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Bladder transitional cell carcinoma (BTCC) forms more than 90% of bladder cancer cases. It brings challenges to the early diagnosis and therapy of BTCC, due to lack of efficient screening biomarkers. We used weighted gene co-expression network analysis (WGCNA) combined competing endogenous RNA (ceRNA) network construction depending on TCGA datasets to investigate potential hub genes and regulatory pathways associated with occurrence and progression of BTCC. We further used real-time polymerase chain reaction (RT-PCR) to validate the relative expression genes correlated with BTCC. By WGCNA, the gene co-expression module with 11 genes was found corelated with BTCC tumour stage and prognosis after survival analyses. Ultimately, we put 100 highly stage-related genes into the above constructed ceRNA network and then constructed another new network. Among them, all elements in AC112721.1/LINC00473/AC128709.1-hsa-mir-195-RECK and LINC00460-hsa-mir-429-ZFPM2 axes were simultaneously corelated with overall survival. RT-PCR showed that AKAP12 was downregulated in tumour tissues. The hub genes screened out in the present study may provide ideals for further treatment on BTCC.
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Plenty of epidemiological studies have assessed the effects of AXIN2 polymorphisms on the risk of developing cancer, but the available results were somewhat inconclusive. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to investigate the relationship between three AXIN2 variants (rs2240308 C/T, rs1133683 C/T, and rs4791171 A/G) and overall cancer susceptibility. In silico tools were undertaken to investigate the correlation of AXIN2 expression with cancer risk and survival time. Furthermore, we explored the serum expression of AXIN2 by enzyme-linked immunosorbent assay. A total of 4167 cancer patients and 3515 control subjects were evaluated. The overall results demonstrated that there was no major association of these polymorphisms on cancer risk. However, stratified analysis by cancer type showed evidence that rs2240308 C/T polymorphism had a lower risk in lung cancer (OR, 0.76; 95% CI, 0.63-0.92; Pheterogeneity = 0.865) and prostate cancer (OR, 0.54; 95% CI, 0.35-0.84; Pheterogeneity = 0.088) by heterozygote comparison. Similar results were indicated in Asian descendants and population-based studies. In silico analysis showed evidence that AXIN2 expressions in lung cancer and prostate cancer were lower than that in normal counterpart. High expression of AXIN2 may have longer overall survival time than low expression group for lung cancer participants. In addition, individuals who were CC/TC carriers had a higher serum expression level than TT carriers. In conclusion, this pooled analysis suggested that AXIN2 rs2240308 C/T variant may decrease both lung and prostate cancer susceptibility, particularly in Asian descendants and population-based studies. Future large scale and well-designed research are required to validate these effects in more detail.
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Proteína Axina/genética , Predisposición Genética a la Enfermedad , Neoplasias Pulmonares/genética , Neoplasias de la Próstata/genética , Pueblo Asiatico/genética , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Estudios de Asociación Genética , Genotipo , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/patología , Masculino , Polimorfismo de Nucleótido Simple/genética , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/patología , Factores de RiesgoRESUMEN
When it comes to Pb-Zn ores with high amounts of pyrite, the major problem encountered is the low separation efficiency between galena and pyrite. By virtue of high dosage of lime and collector sodium diethyl dithiocarbamate (DDTC), pyrite and zinc minerals are depressed, allowing the galena to be floated. However, there have been significant conflicting reports on the flotation behavior of galena at high pH. In this context, correlation of the surface adsorption and oxidation with the floatability difference of galena and pyrite in high-alkaline lime systems would be a key issue for process optimization. Captive bubble contact angle measurements were performed on freshly polished mineral surfaces in situ exposed to lime solutions of varying pH as a function of immersion time. Furthermore, single mineral microflotation tests were conducted. Both tests indicated that the degree of hydrophobicity on the surfaces of galena and pyrite increased in the presence of DDTC at natural or mild pulp pH. While in a saturated lime solution, at pH 12.5, DDTC only worked for galena, but not for pyrite. Surface chemistry analysis by time-of-flight secondary ion mass spectrometry (Tof-SIMS) confirmed the preference of DDTC on the galena surface at pH 12.5, which contributed to a merit recovery. Further important evidence through measurements of Tof-SIMS, ion chromatography, and high-performance liquid chromatography indicated that in high-alkaline lime systems, the merit floatability of galena could exclude the insignificant contribution of elemental sulfur (S8) and was dominantly attributed by the strong adsorption of DDTC. In contrast, the poor flotation response of pyrite at high pH was due to the prevailing adsorption of CaOH+ species. This study provides an important surface chemistry evidence for a better understanding of the mechanism on the better selectivity in the galena-pyrite separation adopting high-alkaline lime systems.
