Regulation of Mycobacterium biofilm development and novel measures against antibiotics resistance.

Currently, there are over 170 recognized species of Mycobacterium, the only genus in the family Mycobacteriaceae. Organisms belonging to this genus are quite diverse with respect to their ability to cause disease in humans. The Mycobacterium genus includes human pathogens (Mycobacterium tuberculosis complex and Mycobacterium leprae) and environmental microorganisms known as non-tuberculosis mycobacteria (NTM). A common pathogenic factor of Mycobacterium is the formation of biofilms. Bacterial biofilms are usually defined as bacterial communities attached to the surface, and are also considered as shared spaces of encapsulated microbial cells, including various extracellular polymeric substrates (EPS), such as polysaccharides, proteins, amyloid proteins, lipids, and extracellular DNA (EDNA), as well as membrane vesicles and humic like microorganisms derived refractory substances. The assembly and dynamics of the matrix are mainly coordinated by second messengers, signaling molecules, or small RNAs. Fully deciphering how bacteria provide structure for the matrix, thereby promoting extracellular reactions and benefiting from them, remains a challenge for future biofilm research. This review introduces a five step development model for biofilms and a new model for biofilm formation, analyses the pathogenicity of biofilms, their interactions with bacteriophages and host immune cells, and the key genes and regulatory networks of mycobacterial biofilms, as well as mycobacterial biofilms and drug resistance, in order to provide a basis for clinical treatment of diseases caused by biofilms.

Thermal/Redox-triggered release of pyrazinic functional molecules by coordination polymers with luminescence monitoring ability.

Storage of volatile active molecules, along with the prolongation of their specific functions, requires the use of regulatable carriers. Pyrazine derivatives are highly volatile compounds with a broad application owing to their flavoring, pharmaceutical, antimicrobial, antiseptic, and insecticidal properties. In this study, pyrazines were stored by coordinating them with cuprous iodide to easily generate a series of luminescent coordination polymer (CP)-based carriers. The CPs could respond to thermal-redox stimuli and manipulate pyrazine release by breaking the labile Cu-N bonds when triggered by the two stimuli. Moreover, the release process could be visualized by decreased luminescence caused by the gradual decomposition of CP structures. The loading efficiencies ranged from 31% to 38%, and the controlled release behaviors accord with the zero-order kinetics. This work is the first to prove that CPs could function as dual stimuli-mediated delivery systems, which hold the potential to control the release and strengthen the usability of functional molecules.

Diatom Frustules Decorated with Co Nanoparticles for the Advanced Anode of Li-Ion Batteries.

Silica is regarded as a promising anode material for lithium-ion batteries (LIBs) because of its high theoretical capacity. However, large volume variation and poor electrical conductivity are limiting factors for the development of SiO2 anode materials. To solve this problem, combining SiO2 with a conductive phase and designing hollow porous structures are effective ways. In this work, The Co(II)-EDTA chelate on the surface of diatom biosilica (DBS) frustules and obtained DBS@C-Co composites decorated with Co nanoparticles by calcination without a reducing atmosphere is first precipitated. The unique three-dimensional structure of diatom frustules provides enough space for the volume change of silica during lithiation/delithiation. Co nanoparticles effectively improve the electrical conductivity and electrochemical activity of silica. Through the synergistic effect of the hollow porous structure, carbon layer and Co nanoparticles, the DBS@C-Co-60 composite delivers a high reversible capacity of >620 mAh g-1 at 100 mA g-1 after 270 cycles. This study provides a new method for the synthesis of metal/silica composites and an opportunity for the development of natural resources as advanced active materials for LIBs.

Copper(I)-Iodide Clusters as Carriers for Regulating and Visualizing Release of Aroma Molecules.

Achieving the controlled release of functional substances is indispensable in many aspects of life. Especially for the aroma molecules, their effective delivery of flavor and fragrance is challenging. Here, selected pyridines, as highly volatile odorants, were individually coordinated with copper(I) iodide (CuII) via a straightforward one-pot synthesis method, rapidly forming pure or even crystalline CuII cluster-based profragrances at room temperature. The obtained profragrances enabled the stable and high loading of volatile fragrances under ambient conditions and guaranteed their long-lasting release during heating. Furthermore, the intrinsic emission luminescence of these solid-state profragrances decayed along with the aroma release, which can serve as an additional indicator for monitoring the delivery process. This research sets a precedent for using CuII clusters as dual-purpose release agents and greatly expands their potential applications.

USP18-mediated protein deISGylation and its role in tuberculosis and other infectious diseases.

The transcription of interferon-stimulated gene 15 (isg15) is induced by type I interferons. ISG15 can covalently modify target proteins through the sequential action of enzymesE1, E2, and E3, a process known as ISGylation. The ISGylation of host proteins is widely involved in immune responses, such as host antiviral defence. Ubiquitin-specific protease 18 (USP18), as a deubiquitinase (DUB), can remove ISG15 conjugated to target proteins and inhibit host immune responses by suppressing the type I interferon signaling. The dynamic balance between ISGylation and deISGylation mediated by ISG15 or USP18 respectively plays a significant role in the tuberculosis. Furthermore, similar to ISG15, USP18 is extensively involved in virus-host interaction. In this review, we summarize the roles of ISGylation and deISGylation in tuberculosis and other important diseases mediated by ISG15 and USP18 respectively, underlying regulator network. Further studies in this aspect will inspire new host-targeted strategies to control important diseases such as tuberculosis.

Progress on the function of Mycobacterium T7SS (ESX) secretion system.

Mycobacterium infection can affect the host's immune function by secreting extracellular effector proteins. ESX (or type VII) system plays an important role in the secretion of effector proteins. ESX system is the protein export system in mycobacteria and many actinomycetes. However, how ESX system secretes and underlying mechanism of action remain unclear. In this review, we introduce the components, function, classification of ESX system and the process of substrates transfer to the peripheral space via this system, and discuss the roles of ESX system in antibiotics resistance, persistence, host-phage interaction, new drug targets. We hope to provide insights into the discovery of new drugs and vaccine antigens for tuberculosis.

Progress on the non-canonical mismatch repair in Mycobacterium and its role in antibiotic resistance.

Mismatch repair (MMR) is a common repair system after DNA replication, which is critical for maintaining genomic stability. Members of the MutS and MutL protein families are involved in key steps of mismatch repair. Despite the major importance of this repair pathway, MutS-MutL are absent in almost all Actinobacteria and many Archaea. Mycobacteria and others have another non-canonical MMR pathway, in which EndoMS/NucS plays a key role and has no structural homology compared to canonical MMR proteins (MutS/MutL). EndoMS/NucS mediated non-canonical mismatch repair plays an important role in DNA repair, mutation, homologous recombination and antibiotic resistance of Mycobacterium. By comparing the classical and non-canonical MMR pathways, this paper reviews the EndoMS/NucS-mediated non-canonical MMR pathway in Mycobacterium and its recent progress. We hope to bring new insights into the molecular mechanism of mycobacterial mismatch repair as well as to provide new research clues for mycobacterial antibiotic therapy.

miR-597-3p inhibits invasion and migration of thyroid carcinoma SW579 cells by targeting RAB23.

INTRODUCTION: Nowadays, it is indicated that miRNA was anomaly expressed in tumour. Previous studies have shown that miRNAs can regulate the proliferation, invasion, and migration of cancer cell-related processes. Meanwhile, current investigations show that RAB23 also plays an important role in cancer cell-related processes. But the potential mechanism remains unclear. MATERIAL AND METHODS: SW579 cells were selected and transfected with miR-597-3p mimics. Then the expression of miR-597-3p and RAB23 were measured by quantitative real-time polymerase chain reaction (PCR) and western blotting, respectively. Subsequently, the abilities of proliferation, invasion, and migration of SW579 cells were researched. For further study, the Luciferase reporter assay proved that miR-597-3p could target the expression of RAB23, and the proteins of invasion and migration were also measured to clear the mechanism. RESULTS: After being transfected with miR-597-3p mimics, the expression of miR-597-3p was remarkably increased and RAB23 was significantly decreased. The abilities of proliferation, invasion, and migration also decreased significantly. The miRTarase Database predicated and Luciferase reporter assay proved that RAB23 was the target gene of miR-597-3p. The expression of matrix metalloproteinase (MMP)-2, MMP-9, and N-cadherin was down-regulated, and the expression of E-cadherin was up-regulated. CONCLUSION: miR-597-3p could reduce the proliferation, invasion and migration abilities of SW579 cells, which may be related to the targeted inhibition of RAB23 expression and down-regulation of the expression levels of MMP-2, MMP-9 and N-cadherin proteins of SW579 cells.

Long noncoding RNAs SET-binding factor 2-antisense RNA1 promotes cell growth through targeting miR-431-5p/CDK14 axis in human papillary thyroid cancer.

