In vitro and in vivo activity of ceftazidime/avibactam and aztreonam alone or in combination against mcr-9, serine- and metallo-ß-lactamases-co-producing carbapenem-resistant Enterobacter cloacae complex.

PURPOSE: Enterobacteriaceae carrying mcr-9, in particularly those also co-containing metallo-ß-lactamase (MBL) and TEM type ß-lactamase, present potential transmission risks and lack adequate clinical response methods, thereby posing a major threat to global public health. The aim of this study was to assess the antimicrobial efficacy of a combined ceftazidime/avibactam (CZA) and aztreonam (ATM) regimen against carbapenem-resistant Enterobacter cloacae complex (CRECC) co-producing mcr-9, MBL and TEM. METHODS: The in vitro antibacterial activity of CZA plus ATM was evaluated using a time-kill curve assay. Furthermore, the in vivo interaction between CZA plus ATM was confirmed using a Galleria mellonella (G. mellonella) infection model. RESULTS: All eight clinical strains of CRECC, co-carrying mcr-9, MBL and TEM, exhibited high resistance to CZA and ATM. In vitro time-kill curve analysis demonstrated that the combination therapy of CZA + ATM exerted significant bactericidal activity against mcr-9, MBL and TEM-co-producing Enterobacter cloacae complex (ECC) isolates with a 100% synergy rate observed in our study. Furthermore, in vivo survival assay using Galleria mellonella larvae infected with CRECC strains co-harboring mcr-9, MBL and TEM revealed that the CZA + ATM combination significantly improved the survival rate compared to the drug-treatment alone and untreated control groups. CONCLUSION: To our knowledge, this study represents the first report on the in vitro and in vivo antibacterial activity of CZA plus ATM against CRECC isolates co-harboring mcr-9, MBL and TEM. Our findings suggest that the combination regimen of CZA + ATM provides a valuable reference for clinicians to address the increasingly complex antibiotic resistance situation observed in clinical microorganisms.

Robust Single-Supermolecule Switches Operating in Response to Two Different Noncovalent Interactions.

Supramolecular electronics provide an opportunity to introduce molecular assemblies into electronic devices through a combination of noncovalent interactions such as [π···π] and hydrogen-bonding interactions. The fidelity and dynamics of noncovalent interactions hold considerable promise when it comes to building devices with controllable and reproducible switching functions. Here, we demonstrate a strategy for building electronically robust switches by harnessing two different noncovalent interactions between a couple of pyridine derivatives. The single-supermolecule switch is turned ON when compressing the junction enabling [π···π] interactions to dominate the transport, while the switch is turned OFF by stretching the junction to form hydrogen-bonded dimers, leading to a dramatic decrease in conductance. The robustness and reproducibility of these single-supermolecule switches were achieved by modulating the junction with Ångström precision at frequencies of up to 190 Hz while obtaining high ON/OFF ratios of ∼600. The research presented herein opens up an avenue for designing robust bistable mechanoresponsive devices which will find applications in the building of integrated circuits for microelectromechanical systems.

Molecular characterization of metallo-ß-lactamase- producing carbapenem-resistant Enterobacter cloacae complex isolated in Heilongjiang Province of China.

BACKGROUND: Enterobacter cloacae complex (ECC) is one of the most common extended-spectrum ß-lactamase and carbapenemase-producing pathogen that threatens millions of the elderly and vulnerable sick persons. The objective of this study was to perform the molecular characteristics of the carbapenem-resistant E. cloacae complex (CREC) emerged in Heilongjiang Province of China. METHODS: Six CREC strains were isolated from the patients with infectious diseases. The identities of ECC isolates were confirmed by sequencing the polymerase chain reaction (PCR) products of 16S rRNA gene. The characterization of the CREC isolates were analyzed by sequencing PCR products of the carbapenemase, ampC and fluoroquinolone resistance genes and performing multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and whole genome sequencing. RESULTS: All 6 isolates harbored multiple resistance genes. Of them, 5 carried metallo-ß-lactamases and one was blaKPC-2-positive. The levofloxacin and ciprofloxacin-resistant strains had substitutions of gyrA83, gyrA87, and parC80 in the quinolone-resistance determining regions. The MLST analyses revealed that 6 isolates belonged to five sequence types (ST520, ST528, ST1119, ST1120, and ST93) while the PFGE patterns of the isolates fallen into four clusters. The strain ST1120 was found to carry two separated plasmids that encode blaNDM-1 and blaIMP-4. CONCLUSIONS: Our study, for the first time, identified a CREC strain that co-produces blaNDM-1 and blaIMP-4 in the Northeast China. Our finding emphasizes an urgent need for more intensive surveillance and precaution measures to prevent the CERC spread.

