Mitigating air pollution benefits multiple sustainable development goals in China.

Achieving the United nations 2030 Sustainable Development Goals (SDGs) remains a significant challenge, necessitating urgent and prioritized strategies. Among the various challenges, air pollution continues to pose one of the most substantial threats to the SDGs due to its widespread adverse effects on human health and ecosystems. However, the connections between air pollution and the SDGs have often been overlooked. This study reveals that out of the 169 SDG targets, 71 are adversely impacted by air pollution, while only 6 show potential positive effects. In China, two major atmospheric nitrogen pollutants, ammonia and nitrogen oxides, resulted in an economic loss of 400 billion United States Dollar (USD) in 2020, which could be reduced by 33% and 34% by 2030, respectively. It would enhance the progress towards SDGs in China by 14%, directly contributing to the achievement of SDGs 1 to 6 and 11 to 15. This improvement is estimated to yield overall benefits totaling 119 billion USD, exceeded the total implementation cost of 82 billion USD with ammonia as the preferential mitigation target. This study underscores the importance of robust scientific evidence in integrated policies aimed at aligning improvements in environmental quality with the priorities of sustainable development.

Cefotaxime Exposure Selects Mutations within the CA-Domain of envZ Which Promote Antibiotic Resistance but Repress Biofilm Formation in Salmonella.

Cephalosporins are important beta lactam antibiotics, but resistance can be mediated by various mechanisms including production of beta lactamase enzymes, changes in membrane permeability or active efflux. We used an evolution model to study how Salmonella adapts to subinhibitory concentrations of cefotaxime in planktonic and biofilm conditions and characterized the mechanisms underpinning this adaptation. We found that Salmonella rapidly adapts to subinhibitory concentrations of cefotaxime via selection of multiple mutations within the CA-domain region of EnvZ. We showed that changes in this domain affect the ATPase activity of the enzyme and in turn impact OmpC, OmpF porin expression and hence membrane permeability leading to increased tolerance to cefotaxime and low-level resistance to different classes of antibiotics. Adaptation to cefotaxime through EnvZ also resulted in a significant cost to biofilm formation due to downregulation of curli. We assessed the role of the mutations identified on the activity of EnvZ by genetic characterization, biochemistry and in silico analysis and confirmed that they are responsible for the observed phenotypes. We observed that sublethal cefotaxime exposure selected for heterogeneity in populations with only a subpopulation carrying mutations within EnvZ and being resistant to cefotaxime. Population structure and composition dynamically changed depending on the presence of the selection pressure, once selected, resistant subpopulations were maintained even in extended passage without drug. IMPORTANCE Understanding mechanisms of antibiotic resistance is crucial to guide how best to use antibiotics to minimize emergence of resistance. We used a laboratory evolution system to study how Salmonella responds to cefotaxime in both planktonic and biofilm conditions. In both contexts, we observed rapid selection of mutants within a single hot spot within envZ. The mutations selected altered EnvZ which in turn triggers changes in porin production at the outer membrane. Emergence of mutations within this region was repeatedly observed in parallel lineages in different conditions. We used a combination of genetics, biochemistry, phenotyping and structural analysis to understand the mechanisms. This data show that the changes we observe provide resistance to cefotaxime but come at a cost to biofilm formation and the fitness of mutants changes greatly depending on the presence or absence of a selective drug. Studying how resistance emerges can inform selective outcomes in the real world.

Novel aerosol treatment of airway hyper-reactivity and inflammation in a murine model of asthma with a soluble epoxide hydrolase inhibitor.

