Fusobacterium periodonticum BCT protein targeting glucose metabolism to promote the epithelial-mesenchymal transition of esophageal cancer cells by lactic acid.

BACKGROUND: The cancer microbiota was considered the main risk factor for cancer progression. We had proved that Fusobacterium periodonticum (F.p) was higher abundance in Esophageal cancer(EC)tissues. Bioinformation analysis found that BCT was a key virulence protein of F.p. However, little is known about the role and mechanism of BCT in EC. This study aimed to recognize the key virulence protein of F.p and explore the mechanism of BCT in promoting EC. METHODS: We constructed a eukaryotic expression vector and purified the recombinant protein BCT. CCK8 used to analyzed the activity of EC after treated by different concentration of BCT. UPLC-MS/MS and ELISA used to detect the metabonomics and metabolites. The ability of migration and invasion was completed by transwell assay. RT-QPCR, WB used to analyze the expression of relevant genes. RESULTS: Our data showed that BCT was higher expression in EC tumor tissues (p < 0.05) and BCT in 20 µg/mL promoted the survival, invasion and migration of EC cells (EC109) (p < 0.05). Meanwhile, UPLC-MS/MS results suggested that BCT resulted in an augmentation of hypotaurine metabolism, arachidonic acid metabolism, glycolysis/gluconeogenesis, tryptophan metabolism, citrate cycle activity in EC109. The metabolic changes resulted in decreasing in glucose and pyruvate levels but increase in lactate dehydrogenase (LDH) activity and lactic acid (LA) as well as the expression of glucose transporter 1, Hexokinase 2, LDH which regulated the glycolysis were all changed (p < 0.05). The BCT treatment upregulated the expression of TLR4, Akt, HIF-1α (p < 0.05) which regulated the production of LA. Furthermore, LA stimulation promoted the expression of GPR81, Wnt, and ß-catenin (p < 0.05), thereby inducing EMT and metastasis in EC109 cells. CONCLUSION: Altogether, these findings identified that impact of BCT in regulation of glycolysis in EC109 and its involves the TLR4/Akt/HIF-1α pathway. Meanwhile, glycolysis increasing the release of LA and promote the EMT of EC109 by GPR81/Wnt/ß-catenin signaling pathway. In summary, our findings underscore the potential of targeting BCT as an innovative strategy to mitigate the development of EC.

A critical review of advances in tumor metabolism abnormalities induced by nitrosamine disinfection by-products in drinking water.

Intensified sanitation practices amid the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak might result in the increased release of chloramine disinfectants into surface water, significantly promoting the formation of nitrosamine disinfection by-products (DBPs) in drinking water. Unfortunately, these nitrosamine DBPs exhibit significant genotoxic, carcinogenic, and mutagenic properties, whereas chlorinating disinfectants remain in global practice. The current review provides valuable insights into the occurrence, identification, contamination status, exposure limits, and toxicity of the new unregulated disinfection by-products (nitrosamine DBPs) in drinking water. As a result, concentrations of nitrosamine DBPs far exceed allowable limits in drinking water, and prolonged exposure has the potential to cause metabolic disorders, a critical step in tumor initiation and progression. Importantly, based on recent research, we have concluded the role of nitrosamines DBPs in different metabolic pathways. Remarkably, nitrosamine DBPs can induce chronic inflammation and initiate tumors by activating sphingolipid and polyunsaturated fatty acid metabolism. Regarding amino acid and nucleotide metabolism, nitrosamine DBPs can inhibit tryptophan metabolism and de novo nucleotide synthesis. Moreover, inhibition of de novo nucleotide synthesis fails to repair DNA damage induced by nitrosamines. Additionally, the accumulation of lactate induced by nitrosamine DBPs may act as a pivotal signaling molecule in communication within the tumor microenvironment. However, with the advancement of tumor metabolomics, understanding the role of nitrosamine DBPs in causing cancer by inducing metabolic abnormalities significantly lags behind, and specific mechanisms of toxic effects are not clearly defined. Urgently, further studies exploring this promising area are needed.

HMGB1 promotes chemoresistance in small cell lung cancer by inducing PARP1-related nucleophagy.

