bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Chiral Labtb and Visualization of Its Enantiomeric Excess by Induced Circular Dichroism Imaging
Authors: Yamada Teppei , Eguchi Toshiki , Wakiyama Taro , Narushima Tetsuya , Okamoto Hiromi , Kimizuka Nobuo
Published: April 2019

Crystalline particles of a microporous, robust, and chiral metal–organic framework (MOF) were synthesized and their enantiomer excess (ee) was visualized for each microparticle by CD imaging. Labtb, a thermally and chemically robust MOF, was employed in this study because it shows a chiral space group. Although Labtb has been obtained as a racemic conglomerate, enantioselective synthesis of Labtb was achieved via a chiral precursor complex consisting of lanthanum and homochiral phenylalanine. Methyl orange (MO) was introduced into the micropores of chiral Labtb, which showed a strong induced CD signal for the absorption band of MO chromophores. High ee of the chiral Labtb was revealed by microscopic CD observation at the particle‐level. This result provides a facile way to obtain a robust MOF that has chiral nanospace.
Enantioselective Desymmetrization of 1,4‐Dihydropyridines by Oxidative NHC Catalysis
Authors: Di Carmine Graziano , Ragno Daniele , Brandolese Arianna , Bortolini Olga , Pecorari Daniel , Sabuzi Federica , Mazzanti Andrea , Massi Alessandro
Published: April 2019

The unprecedented desymmetrization of prochiral dialdehydes catalyzed by N‐heterocyclic carbenes under oxidative conditions was applied to the highly enantioselective synthesis of 1,4‐dihydropyridines (DHPs) starting from 3,5‐dicarbaldehyde substrates. Synthetic elaboration of the resulting 5‐formyl‐1,4‐DHP‐3‐carboxylates allowed for access to the class of pharmaceutically relevant 1,4‐DHP‐3,5‐dicarboxylates (Hantzsch esters). DFT calculations suggested that the enantioselectivity of the process is determined by the transition state involving the oxidation of the Breslow intermediate by the external quinone oxidant.
Chrysene‐Bridged Porphyrin Tweezers: Chiral Receptors for Fullerenes
Authors: Mori Shigeki , Kawamoto Naoki , Uno Hidemitsu
Published: April 2019

Bis(bicyclic) molecules dimethanochrysene and diethanochrysene were prepared by Diels‐Alder reaction of the naphthodiyne equivalent with cyclopentadiene and 1,3‐cyclohexadiene, respectively. Reaction of dimethanochrysene and 7,9‐diphenyl‐8H‐cyclopent[a]acenaphthylen‐8‐one resulted in the generation of a fluorescent hydrocarbon in unexpected multistep pericyclic reactions. Syn‐oriented diethanochrysene‐connected bisporphyrin tweezers was prepared from the reaction of chrysene‐bridged syn‐dipyrrole with tripyrranedicarbaldehyde. The structure of the receptor and its 1 : 1 complex with C60 or C70 was determined by X‐ray diffraction analysis. The dihedral angles of the bicyclo[2.2.2]octadiene moieties were narrowed by complexation of the receptor with the fullerenes. The binding affinities of the tweezers with C60 and C70 were calculated to be 2.7(4)×104 and 8.01(7)×104 M−1, respectively by UV‐vis and fluorescence spectroscopy.
Dual Colorimetric/Fluorometric Double‐Throw pH‐Switches: The Dimroth Rearrangement of N,9‐Diaryl 8‐Azaadenines
Authors: Li Bo , Jiang Shichao , Gao Jingshuo , Wu Xueting , Deng Jiajie , Zhang Linmeng , Yu Zhipeng
Published: April 2019

A library of 12N,9‐Diaryl 2‐methyl‐8‐azaadenine (DAMA) compounds was designed and constructed through an aryl‐pairing combination strategy for identifying a nucleobase‐containing molecular switch that functions by the pH‐regulated Dimroth rearrangement. By utilizing 2D thin‐layer chromatography/mass spectrometry (2D‐TLC‐MS), the DAMA compounds were easily screened to identify which compounds could be used as molecular switches. The pH‐switching ability of the DAMA was achieved by incorporating the acridine group as the key structural unit, as well as dual‐modal colorimetric/fluorometric on/off properties as the probe functions. The real‐time tracing of the switching process clearly indicated that the paired aromatics on both terminals of the DAMA molecule play a key role in tuning the switching kinetics.
DSM‐5 eating disorder symptoms in adolescents with and without attention‐deficit/hyperactivity disorder: A population‐based study
Authors: Bisset Matthew , Rinehart Nicole , Sciberras Emma
Published: April 2019

Objective

Attention‐deficit/hyperactivity disorder (ADHD) is associated with increased eating disorder symptoms, yet little research examining this association has taken a diagnostic approach using a population‐based sample. This cross‐sectional study examined differences in DSM‐5 eating disorder symptoms and partial‐syndrome diagnoses at 14–15 years of age in adolescents with and without ADHD in a population‐based sample.

Method

This study uses data from waves 1, 5 and 6 of the Longitudinal Study of Australian Children (N = 2,672). ADHD (6.9%) was defined at 12–13 years of age by both parent‐ and teacher‐reported hyperactivity‐inattention scores ≥90th percentile on the Strengths and Difficulties Questionnaire, parent‐reported ADHD diagnosis, and/or ADHD medication treatment. Adolescents reported eating disorder symptoms at 14–15 years of age via the Branched Eating Disorders Test.

Results

Boys with ADHD had greater odds of regular objective binge eating than boys without ADHD (OR: 9.4; 95% CI: 1.7–52.8; p = .01). Groups did not differ in prevalence of any other eating disorder symptoms or partial‐syndrome diagnoses.