Asthma currently affects more than 339 million people worldwide. In the present preliminary study, we examined the efficacy of a new, inhalable soluble epoxide hydrolase inhibitor (sEHI), 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), to attenuate airway inflammation, mucin secretion, and hyper-responsiveness (AHR) in an ovalbumin (OVA)-sensitized murine model. Male BALB/c mice were divided into phosphate-buffered saline (PBS), OVA, and OVA+TPPU (2- or 6-h) exposure groups. On days 0 and 14, the mice were administered PBS or sensitized to OVA in PBS. From days 26-38, seven challenge exposures were performed with 30 min inhalation of filtered air or OVA alone. In the OVA+TPPU groups, a 2- or 6-h TPPU inhalation preceded each 30-min OVA exposure. On day 39, pulmonary function tests (PFTs) were performed, and biological samples were collected. Lung tissues were used to semi-quantitatively evaluate the severity of inflammation and airway constriction and the volume of stored intracellular mucosubstances. Bronchoalveolar lavage (BAL) and blood samples were used to analyze regulatory lipid mediator profiles. Significantly (p < 0.05) attenuated alveolar, bronchiolar, and pleural inflammation; airway resistance and constriction; mucosubstance volume; and inflammatory lipid mediator levels were observed with OVA+TPPU relative to OVA alone. Cumulative findings indicated TPPU inhalation effectively inhibited inflammation, suppressed AHR, and prevented mucosubstance accumulation in the murine asthmatic model. Future studies should determine the pharmacokinetics (i.e., absorption, distribution, metabolism, and excretion) and pharmacodynamics (i.e., concentration/dose responses) of inhaled TPPU to explore its potential as an asthma-preventative or -rescue treatment.

Short-term effects of different PM2.5 ranges on daily all-cause mortality in Jinan, China.

To examine the effects of different PM2.5 concentration ranges on daily all-cause mortality, 8768 all-cause deaths were recorded in the database of the Shandong Provincial Hospital Affiliated to Shandong First Medical University. Data of air pollutants (PM2.5 and O3) concentration were provided by the Jinan Environment Monitoring Center. The relative risk of all-cause mortality was assessed using a quasi-Poisson regression model after adjusting for confounding factors. The concentrations of PM2.5 were divided into four ranges 0-35 µg/m3; 35-75 µg/m3; 75-115 µg/m3; 115-150 µg/m3. There was no significant relationship between PM2.5 exposure and all-cause deaths in individuals aged < 60 years. However, for individuals aged ≥ 60 years, there was a significant positive association between exposure concentrations and all-cause deaths within the ranges 0-35 µg/m3, 35-75 µg/m3, and 115-150 µg/m3 with a mortality increase of 1.07 (1.01, 1.13), 1.03 (1.00, 1.05), and 1.05 (1.01, 1.08), respectively. When the population aged ≥ 60 years was stratified into gender groups, exposure to PM2.5 in the range 0-35 µg/m3 increased the mortality risk in men but not women. All-cause mortality in women, but not men, increased significantly with exposure to PM2.5 in the ranges of 35-75, 75-115, and 115-150 µg/m3.

Effects of life-stage and passive tobacco smoke exposure on pulmonary innate immunity and influenza infection in mice.

Limited data are available on the effects of perinatal environmental tobacco smoke (ETS) exposure for early childhood influenza infection. The aim of the present study was to examine whether perinatal versus adult ETS exposure might provoke more severe systemic and pulmonary innate immune responses in mice inoculated with influenza A/Puerto Rico/8/34 virus (IAV) compared to phosphate-buffered saline (PBS). BALB/c mice were exposed to filtered air (FA) or ETS for 6 weeks during the perinatal or adult period of life. Immediately following the final exposure, mice were intranasally inoculated with IAV or PBS. Significant inflammatory effects were observed in bronchoalveolar lavage fluid of neonates inoculated with IAV (FA+IAV or ETS+IAV) compared to PBS (ETS+PBS or FA+PBS), and in the lung parenchyma of neonates administered ETS+IAV versus FA+IAV. Type I and III interferons were also elevated in the spleens of neonates, but not adults with ETS+IAV versus FA+IAV exposure. Both IAV-inoculated neonate groups exhibited significantly more CD4 T cells and increasing numbers of CD8 and CD25 T cells in lungs relative to their adult counterparts. Taken together, these results suggest perinatal ETS exposure induces an exaggerated innate immune response, which may overwhelm protective anti-inflammatory defenses against IAV, and enhances severity of infection at early life stages (e.g., in infants and young children).

Elucidating the relationship between nutrition indices and coronary artery calcification in patients undergoing maintenance hemodialysis.

