Differential Expression of KIF18B in Gastric Cancer and Its Role in Chemotherapy Sensitivity.

Gastric cancer (GC) is a main cause of cancer death in the world, and improving the chemotherapy sensitivity can enhance the chemotherapy efficacy of GC. The study objective is to explore the differential KIF18B expression in GC and its effect on GC chemotherapy sensitivity. The KIF18B expression in GC tissues and adjacent normal tissues was analyzed by real-time quantitative polymerase chain reaction. The relationship between differential KIF18B expression and different clinicopathological features was detected. It was found that KIF18B was highly expressed in GC tissues, and KIF18B expression was differential in patients with different clinicopathological features. The upregulation of KIF18B has a positive correlation with the poor therapeutic effect and high KIF18 was associated with lower 3-year overall survival and disease-free survival. The KIF18B-downregulated NCI-N87 cells were constructed and tested by cell counting kit-8 assay and colony formation. Cell migration and invasion were detected by Transwell assay. The xenograft tumor model was established to observe the effect of KIF18B on the efficacy of chemotherapy. The upregulation of KIF18B reduced the chemotherapy sensitivity of GC cells and enhanced their proliferation, migration, and invasion. Silencing KIF18B inhibited tumor growth and promoted chemotherapy efficacy in vivo. In summary, KIF18B inhibitor may have a potential function for improving the efficacy of chemotherapy in GC.

Therapeutic Evaluation of Bifidobacterium animalis subsp. lactis MH-02 as an Adjunctive Treatment in Patients with Reflux Esophagitis: A Randomized, Double-Blind, Placebo-Controlled Trial.

Proton pump inhibitors (PPIs) are currently routinely used for the treatment of reflux esophagitis (RE); however, with frequent symptom recurrence after discontinuation and limited clinical improvement in accompanying gastrointestinal symptoms. This study aims to explore the adjuvant therapeutic effect of Bifidobacterium supplement for RE patients. A total of 110 eligible RE patients were recruited and randomly assigned to the placebo and probiotic groups. All patients were treated with rabeprazole tablets and simultaneously received either Bifidobacterium animalis subsp. lactis MH-02 or placebo for 8 weeks. Patients who achieved clinical remission then entered the next 12 weeks of follow-up. RDQ, GSRS scores, and endoscopy were performed to assess clinical improvement, and changes in intestinal microbiota were analyzed with high-throughput sequencing. Our results revealed that MH-02 combined therapy demonstrated an earlier time to symptom resolution (50.98% vs. 30.61%, p = 0.044), a significant reduction in the GSRS score (p = 0.0007), and a longer mean time to relapse (p = 0.0013). In addition, high-throughput analyses showed that MH-02 combined therapy increased the α (p = 0.001) diversity of gut microbiota and altered microbial composition by beta diversity analysis, accompanied with significantly altered gut microbiota taxa at the genus level, where the abundance of some microbial genera including Bifidobacterium, Clostridium, and Blautia were increased, while the relative abundance of Streptococcus and Rothia were decreased (p < 0.05). Collectively, these results support the beneficial effects of MH-02 as a novel complementary strategy in RE routine treatment.

Tripartite motif 31 drives gastric cancer cell proliferation and invasion through activating the Wnt/ß-catenin pathway by regulating Axin1 protein stability.

Mounting evidence has proposed the importance of the Wnt/ß-catenin pathway and tripartite motif 31 (TRIM31) in certain malignancies. Our research aimed to clarify the correlation between aberrant TRIM31 expression and the Wnt/ß-catenin pathway during gastric cancer (GC) oncogenesis and development. TRIM31 was drastically elevated in GC tissues and was closely associated with aggressive clinical outcomes and poor prognosis. Moreover, TRIM31 downregulation attenuated GC cell proliferation and invasion in vitro. Mechanistically, TRIM31 could bind and ubiquitinate Axin1 protein, thereby facilitating the activation of the Wnt/ß-catenin pathway. Additionally, Axin1 knockdown partially abrogated the inhibitory effects on the proliferative, invasive and migratory abilities of GC cells induced by TRIM31 silencing. Furthermore, TRIM31 was negatively correlated with Axin1 protein expression in GC tissues. In summary, we revealed a new TRIM31-Axin1-Wnt/ß-catenin axis that contributed greatly to the progression of GC, and targeting this regulatory axis may represent an effective treatment for GC patients.