INTRODUCTION: Small cell lung cancer (SCLC) is prone to chemoresistance, which is closely related to genome homeostasis-related processes, such as DNA damage and repair. Nucleophagy is the elimination of specific nuclear substances by cells themselves and is responsible for maintaining genome and chromosome stability. However, the roles of nucleophagy in tumour chemoresistance have not been investigated. OBJECTIVES: The aim of this work was to elucidate the mechanism of chemoresistance in SCLC and reverse this chemoresistance. METHODS: RNA-seq data from SCLC cohorts, chemosensitive SCLC cells and the corresponding chemoresistant cells were used to discover genes associated with chemoresistance and patient prognosis. In vitro and in vivo experiments were performed to verify the effect of high-mobility group box 1 (HMGB1) knockdown or overexpression on the chemotherapeutic response in SCLC. The regulatory effect of HMGB1 on nucleophagy was then investigated by coimmunoprecipitation (co-IP) and mass spectrometry (MS), and the underlying mechanism was explored using pharmacological inhibitors and mutant proteins. RESULTS: HMGB1 is a factor indicating poor prognosis and promotes chemoresistance in SCLC. Mechanistically, HMGB1 significantly increases PARP1-LC3 binding to promote nucleophagy via PARP1 PARylation, which leads to PARP1 turnover from DNA lesions and chemoresistance. Furthermore, chemoresistance in SCLC can be attenuated by blockade of the PARP1-LC3 interaction or PARP1 inhibitor (PARPi) treatment. CONCLUSIONS: HMGB1 can induce PARP1 self-modification, which promotes the interaction of PARP1 with LC3 to promote nucleophagy and thus chemoresistance in SCLC. HMGB1 could be a predictive biomarker for the PARPi response in patients with SCLC. Combining chemotherapy with PARPi treatment is an effective therapeutic strategy for overcoming SCLC chemoresistance.

Spatiotemporal distribution and ecological risk assessment of pharmaceuticals and personal care products (PPCPs) from Luoma Lake, an important node of the South-to-North Water Diversion Project.

PPCPs (pharmaceuticals and personal care products) are widely found in the environment and can be a risk to human and ecosystem health. In this study, spatiotemporal distribution, critical risk source identification and potential risks of 14 PPCPs found in water collected from sampling points in Luoma Lake and its inflowing rivers in two seasons in 2019 and 2020 were investigated. The PPCPs concentrations ranged from 27.64 ng·L-1 to 613.08 ng·L-1 in December 2019, and from 16.67 ng·L-1 to 3287.41 ng·L-1 in April 2020. Ketoprofen (KPF) dominated the PPCPs with mean concentrations of 125.85 ng·L-1 and 640.26 ng·L-1, respectively. Analysis of sources showed that the pollution in Luoma Lake mostly originated from sewage treatment plant effluents, inflowing rivers and domestic wastewater. Among them, the inflowing rivers contributed the most (82.95%) to the concentration of total PPCPs. The results of ecological risk assessment showed that there was a moderate risk (0.1 < RQs < 1) from carbamazepine (CBZ) in December 2019 and a high risk (RQs > 1) from naproxen (NPX) in April 2020. The results of human risk assessment found that NPX posed a high risk to infant health, and we found that NPX was associated with 83 diseases according to Comparative Toxicogenomics Database. NPX was identified as a substance requiring major attention. The results provide an understanding of the concentrations and ecological risks of PPCPs in Luoma Lake. We believe the data will support environmental departments to develop management strategies and prevent PPCPs pollution.

Pathogens and antibiotic resistance genes during the landfill leachate treatment process: Occurrence, fate, and impact on groundwater.