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The Type III Secretion Systems (T3SSs) play a pivotal role in host-pathogen interactions by mediating the secretion of type III secretion system effectors (T3SEs) into host cells. These T3SEs mimic host cell protein functions, influencing interactions between Gram-negative bacterial pathogens and their hosts. Identifying T3SEs is essential in biomedical research for comprehending bacterial pathogenesis and its implications on human cells. This study presents EDIFIER, a novel multi-channel model designed for accurate T3SE prediction. It incorporates a graph structural channel, utilizing graph convolutional networks (GCN) to capture protein 3D structural features and a sequence channel based on the ProteinBERT pre-trained model to extract the sequence context features of T3SEs. Rigorous benchmarking tests, including ablation studies and comparative analysis, validate that EDIFIER outperforms current state-of-the-art tools in T3SE prediction. To enhance EDIFIER's accessibility to the broader scientific community, we developed a webserver that is publicly accessible at http://edifier.unimelb-biotools.cloud.edu.au/. We anticipate EDIFIER will contribute to the field by providing reliable T3SE predictions, thereby advancing our understanding of host-pathogen dynamics.
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Motivation: PE/PPE proteins, highly abundant in the Mycobacterium genome, play a vital role in virulence and immune modulation. Understanding their functions is key to comprehending the internal mechanisms of Mycobacterium. However, a lack of dedicated resources has limited research into PE/PPE proteins. Results: Addressing this gap, we introduce MycobactERIal PE/PPE proTeinS (MERITS), a comprehensive 3D structure database specifically designed for PE/PPE proteins. MERITS hosts 22 353 non-redundant PE/PPE proteins, encompassing details like physicochemical properties, subcellular localization, post-translational modification sites, protein functions, and measures of antigenicity, toxicity, and allergenicity. MERITS also includes data on their secondary and tertiary structure, along with other relevant biological information. MERITS is designed to be user-friendly, offering interactive search and data browsing features to aid researchers in exploring the potential functions of PE/PPE proteins. MERITS is expected to become a crucial resource in the field, aiding in developing new diagnostics and vaccines by elucidating the sequence-structure-functional relationships of PE/PPE proteins. Availability and implementation: MERITS is freely accessible at http://merits.unimelb-biotools.cloud.edu.au/.
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INTRODUCTION: The CXC chemokines are unique cytokines that play a vital role in the progression of many cancers. Association between chemokine (C-X-C motif) receptor 2 (IL8RB) C1208T mutation and cancer risk remains incomprehensive. METHODS: We therefore utilized odds ratios and in silico analysis to explore the relationship of IL8RB polymorphism on risk to cancer. Furthermore, we adopted gene set enrichment analysis to investigate the IL8RB expression in prostate adenocarcinoma. RESULTS: A total of 14 case-control studies combined with 5299 cases and 6899 controls were included in our analysis. We revealed that individuals carrying TT genotype had an 14% increased cancer risk compared with those with TCâ+âcolon cancer (CC) genotype (odds ratio [OR]â=â1.14, 95% CIâ=â1.05-1.25, Pâ=â.003, I2â=â35.6). Stratification analysis by race showed that East Asians with TTâ+âTC genotype may have a 25% decreased cancer risk compared with control. Stratification analysis by cancer type revealed that individuals with TT genotype were associated with elevated risk of urinary cancer than control. The expression of IL8RB was attenuated in prostate adenocarcinoma. CONCLUSIONS: IL8RB C1208T may be correlated with the risk of cancer, especially prostate adenocarcinoma.
