Cannabidiol Inhibits Epithelial Ovarian Cancer: Role of Gut Microbiome.

Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.

Fusobacterium nucleatum upregulates MMP7 to promote metastasis-related characteristics of colorectal cancer cell via activating MAPK(JNK)-AP1 axis.

BACKGROUND: Colorectal cancer (CRC) is the third most common malignant tumor. Fusobacterium nucleatum (F. nucleatum) is overabundant in CRC and associated with metastasis, but the role of F. nucleatum in CRC cell migration and metastasis has not been fully elucidated. METHODS: Differential gene analysis, protein-protein interaction, robust rank aggregation analysis, functional enrichment analysis, and gene set variation analysis were used to figure out the potential vital genes and biological functions affected by F. nucleatum infection. The 16S rDNA sequencing and q-PCR were used to detect the abundance of F. nucleatum in tissues and stools. Then, we assessed the effect of F. nucleatum on CRC cell migration by wound healing and transwell assays, and confirmed the role of Matrix metalloproteinase 7 (MMP7) induced by F. nucleatum in cell migration. Furthermore, we dissected the mechanisms involved in F. nucleatum induced MMP7 expression. We also investigated the MMP7 expression in clinical samples and its correlation with prognosis in CRC patients. Finally, we screened out potential small molecular drugs that targeted MMP7 using the HERB database and molecular docking. RESULTS: F. nucleatum infection altered the gene expression profile and affected immune response, inflammation, biosynthesis, metabolism, adhesion and motility related biological functions in CRC. F. nucleatum was enriched in CRC and promoted the migration of CRC cell by upregulating MMP7 in vitro. MMP7 expression induced by F. nucleatum infection was mediated by the MAPK(JNK)-AP1 axis. MMP7 was highly expressed in CRC and correlated with CMS4 and poor clinical prognosis. Small molecular drugs such as δ-tocotrienol, 3,4-benzopyrene, tea polyphenols, and gallic catechin served as potential targeted therapeutic drugs for F. nucleatum induced MMP7 in CRC. CONCLUSIONS: Our study showed that F. nucleatum promoted metastasis-related characteristics of CRC cell by upregulating MMP7 via MAPK(JNK)-AP1 axis. F. nucleatum and MMP7 may serve as potential therapeutic targets for repressing CRC advance and metastasis.

Emerging Opportunities for 2D Materials in Neuromorphic Computing.

Recently, two-dimensional (2D) materials and their heterostructures have been recognized as the foundation for future brain-like neuromorphic computing devices. Two-dimensional materials possess unique characteristics such as near-atomic thickness, dangling-bond-free surfaces, and excellent mechanical properties. These features, which traditional electronic materials cannot achieve, hold great promise for high-performance neuromorphic computing devices with the advantages of high energy efficiency and integration density. This article provides a comprehensive overview of various 2D materials, including graphene, transition metal dichalcogenides (TMDs), hexagonal boron nitride (h-BN), and black phosphorus (BP), for neuromorphic computing applications. The potential of these materials in neuromorphic computing is discussed from the perspectives of material properties, growth methods, and device operation principles.

Characterization of the Arn lipopolysaccharide modification system essential for zeamine resistance unveils its new roles in Dickeya oryzae physiology and virulence.

The zeamines produced by Dickeya oryzae are potent polyamine antibiotics and phytotoxins that are essential for bacterial virulence. We recently showed that the RND efflux pump DesABC in D. oryzae confers partial resistance to zeamines. To fully elucidate the bacterial self-protection mechanisms, in this study we used transposon mutagenesis to identify the genes encoding proteins involved in zeamine resistance in D. oryzae EC1. This led to the identification of a seven-gene operon, arnEC1 , that encodes enzyme homologues associated with lipopolysaccharide modification. Deletion of the arnEC1 genes in strain EC1 compromised its zeamine resistance 8- to 16-fold. Further deletion of the des gene in the arnEC1 mutant background reduced zeamine resistance to a level similar to that of the zeamine-sensitive Escherichia coli DH5α. Intriguingly, the arnEC1 mutants showed varied bacterial virulence on rice, potato, and Chinese cabbage. Further analyses demonstrated that ArnBCATEC1 are involved in maintenance of the bacterial nonmucoid morphotype by repressing the expression of capsular polysaccharide genes and that ArnBEC1 is a bacterial virulence determinant, influencing transcriptional expression of over 650 genes and playing a key role in modulating bacterial motility and virulence. Taken together, these findings decipher a novel zeamine resistance mechanism in D. oryzae and document new roles of the Arn enzymes in modulation of bacterial physiology and virulence.

