Dihydroergotamine and Bromocriptine: Potential Drugs for the Treatment of Major Depressive Disorder and Alzheimer's Disease Comorbidity.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease that is characterized by memory loss and cognitive impairment. Evidence shows that depression is a common co-occurrence in AD patients, and major depressive disorder (MDD) is considered a risk factor for AD. The crosstalk between the biological procedures related to the two disorders makes it very difficult to treat the comorbid conditions caused by them. Considering the common pathophysiological mechanisms underlying AD and MDD, antidepressant drugs may have beneficial therapeutic effects against their concurrence. In this study, we aimed to explore the potential drug candidates for the prevention and treatment of the comorbidity of AD and MDD. First, we screened the potential drugs for treating MDD by evaluating the distances of drug targets to MDD-related genes on the human protein-protein interaction network (PPIN) via a network-based algorithm. Then, the drugs were further screened to identify those that may be effective for AD treatment by analyzing their affinities with tau protein and Aß42 peptide via molecular docking. Furthermore, the most stable binding modes were identified via molecular dynamics simulations, and the regulatory effects of drug candidates on genes involved in the pathogenesis of AD and MDD were analyzed. A total of 506 MDD-related genes were retrieved, and 831 drug candidates for MDD treatment were screened via the network-based approach. The results from molecular docking and molecular dynamics simulations indicated dihydroergotamine had the lowest binding affinity with tau protein and bromocriptine could form the most stable binding mode with Aß42 peptide. Further analyses found that both dihydroergotamine and bromocriptine could regulate the expression of genes involved in the pathogenesis of AD and/or MDD in the brain. The exact mechanisms of the two drugs in treating AD and MDD, as well as their comorbidity, are still unclear, and further exploration is needed to evaluate their roles and mechanisms, both in vitro and in vivo. This study revealed that dihydroergotamine and bromocriptine may be the potential drug candidates for the treatment of the comorbidity of AD and MDD, and the therapeutic effects may be achieved by inhibiting the accumulation and aggregation of Aß42 and tau protein and regulating the expression of disease-related genes in the brain.

α-Mangostin reduces hypertension in spontaneously hypertensive rats and inhibits EMT and fibrosis in Ang II-induced HK-2 cells.

Hypertension affects a large number of individuals globally and is a common cause of nephropathy, stroke, ischaemic heart disease and other vascular diseases. While many anti-hypertensive medications are used safely and effectively in clinic practice, controlling hypertensive complications solely by reducing blood pressure (BP) can be challenging. α-Mangostin, a xanthone molecule extracted from the pericarp of Garcinia mangostana L., has shown various beneficial effects such as anti-tumor, anti-hyperuricemia, and anti-inflammatory properties. However, the effects of α-Mangostin on hypertension remain unknown. In this study, we observed that α-Mangostin significantly decreased systolic and diastolic blood pressure in spontaneously hypertensive rats (SHR), possibly through the down-regulation of angiotensin II (Ang II). We also identified early markers of hypertensive nephropathy, including urinary N-acetyl-ß-D-glucosaminidase (NAG) and ß2-microglobulin (ß2-MG), which were reduced by α-Mangostin treatment. Mechanistic studies suggested that α-Mangostin may inhibit renal tubular epithelial-to-mesenchymal transformation (EMT) by down-regulating the TGF-ß signaling pathway, thus potentially offering a new therapeutic approach for hypertension and hypertensive nephropathy.

Antimicrobial drugs for Parkinson's disease: Existing therapeutic strategies and novel drugs exploration.

