ESRP1-mediated biogenesis of circPTPN12 inhibits hepatocellular carcinoma progression by PDLIM2/ NF-κB pathway.

BACKGROUND: Emerging evidence indicates the pivotal involvement of circular RNAs (circRNAs) in cancer initiation and progression. Understanding the functions and underlying mechanisms of circRNAs in tumor development holds promise for uncovering novel diagnostic indicators and therapeutic targets. In this study, our focus was to elucidate the function and regulatory mechanism of hsa-circ-0003764 in hepatocellular carcinoma (HCC). METHODS: A newly discovered hsa-circ-0003764 (circPTPN12) was identified from the circbase database. QRT-PCR analysis was utilized to assess the expression levels of hsa-circ-0003764 in both HCC tissues and cells. We conducted in vitro and in vivo experiments to examine the impact of circPTPN12 on the proliferation and apoptosis of HCC cells. Additionally, RNA-sequencing, RNA immunoprecipitation, biotin-coupled probe pull-down assays, and FISH were employed to confirm and establish the relationship between hsa-circ-0003764, PDLIM2, OTUD6B, P65, and ESRP1. RESULTS: In HCC, the downregulation of circPTPN12 was associated with an unfavorable prognosis. CircPTPN12 exhibited suppressive effects on the proliferation of HCC cells both in vitro and in vivo. Mechanistically, RNA sequencing assays unveiled the NF-κB signaling pathway as a targeted pathway of circPTPN12. Functionally, circPTPN12 was found to interact with the PDZ domain of PDLIM2, facilitating the ubiquitination of P65. Furthermore, circPTPN12 bolstered the assembly of the PDLIM2/OTUD6B complex by promoting the deubiquitination of PDLIM2. ESRP1 was identified to bind to pre-PTPN12, thereby fostering the generation of circPTPN12. CONCLUSIONS: Collectively, our findings indicate the involvement of circPTPN12 in modulating PDLIM2 function, influencing HCC progression. The identified ESRP1/circPTPN12/PDLIM2/NF-κB axis shows promise as a novel therapeutic target in the context of HCC.

Characterization of metallothionein genes from Broussonetia papyrifera: metal binding and heavy metal tolerance mechanisms.

BACKGROUND: Broussonetia papyrifera is an economically significant tree with high utilization value, yet its cultivation is often constrained by soil contamination with heavy metals (HMs). Effective scientific cultivation management, which enhances the yield and quality of B. papyrifera, necessitates an understanding of its regulatory mechanisms in response to HM stress. RESULTS: Twelve Metallothionein (MT) genes were identified in B. papyrifera. Their open reading frames ranged from 186 to 372 bp, encoding proteins of 61 to 123 amino acids with molecular weights between 15,473.77 and 29,546.96 Da, and theoretical isoelectric points from 5.24 to 5.32. Phylogenetic analysis classified these BpMTs into three subclasses: MT1, MT2, and MT3, with MT2 containing seven members and MT3 only one. The expression of most BpMT genes was inducible by Cd, Mn, Cu, Zn, and abscisic acid (ABA) treatments, particularly BpMT2e, BpMT2d, BpMT2c, and BpMT1c, which showed significant responses and warrant further study. Yeast cells expressing these BpMT genes exhibited enhanced tolerance to Cd, Mn, Cu, and Zn stresses compared to control cells. Yeasts harboring BpMT1c, BpMT2e, and BpMT2d demonstrated higher accumulation of Cd, Cu, Mn, and Zn, suggesting a chelation and binding capacity of BpMTs towards HMs. Site-directed mutagenesis of cysteine (Cys) residues indicated that mutations in the C domain of type 1 BpMT led to increased sensitivity to HMs and reduced HM accumulation in yeast cells; While in type 2 BpMTs, the contribution of N and C domain to HMs' chelation possibly corelated to the quantity of Cys residues. CONCLUSION: The BpMT genes are crucial in responding to diverse HM stresses and are involved in ABA signaling. The Cys-rich domains of BpMTs are pivotal for HM tolerance and chelation. This study offers new insights into the structure-function relationships and metal-binding capabilities of type-1 and - 2 plant MTs, enhancing our understanding of their roles in plant adaptation to HM stresses.

Morphological variation and expressed sequence tags-simple sequence repeats-based genetic diversity of Aspergillus cristatus in Chinese dark tea.