Molecular characterization and epidemiology of carbapenem non-susceptible Enterobacteriaceae isolated from the Eastern region of Heilongjiang Province, China.

BACKGROUND: The aim of this study was to elucidate the molecular epidemiology of carbapenem non-susceptible Enterobacteriaceae(CNSE) isolated in the Eastern region of Heilongjiang Province, China, and the mechanism of carbapenem resistance. METHODS: A total of 53 CNSE isolates were collected in a grade-3 hospital in Heilongjiang province. Sensitivity to antibiotics was determined using the VITEK-2 Compact automatic system. The modified Hodge test (MHT) and modified carbapenem inactivation test (mCIM) were performed for phenotypic identification. Beta-lactamases gene were detected by Polymerase chain reaction(PCR) and DNA sequencing. The transfer of blaNDM and blaKPC was investigated through conjugation experiment. The clinical data of patients were retrospectively reviewed. Homology of Carbapenem-resistant Klebsiella pneumoniae(CRKP) was conducted by multilocus sequence typing (MLST). RESULTS: CNSE were highly resistant to the majority of antimicrobial agents. The resistance rate was 100% for first, third, fourth generation cephalosporins and enzyme inhibitor compounds. Gentamicin and tobramycin recorded a resistance rate higher than 80%. Less than 30% resistance was detected for amikacin and levofloxacin. Among CNSE 52(98.1%) and 48(90.6%) of CNSE were positive for mCIM and MHT respectively. There were 42 positive blaKPC genes, three blaNDM-1 genes, three blaNDM-5 genes, one blaNDM-7 gene, and six blaIMP-4 genes. Most isolates harbored multiple drug resistance gene, especially as related to extended-spectrum-ß-lactamases, blaSHV, blaTEM and blaCTX-M-15 genes.The resistant gene was transferred into recipient Escherichia coli J53 through conjugation in 21.3% (10/47) of the strains. MLST revealed that ST76 (n = 36) was the most predominant clone, followed by ST896, ST323 and ST11. A new one ST 2946 was identity by this study. CONCLUSION: The carbapenem resistance phenomenon is alarming and blaKPC-2 is the main resistant gene of CNSE in our hospital. This is the first report of an outbreak caused by blaKPC-2 positive K. pneumoniae ST76 in the Eastern region of Heilongjiang Province, China. Relevant departments should implement infection control and prevention measures to avoid further dissemination of the multi drug-resistant bacteria (MDR).

Correlations of IFN-γ genetic polymorphisms with susceptibility to breast cancer: a meta-analysis.