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by loss of dopaminergic neurons in the substantia nigra, as well as the abnormal accumulation of misfolded α-synuclein. Clinically, PD is featured by typical motor symptoms and some non-motor symptoms. Up to now, although considerable progress has been made in understanding the pathogenesis of PD, there is still no effective therapeutic treatment for the disease. Thus, exploring new therapeutic strategies has been a topic that needs to be addressed urgently. Noteworthy, with the proposal of the microbiota-gut-brain axis theory, antimicrobial drugs have received significant attention due to their effects on regulating the intestinal microbiota. Nowadays, there is growing evidence showing that some antimicrobial drugs may be promising drugs for the treatment of PD. Data from pre-clinical and clinical studies have shown that some antimicrobial drugs may play neuroprotective roles in PD by modulating multiple biochemical and molecular pathways, including reducing α-synuclein aggregation, inhibiting neuroinflammation, regulating mitochondrial structure and function, as well as suppressing oxidative stress. In this paper, we summarized the effects of some antimicrobial drugs on PD treatment from recent pre-clinical and clinical studies. Then, we further discussed the potential of a few antimicrobial drugs for treating PD based on molecular docking and molecular dynamics simulation. Importantly, we highlighted the potential of clorobiocin as the therapeutic strategy for PD owing to its ability to inhibit α-synuclein aggregation. These results will help us to better understand the potential of antimicrobial drugs in treating PD and how antimicrobial drugs may alleviate or reverse the pathological symptoms of PD.

Preparation of sulfur self-doped coal-based adsorbent and its adsorption performance for Cu2.

The limited application of high-sulfur coal (HSC) and the increasing severity of copper pollution in solution are two pressing issues. To alleviate such issues, a sulfur self-doped coal-based adsorbent (HSC@ZnCl2) was obtained by pyrolysis (850 °C, 60 min holding time) of HSC and ZnCl2 with a mass ratio of 1:0.5. The results adsorption experiment revealed that the endothermic and spontaneous adsorption process was consistent with the Sips isothermal model (R2 = 0.992) and pseudo-second-order kinetic (R2 = 0.994), and that the adsorption process with a maximum adsorption capacity of 11.97 mg/g. Meanwhile, the adsorption of Cu2+ onto HSC@ZnCl2 was a result of the synergistic effects of various interactions, such as the complexation by oxygen-containing functional groups, electrostatic attraction and surface precipitation by ZnS on the adsorbent surface, and the process also included redox reaction. The findings of this work indicate that the preparation of sulfur self-doped coal-based adsorbent prepared from high-sulfur coal is a promising method for its large-scale utilization.

Hypericin as a potential drug for treating Alzheimer's disease and type 2 diabetes with a view to drug repositioning.

AIMS: Alzheimer's disease (AD) and type 2 diabetes (T2D) are two of the most common diseases in elderly population and they have a high rate of comorbidity. Study has revealed that T2D is a major risk factor of AD, and thus exploring therapeutic approaches that can target both diseases has drawn much interest in recent years. In this study, we tried to explore drugs that could be potentially used to prevent or treat both AD and T2D via a drug repositioning approach. METHODS: We first searched the known drugs that may be effective to T2D treatment based on the network distance between the T2D-associated genes and drugs deposited in the DrugBank database. Then, via molecular docking, we further screened these drugs by examining their interaction with islet amyloid polypeptide (IAPP) and Aß42 peptide, the key components involved in the pathogenesis of T2D or AD. Finally, the binding between the selected drug candidates and the target proteins was verified by molecular dynamics (MD) simulation; and the potential function of the drug candidates and the corresponding targets were analyzed. RESULTS: From multiple resources, 734 T2D-associated genes were collected, and a list of 1109 drug candidates for T2D was obtained. We found that hypericin had the lowest binding energy and the most stable interaction with either IAPP or Aß42 peptide. In addition, we also found that the target genes regulated by hypericin were differentially expressed in the tissues related to the two diseases. CONCLUSION: Our results show that hypericin may be able to bind with IAPP and Aß42 stably and prevent their accumulation, and thus could be a promising drug candidate for treating the comorbidity of AD and T2D.

3-Phosphoinositide-dependent kinase 1 drives acquired resistance to osimertinib.

