Comprehensive comparison of water quality risk and microbial ecology between new and old cast iron pipe distribution systems.

The effects of cast iron pipe corrosion on water quality risk and microbial ecology in drinking water distribution systems (DWDSs) were investigated. It was found that trihalomethane (THMs) concentration and antibiotic resistance genes (ARGs) increased sharply in the old DWDSs. Under the same residual chlorine concentration conditions, the adenosine triphosphate concentration in the effluent of old DWDSs (Eff-old) was significantly higher than that in the effluent of new DWDSs. Moreover, stronger bioflocculation ability and weaker hydrophobicity coexisted in the extracellular polymeric substances of Eff-old, meanwhile, iron particles could be well inserted into the structure of the biofilms to enhance the mechanical strength and stability of the biofilms, hence enhancing the formation of THMs. Old DWDSs significantly influenced the microbial community of bulk water and triggered stronger microbial antioxidant systems response, resulting in higher ARGs abundance. Corroded cast iron pipes induced a unique interaction system of biofilms, chlorine, and corrosion products. Therefore, as the age of cast iron pipes increases, the fluctuation of water quality and microbial ecology should be paid more attention to maintain the safety of tap water.

Hydroxylamine enhanced the degradation of diclofenac in Cu(II)/peracetic acid system: Formation and contributions of CH3C(O)O•, CH3C(O)OO•, Cu(III) and •OH.

The slow reduction of Cu(II) into Cu(I) through peracetic acid (PAA) heavily limited the widespread application of Cu(II)/PAA system. Herein, hydroxylamine (HA) was proposed to boost the oxidative capacity of Cu(II)/PAA system by facilitating the redox cycle of Cu(I)/Cu(II). HA/Cu(II)/PAA system was quite rapid in the removal of diclofenac within a broad pH range of 4.5-9.5, with a 10-fold increase in the removal rate of diclofenac compared with the Cu(II)/PAA system at an optimal initial pH of 8.5. Results of UV-Vis spectra, electron paramagnetic resonance, and alcohol quenching experiments demonstrated that CH3C(O)O•, CH3C(O)OO•, Cu(III), and •OH were involved in HA/Cu(II)/PAA system, while CH3C(O)OO• was verified as the predominant reactive species of diclofenac elimination. Different from previously reported Cu-catalyzed PAA processes, CH3C(O)OO• mainly generated from the reaction of PAA with Cu(III) rather than CH3C(O)O• and •OH. Four possible elimination pathways for diclofenac were proposed, and the acute toxicity of treated diclofenac solution with HA/Cu(II)/PAA system significantly decreased. Moreover, HA/Cu(II)/PAA system possessed a strong anti-interference ability towards the commonly existent water matrix. This research proposed an effective strategy to boost the oxidative capacity of Cu(II)/PAA system and might promote its potential application, especially in copper-contained wastewater.

Calcium sulfite oxidation activated by ferrous iron integrated with membrane filtration for removal of typical algal contaminants.

Oxidation treatment of algae-laden water may cause cells rupture and emission of intracellular organics, thus restricting its further popularization. As a moderate oxidant, calcium sulfite could be slowly released in the liquid phase, thus exhibiting a potential to maintain the cells integrity. To this end, calcium sulfite oxidation activated by ferrous iron was proposed integrated with ultrafiltration (UF) for removal of Microcystis aeruginosa, Chlorella vulgaris and Scenedesmus quadricauda. The organic pollutants were significantly eliminated, and the repulsion between algal cells was obviously weakened. Through fluorescent components extraction and molecular weights distribution analyses, the degradation of fluorescent substances and the generation of micromolecular organics were verified. Moreover, the algal cells were dramatically agglomerated and formed larger flocs under the premise of maintaining high cell integrity. The terminal normalized flux was ascended from 0.048-0.072 to 0.711-0.956, and the fouling resistances were extraordinarily decreased. Due to the distinctive spiny structure and minimal electrostatic repulsion, Scenedesmus quadricauda was easier to form flocs, and its fouling was more readily mitigated. The fouling mechanism was remarkably altered through postponing the formation of cake filtration. The membrane interface characteristics including microstructures and functional groups firmly proved the fouling control efficiency. The reactive oxygen species (i.e., SO4•- and 1O2) generated through the principal reactions and Fe-Ca composite flocs played dominant roles in alleviating membrane fouling. Overall, the proposed pretreatment exhibits a brilliant application potential for enhancing UF in algal removal.

