bluuebunny/crossref_metadata_2025 huggingface dataset:
Role and Potential of Metal Sulfide Catalysts in Lithium‐Sulfur Battery Applications
Authors: Kim Seong‐Jun , Kim Kookhan , Park Jungjin , Sung Yung‐Eun
Published: March 2019

Sulfur has been explored as a cathode active material for post rechargeable batteries because of their various attractive features such as their high theoretical specific capacity which is more than six times that of typical Li‐ion battery (LIB) cathode materials (LiCoO2). Furthermore, as a by‐product of the oil refining process, it is abundant and inexpensive. Despite this, the low electrical conductivity of sulfur and the polysulfide shuttle effect in ether‐based electrolytes has become a major obstacle to the industrialization of lithium‐sulfur (Li−S) batteries. Among them, the polysulfide shuttle effect is the critical limitation to be solved and thus many researchers have been engaged in its solution. This work summarizes a variety of metal sulfide catalysts that have recently attracted attention as additives. In addition, a brief description of the metal sulfides interprets their ability to anchor polysulfides via surface polarity and to act as an electrocatalyst during polysulfide redox reactions. We describe the electrocatalytic activity and anchoring effect of metal sulfides in Li−S batteries and their future possibilities.
Ultrathin‐Polyaniline‐Coated Pt–Ni Alloy Nanooctahedra for the Electrochemical Methanol Oxidation Reaction
Authors: Kim Kyung Soo , Hong Youngmin , Kim Heon Chul , Choi Sang‐Il , Hong Jong Wook
Published: March 2019

Controlling the morphology and composition of nanocatalysts constructed from metals and conductive polymers has attracted attention owing to their great potential for the development of high‐efficiency catalysts for various catalytic applications. Herein, a facile synthetic approach for ultrathin‐polyaniline‐coated Pt–Ni nanooctahedra (Pt‐Ni@PANI hybrids) with controllable PANI shell thicknesses is presented. Pt–Ni nanooctahedra/C catalysts enclosed by PANI shells with thicknesses from 0.6 to 2.4 nm were obtained by fine control over the amount of aniline. The various Pt‐Ni@PANI hybrids exhibited electrocatalytic activity toward the methanol oxidation reaction that is highly dependent on the thickness of the PANI shell. Pt‐Ni@PANI hybrids with the thinnest PANI shells (0.6 nm) showed markedly improved electrocatalytic performance for the methanol oxidation reaction compared with Pt‐Ni@PANI hybrids with thicker PANI shells, Pt–Ni nanooctahedra/C, and commercial Pt/C due to synergistic benefits of ultrathin PANI shells and Pt–Ni alloy.
Synthetic Routes towards Multifunctional Cyclopentadienes
Authors: Frei Angelo
Published: March 2019

Cyclopentadiene, and more importantly its functionalized derivatives, are a cornerstone of synthetic chemistry. Nowadays, they find applications in (chiral) catalysis, as ligands for organometallic complexes with potential diagnostic and therapeutic applications, and many more. This Minireview highlights the progress that has been made in the development of flexible and robust synthetic routes towards multifunctional cyclopentadienes in the last 20 years.
Does the transversal screw design increase the risk of mechanical complications in dental implants? A finite elements analysis
Authors: Sánchez Lasheras Fernando , Gracia Rodríguez Javier , Mauvezín‐Quevedo Mario , Martín‐Fernández Elena , Bobes‐Bascarán Javier , de Llanos‐Lanchares Hector , Álvarez‐Arenal Ángel
Published: March 2019

The transversal screw was introduced in order to overcome some disadvantages of the transocclusal screw. However, its mechanical risk has not been studied sufficiently. The main purpose of this research was to assess and compare stress distribution in the screws and abutment of a single‐crown implant with transversal and transocclusal screw models. Two 3D models were assembled to analyse a single‐implant–supported prosthesis with transversal and transocclusal screws embedded in the jawbone. The crown was subjected to a static load of value 300 N with different levels of inclination. The transversal screw model, with an axial load of 15°, was the one with lowest stress values in all its components. However, the stress was greater with more inclined loads when compared with the transocclusal model. The prosthetic transversal screw showed much less stress than the rest of the components for any load inclination. The transversal screw design is the option with the lowest risk of mechanical complications, both in the prosthetic screw and in the abutment screw, when applying forces of lower inclination. The more oblique forces favoured a better biomechanical environment in the abutment and its screw in the transocclusal screw model.
Global recurrence rates in diabetic foot ulcers: A systematic review and meta‐analysis
Authors: Fu Xue‐Lei , Ding Hui , Miao Wei‐Wei , Mao Chun‐Xing , Zhan Min‐Qi , Chen Hong‐Lin
Published: March 2019

Recurrence rates of diabetic foot ulcers vary widely in the published literature. The aim of this systematic review is to estimate recurrence rates of diabetic foot ulcers. We did a PubMed search and performed a review of reference lists for studies reporting recurrence of diabetic foot ulcers. The weighted relative risk (RR) and corresponding 95% confidence interval (CI) for recurrence was estimated. Forty‐nine studies reporting recurrence of diabetic foot ulcers were included. A pooled estimate for recurrence rate was 22.1% per person‐year (py) (95% CI, 19.0‐25.2%). Recurrence rate was 24.9% per py in Europe (95% CI, 20.0%‐29.7%), 17.8% per py in North America (95% CI, 12.7%‐22.9%), 16.9% per py in Africa (95% CI, 4.7%‐29.0%), and 17.0% per py in Asia (95% CI, 11.1%‐23.0%). Turkey had the highest recurrence rate of 44.4% per py (95% CI, 24.9%‐63.9%), and Bangladesh had the lowest of 4.3% per py (95% CI, 2.3%‐6.3%). Recurrence rates of diabetic foot ulcers before 2002, between 2002 and 2008, and after 2008 were 22.2% per py (95% CI, 17.6%‐26.8%), 21.9% per py (95% CI, 17.0%‐26.8%), and 21.8% per py (95% CI, 16.3%‐27.2%), respectively. Recurrence rates of diabetic foot ulcers are high. Recurrence rates vary widely in different regions and have decreased recently. More attention towards recurrence of diabetic foot ulcers is urgently required.
Next‐generation phylogeography of the cockle Cerastoderma glaucum: Highly heterogeneous genetic differentiation in a lagoon species
Authors: Sromek Ludmila , Forcioli Didier , Lasota Rafal , Furla Paola , Wolowicz Maciej
Published: March 2019

