Terahertz spectroscopic detection of antifatigue illegal additives in health care product matrices.

Tadalafil is an illegal additive in antifatigue supplements. It is often misused in various plant dietary supplements (BDS), resulting in serious health risks. In this paper, terahertz spectroscopy combined with chemometrics is used to quantitatively analyze the content of tadalafil in nutritional and health products. The absorption coefficient spectrum of tadalafil in the range of 0.1-2.5 THz was obtained, and an obvious characteristic absorption peak appeared at 1.7 THz. To verify the accuracy of this characteristic absorption peak theoretically, tadalafil was simulated by density functional theory, and the calculated terahertz vibration spectrum matched well with the experimental spectrum. Then, the pure fatigue-based nutraceutical matrix and pure tadalafil were mixed in different proportions, and the terahertz absorption coefficient spectra of the mixtures were obtained. Finally, a quantitative analysis model of the tadalafil mixture was developed based on the support vector regression (SVR) algorithm, and the SVR model was optimized using particle swarm optimization (PSO) and genetic algorithm (GA), respectively. Compared with the SVR model, both PSO-SVR and GA-SVR enabled some improvement in their prediction accuracy, but the PSO-SVR model ran faster at 4.85 s, whereas the GA-SVR model had a higher prediction accuracy with a prediction set correlation coefficient (R P) of 0.9996 and a root mean square error (RMSEP) of 0.011. In summary, this study used terahertz time-domain spectroscopy for the identification and quantification of tadalafil in health product matrices. This study provides a new solution for the nondestructive detection of illegally added tadalafil in antifatigue health products, which is pivotal to the quality control of the health product industry.

Synergy of CO2-response and aggregation induced emission in a small molecule: renewable liquid and solid CO2 chemosensors with high sensitivity and visibility.

A tetraphenylethylene (TPE) derivative (N,N-dimethyl-N'-(4-(1,2,2-triphenylvinyl)phenyl)acetimidamide, TPE-amidine) was designed and synthesized, and used to prepare visible CO2 chemosensors, TPE-amidine-L (liquid) and TPE-amidine-S (solid). The hydrophilicity of TPE-amidine thoroughly changed because of the unique reversible reaction between the amidine group and CO2, which controlled the molecular aggregation extent in water by CO2. Combining with the well-known aggregate-induced emission effect, the highly selective CO2 chemosensor TPE-amidine-L was developed, which has the lowest CO2 detection limit of 24.6 ppm compared with other reported CO2 chemosensors, and can be regenerated within 10 s by adding triethylamine. With the aim of being safer and more convenient to use, a polyacrylamide hydrogel containing TPE-amidine was prepared as a renewable CO2 sensing "tape" (TPE-amidine-S). The flexibility, adhesivity, CO2 sensitivity and reversibility of the "tape" is systematically investigated, showing great potential for "on-site" and "real-time" CO2 detection in practical applications.

The phenotypic and molecular characteristics of antimicrobial resistance of Salmonella enterica subsp. enterica serovar Typhimurium in Henan Province, China.

BACKGROUND: Salmonella enterica subsp. enterica serovar Typhimurium infections continue to be a significant public health threat worldwide. The aim of this study was to investigate antibiotic resistance among 147 S. Typhimurium isolates collected from patients in Henan, China from 2006 to 2015. METHODS: 147 S. Typhimurium isolates were collected from March 2006 to November 2015 in Henan Province, China. Antimicrobial susceptibility testing was performed, and the resistant genes of ciprofloxacin, cephalosporins (ceftriaxone and cefoxitin) and azithromycin were detected and sequenced. Clonal relationships were assessed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). RESULTS: Of the 147 isolates, 91.1% were multidrug resistant (MDR), with 4.1% being resistant to all antibiotic classes tested. Of concern, 13 MDR isolates were co-resistant to the first-line treatments cephalosporins and ciprofloxacin, while three were also resistant to azithromycin. Seven PFGE patterns were identified among the 13 isolates. All of the isolates could be assigned to one of four main groups, with a similarity value of 89%. MLST assigned the 147 isolates into five STs, including two dominant STs (ST19 and ST34). Of the 43 ciprofloxacin-resistant isolates, 39 carried double gyrA mutations (Ser83Phe, Asp87Asn/Tyr/Gly) and a single parC (Ser80Arg) mutation, including 1 isolate with four mutations (gyrA: Ser83Phe, Asp87Gly; parC: Ser80Arg; parE: Ser458Pro). In addition, 12 isolates not only carried mutations in gyrA and parC but also had at least one plasmid-mediated quinolone resistance (PMQR) gene. Among the 32 cephalosporin-resistant isolates, the most common extended-spectrum ß-lactamase (ESBL) gene was blaOXA-1, followed by blaCTX-M, blaTEM-1, and blaCMY-2. Moreover, the mphA gene was identified in 5 of the 15 azithromycin-resistant isolates. Four MDR isolates contained ESBL and PMQR genes, and one of them also carried mphA in addition. CONCLUSION: The high level of antibiotic resistance observed in S. Typhimurium poses a great danger to public health, so continuous surveillance of changes in antibiotic resistance is necessary.

