Chirality without Stereoisomers: Insight from the Helical Response of Bond Electrons.

The association between molecular chirality and helical characteristics known as the chirality-helicity equivalence is determined for the first time by quantifying a chirality-helicity measure consistent with photoexcitation circular dichroism experiments. This is demonstrated using a formally achiral SN 2 reaction and a chiral SN 2 reaction. Both the achiral and chiral SN 2 reactions possess significant values of the chirality-helicity measure and display a Walden inversion, i. e. an inversion of the chirality between the reactant and product. We also track the chirality-helicity measure along the reaction path and discover the presence of chirality at the transition state and two intermediate structures for both reactions. We demonstrate the need for the chirality-helicity measure to differentiate between steric effects due to eclipsed conformations and chiral behaviors in formally achiral species. We explain the significance of this work for asymmetric synthetic reactions including the intermediate structures where the Cahn-Ingold-Prelog (CIP) rules cannot be used.

[Plasmakinetic energy transurethral resection versus transurethral bipolar plasmakinetic enucleation and resection of the prostate in the treatment of BPH with the prostate volume <100 ml].

OBJECTIVE: To investigate the influence of plasmakinetic energy transurethral resection of the prostate (PKRP) versus that of transurethral bipolar plasmakinetic enucleation and resection of the prostate (PKERP) on the bladder function, sexual function and incidence of complications in BPH patients with the prostate volume <100 ml. METHODS: We randomly assigned 140 BPH patients with the prostate volume <100 ml to receive PKRP (n = 70) or PKERP (n = 70) in our hospital from July 2013 to July 2015. We compared the maximum urinary flow rate (Qmax), residual urine volume (RUV), and the rates of ED and retrograde ejaculation before and after surgery as well as the incidence of postoperative complications between the two groups of patients. RESULTS: The Qmax and RUV of the patients were (25.11 ± 7.12) ml/s and (4.06 ± 1.74) ml in the PKERP group postoperatively, significantly improved as compared with the baseline (ï¼»8.60 ± 2.33ï¼½ ml/s and ï¼»66.85 ± 14.33ï¼½ ml, P < 0.05), and even better than (18.87 ± 4.07) ml/s and (9.45 ± 2.66) ml in the PKRP group (P < 0.05). The incidence rates of ED and retrograde ejaculation were 61.43% and 28.57% in the PKRP group, significantly higher than in the PKERP group (40.00% and 14.29%) (P < 0.05) and the baseline (35.71% and 10.00%) (P < 0.05). The postoperative incidence rate of transient urinary incontinence was remarkably higher in the PKERP than in the PKRP group (22.86% vs 8.57%, P < 0.05). There were no statistically significant differences between the two groups in the incidence rates of secondary hemorrhage, urethral injury, or genuine urinary incontinence after operation (P > 0.05). CONCLUSIONS: Compared with PKRP, PKERP can effectively improve the clinical symptoms and signs and protect the bladder function of the BPH patients with the prostate volume <100 ml, but may increase the risk of transient urinary incontinence.

Palladium(II)-Catalyzed Enantioselective Arylation of Unbiased Methylene C(sp3 )-H Bonds Enabled by a 2-Pyridinylisopropyl Auxiliary and Chiral Phosphoric Acids.

Enantioselective functionalizations of unbiased methylene C(sp3 )-H bonds of linear systems by metal insertion are intrinsically challenging and remain a largely unsolved problem. Herein, we report a palladium(II)-catalyzed enantioselective arylation of unbiased methylene ß-C(sp3 )-H bonds enabled by the combination of a strongly coordinating bidentate PIP auxiliary with a monodentate chiral phosphoric acid (CPA). The synergistic effect between the PIP auxiliary and the non-C2 -symmetric CPA is crucial for effective stereocontrol. A broad range of aliphatic carboxylic acids and aryl bromides can be used, providing ß-arylated aliphatic carboxylic acid derivatives in high yields (up to 96 %) with good enantioselectivities (up to 95:5 e.r.). Notably, this reaction also represents the first palladium(II)-catalyzed enantioselective C-H activation with less reactive and cost-effective aryl bromides as the arylating reagents. Mechanistic studies suggest that a single CPA is involved in the stereodetermining C-H palladation step.

Site-Selective δ-C(sp3 )-H Alkylation of Amino Acids and Peptides with Maleimides via a Six-Membered Palladacycle.

The site-selective functionalization of unactivated C(sp3 )-H bonds remains one of the greatest challenges in organic synthesis. Herein, we report on the site-selective δ-C(sp3 )-H alkylation of amino acids and peptides with maleimides via a kinetically less favored six-membered palladacycle in the presence of more accessible γ-C(sp3 )-H bonds. Experimental studies revealed that C-H bond cleavage occurs reversibly and preferentially at γ-methyl over δ-methyl C-H bonds while the subsequent alkylation proceeds exclusively at the six-membered palladacycle that is generated by δ-C-H activation. The selectivity can be explained by the Curtin-Hammett principle. The exceptional compatibility of this alkylation with various oligopeptides renders this procedure valuable for late-stage peptide modifications. Notably, this process is also the first palladium(II)-catalyzed Michael-type alkylation reaction that proceeds through C(sp3 )-H activation.

Enhanced Peroxidase-Like Performance of Gold Nanoparticles by Hot Electrons.

Enzyme mimics have been widely used as alternatives to natural enzymes. However, the catalytic performances of enzyme mimics are often decreased due to different spatial structures or absence of functional groups compared to natural enzymes. Here, we report a highly efficient enzyme-like catalytic performance of gold nanoparticles (AuNPs) by visible-light stimulation. The enzyme-like reaction is evaluated by the catalytic reaction of AuNPs oxidizing a typical chromogenic substrate 3,3',5,5'-tetramethylbenzydine (TMB) with hydrogen peroxide as an oxidant. From investigations of the wavelength-dependent reaction rate, radical capture, hole-donor addition, and dark-field scattering spectroscopy experiments, it is revealed that the strong plasmonic absorption of AuNPs facilitates generation of hot electrons, which are transfered from AuNPs to the adsorbed reactant molecule, greatly promoting the catalytic performance of the enzyme-like catalytic reaction. The present work provides a simple method for improving the performance of enzyme mimics, which is expected to find further application in the field of plasmon-enhanced biocatalysis and biosensors.

[Epidemiological analysis of selected congenital limb malformations in Hengyang].

OBJECTIVE: To describe the epidemiological characteristics of selected congenital limb malformations (CLM) in newborns of Hengyang. METHODS: During the period of 2008-2010, cluster sampling survey was adopted to investigate the congenital limb malformations of neonates born to women resident in Hengyang, including Nanyue District, Zhuhui District, Changning City and Hengshan County. Each newborn was examined for the screening of CLM after birth. Limb malformations were grouped into the isolated (ILM) and the syndromic (SLM) form, depending on associated malformations of the affected. Prevalence rates, CLM spectrum and clinical manifestations were analyzed. RESULTS: A total of 170 CLM cases were identified among 52,307 newborns during the study period, resulting overall rate of 32.50/10(4). The rates for isolated and syndromic CLM were 28.29 and 4.21 per 10 000 births respectively. The rates for polydactyly, congenital talipes equinovarus, syndactyly and limb reduction defects were 13.00/10(4), 9.56/10(4), 5.16/10(4) and 3.63/10(4), respectively. No significant difference in rates of overall CLM or specified CLM was observed across urban-rural, gender and maternal age groups. Of the cases affected by polydactyly, syndactyly and limb reduction defects, malformation involved upper limbs, lower limbs and the both accounted for 68.14%, 14.16% and 17.70%. Preterm birth, low birth-weight, still birth and neonatal death were observed more frequently in syndromic cases than in isolated patients. CONCLUSION: The high CLM prevalence rate and fatality rate in Hengyang suggest that effective measures should be taken to prevent malformations and to improve survival of the affected.

Epidemiological Survey of Hemoglobinopathies Based on Next-Generation Sequencing Platform in Hunan Province, China.

Objective: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and ß-globin gene mutations in Hunan Province. Methods: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. Results: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for ß-thalassemia, and 0.12% for both α- and ß-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and ß-thalassemia was -α 3.7/αα (50.23%) and ß IVS-II-654/ß N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six ß-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. Conclusion: Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.

[Effects of oxymatrine on the expressions of pro-collagen and fibronectin of fibroblasts derived from human hyperplastic scars].

OBJECTIVE: To study the effects of oxymatrine (OM) on the expressions of pro-collagen I (PC I), pro-collagen II (PC III), fibronectin (FN), matrix metalloproteinase-1 (MMP-1) mRNA of fibroblasts from keloid (KFb), hyperplastic scar (HFb), and normal skin (NFb), and to compare with hydrocortisone (HC). METHODS: The primary KFb, HFb and NFb were derived from patients and cultured in vitro using tissue block culture method. The fibroblasts were treated with 500 microg/mL OM, 2 microg/mL HC, or without any medicine (as the control). The mRNA expressions of PC I, PC III, FN, MMP-1 of the fibroblasts were detected using RT-PCR. RESULTS: Under the normal condition, when compared with NFb, the mRNA expressions of PC I of KFb and HFb increased by 31.7% and 34.2% (both P < 0.05). Besides, the mRNA expression of PC III of KFb increased by 44.9% (P < 0.01). OM down-regulated the mRNA expressions of FN and PC I of HFb by 18.8% and 23.6% respectively (both P < 0.05). HC decreased the mRNA expressions of FN and PC I of HFb by 26.8% and 43.6% respectively (P < 0.05, P < 0.01). Meantime, OM up-regulated the mRNA expression of MMP-1 of KFb by 21.8% (P < 0.05). CONCLUSIONS: OM suppressed the synthesis of extracellular matrix (ECM) possibly through down-regulating the mRNA expressions of PC I and FN. Compared with HC, OM could promote the degradation of ECM through inducing the MMP-1 mRNA expressions of KFb. Therefore, OM could be potentially used in treatment of hypertrophic scar and keloid.

Promoters for Improved Adhesion Strength between Addition-Cured Liquid Silicone Rubber and Low-Melting-Point Thermoplastic Polyurethanes.

A polydimethylsiloxane armed with epoxy, alkoxy and acrylate groups was synthesized from silanol terminated-PDMS and epoxy and acrylate groups functionalized silane coupling agents, and utilized as the adhesion promoter (AP) to prepare addition-cured liquid silicone rubber that exhibited self-adhesion ability (SA-LSR) with biocompatible thermoplastic polyurethanes (TPU) sheets. The structural characteristics of AP were characterized by Fourier transform infrared (FTIR) spectroscopy, which demonstrated the strong adhesion to polyester-based TPU sheets due to a sufficient amount of acrylate groups, epoxy groups and silanol groups obtained by the hydrolysis of alkoxy groups. In detail, the peel-off strength of SA-LSR and TPU joints reached up to 7.63 N mm-1 after the optimization of adhesion promoter including type and content, and curing condition including time and temperature. The cohesive failure was achieved during the sample breakage process. Moreover, the SA-LSR showed a good storage stability under proper storage conditions. This design strategy provided the feasibility to combine the advantages of addition-cured liquid silicone rubber and plastics with low melting points, promoting the potential application range of those silicone-based materials.

CBX3 predicts an unfavorable prognosis and promotes tumorigenesis in osteosarcoma.

CBX3, namely chromobox protein homolog 3, a member of the heterochomatin protein 1 (HP1) family, has been shown to be associated with the tumorigenesis of various types of cancer. The aim of the present study was to assess the biological role and the clinicopathological importance of CBX3 in osteosarcoma. The Oncomine database was utilized to determine the CBX3 expression in sarcoma patients. A retrospective cohort study was conducted to evaluate the prognostic value of CBX3 expression. In addition, correlations between the clinicopathological features of the osteosarcoma patients and CBX3 expression were assessed and involved recurrence, distant metastasis, lymph node metastasis, response to chemotherapy, pathological differentiation, clinical stage, anatomic location, tumor size and age. To investigate the function of CBX3 in osteosarcoma, a small interfering RNA for CBX3 was designed and this was used for the transfection of osteosarcoma MG63 cells. Then, the effects of CBX3 on proliferation, cell cycle distribution and apoptosis of osteosarcoma cells were investigated via CCK­8 assay and cell cycle assay and cell apoptosis analysis, respectively. Based on our findings, upregulation of CBX3 expression was noted both in osteosarcoma and also other sarcoma types, which included pleomorphic liposarcoma, myxofibrosarcoma, myxoid/round cell liposarcoma and dedifferentiated liposarcoma. In addition, based on the retrospective cohort study, CBX3 expression was associated with the disease­free survival (DFS) and overall survival (OS) of the osteosarcoma patients and a large tumor size, high distant metastasis rate and high clinical stage rate. In addition, the proliferation ability was blocked by the knockdown of CBX3 through the application of CBX3 siRNA, and CBX3 knockdown also led to increased apoptosis and cell cycle arrest at G0 and G1 phases in osteosarcoma cells. CBX3 is highly expressed in human osteosarcoma tissues. Meanwhile, high CBX3 is a predictor of the poor prognosis of osteosarcoma patients. To conclude, the growth of osteosarcoma can be promoted by CBX3, which may be used as an independent potential prognostic biomarker for patients suffering from osteosarcoma.