Combined Use of Immune Checkpoint Inhibitors and Phytochemicals as a Novel Therapeutic Strategy against Cancer.

Immune checkpoint inhibitor (ICI) therapy has dramatically changed cancer treatment, opening novel opportunities to cure malignant diseases. To date, most prevalently targeted immune checkpoints are programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), with many others being under extensive investigations. However, according to available data, only a fraction of patients may respond to ICI therapy. Additionally, this therapy may cause severe adverse immune-related side effects, such as diarrhea, headache, muscle weakness, rash, hepatitis and leucopenia, although most of them are not fatal, they can affect the patient's treatment outcome and quality of life. On the other hand, growing evidence has shown that phytochemicals with anticancer effects may combine ICI therapy to augment the safety and effectiveness of the treatment against cancer while reducing the adverse side effects. In this review, we summarize the state of art in the various experiments and clinical application of ICIs plus phytochemicals, with a focus on their combined use as a novel therapeutic strategy to cure cancer.

Enterolactone and trabectedin suppress epithelial ovarian cancer synergistically via upregulating THBS1.

Epithelial ovarian cancer (EOC) is the most common and fatal subtype of ovarian malignancies, with no effective therapeutics available. Our previous studies have demonstrated extraordinary suppressive efficacy of enterolactone (ENL) on EOC. A chemotherapeutic agent, trabectedin (Trabe), is shown to be effective on ovarian cancer, especially when combined with other therapeutics, such as pegylated liposomal doxorubicin or oxaliplatin. Thrombospondin 1 (THBS1), a kind of matrix glycoprotein, plays important roles against cancer development through inhibiting angiogenesis but whether it is involved in the suppression of EOC by ENL or Trabe remains unknown. To test combined suppressive effects of ENL and Trabe on EOC and possible involvement of THBS1 in the anticancer activities of ENL and Trabe. The EOC cell line ES-2 was transfected with overexpressed THBS1 by lentivirus vector. We employed tube formation assay to evaluate the anti-angiogenesis activity of ENL and of its combined use with Trabe after THBS1 overexpression and established drug intervention and xenograft nude mouse cancer models to assess the in vivo effects of the hypothesized synergistic suppression between the agents and the involvement of THBS1. Mouse fecal samples were collected for 16S rDNA sequencing and microbiota analysis. We detected strong inhibitory activities of ENL and Trabe against the proliferation and migration of cancer cells and observed synergistic effects between ENL and Trabe in suppressing EOC. ENL and Trabe, given either separately or in combination, could suppress the tube formation capability of human microvascular endothelial cells, and this inhibitory effect became even stronger with THBS1 overexpression. In the ENL plus Trabe combination group, the expression of tissue inhibitor of metalloproteinases 3 and cluster of differentiation 36 was both upregulated, whereas matrix metalloproteinase 9, vascular endothelial growth factor, and cluster of differentiation 47 were all decreased. With the overexpression of THBS1, the results became even more pronounced. In animal experiments, combined use of ENL and Trabe showed superior inhibitory effects to either single agent and significantly suppressed tumor growth, and the overexpression of THBS1 further enhanced the anti-cancer activities of the drug combination group. ENL and Trabe synergistically suppress EOC and THBS1 could remarkably facilitate the synergistic anticancer effects of ENL and Trabe.

Gram-negative bacteria resist antimicrobial agents by a DzrR-mediated envelope stress response.