Introduction: Aspergillus cristatus is a homothallic fungus that is used in the natural fermentation process of Chinese Fuzhuan tea and has been linked to the production of bioactive components. However, not much is known about the variations present in the fungus. To understand the variation of the dominant microorganism, A. cristatus, within dark tea, the present study investigated the genetic and morphological diversity of 70 A. cristatus collected across six provinces of China. Methods: Expressed sequence tags-simple sequence repeats (EST-SSR) loci for A. cristatus were identified and corresponding primers were developed. Subsequently, 15 specimens were selected for PCR amplification. Results: The phylogenetic tree obtained revealed four distinct clusters with a genetic similarity coefficient of 0.983, corresponding to previously identified morphological groups. Five strains (A1, A11, B1, D1, and JH1805) with considerable differences in EST-SSR results were selected for further physiological variation investigation. Microstructural examinations revealed no apparent differentiation among the representative strains. However, colony morphology under a range of culture media varied substantially between strains, as did the extracellular enzymatic activity (cellulase, pectinase, protease, and polyphenol oxidase); the data indicate that there are differences in physiological metabolic capacity among A. cristatus strains. Discussion: Notably, JH1805, B1, and A11 exhibited higher enzymatic activity, indicating their potential application in the production of genetically improved strains. The findings provide valuable insights into species identification, genetic diversity determination, and marker-assisted breeding strategies for A. cristatus.

PIN1 promotes the metastasis of cholangiocarcinoma cells by RACK1-mediated phosphorylation of ANXA2.

BACKGROUND: Cholangiocarcinoma (CCA), a primary hepatobiliary malignancy, is characterized by a poor prognosis and a lack of effective treatments. Therefore, the need to explore novel therapeutic approaches is urgent. While the role of Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (PIN1) has been extensively studied in various tumor types, its involvement in CCA remains poorly understood. METHODS: In this study, we employed tissue microarray (TMA), reverse transcription-polymerase chain reaction (RT-PCR), and The Cancer Genome Atlas (TCGA) database to assess the expression of PIN1. Through in vitro and in vivo functional experiments, we investigated the impact of PIN1 on the adhesion and metastasis of CCA. Additionally, we explored downstream molecular pathways using RNA-seq, western blotting, co-immunoprecipitation, immunofluorescence, and mass spectrometry techniques. RESULTS: Our findings revealed a negative correlation between PIN1 overexpression and prognosis in CCA tissues. Furthermore, high PIN1 expression promoted CCA cell proliferation and migration. Mechanistically, PIN1 functioned as an oncogene by regulating ANXA2 phosphorylation, thereby promoting CCA adhesion. Notably, the interaction between PIN1 and ANXA2 was facilitated by RACK1. Importantly, pharmacological inhibition of PIN1 using the FDA-approved drug all-trans retinoic acid (ATRA) effectively suppressed the metastatic potential of CCA cells in a nude mouse lung metastasis model. CONCLUSION: Overall, our study emphasizes the critical role of the PIN1/RACK1/ANXA2 complex in CCA growth and functionality, highlighting the potential of targeting PIN1 as a promising therapeutic strategy for CCA.

Translating imaging traits of mass-forming intrahepatic cholangiocarcinoma into the clinic: From prognostic to therapeutic insights.

