bluuebunny/crossref_metadata_2025 huggingface dataset:
One‐Pot Transformation of Ketoximes into Optically Active Alcohols and Amines by Sequential Action of Laccases and Ketoreductases or ω‐Transaminases
Authors: Correia Cordeiro Raquel S. , Ríos‐Lombardía Nicolás , Morís Francisco , Kourist Robert , González‐Sabín Javier
Published: January 2019

An enzymatic one‐pot process for asymmetric transformation of prochiral ketoximes into alcohols or amines was developed by sequential coupling of a laccase‐catalyzed deoximation either with a ketone reduction (ketoreductase, KRED) or bioamination (ω‐transaminase, ω‐TA) in aqueous medium. An accurate selection of biocatalysts provided the corresponding products in excellent enantiomeric excesses and overall conversions ranging from 83 to >99 % for alcohols and 70 to >99 % for amines. Likewise, the employment of exclusively 1 % (w/w) of Cremophor®, a polyethoxylated castor oil, as co‐solvent enabled to reach concentrations up to 100 mM in the chiral alcohols cascade.
Driving Force of Crystallization Based on Diffusion in the Boundary and the Integration Layers
Authors: Borissova Antonia
Published: January 2019

Crystal growth rates are notoriously difficult to predict and even experimental data are often inconsistent. By allowing for mass and energy diffusion through the molecular and thermal layers surrounding a growing crystal and for the heat effect of crystallization, a new model of crystal growth from solution is proposed and applied to crystallization of potassium chloride from aqueous solution. The driving force for crystal growth was calculated using the solubility at the interface temperature in contrast to the conventional one based on bulk temperature. A positive heat effect at the crystal interface as well as the resistances to the mass and energy transfer processes to and from the crystal surface can reduce the conventional driving force for crystal growth by more than 20 %.
Assembly of Tetrazolylfuroxan Organic Salts: Multipurpose Green Energetic Materials with High Enthalpies of Formation and Excellent Detonation Performance
Authors: Larin Alexander A. , Muravyev Nikita V. , Pivkina Alla N. , Suponitsky Kyrill Yu. , Ananyev Ivan V. , Khakimov Dmitry V. , Fershtat Leonid L. , Makhova Nina N.
Published: January 2019

A series of highly energetic organic salts comprising a tetrazolylfuroxan anion, explosophoric azido or azo functionalities, and nitrogen‐rich cations were synthesized by simple, efficient, and scalable chemical routes. These energetic materials were fully characterized by IR and multinuclear NMR (1H, 13C, 14N, 15N) spectroscopy, elemental analysis, and differential scanning calorimetry (DSC). Additionally, the structure of an energetic salt consisting of an azidotetrazolylfuroxan anion and a 3,6,7‐triamino‐7H‐[1,2,4]triazolo[4,3‐b][1,2,4]triazolium cation was confirmed by single‐crystal X‐ray diffraction. The synthesized compounds exhibit good experimental densities (1.57–1.71 g cm−3), very high enthalpies of formation (818–1363 kJ mol−1), and, as a result, excellent detonation performance (detonation velocities 7.54–8.26 kms−1 and detonation pressures 23.4–29.3 GPa). Most of the synthesized energetic salts have moderate sensitivity toward impact and friction, which makes them promising candidates for a variety of energetic applications. At the same time, three compounds have impact sensitivity on the primary explosives level (1.5–2.7 J). These results along with high detonation parameters and high nitrogen contents (66.0–70.2 %) indicate that these three compounds may serve as potential environmentally friendly alternatives to lead‐based primary explosives.
A UGT1A1 genotype‐guided dosing study of modified FOLFIRINOX in previously untreated patients with advanced gastrointestinal malignancies
Authors: Sharma Manish R. , Joshi Smita S. , Karrison Theodore G. , Allen Kenisha , Suh Grace , Marsh Robert , Kozloff Mark F. , Polite Blase N. , Catenacci Daniel V. T. , Kindler Hedy L.
Published: January 2019

Background

FOLFIRINOX (5‐fluorouracil [5‐FU], leucovorin, irinotecan, oxaliplatin) is an effective but toxic therapy for pancreatic cancer. UGT1A1 (UDP glucuronosyltransferase 1A1) eliminates the active metabolite of irinotecan. Polymorphisms reduce UGT1A1 activity, leading to toxicity. The primary objective was to determine the dose‐limiting toxicity (DLT) rate in cycle 1 of modified FOLFIRINOX (mFOLFIRINOX) using genotype‐guided dosing of irinotecan for the most common UGT1A1 genotypes (*1/*1, *1/*28) in advanced gastrointestinal malignancies, with expansion in pancreatic and biliary tract cancers.

Method

5‐FU (2400 mg/m2 over 46 hours), leucovorin (400 mg/m2), oxaliplatin (85 mg/m2), and irinotecan were given every 14 days. Irinotecan doses of 180, 135, and 90 mg/m2 were administered for UGT1A1 genotypes *1/*1, *1/*28, and *28/*28, respectively. Prophylactic pegfilgrastim was omitted in cycle 1 for cohort 1 (tolerability by genotype), but was given in cohort 2 (tolerability by tumor type). Doses were tolerable if the upper limit of a 2‐sided 80% confidence interval for DLT rate was ≤33%.

Results

In cohort 1, DLTs (most commonly febrile neutropenia, fatigue, diarrhea) occurred in 2/15 (13%), 3/16 (19%), and 4/10 (40%) patients with *1/*1, *1/*28, and *28/*28 genotypes, respectively. In cohort 2, 6/19 (32%) pancreatic and 4/19 (21%) biliary tract cancer patients experienced DLTs (most commonly fatigue, diarrhea, nausea/vomiting). In cohort 2, upper confidence limits of DLT rates exceeded 33%. Response rates were 38% in pancreatic and 21% in biliary tract cancers.