Exosomes from adipose-derived mesenchymal stem cells improve liver fibrosis by regulating the miR-20a-5p/TGFBR2 axis to affect the p38 MAPK/NF-κB pathway.

OBJECTIVE: Human adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) are active constituents for treating liver fibrosis. This paper attempted to preliminarily explain the functional mechanism of ADSC-Exos in liver fibrosis through the p38 MAPK/NF-κB pathway. METHODS: The cell models of hepatic fibrosis were established by inducing LX-2 cells with TGF-ß1. Mouse models of liver fibrosis were established by treating mice with CCl4. The in vivo and in vitro models of liver fibrosis were treated with ADSC-Exos. ADSCs were identified by flow cytometry/Alizarin red/oil red O/alcian blue staining. ADSC-Exos were identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. LX-2 cell proliferation/viability were evaluated by MTT/BrdU assays. Exosomes were tracked in vivo and body weight changes in mice were monitored. Hepatic pathological changes were observed by HE/Masson staining. α-SMA/collagen I levels in liver tissues were assessed by immunohistochemistry. HA/PIIINP concentrations were measured using the magnetic particle chemiluminescence method. Liver function was assessed using an automatic analyzer. miR-20a-5p level was measured by RT-qPCR. The mRNA levels of fibrosis markers were determined by RT-qPCR, and their protein levels and levels of MAPK/NF-κB pathway-related proteins, as well as TGFBR2 protein level were measured by Western blot. The P65 nuclear expression in mouse liver tissues was quantified by immunofluorescence. RESULTS: ADSC-Exos suppressed TGF-ß1-induced LX-2 cell proliferation and fibrosis and reduced mRNA and protein levels of fibrosis markers in vitro. ADSC-Exos ameliorated liver fibrosis by inhibiting the p38 MAPK/NF-κB pathway activation. ADSC-Exos inhibited activation of the p38 MAPK/NF-κB pathway via regulating the miR-20a-5p/TGFBR2 axis. The in vivo experiment asserted that ADSC-Exos were mainly distributed in the liver, and ADSC-Exos relieved liver fibrosis in mice, which was evidenced by alleviating decreased body weight, reducing collagen and enhancing liver function, and repressed the activation of the p38 MAPK/NF-κB pathway via the miR-20a-5p/TGFBR2 axis. CONCLUSION: ADSC-Exos attenuated liver fibrosis by suppressing the activation of the p38 MAPK/NF-κB pathway via the miR-20a-5p/TGFBR2 axis.

Serum basic fibroblast growth factor and interleukin-1ß predict the effect of first-line chemotherapy in patients with advanced gastric cancer.

BACKGROUND: The incidence and mortality rates of gastric cancer in China are the second-highest in the world, and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis. AIM: To explore the predictive potential of serum basic fibroblast growth factor and interleukin-1ß levels for the effect of first-line chemotherapy in patients with advanced gastric cancer. METHODS: From the gastric cancer patients admitted to our hospital from May 2019 to April 2023, 84 patients were selected and randomly and equally assigned to the experimental or control group. The FLOT group received the FLOT chemotherapy regimen (composed of oxaliplatin + calcium folinate + fluorouracil + paclitaxel), while the SOX group received the SOX chemotherapy regimen (composed of oxaliplatin + tiga capsules). The clinical efficacy, tumor marker levels, adverse reactions, and survival rates of the two groups were compared 7 days after the end of the relevant treatments. RESULTS: The target effective rate of the FLOT group was 54.76%, which was much higher than that of the SOX group (33.33%; P < 0.05). After treatment, both the groups demonstrated lower levels of cancer antigen (CEA), carbohydrate antigen 199 (CA199), and peptide tissue antigen (TPS). For several patients before treatment (P < 0.05). Third and fourth grades. In terms of adverse reactions, the level of white blood cells in both the groups was lower. Moreover, the incidence of hand-foot skin reactions in these two study groups was lower (P < 0.05), while those of peripheral neuritis, vomiting, diarrhea, and abnormal liver function were significant (P < 0.05). No statistically significant difference was noted between the two groups (P < 0.05). The 1-year survival rate was higher in the FLOT group (P < 0.05). CONCLUSION: The FLOT regimen was effective in reducing the serum CEA, CA199, and TPS levels as well as in improving the 1-year survival rate of patients with good tolerability, making it worthy of clinical promotion and application.