BACKGROUND: Envelope stress responses (ESRs) are critical for adaptive resistance of Gram-negative bacteria to envelope-targeting antimicrobial agents. However, ESRs are poorly defined in a large number of well-known plant and human pathogens. Dickeya oryzae can withstand a high level of self-produced envelope-targeting antimicrobial agents zeamines through a zeamine-stimulated RND efflux pump DesABC. Here, we unraveled the mechanism of D. oryzae response to zeamines and determined the distribution and function of this novel ESR in a variety of important plant and human pathogens. RESULTS: In this study, we documented that a two-component system regulator DzrR of D. oryzae EC1 mediates ESR in the presence of envelope-targeting antimicrobial agents. DzrR was found modulating bacterial response and resistance to zeamines through inducing the expression of RND efflux pump DesABC, which is likely independent on DzrR phosphorylation. In addition, DzrR could also mediate bacterial responses to structurally divergent envelope-targeting antimicrobial agents, including chlorhexidine and chlorpromazine. Significantly, the DzrR-mediated response was independent on the five canonical ESRs. We further presented evidence that the DzrR-mediated response is conserved in the bacterial species of Dickeya, Ralstonia, and Burkholderia, showing that a distantly located DzrR homolog is the previously undetermined regulator of RND-8 efflux pump for chlorhexidine resistance in B. cenocepacia. CONCLUSIONS: Taken together, the findings from this study depict a new widely distributed Gram-negative ESR mechanism and present a valid target and useful clues to combat antimicrobial resistance.

Naringenin suppresses epithelial ovarian cancer by inhibiting proliferation and modulating gut microbiota.

BACKGROUND: Ovarian cancer has the highest mortality among all gynecological malignancies; currently, no effective therapeutics are available for its treatment. Naringenin has been shown to inhibit the progression of various cancers, but its inhibitory effect on ovarian cancer remains unknown. PURPOSE: This study aimed to evaluate the inhibitory effects of naringenin on ovarian cancer and elucidate the underlying mechanisms. METHODS: Cancer cell proliferation was detected by cell counting kit-8 and crystal violet assays, and the migration capability was determined by wound healing and transwell assays. Western blotting and immunohistochemistry assays were employed to determine the expression levels of the epidermal growth factor receptor, phosphatidylinositol 3-kinase (PI3K) and cyclin D1 in vitro and in vivo, respectively. An ES-2 xenograft nude mouse model was established for the in vivo experiments, and fecal samples were collected for intestinal microbiota analysis by 16S rDNA sequencing. RESULTS: Naringenin suppressed the proliferation and migration of A2780 and ES-2 cancer cell lines and downregulated PI3K in vitro. In animal experiments, naringenin treatment significantly decreased the tumor weight and volume, and oral administration exhibited greater effects than intraperitoneal injection. Additionally, naringenin treatment ameliorated the population composition of the microbiota in animals with ovarian cancer and significantly increased the abundances of Alistipes and Lactobacillus. CONCLUSION: Naringenin suppresses epithelial ovarian cancer by inhibiting PI3K pathway expression and ameliorating the gut microbiota, and the oral route is more effective than parenteral administration.

KAZN as a diagnostic marker in ovarian cancer: a comprehensive analysis based on microarray, mRNA-sequencing, and methylation data.

BACKGROUND: Ovarian cancer (OC) is among the deadliest malignancies in women and the lack of appropriate markers for early diagnosis leads to poor prognosis in most cases. Previous studies have shown that KAZN is involved in multiple biological processes during development, such as cell proliferation, differentiation, and apoptosis, so defects or aberrant expression of KAZN might cause queer cell behaviors such as malignancy. Here we evaluated the KAZN expression and methylation levels for possible use as an early diagnosis marker for OC. METHODS: We used data from Gene Expression Omnibus (GEO) microarrays, The Cancer Genome Atlas (TCGA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) to investigate the correlations between KAZN expression and clinical characteristics of OC by comparing methylation levels of normal and OC samples. The relationships among differentially methylated sites in the KAZN gene, corresponding KAZN mRNA expression levels and prognosis were analyzed. RESULTS: KAZN was up-regulated in ovarian epithelial tumors and the expression of KAZN was correlated with the patients' survival time. KAZN CpG site cg17657618 was positively correlated with the expression of mRNA and the methylation levels were significantly differential between the group of stage "I and II" and the group of stage "III and IV". This study also presents a new method to classify tumor and normal tissue in OC using DNA methylation pattern in the KAZN gene body region. CONCLUSIONS: KAZN was involved in ovarian cancer pathogenesis. Our results demonstrate a new direction for ovarian cancer research and provide a potential diagnostic biomarker as well as a novel therapeutic target for clinical application.