Background & Aims: The progress toward clinical translation of imaging biomarkers for mass-forming intrahepatic cholangiocarcinoma (MICC) is slower than anticipated. Questions remain on the biologic behaviour underlying imaging traits. We developed and validated imaging-based prognostic systems for resected MICCs with an appraisal of the tumour immune microenvironment (TIME) underpinning patient-specific imaging traits. Methods: Between January 2009 and December 2019, a total of 322 patients who underwent dynamic computed tomography/magnetic resonance imaging and curative-intent resection for MICC at three hepatobiliary institutions were retrospectively recruited, divided into training (n = 193) and validation (n = 129) datasets. Two radiological and clinical scoring (RACS) systems, one integrating preoperative variables and one integrating preoperative and postoperative variables, were developed using Cox regression analysis. We then prospectively analysed the TIME of tissue samples from 20 patients who met study criteria from January 2021 to December 2021 using multiplexed immunofluorescence. Results: Preoperative and postoperative MICC-RACS systems built on carbohydrate antigen 19-9, albumin, tumour number, radiological/pathological nodal status, pathological necrosis, and three radiological traits (arterial enhancement pattern, tumour boundary, and capsular retraction) demonstrated good performance in predicting disease-specific (C-statistic >0.80) and disease-free (C-statistic >0.75) survival that outperformed rival models and staging systems across study cohorts (P <0.05 for all). Patients with MICC-RACS score of 0-2 (low risk), 3-5 (medium risk), and ≥6 (high risk) had incrementally worse prognosis after surgery. Significant differences in spatial distribution and infiltration level of immune cells were identified between arterial enhancement patterns. Enhanced infiltration of immunosuppressive regulatory T cells and M2-like macrophages at the invasive margin were noted in tumours with distinct boundary and capsular retraction, respectively. Conclusions: Our MICC-RACS systems are simple but powerful prognostic tools that may facilitate the understanding of spatially distinct TIMEs and patient-tailored immunotherapy approach. Impact and Implications: The progress toward clinical translation of imaging biomarkers for mass-forming intrahepatic cholangiocarcinoma (MICC) is slower than anticipated. Questions remain on the biologic behaviour of MICC underlying imaging traits. In this study, we proposed novel and easy-to-use tools, built on radiological and clinical features, that demonstrated good performance in predicting the prognosis either before or after surgery and outperformed rival models/systems across major imaging modalities. The characteristic radiological traits integrated into prognostic systems (arterial enhancement pattern, tumour boundary, and capsular retraction) were highly correlated with heterogeneous tumour-immune microenvironments, thereby renovating treatment paradigms for this difficult-to-treat disease.

Imaging features based on CT and MRI for predicting prognosis of patients with intrahepatic cholangiocarcinoma: a single-center study and meta-analysis.

BACKGROUND: To evaluate the prognostic role of imaging features based on CT and MRI in intrahepatic cholangiocarcinoma (ICC). METHODS: Two hundred and four patients from a single-center database who underwent radical ICC surgery from 2010 to 2019 were enrolled in the study. Cox proportional hazard model was used for survival analysis of imaging features. A meta-analysis was performed to determine imaging features that predict overall survival (OS) and event-free survival (EFS) in ICC. RESULTS: In the CT group of the retrospective cohort, tumor multiplicity, infiltrative tumor margin, lymph node metastasis, enhancement pattern in hepatic arterial phase and tumor necrosis correlated with poorer EFS and OS; moreover, enhancing capsules, high carcinoembryonic antigen levels contributed to poor OS. In the MRI group, tumor multiplicity and enhancement pattern were prognostic factors for OS; tumor multiplicity and enhancement pattern resulted in poor EFS. A total of 13 articles containing 1822 patients with ICC were enrolled in the adjusted hazard ratios meta-analysis. The results showed that enhancement pattern and infiltrative tumor margin were predictors of OS and EFS, whereas bile duct invasion was a predictor of OS. CONCLUSIONS: Arterial enhancement patterns and tumor margin status were associated with both OS and EFS of ICC patients following resection.

Paper mulberry leaves as a potential sterilant: evidence from Microtus fortis-a laboratory study.

Introduction: The Yangtze vole (Microtus fortis) is a small herbivorous rodent that usually causes damage to crops and forests in China. Various measures were used to control their population including chemical rodenticides. However, rodenticides may cause secondary damage to the environment and the ecosystem. Therefore, the development of new rodent sterilants is urgent. Considering that some compounds of paper mulberry leaves have been verified that can inhibit the biosynthesis of sexual hormone, we aimed to explore the antifertility effect of paper mulberry leaves on M. fortis. Methods: In this study, voles were divided into three groups including a male group, a female group, and a breeding group, and paper mulberry leaves were added into basal fodder of voles maintained in laboratory, of which the proportion of leaf weight was 50%. In each group, voles were fed with mixed fodder as treatment (BP) and voles were fed with basal fodder as contrast (CK). Results and discussion: After feeding for more than 1 month, the results indicated that paper mulberry leaves attracted voles to feed, but inhibited their growth and reproduction. Since the second week, food intakes of BP have been significantly higher than CK (p< 0.05). However, weights of voles in male and female groups were 72.283 ± 7.394 g and 49.717 ± 2.278 g in the fifth week, and both were significantly reduced compared with their original weight (p< 0.05). Meanwhile, testicular volumes of male voles fed with BP were significantly smaller than CK (former: 318.000 ± 44.654 mm3, latter: 459.339 ± 108.755 mm3); the testosterone level, sperm number, and vitality of BP were obviously weaker than CK. Female uteruses and oophoron of BP grew slower, and the organ coefficients of uterus and oophoron fed BP were both significantly lower than CK (p< 0.05). The first reproduction of BP couple voles spent 45 days, while CK spent only 21 days. These results suggest that paper mulberry leaves could be the potential resource to produce sterilants to control rodent populations by delaying their sexual growth and reproduction. If it was practical, the apparent advantages of paper mulberry are that it is an abundant resource and the inhibitory effect could be effective in both male and female individuals. Our conclusion also supports the transformation of rodent management from lethal management to fertility control, which would be more ecologically friendly to agriculture and the ecosystem.

