was (OR, 1.23; 95% CI: 1.14–1.33), for lung adenocarcinoma was (OR, 1.18; 95% CI: 1.03–1.36), for lung squamous cell carcinoma was (OR, 1.35; 95% CI: 1.19–1.53), and for oral cavity and pharyngeal cancer was (OR, 1.73; 95% CI: 1.22–2.44). Especially noteworthy, the risk for esophageal cancer increased to (OR, 2.57; 95% CI: 1.23–5.37). Mediation analyses further highlighted GERD as a significant mediator in the relationships between BMI, smoking, major depression, and cancer risks. Conclusions: This study identifies a significant causal relationship between GERD and increased cancer risk, highlighting its role in cancer development and underscoring the necessity of incorporating GERD management into cancer prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysregulation is recognized as a significant hallmark of cancer progression. Although numerous studies have linked specific metabolic pathways to cancer incidence, the causal relationship between blood metabolites and lung cancer risk remains unclear. Methods: Genomic data from 29,266 lung cancer patients and 56,450 control individuals from the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium (TRICL-ILCCO) were utilized, and findings were replicated using additional data from the FinnGen consortium. The analysis focused on the associations between 486 blood metabolites and the susceptibility to overall lung cancer and its three major clinical subtypes. Various Mendelian randomization methods, including inverse-variance weighting, weighted median estimation, and MR-Egger regression, were employed to ensure the robustness of our findings. Results: A total of 19 blood metabolites were identified with significant associations with lung cancer risk. Specifically, oleate (OR per SD = 2.56, 95% CI: 1.51 to 4.36), 1-arachidonoylglyceropholine (OR = 1.79, 95% CI: 1.22 to 2.65), and arachidonate (OR = 1.67, 95% CI: 1.16 to 2.40) were associated with a higher risk of lung cancer. Conversely, 1-linoleoylglycerophosphoethanolamine (OR = 0.57, 95% CI: 0.40 to 0.82), ADpSGEGDFXAEGGGVR, a fibrinogen cleavage peptide (OR = 0.60, 95% CI: 0.47 to 0.77), and isovalerylcarnitine (OR = 0.62, 95% CI: 0.49 to 0.78) were associated with a lower risk of lung cancer. Notably, isoleucine (OR = 9.64, 95% CI: 2.55 to 36.38) was associated with a significantly higher risk of lung squamous cell cancer, while acetyl phosphate (OR = 0.11, 95% CI: 0.01 to 0.89) was associated with a significantly lower risk of small cell lung cancer. Conclusion: This study reveals the complex relationships between specific blood metabolites and lung cancer risk, highlighting their potential as biomarkers for lung cancer prevention, screening, and treatment. The findings not only deepen our understanding of the metabolic mechanisms of lung cancer but also provide new insights for future treatment strategies. [ABSTRACT FROM AUTHOR]

Selective removal of 99TcO₄− from radioactive wastewater is a challenging but significant task, which benefits spent fuel reprocessing and radioactive-waste leakage treatment. This work introduces the performance of adsorption ReO4− using a series of novel anion exchange resins, namely MAPE-1, MAPE-2, MAPE-3, and MAGD-1, impregnated with functionalized ionic liquids as active sites. They exhibit a high selectivity towards TcO₄−/ReO₄−, in a wide pH range of pH 5–11 for ReO₄−/TcO₄− adsorption. Among these resins, MAPE-1 has the best adsorption performance for ReO4−, with a maximum adsorption capacity of 202.4 mg/g and a high distribution ratio Kd of 6.2 × 10⁶ mL/g at pH 7. The adsorption mechanism involves anion exchange between functionalized ionic liquids and TcO₄−/ReO₄−, which is supported by X-ray energy dispersive spectroscopy (EDS) and Fourier Transform Infrared spectroscopy (FT-IR) analyses. In addition, X-ray photoelectron spectroscopy (XPS) further illustrates the interaction between the resin and perrhenate. [ABSTRACT FROM AUTHOR]

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]

We study the U.S. Coin Supply Chain from both the demand and supply side perspectives to improve coin circulation in the economy. More specifically, we provide an operating policy for Depository Institutions (DIs) to improve their efficiency in packaging, distributing, coordinating, and managing the inventory of coins. We further propose a new policy (via a Rewards Program) to increase coin circulation in the economy and optimally determine a reward price, which, if implemented by the Federal Reserve System (FRS), can incentivize DIs to process the coins themselves and/or frequently deposit excess coins at the FRS. We identify the structures of DIs' best response to the reward price and FRS's optimal pricing policy. The results and insights developed in this study can be beneficial to both the FRS and DIs in increasing the efficiency of the nation's coin circulation and thereby reducing their operating costs. Additionally, to estimate the societal benefit from the Rewards Program, we formulate the coin flow for an entire FRS region as an optimization problem from the supply side perspective and quantify the societal costs (and benefits) with and without the reward. We show via numerical experiments that both the FRS and Dis reduce their operating costs as a result of the program and produce a surplus benefit for the society. The reward price that maximizes this surplus is determined optimally. We also propose a robust optimization framework to help DIs and the FRS to manage their inventory under uncertain demand while attaining their cost reduction goals. [ABSTRACT FROM AUTHOR]