Osimertinib sensitive and resistant NSCLC NCI-H1975 clones are used to model osimertinib acquired resistance in humanized and non-humanized mice and delineate potential resistance mechanisms. No new EGFR mutations or loss of the EGFR T790M mutation are found in resistant clones. Resistant tumors grown under continuous osimertinib pressure both in humanized and non-humanized mice show aggressive tumor regrowth which is significantly less sensitive to osimertinib as compared with parental tumors. 3-phosphoinositide-dependent kinase 1 (PDK1) is identified as a potential driver of osimertinib acquired resistance, and its selective inhibition by BX795 and CRISPR gene knock out, sensitizes resistant clones. In-vivo inhibition of PDK1 enhances the osimertinib sensitivity against osimertinib resistant xenograft and a patient derived xenograft (PDX) tumors. PDK1 knock-out dysregulates PI3K/Akt/mTOR signaling, promotes cell cycle arrest at the G1 phase. Yes-associated protein (YAP) and active-YAP are upregulated in resistant tumors, and PDK1 knock-out inhibits nuclear translocation of YAP. Higher expression of PDK1 and an association between PDK1 and YAP are found in patients with progressive disease following osimertinib treatment. PDK1 is a central upstream regulator of two critical drug resistance pathways: PI3K/AKT/mTOR and YAP.

Hypouricemic Actions of the Pericarp of Mangosteen in Vitro and in Vivo.

Hyperuricemia is the result of overproduction and/or underexcretion of uric acid, and it is a well-known risk factor for gout, hypertension, and diabetes. However, available drugs for hyperuricemia in the clinic are limited. Recently, a lot of research has been conducted in order to discover new uric acid-lowering agents from plants and foods. We found that the extracts from the pericarp of mangosteen reduced urate. Bioactivity-guided study showed that α-mangostin was the principal constituent. Herein, we reported for the first time the hypouricemic activities and underling mechanism of α-mangostin. The α-mangostin dose- and time-dependently decreased the levels of serum urate in hyperuricemic mice and markedly increased the clearance of urate in hyperuricemic rats, exhibiting a promotion of urate excretion in the kidney. Further evidence showed that α-mangostin significantly decreased the protein levels of GLUT9 in the kidneys. The change in the expression of URAT1 was not observed. Moreover, α-mangostin did not inhibit the activities of xanthine oxidoreductase and uricase in vitro or in vivo. Taken together, these findings suggest that α-mangostin has potential to be developed as a new anti-hyperuricemic agent with promoting uric acid excretion.

Highly active Fenton-like catalyst derived from solid waste-iron ore tailings using wheat straw pyrolysis.

The pollutants degradation rate of iron ore tailings-based heterogeneous catalysts is the main factor limiting its application. Herein, an iron ore tailings-based Fenton-like catalyst (I/W(3:1)-900-60) with a relatively fast catalysis rate was constructed by co-pyrolysis (900°C, 60 min holding time) of iron ore tailings and wheat straw with a mass ratio of 3:1. With wheat straw blending, the generated I/W(3:1)-900-60 presented a larger surface area (24.53 m2/g), smaller pore size (3.76 nm), reduced iron species (Fe2+ from magnetic), and a higher catalytic activity (0.0229 min-1) than I-900-60 (1.32 m2/g, 12.87 nm, 0.012 min-1) pyrolyzed using single iron ore tailing under the same pyrolysis conditions. In addition, biochar and iron ore tailings in I/W(3:1)-900-60 were tightly combined through chemical bonding. The optimal catalyst remains active after three cycles, indicating its catalytic stability and recyclability. The good Fenton-like methylene blue degradation efficiency of I/W(3:1)-900-60 was ascribed to the sacrificial role of biochar, as well as the electron transfer between biochar and iron active sites or the redox cycles of ≡Fe3+/Fe2+. This finding provides a facile construction strategy for highly active iron ore tailings-based Fenton-like catalyst and thereby had a great potential application in wastewater treatment.

Characterization and adsorption applications of composite biochars of clay minerals and biomass.

Composite mineral-biochars of a homogeneous biomass (cellulose) and heterogeneous biomass (oak leaves) were fabricated with either 5 wt% or 10 wt% minerals (montmorillonite (MMT), kaolinite, and sand) and then pyrolyzed at 600 °C for 60 min. Characterizations including proximate analysis, ultimate analysis, surface area and porosity, morphology, and surface chemistry confirmed that minerals were present on the surface of biochar, and MMT/kaolinite-biochar composites showed a strengthening in the chars' aromatic structures, as well as increases in oxygen-containing surface functional groups. Methylene blue adsorption isotherms indicated that the MMT/kaolinite-biochars had higher adsorption capacities than pure biomass or biomass-sand biochars (110 mgMB/gchar and 24 mgMB/gchar for MMT-cellulose char and cellulose char, respectively). A multilinear model relating adsorption capacity and adsorbent properties was developed to measure the relative contribution of biochar properties to adsorption behavior. The model indicates that pore volume and hydrogen bonding were the dominant properties in controlling the adsorption of methylene blue onto the biochars. Findings from this work indicate that composite biochars prepared from biomass and inexpensive clay minerals are a promising adsorbent for remediating organic contaminants from water.

Combination of bis (α-furancarboxylato) oxovanadium (IV) and metformin improves hepatic steatosis through down-regulating inflammatory pathways in high-fat diet-induced obese C57BL/6J mice.

The effects of the combination of bis (α-furancarboxylato) oxovanadium (IV) (BFOV) and metformin (Met) on hepatic steatosis were investigated in high-fat diet-induced obese C57BL/6J mice (HFC57 mice) for 6 weeks. Oral glucose tolerance test was performed to evaluate glucose metabolism. Moreover, blood and hepatic biochemical and histological indices were detected. Besides, Affymetrix-GeneChip analysis and Western blot of the liver were performed. Comparing to the monotherapy group, BFOV + Met showed more effective improvement in glucose metabolism, which decreased the fasting blood glucose, insulin levels and improved insulin sensitivity in HFC57 mice. BFOV + Met significantly decreased serum ALT and AST activities and reduced hepatic triglyceride content and iNOS activities, accompanied by ameliorating intrahepatic fat accumulation and hepatocellular vacuolation. Enhanced hepatic insulin signalling transduction and attenuated inflammation pathway were identified as the major pathways in the BFOV + Met group. BFOV + Met significantly down-regulated the protein expression levels of MMPs, NF-κB, iNOS and up-regulated phosphorylation of AKT and AMPK levels. We concluded that a combination of BFOV and metformin ameliorates hepatic steatosis in HFC57 mice via alleviating hepatic inflammation and enhancing insulin signalling pathway, suggesting that the combination of BFOV and metformin is a potential treatment for hepatic steatosis.

BBB07 contributes to, but is not essential for, Borrelia burgdorferi infection in mice.

Borrelia burgdorferi, a causative agent of Lyme disease, encodes a protein BBB07 on the genomic plasmid cp26. BBB07 was identified as a candidate integrin ligand based on the presence of an RGD tripeptide motif, which is present in a number of mammalian ligands for ß1 and ß3 integrins . Previous work demonstrated that BBB07 in recombinant form binds to ß1 integrins and induces inflammatory responses in synovial cells in culture. Several transposon mutants in bbb07 were attenuated in an in vivo screen of the transposon library in mice. We therefore tested individual transposon mutant clones in single-strain infections in mice and found that they were attenuated in terms of ID50 but did not have significantly reduced tissue burdens in mice. Based on data presented here we conclude that BBB07 is not essential for, but does contribute to, B. burgdorferi infectivity in mice.

Olsalazine Sodium Increases Renal Urate Excretion by Modulating Urate Transporters in Hyperuricemic Animals.

Hyperuricemia is mainly the result of relative underexcretion of urate. Urate is mainly eliminated by kidney and several important transporters expressed on the membrane of renal tubular cells involved in urate excretion. Olsalazine sodium was screened from 3167 authorized small compounds/drugs, targeting xanthine oxidoreductase. In previous study, we reported that olsalazine sodium significantly reduced the serum urate levels, and the anti-hyperuricemic activity linked with inhibiting urate formation by reducing the activity of xanthine oxidoreductase. The current research aimed to assess olsalazine sodium renal urate excretion and likely molecular mechanism. The results showed that administration of olsalazine sodium 5.0 mg/kg decreased the levels of serum urate in hyperuricemic rats, and noticeably improved the fractional excretion of urate and urate clearance, exhibiting an uricosuric action. Moreover, olsalazine sodium (2.5, 5.0, 10.0 mg/kg) reduced the level of blood urea nitrogen in rats. Further study showed that olsalazine sodium reduced the mRNA expression of urate reabsorptive transporter glucose transporter 9 (GLUT9), increased the mRNA expression of urate secretory transporters, organic anion transporter 1 (OAT1), OAT3 and type 1 sodium-dependent phosphate transporter (NPT1) as well as the protein expression of OAT3 in the kidney in hyperuricemic mice. In conclusion, olsalazine sodium exhibited a promotion of urate excretion in kidney by increasing the expression of OAT3.

Mangiferin promotes intestinal elimination of uric acid by modulating intestinal transporters.

Increasing evidence shows that the intestinal tract plays an important role in maintaining urate homeostasis and might be a potential therapeutic target for hyperuricaemia. However, uric acid-lowering drugs available in the clinic do not target intestinal excretion as a therapeutic strategy. We previously reported that mangiferin had potent hypouricaemic effects in hyperuricaemic animals. However, the underlying mechanisms are not completely clear. Here, we investigated the effects of mangiferin on the intestinal excretion of urate and its underlying mechanisms. The data revealed that mangiferin concentration-dependently promoted the intestinal secretion of endogenous urate in in situ intestinal closed loops in normal and hyperuricaemic mice, as well as inhibited the absorption of exogenous uric acid perfused into the intestinal loops in rats. Administration of mangiferin not only decreased the serum urate levels in the hyperuricaemic mice but also increased the protein expression of ATP-binding cassette transporter, subfamily G, member 2 (ABCG2) and inhibited the protein expression of glucose transporter 9 (GLUT 9) in the intestine. These findings suggested that intestinal ABCG2 and GLUT9 might be pivotal and possible action sites for the observed hypouricaemic effects. Moreover, no significant changes in intestinal xanthine oxidoreductase activities were observed, suggesting that mangiferin did not affect intestinal uric acid generation in the hyperuricaemic mice. Overall, promoting intestinal elimination of urate by upregulating ABCG2 expression and downregulating GLUT9 expression might be an important mechanism underlying mangiferin lowering serum uric acid levels. Mangiferin supplementation might be beneficial for the prevention and treatment of hyperuricaemia.

Synergistic Effect and Chlorine-Release Behaviors During Co-pyrolysis of LLDPE, PP, and PVC.

