Background:Despite improvements in objective response rates to cisplatin-based combination chemotherapy,the majority of advanced ovarian cancer remains suboptimal,resulting in poor survival.it has been found that non-...Background:Despite improvements in objective response rates to cisplatin-based combination chemotherapy,the majority of advanced ovarian cancer remains suboptimal,resulting in poor survival.it has been found that non-coding RNAs(ncRNAs)not only participate in the transmission of signals between various cells but also participate in tumor immunity and anti-tumor immune responses,thereby regulating tumor occurrence and development.However,the function and detailed mechanism of ultraconserved RNA(ucRNA)in ovarian cancer chemoresistance is still unclear.Methods:Western blotting assay,Quantitative real-time PCR analysis(qPCR),and Kaplan-Meier Plotter analysis were performed to analyze the expression and prognosis of uc.243 in ovarian carcinoma.Cytotoxicity assay and Annexin V assay were performed to analyze the function of uc.243 in cisplatin resistance in ovarian cancer cells.RNA pull-down and qPCR experiments were performed to explore the molecular mechanism of uc.243 enhancing cisplatin resistance in ovarian cancer cells.Results:Herein,we found that uc.243 was remarkably upregulated and correlated with patient survival in chemoresistance ovarian cancer patients compared with chemo-sensitive ovarian cancer.Functional experiment displayed that uc.243 induced cisplatin resistance on ovarian cancer cells by facilitating the efflux of cisplatin(CDDP);but inhibiting the expression of uc.243 significantly reverses this function.Mechanistically,uc.243 can inhibit the binding of RNA binding protein DGCR8 microprocessor complex subunit to pri-miR-155,thereby inhibiting the cleavage of pri-miR-155 and decrease in mature miR-155,subsequently upregulates the expression of ATP binding cassette subfamily B member(ABCB1,ABCC2).Conclusion:Our research findings indicate that uc.243 can induce chemotherapy resistance in ovarian cancer,suggesting that it may become a new prognostic biomarker for malignant ovarian cancer.展开更多
The upsurge of multiple drug resistance(MDR)bacteria substantially diminishes the effectiveness of antibiotic arsenal and therefore intensifies the rate of therapeutic failure.The major factor in MDR is efflux pump-me...The upsurge of multiple drug resistance(MDR)bacteria substantially diminishes the effectiveness of antibiotic arsenal and therefore intensifies the rate of therapeutic failure.The major factor in MDR is efflux pump-mediated resistance.A unique pump can make bacteria withstand a wide range of structurally diverse compounds.Therefore,their inhibition is a promising route to eliminate resistance phenomenon in bacteria.Phytochemicals are excellent alternatives as resistance-modifying agents.They can directly kill bacteria or interact with the crucial events of pathogenicity,thereby decreasing the ability of bacteria to develop resistance.Numerous botanicals display noteworthy efflux pumps inhibitory activities.Edible plants are of growing interest.Likewise,some plant families would be excellent sources of efflux pump inhibitors(EPIs)including Apocynaceae,Berberidaceae,Convolvulaceae,Cucurbitaceae,Fabaceae,Lamiaceae,and Zingiberaceae.Easily applicable methods for screening plant-derived EPIs include checkerboard synergy test,berberine uptake assay and ethidium bromide test.In silico highthroughput virtual detection can be evaluated as a criterion of excluding compounds with efflux substrate-like characteristics,thereby improving the selection process and extending the identification of EPIs.To ascertain the efflux activity inhibition,real-time PCR and quantitative mass spectrometry can be applied.This review emphasizes on efflux pumps and their roles in transmitting bacterial resistance and an update plant-derived EPIs and strategies for identification.展开更多
AIM:To evaluate the effect of efflux pump inhibitors (EPIs) on multidrug resistance of Helicobacter pylori (H. pylori).METHODS: H. pylori strains were isolated and cultured on Brucella agar plates with 10% sheep's...AIM:To evaluate the effect of efflux pump inhibitors (EPIs) on multidrug resistance of Helicobacter pylori (H. pylori).METHODS: H. pylori strains were isolated and cultured on Brucella agar plates with 10% sheep's blood. The multidrug resistant (MDR) H. pylori were obtained with the inducer chloramphenicol by repeated doubling of the concentration until no colony was seen, then the susceptibilities of the MDR strains and their parents to 9 antibiotics were assessed with agar dilution tests. The present study included periods before and after the advent of the EPIs, carbonyl cyanide m-chlorophenyl hydrazone (CCCP), reserpine and pantoprazole), and the minimum inhibitory concentrations (MICs) were determined accordingly. In the same way, the effects of 5 proton pump inhibitors (PPIs), used in treatment of H. pylori infection, on MICs of antibiotics were evaluated.RESULTS: Four strains of MDR H. pylori were induced successfully, and the antibiotic susceptibilities of MDR strains were partly restored by CCCP and pantoprazole, but there was little effect of reserpine. Rabeprazole was the most effective of the 5 PPIs which could decrease the MICs of antibiotics for MDR H. pylori significantly.CONCLUSION: In vitro, some EPIs can strengthen the activities of different antibiotics which are the putative substrates of the efflux pump system in H. pylori.展开更多
AIM: To determine whether efflux systems contribute to multidrug resistance of H pylori. METHODS: A chloramphenicol-induced multidrug resistance model of six susceptible H pylori strains (5 isolates and H pylori NCTC1...AIM: To determine whether efflux systems contribute to multidrug resistance of H pylori. METHODS: A chloramphenicol-induced multidrug resistance model of six susceptible H pylori strains (5 isolates and H pylori NCTC11637) was developed. Multidrug-resistant (MDR) strains were selected and the minimal inhibitory concentration (MIC) of eryth-romycin, metronidazole, penicillin G, tetracycline, and ciprofloxacin in multidrug resistant strains and their parent strains was determined by agar dilution tests. The level of mRNA expression of hefA was assessed by fluorescence real-time quantitative PCR. A H pylori LZ1026 knockout mutant (ΔH pylori LZ1026) for (puta-tive) efflux protein was constructed by inserting the kanamycin resistance cassette from pEGFP-N2 into hefA, and its susceptibility profiles to 10 antibiotics were evaluated. RESULTS: The MIC of six multidrug-resistant strains (including 5 clinical isolates and H pylori NCTC11637) increased signifi cantly (≥ 4-fold) compared with their parent strains. The expression level of hefA gene was significantly higher in the MDR strains than in their parent strains (P = 0.033). A H pylori LZ1026 mutant was successfully constructed and the ΔH pylori LZ1026 was more susceptible to four of the 10 antibiotics. All the 20 strains displayed transcripts for hefA that con-fi rmed the in vitro expression of these genes.CONCLUSION: The efflux pump gene hefA plays an important role in multidrug resistance of H pylori.展开更多
To evaluate the role of biofilm formation on the resistance of Helicobacter pylori (H. pylori) to commonly prescribed antibiotics, the expression rates of resistance genes in biofilm-forming and planktonic cells were ...To evaluate the role of biofilm formation on the resistance of Helicobacter pylori (H. pylori) to commonly prescribed antibiotics, the expression rates of resistance genes in biofilm-forming and planktonic cells were compared.METHODSA collection of 33 H. pylori isolates from children and adult patients with chronic infection were taken for the present study. The isolates were screened for biofilm formation ability, as well as for polymerase chain reaction (PCR) reaction with HP1165 and hp1165 efflux pump genes. Susceptibilities of the selected strains to antibiotic and differences between susceptibilities of planktonic and biofilm-forming cell populations were determined. Quantitative real-time PCR (qPCR) analysis was performed using 16S rRNA gene as a H. pylori-specific primer, and two efflux pumps-specific primers, hp1165 and hefA.RESULTSThe strains were resistant to amoxicillin, metronidazole, and erythromycin, except for one strain, but they were all susceptible to tetracycline. Minimum bactericidal concentrations of antibiotics in the biofilm-forming cells were significantly higher than those of planktonic cells. qPCR demonstrated that the expression of efflux pump genes was significantly higher in the biofilm-forming cells as compared to the planktonic ones.CONCLUSIONThe present work demonstrated an association between H. pylori biofilm formation and decreased susceptibility to all the antibiotics tested. This decreased susceptibility to antibiotics was associated with enhanced functional activity of two efflux pumps: hp1165 and hefA.展开更多