The meta-analysis was conducted to evaluate the correlations between common genetic polymorphisms in the IFN-γ gene and susceptibility to breast cancer. The following electronic databases were searched without language restrictions: MEDLINE (1966 ~ 2013), the Cochrane Library Database (issue 12, 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), Web of Science (1945 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013). Meta-analysis was performed with the use of the STATA statistical software. Odds ratios (OR) with their 95 % confidence intervals (95 % CIs) were calculated. Nine clinical case-control studies met all the inclusion criteria and were included in this meta-analysis. A total of 1,182 breast cancer patients and 1,525 healthy controls were involved in this meta-analysis. Three functional polymorphisms were assessed, including rs2069705 C>T, rs2430561 T>A, and CA repeats 2/X. Our meta-analysis results indicated that IFN-γ genetic polymorphisms might be significantly associated with an increased risk of breast cancer (allele model: OR = 1.37, 95 % CI = 1.03 ~ 1.83, P = 0.031; dominant model: OR = 1.55, 95 % CI = 1.01 ~ 2.37, P = 0.046; homozygous model: OR = 2.23, 95 % CI = 1.30 ~ 3.82, P = 0.004; respectively), especially the rs2430561 T>A polymorphism. Subgroup analysis based on ethnicity suggested that genetic polymorphisms in the IFN-γ gene were closely correlated with increased breast cancer risk among Asians (allele model: OR = 1.21, 95 % CI = 1.02 ~ 1.58, P = 0.017; dominant model: OR = 3.44, 95 % CI = 2.07 ~ 5.71, P < 0.001; recessive model: OR = 1.58, 95 % CI = 1.06 ~ 2.37, P = 0.025; homozygous model: OR = 1.83, 95 % CI = 1.19 ~ 2.80, P = 0.006; respectively), but not among Caucasians (all P > 0.05). Our meta-analysis supported the hypothesis that IFN-γ genetic polymorphisms may contribute to an increased risk of breast cancer, especially the rs2430561 T>A polymorphism among Asians.

Patient-tailored scan delay for multiphase liver CT: improved scan quality and lesion conspicuity with a novel timing bolus method.

OBJECTIVE: The purpose of this study was to compare scan quality and lesion conspicuity for late arterial and portal venous phase liver CT scans using fixed versus patient-tailored scan delay derived with an evidence-based timing bolus method. MATERIALS AND METHODS: We retrospectively identified the cases of 73 patients who underwent both multiphase liver CT with fixed late arterial and portal venous phase scan delay times of 45 and 80 seconds and subsequent multiphase liver CT with patient-tailored scan delay determined with a timing bolus and a previously reported relation between the time to peak aortic and liver enhancement. Both late arterial and portal venous phase scans were graded in terms of scan quality. Hepatic lesion conspicuity (difference in attenuation between lesion and liver parenchyma) for hypervascular lesions (late arterial phase) and hypovascular lesions (portal venous phase) was recorded. RESULTS: Patient-tailored scan delay reflected a wide range of times to peak aortic enhancement (mean, 24 seconds; range, 18-32 seconds) and yielded a greater proportion of optimal scans compared with fixed scan delay for both late arterial phase (92% versus 74%, p < 0.01) and portal venous phase (86% versus 70%, p < 0.05) scans. Mean hypervascular lesion conspicuity was greater for lesions imaged with patient-tailored scan delay rather than fixed scan delay (84.0 versus 57.0 HU, p < 0.01). CONCLUSION: Compared with examinations with fixed scan delay, multiphase liver CT that incorporates patient-tailored scan delay produces more optimally timed late arterial and portal venous phase CT scans with greater lesion conspicuity.

Extravasated contrast material in penetrating abdominopelvic trauma: dual-contrast dual-energy CT for improved diagnosis--preliminary results in an animal model.

PURPOSE: To compare the diagnostic performance of dual-energy (DE) computed tomography (CT) with two simultaneously administered contrast agents (hereafter, dual contrast) with that of conventional CT in the evaluation of the presence and source of extravasation in penetrating abdominopelvic trauma. MATERIALS AND METHODS: Institutional animal care and use committee approval was obtained, and the study was performed in accordance with National Institutes of Health guidelines for the care and use of laboratory animals. Five rabbits with bowel trauma, vascular penetrating trauma, or both were imaged with simultaneous iodinated intravenous and bismuth subsalicylate enteric contrast material at DE CT. Four attending radiologists and six radiology residents without prior DE CT experience each evaluated 10 extraluminal collections to identify the vascular and/or enteric origin of extravasation and assess their level of diagnostic confidence, first with virtual monochromatic images simulating conventional CT and then with DE CT material decomposition attenuation maps. RESULTS: Overall accuracy of identification of source of extravasation increased from 78% with conventional CT to 92% with DE CT (157 of 200 diagnoses vs 184 of 200 diagnoses, respectively; P < .001). Nine radiologists were more accurate with DE CT; one had no change. Mean confidence increased from 67% to 81% with DE CT (P < .001). CONCLUSION: In a rabbit abdominopelvic trauma model, dual-contrast DE CT significantly increased accuracy and confidence in the diagnosis of vascular versus enteric extravasated contrast material.