Aim

Coastal lagoons form an intriguing example of fragmented marine habitats. Restricted gene flow among isolated populations of lagoon species may promote their genetic divergence and may thus provide a first step toward speciation. In the present study, the population genetic structure of the lagoon cockle Cerastoderma glaucum has been investigated to clarify the complex phylogeographic pattern found in previous studies, to localize major genetic breaks, and to discuss their origin and maintenance.

Location

The Atlantic and Mediterranean coasts, including the Baltic, North Sea, and Black Sea.

Methods

A total of 204 C. glaucum individuals from 14 populations were genotyped using restriction site‐associated DNA sequencing (RADseq). The genetic diversity, divergence, and structure were analyzed using genome‐wide single nucleotide polymorphisms (SNPs). Phylogenetic relationships were inferred under a coalescent model using SVDquartets.

Results

The RADseq approach allowed inferring phylogeographic relationships with an unprecedented resolution. Three deeply divergent lineages were identified within C. glaucum that are separated by many genetic barriers: one lineage in the Aegean–Black Sea region, one in the Ionian Sea, and the last one widely distributed from the Western Mediterranean to the Baltic Sea. The nested branching pattern displayed on the species tree largely agrees with the likely scenario of C. glaucum postglacial expansion from the Mediterranean to the Baltic Sea.

Main conclusion

The genetic differentiations between geographically separated lagoons proved to be strong, highlighting the evolutionary influence of these naturally fragmented habitats. The postglacial expansion created complex patterns of spatial segregation of genetic diversity with allele frequency gradients in many outlier loci, but also discrepancies between the nuclear and mitochondrial genetic markers that probably arose from genetic surfing of mitochondrial variation.
Plant–herbivore coevolution and plant speciation
Authors: Maron John L. , Agrawal Anurag A. , Schemske Douglas W.
Published: March 2019

More than five decades ago, Ehrlich and Raven proposed a revolutionary idea–that the evolution of novel plant defense could spur adaptive radiation in plants. Despite motivating much work on plant–herbivore coevolution and defense theory, Ehrlich and Raven never proposed a mechanism for their "escape and radiate" model. Recent intriguing mechanisms proposed by Marquis et al. include sympatric divergence, pleiotropic effects of plant defense traits on reproductive isolation, and strong postzygotic isolation, but these may not be general features of herbivore‐mediated speciation. An alternate view is that herbivores may impose strong divergent selection on defenses in allopatric plant populations, with plant–herbivore coevolution driving local adaptation resulting in plant speciation. Building on these ideas, we propose three scenarios that consider the role of herbivores in plant speciation. These include (1) vicariance, subsequent coevolution within populations and adaptive divergence between geographically isolated populations, (2) colonization of a new habitat lacking effective herbivores followed by loss of defense and then re‐evolution and coevolution of defense in response to novel herbivores, and (3) evolution of a new defense followed by range expansion, vicariance, and coevolution. We discuss the general role of coevolution in plant speciation and consider outstanding issues related to understanding: (1) the mechanisms behind cospeciation of plants and insects, (2) geographic variation in defense phenotypes, (3) how defensive traits and geography map on plant phylogenies, and (4) the role of herbivores in driving character displacement in defense phenotypes of related species in sympatry.
Male hypogonadism: 14‐year prospective outcome in 550 men with type 2 diabetes
Authors: Malipatil Nagaraj S. , Yadegarfar Ghasem , Lunt Mark , Keevil Brian , Siddals Kirk , Livingston Mark , Roberts Siriol , Narayanan Prakash , Rutter Martin , Gibson J. Martin , Donn Rachelle , Hackett Geoff , Jones T. Hugh , Heald Adrian
Published: March 2019

Introduction

Hypogonadism is more prevalent in men with type 2 diabetes (T2DM) (25%‐40%) than in men without T2DM. Hypogonadism has been associated with poorer glycaemic outcomes and increased cardiovascular morbidity/mortality. We report a 14‐year follow‐up study to evaluate the influence of baseline testosterone level on T2DM outcomes.

Research design and methods

A total of 550 men with T2DM underwent baseline total testosterone and dihydrotestosterone measurement by tandem mass spectrometry. Mean age of the men was 59.7 ± 12 (mean ± SD) years. Sex hormone‐binding globulin (SHBG) was measured and free testosterone estimated. Patients were followed up between 2002 and 2016. Mean follow‐up period was 12.2 ± 4 years using the Salford (UK) Integrated Health Records system.

Results

Mean baseline total testosterone was 13.7 ± 5.8 nmol/L, and mean free testosterone was 245.7 ± 88.0 pmol/L. Mean for low total testosterone (<10 nmol/L) was 7.6 ± 2.0 nmol/L (n = 154) and 142 men had a free testosterone <190 pmol/L. During the 14‐year duration follow‐up, 22% of men experienced a myocardial infarction, 18% experienced a stroke, 11% developed angina, 14% underwent coronary revascularization. About 38% of the men initially recruited died. A lower total testosterone was associated with a higher body mass index (kg/m2) at follow‐up: regression coefficient −0.30 (95% CI −0.445 to −0.157), P = 0.0001. The mortality rate was higher in patients with lower total testosterone compared to normal baseline total testosterone (5.0% vs 2.8% per year, P < 0.0001). A similar phenomenon was seen for dihydrotestosterone (4.3% vs 2.9% per year, P = 0.002) for normal vs low dihydrotestosterone) and for lower SHBG. Over the whole follow‐up period 36.1% (143/396), men with normal baseline testosterone died vs 55.8% (86/154) of hypogonadal men at baseline. In Cox regression, the age‐adjusted hazard ratio (HR) for higher mortality associated with low total testosterone was 1.54 (95% CI: 1.2‐2.0, P < 0.002), corresponding to a 3.2 year reduced life expectancy for hypogonadal T2DM men.

Conclusion

Low testosterone and dihydrotestosterone levels are associated with higher all‐cause mortality in T2DM men. Hypogonadal men with T2DM should be considered as very high risk for cardiovascular events/death.
Fabrication of an Fe‐Doped SrTiO3 Photocatalyst with Enhanced Dinitrogen Photofixation Performance
Authors: Ying Zihao , Chen Shengtao , Peng Tianyou , Li Renjie , Zhang Jing
Published: March 2019

SrTiO3 as semiconducting photocatalyst has been extensively investigated due to its band edges meeting the thermodynamic requirements for water splitting, but a few attention has been concentrated on its application in the NH3 synthesis via N2 photofixation process. Herein, Fe‐doped SrTiO3 (FexSr1–xTiO3) products (0 ≤ x ≤ 0.20) were synthesized via a hydrothermal process followed by calcination at 700 °C. All FexSr1–xTiO3 products (0.03 ≤ x ≤ 0.20) deliver an enhanced N2 fixation ability, and FexSr1–xTiO3 (x = 0.10) achieves the best NH3 production activity of 30.1 µmol g–1 h–1, which is 3.2‐hold higher than that of SrTiO3 alone. Once the x value is higher than 0.10, FexSr1–xTiO3 will transform into composites containing Fe‐doped SrTiO3 and α‐Fe2O3, which acts as charge recombination sites, thus causes a decreased N2 fixation activity. Further investigations demonstrate that the surface Fe3+‐doped sites can not only chemisorb and activate N2 molecules, but also promote the interfacial electron transfer from Fe‐doped SrTiO3 to N2 molecules, and thus significantly improve the N2 fixation ability. The present Fe‐doped SrTiO3 products exhibit characteristic features such as stable and efficient N2 fixation ability as well as simultaneous realization of N2 reduction and H2O oxidation without co‐catalyst, which are of significance in artificial photosynthesis with H2O as electron and proton sources.
Investigation of the Adhesion Strength along the Electrode Manufacturing Process for Improved Lithium‐Ion Anodes
Authors: Billot Nicolas , Günther Till , Schreiner David , Stahl Ralf , Kranner Jakob , Beyer Moritz , Reinhart Gunther
Published: March 2019

Nowadays, lithium‐ion batteries (LIBs) represent a key technology for energy storage in electromobility or stationary applications. Lithium‐ion electrodes, more specifically their mechanical properties, such as the adhesion strength, play an active role for the life span of LIBd. Herein, parameter‐ and process‐oriented investigations are conducted within electrode manufacturing to identify the main levers to improve the mechanical characteristics of electrodes. Among the investigated factors and processes, the binder amount, the coating thickness, and the calendaring represent the main influencing factors of the adhesion strength. A transfer of these findings can play an important role for the implementation of new anode materials, such as silicon, enabling high‐energy batteries with increased lifetime.
The standardization of the report for urine cell counting—A converting factor for Sysmex UF‐1000i
Authors: Wang Lina , Wang Huacheng , Zhao Chanjing , Chen Cha
Published: March 2019

Background

Multicenter laboratory may apply both automated flow cytometer and microscopy for urinalysis. Automated flow cytometer such as Sysmex UF‐1000i evaluates particles with native urine without centrifugation and reports as “counts per μL.” Microscopic examination recommended as the reference method for urine sediment analysis reports results as “counts per HPF (or μL).” Moreover, some results from flow cytometer are needed to be checked visually under microscopy. Therefore, it is worth to establish the consistency of the results from these two methods.

Methods

Urine specimens from 412 patients were examined with Sysmex UF‐1000i and manual microscopy using FAST‐READ disposable counting chambers. White blood cell (WBC) and red blood cell (RBC) counting results from UF‐1000i after transferred with the converting factor (0.297) we estimated were compared with that from microscopic examination. Method comparison was performed using Passing‐Bablok analysis.

Results

After transferred with the converting factor (0.297), cell counting results from UF‐1000i showed a good correlation with that derived by the reference method (R2 was 0.868 for RBCs (P < 0.001), 0.882 for WBCs (P < 0.001)). Passing‐Bablok analysis showed no systematic difference (intercept estimate, −1 [95%CI, −7 to 3] and slightly proportional (slope estimate, 1.2 [95%CI, 1.0 to 1.7]) bias between concentrations of cells measured by manual microscopy and Sysmex UF‐1000i using the converting factor.