Objective: Medial opening‐wedge high tibial osteotomy (MOWHTO) is considered to be an effective treatment for symptomatic knee osteoarthritis (KOA) of isolated the medial compartment with varus alignment of the lower extremity. However, the choice of material to fill the void remains controversial. This study aims to evaluate the bone union of the osteotomy gap using a novel wedge‐shaped cancellous allograft after MOWHTO and its effect on clinical outcomes. Methods: All patients who underwent MOWHTO using a novel wedge‐shaped cancellous allograft combined with TomoFix locking compression plate (LCP) fixation between January 2016 and July 2020 were enrolled. The radiographic parameters including hip‐knee‐ankle angle (HKAA), medial proximal tibial angle (MPTA), femorotibial angle (FTA) and posterior tibial slope angle (PTSA) were measured between pre‐operative and post‐operative radiographs. Knee Society score (KSS) and range of motion (ROM) were assessed preoperatively and at last follow‐up. Patients included in this study were divided into two groups according to the correction angle: small correction group (< 10°; SC group) and large correction group (≥ 10°; LC group). The modified Radiographic Union score for tibial fractures (mRUST) was used to assess the difference in bone healing between the two groups at 1, 3, 6, and 12 months postoperatively and at the final follow‐up. A paired student's t test was conducted for comparison of differences of the relevant data pre‐operatively and post‐operatively. Results: A total of 82 patients (88 knees) were included in this study. The HKAA, MPTA, FTA and PTSA increased from −6.4° ± 3.0°, 85.1° ± 2.6°, 180.1° ± 3.2° and 7.7° ± 4.4° preoperatively to 1.2° ± 4.3° (p < 0.001), 94.4° ± 3.3° (p < 0.001), 171.0° ± 2.8° and 11.8° ± 5.8° (p < 0.001) immediately postoperatively, respectively. However, no significant statistic difference was found in above‐mentioned parameters at last follow‐up compared to immediate postoperative data (p > 0.05). All patients in this study achieved good bone healing at the final follow‐up and no significant differences in mRUST scores were seen between the SC group and LC group. The KSS‐Knee score and KSS‐Function score improved significantly from 55.4 ± 3.7 and 63.3 ± 4.6 preoperatively to 86.4 ± 2.8 (p < 0.001) and 89.6 ± 2.9 (p < 0.001) at last follow‐up, respectively. Nevertheless, there was no significant difference in ROM between pre‐operation and last follow‐up (p > 0.05). Conclusion: For MOWHTO, the wedge‐shaped cancellous allograft was a reliable choice for providing good bone healing and clinical outcomes. [ABSTRACT FROM AUTHOR]

The enzymatic approach is a highly effective and the major scientific method to eliminating bitter components in citrus-derived products nowadays. Microbial production of limonin invertase stands out due to its pivotal role in the removal of the bitter substance, limonin. The optimization of fermentation parameters and the study of scale-up fermentation are imperative for product commercialization. In this study, we focused on optimizing stirring speed, fermentation temperature, and initial pH to enhance the growth and limonin invertase production by the Aspergillus tabin strain UA13 in a 5-l stirred-tank bioreactor. Our results revealed the following optimal parameters are: a stirring speed of 300 rpm, a fermentation temperature of 35°C and a pH 5.0. Under these optimized conditions, the limonin invertase activity reached its peak at 63.38 U ml−1, representing a 1.67-fold increase compared to the unoptimized conditions (38.10 U ml−1), while also reducing the fermentation duration by 12 h. Furthermore, our research demonstrated that limonin invertase effectively hydrolyze limonin in grapefruit juice, reducing its content from 13.28 to 2.14 μg ml−1, as determined by HPLC, resulting in a 6.21-fold reduction of the bitter substance. [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]

Introduction: This study aimed to compare the Forgotten Joint Score-12(FJS) outcomes and the minimum clinically important difference (MCID) of the FJS after high tibial osteotomy (HTO), unicompartmental knee arthroplasty (UKA), and total knee arthroplasty (TKA) with short-term follow-up (at least 2 years). Another objective of the study is to investigate the factors influencing FJS. It is hypothesized that there are differences in FJS outcomes among the three procedures. Methods: Patients who underwent HTO, UKA, and TKA from January 2016 to December 2020 and were followed up for a minimum of 2 years were included in the study. The FJS were analyses from a cohort of people who submitted data to two years. The preoperative and postoperative clinical outcomes were compared and evaluated the patient-related factor. The FJS scores were predicted using multiple linear regression analysis. Additionally, Patient's Joint Perception (PJP) questions were used as anchors to determine the achievement of the forgotten joint, and FJS MCID were calculated using the receiver operating characteristic curve (ROC). Results: Three hundred eighty-nine patients were included in the final study, and there were 111 patients in HTO groups,128patients in UKA groups, and 150 patients in TKA groups. The mean follow-up was 47.0 months. There was a significant difference in the total FJS, between the HTO, UKA, and TKA groups (FJS:59.38 ± 7.25, 66.69 ± 7.44 and 56.90 ± 6.85, p < 0.001. We found the MCID of the FJS of HTO, UKA, and TKA were 63.54, 69.79, and 61.45, respectively. In multiple linear regression, younger age, and higher FS were significant predictors of better FJS. Conclusion: Medial UKA demonstrated lower patient awareness in comparison to HTO and TKA, as assessed by the FJS. Younger age and higher FS were identified as significant predictors of improved FJS, providing valuable guidance for surgical decision-making. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the efficacy and outcomes of different surgical procedures, namely unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO), for the treatment of bilateral medial compartment knee osteoarthritis in the same patient. The joint awareness and function of these two surgical methods were evaluated. Methods: A total of 15 patients with bilateral medial compartment knee osteoarthritis who underwent either UKA or HTO between 2012 and 2020 were included in the study. Patient data, including age, gender, body mass index and length of hospital stay, were collected. Pre- and post-operative measurements were conducted, including tibiofemoral angle, tibial plateau posterior inclination angle, proximal tibial medial angle, distance from mechanical axis to knee joint center, hip-knee-ankle angle, pre- and post-operative knee joint scores, knee joint range of motion, and FIS-12 scores at 3, 6, 12, and 24 months postoperatively. The latest follow-up was used for evaluating the outcomes of osteoarthritis treatment. Normality of continuous variables was assessed using the Shapiro–Wilk test. Between-group comparisons were performed using the paired sample t-test or Wilcoxon rank-sum test. Repeated measures analysis of variance was utilized to analyze FJS-12 measurements at different time points, and the correlation between FJS-12 and postoperative clinical results was examined using Pearson's correlation coefficient. Statistical significance was set at P < 0.05. Results: Significant differences were observed in FJS between the UKA and HTO groups at 3 and 6 months postoperatively, but no significant difference was found at 1 and 2 years postoperatively. FJS in the UKA group demonstrated a significant increase from 3 to 6 months postoperatively, but no significant difference was observed from 6 to 24 months postoperatively. In contrast, FJS in the HTO group showed a significant increase from 3 to 24 months postoperatively. Conclusions: Patients who underwent UKA exhibited superior joint awareness compared to those who underwent HTO during the early postoperative period. Furthermore, the rate of joint awareness in UKA patients was faster than in HTO patients. [ABSTRACT FROM AUTHOR]