The objective of this study was to verify the supposition that efflux might be involved in the drug resistance of Riemerella anatipestifer isolates. Two broad-spectrum effiux pump inhibitors, carbonyl cyanide 3-chloro...The objective of this study was to verify the supposition that efflux might be involved in the drug resistance of Riemerella anatipestifer isolates. Two broad-spectrum effiux pump inhibitors, carbonyl cyanide 3-chlorophenylhydrazone （CCCP） and Phe-Arg-β-naphthylamide （PAL3N）, on the contribution of minimum inhibitory concentrations of amikacin, streptomycin, chloramphenicol, tetracycline, ceftdaxone, ceftazidime, nalidixic acid, levofloxacin, enrofloxacin, as well as ciprofloxacin against 69 clinical R. anatipestifer isolates were investigated. We first reported that the two efflux pump inhibitors could restore the antimicrobial susceptibility of R. anatipestiferisolates. It is suggested that active efflux system is possible to be linked with the development of resistance in R. anatipestifer isolates.展开更多
The barriers present in the interfaces between the blood and the central nervous system form a major hurdle for the pharmacological treatment of central nervous system injuries and diseases.The family of ATP-binding c...The barriers present in the interfaces between the blood and the central nervous system form a major hurdle for the pharmacological treatment of central nervous system injuries and diseases.The family of ATP-binding cassette(ABC)transporters has been widely studied regarding efflux of medications at blood-central nervous system barriers.These efflux transporters include P-glycoprotein(abcb1),‘breast cancer resistance protein'(abcg2)and the various‘multidrug resistance-associated proteins'(abccs).Understanding which efflux transporters are present at the blood-spinal cord,blood-cerebrospinal fluid and cerebrospinal fluid-spinal cord barriers is necessary to determine their involvement in limiting drug transfer from blood to the spinal cord tissue.Recent developments in the blood-brain barrier field have shown that barrier systems are dynamic and the profile of barrier defenses can alter due to conditions such as age,disease and environmental challenge.This means that a true understanding of ABC efflux transporter expression and localization should not be one static value but instead a range that represents the complex patient subpopulations that exist.In the present review,the blood-central nervous system barrier literature is discussed with a focus on the impact of ABC efflux transporters on:(i)protecting the spinal cord from adverse effects of systemically directed drugs,and(ii)limiting centrally directed drugs from accessing their active sites within the spinal cord.展开更多
Significant CO2 fluxes from snow-covered soils occur in cold biomes. However, little is known about winter soil respiration on the eastern Tibetan Plateau of China. We therefore measured winter soil CO2 fluxes and est...Significant CO2 fluxes from snow-covered soils occur in cold biomes. However, little is known about winter soil respiration on the eastern Tibetan Plateau of China. We therefore measured winter soil CO2 fluxes and estimated annual soil respiration in two contrasting coniferous forest ecosystems （a Picea asperata plantation and a natural forest）. Mean winter soil CO2 effluxes were 1.08 μmol m-2 s-1 in the plantation and 1.16 μmol m-2 s-1 in the natural forest. These values are higher than most reported winter soil CO2 efflux values for temperate or boreal forest ecosystems. Winter soil respiration rates were similar for our two forest ecosystems but mean soil CO2 efflux over the growing sea- son was higher in the natural forest than in the plantation. The estimated winter and annual soil effluxes for the natural forest were 176.3 and 1070.3 g m-2, respectively, based on the relationship between soil respiration and soil temperature, which were 17.2 and 9.7 % greater than their counterparts in the plantation. The contributions of winter soil respiration toannual soil efflux were 15.4 % tor the plantation and 16.5R for the natural forest and were statistically similar. Our results indicate that winter soil CO2 efflux from frozen soils in the alpine coniferous forest ecosystems of the eastern Tibetan Plateau was considerable and was an important component of annual soil respiration. Moreover, reforesta- tion （natural coniferous forests were deforested and refor- ested with P. asperata plantation） may reduce soil respiration by reducing soil carbon substrate availability and input.展开更多
Polar auxin transport plays a divergent role in plant growth and developmental processes including root and embryo development, vascular pattern formation and cell elongation. Recently isolated Arabidopsis pin gene fa...Polar auxin transport plays a divergent role in plant growth and developmental processes including root and embryo development, vascular pattern formation and cell elongation. Recently isolated Arabidopsis pin gene family was believed to encode a component of auxin efflux carrier (G(?)lweiler et al, 1998). Based on the Arabidopsis pin1 sequence we have isolated a Brassica juncea cDNA (designated Bjpin1), which encoded a 70-kDa putative auxin efflux carrier. Deduced BjPIN1 shared 65% identities at protein level with AtPINl and was highly homologous to other putative PIN proteins of Arabidopsis (with highest homology to AtPIN3). Hydrophobic analysis showed similar structures between BjPINl and AtPIN proteins. Presence of 6 exons (varying in size between 65 bp and 1229 bp) and 5 introns (sizes between 89 bp and 463 bp) in the genomic fragment was revealed by comparing the genomic and cDNA sequences. Northern blot analysis indicated that Bjpin1 was expressed in most of the tissues tested, with a relatively higher level of transcript in flowers and a lower level in root tissues. Promoter-reporter gene fusion studies further revealed the expression of Bjpin1 in the mature pollen grains, young seeds, root tip, leaf vascular tissue and trace bundle, stem epidermis, cortex and vascular cells. BjPINl was localized on the plasma membrane as demonstrated through fusion expression of green fluorescent protein (GFP). Auxin efflux carrier activity was elevated in transgenic Arabidopsis expressing BjPIN1.展开更多
Based on the sequence information of Arabidopsis PIN1, two cDNAs encoding PIN homologues fromBrassica juncea, Bjpin2 and Bjpin3, were isolated through cDNA library screening. Bjpin2 and Bjpin3encoded proteins containi...Based on the sequence information of Arabidopsis PIN1, two cDNAs encoding PIN homologues fromBrassica juncea, Bjpin2 and Bjpin3, were isolated through cDNA library screening. Bjpin2 and Bjpin3encoded proteins containing 640 and 635 amino acid residues, respectively, which shared 97.5% identities witheach other and were highly homologous to Arabidopsis PIN1, PIN2 and other putative PIN proteins. BjPIN2and BjPIN3 had similar structures as AtPIN proteins. Northern blot analysis indicated that Bjpin2 wasexpressed in stem, leaf and floral tissues, while Bjpin3 was expressed predominantly in stem and hypocotyls.Two promoter fragments of pin genes, Bjpin-X and Bjpin-Z, were isolated by 'genome walking' techniqueusing primers at 5'-end of pin cDNA. Promoter-gus fusion studies revealed the GUS activities driven byBjpin-X were at internal side of xylem and petal; while those driven by Bjpin-Z were detected at leaf vein,epidermal cell and cortex of stem, vascular tissues and anther. Results of the pin genes with differentexpression patterns in B. juncea suggested the presence of a gene family.展开更多