Papillary thyroid cancer (PTC) is a frequent thyroid malignancy. With the significant regulatory role in tumor progression, more attention has been employed to investigate mechanism of long noncoding RNAs (lncRNAs) in progression of PTC. We prospectively explored the mechanism whereby lncRNA SET-binding factor 2-antisense RNA1 (SBF2-AS1) is implicated in pathogenesis of PTC. First, differentially expressed SBF2-AS1 between PTC and normal adjacent thyroid tissues was determined, and result indicated a higher SBF2-AS1 expression in PTC tissues than adjacent normal tissues. Moreover, highly SBF2-AS1 expression predicted a poor prognosis in PTC patients. Second, SBF2-AS1 overexpression promoted cell viability and cycle of PTC, while inhibited cell apoptosis. However, SBF2-AS1 downregulation reduced viability and cycle, while promoted cell apoptosis. Moreover, SBF2-AS1 could bind with miR-431-5p and showed negative correlation with miR-431-5p in PTC patients. Furthermore, miR-431-5p bind with cyclin-dependent kinase (CDK) 14 and showed negative correlation with CDK14 in PTC patients. Finally, overexpression of CDK14 counteracted with the inhibitory role of SBF2-AS1 downregulation on cell viability, cycle, and apoptosis of PTC. In conclusion, SBF2-AS1 exhibited oncogenic property in PTC, and knockdown of SBF2-AS1 could be a therapeutic strategy for PTC.

Prophylactic Effects of Bifidobacterium adolescentis on Anxiety and Depression-Like Phenotypes After Chronic Stress: A Role of the Gut Microbiota-Inflammation Axis.

Stress disturbs the balance of the gut microbiota and stimulates inflammation-to-brain mechanisms. Moreover, stress leads to anxiety and depressive disorders. Bifidobacterium adolescentis displays distinct anti-inflammatory effects. However, no report has focused on the anxiolytic and antidepressant effects of B. adolescentis related to the gut microbiome and the inflammation on chronic restraint stress (CRS) in mice. We found that pretreatment with B. adolescentis increased the time spent in the center of the open field apparatus, increased the percentage of entries into the open arms of the elevated plus-maze (EPM) and the percentage of time spent in the open arms of the EPM, and decreased the immobility duration in the tail suspension test as well as the forced swimming test (FST). Moreover, B. adolescentis increased the sequence proportion of Lactobacillus and reduced the sequence proportion of Bacteroides in feces. Furthermore, B. adolescentis markedly reduced the protein expression of interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), p-nuclear factor-kappa B (NF-κB) p65 and Iba1 and elevated brain derived neurotrophic factor (BDNF) expression in the hippocampus. We conclude that the anxiolytic and antidepressant effects of B. adolescentis are related to reducing inflammatory cytokines and rebalancing the gut microbiota.

Wogonoside promotes apoptosis in gastric cancer AGS and SGC-7901 cells through induction of mitochondrial dysfunction and endoplasmic reticulum stress.

Wogonoside (Wg), a natural flavonoid, has anticancer effects against several human cancers. The purpose of the present study was to investigate the antitumor effects and underlying mechanisms of Wg on gastric cancer (GC) cell lines. We report that Wg treatment inhibited cell viability and induced apoptosis in human GC cell lines AGS and SGC-7901, and also retarded GC tumor growth in xenograft mice in vivo. We also found that the Wg exerted its antitumor effects against GC cells via induction of reaction oxygen species accumulation, mitochondrial dysfunction, and endoplasmic reticulum stress. Furthermore, C/EBP homologous protein knockdown inhibited apoptosis and increased the viability of Wg-treated GC cells. Our findings may facilitate the development of novel therapeutic agents for the treatment of GC.

Alteration of microRNA-4474/4717 expression and CREB-binding protein in human colorectal cancer tissues infected with Fusobacterium nucleatum.

Colorectal cancer (CRC) is a common and highly lethal form of cancer. Although the etiologic role of Fusobacterium nucleatum (F. nucleatum) in the development of CRC has been elucidated, the specific tumor molecules involved in the progression of CRC induced by F. nucleatum have not been identified. This study investigated several miRNAs and genes involved in the progression of F. nucleatum-induced CRC by Affymetrix miRNA microarray technology and GeneChip Human Transcriptome Array 2.0. The results suggest that miR-4474 and miR-4717 are up-regulated in CRC tissues in response to F. nucleatum infection, compared with the control group (paracancerous tissues), while other genes associated with signaling pathways in cancer, including CREB-binding protein (CREBBP), STAT1, PRKACB, CAMK2B, JUN, TP53 and EWSR1, were dysregulated. Bioinformatic analysis identified CREBBP as the primary aberrantly expressed gene in F. nucleatum-induced CRC. Consistent with the microarray analysis results, real-time RT-PCR analysis demonstrated that the expression of miR-4474/4717 was upregulated while that of CREBBP mRNA was downregulated in CRC patients infected with F. nucleatum. Additionally, CREBBP was identified as a novel target of miR-4474/4717. The results of this study suggest that miR-4474 and miR-4717 are involved in the progression of F. nucleatum-induced CRC by posttranscriptionally regulating the target gene CREBBP.

