Assessment of vibration modulated regional cerebral blood flow with MRI.

Human brain experiences vibration of certain magnitude and frequency during various physical activities such as vehicle transportation and machine operation, which may cause traumatic brain injury or other brain diseases. However, the mechanisms of brain pathogenesis due to vibration are not fully elucidated due to the lack of techniques to study brain functions while applying vibration to the brain at a specific magnitude and frequency. Here, this study reported a custom-built head-worn electromagnetic actuator that applied vibration to the brain in vivo at an accurate frequency inside a magnetic resonance imaging scanner while cerebral blood flow (CBF) was acquired. Using this technique, CBF values from 45 healthy volunteers were quantitatively measured immediately following vibration at 20, 30, 40 Hz, respectively. Results showed increasingly reduced CBF with increasing frequency at multiple regions of the brain, while the size of the regions expanded. Importantly, the vibration-induced CBF reduction regions largely fell inside the brain's default mode network (DMN), with about 58 or 46% overlap at 30 or 40 Hz, respectively. These findings demonstrate that vibration as a mechanical stimulus can change strain conditions, which may induce CBF reduction in the brain with regional differences in a frequency-dependent manner. Furthermore, the overlap between vibration-induced CBF reduction regions and DMN suggested a potential relationship between external mechanical stimuli and cognitive functions.

Modeling pyranose ring pucker in carbohydrates using machine learning and semi-empirical quantum chemical methods.

Pyranose ring pucker is a key coordinate governing the structure, interactions and reactivity of carbohydrates. We assess the ability of the machine learning potentials, ANI-1ccx and ANI-2x, and the GFN2-xTB semiempirical quantum chemical method, to model ring pucker conformers of five monosaccharides and oxane in the gas phase. Relative to coupled-cluster quantum mechanical calculations, we find that ANI-1ccx most accurately reproduces the ring pucker energy landscape for these molecules, with a correlation coefficient r2 of 0.83. This correlation in relative energies lowers to values of 0.70 for ANI-2x and 0.60 for GFN2-xTB. The ANI-1ccx also provides the most accurate estimate of the energetics of the 4 C1 -to-1 C4 minimum energy pathway for the six molecules. All three models reproduce chair more accurately than non-chair geometries. Analysis of small model molecules suggests that the ANI-1ccx model favors puckers with equatorial hydrogen bonding substituents; that ANI-2x and GFN2-xTB models overstabilize conformers with axially oriented groups; and that the endo-anomeric effect is overestimated by the machine learning models and underestimated via the GFN2-xTB method. While the pucker conformers considered in this study correspond to a gas phase environment, the accuracy and computational efficiency of the ANI-1ccx approach in modeling ring pucker in vacuo provides a promising basis for future evaluation and application to condensed phase environments.

Integration of the blaNDM-1 carbapenemase gene into a novel SXT/R391 integrative and conjugative element in Proteus vulgaris.

OBJECTIVES: To characterize the genetic environment of the carbapenem resistance determinant in Proteus vulgaris of swine origin. METHODS: The carbapenem-resistant P. vulgaris strain BC22 was isolated from a faecal swab from a diseased pig with diarrhoea in Sichuan Province of China in 2018. The presence of carbapenemase genes was screened by PCR. WGS and bioinformatics analysis were performed to analyse the genetic environment of the carbapenem resistance determinant. RESULTS: P. vulgaris strain BC22 was found to harbour the carbapenemase gene blaNDM-1. WGS data revealed that blaNDM-1 was located in a truncated ISAba125 composite transposon. The carbapenem resistance gene blaNDM-1 and 20 other resistance genes, including the multiresistance gene cfr and the bifunctional aminoglycoside/quinolone resistance gene aac(6')-lb-cr, were located in a novel SXT/R391 integrative and conjugative element (ICE). This new SXT/R391 ICE of 148.7 kb was chromosomally located, and could be transferred to Escherichia coli. CONCLUSIONS: Here, we report a carbapenemase gene, blaNDM-1, integrated into an SXT/R391 ICE. Our study highlights that this SXT/R391 ICE may facilitate the dissemination of clinically important resistance genes such as blaNDM-1, cfr and aac(6')-lb-cr.

A novel cfr-carrying Tn7 transposon derivative characterized in Morganella morganii of swine origin in China.