Discussion

Boys with ADHD appear to be at a greater risk of regular binge eating classified by DSM‐5 criteria at 14–15 years of age. Overall, the risk for eating disorder symptoms and partial‐syndrome diagnoses in adolescents with ADHD does not appear to be high at 14–15 years of age when using DSM‐5 criteria with population‐based sampling.
The use of DNA barcodes to estimate phylogenetic diversity in forest communities of southern China
Authors: Liu Jiajia , Liu Juan , Shan You-Xia , Ge Xue‐Jun , Burgess Kevin S.
Published: April 2019

To elucidate potential ecological and evolutionary processes associated with the assembly of plant communities, there is now widespread use of estimates of phylogenetic diversity that are based on a variety of DNA barcode regions and phylogenetic construction methods. However, relatively few studies consider how estimates of phylogenetic diversity may be influenced by single DNA barcodes incorporated into a sequence matrix (conservative regions vs. hypervariable regions) and the use of a backbone family‐level phylogeny. Here, we use general linear mixed‐effects models to examine the influence of different combinations of core DNA barcodes (rbcL, matK, ITS, and ITS2) and phylogeny construction methods on a series of estimates of community phylogenetic diversity for two subtropical forest plots in Guangdong, southern China. We ask: (a) What are the relative influences of single DNA barcodes on estimates phylogenetic diversity metrics? and (b) What is the effect of using a backbone family‐level phylogeny to estimate topology‐based phylogenetic diversity metrics? The combination of more than one barcode (i.e., rbcL + matK + ITS) and the use of a backbone family‐level phylogeny provided the most parsimonious explanation of variation in estimates of phylogenetic diversity. The use of a backbone family‐level phylogeny showed a stronger effect on phylogenetic diversity metrics that are based on tree topology compared to those that are based on branch lengths. In addition, the variation in the estimates of phylogenetic diversity that was explained by the top‐rank models ranged from 0.1% to 31% and was dependent on the type of phylogenetic community structure metric. Our study underscores the importance of incorporating a multilocus DNA barcode and the use of a backbone family‐level phylogeny to infer phylogenetic diversity, where the type of DNA barcode employed and the phylogenetic construction method used can serve as a significant source of variation in estimates of phylogenetic community structure.
Palladium Catalyzed Cross‐Dehydrogenative Coupling/Annulation Reaction: A Practical and Efficient Approach to Hydroxyisoindolo[1,2‐b]quinazolinone
Authors: Dabiri Minoo , Lehi Noushin Farajinia , Movahed Siyavash Kazemi , Khavasi Hamid Reza
Published: April 2019

The palladium‐catalyzed cross‐dehydrogenative coupling (CDC) followed by an intramolecular cyclization between arylquinazolinones and aldehydes has been described. This viable transformation provides a variety of novel substituted hydroxyisoindolo[1,2‐b]quinazolinone compounds in moderate to good yields. Additionally, the reaction is performed with toluene in place of benzaldehyde by using an excess amount of tert‐butyl hydroperoxide (TBHP) as the oxidant in good yield.
Applicability of various adsorption isotherm models on adsorption of methane and CO2 on Indian shales
Authors: Rani Sneha , Prusty Basanta K. , Padmanabhan Eswaran , Pal Samir K.
Published: April 2019

To produce natural gas (methane) and simultaneously sequester CO2 in unconventional geologic reservoirs such as gas shale, coalbeds and so on, it is necessary to understand the adsorption behavior of methane and CO2 in these reservoir formations. In this article, adsorption behavior of methane and CO2 on shale samples from Gondwana Basin and KG Basin of India are studied. Adsorption experiments are conducted on as‐received shale samples from these basins at a temperature of 313 K to a maximum equilibrium pressure of approximately 9 MPa for methane and 6 MPa for CO2. The methane and CO2 adsorption data are applied to test the applicability of Langmuir, Dubinin‐Polanyi, BET, and Ono‐Kondo models. A comparison of these models is performed using linear and nonlinear Chi‐squared methods. It was observed that Dubinin‐Astakhov equation was the most accurate adsorption isotherm model for adsorption of methane and CO2 on tested shales. Further, the better fitting by Dubinin‐Polanyi equation over BET, Langmuir, and Ono‐Kondo models suggest that the mechanism of volume filling may be applicable during the adsorption of methane and CO2 on shales. The preferential adsorption of methane and carbon dioxide on Pakur, KG, and Salanpur shales were investigated. The Pakur shale had CO2:CH4 adsorption ratio ~1. © 2019 American Institute of Chemical Engineers Environ Prog, 38: 13222, 2019
Quality function deployment modified for the food industry: An example of a granola bar
Authors: Wang Tzu‐Yun , Hsiao Hsin‐I , Sung Wen‐Chieh
Published: April 2019

Applying quality function deployment (QFD) in the food industry is complex. The objective of this study was to provide a modified QFD approach to facilitate its use and test it on a granola bar. A 7‐step model is proposed (modified from the 9‐step sensory attributes model) incorporating competitive analysis to acquire final importance ratings of customer needs, the application of fuzzy logic in surveys and interviews, and replacing precise value of relative technical ratings by priority rankings. The 7‐step model starts with understanding customer needs (WHATs) and prioritizing their importance based on the customer survey and competitive analysis, followed by identification of product's sensory attributes (HOWs) and the strength of their relationship with customer needs. Lastly, relative technical ratings—to develop priority rankings for the product development team—are determined based on the degree of importance of the WHATs and the strength of the relationships between the WHATs and the HOWs. Testing the 7‐step model on granola bars showed that the relative technical ratings reflected the majority of customer needs and the importance they attached to those needs.
The expression profiling of circulating miR‐204, miR‐182, and lncRNA H19 as novel potential biomarkers for the progression of peptic ulcer to gastric cancer
Authors: Mohamed Waleed A. , Schaalan Mona F. , Ramadan Basma
Published: April 2019