Positive efficacy of Lactiplantibacillus plantarum MH-301 as a postoperative adjunct to endoscopic sclerotherapy for internal hemorrhoids: a randomized, double-blind, placebo-controlled trial.

Background: Endoscopic sclerotherapy is a widely used minimally invasive procedure for internal hemorrhoids, yet postoperative symptoms remain a concern. The purpose of this study is to investigate the postoperative adjuvant efficacy of Lactiplantibacillus plantarum. Method: In this study, patients (≥18 years) with internal hemorrhoids that conformed to Goligher's classification of grade I-III received administration of L. plantarum MH-301 for 4 weeks following endoscopic sclerotherapy. The primary clinical endpoint in this study was the improvement rate, which was defined as the percentage of patients whose n-HDSS score decreased to 0 following the procedure. Stools were collected for high-throughput sequencing analysis post operation. Result: A total of 103 participants (51 in the LP group and 52 in the C group) were recruited, with 96 completing the entire trial (49 in the LP group and 47 in the C group). The primary clinical endpoint showed a higher improvement rate in the LP group (87.8% vs. 70.2%, P = 0.045). High-throughput sequencing analysis demonstrated that the LP group had a greater diversity of intestinal microbiota and a higher relative abundance of beneficial bacteria such as Bifidobacterium, Megamonas, and Lactobacillus. No significant difference in postoperative complications and adverse events was found. Conclusion: This paper concludes that the administration of L. plantarum MH-301 after endoscopic sclerotherapy can further increase the efficacy of the procedure and improve bowel movements. Regulation of intestinal microbiota may be the potential mechanism for the efficacy of L. plantarum MH-301.

From waste to resource: Metagenomics uncovers the molecular ecological resources for plastic degradation in estuaries of South China.

Estuaries are hotspots of plastic pollution due to accumulated waste from surrounding rivers and coasts. However, the molecular ecological resources that possess plastic-degrading traits and their biogeographic distributions in estuarine waters remain to be elucidated. In this study, we mapped the distribution profiles of plastic-degrading genes (PDGs) in 30 subtropical estuaries in China based on metagenomic sequencing. A total of 41 PDG subtypes were observed in these estuaries. The Pearl River Estuary had higher diversity and abundance of PDGs than the east and west region estuaries. Genes for degrading synthetic heterochain and natural plastics were the most diverse and abundant types, respectively. The abundance of synthetic PDGs was significantly higher in estuaries affected by intense anthropogenic activities. Further binning strategies revealed diverse microbes with plastic-degrading ability in these estuaries. Rhodobacteraceae, a dominant plastic-degrading bacterial family, primarily carried PDGs for degrading natural plastics. Pseudomonas veronii carrying diverse PDGs was identified, which may be of value for further technical improvement of plastic degradation. In addition, phylogenetic and structural analyses of 19 putative 3HV dehydrogenases, the most diverse and abundant DPGs, showed inconsistent evolution with their hosts, but different sequences were conserved with consistent key functional amino acids. A potential biodegradation pathway for polyhydroxybutyrate by Rhodobacteraceae was proposed. The result implied that plastic-degrading functions are widely distributed in estuarine waters and metagenomics could be used as a promising screening tool for large-scale profiling of plastic-degrading potential in the natural environment. Our findings have important implications and provide potential molecular ecological resources for developing plastic waste removal technologies.

Rapid membrane surface functionalization with Ag nanoparticles via coupling electrospray and polymeric solvent bonding for enhanced antifouling and catalytic performance: Deposition and interfacial reaction mechanisms.