Hepatic fibrosis: evaluation with semiquantitative contrast-enhanced CT.

PURPOSE: To evaluate the feasibility of using contrast material-enhanced computed tomographic (CT) measurements of hepatic fractional extracellular space (fECS) and macromolecular contrast material (MMCM) uptake to measure severity of liver fibrosis. MATERIALS AND METHODS: All procedures were approved by and executed in accordance with University of California, San Francisco, institutional animal care and use committee regulations. Twenty-one rats that received intragastric CCl(4) for 0-12 weeks were imaged with respiratory-gated micro-CT by using both a conventional contrast material and a novel iodinated MMCM. Histopathologic hepatic fibrosis was graded qualitatively by using the Ishak fibrosis score and quantitatively by using morphometry of the fibrosis area. Hepatic fECS and MMCM uptake were calculated for each examination and correlated with histopathologic findings by using uni- and multivariate linear regressions. RESULTS: Ishak fibrosis scores ranged from a baseline of 0 in untreated animals to a maximum of 5. Histopathologic liver fibrosis area increased from 0.46% to 3.5% over the same interval. Strong correlations were seen between conventional contrast-enhanced CT measurements of fECS and both the Ishak fibrosis scores (R(2) = 0.751, P < .001) and the fibrosis area (R(2) = 0.801, P < .001). Strong negative correlations were observed between uptake of MMCM in the liver and Ishak fibrosis scores (R(2) = 0.827, P < .001), as well as between uptake of MMCM in the liver and fibrosis area (R(2) = 0.643, P = .001). Multivariate linear regression analysis showed a trend toward independence for fECS and MMCM uptake in the prediction of Ishak fibrosis scores, with an R(2) value of 0.86 (P = .081 and P = .033, respectively). CONCLUSION: Contrast-enhanced CT measurements of fECS and MMCM uptake are individually capable of being used to estimate the degree of early hepatic fibrosis in a rat model. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112452/-/DC1.

Gut microbiota were altered with platelet count and red blood cell count in immune thrombocytopenia patients with different treatments.

The gut microbiome is clearly linked to the development of various autoimmune diseases, however, its association with immune thrombocytopenia (ITP) is less well understood. The current study collected 73 samples, including 36 from healthy individuals and 37 from ITP patients. The gut microbial community was assessed using 16s rRNA sequencing. Findings illustrated that the abundance of key microbiota was significantly higher in the ITP group. This group was further divided into three subgroups that received different treatments for ITP. A random forest model was used to predict the key microbiota and the identified bacteria were shown to easily distinguish between the healthy and the ITP treatment groups. Microbial function annotation and difference analysis showed that drug treatment changed the gut microbiota and may play a role in inducing host autoimmune responses by changing microbial metabolism pathways. Clinical indices also correlated negatively with changes in the microbiota after treatment. In summary, ITP patients who received drug treatment had significant differences in their microbiota along with a high abundance of bacteria. Thus, the microbiome could be used as a biomarker to distinguish between healthy and ITB groups. The key differential bacteria could help to regulate the number of platelets in ITP patients and provide a red blood cell overstock.

Exceptional green hydrogen production performance of a ruthenium-modulated nickel selenide.