Conclusion

On the basis of our prespecified criteria, tolerability of UGT1A1 genotype‐guided mFOLFIRINOX was not established in pancreatic and biliary tract cancers. However, this regimen was effective.
Biliary tract cancer incidence and trends in the United States by demographic group, 1999‐2013
Authors: Van Dyke Alison L. , Shiels Meredith S. , Jones Gieira S. , Pfeiffer Ruth M. , Petrick Jessica L. , Beebe‐Dimmer Jennifer L. , Koshiol Jill
Published: January 2019

Background

Biliary tract cancers (BTCs) are rare but deadly cancers (gallbladder cancer [GBC], intrahepatic cholangiocarcinoma [ICC], extrahepatic cholangiocarcinoma [ECC], and ampulla of Vater cancer [AVC]). A recent US study reported increasing GBC incidence among people younger than 45 years and blacks; however, it did not examine trends for other biliary tract sites.

Methods

This study characterized demographic differences in BTC incidence rates and time trends by anatomic site. Population‐based North American Association of Central Cancer Registries data were used to calculate age‐adjusted incidence rates, incidence rate ratios (IRRs), and estimated annual percent changes (eAPCs) for 1999‐2013 by site and demographic group. For sites with significant differences in eAPC by age group, IRRs were compared by age group.

Results

GBC incidence rates declined among women (eAPC, –0.5%/y; P = .01) and all racial/ethnic groups except for non‐Hispanic blacks, among whom rates increased (1.8%/y; P < .0001). Although GBC rates increased among 18‐ to 44‐year‐olds (eAPC, 1.8%/y; P = .01), they decreased among people 45 years old or older (–0.4%/y; P = .009). Sex (P < .0001) and racial/ethnic differences (P = .003 to .02) in GBC incidence were larger for younger people than older people. During this period, ICC (eAPC, 3.2%/y; P < .0001) and ECC rates (1.8%/y; P = .001) steadily increased across sex and racial/ethnic groups. Although AVC incidence rates increased among younger adults (eAPC, 1.8%/y; P = .03) but not older adults (–0.20%/y; P = .30), sex and racial/ethnic IRRs did not differ by age.

Conclusions

Differential patterns of BTC rates and temporal trends have been identified by anatomic site and demographic groups. These findings highlight the need for large pooling projects to evaluate BTC risk factors by anatomic site.
Thyroid cancer risk in women with infertility and association with fertility medications in Taiwan
Authors: Ding Dah‐Ching , Chen Weishan , Wang Jen‐Hung , Lin Shinn‐Zong , Sung Fung‐Chang
Published: January 2019

Background

The current study evaluated whether the risk of developing thyroid cancer in Asian women was associated with infertility and the use of fertility drugs.

Methods

The authors conducted a large, retrospective cohort study using Taiwan's National Health Insurance Research Database. From the insurance claims data, a total of 13,356 women aged 20 to 49 years who were diagnosed with infertility from 2000 through 2013 were included in the infertile group, and 53,424 women without a history of infertility were selected as fertile comparisons and were frequency matched by age and year of diagnosis. Both groups were followed up to 2013 to calculate incident thyroid cancer. Poisson regression analysis was used to estimate the incidence rate ratio (IRR).

Results

The incidence of thyroid cancer was 1.9‐fold greater in the infertile group compared with the comparison group (2.85 vs 1.53 per 10,000 person‐years), with an adjusted IRR of 1.80 (95% confidence interval [95% CI], 1.70‐1.92) for the infertile group. Higher cancer incidence was demonstrated for the infertile group after 7 years of follow‐up, with an adjusted IRR of 4.39 (95% CI, 4.03‐4.78) compared with the comparison group. Among infertile women, those who had taken the fertility drug clomiphene were found to have a reduced incidence of thyroid cancer compared with those who were treated without the drug (2.69 vs 3.42 per 10,000 person‐years), with an adjusted IRR of 0.86 (95% CI, 0.75‐0.99). However, the cancer incidence in infertile women being treated with clomiphene was nearly 6‐fold greater than that in fertile women taking the drug.

Conclusions

The results of the current study provide evidence that women with infertility are at an increased risk of developing thyroid cancer.
One Pot Synthesis of Amphiphilic Carbogenic Fluorescent Nanodots for Bioimaging
Authors: Rao Chethana , Singh Ashutosh , Verma Navneet Chandra , Garg Neha , Nandi Chayan Kanti
Published: January 2019

Carbogenic fluorescent nanodots (FND) have recently drawn increasing attention in bioimaging. This is mainly due to their unique attractive photoluminescence properties. Although a vast number of reports are available, amphiphilic FND (aFND) are scarcely reported. In addition, the synthetic methods for amphiphilic FND are either tedious multistep processes or in most cases require additional surface passivation. Here, for the first time, using Maillard reaction protocol, we report an easy one pot synthesis aFND using sucrose and diaminooctane as the main precursors. The amphiphilic nature could be regulated easily upon changing the diaminooctane concentration. We demonstrate that the greater the hydrophobic nature in aFND, the more cell‐penetrating capability is observed. Flow cytometry measurements quantitatively show the fast live cell internalisation of the aFND inside HeLa cells. All the above features mark the excellent bio‐compatibility of aFND and give insight into its use as an excellent bioimaging tool.
Riboflavin as a Bioorganic Solar Fuel: Photoredox Chemistry Rationalized and Accelerated in a Miniaturized Flow Photoreactor
Authors: Lin Lyangya , Xie Kaihui , Beaucamp Mathieu , Job Nathalie , Penhoat Maël
Published: January 2019

