Background and Aim
Patients with cholelithiasis (CL) or cholecystectomy (CE) would have more chances of getting colorectal adenoma (CRA) or cancer (CRC). We aimed to figure out the effects of gut ...microbiota and bile acid on colorectal neoplasm in CL and CE patients.
Methods
This was a retrospective observational study that recruited 514 volunteers, including 199 people with normal gallbladders (normal), 152 CL, and 163 CE patients. Discovery cohort was established to explore the difference in gut microbiota through 16S rRNA and metagenomics sequencing. Validation cohort aimed to verify the results through quantitative polymerase chain reaction (qPCR).
Results
Significant enrichment of Escherichia coli was found in patients with cholelithiasis or cholecystectomy both in the discovery cohort (16S rRNA sequencing, PNormal‐CL = 0.013, PNormal‐CE = 0.042; metagenomics sequencing, PNormal‐CE = 0.026) and validation cohort (PNormal‐CL < 0.0001, PNormal‐CE < 0.0001). Pks+ E. coli was found enriched in CL and CE patients through qPCR (in discovery cohort: PNormal‐CE = 0.018; in validation cohort: PNormal‐CL < 0.0001, PNormal‐CE < 0.0001). The differences in bile acid metabolism were found both through Tax4Fun analysis of 16S rRNA sequencing (Ko00120, primary bile acid biosynthesis, PNormal‐CE = 0.014; Ko00121, secondary bile acid biosynthesis, PNormal‐CE = 0.010) and through metagenomics sequencing (map 00121, PNormal‐CE = 0.026). The elevation of serum total bile acid of CE patients was also found in validation cohort (PNormal‐CE < 0.0001). The level of serum total bile acid was associated with the relative abundance of pks+ E. coli (r = 0.1895, P = 0.0012).
Conclusions
E. coli, especially pks+ species, was enriched in CL and CE patients. Pks+ E. coli and bile acid metabolism were found associated with CRA and CRC in people after cholecystectomy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background and Aim
Microbial dysbiosis is involved in the development of colorectal cancer and its most common precancerous lesion, colorectal adenoma. Endoscopic resection is one of the procedures ...for primary prevention of colorectal cancer, yet little is known about how the endoscopic therapy influences gut microbiota.
Methods
We conducted a prospective study of 20 patients who underwent endoscopic resection of colorectal adenoma and analyzed the fecal microbiota before and 3 months after adenoma resection. MiSeq sequencing of 16S rRNA genes was performed to determine the alterations in microbial diversity and structure. To discriminate the microbiota of the two groups, random forest and receiver operating characteristic analysis were applied, and a genus‐based microbiota signature was obtained.
Results
Despite few alterations in overall microbial structure after adenoma resection, the abundance of Parabacteroides revealed a significant increase postoperatively (3.8% vs 1.5%, 0.1160), and the microbiota signature of Parabacteroides, Streptococcus, and Ruminococcus showed an optimal discriminating performance of postoperative status with the area under the curve 0.788, P < 0.001.
Conclusion
Fecal microbial alterations indicate the moderate influence of adenoma resection on gut microbiota and lay the groundwork for microbial prediction of adenoma recurrence. Larger sample studies are further required to validate the findings.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background and Aim
Fusobacterium nucleatum is increasingly being recognized as an important risk factor in colorectal cancer and colorectal adenoma. Endoscopic polypectomy is associated with a ...decreased incidence of colorectal cancer; however, patients still suffer from a risk of metachronous adenoma. Currently, there are few effective non‐invasive factors that may predict metachronous colorectal adenoma. Here, we evaluated the performance of F. nucleatum in predicting metachronous adenoma.
Methods
Fecal samples and clinical information of patients before endoscopic polypectomy were collected from 367 patients in a retrospective cohort, and 238 patients in a prospective cohort. The abundance of fecal F. nucleatum was measured via quantitative polymerase chain reaction. Surveillance colonoscopies were conducted between 1 and 3 years after polypectomy (average follow‐up 27.07 months for the retrospective cohort & 22.57 months for the prospective cohort) to identify metachronous adenoma. Candidate predictive factors and cut‐off value of F. nucleatum abundance were identified from the retrospective cohort and then validated in the prospective cohort.
Results
A high abundance of fecal F. nucleatum was found to be an independent risk factor for metachronous adenomas (odds ratio, 6.38; P < 0.001) in the retrospective cohort and was validated in the prospective cohort with a specificity of 65.00%, and a sensitivity of 73.04%, and an overall performance with the area under the curve of 0.73.
Conclusion
Fecal abundance of F. nucleatum may be a reliable predictor for metachronous adenoma after endoscopic polypectomy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Colorectal cancer (CRC) incidence has increased among patients aged <50 years. Exploring high-risk factors and screening high-risk populations may help lower early-onset CRC (EO-CRC) incidence. We ...developed noninvasive predictive models for EO-CRC and investigated its risk factors.
This retrospective multicenter study collected information on 1756 patients (811 patients with EO-CRC and 945 healthy controls) from two medical centers in China. Sociodemographic features, clinical symptoms, medical and family history, lifestyle, and dietary factors were measured. Patients from one cohort were randomly assigned (8:2) to two groups for model establishment and internal validation, and another independent cohort was used for external validation. Multivariable logistic regression, random forest, and eXtreme Gradient Boosting (XGBoost) were performed to establish noninvasive predictive models for EO-CRC. Some variables in the model influenced EO-CRC occurrence and were further analyzed. Multivariable logistic regression analysis yielded adjusted odd ratios (ORs) and 95% confidence intervals (CIs).
All three models showed good performance, with areas under the receiver operator characteristic curves (AUCs) of 0.82, 0.84, and 0.82 in the internal and 0.78, 0.79, and 0.78 in the external validation cohorts, respectively. Consumption of sweet (OR 2.70, 95% CI 1.89-3.86, P < 0.001) and fried (OR 2.16, 95% CI 1.29-3.62, P < 0.001) foods ≥3 times per week was significantly associated with EO-CRC occurrence.
We established noninvasive predictive models for EO-CRC and identified multiple nongenetic risk factors, especially sweet and fried foods. The model has good performance and can help predict the occurrence of EO-CRC in the Chinese population.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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•Sorption/desorption of Avermectin B1a and derivatives by three soils and HA were investigated.•13C NMR and PCA revealed the positive correlation of N-alkyl/O-alkyl carbon on the ...sorption.•Aliphatic/aromatic carbon showed a negative correlation on sorption.•Polar functional group of HA is the main sorption site for Avermectin B1a and derivatives.•H-bonding is the main mechanism of pesticide sorption by HA.
Sorption is the key process that regulates the dispersion of pesticides in the environment once they are introduced into the soil. However, the relationship between the molecular structures of these compounds and the sorption mechanism needs to be further clarified. Our objectives were to uncover sorption drivers in distinct soil samples for the parent avermectin B1a (–OH:3) and pharmacophore-altered derivatives derivative-1 (–OH:2) and derivative-2 (–OH:1) series. Avermectin B1a sorption to soil was extensive and essentially irreversible, with avermectin B1a exhibiting significantly greater sorption than the derivatives. The sorption difference between avermectin B1a and derivatives in soil suggested that –OH pharmacophore was the main sorption site for avermectin B1a in soil. Further sorption tests on avermectin B1a and derivatives were carried out on humic acid fractions (HA1 and HA2) that we extracted from the soil. Avermectin B1a sorbed most extensively to humic acid fractions, followed by derivative-1 and derivative-2, thereby indicating the –OH pharmacophore remains the main site for the sorption of avermectin B1a and derivatives by the humic acid fractions. The HA1 fraction showed significantly greater sorption of the compound than the HA2 fraction. Elemental analysis and 13C NMR analysis demonstrated that the HA1 fraction contains more polar functional groups than the HA2 fraction. This suggests that the sorption of avermectin B1a and derivatives by the soil is due to the interaction between the –OH pharmacophore and the polar functional groups in the humic acid, implying that hydrogen bonding may be the main sorption mechanism. This study highlighted the potential sorption mechanisms of pharmacophores in pesticide compounds with humic acid fractions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Plant invasion and water eutrophication severely damage wetland plant growth. However, the effects of plant invasion and water nutrient levels on the growth of submerged plants with different leaf ...types remain unclear. Here, we conducted a greenhouse experiment with three
Eichhornia crassipes
(Mart.) invasion intensity levels, two water nutrient levels, and three planting models (the flat-leaf plant
Hydrilla verticillata
(L.f.) Royle alone, the needle-leaf plant
Myriophyllum verticillatum
L. alone, and a mixture two species). Under the single planting mode, the biomass of
H. verticillata
increased, while that of
M. verticillatum
decreased with increasing water nutrient levels. Moreover, the submerged plant interspecific relationship changed from promotion to competition as the invasion intensity increased. Structural equation modeling showed that invasion intensity and water nutrient level had significant negative and positive effects on
H. verticillata
growth, respectively, but did not significantly affect
M. verticillatum
. Our findings highlight that
H. verticillata
(the needle-leaf plant) was more sensitive to invasion intensity and water nutrient levels than
M. verticillatum
(the flat-leaf plant), and the growth of
H. verticillata
was significantly inhibited by invasion intensity but benefited from more water nutrients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Genetic introgression not only provides material for adaptive evolution but also confounds our understanding of evolutionary history. This is particularly true for canids, a species complex in which ...genome sequencing and analysis has revealed a complex history of admixture and introgression. Here, we sequence 19 new whole genomes from high-altitude Tibetan and Himalayan wolves and dogs and combine these into a larger data set of 166 whole canid genomes. Using these data, we explore the evolutionary history and adaptation of these and other canid lineages. We find that Tibetan and Himalayan wolves are closely related to each other, and that ∼39% of their nuclear genome is derived from an as-yet-unrecognized wolf-like lineage that is deeply diverged from living Holarctic wolves and dogs. The EPAS1 haplotype, which is present at high frequencies in Tibetan dog breeds and wolves and confers an adaptive advantage to animals living at high altitudes, was probably derived from this ancient lineage. Our study underscores the complexity of canid evolution and demonstrates how admixture and introgression can shape the evolutionary trajectories of species.