P1B-type heavy metal ATPases(HMAs)are transmembrane metal-transporting proteins that play a key role in metal homeostasis.We here reported the characterization of rice OsHMA6,a member of the P1B-type ATPase family.Phy...P1B-type heavy metal ATPases(HMAs)are transmembrane metal-transporting proteins that play a key role in metal homeostasis.We here reported the characterization of rice OsHMA6,a member of the P1B-type ATPase family.Phylogenetic tree analysis showed that OsHMA6 belonged to the Cu/Ag subgroup of the HMA family and had a close evolutionary relationship with OsHMA9.Amino acid sequence alignment showed 82.78%consistency between OsHMA6 and OsHMA9.OsHMA6 expressed in all organs at different growth stages,including spikelet,and abundant in leaf blades,however,OsHMA9 most strongly expressed in roots,but very low in spikelet.Excessive Cu^2+can up-regulate the expression of OsHMA6 and OsHMA9 in rice seedlings.The heterologous expression in yeast showed that OsHMA6 can significantly rescue the growth of yeast strain CM52 when supplied with 3 or 6 mmol/L Cu^2+.Compared with the empty vector pYES2,the Cu concentration in OsHMA6-pYES2 decreased by 23.4%and 30.3%under 3 or 6 mmol/L Cu2+,respectively.Subcellular localization revealed that OsHMA6 was located in the plasma membrane.These results suggested that OsHMA6,similar to OsHMA9,is likely a copper efflux protein located in the plasma membrane.展开更多
In order to investigate the role of the MexA-MexB-OprM efflux pump system in the pathogenesis of Pseudomonas aeruginosa(PA)-induced pulmonary infection,pulmonary infection models were established by intratracheal inje...In order to investigate the role of the MexA-MexB-OprM efflux pump system in the pathogenesis of Pseudomonas aeruginosa(PA)-induced pulmonary infection,pulmonary infection models were established by intratracheal injection of K767(wild type),nalB(MexA-MexB-OprM up-regulated mutant),and △m exB(knockout) strains,separately.All mice were treated with Meropenem(intraperitoneal injection,100 mg/kg body weight,twice every day),and strain-related pathology,bacteria count,cytokine level,myeloperoxidase(MPO,indicator of neutrophil recruitment) activity,and macrophage inflammatory protein-2(MIP-2) expression were evaluated at early(3rd day post-infection) and late(7th and 14th day post-infection) stages of infection.E-test showed that △mexB was more significantly sensitive to panipenan(ETP),meropenem(MP) and imipenem(IP) than K767 and nalB strains.There was no significant difference in sensitivity to cefepime(TM) among the three stains.In contrast to the K767 and nalB groups,the △ mexB group showed decreased bacteria burden over time and less extensive pathological change.Additionally,MPO activity and levels of inflammatory cytokines(IL-1b,IL-12,and TNF-α) were increased at the early stage(day 3) and decreased at the later stage(day 14).Serum MIP-2 expression level was steadily increased in all three groups from early to late stages,but significantly higher in △m exB group than in K767 and nalB groups(P<0.05).In conclusion,the MexA-MexB-OprM efflux pump system might play an important role in PA-induced chronic pulmonary infection.High expression of the MexA-MexB-OprM efflux pump could increase antibacterial resistance and promote infection.展开更多
Most soil respiration measurements are conducted during the growing season.In tundra and boreal forest ecosystems,cumulative,non-growing season soil CO2 fluxes are reported to be a significant component of these syst...Most soil respiration measurements are conducted during the growing season.In tundra and boreal forest ecosystems,cumulative,non-growing season soil CO2 fluxes are reported to be a significant component of these systems＇ annual carbon budgets.However,little information exists on soil CO2 efflux during the non-growing season from alpine ecosystems.Therefore,comparing measurements of soil respiration taken annually versus during the growing season will improve the accuracy of estimating ecosystem carbon budgets,as well as predicting the response of soil CO2 efflux to climate changes.In this study,we measured soil CO2 efflux and its spatial and temporal changes for different altitudes during the non-growing season in an alpine meadow located in the Qilian Mountains,Northwest China.Field experiments on the soil CO2 efflux of alpine meadow from the Qilian Mountains were conducted along an elevation gradient from October 2010 to April 2011.We measured the soil CO2 efflux,and analyzed the effects of soil water content and soil temperature on this measure.The results show that soil CO2 efflux gradually decreased along the elevation gradient during the non-growing season.The daily variation of soil CO2 efflux appeared as a single-peak curve.The soil CO2 efflux was low at night,with the lowest value occurring between 02：00-06：00.Then,values started to rise rapidly between 07：00-08：30,and then descend again between 16：00-18：30.The peak soil CO2 efflux appeared from 11：00 to 16：00.The soil CO2 efflux values gradually decreased from October to February of the next year and started to increase in March.Non-growing season Q10 （the multiplier to the respiration rate for a 10℃ increase in temperature） was increased with raising altitude and average Q10 of the Qilian Mountains was generally higher than the average growing season Q10 of the Heihe River Basin.Seasonally,non-growing season soil CO2 efflux was relatively high in October and early spring and low in the winter.The soil CO2 efflux was positively correlated with soil temperature and soil water content.Our results indicate that in alpine ecosystems,soil CO2 efflux continues throughout the non-growing season,and soil respiration is an important component of annual soil CO2 efflux.展开更多
Objective: To explore the characterization and frequency of antibiotic resistance related to membrane porin and efflux pump genes among Acinetobacter baumannii (A. baumannii) strains obtained from burn patients in Teh...Objective: To explore the characterization and frequency of antibiotic resistance related to membrane porin and efflux pump genes among Acinetobacter baumannii (A. baumannii) strains obtained from burn patients in Tehran, Iran. Methods: In this cross-sectional descriptive study, 100 strains of A. baumannii isolated from burn patients visiting teaching hospitals of Tehran were collected from January 2016 to November 2017. After A. baumannii strains were confirmed, antimicrobial susceptibility testing was done via Kirby-Bauer disc diffusion method according to the Clinical and Laboratory Standards Institute guidelines. PCR amplification was performed for detection of β-lactamase adeR, OprD, adeS genes among A. baumannii strains. Results: All isolates (100%) were resistant to ceftazidime, cefotaxime, cefepime, ciprofloxacin, and piperacillin, and most isolates indicated high resistance (95%-97%) to meropenem, imipenem, gentamicin, ceftriaxone, trimethoprim-sulfamethoxazole, piperacillin-tazobactam, amikacin, and tetracycline. The most effective antibiotic against A. baumannii isolates was colistin (97% sensitivity), followed by tigecycline. The frequency of OprD, adeS, and adeR genes were 98%, 91%, and 77%, respectively. Conclusions: This study shows that the majority of A. baumannii isolates are highly resistant to the antibiotics most commonly used in burn patients. Also, high distribution of OprD and adeRS genes may be responsible for the observed resistances among A. baumannii isolates that demonstrate the possible role of both efflux pumps in simultaneous of carbapenemase production during antibiotic resistance.展开更多
Spatial variation in soil surface CO2 efflux was measured in a stand of Populus euphratica in the Ejina Oasis of desert riparian forest in the extreme arid region in northwestern China from April 2007 through October ...Spatial variation in soil surface CO2 efflux was measured in a stand of Populus euphratica in the Ejina Oasis of desert riparian forest in the extreme arid region in northwestern China from April 2007 through October 2007.Measurements were taken with a gas-exchange analyzer linked to a soil-respiration chamber.The mean soil CO2 efflux in the stand was 2.71 μmol/(m2·s) during the growing season and 1.38 μmol/(m2·s) in the nongrowing season.The seasonal maximum (end of May through early June) andminimum (October) CO2 efflux were 3.38 and 0.69 μmol/(m2·s),respectively.The diurnal fluctuation of CO2 efflux was relatively small (< 20 percent),with theminimum appearing around 05:00 and the maximum around 15:00.Linear regression analysis showed soil-surface CO2 efflux to be most highly correlated with soil temperature (R2=0.435) and soil moisture (R2=0.213).When all variables were considered simultaneously,only soil temperature (R2=0.378),soil moisture (R2=0.147),and root volume density (R2=0.021) explained a significant amount of variance in soil surface CO2 efflux.Stand volumes were not correlated with soil CO2 efflux on our sites.展开更多
