bluuebunny/crossref_metadata_2025 huggingface dataset:
The Origin of the Electrocatalytic Activity for CO2 Reduction Associated with Metal‐Organic Frameworks
Authors: Zhang Ying , Zhang Xiaolong , Zhu Yinlong , Qian Binbin , Bond Alan M. , Zhang Jie
Published: March 2020

There has been a rapid growth in the use of metal–organic framework (MOF) materials as electrocatalysts. However, simple anodic stripping analysis reveals that some well‐known previously reported stable MOFs are in fact unstable at the negative potentials used to catalytically reduce CO2 in aqueous electrolyte media. Thus, it is the resulting metal nanoparticles derived from reduction of the MOFs rather than the MOFs themselves that are the electrocatalysts. The results reported herein therefore suggest that stability data and the origin of the activity for MOF electrocatalysts may need careful re‐evaluation and that suitable strategies are needed to ensure that stable MOF electrocatalysts have been synthesized. The use of the readily accessible stripping analysis method provides a powerful tool to assess MOF stability under turnover conditions.
Does breeding season variation affect evolution of a sexual signaling trait in a tropical lizard clade?
Authors: Gray Levi N. , Barley Anthony J. , Hillis David M. , Pavón‐Vázquez Carlos J. , Poe Steven , White Brittney A.
Published: March 2020

Sexually selected traits can be expected to increase in importance when the period of sexual behavior is constrained, such as in seasonally restricted breeders.Anolislizard male dewlaps are classic examples of multifaceted signaling traits, with demonstrated intraspecific reproductive function reflected in courtship behavior. Fitch and Hillis found a correlation between dewlap size and seasonality in mainlandAnolisusing traditional statistical methods and suggested that seasonally restricted breeding seasons enhanced the differentiation of this signaling trait. Here, we present two tests of the Fitch–Hillis Hypothesis using new phylogenetic and morphological data sets for 44 species of MexicanAnolis. A significant relationship between dewlap size and seasonality is evident in phylogenetically uncorrected analyses but erodes once phylogeny is accounted for. This loss of strong statistical support for a relationship between a key aspect of dewlap morphology and seasonality also occurs within a species complex (A. sericeusgroup) that inhabits seasonal and aseasonal environments. Our results fail to support seasonality as a strong driver of evolution ofAnolisdewlap size. We discuss the implications of our results and the difficulty of disentangling the strength of single mechanisms on trait evolution when multiple selection pressures are likely at play.
The impact of coenzyme Q10 on metabolic and cardiovascular disease profiles in diabetic patients: A systematic review and meta‐analysis of randomized controlled trials
Authors: Dludla Phiwayinkosi V. , Nyambuya Tawanda M. , Orlando Patrick , Silvestri Sonia , Mxinwa Vuyolwethu , Mokgalaboni Kabelo , Nkambule Bongani B. , Louw Johan , Muller Christo J. F. , Tiano Luca
Published: March 2020

Aims

Coenzyme Q10 (CoQ10) is well known for its beneficial effects in cardiovascular disease (CVD); however, reported evidence has not been precisely synthesized to better inform on its impact in protecting against cardiovascular‐related complications in diabetic patients.

Materials and Methodology

The current meta‐analysis included randomized controlled trials published in the past 5 years reporting on the effect of CoQ10 on metabolic and CVD‐related risk profiles in individuals with diabetes or metabolic syndrome. We searched electronic databases such as MEDLINE, Cochrane Library, Scopus and EMBASE for eligible studies. In addition to assessing the risk of bias and quality of evidence, the random and fixed‐effect models were used to calculate the standardized mean difference and 95% confidence intervals for metabolic parameters and CVD outcomes.

Results

Overall, 12 studies met the inclusion criteria, enrolling a total of 650 patients. Although CoQ10 supplementation did not statistically affect all metabolic profiles measured, it significantly reduced CVD‐risk‐related indexes such as total cholesterol and low‐density lipoprotein (LDL) levels in diabetic patients when compared to those on placebo [SMD = 0.13, 95% CI (0.03; 0.23), Chi2 = 43.62 and I2 = 29%, P = .07].

Conclusions

The overall results demonstrated that supplementation with CoQ10 shows an enhanced potential to lower CVD risk in diabetic patients by reducing total cholesterol and LDL. Moreover, the beneficial effects of CoQ10 in lowering the CVD risk are associated with its ameliorative properties against oxidative stress and improving endothelial health.
Pseudoceroximes A–E and Pseudocerolides A–E – Bromotyrosine Derivatives from a Pseudoceratina sp. Marine Sponge Collected in the South China Sea
Authors: Chen Mengxuan , Yan Yizhen , Ge Hengju , Jiao Wei‐Hua , Zhang Zhizhen , Lin Hou‐Wen
Published: March 2020

15 new bromotyrosine‐derived compounds, pseudoceroximes A–E (1–5), pseudocerolides A–E (6–10), 13‐ketohemifistularin 3 (11), and ceratinines J–M (12–15), were isolated from a Pseudoceratina sp. marine sponge collected in the South China Sea. The planar structures of all compounds were established based on extensive NMR spectroscopic analyses and HRESIMS data. Their absolute configurations were assigned by a combination of modified Mosher's method, ECD calculations and a single‐crystal X‐ray diffraction experiment. Pseudoceroximes A–D (1–4) represent the first examples of the oxime‐type bromotyrosine derivatives possessing the 2‐oxazolidone ring. Pseudoceroximes A (1) and B (2) and pseudocerolide C (8) showed antibacterial activity against methicillin‐resistant Staphylococcus aureus ATCC 43300 with MIC values of 5.2–7.1 µm. Additionally, pseudoceroximes B (2) and D (4) exhibited moderate antiproliferative activity against two human glioma cell lines U87MG and U251.
GABAergic modulation of secondary hyperalgesia: A randomized controlled 4‐way crossover trial with the α2‐subunit preferring GABA positive allosteric modulator, N‐desmethyl‐clobazam in healthy volunteers
Authors: Matthey Alain , Daali Youssef , Curtin François , Poncet Antoine , Desmeules Jules , Besson Marie
Published: March 2020