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•The Ni@Fe/NC shows good activity and selectivity for cleaving C-O bond in lignin.•NiFe alloy is formed in the catalyst which plays a crucial role in hydrogenolysis.•Aromatics ...especially guaiacols are dominant products from hydrogenolysis of lignin.•Possible reaction pathways based on hydrogenolysis of BPE and lignin were proposed.
The utilization of lignin to produce high value-added chemicals is conducive to alleviating the fossil energy crisis. Herein, Ni nanoparticles supported on iron/nitrogen co-doped carbon was prepared by co-pyrolysis and solvothermal reduction method for catalytic hydrogenolysis (CH) of dealkaline lignin and its model compounds. The catalysts were prepared under different calcination temperature, N/C ratio and Ni loading, and the optimal catalyst was Ni10%@Fe/NC0.33–800 (calcination temperature: 800 °C, N/C ratio: 0.33, Ni loading: 10%) based the on the CH of benzyl phenyl ether (BPE). Ni10%@Fe/NC0.33–800 showed good catalytic performance on the selective cleavage of C-O bond of lignin and its model compounds. The BPE conversion reached up to 97.7% over Ni10%@Fe/NC0.33–800 under mild conditions (230 °C, 1 MPa H2, and 0.5 h) with toluene and cyclohexanol as major products. Catalyst characterizations suggest that N content affects the formation of NiFe alloy and the synergistic effect between Ni and Fe plays an important role in CH of BPE. Moreover, Ni10%@Fe/NC0.33–800 could promote the cleavage of C-O bonds in dealkaline lignin through CH and hence enhance producing aromatics such as phenols, aromatic ethers, and aromatic esters, among which phenols are the main aromatics with guaiacols predominant.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa.
This was an ...observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort.
Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test Sa∪Sc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and Sa∪Sc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and Sa∪Sc: 64.0% vs 73.4%). Fecal signature Sa∪Sc outperformed Sa∪CEA/Sc∪CEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of Sa∪Sc in the diagnosis of both early and advanced GCa was verified in the validation cohort.
Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).
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Fecal Streptococcus anginosus and Streptococcus constellatus are noninvasive, accurate, and sensitive signatures in screening and early warning of gastric cancer, particularly at the early stage, with potential implications for gastric cancer prevention.
Colorectal carcinoma (CRC) is the second most deadly cancer worldwide. Therapies that take advantage of DNA repair defects have been explored in various tumors but not yet systematically in CRC. ...Here, we found that Diphosphoinositol Pentakisphosphate Kinase 2 (PPIP5K2), an inositol pyrophosphate kinase, was highly expressed in CRC and associated with a poor prognosis of CRC patients. In vitro and in vivo functional studies demonstrated that PPIP5K2 could promote the proliferation and migration ability of CRC cells independent of its inositol pyrophosphate kinase activity. Mechanically, S1006 dephosphorylation of PPIP5K2 could accelerate its dissociation with 14-3-3 in the cytoplasm, resulting in more nuclear distribution. Moreover, DNA damage treatments such as doxorubicin (DOX) or irradiation (IR) could induce nuclear translocation of PPIP5K2, which subsequently promoted homologous recombination (HR) repair by binding and recruiting RPA70 to the DNA damage site as a novel scaffold protein. Importantly, we verified that S1006 dephosphorylation of PPIP5K2 could significantly enhance the DNA repair ability of CRC cells through a series of DNA repair phenotype assays. In conclusion, PPIP5K2 is critical for enhancing the survival of CRC cells via facilitating DNA HR repair. Our findings revealed an unrecognized biological function and mechanism model of PPIP5K2 dependent on S1006 phosphorylation and provided a potential therapeutic target for CRC patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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