Niche partition of Bacteriovorax operational taxonomic units along salinity and temporal gradients in the Chesapeake Bay reveals distinct estuarine strains.

The predatory Bacteriovorax are Gram-negative bacteria ubiquitous in saltwater systems that prey upon other Gram-negative bacteria in a similar manner to the related genus Bdellovibrio. Among the phylogenetically defined clusters of Bacteriovorax, cluster V has only been isolated from estuaries suggesting that it may be a distinct estuarine phylotype. To assess this hypothesis, the spatial and temporal distribution of cluster V and other Bacteriovorax phylogenetic assemblages along the salinity gradient of Chesapeake Bay were determined. Cluster V was expected to be found in significantly greater numbers in low to moderate salinity waters compared to high salinity areas. The analyses of water and sediment samples from sites in the bay revealed cluster V to be present at the lower salinity and not high salinity sites, consistent with it being an estuarine phylotype. Cluster IV had a similar distribution pattern and may also be specifically adapted to estuaries. While the distribution of clusters V and IV were similar for salinity, they were distinct on temperature gradients, being found in cooler and in warmer temperatures, respectively. The differentiation of phylotype populations along the salinity and temporal gradients in Chesapeake Bay revealed distinct niches inhabited by different phylotypes of Bacteriovorax and unique estuarine phylotypes.

A bibliometric analysis of studies on gut microbiota in attention-deficit and hyperactivity disorder from 2012 to 2021.

Background: An increasing number of studies have focused on the role of gut microbiota in the treatment of ADHD, but its related molecular mechanisms are not yet clear, and there is still room for development of studies targeting this area. This study analyzes publications from 2012 to 2021 in a comprehensive and multi-faceted visualization, with the aim of grasping the existing research profile and guiding scholars to make more in-depth studies. Methods: The 1,677 articles and 298 review articles on gut microbiota in ADHD were retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, Microsoft Excel 2019, Scimago Graphica, Bibliometrix and Pajek metrics software were used for visualization and analysis of the included literature. Results: On August 3, 2022, a total of 1975 English-language articles on gut microbiota in ADHD were retrieved from Web of Science Core Collection (WoSCC) from January 2012 to December 2021, with a steady upward trend in the number of articles published in this field over the decade. The top three countries in terms of the number of articles published are the United States, China, and Spain. Meanwhile, CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS CSIC, UNIV OF CALIFORNIA SYSTEM, and UDICE FRENCH RESEARCH UNIV have made significant contributions in this field. In the analysis of the published journals, PLoS One was not only the first in terms of number of articles published but also the most cited. Wang J was the most prolific author and CAPORASO JG ranked first in terms of co-cited authors. In addition, "Diet rapidly and reproducibly alters the human gut microbiome," published by David LA et al., has the highest citation frequency in this field. The most frequently occurring keyword was "gut microbiota." Conclusion: The results of this paper clarify the current status of research on gut microbiota in ADHD. Based on the research on the mechanism of gut microbiota in other diseases, there is reason to believe that the exploration of gut microbiota in ADHD must be increasingly mature. And the study speculates that future research may focus on "nutrition supplements," "lipid metabolism," and "gut brain axis." It is imperative to promote a closer international cooperation among scholars in this field.

Detecting the prevalence of bacterial colonization on tunneled cuffed hemodialysis catheters using quantitative PCR targeting 16S rRNA and scanning electron microscopy.