[Acid-resistant genes in Mycobacterium tuberculosis and the underlying regulatory network].

The molecular mechanisms of pathogen persistence within host cells are emerging hotspots, and one of the causes of its persistence is the acid resistance of bacteria. Currently, tuberculosis remains a serious threat to global public health and it is caused by Mycobacterium tuberculosis. In particular, acid resistance of M. tuberculosis and its persistence within macrophages contribute significantly to tuberculosis. Investigations have uncovered three major mechanisms underlying its acid resistance: the control of proton entry, metabolic regulation of intracellular acid-base balance and regulation of the two-component signaling system. In this review, we summarize the overall regulation network of M. tuberculosis in the acidic environment, aiming at providing a new overall idea for treating M. tuberculosis persistence and exploring new targets for tuberculosis control.

Steam distillation/drop-by-drop extraction with gas chromatography-mass spectrometry for fast determination of volatile components in jujube (Ziziphus jujuba Mill.) extract.

BACKGROUND: Jujube extract is commonly used as a food additive and flavoring. The unique jujube aroma and the mild sweet aroma of the extract are critical factors that determine product quality and affect consumer acceptability. The aroma changes with changes in the extraction condition, which is typically dependent on the characteristics of volatile oils in the extract. Despite their importance, the volatile oils of jujube extract have received less attention compared with the soluble components. So, an appropriate qualitative and quantitative method for determination of the volatile oils is vitally important for quality control of the product. RESULTS: A method coupling steam distillation/drop-by-drop extraction with gas chromatography-mass spectrometry (S3DE/GC-MS) was developed to determine the volatile components of jujube extract. Steam distillation was coupled with solvent extraction; the resulting condensate containing volatile components from jujube extract was drop-by-drop extracted using 2 mL of methyl tertiary butyl ether. The solvent served two purposes. First, the solvent extracted the volatile components from the condensate. Second, the volatile components were pre-concentrated by drop-by-drop accumulation in the solvent. As a result, the extraction, separation, and concentration of analytes in the sample were simultaneously completed in one step. The main parameters affecting the S3DE procedure, such as the water steam bubbling rate, extraction solvent volume, sample weight and S3DE time, were optimized. The standard addition approach was essential to obtain accurate measurements by minimizing matrix effects. Good linearity (R2 ≥ 0.9887) and good repeatability (RSDs ≤ 10.35%, n = 5) for 16 analytes in spiked standard analyte samples were achieved. CONCLUSIONS: With the S3DE/GC-MS method, seventy-six volatile compounds from jujube extract were identified and the content of 16 compounds was measured. The results were similar to those from simultaneous distillation extraction. The developed method was simple, fast, effective, sensitive, and provided an overall profile of the volatile components in jujube extract. Thus, this method can be used to determine the volatile components of extracts. Graphical abstract The diagram of steam distillation/drop-by-drop extraction device.

The relationship between iodine intake and the risk of thyroid cancer: A meta-analysis.

Thyroid cancer (TC) is the most common malignancy of the endocrine system. The relationship between iodine intake and TC risk is controversial always. We aim to figure out the relationship between iodine intake and TC using meta-analysis. Literature research in MEDLINE, Embase, China National Knowledge Infrastructure, and China BioMedicine was performed up to April 2016, searched for relevant case-control and cohort studies. The effect of iodine consumption on the risk of TC was assessed using the pooled odds ratio (OR) and 95% confidence interval (CI). The meta-analysis included 8 case-control studies (n = 4974; 2213 cases; 2761 controls). More than adequate or excess iodine intake (>300 µg/d) decreased the risk of TC (OR 0.74, 95% CI 0.60, 0.92). High consumption of saltwater fish or shellfish decreased the risk of TC (OR 0.72, 95% CI 0.55, 0.95; OR 0.70, 95% CI 0.52, 0.96; respectively). A higher intake of dietary iodine was as a protective factor for TC. However, the available data are very limited and more studies are required.

[Synthesis and Fluorescence Properties of Rare Earth Ions Co-Doped CaMoO(4)].