Background:Stem CO_(2) efflux(E_(S))plays a critical role in the carbon budget of forest ecosystems.Thinning is a core practice for sustainable management of plantations.It is therefore necessary and urgent to study t...Background:Stem CO_(2) efflux(E_(S))plays a critical role in the carbon budget of forest ecosystems.Thinning is a core practice for sustainable management of plantations.It is therefore necessary and urgent to study the effect and mechanism of thinning intensity(TI)on E_(S).Methods:In this study,five TIs were applied in Larix principis-rupprechtii Mayr 21-,25-,and 41-year-old stands in North China in 2010.Portable infrared gas analyzer(Li-8100 A)was used to measure ES and its association with environmental factors at monthly intervals from May to October in 2013 to 2015.In addition,nutrients,wood structure and nonstructural carbon(NSC)data were measured in August 2016.Results:The results show that ES increased with increasing TI.The maximum ES values occurred at a TI of 35%(3.29,4.57 and 2.98μmol·m^(-2)·s^(-1))and were 1.54-,1.94-and 2.89-fold greater than the minimum E_(S) value in the CK stands(2.14,2.35 and 1.03μmol·m^(-2)·s^(-1))in July for the 21-,25-and 41-year-old forests,respectively.The E_(S) of the trees in low-density stands was more sensitive to temperature than that of the trees in high-density stands.Soluble sugars(SS)and temperature are the main factors affecting ES.When the stand density is low enough as 41-year-old L.principis-rupprechtii forests with TI 35%,bark thickness(BT)and humidity should be considered in addition to air temperature(T_(a)),wood temperature(T_(w)),sapwood width(SW),nitrogen concentration(N)and SS in the evaluation of ES.If a change in stand density is ignored,the CO_(2) released from individual 21-,25-and 41-year-old trees could be underestimated by 168.89%,101.94% and 200.49%,respectively.CO_(2) release was estimated based on the stem equation in combination with the factors influencing ES for reference.Conclusions:We suggest that it is not sufficient to conventional models which quantify ES only by temperature and that incorporating the associated drivers(e.g.density,SS,SW and N)based on stand density into conventional models can improve the accuracy of ES estimates.展开更多
The reverse cholesterol transport pathway (RCT) is the focus of many cholesterol-lowering therapies. By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and ...The reverse cholesterol transport pathway (RCT) is the focus of many cholesterol-lowering therapies. By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and gastrointestinal tract for excretion from the body. For a long time this removal via the hepatobiliary secretion was considered to be the sole route involved in the RCT. However, observations from early studies in animals and humans already pointed towards the possibility of another route. In the last few years it has become evident that a nonbiliary cholesterol secretion pathway exists in which the intestine plays a central role. This transintestinal cholesterol efflux (TICE) pathway contributes significantly to the total fecal neutral sterol excretion. Moreover, recent studies have shown that TICE is also sensitive to stimulation. As a consequence, the direct role of cholesterol secretion from blood via TICE makes the intestine a suitable and approachable target for cholesterol removal from the body and possibly reduction of atherosclerosis. In this review, the discovery and recent findings contributing to understanding the mechanism of TICE will be discussed.展开更多
Acinetobacter baumannii has greatly increased its degree of resistance to become multidrug resistant (MDR) over the past 30 years and is on the red line of the most widely replicated bacteria according to World Health...Acinetobacter baumannii has greatly increased its degree of resistance to become multidrug resistant (MDR) over the past 30 years and is on the red line of the most widely replicated bacteria according to World Health Organization (WHO). The efflux pumps are the main cause for the increasing antibiotic resistance of A. baumannii originated from nosocomial infection. The progressive resistance of A. baumannii even on the recent drugs (tigecycline and fosfomycin) reduces to very effective antibiotic scale. With attention focused on MDR and pan-drug-resistant (PDR) in A. baumannii multiple works on efflux pumps chemical inhibitor (NMP, PAβN, omeprazole, verapamil, reserpine, CCCP) are still in progress. Certain inhibitors from plants (Biricodar and timcodar, Falvone, Mahonia, Dalea versicolor, Lycopus europaeus, and Rosmarinus officinalis) have the capability to have such compounds according to their very significant synergistic effect with antibiotics. In this review we focused on the growth of antibiotic resistance to explain the mechanism of efflux pumps into these different super families and a comprehensive understanding of the extrusion, regulation and physiology role of drug efflux pumps in the essential development of anti-resistivity drugs. We recapitulated the evolution of the work carried out in these fields during the last years and in the course of elaboration, with the aim of increasing the chances of decreasing bacterial resistivity to antibiotics.展开更多
Objective:To evaluate the inhibitory activity of ferulic acid and four of its esterified derivatives(methyl,ethyl,propyl,and butyl)against resistance mechanisms in Staphylococcus aureus strains.Methods:Ferulic acid de...Objective:To evaluate the inhibitory activity of ferulic acid and four of its esterified derivatives(methyl,ethyl,propyl,and butyl)against resistance mechanisms in Staphylococcus aureus strains.Methods:Ferulic acid derivatives were obtained by esterification with methanol,ethanol,propanol,and butanol,and then characterized by hydrogen and carbon-13 nuclear magnetic resonance analysis.The minimum inhibitory concentrations(MIC)of ferulic acid and its esterified derivatives,ethidium bromide,and norfloxacin were obtained using the microdilution test,while the efflux pump inhibition test was conducted by examining reduction in the MICs of norfloxacin and ethidium bromide.Molecular docking was also carried out using the Schrodinger Suite 2015 molecular modeling software.A three-dimensional model of NorA efflux pump was generated using I-TASSER.The best scoring model was used as a receptor for ligand-receptor docking.Results:The methyl and butyl ester derivatives did not demonstrate significant antimicrobial activity.However,a significant synergic effect was evidenced when norfloxacin was combined with the ethyl and propyl esterified derivatives.The docking study demonstrated favorable energy of interaction between ferulate derivatives and NorA,and amino acid residues TYR57,TYR58,and LEU255 were present commonly in stabilizing all complexes.The PCA analysis corroborated the docking hypothesis that the lipophilic character and hydrogen bond interactions were the most relevant characteristics involved with NorA inhibitors.The pharmacokinetic parameters of ferulic acid derivatives showed good ADMET properties,demonstrating that they can be easily absorbed and have no effect or inhibit the cytochrome P450 enzyme complex,revealing their potential as drug candidates.Conclusions:This study provides strong evidence that the molecular basis for this activity is potentially due to the NorA efflux pump.展开更多