Cardiovascular diseases (CVD) are common in maintenance hemodialysis (MHD) patients, and vascular calcification is associated with the incidence of CVD. Malnourished MHD patients are particularly prone to CVD events. Thus far, there is no clear explanation for the relationship of nutrition status with vascular calcification; therefore, we investigated the relationship between malnutrition and vascular calcification. One hundred thirty-one patients underwent laboratory testing, assessment of vascular calcification, modified quantitative subjective global assessment (MQSGA), bioelectrical impedance analysis (BIA), and anthropometric measurements. The patients were divided into two groups based on the presence or absence of coronary artery calcification (CAC), and nutritional statuses were compared between the two groups. The MQSGA score was higher in the CAC group (mean 10.9 ± 1.81) than in the no-CAC group (mean 10.2 ± 1.51); in addition, the mean phase angle (PA) value was significantly lower in the CAC group than in the no-CAC group. Stratification according to CAC score showed that age, Kt/V, incidence of valve calcification, incidence of abdominal aortic calcification, MQSGA score, and blood cell mass were related to the severity of CAC. In addition, quartile analysis revealed that MQSGA score and PA value were related to the incidence and severity of vascular calcification. Binary regression analysis showed that MQSGA score, age, hemoglobin level, and high-density lipoprotein level were independent risk factors for dialysis-related CAC. Patients on MHD who exhibited malnutrition were more likely to have vascular calcification, especially CAC. Namely, the higher the MQSGA score, the lower the PA, and the more likely the occurrence of CAC.

Creation of Golden Gate constructs for gene doctoring.

BACKGROUND: Gene doctoring is an efficient recombination-based genetic engineering approach to mutagenesis of the bacterial chromosome that combines the λ-Red recombination system with a suicide donor plasmid that is cleaved in vivo to generate linear DNA fragments suitable for recombination. The use of a suicide donor plasmid makes Gene Doctoring more efficient than other recombineering technologies. However, generation of donor plasmids typically requires multiple cloning and screening steps. RESULTS: We constructed a simplified acceptor plasmid, called pDOC-GG, for the assembly of multiple DNA fragments precisely and simultaneously to form a donor plasmid using Golden Gate assembly. Successful constructs can easily be identified through blue-white screening. We demonstrated proof of principle by inserting a gene for green fluorescent protein into the chromosome of Escherichia coli. We also provided related genetic parts to assist in the construction of mutagenesis cassettes with a tetracycline-selectable marker. CONCLUSIONS: Our plasmid greatly simplifies the construction of Gene Doctoring donor plasmids and allows for the assembly of complex, multi-part insertion or deletion cassettes with a free choice of target sites and selection markers. The tools we developed are applicable to gene editing for a wide variety of purposes in Enterobacteriaceae and potentially in other diverse bacterial families.

Emergence of ciprofloxacin heteroresistance in foodborne Salmonella enterica serovar Agona.

BACKGROUND: Bacterial heteroresistance has been increasingly identified as an important phenomenon for many antibiotic/bacterium combinations. OBJECTIVES: To investigate ciprofloxacin heteroresistance in Salmonella and characterize mechanisms contributing to ciprofloxacin heteroresistance. METHODS: Ciprofloxacin-heteroresistant Salmonella were identified by population analysis profiling (PAP). Target mutations and the presence of PMQR genes were detected using PCR and sequencing. Expression of acrB, acrF and qnrS was conducted by quantitative RT-PCR. Competition ability and virulence were also compared using pyrosequencing, blue/white screening, adhesion and invasion assays and a Galleria model. Two subpopulations were whole-genome sequenced using Oxford Nanopore and Illumina platforms. RESULTS: PAP identified one Salmonella from food that yielded a subpopulation demonstrating heteroresistance to ciprofloxacin at a low frequency (10-9 to 10-7). WGS and PFGE analyses confirmed that the two subpopulations were isogenic, with six SNPs and two small deletions distinguishing the resistant from the susceptible. Both subpopulations possessed a T57S substitution in ParC and carried qnrS. The resistant subpopulation was distinguished by overexpression of acrB and acrF, a deletion within rsxC and altered expression of soxS. The resistant population had a competitive advantage against the parental population when grown in the presence of bile salts but was attenuated in the adhesion and invasion of human intestinal cells. CONCLUSIONS: We determined that heteroresistance resulted from a combination of mutations in fluoroquinolone target genes and overexpression of efflux pumps associated with a deletion in rsxC. This study warns that ciprofloxacin heteroresistance exists in Salmonella in the food chain and highlights the necessity for careful interpretation of antibiotic susceptibility.

Impact of genetic variants of ABCB1, APOB, CAV1, and NAMPT on susceptibility to pancreatic ductal adenocarcinoma in Chinese patients.