Conclusion

The converting factor (0.297) helps to transfer “counts per μL (non‐centrifugal urine)” to “counts per μL (equal to centrifugal urine),” and to keep the urine particle analysis results of Sysmex UF‐1000i consistent with the results from the reference method.
Microvesicles of osteoblasts modulate bone marrow mesenchymal stem cell‐induced apoptosis to curcumin in myeloid leukemia cells
Authors: Zahedpanah Mahdi , Takanlu Javid Sabour , Nikbakht Mohsen , Rad Fariba , Farhid Fatemeh , Mousavi Seyed Asadollah , Rad Soroush , Fumani Hosein Kamranzadeh , Hosseini Rad Seyed Mohammad Ali , Mohammadi Saeed
Published: March 2019

Microvesicles (MVs) derived from bone marrow niche components have an important role in genetic reprogramming and subsequent drugs induce apoptosis in leukemic cells. Here, we have found that undertreatment of curcumin or daunorubicin, the cross‐talk through MVs of KG‐1‐bone marrow mesenchymal stem cells (BMSCs), significantly downregulates the expression of the survival gene osteopontin (OPN), CXCL‐12, IL‐6 (interleukin‐6), STAT‐3, and VCAM‐1 (vascular cell adhesion molecule 1) in treated‐KG‐1 cells as well as exclusively upregulates CXCL‐12 in BMSCs. Drug treated‐cell populations’ MVs of both single cultured osteoblasts (OBs) and cocultured KG‐1 + BMSCs + OBs similarly upregulate survival mediators’ OPN, CXCL‐12, IL‐6, STAT‐3, and VCAM‐1 in treated‐KG‐1 cells. Likewise, isolated MVs from KG‐1 cells or communication between KG‐1, BMSCs, and OBs treated by drugs increase the expression of genes OPN, CXCL‐12, IL‐6, STAT3, and VCAM‐1 by OBs. MVs derived from KG‐1 + BMSCs + OBs reduce drug‐induced apoptosis in KG‐1 cells. This suggests MVs‐mediated information transfer is a procedure whereby OBs could overcome BMSCs‐induced apoptosis in drug‐treated‐KG‐1 cells.
Deletion of Htt cause alterations in cAMP signaling and spatial patterning in Dictyostelium discoideum
Authors: Bhadoriya Pooja , Jain Mukul , Kaicker Geeta , Saidullah Bano , Saran Shweta
Published: March 2019

In the present study, we have analyzed in detail the functions of Htt during growth and development of the protist, Dictyostelium discoideum by creating mutants (both overexpressor and knockout). The mRNA was present at all stages of growth and development. Overexpression of
htt did not show any major anomaly, while deletion resulted in delayed aggregation territory formation and showed asynchronous development especially after slug stage. The slugs formed by
htt
− cells showed aberration in anterior–posterior boundary, showing increased prestalk region. DdHtt regulates STAT transcription factors in the tip organizer region that help maintain patterning and culmination. In chimeras with the wild‐type,
htt
− cells preferentially localized to the tip of the slug and basal disc regions of the fruiting body showing prestalk/stalk bias, while the overexpressing cells majorly populated the prespore/spore region showing spore bias. These differences could be attributed to protein kinase A (PKA)‐regulated cyclic adenosine monophosphate (cAMP) signaling.
miR‐31 shuttled by halofuginone‐induced exosomes suppresses MFC‐7 cell proliferation by modulating the HDAC2/cell cycle signaling axis
Authors: Xia Xiaojing , Wang Xin , Zhang Shouping , Zheng Yi , Wang Lei , Xu Yanzhao , Hang Bolin , Sun Yawei , Lei Liancheng , Bai YueYu , Hu Jianhe
Published: March 2019

Traditional Chinese medicine (TCM) are both historically important therapeutic agents and important source of new drugs. Halofuginone (HF), a small molecule alkaloid derived from febrifugine, has been shown to exert strong antiproliferative effects that differ markedly among various cell lines. However, whether HF inhibits MCF‐7 cell growth in vitro and underlying mechanisms of this process are not yet clear. Here, we offer the strong evidence of the connection between HF treatment, exosome production and proliferation of MCF‐7 cells. Our results showed that HF inhibits MCF‐7 cell growth in both time‐ and dose‐dependent manner. Further microRNA (miRNA) proﬁles analysis in HF treated and nontreated MCF‐7 cell and exosomes observed that six miRNAs are particularly abundant and sorted in exosomes. miRNAs knockdown experiment in exosomes and the MCF‐7 growth inhibition assay showed that exosomal microRNA‐31 (miR‐31) modulates MCF‐7 cells growth by specially targeting the histone deacetylase 2 (HDAC2), which increases the levels of cyclin‐dependent kinases 2 (CDK2) and cyclin D1 and suppresses the expression of p21. In conclusion, these data indicate that inhibition of exosome production reduces exosomal miR‐31, which targets the HDAC2 and further regulates the level of cell cycle regulatory proteins, contributing to the anticancer functions of HF. Our data suggest a new role for HF and the exosome production in tumorigenesis and may provide novel insights into prevention and treatment of breast cancer.
Atomic force microscopy and energy dispersive X‐ray spectrophotometry analysis of reciprocating and continuous rotary nickel‐titanium instruments following root canal retreatment
Authors: Üreyen Kaya Bulem , Erik Cevat Emre , Kiraz Gülsen
Published: March 2019

The aim was to examine the effect of retreatment process on the surface roughness and nickel titanium (NiTi) composition of ProTaper Universal Retreatment (PTUR; consists of 3 files; D1, D2, D3) and WaveOne Gold (WOG) (primary) instruments. Twenty extracted mandibular molar teeth with severe curved (30–40°) mesial roots were selected and divided into two groups (n = 10) based on the instrument used for the removal of the root canal filling. Before and after using the instruments in two canals, they were subjected to atomic force microscopy (AFM) and energy dispersive X‐ray spectrophotometry (EDX) analysis. The EDX analysis data and roughness average (Ra) and root mean square (RMS) values were analyzed statistically using a one‐way analysis of variance and post hoc Tukey's test at the 5% significant level. There was no significant difference between the new and used D1 and D2 PTUR and WOG instruments in terms of the Ni composition (p > .05). The Ti contents of the used D2 and D3 PTUR instruments were lower those of the new instruments (p < .05). In both new and used instruments, PTUR and WOG have no difference in terms of Ra and RMS values. (p > .05). The Ra and RMS values of the PTUR and WOG systems significantly increased after removal of the root canal filling (p < .05). The use of PTUR and WOG instruments for removal of root canal filling in severely curved root canals affected the surface topography of the files. The NiTi composition of the WOG instruments was unaffected by the retreatment process.
Synthesis, Characterization, and Investigation of Cholinesterase Inhibitory Properties of Novel Phthalocyanines
Authors: Demirbaş Ümit , Barut Burak , Yalçın İzzet , Değirmencioğlu İsmail , Yıldırmış Sermet , Özel Arzu
Published: March 2019

