bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of sterilization methods on pomegranate juice evaluated by descriptive sensory analysis and gas chromatography‐mass spectrometry through partial least‐squares regression
Authors: Tian Honglei , Lu Cong , Zhan Ping , Wang Peng , Zhao Yu , Tian Peng
Published: July 2020

This study aimed to investigate the effects of different sterilization methods on the flavor characteristics and volatile compounds of pomegranate (PG) juice. We analyzed three PG samples, namely conventional‐pasteurized, high‐temperature short‐time‐treated, and ultrasonic‐sterilized (US) juice samples. Fresh‐pressed PG (FJ) sample was used as the control. A total of 33 volatile compounds and six sensory attributes (floral, fruity, earthy/musty, sweet, green, and cooked flavor) of PG samples were analyzed by gas chromatography‐mass spectrometry and quantitative descriptive sensory analysis. Results revealed differences in the samples’ sensory profiles. Compared with thermal‐sterilization methods, the low temperature and relatively mild sterilization conditions of US considerably preserved the amount of volatile compounds. Partial least‐squares regression (PLSR) was performed to identify the relationships among sensory attributes, volatile compounds, and sterilization methods. Results showed that limonene, linalool, hexanal, and 6‐methyl‐5‐hepten‐2‐one contributed greatly to the key aroma of FJ and US. Meanwhile, p‐Cymene, (E)‐2‐nonenal, naphthalene, and benzothiazole were significantly correlated with the cooked flavor after thermal sterilization. PLSR further confirmed that compared with thermal‐sterilization methods, US may be more beneficial in preserving the volatile compound amount and sensory profiles of PG juice.
Evaluating shared genetic influences on nonsyndromic cleft lip/palate and oropharyngeal neoplasms
Authors: Howe Laurence J. , Hemani Gibran , Lesseur Corina , Gaborieau Valérie , Ludwig Kerstin U. , Mangold Elisabeth , Brennan Paul , Ness Andy R. , St Pourcain Beate , Davey Smith George , Lewis Sarah J.
Published: July 2020

It has been hypothesised that nonsyndromic cleft lip/palate (nsCL/P) and cancer may share aetiological risk factors. Population studies have found inconsistent evidence for increased incidence of cancer in nsCL/P cases, but several genes (e.g., CDH1, AXIN2) have been implicated in the aetiologies of both phenotypes. We aimed to evaluate shared genetic aetiology between nsCL/P and oral cavity/oropharyngeal cancers (OC/OPC), which affect similar anatomical regions. Using a primary sample of 5,048 OC/OPC cases and 5,450 controls of European ancestry and a replication sample of 750 cases and 336,319 controls from UK Biobank, we estimate genetic overlap using nsCL/P polygenic risk scores (PRS) with Mendelian randomization analyses performed to evaluate potential causal mechanisms. In the primary sample, we found strong evidence for an association between a nsCL/P PRS and increased odds of OC/OPC (per standard deviation increase in score, odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.04, 1.13; p = .000053). Although confidence intervals overlapped with the primary estimate, we did not find confirmatory evidence of an association between the PRS and OC/OPC in UK Biobank (OR 1.02; 95% CI: 0.95, 1.10; p = .55). Mendelian randomization analyses provided evidence that major nsCL/P risk variants are unlikely to influence OC/OPC. Our findings suggest possible shared genetic influences on nsCL/P and OC/OPC.
Sequential changes in histone modifications shape transcriptional responses underlying microglia polarization by glioma
Authors: Maleszewska Marta , Steranka Aleksandra , Smiech Magdalena , Kaza Beata , Pilanc Paulina , Dabrowski Michal , Kaminska Bozena
Published: July 2020

Microglia, resident myeloid cells of the central nervous system (CNS), act as immune sentinels that contribute to maintenance of physiological homeostasis and respond to any perturbation in CNS. Microglia could be polarized by various stimuli to perform dedicated functions and instigate inflammatory or pro‐regenerative responses. Microglia and peripheral macrophages accumulate in glioblastomas (GBMs), malignant brain tumors, but instead of initiating antitumor responses, these cells are polarized to the pro‐invasive and immunosuppressive phenotype which persists for a long time and contributes to a “cold” immune microenvironment of GBMs. Molecular mechanisms underlying this long‐lasting “microglia memory” are unknown. We hypothesized that this state may rely on epigenetic silencing of inflammation‐related genes. In this study, we show that cultured microglia pre‐exposed to glioma‐conditioned medium (GCM) acquire a “transcriptional memory” and display reduced expression of inflammatory genes after re‐stimulation with lipopolysaccharide. Unstimulated microglia have unmethylated DNA and active histone marks at selected gene promoters indicating chromatin accessibility. Adding GCM increases expression and enzymatic activity of histone deacetylases (Hdac), leading to erasure of histone acetylation at tested genes. Later inflammatory genes acquire repressive histone marks (H3K27 trimethylation), which correlates with silencing of their expression. GCM induced genes acquire active histone marks. Hdac inhibitors block GCM‐induced changes of histone modifications and restore microglia ability to initiate effective inflammatory responses. Altogether, we show a scenario of distinct histone modifications underlying polarization of microglia by glioma. We demonstrate contribution of epigenetic mechanisms to glioma‐induced “transcriptional memory” in microglia resulting in the tumor‐supportive phenotype.
Causal role of lateral prefrontal cortex in mental effort and fatigue
Authors: Soutschek Alexander , Tobler Philippe N.
Published: July 2020

