Macrophage Tim-3 maintains intestinal homeostasis in DSS-induced colitis by suppressing neutrophil necroptosis.

T-cell immunoglobulin domain and mucin domain-3 (Tim-3) is a versatile immunomodulator that protects against intestinal inflammation. Necroptosis is a type of cell death that regulates intestinal homeostasis and inflammation. The mechanism(s) underlying the protective role of macrophage Tim-3 in intestinal inflammation is unclear; thus, we investigated whether specific Tim-3 knockdown in macrophages drives intestinal inflammation via necroptosis. Tim-3 protein and mRNA expression were assessed via double immunofluorescence staining and single-cell RNA sequencing (sc-RNA seq), respectively, in the colonic tissues of patients with inflammatory bowel disease (IBD) and healthy controls. Macrophage-specific Tim3-knockout (Tim-3M-KO) mice were generated to explore the function and mechanism of Tim-3 in dextran sodium sulfate (DSS)-induced colitis. Necroptosis was blocked by pharmacological inhibitors of receptor-interacting protein kinase (RIP)1, RIP3, and reactive oxygen species (ROS). Additionally, in vitro experiments were performed to assess the mechanisms of neutrophil necroptosis induced by Tim-3 knockdown macrophages. Although Tim-3 is relatively inactive in macrophages during colon homeostasis, it is highly active during colitis. Compared to those in controls, Tim-3M-KO mice showed increased susceptibility to colitis, higher colitis scores, and increased pro-inflammatory mediator expression. Following the administration of RIP1/RIP3 or ROS inhibitors, a significant reduction in intestinal inflammation symptoms was observed in DSS-treated Tim-3M-KO mice. Further analysis indicated the TLR4/NF-κB pathway in Tim-3 knockdown macrophages mediates the TNF-α-induced necroptosis pathway in neutrophils. Macrophage Tim-3 regulates neutrophil necroptosis via intracellular ROS signaling. Tim-3 knockdown macrophages can recruit neutrophils and induce neutrophil necroptosis, thereby damaging the intestinal mucosal barrier and triggering a vicious cycle in the development of colitis. Our results demonstrate a protective role of macrophage Tim-3 in maintaining gut homeostasis by inhibiting neutrophil necroptosis and provide novel insights into the pathogenesis of IBD.

Impact of Helicobacter pylori colonization density and depth on gastritis severity.

BACKGROUND AND OBJECTIVES: Helicobacter pylori (H. pylori) infection is the most common etiology of chronic gastric. H. pylori gastritis would gradually evolve into gastric atrophy, intestinal metaplasia, dysplasia and malignant lesions. Herein, this study aimed to investigate the potential impact of H. pylori colonization density and depth on the severity of histological parameters of gastritis. METHODS: A prospective monocentric study was conducted from December 2019 to July 2022, enrolling patients with confirmed chronic H. pylori infection via histopathological evaluation. H. pylori colonization status was detected by immunohistochemical staining, pathological changes of gastric specimens were detected by hematoxylin eosin staining. Epidemiological, endoscopic and histopathological data were collected. RESULTS: A total of 1120 patients with a mean age of 45.8 years were included. Regardless of the previous history of H. pylori eradication treatment, significant correlations were observed between the density and depth of H. pylori colonization and the intensity of gastritis activity (all P < 0.05). Patients with the lowest level of H. pylori colonization density and depth exhibited the highest level of mild activity. In whole participants and anti-H. pylori treatment-naive participants, H. pylori colonization density and depth were markedly correlated with the severity of chronic gastritis and gastric atrophy (all P < 0.05). H. pylori colonization density (P = 0.001) and depth (P = 0.047) were significantly associated with ulcer formation in patients naive to any anti-H. pylori treatment. No significant associations were observed between the density and depth of H. pylori colonization and other histopathological findings including lymphadenia, lymphoid follicle formation and dysplasia. CONCLUSIONS: As the density and depth of H. pylori colonization increased, so did the activity and severity of gastritis, along with an elevated risk of ulcer formation.

Preparation of tough and stiff ionogels via phase separation.

