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Silver nanoparticles show non-negligible impacts on the microbiome and antibiotic resistome in biofilm during colonization.

The abundant production and wide usage of silver nanoparticles (Ag NPs) inevitably lead to their release into aquatic ecosystems. However, it is still unclear about how Ag NPs influence denitrification and anammox (DA) in freshwater sediments. To address this, the sediments of hypertrophic and mesotrophic lakes were exposed to 0.5 and 50 mg/L Ag NPs under anaerobic conditions for 7 days to explore the effects of Ag NPs on environmental variables, including redox potential (Eh), pH, organic matter (OM) and acid volatile sulfide (AVS), and the resulting influence on DA. Experimental results indicated that NO

Soil arsenic (As) pollution has become a global problem. It is urgent to improve the phytoextraction efficiency of soil As. This study found chemical activators (Span 80/SDS and GSH/Span 80/SDS) that can significantly improve the availability of As and the phytoextraction efficiency of As by Pteris vittata L. in As-contaminated soil. Compared with the control, in the soil screening experiment, Span 80/SDS and GSH/Span 80/SDS significantly increased available As in soil by 73.4% and 81.4%, respectively. And in the soil pot experiment, the Span 80/SDS and GSH/Span 80/SDS significantly increased the As concentration in the pinnae of Pteris vittata L. by 53.4% and 41.2%, respectively, and the total As amount extraction by Pteris vittata L. increased significantly by 31.7% and 94.2%, respectively. The results suggest that adding Span 80/SDS and GSH/Span 80/SDS to As-contaminated soil can be considered as an effectively method to improve the efficiency of phytoextraction.

BackgroundThe existing cell surface markers used for sorting glioma stem cells (GSCs) have obvious limitations, such as vulnerability to the enzymatic digestion and time-consuming labeling procedure. Reduced nicotinamide adenine dinucleotide (NADH) as a cellular metabolite with property of autofluorescence has the potential to be used as a new biomarker for sorting GSCs.MethodsA method for sorting GSCs was established according to the properties of the autofluorescence of NADH. Then, the NADHhighand NADHlowsubpopulations were sorted. The stem-like properties of the subpopulations were evaluated by qRT-PCR, western blot analyses, limiting dilution assay, cell viability assay, bioluminescence imaging, and immunofluorescence analysis in vitro and in vivo. The relationship between CD133+/CD15+cells and NADHhighsubpopulation was also assessed.ResultsNADHhighcells expressed higher stem-related genes, formed more tumor spheres, and harbored stronger pluripotency in vitro and higher tumorigenicity in vivo, compared to NADHlowsubpopulation. NADHhighglioma cells had the similar stemness with CD133+or CD15+GSCs, but the three subpopulations less overlaid each other. Also, NADHhighglioma cells were more invasive and more resistant to chemotherapeutic drug temozolomide (TMZ) than NADHlowcells. In addition, the autofluorescence of NADH might be an appropriate marker to sort cancer stem cells (CSCs) in other cancer types, such as breast and colon cancer.ConclusionOur findings demonstrate that intracellular autofluorescence of NADH is a non-labeling, sensitive maker for isolating GSCs, even for other CSCs.

Zinc oxide nanoparticles (ZnO NPs) and its sulfidized form (ZnS NPs) are increasingly entering into freshwater systems through multiple pathways. However, their impacts on the composition and function of sedimentary microbial communities are still largely unknown. Here, two kinds of lake-derived microcosms were constructed and incubated with ZnO NPs, or ZnS NPs to investigate the short-term (7 days) and long-term (50 days) impacts on sedimentary microbial communities and nitrogen cycling. After 7 days, both ZnO NPs and ZnS NPs dosed microbial communities experienced distinct alterations as compared to the undosed controls. By day 50, the structural shifts of microbial communities caused by ZnO NPs were significantly enlarged, while the microbial shifts induced by ZnS NPs were largely resolved. Additionally, ZnO NPs and ZnS NPs could significantly alter nitrogen species and nitrogen cycling genes in sediments, revealing their non-negligible impacts on nitrogen cycling processes. Furthermore, our data clearly indicated that the impacts of ZnO NPs and ZnS NPs on nitrogen cycling differed distinctly in different lake-derived microcosms, and the impacts were significantly correlated with microbial community structure. Overall, this research suggests that the entrance of pristine or sulfidized ZnO NPs into freshwater systems may significantly impact the sedimentary microbial community structure and nitrogen cycling.