Landfill leachate is an essential source of pathogens and antibiotic resistance genes (ARGs) in the environment. However, information on the removal behavior of pathogens and ARGs during the leachate treatment and the impact on surrounding groundwater is limited. In this study, we investigated the effects of leachate treatment on the removal of pathogens and ARGs with metagenomic sequencing, as well as the impact of landfill effluent on groundwater. It is shown that the leachate treatment could not completely remove pathogens and ARGs. Twenty-nine additional pathogens and twenty-nine ARGs were newly identified in the landfill effluent. The relative abundance of pathogens and multiple antibiotic resistance genes decreased after ultrafiltration but relative abundance increased after reverse osmosis. In addition, the relative abundances of Acinetobacter baumannii, Erwinia amylovora, Escherichia coli, Fusarium graminearum, Klebsiella pneumoniae, and Magnaporthe oryzae, as well as mdtH, VanZ, and blaOXA-53 increased significantly in the landfill effluent compared to the untreated leachate. The relative abundance of some mobile genetic elements (tniA, tniB, tnpA, istA, IS91) in leachate also increased after ultrafiltration and reverse osmosis. The size of pathogens, the size and properties of ARGs and mobile genetic elements, and the materials of ultrafiltration and reverse osmosis membranes may affect the removal effect of pathogens, ARGs and mobile genetic elements in leachate treatment process. Interestingly, the pathogens and ARGs in landfill effluent were transferred to groundwater according to SourceTracker. The ARGs, mobile genetic elements, and pathogens that are difficult to remove in the leachate treatment process, provide a reference for optimizing the leachate treatment process and improving the control of pathogens and ARGs. Furthermore, this study clarifies the effect of landfill leachate sources of pathogens and ARGs in groundwater.

METTL3 promotes chemoresistance in small cell lung cancer by inducing mitophagy.

BACKGROUND: Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancer. Although most patients are initially sensitive to first-line combination chemotherapy with cisplatin and etoposide, chemotherapy drug resistance easily develops and quickly leads to tumour progression. Therefore, understanding the mechanisms of chemotherapy drug resistance and how to reverse it is key to improving the prognosis of patients with SCLC. Moreover, N6-methyladenosine (m6A) is the most abundant mRNA modification and is catalysed by the methyltransferase complex, in which methyltransferase-like 3 (METTL3) is the sole catalytic subunit. METHODS: The effects of METTL3 on chemoresistance in SCLC cells were determined using qRT-PCR, Western blotting, immunohistochemistry, cell counting kit (CCK-8) assays, flow cytometry, and tumorigenicity experiments. Methylated RNA immunoprecipitation sequencing (MeRIP-seq), MeRIP qPCR, immunofluorescence, and drug inhibitor experiments were performed to confirm the molecular mechanism of Decapping Protein 2 (DCP2), which is involved in the chemoresistance of SCLC. RESULTS: In the present study, we found that METTL3 is a marker for poor SCLC prognosis, and it is highly expressed in chemoresistant SCLC cells. METTL3 promotes SCLC chemoresistance by positively regulating mitophagy. METTL3 induces m6A methylation of DCP2 and causes the degradation of DCP2, which promotes mitochondrial autophagy through the Pink1-Parkin pathway, leading to chemotherapy resistance. We also found that STM2457, a novel METTL3 inhibitor, can reverse SCLC chemoresistance. CONCLUSIONS: The m6A methyltransferase METTL3 regulates Pink1-Parkin pathway-mediated mitophagy and mitochondrial damage in SCLC cells by targeting DCP2, thereby promoting chemotherapy resistance in patients with SCLC.

Lipopolysaccharide exacerbates to the migration, invasion, and epithelial-mesenchymal transition of esophageal cancer cells by TLR4/NF-κB axis.

Previous studies have shown the role of bacterial lipopolysaccharide (LPS) in promoting tumor progression. Our previous study found that the community richness of LPS-producing bacteria was significantly increased in the fresh stool samples of esophageal cancer (EC) patients, but the relative LPS levels and underlying mechanism in EC progression remain unknown. In this study, an case-control study found that the content of LPS was higher in serum of EC patients. Functional experiments of CCK8 assay and transwell assay showed that LPS contributed to the proliferation, migration, invasion of EC109 cells. Meanwhile, LPS induced EC109 to secrete IL-6 and TGF-ß1. Western blot analysis revealed the level of TLR4 and NF-κB increased significantly after LPS treatment. Epithelial marker E-cadherin was significantly down-regulated and interstitial marker N-cadherin and Vimentin were up-regulated after LPS treatment. However, TAK242 (TLR4 inhibitor) or PDTC (NF-κB inhibitor) could eliminate the inflammatory and EMT-promoting effects of LPS. In total, our results suggested that LPS exacerbated to the migration, invasion, and epithelial-mesenchymal transition of EC109 cells by TLR4/NF-κB axis. High level LPS may have a critical effect on the occurrence and development of EC.