Ionogels have the advantages of thermal stability, non-volatility, ionic conductivity and environmental friendliness, and they can be used in the field of flexible electronics and soft robotics. However, their poor mechanical strength and complex preparation methods limit their practical application. Herein, we propose a simple strategy to improve the performance of ionogels by adjusting their phase separation behavior. In a polymer-ionic liquid (IL) binary system with an upper critical solution temperature (UCST) and Berghmans' point, the phase separation behavior will be frozen below the temperature corresponding to the Berghmans' point, and thus, the degree of phase separation can be adjusted by controlling the cooling rate. We found that a polyacrylamide (PAM)-IL binary system possessed a UCST and Berghmans' point and the resulting ionogels had excellent mechanical properties. Their tensile strength, tensile modulus, compressive strength and compressive modulus reached 31.1 MPa, 319.8 MPa, 122 MPa and 1.7 GPa, respectively, while these properties of the other ionogels were generally less than 10 MPa. Furthermore, they were highly transparent, stretchable, stable and multifunctional.

Design and simulation of a cross-regional collaborative recycling system for secondary resources: A case of lead-acid batteries.

In emerging economies, a significant amount of secondary resources are recycled by the informal sector, which can seriously harm the environment. However, some previous studies of industry management policy design ignored geographical factors. This paper introduces Geographic Information Systems into an agent-based cross-regional recycling model, and employs lead-acid batteries as an example. The model quantitatively displays the evolution of recycling markets in 31 provinces in Mainland China. Results show that: (1) High subsidies can significantly increase the number of formal enterprises in the short term, but their effectiveness decreases when the proportion of government funds in subsidies is above 80% in the long run; (2) The number of illegal recycling enterprises increases by 294% in eight inland provinces (e.g., Ningxia, Xinjiang) when all funds are invested in supervision, but this number is quite small in subsidy policy scenarios; (3) In four eastern regions, including Beijing and Tianjin, the number of illegal recycling enterprises decreases by 84% if supervision is more favored than subsidy; (4) In the optimal case where spatiotemporal factors are considered in all 31 regions, illegal recycling enterprises and waste lead emissions can be reduced by 95.59% and 45.85% nationwide. Our proposed recycling model offers a detailed simulation of multiple regions and diverse stakeholders, and serves as a useful reference for targeted recovery policies. Governments in inland regions like Ningxia and Xinjiang should implement subsidy policies, while supervision policies should be implemented in developed regions like Beijing and Tianjin.

Helicobacter pylori infection reduces the efficacy of cancer immunotherapy: A systematic review and meta-analysis.

BACKGROUND: Cancer immunotherapy has shown promising results in several tumors, but its efficacy is influenced by the immune state of the body. Helicobacter pylori (H. pylori) infection can modulate the immune function of the body through various pathways, ultimately affecting the effectiveness of cancer immunotherapy. AIM: In this meta-analysis, we aimed to explore the association between H. pylori infection and the efficacy of cancer immunotherapy. METHODS: We conducted a comprehensive search of PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials to identify relevant articles. We extracted and pooled the hazard ratio (HR) of the overall survival (OS) and progression-free survival (PFS) by Review Manager 5.4. RESULTS: Our analysis included four studies with a total of 263 participants. Compared to the control group, patients receiving cancer immunotherapy with H. pylori infection had a shorter OS (HR = 2.68, 95% CI: 2.00-4.11, p < 0.00001) and PFS (HR = 2.25, 95% CI: 1.66-3.60, p < 0.00001). CONCLUSION: Our meta-analysis suggested that H. pylori infection has a detrimental effect on cancer immunotherapy.

Green illusions in self-reporting? Reassessing the intention-behavior gap in waste recycling behaviors.

Improving residents' waste recycling behavior is crucial for enhancing resource efficiency and reducing carbon emissions. Previous questionnaire-based studies have reported that individuals exhibit a high willingness to recycle, yet often fail to convert this intention into action. Analyzing 180,417 Internet of Things (IoT) behavior data points, we discovered that the intention-behavior gap might be larger than anticipated. Our findings indicate that: 1) Intentions to recycle alone can predict self-reported recycling behavior (p < 0.01, t = 2.841), but not actual recycling behavior in the absence of other possible moderators (p > 0.1, t = 0.777); 2) Self-reported behavior predicts real behavior, but with limited explanatory power; and 3) The intention-behavior gap primarily results from forgetting or habituation (p < 0.01, t = 2.653), while social desirability plays an insignificant role (p > 0.1, t = 0.246). This study contributes to our understanding of the intention-behavior gap and provides direction for future pro-environmental behavior research.