Trabectedin in Cancers: Mechanisms and Clinical Applications.

Trabectedin, a tetrahydroisoquinoline alkaloid, is the first marine antineoplastic agent approved with special anticancer mechanisms involving DNA binding, DNA repair pathways, transcription regulation and regulation of the tumor microenvironment. It has favorable clinical applications, especially for the treatment of patients with advanced soft tissue sarcoma, who failed in anthracyclines and ifosfamide therapy or could not receive these agents. Currently, trabectedin monotherapy regimen and regimens of combined therapy with other agents are both widely used for the treatment of malignancies, including soft tissue sarcomas, ovarian cancer, breast cancer, and non-small-cell lung cancer. In this review, we have summarized the basic information and some updated knowledge on trabectedin, including its molecular structure, metabolism in various cancers, pharmaceutical mechanisms, clinical applications, drug combination, and adverse reactions, along with prospects of its possibly more optimal use in cancer treatment.

Irrational Use of Medicine in the Treatment of Presumptive Asthma Among Rural Primary Care Providers in Southwestern China.

Poor knowledge, scarce resources, and lack of or misaligned incentives have been widely documented as drivers of the irrational use of medicine (IUM), which significantly challenges the efficiency of health systems across the globe. However, there is limited understanding of the influence of each factor on IUM. We used detailed data on provider treatment of presumptive asthma cases in rural China to assess the contributions of provider knowledge, resource constraints, and provider behavior on IUM. This study enrolled 370 village providers from southwest China. All providers responded to a clinical vignette to test their knowledge of how to treat presumptive asthma. Resource constraints ("capacity") were defined as the availability of the prescribed medicines in vignette. To measure provider behavior ("performance"), a subset of providers (104 of 370) were randomly selected to receive unannounced visits by standardized patients (SPs) who performed of presumptive asthma symptoms described in the vignette. We found that, 54% (201/370) of providers provided the vignette-based patients with prescriptions. Moreover, 67% (70/104) provided prescriptions for the SPs. For the vignette, only 10% of the providers prescribed the correct medicines; 38% prescribed only unnecessary medicines (and did not provide correct medicine); 65% prescribed antibiotics (although antibiotics were not required); and 55% prescribed polypharmacy prescriptions (that is, they prescribed five or more different types of drugs). For the SP visits, the numbers were 12%, 51%, 63%, and 0%, respectively. The lower number of medicines in the SP visits was due, in part, to the injections' not being allowed based on ethical considerations (in response to the vignette, however, 65% of providers prescribed injections). The difference between provider knowledge and capacity is insignificant, while a significant large gap exists between provider performance and knowledge/capacity (for 11 of 17 indicators). Our analysis indicated that capacity constraints play a minor role in driving IUM compared to provider performance in the treatment of asthma cases in rural China. If similar findings hold for other disease cases, this suggests that policies to reduce the IUM in rural China have largely been unsuccessful, and alternatives for improving aligning provider incentives with appropriate drug use should be explored.

Pharmacological Effects of Natural Components Against Ovarian Cancer and Mechanisms.