In this paper, a series of CaMoO4 phosphor co-doped rare earth ions were prepared with chemistry co-precipitation method. The concentration of Pr(3+)/Tb(3+) and temperature had obvious influence on the luminescent properties. The crystal structures and spectrum characteristics of the samples were identified with X-ray powder diffraction (XRD) and fluorescence spectrophotometer (PL). According to XRD analysis, the main diffraction peaks of samples are consistent with the standard card (JCPDS 29-0351) of the diffraction peak data. This showed doped rare earth ions did not change matrix lattice structure. The emission spectrum excited by 275 nm exhibit sharp lines peaking at 488, 560, 621 and 560 nm assigned to the (3)P(0)­(3)H(4), (3)P(0)­(3)H(5)，(1)D(2)­(3)H(4) and (3)P(0)­(3)F(2) transitions of the Pr(3+) ions. The intensity of fluorescence reached the strongest when the concentration of the doping amount was 3%. The optimum calcination temperatures of CaMoO(4)∶0.03Pr(3+) and CaMoO(4)∶0.05Tb(3+) were 800 and 600 ℃. Furthermore, the intensity of excitation spectra and emission spectra are dependent on the concentration of the doping amount. The emission spectra intensities of CaMoO(4)∶Pr(3+) phosphors decrease and CaMoO(4)∶Tb(3+) phosphors firstly increase and then decrease because of concentration quenching effect with increasing Pr(3+) and Tb(3+) concentration. In addition, the luminescence properties of Pr(3+) ion in CaMoO(4)∶0.03Pr(3+), yTb(3+) system could be evidently improved with co-doping of Tb(3+) ions which was due to the efficient energy transfer process from Tb(3+) to Pr(3+) ions.

Research advances on microbial genetics in China in 2015.

In 2015, there are significant progresses in many aspects of the microbial genetics in China. To showcase the contribution of Chinese scientists in microbial genetics, this review surveys several notable progresses in microbial genetics made largely by Chinese scientists, and some key findings are highlighted. For the basic microbial genetics, the components, structures and functions of many macromolecule complexes involved in gene expression regulation have been elucidated. Moreover, the molecular basis underlying the recognition of foreign nucleic acids by microbial immune systems was unveiled. We also illustrated the biosynthetic pathways and regulators of multiple microbial compounds, novel enzyme reactions, and new mechanisms regulating microbial gene expression. And new findings were obtained in the microbial development, evolution and population genetics. For the industrial microbiology, more understanding on the molecular basis of the microbial factory has been gained. For the pathogenic microbiology, the genetic circuits of several pathogens were depicted, and significant progresses were achieved for understanding the pathogen-host interaction and revealing the genetic mechanisms underlying antimicrobial resistance, emerging pathogens and environmental microorganisms at the genomic level. In future, the genetic diversity of microbes can be used to obtain specific products, while gut microbiome is gathering momentum.

Two-Step Oxidation of Refractory Gold Concentrates with Different Microbial Communities.

Bio-oxidation is an effective technology for treatment of refractory gold concentrates. However, the unsatisfactory oxidation rate and long residence time, which cause a lower cyanide leaching rate and gold recovery, are key factors that restrict the application of traditional bio-oxidation technology. In this study, the oxidation rate of refractory gold concentrates and the adaption of microorganisms were analyzed to evaluate a newly developed two-step pretreatment process, which includes a high temperature chemical oxidation step and a subsequent bio-oxidation step. The oxidation rate and recovery rate of gold were improved significantly after the two-step process. The results showed that the highest oxidation rate of sulfide sulfur could reach to 99.01 % with an extreme thermophile microbial community when the pulp density was 5%. Accordingly, the recovery rate of gold was elevated to 92.51%. Meanwhile, the results revealed that moderate thermophiles performed better than acidophilic mesophiles and extreme thermophiles, whose oxidation rates declined drastically when the pulp density was increased to 10% and 15%. The oxidation rates of sulfide sulfur with moderate thermophiles were 93.94% and 65.73% when the pulp density was increased to 10% and 15%, respectively. All these results indicated that the two-step pretreatment increased the oxidation rate of refractory gold concentrates and is a potential technology to pretreat the refractory sample. Meanwhile, owing to the sensitivity of the microbial community under different pulp density levels, the optimization of microbial community in bio-oxidation is necessary in industry.

[Overview of patents on targeted genome editing technologies and their implications for innovation and entrepreneurship education in universities].

Zinc finger nuclease, transcription activator-like effector nuclease, and clustered regularly interspaced short palindromic repeats/Cas9 nuclease are important targeted genome editing technologies. They have great significance in scientific research and applications on aspects of functional genomics research, species improvement, disease prevention and gene therapy. There are past or ongoing disputes over ownership of the intellectual property behind every technology. In this review, we summarize the patents on these three targeted genome editing technologies in order to provide some reference for developing genome editing technologies with self-owned intellectual property rights and some implications for current innovation and entrepreneurship education in universities.