OBJECTIVES: To characterize the presence and genetic environment of the multiresistance gene cfr in bacterial isolates from a swine farm. METHODS: A total of 97 bacterial isolates, recovered from 32 faecal swabs obtained on one farm, were tested for the presence of the cfr gene by PCR. Species identification of the one cfr-positive strain was conducted using the BD PhoenixTM 100 Automated Microbiology System. Susceptibility testing was carried out by broth microdilution. The genetic environment of the cfr gene was analysed by WGS. RESULTS: The Morganella morganii isolate BCMM24 was the only cfr-positive strain. The cfr gene, as well as 15 other resistance genes, is located on a novel 111238 bp transposon derived from Tn7, designated as Tn6451, which comprises various genetic materials including a novel class 1 integron with five gene cassettes. The cfr-containing region consists of a novel genetic structure IS26-cfr-ΔTn554 tnpB-ΔTn3 family tnpA-IS26, differing from previous reports. Two-step PCR results show that the structure can be looped out and that Tn6451 cannot be excised from the chromosome. CONCLUSIONS: To the best of our knowledge, we report the cfr gene in M. morganii for the first time. The cfr gene and 15 other resistance genes are located on a novel Tn7 transposon derivative, suggesting that the Tn7 transposon may act as a reservoir for various antimicrobial resistance genes and more Tn7 derivatives carrying multiple resistance genes are likely to be discovered in Gram-negative bacteria of both animal and human origin.

Characterization of a Novel SXT/R391 Integrative and Conjugative Element Carrying cfr, blaCTX-M-65, fosA3, and aac(6')-Ib-cr in Proteus mirabilis.

A novel 139,487-bp SXT/R391 integrative and conjugative element, ICEPmiChnBCP11, was characterized in Proteus mirabilis of swine origin in China. ICEPmiChnBCP11 harbors 20 different antimicrobial resistance genes, including the clinically important rRNA methyltransferase gene cfr, the extended-spectrum ß-lactamase gene blaCTX-M-65, fosfomycin resistance gene fosA3, and fluoroquinolone resistance gene aac(6')-Ib-cr An ISPpu12-mediated composite transposon containing various resistance genes and 10 copies of IS26 is inserted in hot spot 4. ICEPmiChnBCP11 was successfully transferred to Escherichia coli.

PGI2 Is a Novel SGI1-Relative Multidrug-Resistant Genomic Island Characterized in Proteus mirabilis.

A novel 61,578-bp genomic island named Proteus genomic island 2 (PGI2) was characterized in Proteus mirabilis of swine origin in China. The 23.85-kb backbone of PGI2 is related to those of Salmonella genomic island 1 and Acinetobacter genomic island 1. The multidrug resistance (MDR) region of PGI2 is a complex class 1 integron containing 14 different resistance genes. PGI2 was conjugally mobilized in trans to Escherichia coli in the presence of a conjugative IncC helper plasmid.

Tn6450, a Novel Multidrug Resistance Transposon Characterized in a Proteus mirabilis Isolate from Chicken in China.

A novel 65.8-kb multidrug resistance transposon, designated Tn6450, was characterized in a Proteus mirabilis isolate from chicken in China. Tn6450 contains 18 different antimicrobial resistance genes, including cephalosporinase gene blaDHA-1 and fluoroquinolone resistance genes qnrA1 and aac(6')-Ib-cr It carries a class 1/2 hybrid integron composed of intI2 and a 3' conserved segment of the class 1 integron. Tn6450 is derived from Tn7 via acquisition of new mobile elements and resistance genes.

Colocation of the Multiresistance Gene cfr and the Fosfomycin Resistance Gene fosD on a Novel Plasmid in Staphylococcus arlettae from a Chicken Farm.

The novel 63,558-bp plasmid pSA-01, which harbors nine antibiotic resistance genes, including cfr, erm(C), tet(L), erm(T), aadD, fosD, fexB, aacA-aphD, and erm(B), was characterized in Staphylococcus arlettae strain SA-01, isolated from a chicken farm in China. The colocation of cfr and fosD genes was detected for the first time in an S. arlettae plasmid. The detection of two IS431-mediated circular forms containing resistance genes in SA-01 suggested that IS431 may facilitate dissemination of antibiotic resistance genes.

Various Sequence Types of Escherichia coli Isolates Coharboring blaNDM-5 and mcr-1 Genes from a Commercial Swine Farm in China.

Sixteen different sequence types (STs) of Escherichia coli isolates from a commercial swine farm in China were confirmed to coharbor the carbapenem resistance gene blaNDM-5 and the colistin resistance gene mcr-1 Whole-genome sequencing revealed that blaNDM-5 and mcr-1 were located on a 46-kb IncX3 plasmid and a 32-kb IncX4 plasmid, respectively. The two plasmids can transfer together with a low fitness cost, which might explain the presence of various STs of E. coli coharboring blaNDM-5 and mcr-1.