In this study, 4‐{2‐(2‐thienyl)ethoxy}phthalonitrile (3) and its tetra substituted peripherally metal‐free (4), lead (II) (5), magnesium (II) (6), and cobalt (II) (7) phthalocyanines were synthesized. The structural characterization of the obtained compounds was performed by a combination of FTIR,1H‐NMR, UV–vis, and MALDI‐TOF techniques. The inhibitory properties of these compounds were determined using Ingkaninan's methods against cholinesterase enzymes. Compound (7) had the highest enzyme inhibitory effect toward AChE and BuChE enzymes with IC50values of 23.71 ± 0.39 and 27.29 ± 0.22 μM, respectively. The enzyme kinetic study of compound (7) demonstrated noncompetitive AChE inhibition and uncompetitive BuChE inhibition. TheKivalues of compound (7) against AChE and BuChE were found to 39.15 and 7.25 μM, respectively. In the tested compounds, (7) deserves further investigation for potential therapeutic candidates of Alzheimer's disease.
Exploiting epigenetics for the treatment of inborn errors of metabolism
Authors: Rutten Martijn G. S. , Rots Marianne G. , Oosterveer Maaike H.
Published: March 2019

Gene therapy is currently considered as the optimal treatment for inborn errors of metabolism (IEMs), as it aims to permanently compensate for the primary genetic defect. However, emerging gene editing approaches such as CRISPR‐Cas9, in which the DNA of the host organism is edited at a precise location, may have outperforming therapeutic potential. Gene editing strategies aim to correct the actual genetic mutation, while circumventing issues associated with conventional compensation gene therapy. Such strategies can also be repurposed to normalize gene expression changes that occur secondary to the genetic defect. Moreover, besides the genetic causes of IEMs, it is increasingly recognized that their clinical phenotypes are associated with epigenetic changes. Because epigenetic alterations are principally reversible, this may offer new opportunities for treatment of IEM patients. Here, we present an overview of the promises of epigenetics in eventually treating IEMs. We discuss the concepts of gene and epigenetic editing, and the advantages and disadvantages of current and upcoming gene‐based therapies for treatment of IEMs.
Toward a better definition of EPCAM deletions in Lynch Syndrome: Report of new variants in Italy and the associated molecular phenotype
Authors: Cini Giulia , Quaia Michele , Canzonieri Vincenzo , Fornasarig Mara , Maestro Roberta , Morabito Alberto , D'Elia Angela Valentina , Urso Emanuele Damiano , Mammi Isabella , Viel Alessandra
Published: March 2019

Background

Inherited epimutations of Mismatch Repair (MMR) genes are responsible for Lynch Syndrome (LS) in a small, but well defined, subset of patients. Methylation of the MSH2 promoter consequent to the deletion of the upstream EPCAM gene is found in about 1%–3% of the LS patients and represents a classical secondary, constitutional and tissue‐specific epimutation. Several different EPCAM deletions have been reported worldwide, for the most part representing private variants caused by an Alu‐mediated recombination.

Methods

712 patients with suspected LS were tested for MMR mutation in our Institute. EPCAM deletions were detected by multiplex ligation‐dependent probe amplification (MLPA) and then defined by Long‐Range polymerase chain reaction (PCR)/Sanger sequencing. A comprehensive molecular characterization of colorectal cancer (CRC) tissues was carried out by immunohistochemistry of MMR proteins, Microsatellite Instability (MSI) assay, methylation specific MLPA and transcript analyses. In addition, somatic deletions and/or variants were investigated by MLPA and next generation sequencing (NGS).

Results

An EPCAM deletion was found in five unrelated probands in Italy: variants c.556‐490_*8438del and c.858+1193_*5826del are novel; c.859‐1430_*2033del and c.859‐670_*530del were previously reported. All probands were affected by CRC at young age; tumors showed MSI and abnormal MSH2/MSH6 proteins expression. MSH2 promoter methylation, as well as aberrant in‐frame or out‐of‐frame EPCAM/MSH2 fusion transcripts, were detected in CRCs and normal mucosae.

Conclusion

An EPCAM deletion was the causative variant in about 2% of our institutional series of 224 LS patients, consistent with previously estimated frequencies. Early age and multiple CRCs was the main clinical feature of this subset of patients.
The Matrix Metalloproteinase‐13 Inhibitor Poricoic Acid ZI Ameliorates Renal Fibrosis by Mitigating Epithelial‐Mesenchymal Transition
Authors: Chen Lin , Cao Gang , Wang Ming , Feng Ya‐Long , Chen Dan‐Qian , Vaziri Nosratola D. , Zhuang Shougang , Zhao Ying‐Yong
Published: March 2019

Scope

Fibrosis plays a key role in the progression of various diseases. Matrix metalloproteinases (MMPs) are important for epithelial‐mesenchymal transition (EMT), which contributes to organ fibrosis. Four new poricoic acids are identified, poricoic acid ZI, ZJ, ZK, and ZL, as novel MMP inhibitors from edible mushroom Poria cocos.

Methods

Molecular docking, siRNA techniques, TGF‐β1‐treated renal cells, and unilateral ureteral obstructed (UUO) mice are used to explore the potential efficacy of the novel MMP inhibitors in mitigating the fibrotic process.