Electrospray is an effective, fast, and potentially scalable approach for membrane surface functionalization using various engineered nanomaterials (ENMs). However, the lack of fundamental understandings of the deposition process hinders the controlled deposition, efficient utilization, and long-term stabilization of the ENMs, and thus the practical applications of the nanocomposite membranes. To bridge this critical knowledge gap, advanced online characterization techniques (laser diffraction size measurement and laser doppler velocimetry) coupled with mathematical aerosol modeling are utilized to understand the three key process parameters: droplet size, deposition velocity, and evaporation rate. After deposition, polymeric solvent bonding (i.e., interdiffusion and subsequent entanglement of polymers) was found to substantially stabilize the deposited Ag NPs. We further provide a comprehensive description of such interfacial reaction mechanisms. Our results show a consistency between theoretical predication and measurement of the droplet size or deposition velocity, whereas realistic droplet evaporation rate is lower than the theoretical value due to the addition of the polymer. Successful stabilization of Ag NPs via interfacial polymeric bonding occurs under the conditions of large material contact area, high material compatibility, proper temperature (e.g., 22 °C), and polymer-to-solvent ratio (e.g., 3-5%). Our coupled approach achieves superior Ag NP coverage with high stability within minutes. Despite some reduction in water permeance, the resultant membrane shows markedly improved catalytic and antimicrobial (antibiofouling) performance (>90% enhancement) and maintained rejection. Taken together, our findings provide fundamental insights into the coupled process of electrospray deposition and polymeric solvent bonding to enable additive manufacturing of novel nanocomposite membranes with diverse structures and multiple functions.

Biogeographic Patterns and Community Assembly Processes of Bacterioplankton and Potential Pathogens in Subtropical Estuaries in China.

Microbial communities in coastal waters are diverse and dynamic and play important roles in ecosystem functions and services. Despite the ecological impact of bacterioplankton or pathogens, little is known about whether bacterioplankton and pathogen communities exhibit similar patterns. Here, using 16S RNA gene amplicon sequencing, the geographic patterns and assembly processes of bacterioplankton and pathogen communities in 30 subtropical estuaries were studied. Results showed that the estuarine bacterioplankton communities mainly consisted of Proteobacteria (49.06%), Actinobacteria (17.62%), and Bacteroidetes (16.33%), among which 31 pathogen genera (186 amplicon sequence variants [ASVs]) were identified. Under the influence of salinity, bacterioplankton and pathogens showed similar biogeographic patterns. Redundancy and correlation analyses indicated that the bacterioplankton communities were strongly correlated with estuarine environmental factors, but potential pathogens were less influenced. Co-occurrence network analysis revealed a close relationship between bacterioplankton and potential pathogens, with two pathogens identified as connectors (i.e., ASV340 [Clostridium perfringens] and ASV1624 [Brevundimonas diminuta]), implying potential impacts of pathogens on structure, function, and stability of estuarine bacterioplankton communities. Null-model analysis revealed that deterministic processes (heterogeneous selection) dominated bacterioplankton community assembly, while stochastic processes (undominated effect) shaped the potential pathogen community. Our findings illustrate the biogeographic patterns and community assembly mechanisms of bacterioplankton and pathogens in estuaries, which should provide guidance and a reference for the control of potential pathogenic bacteria. IMPORTANCE Bacterioplankton play an important role in estuarine ecosystem functions and services; however, potentially pathogenic bacteria may exhibit infectivity and pose a serious threat to environmental and human health. In this study, geographic patterns and assembly processes of bacterioplankton communities in 30 subtropical estuaries were explored, and potential pathogenic bacteria in the estuaries were detected and profiled. Our results demonstrate here that bacterioplankton and pathogens show similar biogeographic patterns under the influence of salinity. Interestingly, heterogeneous selection dominated bacterioplankton assembly, while stochasticity dominated pathogen assembly. This study provides important information for future risk assessment of potential pathogenic bacteria as well as management in estuarine ecosystems.

Predicting the abundance of metal resistance genes in subtropical estuaries using amplicon sequencing and machine learning.