With the depletion of fossil‐fuel‐based energies and the corresponding growing environmental concerns, the design of new strategies to store renewable solar energy is highly attractive. Herein, we studied a biomimetic organic solar fuel (Riboflavin – Vitamin B2) to photochemically store solar light into its amphoteric form (leucodeuteroflavin), working as a charge carrier towards a flow fuel cell. We demonstrate that miniaturization of the photoreactor permits significant reduction of the full time solar charge. Nevertheless, due to inherent leucodeuteroflavin (LDH2) degradation into lumichrome (LC), the maximum system charge (at pH=5) is limited to 13 % corresponding to a maximum power density of 0.11 mW cm−2 after 90 min. In comparison with other described photoredox electroactive systems (e. g. polyoxometalates, quinones), organic solar fuels based on flavins appear particularly promising and their chemical structure should be optimized to fit both photostability and economical requirements. In any case, this study enables a clear rationalization and quantification of the mechanism of riboflavin degradation under anaerobic conditions, which has been the topic of many discussions during the last century, and opens the way towards the development of a new generation of low‐cost renewable organic solar fuels.
Stereoinformation Relay: Coupling Diastereoselectivity of a Thermal Diels‐Alder Reaction with the Photochemical Ring‐Closure of Diarylethenes
Authors: Broi Kevin , Fuhrmann Anne , Dallmann André , Berger Fabian , Hecht Stefan
Published: January 2019

Controlling the stereochemistry, ideally in a reversible manner using external stimuli, is of great importance and appeal for biomedical and materials applications. By incorporating a Diels‐Alder adduct into one of the heteroaromatic rings of a diarylethene, we were able to transfer theexoselectivity of the thermal Diels‐Alder reaction upon photocyclization, leading to the preferred formation of one ring‐closedexodiastereomer in a diastereomeric ratio of 90 : 10. The structures of both ring‐closedexoisomers were assigned based on 2D NMR spectroscopy and DFT calculations. As indicated by both experimental and computational results, the conformational equilibrium of the Diels‐Alder adducts was kinetically trapped in the ring‐closed diarylethenes, leading to successful transfer of stereoinformation. The combination of thermal cycloaddition and photochemical cyclization steps and their associated diastereoselectivity provides ample opportunities to remotely control the transfer of stereoinformation and materials properties with light.
Landscape genetics reveal broad and fine‐scale population structure due to landscape features and climate history in the northern leopard frog (Rana pipiens) in North Dakota
Authors: Waraniak Justin M. , Fisher Justin D. L. , Purcell Kevin , Mushet David M. , Stockwell Craig A.
Published: January 2019

Prehistoric climate and landscape features play large roles structuring wildlife populations. The amphibians of the northern Great Plains of North America present an opportunity to investigate how these factors affect colonization, migration, and current population genetic structure. This study used 11 microsatellite loci to genotype 1,230 northern leopard frogs (Rana pipiens) from 41 wetlands (30 samples/wetland) across North Dakota. Genetic structure of the sampled frogs was evaluated using Bayesian and multivariate clustering methods. All analyses produced concordant results, identifying a major east–west split between two R. pipiens population clusters separated by the Missouri River. Substructuring within the two major identified population clusters was also found. Spatial principal component analysis (sPCA) and variance partitioning analysis identified distance, river basins, and the Missouri River as the most important landscape factors differentiating R. pipiens populations across the state. Bayesian reconstruction of coalescence times suggested the major east–west split occurred ~13–18 kya during a period of glacial retreat in the northern Great Plains and substructuring largely occurred ~5–11 kya during a period of extreme drought cycles. A range‐wide species distribution model (SDM) for R. pipiens was developed and applied to prehistoric climate conditions during the Last Glacial Maximum (21 kya) and the mid‐Holocene (6 kya) from the CCSM4 climate model to identify potential refugia. The SDM indicated potential refugia existed in South Dakota or further south in Nebraska. The ancestral populations of R. pipiens in North Dakota may have inhabited these refugia, but more sampling outside the state is needed to reconstruct the route of colonization. Using microsatellite genotype data, this study determined that colonization from glacial refugia, drought dynamics in the northern Great Plains, and major rivers acting as barriers to gene flow were the defining forces shaping the regional population structure of R. pipiens in North Dakota.
Investigating the role ofOsirisgenes inDrosophila sechellialarval resistance to a host plant toxin
Authors: Lanno Stephen M. , Shimshak Serena J. , Peyser Rubye D. , Linde Samuel C. , Coolon Joseph D.
Published: January 2019

The underlying genetic basis of adaptive phenotypic changes is generally poorly understood, yet a growing number of case studies are beginning to shed light on important questions about the molecular nature and pleiotropy of such changes. We useDrosophila sechellia, a dietary specialist fruit fly that evolved to specialize on a single toxic host plant,Morinda citrifolia, as a model for adaptive phenotypic change and seek to determine the genetic basis of traits associated with host specialization in this species. The fruit ofM. citrifoliais toxic to other drosophilids, primarily due to high levels of the defense chemical octanoic acid (OA), yetD. sechelliahas evolved resistance to OA. Our prior work identified threeOsirisfamily genes that reside in a fine‐mapped QTL for OA resistance:Osiris 6(Osi6),Osi7, andOsi8, which can alter OA resistance in adultD. melanogasterwhen knocked down with RNA interference suggesting they may contribute to OA resistance inD. sechellia. Genetic mapping identified overlapping genomic regions involved in larval and adult OA resistance inD. sechellia, yet it remains unknown whetherOsirisgenes contribute to resistance in both life stages. Furthermore, because multiple genomic regions contribute to OA resistance, we aim to identify other gene(s) involved in this adaptation. Here, we identify candidate larval OA resistance genes using RNA sequencing to measure genome‐wide differential gene expression inD. sechellialarvae after exposure to OA and functionally test identified genes for a role in OA resistance. We then test theOsirisgenes previously shown to alter adult OA resistance for effects on OA resistance in larvae. We found thatOsi8knockdown decreased OA resistance inD. melanogasterlarvae. These data suggest that evolved changes inOsi8could impact OA resistance in multiple life stages whileOsi6andOsi7may only impact adult resistance to OA.
Effects of river damming on ground‐dwelling arthropods along riparian–upland habitats
Authors: Wang Kehong , Yuan Xingzhong , Wu Shuaikai , Zhang Guanxiong , Liu Hong , Zhou Lilei , Zhang Mengjie
Published: January 2019