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Adenocarcinoma/genética , Neoplasias de la Próstata/genética , Receptores de Interleucina-8B/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Mutación/genética , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
OBJECTIVE: To study the expressions of interleukin-15 (IL-15), osteopontin (OPN), granzyme B (GraB) and perforin (PFP) mRNA in early stage of acute rejection (AR) of renal allograft in rats. METHODS: The rat renal transplantation model was established. Male Brown Norway and Lewis rats were used as donors and recipients. Four groups were designated: CsA group (BN-->LEW, n = 10, recipients were treated with CsA i.p.); AB group (BN-->LEW, n = 10, recipients were treated with anti-IL-15 neutralizing antibody i.p.); AR group (BN-->LEW, n = 10, recipients were treated with normal saline i.p.) and control group (LEW-->LEW, n = 6, recipients were treated with normal saline i.p.). The blood samples of recipients were drawn at Days 1, 3, 5 and 7 post-transplantation. The serum expressions of IL-15, OPN, PFP and GraB mRNA of recipients were detected by real-time PCR. Allograft tissues were analyzed by pathological assays. RESULTS: In comparison with other groups, the expressions of OPN, IL-15, PFP and GraB mRNA in AR group were gradually up-regulated and peaked at Day 5. The expressions of IL-15 mRNA in CsA and AB groups were 9685 +/- 1440 and 4346 +/- 741 respectively at Day 5 post-operation. It was significantly lower than that in AR group (17 022 +/- 2153, P < 0.01). The expression of IL-15 mRNA in AB group was significantly lower than that in CsA group (P < 0.01). The expressions of OPN mRNA in CsA and AB groups (13 226 +/- 1565 vs 19 112 +/- 2908) were both significantly lower than that in AR group (24 663 +/- 2449, P < 0.01). But the expression of OPN mRNA in AB group was higher than that in CsA group (P < 0.01). At Day 5 post-transplantation, both the expressions of PFP and GraB mRNA in AB and CsA groups was lower than that in AR group (P < 0.01). The pathological results showed that severe AR occurred at Day 7 post-transplantation in AR group and whereas the extent of rejection sign relieved in AB group. CONCLUSION: In early stage of AR of renal allograft in rats, the expressions of OPN, IL-15, PFP and GraB mRNA are up-regulated. Blocking IL-15/IL-15R pathway in early stage of AR can down-regulate the expressions of PFP and GraB mRNA.
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Rechazo de Injerto/inmunología , Rechazo de Injerto/metabolismo , Interleucina-15/metabolismo , Trasplante de Riñón , Osteopontina/metabolismo , Animales , Rechazo de Injerto/patología , Granzimas/metabolismo , Masculino , Proteínas Citotóxicas Formadoras de Poros/metabolismo , ARN Mensajero/genética , Ratas , Ratas Endogámicas BN , Ratas Endogámicas Lew , Trasplante HomólogoRESUMEN
Mining waste rocks containing sulfide minerals naturally provide the habitat for iron- and sulfur-oxidizing microbes, and they accelerate the generation of acid mine drainage (AMD) by promoting the oxidation of sulfide minerals. Sulfate-reducing bacteria (SRB) are sometimes employed to treat the AMD solution by microbial-induced metal sulfide precipitation. It was attempted for the first time to grow SRB directly in the pyritic heap bioleaching residue to compete with the local iron- and sulfur-oxidizing microbes. The acidic SRB and iron-reducing microbes were cultured at pH 2.0 and 3.0. After it was applied to the acidic heap bioleaching residue, it showed that the elevated pH and the organic matter was important for them to compete with the local bioleaching acidophiles. The incubation with the addition of organic matter promoted the growth of SRB and iron-reducing microbes to inhibit the iron- and sulfur-oxidizing microbes, especially organic matter together with some lime. Under the growth of the SRB and iron-reducing microbes, pH increased from acidic to nearly neutral, the Eh also decreased, and the metal, precipitated together with the microbial-generated sulfide, resulted in very low Cu in the residue pore solution. These results prove the inhibition of acid mine drainage directly in situ of the pyritic waste rocks by the promotion of the growth of SRB and iron-reducing microbes to compete with local iron and sulfur-oxidizing microbes, which can be used for the source control of AMD from the sulfidic waste rocks and the final remediation.