Advantages and Limitations of Monitoring Circulating Tumor DNA Levels to Predict the Prognosis of Patients Diagnosed With Gastric Cancer.

Next-generation sequencing-based genomic profiling facilitates biomarker detection by cell-free DNA (cfDNA) liquid biopsy. However, the efficiency of mutation calling and the prognostic value of cfDNA biomarkers are disputed. We investigated 24 patients with gastric cancer in this study, using a 605-gene sequencing panel to sequence their plasma cfDNA and tumor tissue DNA. The mutation concordance between plasma cfDNA and tumor tissue DNA was 70.6% in stage IV gastric cancer and 30.2% in stage III gastric cancer, indicating insufficient mutation detection rates in stage III and early-stage cancer. When compared with total cfDNA load and blood tumor mutation burden (bTMB), the variant allele frequencies (VAF) of commonly mutated genes are highly accurate in representing disease burden. Further, VAF are a better prognostic indicator compared with serum biomarkers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), cancer antigen 125 (CA125), and alpha-fetoprotein (AFP). The use of cfDNA in molecular profiling of patients allows prediction of patient survival and clinical response, as well as the development of personalized therapy regimens.

Study on the angiogenesis ability of Polymethyl methacrylate-mineralized collagen/Mg-Ca composite material in vitro and the bone formation effect in vivo.

Magnesium (Mg) and its alloys show high degrees of biocompatibility and biodegradability, used as biodegrad able materials in biomedical applications. In this study, Polymethyl methacrylate (PMMA) - mineralized collagen (nano-Hydroxyapatite/collagen; nHAC)/Mg-Ca composite materials were prepared, to study the angiogenesis ability of its composite materials on Human umbilical vein endothelial cells (HUVECs) and its osteogenesis effect in vivo. The results showed that the PMMA-nHAC reinforcement materials can promote the proliferation and adhesion in HUVECs of Mg matrix significantly, it can enhance the migration motility and VEGF expression of HUVECs. In vivo, Micro-CT examination showed that with coated samples presenting the highest bone formation. Histologically, the materials and their corrosion products caused no systematic or local cytotoxicological effects. Therefore, the Mg matrix composites prepared in the present study has good biocompatibility and PMMA-nHAC/Mg-Ca composite may be an ideal orthopedic material to improve the bone formation, and biodegradable magnesium based implants with bioactivity have potential applications in bone tissue.

Improved Electron Efficiency of Zero-Valent Iron towards Cr(VI) Reduction after Sequestering in Al2O3 Microspheres.

Zero-valent iron (ZVI) is widely used for groundwater remediation, but suffers from high electron consumption because of its free contact with non-target substrates such as O2. Here, ZVI-ALOX particles were prepared via in situ NaBH4 aqueous-phase reduction of ferrous ions (Fe2+) preabsorbed into Al2O3 microspheres. The electron efficiency (EE) and long-term performance of the material were improved by sequestering ZVI in the interspace of the Al2O3 microspheres (ZVI-ALOX). During long-term (350 days) continuous flow, Cr(VI) was removed to below the detection limit for over 23 days. Based on the high reactivity of ZVI towards Cr(VI), the EE of ZVI-ALOX was evaluated by measuring its Cr(VI) removal efficiency at neutral pH and comparing it with that of ZVI. The results showed that the EE of ZVI-ALOX during long-term continuous flow could reach 39.1%, which was much higher than that of ZVI (8.68%). The long-term continuous flow results also demonstrated that treatment of the influent solution achieved higher EE values than in the batch mode, where the presence of dissolved oxygen reduced EE values. At lower pollutant concentrations, the sequestering of ZVI was beneficial to its performance and long-term utility. In addition, measurement of the acute toxicity of treated column effluent using the indicator organism Photobacterium phosphoreum T3 showed that ZVI-ALOX could reduce the toxicity of 5 mg/L Cr(VI) solution by ~70% in 350 d. The results from this study provide a basis for the development of permeable reactive barriers for groundwater remediation based on sequestered ZVI.