A novel type 1/2 hybrid IncC plasmid carrying fifteen antimicrobial resistance genes recovered from Proteus mirabilis in China.

IncC plasmids are of great concern as vehicles of broad-spectrum cephalosporins and carbapenems resistance genes blaCMY and blaNDM. The aim of this study was to sequence and characterize a multidrug resistance (MDR) IncC plasmid (pPm14C18) recovered from Proteus mirabilis. pPm14C18 was identified in a CMY-2-producing P. mirabilis isolate from chicken in China in 2014, and could be transferred to Escherichia coli conferring an MDR phenotype. Whole genome sequencing confirmed pPm14C18 was a novel type 1/2 hybrid IncC plasmid 165,992bp in size, containing fifteen antimicrobial resistance genes. It harboured a novel MDR mosaic region comprised of a hybrid Tn21tnp-pDUmer, in which blaCTX-M-65, dfrA32 and ereA were firstly reported in IncC plasmid. Phylogenetic relationship reconstruction based on the nucleotide sequences of the 52 IncC backbones showed all type 1 IncC plasmids were clustered into one clade, and then merged with pPm14C18 and finally with the type 2 IncC plasmids and another type 1/2 hybrid IncC plasmid pYR1. The MDR IncC plasmids in P. mirabilis of animal origin might threaten public health, which should be drawn more attention.

Prevalence, Antimicrobial Resistance, and Relatedness of Salmonella Isolated from Chickens and Pigs on Farms, Abattoirs, and Markets in Sichuan Province, China.

This study aims at investigating the distribution, antimicrobial resistance, and genetic relationship of Salmonella isolated from 18 farms, their downstream abattoirs, and markets of chickens and pigs in Sichuan province, China. A total of 193 Salmonella isolates were identified from 693 samples with an isolation rate of 26.27% (88/335) in chickens and 29.33% (105/358) in pigs. Salmonella was isolated more frequently in abattoirs and markets than from farms. Serotypes were determined according to the White-Kauffmann-Le Minor scheme and 16 different serotypes were identified, with Derby being the most common, followed by Typhimurium and Meleagridis. Antimicrobial resistance phenotypes and genotypes were studied by using the disk diffusion method and polymerase chain reaction (PCR) amplification, respectively. Overall, 44.04% (n = 85) of all isolates were multidrug resistant (MDR) and resistance to nalidixic acid (51.30%) was the most frequently observed. blaCTX-M-55 was the most prevalent extended-spectrum ß-lactamases gene, and polymyxin resistance gene mcr-1 was present in strains with various serotypes. Multilocus sequence typing indicated that sequence type (ST) had a close relationship with serotype, and 34.20% of all strains were ST40, which was the most prevalent. The unweighted pair group method with arithmetic means (UPGMA) dendrogram of pulsed-field gel electrophoresis showed that Salmonella isolates belonging to the same serovar from different parts of the production chain were highly genetic related, indicating that Salmonella as well as resistance genes could potentially be transmitted from farms to markets. Our study highlights the fact that Salmonella isolates from chicken and pig production chain were frequently exhibiting MDR profiles, and the dissemination of MDR Salmonella from farm to market could pose significant threats to food safety and public health.

Prevalence of Plasmid-Mediated Fosfomycin Resistance Gene fosA3 Among CTX-M-Producing Escherichia coli Isolates from Chickens in China.

The aim of this study was to investigate the prevalence of fosfomycin resistance gene fosA3 and characterize plasmids harboring fosA3 among CTX-M-producing Escherichia coli from chickens in China. A total of 234 CTX-M-producing E. coli isolates collected from chickens from 2014 to 2016 were screened for the presence of plasmid-mediated fosfomycin resistance genes (fosA, fosA3, and fosC2). Clonal relatedness of fosA3-positive isolates was determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The genetic environment of fosA3 was analyzed by polymerase chain reaction (PCR) mapping. Plasmids were studied by using conjugation experiments, PCR-based replicon typing and plasmid MLST. Sixty-four (27.4%) fosA3-positive E. coli isolates were identified in this study. The gene blaCTX-M-55 (31/64) was predominant among these strains, followed by blaCTX-M-14 (18/64) and blaCTX-M-65 (14/64). Various PFGE patterns and sequence types (STs) indicated that these isolates were clonally unrelated. Seven different genetic environments of fosA3 were identified and two new combinations (ISEcp1-blaCTX-M-65-ΔIS903D-IS26-fosA3-orf1-orf2-Δorf3-IS26 and IS26-ISEcp1-blaCTX-M-3-orf477-blaTEM-1-IS26-fosA3-orf1-orf2-Δorf3-IS26) were discovered for the first time. Conjugation experiments were successful for 47 isolates and 33 transconjugants harbored a single plasmid. Plasmids carrying fosA3 belonged to incompatibility group IncFII (17/33), IncI1 (2/33), IncHI2 (3/33), and IncB/O (1/33). F33:A-:B- plasmids carrying blaCTX-M-55, IncHI2/ST3 plasmids carrying blaCTX-M-65, and F2:A-:B-plasmids carrying blaCTX-M-55 were found in E. coli isolates from different provinces. Our results revealed a considerable prevalence of fosA3 gene among CTX-M-producing E. coli with clonal diversity from chickens in China. The transmission of different kinds of plasmids is responsible for the dissemination of fosA3 in chicken farms in China.