River damming is one of the most serious anthropogenic disturbances impacting river ecosystems. Little is known about the consequences of river damming on ground‐dwelling arthropods, although they represent a functionally important component of riverine ecosystems because they provide an essential link between aquatic and terrestrial ecosystems. We investigated the effects of river damming on the composition and structure of arthropod communities in the Baijia Stream located in the centre of the Three Gorges Reservoir. Our results revealed that (a) river damming modified the community composition of riparian arthropods, as 24 taxa disappeared and 11 taxa colonized the new habitat after damming; (b) river damming altered the community structure of arthropods because higher richness and abundance of arthropods were recorded in the regulated section, especially for predators, detritivores, and herbivores; and (c) river damming altered the lateral distribution along riparian–upland gradients and the temporal dynamics of arthropod communities. Interestingly, upland habitats of streams supported more species than the riparian habitat in the regulated section, suggesting that uplands may become an important habitat for riparian species after river damming. Although higher total abundance and richness and higher abundance of some feeding guilds of arthropods were observed in the regulated section, the negative effects of river damming on biodiversity are addressed in this paper. Thus, ground‐dwelling arthropods appear to be sensitive indicators of the ecological effects of river damming. Assessment of the consequences of river damming and dam management plans should consider ground‐dwelling arthropod communities in associated riparian and upland habitats.
Zinc and Copper Complexes of Methylated Di‐ and Tetraaminocyclodextrins
Authors: Warren Julia , Bols Mikael
Published: January 2019

The α‐ and β‐cyclodextrins with two dimethylamino groups or two trimethylethylenediamino groups attached to the primary face were synthesized and their pKa values were determined by potentiometric titration. The complexation of the four cyclodextrin analogues with zinc and copper was studied by NMR and showed one or two cyclodextrins bound to the metal. Inclusion of 4‐halophenols in the metal complexes were also studied.
International student enrollment in the United States: 2017–18
Authors: Dennis Marguerite J.
Published: January 2019

According to the Open Doors Report on International Educational Exchange, a report presented by the Institute for International Education and the U.S. Department of State's Bureau of Educational and Cultural Affairs, the following are the international student enrollment statistics for American colleges and universities in 2017–18.
Implement low‐cost strategies to retain employees facing shrinking salaries
Authors: Tolman Steven
Published: January 2019

In a utopian world, the decision of which job to take (or how long to stay in it) would be motivated by purely intrinsic reasons. However, this unfortunately isn't the reality. In fact, for many, the financial compensation serves as the primary driver in career choices. The bottom line is that campus employees do need to be able to provide for themselves and their families.
Tungsten‐Doped Nanocrystalline V6O13 Nanoparticles as Low‐Cost and High‐Performance Electrodes for Energy Storage Devices
Authors: Wang Shujun , Qin Jiadong , Zhang Yubai , Xia Fang , Liu Minsu , Chen Hao , Al‐Mamun Mohammad , Liu Porun , Rigway Regan , Shi Ge , Song Jingchao , Zhong Yu Lin , Zhao Huijun
Published: January 2019

Vanadium oxide (VOx) nanomaterials are promising candidates for energy storage devices, such as lithium‐ and sodium‐ion batteries and supercapacitors, in which many complicated structural designs and composite strategies are applied to harness the high theoretical capacity of these materials. Herein, a simple yet effective method to achieve improved performance of electrodes via tungsten doping in a green hydrothermal reaction is demonstrated. The evolution of three VOx phases (V2O5, VO2, and V6O13) during the synthesis of the VOx nanostructures is revealed by the systematic investigation of the reaction products. The dopants are critical for the formation of nanocrystalline structures. The as‐fabricated VOx is tested for lithium‐ion batteries, which shows that tungsten doping significantly improves the battery performance, including initial discharge capacity of the VOx (doped VOx = 615.2 ± 41.6 mAh g–1, undoped VOx = 377.9 ± 72.8 mAh g–1, and precursor V2O5 = 393.4 ± 74.0 mAh g–1), cycle stability, and rate performance. This research provides important insights into the understanding of the dopant‐induced phase tuning of VOx nanostructures for energy storage–related applications.
Locoregional failures and their relation to radiation fields following stereotactic body radiotherapy boost for oropharyngeal squamous cell carcinoma
Authors: Baker Sarah , Verduijn Gerda , Petit Steven , Nuyttens Joost J , Sewnaik Aniel , van der Lugt Aad , Heemsbergen Wilma D.
Published: January 2019

Background

To investigate the location of recurrences with respect to the radiation fields in oropharynx cancer after intensity‐modulated radiotherapy and stereotactic body radiotherapy (SBRT) boost.

Methods

Local and regional recurrences were delineated on diagnostic scans which were rigidly coregistered with treatment planning scans, then classified based on the location of the center of mass (COM) as well as volumetrically.

Results

In 195 patients, the 5‐year local and regional control were 90% and 93%, respectively. By COM, 76% of local recurrences were in‐field; 24% were out‐of‐field, significantly higher than 0%‐5% in the literature for conventional regimens (P < 0.01). Regional recurrences (19 in 12 patients) were largely within unirradiated neck levels (47%) and electively irradiated regions (42%).

Conclusions

The regimen with biological equivalent dose intensification provides excellent overall and in‐field local control. The highly conformal boost technique was, however, associated with increased out‐of‐field local failure.
Classics in Their Own “Words”: Analytical Remixes in a Land of Essays
Authors: Baize Jonathan
Published: January 2019

The author shares his experience in effecting change in anAPEnglish Literature and Composition course by employing book trailers as an assessment. Using multimodal responses fostered a shared classroom space that combined the students’ preferred, everyday communicative modes with the canonical literature study required by the curriculum. This inclusive space proved valuable in helping a diverse group of students produce competent literary analyses and in scaffolding their comfort and efficacy with the language of literature study.
The antileukemic effects of saffron (Crocus sativus L.) and its related molecular targets: A mini review
Authors: Moradzadeh Maliheh , Kalani Mohamad Reza , Avan Amir
Published: January 2019

Saffron (Crocus sativus L.), and its main constituents, crocin, and crocetin have shown promising effects as an antileukemic agent in animal models and cell culture systems. Saffron retards the growth of cancer cells via inhibiting nucleic acid synthesis and enhancing antioxidative system. It can induce apoptosis and chemosensitivity via inhibiting multidrug resistance proteins. Saffron also induces differentiation pathways via inhibiting promyelocytic leukemia/retinoic acid receptor‐α, histone deacetylase1, and tyrosyl DNA phosphodiesterase‐1 as well. The present review highlights the most recent findings on the antileukemic effects of saffron and its underlying molecular targets. The emerging evidence suggests that saffron has a selective toxicity effect against leukemic cells while is safe for the normal cells.
Passage‐dependent expression of STRO‐1 in human gingival mesenchymal stem cells
Authors: Ranga Rao Suresh , Subbarayan Rajasekaran
Published: January 2019

The expression of STRO‐1, the essential mesenchymal stem cell marker, was found to decrease with advancing passages in few tissues. Because STRO‐1 was identified and isolated from human gingiva, we were interested to know its status after a few passages. Human gingival mesenchymal stem cells (HGMSCs) were isolated from human gingiva. Flow cytometry was carried out with STRO‐1, mesenchymal stem cell (MSC) positive marker CD73, and negative marker CD34/CD45. Samples were also subjected to CD90 and STRO‐1 immunofluorescence staining. Gene expression was carried out for transcription factors OCT‐4, NANOG, and NESTIN. The results showed a gradual decrease in STRO‐1 and transcription factor expression with an increase in passage numbers. MSC positive marker CD73 was consistently expressed in all the passages. Negative markers were absent in all the passages. We conclude that STRO‐1 may be a useful marker to isolate undifferentiated (potent) mesenchymal cells from gingiva.
microRNA‐135a protects against myocardial ischemia‐reperfusion injury in rats by targeting protein tyrosine phosphatase 1B
Authors: Wang Sheng , Cheng Zhaoyun , Chen Xianjie , Xue Huanzhou
Published: January 2019

microRNAs are an emerging class of molecules that regulate pathogenesis of cardiovascular diseases. Here we aim to elucidate the effects and mechanism of miR‐135a, a previously reported regulator of ischemia‐reperfusion (I/R) injury, in myocardial I/R injury. Quantitative real‐time polymerase chain reaction analysis revealed that the expression level of miR‐135a was significantly decreased both in the rat I/R group and H9c2 cells subjected to hypoxia/reoxygenation. Overexpression of miR‐135a in vivo markedly decreased the infarct size and inhibited the I/R‐induced cardiomyocyte apoptosis. Overexpression of miR‐135a in H9c2 also exerted antiapoptosis effects. Furthermore, bioinformatics analysis, luciferase activity, and the Western blot assay indicated that protein tyrosine phosphatase 1B (PTP1B) is a direct target of miR‐135a. In addition, the expression of proapoptotic‐related genes, such as p53, Bax, and cleaved caspase3, were decreased in association with the downregulation of PTP1B. In summary, this study demonstrates that miR‐135a exerts protective effects against myocardial I/R injury by targeting PTP1B.
LncRNA UCA1/miR‐124 axis modulates TGFβ1‐induced epithelial‐mesenchymal transition and invasion of tongue cancer cells through JAG1/Notch signaling
Authors: Zhang Tong‐han , Liang Li‐zhong , Liu Xiao‐ling , Wu Ji‐nan , Su Kui , Chen Jue‐yao , Zheng Qiao‐yi
Published: January 2019