BACKGROUND: Among the different types of cancer, pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), is the most lethal malignancy, with poor early detection rates and prognosis. The aim of the present study was to investigate the potential genetic effects of the single-nucleotide polymorphisms (SNPs) in ABCB1 (rs1045642, rs3789243, rs4148737), APOB (rs693, rs1042031), CAV1 (rs12672038, rs1997623, rs3807987, rs7804372), and NAMPT (rs9034, rs2505568, rs61330082) on PDAC. METHODS: A total of 273 patients with PDAC and 263 healthy controls were genotyped using PCR and direct Sanger sequencing. Unconditional logistic regression models were used to evaluate the potential effects of the genotypes, alleles, and haplotypes on the risk of developing PDAC. RESULTS: Patients with PDAC possessed a considerably lower frequency of genotypes AG, GG, and allele G at ABCB1 rs4148737 compared with controls. Based on age, sex, smoking status, drinking status, diabetes, and family history of cancer, stratified analyses showed a significant correlation between SNPs at rs4148737 and PDAC. According to specific SNPs, eight haplotypes were constructed along with ABCB1 rs4148737, rs1045642, and rs3789243. Carriers with haplotypes ACC and ATC were more susceptible to developing PDAC, whereas haplotypes GCC and GTC were associated with a reduced likelihood of developing PDAC. The distributions of the other SNPs in each group were not significantly associated with PDAC risk. CONCLUSIONS: These results suggested that genetic polymorphisms of ABCB1 rs4148737 may influence an individual's risk of developing PDAC.

Comparison of the pharmacokinetics of tilmicosin in plasma and lung tissue in healthy chickens and chickens experimentally infected with Mycoplasma gallisepticum.

The objectives of this study were to compare the plasma and lung tissue pharmacokinetics of tilmicosin in healthy and Mycoplasma gallisepticum-infected chickens. Tilmicosin was orally administered at 4, 7.5 and 10 mg/kg body weight (b.w) for the infected and 7.5 mg/kg b.w for the uninfected control group. We found no significant differences in plasma tilmicosin pharmacokinetics between diseased and healthy control chickens. In contrast, the lung tissues in M. gallisepticum-infected chickens displayed a t1/2 (elimination half-life) 1.76 times longer than for healthy chickens. The Cmax (the maximum concentration of drug in samples) of tilmicosin in M. gallisepticum-infected chickens was lower than for controls at 7.5 mg/kg b.w (p < .05), and the AUCinf (the area under the concentration-time curve from time 0 extrapolated to infinity) in infected chickens was higher than for the healthy chickens (p < .05). The mean residence time of tilmicosin in infected chickens was also higher than the healthy chickens. These results indicated that the lungs of healthy chickens had greater absorption of tilmicosin than the infected chickens, and the rate of elimination of tilmicosin from infected lungs was slower.

An assessment of how distance and diesel oxidation catalyst will impact thermal decomposition behaviors of particles.

Decomposition mass loss and pyrolysis products analyses of particles sampled at various locations along the tailpipe of a Euro-IV diesel engine were performed using a thermogravimetry in conjunction with Fourier transformation infrared spectrometry-mass spectrum. Diesel particles were collected at the same location with and without diesel oxidation catalyst (DOC) mounted on the test engine separately. The three poles in thermal gravity-differential thermal gravity images suggested that the decomposition process of diesel particles could be divided into three stages which correspond to the decompositions of lower boiling substances, higher boiling substances and soot respectively. It is noticed that no matter whether DOC was mounted or not, the further the particles were sampled away from the engine block, the lower the peak temperatures and the heavier the mass losses within the first two stages, which indicated that the soluble organic fraction in the particle samples increased and therefore lowering the activation energy of thermal decomposition. Hydroxyl, ammonia, CxHy fragments, benzene, toluene, and phenol were found to be the primary products of particle decomposition, which didn't change with the location of particle sample point. The employment of DOC increased the activation energy for particle oxidation and resulted in a higher peak temperature and lower mass loss within the first-stage. Moreover, the CO stretching bands of aldehyde and ketone at 1771 cm-1 was only detected without a DOC, while the NO2 peak at 1634 cm-1 was solely noticed with the presence of DOC. Compared to the first-stage pyrolysis products, more polycyclic aromatic hydrocarbons and less CxHy fragments were seen in the second-stage.

The Emergence of Chromosomally Located bla CTX-M-55 in Salmonella From Foodborne Animals in China.