Deregulation of noncoding RNAs, microRNAs (miRNAs) and long noncoding RNA (lncRNA), are implicated in the initiation and progression of gastric cancer (GC). This study is a pilot case‐control study carried out on 75 subjects, 40 of them were Helicobacter pylori‐gastric ulcer patients and 35 were GC patients recruited from the Gastrointestinal Endoscopy Unit in Al‐Kasr Al‐Aini Hospital, Cairo University in Egypt. Real‐time PCR was performed to evaluate the expression level of serum miR‐204, miR‐182, and lncRNA H19 in patients with peptic ulcer‐progressed GC vs nonprogressed peptic ulcer patients. Fibroblast growth factor 18 (FGF‐18)/FGF receptor 2 (FGFR2) expression and their downstream immunological and inflammatory signaling markers were assessed and their association with the addressed noncoding RNAs investigated. As regards miR‐204 and miR‐182, they were significantly increased (12.5 and 2.6 folds, respectively) in GU samples, compared with those of healthy control levels. The elevated levels of these miRNAs were significantly de‐escalated in GC samples compared with GU and the fold decrease valued 2.2 fold for miR‐204 and 1.8 folds for miR‐182. On the other hand, the significant escalation in the level of lnRNA H19 in GU recorded a 16.6 fold increase and further elevation in its levels was evident in GC samples. The herein assessed miRNAs are correlated with disease duration and FGFR2 with miR‐182 being significantly correlated with all inflammatory markers, TAC, INF‐γ, matrix metallopeptidase 9, and FGF‐18. In terms of diagnostic accuracy of assessed miRNAs (stages III to IV), the receiver operating characteristic analysis indicated that serum lncRNA H19 showed the highest diagnostic accuracy (95.5%), specificity (100%), and sensitivity (90.9%), compared with miR‐204 and miR‐182, which showed the same specificity (60%), sensitivity (72.7%), and diagnostic accuracy (68.8%). Our findings conclude that lnRNA H19, miR‐204, and miR‐182 may function as novel prospective plasma biomarkers to detect GC and its progression from H. pylori‐peptic ulcer, which would be helpful to improve the theranostics of GC.
Platycodin D protects cortical neurons against oxygen‐glucose deprivation/reperfusion in neonatal hypoxic‐ischemic encephalopathy
Authors: Wang Guifang , Guo Hongxiang , Wang Xiaofang
Published: April 2019

Neonatal hypoxic‐ischemic encephalopathy is one of the leading causes of death in infants. Increasing evidence indicates that oxidative stress and apoptosis are major contributors to hypoxic‐ischemic injury and can be used as particularly promising therapeutic targets. Platycodin D (PLD) is a triterpenoid saponin that exhibits antioxidant properties. The aim of this study was to evaluate the effects of PLD on hypoxic‐ischemic injury in primary cortical neurons. We found that oxygen‐glucose deprivation/reperfusion (OGD/R) induced inhibition of cell viability and cytotoxicity, which were attenuated by PLD treatment. PLD treatment inhibited oxidative stress induced by OGD/R, which was evidenced by the reduced level of reactive oxygen species and increased activities of catalase, superoxide dismutase, and glutathione peroxidase. Histone‐DNA enzyme‐linked immunosorbent assay revealed that apoptosis was significantly decreased after PLD treatment in OGD/R‐treated cortical neurons. The increased bax expression and decreased bcl‐2 expression induced by OGD/R were reversed by PLD treatment. Furthermore, PLD treatment caused the activation of the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway in OGD/R‐stimulated cortical neurons. Suppression of this pathway blocked the protective effects of PLD on OGD/R‐induced cell injury. These findings suggested that PLD executes its protective effects on OGD/R‐induced cell injury via regulating the PI3K/Akt/mTOR pathway in cortical neurons.
Wnt pathway targeting reduces triple‐negative breast cancer aggressiveness through miRNA regulation in vitro and in vivo
Authors: Mohammadi‐Yeganeh Samira , Hosseini Vahedeh , Paryan Mahdi
Published: April 2019

Triple‐negative breast cancer, devoid of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER‐2) expression, is deprived of commonly used targeted therapies. MicroRNAs (miRNAs) are undergoing a revolution in terms of potentially diagnostic or therapeutic elements. Combining computational approaches, we enriched miRNA binding motifs of Wnt pathway‐associated upregulated genes. Our in‐depth bioinformatics, in vitro and in vivo analyses indicated that miR‐381 targets main genes of the Wnt signaling pathway including CTNNB1, RhoA, ROCK1, and c‐MYC genes.

The expression level of miR‐381 and target genes was assessed by quantitative real‐time polymerase chain reaction (RT‐qPCR) in MCF‐7, MDA‐MB‐231, and MCF‐10A as well as 20 breast cancer samples and normal tissues. Luciferase reporter assay was performed. Lentiviral particles containing miR‐381 were used to evaluate the effect of miR‐381 restoration on cell proliferation, migration, and invasion of the invasive triple‐negative MDA‐MB‐231 cell line and also in a mouse model of breast cancer.