Ovarian cancer, one of the three leading malignancies in women, has high incidence and mortality worldwide. It is hard to diagnose until very late stages and the 5-year survival rate is very low, due mostly to its distant metastasis. Chemotherapy is currently the most common treatment to inhibit cancer growth, but long-term use could result in resistance and tumor recurrence in addition to damages to normal tissues and functions of the patients. In order to achieve safe and curative effects against cancers, many investigators have focused their attention on traditional Chinese herbal medicines. Paclitaxel, a natural antitumor agent, has significant effects on advanced malignancies including ovarian cancer and is in the standard front-line treatment. Additional natural anticancer substances have continually been discovered for their high effectiveness and low side-effects in ovarian cancer prevention and therapy. In this chapter, we summarize recent work on a selected group of natural components, including lignans, ellagic acid, luteolin, mangiferin, and Acanthopanax senticosus, which have all been demonstrated to reduce the progress of epithelial ovarian cancer in a dose-depend manner, by both in vitro and in vivo experiments. The mechanisms of the anticancer activities by these natural components involve expression suppression of MMP2 and MMP9.

Suppressive activities of mangiferin on human epithelial ovarian cancer.

BACKGROUND: Epithelial carcinoma is a subtype of ovarian cancers, with the highest lethality among all ovarian cancer subtypes. Hitherto surgical excision combined with chemotherapy has been the most extensively employed method in clinical treatment. However, the disease relapses very frequently, calling for more effective therapies. Mangiferin, a natural xanthone glucoside, has displayed promising anti-cancer activities by in vitro studies, but its therapeutic value in epithelial ovarian cancer treatment, either by in vivo or in vitro studies, remained to be known. PURPOSE: This study aimed to determine the suppressive activities of mangiferin on human epithelial ovarian cancer and elucidate the underlying molecular mechanisms. STUDY DESIGN AND METHODS: We employed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the crystal violet assay to determine the half maximal inhibitory concentration (IC50) values of mangiferin with paclitaxel as a positive control and the inhibitory effects of mangiferin on the proliferation of two human epithelial ovarian cancer cell lines. Wound healing and Transwell assays were used to determine anti-metastastic activities of mangiferin. ES-2 xenograft nude mouse model was used for the in vivo experiments. Western blotting, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) assays were carried out for evaluating the expression level of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9). RESULTS: In the present study, we demonstrated by both in vitro and in vivo assays that mangiferin suppressed the progress of epithelial ovarian cancer in a dose-dependent manner. In the animals treated with mangiferin, the tumor volume and weight were reduced significantly. Analyses of involved molecular events demonstrated that mangiferin down-regulated the expression of metastasis-associated proteins MMP2 and MMP9. CONCLUSION: Mangiferin strongly inhibited the progression of human epithelial ovarian cancer by down-regulating MMP2 and MMP9.

The Oncogenic Functions of Insulin-like Growth Factor 2 mRNA-Binding Protein 3 in Human Carcinomas.

IGF2BP3 (also known as IMP3, KOC), a member of the insulin-like growth factor mRNA-binding protein family (IMPs), has been a research target in recent studies of promoting embryo development and exacerbating cancer. IGF2BP3 is ubiquitously expressed in early embryogenesis stages but limited in postembryonic stages, which is important in many physiological aspects such as stem cell renewal, morphological development and metabolism. A large number of studies show that IGF2BP3 interacts with many kinds of non-coding RNAs and proteins to promote cancer cell proliferation and metastasis and inhibit cancer cell apoptosis. As IGF2BP3 is highly expressed in advanced cancers and associated with poor overall survival rates of patients, it may be a potential molecular marker in cancer diagnosis for the detection of cancerous tissues and an indicator of cancer stages. Therefore, anti-IGF2BP3 drugs or monoclonal antibodies are expected as new therapeutic methods in cancer treatment. This review summarizes recent findings among IGF2BP3, RNA and proteins in cancer processes, with a focus on its cancer-promoting mechanisms and potential application as a new biomarker for cancer diagnosis and treatment.

Thrombospondin-1 as a Potential Therapeutic Target: Multiple Roles in Cancers.