Activated Mast Cells Combined with NRF2 Predict Prognosis for Esophageal Cancer.

Background: Esophageal cancer (EC) had the sixth-highest mortality rate of all cancers due to its poor prognosis. Immune cells and mutation genes influenced the prognosis of EC, but their combined effect on predicting EC prognosis was unknown. In this study, we comprehensively analyzed the immune cell infiltration (ICI) and mutation genes and their combined effects for predicting prognosis in EC. Methods: The CIBERSORT and ESTIMATE algorithms were used to analyse the ICI scape based on the TCGA and GEO databases. EC tissues and pathologic sections from Huai'an, China, were used to verify the key immune cells and mutation genes and their interactions. Results: Stromal/immune score patterns and ICI/gene had no statistical significance in overall survival (OS) (p > 0.05). The combination of ICI and tumor mutation burden (TMB) showed that the high TMB and high ICI score group had the shortest OS (p = 0.004). We recognized that the key mutation gene NRF2 was significantly different in the high/low ICI score subgroups (p = 0.002) and positivity with mast cells (MCs) (p < 0.05). Through experimental validation, we found that the MCs and activated mast cells (AC-MCs) were more infiltration in stage II/III (p = 0.032; p = 0.013) of EC patients and that NRF2 expression was upregulated in EC (p = 0.045). AC-MCs combined with NRF2 had a poor prognosis, according to survival analysis (p = 0.056) and interactive analysis (p = 0.032). Conclusions: We presume that NRF2 combined with AC-MCs could be a marker to predict prognosis and could influence immunotherapy through regulating PD-L1 in the EC.

PARP1 controls the transcription of CD24 by ADP-ribosylating the RNA helicase DDX5 in pancreatic cancer.

The PARP1 protein plays a key role in DNA damage repair and ADP-ribosylation to regulate gene expression. Strategies to target PARP1 have rapidly been developed for cancer treatment. However, the role of the innate immune response in targeted anti-PARP1 therapy remains poorly understood. In this work, we aimed to elucidate the regulatory mechanism underlying the immunogenicity of PARP1 and explore efficient therapeutic strategies to enhance the antitumor effect of PARP inhibitors. The relationships between PARP1 expression and immunosuppressive factors were examined by qRTPCR and immunoblot analysis. DNA pull-down, chromatin immunoprecipitation-quantitative PCR (ChIPqPCR) and luciferase reporter assays were employed to reveal the mechanism by which the expression of the immune checkpoint regulator CD24 is regulated by PARP1. Phagocytosis assays and pancreatic cancer animal models were applied to evaluate the therapeutic effect of simultaneous disruption of PARP1 and the antiphagocytic factor CD24. Upregulation of the innate immunosuppressive factor CD24 was observed in pancreatic cancer during PARP1 inhibition. The activating effect of targeting CD24 on macrophage phagocytosis was verified. Then, we showed that PARP1 attenuated the transcription of CD24 by ADP-ribosylating the transcription factor DDX5 in pancreatic cancer. Combined blockade of PARP1 and the antiphagocytic factor CD24 elicited a synergetic antitumor effect in pancreatic cancer. Our research provided evidence that combination treatment with PARP inhibitors and CD24 blocking monoclonal antibodies (mAbs) could be an effective strategy to improve the clinical therapeutic response in pancreatic cancer.

CEOs' Financial Background and Non-financial Enterprises' Shadow Banking Business.