Background and objective: At present, the influence of the internal metallic endoskeleton of Spacer on the biomechanical strength of Spacer remains unclear. The aim of this study was to analyze the mechanical stability of a novel Spacer applying a annular skeleton that mimics the structure of trabecular bone using finite element methods. Metheds: The femur models of three healthy individuals and skeletonless Spacer, K-Spacer, and AD-Spacer were assembled to create 15 3D models. Finite element analysis was performed in an Ansys Bench2022R1. Biomechanical parameters such as stress and strain of the Spacer, internal skeleton and femur were evaluated under three loads, which were applied with the maximum force borne by the hip joint (2100 N), standing on one leg (700 N), and standing on two legs (350 N). The mechanical properties of the new hip Spacer were evaluated. Result: The stresses on the medial and lateral surfaces of the AD-Spacer and K-Spacer were smaller than the stresses in the state without skeletal support. The maximum stresses on the medial and lateral surfaces of the AD-Spacer were smaller than those of the inserted K-Spacer, and the difference gradually increased with the increase of force intensity. When the skeleton diameter was increased from 3 to 4 mm, the stresses in the medial and lateral sides of the AD-Spacer and K-Spacer necks decreased. The stress of both skeletons was concentrated at the neck, but the stress of the annular skeleton was evenly distributed on the medial and lateral sides of the skeleton. The mean stress in the proximal femur was higher in femurs with K-Spacer than in femurs with AD-Spacer. Conclusions: AD-Spacer has lower stress and higher load-bearing capacity than K-Spacer, and the advantages of AD-Spacer are more obvious under the maximum load state of hip joint. [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]

Plant mitochondrial genomes (mitogenomes) exhibit fluid genome architectures, which could lead to the rapid erosion of genome synteny over a short evolutionary time scale. Among the species-rich orchid family, the leafy Cymbidium lancifolium and leafless Cymbidium macrorhizon are sister species with remarkable differences in morphology and nutritional physiology. Although our understanding of the evolution of mitochondria is incomplete, these sister taxa are ideal for examining this subject. In this study, the complete mitogenomes of C. lancifolium and C. macrorhizon, totaling 704,244 bp and 650,751 bp, respectively, were assembled. In the 2 mitogenomes, 38 protein-coding genes, 18 cis- and 6 trans-spliced introns, and approximately 611 Kb of homologous sequences are identical; overall, they have 99.4% genome-wide similarity. Slight variations in the mitogenomes of C. lancifolium and C. macrorhizon in repeat content (21.0 Kb and 21.6 Kb, respectively) and mitochondrial DNA of plastid origin (MIPT; 38.2 Kb and 37.5 Kb, respectively) were observed. The mitogenome architectures of C. lancifolium and C. macrorhizon are complex and comprise 23 and 22 mini-circular chromosomes, respectively. Pairwise comparisons indicate that the two mitogenomes are largely syntenic, and the disparity in chromosome numbers is likely due to repeat-mediated rearrangements among different chromosomes. Notably, approximately 93.2 Kb C. lancifolium mitochondrial sequences lack any homology in the C. macrorhizon mitogenome, indicating frequent DNA gains and losses, which accounts mainly for the size variation. Our findings provide unique insights into mitogenome evolution in leafy and leafless plants of sister species and shed light on mitogenome dynamics during the transition from mixotrophy to mycoheterotrophy. [ABSTRACT FROM AUTHOR]

Mitral regurgitation is a serious complication of post-myocardial infarction, with increasing mortality. Surgery as the primary treatment carries a high risk. MitraClip is a new therapeutic to treat post-myocardial infarction mitral regurgitation. In this case, a 62-year-old male patient suffered from severe heart failure symptoms after emergency coronary intervention and extracorporeal membrane oxygenation support. Based on cardiac echocardiography, severe mitral regurgitation was monitored in this patient. After MitraClip treatment, the patient's condition was gradually improved and discharged successfully. This case highlights that MitraClip is a safe and effective strategy for post-myocardial infarction mitral regurgitation. [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]

The Pt-chitosan-TiO2 charge transfer (CT) complex was synthesized via the sol-gel and impregnation method. The synthesized photocatalysts were thoroughly characterized, and their photocatalytic activity were evaluated toward H2 production through water reduction under visible-light irradiation. The effect of the preparation conditions of the photocatalysts (the degree of deacetylation of chitosan, addition amount of chitosan, and calcination temperature) on the photocatalytic activity was discussed. The optimal Pt-10%DD75-T200 showed a H2 generation rate of 280.4 μmol within 3 h. The remarkable visible-light photocatalytic activity of Pt-chitosan-TiO2 was due to the CT complex formation between chitosan and TiO2, which extended the visible-light absorption and induced the ligand-to-metal charge transfer (LMCT). The photocatalytic mechanism of Pt-chitosan-TiO2 was also investigated. This paper outlines a new and facile pathway for designing novel visible-light-driven photocatalysts that are based on TiO2 modified by polysaccharide biomass wastes that are widely found in nature. [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]