The antihyperalgesic and sedative effects of the α2‐subunit preferring GABAA positive allosteric modulator (GAM), N‐desmethyl‐clobazam (NDMC), 20 and 60 mg, were assessed in a randomized, placebo and active‐controlled (clonazepam 1,5 mg), 4‐way crossover study, in healthy volunteers, using the ultraviolet B‐induced experimental pain model. Single (20, 40, 60 mg) and repeated doses (20 mg over 15 days) of NDMC pharmacokinetics were evaluated. Thirty‐two subjects participated in the study. Primary outcome parameter was maximal change in the area of cutaneous UVB irradiation‐induced secondary hyperalgesia (ASH). ASH decreased under all treatments. Mean (SD) relative change was 79 (22)%, 83 (24)%, 77 (30)% and 92 (16)% for placebo, NDMC20, NDMC60 and clonazepam, respectively. Neither absolute change nor relative change in ASH was significantly different between NDMC60 and placebo (mean difference = 2.3 cm2 [95% CI 4.0–8.5], p = .462 and 0.4% [−11.9 to 12.6], p = .952, respectively). An overall treatment effect was found on level of sedation. Compared to placebo, sedation was higher under clonazepam (mean difference = 39 mm [30–49] on a visual analogue scale, p < .001) while NDMC was free of sedative effect. NDMC pharmacokinetics after single doses showed poor absorption, but was linear. Steady‐state plasma concentrations of NDMC20 were attained within 14 days, with low between‐subjects variability. Mean steady‐state concentration (CS‐S, SD) reached 209 (22) ng/ml. NDMC absence of sedative effect and its overall well‐characterized safety coming from years of utilization as a metabolite from clobazam, raise the prospect of dose escalating trials in patients to quantify its clinical utility.

Significance

This article, presenting the Phase I data of the new antihyperalgesic compound, α2‐subunit GABAA positive allosteric modulator, N‐desmethyl‐clobazam (NDMC) is exploring the modulation of a new target in the treatment of neuropathic pain. Based on these results and on its preclinical properties NDMC would qualify as a good tool compound to seek confirmation of the clinical utility of selective GABA allosteric modulators in neuropathic pain patients.
Acute pain measured with the modified Bernese Pain Scale for Neonates is influenced by individual contextual factors
Authors: Schenk Karin , Stoffel Lilian , Bürgin Reto , Stevens Bonnie , Bassler Dirk , Schulzke Sven , Nelle Mathias , Cignacco Eva
Published: March 2020

Background

Individual contextual factors like gestational age (GA) or previous painful experiences have an influence on neonates’ pain responses and may lead to inaccurate pain assessment when not appropriately considered.

Objectives

We set out to determine the influence of individual contextual factors on variability in pain response in neonates, measured with the modified Bernese Pain Scale for Neonates (BPSN), and, if necessary, to incorporate relevant individual factors into a revised version of the BPSN.

Methods

We videotaped 154 full‐term and preterm neonates of different GAs during 1–5 capillary heel sticks in their first 14 days of life. For each heel stick, we produced three video sequences: baseline, heel stick, and recovery. The randomized sequences were rated on the BPSN by five blinded nurses. Individual contextual factors were retrospectively extracted from patient charts and from the video recordings. We analysed the data in single and multiple linear mixed models.

Results

Premature birth (b = −0.721), caffeine (b = −0.302), and the behavioural states quiet and awake (b = −0.283), active and asleep (b = −0.158), and quiet and asleep (b = −0.498) were associated with changes in behavioural pain scores. Premature birth (b = −0.232), mechanical ventilation (b = −0.196), and duration of the heel stick procedure (b = 0.0004) were associated with changes in physiological pain scores. Premature birth (b = −0.907), Caffeine (b = −0.402), the behavioural states quiet and awake (b = −0.274), and quiet and asleep (b = −0.459), and duration of the heel stick procedure (b = 0.001) were associated with changes in the modified BPSN total scores.

Conclusions

Postmenstrual age, behavioural state, caffeine, and ventilation status have an influence on neonates’ pain response and should be incorporated in the revised BPSN to enhance clinical pain assessment in neonates with different GAs.

Significance

We identified individual contextual factors associated with dampened pain response in neonates and will incorporate them into a revised version of the Bernese Pain Scale for Neonates to provide clinicians with a tool they can use to more accurately assess and manage pain in this vulnerable population.
Anodal transcranial direct current stimulation over the primary motor cortex attenuates capsaicin‐induced dynamic mechanical allodynia and mechanical pain sensitivity in humans
Authors: Hughes Sam W. , Ward Grace , Strutton Paul H.
Published: March 2020

Background

Anodal transcranial direct current stimulation over the primary cortex has been shown to activate regions of the brain involved in the descending modulation of pain sensitivity. However, more research is required to dissect the spinal cord analgesic mechanisms associated with the development of central sensitization.