Results

Treatment with four poricoic acids downregulates profibrotic protein expression in TGF‐β1‐induced HK‐2 cells. Similar results are observed in NRK‐52E and NRK‐49F cells, indicating that poricoic acids can suppress EMT. Furthermore, both in vitro and in vivo experiments demonstrate that poricoic acid ZI (PZI) exerts a stronger inhibitory effect on protein expression and enzymatic activity of MMP‐13 than the other three compounds, which is consistent with the docking results. The inhibitory effect of PZI on MMP‐13 is partially attenuated by MMP‐13 RNAi in HK‐2 cells and UUO mice.

Conclusions

The findings indicate that as a specific MMP‐13 inhibitor, PZI attenuates EMT and renal fibrosis. Therefore, the MMP‐13 inhibitor PZI can be a novel therapeutic candidate for limiting EMT and renal fibrosis.
The effect of orthodontic appliances on oral microflora: A case‐control study
Authors: Dallel Ines , Merghni Abderrahmen , Ben Tanfouss Safa , Tobji Samir , Ben Amor Adel , Mastouri Maha
Published: March 2019

Aim

Several studies have shown that orthodontic treatment affects oral flora. The aim of this study was to evaluate the effect of orthodontic treatment on the oral environment.

Materials and Methods

One hundred and one healthy subjects, divided into two groups, were included in this study. The control group consisted of 51 subjects and the test group included 50 patients wearing orthodontic fixed appliances. The microbiological analyses of saliva and bacterial supra‐gingival plaque were performed for the two groups.

Results

The results showed that fixed orthodontic appliances alter the oral microbial flora, with a significant predominance of opportunistic Staphylococcus aureus in the oral cavity of patients after orthodontic treatment with fixed appliances.

Conclusion

Orthodontic appliances may act as a reservoir for opportunistic pathogens. Hence, our findings underline the necessity of paying more attention to the prevalence of opportunistic bacteria after orthodontic treatment.
Delayed onset of smooth muscle cell differentiation leads to hydroureter formation in mice with conditional loss of the zinc finger transcription factor gene Gata2 in the ureteric mesenchyme
Authors: Weiss Anna‐Carina , Bohnenpoll Tobias , Kurz Jennifer , Blank Patrick , Airik Rannar , Lüdtke Timo H , Kleppa Marc‐Jens , Deuper Lena , Kaiser Marina , Mamo Tamrat M , Costa Rui , von Hahn Thomas , Trowe Mark‐Oliver , Kispert Andreas
Published: March 2019

The establishment of the peristaltic machinery of the ureter is precisely controlled to cope with the onset of urine production in the fetal kidney. Retinoic acid (RA) has been identified as a signal that maintains the mesenchymal progenitors of the contractile smooth muscle cells (SMCs), while WNTs, SHH, and BMP4 induce their differentiation. How the activity of the underlying signalling pathways is controlled in time, space, and quantity to activate coordinately the SMC programme is poorly understood. Here, we provide evidence that the Zn‐finger transcription factor GATA2 is involved in this crosstalk. In mice, Gata2 is expressed in the undifferentiated ureteric mesenchyme under control of RA signalling. Conditional deletion of Gata2 by a Tbx18cre driver results in hydroureter formation at birth, associated with a loss of differentiated SMCs. Analysis at earlier stages and in explant cultures revealed that SMC differentiation is not abrogated but delayed and that dilated ureters can partially regain peristaltic activity when relieved of urine pressure. Molecular analysis identified increased RA signalling as one factor contributing to the delay in SMC differentiation, possibly caused by reduced direct transcriptional activation of Cyp26a1, which encodes an RA‐degrading enzyme. Our study identified GATA2 as a feedback inhibitor of RA signalling important for precise onset of ureteric SMC differentiation, and suggests that in a subset of cases of human congenital ureter dilatations, temporary relief of urine pressure may ameliorate the differentiation status of the SMC coat. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Application of UPLC‐MS/MS to simultaneously detect four bioactive compounds in the tumour‐shrinking decoction (FM1523) for uterine fibroids treatment
Authors: Cheng Issac Chi‐Chung , Li Ren‐Kai , Leung George Pak‐Heng , Li Song‐Lin , Kong Ming , Lao Li‐Xing , Zhang Zhang‐Jin , Lin Wai‐Ling , Ng Ernest Hung‐Yu , Rong Jian‐Hui , Chen Jian‐Ping , Su Jing , Zhang Kalin Yan‐Bo , Meng Wei
Published: March 2019

Introduction

The Chinese medicine formulation, tumour‐shrinking decoction (TSD, FM1523), which consists of 15 natural medicines, is used for uterine fibroids (UFs) therapy and possesses excellent clinical therapeutic effect.

Objective

To develop a sensitive and validated analytical method for the simultaneous quantification of four crucial bioactive compounds including isorhamnetin‐3‐O‐neohesperidoside, curcumin, peimine and tetrahydropalmatine in the principal formulation of this decoction.

Methods

An ultra‐performance liquid chromatography coupled tandem mass spectrometry (UPLC‐MS/MS) with an electrospray ionisation (ESI) source in multiple reaction monitoring (MRM) mode was conducted to investigate these bioactive compounds in the TSD. The chromatographic separation was performed on a C18 column when the flow rate was adjusted at 0.2 mL/min with gradient elution of acetonitrile–water with 0.1% formic acid. Accelerated solvent extraction (ASE) method with higher extraction efficiency was employed for TSD sample pre‐treatment.

Results

The linearity, limit of detection (LOD) and limit of quantification (LOQ) were determined for this analytical method. The mean recoveries of the compounds were determined between 100.23% and 104.02% with satisfactory relative standard deviation (RSD) in the ranges of 2.65% to 3.81%. The precision was evaluated by intra‐day and inter‐day tests, which revealed RSD within the ranges of 1.21% to 2.14% and 1.24% to 2.32%, respectively.