The emergence and increase in prevalence of resistance to cephalosporins amongst isolates of Salmonella from food animals imposes a public health threat. The aim of the present study was to investigate the prevalence and characteristics of CTX-M-producing Salmonella isolates from raw meat and food animals. 27 of 152 (17.76%) Salmonella isolates were ESBL-positive including 21/70 (30%) from food animals and 6/82 (7.32%) from raw meat. CTX-M-55 was the most prevalent ESBL type observed (12/27, 44.44%). 7 of 12 CTX-M-55-positive Salmonella isolates were Salmonella Indiana, 2 were Salmonella Typhimurium, 2 were Salmonella Chester, and the remaining isolate was not typeable. Eight CTX-M-55-positive Salmonella isolates were highly resistant to fluoroquinolones (MICCIP = 64 ug/mL) and co-harbored aac(6')-Ib-cr and oqxAB. Most of the CTX-M-55 positive isolates (11/12) carried bla CTX-M-55 genes on the chromosome, with the remaining isolate carrying this gene on a transferable 280 kb IncHI2 plasmid. A chromosomal bla CTX-M-55 gene from one isolate transferred onto a 250 kb IncHI2 plasmid which was subsequently conjugated into recipient strain J53. PFGE and MLST profiles showed a wide range of strain types were carrying bla CTX-M-55. Our study demonstrates the emergence and prevalence of foodborne Salmonella harboring a chromosomally located bla CTX-M-55 in China. The co-existence of PMQR genes with bla CTX-M-55 in Salmonella isolates suggests co-selection and dissemination of resistance to both fluoroquinolones and cephalosporins in Salmonella via the food chain in China represents a public health concern.

Relationship between danofloxacin PK/PD parameters and emergence and mechanism of resistance of Mycoplasma gallisepticum in In Vitro model.

Mycoplasma gallisepticum is a serious pathogen for poultry that causes chronic respiratory disease in chickens. Increased embryonic mortality, as well as reduced weight gain and egg production have been found in infected chickens, which can lead to considerable economic losses in poultry production. Increased antibiotic resistance compromises the use of tetracyclines, macrolides and quinolones in the farm environment. In the present study, danofloxacin concentrations were simulated below the MIC99, between the MIC99 and MPC (the mutant prevention concentration), and above the MPC in an in vitro dynamic model against M. gallisepticum. The relationship between the simulated danofloxacin pharmacokinetics, pharmacodynamics (PK/PD) parameters and development of resistance for M. gallisepticum was explored based on the available data obtained from various dosing regimens in the in vitro model. Danofloxacin concentration, counts of viable cell and susceptibility were determined during the experiment. The mutations in gyrA, gyrB, parC and parE as well as efflux pumps were examined. The MIC of danofloxacin against M. gallisepticum was increased when drug concentrations were between the lower and upper boundaries of the mutant selection window. The upper boundary of the selection window in vitro was estimated as a Cmax/MPC value of 1. The lower boundary was estimated as Cmax/MPC value of 0.05. Both in terms of the MIC and resistance frequency, M. gallisepticum resistance was developed when danofloxacin concentrations fell inside the mutant selection window (ratios of Cmax to MPC between 0.05 and 1). The single mutation in gyrA (Ser-83→Arg) was found in all mutants, while double mutations in gyrA and parC (Ala-64→Ser) were observed only in the mutant with the highest MIC. In addition, no change of susceptibility in the mutants was observed in the presence of reserpine and carbonyl cyanide 3-chlorophenylhydrazone (CCCP). This suggested that ATP-binding cassette superfamily (ABC transporter) and major facilitator superfamily (MFS transporter) did not play a role in danofloxacin efflux.

Upregulation of AcrEF in Quinolone Resistance Development in Escherichia coli When AcrAB-TolC Function Is Impaired.

We studied mechanisms of drug resistance development in Escherichia coli strains lacking efflux pump components. E. coli K12 deletion mutants were subjected to increasing concentrations of ciprofloxacin (CIP) to determine the frequency of target gene mutations. We generated a series of mutants that were selected based on their minimum inhibitory concentrations (MICs) to CIP, as well as their corresponding point mutations in target genes. The mutants displayed a number of target modifications and, in particular, gyrA mutations altering codons Ser83Leu, Asp87Gly, and Asp87His as well as a change in parC at 78 (substitution of Gly for Asp). All these mutations were related to drug resistance. When exposed to CIP, mutants lacking efflux pump genes acrA and acrB demonstrated a low level of resistance that was because of point mutations in the target genes. High-level resistance was achieved with a 100- to 500-fold increase in expression of efflux pump genes acrE and acrF that compensated for the loss of AcrA and AcrB, and thus resulted in an obvious increase of CIP MIC. We demonstrate that an intact AcrAB-TolC efflux pump is crucial to the development of bacterial resistance. Its activity is complemented by expression of the alternative AcrEF efflux pump.