Methods

In this randomized, double blind, crossover study 12 healthy participants had baseline mechanical stimulus response (S/R) functions measured before and after the development of capsaicin‐induced ongoing pain sensitivity. The effects of 20 min of either real or sham transcranial direct current stimulation (tDCS, 2 mA) over the primary motor cortex on dynamic mechanical allodynia (DMA) and mechanical pain sensitivity (MPS) were then investigated.

Results

Topical application of capsaicin resulted in an increase in area under the pain ratings curve for both DMA (p < .01) and MPS (p < .01). The effects of tDCS on the area under the curve ratio (i.e. post‐/pre‐treatment) revealed significant analgesic effects over DMA (p < .05) and MPS (p < .05) when compared with sham.

Conclusions

This study demonstrates that anodal tDCS over the primary motor cortex can reduce both dynamic and static forms of mechanical pain sensitivity associated with the development of DMA and MPS, respectively. The use of tDCS may provide a novel mechanism‐driven therapy in chronic pain patients with altered mechanical S/R functions.

Significance

This research shows new evidence that anodal tDCS over the primary motor cortex can reduce dynamic and static forms of mechanical pain sensitivity in the capsaicin model of ongoing pain. By using this approach, it may be possible to provide mechanism‐driven analgesia in chronic pain patients who have dynamic mechanical allodynia and/or secondary mechanical hyperalgesia.
Investigation of the synergistic effect with chiral D‐penicillamine functionalized gold nanoparticle as an additive for enantiomeric separation in capillary electrophoresis
Authors: Feng Zijie , Yang Yue , Xu Guangfu , Du Yingxiang , Sun Xiaodong
Published: March 2020

The authors describe a synergistic system for nanoparticle based chiral separation. It is based on the use of a conventional chiral selector hydroxyproyl‐β‐cyclodextrin and a kind of gold nanoparticle functionalized with D‐penicillamine as an additive. This nanomaterial displays a synergistic effect on the efficiency of the enantioseparation of the chiral drugs amlodipine, tropicamide, and ofloxacin. A comparative study on the enantioseparation capability of three separation systems, viz. (a) single hydroxyproyl‐β‐cyclodextrin system, (b) achiral citrate capped gold nanoparticle/ hydroxyproyl‐β‐cyclodextrin system, and (c) chiral D‐penicillamine functionalized gold nanoparticle/ hydroxyproyl‐β‐cyclodextrin system was performed. The results show that the D‐penicillamine functionalized gold nanoparticle/hydroxyproyl‐β‐cyclodextrin synergistic system has remarkable superiority. The effects of concentrations of D‐penicillamine functionalized gold nanoparticle and hydroxyproyl‐β‐cyclodextrin, of buffer pH value and concentration, and of applied voltage on the performance of enantioseparation were investigated.
Challenges and applications of isotachophoresis coupled to mass spectrometry: A review
Authors: Melzer Tanja , Wimmer Benedikt , Bock Stephanie , Posch Tjorben Nils , Huhn Carolin
Published: March 2020

Electrophoretic separations are of growing interest to tackle complex analytical challenges. Nevertheless, capillary electrophoresis, as the most common mode, still suffers from insufficient detection limits due to low capillary loadability. ITP is of growing interest as preconcentration method for capillary electrophoresis and is also interesting to be applied as an independent analytical method. While mass spectrometric detection is common for capillary electrophoresis, the combination of ITP with MS is still a niche technique. In this work, we want to give an overview on isotachophoretic effects in CE‐MS and ITP‐MS methods, as well as coupling techniques of ITP with CE‐MS. The challenges and possibilities associated with mass spectrometric detection in ITP and its coupling to capillary electrophoresis are critically discussed.
Effect of temperature on the hydrolysis of levan treated with compressed hot water fluids
Authors: Shimizu Naoto , Abea Andres , Ushiyama Tetsuya , Toksoy Öner Ebru
Published: March 2020

The hydrolysis of levan using compressed hot water for the production of functional fructooligosaccharides (FOSs) was investigated. Levans from Erwinia herbicola (EH) and Halomonas smyrnensis (HS) were characterized using scanning electron microscopy and light scattering techniques, and hydrolyzed using compressed hot water at four temperatures (120, 140, 160, and 180°C). The hydrolysates were analyzed using high‐performance liquid chromatography and electrospray ionization‐mass spectrometry. Levan HS showed a crystalline morphology, whereas levan EH showed an aggregated structure. Both levans had molar masses on the order of 106 g/mol, but levan EH had a smaller radius of gyration, hydrodynamic radius, and intrinsic viscosity. Levan EH hydrolyzed into FOSs at approximately 120°C, whereas levan HS required a temperature of at least 160°C, possibly because of differences in the degree of branching of the two levans. Both samples were degraded to fructose when treated at 180°C.
Comprehensive evaluation of physicochemical properties and antioxidant activity of B. subtilis‐fermented polished adlay subjected to different drying methods
Authors: Wen Anyan , Qin Likang , Zeng Haiying , Zhu Yi
Published: March 2020