In recent years, the "financial-like" behavior of non-financial enterprises has contributed to the "off real to virtual," which has seriously restricted the virtuous cycle of finance and economy. This study selects non-financial enterprises listed on Chinese A-shares from 2008 to 2019 as the research sample, and empirically analyzes the impact of CEOs' financial background (FB) on the shadow banking business of non-financial enterprises and its mechanism. The results show that: (1) CEOs' FB has a positive effect on shadow banking business of non-financial enterprises; among which, the positive effect generated by non-banking FB is stronger. The conclusions still hold after robustness tests by replacing the measurement of variables, controlling for other shocks, changing the parameter estimation method, and considering the endogeneity problem. (2) The mechanism analysis reveals the positive effect mainly by reducing the level of entity investment by enterprises. (3) The heterogeneity analysis finds that, on the one hand, with respect to the internal micro characteristics of enterprises, the positive effect is more significant in state-owned enterprises, non-manufacturing enterprises, and non-growth stage enterprises. On the other hand, with respect to the external macro environment, the positive effect is more significant in periods of easy monetary policy, in industries with a higher competition or in regions with a better institutional environment. This study reveals the intrinsic mechanism of CEOs' FB and non-financial enterprises' shadow banking business, enriches the study of the influencing factors of non-financial enterprises' shadow banking business, and provides micro-level empirical support to alleviate the "off real to virtual" of the economy.

Seasonal variability of the correlation network of antibiotics, antibiotic resistance determinants, and bacteria in a wastewater treatment plant and receiving water.

Sewage treatment plants are an essential source of antibiotics, antibiotic resistance determinants, and bacteria in environmental waters. However, it is still unclear whether they can maintain a relatively stable relationship in wastewater and environmental waters. This study analyzed the removal capacity of the above three pollutants in the sewage treatment plant in summer and their impact on environmental waters, and then examines the relationship between the three contaminants in the wastewater and environmental waters in summer and winter based on our previous study. The results found that the removal capacity of bacteria in summer was poor, the concentration of fluoroquinolone in the effluent was higher than that in influent, and the abundance of intI1, tetW, qnrB, and ermB increased after wastewater treatment. Proteobacteria and Bacteroides were the main bacteria that constitute the correlation network between bacteria, and they existed stably in summer and winter. However, fluoroquinolones occupied a significant position in the determinant network of antibiotics and antibiotic resistance in summer and winter. There are fewer correlation between antibiotics and antibiotics resistance determinants in winter. Interestingly, the relationship between bacteria, antibiotics, and antibiotic resistance determinants was a mainly positive correlation in summer and negative correlation in winter. This study analyzed the relationship between bacteria, antibiotics, and antibiotic resistance determinants that were stable in the wastewater and environmental waters and pointed out the direction for subsequent targeted seasonal control of novel pollutants in wastewater and environmental waters.

NRBF2 regulates the chemoresistance of small cell lung cancer by interacting with the P62 protein in the autophagy process.

Reversing chemotherapy resistance in small cell lung cancer (SCLC) is crucial to improve patient prognosis. The present study aims to investigate the underlying mechanisms in SCLC chemoresistance. We see that nuclear receptor binding factor 2 (NRBF2) is a poor prognostic factor in SCLC. The effects of NRBF2 on chemoresistance were determined in SCLC. The underlying molecular mechanisms of NRBF2 in the autophagy process in SCLC were examined. NRBF2 positively regulated autophagy, leading to drug resistance in SCLC. The MIT domain of NRBF2 directly interacted with the PB1 domain of P62. This interaction increased autophagic P62 body formation, revealing the regulatory role of NRBF2 in autophagy. Notably, NRBF2 was directly modulated by the transcription factor XRCC6. The MIT domain of NRBF2 interacts with the PB1 domain of P62 to regulate the autophagy process, resulting in SCLC chemoresistance. NRBF2 is likely a useful chemotherapy response marker and therapeutic target in SCLC.

THSD7B Mutation Induces Platinum Resistance in Small Cell Lung Cancer Patients.

Aim: Several cases of small cell lung cancer (SCLC) patients demonstrate resistance to the treatment initiatives such as cisplatin after platinum chemotherapy. It is crucial to the improvement of the overall survival (OS) of SCLC patients to discover the gene mutation inducing platinum resistance within this cohort. Patients and Methods: We analyzed the gene mutations significantly associated with the OS from 2 cohorts of SCLC platinum-treated patients. And then we screened out THSD7B mutation. In order to understand the mechanism between THSD7B mutation and platinum resistance, we designed gene mutation co-occurrence and mutual exclusivity analysis, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) analysis, and Connectivity Map (CMap) analysis. Results: The poor prognosis of THSD7B mutant patients may be related to the inhibition of cell death-related pathways, the up-regulation of cell invasion and metastasis pathways, and the down-regulation of immune response pathways. Lovastatin and cyclooxygenase inhibitors could be used as potential target compounds in THSD7B mutant patients, which provides reference for future research on platinum resistance. Conclusion: THSD7B can be considered a reliable biomarker that effectively facilitates the prediction of poor survival in SCLC platinum-treated patients.