A Gram-stain-negative, aerobic, rod-shaped, non-motile, pink-pigmented bacterium, designated NLT, was isolated from arsenic-contaminated farmland soil. Strain NLT showed the highest 16S rRNA gene sequence similarities with those of Hymenobacter jeollabukensis 1-3-3-8T (98.9 %), Hymenobacter gummosus ANT-18T (97.5 %), Hymenobacter paludis KBP-30T (97.4 %), Hymenobacter ocellatus Myx2105T (97.1 %) and Hymenobacter coalescens WW84T (96.4 %). The values of genomic orthoANI and dDDH between strain NLT and Hymenobacter jeollabukensis KCTC 52741T was 90.5 and 41.2 %, respectively, and those between strain NLT and Hymenobacter gummosus KCTC 52166T was 84.4 and 28.4 %, respectively. Strain NLT exhibited DNA–DNA hybridisation values of 41.3 and 44.1 % with Hymenobacter paludis KCTC 32237T and Hymenobacter ocellatus DSM 11117T, respectively. Strain NLT had major fatty acids (>10 %) of summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B), iso-C15 : 0 and anteiso-C15 : 0 and the predominant polyamine of homospermidine. The only respiratory quinone was menaquinone-7. The polar lipids were phosphatidylethanolamine, phospholipid, three unidentified lipids and two amino lipids. Strain NLT had a genome size of 6.04 Mb and the average G+C content of 65.6 %. Compared to the other Hymenobacter spp., strain NLT is different in polar lipid profile (without aminophospholipid) and leucine arylamidase activity. Based on the data of the polyphasic analysis, it is considered that strain NLT represented a novel species of genus Hymenobacter , for which the name Hymenobacter edaphisp. nov. is proposed. The type strain is NLT (=KCTC 62521T=CCTCC AB 2018028T).

Medulloblastoma (MB) is one of the most common childhood malignant brain tumors (WHO grade IV), traditionally divided into WNT, SHH, Group 3, and Group 4 subgroups based on the transcription profiles, somatic DNA alterations, and clinical outcomes. Unlike WNT and SHH subgroup MBs, Group 3 and Group 4 MBs have similar transcriptomes and lack clearly specific drivers and targeted therapeutic options. The recently revised WHO Classification of CNS Tumors has assigned Group 3 and 4 to a provisional non-WNT/SHH entity. In the present study, we demonstrate that Kir2.1, an inwardly-rectifying potassium channel, is highly expressed in non-WNT/SHH MBs, which promotes tumor cell invasion and metastasis by recruiting Adam10 to enhance S2 cleavage of Notch2 thereby activating the Notch2 signaling pathway. Disruption of the Notch2 pathway markedly inhibited the growth and metastasis of Kir2.1-overexpressing MB cell-derived xenograft tumors in mice. Moreover, Kir2.1high/nuclear N2ICDhigh MBs are associated with the significantly shorter lifespan of the patients. Thus, Kir2.1high/nuclear N2ICDhigh can be used as a biomarker to define a novel subtype of non-WNT/SHH MBs. Our findings are important for the modification of treatment regimens and the development of novel-targeted therapies for non-WNT/SHH MBs.

Background: Platinum-based regimens have been routinely used in the clinical treatment of patients with esophageal squamous cell carcinoma (ESCC). However, administration of these drugs is frequently accompanied by drug resistance. Revealing the underlying mechanisms of the drug resistance and developing agents that enhance the sensitivity to platinum may provide new therapeutic strategies for the patients. Methods: Immunohistochemistry, western blotting, RT-PCR, flow cytometry and immunofluorescence microscopy were used to detect the expression of Shh pathway members and cancer stem cell(CSC) biomarkers in ESCC specimens and cell lines. Functional assays, including MTT, tumorsphere formation assay, RTCA and an in vivo tumour growth assay, were conducted to assess the effect of Dihydroartemisinin (DHA) on the proliferation and renewal ability of ESCC cells. HPLC was used to examine the concention of cisplatin in ESCC cells.Results: We found that the poor outcome of ESCC patients receiving platinum-based regimens was associated with co-expression of Shh and Sox2. The sensitivity of ESCC cell lines to cisplatin was related to their activity of Shh signaling. Manipulating of Shh expression markedly changed the sensitivity of ESCC cells to platinum. Continuous treatment with cisplatin resulted in the activation of Shh signaling and enhanced cancer stem cell-like phenotypes in ESCC cells. DHA, a classic antimalarial drug, was identified as a novel inhibitor of Shh pathway. Treatment with DHA attenuated the cisplatin-induced activation of the Shh pathway in ESCC cells and synergized the inhibitory effect of cisplatin on proliferation, sphere and colony formation of ALDH-positive ESCC cells in vitro and growth of ESCC cell-derived xenograft tumors in vivo. Conclusion: These results demonstrate that the Shh pathway is an important player in cisplatin-resistant ESCC and DHA acts as a promising therapeutic agent to sensitize ESCC to cisplatin treatment.

Systematic autopsy and comprehensive pathological analyses of COVID-19 decedents should provide insights into the disease characteristics and facilitate the development of novel therapeutics. In this study, we report the autopsy findings from the lungs and lymphatic organs of 12 COVID-19 decedents—findings that evaluated histopathological changes, immune cell signature and inflammatory factor expression in the lungs, spleen and lymph nodes. Here we show that the major pulmonary alterations included diffuse alveolar damage, interstitial fibrosis and exudative inflammation featured with extensive serous and fibrin exudates, macrophage infiltration and abundant production of inflammatory factors (IL-6, IP-10, TNFα and IL-1β). The spleen and hilar lymph nodes contained lesions with tissue structure disruption and immune cell dysregulation, including lymphopenia and macrophage accumulation. These findings provide pathological evidence that links injuries of the lungs and lymphatic organs with the fatal systematic respiratory and immune malfunction in critically ill COVID-19 patients.

Synthetic hydrogels are widely used as biomimetic in vitro model systems to understand how cells respond to complex microenvironments. The mechanical properties of hydrogels are deterministic for many cellular behaviors, including cell migration, spreading, and differentiation. However, it remains a major challenge to engineer hydrogels that recapture the dynamic mechanical properties of native extracellular matrices. Here, we provide a new hydrogel platform with spatiotemporally tunable mechanical properties to assay and define cellular behaviors under light. The change in the mechanical properties of the hydrogel is effected by a photo-induced switch of the cross-linker fluorescent protein, Dronpa145N, between the tetrameric and monomeric states, which causes minimal changes to the chemical properties of the hydrogel. The mechanical properties can be rapidly and reversibly tuned for multiple cycles using visible light, as confirmed by rheological measurements and atomic force microscopybased nano-indentation. We further demonstrated real-time and reversible modulation of cell migration behaviors on the hydrogels through photo-induced stiffness switching, with minimal invasion to the cultured cells. Hydrogels with a programmable mechanical history and a spatially defined mechanical hierarchy might serve as an ideal model system to better understand complex cellular functions.

A growing body of evidence shows that the development and progression of gastric cancer (GC) is mainly associated to the presence of gastric cancer stem-like cells (GCSLCs). However, it is unclear how GCSLC population is maintained. This study aimed to explore the role of capillary morphogenesis gene 2 (CMG2) in GCSLC maintenance and the relevance to GC progression. We found that CMG2 was highly expressed in GC tissues and the expression levels were associated with the invasion depth and lymph node metastasis of GC, and inversely correlated with the survival of GC patients. Sorted CMG2High GC cells preferentially clustered in CD44High stem-like cell population, which expressed high levels of stemness-related genes with increased capabilities of self-renewal and tumorigenicity. Depletion of CMG2 gene resulted in reduction of GCSLC population with attenuated stemness and decrease of invasive and metastatic capabilities with subdued epithelial–mesenchymal transition phenotype in GC cells. Mechanistically, CMG2 interacted with LRP6 in GCSLCs to activate a Wnt/β-catenin pathway. Thus, our results demonstrate that CMG2 promotes GC progression by maintaining GCSLCs and can serve as a new prognostic indicator and a target for human GC therapy.

An ultrasensitive photoelectrochemical (PEC) bioassay for determination of microRNA was proposed based on an integrative photoactive heterojunction nanomaterial to provide the basis of excellent PEC responses and an efficient redox cycling amplification system to improve the detection performances. To establish the bioassay system, the biosensor was firstly modified with Bi2WO6@Bi2S3 and alkaline phosphatase (ALP). The detection solution was composed of ascorbic acid phosphate (AAP) and ferrocenecarboxylic acid (FcA), where ALP converted AAP into ascorbic acid (AA) to trigger a process of redox cycling amplification by reducing FcA+ to FcA, resulting in enhanced photocurrent responses of Bi2WO6@Bi2S3. In the presence of microRNA 21, it could trigger a hybridization chain reaction via the special designed hairpin DNA to produce a long repeated DNA sequences to inhibit ALP activity. Thus the reduced ALP activity and consequently decreased photocurrent signal could be obtained for detection of microRNA 21. As expected, this bioassay system performed the satisfactory performances for the ultrasensitive detection of microRNA 21 in the range from 1 fM to 1 nM with an experimental detection limit of 0.26 fM and acceptable practical applicability. Collectively, an efficient PEC bioassay for microRNA 21 is established and this strategy can be expanded to detect other microRNAs, even other molecules in cells.

Additional file 1: Table S1. The clinical features of the glioma specimens used in this study, Table S2. Primers used for qRT-PCR analyses in this study. Table S3. Tumor formation rates of xenograft implanted with different cell number of NADHhigh and NADHlow LN229 cells. Figure S1. Intensity of NADH autofluorescence in different WHO grade glioma tissues detected by FACS. Figure S2. Representative images of flow cytometry analysis for proportion of CD133+ cells in NADHhigh and NADHlow subpopulations in glioma cells. Figure S3. Representative images of flow cytometry analysis for proportion of CD15+ cells in NADHhigh and NADHlow subpopulations in glioma cells. Figure S4. The representative flow cytometry images of the percentage of NADHhigh cells in CD133+/CD15+ populations. Figure S5. Both NADHhigh and CD15+ giloma cells possess the properties of CSCs, but are partially overlapped. Figure S6. The representative flow cytometry images of the relationship between CD133+, CD15+ and NADHhigh populations. Figure S7. The representative flow cytometry images of the relationship between CD133+, CD15+ and NADHhigh populations. Figure S8. The representative images of invasion assay for NADHhigh and NADHlow, CD133+/- and CD15+/- subpopulations in GBM1 and LN229 cell lines. Compared to CD133-, CD15- NADHlow subsets, CD133+, CD15+ and NADHhigh cells exhibited stronger invasive ability in GBM1 and LN229 cell lines.

Invasion and metastasis are major malignant characteristics of human gastric cancer (GC), but the underlying molecular mechanisms are poorly understood. Recent studies have shown that scinderin (SCIN), an actin severing and capping protein that regulates the actin cytoskeleton, is involved in the proliferation and migration of certain cancer cells. Accordingly, this study aimed to investigate the potential role of SCIN in the invasion and metastasis of human GC cells and to evaluate its prognostic value for GC patients. We found that high levels of SCIN expression in GC tumors were correlated with poor overall survival of patients. Silencing of SCIN effectively suppressed the migratory and invasive capabilities of human GC cells in vitro and tumorigenicity and metastasis in vivo. Furthermore, knockdown of SCIN markedly inhibited the formation of filopodia, decreasing GC cell migration and the expression of Cdc42, an important regulator of filopodia by GC cells. These findings suggest that SCIN may be a novel prognostic marker and a potential therapeutic target in human GC.

Runt-related transcription factor 2 (RUNX2) is a regulator of embryogenesis and development, but has also been implicated in the progression of certain human cancer. This study aimed to elucidate the role of RUNX2 in the invasive and metastatic potentials of human gastric cancer (GC) and the underlying mechanisms. We found that the levels of RUNX2 expression in gastric cancer tissues were correlated with the differentiation degrees, invasion depth and lymph node metastasis. COX regression analysis indicated that RUNX2 was an independent prognostic indicator for GC patients. RUNX2 significantly increased the migration and invasion ability of GC cells in vitro and enhanced the invasion and metastatic potential of GC cells in an orthotopic GC model of nude mice. Mechanistically, RUNX2 directly bound to the promoter region of the gene coding for the chemokine receptor CXCR4 to enhance its transcription. CXCR4 knockdown or treatment with AMD3100, a CXCR4 inhibitor, attenuated RUNX2-promoted invasion and metastasis. These results demonstrate that RUNX2 promotes the invasion and metastasis of human GC by transcriptionally up-regulating the chemokine receptor CXCR4. Therefore, the RUNX2-CXCR4 axis is a potential therapeutic target for GC.