BACKGROUND AND OBJECTIVES: Tunneled cuffed hemodialysis catheters (TCC) get colonized by microorganisms, increasing risk for catheter related bacteremia (CRB). Our objective was to detect the prevalence of bacterial colonization of TCC by using quantitative PCR (qPCR) targeting 16S rRNA and by determining the intraluminal adherent biological material (ABM) coverage. METHODS: A total of 45 TCC were investigated. The 16S rRNA qPCR technique was used to detect bacterial colonization after scraping the intraluminal ABM. Proximal, middle, and distal TCC were evaluated by scanning electron microscopy (SEM) to determine the percentage (%) of intraluminal ABM coverage. All catheters were cultured following sonication. RESULTS: A total of 45 TCC were removed: 7 due to CRB, 3 for suspected CRB and 35 were removed for non-infectious etiologies. Bacterial colonization was detected in 27 TCC by documenting 16S rRNA qPCR (+) results (60%). Seven of these 16S rRNA qPCR (+) catheters were removed due to CRB. There was no difference in demographic, clinical, or laboratory values between the 16S rRNA (+) versus (-) TCC. The 16S rRNA qPCR (-) outcome was highly associated with CRB-free status with negative predictive value of 100%. Bacterial colonization was documented in 10 TCC using catheter cultures (22%), which was significantly less compared to qPCR method (p = 0.0002). ABM were detected in all catheter pieces, with mean intraluminal surface coverage (ABMC) of 68.4 ± 26.1%. ABM was unlikely to be microbial biofilm in at least 36% of removed TCC as their 16S rRNA qPCR and catheter culture results were both negative. CONCLUSIONS: Detecting bacterial colonization of TCC was significantly higher with 16S rRNA qPCR compared to catheter cultures. The 16S rRNA qPCR (-) cannot be predicted and was strongly associated with absence of CRB. Intraluminal ABM was not associated with microbial presence in about 1/3 of the TCC. These pieces of evidence may help to improve prophylactic strategies against CRB.

Design and biological features of platinum (II) complexes with 3-hydroxy-3-(Trifluoromethyl)cyclobutane-1,1-Dicarboxylate as a leaving ligand.

A series of platinum compounds 2a-5a and 2b-5b with fluoro-functional groups are designed and synthesized. Among them, complex 2b is the most effective agent with 3-hydroxy-3-(trifluoromethyl)cyclobutane-1,1-dicarboxylate as a leaving ligand, which showed better cytotoxic activity than compounds containing only CF3 or OH group at 3-position of cyclobutane-1,1-dicarboxylate. The water solubility of 2a is better than that of carboplatin (32 mg/mL vs. 16 mg/mL), and its antitumor activity on A549 is 4.6-fold higher than that of carboplatin. The IC50 value of 2b on A549 cells is 4.73 ± 0.64 µM, which is comparable to that of oxaliplatin and higher than that of carboplatin. Meanwhile, 2a and 2b are less toxic than oxaliplatin and cisplatin toward BEAS-2B cells. Moreover, 2a and 2b induce cell apoptosis in vitro by the Bax-Bcl-2-caspase-3 pathway and ferroptosis through inhibiting GPx-4 and elevating COX2. Results from in vivo experiment show that the inhibition rate of A549 xenograft tumor is cisplatin > 2b > oxaliplatin > 2a > carboplatin.

Inflammatory Cells Accelerated Carotid Artery Calcification via MMP9: Evidences From Single-Cell Analysis.

Background: Vascular calcification (VC) is an important predictor of prognosis in atherosclerosis, the phenotypic transformation of vascular smooth muscle cells (VSMCs) is thought to be a process of VC. However, the implications and potential mechanisms for VSMCs phenotypic transition remain unknown. Methods: To study the transformation of vascular smooth muscle cells (VSMCs) in the calcification early period, we analyzed single-cell sequencing data from carotid artery calcified core and paracellular tissue, based on the results of enrichment analysis and protein-protein interaction analysis. Upstream transcription factors were tracked and finally the results were validated using the MESA database. Results: We successfully identified a subpopulation of inflammatory macrophage-like VSMCs and determined that MMP9 is an important factor in the phenotypic transformation of VSMCs. We found that RELA regulates MMP9 expression and that knockdown of RELA attenuated MMP9 expression and reduced the expression of BMP2 and the macrophage marker LGALS3 in vascular smooth muscle in inflammatory states, while serum levels of MMP9 correlated significantly with the inflammatory response. Conclusion: This study reveals that the phenotypic transformation of VSMCs can be regulated by modulating MMP9, providing a new idea for the early treatment of VC.