Plastic wastes are environmentally problematic and costly to treat, but they also represent a vast untapped resource for the renewable chemical and fuel production. Pyrolysis has received extensive attention in the treatment of plastic wastes because of its technical maturity. A sole polymer in the waste plastic is easy to recycle by any means of physical or chemical techniques. However, the majority of plastic in life are mixtures and they are hard to separate, which make pyrolysis of plastic complicated compared with pure plastic because of its difference in physical/chemical properties. This work focuses on the synergistic effect and its impact on chlorine removal from the pyrolysis of chlorinated plastic mixtures. The pyrolysis behavior of plastic mixtures was investigated in terms of thermogravimetric analysis, and the corresponding kinetics were analyzed according to the distributed activation energy model (DAEM). The results show that the synergistic effect existed in the pyrolysis of a plastic mixture of LLDPE, PP, and PVC, and the DAEM could well predict the kinetics behavior. The decomposition of LLDPE/PP mixtures occurred earlier than that of calculated ones. However, the synergistic effect weakened with the increase of LLDPE in the mixtures. As for the chlorine removal, the LLDPE and PP hindered the chlorine removal from PVC during the plastic mixture pyrolysis. A noticeable negative effect on dechlorination was observed after the introduction of LLDPE or PP. Besides, the chlorine-releasing temperature became higher during the pyrolysis of plastic mixtures ([LLDPE/PVC (1:1), PP/PVC (1:1), and LLDPE/PP/PVC (1:1:1)]. These results imply that the treatment of chlorinated plastic wastes was more difficult than that of PVC in thermal conversion. In other words, more attention should be paid to both the high-temperature chlorine corrosion and high-efficient chlorine removal in practical. These data are helpful for the treatment and thermal utilization of the yearly increased plastic wastes.

The intergenic small non-coding RNA ittA is required for optimal infectivity and tissue tropism in Borrelia burgdorferi.

Post-transcriptional regulation via small regulatory RNAs (sRNAs) has been implicated in diverse regulatory processes in bacteria, including virulence. One class of sRNAs, termed trans-acting sRNAs, can affect the stability and/or the translational efficiency of regulated transcripts. In this study, we utilized a collaborative approach that employed data from infection with the Borrelia burgdorferi Tn library, coupled with Tn-seq, together with borrelial sRNA and total RNA transcriptomes, to identify an intergenic trans-acting sRNA, which we designate here as ittA for infectivity-associated and tissue-tropic sRNA locus A. The genetic inactivation of ittA resulted in a significant attenuation in infectivity, with decreased spirochetal load in ear, heart, skin and joint tissues. In addition, the ittA mutant did not disseminate to peripheral skin sites or heart tissue, suggesting a role for ittA in regulating a tissue-tropic response. RNA-Seq analysis determined that 19 transcripts were differentially expressed in the ittA mutant relative to its genetic parent, including vraA, bba66, ospD and oms28 (bba74). Subsequent proteomic analyses also showed a significant decrease of OspD and Oms28 (BBA74) proteins. To our knowledge this is the first documented intergenic sRNA that alters the infectivity potential of B. burgdorferi.

Yunnan Baiyao diminishes lipopolysaccharide-induced inflammation in osteoclasts.

Yunnan Baiyao (YNBY) has been refined for hundreds of years and has become a treasure of proprietary Chinese medicine that has significant curative effects in the field of hemostasis, blood circulation, and callus. In past years, YNBY has been demonstrated to play an anti-inflammatory role in bone-related diseases, such as rheumatoid arthritis and osteoporosis. However, the osteoclasts are multinucleated giant cells that resorb bone and participate in the occurrence, development, and progression of these bone-related diseases. Previous studies have reported that the inflammatory function is closely associated with arachidonic acid (AA) metabolism, as well as some inflammatory-related pathways, including the nuclear factor кB (NF-кB), mitogen-activated protein kinase (MAPK), and Wnt5a pathways. Therefore, we speculated that the anti-inflammatory effect of YNBY might be associated with the NF-кB, MAPK, and Wnt5a pathways. In order to further excavate the anti-inflammatory roles of YNBY, lipopolysaccharide (LPS) with an optimal concentration of 1,000 pg/ml was used to induce inflammation in osteoclasts. Our results showed that YNBY with a time- and dose-dependent method decreased the concentration of pro-inflammatory cytokines and the expression levels of cyclooxygenase-1 (COX-1), COX-2, 5-lipoxygenase, and prostaglandin E2. Moreover, it was found that COX-2 was the target gene regulated by YNBY. Finally, using NF-кB and MAPK pathway inhibitors or miRNA101b (involved in the Wnt5a pathway) in tandem with YNBY and the results exhibited that these groups caused a reduction in COX-1 and COX-2 expression, indicating that the anti-inflammatory function of YNBY might directly affect the NF-кB, MAPK, and Wnt5a pathways. PRACTICAL APPLICATIONS: Yunnan Baiyao (YNBY) is mainly extracted from precious Chinese medicines such as Panax notoginseng, borneol, musk, and yam and has a wide range of clinical applications. It is not only used to treat various types of traumatic injuries, but also used for upper gastrointestinal bleeding and wound ulcers, neonatal umbilitis, recurrent oral ulcers, esophagitis, bacterial dysentery, and so on. Although the detailed mechanism of action is not clear at present, it is believed that this is related to its anti-inflammatory, hemostatic, and immune-enhancing effects. Many bone-related diseases, such as rheumatoid arthritis and osteoporosis, are regarded to be intimately related to the inflammatory reaction. Thus, this study aimed to explore the underlying mechanisms of YNBY at anti-inflammatory roles. And our results suggested that YNBY directly affected the inflammatory cytokines and AA metabolic products which referred to the NF-кB, MAPK, and Wnt5a pathways, as well as AA metabolism, respectively. Hence, the practical applications of YNBY are the anti-inflammatory effects used to treat for bone-related diseases.