Analysis of brain structural covariance network in Cushing disease.

Background: Cushing disease (CD) is a rare clinical neuroendocrine disease. CD is characterized by abnormal hypercortisolism induced by a pituitary adenoma with the secretion of adrenocorticotropic hormone. Individuals with CD usually exhibit atrophy of gray matter volume. However, little is known about the alterations in topographical organization of individuals with CD. This study aimed to investigate the structural covariance networks of individuals with CD based on the gray matter volume using graph theory analysis. Methods: High-resolution T1-weighted images of 61 individuals with CD and 53 healthy controls were obtained. Gray matter volume was estimated and the structural covariance network was analyzed using graph theory. Network properties such as hubs of all participants were calculated based on degree centrality. Results: No significant differences were observed between individuals with CD and healthy controls in terms of age, gender, and education level. The small-world features were conserved in individuals with CD but were higher than those in healthy controls. The individuals with CD showed higher global efficiency and modularity, suggesting higher integration and segregation as compared to healthy controls. The hub nodes of the individuals with CD were Short insular gyri (G_insular_short_L), Anterior part of the cingulate gyrus and sulcus (G_and_S_cingul-Ant_R), and Superior frontal gyrus (G_front_sup_R). Conclusions: Significant differences in the structural covariance network of patients with CD were found based on graph theory. These findings might help understanding the pathogenesis of individuals with CD and provide insight into the pathogenesis of this CD.

One-step preparation of magnetic N-doped sodium alginate-based porous carbon and efficient adsorption of bisphenol A.

To resourcefully utilize algal biomass and effectively remove bisphenol A (BPA) from water, sodium alginate (SA) was prepared as the nitrogen-doped magnetic porous carbon material (SAC/N/Fe) with well-developed pore structure according to a one-step method using K2CO3, melamine, Fe(NO3)3·9H2O as the activator, nitrogen dopant, and magnetic precursor, respectively, in this study. The best product, SAC/N/Fe-0.2, was obtained by adjusting the mass ratio of raw materials, and its specific surface area and pore volume were 2240.65 m2 g-1 and 1.44 cm3 g-1, respectively, with a maximum adsorption capacity of 1248.23 mg g-1 for BPA at 308 K. SEM, XRD, XPS, VSM, and FT-IR characterization confirmed that the iron was successfully doped, giving the porous carbon a magnetic separation function. The adsorption process of BPA was more consistent with the Langmuir model and the proposed secondary kinetics, and the adsorption effect was stable and efficient in a wide pH range and under the interference of different metal ions. At the same time, the porous carbon was easy to separate and recover with good regeneration performance.

Cellulose Iß microfibril interaction with pristine graphene in water: Effects of amphiphilicity by molecular simulation.

Graphene-cellulose interactions have considerable potential in the development of new materials. In previous computational work (Biomacromolecules2016, 16, 1771), we predicted that the model 100 hydrophobic surface of cellulose interacted favourably with pristine graphene in aqueous solution molecular dynamics simulations; conversely, a model of the hydrophilic 010 surface of cellulose exhibited progressive rearrangement to present a more hydrophobic face with the graphene, with weakened hydrogen bonds between cellulose chains and partial permeation of water. Here, we extend this work by simulating the interaction in aqueous solution of the amphiphilic 110 surface of a cellulose Iß microfibril model, comprising 36 chains of 40 glucosyl residues, with an infinite sheet of pristine graphene. This face of the microfibril is of intermediate hydrophilicity and progressively associates with graphene over replicate simulations. As cellulose chains adhere to the graphene surface, forming interactions via its CH and OH groups, we observe a degree of local and global untwisting of the microfibril. Complementary rippling of the graphene surface is also observed, as it adapts to interaction with the microfibril. This adsorption process is accompanied by increased exclusion of water between cellulose and graphene although some water localises between chains at the immediate interface. The predicted propensity of a cellulose microfibril to adsorb spontaneously on the graphene surface, with mutual structural accommodation, highlights the amphiphilic nature of cellulose and the types of interactions that can be harnessed to design new graphene-carbohydrate biopolymer materials.

