bluuebunny/crossref_metadata_2025 huggingface dataset:
rBPI21 (opebacan) promotes rapid trilineage hematopoietic recovery in a murine model of high‐dose total body irradiation
Authors: Janec Kenneth J. , Yuan Huaiping , Norton Jr James E. , Kelner Rowan H. , Hirt Christian K. , Betensky Rebecca A. , Guinan Eva C.
Published: May 2018

The complexity of providing adequate care after radiation exposure has drawn increasing attention. While most therapeutic development has focused on improving survival at lethal radiation doses, acute hematopoietic syndrome (AHS) occurs at substantially lower exposures. Thus, it is likely that a large proportion of such a radiation‐exposed population will manifest AHS of variable degree and that the medical and socioeconomic costs of AHS will accrue. Here, we examined the potential of rBPI21 (opebacan), used without supportive care, to accelerate hematopoietic recovery after radiation where expected survival was substantial (42%‐75%) at 30 days. rBPI21 administration was associated with accelerated recovery of hematopoietic precursors and normal marrow cellularity, with increases in megakaryocyte numbers particularly marked. This translated into attaining normal trilineage peripheral blood counts 2‐3 weeks earlier than controls. Elevations of hematopoietic growth factors observed in plasma and the marrow microenvironment suggest the mechanism is likely multifactorial and not confined to known endotoxin‐neutralizing and cytokine downmodulating activities of rBPI21. These observations deserve further exploration in radiation models and other settings where inadequate hematopoiesis is a prominent feature. These experiments also model the potential of therapeutics to limit the allocation of scarce resources after catastrophic exposures as an endpoint independent of lethality mitigation.
Epstein‐Barr virus antibody titer as a stress biomarker and its association with social capital in rural Fujian communities, China
Authors: Yazawa Aki , Inoue Yosuke , Cai Guoxi , Tu Raoping , Huang Meng , He Fei , Chen Jie , Yamamoto Taro , Watanabe Chiho
Published: May 2018

Objectives

There has been little research on the association between social capital and psychological stress measured by a biomarker, particularly in developing countries. Our objective was to investigate the association between Epstein‐Barr virus (EBV) antibody titer, an indicator of cellular immune function previously shown to be associated with psychological stress, and social capital among rural community dwellers in Fujian Province, China.

Methods

We conducted a cross‐sectional survey in seven rural communities in Fujian in 2015. We used questionnaire data and dried blood spot samples for the measurement of biomarkers collected from 734 local residents for the analysis. We conducted a mixed effects regression analysis to investigate the association between EBV antibody titer and four social capital variables, which included cognitive and structural social capital assessed both at individual and community levels.

Results

Community‐level structural social capital was inversely associated with psychological stress (coefficient = −0.96, 95% confidence interval [CI] = −1.91, −0.01) while individual‐level structural social capital was positively associated with it (coefficient = 0.21, 95% CI = 0.07, 0.36). Neither individual‐ nor community‐level cognitive social capital was associated with psychological stress status.

Conclusions

In rural Fujian, China, social capital seemed to be an important determinant of psychological health. While living in a community with active social interaction may benefit the residents psychologically, social interaction in the form of strongly bonded relationships may be a source of psychological stress at the individual level due to the potential demands and obligations that may be associated with such connections.
Preliminary evidence that androgen signaling is correlated with men's everyday language
Authors: Mascaro Jennifer S. , Rentscher Kelly E. , Hackett Patrick D. , Lori Adriana , Darcher Alana , Rilling James K. , Mehl Matthias R.
Published: May 2018

Objectives

Testosterone (T) has an integral, albeit complex, relationship with social behavior, especially in the domains of aggression and competition. However, examining this relationship in humans is challenging given the often covert and subtle nature of human aggression and status‐seeking. The present study aimed to investigate whether T levels and genetic polymorphisms in the AR gene are associated with social behavior assessed via natural language use.

Methods

We used unobtrusive, behavioral, real‐world ambulatory assessments of men in partnered heterosexual relationships to examine the relationship between plasma T levels, variation in the androgen receptor (AR) gene, and spontaneous, everyday language in three interpersonal contexts: with romantic partners, with co‐workers, and with their children.

Results

Men's T levels were positively correlated with their use of achievement words with their children, and the number of AR CAG trinucleotide repeats was inversely correlated with their use of anger and reward words with their children. T levels were positively correlated with sexual language and with use of swear words in the presence of their partner, but not in the presence of co‐workers or children.

Conclusions

Together, these results suggest that T may influence social behavior by increasing the frequency of words related to aggression, sexuality, and status, and that it may alter the quality of interactions with an intimate partner by amplifying emotions via swearing.
Evolution of Isoindigo‐Based Electron‐Deficient Units for Organic Electronics: From Natural Dyes to Organic Semiconductors
Authors: Li Jiu‐Long , Cao Jing‐Jing , Duan Lin‐Lin , Zhang Hao‐Li
Published: May 2018

Isoindigo, a classical electron‐deficient unit for organic optoelectronic materials, has been widely used in organic field‐effect transistors (OFETs) and organic photovoltaic devices (OPVs). However, several intrinsic drawbacks, such as its non‐coplanarity and weak absorption in the visible‐light region, have hindered its further development. Recently, many optimized isoindigo derivatives have been successfully applied to OFETs and OPVs. This Focus Review discusses recent progress in the structural optimization of isoindigo‐based organic optoelectronic materials and provides meaningful guidelines for the design of high‐performance isoindigo derivatives for organic electronics.
Rhodium(III)‐Catalyzed Direct Alkenylation of Benzothiophenes and Related Heterocycles with Alkynes
Authors: Morita Tomohiro , Morisaka Hideaki , Satoh Tetsuya , Miura Masahiro
Published: May 2018