Coordinated Expression of acrAB-tolC and Eight Other Functional Efflux Pumps Through Activating ramA and marA in Salmonella enterica serovar Typhimurium.

The aim of this study was to determine the expression of eight other functional transporter genes upon acrAB inactivation and also the expression of acrAB when the function of eight other transporters are impaired in Salmonella enterica. We used single- or multigene deletion mutants (i.e., ΔacrA, ΔacrB, ΔtolC, ΔacrAB, ΔacrEF, ΔacrD, ΔmdsABC, ΔmdtABC, ΔemrAB, ΔmacAB, ΔmdfA, ΔmdtK, ΔacrABramA, ΔacrABmarA, and ΔacrABsoxS) and real time (RT)-PCR to quantify the expression of different pump and regulator genes; infection ability was characterized by adhesion and invasion assays. The expression of acrAB operon was increased upon acrB inactivation. Single deletion of acrA or tolC also increased expression of acrB. The deletion of acrAB increased expression of eight other functional efflux pumps genes and vice versa, in which increased expression of ramA and marA was also detected. Mutants containing single deletions of functional pump genes were attenuated in cells. In conclusion, there is a feedback mechanism that coordinates regulation of AcrAB-TolC and eight other functional efflux pumps through the global transcriptional regulators ramA and marA in S. enterica serovar Typhimurium.

Resistance mechanisms and fitness of Salmonella Typhimurium and Salmonella Enteritidis mutants evolved under selection with ciprofloxacin in vitro.

The aim of this study was to investigate the difference in resistance mechanisms and fitness of Salmonella Typhimurium (ST) and Salmonella Enteritidis (SE) mutants selected during the evolution of resistance under exposure to increasing ciprofloxacin concentrations in vitro. Mutations in quinolone target genes were screened by PCR. Phenotypic characterization included susceptibility testing by the broth dilution method, investigation of efflux activity and growth rate, and determination of the invasion of human intestinal epithelium cells in vitro. The two Salmonella serotypes exhibited differences in target gene mutations and efflux pump gene expression during the development of resistance. In the parental strains, ST had a competitive advantage over SE. During the development of resistance, initially, the SE strain was more competitive. However, once ciprofloxacin resistance was acquired, ST once again became the more competitive strain. In the absence of bile salts or at 0.1% bile, the growth rate of SE was initially greater than that of ST, but once ciprofloxacin resistance was acquired, ST had higher growth rates. ST strains showed decreased invasion of epithelial cells in 0.1% bile. These data indicate that ciprofloxacin-resistant ST strains are more competitive than ciprofloxacin-resistant SE strains.

On-board measurement of particle numbers and their size distribution from a light-duty diesel vehicle: Influences of VSP and altitude.

In this study, the particle size-resolved distribution from a China-3 certificated light-duty diesel vehicle was measured by using a portable emission measurement system (PEMS). In order to examine the influences of vehicle specific power (VSP) and high-altitude operation, measurements were conducted at 8 constant speeds, which ranged from 10 to 80km/hr at 10km/hr intervals, and two different high altitudes, namely 2200 and 3200m. The results demonstrated that the numbers of particles in all size ranges decreased significantly as VSP increased when the test vehicle was running at lower speeds (<20km/hr), while at a moderate speed (between 30 and 60km/hr), the particle number was statistically insensitive to increase VSP. Under high-speed cruising conditions, the numbers of ultrafine particles and PM2.5 were insensitive to changes in VSP, but the numbers of nanoparticles and PM10 surged considerably. An increase in the operational altitude of the test vehicle resulted in increased particle number emissions at low and high driving speeds; however, particle numbers obtained at moderate speeds decreased as altitude rose. When the test vehicle was running at moderate speeds, particle numbers measured at the two altitudes were very close, except for comparatively higher number concentrations of nanoparticles measured at 2200m.