Tongue cancer remains a massive threat to public health due to the high rate of metastasis. Tumor cell epithelial‐mesenchymal transition (EMT), which can be induced by transforming growth factor β1 (TGFβ1), has been regarded as a significant contributor to cancer invasion and migration. In our previous study, long noncoding RNA (lncRNA) MALAT1/miR‐124/JAG1 axis modulates the growth of tongue cancer. In addition to metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1), another lncRNA, urothelial cancer associated 1 (UCA1), can promote EMT and cancer metastasis. In the present study, UCA1 was overexpressed in tongue cancer tissues and cell lines. UCA1 overexpression was correlated to the poorer prognosis of patients with tongue cancer. UCA1 knockdown significantly suppressed TGFβ1‐induced tongue cancer cell invasion and EMT by decreasing vimentin and increasing E‐cadherin. Regarding the molecular mechanism, UCA1 could directly bind to microRNA‐124 (miR‐124) and negatively regulate each other. UCA1 knockdown ameliorated, whereas miR‐124 inhibition exacerbated TGFβ1‐induced EMT and invasion in tongue cancer cells through miR‐124 downstream jagged 1 (JAG1) and Notch signaling. Moreover, miR‐124 inhibition partially impaired the effect of UCA1 knockdown. In tongue cancer tissues, miR‐124 expression was remarkably decreased, whereas JAG1 mRNA expression was increased. miR‐124 was negatively correlated with UCA1 and JAG1. UCA1 and JAG1 were positively correlated. In summary, we provided a novel mechanism by which the EMT process and cancer cell invasion in tongue cancer could be modulated from the perspective of lncRNA‐miRNA‐mRNA regulation.
Vascular endothelial growth factor‐modified macrophages accelerate reendothelialization and attenuate neointima formation after arterial injury in atherosclerosis‐prone mice
Authors: Yan Dan , Zhang Danna , Lu Lili , Qiu Hui , Wang Jun
Published: January 2019

Vascular endothelial growth factor (VEGF) is a promising molecule for cardiovascular diseases therapy. But lack of a targeted delivery system limits its translation into clinical application. This study aimed to develop stably overexpressing VEGF macrophages for targeted VEGF delivery to injured arteries and determine their potential for repairing of the damaged endothelium. Wire‐induced carotid artery injury model was established in atherosclerosis‐prone mice. It was observed that the VEGF‐modified macrophages were recruited to the site of vascular injury and incorporated into new endothelium formation. VEGF‐modified macrophages therapy accelerated reendothelialization and attenuated neointima formation. The VEGF protein level in tissues of injured arteries treated with VEGF‐modified macrophages was increased. The upregulated C‐C chemokine receptor type 5 (CCR5) and unaltered CCR2 protein levels were verified in VEGF‐modified macrophages in vitro. Moreover, enhanced nitric oxide (NO) production in the culture medium of VEGF‐modified macrophages was demonstrated. Our results indicated that VEGF‐modified macrophages acted as vectors of VEGF targeting injured arteries, promoting the repairing directly by incorporating into new endothelium formation and indirectly by secreting sustainable VEGF and producing NO locally. This study represents a novel therapeutic application of targeted cell therapy with VEGF‐modified macrophages for cardiovascular diseases.
Deletion of insulin receptor in the proximal tubule and fasting augment albumin excretion
Authors: Kumari Manju , Sharma Rajni , Pandey Gaurav , Ecelbarger Carolyn M. , Mishra Prabhaker , Tiwari Swasti
Published: January 2019

The contribution of proximal tubules (PT) to albumin uptake is now well recognized, however, its regulation is understudied area. There are reports suggesting that insulin resistance is associated with the development of albuminuria in nondiabetic individuals. We have previously reported reduced insulin receptor (IR) expression in renal‐tubular‐epithelial cells, including PT in various models of insulin resistance. However, the effect of a physiological fall in insulin levels and the role for IR in PT in tubular albumin uptake is not clear. To address these gaps in our understanding, we estimated urine excretion and renal uptake of albumin in fasted and fed C57Bl/6 mice injected with fluorescein isothiocyanate (FITC)‐albumin (5 µg/mL/kg body weight, intraperitoneal,
n = 6 per group). In addition, we compared spot urine analysis from 33 clinically healthy humans after overnight fasting (when insulin levels are lower than in the fed state) and then at 2 hours after 75 g oral glucose challenge (postprandial). Fasted mice had attenuated renal uptake of FITC‐albumin and higher excretion in urine, relative to fed mice (
P = 0.04). Moreover, a significant drop in urine albumin‐to‐creatinine ratio (ACR) and urine albumin concentration (UAC) was observed in the postprandial state in these subjects (
P = 0.001 and
P = 0.017, for ACR and UAC, respectively). The drop was negatively associated with postprandial blood glucose levels (ρ = −0.36,
P = 0.03 for ΔUAC and ρ = −0.34,
P = 0.05 for ΔACR). To test the role of IR in PT, we analyzed 24‐hour urine albumin excretion in male mice with targeted deletion of IR from PT (insulin receptor knockout [IRKO]) and their wild‐type (WT) littermates (
n = 7 per group). IRKO mice had significantly higher 24‐hour urine albumin excretion relative to WT. Moreover, kidneys from KO mice revealed reduced expression of megalin and cubulin proteins in the PT relative to the WT. We also demonstrated insulin (100 nM) induced albumin internalization in human proximal tubule cells (hPT) and this effect of insulin was attenuated in hydroxy‐2‐naphthalenylmethylphosphonic acid (100 µM), a tyrosine kinase inhibitor, pretreated hPT. Our findings revealed albumin excretion was attenuated by glucose administration to fasting individuals implying a regulatory role for insulin in PT albumin reabsorption. Thus albuminuria associated with insulin resistance/diabetes may relate not only to glomerular dysfunction but also to impairment in insulin‐mediated reabsorption.
Troubling stereotypes: South African elite disability athletes and the paradox of (self‐)representation
Authors: Bantjes Jason , Swartz Leslie , Botha Jeanine
Published: January 2019