RP11-40C6.2 Inactivates Hippo Signaling by Attenuating YAP1 Ubiquitylation in Hepatitis B Virus-associated Hepatocellular Carcinoma.

Background and Aims: Chronic hepatitis caused by hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). We investigated the roles of oncogenic HBV infection-associated long noncoding RNAs in HCC. Methods: Bioinformatics analysis of data from the Cancer Genome Atlas (TCGA) was performed to screen potential oncogenic HBV-related lncRNAs. Next, we assessed their expression in clinical samples and investigated their correlation with clinical characteristics. The detailed oncogenic effects were analyzed by performing in vitro and in vivo studies. Results: RP11-40C6.2, an HBV infection-related lncRNA, was identified by analysis of the TCGA-Liver Hepatocellular Carcinoma database. Gene Set Enrichment Analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes revealed a strong association of RP11-40C6.2 with the Hippo signaling pathway. RP11-40C6.2 was overexpressed in HCC patients with HBV infection compared to those without HBV infection. RP11-40C6.2 transcription showed a positive association with HBV-X protein (HBx), but not HBV core protein (HBc) expression, both of which are carcinogenic proteins. Luciferase gene reporter and ChIP assays revealed that YAP1/TAZ/TEADs complex enhanced RP11-40C6.2 transcription by binding to its promoter area. RP11-40C6.2 showed oncogenic characteristics in HCC cell lines and in animal models that were mediated via activation of YAP1. In vitro ubiquitylation assay revealed that RP11-40C6.2 can promote the stabilization of YAP1 by stopping phosphorylation at its s127 residue and further stopping its degradation through binding to 14-3-3. Conclusions: RP11-40C6.2 is an HBV infection-related lncRNA that exerts its oncogenic effects by targeting the Hippo signaling pathway.

Ecological function zoning based on ecosystem service bundles and trade-offs: a study of Dongjiang Lake Basin, China.

Although the research framework of ecological function zoning is complex and diverse, there are not many spatially continuous zoning results, which can be effectively applied to watershed management practices. Ecosystem service bundles and trade-offs can identify interactions among multiple ecosystem services, and achieve better social-ecosystem management when applying to ecological function zoning. Taking the Dongjiang Lake Basin, China, as research area, the study used the InVEST model to investigate the trade-offs and synergies of ecosystem services at township and grid scales, respectively. Then, the study conducted ecological function zoning based on the bundles and trade-off intensity among ecosystem services. The results showed that food production showed extremely significant trade-offs with other services in the two scales, in which the trade-off intensity between food production and water purification was the largest, and the water areas were the hotspots of trade-off intensity. Based on the ecosystem service bundles at the township, combined with the trade-off intensity, the watershed was finally divided into four ecological functional zones, namely, agricultural product supply area (southern part in the study area), economic forestry area (northeast regions in the study area), water supply area (western areas of the study area), and forest conservation area (northern areas in the study area), accounting for 29.27%, 14.63%, 17.07%, and 39.03%, respectively. The study contributed to the ecological function maintenance and sustainable development in Dongjiang Lake Basin and provided an important reference in ecological zoning.

Woody plants have the advantages in the phytoremediation process of manganese ore with the help of microorganisms.