Developing low-cost, high-efficiency and stable electrocatalysts for the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) is crucial but highly challenging. Density functional theory (DFT) calculations reveal that doping ruthenium (Ru) into catalysts can effectively optimize their electronic structure, hence leading to an optimal Gibbs free energy on the catalyst surface. Herein, an ultra-low Ru (about 2.34 wt%)-doped Ni3Se2 nanowire catalyst (i.e., Ru/Ni3Se2) supported on nickel foam has been fabricated by a hydrothermal reaction followed by a chemical etching process. The unique three-dimensional (3D) interconnected nanowires not only endow Ru and Ni3Se2 with uniform distribution and coupling, but also provide higher electrical conductivity, more active sites, an optimized electronic structure and favorable reaction kinetics. Therefore, the as-obtained Ru/Ni3Se2 catalyst exhibits excellent electrocatalytic performance, with low overpotentials of 24 and 211 mV to supply a current density value of 10 mA cm-2 towards the HER and OER in an alkaline environment, respectively. Notably, the as-fabricated Ru/Ni3Se2 catalyst only requires a low voltage of 1.476 V to derive a current density of 10 mA cm-2 in the constructed two-electrode alkaline electrolyzer and exhibits exceptionally high stability. This work will provide a novel strategy for the design and fabrication of low-cost and high-performance bifunctional electrocatalysts for hydrogen production by water electrolysis.

A label-free fiber ring laser biosensor for ultrahigh sensitivity detection of Salmonella Typhimurium.

The rapid detection of low concentrations of Salmonella Typhimurium (S. Typhimurium) is an essential preventive measure for food safety and prevention of foodborne illness. The study presented in this paper addresses this critical issue by proposing a single mode-tapered seven core-single mode (STSS) fiber ring laser (FRL) biosensor for S. Typhimurium detection. The experimental results show that the specific detection time of S. Typhimurium is less than 20 min and the wavelength shift can achieve -0.906 nm for an S. Typhimurium solution (10 cells/mL). Furthermore, at a lower concentration of 1 cell/mL applied to the biosensor, a result of -0.183 nm is observed in 9% of samples (1/11), which indicates that the proposed FRL biosensor has the ability to detect 1 cell/mL of S. Typhimurium. In addition, the detection results in chicken and pickled pork samples present an average deviation of -27% and -23%, respectively, from the measured results in phosphate buffered saline. Taken together, these results show the proposed FRL biosensor may have potential applications in the fields of food safety monitoring, medical diagnostics, etc.

Gadolinium accumulation and fibrosis in the liver after administration of gadoxetate disodium in a rat model of active hepatic fibrosis.

PURPOSE: To evaluate the effect of gadoxetate disodium on fibrosis in a rat model of active hepatic fibrosis. MATERIALS AND METHODS: The local committee for animal research approved this study. Hepatic fibrosis was induced during 12 weeks of intraperitoneal injection of carbon tetrachloride (CCl(4)). Gadoxetate disodium was administered at 10 mmol/kg for 5 consecutive days starting after the final dose of CCl(4) (clinical dose of gadoxetate disodium is 0.25 mmol/kg). Three groups of Sprague-Dawley rats were studied. Group 1 consisted of six rats treated only with gadoxetate disodium, group 2 consisted of nine rats treated only with CCl(4), and group 3 consisted of nine rats treated with both gadoxetate disodium and CCl(4). Seven days after the final injection of gadoxetate disodium, the rats were sacrificed, and histologic findings and gadolinium deposition in the liver were examined. Fibrosis stage and gadolinium deposition were compared by using the Mann-Whitney test and Student t test. RESULTS: Fibrosis grading in groups 2 and 3 did not differ significantly (mean Batts-Ludwig fibrosis stage in group 2 was 2.67 and in group 3 was 2.78, P = .70; mean Ishak fibrosis stage in group 2 was 3.89 and in group 3 was 4.11, P = .71). Gadolinium deposition in the liver was slightly increased in group 3 in comparison to group 1 (3.2 ppm versus 4.0 ppm, P = .01), although this reversed when corrected as a percentage of total injected dose (0.022% versus 0.017%, P = .003). CONCLUSION: The high-dose administration of gadoxetate disodium in the setting of active hepatic fibrosis was not associated with increased fibrosis, suggesting that gadoxetate disodium does not incite a nephrogenic systemic fibrosis-like fibrotic change in the setting of active hepatic inflammation.

In vivo differentiation of complementary contrast media at dual-energy CT.

PURPOSE: To evaluate the feasibility of using a commercially available clinical dual-energy computed tomographic (CT) scanner to differentiate the in vivo enhancement due to two simultaneously administered contrast media with complementary x-ray attenuation ratios. MATERIALS AND METHODS: Approval from the institutional animal care and use committee was obtained, and National Institutes of Health guidelines for the care and use of laboratory animals were observed. Dual-energy CT was performed in a set of iodine and tungsten solution phantoms and in a rabbit in which iodinated intravenous and bismuth subsalicylate oral contrast media were administered. In addition, a second rabbit was studied after intravenous administration of iodinated and tungsten cluster contrast media. Images were processed to produce virtual monochromatic images that simulated the appearance of conventional single-energy scans, as well as material decomposition images that separate the attenuation due to each contrast medium. RESULTS: Clear separation of each of the contrast media pairs was seen in the phantom and in both in vivo animal models. Separation of bowel lumen from vascular contrast medium allowed visualization of bowel wall enhancement that was obscured by intraluminal bowel contrast medium on conventional CT scans. Separation of two vascular contrast media in different vascular phases enabled acquisition of a perfectly coregistered CT angiogram and venous phase-enhanced CT scan simultaneously in a single examination. CONCLUSION: Commercially available clinical dual-energy CT scanners can help differentiate the enhancement of selected pairs of complementary contrast media in vivo.

Fringe projection profilometry based on a novel phase shift method.

Fringe projection profilometry is generally used to measure the 3D shape of an object. In oblique-angle projection, the grating fringe cycle is broadened on the reference surface. A well-fitted, convenient, and quick cycle correction method is proposed in this study. Based on the proposed method, an accurate four-step phase shift method is developed. Comparative experiments show that the fringe projection profilometry based on the novel phase shift method can eliminate cycle error and significantly improve measurement accuracy. The relative error of the measurement is less than 1.5%. This method can be widely employed for measuring large objects.

Clinical significance and prognostic value of C-reactive protein/albumin ratio in gastric cancer.

PURPOSE: This study was aimed to evaluate the clinical significance and prognostic value of CRP/albumin ratio (CAR) in patients with gastric cancer. METHODS: The data of 205 gastric cancer patients who underwent surgery was analyzed retrospectively. The association of CAR with the clinical features and prognostic value in gastric cancer was analyzed. The data of this study was combined with previous studies to further determine the prognostic value of CAR in patients with gastric cancer using a meta-analysis method. RESULTS: Cox analysis revealed that preoperative CAR was an independent prognosis indicator in patients with gastric cancer. High expression of CAR indicated a shorter survival time than in those with lower expression. CAR has a higher prognostic value in the 1-, 3-, and 5-year overall survival in patients with gastric cancer. CAR showed significant difference regarding the gastric cancer patients' age, M stage, and clinical stage. The discriminate value of CAR in M stage of gastric cancer was high (area under the curve, 0.809). A meta-analysis combining previous data and our data showed that preoperative CAR demonstrated a significant association with the overall survival of patients with gastric cancer. CONCLUSION: This study demonstrated that preoperative CAR could serve as an important prognostic indicator in patients with gastric cancer.

Visualization of renal medullary hyperattenuation at unenhanced CT: what is the effect of furosemide administration?

PURPOSE: To retrospectively investigate the effects of furosemide on the visualization of renal medullary hyperattenuation at unenhanced computed tomography (CT). MATERIALS AND METHODS: This retrospective single-institution study was HIPAA compliant and approved by the institutional review board; requirement for informed consent was waived. This study identified 289 consecutive patients (152 men, 137 women; mean age, 59 years) without ureteral obstruction who underwent unenhanced scanning as part of CT urography; of these, 178 patients did not receive intravenous furosemide prior to imaging and 111 did. The presence of renal medullary hyperattenuation, renal stones, and bladder urine attenuation levels were recorded and compared between patients who did not receive furosemide prior to imaging and those who did by using the chi(2) and unpaired Student t tests. A multiple logistic regression model was used to evaluate independent predictors of visualization of renal medullary hyperattenuation. RESULTS: Renal medullary hyperattenuation was seen less commonly in patients who received furosemide (27 of 111, 24%) than in those who did not receive furosemide prior to imaging (79 of 178, 44%, P = .001). Bladder urine attenuation was lower in patients who received furosemide (-0.1 HU) compared with those who did not (6.4 HU, P < .001). A multiple logistic regression model revealed independent associations between the visualization of renal medullary hyperattenuation and the absence of furosemide administration (P = .002), younger age (P < .001), and presence of renal stones (P = .047). CONCLUSION: Furosemide administration prior to unenhanced CT is associated with decreased visualization of renal medullary hyperattenuation.

Origin of nonequilibrium 1/f noise in solid-state nanopores.

Nanopore devices are applied in many fields such as molecular sensing and DNA sequencing, and the detection precision is primarily determined by 1/f noise. The mechanism of 1/f noise in nanopores is still not clearly understood, especially the nonequilibrium 1/f noise in rectifying nanopores. Hereby, we propose that 1/f noise in solid-state nanopores originates from the electrolyte ion trapping-detrapping process occurring on the inner surface of the nanopores, which can nonlinearly affect the ion number inside the rectifying nanopores due to the specific ion enrichment/depletion effect. Our model can not only quantitatively explain the nonlinear dependence of 1/f noise on the applied voltage, i.e., the nonequilibrium 1/f noise, for current rectifying nanopores, but also provide a unified explanation on the influence of the electrolyte concentration, pH value, and geometry of the nanopores. From our model, we observe a new flattening phenomenon of 1/f noise in conical nanopores, and this is further confirmed by our experimental results. Our research can be helpful in understanding and reducing 1/f noise in other nanopore devices, especially where the enrichment or depletion of ions exists.

Dehydration-Determined Ion Selectivity of Graphene Subnanopores.

Graphene membranes with subnanopores are considered to be the next-generation materials for water desalination and ion separation, while their performance is mainly determined by the relative ion selectivity of the pores. However, the origin of this phenomenon has been controversial in the past few years, which strongly limits the development of related applications. Here, using direct Au ion bombardment, we fabricated the desired subnanopores with average diameters of 0.8 ± 0.16 nm in monolayer graphene. The pores showed the ability to sieve K+, Na+, Li+, Cs+, Mg2+, and Ca2+ cations, and the observed K+/Mg2+ selectivity ratio was over 4. With further molecular dynamics simulations, we demonstrated that the ion selectivity is primarily attributed to the dehydration process of ions that can be quantitatively described by the ion-dependent free-energy barriers. Hopefully, this work is helpful in further enhancing the ion selectivity of graphene nanopores and also presenting a new paradigm for improving the performance of other nanoporous atomically thin membranes, such as MXenes and MoS2.

The efficacy of colistin monotherapy versus combination therapy with other antimicrobials against carbapenem-resistant Acinetobacter baumannii ST2 isolates.

This study aimed to investigate the efficacy of colistin both alone and in combination with either meropenem or levofloxacin against CRAB clinical isolates. The OXA carbapenemase genes and multilocus sequence typing were detected after 35 CRAB isolates biochemical identification. Then, the minimum inhibitory concentrations, minimum bactericidal concentrations, antibiotic interactions of the test antibiotics, and synergistic effects were determined by the checkerboard method and time-kill assays. The chromosomal gene bla OXA-51-like was detected in all isolates, and bla OXA-23-like and bla OXA-24-like were present in 91.4% and 25.7% of the isolates, respectively. The combination of colistin and meropenem displayed the highest rate of synergy (51.4%) against the 35 isolates, while the colistin-levofloxacin combination showed a higher rate of indifference interaction (22.9%) than that of the colistin-meropenem (8.6%) combination. The synergistic effect of colistin against the CRAB isolates was confirmed. The combination of colistin with meropenem is recommended against CRAB isolates.