Transferable Plasmid-Borne mcr-1 in a Colistin-Resistant Shigella flexneri Isolate.

Since the initial discovery of mcr-1 in an Escherichia coli isolate from China, the gene has also been detected in Klebsiella pneumoniae and Salmonella enterica but is rarely reported in other Enterobacteriaceae Here, we report the isolation and identification of a Shigella flexneri strain harboring mcr-1 from stool samples in a pig farm in China from 2009. The MIC of colistin for the isolate is 4 µg/ml. Conjugation assays showed that the donor S. flexneri strain has functional and transferable colistin resistance. Sequencing revealed that mcr-1 was present on a putative composite transposon flanked by inverted repeats of ISApl1IMPORTANCE There are four species of Shigella, and Shigella flexneri is the most frequently isolated species in low- and middle-income countries (LMICs). In this study, we report a functional, transferable, plasmid-mediated mcr-1 gene in S. flexneri We have shown that mcr-1 is located on a novel composite transposon which is flanked by inverted repeats of ISApl1 The host strain is multidrug resistant, and this multidrug resistance is also transferable. The finding of a functional mcr-1 gene in S. flexneri, a human-associated Enterobacteriaceae family member, is a cause for concern as infections due to S. flexneri are the main Shigella infections in most low- and middle-income countries.

Microvalve controlled multi-functional microfluidic chip for divisional cell co-culture.

Pneumatic micro-valve controlled microfluidic chip provides precise fluidic control for cell manipulation. In this paper, a multi-functional microfluidic chip was designed for three separate experiments: 1. Different cell lines were dispensed and cultured; 2. Three transfected SH-SY5Y cells were introduced and treated with methyl-phenyl-pyridinium (MPP+) as drug delivery mode; 3. Specific protection and interaction were observed among cell co-culture after nerve damage. The outcomes revealed the potential and practicability of our entire multi-functional pneumatic chip system on different cell biology applications.

An Optical Algorithm for Relative Thickness of Each Monochrome Component in Multilayer Transparent Mixed Films.

A modification of the two-flux Kubelka-Munk (K-M) model was proposed to describe the energy conservation of scattered light in colored mixed material with a defined scattered photometric, which is applied for the relative quantity distribution of each colored monochrome component in mixed material. A series of systematical experiments demonstrated a higher consistency with the reference quantity distribution than the common Lambert-Beer (L-B) law. Its application in the fibrogram of each component for measuring the cotton fiber's length was demonstrated to be good, extending its applicability to white and dark colored blended fibers, the length of which is harder to measure using L-B law.

Development of high-resolution multidimensional native protein microfluidic chip electrophoresis fingerprinting and its application in the quick analysis of unknown microorganisms.

The unascertained, constant mutation and emergence of new types of microorganisms present significant challenges to their detection. Differing from the focus on the limited local 16S rRNA gene or protein markers, characteristic whole fingerprint technologies at the omic level are particularly suitable for unknown analytes since accurate knowledge about the constituents is not necessarily required. Herein, through a combination of several innovative strategies, including pure water isotachophoresis integrated (2 + 1)D electrophoresis, inversion-funnel peak stacking channel geometry and COMSOL computer-aided fluid simulation, high-resolution whole protein 2D native microfluidic chip electrophoresis was achieved within less than 1 min. The highest ever reported peak capacity for native 2D chip electrophoresis was obtained. Furthermore, taking Escherichia coli, Staphylococcus aureus, and Bacillus subtilis as model analytes without protein biomarker information, the feasibility of the identification and semiqualification of unknown microbes in pure or mixed samples was explored with the utilisation of original algorithms, including SIFT feature abstraction and a global information entropy combined support vector machine. As such, the multidisciplinary cooperation in the present study demonstrates monstrated promising prospects for microfluidic chip electropherogram fingerprint-based quick microorganism assays, biointeraction studies, and drug screenings, even if the analytes are not fully ascertained.