Viscoelastic Characterization of Soft Tissue-Mimicking Gelatin Phantoms using Indentation and Magnetic Resonance Elastography.

Characterization of biomechanical properties of soft biological tissues is important to understand the tissue mechanics and explore the biomechanics-related mechanisms of disease, injury, and development. The mechanical testing method is the most straightforward way for tissue characterization and is considered as verification for in vivo measurement. Among the many ex vivo mechanical testing techniques, the indentation test provides a reliable way, especially for samples that are small, hard to fix, and viscoelastic such as brain tissue. Magnetic resonance elastography (MRE) is a clinically used method to measure the biomechanical properties of soft tissues. Based on shear wave propagation in soft tissues recorded using MRE, viscoelastic properties of soft tissues can be estimated in vivo based on wave equation. Here, the viscoelastic properties of gelatin phantoms with two different concentrations were measured by MRE and indentation. The protocols of phantom fabrication, testing, and modulus estimation have been presented.

Characterization and Public Health Insights of the New Delhi Metallo-ß-Lactamase-Producing Enterobacterales from Laying Hens in China.

The New Delhi metallo-ß-lactamase (NDM) is a major element for the rapid expansion of the carbapenem-resistant Enterobacterales, which poses a great challenge to public health security. NDM-producing Enterobacterales strains (50 Escherichia coli, 40 Klebsiella pneumoniae, and 5 Enterobacter cloacae) were isolated from laying hens in China for the surveillance of antibiotic-resistant pathogens, and all were found to be multi-drug resistant bacteria. The genomic analysis of these NDM-positive bacteria revealed the ST167, ST617, and ST410 of the fifteen ST-type E. coli clones and ST37 of the four ST-type K. pneumoniae clones to be the same types as the human-derived strains. Among them, some new clone types were also found. Most of the blaNDM genes (blaNDM-1 or blaNDM-5) were on the IncX3 plasmids (n = 80) and were distributed in E. coli, K. pneumoniae, and E. cloacae, while the remaining blaNDM-5 genes were harbored in the E. coli ST167 with IncFII plasmids (n = 15). The typeⅠ1 of the eight IncX3 plasmid subtypes was consistent with the human-derived pNDM5_020001 plasmid (accession no. CP032424). In addition, these two plasmids did not affect the growth of the host bacteria and could be reproduced stably without antibiotics. Our study revealed the high genetic propensity of the NDM-positive Enterobacterales from the laying hens and human commensal Enterobacterales, suggesting the potentially enormous risk of its transmission to humans.

Correlation analysis of structural and biomechanical properties of hepatocellular carcinoma tissue.

It is known that biomechanical and structural properties of tumor tissues are potential biomarkers for the diagnosis and prognosis of tumors such as Hepatocellular carcinoma (HCC). Although there are many studies on the characterization of biomechanical properties of HCC at the cellular level, limited information is known from in vitro studies. Here, tissue samples from 14 patients diagnosed with HCC were analyzed. Indentation tests showed the instantaneous shear modulus and long-term shear modulus of the HCC tissue were 1.19 ± 0.86 kPa and 0.29 ± 0.25 kPa, respectively. The volume fraction of collagen fibers estimated by analyzing the histology images was positively correlated with either instantaneous shear modulus (r = 0.64, p = 0.016) or long-term shear modulus (r = 0.76, p = 0.002). Diffusion-weighted images with 13b-values were also collected and the diffusivity from Intravoxel Incoherent Motion (IVIM) and Diffusion Kurtosis Imaging (DKI) models were 1.09 ± 0.47 ∙ 10-3 mm2/s and 2.06 ± 0.83∙10-3 mm2/s, respectively. Significant positive correlations were observed between long-term shear modulus and the diffusivity estimated from IVIM (r = 0.600, p = 0.026). The shifted apparent diffusion coefficient (ADC) estimated based on b = 600 and 2000 s/mm2 was negatively correlated with both instantaneous shear modulus (r = -0.745, p = 0.003) and long-term shear modulus (r = -0.591, p = 0.029). In addition, the diffusivity and non-Gaussian Kurtosis parameters estimated at different b values showed a significant negative correlation (r = -0.675, p = 0.010). Results revealed the close relationships between the structural and biomechanical properties of HCC tissue. The interrelation of diffusion and biomechanical properties are not only crucial for HCC characterization but could also provide helpful information for HCC diagnosis and prognosis.