Reinforced medication adherence improves Helicobacter pylori eradication rate in developing countries: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The eradication rate of Helicobacter pylori (H. pylori) remains variable for the same eradication regime even in the identical region, especially in developing countries. Herein, we conducted a systematic review to assess the effect of reinforced medication adherence on H. pylori eradication rate in developing countries. MATERIALS AND METHODS: A systematic review was conducted in literature databases to identify relevant randomized controlled trials (RCTs) from inception to March 2023. The core indicator was the changes in eradication rate after enhanced adherence. A meta-analysis was performed to estimate the pooled relative risk (RR) or weighted mean difference (WMD) with 95% confidence intervals (CI). RESULTS: Nineteen RCTs that included a total of 3286 patients were assessed. The measures to enhance compliance were mainly through face-to-face communication, phone calls, text messages, and social software. Compared with the control group, patients received reinforced measures showed a better medication adherence (89.6% vs. 71.4%, RR = 1.26 95% CI: 1.16-1.37), higher H. pylori eradication rate (intention-to-treat analysis: 80.2% vs. 65.9%, RR = 1.25, 95% CI: 1.12-1.31; per-protocol analysis: 86.8% vs. 74.8%, RR = 1.16, 95% CI: 1.09-1.23), higher symptom relief rates (81.8% vs. 65.1%, RR = 1.23, 95% CI: 1.09-1.38), higher degree of satisfaction (90.4% vs. 65.1%, RR = 1.26, 95% CI: 1.19-1.35), higher disease knowledge rates (SMD = 1.82, 95% CI: 0.77-2.86, p = 0.0007), and lower incidence of total adverse events (27.3% vs. 34.7%, RR = 0.72, 95% CI: 0.52-0.99). CONCLUSION: Based on available evidence, reinforced medication adherence as a nonnegligible measure improves H. pylori eradication rate in developing countries.

Assisted reproductive technology and neurodevelopmental outcomes in offspring: a prospective birth cohort study in East China.

RESEARCH QUESTION: Is ART associated with adverse neurodevelopmental outcome in 12-month-old offspring compared with those conceived through natural conception? DESIGN: In this prospective cohort study, 488 infertile women undergoing ART and 1397 women with natural conception were recruited and followed until their offspring were 12 months old. The primary outcome was the neurodevelopment in the offspring. The association between exposure to ART and Gesell developmental scale scores was investigated using multiple linear regression models after adjusting for confounders. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to verify the results. RESULTS: In total, 18 (3.7%) and 40 (2.9%) children in the ART and natural conception groups, respectively, had been diagnosed with neurodevelopmental delay at 12 months of age. It was found that gross motor, adaptive behaviour, language and total development quotient scores were comparable between the groups. Following multivariate linear regression and IPTW, social behaviour development quotient scores were found to be slightly higher in the ART group than the natural conception group. Higher social behaviour development quotient scores in the ART group were also observed in the male and the singleton subgroups. CONCLUSIONS: At 12 months, offspring born after ART appeared to have similar motor, language and adaptive behaviour skills, and total development quotient scores, to those born after natural conception. However, social behaviour development in 12-month-old infants was slightly higher in those conceived using ART than in naturally conceived offspring, especially in male or singleton infants. These findings may provide new information in evaluating the potential benefits and risks of ART.

Electrostatically Assisted Construction Modified MXene-IL-Based Nanofluids for Photothermal Conversion.

Solar energy, as renewable energy, has paid extensive attention for solar thermal utilization due to its unique characteristics such as rich resources, easy access, clean, and pollution-free. Among them, solar thermal utilization is the most extensive one. Nanofluid-based direct absorption solar collectors (DASCs), as an important alternative method, can further improve the solar thermal efficiency. Notably, the stability of photothermal conversion materials and flowing media is critical to the performance of DASC. Herein, we first proposed novel Ti3C2Tx-IL-based nanofluids by the electrostatic interaction, which consists of functional Ti3C2Tx modified with PDA and PEI as a photothermal conversion material and ionic liquid with low viscosity as the flow medium. Ti3C2Tx-IL-based nanofluids exhibit excellent cycle stability, wide spectrum, and efficient solar energy absorption performance. Besides, Ti3C2Tx-IL-based nanofluids maintain liquid state in a range of -80 to 200 °C, and its viscosity was as low as 0.3 Pa·s at 0 °C. Moreover, the equilibrium temperature of Ti3C2Tx@PDA-IL at a very low mass fraction of 0.04% reached 73.9 °C under 1 Sun, indicating an excellent photothermal conversion performance. Furthermore, the application of nanofluids in photosensitive inks has been preliminarily explored, which is expected to play a role in the fields of injectable biomedical materials and photo/electric double-generation thermal and hydrophobic anti ice coatings.