[Advances in microfluidic chip-based extracellular vesicle separation].

Extracellular vesicles (EVs) are hemispherical vesicles that have a lipid bilayer. Studies have shown that EVs have important biological functions. The amount, types, and compositional changes of proteins, lipids and ribonucleic acids are closely related to diseases. The separation and capture of EVs from the complicated body fluid samples is a prerequisite for medical research and liquid biopsy based on EVs. However, presently the majority of EVs separation and capture still use the traditional separation methods with low purity and low efficiency. Therefore, efficient and highly selective EVs separation method is in urgent need. To meet this challenge, advanced microfluidic chip technology, which has the advantages of miniaturization, integration, and automation, can be utilized. The development of EV separation technology combined with microfluidic chips has become the focus of research. This paper summarizes the latest research progress in this area.

Microfluidic chip coupled with optical biosensors for simultaneous detection of multiple analytes: A review.

This article reviews the recent advances in microfluidic-chip integrated optical biosensors for simultaneous detection of multiple analytes. In particular, the principles and recent progress in different kinds of multiplex optical biosensors and their biological application were reviewed comprehensively. Sensors based on multiplexed detection have absolute advantages in analysis throughput than single assay. The microfluidic chip, a type of micro-total analysis system (µTAS), provides an ideal platform for integration of high-throughput biosensors. Compared with electronic biosensors, benefitted from the technical development in Micro-Electro-Mechanical System, there have been greater advances in the fabrication of optical sensors and microfluidic chip, and then promoting microfluidic-chip integrated optical biosensors for simultaneous detection of multiple analytes.

Multifunctionalized Microscale Ultrasound Contrast Agents for Precise Theranostics of Malignant Tumors.

In ultrasonography, ultrasound contrast agents (UCAs) that possess high acoustic impedance mismatch with the bulk medium are frequently employed to highlight the borders between tissues by enhanced ultrasound scattering in a clinic. Typically, the most common UCA, microbubble, is generally close in size to a red blood cell (<∼10 µm). These microscale UCAs cannot be directly entrapped into the target cells but generate several orders of magnitude stronger echo signals than the nanoscale ones. And their large containment and high ultrasound responsiveness also greatly facilitate to perform combined treatments, e.g., drug delivery and other imaging techniques. So multifunctionalized microscale UCAs appear on this scene and keep growing toward a promising direction for precise theranostics. In this review, we systematically summarize the new advances in the principles and preparations of multifunctionalized microscale UCAs and their medical applications for malignant tumors.

Dominant serotype distribution and antimicrobial resistance profile of Shigella spp. in Xinjiang, China.

Shigella represents one of the major diarrhea-inducing pathogens threatening public health, but its prevalence and antimicrobial resistance profile in Xinjiang Uygur Autonomous region, China, remains unclear. We conducted comprehensive investigation of Shigella serotype distribution and antimicrobial resistance pattern in Xinjiang, identifying 458 Shigella isolates between 2008 to 2014. Shigella flexneri was identified as predominant species, and several S. flexneri serotypes were isolated, including atypical serotypes 1c, 2c, and 4s. Dominant S. flexneri serotypes were 2a, 1b, 2b, and Xv, different from those generally dominant in China. A hybrid serotype pattern was observed, which included the major Chinese serotypes (2a, Xv) and those predominant in Pakistan (1b, 2b). Shigella sonnei was shown to have a lower frequency compared with that generally observed in China, but an increasing trend of infections associated with this pathogen was observed. Furthermore, a high frequency of drug resistance and different Shigella antimicrobial resistance patterns were demonstrated as well, including very severe resistance phenotypes, such as multidrug resistance and resistance to frontline antibiotics. Seventy-five cephalosporin-resistant Shigella isolates were frequently identified with the resistance determinants that can undergo horizontal transfer, such as blaOXA, blaTEM, blaCTX-M, and integrons, facilitating the development of cephalosporin resistance among Shigella subtypes. Additionally, genetic analyses demonstrated that all 86 quinolone-resistant S. flexneri isolates possess 3-4 mutation sites in quinolone resistance-determining regions, primarily contributing to their resistance to quinolone. However, S. sonnei isolates were not shown to be quinolone resistant. Co-resistance to cephalosporins and quinolones was detected in 17 S. flexneri isolates, and these isolates were additionally multidrug resistant and carried ß-lactamase genes and quinolone-resistance determinants. As is demonstrated in this study, dominant serotypes of Shigella were distributed in unique trend with dangerous drug resistance patterns. Novel strategies are urgently required to prevent the development of drug resistance among diarrhea-inducing pathogens.