In Vitro Development of Ciprofloxacin Resistance of Salmonella enterica Serovars Typhimurium, Enteritidis, and Indiana Isolates from Food Animals.

Difference in the development of resistance may be associated with the epidemiological spread and drug resistance of different Salmonella enterica serovar strains. In the present study, three susceptible S. enterica serovars, Typhimurium (ST), Enteritidis (SE), and Indiana (SI) strains, were subjected to stepwise selection with increasing ciprofloxacin concentrations. The results indicated that the mutation frequencies of the SI group were 101-104 higher and developed resistance to ciprofloxacin more rapidly compared with the ST and SE groups. Ciprofloxacin accumulation in the SI strain was also higher than the other two strains in the presence of an efflux pump inhibitor. The development of ciprofloxacin resistance was quite different among the three serovar strains. In SI, increasing AcrAB-TolC efflux pump expression and single or double mutations in gyrA with or without a single parC mutation (T57S) were found in the development of ciprofloxacin resistance. In SE, an increase in the AcrAB-TolC efflux pump regulatory gene ramA gradually decreased as resistant bacteria developed; then resistance resulted from gyrA D87G and gyrB E466D mutations and/or in other active efflux pumps besides AcrAB-TolC. For ST, ramA expression increased rapidly along with gyrA D87 N and/or gyrB S464F mutations. In conclusion, persistent use of ciprofloxacin may aggravate the resistance of different S. enterica serovars and prudent use of the fluoroquinolones is needed. The quicker resistance and higher mutation frequency of the SI isolates present a potential public health threat.

Quantitative assessment of the association between Fas/FasL gene polymorphism and susceptibility to esophageal carcinoma in a north Chinese population.

The case-control study aims to investigate the association of Fas and FasL genetic polymorphisms (Fas-670A/G (rs1800682), Fas-1377G/A (rs2234767) and FasL-844T/C (rs763110)) with esophageal carcinoma susceptibility in a north Chinese population. A total of 204 patients with esophageal carcinoma and 248 healthy controls were enrolled from Henan, China and genotyped by the polymerase chain reaction and restriction fragment length polymorphism method. There were no significant differences in distributions of their genotypes frequencies between patients and controls in Fas-670A/G, Fas-1377G/A and FasL-844T/C polymorphisms (P > 0.05). Stratified analysis showed that no significant association was found between esophageal carcinoma and gene polymorphisms of Fas-670 A/G, Fas-1377G/A, and FasL-844T/C (P > 0.05). Genetic polymorphisms in the death pathway genes Fas and FasL were not associated with risk of developing esophageal carcinoma in a north Chinese population.

Genetic polymorphisms of NAMPT related with susceptibility to esophageal squamous cell carcinoma.

BACKGROUND: Nicotinamide phosphoribosyl transferase (Nampt) plays a crucial role in tumorigenesis. The present study examines whether genetic polymorphisms of NAMPT are related to the risk of developing esophageal squamous cell carcinoma (ESCC). METHODS: A total of 810 subjects were enrolled in this study, including 405 ESCC patients and 405 healthy controls. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), genotypes at rs61330082, rs2505568 and rs9034 of NAMPT were identified. Haplotypes were constructed using PHASE software. Multivariate logistic regression models were used to evaluate the potentiating effects of the genotypes, alleles and haplotypes on the development of ESCC. RESULTS: The presence of genotypes CT and TT and allele T at rs61330082 was less frequent in ESCC cases than in controls (48.89% vs. 53.33%, P < 0.01, 95% CI: 0.33-0.68; 18.52% vs. 30.37%, P < 0.01, 95% CI: 0.22-0.50; 42.96% vs. 57.04%, P < 0.01, 95% CI: 0.38-0.61; respectively). No statistically significant differences existed in the distributions of genotypes or alleles at rs2505568 or rs9034 between ESCC cases and controls. Of five haplotypes constructed, haplotypes CTC, CTT and CAC were higher in ESCC cases (P < 0.01, OR = 1.57, 95% CI: 1.16-2.12; P = 0.04, OR = 1.72, 95% CI: 1.03-2.85; P < 0.01, OR = 3.39, 95% CI: 1.99-5.75; respectively) than in controls. CONCLUSION: Genetic polymorphisms of NAMPT, specifically genotype CC and allele C at rs61330082 as well as haplotypes CTC, CTT and CAC, were significantly correlated with ESCC susceptibility.