The expression of miR‐381 was lower than that of normal cells, especially in TNBC cell line and breast tissues. Luciferase assay results confirmed that miR‐381 targets all the predicted 3′‐untranslated regions (3′‐UTRs). Upon miR‐381 overexpression, the expression of target genes declined, and the migration and invasion potential of miR‐381‐receiving MDA‐MB‐231 cells decreased. In a mouse model of triple‐negative breast cancer, miR‐381 re‐expression inhibited the invasion of cancer cells to lung and liver and prolonged the survival time of cancer cell‐bearing mice. Therefore, miR‐381 is a regulator of Wnt signaling and its re‐expression provides a potentially effective strategy for inhibition of TNBC.
Inflammation‐dependent downregulation of miR‐194‐5p contributes to human intervertebral disc degeneration by targeting CUL4A and CUL4B
Authors: Chen Zhi , Han Yingchao , Deng Chao , Chen Wei , Jin Linyu , Chen Hao , Wang Kun , Shen Hongxing , Qian Lie
Published: April 2019

Inflammation is one of the major causes of intervertebral disc degeneration (IDD). Emerging evidence has revealed that increase in the levels of pro‐inflammatory cytokines, such as interleukin 6 (IL‐6) and tumor necrosis factor alpha (TNF‐α), can activate a variety of signaling pathways, eventually resulting in IDD. Here, we show that the two cullin family genes, CUL4A and CUL4B, but not other cullins, are specifically overexpressed in IDD samples compared with healthy controls, and the CUL4A and CUL4B levels are positively correlated with the severity of IDD. In vitro analyses in human osteoblast cells (hFOB1.19), nucleus pulposus cells (hNPCs), and annulus fibrosus cells (hAFCs) indicated that treatment with IL‐6 and TNF‐α can increase CUL4A and CUL4B levels. By performing a microRNA‐based microarray analysis, we found a set of microRNAs (miRNAs) that were differentially expressed in IDD samples compared with samples from healthy controls. Of these miRNAs, miR‐194‐5p, was significantly downregulated in IDD samples and could bind to the three prime untranslated regions (3′‐UTRs) of both CUL4A and CUL4B, thereby downregulating their expression. The in vitro overexpression or downregulation of miR‐194‐5p, with a miR‐194‐5p‐mimic or with anti‐miR‐194‐5p, can cause the repression or induction of both CUL4A and CUL4B, respectively. Interestingly, treatment with IL‐6 and TNF‐α inhibitors in primary hNPCs and hAFCs that were isolated from patients with IDD led to the downregulation of CUL4A and CUL4B. Together, these findings provide insight into how the inflammation‐dependent downregulation of miR‐194‐5p contributes to the pathogenesis of IDD, which may aid in the development of new therapeutic approaches for IDD by directly targeting miR‐194‐5p or CUL4A and CUL4B.
NLRC5 negatively regulates LTA‐induced inflammation via TLR2/NF‐κB and participates in TLR2‐mediated allergic airway inflammation
Authors: Wang Muzi , Wang Lixia , Fang Lei , Li Shuai , Liu Rongyu
Published: April 2019

NLRC5, the largest member of the Nod‐like receptor (NLR) family, has been reported to play a pivotal role in regulating inflammatory responses. Recent evidence suggests that NLRC5 participates in Toll‐like receptor (TLR) signaling pathways and negatively modulates nuclear factor‐κB (NF‐κB) activation. In this study, we investigated the interaction between NLRC5 and TLR2 in the NF‐κB inflammatory signaling pathway and the involvement of NLRC5 in TLR2‐mediated allergic airway inflammation. We knocked down TLR2 and NLRC5, respectively in the RAW264.7 macrophage cell line by small interfering RNA (siRNA) and then stimulated the knockdown cells with lipoteichoic acid (LTA). In comparison with the negative siRNA group, the level of NLRC5 expression was lower in the TLR2 siRNA group, with a reduction in the NF‐κB‐related inflammatory response. Conversely, in the NLRC5 knockdown cells, after LTA‐treated the level of TLR2 expression did not change but the expression levels of both NF‐κB pp65 and NLRP3 increased remarkably. Thus, we hypothesize that NLRC5 participates in the LTA‐induced inflammatory signaling pathway and regulates the inflammation via TLR2/NF‐κB. Similarly, in subsequent in vivo experiments, we demonstrated that the expression level of NLRC5 was significantly increased in the ovalbumin‐induced allergic airway inflammation. However, this effect disappeared in TLR2‐deficient (TLR2
−/−) mice and was accompanied by reduced levels of NF‐κB expression and airway inflammation. In conclusion, NLRC5 negatively regulates LTA‐induced inflammatory response via a TLR2/NF‐κB pathway in macrophages and also participates in TLR2‐mediated allergic airway inflammation.
Effect of long‐term exposure of silver nanoparticles on growth indices, hematological and biochemical parameters and gonad histology of male goldfish (Carassius auratus gibelio)
Authors: Forouhar Vajargah Mohammad , Imanpoor Mohammad R. , Shabani Ali , Hedayati Aliakbar , Faggio Caterina
Published: April 2019

Studying the impact of emerging pollutants such as nanoparticles is necessary to reveal the adverse effect. In this study, the effects of silver nanoparticles (Ag‐NPs) on hematological, biochemical, and gonad histopathological indices of male goldfish were examined. Sublethal toxicity were calculated based on acute toxicity and three dosages were selected. Live specimen of Carassius auratus gibelio larval were treated in 1, 2, and 3 ppm Ag‐NP with one control group. Blood and tissue samples were extracted after 6 months exposure to sublethal concentrations. Results showed that Ag‐NPs have reduced growth rate and effected on all blood indices significantly. Biochemical analysis revealed that Ag‐NPs significantly reduced blood glucose and total protein than in comparison to the control group and caused significantly differences in the concentrations of serum cholesterol (p < .05). Furthermore, histological observation of intestine after 6 months exposure showed definite alterations in tissue and maximum hypertrophy injuries were found after long‐term exposure to 3 ppm Ag‐NPs concentration. In addition, indicated that long‐term exposure to Ag‐NPs postponed sexual maturity in male gibel carp.
Successful treatment of intractable menstrual migraine with the traditional herbal medicine tokishakuyakusan
Authors: Akaishi Tetsuya , Takayama Shin , Ohsawa Minoru , Kikuchi Akiko , Arita Ryutaro , Nakashima Ichiro , Aoki Masashi , Ishii Tadashi
Published: April 2019

In this report, we present the successful treatment of five consecutive cases of premenopausal women suffering from severe menstrual migraine with tokishakuyakusan (TSS). Two patients were complicated by tension‐type headache (TTH), and another patient was by medication overuse headache (MOH). The effects of triptans were limited in all of them. After starting TSS, they showed dramatic improvement in the severity and frequency of their attacks. The patients with TTH and MOH also showed dramatic improvement in their symptoms. TSS could be a promising alternative choice for patients with intractable menstruation–related headaches that are refractory to conventional treatments, including triptans.
Augmentation with pre‐emptive macrogol‐based osmotic laxative does not significantly improve standard bowel preparation in unselected patients: A randomized trial
Authors: Mangira Dileep , Ket Shara , Dwyer Jeremy , Secomb Robyn , Reynolds John , Brown Gregor
Published: April 2019

Background and Aim

The addition of a laxative prior to a standard bowel preparation (BP) has shown variable results in efficacy, safety, and tolerability of the BP. This study compared the efficacy and tolerability of a macrogol‐augmented BP (M‐BP) with standard BP for routine colonoscopy in unselected patients.

Methods

Adults undergoing outpatient colonoscopy were randomized to either M‐BP (one sachet of macrogol‐based osmotic laxative (MBOL) twice daily for eight doses prior to standard preparation) or BP (split‐dose of polyethylene glycol and sodium picosulfate). Bowel cleansing was assessed using the Ottawa BP scale. Risk factors for poor BP, patient satisfaction, and tolerance were recorded.

Results

This randomized trial was stopped due to futility after 14 months; at that point, 92 subjects were randomized to the study arm and 102 to the control arm. M‐BP had a success rate of 71.7% (95% CI: 58.5–82.7%), while the BP had a success rate of 67.7% (95% CI: 54.9–78.8%), with a Pearson χ2 test P‐value of 0.639, which exceeded the cut‐off for futility (0.313). In subgroup analyses, there were statistically significant decreases in the rates of successful BP in patients taking regular opioids and regular laxatives. Both preparations were well tolerated, with no difference between groups (BP – 5.3% and M‐BP – 6.6% P = 0.66).

Conclusion

The addition of MBOL prior to a standard BP in unselected subjects does not significantly improve bowel cleanliness at routine colonoscopy. The role of this laxative in patients at high risk of poor preparation warrants further investigation.
Propofol inhibits pancreatic cancer progress under hypoxia via ADAM8
Authors: Gao Yutong , Yu Xiangdi , Zhang Fangxiang , Dai Jing
Published: April 2019

Background

To investigate the potential anti‐tumoral properties of propofol in pancreatic cancer and elucidate the underlying mechanisms.

Methods

The relative expression of ADAM metallopeptidase domain 8 (ADAM8) in response to hypoxia in Panc1 cells was analyzed by western blotting. The enzymatic activity was determined by fluorescence release from PEPDAB013 decomposition. Cell growth was measured via cell counting and cell viability was measured using CCK‐8 kit. Cell migrative capacity was evaluated by transwell and adhesion assay. The relative abundance of angiogenesis‐related markers including platelet‐derived growth factor AA, angiogenin, endothelin‐1 and vascular endothelial growth factor were determined by real‐time polymerase chain reaction and western blotting. The anti‐tumoral activity of propofol was investigated with Panc1‐derived xenograft mice model.

Results

ADAM8 was significantly induced by hypoxia and efficiently inhibited by co‐treatment with propofol. Propofol suppressed proliferation and compromised viability of Panc1 cells. In addition, the migrative capacity was greatly inhibited by propofol dosage. Comprehensive profiling of angiogenesis‐related markers demonstrated that propofol remarkably suppressed neovascularization response in Panc1 cells under hypoxia. We further uncovered that propofol administration via subcutaneous injection delayed xenograft tumor progression.

Conclusion

Propofol specifically inhibited ADAM8 expression and activation in response to hypoxia in pancreatic cancer, and held great value for therapeutic effects.
Synthesis of Novel Pterocarpen Analogues via [3 + 2] Coupling‐Elimination Cascade of α,α‐Dicyanoolefins with Quinone Monoimines
Authors: Chen Hui , Zhao Sihan , Cheng Shaobing , Dai Xingjie , Xu Xiaoying , Yuan Weicheng , Zhang Xiaomei
Published: April 2019

By employing triethylamine as a catalyst, [3 + 2] coupling‐elimination cascade of α,α‐dicyanoolefins with quinone monoimines was realized. The reactions afforded various novel pterocarpen analogues with generally moderate yields (up to 75%). In addition, a plausible reaction mechanism was proposed.
Synthesis and Anticancer Evaluation of Some Novel Quinazolin‐4(3H)‐one Derivatives
Authors: Gouhar Rasha S. , Haneen David S. A. , El‐Hallouty Salwa M.
Published: April 2019

A new series of quinazolinone derivatives bearing pyridine, pyrimidine, pyrazole, or pyran moieties were synthesized for the purpose of anticancer cell line evaluation. Synthesis of these derivatives was achieved by the reaction of the ketone 2 with the appropriate aldehydes in the presence of either ethylcyanoacetate or malononitrile and ammonium acetate in one‐pot reaction. Chalcones 6 reacted also with hydrazine hydrate to give the corresponding pyrazolines 7 and reacted with urea or thiourea to give the 2‐oxopyrimidines or the 2‐thioxopyrimidines 8, respectively. Evaluation of some representative examples of the newly synthesized compounds against cancer cell lines showed promising activity as anticancer agents.
Mutations in the translocon‐associated protein complex subunit SSR3 cause a novel congenital disorder of glycosylation
Authors: Ng Bobby G. , Lourenço Charles M. , Losfeld Marie‐Estelle , Buckingham Kati J. , Kircher Martin , Nickerson Deborah A. , Shendure Jay , Bamshad Michael J. ,   University of Washington Center for Mendelian Genomics, Freeze Hudson H.
Published: April 2019