Heavy metals are a group of anthropogenic contaminants in estuary ecosystems. Bacteria in estuaries counteract the highly concentrated metal toxicity through metal resistance genes (MRGs). Presently, metagenomic technology is popularly used to study MRGs. However, an easier and less expensive method of acquiring MRG information is needed to deepen our understanding of the fate of MRGs. Thus, this study explores the feasibility of using a machine learning approach-namely, random forests (RF)-to predict MRG abundance based on the 16S rRNA amplicon sequenced datasets from subtropical estuaries in China. Our results showed that the total MRG abundance could be predicted by RF models using bacterial composition at different taxonomic levels. Among them, the relative abundance of bacterial phyla had the highest predicted accuracy (71.7 %). In addition, the RF models constructed by bacterial phyla predicted the abundance of six MRG types and nine MRG subtypes with substantial accuracy (R2 > 0.600). Five bacterial phyla (Firmicutes, Bacteroidetes, Patescibacteria, Armatimonadetes, and Nitrospirae) substantially determined the variations in MRG abundance. Our findings prove that RF models can predict MRG abundance in South China estuaries during the wet season by using the bacterial composition obtained by 16S rRNA amplicon sequencing.

Improvement Effect of Bifidobacterium animalis subsp. lactis MH-02 in Patients Receiving Resection of Colorectal Polyps: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Postoperative symptoms, bowel dysfunction and recurrence are common problems after resection of colorectal polyps. We aimed to evaluate the efficacy of Bifidobacterium in the postoperative patients. Methods: In this single-center, randomized, double-blind, placebo-controlled trial, adults (≥ 18 years) undergoing endoscopic resection of colorectal polyps were treated with probiotics (Bifidobacterium animalis subsp. lactis MH-02, 2 × 109 colony-forming units per packet) or placebo once daily for 7 days. The primary clinical endpoint was a reduction in the mean total postoperative symptoms score within 7 days postoperatively. Secondary clinical endpoints were the single symptom scores, time to recovery of bowel function, and changes in the intestinal microbiota. This study is registered with the number ChiCTR2100046687. Results: A total of 100 individuals were included (48 in probiotic group and 52 in placebo group). No difference was seen in the mean scores between the two groups (0.29 vs. 0.43, P = 0.246). Colorectal polyps size (P = 0.008) and preoperative symptoms (P = 0.032) were influential factors for the primary endpoint. Besides, MH-02 alleviated difficult defecation (P = 0.045), and reduced the time to recovery of bowel function (P = 0.032). High-throughput analysis showed that MH-02 can help restore the diversity of intestinal microbiota, and increased the relative abundance of Bifidobacterium, Roseburia, Gemmiger, Blautia and Ruminococcus, while reduced the relative abundance of Clostridium at genus level (P < 0.05). Conclusion: In this prospective trial, MH-02 showed efficacy in patients with resection of colorectal polyps, particularly in the recovery of bowel function, and the changes in the intestinal microbiota may provide evidence for further exploration of the therapeutic mechanisms.

Small Proline-Rich Protein 2B Facilitates Gastric Adenocarcinoma Proliferation via MDM2-p53/p21 Signaling Pathway.

BACKGROUND: The small proline-rich protein 2B (SPRR2B) was firstly reported as a member of the cross-linked envelope protein in keratinocytes. The effect of SPRR2B in gastric adenocarcinoma (GC) remains unclear. This study initially explored the clinical significance of SPRR2B in GC patients as well as its role in tumor progression. METHODS: Immunohistochemistry was performed to characterize the expression of SPRR2B in GC tissues and adjacent tissues. The relationship between SPRR2B expression and clinicopathological features of GC patients was analyzed by Chi-square test. Kaplan-Meier method and Cox regression analyses were utilized to identify the prognostic factors of GC. Overexpression and knockdown assays were conducted to investigate possible signaling pathways downstream of SPRR2B. Flow cytometry assays were performed to evaluate cell cycle and apoptosis. Xenograft experiments were performed to validate tumor-related role of SPRR2B in vivo. RESULTS: Both mRNA and protein levels of SPRR2B in cancerous tissue were significantly higher than those in non-cancerous tissues. Meanwhile, SPRR2B expression was significantly associated with tumor size and tumor stage. Survival analysis revealed SPRR2B as one of the independent prognosis factors for overall survival of GC patients. Cellular and xenografts data implicated that silencing SPRR2B blocked the cell cycle of GC cells perhaps through MDM2-p53/p21-CDK1 pathway, while overexpressing SPRR2B exhibited opposite effects. CONCLUSION: Our data suggest that SPRR2B may serve as a novel prognostic marker in GC, which functions at least partially by MDM2-p53/p21-CDK1 signaling pathway.