Despite the increasing prominence of competitive disability sport, the literature on the experiences of disabled athletes, particularly in low‐ and middle‐ income countries, is sparse. We aimed to describe the participation experiences of a group of athletes in competitive disability sport in South Africa, as well as exploring the ways they talk about issues of identity and self‐representation in the context of elite disability sport. Data were collected via in‐depth, semistructured interviews with a purposefully sampled group of 22 athletes competing at a national level. Interviews were analyzed using thematic analysis. Participants reported that disability sport is personally transformative and that sport allows them to experience their bodies as capable and to feel a sense of pride. Participant narratives reinforced supercrip discourses and both reproduced stereotypes and challenged them. Participants experienced pride and social inclusion by reproducing aspects of supercrip discourse. The findings imply that participating in competitive disability sport can reinforce stereotypes about disability by strengthening supercrip discourses while simultaneously providing a context for internal personal transformation and private political struggles.
A dynamic reversible RNA N6‐methyladenosine modification: current status and perspectives
Authors: Bi Zhen , Liu Youhua , Zhao Yuanling , Yao Yongxi , Wu Ruifan , Liu Qing , Wang Yizhen , Wang Xinxia
Published: January 2019

N6‐methyladenosine (m6A), as the most abundant RNA epigenetic modifications, has been shown to play critical roles in various biological functions. Research about enzymes that can catalyze and remove m6A have revealed its comprehensive roles in messenger RNA (mRNA) metabolism and other physiological processes. The “readers” including YTH domain‐containing proteins, hnRNPC, hnRNPG, hnRNPA2B1, IGF2BP1, IGF2BP2, and IGF2BP3, which can affect the fates of mRNA in an m6A‐dependent manner. In this review, we focus on recent advances in the research of the m6A modifications, especially about the latest functions of its writers, erasers, readers in RNA metabolism, cancer, and lipid metabolism. In the end, we provide insights into the underlying molecular mechanisms of m6A modifications.
Therapeutics for advanced hepatocellular carcinoma: Recent advances, current dilemma, and future directions
Authors: Zhu Jing , Yin Tailang , Xu Yong , Lu Xiao‐Jie
Published: January 2019

Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a serious threat to people's health worldwide. The prognosis of advanced HCC is dim if left untreated. In the clinic, the treatment options for advanced HCC include surgery, radiotherapy, transcatheter arterial chemoembolization, and so forth. In recent years, molecular targeted therapy and immunotherapy have also made great progress, bringing new hope to patients with advanced HCC. In this study, therapeutic advances, current dilemma, and future directions of advanced HCC are reviewed, which might serve as a summary for clinicians and may stimulate future research.
Region‐resolved proteomics profiling of monkey heart
Authors: Hu Hao‐Liang , Kang Yu , Zeng Yong , Zhang Ming , Liao Qiong , Rong Ming‐Qiang , Zhang Qin , Lai Ren
Published: January 2019

Nonhuman primates (NHPs) play an indispensable role in biomedical research because of their similarities in genetics, physiological, and neurological function to humans. Proteomics profiling of monkey heart could reveal significant cardiac biomarkers and help us to gain a better understanding of the pathogenesis of heart disease. However, the proteomic study of monkey heart is relatively lacking. Here, we performed the proteomics profiling of the normal monkey heart by measuring three major anatomical regions (vessels, valves, and chambers) based on iTRAQ‐coupled LC‐MS/MS analysis. Over 3,200 proteins were identified and quantified from three heart tissue samples. Furthermore, multiple bioinformatics analyses such as gene ontology analysis, protein–protein interaction analysis, and gene‐diseases association were used to investigate biological network of those proteins from each area. More than 60 genes in three heart regions are implicated with heart diseases such as hypertrophic cardiomyopathy, heart failure, and myocardial infarction. These genes associated with heart disease are mainly enriched in citrate cycle, amino acid degradation, and glycolysis pathway. At the anatomical level, the revelation of molecular characteristics of the healthy monkey heart would be an important starting point to investigate heart disease. As a unique resource, this study can serve as a reference map for future in‐depth research on cardiac disease‐related NHP model and novel biomarkers of cardiac injury.
Autosomal dominant polycystic kidney disease: Disrupted pathways and potential therapeutic interventions
Authors: Malekshahabi Talieh , Khoshdel Rad Niloofar , Serra Andreas L. , Moghadasali Reza
Published: January 2019

Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic inherited renal cystic disease that occurs in different races worldwide. It is characterized by the development of a multitude of renal cysts, which leads to massive enlargement of the kidney and often to renal failure in adulthood. ADPKD is caused by a mutation in PKD1 or
PKD2 genes encoding the proteins polycystin‐1 and polycystin‐2, respectively. Recent studies showed that cyst formation and growth result from deregulation of multiple cellular pathways like proliferation, apoptosis, metabolic processes, cell polarity, and immune defense. In ADPKD, intracellular cyclic adenosine monophosphate (cAMP) promotes cyst enlargement by stimulating cell proliferation and transepithelial fluid secretion. Several interventions affecting many of these defective signaling pathways have been effective in animal models and some are currently being tested in clinical trials. Moreover, the stem cell therapy can improve nephropathies and according to studies were done in this field, can be considered as a hopeful therapeutic approach in future for PKD. This study provides an in‐depth review of the relevant molecular pathways associated with the pathogenesis of ADPKD and their implications in development of potential therapeutic strategies.
Potential biomarkers to detect traumatic brain injury by the profiling of salivary extracellular vesicles
Authors: Cheng Yan , Pereira Mandy , Raukar Neha , Reagan John L. , Queseneberry Mathew , Goldberg Laura , Borgovan Theodor , LaFrance W Curt , Dooner Mark , Deregibus Maria , Camussi Giovanni , Ramratnam Bharat , Quesenberry Peter
Published: January 2019