In vitro evaluation of freeze-drying chitosan-mineralized collagen/Mg-Ca alloy composites for osteogenesis.

Magnesium (Mg) alloy with good mechanical properties and biodegradability is considered as one of the ideal bone repair materials. However, the rapid corrosion of Mg-based metals can pose harm to the function of an implant in clinical applications. In this study, micro-arc oxidation coating was prepared on the surface of the Mg-Ca matrix, then the chitosan and mineralized collagen (nano-hydroxyapatite/collagen; nHAC) were immobilized on the surface of the MAO/Mg-Ca matrix to construct the CS-nHAC/Mg-Ca composites of different component proportions (the ratio of CS to nHAC is 2:1, 1:1, and 1:2, respectively). The corrosion resistance, osteogenic activity, and angiogenic ability were extensively investigated. The results indicated that the CS-nHAC reinforcement materials can improve the corrosion resistance of the Mg matrix significantly and promote the proliferation and adhesion of mouse embryo osteoblast precursor cells (MC3T3-E1) and human umbilical vein endothelial cells (HUVECs). In addition, the CS-nHAC/Mg-Ca composites can not only promote the alkaline phosphatase (ALP) activity and extracellular matrix mineralization of MC3T3-E1 cells but also enhance the migration motility and vascular endothelial growth factor (VEGF) expression of HUVECs. Meanwhile, the 2CS-1nHAC/Mg-Ca composite exhibited the optimum function characteristics compared with other samples. Therefore, considering the improvement of corrosion resistance and biocompatibility, the CS-nHAC/Mg-Ca composites are expected to be a promising orthopedic implant.

Inhibition of lung cancer by vitamin D depends on downregulation of histidine-rich calcium-binding protein.

Introduction: Intrinsic vitamin D affects the proliferation, apoptosis, invasion, metastasis, and tumorigenesis of lung cancer by regulating tumor signaling pathways. Histidine-rich calcium-binding protein (HRC) maintains Ca2+ homeostasis, which plays crucial roles in the occurrence and development of cancer. Objectives: Our study aims to investigate the ability of vitamin D in the regulation of HRC and the role of HRC playing in lung cancer. Methods: We investigated the effects of vitamin D on lung cancer and the underlying mechanisms, by measuring HRC and vitamin D receptor (VDR) expression in lung cancer, paracancer, and normal tissues from patients using immunohistochemistry, western blotting, and real time RT-PCR. We transfected H460 lung cancer cells (supplemented or not with vitamin D) with PX458-HRC and pcDNA3.1-HRC plasmids and injected mice with lung cancer cells harboring pcDNA3.1-vector or pcDNA3.1-HRC plasmids. Results: Vitamin D inhibited HRC expression and H460 cell migration and proliferation, and promoted apoptosis compared with controls. The expression of HRC and VDR was significantly upregulated and downregulated, respectively, in lung cancer versus paracancer or normal tissues. Cell proliferation and migration were reduced, apoptotic cells were more and tumors were smaller in mice treated with vitamin D/cholecalciferol cholesterol emulsion (CCE) than in vitamin D/CCE+HRC+/+ mice. Conclusion: Vitamin D inhibited lung cancer tumor growth, migration, and proliferation by downregulating HRC.

In vivo antiviral activity and disassembly mechanism of novel 1-phenyl-5-amine-4-pyrazole thioether derivatives against Tobacco mosaic virus.