Conclusion

The bioactive compounds of TSD samples were successfully quantified via UPLC‐MS/MS with MRM mode. This study could help to evaluate the pharmacokinetic study of TSD during clinical applications and present a facile strategy for quantifying bioactive compounds in traditional Chinese Medicine decoction.
Mother‐to‐child transmission of hepatitis B virus after amniocentesis: A retrospective matched cohort study
Authors: Han Zhenyan , Zhang Yuan , Bai Xiaoyi , Yin Yuzhu , Xu Chengfang , Hou Hongying
Published: March 2019

Objective

The objective of this study is to determine whether amniocentesis increases the risk of mother‐to‐child transmission (MTCT) of hepatitis B virus (HBV) and evaluate risk factors for MTCT.

Methods

One hundred forty‐three hepatitis B surface antigen (HBsAg)–positive women with amniocentesis were enrolled into the amniocentesis group. Six hundred five nonamniocentesis cases were matched with amniocentesis cases based on maternal viral loads, antiviral therapy regimens, and delivery dates. MTCT of HBV was defined as HBsAg and/or DNA positivity in infants from birth to age 7 to 12 months.

Results

Mother‐to‐child transmission rate was significantly higher in HBsAg‐positive women with amniocentesis than in those without amniocentesis (2.80% vs 0.50%; relative risk [RR], 5.64; 95% CI, 1.28‐24.93). In the amniocentesis group, maternal HBV DNA more than or equal to 7.0 log10 IU/mL and hepatitis B e‐antigen (HBeAg) positivity were associated with higher MTCT rates than maternal HBV DNA less than 7.0 log10 IU/mL (10.81% vs 0%, p = .004) and HBeAg negativity (8.16% vs 0%, p = .013), and antiviral therapy reduced MTCT rate from 14.3% to 0% (p = .554) when maternal HBV DNA was more than or equal to 7.0 log10 IU/mL.

Conclusions

Amniocentesis increases the risk of MTCT in women with hepatitis B, and maternal HBV DNA more than or equal to 7.0 log10 IU/mL and HBeAg positivity are risk factors for MTCT. Antiviral therapy may be effective to prevent MTCT after amniocentesis in highly viremic mothers.
Preparation and properties of phosphorus‐ and silicon‐modified phenolic resin with high ablation resistance
Authors: Bao Qiuru , Li Wenzhi , Liu Yuan , Wang Qi
Published: March 2019

In order to further improve the ablation resistance of common phenolic resins, a modified phenolic resin containing phosphorus and silicon (SPPR) was synthesized and the corresponding properties were evaluated. With phosphorus and silicon involved in the macromolecule, SPPR showed excellent flame retardancy and obviously enhanced value (44.8%) of the limiting oxygen index. The thermal stability and charring performance of SPPR were greatly improved, with maximum decomposition temperature of over 500 °C and carbon yield of 60.1% in nitrogen. Differential scanning calorimetry indicated that the curing temperature shifted from 157 °C for the conventional phenolic resin to 182 °C for SPPR. Moreover, an improvement of impact strength from 4.3 to 16.5 kJ m−2 confirmed that incorporation of flexible SiO chain had a noticeable effect on the mechanical properties of SPPR. Such a modified phenolic resin has promising application prospects serving as an ablation material with high performance. © 2019 Society of Chemical Industry
High‐efficiency photovoltaic modules on a chip for millimeter‐scale energy harvesting
Authors: Moon Eunseong , Lee Inhee , Blaauw David , Phillips Jamie D.
Published: March 2019

Photovoltaic modules at the millimeter scale are demonstrated in this work to power wirelessly interconnected millimeter‐scale sensor systems operating under low‐flux conditions, enabling applications in the Internet of things and biological sensors. Module efficiency is found to be limited by perimeter recombination for individual cells and shunt leakage for the series‐connected module configuration. We utilize GaAs and AlGaAs junction barrier isolation between interconnected cells to dramatically reduce shunt leakage current. A photovoltaic module with eight series‐connected cells and total area of 1.27 mm2 demonstrates a power conversion efficiency of greater than 26% under low‐flux near‐infrared illumination (850 nm at 1 μW/mm2). The output voltage of the module is greater than 5 V, providing a voltage up‐conversion efficiency of more than 90%. We demonstrate direct photovoltaic charging of a 16‐μAh pair of thin‐film lithium‐ion batteries under dim light conditions, enabling the perpetual operation of practical millimeter‐scale wirelessly interconnected systems.
Systemic Absorption and Side Effects of Locally Injected Glucocorticoids
Authors: Stout Alison , Friedly Janna , Standaert Christopher J.
Published: March 2019

Local glucocorticoid injections are often used to treat joint, soft tissue, or spinal pain, but the systemic side effects associated with these injections are poorly understood and not well recognized. There are significant known risks to systemic administration of glucocorticoids. However, there are no guidelines that address issues of systemic absorption, overall systemic risks, or other side effects of locally injected glucocorticoids. For this review, a literature search was performed, and the available evidence on systemic absorption and clinical side effects of intra‐articular and epidural glucocorticoids was synthesized. The goal was to improve clinical understanding of risks associated with these injections. Existing data suggest there is significant individual variability in the amount of systemic absorption and clinical effects of locally injected glucocorticoids. However, it is clear that both intra‐articular and epidural injections can have systemic effects for weeks and that complications may be associated with their use, including Cushing syndrome, loss of bone density, infection, and hyperglycemia. The concurrent use of oral steroids, the number of injections, and the type and dose of glucocorticoids used all are important considerations in estimating risks. The total dose calculation of cumulative glucocorticoid exposure should include all local injections. Caution should be exercised when local glucocorticoid injections are used in higher risk patients, such as postmenopausal women, people with diabetes, and those considering surgery in the near term. Better provider awareness of possible systemic risks should improve decision making and informed consent with patients when considering intra‐articular and epidural steroid injections for painful conditions.

