Toll-like receptor 2 -196 to -174 del polymorphism influences the susceptibility of Han Chinese people to Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Toll-like receptor 2 (<it>TLR2</it>) represents a reasonable functional and positional candidate gene for Alzheimer's disease (AD) as it is located under the linkage region of AD on chromosome 4q, and functionally is involved in the microglia-mediated inflammatory response and amyloid-β clearance. The -196 to -174 del polymorphism affects the <it>TLR2 </it>gene and alters its promoter activity.</p> <p>Methods</p> <p>We recruited 800 unrelated Northern Han Chinese individuals comprising 400 late-onset AD (LOAD) patients and 400 healthy controls matched for gender and age. The -196 to -174 del polymorphism in the <it>TLR2 </it>gene was genotyped using the polymerase chain reaction (PCR) method.</p> <p>Results</p> <p>There were significant differences in genotype (P = 0.026) and allele (P = 0.009) frequencies of the -196 to -174 del polymorphism between LOAD patients and controls. The del allele was associated with an increased risk of LOAD (OR = 1.31, 95% CI = 1.07-1.60, Power = 84.9%). When these data were stratified by apolipoprotein E (<it>ApoE</it>) ε4 status, the observed association was confined to <it>ApoE </it>ε4 non-carriers. Logistic regression analysis suggested an association of LOAD with the polymorphism in a recessive model (OR = 1.64, 95% CI = 1.13-2.39, Bonferroni corrected P = 0.03).</p> <p>Conclusions</p> <p>Our data suggest that the -196 to -174 del/del genotype of <it>TLR2 </it>may increase risk of LOAD in a Northern Han Chinese population.</p

Electrocatalysis of Oxygen Reduction on Te-Modified Platinum Stepped Crystal Surfaces

Te-modified platinum single-crystal surfaces in the [011̅] zone have been used as model electrocatalysts for oxygen reduction reaction (ORR). The results clearly show that (1) except for Pt(111), all other electrodes display enhanced ORR activity when Te is deposited on the surface; (2) the intrinsic ORR activity for Pt(hkl) decreases in the order of Pt(322) > Pt(755) > Pt(977) > Pt(111) > Pt(311) > Pt(100), while the enhancement factor for ORR with Te modification decreases in the order of Pt(100) > Pt(311) > Pt(977) > Pt(755) > Pt(322); (3) metallic Te and its charge transfer to Pt as well as the consequent lower d-band center and OHad binding energy are probably the reasons for the enhanced electrocatalysis for ORR with Te modification; and (4) the inhibition of Te at Pt(111) as well as the smaller extent for the enhancement of Te at Pt(S)-[n(111) × (100)] with longer terraces in the kinetic region for ORR are a result of partial oxidation of Te. The weaker electronic interaction of Te with the Pt substrate is probably the origin of its facile oxidation at lower potential. Our results imply that modification of Pt with species that can transfer electrons to Pt may be an efficient strategy to enhance the ORR activity.This work was supported by the National Natural Science Foundation of China (No. 22172151, 21972131, and 21832004). E.H. gratefully acknowledged the International Professorship by USTC and financial support from the Ministerio de Ciencia e Innovación (project PID2022–137350NB-I00)

Mobilization of Tn1721-like structure harboring blaCTX-M-27 between P1-like bacteriophage in Salmonella and plasmids in Escherichia coli in China

The aim of this study was to explore the characteristics of blaCTX-M-27 carriage and mobilization in Salmonella and Escherichia coli isolates from food-producing animals in China. A total of 2280 E. coli and 229 Salmonella isolates collected from food animals from June 2003 to September 2014 were screened for the presence of blaCTX-M-27 gene. The blaCTX-M-27-positive isolates were typed and plasmid DNA sequenced to determine the genetic context of blaCTX-M-27 and plasmid types present. Bacterial fitness was evaluated by growth curve and plasmid stability in vitro. CTX-M-27-positive E. coli (18, 0.79 %) and Salmonella (34, 14.85 %) were detected. PFGE profiles of CTX-M-27-positive strains revealed a wide variety of genotypes and S. Indiana was the most prevalent serotype. Replicon typing, S1-PFGE and hybridization of CTX-M-27-carrying plasmids confirmed that blaCTX-M-27 gene was located on IncFII (12/18), IncN (4/18), and non-typeable (2/18) plasmids in E. coli and on P1-like bacteriophage (21/34), IncP (4/34), IncFIB (4/34), IncN (2/34), IncHI2 (2/34), and IncA/C (1/34) plasmids in Salmonella. Comparison and analysis of gene context of blaCTX-M-27 in P1-like bacteriophage and plasmids revealed they shared the same structure and contained an identical genetic context with the Tn1721-like structure ΔISEcp1B-blaCTX-M-27-IS903D-iroN-Δmap-Tn1721. In addition, plasmid stability tests indicated that the blaCTX-M-27 P1-like bacteriophage were more stable than plasmids in the absence of cefotaxime selective pressure. These results demonstrate that Tn1721-like transposons harboring CTX-M-27 could be mobilized between different plasmids in E. coli and P1-like bacteriophage disseminated among Salmonella