The serious ecological damage caused by mining activities cannot be ignored. The use of an environmentally friendly restoration method to rebuild the vegetation and soil environment in the mining area has attracted more and more attention. This paper aims to study soil quality as well as vegetation characteristics of four woody species including Pinus massoniana (P. massoniana), Broussonetia papyrifera (B. papyrifera), Koelreuteria paniculata (K. paniculata), Osmanthus fragrans (O. fragrans), and two herbaceous species including Setaria viridis (S. viridis) and Cynodon dactylon (C. dactylon). In addition, we further clarified the effects of B. papyrifera and K. paniculata on soil nutrients and microbial communities after restoration. The results showed that the vegetation restoration area had better soil quality and plant community diversity, and the woody plants restoration effect were better. Compared with slag, B. papyrifera and K. paniculata remediation could improve soil pH and mitigate heavy metal contamination in mining areas, but was not effective in enhancing Soil Organic Matter (SOM), Total Nitrogen (TN), Total Potassium (TK) and Total Phosphorus (TP). In addition, the abundance and diversity of soil bacterial communities were increased. Of all the study sites, Proteobacteria had the greatest dominance. Vegetation restoration resulted in an increase in the relative abundance of Acidobacteria, while a decrease in Actinobacteria, Cyanobacteria and Firmicutes. With the restoration of vegetation, the increase of pH, the change of TN, SOM, TK, TP and the mitigation of Manganese (Mn) pollution were the main reasons affecting the soil microbial community. This study has great significance for understanding the ecological changes in the mining area after artificially mediated vegetation restoration, including changes in soil environment, plant community and microbial community, and woody plants will be more encouraged for the restoration of manganese mining areas.

Metformin Suppresses Hepatocellular Carcinoma through Regulating Alternative Splicing of LGR4.

Methods: First, the expression of LGR4 in HCC tumor tissues and cell lines was detected by western blotting and immunofluorescence. The ability of cell proliferation, migration, and invasion was detected with CCK8, wound-healing, and transwell assays when overexpressing LGR4 or treating with metformin. The ß-catenin expression was detected by immunofluorescence. In order to investigate novel AS-associated LGR4, we discarded LGR4 isoforms from GSO databases. We used siRNA to knock down the specific isoform to check the cell proliferation, migration, and invasion when treated with metformin. Results: The level of LGR4 expression was higher in HCC cell lines and tumor tissues. The HCC cell proliferation, migration, and invasion were increased when overexpressing LGR4, which could be reduced by metformin treatment. The GEO database (GSE190076) showed that LGR4 had switching properties in HCC cell lines treated with metformin. We used siRNA to knock down the specific isoform, and the result showed that the specific isoform siRNA could promote the inhibition of cell invasion caused by metformin treatment. Conclusions: LGR4 could promote the ability of cell proliferation, migration, and invasion in HCC, which could be reduced by metformin through alternative splicing.

CircMYH9 increases KPNA2 mRNA stability to promote hepatocellular carcinoma progression in an EIF4A3-dependent manner.

Hepatocellular carcinoma (HCC) is the most commonly diagnosed cancer worldwide with a high incidence of recurrence and metastasis; however, the molecular mechanisms underlying HCC development remain to be fully understood. In this study, we identified circMYH9 as an important regulator of HCC. Overexpression of circMYH9 induced, while knockdown of circMYH9 inhibited, the proliferation, migration, and invasion of HCC cells. Mechanistically, circMYH9 bound to eukaryotic translation initiation factor 4A3 (EIF4A3) and increased karyopherin subunit alpha 2 (KPNA2) mRNA stability. circMYH9 knockdown in HCC cells reduced the stability of KPNA2 mRNA. Importantly, circMYH9 regulation of HCC required the activity of KPNA2. In support with this, circMYH9 level was positively correlated with the expression of KPNA2 in HCC patient samples. Taken together, our study was the first to uncover the oncogenic role of circMYH9 in HCC and further elucidated the functional mechanism of circMYH9 by interacting with EIF4A3 to increase KPNA2 mRNA stability. Our findings might provide a novel potential target for the diagnose and treatment of HCC.

Effects of g-C3N4 on bacterial community and tetracycline resistance genes in two typical sediments in tetracycline pollution remediation.