A bibliometric analysis of inflammatory bowel disease and COVID-19 researches.

Background: Patients with inflammatory bowel disease (IBD) often require immunosuppressive therapy and are hence susceptible to various opportunistic viral and bacterial infections. In this regard, many studies on IBD and COVID-19 have been conducted. However, no bibliometric analysis has been performed. This study provides a general overview of IBD and COVID-19. Methods: Publications about IBD and COVID-19 from 2020 to 2022 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using VOSviewer, CiteSpace, and HistCite. Results: A total of 396 publications were retrieved and considered in this study. The maximum number of publications were from the United States, Italy, and England, and the contributions of these countries were significant. Kappelman ranked first in article citations. The Icahn School of Medicine at Mount Sinai and Inflammatory Bowel Diseases were the most prolific affiliation and journal, respectively. The most influential research topics were "management", "impact", "vaccination", and "receptor". The following keywords represented research frontiers: "depression", "the quality of life of IBD patients", "infliximab", "COVID-19 vaccine", and "second vaccination". Conclusions: Over the past 3 years, most studies on IBD and COVID-19 have focused on clinical research. In particular, topics such as "depression", "the quality of life of IBD patients", "infliximab", "COVID-19 vaccine", and "second vaccination" were noted to have received much attention recently. Future research should focus on our understanding of the immune response to COVID-19 vaccination in biologically treated patients, the psychological impact of COVID-19, IBD management guidelines, and the long-term impact of COVID-19 in IBD patients. This study will provide researchers with a better understanding of research trends on IBD during COVID-19.

Iatrogenic factors of Helicobacter pylori eradication failure: lessons from the frontline.

BACKGROUND: Iatrogenic factors play an important role in H. pylori eradication failure, whereas it can be easily missed. Therefore, we aimed to investigate and analyze these related iatrogenic factors of H. pylori eradication failure. METHODS: A total of 508 patients who experienced H. pylori eradication failure were included in this study conducted from December 2019 to February 2022. All the patients filled out a questionnaire including demographic characteristics, duration of treatment, regimens, dosage, and time intervals in rescue treatment. RESULTS: In the first-line treatment, 89 patients (17.5%, 89/508) used at least one antibiotic with high resistance rate in triple therapy and 57 patients (11.2%, 57/508) used two antibiotics with high resistance rates or other not recommended antibiotics in quadruple therapy. In the rescue therapy, 85 regimens were repeatedly used as salvage regimens in 58 patients (22.6%, 58/257) and 178 regimens containing antibiotics with high resistance rates were repeatedly used in 85 patients (33.1%, 85/257). CONCLUSION: To decrease the risk of H. pylori eradication failure, iatrogenic factors need to gain more attention. Clinicians should enhance their education and training to standardize the treatment regimens, better manage the H. pylori infection, and improve the eradication rate eventually.

Construction of a novel choline metabolism-related signature to predict prognosis, immune landscape, and chemotherapy response in colon adenocarcinoma.