Dorsolateral prefrontal cortex (DLPFC) is well‐known for its role in exerting mental work, however the contribution of DLPFC for deciding whether or not to engage in effort remains unknown. Here, we assessed the causal role of DLPFC in effort‐based decision making. We disrupted functioning of DLPFC with noninvasive brain stimulation before participants repeatedly decided whether to exert mental effort in a working memory task. We found the same DLPFC subregion involved in mental effort exertion to influence also effort‐based decisions: First, it enhanced effort discounting, suggesting that DLPFC may signal the capacity to successfully deal with effort demands. Second, a novel computational model integrating the costs of enduring effort into the effort‐based decision process revealed that DLPFC disruption reduced fatigue after accumulated effort exertion, linking DLPFC activation with fatigue. Together, our findings indicate that in effort‐based decisions DLPFC represents the capacity to exert mental effort and the updating of this information with enduring time‐on‐task, informing theoretical accounts on the role of DLPFC in the motivation to exert mental effort and the fatigue arising from it.
Pluripotency transcription factor Nanog and its association with overall oral squamous cell carcinoma progression, cisplatin‐resistance, invasion and stemness acquisition
Authors: Kashyap Tanushree , Nath Nidhi , Mishra Prajna , Jha Arpita , Nagini Siddavaram , Mishra Rajakishore
Published: July 2020

Background

Cisplatin‐resistant oral squamous cell carcinoma (OSCC) cells acquire stem‐like characteristics and are difficult to treat. Nanog is a transcription factor and needed for maintenance of pluripotency, but its transcription‐promoting role in OSCC progression and cisplatin resistance is poorly understood.

Methods

Here, 110 fresh human tissue specimens of various stages, including invasive (N1‐3)/chemoradiation‐resistant OSCC samples, cisplatin‐resistant (CisR‐SCC‐4/‐9) OSCC cells/parental cells, photochemical ECGC, and siRNA (Nanog) were used.

Results

Nanog overexpression was associated with overall progression, chemoresistance, and invasion of OSCC. Nanog recruitment to c‐Myc, Slug, E‐cadherin, and Oct‐4 gene promoter was observed. Positive correlation of Nanog protein expression with c‐Myc, Slug, cyclin D1, MMP‐2/‐9, and Oct‐4 and negative correlation with E‐cadherin gene expression were found. Knockdown of Nanog and treatment of epicatechin‐3‐gallate reversed cisplatin resistance and diminished invasion/migration potential.

Conclusion

Nanog directly participated in the regulation of Slug, E‐cadherin, Oct‐4, and c‐Myc genes, causing cisplatin resistance/recurrence of OSCC.
Optogenetic “low‐theta” pacing of the septohippocampal circuit is sufficient for spatial goal finding and is influenced by behavioral state and cognitive demand
Authors: Mouchati Philippe R. , Kloc Michelle L. , Holmes Gregory L. , White Sheryl L. , Barry Jeremy M.
Published: July 2020

Hippocampal theta oscillations show prominent changes in frequency and amplitude depending on behavioral state or cognitive demands. How these dynamic changes in theta oscillations contribute to the spatial and temporal organization of hippocampal cells, and ultimately behavior, remain unclear. We used low‐theta frequency optogenetic stimulation to pace coordination of cellular and network activity between the medial septum (MS) and hippocampus during baseline and MS stimulation while rats were at rest or performing a spatial accuracy task with a visible or hidden goal zone. Hippocampal receptivity to pan‐neuronal septal stimulation at low‐theta frequency was primarily determined by speed and secondarily by task demands. Competition between artificial and endogenous field potentials at theta frequency attenuated hippocampal phase preference relative to local theta, but the spike‐timing activity of hippocampal pyramidal cells was effectively driven by artificial septal output, particularly during the hidden goal task. Notwithstanding temporal reorganization by artificial theta stimulation, place field properties were unchanged and alterations to spatial behavior were limited to goal zone approximation. Our results indicate that even a low‐theta frequency timing signal in the septohippocampal circuit is sufficient for spatial goal finding behavior. The results also advance a mechanistic understanding of how endogenous or artificial somatodendritic timing signals relate to displacement computations during navigation and spatial memory.
Zero‐mass flux and Cattaneo–Christov heat flux through a Prandtl non‐Newtonian nanofluid in Darcy–Forchheimer porous space
Authors: Reddy M. G. , Vijayakumari P. , Kumar K. G. , Shehzad S. A.
Published: July 2020

The Darcy–Forchheimer Prandtl fluid flow due to moving sheet is described here. The familiar energy transfer model, namely, the Cattaneo–Christov model of heat transportation, is adopted under thermal radiation phenomenon. The Prandtl non‐Newtonian nanofluid is accounted as a functioning fluid. The functioning fluid flows in Darcy–Forchheimer porosity space. The boundary‐layer and similarity variables are executed to reframe the mathematical expressions into simplified and single independent variable. Numerical solutions of nonlinear dimensionless expressions are calculated. The variations of distinct constraints on important quantities are demonstrated through tabular and pictorial forms. It is visualized that the velocity of non‐Newtonian nanofluid is enhanced significantly by incrementing the elastic parameter. Improving the thermophoretic and Brownian movement parametric values leads to higher profile of Prandtl nanofluid temperature.
Numerical simulation of mixed convective 3D flow of a chemically reactive nanofluid subject to convective Nield's conditions with a nonuniform heat source/sink
Authors: Faisal Muhammad , Ahmad Iftikhar , Javed Tariq
Published: July 2020

The present investigation aims to explore the influence of a mixed convection and nonuniform heat source/sink on unsteady flow of a chemically reactive nanofluid driven by a bidirectionally expandable surface. Convective heat transport phenomenon is used to maintain the temperature of the surface. Moreover, zero mass flux is also accounted at the surface such that the fraction of nanomaterial maintains itself on strong retardation. The governing nonlinear set of partial differential equations is transformed into a set of ordinary differential equations via a suitable combination of variables. The Keller‐Box scheme has been incorporated to make a numerical inspection of the transformed problem. The spectacular impacts of the pertinent constraints on thermal and concentration distributions are elucidated through various plots. Graphical outcomes indicate that the thermal state of nanomaterial and nanoparticles concentration are escalated for elevated amounts of Biot number, porosity parameter and nonuniform heat source/sink constraints. Furthermore, it is also seen that escalating amounts of unsteady parameter, temperature controlling indices, Prandtl number, and expansion ratio parameter reduce the thermal and concentration distributions. Numerical results for the rate of heat transference have been reported in tabular form. The grid independence approach is used to verify the convergence of the numerical solution and the CPU run time is also obtained to check the efficiency of the numerical scheme adopted for finding the solution.
Turboexpander wheel design for helium liquefaction plant
Authors: Rajmane Swapnil N. , Gupta Manoj K. , Sahu Anant K.
Published: July 2020

A turboexpander wheel, that is, turbine, is one of the critical components for a helium liquefaction plant. It helps to provide the cooling effect required for the liquefaction. The percentage of liquefaction depends upon the effective design of the turbine. The present work includes the design of a radial turbine for the intended power output of approximately 1.5 kW, with input conditions of 40‐g/s mass flow rate at inlet, inlet total pressure of 14 bar, inlet temperature of 40 K, and outlet static pressure of 6 bar. The pressure values are taken to be absolute. Inlet conditions are selected on the basis of required refrigeration effect of approximately 1 kW. The outlet static pressure of 6 bar is maintained to avoid the turbulence, which may occur due to expansion for high pressure ratios. The present work involves the design and optimization of a turbine on the basis of the mean line analysis, initiating with the assumption of values for total‐to‐static efficiency. As per mean line design concept, a one‐dimensional flow is considered for this analysis and the mean values of different parameters are considered at different sections. Losses are considered as the main constraint in design and it is desirable to get optimum net power. Besides, it is also desirable to achieve values for other design parameters in a specified range.
Forecasting the volatility of Chinese stock market: An international volatility index
Authors: Lei Likun , Zhang Yaojie , Wei Yu , Zhang Yi
Published: July 2020

To forecast the volatility of Chinese stock market, we use information from 28 international markets rather than relying on the Chinese market alone. A common factor, which we call the international volatility index, is constructed by the first principal component of all the 28 cross‐national stock market volatilities. We then add the international volatility index into the prevailing heterogeneous autoregressive model of realized volatility (HAR‐RV). The in‐sample estimation results show that the impact of this common index on future Chinese market volatility is statistically significant and positive. More importantly, the out‐of‐sample forecasting results suggest that our proposed model outperforms competing models including the HAR‐RV, kitchen sink model, and combination approaches. The results are similar when we use a wide range of robustness checks. Furthermore, the international volatility index also yields the highest economic value from an asset allocation perspective.
Short‐selling costs and asymmetric price response to economic shocks: A transaction cost explanation to price overshooting
Authors: Ornelas José Renato Haas , de Carvalho Pablo José Campos
Published: July 2020

We propose a model that combines performance‐based arbitrage, short‐sale constraints, and costly arbitrage. In the model, good earnings surprises trigger short‐covering causing price overshooting for highly shorted stocks. However, price overshooting is on average lower than short‐selling costs. Model predictions are empirically tested using Brazilian short‐selling data. We find empirical support for the short‐covering and overshooting phenomena. Furthermore, there is evidence that the intensity of overshooting is lower than the short‐selling borrowing fee, for both U.S. and Brazilian markets. Theoretical and empirical results suggest that arbitrageurs behave asymmetrically to good and bad earnings news.
Mapping US presidential terms with S&P500 index: Time series analysis approach
Authors: Gil‐Alana Luis A. , Mudida Robert , Yaya OlaOluwa S. , Osuolale Kazeem A. , Ogbonna Ahamuefula E.
Published: July 2020

This paper maps the US presidential terms with price dynamics in US stock markets by focusing on the S&P500 index. Fractional integration techniques, which are more general than other standard methods, are used and the results obtained produce interesting findings. It was found that during the second presidential terms, S&P500 stock market is less efficient and present higher degrees of persistence in its volatility. This is observed independently of the political affiliations of the president in power. The volatility, in general, reflects the spillover of economic excesses at the end of the first presidential term when seeking re‐election into the second term in office. Expansionary monetary and fiscal policies at the end of the first term may create disequilibria in the economy which are amplified in the second term through a transmission mechanism resulting in contractionary interventionist policies in a situation where no incentive for re‐election exists by the incumbent. The existence of stock's price cycles as induced by US presidential terms contradicts market efficiency theory but this helps investors decisions.
Do staggered board elections affect firms' financing costs? Evidence from China
Authors: Yugang Chen , Yu Liu , Shahab Yasir , Yuan Zhou
Published: July 2020

As an important provision in a company's charter, the requirement of staggered board elections can help management protect themselves or protect the interests of investors. We examined a unique dataset of Chinese listed firms from the period of 2004–2014, and our findings are twofold. First, we find that the establishment of a staggered board in a company's article of association increases the equity financing costs as well as the debt financing costs. This result is in line with management defense hypothesis that staggered boards are an overprotection for the management. Second, our results show that a cumulative voting system plays an effective role in reducing the impact of a staggered board on a firm's financing costs. This moderating impact is higher for the debt financing costs and lower for the equity financing costs. The result shows that “debt investors” value a cumulative voting system because of its control of the corporate operations and board activities, while “equity investors” believe staggered board elections have a larger influence on the corporate governance.
Oil and currency volatilities: Co‐movements and hedging opportunities
Authors: Olstad Aleksander , Filis George , Degiannakis Stavros
Published: July 2020

The current literature concentrates its attention to the interactions between oil and exchange rates, focusing only on the first moments. Extending this line of research, we investigate the time‐varying correlation between the volatilities of two oil benchmarks (Brent and WTI) and six currencies of the major oil‐importers and oil‐exporters, for the period from February 1, 1999 to May 30, 2016, using a Diag‐BEKK model. The optimal portfolio weights and hedge ratios for portfolios comprised of the aforementioned volatilities, are also examined. The analysis reveals that oil and currency volatilities exhibit positive correlations during major global or region‐specific economic events (such as the Global Financial Crisis of 2007–2009 and the EU debt crisis period). By contrast, country‐specific events yield heterogeneous time‐varying correlations between oil and the different currencies in our sample. Both the optimal portfolio weights and optimal hedge ratios estimations demonstrate a time‐varying behaviour, suggesting that continuous portfolio rebalancing is necessary for diversification purposes. The findings also show that risk reduction based on the optimal portfolio weight strategy is primarily beneficial for oil volatility investors, whereas currency volatility investors achieve better hedging using the optimal hedge ratio strategy.
Do financial constraints really matter? A case of understudied African firms
Authors: Machokoto Michael
Published: July 2020

Using a system of equations to account for the simultaneity, inter‐temporal and interdependent nature of corporate decisions, we document several new insights into how emerging market firms allocate funds across competing uses‐of‐funds. Emerging market firms save most of the operating cash flow. When the firms spend, they allocate the remainder to dividend payments first, followed by debt retirements, then equity repurchases and lastly investments. This pecking order of prioritizing savings and dividends ahead of other uses‐of‐funds highlight difficulties in accessing external finance and a stubbornly resilient signalling motive for firms operating under a high degree of information asymmetry and agency costs. We further find significant asymmetry and heterogeneity in the allocation of funds conditional on credit constraints, deviations from target and around the financial crisis. Our findings signal the need for policies that improve access to external finance and information disclosure in emerging markets.
Foreign equity portfolio flow and corruption: A cross‐country evidence
Authors: Kwabi Frank , Boateng Agyenim , Fosu Samuel , Zhu TingTing , Chijoke‐Mgbame Marian
Published: July 2020

This study examines the impact of foreign equity portfolio investment on corruption. Employing a large dataset of 44 countries from 2001 to 2015 and three different measures of corruption, our results show that foreign investors from well‐governed countries tend to foster public accountability, reduce asymmetry information and corruption. We find empirical evidence that foreign equity portfolio investment interacts with stock market development and central bank transparency to reduce corruption. Our results suggest that stock market development and central bank transparency are regarded as complementary by international portfolio investors. Further analysis indicates that corruption appears more prevalent in countries where domestic investors dominate the stock market. Our results are robust to endogeneity using dynamic generalized methods of moments (GMM). The findings suggest that attracting foreign equity investors reduces corruption, implying significant benefits for portfolio diversification.
Identification of continuous immunoglobulin G epitopes of Dermatophagoides farinae allergens by peptide microarray immunoassay
Authors: Teng Feixiang , Han Feifei , Zhu Xuming , Yu Lili , Gai Dongzheng , Xu Cong , Cui Yubao
Published: July 2020

Dermatophagoides farinae, as a common house dust mite species, is one of the main sources of allergens in the world. At present, Dermatophagoides farinae is found to contain more than 30 groups of allergens. These allergens are used for allergen‐specific immunotherapy (AIT) of allergic diseases. During the AIT process, immunoglobulin G (IgG) antibodies can block immunoglobulin E (IgE) antibody‐induced allergic reactions in the human body. One of the mechanisms may be that IgG and IgE competitively bind to the same allergic protein, so it is necessary to explore the binding sites (epitopes) of IgG antibodies to allergens. In this study, peptide arrays were constructed to react with the serums from patients with allergic asthma to find the IgG epitopes of several allergens including major allergens (Der f 1, 2) and mid‐tier allergens (Der f 4, 5, and 7), and then verified by enzyme‐linked immunosorbent assay (ELISA) test. Relevant epitopic sequences were located on the tertiary structure of individual allergens, as reconstructed by homology modeling. One IgG epitope of Der f 1 (90–106aa, NVPSELDLRSLRTVTPI), five IgG epitopes of Der f 4 (61–77aa, ERYQPVSYDIHTRSGDE; 193–209aa, FRSDASTHQWPDDLRSI; 226–242aa, HPFIYHETIYYGGNGIN; 271–287aa, LRWLRNFGTEWGLVPSG; 352–368aa, NDWVGPPTDQHGNILSV), and one IgG epitope of Der f 5 (84–101aa, RYNVEIALKSNEILERDL) were identified. IgG epitopes of Der f 2, 7 were not found. There are overlaps between the IgG and IgE epitopes of Der f 1, 4, and 5. These findings not only reflect the practicality of peptide array and ELISA test in the allergen IgG epitope identification, but also provide more information for further understanding of the human immunological changes during AIT and the molecular mechanisms of IgG blocking IgE activity.
Oleuropein protects against lipopolysaccharide‐induced sepsis and alleviates inflammatory responses in mice
Authors: Alsharif Khalaf F. , Almalki Abdulraheem A. , Al‐Amer Osama , Mufti Ahmad H. , Theyab Abdulrahman , Lokman Maha S. , Ramadan Shimaa S. , Almeer Rafa S. , Hafez Mohamed M. , Kassab Rami B. , Abdel Moneim Ahmed E.
Published: July 2020

Sepsis results from a major systemic inflammatory response and can induce disorders in multiple organs. The present study evaluated the potential protective effects of oleuropein (OLE) against hyperinflammatory responses during lipopolysaccharide (LPS)‐induced sepsis in mice. Sixty male Balb/c mice were randomly categorized into five groups of 12 animals each: control, intraperitoneally injected with OLE (50 mg/kg), injected with LPS (10 mg/kg, intraperitoneal), and two groups administered OLE (25 and 50 mg/kg) for 3 days prior to LPS injection. Twenty‐four hours after lipopolysaccharide injection, the animals were sacrificed. Serum, liver, and kidney tissue samples were collected for biochemical analyses, histopathological examinations, and investigation of inflammation‐related gene expression. OLE pretreatment significantly reduced liver damage parameters (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase) and kidney damage parameters (blood urea nitrogen, creatinine, and kidney injury molecule‐1) in the septic mice. OLE pretreatment ameliorated LPS‐induced liver and kidney histological changes. OLE significantly mitigated the increased levels of malondialdehyde in the liver and kidneys and reduced levels of reduced glutathione induced by LPS. LPS injection also resulted in increased expression of the proinflammatory cytokines (TNF‐α, IL‐1β, and IL‐6) and inflammation‐related genes (Nos2, Hmgb1, Mpo, Cd46, Map2k4, and Map2k7) in the hepatic and renal tissues. OLE reduced these expressions to ameliorate the inflammatory response. Moreover, OLE pretreatment enhanced the survival rate of septic mice. In conclusion, OLE alleviated the inflammatory response to protect against LPS‐induced sepsis in mice.
The influence of structure and morphology on ion permeation in commercial silicone hydrogel contact lenses
Authors: Saez‐Martinez Virginia , Mann Aisling , Lydon Fiona , Molock Frank , Layton Siân A. , Toolan Daniel T. W. , Howse Jonathan R. , Topham Paul D. , Tighe Brian J.
Published: July 2020

The importance of the microstzructure of silicone hydrogels is widely appreciated but is poorly understood and minimally investigated. To ensure comfort and eye health, these materials must simultaneously exhibit both high oxygen and high water permeability. In contrast with most conventional hydrogels, the water content and water structuring within silicone hydrogels cannot be solely used to predict permeability. The materials achieve these opposing requirements based on a composite of nanoscale domains of oxygen‐permeable (silicone) and water‐permeable hydrophilic components. This study correlated characteristic ion permeation coefficients of a selection of commercially available silicone hydrogel contact lenses with their morphological structure and chemical composition. Differential scanning calorimetry measured the water structuring properties through subdivision of the freezing water component into polymer‐associated water (loosely bound to the polymer matrix) and ice‐like water (unimpeded with a melting point close to that of pure water). Small‐angle x‐ray scattering, and environmental scanning electron microscopy techniques were used to investigate the structural morphology of the materials over a range of length scales. Significant, and previously unrecognized, differences in morphology between individual materials at nanometer length scales were determined; this will aid the design and performance of the next generation of ocular biomaterials, capable of maintaining ocular homeostasis.
Protective roles and mechanisms of rosmarinic acid in cyclophosphamide‐induced premature ovarian failure
Authors: Yao Yang , Xu Yinglei , Wang Yong
Published: July 2020

The aim of this study was to investigate the protective effect of rosmarinic acid (RA) in a premature ovarian failure (POF) mouse model and the potential mechanisms. The POF model was induced by a single intraperitoneal injection of 120 mg/kg cyclophosphamide (CP). Additionally, 40 mg/kg RA was administered for 7 days before CP injection. The concentration of sex hormones was determined by fluorescence immunohistochemistry. Histological analysis was performed after ovarian tissue sections were stained with hematoxylin and eosin. The expression of the NLRP3 inflammasome was examined by western blot analysis and polymerase chain reaction. The expression of apoptosis markers of cytochrome c and caspase‐3 was also detected by western blot analysis and immunohistochemistry. The results showed that RA not only decreased the ovarian index in POF mice but also improved the abnormal secretion of reproductive hormones associated with POF. Treatment with RA suppressed the ovarian expression of the NLRP3 inflammasome and regulated the ovarian expression of apoptosis‐related proteins. The results suggested that RA exhibited a protective effect against CP‐induced POF potentially by suppressing apoptosis and the NLRP3 inflammasome.
Quantitative proteomics reveals the regulatory networks of circular RNA BTBD7_hsa_circ_0000563 in human coronary artery
Authors: Chen Jia‐Xin , Hua Lei , Zhao Chen‐Hui , Jia Qiao‐Wei , Zhang Jing , Yuan Jin‐Xia , Zhang Yong‐Jie , Jin Jian‐Liang , Gu Mu‐Feng , Mao Zhi‐Yuan , Sun Hai‐Jian , Wang Lian‐Sheng , Ma Wen‐Zhu , Jia En‐Zhi
Published: July 2020

Background

BTBD7_hsa_circ_0000563, which is located on chromosome 14, contains conserved binding sites with miR‐155/130a and RNA‐binding proteins according to bioinformatic prediction. We investigated the association of BTBD7_hsa_circ_0000563 expression in coronary artery segments with atherosclerotic stenosis and identified the proteome‐wide BTBD7_hsa_circ_0000563‐regulated proteins in human coronary artery.