Transcriptional activation of USP16 gene expression by NFκB signaling.

Ubiquitin Specific Peptidase 16 (USP16) has been reported to contribute to somatic stem-cell defects in Down syndrome. However, how this gene being regulated is largely unknown. To study the mechanism underlying USP16 gene expression, USP16 gene promoter was cloned and analyzed by luciferase assay. We identified that the 5' flanking region (- 1856 bp ~ + 468 bp) of the human USP16 gene contained the functional promotor to control its transcription. Three bona fide NFκB binding sites were found in USP16 promoter. We showed that p65 overexpression enhanced endogenous USP16 mRNA level. Furthermore, LPS and TNFα, strong activators of the NFκB pathway, upregulated the USP16 transcription. Our data demonstrate that USP16 gene expression is tightly regulated at transcription level. NFκB signaling regulates the human USP16 gene expression through three cis-acting elements. The results provide novel insights into a potential role of dysregulation of USP16 expression in Alzheimer's dementia in Down Syndrome.

Meta-analysis of the prognostic value of long non-coding RNA PVT1 for cancer patients.

BACKGROUND: Plasmacytoma variant translocation 1 (PVT1) is reported to be dysregulated in various cancers. Therefore, this meta-analysis was performed to clarify its utility as a prognosis marker in malignant tumors. METHODS: Electronic databases, including PubMed, OVID, Cochrane Library, and Web of Science databases, were retrieved from inception to December 16, 2017. Typically, hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated, so as to explore the relationship between PVT1 expression and patient survival. In addition, odds ratios (OR) were calculated to assess the association of PVT1 expression with pathological parameters. RESULTS: A total of 23 studies involving 2350 patients were included in this meta-analysis. The pooled HR suggested that high PVT1 expression levels were correlated with poor overall survival (OS, HR = 1.99, 95% CI: 1.73-2.28), disease-free survival (DFS, HR = 1.76, 95% CI: 1.45-2.14), and recurrence-free survival (RFS, HR = 1.74, 95% CI: 1.26-2.39) in cancer patients without obvious heterogeneity. Moreover, high PVT1 expression levels were also correlated with larger tumor size (OR = 1.47, 95% CI: 1.02-2.11), poor differentiation grade (OR = 1.79, 95% CI: 1.39-2.30), advanced tumor stage (pooled OR = 3.28, 95% CI: 2.46-4.38), lymph node metastasis (OR = 2.67, 95% CI: 1.66-4.29) and distant metastasis (OR = 4.00, 95% CI: 1.39-11.50) in cancer patients. CONCLUSIONS: Findings of this meta-analysis suggest that a high PVT1 expression level may serve as a novel biomarker of poor prognosis in cancers.

Direct Plasmon-Accelerated Electrochemical Reaction on Gold Nanoparticles.

Direct photocatalysis making use of plasmonic metals has attracted significant attention due to the light-harnessing capabilities of these materials associated with localized surface plasmon resonance (LSPR) features. Thus far, most reported work has been limited to plasmon-induced chemical transformations. Herein, we demonstrate that electrochemical reactions can also be accelerated by plasmonic nanoparticles upon LSPR excitation. Using glucose electrocatalysis as a model reaction system, the direct plasmon-accelerated electrochemical reaction (PAER) on gold nanoparticles is observed. The wavelength- and solution-pH-dependent electrochemical oxidation rate and the dark-field scattering spectroscopy results confirm that the hot charge carriers generated during plasmon decay are responsible for the enhanced electrocatalysis performance. Based on the proposed PAER mechanism, a plasmon-improved glucose electrochemical sensor is constructed, demonstrating the enhanced performance of the non-enzyme sensor upon LSPR excitation. This plasmon-accelerated electrochemistry promises potential applications in (bio)electrochemical energy conversion, electroanalysis, and electrochemical devices.

Experimental study on the action of allitridin against human cytomegalovirus in vitro: Inhibitory effects on immediate-early genes.