Level of Evidence

IV
Structural origin for the strain rate dependence of mechanical response of fluoroelastomer F2314
Authors: Chang Jiarui , Lin Yuanfei , Chen Wei , Tian Fucheng , Chen Pinzhang , Zhao Jingyun , Li Liangbin
Published: March 2019

The structural evolution of fluoroelastomer F2314 is studied during uniaxial tensile in a large strain rate range (0.1–150 s−1) with the combination of a homemade high‐speed stretching device and in situ small‐ and wide‐angle X‐ray scattering techniques. Based on the mechanical behaviors and structural evolutions, three strain rate regions (I–III) are defined. The microphase‐separated structure plays an important role in the mechanical response of F2314. In Region I, deformation of soft domains is the main process before yielding, accompanied by the destruction of lamellar crystals in hard domains. In the stress plateau zone, deformation of hard domains is confirmed as the primary mechanism of energy dissipation. With the orientation parameter of the amorphous phase reaching a critical value, strain hardening is triggered. Recrystallization also takes place in strain hardening zone. In Region II, due to the mismatch between the mobility of molecular chains in hard domains and the acting time of stress, large deformation of hard domains is more and more difficult to occur with the disappearance of recrystallization. In Region III, as almost all molecular chains have no time to adjust or relax to fit the stress field, the sample presents a brittle fracture. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 607–620
Extracellular Vesicles Released by Allogeneic Human Cardiac Stem/Progenitor Cells as Part of Their Therapeutic Benefit
Authors: Hocine Hocine Rachid , Brunel Simon , Chen Qian , Giustiniani Jerome , San Roman Mabel Jouve , Ferrat Yann J. , Palacios Itziar , Rosa Olga , Lombardo Eleuterio , Bensussan Armand , Charron Dominique , Jabrane-Ferrat Nabila , Al-Daccak Reem
Published: March 2019

The positive effects of therapeutic human allogeneic cardiac stem/progenitor cells (hCPC) in terms of cardiac repair/regeneration are very likely mediated by paracrine effects. Our previous studies revealed the advantageous immune interactions of allogeneic hCPC and proposed them as part of the positive paracrine effects occurring upon their application postmyocardial infarction (MI). Currently, extracellular vesicles/exosomes (EV/Exs) released by stem/progenitor cells are also proposed as major mediators of paracrine effects of therapeutic cells. Along this line, we evaluated contribution of EV/Exs released by therapeutic hCPC to the benefit of their successful allogeneic clinical application. Through tailored allogeneic in vitro human assay models mimicking the clinical setting, we demonstrate that hCPC-released EV/Exs were rapidly and efficiently up-taken by chief cellular actors of cardiac repair/regeneration. This promoted MAPK/Erk1/2 activation, migration, and proliferation of human leukocyte antigens (HLA)-mismatched hCPC, mimicking endogenous progenitor cells and cardiomyocytes, and enhanced endothelial cell migration, growth, and organization into tube-like structures through activation of several signaling pathways. EV/Exs also acted as pro-survival stimuli for HLA-mismatched monocytes tuning their phenotype toward an intermediate anti-inflammatory pro-angiogenic phenotype. Thus, while positively impacting the intrinsic regenerative and angiogenic programs, EV/Exs released by therapeutic allogeneic hCPC can also actively contribute to shaping MI-inflammatory environment, which could strengthen the benefits of hCPC allogeneic interactions. Collectively, our data might forecast the application of allogeneic hCPC followed by their cell-free EV/Exs as a strategy that will not only elicit the cell-contact mediated reparative/regenerative immune response but also have the desired long-lasting effects through the EV/Exs. Stem Cells Translational Medicine  2019;8:911–924
Prestressing concrete members with fibre‐reinforced polymer reinforcement: State of research
Authors: Zdanowicz Katarzyna , Kotynia Renata , Marx Steffen
Published: March 2019

The technology of prestressing concrete structures has been a well‐established field in structural engineering since the last century. Nowadays, new materials developed for reinforcing concrete structures, such as fibre‐reinforced polymers (FRPs), open further possibilities for engineers. FRP tendons are more and more often investigated as an efficient and suitable material for prestressing, and there are already some field applications of this technology. This paper aims to describe the current state of knowledge in the field of prestressing with FRP tendons, with regard to available materials, developed anchorages and undertaken investigations. Researches conducted in areas such as bond strength, ductility, durability, long‐term behavior, and high‐temperature resistance are described and summarized. Our goal was to provide a summary of what has been achieved so far in the research field of prestressing concrete structures with FRP tendons; however, field applications and standardization issues are not part of this review.
Twisting and localization in supergravity: equivariant cohomology of BPS black holes
Authors: Jeon Imtak , Murthy Sameer
Published: March 2019

Abstract

We develop the formalism of supersymmetric localization in supergravity using the deformed BRST algebra defined in the presence of a supersymmetric background as recently formulated in [1]. The gravitational functional integral localizes onto the cohomology of a global supercharge Q
eq, obeying Q
eq
2
 = H, where H is a global symmetry of the background. Our construction naturally produces a twisted version of supergravity whenever supersymmetry can be realized off-shell. We present the details of the twisted graviton multiplet and ghost fields for the superconformal formulation of four-dimensional

$$ \mathcal{N} $$

N

= 2 supergravity. As an application of our formalism, we systematize the computation of the exact quantum entropy of supersymmetric black holes. In particular, we compute the one-loop determinant of the Q
eq

$$ \mathcal{V} $$

V

deformation operator for the off-shell fluctuations of the Weyl multiplet around the AdS2 × S
2 saddle. This result, which is consistent with the corresponding large-charge on-shell analysis, is needed to complete the first-principles computation of the quantum entropy.