XPD inhibits cell growth and invasion and enhances chemosensitivity in esophageal squamous cell carcinoma by regulating the PI3K/AKT signaling pathway.

Esophageal squamous cell carcinoma (ESCC) is a lethal disease due to its high aggressiveness. The aim of the present study was to investigate the role of xeroderma pigmentosum complementation group D (XPD) in the growth and invasion of ESCC and to elucidate the potential underlying molecular mechanisms. Western blot analysis and RT­qPCR were used to detect the expression level of XPD in ESCC tissue samples and adjacent normal esophageal tissue samples. The pEGFP­N2/XPD plasmid was transfected into human ESCC cell lines (EC9706 and EC109). The proliferation, apoptosis, migration and invasion of EC9706 or EC109 cells were assessed following transfection with the XPD overexpression plasmid. The chemosensitivity of EC9706 or EC109 cells to cisplatin or fluorouracil was evaluated by CCK­8 assay. The expression levels of phosphoinositide 3­kinase (PI3K)/AKT, nuclear factor (NF)­κB, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and mitogen­activated protein kinase (MAPK) signaling pathway­related genes were detected by RT­qPCR and western blot analysis. The results demonstrated that the expression level of XPD was markedly lower in ESCC tissue samples than in adjacent normal esophageal tissue samples. The pEGFP­N2/XPD plasmid was successfully transfected into EC9706 or EC109 cells, inducing XPD overexpression. A High XPD expression markedly suppressed cell proliferation, migration and invasion, and increased the apoptotic rate of EC9706 and EC109 cells. Furthermore, the overexpression of XPD significantly increased the chemosensitivity of EC9706 and EC109 cells to cisplatin or fluorouracil. Following XPD overexpression, the expression levels of PI3K, p­AKT, c­Myc, Cyclin D1, Bcl­2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)­9 were markedly downregulated, while the expression level of p21 was markedly upregulated. On the whole, the findings of the present study demonstrate that XPD inhibits the growth and invasion of EC9706 and EC109 cells, whilst also enhancing the chemosensitivity of EC9706 and EC109 cells to cisplatin or fluorouracil by regulating the PI3K/AKT signaling pathway. XPD may thus be an underlying target for ESCC treatment and drug resistance.

Upregulation of MANCR predicts poor survival in patients with gastric cancer.

A previous study revealed that MANCR (mitotically associated long non-coding RNA) is implicated in breast cancer. The present study investigated the potential role of MANCR in gastric cancer (GC) and revealed that MANCR was upregulated in GC tissues compared with non-cancerous tissues. MANCR expression was not affected by clinical stages and a high MANCR expression level was associated with poor survival time. MicroRNA (miR)-101 was downregulated in cancer tissues compared with non-cancerous tissues and was inversely associated with MANCR expression. MANCR overexpression in GC cell lines in vitro resulted in miR-101 downregulation; however, miR-101 overexpression did not alter MANCR expression. Furthermore, MANCR overexpression promoted, while miR-101 overexpression inhibited GC cell proliferation. In addition, miR-101 overexpression decreased the effect of MANCR overexpression. The results obtained in the present study revealed that MANCR expression was associated with the survival of patients with GC, and MANCR overexpression in vitro may promote GC by downregulating miR-101 and increasing the proliferation of GC cells.

pH dependence of the binding interactions between humic acids and bisphenol A - A thermodynamic perspective.