Potassium ion channels are emerging as promalignant factors involved in cancer progression. In this study, we found that invading human gastric cancer cells express high levels of inwardly rectifying potassium channel 2.1 (Kir2.1). Silencing Kir2.1 markedly reduced the invasive and metastatic capabilities as well as the epithelial–mesenchymal transition (EMT) of gastric cancer cells. The promalignant nature of Kir2.1 in gastric cancer cells was independent of potassium permeation but relied on its interaction with serine/threonine-protein kinase 38 (Stk38) to inhibit ubiquitination and degradation of mitogen-activated protein kinase kinase kinase 2 (MEKK2). Degradation of MEKK2 was mediated by small mothers against decapentaplegic-specific E3 ubiquitin protein ligase 1 (Smurf1), which resulted in activation of the MEK1/2–ERK1/2–Snail pathway in gastric cancer cells. In human gastric cancer tissues, expression was high and positively correlated with invasion depth and metastatic status of the tumors as well as poor overall patient survival. Cox regression analysis identified Kir2.1 as an independent prognostic indicator for patients with gastric cancer. Our results suggest that Kir2.1 is an important regulator of gastric cancer malignancy and acts as a novel prognostic marker and a therapeutic target for gastric cancer. Significance: Kir2.1 contributes to invasion and metastasis by a noncanonical ion permeation–independent signaling pathway and may act as a novel prognostic marker and therapeutic target for gastric cancer. Cancer Res; 78(11); 3041–53. ©2018 AACR.

Formyl peptide receptor 2 (FPR2), a classical chemoattractant receptor of G-protein-coupled receptors, is reported to be involved in invasion and metastasis of some cancers, but the role of FPR2 in gastric cancer (GC) has not yet been elucidated. In this study, we found that the levels of FPR2 expression in GC were positively correlated with invasion depth, lymph node metastasis and negatively correlated with the patients’ overall survival. Multivariate analysis indicated that FPR2 expression was an independent prognostic marker for GC patients. FPR2-knockdown significantly abrogated the migration and invasion stimulated by Hp(2–20) and Ac(2–26), two well-characterized ligands for FPR2 in GC cells. FPR2 deletion also reduced the tumorigenic and metastatic capabilities of GC cells in vivo. Mechanistically, stimulation with FPR2 ligands resulted in down-regulation of E-cadherin and up-regulation of vimentin, which were reversed by FPR2 knock-down, implying the involvement of epithelial–mesenchymal transition (EMT). Moreover, the activation of FPR2 was accompanied with ERK1/2 phosphorylation, which could be attenuated by FPR2 silencing or treatment with MEK inhibitor, PD98059. Altogether, our results demonstrate that FPR2 is functionally involved in invasion and metastasis, and potentially acts as a novel prognostic marker as well as a potential therapeutic target in human GC.

This study investigated the clinical characteristics of internet addiction using a cross-sectional survey and psychiatric interview.A structured questionnaire consisted of demographics, Symptom Checklist 90, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and Young's Internet Addiction Test (YIAT) was administered to students of two secondary schools in Wuhan, China. Students with a score of 5 or higher on the YIAT were classified as having Internet Addiction Disorder (IAD). Two psychiatrists interviewed students with IAD to confirm the diagnosis and evaluate their clinical characteristics.Of a total of 1076 respondents (mean age 15.4 ± 1.7 years; 54.1% boys), 12.6% (n = 136) met the YIAT criteria for IAD. Clinical interviews ascertained the Internet addiction of 136 pupils and also identified 20 students (14.7% of IAD group) with comorbid psychiatric disorders. Results from multinomial logistic regression indicated that being male, in grade 7-9, poor relationship between parents and higher self-reported depression scores were significantly associated with the diagnosis of IAD.These results advance our understanding of the clinical characteristics of Internet addiction in Chinese secondary school students and may help clinicians, teachers, and other stakeholders better manage this increasingly serious mental condition.