The physicochemical properties and antioxidant activity of B. subtilis‐fermented polished adlay (BPA) subjected to different drying methods (hot‐air drying, HAD; infrared‐radiation drying, IRD; vacuum drying, VD; microwave‐vacuum drying, MVD; and freeze‐vacuum drying, FVD) were evaluated in this study. Results showed FVD was ideal for maintaining the natural appearance and higher contents of proximate compositions, free fatty acids, tetramethylpyrazine (6.91 mg/g DW), coixol (0.62 mg/g DW), coixenolide (4.21% DW), coixan (35.10% DW), and triterpenoids (17.41 mg/g DW). The higher contents of total phenolics and flavonoids, stronger antioxidant activity, and higher color differences were observed in HAD and IRD samples. MVD displayed the shorter drying time, higher γ‐aminobutyric acid content, and higher retention ratios of tetramethylpyrazine (75.54%), coixol (87.10%), coixenolide (98.57%), and coixan (99.11%). Pearson's correlation coefficient exhibited that the positive correlation between the contents of phenolics and flavonoids and the antioxidant activities of all dried BPA samples was observed (R2 > 0.881, p < .05). Principal component analysis showed that the top three categories of comprehensive quality were FVD‐, MVD‐, and VD‐treated BPA samples. In conclusion, MVD should be a potential preservation method to obtain high‐quality dried BPA for short drying time and high comprehensive quality.
Variant WWTR1 gene fusions in epithelioid hemangioendothelioma—A genetic subset associated with cardiac involvement
Authors: Suurmeijer Albert J. H. , Dickson Brendan C. , Swanson David , Sung Yun S. , Zhang Lei , Antonescu Cristina R.
Published: March 2020

The genetic hallmark of epithelioid hemangioendothelioma (EHE) is a recurrent WWTR1‐CAMTA1 fusion, which is present in most cases bearing a conventional histology. A subset of cases is characterized by a distinct morphology and harbors instead of YAP1‐TFE3 fusion. Nevertheless, isolated cases lack these canonical fusions and remain difficult to classify. Triggered by an index case of a left atrial mass in a 76‐year‐old female with morphologic features typical of EHE, but which showed a WWTR1‐MAML2 fusion by targeted RNA sequencing, we searched our files for similar cases displaying alternative WWTR1 fusions. A total of 6 EHE cases were identified with variant WWTR1 fusions, four of them presenting within the heart. There were three females and three males, with a wide age range at diagnosis (21‐76 years, mean 62, median 69). The four cardiac cases occurred in older adults (mean age of 72, equal gender distribution); three involved the left atrium and one the right ventricle. One case presented in the vertebral bone and one in pelvic soft tissue. Microscopically, all tumors had morphologic features within the spectrum of classic EHE; two of the cases appeared overtly malignant. All cases were tested by FISH and four were investigated by targeted RNA sequencing. Two tumors harbored WWTR1‐MAML2 fusions, one WWTR1‐ACTL6A, and in three cases, no WWTR1 partner was identified. Of the four patients with follow‐up, two died of disease, one was alive with lung metastases, and the only patient free of disease was s/p resection of a T11 vertebral mass. Our findings report on additional genetic variants involving WWTR1 rearrangements, with WWTR1‐MAML2 being a recurrent event, in a small subset of EHE, which appears to have predilection for the heart.
Glutamate transporter 1‐expressing glia in the rat substantia nigra—Morphometric analysis and relationships to synapses
Authors: Kessler Jean‐Pierre , Salin Pascal , Kerkerian‐Le Goff Lydia
Published: March 2020

Glial cells have a major role in protecting neurons against various forms of stress. Especially, astrocytes mediate the bulk of glutamate clearance in the brain via specific membrane transporters (GLAST and GLT1), thereby preventing the occurrence of excitotoxic events. Although glutamate‐mediated mechanisms are thought to contribute to nigral dopaminergic neuron degeneration in Parkinson's disease, detailed information on the organization of glia in the substantia nigra is still lacking. The present study was performed to provide quantitative information on the organization of astroglia and on the relationships between astrocytes and excitatory synapses in the rat substantia nigra. Using immunolabeling of GLT1 and confocal imaging, we found that the substantia nigra was filled with a dense meshwork of immunoreactive astrocyte processes. Stereological analysis performed on electron microscope images revealed that the density of immunoreactive astrocyte plasma membranes was substantial, close to 1 μm2/μm3, in the substantia nigra neuropil, both in the pars compacta and the pars reticulata. Excitatory synapses had on average two thirds of their perimeters free from glia, a disposition that may favor transmitter spillover. The density of glutamatergic synapses, as quantified on confocal images by the simultaneous detection of bassoon and of vesicular glutamate transporter 1 or 2, was very low (0.01 and 0.025 per μm3 in the reticulata and compacta subdivisions, respectively). Thus the ratio of GLT1‐expressing glial membrane surface to glutamatergic synapses was very high (40–100 μm2), suggesting an efficient regulation of extracellular glutamate concentrations.
Hepatitis B Virus–Telomerase Reverse Transcriptase Promoter Integration Harnesses Host ELF4, Resulting in Telomerase Reverse Transcriptase Gene Transcription in Hepatocellular Carcinoma
Authors: Sze Karen Man‐Fong , Ho Daniel Wai‐Hung , Chiu Yung‐Tuen , Tsui Yu‐Man , Chan Lo‐Kong , Lee Joyce Man‐Fong , Chok Kenneth Siu‐Ho , Chan Albert Chi‐Yan , Tang Chung‐Ngai , Tang Victor Wai‐Lun , Lo Irene Lai‐Oi , Yau Derek Tsz‐Wai , Cheung Tan‐To , Ng Irene Oi‐Lin
Published: March 2020

Background and Aims

Hepatitis B virus (HBV) integrations are common in hepatocellular carcinoma (HCC). In particular, alterations of the telomerase reverse transcriptase (TERT) gene by HBV integrations are frequent; however, the molecular mechanism and functional consequence underlying TERT HBV integration are unclear.