The translocon‐associated protein (TRAP) complex facilitates the translocation of proteins across the endoplasmic reticulum membrane and associates with the oligosaccharyl transferase (OST) complex to maintain proper glycosylation of nascent polypeptides. Pathogenic variants in either complex cause a group of rare genetic disorders termed, congenital disorders of glycosylation (CDG). We report an individual who presented with severe intellectual and developmental disabilities and sensorineural deafness with an unsolved type I CDG, and sought to identify the underlying genetic basis. Exome sequencing identified a novel homozygous variant c.278_281delAGGA [p.Glu93Valfs*7] in the signal sequence receptor 3 (SSR3) subunit of the TRAP complex. Biochemical studies in patient fibroblasts showed the variant destabilized the TRAP complex with a complete loss of SSR3 protein and partial loss of SSR1 and SSR4. Importantly, all subunit levels were corrected by expression of wild‐type SSR3. Abnormal glycosylation status in fibroblasts was confirmed using two markers proteins, GP130 and ICAM1. Our findings confirm mutations in SSR3 cause a novel CDG.

A novel frameshift variant in the translocon associated protein, SSR3, disrupts the stability of the TRAP complex and causes a novel Congenital Disorder of Glycosylation.
Advances in understanding of presbycusis
Authors: Tawfik Kareem O. , Klepper Kristin , Saliba Joe , Friedman Rick A.
Published: April 2019

The pathophysiology of age‐related hearing loss (ARHL), or presbycusis, involves a complex interplay between environmental and genetic factors. The fundamental biomolecular mechanisms of ARHL have been well described, including the roles of membrane transport, reactive oxygen species, cochlear synaptopathy, vascular insults, hormones, and microRNA, to name a few. The genetic basis underlying these mechanisms remains under‐investigated and poorly understood. The emergence of genome‐wide association studies has allowed for the identification of specific groups of genes involved in ARHL. This review highlights recent advances in understanding of the pathogenesis of ARHL, the genetic basis underlying these processes and suggests future directions for research and potential therapeutic avenues.
Copolymers of Diallyldimethylammonium Chloride and Vinyl Ether of Monoethanolamine: Synthesis, Flocculating, and Antimicrobial Properties
Authors: Dauletov Yerbol , Nuraje Nurxat , Abdiyev Kaldibek , Toktarbay Zhexenbek , Zhursumbaeva Maryamgul
Published: April 2019

N,N‐diallyl‐N,N‐dimethylammonium chloride (DADMAC) and vinyl ether of monoethanolamine (VEMEA) copolymer P(DADMAC‐VEMEA) were synthesized using radical polymerization in water media using ammonium persulfate as an initiator. The synthesis of this copolymer was investigated over a wide composition range at low conversion levels. The viscosity of the copolymers was measured in aqueous 1 M NaCl. Flocculating action and antimicrobial activities of the copolymers P(DADMAC‐VEMEA) against microbacteria and sulfate‐reducing bacteria (SRB) were studied. Synthesized copolymers had flocculating effects and can be used to purify wastewater from particles of bentonite clays. Also, the copolymer with a molar composition [DADMAC]: [VEMEA] = (80÷20):(20÷80) retarded the population of both bacteria, Gram‐positive (Staphylococcus aureus) and Gram‐negative (Escherichia coli) in the diffusion zone. Furthermore, the copolymer with a molar composition [DADMAC]:[VEMEA] = (90÷10):(20÷80) had bactericidal properties against SRB. Minimum inhibitory concentration (MIC) of the copolymer varied from 0.01% to 0.1% depending on the molar composition of the copolymer.
Studies of Superb Microvascular Imaging and Contrast‐Enhanced Ultrasonography in the Evaluation of Vascularization in Early Bone Regeneration
Authors: Jin Lin , Li Ping , Wang Ying‐Chun , Feng Lan , Xu Rong , Yang De‐Bin , Yao Xiao‐Hua
Published: April 2019

Objective

The aim of this study was to investigate value of superb microvascular imaging (SMI) and contrast‐enhanced ultrasonography (CEUS) in evaluating the neovascularization of early bone regeneration.

Methods

Twenty‐five Sprague‐Dawley male rats were implanted with recombinant human bone morphogenetic protein‐2/calcium phosphate cement (rhBMP‐2/) in the muscle space of the left hind limb near the femoral head to establish the rat model of intramuscular ectopic osteogenesis. Ultrasonography and pathologic analysis were performed on the 3rd, 7th, 14th, 21st, and 28th days after modeling. Two‐dimensional ultrasonography, SMI, and CEUS were used to assess neovascularization and bone formation.

Results

Pathologic examination showed that different levels of neovascularization were observed in the graft bone over time after modeling, which increased significantly from the 3rd to 14th day, and then gradually decreased. CEUS and SMI showed no obvious microvessels inside the graft bone on the 3rd day. On the 7th day after modeling, a small number of neovascular vessels were observed around the graft bone. On the 14th day, neovascularization was observed in both the peripheral and inner parts of the graft bone. The number of neovascular vessels inside the graft bone had decreased gradually by the 21st and 28th days. The results of SMI and CEUS indexes showed that the vascular index, peak intensity, enhancement intensity, and enhancement rate first increased and then decreased with time. Their peak points were found on the 14th day. Arrival time, time to peak, and enhancement time decreased gradually over time (P < .05).