Silvicultural practices applied in managed forest plantations may help counteract the effects of climate change by influencing soil surface CO_(2)efflux(Fs).Understanding the effects of silvicultural practices on Fs w...Silvicultural practices applied in managed forest plantations may help counteract the effects of climate change by influencing soil surface CO_(2)efflux(Fs).Understanding the effects of silvicultural practices on Fs will provide unbiased estimates of carbon fluxes and allow better silvicultural decisions for carbon sequestration.Therefore,we assessed how Fs differed seasonally across silvicultural practices(i.e.,stocking levels,clone,fertilization and weed control treatments)and evaluated the effects of soil temperature(Ts)and soil volumetric water content(θv)on Fs across these practices for a mid-rotation(14 year-old)Pinus radiata plantation in the Canterbury region of New Zealand.There were significant differences in Fs(p<0.05)over the four seasons,three levels of stocking,and five clones.The effects of fertilization and weed control applied 12 years previously on Fs were insignificant.Annual estimate of Fs(mean±1 standard deviation)from the study site was 22.7±7.1 t ha^(-1)a^(-1)in the form of CO_(2)(6.2±2.1 t ha^(-1)a^(-1)in the form of C).Fs values were consistently higher in plots with 1250 stems ha^(-1)compared to 2500 stems ha^(-1),which may be related to a strong soil resource limitation because of the close spacing in the latter plantation.Significant differences in Fs across clones suggest that variations in carbon partitioning might explain their growth performance.Silvicultural treatments influenced Fs response to soil temperature(p<0.05),resulting in models explaining 28-49%of the total variance in Fs.These findings provide insights into how silvicultural management decisions may impact Fs in mid-rotation radiata pine plantations,contributing towards developing more precise and unbiased plantation carbon budgets.展开更多
文摘Background:Despite improvements in objective response rates to cisplatin-based combination chemotherapy,the majority of advanced ovarian cancer remains suboptimal,resulting in poor survival.it has been found that non-coding RNAs(ncRNAs)not only participate in the transmission of signals between various cells but also participate in tumor immunity and anti-tumor immune responses,thereby regulating tumor occurrence and development.However,the function and detailed mechanism of ultraconserved RNA(ucRNA)in ovarian cancer chemoresistance is still unclear.Methods:Western blotting assay,Quantitative real-time PCR analysis(qPCR),and Kaplan-Meier Plotter analysis were performed to analyze the expression and prognosis of uc.243 in ovarian carcinoma.Cytotoxicity assay and Annexin V assay were performed to analyze the function of uc.243 in cisplatin resistance in ovarian cancer cells.RNA pull-down and qPCR experiments were performed to explore the molecular mechanism of uc.243 enhancing cisplatin resistance in ovarian cancer cells.Results:Herein,we found that uc.243 was remarkably upregulated and correlated with patient survival in chemoresistance ovarian cancer patients compared with chemo-sensitive ovarian cancer.Functional experiment displayed that uc.243 induced cisplatin resistance on ovarian cancer cells by facilitating the efflux of cisplatin(CDDP);but inhibiting the expression of uc.243 significantly reverses this function.Mechanistically,uc.243 can inhibit the binding of RNA binding protein DGCR8 microprocessor complex subunit to pri-miR-155,thereby inhibiting the cleavage of pri-miR-155 and decrease in mature miR-155,subsequently upregulates the expression of ATP binding cassette subfamily B member(ABCB1,ABCC2).Conclusion:Our research findings indicate that uc.243 can induce chemotherapy resistance in ovarian cancer,suggesting that it may become a new prognostic biomarker for malignant ovarian cancer.
基金We are grateful to Chinese Academy of Sciences(CAS)for jointly supports(project No.2018PB0089 to AJS and project No.2019VBA0026 to SDS)under CAS President’s International Fellowship Initiative(CAS-PIFI)projectsthe Major Project for Special Technology Innovation of Hubei Province(Grant No.2017AHB054 to MG).
文摘The upsurge of multiple drug resistance(MDR)bacteria substantially diminishes the effectiveness of antibiotic arsenal and therefore intensifies the rate of therapeutic failure.The major factor in MDR is efflux pump-mediated resistance.A unique pump can make bacteria withstand a wide range of structurally diverse compounds.Therefore,their inhibition is a promising route to eliminate resistance phenomenon in bacteria.Phytochemicals are excellent alternatives as resistance-modifying agents.They can directly kill bacteria or interact with the crucial events of pathogenicity,thereby decreasing the ability of bacteria to develop resistance.Numerous botanicals display noteworthy efflux pumps inhibitory activities.Edible plants are of growing interest.Likewise,some plant families would be excellent sources of efflux pump inhibitors(EPIs)including Apocynaceae,Berberidaceae,Convolvulaceae,Cucurbitaceae,Fabaceae,Lamiaceae,and Zingiberaceae.Easily applicable methods for screening plant-derived EPIs include checkerboard synergy test,berberine uptake assay and ethidium bromide test.In silico highthroughput virtual detection can be evaluated as a criterion of excluding compounds with efflux substrate-like characteristics,thereby improving the selection process and extending the identification of EPIs.To ascertain the efflux activity inhibition,real-time PCR and quantitative mass spectrometry can be applied.This review emphasizes on efflux pumps and their roles in transmitting bacterial resistance and an update plant-derived EPIs and strategies for identification.
基金Supported by Henan Distinguished Junior Scholar Grant,No.074100510017
文摘AIM:To evaluate the effect of efflux pump inhibitors (EPIs) on multidrug resistance of Helicobacter pylori (H. pylori).METHODS: H. pylori strains were isolated and cultured on Brucella agar plates with 10% sheep's blood. The multidrug resistant (MDR) H. pylori were obtained with the inducer chloramphenicol by repeated doubling of the concentration until no colony was seen, then the susceptibilities of the MDR strains and their parents to 9 antibiotics were assessed with agar dilution tests. The present study included periods before and after the advent of the EPIs, carbonyl cyanide m-chlorophenyl hydrazone (CCCP), reserpine and pantoprazole), and the minimum inhibitory concentrations (MICs) were determined accordingly. In the same way, the effects of 5 proton pump inhibitors (PPIs), used in treatment of H. pylori infection, on MICs of antibiotics were evaluated.RESULTS: Four strains of MDR H. pylori were induced successfully, and the antibiotic susceptibilities of MDR strains were partly restored by CCCP and pantoprazole, but there was little effect of reserpine. Rabeprazole was the most effective of the 5 PPIs which could decrease the MICs of antibiotics for MDR H. pylori significantly.CONCLUSION: In vitro, some EPIs can strengthen the activities of different antibiotics which are the putative substrates of the efflux pump system in H. pylori.
文摘AIM: To determine whether efflux systems contribute to multidrug resistance of H pylori. METHODS: A chloramphenicol-induced multidrug resistance model of six susceptible H pylori strains (5 isolates and H pylori NCTC11637) was developed. Multidrug-resistant (MDR) strains were selected and the minimal inhibitory concentration (MIC) of eryth-romycin, metronidazole, penicillin G, tetracycline, and ciprofloxacin in multidrug resistant strains and their parent strains was determined by agar dilution tests. The level of mRNA expression of hefA was assessed by fluorescence real-time quantitative PCR. A H pylori LZ1026 knockout mutant (ΔH pylori LZ1026) for (puta-tive) efflux protein was constructed by inserting the kanamycin resistance cassette from pEGFP-N2 into hefA, and its susceptibility profiles to 10 antibiotics were evaluated. RESULTS: The MIC of six multidrug-resistant strains (including 5 clinical isolates and H pylori NCTC11637) increased signifi cantly (≥ 4-fold) compared with their parent strains. The expression level of hefA gene was significantly higher in the MDR strains than in their parent strains (P = 0.033). A H pylori LZ1026 mutant was successfully constructed and the ΔH pylori LZ1026 was more susceptible to four of the 10 antibiotics. All the 20 strains displayed transcripts for hefA that con-fi rmed the in vitro expression of these genes.CONCLUSION: The efflux pump gene hefA plays an important role in multidrug resistance of H pylori.