Thrombospondin-1, an extracellular matrix protein, is the first identified natural angiogenesis inhibitor. Thrombospondin-1 participates in a great number of physiological and pathological processes, including cell-cell and cell-matrix interactions via a number of cell receptors, including CD36 and CD47, which plays a vital role in mediating inflammation and performs a promoting effect in pulmonary arterial vasculopathy and diabetes. Thrombospondin-1 consists of six domains, which combine with different molecules and participate in various functions in cancers, serving as a critical member in diverse pathways in cancers. Thrombospondin-1 works as a cancer promotor in some pathways but as a cancer suppressor in others, which makes it highly possible that its erroneous functioning might lead to opposite effects. Therefore, subdividing the roles of thrombospondin-1 and distinguishing them in cancers are necessary. Complex structure and multiple roles take disadvantage of the research and application of thrombospondin-1. Compared with the whole thrombospondin-1 protein, each thrombospondin- 1 active peptide performs an uncomplicated structure and, nevertheless, a specific role. In other words, various thrombospondin-1 active peptides may function differently. For instance, thrombospondin-1 could both promote and inhibit glioblastoma, which is significantly inhibited by the three type I repeats, a thrombospondin-1 active peptide but promoted by the fragment 167-569, a thrombospondin-1 active peptide consisting of the procollagen homology domain and the three type I repeats. Further studies of the functions of thrombospondin-1 active peptides and applying them reasonably are necessary. In addition to mediating cancerogenesis, thrombospondin-1 is also affected by cancer development, as reflected by its expression in plasma and the cancer tissue. Therefore, thrombospondin-1 may be a potential biomarker for pre-clinical and clinical application. This review summarizes findings on the multiple roles of thrombospondin-1 in cancer processes, with a focus on its use as a potential therapeutic target.

The competence of village clinicians in the diagnosis and management of childhood epilepsy in Southwestern China and its determinants: A cross-sectional study.

BACKGROUND: Due to lack of neurologists in low- and middle-income countries, communities of patients living with epilepsy are calling for task-shifting of diagnosis and management from physicians to paramedical providers in the primary health care systems to narrow the huge treatment gap. Evidence to guide this work has been limited. This study assesses the competence of village clinicians (VC)- mostly paramedical providers- in the diagnosis and management of a presumptive case of childhood epilepsy and its determinants. METHODS: A cross-sectional study was conducted in rural areas of a province in Southwestern China from July 2017 to January 2018. We randomly selected 370 VCs who practiced Western medicine and assumed the main responsibility of providing medical services in his/her clinic. A standardized clinical vignette based on national clinical practice guidelines was used to evaluate clinicians' competence in three domains: number and proportion of recommended (and essential) checklist (questions, examinations, and tests) completed, correctness of diagnosis, and correctness of case management. FINDINGS: Though VCs completed 14•3% (IQR 9•5%-19•1%) of the recommended checklist, 63•2% (234/370, 95%CI 58•2%-68•0%) provided a correct diagnosis. Only 1•6% of VCs (6/370, 95%CI 0•7%-3•5%) gave correct management with both correct medication and referral, however 90•3% (334/370, 95%CI 86•8%-92•9%) provided partially correct management by referring patients to upper-level health facilities (89•5%, 331/370, 95%CI 85•9%-92•2%) or prescribing anti-epileptic drugs (AEDs) correctly (0•8%, 3/370, 95%CI 0•3%-2•4%). Around 1/4 VCs referred patients to Township Health Centers which usually were not staffed with pediatric neurologists. Fewer provided helpful medical advice to patients for daily management. The heuristic process was found to be negatively associated with the proportion of the recommended checklist that VCs completed, which is positively associated with correctness of diagnosis. INTERPRETATION: Most VCs could diagnose and refer childhood epilepsy patients correctly; however, they lacked competence when it came to assuming the responsibility of primary care providers, referring efficiently, refilling AEDs, as well as supervising and instructing daily management of patients. FUNDING: HY received the funding for this study from the "Health and Hope Fund" of the Business Development Center of the RCSC (Beijing) and UCB (Belgium). UCB provided support in the form of a salary for author DET.