A series of novel 1-phenyl-5-amine-4-pyrazole thioether derivatives containing a 1,3,4-oxadiazole moiety was designed and synthesised. In vivo antiviral bioassay results showed that most of the target compounds exhibited excellent inactivation activity against Tobacco mosaic virus (TMV). The EC50 values of the inactivation activities for T2, T7, T9, T24, T25 and T27 were 15.7, 15.7, 15.5, 11.9, 12.5 and 16.5 µg/mL, respectively, which were remarkably superior over that of the commercialised antiviral agent ningnanmycin (40.3 µg/mL). Morphological study using AFM and TEM of TMV treated with T24 showed that T24 could significantly shorten the polymerization length of TMV particles and formed a distinct break on the rod-shaped TMV. Investigations for virus infection efficiency on tobacco leaves demonstrated that infectivity of virion had been reduced obviously upon T24 treatment. Subsequently, a strong interaction between T24 and TMV-CP (Kd = 3.8 µM, score 6.11) was observed through MST experiments. Molecular docking study further revealed that target compounds interact with amino acid residue Glu50 in TMV CP, causing disassembly of virion, shorting the length of the virion and reducing the infectivity of virion, and resulting in high inactivating activity of target compounds. This study provides a new insight for discovery of antiviral compounds through a new action mechanism with a new binding site.

Vitamin D alleviates liver fibrosis by inhibiting histidine-rich calcium binding protein (HRC).

BACKGROUND: Liver fibrosis may progress toward cirrhosis and cancer without effective therapy. Here, we investigated the underlying mechanism of Vitamin D as a therapeutic approach. METHODS: Carbon tetrachloride (CCL4)-induced mice model and transforming growth factor-ß1 (TGF-ß1) induced human hepatic stellate cell line LX-2 were used in vivo and in vitro. The fibrotic profiles, degree of liver injury and HRC expression were assessed by histology, Western blot, immunohistochemistry and Real-Time PCR. The proliferation of cells transfected with HRC +/+ and HRC-/- plasmids was detected by MTS and cell cycle methods. RESULTS: Vitamin D significantly suppressed the expression of HRC in liver fibrosis model both in vivo and in vitro (P < 0.01). The cell with overexpression of HRC significantly increased TGF-ß1/Smad3 expressions and the percentage of the S peak in cell cycle (P < 0.05). However, Vitamin D can significantly reverse the levels of TGF-ß1, Smad3 and p-smad3 caused by HRC in vitro. Furthermore, the overexpression of HRC in cell lines can attenuate the function of Vitamin D, suggesting that VD played a role by regulating HRC. Mechanically, HRC as the target of VDR is detected by CHIP method. CONCLUSIONS: Vitamin D can delay hepatic fibrosis by reducing activation of hepatic stellate cells and TGF-ß/Smad signaling through negative regulation of HRC. The findings revealed the important regulatory effect of Vitamin D in hepatic stellate cells and provided new insights into the therapeutic function of Vitamin D on liver fibrosis.

A novel SLC6A8 mutation associated with intellectual disabilities in a Chinese family exhibiting creatine transporter deficiency: case report.

BACKGROUND: X-linked creatine transporter deficiency (OMIM#300036,CRTR-D) is characterized by cerebral creatine deficiency, intellectual disabilities, severe speech impairment, seizures and behavioral problems. Mutations in the creatine transporter gene SLC6A8, a member of the solute-carrier family 6 mapped to Xq28, have been reported to cause the creatine transporter deficiency. CASE PRESENTATION: The proband presented at 5 yrs. 1 month of age with delays in intellectual and development, seizures and behavioral problems. A novel missense mutation, c.1181C > A (p.Thr394Lys), in the SLC6A8 gene (NM_005629.3) was detected via targeted exome sequencing, and then validated by Sanger sequencing. Multiple in silico variant effect analysis methods, including SIFT, PolyPhen2, PROVEAN, and Mutation Taster predicted that this variant was likely damaging or diseasing-causing. This hemizygous variation was also identified in the affected brother with the same clinical condition and inherited from the heterozygous carrier mother. The diagnosis was suggested by increased urinary creatine/creatinine (Cr:Crn) ratio and markedly reduced creatine content peak by brain proton magnetic resonance spectroscopy (MRS). The proband's mother became pregnant with a 3rd sibling, in whom the Sanger sequencing result of c.1181C > A was negative. CONCLUSION: The novel mutation c.1181C > A in the SLC6A8 gene reported in a Chinese family has expanded the mutation spectrum of CRTR-D. The combination of powerful new technologies such as targeted exome sequencing with thorough systematic clinical evaluation of patients will improve the diagnostic yield, and assist in genetic counselling and prenatal diagnosis for suspected genetic disorders.