文摘To evaluate the role of biofilm formation on the resistance of Helicobacter pylori (H. pylori) to commonly prescribed antibiotics, the expression rates of resistance genes in biofilm-forming and planktonic cells were compared.METHODSA collection of 33 H. pylori isolates from children and adult patients with chronic infection were taken for the present study. The isolates were screened for biofilm formation ability, as well as for polymerase chain reaction (PCR) reaction with HP1165 and hp1165 efflux pump genes. Susceptibilities of the selected strains to antibiotic and differences between susceptibilities of planktonic and biofilm-forming cell populations were determined. Quantitative real-time PCR (qPCR) analysis was performed using 16S rRNA gene as a H. pylori-specific primer, and two efflux pumps-specific primers, hp1165 and hefA.RESULTSThe strains were resistant to amoxicillin, metronidazole, and erythromycin, except for one strain, but they were all susceptible to tetracycline. Minimum bactericidal concentrations of antibiotics in the biofilm-forming cells were significantly higher than those of planktonic cells. qPCR demonstrated that the expression of efflux pump genes was significantly higher in the biofilm-forming cells as compared to the planktonic ones.CONCLUSIONThe present work demonstrated an association between H. pylori biofilm formation and decreased susceptibility to all the antibiotics tested. This decreased susceptibility to antibiotics was associated with enhanced functional activity of two efflux pumps: hp1165 and hefA.
基金supported by the Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China (IRT13063)the National Natural Science Foundation of China (31072169)
文摘The objective of this study was to verify the supposition that efflux might be involved in the drug resistance of Riemerella anatipestifer isolates. Two broad-spectrum effiux pump inhibitors, carbonyl cyanide 3-chlorophenylhydrazone （CCCP） and Phe-Arg-β-naphthylamide （PAL3N）, on the contribution of minimum inhibitory concentrations of amikacin, streptomycin, chloramphenicol, tetracycline, ceftdaxone, ceftazidime, nalidixic acid, levofloxacin, enrofloxacin, as well as ciprofloxacin against 69 clinical R. anatipestifer isolates were investigated. We first reported that the two efflux pump inhibitors could restore the antimicrobial susceptibility of R. anatipestiferisolates. It is suggested that active efflux system is possible to be linked with the development of resistance in R. anatipestifer isolates.
文摘The barriers present in the interfaces between the blood and the central nervous system form a major hurdle for the pharmacological treatment of central nervous system injuries and diseases.The family of ATP-binding cassette(ABC)transporters has been widely studied regarding efflux of medications at blood-central nervous system barriers.These efflux transporters include P-glycoprotein(abcb1),‘breast cancer resistance protein'(abcg2)and the various‘multidrug resistance-associated proteins'(abccs).Understanding which efflux transporters are present at the blood-spinal cord,blood-cerebrospinal fluid and cerebrospinal fluid-spinal cord barriers is necessary to determine their involvement in limiting drug transfer from blood to the spinal cord tissue.Recent developments in the blood-brain barrier field have shown that barrier systems are dynamic and the profile of barrier defenses can alter due to conditions such as age,disease and environmental challenge.This means that a true understanding of ABC efflux transporter expression and localization should not be one static value but instead a range that represents the complex patient subpopulations that exist.In the present review,the blood-central nervous system barrier literature is discussed with a focus on the impact of ABC efflux transporters on:(i)protecting the spinal cord from adverse effects of systemically directed drugs,and(ii)limiting centrally directed drugs from accessing their active sites within the spinal cord.
基金supported by the National Natural Science Foundation of China(31200474,31270552)the National Key Technologies R&D in China(2011BAC09B05)Postdoctoral Science Foundation of China(2013M540714 and 2014T70880)
文摘Significant CO2 fluxes from snow-covered soils occur in cold biomes. However, little is known about winter soil respiration on the eastern Tibetan Plateau of China. We therefore measured winter soil CO2 fluxes and estimated annual soil respiration in two contrasting coniferous forest ecosystems （a Picea asperata plantation and a natural forest）. Mean winter soil CO2 effluxes were 1.08 μmol m-2 s-1 in the plantation and 1.16 μmol m-2 s-1 in the natural forest. These values are higher than most reported winter soil CO2 efflux values for temperate or boreal forest ecosystems. Winter soil respiration rates were similar for our two forest ecosystems but mean soil CO2 efflux over the growing sea- son was higher in the natural forest than in the plantation. The estimated winter and annual soil effluxes for the natural forest were 176.3 and 1070.3 g m-2, respectively, based on the relationship between soil respiration and soil temperature, which were 17.2 and 9.7 % greater than their counterparts in the plantation. The contributions of winter soil respiration toannual soil efflux were 15.4 % tor the plantation and 16.5R for the natural forest and were statistically similar. Our results indicate that winter soil CO2 efflux from frozen soils in the alpine coniferous forest ecosystems of the eastern Tibetan Plateau was considerable and was an important component of annual soil respiration. Moreover, reforesta- tion （natural coniferous forests were deforested and refor- ested with P. asperata plantation） may reduce soil respiration by reducing soil carbon substrate availability and input.
基金Studies were supported by "the National NaturalScience Foundation of China, No. 30070073", StateKey Project of Basic Research, No. G199901l604"and "National Natural Science Foundation of Pan-Deng". We thank Dr. Charles Brearley and JianXu for hel
文摘Polar auxin transport plays a divergent role in plant growth and developmental processes including root and embryo development, vascular pattern formation and cell elongation. Recently isolated Arabidopsis pin gene family was believed to encode a component of auxin efflux carrier (G(?)lweiler et al, 1998). Based on the Arabidopsis pin1 sequence we have isolated a Brassica juncea cDNA (designated Bjpin1), which encoded a 70-kDa putative auxin efflux carrier. Deduced BjPIN1 shared 65% identities at protein level with AtPINl and was highly homologous to other putative PIN proteins of Arabidopsis (with highest homology to AtPIN3). Hydrophobic analysis showed similar structures between BjPINl and AtPIN proteins. Presence of 6 exons (varying in size between 65 bp and 1229 bp) and 5 introns (sizes between 89 bp and 463 bp) in the genomic fragment was revealed by comparing the genomic and cDNA sequences. Northern blot analysis indicated that Bjpin1 was expressed in most of the tissues tested, with a relatively higher level of transcript in flowers and a lower level in root tissues. Promoter-reporter gene fusion studies further revealed the expression of Bjpin1 in the mature pollen grains, young seeds, root tip, leaf vascular tissue and trace bundle, stem epidermis, cortex and vascular cells. BjPINl was localized on the plasma membrane as demonstrated through fusion expression of green fluorescent protein (GFP). Auxin efflux carrier activity was elevated in transgenic Arabidopsis expressing BjPIN1.
文摘Based on the sequence information of Arabidopsis PIN1, two cDNAs encoding PIN homologues fromBrassica juncea, Bjpin2 and Bjpin3, were isolated through cDNA library screening. Bjpin2 and Bjpin3encoded proteins containing 640 and 635 amino acid residues, respectively, which shared 97.5% identities witheach other and were highly homologous to Arabidopsis PIN1, PIN2 and other putative PIN proteins. BjPIN2and BjPIN3 had similar structures as AtPIN proteins. Northern blot analysis indicated that Bjpin2 wasexpressed in stem, leaf and floral tissues, while Bjpin3 was expressed predominantly in stem and hypocotyls.Two promoter fragments of pin genes, Bjpin-X and Bjpin-Z, were isolated by 'genome walking' techniqueusing primers at 5'-end of pin cDNA. Promoter-gus fusion studies revealed the GUS activities driven byBjpin-X were at internal side of xylem and petal; while those driven by Bjpin-Z were detected at leaf vein,epidermal cell and cortex of stem, vascular tissues and anther. Results of the pin genes with differentexpression patterns in B. juncea suggested the presence of a gene family.
基金the Agricultural Science and Technology Innovation Program Cooperation and Innovation Mission(Grant No.CAAS-XTCX2016001)Shenzhen Science and Technology Projects(Grant No.JSGG20160608160725473)+1 种基金China Postdoctoral Science Foundation(Grant No.2018M641558)Fundamental Research Funds for Science,Technology and Innovation Commission of Shenzhen Municipality(Grant No.JCYJ20160530191619099).