Background: Single‐cell transcriptomics has been used to investigate various tumors to elucidate the molecular distinction of all cell type compositions of a complex mix. Aims: This study aimed to investigate malignant‐cell‐specific genes to explore diagnostic and therapeutic biomarkers using single‐cell transcriptomic data of lung adenocarcinoma. Materials & Methods: 10X single‐cell RNA‐seq data of fourteen patients with lung adenocarcinoma were analyzed. Genes that expressed differentially and those with higher confidence to distinguish tumor cells from normal cells were picked out using the ROC curves. The LASSO regression method was used to select most markedly correlated genes to predict the malignancy of every single cell within a model. We also conducted further experiments to determine their roles in lung cancer in vitro. Results: Twenty two thousand four hundred and ninety one tumor and 181 666 normal single cells were analyzed where 369 genes were found to be specifically expressed in single malignant cells. Seventy of them, encoding secreted or membrane‐bound proteins, showed involvement in cell‐to‐cell communications in tumor biology. KRT18 and the other six genes were identified as predictors to distinguish single malignant cells and were integrated to construct an accurate (96.1%) predicting model. Notably, IRX2, SPINK13, and CAPN8 outperformed the other four genes. Further experiments confirmed the upregulation of them in lung adenocarcinoma at both tissue and cell levels. Proliferative capacities of lung adenocarcinoma cells were attenuated by knocking‐down of either of them. However, targeting CAPN8, IRX2, or SPINK13 hardly exerted a cytotoxic effect on these cells. Discussion: Apart from the current model, similar tools were still warranted using single‐cell RNA‐seq data of more types of tumors. The three genes identified as potential therapeutic targets in the present study still need to be validated in more in lung cancer. Conclusion: Our model can aid the analyses of single‐cell sequencing data. CAPN8, IRX2, and SPINK13 may serve as novel targets of targeted and immune‐based therapies in lung adenocarcinoma. [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]

The proliferation of IEEE 802.11 or WiFi networks, and the explosive growth in traffic demands call for solutions to maximize the capacity of WiFi networks. Hence, maximizing the spatial reuse of WiFi networks is critical as doing so allows multiple concurrent transmissions. In this respect, a critical network parameter, Clear Channel Assessment (CCA) threshold, plays a vital role as it dictates whether a node is allowed to transmit after sensing the channel. In this paper, we propose to use Deep Q-network (DQN) under two learning patterns to select the CCA threshold of devices. We further consider Transmit Power Control (TPC) in conjunction with CCA threshold selection to improve the capacity of a WiFi network. The simulation results show that our approach is capable of selecting the optimal CCA threshold for each device. As a result, the average throughput is 62.4% higher than that of a legacy Dynamic Sensitivity Control (DSC) algorithm. [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]

Objectives: Platinum-based chemotherapies are currently the first-line treatment of non-small cell lung cancer. This study will improve our understanding of the causes of resistance to cisplatin, especially in lung adenocarcinoma (LUAD) and provide a reference for therapeutic decisions in clinical practice.Methods: Cancer Cell Line Encyclopedia (CCLE), The Cancer Genome Atlas (TCGA) and Zhongshan hospital affiliated to Fudan University (zs-cohort) were used to identify the multi-omics differences related to platinum chemotherapy. Cisplatin-resistant mRNA and miRNA models were constructed by Logistic regression, classification and regression tree and C4.5 decision tree classification algorithm with previous feature selection performed via least absolute shrinkage and selection operator (LASSO). qRT-PCR and western-blotting of A549 and H358 cells, as well as single-cell Seq data of tumor samples were applied to verify the tendency of certain genes.Results: 661 cell lines were divided into three groups according to the IC50 value of cisplatin, and the top 1/3 (220) with a small IC50 value were defined as the sensitive group while the last 1/3 (220) were enrolled in the insensitive group. TP53 was the most common mutation in the insensitive group, in contrast to TTN in the sensitive group. 1348 mRNA, 80 miRNA, and 15 metabolites were differentially expressed between 2 groups (P < 0.05). According to the LASSO penalized logistic modeling, 6 of the 1348 mRNAs, FOXA2, BATF3, SIX1, HOXA1, ZBTB38, IRF5, were selected as the associated features with cisplatin resistance and for the contribution of predictive mRNA model (all of adjusted P-values < 0.001). Three of 6 (BATF3, IRF5, ZBTB38) genes were finally verified in cell level and patients in zs-cohort.Conclusions: Somatic mutations, mRNA expressions, miRNA expressions, metabolites and methylation were related to the resistance of cisplatin. The models we created could help in the prediction of the reaction and prognosis of patients given platinum-based chemotherapies. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is a serious stress disorder that occurs in individuals who have experienced major traumatic events. The underlying pathological mechanisms of PTSD are complex, and the related predisposing factors are still not fully understood. In this study, label-free quantitative proteomics and untargeted metabolomics were used to comprehensively characterize changes in a PTSD mice model. Differential expression analysis showed that 12 metabolites and 27 proteins were significantly differentially expressed between the two groups. Bioinformatics analysis revealed that the differentiated proteins were mostly enriched in: small molecule binding, transporter activity, extracellular region, extracellular space, endopeptidase activity, zymogen activation, hydrolase activity, proteolysis, peptidase activity, sodium channel regulator activity. The differentially expressed metabolites were mainly enriched in Pyrimidine metabolism, D-Glutamine and D-glutamate metabolism, Alanine, aspartate and glutamate metabolism, Arginine biosynthesis, Glutathione metabolism, Arginine, and proline metabolism. These results expand the existing understanding of the molecular basis of the pathogenesis and progression of PTSD, and also suggest a new direction for potential therapeutic targets of PTSD. Therefore, the combination of urine proteomics and metabolomics explores a new approach for the study of the underlying pathological mechanisms of PTSD. [ABSTRACT FROM AUTHOR]