The determination of gyrA and parC mutations and the prevalence of plasmid-mediated quinolone resistance genes in carbapenem resistant Klebsiella pneumonia ST11 and ST76 strains isolated from patients in Heilongjiang Province, China.

BACKGROUND: There is increasing resistance to carbapenems among Klebsiella pneumoniae,and fluoroquinolones (FQ) are increasingly used to treat infections from extended-spectrum ß- lactamase(ESBLs) and carbapenemase-producing Klebsiella pneumoniae. However, the acquisition of plasmid-mediated quinolone resistance (PMQR) or the spontaneous mutation of the quinolone resistance-determining regions (QRDR) of the gyrA and parC genes can severely affect the therapeutic effect of quinolones. The goal of this study was to investigate the molecular determinants of FQ resistance(FQ-R) in carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from Heilongjiang Province,China. MATERIALS AND METHODS: We isolated 40 strains of CRKP from a treatment center in the eastern part of Heilongjiang Province from January 2016 to December 2018. The VITEK2 Compact analyzer was used to identify and detect drug sensitivity. Different types of drug resistance genes were detected by polymerase chain reaction (PCR). PCR and DNA sequencing were used to assess the presence of qnrA, qnrB, qnrS,qepA and acc(6') Ib-cr genes,which are plasmid-encode genes that can contribute to resistance. The sequences of gyrA and parC genes were sequenced and compared with the sequences of standard strains to determine if mutations were present.Multi-site sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed on the strains to assess homology. RESULTS: The isolated CRKP strains showed rates of resistance to fluoroquinolones of 22.5% to 42.5%. The resistance rate of ciprofloxacin was significantly higher than that of levofloxacin.Nine CRKP strains (22.5%) showed co-resistance to ciprofloxacin and levofloxacin.The quinolone resistant strains were screened for plasmid-encoded genes that can contribute to resistance (PMQR genes).Among the 17 quinolone resistant strains,one strain contained no PMQR genes,twelve strains contained two PMQR genes,and four strains contained four PMQR genes.Acc (6') Ib-cr was the most frequently detected PMQR gene, detected in 95% of strains tested (38 of 40) and in 94.1% of the quinolone-resistant strains (16 of 17). The qepA gene encoding an efflux pump was not detected in any strains.No isolate carried five different PMQRs simultaneously.Changes of S83I and D87G changes in gyrA, and the S80I change in parC,which were mediated by QRDR,were identified in two isolates,which showed resistance to both ciprofloxacin and levofloxacin.Most of the FQ-R strains(58.8%,10/17) belong to ST(sequence type) 76, which is dominant in the local area, while all the mutant strains (100%,2/2),that differ in at least one site from standard bacteria, belong to the ST11 group. The strains were isolated from a hospital where there had been a recent outbreak of ST76 type CRKP in the neurosurgery ward and intensive care unit. CONCLUSION: CRKP strains were identified that were insensitive or even resistant to quinolones,and this resistance is common in Heilongjiang Province of eastern China;fluoroquinolone-resistance in these clinical CRKP strains is a complex interplay between PMQR determinants and mutations in gyrA and parC.The resistance level caused by QRDR mutation is higher than that caused by PMQR, however, the high frequency of PMQR genes in the isolated CRKP strains suggests the potential for impact of these genes.PMQR determinants are often found in carbapenemase-producing or ESBLs-producing Klebsiella pneumoniae,and some resistance genes,such as:SHV,TEM, CTX-M-15,and OXA-1 are closely associated with FQ-R. Finally, geographical factors can affect the emergence and spread of PMQR and QRDR.Some genetic lineages have higher potential risks, and continuous close monitoring is required.