Ellagic Acid Ameliorates Renal Ischemic-Reperfusion Injury Through NOX4/JAK/STAT Signaling Pathway.

Ellagic acid (EA), a natural polyphenolic compound, has been proved to possess multiple biological activities including alleviating ischemic-reperfusion (I/R) injury. The aim of this current study was to investigate whether EA alleviates I/R injury via regulating inflammatory signaling pathway. Rats were subjected to ischemic-reperfusion (I/R) injury and given orally with different doses of EA before surgery. H&E staining, ELISA assay, and biochemical index analysis were performed to evaluate renal injury and inflammatory factors. Oxidative stress level was detected by DCFH-DA staining and corresponding assay kits. In addition, TUNEL assay and flow cytometric assay were applied for exploring the apoptosis of tissue and cells, respectively. Western blot assay was used to assess protein expressions in tissue and cells. The results showed that EA attenuated the renal I/R injury and reserved renal cell function in vivo. The levels of TNF-a, IL-1ß, IL-6, and MCP-1, oxidative stress level, and apoptosis were suppressed in EA-treated rats. Mechanistic studies showed that EA suppressed the phosphorylation of JAK1, JAK2, and STAT1 and reduced the NOX4 level. EA reduced apoptosis, hypoxia-induced inflammatory response, and ROS levels. Moreover, overexpression of NOX4 reversed the protective function with NOX4 inhibition, indicating that the effect of EA against renal IRI or cell hypoxia/reoxygenation might mainly depend on NOX4. The results suggest that EA exerts the renoprotective effect via suppressing NOX4/JAK/STAT signaling pathway, which may be a novel potential therapy for the treatment of acute kidney injury in clinic.

[The effects of high frequency signal investigated in a neuron model].

We have investigated the effects of high frequency (HF) signal on firing activity in a biologically realistic system--the noisy Hodgkin-Huxley (HH) neuron model via numerical simulations. The results show that when the HF amplitude to frequency ratio (AFR) increases, the firing rate is diminished and stochastic resonance disappears, even the HH neuron model is processing a stimulus of its most sensitive frequency. When the noise intensity is strong, the vibration resonance can be observed. Moreover, the fluctuation around the resting potential will be replaced by an oscillation of the same high frequency with the increasing AFR. The inhibition of the firing activity is consistent with the results of experiment in vivo that HF current can stop the transmission of action potential in peripheral nerve. This study is of functional significance to the biomedical research on the damages caused by electro-pollution in vivo and signal processing.

[Research progress of stochastic resonance in neural models].

In nonlinear systems, noise can improve the responses of the systems with appropriate noise intensity. This phenomenon is called stochastic resonance. Biological neural systems are noisy and stochastic resonance has been found in them experimentally and theoretically. Now many researches focus on the signal transmission and processing in neural models. So this paper introduces the researches of stochastic resonance in noisy neural models. Then the recent research achievement and progress are reviewed in the following three aspects: noise; the development of stochastic resonance; and neural network. At last, the foreground of the study is discussed.

Adverse Effects Profile of Dicycloplatin (DCP) Offers Chemotherapeutic Advantage Over Cisplatin and Carboplatin.

BACKGROUND/AIM: Platinum-based chemotherapy often fails due to its severe adverse effects. The aim of this study was to examine the adverse effects profile and efficacy of dicycloplatin and compare them to those of cisplatin and carboplatin. MATERIALS AND METHODS: Cystoscopy surveillance of the first American cancer patient treated with dicycloplatin was performed quarterly. In vitro and in vivo studies were conducted using immunoblotting and flow cytometry to assess immune status of spleen and bone marrow of mice treated with dicycloplatin, cisplatin and carboplatin. RESULTS: The American patient did not suffer clinically significant myelosuppression; dicycloplatin has sustained remission in this patient to date. Experimental studies showed that dicycloplatin is less toxic to bone marrow and spleen of mice than cisplatin and carboplatin. CONCLUSION: Dicycloplatin is a promising drug in cancer chemotherapy with less aggressive side-effects than those typically associated with cisplatin and carboplatin. This is an important therapeutic advantage in cancer chemotherapy. Clinical investigation of dicycloplatin as an alternative to cisplatin or carboplatin is warranted.

Ellagic acid promotes A549 cell apoptosis via regulating the phosphoinositide 3-kinase/protein kinase B pathway.

The present study aimed to evaluate the anti-cancer effect of ellagic acid in human non-small cell lung cancer (NSCLC) A549 cells and to reveal the potential underlying mechanism. The effects of ellagic acid on the cell proliferation of A549 cells were determined by MTT assay. Cell cycle and apoptosis were measured with flow cytometry and Annexin V-propidium iodide staining. Western blotting was used to measure the expression levels of the phosphatidylinositol 3-kinase (PI3K)/protein kinas B (Akt) signaling pathway and apoptosis-associated proteins. It was demonstrated that ellagic acid exerted an inhibitory effect in the proliferation of human NSCLC A549 cells. Flow cytometry demonstrated that G1 phase retention and apoptosis rates were significantly increased after treatment with ellagic acid. Further investigation revealed that ellagic acid treatment diminished the phosphorylation of PI3K and Akt and regulated the expression of apoptosis-associated proteins in A549 cells. In conclusion, the present results indicated that ellagic acid suppresses cell proliferation, arrests cell cycle and induces apoptosis in human NSCLC A549 cells by inhibiting the PI3K/Akt signaling pathway.

The promotive effects of peer support and active coping on the relationship between bullying victimization and depression among chinese boarding students.

We examined the relationship between bully victimization experience and depression in rural adolescents and analyzed the moderating roles of peer support and active coping in male and female students. The sample comprised N=755 adolescents (376 females) with a mean age of 13.52 years. Through structural model and multi-group analysis, the results indicated: (1) a significant gender difference on the positive association between bullying victimization and depression; (2) peer support had a directly negative effect on depression among all boarding adolescents; and (3) significant moderating effect of active coping on the association between victimization and depression, without significant gender difference. We discuss enhancing active coping and peer support as a prevention strategy to reduce adverse mental health outcomes in adolescents due to bullying victimization.

Protein phosphatase 2A interacts with Chk2 and regulates phosphorylation at Thr-68 after cisplatin treatment of human ovarian cancer cells.

High-fidelity maintenance of genomic integrity in eukaryotes is ensured by cell cycle checkpoints and DNA repair. The checkpoint kinase, Chk2, has been implicated in both of these responses. In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation. The fully activated Chk2 then phosphorylates downstream substrates of cell cycle control. However, the mechanism of inactivation of Chk2 is still unknown. Protein phosphatase type 2A (PP2A) plays an essential role in cell cycle regulation and induction of G2 arrest by a mechanism of phosphorylation/dephosphorylation with a variety of protein kinases. Data from our investigation provide evidence that, in response to cisplatin exposure, PP2A associates with Chk2 as a complex in cells and functions as a negative regulator of Chk2 activation by dephosphorylating p-Chk2. Results from immunostaining and coimmunoprecipitation demonstrate that Chk2 and PP2A can colocalize in cells, and the holoenzyme of PP2A (subunits A, B and C) coimmunoprecipitates with p-Chk2. Further, inhibition of PP2A by okadaic acid, an inhibitor of PP2A, and by small interfering RNA (siRNA) to PP2A results in enhanced Chk2 phosphorylation, implicating a direct enzyme-substrate relationship. An in vitro PP2A dephosphorylation assay shows that PP2A dephosphorylates p-Chk2 in a cell-free system. These findings suggest that the protein serine/threonine kinase, Chk2, is activated after cisplatin exposure and negatively regulated by a tightly associated protein serine/threonine phosphatase, PP2A.

Confirmation of 42-bp deletion within the ERCC1 5' UTR.

Our previous studies revealed a splicing variant (lacking a 42 base pair segment) within the 5'-UTR of the ERCC1 gene, a critical component of the nucleotide excision repair (NER) pathway that plays an important role in the development of chemoresistance in platinum-based anticancer therapy. This 42-bp segment seems to possess a regulatory function in ERCC1 expression and representing the level of clinical response to platinum-treatment in ovarian cancer patients. To confirm the existence of the 42-bp deletion and to investigate the 42-bp function, we performed several experiments and assays. Northern blot analysis and RNase protection assay provide evidence that the 42-bp deletion occurs at RNA level of ERCC1 5'-UTR in both ovarian cancer cell lines and ovarian cancer tissues. Luciferase assay suggests that this gene fragment possesses a regulatory function as an enhancer of ERCC1 gene expression in ovarian cancer cells. In Electrophoretic Mobility Shift Assay (EMSA), a shift band present in the ovarian cancer cell line extracts is consistent with the presence of an intracellular protein that recognizes this specific 42-bp sequence. Further, specific EMSA results with 42-bp probe mutated at the site of RFX-1 indicate different putative-DNA binding proteins, rather than RFX-1. We conclude that the 42-bp sequence within the 5'-UTR influences the expression of ERCC1 and hence can influence response to cisplatin in ovarian cancer therapy.

Excision repair cross complementing-group 1: gene expression and platinum resistance.

Platinum compounds induce their cytotoxic effect by binding to a DNA molecule in the form of a platinum-DNA-adduct. Many previous studies have shown that the level of platinum-DNA-adduct correlats with response to platinum-based chemotherapy. Although the mechanism of platinum resistance in vivo is not clearly understood, laboratory studies on cancer cell lines suggest that nucleotide excision repair (NER) is the main mechanism responsible for this resistance by increased platinum-DNA-adduct removal. NER pathway is a network of many proteins gathered in a DNA-repair system. The excision repair cross complementing-group 1 (ERCC1) gene has the leading role in NER-pathway because of its damage recognition and excision ability. In this report we reviewed the pathway leading to ERCC1 gene transcription and translation in cancer cells when exposed to cisplatin. We summarized data from different cancer cell lines and human cancers showing that the high level of ERCC1-mRNA and/or ERCC1 protein is associated with resistance to platinum compounds with direct impact on cancer patient survival and finally we analyzed drugs interfering with ERCC1 gene expression and causing the reversal of the platinum resistance when given to cancer cells prior to platinum-based chemotherapy.

The Role of Wild-Type p53 in Cisplatin-Induced Chk2 Phosphorylation and the Inhibition of Platinum Resistance with a Chk2 Inhibitor.

The major obstacle in platinum chemotherapy is the repair of platinum-damaged DNA that results in increased resistance, reduced apoptosis, and finally treatment failure. Our research goal is to determine and block the mechanisms of platinum resistance. Our recent studies demonstrate that several kinases in the DNA-repair pathway are activated after cells are exposed to cisplatin. These include ATM, p53, and Chk2. The increased Chk2 phosphorylation is modulated by p53 in a wild-type p53 model. Overexpression of p53 by cDNA transfection in wt-p53 (but not p53 deficient) cells doubled the amount of Chk2 phosphorylation 48 hours after cisplatin treatment. p53 knockdown by specific siRNA greatly reduced Chk2 phosphorylation. We conclude that wild-type p53, in response to cisplatin stimulation, plays a role in the upstream regulation of Chk2 phosphorylation at Thr-68. Cells without normal p53 function survive via an alternative pathway in response to the exogenous influence of cisplatin. We strongly suggest that it is very important to include the p53 mutational status in any p53 involved studies due to the functional differentiation of wt p53 and p53 mutant. Inhibition of Chk2 pathway with a Chk2 inhibitor (C3742) increased cisplatin efficacy, especially those with defective p53. Our findings suggest that inhibition of platinum resistance can be achieved with a small-molecule inhibitor of Chk2, thus improving the therapeutic indices for platinum chemotherapy.