Photocatalysis, as a novel technique, has been widely used for antibiotic pollution remediation in wastewater. In the processes of degradation and removal of antibiotics, the impact of photocatalysts on microenvironment is very important but remains poorly understood. In the present study, the effect of typical photocatalyst g-C3N4 (Graphitic carbon nitride) on microbial community was investigated in two sediment types (riverbed sediment and pig-farm sediment) polluted by tetracycline (TC) in central southern China. The riverbed sediment and pig farm sediment samples were respectively exposed to g-C3N4 (25, 75, 125 mg⋅kg-1) and TC (60, 120, 180 mg⋅L-1) treatments alone or combination for 30 days, respectively. The bacterial community and antibiotic resistance genes (ARGs) of the treated sediments were analyzed by Illumina sequencing and metagenomic sequencing. Studies had shown that: TC, g-C3N4, and TC/g-C3N4 have significant effects on the changes of microbial communities and components in riverbed sediment, but they do not exist in pig farm sediment. The most alterations of microbial taxa were Acidobacteriota, Actinobacteriota, and Desulfobacterota in riverbed sediment, and Elusimicrobiota in the pig farm sediment under various treatments. Through network analysis, it was found that the distribution of microorganisms in the pig farm sediment is more complex and more stable. The addition of g-C3N4 reduced the absolute abundance of ARGs in the two examined sediments, but not significantly changed their relative abundance of ARGs. The g-C3N4 application was beneficial to the removal of TC residues and to the prevention of the generation and transmission of ARGs in sediments. Our results suggested that g-C3N4 was a suitable photocatalyst with excellent application prospect for the removal of TC residues and the control of ARGs in environment.

A comprehensive framework of the right posterior section for tailored anatomical liver resection based on three-dimensional simulation system.

Background: The anatomical right posterior sectionectomy (ARPS) is a technically challenging procedure. We aimed to develop and validate a novel framework of the right posterior section for a safe and tailored anatomical liver resection (ALR) based on a three-dimensional (3D) simulation system. Methods: 3D hepatectomy simulations of healthy participants who underwent contrast-enhanced computed tomography of the upper abdomen were retrospectively reviewed to develop the framework according to the relationship between the simulated plane determined by the right posterior portal pedicle (RPP) and the course of the right hepatic vein (RHV) trunk. The framework was validated in the practice of ARPS for hepatocellular carcinoma (HCC) prospectively. Results: Scans from 336 eligible participants were assessed. The framework was summarized into four types: normal, caudal-redundant, cranial-deficient, and combined types, accounting for 43.4% (146/336), 25.3% (85/336), 18.5% (62/336), and 12.8% (43/336) respectively. The caudal-redundant type was associated with the variable portal branches of the RPP or segment 6 branch across the ventral side of RHV. The mean aberrant volume proportion in type IIa was significantly greater than that in type IIb (P<0.001), which were 7.0%±3.5% and 4.4%±1.8% respectively. The cranial-deficient type was associated with the aberrant segment 7 portal pedicle originating from the right portal trunk or the dorsal portal branch of segment 8 crossing over to the RHV. The median aberrant volume proportion in type IIIa was significantly greater than that in type IIIb (P<0.001), which were 10.9% (8.5-13.3%) and 4.0% (3.0-6.1%), respectively. The combined type represented a combination of the caudal-redundant type and the cranial-deficient type. The framework provided instructions on tailored ARPS in 6 patients with HCC by maximizing lesion removal and functional liver remnant with favorable perioperative outcomes. Conclusions: Precise preoperative planning with an individualized surgical approach based on our framework allows safe anatomical liver resections for cases with lesions in the right posterior section.

The effects of g-C3N4/biochar and g-C3N4 on bacterial community in riverbed sediment.