Enhancement of floatability of low-rank coal using oxidized paraffin soap.

The processing of low-rank coal is becoming more urgent with depletion of high-rank coal and severe environmental pollution in China. The flotation of low-rank coal suffers poor efficiency with hydrocarbon oils unless it is at a high dose. A representative non-polar oil, diesel oil (DO), was used as a collector to float a long-frame coal. The feasibility of oxidized paraffin soap (OPS) was explored to improve flotation performance. Experimental measurements (polarized optical microscopy, zeta potential, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, contact-angle analysis) were used to explore the influence of OPS in low-rank-coal flotation. Poor flotation performances of coal samples were received using OPS or DO as collectors at an economical dose. The flotation efficiency of coal samples was improved considerably upon addition of OPS plus DO. OPS reduced the surface tension of aqueous solutions and promoted dispersion of DO in suspensions. Addition of OPS plus DO reduced the absolute value of the zeta potential on coal particles. Moreover, OPS improved DO adsorption on low-rank coal particles, and the hydrophobicity of low-rank coal was improved visibly. OPS reduced the contact angles of coal-bubble and coal-DO in aqueous solution, which enhanced the adhesion probability of particles to bubbles. This study suggests that OPS is an effective surfactant for improving the floatability of low-rank coal.

Genome-wide screen identifies novel genes required for Borrelia burgdorferi survival in its Ixodes tick vector.

Borrelia burgdorferi, the causative agent of Lyme disease in humans, is maintained in a complex biphasic life cycle, which alternates between tick and vertebrate hosts. To successfully survive and complete its enzootic cycle, B. burgdorferi adapts to diverse hosts by regulating genes required for survival in specific environments. Here we describe the first ever use of transposon insertion sequencing (Tn-seq) to identify genes required for B. burgdorferi survival in its tick host. We found that insertions into 46 genes resulted in a complete loss of recovery of mutants from larval Ixodes ticks. Insertions in an additional 56 genes resulted in a >90% decrease in fitness. The screen identified both previously known and new genes important for larval tick survival. Almost half of the genes required for survival in the tick encode proteins of unknown function, while a significant portion (over 20%) encode membrane-associated proteins or lipoproteins. We validated the results of the screen for five Tn mutants by performing individual competition assays using mutant and complemented strains. To better understand the role of one of these genes in tick survival, we conducted mechanistic studies of bb0017, a gene previously shown to be required for resistance against oxidative stress. In this study we show that BB0017 affects the regulation of key borrelial virulence determinants. The application of Tn-seq to in vivo screening of B. burgdorferi in its natural vector is a powerful tool that can be used to address many different aspects of the host pathogen interaction.