HPV infection and EGFR activation/alteration in HIV-infected East African patients with conjunctival carcinoma.

BACKGROUND: There has been substantial growth in the numbers of patients with conjunctival squamous cell carcinoma infected with HIV in East Africa. The natural history of the conjunctival squamous cell carcinoma appears to be unique in this region of the world, but the etiologic mechanism unclear and therapeutic options limited. This research was carried out to determine if conjunctival squamous cell carcinoma harbors human papillomavirus DNA and is associated with activation of the EGFR signaling pathway. Positive findings would identify etiologic causes and provide clinical guidance to improve treatment. METHODS/FINDINGS: Expression of p-MAPK/MAPK, p-Akt/Akt and p-EGFR/EGFR in cell nuclei and cytoplasm of 38 FFPE specimens were assessed by immunohistochemistry; HPV genotype was detected by qPCR assay; EGFR mutation was assessed by DNA sequencing analysis; and EGFR mRNA expression was measured using relative qPCR. Statistical analyses included two-sided Fisher exact test or chi-square test, Spearman correlation coefficient and ANOVA. HPV 18 was found in 61% of samples, with HPV 16 double-genotype in 6 patients (16%). Immunohistochemistry and qPCR data suggest that activation and expression of the EGFR signaling pathway is related to disease progression of conjunctival cancer. The associations between cytoplasmic p-MAPK, cytoplasmic p-Akt and tumor invasiveness were significant (p = 0.05 or 0.028). Nuclear p-EGFR appeared only in invasive tumors. A significant positive association between EGFR expression and disease invasiveness was observed (p = 0.01). A SNP in 10 patients and one missense mutation were found within EGFR tyrosine kinase domain. Statistical analysis indicates that patients with measurable EGFR expression more likely harbor EGFR mutations, compared to those with negative EGFR expression (35.3% vs. 0%). CONCLUSIONS/SIGNIFICANCE: We conclude that HPV types 16/18 infection is frequent in East African patients with AIDS-associated squamous cell carcinoma of the conjunctiva. EGFR activation/alteration may contribute to and sustain the high prevalence of this cancer. Our findings hint that adoption of HPV vaccination strategies may impact the incidence of conjunctival carcinoma. Agents that target the EGFR pathway may have potential therapeutic benefit.

[Residue of PCBs and OCPs in the paddy soil from Hongfeng reservoir area, Guizhou, China].

Distributions of seven PCBs (polychlorinated biphenyls) congeners and 13 OCPs (organochlorinated pesticides) were investigated in paddy soil section in Hongfeng reservoir area. The results showed that DDTs and its metabolized compounds, isomer of HCHs, Endrin, heptachlor, PCB 28 and PCB 52 were detected in all soil samples. Compared to the polluted area, the concentrations of PCBs were lower in study area, while the compositions of organic pollutants in soil samples were similar. The dominant compositions of PCBs and OCPs were tri-, tetra-, and penta-chlorinated PCB congeners and DDTs respectively. The proportion of tri-, tetra-and penta-CB was 89 percent. The contents of DDTs were between 4.7 ng/g and 42.6 ng/g and p, p'-DDE, p, p'-DDT were the major isomers. The ratios of DDT/ (DDD + DDE) showed that the rate of DDTs degradation and environment status were different. The range of alpha-HCH/gamma-HCH was 0.28 - 0.90, indicating that HCHs had stayed for long time in environment. By photolysis and microbial, the proportion of the HCHs isomers had changed in Hongfeng reservoir area. SigmaTEQ of PCB118 and PCB180 were 0.06 - 0.51 pg/g.