Methods

The atherosclerotic grade and extent in coronary artery segments were determined by hematoxylin and eosin staining. BTBD7_hsa_circ_0000563 expression in eight coronary artery segments from one patient was quantified by RT‐qPCR assay. A proteomic approach was adopted to reveal significant differences in protein expression between among four groups differing in their BTBD7_hsa_circ_0000563 expression levels.

Results

The RT‐qPCR assay revealed that coronary artery segments with severe atherosclerotic stenosis had significantly low BTBD7_hsa_circ_0000563 levels. The proteomic analysis identified 49 differentially expressed proteins among the segment groups with different BTBD7_hsa_circ_0000563 expression levels, of which 10 were downregulated and 39 were upregulated with increases in the BTBD7_hsa_circ_0000563 level. The 10 downregulated proteins were P61626 (LYSC_HUMAN), P02760 (AMBP_HUMAN), Q02985 (FHR3_HUMAN), P01701 (LV151_HUMAN), P06312(KV401_HUMAN), P01624 (KV315_HUMAN), P13671 (CO6_HUMAN), P01700(LV147_HUMAN), Q9Y287(ITM2B_HUMAN), and A0A075B6I0 (LV861_HUMAN). The top 10 upregulated proteins were Q92552 (RT27_HUMAN), Q9UJY1(HSPB8_HUMAN), Q9Y235(ABEC2_HUMAN), P19022 (CADH2_HUMAN), O43837(IDH3B_HUMAN), Q9H479(FN3K_HUMAN), Q9UM22(EPDR1_HUMAN), P48681(NEST_HUMAN), Q9NRP0(OSTC_HUMAN), and Q15628(TRADD_HUMAN).

Conclusion

BTBD7_hsa_circ_0000563 is involved in the atherosclerotic changes in human coronary artery segments. Verification, mechanistic, and function studies are needed to confirm whether patients with coronary artery disease would benefit from such personalized medicine in the future.
Lutein inhibits breast cancer cell growth by suppressing antioxidant and cell survival signals and induces apoptosis
Authors: Kavalappa Yogendra Prasad , Gopal Sowmya Shree , Ponesakki Ganesan
Published: July 2020

Reduced risk of breast cancer upon intake of lutein‐rich food supplements creates an interest to investigate the molecular mechanism underlying the growth inhibitory potential of lutein in MCF‐7 and MDA‐MB‐231 cells. Lutein purified from Spinacia oleracea was identified by high‐performance liquid chromatography and liquid chromatography–mass spectrometry. The cell viability was measured by water‐soluble tetrazolium‐1 assay. The intracellular reactive oxygen species level was examined by 2′,7′‐dichlorofluorescein assay. The protein expression of the markers of antioxidant defense, cell survival, and apoptosis was analyzed by western blot analysis. The induction of apoptosis by lutein was measured by 4′,6‐diamidino‐2‐phenylindole staining and caspase‐3 activity assay. The purified lutein inhibited the viability of MCF‐7 and MDA‐MB‐231 cells. The growth inhibitory effect of lutein was associated with suppressed protein expression of superoxide dismutase‐2 and heme oxygenase‐1, and its transcription factor nuclear factor erythroid 2‐related factor‐2. Lutein treatment subsequently blocked the expression of intracellular cell survival proteins, phosphorylated protein kinase B, phosphorylated extracellular‐regulated kinase 1/2, and nuclear factor‐kB. Suppression of antioxidant defense and cell survival markers by lutein was further linked to apoptosis induction with elevated caspase‐3 activity and downregulated expression of Bcl‐2 and poly‐ADP ribose polymerase. Our results emphasize a significant role of lutein as an effective inhibitor of human breast cancer cell growth that activates cell death partly through the modulation of antioxidant defense response‐linked cell survival signaling markers.
NPY promotes macrophage migration by upregulating matrix metalloproteinase‐8 expression
Authors: Wu Weiqiang , Peng Song , Shi Yanchuan , Li Linyu , Song Zhiyuan , Lin Shu
Published: July 2020