Biochar had been widely used to improve the activity of photocatalysts, the biochar-based photocatalysts had more potential for environmental pollution remediation, but their effect on the sediment remained unknown. To understand these, the typical photocatalyst g-C3N4 was modified by biochar to develop g-C3N4/biochar with enhanced photocatalytic ability. Riverbed sediment was exposed to g-C3N4 and g-C3N4/biochar respectively for 30 days, and Illumina sequencing was utilized to examine the changes in the bacterial community in the sediment. The results showed that in riverbed sediment, g-C3N4 exposure had a concentration-dependent effect on the diversity of bacteria, while g-C3N4/biochar exposure had a slight influence on the bacterial diversity and the diversity almost maintained stable with different g-C3N4/biochar concentration. The application of g-C3N4 exhibited an inhibition influence on the growth of Acidobacteria, Gemmatimonadetes, and Rokubacteria in sediment, whose relative abundance increased when g-C3N4 was 25 mg/kg, and then decreased when g-C3N4 beyond this concentration. The presence of g-C3N4/biochar increased the relative abundance of Cyanobacteria in sediment and showed no obvious impact on other dominant phyla. Both g-C3N4 and g-C3N4/biochar could alter the levels of TP, NN, and AN in the sediment, but the magnitude of the changes of these physicochemical factors caused by g-C3N4/biochar was much smaller than those caused by g-C3N4. In addition, the complexity of the bacterial community network was reduced in a high concentration of g-C3N4, while it remained stable with different concentrations of g-C3N4/biochar treatments. Totally, this study demonstrated that, compared to g-C3N4, g-C3N4/biochar was able to maintain the relative stability of the bacterial community in riverbed sediment and mitigate the negative effects of photocatalysts to some extent, making biochar an ecological remediation agent with great potential for application.

CircASPH Promotes Hepatocellular Carcinoma Progression Through Methylation and Expression of HAO2.

CircRNAs have been reported to be related to hepatocellular carcinoma (HCC) development. Limited studies have revealed the expression profile of circRNAs in tumor and para-tumor normal samples in HCC patients. We found that circASPH was significantly increased in HCC tumor samples and that the level of circASPH was closely related to the overall survival of HCC patients. Mechanistically, circASPH could regulate the methylation of the promoter and expression of hydrocyanic oxidase 2 (HAO2) to promote HCC progression by acting as a sponge for miR-370-3p, and miR-370-3p could target DNMT3b and increase the 5mC level. In summary, our study determined that circASPH could regulate the methylation and expression of HAO2 and it could be considered an important epigenetic regulator in HCC progression.

Integrating Broussonetia papyrifera and Two Bacillus Species to Repair Soil Antimony Pollutions.

Heavy metal resistant bacteria play an important role in the metal biogeochemical cycle in soil, but the benefits of microbial oxidation for plants and soil have not been well-documented. The purpose of this study was to explore the contribution of two Bacillus spp. to alleviate the antimony (Sb) toxicity in plants, and, then, to propose a bioremediation method for Sb contaminated soil, which is characterized by environmental protection, high efficiency, and low cost. This study explored the effects of Bacillus cereus HM5 and Bacillus thuringiensis HM7 inoculation on Broussonetia papyrifera and soil were evaluated under controlled Sb stressed conditions (0 and 100 mmol/L, antimony slag) through a pot experiment. The results show that the total root length, root volume, tips, forks, crossings, and root activities of B. papyrifera with inoculation are higher than those of the control group, and the strains promote the plant absorption of Sb from the soil environment. Especially in the antimony slag treatment group, B. cereus HM5 had the most significant effect on root promotion and promoting the absorption of Sb by B. papyrifera. Compared with the control group, the total root length, root volume, tips, forks, crossings, and root activities increased by 64.54, 70.06, 70.04, 78.15, 97.73, and 12.95%, respectively. The absorption of Sb by root, stem, and leaf increased by 265.12, 250.00, and 211.54%, compared with the control group, respectively. Besides, both B. cereus HM5 and B. thuringiensis HM7 reduce the content of malondialdehyde, proline, and soluble sugars in plant leaves, keeping the antioxidant enzyme activity of B. papyrifera at a low level, and alleviating lipid peroxidation. Principal component analysis (PCA) shows that both B. cereus HM5 and B. thuringiensis HM7 are beneficial to the maintenance of plant root functions and the improvement of the soil environment, thereby alleviating the toxicity of Sb. Therefore, B. cereus HM5 and B. thuringiensis HM7 in phytoremediation with B. papyrifera is a promising inoculant used for bacteria-assisted phytoremediation on Sb contaminated sites.

DNA metabarcoding uncovers the diet of subterranean rodents in China.