Background: Colon adenocarcinoma (COAD) is a common digestive system malignancy with high mortality and poor prognosis. Accumulating evidence indicates that choline metabolism is closely related to tumorigenesis and development. However, the efficacy of choline metabolism-related signature in predicting patient prognosis, immune microenvironment and chemotherapy response has not been fully clarified. Methods: Choline metabolism-related differentially expressed genes (DEGs) between normal and COAD tissues were screened using datasets from The Cancer Genome Atlas (TCGA), Kyoto Encyclopedia of Genes and Genomes (KEGG), AmiGO2 and Reactome Pathway databases. Two choline metabolism-related genes (CHKB and PEMT) were identified by univariate and multivariate Cox regression analyses. TCGA-COAD was the training cohort, and GSE17536 was the validation cohort. Patients in the high- and low-risk groups were distinguished according to the optimal cutoff value of the risk score. A nomogram was used to assess the prognostic accuracy of the choline metabolism-related signature. Calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) were used to improve the clinical applicability of the prognostic signature. Gene Ontology (GO) and KEGG pathway enrichment analyses of DEGs in the high- and low-risk groups were performed. KEGG cluster analysis was conducted by the KOBAS-i database. The distribution and expression of CHKB and PEMT in various types of immune cells were analyzed based on single-cell RNA sequencing (scRNA-seq). The CIBERSORT and ESTIMATE algorithms evaluated tumor immune cell infiltration in the high- and low-risk groups. Evaluation of the half maximal inhibitory concentration (IC50) of common chemotherapeutic drugs based on the choline metabolism-related signature was performed. Small molecule compounds were predicted using the Connectivity Map (CMap) database. Molecular docking is used to simulate the binding conformation of small molecule compounds and key targets. By immunohistochemistry (IHC), Western blot, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) experiments, the expression levels of CHKB and PEMT in human, mouse, and cell lines were detected. Results: We constructed and validated a choline metabolism-related signature containing two genes (CHKB and PEMT). The overall survival (OS) of patients in the high-risk group was significantly worse than that of patients in the low-risk group. The nomogram could effectively and accurately predict the OS of COAD patients at 1, 3, and 5 years. The DCA curve and CIC demonstrate the clinical utility of the nomogram. scRNA-seq showed that CHKB was mainly distributed in endothelial cells, while PEMT was mainly distributed in CD4+ T cells and CD8+ T cells. In addition, multiple types of immune cells expressing CHKB and PEMT differed significantly. There were significant differences in the immune microenvironment, immune checkpoint expression and chemotherapy response between the two risk groups. In addition, we screened five potential small molecule drugs that targeted treatment for COAD. Finally, the results of IHC, Western blot, and qRT-PCR consistently showed that the expression of CHKB in human, mouse, and cell lines was elevated in normal samples, while PMET showed the opposite trend. Conclusion: In conclusion, we constructed a choline metabolism-related signature in COAD and revealed its potential application value in predicting the prognosis, immune microenvironment, and chemotherapy response of patients, which may lay an important theoretical basis for future personalized precision therapy.

Identification of a glycolysis- and lactate-related gene signature for predicting prognosis, immune microenvironment, and drug candidates in colon adenocarcinoma.

Background: Colon adenocarcinoma (COAD), a malignant gastrointestinal tumor, has the characteristics of high mortality and poor prognosis. Even in the presence of oxygen, the Warburg effect, a major metabolic hallmark of almost all cancer cells, is characterized by increased glycolysis and lactate fermentation, which supports biosynthesis and provides energy to sustain tumor cell growth and proliferation. However, a thorough investigation into glycolysis- and lactate-related genes and their association with COAD prognosis, immune cell infiltration, and drug candidates is currently lacking. Methods: COAD patient data and glycolysis- and lactate-related genes were retrieved from The Cancer Genome Atlas (TCGA) and Gene Set Enrichment Analysis (GSEA) databases, respectively. After univariate Cox regression analysis, a nonnegative matrix factorization (NMF) algorithm was used to identify glycolysis- and lactate-related molecular subtypes. Least absolute shrinkage and selection operator (LASSO) Cox regression identified twelve glycolysis- and lactate-related genes (ADTRP, ALDOB, APOBEC1, ASCL2, CEACAM7, CLCA1, CTXN1, FLNA, NAT2, OLFM4, PTPRU, and SNCG) related to prognosis. The median risk score was employed to separate patients into high- and low-risk groups. The prognostic efficacy of the glycolysis- and lactate-related gene signature was assessed using Kaplan-Meier (KM) survival and receiver operating characteristic (ROC) curve analyses. The nomogram, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) were employed to improve the clinical applicability of the prognostic signature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on differentially expressed genes (DEGs) from the high- and low-risk groups. Using CIBERSORT, ESTIMATE, and single-sample GSEA (ssGSEA) algorithms, the quantities and types of tumor-infiltrating immune cells were assessed. The tumor mutational burden (TMB) and cytolytic (CYT) activity scores were calculated between the high- and low-risk groups. Potential small-molecule agents were identified using the Connectivity Map (cMap) database and validated by molecular docking. To verify key core gene expression levels, quantitative real-time polymerase chain reaction (qRT-PCR) assays were conducted. Results: We identified four distinct molecular subtypes of COAD. Cluster 2 had the best prognosis, and clusters 1 and 3 had poor prognoses. High-risk COAD patients exhibited considerably poorer overall survival (OS) than low-risk COAD patients. The nomogram precisely predicted patient OS, with acceptable discrimination and excellent calibration. GO and KEGG pathway enrichment analyses of DEGs revealed enrichment mainly in the "glycosaminoglycan binding," "extracellular matrix," "pancreatic secretion," and "focal adhesion" pathways. Patients in the low-risk group exhibited a larger infiltration of memory CD4+ T cells and dendritic cells and a better prognosis than those in the high-risk group. The chemotherapeutic agent sensitivity of patients categorized by risk score varied significantly. We predicted six potential small-molecule agents binding to the core target of the glycolysis- and lactate-related gene signature. ALDOB and APOBEC1 mRNA expression was increased in COAD tissues, whereas CLCA1 and OLFM4 mRNA expression was increased in normal tissues. Conclusion: In summary, we identified molecular subtypes of COAD and developed a glycolysis- and lactate-related gene signature with significant prognostic value, which benefits COAD patients by informing more precise and effective treatment decisions.