文摘P1B-type heavy metal ATPases(HMAs)are transmembrane metal-transporting proteins that play a key role in metal homeostasis.We here reported the characterization of rice OsHMA6,a member of the P1B-type ATPase family.Phylogenetic tree analysis showed that OsHMA6 belonged to the Cu/Ag subgroup of the HMA family and had a close evolutionary relationship with OsHMA9.Amino acid sequence alignment showed 82.78%consistency between OsHMA6 and OsHMA9.OsHMA6 expressed in all organs at different growth stages,including spikelet,and abundant in leaf blades,however,OsHMA9 most strongly expressed in roots,but very low in spikelet.Excessive Cu^2+can up-regulate the expression of OsHMA6 and OsHMA9 in rice seedlings.The heterologous expression in yeast showed that OsHMA6 can significantly rescue the growth of yeast strain CM52 when supplied with 3 or 6 mmol/L Cu^2+.Compared with the empty vector pYES2,the Cu concentration in OsHMA6-pYES2 decreased by 23.4%and 30.3%under 3 or 6 mmol/L Cu2+,respectively.Subcellular localization revealed that OsHMA6 was located in the plasma membrane.These results suggested that OsHMA6,similar to OsHMA9,is likely a copper efflux protein located in the plasma membrane.
基金supported by grants from the National Natural Science Foundation of China (No. 30873189)the Natural Science Foundation of Hubei Province,China (No.2008CDB165)
文摘In order to investigate the role of the MexA-MexB-OprM efflux pump system in the pathogenesis of Pseudomonas aeruginosa(PA)-induced pulmonary infection,pulmonary infection models were established by intratracheal injection of K767(wild type),nalB(MexA-MexB-OprM up-regulated mutant),and △m exB(knockout) strains,separately.All mice were treated with Meropenem(intraperitoneal injection,100 mg/kg body weight,twice every day),and strain-related pathology,bacteria count,cytokine level,myeloperoxidase(MPO,indicator of neutrophil recruitment) activity,and macrophage inflammatory protein-2(MIP-2) expression were evaluated at early(3rd day post-infection) and late(7th and 14th day post-infection) stages of infection.E-test showed that △mexB was more significantly sensitive to panipenan(ETP),meropenem(MP) and imipenem(IP) than K767 and nalB strains.There was no significant difference in sensitivity to cefepime(TM) among the three stains.In contrast to the K767 and nalB groups,the △ mexB group showed decreased bacteria burden over time and less extensive pathological change.Additionally,MPO activity and levels of inflammatory cytokines(IL-1b,IL-12,and TNF-α) were increased at the early stage(day 3) and decreased at the later stage(day 14).Serum MIP-2 expression level was steadily increased in all three groups from early to late stages,but significantly higher in △m exB group than in K767 and nalB groups(P<0.05).In conclusion,the MexA-MexB-OprM efflux pump system might play an important role in PA-induced chronic pulmonary infection.High expression of the MexA-MexB-OprM efflux pump could increase antibacterial resistance and promote infection.
基金funded by the National Natural Science Foundation of China(31270482,41101026,91025002)the Natural Science Foundation of Gansu Province(1107RJZA089)+1 种基金the West Light Foundation of the Chinese Academy of Sciencesthe National Key Technology R & D Program(2012BAC08B05)
文摘Most soil respiration measurements are conducted during the growing season.In tundra and boreal forest ecosystems,cumulative,non-growing season soil CO2 fluxes are reported to be a significant component of these systems＇ annual carbon budgets.However,little information exists on soil CO2 efflux during the non-growing season from alpine ecosystems.Therefore,comparing measurements of soil respiration taken annually versus during the growing season will improve the accuracy of estimating ecosystem carbon budgets,as well as predicting the response of soil CO2 efflux to climate changes.In this study,we measured soil CO2 efflux and its spatial and temporal changes for different altitudes during the non-growing season in an alpine meadow located in the Qilian Mountains,Northwest China.Field experiments on the soil CO2 efflux of alpine meadow from the Qilian Mountains were conducted along an elevation gradient from October 2010 to April 2011.We measured the soil CO2 efflux,and analyzed the effects of soil water content and soil temperature on this measure.The results show that soil CO2 efflux gradually decreased along the elevation gradient during the non-growing season.The daily variation of soil CO2 efflux appeared as a single-peak curve.The soil CO2 efflux was low at night,with the lowest value occurring between 02：00-06：00.Then,values started to rise rapidly between 07：00-08：30,and then descend again between 16：00-18：30.The peak soil CO2 efflux appeared from 11：00 to 16：00.The soil CO2 efflux values gradually decreased from October to February of the next year and started to increase in March.Non-growing season Q10 （the multiplier to the respiration rate for a 10℃ increase in temperature） was increased with raising altitude and average Q10 of the Qilian Mountains was generally higher than the average growing season Q10 of the Heihe River Basin.Seasonally,non-growing season soil CO2 efflux was relatively high in October and early spring and low in the winter.The soil CO2 efflux was positively correlated with soil temperature and soil water content.Our results indicate that in alpine ecosystems,soil CO2 efflux continues throughout the non-growing season,and soil respiration is an important component of annual soil CO2 efflux.
文摘Objective: To explore the characterization and frequency of antibiotic resistance related to membrane porin and efflux pump genes among Acinetobacter baumannii (A. baumannii) strains obtained from burn patients in Tehran, Iran. Methods: In this cross-sectional descriptive study, 100 strains of A. baumannii isolated from burn patients visiting teaching hospitals of Tehran were collected from January 2016 to November 2017. After A. baumannii strains were confirmed, antimicrobial susceptibility testing was done via Kirby-Bauer disc diffusion method according to the Clinical and Laboratory Standards Institute guidelines. PCR amplification was performed for detection of β-lactamase adeR, OprD, adeS genes among A. baumannii strains. Results: All isolates (100%) were resistant to ceftazidime, cefotaxime, cefepime, ciprofloxacin, and piperacillin, and most isolates indicated high resistance (95%-97%) to meropenem, imipenem, gentamicin, ceftriaxone, trimethoprim-sulfamethoxazole, piperacillin-tazobactam, amikacin, and tetracycline. The most effective antibiotic against A. baumannii isolates was colistin (97% sensitivity), followed by tigecycline. The frequency of OprD, adeS, and adeR genes were 98%, 91%, and 77%, respectively. Conclusions: This study shows that the majority of A. baumannii isolates are highly resistant to the antibiotics most commonly used in burn patients. Also, high distribution of OprD and adeRS genes may be responsible for the observed resistances among A. baumannii isolates that demonstrate the possible role of both efflux pumps in simultaneous of carbapenemase production during antibiotic resistance.
基金supported by National Natural Science Foundation of China (40801001,40671010,40701054)National Key Technologies R&D Program of China during the 11th Five-Year Plan Period (2007BAD46B01)
文摘Spatial variation in soil surface CO2 efflux was measured in a stand of Populus euphratica in the Ejina Oasis of desert riparian forest in the extreme arid region in northwestern China from April 2007 through October 2007.Measurements were taken with a gas-exchange analyzer linked to a soil-respiration chamber.The mean soil CO2 efflux in the stand was 2.71 μmol/(m2·s) during the growing season and 1.38 μmol/(m2·s) in the nongrowing season.The seasonal maximum (end of May through early June) andminimum (October) CO2 efflux were 3.38 and 0.69 μmol/(m2·s),respectively.The diurnal fluctuation of CO2 efflux was relatively small (< 20 percent),with theminimum appearing around 05:00 and the maximum around 15:00.Linear regression analysis showed soil-surface CO2 efflux to be most highly correlated with soil temperature (R2=0.435) and soil moisture (R2=0.213).When all variables were considered simultaneously,only soil temperature (R2=0.378),soil moisture (R2=0.147),and root volume density (R2=0.021) explained a significant amount of variance in soil surface CO2 efflux.Stand volumes were not correlated with soil CO2 efflux on our sites.