OBJECTIVE: A type of rodent called a zokor causes great harm to agriculture and forestry production due to its large and sophisticated diet. As this rodent lives subterrane for most of its life, researchers know little about its dietary habits. Further understanding of its diet is important for developing green and sustainable control strategies for the zokor. METHODS: Chloroplast trnL gene and internal transcription spacer 1 primers were selected for high-throughput sequencing of stomach contents of captured zokor by DNA metabarcoding. RESULTS: A total of 25 zokors were selected, the food list of 32 families, 80 genera, and 154 species was obtained. At the family level, it was found that zokors mainly fed on Asteraceae, Poaceae, Rosaceae, Pinaceae, Brassicaceae, and Apiaceae. At the genus level, zokors mainly fed on Echinops, Littledalea, Artemisia, Picea, Cirsium, and Elymus. The diet alpha diversity of Eospalax cansus was slightly higher than that of Eospalax cansus (P>0.05). The zokor's diet is highly phconsistent with the resources of its habitat. Most food choices tend to be the same between the two zokors. They fed primarily on Calamagrostis, Cirsium, Echinops, Medicago, Sanguisorba, and Taraxacum. Zokors mainly fed on the roots of perennial herbs, which are important source of energy. CONCLUSION: High-throughput sequencing-based DNA metabarcoding technology has effectively revealed the diet of zokors and indicated that zokors are food generalists.

Development and validation of a gradient boosting machine to predict prognosis after liver resection for intrahepatic cholangiocarcinoma.

BACKGROUND: Accurate prognosis assessment is essential for surgically resected intrahepatic cholangiocarcinoma (ICC) while published prognostic tools are limited by modest performance. We therefore aimed to establish a novel model to predict survival in resected ICC based on readily-available clinical parameters using machine learning technique. METHODS: A gradient boosting machine (GBM) was trained and validated to predict the likelihood of cancer-specific survival (CSS) on data from a Chinese hospital-based database using nested cross-validation, and then tested on the Surveillance, Epidemiology, and End Results (SEER) database. The performance of GBM model was compared with that of proposed prognostic score and staging system. RESULTS: A total of 1050 ICC patients (401 from China and 649 from SEER) treated with resection were included. Seven covariates were identified and entered into the GBM model: age, tumor size, tumor number, vascular invasion, number of regional lymph node metastasis, histological grade, and type of surgery. The GBM model predicted CSS with C-Statistics ≥ 0.72 and outperformed proposed prognostic score or system across study cohorts, even in sub-cohort with missing data. Calibration plots of predicted probabilities against observed survival rates indicated excellent concordance. Decision curve analysis demonstrated that the model had high clinical utility. The GBM model was able to stratify 5-year CSS ranging from over 54% in low-risk subset to 0% in high-risk subset. CONCLUSIONS: We trained and validated a GBM model that allows a more accurate estimation of patient survival after resection compared with other prognostic indices. Such a model is readily integrated into a decision-support electronic health record system, and may improve therapeutic strategies for patients with resected ICC.

Effect of g-C3N4 on biodiversity and structure of bacterial community in sediment of Xiangjiang River under tetracycline pressure.

Photocatalysts have been widely prepared and used in wastewater treatment. Although the influence of photocatalyst application on survival and activity of organisms has been examined, its impact on composition and diversity of microbial community is not fully understood. In this study, the impact of photocatalyst g-C3N4 (Graphitic carbon nitride) on microbial communities in riverbed sediments polluted by antibiotic tetracycline (TC) was investigated. The sediment samples collected from the Xiangjiang River of China were exposed to different concentrations of TC, g-C3N4 and TC/g-C3N4 and the bacterial community were analyzed by Illumina sequencing. The results showed that the dominant bacterial phyla were Acidobacteriota, Proteobacteria, Actinobacteriota, and Chloroflexi in the study site. When compared to the control treatments, the application of TC, g-C3N4 and TC/g-C3N4 exhibited distinguishable effects on bacterial community structure in sediments. The presence of TC had greater influence on bacterial composition, while g-C3N4 and TC/g-C3N4 had less influence on bacteria. The diversity and richness of microorganisms in sediment increased under g-C3N4 application and reached the highest values when g-C3N4 was 75 mg/kg. The photocatalyst g-C3N4 restored bacterial community diversity affected by TC, reduced the TC residues in aquatic environment, and eliminated the side effects of TC application in sediments. Our study indicated that g-C3N4 was an environmentally friendly photocatalyst with lightly negative effects on microbial community in riverbed sediments, and could be used for effective remediation of TC-contaminated environments.