Macrophage migration is thought to participate in obesity‐related cardiovascular diseases. Matrix metalloproteinase‐8 (MMP‐8) possesses proteolytic activity on the extracellular matrix (ECM), which promotes macrophage migration to the site of vascular injury. Neuropeptide Y (NPY) is a bioactive peptide involved in MMP expression. However, it is uncertain whether NPY can regulate the expression of matrix metalloproteinase‐8 (MMP‐8) in macrophages. In this study, wild‐type C57BL/6 and NPY−/− mice were fed a high‐fat diet and subjected to subcutaneous carotid artery injury with ferric chloride, to observe the role of NPY and macrophages in neointima formation. In addition, Raw264.7 cells were treated with NPY and its antagonists to observe MMP‐8 expression and macrophage migration. We found that NPY−/− mice exhibited significantly reduced neointima formation after carotid artery injury. The content of macrophages and MMP‐8 in the neointima and media were also significantly reduced in NPY−/− mice compared with C57BL/6 mice. Moreover, the expression of MMP‐8 in macrophages was also decreased in NPY−/− mice. NPY increased MMP‐8 messenger RNA and protein expression in Raw264.7 cells in vitro, and this effect was abrogated by the Y1R antagonist. In addition, NPY increased the phosphorylation of ERK1/2, which was significantly attenuated by co‐treatment with the Y1R antagonist. Moreover, NPY‐induced MMP‐8 expression could be decreased by the ERK1/2 inhibitor PD98059. Furthermore, NPY promoted macrophage migration across type I collagen in vitro. In conclusion, NPY promotes macrophage migration by upregulating MMP‐8 expression, which we believe to be an underappreciated mechanism of the increased progression of neointima formation.
Recombinant l‐asparaginase production using Pichia pastoris (MUTs strain): establishment of conditions for growth and induction phases
Authors: Pillaca‐Pullo Omar , Rodrigues David , Sánchez‐Moguel Ignacio , Lopes André , Pimenta Marcela , Basi Tajindar , Feitosa Valker , Iris Zavaleta Amparo , Monteiro Gisele , Pessoa Jr Adalberto , Vitolo Michele
Published: July 2020

BACKGROUND

l‐asparaginase (ASNase), a biopharmaceutical enzyme used in the treatment of childhood lymphoid malignancies, is commercially produced from Escherichia coli and Erwinia chrysanthemi. However, it causes severe adverse effects due to allergenic prokaryotic epitopes on the protein surface. ASNase II from Saccharomyces cerevisiae can be a promising alternative source of this enzyme. In this study, conditions to produce ASNase from S. cerevisiae expressed in Pichia pastoris have been investigated in shake flasks and 3 L‐bioreactor. We evaluated if medium composition, concentration of carbon source (i.e. glycerol), growth time, concentration of inducer (i.e. methanol), temperature and initial pH influenced both biomass and ASNase expression.

RESULTS

Biomass of around 53 g L–1 and ASNase volumetric activity of 710 U L–1 were achieved using the buffered glycerol‐complex medium (BMGY) containing 40 g L–1 glycerol, with induction after 141 h using 3.0% (v/v) methanol, at 20 °C and initial pH 6.0.

CONCLUSION

The experiments performed in shake flasks were scalable to a 3 L‐bioreactor, suggesting that this bioprocess could be scaled‐up for industrial production. © 2020 Society of Chemical Industry (SCI)
A simple and efficient route to 2‐arylimidazo[1,2‐a]pyridines and zolimidine using automated grindstone chemistry
Authors: Das Dharmendra , Bhutia Zigmee T. , Panjikar Padmini C. , Chatterjee Amrita , Banerjee Mainak
Published: July 2020

A green and efficient mechanochemical method for the synthesis of a series of 2‐arylimidazo[1,2‐a]pyridines was developed using an electrical grinder. I2 catalyzed mechanochemical grinding facilitates the cyclocondensation reaction between various aryl methyl ketones and 2‐aminopyridines to afford 2‐arylimidazo[1,2‐a]pyridines in good yields at ambient temperature. The method was successfully used for the gram‐scale synthesis of a marketed drug, zolimidine. The noticeable advantages of this environmentally sustainable protocol include mild conditions, simple instrumentation, inexpensive catalyst, atom economy, short reaction time etc.
Neural origins of basal diencephalon in teleost fishes: Radial versus tangential migration
Authors: Wullimann Mario F.
Published: July 2020

Teleost fish possess large lateral diencephalic regions such as the torus lateralis, the preglomerular area, and the diffuse nucleus of the hypothalamic inferior lobe. While their developmental origins traditionally were suggested to lie in diencephalic midline ventricular proliferative zones, more remote midbrain origins were reported recently. This review focuses on the preglomerular region and summarizes the data supporting three existing hypotheses on its developmental origins. The conclusion is that lateral torus, diffuse nucleus of hypothalamic inferior lobe, and preglomerular region are part of the diencephalon, but have a multiregional origin provided by both radially and tangentially migrating cells forming these regions in question.
Validation and performance comparison of three SARS‐CoV‐2 antibody assays
Authors: Paiva Kimberly J. , Grisson Ricky D. , Chan Philip A. , Huard Richard C. , Caliendo Angela M. , Lonks John R. , King Ewa , Tang Eric W. , Pytel‐Parenteau Diane L. , Nam Ga H. , Yakirevich Evgeny , Lu Shaolei
Published: July 2020

Serology testing of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is increasingly being used during the current pandemic of coronavirus disease 2019 (COVID‐19), although its clinical and epidemiologic utilities are still debatable. Characterizing these assays provides scientific basis to best use them. The current study assessed one chemiluminescent assay (Abbott COVID‐2 IgG) and two lateral flow assays (STANDARD Q [SQ] IgM/IgG Duo and Wondfo total antibody test) using 113 blood samples from 71 PCR‐confirmed COVID‐19 hospitalized patients, 119 samples with potential cross‐reactions, and 1068 negative controls including 942 pre‐pandemic samples. SARS‐CoV‐2 IgM antibodies became detectable 3‐4 days post‐symptom onset using SQ IgM test and IgG antibodies were first detected 5‐6 days post‐onset using SQ IgG. Abbott IgG and Wondfo Total were able to detect antibodies 7 to 8 days post‐onset. After 14 days post‐symptom onset, the SQ IgG, Abbott IgG and Wondfo Total tests were able to detect antibodies from 100% of the PCR‐confirmed patients in this series; 87.5% sensitivity for SQ IgM. Overall agreement was 88.5% between SQ IgM/IgG and Wondfo Total and 94.6% between SQ IgG and Abbott IgG. No cross‐reaction due to recent sera with three of the endemic coronaviruses was observed. Viral hepatitis and autoimmune samples were the main source of limited cross‐reactions. The specificities were 100% for SQ IgG and Wondfo Total, 99.62% for Abbott IgG, and 98.87% for SQ IgM. These findings demonstrated high sensitivity and specificity of appropriately validated SARS‐CoV‐2 serologic assays with implications for clinical use and epidemiological seroprevalence studies.
Is it all in the heart? Myocardial injury as major predictor of mortality among hospitalized COVID‐19 patients
Authors: Harmouch Farah , Shah Kashyap , Hippen John T. , Kumar Ashish , Goel Harsh
Published: July 2020