Approach and Results

We adopted a targeted sequencing strategy to survey HBV integrations in human HBV‐associated HCCs (n = 95). HBV integration at the TERT promoter was frequent (35.8%, n = 34/95) in HCC tumors and was associated with increased TERT mRNA expression and more aggressive tumor behavior. To investigate the functional importance of various integrated HBV components, we employed different luciferase reporter constructs and found that HBV enhancer I (EnhI) was the key viral component leading to TERT activation on integration at the TERT promoter. In addition, the orientation of the HBV integration at the TERT promoter further modulated the degree of TERT transcription activation in HCC cell lines and patients’ HCCs. Furthermore, we performed array‐based small interfering RNA library functional screening to interrogate the potential major transcription factors that physically interacted with HBV and investigated the cis‐activation of host TERT gene transcription on viral integration. We identified a molecular mechanism of TERT activation through the E74 like ETS transcription factor 4 (ELF4), which normally could drive HBV gene transcription. ELF4 bound to the chimeric HBV EnhI at the TERT promoter, resulting in telomerase activation. Stable knockdown of ELF4 significantly reduced the TERT expression and sphere‐forming ability in HCC cells.

Conclusions

Our results reveal a cis‐activating mechanism harnessing host ELF4 and HBV integrated at the TERT promoter and uncover how TERT HBV‐integrated HCCs may achieve TERT activation in hepatocarcinogenesis.
Travel times for snowmelt‐dominated headwater catchments: Influences of wetlands and forest harvesting, and linkages to stream water quality
Authors: Leach Jason A. , Buttle James M. , Webster Kara L. , Hazlett Paul W. , Jeffries Dean S.
Published: March 2020

The time it takes water to travel through a catchment, from when it enters as rain and snow to when it leaves as streamflow, may influence stream water quality and catchment sensitivity to environmental change. Most studies that estimate travel times do so for only a few, often rain‐dominated, catchments in a region and use relatively short data records (<10 years). A better understanding of how catchment travel times vary across a landscape may help diagnose inter‐catchment differences in water quality and response to environmental change. We used comprehensive and long‐term observations from the Turkey Lakes Watershed Study in central Ontario to estimate water travel times for 12 snowmelt‐dominated headwater catchments, three of which were impacted by forest harvesting. Chloride, a commonly used water tracer, was measured in streams, rain, snowfall and as dry atmospheric deposition over a 31 year period. These data were used with a lumped convolution integral approach to estimate mean water travel times. We explored relationships between travel times and catchment characteristics such as catchment area, slope angle, flowpath length, runoff ratio and wetland coverage, as well as the impact of harvesting. Travel time estimates were then used to compare differences in stream water quality between catchments. Our results show that mean travel times can be variable for small geographic areas and are related to catchment characteristics, in particular flowpath length and wetland cover. In addition, forest harvesting appeared to decrease mean travel times. Estimated mean travel times had complex relationships with water quality patterns. Results suggest that biogeochemical processes, particularly those present in wetlands, may have a greater influence on water quality than catchment travel times.
Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome
Authors: Sadeghi Asie , Fadaei Reza , Moradi Nariman , Fouani Fatima Z. , Roozbehkia Maryam , Zandieh Zahra , Ansaripour Soheila , Vatannejad Akram , Doustimotlagh Amir H.
Published: March 2020

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting females of reproductive age. It has been associated with cardiometabolic disorders including diabetes mellitus and cardiovascular disorders, and increases the risk of developing fecundity pathologies including recurrent pregnancy loss (RPL) and infertility. C1q/tumor necrosis factor‐α‐related protein‐6 (CTRP6) is a novel adipokine involved in glucose and lipid metabolism, host inflammation, and organogenesis. In the present study, we aimed to determine the association of serum CTRP6 levels with some components of metabolic syndrome in PCOS patients (infertile PCOS [inf‐PCOS] and PCOS‐RPL). This case–control study included 120 PCOS patients (60 inf‐PCOS and 60 PCOS‐RPL) and 60 healthy controls. Serum high‐sensitivity C‐reactive protein (hs‐CRP) and homocysteine were measured using commercial kits, while adiponectin and CTRP6 levels were assessed using ELISA technique. Inf‐PCOS and PCOS‐RPL individuals had higher levels of serum CTRP6 than controls (546.15 ± 125.02 ng/ml and 534.04 ± 144.19 ng/ml vs. 440.16 ± 159.24 ng/ml; both p < .001). Moreover, serum adiponectin levels were significantly reduced, while fasting insulin, homeostasis model assessment of insulin resistance, free testosterone, and hs‐CRP levels were significantly elevated in PCOS group, when compared with controls. Furthermore, serum CTRP6 positively associated with body mass index in all subjects. It showed an inverse correlation with adiponectin in PCOS group and subgroups. However, it had a direct association with hs‐CRP in PCOS group and inf‐PCOS subgroup, but not PCOS‐RPL subgroup. These findings unravel a probable role of CTRP6 in PCOS pathogenesis, which poses a possibility to be a good diagnostic target. However, further investigation is needed.
Exosome‐based targeted RNA delivery for immune tolerance induction in skin transplantation
Authors: Li Chunmin , Guo Fengjie , Wang Xueli , Liu Dongxu , Wu Bolun , Wang Fenghua , Chen Wen
Published: March 2020

Exosomes have been widely applied to the delivery of RNA and small molecules currently. However, the low targeting and specificity greatly limited the effect of exosome delivery. Here we designed an exosome that can perform the targeted delivery of two different types of RNA. Based on the mesenchymal stem cells (MSCs) derived exosomes, the RNA delivery system of targeted dendritic cells (DC‐Exosome) was constructed, using the layer by layer self‐assembly. DC‐Exosomes can specifically bind to DCs, while guiding the endocytosis of chimeras and exosome. Then aptamer/siRNA chimera was cut into mTOR siRNA by Dicer, and microRNA was released from exosome under lysosomal digestion. SIGN aptamer performed the rapid induction of immune tolerance, and later mTOR siRNA was formed to inhibit mTOR pathway and suppress immune responses. Exosomes could maintain long time‐stability after PEG‐PEI polyplexes modification and promote HLA‐G expression in DCs continuously. Animal experiments showed that DC‐Exosomes could induce immune tolerance at 3, 7, and 14 days after skin transplantation. Compared with the microRNA‐Exosome group, the number of CD11c+ DCs in DC‐Exosome group decreased, while the proportion of HLA‐G+ DCs increased remarkably. In conclusion, we constructed a new exosome‐based targeted delivery system which could effectively induce the immune tolerance in transplantation.
Systems toxicology assessment revealed the impact of graphene‐based materials on cell cycle regulators
Authors: Farahani Masoumeh , Rezaei‐Tavirani Mostafa , Zali Hakimeh , Hatamie Shadie , Ghasemi Nazanin
Published: March 2020

Understanding the cellular and molecular toxicity of graphene and its derivatives is essential for their biomedical applications. Herein, gene expression profile of graphene‐exposed cells was retrieved from the Gene expression omnibus database. Differentially expressed genes and their functional roles were then investigated through the pathway, protein–protein interaction (PPI) network, and module analysis. High degree (hub) and high betweenness centrality (bottleneck) nodes were subsequently identified. The functional analysis of central genes indicated that these graphene–gene interactions could be of great value for further investigation. Accordingly, we also followed the expression of five hub–bottleneck genes in graphene‐treated murine peritoneal macrophages and human breast cancer cell line by real‐time PCR. The five hub–bottleneck genes related to graphene cytotoxicity; CDK1, CCNB1, PLK1, TOP2A, and CCNA2 were identified through network analysis, which were highly correlated with regulation of cell cycle processes. The module analysis indicated the cell cycle pathway to be the predominant one. Gene expression evaluation showed downregulation of these genes in the macrophages and cancer cells treated with graphene. These results provided some new intuitions concerning the graphene–cell interactions and unveiled targeting critical cell cycle regulators. The present study indicated some toxic effects of graphene‐based materials through systems toxicology assessment. Integrating gene expression and PPI network may help explaining biological responses of graphene and lead to beneficial impacts in nanomedicine.
Mechanical and degradation properties of poly(methyl methacrylate) cement/borate bioactive glass composites
Authors: Cole Kimberly A. , Funk Grahmm A. , Rahaman Mohamed N. , McIff Terence E.
Published: March 2020

Bone cement is used extensively in orthopedics to anchor prostheses to bone and fill voids. Incorporating bioactive glass into poly(methyl methacrylate) (PMMA)‐based bone cement could potentially improve its effectiveness for these tasks. This study characterizes the mechanical and degradation properties of composites containing PMMA‐based bone cement and particles of borate bioactive glass designated as 13‐93B3. Glass particles of size 5, 33, and 100 μm were mixed with PMMA bone cement to create composites containing 20, 30, and 40 wt % glass. Composites and a bone cement control were soaked in phosphate‐buffered saline. Compressive strength, Young's modulus, weight loss, water uptake, solution pH, and ionic concentrations were measured over 21 days. The compressive strengths of composites decreased over 21 days. Average Young's moduli of the composites remained below 3 GPa. Weight loss and water uptake of specimens did not exceed 2 and 6%, respectively. Boron concentrations and pH of all solutions increased over time, with higher glass weight fractions leading to higher pH values. Results demonstrated that the composite can sustain glass degradation and ionic release without compromising short‐term mechanical strength.
Comparison of two pore sizes of LAE442 scaffolds and their effect on degradation and osseointegration behavior in the rabbit model
Authors: Augustin Julia , Feichtner Franziska , Waselau Anja‐Christina , Julmi Stefan , Klose Christian , Wriggers Peter , Maier Hans Jürgen , Meyer‐Lindenberg Andrea
Published: March 2020

The magnesium alloy LAE442 emerged as a possible bioresorbable bone substitute over a decade ago. In the present study, using the investment casting process, scaffolds of the Magnesium (Mg) alloy LAE442 with two different and defined pore sizes, which had on average a diameter of 400 μm (p400) and 500 μm (p500), were investigated to evaluate degradation and osseointegration in comparison to a ß‐TCP control group. Open‐pored scaffolds were implanted in both greater trochanter of rabbits. Ten scaffolds per time group (6, 12, 24, and 36 weeks) and type were analyzed by clinical, radiographic and μ‐CT examinations (2D and 3D). None of the scaffolds caused adverse reactions. LAE442 p400 and p500 developed moderate gas accumulation due to the Mg associated in vivo corrosion, which decreased from week 20 for both pore sizes. After 36 weeks, p400 and p500 showed volume decreases of 15.9 and 11.1%, respectively, with homogeneous degradation, whereas ß‐TCP lost 74.6% of its initial volume. Compared to p400, osseointegration for p500 was significantly better at week 2 postsurgery due to more frequent bone‐scaffold contacts, higher number of trabeculae and higher bone volume in the surrounding area. No further significant differences between the two pore sizes became apparent. However, p500 was close to the values of ß‐TCP in terms of bone volume and trabecular number in the scaffold environment, suggesting better osseointegration for the larger pore size.
Predictive and prognostic values of preoperative platelet parameters in patients with gynecological tumors
Authors: Yang Wei , Chen Ying‐ying , Bi Chen , Shu Kuang‐yi , Ye Man‐li , Li Fan‐fan , Chen Jie , Wang Xiao‐ou , Chen Xiao‐jian , Jiang Ming‐hua
Published: March 2020

Background

Platelets play a role in tumor cell growth, metastasis, and angiogenesis, and the present study aimed to evaluate diagnostic and prognostic values of platelet parameters in patients with gynecological tumors.