基金funding from National Natural Science Foundation of China(No.31870387),China Scholarship Council.
文摘Background:Stem CO_(2) efflux(E_(S))plays a critical role in the carbon budget of forest ecosystems.Thinning is a core practice for sustainable management of plantations.It is therefore necessary and urgent to study the effect and mechanism of thinning intensity(TI)on E_(S).Methods:In this study,five TIs were applied in Larix principis-rupprechtii Mayr 21-,25-,and 41-year-old stands in North China in 2010.Portable infrared gas analyzer(Li-8100 A)was used to measure ES and its association with environmental factors at monthly intervals from May to October in 2013 to 2015.In addition,nutrients,wood structure and nonstructural carbon(NSC)data were measured in August 2016.Results:The results show that ES increased with increasing TI.The maximum ES values occurred at a TI of 35%(3.29,4.57 and 2.98μmol·m^(-2)·s^(-1))and were 1.54-,1.94-and 2.89-fold greater than the minimum E_(S) value in the CK stands(2.14,2.35 and 1.03μmol·m^(-2)·s^(-1))in July for the 21-,25-and 41-year-old forests,respectively.The E_(S) of the trees in low-density stands was more sensitive to temperature than that of the trees in high-density stands.Soluble sugars(SS)and temperature are the main factors affecting ES.When the stand density is low enough as 41-year-old L.principis-rupprechtii forests with TI 35%,bark thickness(BT)and humidity should be considered in addition to air temperature(T_(a)),wood temperature(T_(w)),sapwood width(SW),nitrogen concentration(N)and SS in the evaluation of ES.If a change in stand density is ignored,the CO_(2) released from individual 21-,25-and 41-year-old trees could be underestimated by 168.89%,101.94% and 200.49%,respectively.CO_(2) release was estimated based on the stem equation in combination with the factors influencing ES for reference.Conclusions:We suggest that it is not sufficient to conventional models which quantify ES only by temperature and that incorporating the associated drivers(e.g.density,SS,SW and N)based on stand density into conventional models can improve the accuracy of ES estimates.
文摘The reverse cholesterol transport pathway (RCT) is the focus of many cholesterol-lowering therapies. By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and gastrointestinal tract for excretion from the body. For a long time this removal via the hepatobiliary secretion was considered to be the sole route involved in the RCT. However, observations from early studies in animals and humans already pointed towards the possibility of another route. In the last few years it has become evident that a nonbiliary cholesterol secretion pathway exists in which the intestine plays a central role. This transintestinal cholesterol efflux (TICE) pathway contributes significantly to the total fecal neutral sterol excretion. Moreover, recent studies have shown that TICE is also sensitive to stimulation. As a consequence, the direct role of cholesterol secretion from blood via TICE makes the intestine a suitable and approachable target for cholesterol removal from the body and possibly reduction of atherosclerosis. In this review, the discovery and recent findings contributing to understanding the mechanism of TICE will be discussed.
文摘Acinetobacter baumannii has greatly increased its degree of resistance to become multidrug resistant (MDR) over the past 30 years and is on the red line of the most widely replicated bacteria according to World Health Organization (WHO). The efflux pumps are the main cause for the increasing antibiotic resistance of A. baumannii originated from nosocomial infection. The progressive resistance of A. baumannii even on the recent drugs (tigecycline and fosfomycin) reduces to very effective antibiotic scale. With attention focused on MDR and pan-drug-resistant (PDR) in A. baumannii multiple works on efflux pumps chemical inhibitor (NMP, PAβN, omeprazole, verapamil, reserpine, CCCP) are still in progress. Certain inhibitors from plants (Biricodar and timcodar, Falvone, Mahonia, Dalea versicolor, Lycopus europaeus, and Rosmarinus officinalis) have the capability to have such compounds according to their very significant synergistic effect with antibiotics. In this review we focused on the growth of antibiotic resistance to explain the mechanism of efflux pumps into these different super families and a comprehensive understanding of the extrusion, regulation and physiology role of drug efflux pumps in the essential development of anti-resistivity drugs. We recapitulated the evolution of the work carried out in these fields during the last years and in the course of elaboration, with the aim of increasing the chances of decreasing bacterial resistivity to antibiotics.
文摘Objective:To evaluate the inhibitory activity of ferulic acid and four of its esterified derivatives(methyl,ethyl,propyl,and butyl)against resistance mechanisms in Staphylococcus aureus strains.Methods:Ferulic acid derivatives were obtained by esterification with methanol,ethanol,propanol,and butanol,and then characterized by hydrogen and carbon-13 nuclear magnetic resonance analysis.The minimum inhibitory concentrations(MIC)of ferulic acid and its esterified derivatives,ethidium bromide,and norfloxacin were obtained using the microdilution test,while the efflux pump inhibition test was conducted by examining reduction in the MICs of norfloxacin and ethidium bromide.Molecular docking was also carried out using the Schrodinger Suite 2015 molecular modeling software.A three-dimensional model of NorA efflux pump was generated using I-TASSER.The best scoring model was used as a receptor for ligand-receptor docking.Results:The methyl and butyl ester derivatives did not demonstrate significant antimicrobial activity.However,a significant synergic effect was evidenced when norfloxacin was combined with the ethyl and propyl esterified derivatives.The docking study demonstrated favorable energy of interaction between ferulate derivatives and NorA,and amino acid residues TYR57,TYR58,and LEU255 were present commonly in stabilizing all complexes.The PCA analysis corroborated the docking hypothesis that the lipophilic character and hydrogen bond interactions were the most relevant characteristics involved with NorA inhibitors.The pharmacokinetic parameters of ferulic acid derivatives showed good ADMET properties,demonstrating that they can be easily absorbed and have no effect or inhibit the cytochrome P450 enzyme complex,revealing their potential as drug candidates.Conclusions:This study provides strong evidence that the molecular basis for this activity is potentially due to the NorA efflux pump.
基金The work was supported by the NZ Ministry of Foreign Aff air and Trade(MFAT)’s NZAID Programme.
文摘Silvicultural practices applied in managed forest plantations may help counteract the effects of climate change by influencing soil surface CO_(2)efflux(Fs).Understanding the effects of silvicultural practices on Fs will provide unbiased estimates of carbon fluxes and allow better silvicultural decisions for carbon sequestration.Therefore,we assessed how Fs differed seasonally across silvicultural practices(i.e.,stocking levels,clone,fertilization and weed control treatments)and evaluated the effects of soil temperature(Ts)and soil volumetric water content(θv)on Fs across these practices for a mid-rotation(14 year-old)Pinus radiata plantation in the Canterbury region of New Zealand.There were significant differences in Fs(p<0.05)over the four seasons,three levels of stocking,and five clones.The effects of fertilization and weed control applied 12 years previously on Fs were insignificant.Annual estimate of Fs(mean±1 standard deviation)from the study site was 22.7±7.1 t ha^(-1)a^(-1)in the form of CO_(2)(6.2±2.1 t ha^(-1)a^(-1)in the form of C).Fs values were consistently higher in plots with 1250 stems ha^(-1)compared to 2500 stems ha^(-1),which may be related to a strong soil resource limitation because of the close spacing in the latter plantation.Significant differences in Fs across clones suggest that variations in carbon partitioning might explain their growth performance.Silvicultural treatments influenced Fs response to soil temperature(p<0.05),resulting in models explaining 28-49%of the total variance in Fs.These findings provide insights into how silvicultural management decisions may impact Fs in mid-rotation radiata pine plantations,contributing towards developing more precise and unbiased plantation carbon budgets.