At present, most of the studies on the influence of cloud on the retrieval accuracy of satellite relative humidity (RH) profiles are mainly concerned with cloud fraction, while there are few studies on the influence of other cloud attributes. Cloud top height is also an important factor affecting the retrieval accuracy of satellite RH profiles. In this study, the L-band encrypted radiosonde data from Shanghai Baoshan Station was used to analyze the accuracy of AIRS/Aqua (Atmospheric Infrared Sounder) retrieved RH profiles under different quality control and cloud conditions from July to September. The purpose of this study is to make preparation for the assimilation of relevant data and to assess the influence of AIRS RH products on the accuracy of regional numerical prediction. The results show that: (1) The error of the AIRS retrieved RH profiles gradually increases with the increase of cloud fraction. With the increase of atmospheric pressure, the difference of the root mean squared errors of RH in each pressure layer tends to increase gradually when there are few clouds or it is cloudy. (2) The higher the cloud top height is, the worse the accuracy of AIRS retrieved RH profiles is. The retrieval accuracy of RH profiles above cloud top is higher, while the retrieval error below cloud top is larger. (3) Under high-level cloud and cloudy conditions, the accuracy of the AIRS retrieved RH profiles is the worst. At 850hPa, the minimum absolute error between the RH data retrieved by AIRS and the radiosonde data reaches -63.51%. (4) Although the accuracy of AIRS retrieved RH profiles in the troposphere is not as high as that of radiosonde when the quality control is 0, the retrieval accuracy is obviously improved compared with that when the quality control is 1. [ABSTRACT FROM AUTHOR]

Background: Most cancer cells have fundamentally different metabolic characteristics, particularly much higher glycolysis rates than normal tissues, which support the increased demand for biosynthesis and promote tumor progression. We found that transforming growth factor (TGF)-β plays a dual function in regulating glycolysis and cell proliferation in non-small cell lung cancer. Methods: We used the PET/MRI imaging system to observe the glucose metabolism of subcutaneous tumors in nude mice. Energy metabolism of non-small cell lung cancer cell lines detected by the Seahorse XFe96 cell outflow analyzer. Co-immunoprecipitation assays were used to detect the binding of Smads and HIF-1α. Western blotting and qRT-PCR were used to detect the regulatory effects of TGF-β and HIF-1α on c-MYC, PKM1/2, and cell cycle-related genes. Results: We discovered that TGF-β could inhibit glycolysis under normoxia while significantly promoting tumor cells' glycolysis under hypoxia in vitro and in vivo. The binding of hypoxia-inducible factor (HIF)-1α to the MH2 domain of phosphorylated Smad3 switched TGF-β function to glycolysis by changing Smad partners under hypoxia. The Smad-p107-E2F4/5 complex that initially inhibited c-Myc expression was transformed into a Smad-HIF-1α complex that promoted the expression of c-Myc. The increased expression of c-Myc promoted alternative splicing of PKM to PKM2, resulting in the metabolic reprogramming of tumor cells. In addition, the TGF-β/Smad signal lost its effect on cell cycle regulatory protein p15/p21. Furthermore, high expression of c-Myc inhibited p15/p21 and promoted the proliferation of tumor cells under hypoxia. Conclusions: Our results indicated that HIF-1α functions as a critical factor in the dual role of TGF-β in tumor cells, and may be used as a biomarker or therapeutic target for TGF-β mediated cancer progression. [ABSTRACT FROM AUTHOR]

Brett Milligan stands out among all the scholars studying the future of the landscape profession in the context of climate change. He studied unique subjects, such as mud and river sediments. His projects often go beyond the usual landscape architecture majors, such as ecological restoration after dam removal and delta habitat creation; His attitude towards landscape is also very characteristic. For example, he treats landscape as a process, believes that people are very important beings in the process of landscape, and that the fluidity of landscape should not be underestimated. Through this article, Milligan points out the responsibility to acknowledge, embrace, and use landscape forces in project planning and design. It is also required to bring about more humility in terms of how we conceptualize the lifespan of a project to cope with climate change impacts. He encourages us to think beyond externalities--such as environment, people, communities, and sediment--as a practice of inclusion, diversity, and justice for humans and others. Relatedly, the public should be included as part of refined transdisciplinary and co-design methods. In the end, he shares his vision of design as a rigorous and unique form of knowledge making through a new Research by Design track. [ABSTRACT FROM AUTHOR]

Solvothermal reaction of 4,4',4'-nitrilotribenzoic acid (H3TCA) with Ca(NO3)2·4H2O and Cd(NO3)2·4H2O successfully afforded a heterometallic compound, that is, [Cd2Ca(TCA)2(DMA)2(H2O)3]n·2n(DMA) (1, DMA = N,N'-dimethylacetamide). The structure of 1 was further characterized through EA, diffraction of single crystal X-ray, and thermogravimetric analysis (TGA) together with powder X-ray diffraction (PXRD). Moreover, complex 1's luminescent performance in solid state was also discussed at environmental temperature. The applications on the ischemic cerebral infarction therapy were evaluated, and the specific mechanism was investigated at the same time. Firstly, the hypersensitivity C-reactive protein (hs-CRP) content in human brain microvascular endothelial cell (HBMEC) was measured with real-time reverse transcription-polymerase chain reaction (RT-PCR). Then, interleukin-18 and interleukin-1β content released through the HBMEC was detected with enzyme-linked immunosorbent assay (ELISA). [ABSTRACT FROM AUTHOR]