Coronavirus disease 2019 (COVID‐19) is an infection caused by the virus SARS‐CoV‐2, and has caused the most widespread global pandemic in over 100 years. Given the novelty of the disease, risk factors of mortality and adverse outcomes in hospitalized patients remain to be elucidated. We present the results of a retrospective cohort study including patients admitted to a large tertiary‐care, academic university hospital with COVID‐19. Patients were admitted with confirmed diagnosis of COVID‐19 between 1 March and 15 April 2020. Baseline clinical characteristics and admission laboratory variables were retrospectively collected. Patients were grouped based on mortality, need for ICU care, and mechanical ventilation. Prevalence of clinical co‐morbidities and laboratory abnormalities were compared between groups using descriptive statistics. Univariate analysis was performed to identify predictors of mortality, ICU care and mechanical ventilation. Predictors significant at P ≤ .10 were included in multivariate analysis. Five hundred and sixty patients were included in the analysis. Age and myocardial injury were only independent predictors of mortality, in patients with/without baseline co‐morbidities. Body mass index, elevated ferritin, elevated d‐dimer, and elevated procalcitonin predicted need for ICU care, and these along with vascular disease at baseline predicted need for mechanical ventilation. Hence, inflammatory markers (ferritin and d‐dimer) predicted severe disease, but not death.
A structural equation model to examine the clinical features of mild‐to‐moderate COVID‐19: A multicenter Italian study
Authors: Barillari Maria Rosaria , Bastiani Luca , Lechien Jerome R. , Mannelli Giuditta , Molteni Gabriele , Cantarella Giovanna , Coppola Nicola , Costa Giuseppe , Trecca Eleonora M. C. , Grillo Calogero , La Mantia Ignazio , Chiesa‐Estomba Carlos M. , Vicini Claudio , Saussez Sven , Nacci Andrea , Cammaroto Giovanni
Published: July 2020

The purpose of this study was to evaluate the clinical features of mild‐to‐moderate coronavirus disease 2019 (COVID‐19) in a sample of Italian patients and to investigate the occurrence of smell and taste disorders. Infected individuals with suspected (clinical diagnosis) or laboratory‐confirmed COVID‐19 infection were recruited. Patients completed a survey‐based questionnaire with the aim of assessing their epidemiological and clinical characteristics, general otorhinolaryngological symptoms, and smell and taste disorders. A total of 294 patients with mild‐to‐moderate COVID‐19 completed the survey (147 females). The most prevalent general symptoms included fever, myalgia, cough, and headache. A total of 70.4% and 59.2% of patients reported smell and taste disorders, respectively. A significant association between the two above‐mentioned disorders was found (rs: 0.412; P < .001). Smell disorders occurred before the other symptoms in 11.6% of patients and was not significantly associated with nasal obstruction or rhinorrhea. Interestingly, our statistical analysis did not show any significant difference, either for general symptoms or otorhinolaryngological features, between the clinical diagnosis group and the laboratory‐confirmed diagnosis (polymerase chain reaction) group. The structural equation model confirmed significant standardized paths (P < .05) between general symptoms, comorbidities, and general otorhinolaryngological complaints in the absence of a significant correlation between these elements and smell and taste alterations. The prevalence of smell and taste disorders in mild‐to‐moderate Italian COVID‐19 patients is significant both in suspected and laboratory‐confirmed cases and reveals a strong correlation between these clinical signs regardless of the presence of general or otorhinolaryngological symptoms, such as nasal obstruction or rhinorrhea.
Prevalence and risk factors of oral HPV infection among a healthy Iranian population; Kurdistan, West of Iran
Authors: Zargaran Massoumeh , Azizi jalilian Farid
Published: July 2020

Human papillomavirus (HPV) infection has implicated in the development of some of the oral/oropharyngeal cancers. However, controversy still exists regarding the prevalence of oral HPV (OHPV) and its risk factors. This study aimed to determine the prevalence and variables of OHPV infection in a healthy Iranian population. This study evaluated 300 oral rinse samples. Following the oral and dental examination of participants and filling out a self‐administered questionnaire; samples collected by swishing and gargling 0.09% saline. The viral DNA extraction, polymerase chain reaction and HPV genotyping then performed. Prevalence of OHPV DNA/OHPV+ infection and OHPV genotypes was 12% and 1% (two cases of HPV6 and one case of HPV53), respectively. Comparison of variables between OHPV+ and OHPV− groups revealed that only income (P = .045), number of cigarettes smoked per day (P = .002), and number of teeth in the mouth (P = .005) were significantly different between the two groups. In conclusion, prevalence of OHPV+ infection and its genotypes were very low in our healthy Iranian population, and its association was not significant with the majority of suggested risk factors. Further studies with a larger sample size are recommended to determine OHPV infection risk factors.