Conclusion

The combined application of SMI and CEUS may be useful in evaluating the neovascularization of early osteoanagenesis.
Visible Light–Induced RAFT Polymerization of Methacrylate with 4‐(N,N‐diphenylamino)benzaldehyde as Organophotoredox Catalyst and the Effect of Temperature on the Polymerization
Authors: Zhang Wenxiu , Zhang Xianhong , Ma Yuhong , Chen Dong , Yang Wantai
Published: April 2019

With UV–vis absorption in the range of 270–435 nm, 4‐(N,N‐diphenylamino)benzaldehyde (DPAB) takes efficient photoreduction quench with 4‐cynao‐4‐(phenylcarbonothioylthio)pentanoic acid (CTP). The polymerization rates of methyl methacrylate (MMA) are 0.019, 0.056, and 0.102 h−1 at 33, 40, and 50 °C, respectively, in the presence of DPAB and CTP under visible‐light irradiation. Dark reaction produces no PMMA at 50 °C for 120 h. The living feature is demonstrated by linearly increasing Mn with the monomer conversions and narrow polydispersity index (PDI), chain extension, and block polymerizations with benzyl methacrylate (BnMA) and poly(ethylene glycol) monomethyl ether methacrylate (PEGMA). With PMMA‐CTP (Mn = 6800, PDI = 1.17), chain extension gives PMMA with Mn = 15 900 and PDI = 1.15. With PMMA‐CTP (Mn = 6000, PDI = 1.21) as macro‐RAFT, PMMA‐b‐PBnMA of Mn = 12 600 (PDI = 1.44) and Mn = 18 500 (PDI = 1.31) are prepared. These results support that there is a positive synergistic effect between polymerization temperature and visible‐light irradiation on the photo‐RAFT without losing the living features.
Impact of advanced age on microvascular reconstruction of the lower facial third: An American College of Surgeons NSQIP study
Authors: Torabi Sina J. , Chouairi Fouad , Dinis Jacob , Alperovich Michael
Published: April 2019

Background

Microvascular reconstruction is the standard of care in head and neck reconstruction, though its perioperative safety in an older population has been controversial due to safety concerns, warranting further investigation.

Materials and methods

An “older” (≥71 years) cohort undergoing reconstruction after mandibulectomy/glossectomy was compared to the remaining population in a National Surgical Quality Improvement Program (2008–2016) analysis. Cases required both a mandibulectomy/glossectomy and microvascular or local flap reconstruction (exclusion criteria: missing ages and simultaneous microvascular and local flap reconstruction). Demographics, comorbidities, and procedure types were analyzed on 985 patients (236 [24.4%] were ≥71). Outcomes were compared by reconstruction type. Regressions were performed calculating the impact of age on length of hospital stay (LOHS) and operative time.

Results

Ablative procedures were comparable, but older patients received local flaps at higher rates (22.5% vs. 9.6%; p < .001). The older population had more comorbidities (higher ASA class [p < .001], diabetes [p < .001], and hypertension [p < .001]). After Bonferroni correction, univariate subgroup analyses of soft tissue and bone/composite microvascular flaps revealed similar outcomes (except increased medical complications in the older cohort undergoing a bone free flap [p = .002]). Controlling for a variety of factors, older age resulted in longer LOHS (B: 1.4 days; 95% CI: 0.1–2.8 days; p = .035), but not operative time (B: −21.90 min; 95% CI: −52.76 to 8.96 min; p = .164).

Conclusion

While increased age (≥70 years) was associated with a longer LOHS, complication rates were comparable. Although limited by the retrospective nature, evidence supports microvascular reconstruction in the elderly population with comparable outcomes.
Effects of thermosensory aging well demonstrated by cold stimulations with high temporal resolution
Authors: Després Olivier , Lithfous Ségolène , Pebayle Thierry , Casadio Claudia , Dufour André
Published: April 2019

Introduction: The method of limits (MLi) is the most commonly used paradigm to measure the threshold of thermal stimuli. However, the threshold measured by MLi is dependent on reaction time (RT). Because RT in adults increases with age, the inclusion of RT in the MLi paradigm may result in an overestimation of thermal threshold in the older individuals. Methods: A device with a very rapid cooling rate (300°C/s) was employed to measure cool thresholds by using the method of levels (MLe), a method independent of RT, in 11 older patients and 14 younger adults. Results: Compared with the MLi, the MLe resulted in a greater than 2°C gain in threshold measurement accuracy in older patients. Discussion: The MLe confirmed that cool perception threshold is dependent on age. The use of MLe provides new opportunities for the study of mechanisms underlying age‐associated alterations in thermal perception. Muscle Nerve 60: 141–146, 2019
Effects of topical estrogen therapy on the vaginal microcirculation in women with vulvovaginal atrophy
Authors: Diedrich Chantal M. , Kastelein Arnoud W. , Verri Filippo M. , Weber Maaike A. , Ince Can , Roovers Jan‐Paul W. R.
Published: April 2019

Aims

This study aims to assess vaginal wall angioarchitecture and function in women with vulvovaginal atrophy (VVA) and determine the effect of topical estrogen on the vaginal microcirculation.

Materials and Methods

In this prospective observational study, incident dark field imaging was used to assess the vaginal microcirculation. In patients with VVA, measurements were performed before and after treatment with topical estrogen and compared to measurements performed in women without VVA. Vaginal angioarchitecture was studied by assessing microcirculatory architecture and capillary tortuosity scores at four regions of the vaginal wall. In addition, the capillary density and microvascular flow index (MFI) were obtained.

Results

Seventeen women were included in this study. Of these, eight women were diagnosed with VVA and nine women were considered healthy controls. Significant differences were observed between groups with regard to microcirculatory architecture scores. The architecture of the microvasculature in women with VVA was characterized by the appearance of a vascular network without capillary loops, whereas an array of capillary loops was predominantly seen in women without VVA. After estrogen treatment, no difference in architecture scores between patients and healthy controls was observed. Capillary tortuosity, capillary density, and MFI were similar in both groups before and after estrogen treatment.