Occurrence and distribution of antibiotics in coastal water of the Taizhou Bay, China: impacts of industrial activities and marine aquaculture.

The occurrence, spatial distribution, and source analysis of antibiotics in global coastal waters and estuaries are not well documented or understood. Therefore, the distribution of 14 antibiotics in inflowing river and bay water of Taizhou Bay, East China Sea, was studied. Thirteen antibiotics, excluding roxithromycin (ROM), were all detected in inflowing river and bay water. The total antibiotic concentrations in bay water ranged from 3126.62 to 26,531.48 ng/L, which were significantly higher than those in the inflowing river (17.20-25,090.25 ng/L). Macrolides (MAs) and sulfonamides (SAs) were dominant in inflowing river (accounting for 24.40% and 74.9% of the total antibiotic concentrations, respectively), while SAs in bay water (93.6% of the total concentrations). Among them, clindamycin (CLI) (concentration range: ND-8414 ng/L, mean 1437.59 ng/L) and sulfadimidine (SMX) (ND-25,184.00 ng/L, mean concentrations: 9107.88 ng/L) were the highest in those surface water samples. Source analysis showed that MAs and SAs in the inflowing river mainly came from the wastewater discharge of the surrounding residents and pharmaceutical companies, while SAs in the bay water mainly came from surrounding industrial activities and mariculture. However, the contribution of the inflowing river to the bay water cannot be ignored. The risk assessment showed that SMX and ofloxacin (OFX) have potential ecological risks. These data will support the various sectors of the environment in developing management strategies and to prevent antibiotic pollution.

Identification of tissue-specific microbial profile of esophageal squamous cell carcinoma by full-length 16S rDNA sequencing.

It was previously believed that the microbial community in the esophagus was relatively stable, but it has been reported that different esophageal diseases have different microbial community characteristics. In this study, we recruited patients with esophageal squamous cell carcinoma (ESCC) and collected 51 pairs of tumor and adjacent non-tumor tissues for full-length 16S rDNAsequencing and qPCR to compare the differences in microbial community structure. The results of sequencing in 19 pairs of tissues showed that Proteobacteria, Firmicutes, Bacteroidetes, Deinococcus-Thermus, and Actinobacteria were the main bacteria in tumor and adjacent non-tumor tissues. At the genus level, the bacteria with the highest relative proportion in tumor and adjacent non-tumor tissues were Streptococcus and Labrys, respectively. At the same time, it was observed that the complexity of microbial interactions in tumor tissues was weaker than that of adjacent non-tumor tissues. The results also found that the relative abundance of 24 taxa was statistically different between tumor and adjacent non-tumor tissues. The findings of qPCR in 32 pairs of tissues further evidence that the relative proportions of Blautia, Treponema, Lactobacillus murinus, Peptoanaerobacter stomatis, and Fusobacteria periodonticum were statistically different in tumor and adjacent non-tumor tissues. The findings of PIRCUSt2 indicated the lipopolysaccharide biosynthesis and biotin metabolism in the microbiome of cancer tissues are more significant. This study supplements the existing information on the structure, function, and interaction of microorganisms in the esophagus in situ and provides a direction for the further exploration of the relationship between esophageal in situ microorganisms and esophageal squamous cell carcinoma. KEY POINTS: • The structure of the microbial community in esophageal cancer tissue and adjacent non-tumor tissues at the phylum level is similar • Streptococcus and Labrys are the most important bacteria in esophageal tumor tissues and adjacent non-tumor tissues, respectively • Microbial interactions in tumor tissues are stronger than in adjacent non-tumor tissues.

The Effect of Smoking on the Immune Microenvironment and Immunogenicity and Its Relationship With the Prognosis of Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer.