Garlic (Allium sativum) extraction has been reported having anti-HCMV efficacy. This study was aimed to investigate the effect of allitridin (diallyl trisulfide, a compound from A. sativum extraction) on the replication of HCMV and the expression of viral immediate-early genes. In HCMV plaque-reduction assay, allitridin appeared a dose-dependent inhibitory ability with EC(50) value of 4.2 microg/ml (selective index, SI=16.7). Time-of-addition and time-of-removal studies showed that allitridin inhibited HCMV replication in earlier period of viral cycle before viral DNA synthesis. Both immediate early gene (ie1) transcription and IEA (IE(1)72 and IE(2)86) expression was suppressed by allitridin, but not by GCV in a single HCMV cycle format. In addition, allitridin appeared stronger inhibition on IE(2)86 than on IE(1)72. Decrease of viral DNA load in infected cells was also detected under allitridin treatment, probably due to an indirect consequence of the reduction in ie gene transcription. In summary, this study indicated that allitridin has anti-HCMV activity and the mechanism is associated with suppression of ie gene transcription.

[Effects of allitridin on the expression of human cytomegalovirus immediate early antigens-IE72 and IE86 in human embryonic lung cells].

OBJECTIVE: To investigate the effect of allitridin injection on the expression of human cytomegalovirus (HCMV) immediate-early antigens (IEAs including IE72 and IE86) in human embryonic lung cells. METHOD: HCMV AD 169 Virus strain infected cell model (MOI = 2.5 and 0.25, respectively) were established, and then treated with ICm5 and MTC doses of allitridin. Western blot was used to analyze the of IE72 and IE86 expression after the treatment, ganciclovir(GCV, IC50 and 2.3 x IC50) treatment as control. RESULT: No matter what kind of MOI was used, both IE86 and IE72 antigens' expression was effectively suppressed by allitridin treatment, and the inhibitory rate of IE86 was almost twice of IE72's. Compared with GCV, allitridin had stronger inhibitory effect on IE86 expressing, although its efficacy on IE72 was weaker than GCV. CONCLUSION: Allitridin could suppress the expression of IE72 and IE86, especially for IE86 expressing, maybe it is ore of key role in the mechanism of allitridin against HCMV.

Fast and sensitive detection of protein concentration in mild environments.

Determination of protein concentration in mild environments is of great significance in the clinic diagnose and bioassay. Herein, a simple, fast and sensitive method for protein quantitative determination in neutral solution (pH 7.0) is developed. This assay is based on competition adsorption of the sample protein and fluorescently labeled dog serum albumin (FITC-DSA) onto gold nanoparticles (AuNPs). As the competitor FITC-DSA molecules are added into the mixture solution of sample protein conjugated AuNPs, they will compete for active sites of AuNPs, resulting in decrease in fluorescence intensity due to the quenching effect of AuNPs via fluorescence resonance energy transfer (FRET). Thus, quantitative determination of sample protein concentration can be achieved. Under the optimum conditions, the decrease in fluorescence intensity of the solution is related to the concentration of sample protein and a low detection limit of 0.01 µg/mL BSA can be achieved in 5 min. For the validation of our strategy in practical applications, the total protein content in human serum was determined using the as-proposed method. The result is in well agreement with that of measured by other conventional methods, suggesting a simple, accurate, and mild approach for protein detection in bioassay.

A micro-computed tomography study of the location and curvature of the lingual canal in the mandibular first premolar with two canals originating from a single canal.

INTRODUCTION: Little is known about the lingual canal in the Vertucci type V mandibular first premolar. This study investigated the location of the lingual canal orifice and the curvature of the lingual canal by using micro-computed tomography. METHODS: One hundred fifteen mandibular first premolars were scanned by micro-computed tomography, reconstructed 3-dimensionally by using Mimics 10.01 software, and displayed in parallel projection mode. Twenty-six teeth with Vertucci type V canal were selected for further study. The lingual canal orifice was located by measurements made in both lingual and proximal views. The angle alpha (α) between the start of the lingual canal and the main canal and the angle beta (ß) of the curvature of lingual canal were also measured. RESULTS: In proximal view, 69% of lingual canals were located in the middle third of the tooth and the remainder in the apical third. In lingual view, 73% were located in the middle third of the root and the remainder in the coronal third. Mean angle α and angle ß were 33.54° and 26.66°, respectively, in proximal view and 8.31° and 11.31°, respectively, in lingual view (P < .05). The highest values of angles α and ß were observed in proximal view (65.24°and 43.39°, respectively). In most cases, angles α and ß were severely curved in proximal view and straight or only slightly curved in lingual view. CONCLUSIONS: Detailed information on the lingual canal is essential for successful endodontic treatment in patients with mandibular first premolar. The view used for imaging influences the information obtained.