An Intratumor Heterogeneity-Related Signature for Predicting Prognosis, Immune Landscape, and Chemotherapy Response in Colon Adenocarcinoma.

Background: Colon adenocarcinoma (COAD) is a frequent malignancy of the digestive system with a poor prognosis and high mortality rate worldwide. Intratumor heterogeneity (ITH) is associated with tumor progression, poor prognosis, immunosuppression, and therapy resistance. However, the relationship between ITH and prognosis, the immune microenvironment, and the chemotherapy response in COAD patients remains unknown, and this knowledge is urgently needed. Methods: We obtained clinical information and gene expression data for COAD patients from The Cancer Genome Atlas (TCGA) database. The DEPTH2 algorithm was utilized to evaluate the ITH score. X-tile software was used to determine the optimal cutoff value of the ITH score. The COAD patients were divided into high- and low-ITH groups based on the cutoff value. We analyzed prognosis, tumor mutation burden (TMB), gene mutations, and immune checkpoint expression between the high- and low-ITH groups. Differentially expressed genes (DEGs) in the high- and low-ITH groups were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. We performed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses to screen the prognosis-related genes for the construction of an ITH-related prognostic signature. The nomogram was used to predict the overall survival (OS) of COAD patients. The protein-protein interaction (PPI) network was constructed by using the GeneMANIA database. Principal component analysis (PCA) and single-sample gene set enrichment analysis (ssGSEA) were employed to explore the differences in biological pathway activation status between the high- and low-risk groups. The proportion and type of tumor-infiltrating immune cells were evaluated by the CIBERSORT and ESTIMATE algorithms. Additionally, we assessed the chemotherapy response and predicted small-molecule drugs for treatment. Finally, the expression of the prognosis-related genes was validated by using the UALCAN database and Human Protein Atlas (HPA) database. Results: The OS of the high-ITH group was worse than that of the low-ITH group. A positive correlation between ITH and TMB was identified. In subgroups stratified by age, gender, and tumor stage, the OS of the low-ITH group remained better than that of the high-ITH group. There were dramatic differences in the mutated genes, single nucleotide variant classes, variant types, immune checkpoints and cooccurring and mutually exclusive mutations of the DEGs between the high- and low-ITH groups. Based on the DEGs between the high- and low-ITH groups, we constructed a five-gene signature consisting of CEACAM5, ENO2, GABBR1, MC1R, and SLC44A4. The COAD patients were divided into high- and low-risk groups according to the median risk score. The OS of the high-risk group was worse than that of the low-risk group. The nomogram was used to accurately predict the 1-, 3- and 5-year OS of COAD patients and showed good calibration and moderate discrimination ability. The stromal score, immune score, and ESTIMATE score of the high-risk group were significantly higher than those of the low-risk group, whereas tumor purity showed the opposite trend. The patients classified by the risk score had distinguishable sensitivity to chemotherapeutic drugs. Finally, two public databases confirmed that CEACAM5 and SLC44A4 were upregulated in normal tissues compared with COAD tissues, and ENO2, GABBR1, and MC1R were upregulated in COAD tissues compared with normal tissues. Conclusion: Overall, we identified an ITH-related prognostic signature for COAD that was closely related to the tumor microenvironment and chemotherapy response. This signature may help clinicians make more personalized and precise treatment decisions for COAD patients.

Core-Shell ZIF67@ZIF8 Modified with Phytic Acid as an Effective Flame Retardant for Improving the Fire Safety of Epoxy Resins.