Genetic boundaries delineate the potential human pathogen Salmonella bongori into discrete lineages: divergence and speciation.

BACKGROUND: Salmonella bongori infect mainly cold-blooded hosts, but infections by S. bongori in warm-blooded hosts have been reported. We hypothesized that S. bongori might have diverged into distinct phylogenetic lineages, with some being able to infect warm-blooded hosts. RESULTS: To inspect the divergence status of S. bongori, we first completely sequenced the parakeet isolate RKS3044 and compared it with other sequenced S. bongori strains. We found that RKS3044 contained a novel T6SS encoded in a pathogenicity island-like structure, in addition to a T6SS encoded in SPI-22, which is common to all S. bongori strains so far reported. This novel T6SS resembled the SPI-19 T6SS of the warm-blooded host infecting Salmonella Subgroup I lineages. Genomic sequence comparisons revealed different genomic sequence amelioration events among the S. bongori strains, including a unique CTAG tetranucleotide degeneration pattern in RKS3044, suggesting non-overlapping gene pools between RKS3044 and other S. bongori lineages/strains leading to their independent accumulation of genomic variations. We further proved the existence of a clear-cut genetic boundary between RKS3044 and the other S. bongori lineages/strains analyzed in this study. CONCLUSIONS: The warm-blooded host-infecting S. bongori strain RKS3044 has diverged with distinct genomic features from other S. bongori strains, including a novel T6SS encoded in a previously not reported pathogenicity island-like structure and a unique genomic sequence degeneration pattern. These findings alert cautions about the emergence of new pathogens originating from non-pathogenic ancestors by acquiring specific pathogenic traits.

Genetic diversity and evolutionary features of type VI secretion systems in Salmonella.

AIM: Type VI secretion systems (T6SS) play key roles in bacterial pathogenesis, but their evolutionary features remain largely unclear. In this study, we conducted systematic comparisons among the documented T6SSs in Salmonella and determined their structural diversity, phylogenetic distribution and lineage-specific properties. MATERIALS & METHODS: We screened 295 Salmonella genomes for 13 T6SS core components by hidden Markov models and identified 363 T6SS clusters covering types i1, i2, i3 and i4a. RESULTS: Type i3 and i4a T6SSs were restricted to Salmonella enterica subspecies enterica and Salmonella bongori, respectively. whereas type i2 T6SSs were conserved between S. enterica subspecies, arizonae and diarizonae. S. enterica subspecies salamae, indica and houtenae harbored only type i1 T6SSs, which had wide distribution and high sequence diversity. CONCLUSION: The diverse Salmonella T6SSs have undergone purifying selection pressures during the bacterial evolution and may be involved in host adaptation.

Three-dimensional reduced graphene oxide aerogel stabilizes molybdenum trioxide with enhanced photocatalytic activity for dye degradation.

By using three-dimensional reduced graphene oxide (rGO) aerogel as a carrier for molybdenum trioxide (MoO3), a series of rGO-MoO3 aerogels were synthesized by a self-assembly process. The results indicated that the as-prepared rGO-MoO3 aerogel had very low density and good mechanical properties, and would not deform under more than 1000 times its own pressure. The rGO-MoO3 aerogel showed more than 90% degradation efficiency for MB within 120 min. After six cycles of recycling, the degradation rate of MB only decreased by 1.6%. As supported by the electron paramagnetic resonance (EPR) measurements, the presence of the rGO aerogel enhanced electron conduction, prolonged carrier lifetime and inhibited electron and hole recombination, thus improving the photocatalytic efficiency of composite aerogel. Besides, the hydroxyl radical (OH˙) and radical anion (˙O2 -) played an important role in the photodegradation of the dye. The outstanding adsorption and photocatalytic degradation performance of the rGO-MoO3 aerogel was attributed to its unique physical properties, such as high porosity, simple recycling process, high hydrophobicity, low density and excellent mechanical stability. The findings presented herein indicated that the rGO-MoO3 aerogel had good application potential, and could serve as a promising photocatalyst for the degradation of dyes in wastewater.