Methods

A total of 1062 women were included. Differences of platelet parameters (platelet count [PLT], plateletcrit [PCT], mean platelet volume [MPV], platelet‐large cell rate [P‐LCR], and platelet distribution width [PDW]) between different categories were analyzed by nonparametric test. The optimal cutoff value was calculated with receiver operating characteristic analysis. Overall survivals were analyzed with Kaplan‐Meier method and log‐rank tests for univariate analysis.

Results

Platelet count and PCT were significantly increased, and MPV and P‐LCR were significantly reduced in malign and benign gynecological tumor groups compared with the controls (P < .001); PDW had no significant differences. There were no significant differences in PLT, PCT, MPV, P‐LCR, and PDW between different tumor locations and pathologic types. The optimal cutoff values of PLT, PCT, MPV and P‐LCR were 274, 0.26, 10.08, and 24.8 (AUC: 0.661, 0.643, 0.593, 0.562), and PCT had preferable sensibility and specificity (50.84% and 70.42%) in predicting the presence of gynecological tumors. According to survival analysis, increased PLT (≥274 × 109/L) and PCT (≥0.26), and induced MPV (<10.08 fL) and P‐LCR (<24.8%) were associated with shorter overall survival.

Conclusions

Platelet count, PCT, MPV, and P‐LCR can be used as preferable auxiliary parameters for predicting the presence of gynecological tumors. Increased PLT and PCT, or decreased MPV and P‐LCR indicated a heavier tumor burden and shorter overall survival.
Facile green synthesis approach for the production of chromium oxide nanoparticles and their different in vitro biological activities
Authors: Iqbal Javed , Abbasi Banzeer Ahsan , Munir Akhtar , Uddin Siraj , Kanwal Sobia , Mahmood Tariq
Published: March 2020

Green synthesis of nanoparticles using plants has become a promising substitute for the conventional chemical synthesis methods. In the present study, our aim was to synthesize chromium oxide nanoparticles (Cr2O3NPs) through a facile, low‐cost, eco‐friendly route using leaf extract of Rhamnus virgata (RV). The formation of Cr2O3NPs was confirmed and characterized by spectroscopic profile of UV–Vis, EDX, FTIR, and XRD analyses. The UV‐visible spectroscopy has confirmed the formation of Cr2O3NPs by the change of color owing to surface plasmon resonance. The bioactive functional groups present in the leaf extract of RV involved in reduction and stabilization of Cr2O3NPs were determined by FTIR analysis. Based on XRD analysis, crystalline nature of Cr2O3NPs was determined. The morphological shape and elemental composition of Cr2O3NPs were investigated using SEM and EDX analyses, respectively. With growing applications of Cr2O3NPs in biological perspectives, Cr2O3NPs were evaluated for diverse biopotentials. Cr2O3NPs were further investigated for its cytotoxicity potentials against HepG2 and HUH‐7 cancer cell lines (IC50: 39.66 and 45.87 μg/ml), respectively. Cytotoxicity potential of Cr2O3NPs was confirmed against promastigotes (IC50: 33.24 μg/ml) and amastigotes (IC50: 44.31 μg/ml) using Leishmania tropica (KMH23). The Cr2O3NPs were further evaluated for antioxidants, biostatic, alpha‐amylase, and protein kinase inhibition properties. Biocompatibility assay was investigated against human macrophages which confirmed the nontoxic nature of Cr2O3NPs. Overall, the synthesized Cr2O3NPs are biocompatible and nontoxic and proved to possess significant biopotentials. In future, different in vivo studies are needed to fully investigate the cytotoxicity and mechanism of action associated with these Cr2O3NPs.
Cyclic fatigue resistance and energy dispersive X‐ray spectroscopy analysis of novel heat‐treated nickel–titanium instruments at body temperature
Authors: Micoogullari Kurt Seniha , Kaval Mehmet Emin , Serefoglu Burcu , Kandemir Demirci Gözde , Çalışkan Mehmet Kemal
Published: March 2020

The aim of this study was to evaluate the cyclic fatigue resistance of Dia‐X, WaveOne Gold and One Curve files in a water bath at intracanal temperature (35°C). Thirty‐nine instruments Dia‐X, WaveOne Gold, and One Curve systems (n = 13) were tested in an artificial canal with a curvature angle of 60° and a radius of 3 mm. A water bath setup at a temperature of 35°C was used to simulate the intracanal temperature and time to fracture (TTF) as seconds was recorded. The mean data were analyzed statistically using one‐way ANOVA, and post hoc Tukey test (p = .05). The fractured surface of the instruments was examined with scanning electron microscopy (SEM) and chemical composition of the instruments were investigated with energy dispersive X‐ray spectroscopy (EDS). Statistically significant differences were detected in TTF values of all the systems as follows: One Curve > WaveOne Gold > Dia‐X (p < .05). One Curve instruments demonstrated the highest TTF values in all the tested instruments. The EDS microanalysis revealed similar NiTi composition of on the surface of One Curve, WaveOne Gold, and Dia‐X instruments. The novel manufacturing process, including C‐wire heat treatment and the variable cross‐section of the One Curve files, could be the main factors affecting the fatigue life of the instruments.
Phasor‐FLIM analysis of Thioflavin T self‐quenching in Concanavalin amyloid fibrils
Authors: Sancataldo Giuseppe , Anselmo Sara , Vetri Valeria
Published: March 2020