Despite many important industrial applications, epoxy resin (EP) suffers from high flammability and toxicity emission, extremely hampering their applications. To circumvent the problem, core-shell structured ZIF67@ZIF8 is successfully synthesized and further functionalized with phytic acid (PA) to obtain PA-ZIF67@ZIF8 hybrids. Then, it is used as an efficient flame retardant to reduce the fire risk of EP. The fire test results show a significant reduction in heat and smoke production. Compared with EP, incorporating 5.0 wt % PA-ZIF67@ZIF8 into EP, the peak heat release rate, total heat release, and peak carbon monoxide production are dramatically reduced by 42.2, 33.0, and 41.5%, respectively. Moreover, the EP/PA-ZIF67@ZIF8 composites achieve the UL-94 V-0 rating and the limiting oxygen index increases by 29.3%. These superior fire safety properties are mainly attributed to the excellent dispersion and the catalytic effect of metal oxide and phosphorus-containing compounds. This work provides an efficient strategy for preparing a promising ZIF-based flame retardant for enhancing flame retardancy and smoke toxicity suppression of EP.

Copy Number Analyses Identified a Novel Gene: APOBEC3A Related to Lipid Metabolism in the Pathogenesis of Preeclampsia.

Background: Preeclampsia is a heterogeneous and complex disease with its pathogenesis mechanism not fully elucidated. A certain subset of patients with preeclampsia exhibit disturbances in lipid metabolism before clinical symptoms. Moreover, there is a tendency for preeclampsia to run in families. Whether genetic factors play a role in abnormal lipid metabolism during the incidence of preeclampsia has not been well investigated. Methods: Preeclampsia patients (n = 110) and healthy age- and gravidity-matched pregnant women (n = 110) were enrolled in this study. Peripheral blood specimens were used for genomic analysis (n = 10/group) or laboratory validation (n = 100/group). We retrospectively obtained the baseline clinical characteristics of 68 preeclampsia patients and 107 controls in early pregnancy (12-14 gestational weeks). Correlation analyses between differential genes and baseline lipid profiles were performed to identify candidate genes. In vitro and in vivo gain-of-function models were constructed with lentivirus and adeno-associated virus systems, respectively, to investigate the role of candidate genes in regulating lipid metabolism and the development of preeclampsia. Results: We observed that preeclampsia patients exhibited significantly elevated plasma TC (P = 0.037) and TG (P < 0.001) levels and increased body mass index (P = 0.006) before the disease onset. Within the region of 27 differential copy number variations, six genes potentially connected with lipid metabolism were identified. The aberrant copies of APOBEC3A, APOBEC3A_B, BTNL3, and LMF1 between preeclampsia patients and controls were verified by quantitative polymerase chain reaction. Especially, APOBEC3A showed a significant positive correlation with TC (P < 0.001) and LDL (P = 0.048) in early pregnancy. Then, our in vitro data revealed that overexpression of APOBEC3A disrupted lipid metabolism in HepG2 cells and affected both cholesterol and fatty acid metabolisms. Finally, in vivo study in a hepatic-specific overexpressed APOBEC3A mouse model revealed abnormal parameters related to lipid metabolism. Pregnant mice of the same model at the end of pregnancy showed changes related to preeclampsia-like symptoms, such as increases in sFlt-1 levels and sFlt-1/PLGF ratios in the placenta and decreases in fetal weight. Conclusion: Our findings established a new link between genetics and lipid metabolism in the pathogenesis of preeclampsia and could contribute to a better understanding of the molecular mechanisms of preeclampsia.

The Interferon Gamma-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Colon Adenocarcinoma.