The Emergence of Chromosomally Located blaCTX-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 blaCTX-M-55 genes on the chromosome, with the remaining isolate carrying this gene on a transferable 280 kb IncHI2 plasmid. A chromosomal blaCTX-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 blaCTX-M-55. Our study demonstrates the emergence and prevalence of foodborne Salmonella harboring a chromosomally located blaCTX-M-55 in China. The co-existence of PMQR genes with blaCTX-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

Surface passivation for highly active, selective, stable, and scalable CO2 electroreduction

Electrochemical conversion of CO2 to formic acid using Bismuth catalysts is one the most promising pathways for industrialization. However, it is still difficult to achieve high formic acid production at wide voltage intervals and industrial current densities because the Bi catalysts are often poisoned by oxygenated species. Herein, we report a Bi3S2 nanowire-ascorbic acid hybrid catalyst that simultaneously improves formic acid selectivity, activity, and stability at high applied voltages. Specifically, a more than 95% faraday efficiency was achieved for the formate formation over a wide potential range above 1.0 V and at ampere-level current densities. The observed excellent catalytic performance was attributable to a unique reconstruction mechanism to form more defective sites while the ascorbic acid layer further stabilized the defective sites by trapping the poisoning hydroxyl groups. When used in an all-solid-state reactor system, the newly developed catalyst achieved efficient production of pure formic acid over 120 hours at 50 mA cm–2 (200 mA cell current)

Transmission of plasmid-borne and chromosomal blaCTX-M-64 among Escherichia coli and Salmonella isolates from food-producing animals via ISEcp1-mediated transposition

Objectives: To clarify the transmission mechanism of the blaCTX-M-64 gene between Escherichia coli and Salmonella isolates from food animals. Methods: A total of 329 E. coli and 60 Salmonella isolates collected from food animals in 2016 were screened for the presence of blaCTX-M-64 genes. The blaCTX-M-64-positive isolates were typed and plasmid and chromosome DNA was sequenced to determine the genetic context of blaCTX-M-64 and the plasmid types present. Results: The blaCTX-M-64 gene was identified in only three E. coli isolates but was the predominant gene in the Salmonella isolates (n = 9). These 12 CTX-M-64-positive isolates were all resistant to ampicillin, cefotaxime, ceftiofur, ceftriaxone, ceftazidime and florfenicol and 9 were resistant to ciprofloxacin. The blaCTX-M-64 gene was located on transferable IncI2 plasmids and an IncHI2 plasmid in three E. coli and one Salmonella isolate, respectively. The remaining eight Salmonella isolates contained blaCTX-M-64 integrated into the chromosome. Different genetic contexts of blaCTX-M-64 genes were found among the 12 isolates: ISEcp1-blaCTX-M-64-orf477-A/C on IncI2 plasmids of 3 E. coli isolates; DISEcp1-blaCTX-M-64-orf477-A/C in the chromosome of 1 Salmonella isolate; and ISEcp1-blaCTX-M-64-orf477 on the IncHI2 plasmid and chromosome of 8 Salmonella isolates. Conclusions: To the best of our knowledge, this is the first report of chromosomally encoded CTX-M-64 in Salmonella isolates. ISEcp1-mediated transposition is likely to be responsible for the spread of blaCTX-M-64 between different plasmids and chromosomes in Enterobacteriaceae especially E. coli and Salmonella

The Growth of Black Holes and Their Host Spheroids in (Sub)mm-loud QSOs at High Redshift

We study the growth of black holes and stellar population in spheroids at high redshift using several (sub)mm-loud QSO samples. Applying the same criteria established in an earlier work, we find that, similar to IR QSOs at low redshift, the far-infrared emission of these (sub)mm-loud QSOs mainly originates from dust heated by starbursts. By combining low-z IR QSOs and high-z (sub)mm-loud QSOs, we find a trend that the star formation rate (\Mstardot) increases with the accretion rate (\Mdot). We compare the values of \Mstardot/\Mdot for submm emitting galaxies (SMGs), far-infrared ultraluminous/hyperluminous QSOs and typical QSOs, and construct a likely evolution scenario for these objects. The (sub)mm-loud QSO transition phase has both high \Mdot and \Mstardot and hence is important for establishing the correlation between the masses of black holes and spheroids.Comment: 19 pages,3 figures,submitted to Chin. J. Astron. Astrophys. This paper was first prepared for publication on August 10th, 200

Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19

Rationale: Use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. Objective: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in COVID-19 patients with hypertension. Methods and Results: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [IQR 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [IQR 57-69]; 53.5% men), who were admitted to nine hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. Unadjusted mortality rate was lower in the ACEI/ARB group versus the non-ACEI/ARB group (3.7% vs. 9.8%; P = 0.01). In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted HR, 0.42; 95% CI, 0.19-0.92; P =0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted HR, 0.37; 95% CI, 0.15-0.89; P = 0.03). Further subgroup propensity score-matched analysis indicated that, compared to use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted HR, 0.30; 95%CI, 0.12-0.70; P = 0.01) in COVID-19 patients with hypertension. Conclusions: Among hospitalized COVID-19 patients with hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB non-users. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk