Enantioselective Arylation of Sulfenamides to Access Sulfilimines Enabled by Palladium Catalysis.

Sulfur-containing functional groups have garnered considerable attention due to their common occurrence in ligands, pharmaceuticals, and insecticides. Nevertheless, enantioselective synthesis of sulfilimines, particularly diaryl sulfilimines remains a challenging and persistent goal. Herein we report a highly enantio- and chemoselective cross-coupling of sulfenamides with aryl diazonium salt to construct diverse S(IV) stereocenters by Pd catalysis. Bisphosphine ligands bearing sulfinamide groups play a crucial role in achieving high reactivity and selectivity. This approach provides a general, modular and divergent framework for quickly synthesizing chiral sulfilimines and sulfoximines that are otherwise challenging to access. In addition, the origins of the high chemoselectivity and enantioselectivity were extensively investigated using density functional theory calculations.

miR-146a-5p promotes replication of infectious bronchitis virus by targeting IRAK2 and TNFRSF18.

Avian infectious bronchitis virus (IBV) is a coronavirus which infects chickens (Gallus gallus) of all ages and causes significant economic losses to the poultry industry worldwide. The present study aims to analyze the miRNAs related to pathogenicity of nephropathogenic IBVs. It was found that four miRNAs (miR-1454, miR-3538, miR-146a-5p and miR-215-5p) were related to the infection of virulent nephropathogenic IBV with transcript per million (TPM) > 500 and more than a 2-fold alteration. In vitro study results showed that the alterations of these four miRNAs were consistent with in vivo data. In vitro, we found that high levels of miR-146a-5p could enhance the replication of IBV at the early stage of infection, and its down regulated level could slow down the replication of IBV. Finally, high levels of exogenous miR-146a-5p in HD11 cells led to down regulation of IL-1 receptor associated kinase-2 (IRAK2) and Tumor necrosis factor receptor superfamily member 18 (TNFRSF18) genes. Luciferase reporter assays revealed that miR-146a-5p could bind to the 3'-UTRs of IRAK2 and TNFRSF18. This is the first study demonstrating that IBV induced miR-146a-5p is related to virus pathogenesis by down regulating IRAK2 and TNFRSF18, which may serve as a therapeutic strategy for the prevention of IBV infections.

Development of an ELISA based on a multi-fragment antigen of infectious bronchitis virus for antibodies detection.

OBJECTIVES: To develop a cost-effective ELISA for detection of antibodies against infectious bronchitis virus (IBV) by using a multi-fragment protein as coating antigen. RESULTS: A multi-fragment antigen, termed BE, which was composed of eight antigenic fragments selected from the three major proteins (S, M, and N) of IBV, was expressed in Escherichia coli. The entire protein had a molecular weight of 61.5 kDa. In addition to it, a smaller truncated protein was also produced; both could react with IBV-positive serum. Next, an indirect ELISA (BE-ELISA) was developed. Coefficients of variation of this assay were lower than 10 %, and no cross-reactivity between the coated antigen BE and antiserum against newcastle disease virus, avian influenza virus, or infectious bursal disease virus was observed. The performance of BE-ELISA was evaluated, and showed 95.4 % coincidence ratio with the whole virus based-ELISA (IDEXX). CONCLUSIONS: The multi-fragment antigen (BE) may represent a promising alternative to the whole virus without safety problems, and this newly established ELISA provides an effective method for anti-IBV antibody detection.

Intrauterine Exposure to Maternal Diabetes is Associated with Adiposity in Children at 6 Years of Age in China.

Children born to mothers with gestational diabetes mellitus (GDM) are more likely to exhibit congenital malformations, high birth weight, and obesity and have an increased risk of developing type 2 diabetes in later life. Children who are exposed to maternal diabetes in utero may be 'programmed' for later development of obesity at a critical period of development. Therefore, the purpose of the present study was to examine the associations among adiposity and systolic blood pressure in children and abnormal maternal glucose levels during pregnancy. A total of 856 mother-child pairs were included in the present retrospective study. Eligible pregnant women underwent a standard 75 g oral glucose tolerance test between 24 and 28 weeks' gestation. Anthropometric characteristics of their children were measured at 6 years of age, including body mass index, the sum of subscapular and tricep skinfold thickness, and systolic blood pressure. The result suggests that children exposed to GDM have higher adiposity; prevention of childhood obesity needs to begin early in life for these children.

Copper-Catalyzed Sulfur Alkylation of Sulfenamides with N-Sulfonylhydrazones.

Sulfilimines are valuable compounds in both organic synthesis and pharmaceuticals. In this study, we present a copper-catalyzed sulfur alkylation of sulfenamides with N-sulfonylhydrazones. In contrast to prior findings, hydrazones derived from aldehydes act as donor-type carbene precursors, effectively engaging in coupling with sulfenamides via a copper catalyst, demonstrating exclusive S selectivity. The utility of the protocol was highlighted in the rapid access to a wide range of sulfoximine derivatives.

Lactococcus lactis anchoring avian infectious bronchitis virus multi-epitope peptide EpiC induced specific immune responses in chickens.

Mucosal immunity is critical in preventing infectious bronchitis virus (IBV) infection. To deliver viral antigens to the mucosal immune system of chickens safely and effectively, we constructed a Lactococcus lactis strain carrying IBV multi-epitope gene EpiC fused with the gene of the cell-wall anchoring domain of Staphylococcus aureus protein A. SDS-PAGE and Western blot results indicated that the fused peptide was located partially on the cell surface. Oral and nasal inoculation with the recombinant L. lactis of chickens elicited significantly high humoral and mucosal immune responses, especially in the nasally immunized group. Eighty percent chickens of the nasally immunized group with recombinant L. lactis did not show any clinical signs after a lethal dose challenge with IBV SAIBk strain, while all the non-recombinant L. lactis immunized chickens exhibited obvious and typical symptoms. These results indicate that needle-free recombinant lactococci anchoring the IBV antigen makes a promising vaccine candidate against the spread of IB.

Using 16S rDNA Sequencing Technology to Preliminarily Analyze Intestinal Flora in Children with Mycoplasma pneumoniae Pneumonia.

Objective: We investigated changes in the intestinal flora of children with Mycoplasma pneumoniae pneumonia (MPP). Methods: Between September 2019 and November 2019, stool samples from 14 children with MPP from The Fourth Hospital of Baotou city, Inner Mongolia Autonomous Region, were collected and divided into general treatment (AF) and probiotic (AFY) groups, according to the treatment of "combined Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus cereus tablets live". High-throughput 16S rDNA sequencing was used to identify intestinal flora. Results: Intestinal flora abundance and diversity in children with MPP were decreased. Both Shannon and Simpson indices were lower in the AF group when compared with healthy controls ( P < 0.05). When compared with healthy controls, the proportion of Enterorhabdus was lower in the AF group, while the proportion of Lachnoclostridium was higher ( P < 0.05). The proportion of Bifidobacteria and Akkermansia was lower in the AFY group but Enterococcus, Lachnoclostridium, Roseburia, and Erysipelatoclostridium proportions were higher. The proportion of Escherichia coli- Shigella in the AFY group after treatment was decreased ( P < 0.05). Conclusions: The intestinal flora of children with MPP is disturbed, manifested as decreased abundance and diversity, and decreased Bifidobacteria. Our probiotic mixture partly improved intestinal flora disorders.

Systematic review and meta-analysis of randomized controlled trials comparing botulinum toxin injection with lateral internal sphincterotomy for chronic anal fissure.

OBJECTIVE: The aim of this review is to systematically analyze the prospective randomized controlled trials on the efficacy of botulinum toxin injection (Botox) vs. lateral internal sphincterotomy (LIS) for the treatment of chronic anal fissure (CAF). MATERIALS AND METHODS: A systematic review of the literature was undertaken. The prospective randomized controlled trials on the effectiveness of Botox vs. LIS for the management of CAF were selected according to specific criteria and analyzed to generate pooling data. RESULTS: Four studies encompassing 279 patients were qualified for the meta-analysis. There was a statistically significant higher healing in LIS group compared with Botox group (RR 1.31[1.57, 1.50] 95% CI, z = 4.11, p < 0.0001). Absolute benefit increase rate (ABI) is 23% for LIS group compared with Botox group. The recurrence rate was statistically significantly higher in Botox groups than in LIS groups (RR 5.83[2.96, 11.49] 95% CI, z = 5.09, p < 0.00001).LIS was associated with a high rate of minor anal incontinence as compared to Botox (RR 0.08[0.01, 0.59] 95% CI, z = 2.47, p = 0.01). CONCLUSION: Botulinum toxin injection was associated with a higher rate of recurrent disease. LIS was more effective in healing chronic anal fissure.

Prediction of neonatal acidosis using the cerebroplacental ratio at different gestational weeks: A case-control study.

We evaluated the clinical value of the cerebroplacental ratio (CPR) in predicting neonatal acidosis according to the gestational weeks in late pregnancy.From July 2016 to June 2017, 1018 neonates without acidosis and 218 neonates with acidosis (confirmed postpartum) underwent a prenatal examination and hospital delivery at 28 to 41 weeks in our hospital. The CPR was calculated as the ratio of the prenatal middle cerebral artery-pulsation index (MCA-PI) to the umbilical artery-pulsation index (UA-PI).In neonates without acidosis, the fetal UA-PI decreased with increased gestational age during late pregnancy. Similarly, the MCA-PI decreased with increased gestational age, and decreased significantly during the full pregnancy term. Additionally, the CPR peaked in the middle of the late pregnancy period and then decreased. In contrast, in neonates with acidosis, the prenatal UA-PI increased significantly, MCA-PI declined significantly, and CPR declined significantly in relation to normal values (P < .05). For the prediction of neonatal acidosis, the UA-PI was suitable after 32 weeks and the MCA-PI was suitable before 37 weeks. The cutoff values of the CPR for the prediction of neonatal acidosis at 28 to 31 weeks, 32 to 36 weeks, and 37 to 41 weeks were 1.29, 1.36, and 1.22, respectively. Unlike the UA-PI and MCA-PI, the CPR was suitable as an independent predictor of neonatal acidosis at all late pregnancy weeks. In neonates with acidosis, the z score of the UA-PI increased significantly, whereas the z scores of the MCA-PI and CPR decreased significantly, in relation to normal values (P < .05).The CPR can be used to evaluate the adverse status of fetuses during late pregnancy, providing an early prediction of neonatal acidosis.

[Digital pulse wave analyzing method in evaluating arterial compliance based on population study in Chinese 415 adults].

OBJECTIVE: To explore the reliability and validity of digital pulse wave analyzing method in evaluating arterial compliance in population-based study. METHODS: All 415 adults (132 men and 283 women) aged 20 to 86 years old were selected from urban (220 persons) and rural (195 persons) areas, respectively by a stratified randomly sampling method. Arterial compliance, evaluated by stiffness index (SI), was measured by using digital pulse wave analyzing method from the Pulse trace machine (Micro medical, London), and the SI value was determined accordingly. RESULTS: In the study on both repeatability and stability, there was a perfect correlation between the frequent measurements for one individual either on one occasion or on two 40-days-apart occasions. The SI values were not significantly different between the urban and the rural, men and women. Multiple stepwise regressions showed that systolic blood pressure and age were positively correlated with SI value, respectively (both P values were less than 0.001). The correlation kept unchanged after taking account of gender, BMI and heart rate. The mean SI values for people aged 20 to 29, 30 to 39, 40 to 49, 50 to 59 and > or = 60 were 7.35, 8.84, 10.41, 10.95 and 12.01 m/s (P < 0.01), respectively. CONCLUSIONS: Both systolic blood pressure and age should be contributed as the main influencing factors of arterial compliance. Digital pulse wave analyzing method is a preferable measurement in evaluating arterial compliance in population-based study due to its better repeatability and stability.

Effects of a restricted fetal growth environment on human kidney morphology, cell apoptosis and gene expression.

OBJECTIVE: Kidney development is key to the onset of hypertension and cardiovascular diseases in adults, and in the fetal stage will be impaired by a lack of nutrients in utero in animal models. However, few human studies have been performed. METHODS: Kidney samples from fetuses in a fetal growth restriction (FGR) environment were collected and the morphological characteristics were observed. Potentially molecular mechanisms were explored by analyzing apoptosis and kidney-development related gene expression. RESULTS: The results indicated that no malformations were observed in the kidney samples of the FGR group, but the mean kidney weight and volume were significantly decreased. Moreover, the ratio of apoptotic cells and Bax-positive cells was increased and the ratio of Bcl-2-positive cells was decreased in the FGR group, indicating potential apoptosis induction under an in utero FGR environment. Finally, aberrant expression of renin and angiotensinogen indicated potential kidney functional abnormalities in the FGR group. CONCLUSIONS: Our study suggested increased apoptosis and decreased renin and angiotensinogen expression during human kidney development in an FGR environment. The current results will be helpful to further explore the molecular mechanism of FGR and facilitate future studies of hypertension and cardiovascular diseases and the establishment of preventive methods.

Polymorphisms of exon 17 of insulin-receptor gene in pathogenesis of human disorders with insulin resistance.

OBJECTIVE: To investigate the relationship between polymorphisms of insulin-receptor (INSR) gene and insulin resistance in a population-based study in China. METHODS: Polymerase Chain Reaction (PCR) was used to the amplify Exon 17 of INSR gene and all amplified products were analyzed by direct sequencing. RESULTS: Six single-nucleotide polymorphisms (SNPs) were found at the following loci: T to TC at the locus of 10699 (Tyr(984)), G to GC at the locus of 10731 (Glu(994)), Deletion G at the locus of 10798 (Asp(1017)), C to T/TC at the locus of 10923 (His(1058)), C to CA at the locus of 10954 (Leu(1069)), and T to TA at the locus of 10961 (Phe(1071)), which might not change the amino acid sequence. The data were in agreement with the test of Hardy-Weinberg balance (P > 0.05). Among the 345 cases, all clinical indices were higher in males than in females except for HDL cholesterol (P < 0.05). The proportion of insulin resistance in males (64.4%) was higher than that in females (35.6%, OR = 1.83). It implied that the relative risk of developing insulin resistance in males was 1.83 times as high as that in females. The biochemical indices in different loci on Exon 17 showed that the individuals with deletion G on the locus of 10798 had lower TG (P = 0.052) and higher HDL (P = 0.027) than those without deletion G on the same site. Homa-Index was lower in those with deletion G than in those without deletion G (P > 0.05). After sex stratification in analysis, all allele frequencies on the six loci of SNPs of Exon 17 had different distributions between the insulin resistant group and the control group, but P > 0.05. CONCLUSION: SNPs of Exon 17 of INSR gene are unlikely to play a direct role in the pathogenesis of human disorders with insulin resistance.

[Ponderal index at birth predicts metabolic syndrome in mid-aged Chinese].

OBJECTIVE: To examine the association between Ponderal index (PI) at birth and metabolic syndrome during middle age. METHODS: Totally, 975 adults (494 men and 481 women) aged 41-52 from the study cohort of Fetal Origin of Adult Disease were recruited in the study for clinic examinations, involving anthropometry and measurements of blood pressure, fasting and 2 hr plasma levels of glucose and insulin, serum lipid profile. Their HOMA-insulin resistance (IR) index was estimated. Metabolic syndrome (MS) was diagnosed according to 1999 WHO definition. Multivariate logistic regression analysis was used to estimate the effect of PI on MS and the interaction between PI at birth and body mass index (BMI) in adulthood. RESULTS: Prevalence of MS was 18.7% in this mid-aged population, 24.8%, 19.4%, 16.3% and 14.0% in those with less than the 25th percentile, the 25th to less than the 50th percentile, the 50th to less than the 75th percentile and more than 75th percentile of PI at birth, respectively, in a decreasing trend (chi2 M-H for trend=9.938 adjusted for gender, P=0.002). Logistic regression analysis showed that both PI at birth and BMI during adulthood could influence their occurrence of MS (beta=-0.125, P=0.002, for PI; and beta=0.430, P=0.000, for BMI). A synergistic effect between PI at birth and BMI in adulthood was observed in this population. Persons who were thin at birth with PI less than the 25th percentile, and became overweight with BMI greater than or equal to 24 kg/m2 later in their life, were at higher risk of suffering from metabolic syndrome (OR=29.1, 95% CI=13.6-62.1), in comparison with those who became overweight during adulthood from a higher PI at birth (OR=16.0, 95% CI=7.9-32.3) and those who were thin at birth and remained a appropriate BMI during their adulthood (OR=2.0, 95% CI=0.7-5.7). Attributable fraction of the interaction to MS was 34.6%. CONCLUSIONS: Thin at birth was a predictor for later occurrence of metabolic syndrome, as well as an effect modifier for the association between of later BMI and metabolic syndrome, i.e., overweight later in his life was most deleterious for a person with growth retardation at birth.

Titanium dioxide nanospheres with wide spectral absorption prepared by low-voltage plasma electrolysis.

TiO(2) nanospheres with diameters mostly in the range of 20-200 nm are prepared by using cathodic plasma electrolysis at low voltage of 70 V. It is found that the low voltage could efficiently depress the particle sizes and their distribution, and result in more anatase phases. The nanospheres have an excellent optical absorption from 240 nm to 2600 nm.

Establishment of reverse genetics system for infectious bronchitis virus attenuated vaccine strain H120.

Infectious bronchitis virus (IBV) strain H120 was successfully rescued as infectious clone by reverse genetics. Thirteen 1.5-2.8 kb fragments contiguously spanning the virus genome were amplified and cloned into pMD19-T. Transcription grade complete length cDNA was acquired by a modified "No See'm" ligation strategy, which employed restriction enzyme Bsa I and BsmB I and ligated more than two fragments in one T4 ligase reaction. The full-length genomic cDNA was transcribed and its transcript was transfected by electroporation into BHK-21 together with the transcript of nucleocapsid gene. At 48 h post transfection, the medium to culture the transfected BHK-21 cells was harvested and inoculated into 10-days old SPF embryonated chicken eggs (ECE) to replicate the rescued virus. After passage of the virus in ECE five times, the rescued H120 virus (R-H120) was successfully recovered. R-H120 was subsequently identified to possess the introduced silent mutation site in its genome. Some biological characteristics of R-H120 such as growth curve, EID50 and HA titers, were tested and all of them were very similar to its parent strain H120. In addition, both R-H120 and H120 induced a comparable titer of HA inhibition (HI) antibody in immunized chickens and also provided up to 85% of immune protection to the chickens that were challenged with Mass41 IBV strain. The present study demonstrated that construction of infectious clone from IBV vaccine strain H120 is possible and IBV-H120 can be use as a vaccine vector for the development of novel vaccines through molecular recombination and the modified reverse genetics approach.

Preparation, characterization and catalytic property of CuO nano/microspheres via thermal decomposition of cathode-plasma generating Cu2(OH)3NO3 nano/microspheres.

CuO nano/microspheres with a wide diametric distribution were prepared by thermal decomposition of Cu(2)(OH)(3)NO(3) nano/microspheres formed in a simple asymmetric-electrode based cathodic-plasma electrolysis. The morphological, componential, and structural information about the two kinds of spheres were characterized in detail by SEM, TEM, EDX, XPS and XRD, and the results revealed that the morphology of the spheres were well kept after the componential and structural transformation from Cu(2)(OH)(3)NO(3) into CuO. The TGA/DSC study showed that the CuO nano/microspheres could be explored to be a promising additive for accelerating the thermal decomposition of ammonium perchlorate (AP). Combining with the current curve and emission spectrum measured in the plasma electrolysis, formation mechanism of the Cu(2)(OH)(3)NO(3) spheres was also discussed.

Plasma-electrolysis synthesis of TiO2 nano/microspheres with optical absorption extended into the infra-red region.

A novel plasma-electrolysis method is introduced to synthesize high-quality TiO(2) nano/microspheres that exhibited excellent optical absorption covering the range from ultraviolet to infra-red. Both experimental and theoretical results show that the oxygen vacancies in the TiO(2) spheres are primarily responsible for this wide absorption.