A Novel mcr-1 Variant Carried by an IncI2-Type Plasmid Identified From a Multidrug Resistant Enterotoxigenic Escherichia coli.

In this study, we discovered a novel mobilized colistin resistance (mcr-1) gene variant, named mcr-1.9, which was identified in a colistin-resistant enterotoxigenic Escherichia coli (ETEC) strain from a clinical diarrhea case. The mcr-1.9 gene differs from mcr-1 at position 1036 due to a single nucleotide polymorphism (G→A), which results in an aspartic acid residue being replaced by an asparagine residue (Asp346→Asn) in the MCR-1 protein sequence. Antimicrobial susceptibility testing showed that the mcr-1.9-harboring ETEC strain is resistant to colistin at a minimum inhibitory concentration of 4 µg/ml. Plasmid profiling and conjugation experiments also suggest that the mcr-1.9 variant can be successfully transferred into the E. coli strain J53, indicating that the gene is located on a transferable plasmid. Bioinformatics analysis of data obtained from genome sequencing indicates that the mcr-1.9 gene is located on a 64,005 bp plasmid which has been named pEC26. This plasmid was found to have high similarity to the mcr-1-bearing IncI2-type plasmids pWF-5-19C (99% identity and 99% coverage) and pmcr1-IncI2 (99% identity and 98% coverage). The mcr-1.9-harboring ETEC also shows multidrug resistance to nine classes of antibiotics, and contains several virulence and antimicrobial-resistance genes suggested by the genome sequence analysis. Our report is the first to identify a new mcr-1 variant in an ETEC isolated from a human fecal sample, raising concerns about the existence of more such variants in human intestinal flora. Therefore, we believe that an undertaking to identify new mcr-1 variants in the bacterial communities of human intestines is of utmost importance, and that measures need to be taken to control the spread of mcr-1 and its variants in human intestinal microflora.

Comparison of virtual unenhanced CT images of the abdomen under different iodine flow rates.

OBJECTIVE: To assess the effect of varying iodine flow rate (IFR) and iodine concentration on the quality of virtual unenhanced (VUE) images of the abdomen obtained with dual-energy CT. METHODS: 94 subjects underwent unenhanced and triphasic contrast-enhanced CT scan of the abdomen, including arterial phase, portal venous phase, and delayed phase using dual-energy CT. Patients were randomized into 4 groups with different IFRs or iodine concentrations. VUE images were generated at 70 keV. The CT values, image noise, SNR and CNR of aorta, portal vein, liver, liver lesion, pancreatic parenchyma, spleen, erector spinae, and retroperitoneal fat were recorded. Dose-length product and effective dose for an examination with and without plain phase scan were calculated to assess the potential dose savings. Two radiologists independently assessed subjective image quality using a five-point scale. The Kolmogorov-Smirnov test was used first to test for normal distribution. Where data conformed to a normal distribution, analysis of variance was used to compare mean HU values, image noise, SNRs and CNRs for the 4 image sets. Where data distribution was not normal, a nonparametric test (Kruskal-Wallis test followed by stepwise step-down comparisons) was used. The significance level for all tests was 0.01 (two-sided) to allow for type 2 errors due to multiple testing. RESULTS: The CT numbers (HU) of VUE images showed no significant differences between the 4 groups (p > 0.05) or between different phases within the same group (p > 0.05). VUE images had equal or higher SNR and CNR than true unenhanced images. VUE images received equal or lower subjective image quality scores than unenhanced images but were of acceptable quality for diagnostic use. Calculated dose-length product and estimated dose showed that the use of VUE images in place of unenhanced images would be associated with a dose saving of 25%. CONCLUSIONS: VUE images can replace conventional unenhanced images. VUE images are not affected by varying iodine flow rates and iodine concentrations, and diagnostic examinations could be acquired with a potential dose saving of 25%.

Development and validation of a preoperative prediction model for colorectal cancer T-staging based on MDCT images and clinical information.

OBJECTIVES: This study aimed to establish and evaluate the efficacy of a prediction model for colorectal cancer T-staging. RESULTS: T-staging was positively correlated with the level of carcinoembryonic antigen (CEA), expression of carbohydrate antigen 19-9 (CA19-9), wall deformity, blurred outer edges, fat infiltration, infiltration into the surrounding tissue, tumor size and wall thickness. Age, location, enhancement rate and enhancement homogeneity were negatively correlated with T-staging. The predictive results of the model were consistent with the pathological gold standard, and the kappa value was 0.805. The total accuracy of staging improved from 51.04% to 86.98% with the proposed model. MATERIALS AND METHODS: The clinical, imaging and pathological data of 611 patients with colorectal cancer (419 patients in the training group and 192 patients in the validation group) were collected. A spearman correlation analysis was used to validate the relationship among these factors and pathological T-staging. A prediction model was trained with the random forest algorithm. T staging of the patients in the validation group was predicted by both prediction model and traditional method. The consistency, accuracy, sensitivity, specificity and area under the curve (AUC) were used to compare the efficacy of the two methods. CONCLUSIONS: The newly established comprehensive model can improve the predictive efficiency of preoperative colorectal cancer T-staging.

Analysis of miRNAs Involved in Mouse Brain Damage upon Enterovirus 71 Infection.

Enterovirus 71 (EV71) infects the central nervous system (CNS) and causes brainstem encephalitis in children. MiRNAs have been found to play various functions in EV71 infection in human cell lines. To identify potential miRNAs involved in the inflammatory injury in CNS, our study, for the first time, performed a miRNA microarray assay in vivo using EV71 infected mice brains. Twenty differentially expressed miRNAs were identified (four up- and 16 down-regulated) and confirmed by qRT-PCR. The target genes of these miRNAs were analyzed using KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, revealing that the miRNAs were mainly involved in the regulation of inflammation and neural system function. MiR-150-5p, -3082-5p, -3473a, -468-3p, -669n, -721, -709, and -5107-5p that regulate MAPK and chemokine signaling were all down-regulated, which might result in increased cytokine production. In addition, miR-3473a could also regulate focal adhesion and leukocyte trans-endothelial migration, suggesting a role in virus-induced blood-brain barrier disruption. The miRNAs and pathways identified in this study could help to understand the intricate interactions between EV71 and the brain injury, offering new insight for the future research of the molecular mechanism of EV71 induced brainstem encephalitis.

Antimicrobial Resistance of Salmonella enterica Serovar Typhimurium in Shanghai, China.

We aimed to analyze the antimicrobial resistance phenotypes and to elucidate the molecular mechanisms underlying resistance to cephalosporins, ciprofloxacin, and azithromycin in Salmonella enterica serovar Typhimurium isolates identified from patients with diarrhea in Shanghai. The isolates showed high rates of resistance to traditional antimicrobials, and 20.6, 12.7, and 5.5% of them exhibited decreased susceptibility to cephalosporins, ciprofloxacin, and azithromycin, respectively. Notably, 473 (84.6%) isolates exhibited multidrug resistance (MDR), including 161 (28.8%) isolates that showed an ACSSuT profile. Twenty-two MDR isolates concurrently exhibited decreased susceptibility to cephalosporins and ciprofloxacin, and six of them were co-resistant to azithromycin. Of all the 71 isolates with decreased susceptibility to ciprofloxacin, 65 showed at least one mutation (D87Y, D87N, or D87G) in gyrA, among which seven isolates simultaneously had mutations of parC (S80R) (n = 6) or parC (T57S/S80R) (n = 1), while 49 isolates with either zero or one mutation in gyrA contained plasmid-mediated quinolone resistance (PMQR) genes including qnrB, qnrS, and aac(6')-Ib-cr. Among the 115 cephalosporin-resistant isolates, the most common ESBL gene was blaCTX-M, followed by blaTEM-1, blaOXA-1, and blaSHV -12. Eight subtypes of blaCTX-M were identified and blaCTX-M-14 (n = 22) and blaCTX-M-55 (n = 31) were found to be dominant. To the best of our knowledge, this is the first report of the presence of blaCTX-M-123 and blaCTX-M-125 in S. Typhimurium. Besides, mphA gene was identified in 15 of the 31 azithromycin-resistant isolates. Among the 22 isolates with reduced susceptibility to cephalosporins and ciprofloxacin, 15 contained ESBL and PMQR genes. Coexistence of these genes lead to the emergence of MDR and the transmission of them will pose great difficulties in S. Typhimurium treatments. Therefore, surveillance for these MDR isolates should be enhanced.