The formation of amyloid structures has traditionally been related to human neurodegenerative pathologies and, in recent years, the interest in these highly stable nanostructures was extended to biomaterial sciences. A common method to monitor amyloid growth is the analysis of Thioflavin T fluorescence. The use of this highly selective dye, diffused worldwide, allows mechanistic studies of supramolecular assemblies also giving back important insight on the structure of these aggregates. Here we present experimental evidence of self‐quenching effect of Thioflavin T in presence of amyloid fibrils. A significant reduction of fluorescence lifetime of this dye which is not related to the properties of analyzed amyloid structures is found. This result is achieved by coupling Fluorescence Lifetime Imaging Microscopy with phasor approach as suitable model‐free methods and constitute a serious warning that have to be taken in account if is dye is used for quantitative studies.
Intravital imaging of eosinophils: Unwrapping the enigma
Authors: Nguyen William N T , Jacobsen Elizabeth A , Finney Constance A M , Colarusso Pina , Patel Kamala D
Published: March 2020

Eosinophils are traditionally associated with allergic and parasitic inflammation. More recently, eosinophils have also been shown to have roles in diverse processes including development, intestinal health, thymic selection, and B-cell survival with the majority of these insights being derived from murine models and in vitro assays. Despite this, tools to measure the dynamic activity of eosinophils in situ have been lacking. Intravital microscopy is a powerful tool that enables direct visualization of leukocytes and their dynamic behavior in real-time in a wide range of processes in both health and disease. Until recently eosinophil researchers have not been able to take full advantage of this technology due to a lack of tools such as genetically encoded reporter mice. This mini-review examines the history of intravital microscopy with a focus on eosinophils. The development and use of eosinophil-specific Cre (EoCre) mice to create GFP and tdTomato fluorescent reporter animals is also described. Genetically encoded eosinophil reporter mice combined with intravital microscopy provide a powerful tool to add to the toolbox of technologies that will help us unravel the mysteries still surrounding this cell.
Eosinophils in wound healing and epithelial remodeling: Is coagulation a missing link?
Authors: Coden Mackenzie E , Berdnikovs Sergejs
Published: March 2020

Eosinophils are often cited as playing roles in wound healing and epithelial remodeling; however, the exact triggers and mechanisms of such activity remain poorly understood. Eosinophils show the remarkable capacity to partner with coagulation, which is a highly conserved biologic system evolved to protect an organism from injury by promoting hemostasis and tissue repair. Eosinophils contribute directly by producing key factors in coagulation (tissue factor, thrombin) and fibrinolysis (plasminogen). Moreover, they have been shown to interact with other players in these cascades, such as fibrinogen and the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system, which further promotes coagulation and fibrinolysis. Although primarily thought of in the contexts of blood clotting and vascular repair, coagulation and fibrinolytic systems play key roles within tissue, in particular during epithelial injury and remodeling. Chronic inflammation and remodeling frequently associate with pro-thrombotic and pro-coagulation state. There is a striking association between eosinophils and dysregulated coagulation in animal models and human disease. This review will examine the mechanistic links between eosinophils and the coagulation system in the context of epithelial injury and repair, as well as evidence for this interaction in heart disease, type 2 inflammatory diseases, and cancer. Collectively, multiple emerging studies summarized in this review elucidate an overlooked, but potentially fundamental, biologic mechanism to engage eosinophils in processes of epithelial injury and repair.
Integrated immune gene expression signature and molecular classification in gastric cancer: New insights
Authors: Refolo Maria Grazia , Lotesoriere Claudio , Messa Caterina , Caruso Maria Gabriella , D'Alessandro Rosalba
Published: March 2020

Gastric cancer (GC) is characterized by extreme heterogeneity due to histopathological differences, molecular characteristics, and immune gene expression signature. Until recently, several targeted therapies failed due to this complexity. The recent immunotherapy resulted in more effective and safe approaches in several malignancies. All tumors could be considered potentially immunogenic and the new knowledge regarding the interactions among tumor cells, immune cells, and tumor microenvironment (TME) allowed to reverse possible immune resistance. The immune response is a complex multisteps process that finely regulates the balance between the recognition of non-self and the prevention of autoimmunity. Cancer cells can use these pathways to suppress tumor immunity as a major mechanism of immune resistance. The recent molecular classifications of GCs by The Cancer Genome Atlas (TCGA) and by the Asian Cancer Research (ACRG) networks, together with the identification of multiple biomarkers, open new perspectives for stratification of patients who might benefit from a long-term immune checkpoint therapy. One of the major processes that contribute to an immunosuppressive microenvironment is represented by tumor angiogenesis. The cellular mechanisms inducing both angiogenesis and immunosuppressive responses are often reached by the same cell types and soluble factors, such as vascular endothelial growth factor A (VEGFA). Recent studies point out that combinatorial strategies should be adapted as useful therapeutic approach to reverse the immunosuppressive status of microenvironment occurring in a relevant percentage of gastric tumors.