The wide application of bisphenol A (BPA) leads to the emergence of BPA residuals in natural water environments. Dissolved organic matter (DOM) existed in water can bind with BPA, hence influencing the migration and transformation of BPA in aquatic environments. pH is a crucial factor governing the binding interactions between DOM and BPA. However, the mechanisms driven the binding process under different pH conditions are still unclear. In this study, the interactions between BPA and humic acids (HA), a primary component of DOM, are investigated over a wide pH range of 3-12 by integrating fluorescence quenching, dynamic light scattering and microcalorimetry. pH dependence of the binding interactions between HA and BPA are interpreted from a thermodynamic perspective. The results indicate that HA can spontaneously interact with BPA to form a stable HA-BPA complex. With the increasing pH, the binding interactions change from entropy driven to entropy-enthalpy co-driven. Hydrophobic force dominate the binding interactions under acidic condition. The synergy of hydrophobic force and hydrogen bond promotes the binding process under neutral condition. Under alkaline conditions, electrostatic repulsion participates the binding process in addition to hydrophobic force and hydrogen bond, weakening the binding strength. Therefore, neutral pH is favorable for HA to bind with BPA, consequently enhancing the dissolution of BPA in natural water bodies. The results are beneficial to better understand the pH dependent distribution of BPA in aquatic environments.

Insights into thermodynamic mechanisms driving bisphenol A (BPA) binding to extracellular polymeric substances (EPS) of activated sludge.

Bisphenol A (BPA) in wastewater has high risks of causing biological feminization. During the wastewater treatment process, large amounts of BPA are accumulated in activated sludge. However, the mechanisms of BPA interacted with activated sludge are still unclear. Especially, the roles of extracellular polymeric substances (EPS), which are major components of activated sludge, in the removal of BPA have never been concerned. In this study, the binding interactions between sludge EPS and BPA are explored combining fluorescence spectroscopy and dynamic light scattering. The thermodynamic mechanisms driving the binding behavior of BPA to EPS are illustrated by isothermal titration calorimetry. The results indicate that the binding interaction between BPA and EPS is spontaneous. BPA mainly binds with the proteins of EPS by hydrophobic association. The random-coiled structure of EPS transforms into relatively condensed cores after binding with BPA. A neutral pH, high ionic strength, and high temperature promote the binding process, facilitating to stabilize BPA in sludge EPS. This study provides new insights into the roles of sludge EPS in the migration and removal of BPA in activated sludge system.

Fermentation liquor of CaO2 treated chemically enhanced primary sedimentation (CEPS) sludge for bioplastic biosynthesis.

Chemically enhanced primary sedimentation (CEPS) technology has been widely applied in Hong Kong, exhibiting excellent performance in contaminants removal from sewage. The generated CEPS sludge contains abundance of organics which could be recovered as volatile fatty acids (VFAs) by fermentation for further utilization. In this work, the effect of calcium peroxide (CaO2) on the fermentation of FeCl3 based CEPS sludge was investigated. The feasibility of utilizing the fermentation liquor as substrate for polyhydroxyalkanoates (PHAs) biosynthesis was also evaluated. Results demonstrated that CaO2 addition facilitated the disintegration of CEPS sludge and enhanced VFAs production. The maximum VFAs yield of 455.8 mg COD/g VSS was obtained with the dosage of 0.1 g CaO2/g SS, improving by 44.7% compared with the control sludge. Acetic and propionic acid were the predominant components of the VFAs. Microbial analysis indicated that CaO2 induced microbial reduction of Fe(III), accelerating the initial disintegration of FeCl3 based CEPS sludge. Microbial communities with hydrolysis and acidogenesis functions were enriched effectively. CaO2 treatment had no significant influence on the release of ammonia nitrogen (NH4+-N), while reduced the concentration of orthophosphate (PO43--P) and ferrous (Fe2+) in fermentation liquor, that was beneficial to the further utilization as substrate for PHAs biosynthesis. The VFA-rich fermentation liquor was proved to be a suitable substrate for PHAs biosynthesis. After cultivation, the PHAs content in activated sludge reached 22.3%, which was comparable to those obtained using waste materials as carbon source. This integrated technology could be a superior alternative of realizing sludge disposal and bioplastic production simultaneously.

Homeobox D10 gene, a candidate tumor suppressor, is downregulated through promoter hypermethylation and associated with gastric carcinogenesis.

Homeobox D10 (HoxD10 ) gene plays a critical role in cell differentiation and morphogenesis during development. However, the function of HoxD10 in tumor progression remains largely unknown. We demonstrate that the expression of HoxD10 is commonly downregulated in gastric cancer tissues (n = 33) and cell lines (n = 8) relative to normal stomach tissues. Functionally, reexpression of HoxD10 results in significant inhibition of cell survival, induction of cell apoptosis, and impairment of cell migration and invasion. Moreover, ectopic expression of HoxD10 suppresses gastric tumor growth in a mouse xenograft model. To identify target candidates of HoxD10, we performed cDNA microarray and showed that HoxD10 regulates multiple downstream genes including IGFBP3. Reintroduction of HoxD10 transcriptionally upregulates IGFBP3, activates caspase 3 and caspase 8, and subsequently induces cell apoptosis. Methylation specific PCR revealed that HoxD10 promoter DNA was hypermethylated in gastric cancer cell lines. Additionally, 5-aza demethylation treatment could transiently reactivate the expression of HoxD10 in gastric cancer cells. HoxD10 promoter methylation frequently was detected in gastric cancer tissues obtained from endoscopic biopsies (85.7%, 24/28) and surgically resected samples (82.6%, 57/69). Intestinal metaplasia tissues showed a 60% methylation rate (18/30), but no detectable methylation in normal stomach tissues (0%, 0/10). Taken together, our results suggest that HoxD10 functions as a candidate tumor suppressor in gastric cancer, which is inactivated through promoter hypermethylation.

[DNA methylation of ZIC1 and KLOTHO gene promoters in colorectal carcinomas and its clinicopathological significance].

OBJECTIVE: To determine DNA methylation status of ZIC1 and KLOTHO gene in colorectal carcinomas and its relationship with clinicopathological features of patients. METHODS: The mRNA expression of ZIC1 and KLOTHO genes in colorectal carcinomas was detected by real-time quantitative RT-PCR, and the promoter methylation status was detected by methylation specific PCR (MSP). The relationship of ZIC1 and KLOTHO methylation status with clinicopathological features of colorectal carcinoma was analyzed. RESULT: The mRNA expression levels of ZIC1 and KLOTHO genes were significantly down-regulated in tumor tissues when compared to adjacent nontumor tissues (P<0.001). ZIC1 and KLOTHO methylation was detected in 80.0%(20/25) and 76.0%(19/25) of colorectal tumor tissues, respectively, and the both positive rate was 64.0%(16/25). CONCLUSION: The down-regulated expression of ZIC1 and KLOTHO in colorectal carcinoma may relate to promoter methylation. The detection of methylation of ZIC1 and KLOTHO gene potentially provides biomarkers for diagnosis of colorectal carcinoma.

ZIC1 is downregulated through promoter hypermethylation, and functions as a tumor suppressor gene in colorectal cancer.

The transcription factor, Zinc finger of the cerebellum (ZIC1), plays a crucial role in vertebrate development. Recently, ZIC1 has also been found to participate in the progression of human cancers, including medulloblastomas, endometrial cancers, and mesenchymal neoplasms. However, the function of ZIC1 in colon cancer progression has not been defined. In this study, we demonstrate ZIC1 to be silenced or significantly downregulated in colon cancer cell lines. These effects were reversed by demethylation treatment with 5-aza-2'-deoxycytidine (Aza). ZIC1 expression is also significantly downregulated in primary colorectal cancer tissues relative to adjacent non-tumor tissues (p = 0.0001). Furthermore, methylation of ZIC1 gene promoter is frequently detected in primary tumor tissues (85%, 34/40), but not in adjacent non-tumor tissues. Ectopic expression of ZIC1 suppresses cell proliferation and induces apoptosis, which is associated with MAPK and PI(3)K/Akt pathways, as well as the Bcl-xl/Bad/Caspase3 cascade. To identify target candidates of ZIC1, we employed cDNA microarray and found that 337 genes are downregulated and 95 genes upregulated by ectopic expression of ZIC1, which were verified by 10 selected gene expressions by qRT-PCR. Taken together, our results suggest that ZIC1 may potentially function as a tumor suppressor gene, which is downregulated through promoter hypermethylation in colorectal cancers.