Background: The emergence of immune checkpoint inhibitors (ICIs) has opened a new chapter for the treatment of non-small cell lung cancer (NSCLC), and the best beneficiaries of ICI treatment are still being explored. Smoking status has been repeatedly confirmed to affect the efficacy of ICIs in NSCLC patients, but the specific mechanism is still unclear. Methods: We performed analysis on the Memorial Sloan Kettering Cancer Center (MSKCC) clinical NSCLC cohort receiving ICI treatment, The Cancer Genome Atlas (TCGA) Pan-Lung Cancer cohort, and Gene Expression Omnibus (GEO) database GSE41271 lung cancer cohort that did not receive ICI treatment, including survival prognosis, gene mutation, copy number variation, immunogenicity, and immune microenvironment, and explored the impact of smoking status on the prognosis of NSCLC patients treated with ICIs and possible mechanism. In addition, 8 fresh NSCLC surgical tissue samples were collected for mass cytometry (CyTOF) experiments to further characterize the immune characteristics and verify the mechanism. Result: Through the analysis of the clinical data of the NSCLC cohort treated with ICIs in MSKCC, it was found that the smokers in NSCLC receiving ICI treatment had a longer progression-free survival (HR: 0.69, 95% CI: 0.49-0.97, p = 0.031) than those who never smoked. Further analysis of the TCGA and GEO validation cohorts found that the differences in prognosis between different groups may be related to the smoking group's higher immunogenicity, higher gene mutations, and stronger immune microenvironment. The results of the CyTOF experiment further found that the immune microenvironment of smoking group was characterized by higher expression of immune positive regulatory chemokine, and higher abundance of immune activated cells, including follicular helper CD4+ T cells, gamma delta CD4+ T cells, activated DC, and activated CD8+ T cells. In contrast, the immune microenvironment of non-smoking group was significantly enriched for immunosuppressive related cells, including regulatory T cells and M2 macrophages. Finally, we also found highly enriched CD45RAhighCD4+ T cells and CD45RAhighCD8+ T cells in the non-smoking group. Conclusion: Our research results suggest that among NSCLC patients receiving ICI treatment, the stronger immunogenicity and activated immune microenvironment of the smoking group make their prognosis better.

Association of gut microbiomes with lung and esophageal cancer: a pilot study.

Gut microbiota, especially human pathogens, has been shown to be involved in the occurrence and development of cancer. Esophageal squamous cell carcinoma and lung cancer are two malignant cancers, and their relationship with gut microbiota is still unclear. Virulence factor database (VFDB) is an integrated and comprehensive online resource for curating information about human pathogens. Here, based on VFDB database, we analyzed the differences of bacteria at genus level in the gut of patients with esophageal squamous cell carcinoma, lung cancer, and healthy controls. We proposed the possible cancer-associated bacteria in gut and put forward their possible effects. Apart from this, principal coordinate analysis (PCoA) and analysis of similarities (ANSOIM) suggested that some bacteria in the gut can be used as potential biomarkers to screen esophageal squamous cell carcinoma and lung cancer, and their effectiveness was preliminary verified. The relative abundance of Klebsiella and Streptococcus can be used to distinguish patients with esophageal squamous cell carcinoma and lung cancer from healthy controls. The absolute abundance of Klebsiella can further distinguish patients with esophageal squamous cell carcinoma from patients with lung cancer. In particular, the relative abundance of Fusobacterium can directly distinguish between patients with esophageal squamous cell carcinoma and healthy controls. Additionally, the absolute abundance of Haemophilus can distinguish lung cancer from healthy controls. Our study provided a new way based on VFDB database to explore the relationship between gut microbiota and cancer, and initially proposed a feasible cancer screening method.

Occurrence of antibiotics and antibiotic resistance genes and their correlations in river-type drinking water source, China.