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Bacterias , Biodegradación Ambiental , Minería , Sulfatos , Oxidación-Reducción , Sulfatos/metabolismo , AzufreRESUMEN
Pyrite oxidation by mixed mesophilic acidophiles was conducted under conditions of controlled and non-controlled redox potential to investigate the role of sessile microbes in pyrite oxidation. Microbes attached on pyrite surfaces by extracellular polymeric substances (EPS), and their high coverage rate was characterized by scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) and atomic force microscopy (AFM). The dissolution of pyrite was negligible if the redox potential was controlled below 650 mV (near the rest potential of pyrite), even though the bacteria were highly active and a high coverage rate was observed on pyrite surfaces. However, with un-controlled redox potential the rate of pyrite oxidation increased greatly with an increasing redox potential. This study demonstrates that sessile microbes play a limited role in pyrite oxidation at a redox potential below 650 mV, and highlight the importance of solution redox potential for pyrite oxidation. This has implications for acid mine drainage control and pyrite oxidation control in biometallurgy practice.
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Bacterias/metabolismo , Hierro/química , Sulfuros/química , Concentración de Iones de Hidrógeno , Microscopía de Fuerza Atómica , Microscopía Electrónica de Rastreo , Oxidación-ReducciónRESUMEN
BACKGROUND/AIMS: Interleukin-13 (IL13) is an immunoregulatory cytokine which plays an important role in carcinogenesis through affecting tumor immunosurveillance. Many studies had reported the influence of IL13 rs1800925 and rs20541 polymorphisms on cancer risk, however, with inconclusive results. The aim of the present study was to conduct a meta-analysis to clarify the relationship. METHODS: Twenty studies including a total of 6713 cancer cases and 8693 controls for IL13 rs20541 polymorphism and 4081 cancer cases and 6202 controls for IL13 rs1800925 polymorphism were included in the meta-analysis. Data were extracted from these studies and odds ratios with corresponding 95% confidence intervals were computed to estimate the strength of the association. RESULTS: Overall, the IL13 rs20541 polymorphism were associated with significantly decreased cancer risk in all genetic models (AA vs. GG: OR=0.82, 95%CI=0.71-0.95; GA vs. GG: OR=0.92, 95%CI=0.85-0.99; GA/AA vs. GG: OR=0.90, 95%CI=0.85-0.97; AA vs. GG/GA: OR=0.85, 95CI%=0.74-0.98). In the stratified analyses, significant effects were found among European populations, studies with population-based controls and studies of glioma. No influence of the IL13 rs1800925 polymorphism on the overall cancer risk was observed. However, in the stratified analyses, we found the IL13 rs1800925 polymorphism was significantly associated with decreased risk for glioma (CT vs. TT: OR=0.72, 95%CI=0.55-0.93; CT/TT vs. TT: OR=0.76, 95%CI=0.62-0.89). CONCLUSION: Our meta-analysis suggests that the IL13 rs20541 polymorphism contributes to susceptibility to cancer, especially for glioma; and the IL13 rs1800925 polymorphism may be associated with glioma risk.