Traumatic brain injury (TBI) is a common cause of death and acquired disability in adults and children. Identifying biomarkers for mild TBI (mTBI) that can predict functional impairments on neuropsychiatric and neurocognitive testing after head trauma is yet to be firmly established. Extracellular vesicles (EVs) are known to traffic from the brain to the oral cavity and can be detected in saliva. We hypothesize the genetic profile of salivary EVs in patients who have suffered head trauma will differ from normal healthy controls, thus constituting a unique expression signature for mTBI. We enrolled a total of 54 subjects including for saliva sampling, 23 controls with no history of head traumas, 16 patients enrolled from an outpatient concussion clinic, and 15 patients from the emergency department who had sustained a head trauma within 24 hr. We performed real‐time PCR of the salivary EVs of the 54 subjects profiling 96 genes from the TaqMan Human Alzheimer's disease array. Real‐time PCR analysis revealed 57 (15 genes, p < 0.05) upregulated genes in emergency department patients and 56 (14 genes,
p < 0.05) upregulated genes in concussion clinic patients when compared with controls. Three genes were upregulated in both the emergency department patients and concussion clinic patients: CDC2, CSNK1A1, and CTSD (
p < 0.05). Our results demonstrate that salivary EVs gene expression can serve as a viable source of biomarkers for mTBI. This study shows multiple Alzheimer's disease genes present after an mTBI.
Extracellular CIRP (eCIRP) and inflammation
Authors: Aziz Monowar , Brenner Max , Wang Ping
Published: January 2019

Cold-inducible RNA-binding protein (CIRP) was discovered 2 decades ago while studying the mechanism of cold stress adaptation in mammals. Since then, the role of intracellular CIRP (iCIRP) as a stress-response protein has been extensively studied. Recently, extracellular CIRP (eCIRP) was discovered to also have an important role, acting as a damage-associated molecular pattern, raising critical implications for the pathobiology of inflammatory diseases. During hemorrhagic shock and sepsis, inflammation triggers the translocation of CIRP from the nucleus to the cytosol and its release to the extracellular space. eCIRP then induces inflammatory responses in macrophages, neutrophils, lymphocytes, and dendritic cells. eCIRP also induces endoplasmic reticulum stress and pyroptosis in endothelial cells by activating the NF-κB and inflammasome pathways, and necroptosis in macrophages via mitochondrial DNA damage. eCIRP works through the TLR4-MD2 receptors. Studies with CIRP−/− mice reveal protection against inflammation, implicating eCIRP to be a novel drug target. Anti-CIRP Ab or CIRP-derived small peptide may have effective therapeutic potentials in sepsis, acute lung injury, and organ ischemia/reperfusion injuries. The current review focuses on the pathobiology of eCIRP by emphasizing on signal transduction machineries, leading to discovering novel therapeutic interventions targeting eCIRP in various inflammatory diseases.
An azeotropic drying‐free approach for copper‐mediated radiofluorination without addition of base
Authors: Zhang Xiang , Basuli Falguni , Swenson Rolf E.
Published: January 2019

Copper‐mediated radiofluorination provides a quick and versatile approach for 18F‐labeling of arenes and heteroarenes. However, this method is known to be base sensitive, which has been a barrier for preparative scale radiosynthesis. In this report, we provide an approach for copper‐mediated radiofluorination without azeotropic drying or adding a base. [18F]Fluoride trapped on a PS‐HCO3 Sep‐Pak was quantitatively eluted with a solution of 4‐dimethylaminopyridinium trifluoromethanesulfonate (DMAP·OTf) in anhydrous N,N‐dimethylformamide (DMF). The eluted solution was directly used for copper‐mediated radiofluorination. Twelve boronic ester substrates were tested, yielding fluorinated products in 27% to 83% radiochemical yield based on HPLC analysis. This approach was successfully applied to the radiosynthesis of [18F]flumazenil, a well‐known positron emission tomography (PET) tracer for imaging central benzodiazepine receptors, with a radiochemical yield of 47%. This highly efficient protocol significantly augments the powerful copper‐mediated radiofluorination approach.
Effects of sequential treatment with intermittent parathyroid hormone and zoledronic acid on particle‐induced implant loosening: Evidence from a rat model
Authors: Hu Bin , Wu Haobo , Shi Zhongli , Ying Zhimin , Zhao Xiang , Lin Tiao , Hong Jianqiao , Wang Yangxin , Yang Yute , Cai Xunzi , Yan Shigui
Published: January 2019

Particle‐induced implant loosening is a major challenge to long‐term survival of joint prostheses. Administration of intermittent parathyroid hormone (PTH) has shown potential in the treatment of cases of early‐stage periprosthetic osteolysis, while sequential administration of intermittent PTH (iPTH) and bisphosphonates (Bps) has achieved significant effects on treatment of postmenopausal osteoporosis. The objective of this study was to determine whether sequential treatment could preserve bone mass and implant fixation during a pathological course of peri‐implant osteolysis in a rat model. Ninety male Sprague Dawley rats were randomly divided into nine groups, four of which were used for confirmation of establishment of the peri‐implant osteolysis model at two time points, while the other five were used to determine the efficiency of the sequential treatment on peri‐implant osteolysis. Implant fixation and peri‐implant bone mass were evaluated using biomechanical testing, micro‐CT analysis, and histology at 6 and 12 weeks postoperative. The biomechanical test demonstrated that the maximum loading force during a push‐out test was significantly elevated in the sequential treatment group compared to the osteolysis group and iPTH withdrawal group at 12 weeks. Peri‐implant bone morphology also indicated a robust increase in bone volume in the sequential treatment group. Sequential administration of iPTH and Bps was effective in preventing experimental peri‐implant osteolysis, resulting in improved implant fixation and increased peri‐implant bone volume. Clinical significance: The innovative application of sequential treatment in peri‐implant osteolysis could be used clinically to improve the prognosis of patients with early‐stage periprosthetic osteolysis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1489–1497, 2019.