Colon adenocarcinoma (COAD) is one of the most common clinically malignant tumours of the digestive system, with high incidence and mortality and poor prognosis. Interferon-gamma (IFN-γ) and long noncoding RNAs (lncRNAs) have prognostic values and were closely associated with immune microenvironment in COAD. Thus, identifying IFN-γ-related lncRNAs may be valuable in predicting the survival of patients with COAD. In this study, we identified IFN-γ-related lncRNAs and divided COAD patients from the Cancer Genome Atlas (TCGA) database into training and validation sets. Pearson's correlation analysis and least absolute shrinkage and selection operator (LASSO) Cox regression were performed to select IFN-γ-related lncRNA-associated prognoses. Thirteen lncRNAs (AC025165.8, AC091633.3, FENDRR, LINC00882, LINC01828, LINC01829, MYOSLID, RP11-154H23.4, RP11-20J15.3, RP11-324L17.1, RP11-342A23.2, RP11-805I24.3, SERTAD4-AS1) were identified to construct an IFN-γ-related lncRNA prognostic signature in TCGA training (n =213) and validation (n =213) cohorts. COAD patient risk scores were calculated and classified into high- and low-risk groups based on the median value of the risk scores in each dataset. We compared the overall survival (OS) of patients stratified by age, gender, and stage. The OS in the high-risk group was significantly shorter than that in the low-risk group. In addition, the clinical nomogram incorporating the prognostic signature and clinical features showed a high concordance index of 0.78 and accurately predicted 1-, 3-, and 5-year survival times among COAD patients in the high- and low-risk groups. Based on the risk model, the high- and low-risk groups exhibited distinct differences in the immune system by gene set enrichment analysis (GSEA) functional annotation, and differentially expressed genes (DEGs) between the high- and low-risk groups were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We investigated the expression of multiple immune checkpoint genes in the high- and low-risk groups and plotted Kaplan-Meier survival curves, indicating that immune checkpoint genes, such as LAG3 and PD. L1, STING and TIM 3, were also expressed differently between the two risk groups. Subsequently, there were dramatic differences in mutated genes, SNV (single nucleotide variants) classes, variant types and variant allele frequencies between low- and high-risk patients with COAD. Patients stratified by risk scores had different sensitivities to common chemotherapeutic agents. Finally, we used quantitative real-time polymerase chain reaction (qRT-PCR) assays to demonstrate that three lncRNAs were significantly differentially expressed in COAD tissues and adjacent normal tissues. Considered together, a thirteen-lncRNA prognostic signature has great potential to be a prognostic biomarker and could play an essential role in the immune microenvironment of COAD.

No significant relationship exists between tumor size and prognosis in distant metastatic hepatocellular carcinoma: a propensity score matching analysis based on SEER database.

BACKGROUND: Previous studies have shown that tumor size has an impact on the prognosis of hepatocellular carcinoma (HCC). Whether tumor size is related to the prognosis of distant metastatic HCC is unclear. The purpose of this study was to investigate the effect of tumor size on the prognosis of distant metastatic HCC. METHODS: Data on patients with HCC were collected from the (SEER) database of surveillance, epidemiology and final results. Propensity score matching (PSM) was used to reduce confounding factors and comprehensively evaluate the clinicopathological features and prognosis of distant metastatic HCC. RESULTS: There were 189 patients with distant metastatic HCC whose tumor size was ≤ 50 mm and 615 patients with a tumor size > 50 mm. The tumor sizes of distant metastatic HCC patients were associated with race, grade, surgical treatment, N and AFP. The Kaplan-Meier analysis showed that the mortality rate of patients with a tumor size > 50 mm was higher than that of patients with a tumor size ≤ 50 mm (p = 0.00062). However, there were no significant differences in mortality rates after adjusting for confounding variables by using propensity score matching (p = 0.23). CONCLUSION: This propensity score matching study provides the best data in support of the following assertions: tumor size is not an independent prognostic factor for distant metastatic HCC.

An infinite life cycle assessment model to re-evaluate resource efficiency and environmental impacts of circular economy systems.

Challenges exist in life cycle assessment (LCA) to evaluate resource efficiency and environmental impacts of circular economy systems. Rules attributing recycling benefits/burdens are inconsistent, causing system boundary ambiguity. Besides, LCAs covering one or several life cycles fail to capture the complete resource path, which leads to unfair assessment results for the primary life cycle. This paper develops an infinite life cycle assessment model, which integrates LCA, substance flow analysis, and a state transition matrix into an infinite-life-cycle framework. On this basis, algorithms are formulated to quantify the resource efficiency and attribute environmental impacts following the principle of whole first, then allocation. Our model is demonstrated by a case study of lead-acid batteries. Results show that the resource efficiency of lead in the infinite life cycle assessment model is at least 118.75% higher than that of primary lead derived from the typical finite life cycle models. Measured by the index of environmental toxicity potential, environmental impacts are transferred from the primary product life cycle to recycled product life cycles, with the range fluctuating from 66.26% to 68.12%. Our model enables scholars to make more reasonable assessments for circular economy systems based on traditional LCA adjustment. From the infinite-life-cycle perspective, sustainable production policies should focus on increasing the recycling rate of waste products rather than limiting the exploitation of natural resources.