The occurrence and distribution of antibiotics and antibiotic resistance genes (ARGs) in natural water has attracted worldwide attention. Antibiotic and ARG pollution in the surface water of drinking water sources might directly/indirectly affect human health. In this study, the distribution of 38 antibiotics, 10 ARGs, 2 integrons, and 16S r DNA in river-type water sources in a large city of China were monitored in winter, which was a period with high level of antibiotic pollution. The results showed that 20 antibiotics were detected with different detection frequencies. The antibiotic pollution in December 2019 was relatively high, with the total concentrations of antibiotics ranging from 281.95 to 472.42 ng/L, followed by that in January 2020 (191.70-337.29 ng/L) and November 2019 (161.25-309.72 ng/L). Sulfacetamide was dominant in November 2019 (23.52-219.00 ng/L) and in January 2020 (113.18-209 ng/L), while norfloxacin in December 2019 (146.72-290.20 ng/L). All the target antibiotics posed low or medium risk for aquatic organisms, and posed low health risk for mankind. Sul1 and erm36 were the predominant ARGs, and intI1 was the predominant integron in drinking water sources. Only tetA showed positive correlations with its corresponding antibiotic (tetracycline). The rest of ARGs showed no correlations with antibiotics or positive / negative correlations with their non-corresponding antibiotics. Overall, the antibiotics and ARG pollution in these water sources was relatively low. These findings provided some reference data for the distribution of antibiotics and ARGs in river-type drinking water sources of large cities in China.

CAMSAP1 Mutation Correlates With Improved Prognosis in Small Cell Lung Cancer Patients Treated With Platinum-Based Chemotherapy.

Platinum-based chemotherapy is the first-line treatment for small cell lung cancer (SCLC). However, due to patients developing a resistance to the drug, most experience relapse and their cancer can become untreatable. A large number of recent studies have found that platinum drug sensitivity of various cancers is affected by specific gene mutations, and so with this study, we attempted to find an effective genetic biomarker in SCLC patients that indicates their sensitivity to platinum-based drugs. To do this, we first analyzed whole exome sequencing (WES) and clinical data from two cohorts to find gene mutations related to the prognosis and to the platinum drug sensitivity of SCLC patients. The cohorts used were the Zhujiang cohort (N = 138) and the cohort reported by George et al. (N = 101). We then carried out gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) to investigate possible molecular mechanisms through which these gene mutations affect patient prognosis and platinum drug sensitivity. We found that for SCLC patients, CAMSAP1 mutation can activate anti-tumor immunity, mediate tumor cell apoptosis, inhibit epithelial-mesenchymal transition (EMT), improve prognosis, and improve platinum drug sensitivity, suggesting that CAMSAP1 mutation may be a potential biomarker indicating platinum drug sensitivity and patient prognosis in SCLC.

Food intake and its effect on the species and abundance of intestinal flora in colorectal cancer and healthy individuals.

BACKGROUND/AIM: It is known that an imbalance in the intestinal f lora plays a crucial role in colorectal cancer (CRC), but the effect of food consumption patterns on the types of intestinal flora remains to be clarified. We aimed to analyze the associations between food intake and intestinal flora in healthy and CRC individuals. METHODS: Food intake data were recorded using the Food Frequency Questionnaire (FFQ). The composition and diversity of the intestinal flora detected by 16S rRNA gene sequencing, and the data were analyzed by R version 3.1.1 software. RESULTS: Higher intake of red meat or pickled foods, and lower intake of white meat, fruits, vegetables, beans, nuts were found in the CRC group compared with the healthy group. Higher levels of Fusobacteria and Proteobacteria, and lower levels of Firmicutes were observed in the CRC group. Partial correlation analysis revealed that the intake of fruits, beans, and nuts was negatively correlated with Proteobacteria and Fusobacteria, but pickled food was positively correlated with Fusobacteria (p < 0.05). Fish, beans, and nuts intake was negatively correlated with Escherichia (p = 0.01). Multiple regression analysis revealed that vegetable oil (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.13 to 0.82), vegetables (OR, 0.26; 95% CI, 0.10 to 0.64), eggs (OR, 0.26; 95% CI, 0.10 to 0.69), pickled foods (OR, 21.02; 95% CI, 6.02 to 73.45), and red meat (OR, 4.23; 95% CI, 1.68 to 10.60) had an impact on CRC risk. CONCLUSION: The species and abundance of intestinal flora varies between CRC and healthy individuals and may be affected by their food preference.