Conclusions

The architecture of vaginal microvasculature is altered in patients with VVA. In case of similar vascular architecture, capillary tortuosity and density seem to be comparable. Treatment with topical estrogen results in restoration of the angioarchitecture.
Patterns and predictors of Hunner lesion recurrence in patients with interstitial cystitis
Authors: Han Ji‐Yeon , Shin Jung Hyun , Choo Myung‐Soo
Published: April 2019

Aims

To evaluate the patterns and predictive factors associated with Hunner lesions (HLs) recurrence in patients with interstitial cystitis (IC).

Methods

This study was a retrospective analysis of data from patients with IC who underwent transurethral resection and cauterization (TUR‐C) of HLs between October 2011 and December 2017. Symptoms were evaluated using the Pelvic Pain and Urgency/Frequency Patient Symptom Scale (PUF), O'Leary‐Sant Interstitial Cystitis Symptom Index, and Visual Analogue Scale (VAS). Patients attended follow‐up visits every 3 months; cystoscopy was performed immediately in patients with aggravated symptoms. Recurrence was defined as a VAS score greater than or equal to 4 and HLs recurrence on cystoscopy.

Results

A total of 91 patients were enrolled (25 male, 66 female): median follow‐up was 30.6 months. HLs recurrence occurred in 101 sites (53 patients), 21.8% in the previous TUR‐C site, 18.8% de novo, and 59.4% at both previous and de novo sites. The recurrence rate was approximately 12.7%, 40%, and 55.2% at 6, 12, and 18 months, respectively. A higher PUF bother score was the only predictive factor of recurrence (odds ratio: 1.142, 95% confidence interval: 1.016‐1.284, P = 0.026), with a cut‐off value of 7.5 (sensitivity: 67.9%, specificity: 62.5%). In case of late recurrence (>18 months), there was no predictive factor.

Conclusions

The HLs recurrence pattern was unpredictable, involving both previous TUR‐C and de novo areas. More accurately defining the HLs resection margin may lead to better surgical outcomes but this remains to be proven.
Subspace methods for three‐parameter eigenvalue problems
Authors: Hochstenbach Michiel E. , Meerbergen Karl , Mengi Emre , Plestenjak Bor
Published: April 2019

We propose subspace methods for three‐parameter eigenvalue problems. Such problems arise when separation of variables is applied to separable boundary value problems; a particular example is the Helmholtz equation in ellipsoidal and paraboloidal coordinates. While several subspace methods for two‐parameter eigenvalue problems exist, their extensions to a three‐parameter setting seem challenging. An inherent difficulty is that, while for two‐parameter eigenvalue problems, we can exploit a relation to Sylvester equations to obtain a fast Arnoldi‐type method, such a relation does not seem to exist when there are three or more parameters. Instead, we introduce a subspace iteration method with projections onto generalized Krylov subspaces that are constructed from scratch at every iteration using certain Ritz vectors as the initial vectors. Another possibility is a Jacobi–Davidson‐type method for three or more parameters, which we generalize from its two‐parameter counterpart. For both approaches, we introduce a selection criterion for deflation that is based on the angles between left and right eigenvectors. The Jacobi–Davidson approach is devised to locate eigenvalues close to a prescribed target; yet, it often also performs well when eigenvalues are sought based on the proximity of one of the components to a prescribed target. The subspace iteration method is devised specifically for the latter task. The proposed approaches are suitable especially for problems where the computation of several eigenvalues is required with high accuracy. MATLAB implementations of both methods have been made available in the package MultiParEig (see http://www.mathworks.com/matlabcentral/fileexchange/47844-multipareig).
Future orientation buffers depression in daily and specific stress
Authors: Zheng Lei , Lippke Sonia , Chen Yidi , Li Danyang , Gan Yiqun
Published: April 2019

Future orientation has been regarded as a protective factor that helps prevent problem behaviors, such as drug and alcohol use, smoking, and unprotected sex. Recently, many studies have focused on the relationship between a person's orientation towards the future and his or her depression symptoms; however, relatively few studies have explored the effect of future orientation on depressive responses to ordinary stress. The present study aimed to test whether future orientation could be a protective factor against depression in ordinary stress contexts. We conducted two studies to test this hypothesis and recruited 369 participants. Study 1 was a cross‐sectional study that involved 217 employees from a food‐processing company and examined the effect of future orientation in a daily stress context. Study 2 tested a hierarchical linear model in which 152 college students from an examination training institution in Beijing completed a five‐wave assessment with 3‐week intervals before taking the national entrance examination for postgraduate studies. The results showed that future orientation moderated the stress–depression relationship in the two samples. The present study provides evidence supporting the hypothesis that future orientation helps individuals cope with stress and protects people from depression, suggesting that future orientation plays a protective role in the stress–depression relationship.
Gelating polypeptide matrices based on the difunctional N‐carboxyanhydride diaminopimelic acid cross‐linker
Authors: Murphy Robert D. , Bobbi Elena , de Oliveira Fernando C. S. , Cryan Sally‐Ann , Heise Andreas
Published: April 2019

This work reports the synthesis of a new difunctional N‐carboxyanhydride (NCA) monomer, namely diaminopimelic acid (DAP), and its use in the one‐pot preparation of an organogelating copolypeptide. The organogel is formed in situ through ring‐opening polymerization (ROP) of DAP NCA from helical poly(ε‐carbobenzyloxy‐L‐lysine) (PZLL) blocks in a mixture of dimethylformamide/chloroform. Gelation occurs by immobilizing the solvent through core crosslinking and is stabilized through physical intermolecular conformations. After removal of the carbobenzyloxy (cbz or Z) protecting groups, the network remains intact in exceedingly high aqueous concentrations (99.5%). FTIR is used to characterize the secondary structure, revealing the conformational arrangements that contributed to these stabilized gel networks with their relative mechanical properties determined via real‐time rheological assays. DAP core crosslink of the random coil forming polypeptoid poly(sarcosine) (PSar) is also resulting in networks but is devoid of any stabilized physical interactions, thus yielding significantly weaker gels as a result. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019