This work was aimed to study the risk factors and prognostic treatment for acute ischemic stroke (AIS) patients with early neurological deterioration (END) after intravenous thrombolytic therapy via compressed sensing algorithm-based magnetic resonance imaging (CS-MRI). 231 patients who were diagnosed with AIS were selected, and the final involved number of patients was 182. Patients with AIS were treated with intravenous thrombolysis with alteplase within 4.5 hours of onset. After treatment, patients with early neurological deterioration were defined as the deteriorating group and those without early neurological impairment were defined as the nondeteriorating group. In univariate analysis, hypertension, white blood cell count, and National Institutes of Health Stroke Scale (NIHSS) score were correlated with the occurrence of END. Under the CS-MRI theory, the two groups of patients were evaluated for middle cerebral artery basal ganglia infarction and internal watershed infarction. After univariate analysis, the P < 0.1 variables were taken as the independent variable, and the binary logistic regression model was adopted for multivariate regression analysis. It was disclosed that NIHSS score was not correlated with the occurrence of early neurological function deterioration, while homocysteine was. Hypertension, white blood cell count, homocysteine, and NIHSS score were risk factors for END. The image analysis revealed that the incidence of deteriorating basal ganglia infarction group was lower relative to the nondeteriorating group, and the incidence of watershed infarction was higher in the deteriorating group versus the nondeteriorating group. The image analysis suggested that predicting the occurrence of END through risk factors can actively provide endovascular treatment for patients with AIS. [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]

Background: Generally, cancer cells undergo metabolic reprogramming to adapt to energetic and biosynthetic requirements that support their uncontrolled proliferation. However, the mutual relationship between two critical metabolic pathways, glycolysis and oxidative phosphorylation (OXPHOS), remains poorly defined.Methods: We developed a "double-score" system to quantify glycolysis and OXPHOS in 9668 patients across 33 tumor types from The Cancer Genome Atlas and classified them into four metabolic subtypes. Multi-omics bioinformatical analyses was conducted to detect metabolism-related molecular features.Results: Compared with patients with low glycolysis and high OXPHOS (LGHO), those with high glycolysis and low OXPHOS (HGLO) were consistently associated with worse prognosis. We identified common dysregulated molecular features between different metabolic subgroups across multiple cancers, including gene, miRNA, transcription factor, methylation, and somatic alteration, as well as investigated their mutual interfering relationships.Conclusion: Overall, this work provides a comprehensive atlas of metabolic heterogeneity on a pan-cancer scale and identified several potential drivers of metabolic rewiring, suggesting corresponding prognostic and therapeutic utility. [ABSTRACT FROM AUTHOR]

EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs) have achieved clinical success in lung adenocarcinoma (LUAD). However, tumors often show profound but transient initial response and then gain resistance. We identify transcription factor ZNF263 as being significantly decreased in osimertinib-resistant or drug-tolerant persister LUAD cells and clinical residual tumors. ZNF263 overexpression improves the initial response of cells and delays the formation of persister cells with osimertinib treatment. We further show that ZNF263 binds and recruits DNMT1 to the EGFR gene promoter, suppressing EGFR transcription with DNA hypermethylation. ZNF263 interacts with nuclear EGFR, impairing the EGFR-STAT5 interaction to enhance AURKA expression. Overexpressing ZNF263 also makes tumor cells with wild-type EGFR expression or refractory EGFR mutations more susceptible to EGFR inhibition. More importantly, lentivirus or adeno-associated virus (AAV)-mediated ZNF263 overexpression synergistically suppresses tumor growth and regrowth with osimertinib treatment in xenograft animal models. These findings suggest that enhancing ZNF263 may achieve complete response in LUAD with EGFR-targeted therapies. [Display omitted] • Loss of ZNF263 expression occurs in EGFR TKI-residual lung adenocarcinoma • ZNF263 overexpression combats tumor cell survival and resistance to EGFR inhibition • ZNF263 suppresses the EGFR expression and disrupts the nuclear function of EGFR • AAV-ZNF263 is promising for achieving durable response to EGFR-targeted therapies Liang et al. show that ZNF263 expression is decreased in response to EGFR inhibition in lung adenocarcinoma. ZNF263 expression decrease contributes to cell persistence and resistance by enhancing EGFR expression and its nuclear activity. The authors show that overexpressing ZNF263 in tumors may achieve complete response with EGFR-targeted therapies. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is one of the most common malignancies worldwide. However, the molecular mechanism of LUAD tumorigenesis and development remains unclear. The purpose of this study was to comprehensively illustrate the role of GTF2E2 in the growth and progression of LUAD. Methods and materials: We obtained the mRNA expression data from The Cancer Genome Atlas, Gene Expression Omnibus database, and our institution. Systematic bioinformatical analyses were performed to investigate the expression and prognostic value of GTF2E2 in LUAD. The results were validated by immunohistochemistry and qPCR. The effect of knocking down GTF2E2 using two short hairpin RNAs was investigated by in vitro and in vivo assays. Subsequently, shotgun liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) analyses were applied to identified potential GTF2E2 interacting proteins, and the downstream molecular mechanisms of GTF2E2-signaling were further explored by a series of cellular functional assays. Results: We found that GTF2E2 expression was significantly increased in LUAD tissue compared with adjacent normal tissue and was negatively associated with patients' overall survival. Besides, we demonstrated that GTF2E2 knockdown inhibited LUAD cell proliferation, migration, invasion, and promote apoptosis in vitro, as well as attenuated tumor growth in vivo. Results from LC–MS/MS suggested that RPS4X might physically interact with GTF2E2 and mediated GTF2E2's regulatory effect on LUAD development through the mTOR pathway. Conclusion: Our findings indicate that GTF2E2 promotes LUAD development by activating RPS4X. Therefore, GTF2E2 might serve as a promising biomarker for the diagnosis and prognosis of LUAD patients, thus shedding light on the precise and personalized therapy for LUAD in the future. [ABSTRACT FROM AUTHOR]

Background: Tumor invasiveness reflects many biological changes associated with tumorigenesis, progression, metastasis, and drug resistance. Therefore, we performed a systematic assessment of invasiveness-related molecular features across multiple human cancers.Materials and Methods: Multi-omics data, including gene expression, miRNA, DNA methylation, and somatic mutation, in approximately 10,000 patients across 30 cancer types from The Cancer Genome Atlas, Gene Expression Omnibus, PRECOG, and our institution were enrolled in this study.Results: Based on a robust gene signature, we established an invasiveness score and found that the score was significantly associated with worse prognosis in almost all cancers. Then, we identified common invasiveness-associated dysregulated molecular features between high- and low-invasiveness score group across multiple cancers, as well as investigated their mutual interfering relationships thus determining whether the dysregulation of invasiveness-related genes was caused by abnormal promoter methylation or miRNA expression. We also analyzed the correlations between the drug sensitivity data from cancer cell lines and the expression level of 685 invasiveness-related genes differentially expressed in at least ten cancer types. An integrated analysis of the correlations among invasiveness-related genetic features and drug response were conducted in esophageal carcinoma patients to outline the complicated regulatory mechanism of tumor invasiveness status in multiple dimensions. Moreover, functional enrichment suggests the invasiveness score might serve as a predictive biomarker for cancer patients receiving immunotherapy.Conclusion: Our pan-cancer study provides a comprehensive atlas of tumor invasiveness and may guide more precise therapeutic strategies for tumor patients. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) patients with different American Joint Committee on Cancer stages have different overall 5‐year survival rates. The tumor microenvironment (TME) and intra‐tumor heterogeneity (ITH) have been shown to play a crucial role in the occurrence and development of tumors. However, the TME and ITH in different lesions of LUAD have not been extensively explored. Methods: We present a 204,157‐cell catalog of the TME transcriptome in 29 lung samples to systematically explore the TME and ITH in the different stages of LUAD. Traditional RNA sequencing data and complete clinical information were downloaded from publicly available databases. Results: Based on these high‐quality cells, we constructed a single‐cell network underlying cellular and molecular features of normal lung, early LUAD, and advanced LUAD cells. In contrast with early malignant cells, we noticed that advanced malignant cells had a remarkably more complex TME and higher ITH level. We also found that compared with other immune cells, more differences in CD8+/CTL T cells, regulatory T cells, and follicular B cells were evident between early and advanced LUAD. Additionally, cell‐cell communication analyses, revealed great diversity between different lesions of LUAD at the single‐cell level. Flow cytometry and qRT‐PCR were used to validate our results. Conclusion: Our results revealed the cellular diversity and molecular complexity of cell lineages in different stages of LUAD. We believe our research, which serves as a basic framework and valuable resource, can facilitate exploration of the pathogenesis of LUAD and identify novel therapeutic targets in the future. [ABSTRACT FROM AUTHOR]

A high-resolution air pollutant emission inventory for the Yangtze River Delta (YRD) region was updated for 2017 using emission factors and chemical speciation based mainly on local measurements in this study. The inventory included 424 non-methane volatile organic compounds (NMVOCs) and 43 fine particulate matter (PM 2.5) species from 259 specific sources. The total emissions of SO 2 , NO x , CO, NMVOCs, PM 10 , PM 2.5 , and NH 3 in the YRD region in 2017 were 1552, 3235, 38 507, 4875, 3770, 1597, and 2467 Gg, respectively. SO 2 and CO emissions were mainly from boilers, accounting for 49 % and 73 % of the total. Mobile sources dominated NO x emissions, contributing 57 % of the total. NMVOC emissions, mainly from industrial sources, made up 61 % of the total. Dust sources accounted for 55 % and 28 % of PM 10 and PM 2.5 emissions, respectively. Agricultural sources accounted for 91 % of NH 3 emissions. Major PM 2.5 species were OC, Ca, Si, PSO 4 , and EC, accounting for 9.0 %, 7.0 %, 6.4 %, 4.6 %, and 4.3 % of total PM 2.5 emissions, respectively. The main species of NMVOCs were aromatic hydrocarbons, making up 25.3 % of the total. Oxygenated volatile organic compounds (OVOCs) contributed 21.9 % of the total NMVOC emissions. Toluene had the highest comprehensive contribution to ozone (O 3) and secondary organic aerosol (SOA) formation potentials, while other NMVOCs included 1,2,4-trimethylbenzene, m , p -xylene, propylene, ethene, o -xylene, and ethylbenzene. Industrial process and solvent-use sources were the main sources of O 3 and SOA formation potential, followed by motor vehicles. Among industrial sources, chemical manufacturing, rubber and plastic manufacturing, appliance manufacturing, and textiles made significant contributions. This emission inventory should provide scientific guidance for future control of air pollutants in the YRD region of China. [ABSTRACT FROM AUTHOR]

OBJECTIVES Little is known on the outcome of tracheal allografts after long-term survival. This study aimed to explore the changes in structure and composition by evaluating the status of the mucosa and cartilage of allografts with long-term survival in dogs. METHODS Eight tracheal allografts that survived for ˃9 months were enrolled in our study. Epithelium, revascularization, monocyte infiltration and fibrosis were evaluated histologically. The fluorescent dye 4′-6-diamidino-2-phenylindole was used to evaluate the presence of chondrocyte nuclei. Glycosaminoglycan was detected using safranin-O staining and collagen II was evaluated using immunohistochemistry. RESULTS The 8 animals survived from 277 to 783 days. Bronchoscopy demonstrated that 6 allografts showed no stenosis; 2 cases developed slight stenosis, but could maintain airway patency. Histological examination showed that the epithelium covered the surface of the allografts. In comparison to fresh tracheal controls, allografts demonstrated mild monocyte infiltration, evident revascularization and mild fibrosis in the mucosa or submucosa (all P  <   0.05). There were a few viable chondrocytes scattered in the cartilage after long-term survival. Moreover, glycosaminoglycan and collagen II were significantly decreased in the allografts compared with fresh trachea (all P  <   0.05). CONCLUSIONS For tracheal allografts with long-term survival after transplantation, only a few viable chondrocytes were retained, and the extracellular matrix of the cartilage demonstrated degeneration. Despite this, the airway could maintain patency. Notably, the significance of monocyte infiltration in the mucosa or submucosa at different time points warrants further study. [ABSTRACT FROM AUTHOR]

We study a coin supply chain problem in the context of improving efficiency. While most consumer products are distributed in one direction, coins are recirculated and reused through the economy. The Federal Reserve System (FRS), the central banking system of the United States, plays a crucial role in managing the U.S. coin supply chain (CSC). It spends a significant fraction of its annual budget on operating the U.S. CSC in order to provide banking services to depository institutions (DIs) and the public. The objective of this study is to provide a near‐optimal or an optimal operating policy that minimizes the total cost of producing, supplying, and managing coin inventory in the U.S. CSC. The study demonstrates a modeling approach that not only can be applied for effectively and efficiently managing the coin supply in the United States, but also for managing similar coin supply chains around the world. The extensive tools and insights developed in this study may prove to be beneficial to the Federal Reserve's Cash Product Office (CPO) that manages the distribution of the nation's coin inventory. Managing demand uncertainty and streamlining its processes to be more adaptable to changes in demand are critical for the CPO to reduce supply chain costs. The robust optimization framework and the resulting insights presented in this study could potentially help the CPO to manage shifts in coin demand and achieve its cost reduction goals. [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]

Background: Some lung diseases are cell type-specific. It is essential to study the cellular anatomy of the normal human lung for exploring the cellular origin of lung disease and the cell development trajectory. Methods: We used the Seurat R package for data quality control. The principal component analysis (PCA) was used for linear dimensionality reduction. UMAP and tSNE were used for dimensionality reduction. Muonocle2 was used to extract lung epithelial cells to analyze the subtypes of epithelial cells further and to study the development of these cell subtypes. Results: We showed a total of 20154 high quality of cells from human normal lung tissue. They were initially divided into 17 clusters cells and then identified as seven types of cells, namely macrophages, monocytes, CD8 + T cells, epithelial cells, endothelial cells, adipocytes, and NK cells. 4240 epithelial cells were extracted for further analysis and they were divided into seven clusters. The seven cell clusters include alveolar cell, alveolar endothelial progenitor, ciliated cell, secretory cell, ionocyte cell, and a group of cells that are not clear at present. We show the development track of these subtypes of epithelial cells, in which we speculate that alveolar epithelial progenitor (AEP) is a kind of progenitor cells that can develop into alveolar cells, and find six essential genes that determine the cell fate, including AGER, RPL10, RPL9, RPS18, RPS27, and SFTPB. Conclusion: We provide a transcription map of human lung cells, especially the in-depth study on the development of epithelial cell subtypes, which will help us to study lung cell biology and lung diseases. [ABSTRACT FROM AUTHOR]

Background: Most non-small cell lung cancer patients with enlarged mediastinal lymph nodes (LN) in preoperative computer tomography (CT) images are diagnosed with N0 in the pathological examination after surgery. However, these patients seem to have worse survival than those without enlarged mediastinal LN in our clinical practice. This study aimed to investigate whether the size of mediastinal LN is correlated with the prognosis in pathological N0 patients, which could help us to predict the prognoses further. Methods: The retrospective cohort study involved 758 N0 patients with a thin layer CT scan. We have measured the size of mediastinal LN, including long diameter, short diameter, and volume on CT image, and classified patients by X-tile. Next, we explored the risk factors of enlarged LN by univariate and multivariate logistic analysis. Then, we have compared the 5-year cancer-specific survival by Kaplan–Meier and log-rank method. Multivariate Cox analysis was utilized to further survival analysis. Finally, we have constructed the prediction model by nomogram. Results: A total of 150 N0 patients (19.8%) had mediastinal LN enlargement in our study. After multivariate logistic analysis, we found the LN enlargement was significantly correlated with age (p=0.001), pathology (p < 0.001) and tumor recurrence (p < 0.001). The patients with LN enlargement had a worse 5-year cancer-specific survival (75.3% vs 92.8%, p < 0.001) after Kaplan–Meier analysis. Patients with a larger volume had increased risk of tumor-associated death when compared with the normal group (p < 0.001) by multivariate Cox analyses. Conclusion: N0 patients with larger mediastinal LN had a worse 5-year cancer-specific survival and a higher risk of recurrence. The volume of LN was the most valuable prognostic factor in N0 patients. [ABSTRACT FROM AUTHOR]