A rhodium(III)‐catalyzed direct alkenylation of benzo[b]thiophenes, thieno[3,2‐b]thiophene, and benzo[b]furans with diarylacetylenes proceeds effectively through regioselective C−H bond cleavage at the C2 position and syn‐selective carborhodation on the triple bond.
Filter‐probe diffusion imaging improves spinal cord injury outcome prediction
Authors: Skinner Nathan P. , Lee Seung‐Yi , Kurpad Shekar N. , Schmit Brian D. , Muftuler L. Tugan , Budde Matthew D.
Published: May 2018

Objective

Diffusion‐weighted imaging (DWI) is a powerful tool for investigating spinal cord injury (SCI), but has limited specificity for axonal damage, which is the most predictive feature of long‐term functional outcome. In this study, a technique designed to detect acute axonal injury, filter‐probe double diffusion encoding (FP‐DDE), is compared with standard DWI for predicting long‐term functional and cellular outcomes.

Methods

This study extends FP‐DDE to predict long‐term functional and histological outcomes in a rat SCI model of varying severities (n = 58). Using a 9.4T magnetic resonance imaging (MRI) system, a whole‐cord FP‐DDE spectroscopic voxel was acquired in 3 minutes at the lesion site and compared to DWI at 48 hours postinjury. Relationships with chronic (30‐day) locomotor and histological outcomes were evaluated with linear regression.

Results

The FP‐DDE measure of parallel diffusivity (ADC||) was significantly related to chronic hind limb locomotor functional outcome (R2 = 0.63, p < 0.0001), and combining this measurement with acute functional scores demonstrated prognostic benefit versus functional testing alone (p = 0.0007). Acute ADC|| measurements were also more closely related to the number of injured axons measured 30 days after the injury than standard DWI. Furthermore, acute FP‐DDE images showed a clear and easily interpretable pattern of injury that closely corresponded with chronic MRI and histology observations.

Interpretation

Collectively, these results demonstrate FP‐DDE benefits from greater specificity for acute axonal damage in predicting functional and histological outcomes with rapid acquisition and fully automated analysis, improving over standard DWI. FP‐DDE is a promising technique compatible with clinical settings, with potential research and clinical applications for evaluation of spinal cord pathology. Ann Neurol 2018;83:37–50
Highly Elastic Organic Crystals for Flexible Optical Waveguides
Authors: Liu Huapeng , Lu Zhuoqun , Zhang Zuolun , Wang Yue , Zhang Hongyu
Published: May 2018

The study of elastic organic single crystals (EOSCs) has emerged as a cutting‐edge research of crystal engineering. Although a few EOSCs have been reported recently, those suitable for optical/optoelectronic applications have not been realized. Here, we report an elastic crystal of a Schiff base, (E)‐1‐(4‐(dimethylamino)phenyl)iminomethyl‐2‐hydroxyl‐naphthalene. The crystal is highly bendable under external stress and able to regain immediately its original straight shape when the stress is released. It displays bright orange–red emission with a high fluorescence quantum yield of 0.43. Intriguingly, it can serve as a low‐loss optical waveguide even at the highly bent state. Our result highlights the feature and utility of “elasticity” of organic crystals.
Multipronged Biomimetic Approach To Create Optically Tunable Nanoparticles
Authors: Harmatys Kara M. , Chen Juan , Charron Danielle M. , MacLaughlin Christina M. , Zheng Gang
Published: May 2018

Current biomimetics for medical applications use a single biomimetic approach to imitate natural structures, which can be insufficient for reconstructing structurally complex natural systems. Multipronged efforts may resolve these complexities. To achieve interesting nanostructure‐driven optical properties, a dual‐biomimetic system contained within a single nanoagent was engineered to recapitulate chlorosomes, efficient light‐harvesting organelles that have unique dye assemblies and tunable photonic properties. A series of chlorin dyes was synthesized, and these hydrophobic assemblies were stabilized inside a high‐density lipoprotein, a second biomimetic that enabled in vivo utility. This system resulted in tunable tumor imaging of intact (photoacoustic) and disrupted (activatable fluorescence) nanostructures. The successful demonstration of this multipronged biomimetic approach opens the door for reconstruction of complex natural systems for biomedical applications.
Redox Chemistry of Molybdenum Trioxide for Ultrafast Hydrogen‐Ion Storage
Authors: Wang Xianfu , Xie Yiming , Tang Kai , Wang Chao , Yan Chenglin
Published: May 2018

Hydrogen ions are ideal charge carriers for rechargeable batteries due to their small ionic radius and wide availability. However, little attention has been paid to hydrogen‐ion storage devices because they generally deliver relatively low Coulombic efficiency as a result of the hydrogen evolution reaction that occurs in an aqueous electrolyte. Herein, we successfully demonstrate that hydrogen ions can be electrochemically stored in an inorganic molybdenum trioxide (MoO3) electrode with high Coulombic efficiency and stability. The as‐obtained electrode exhibits ultrafast hydrogen‐ion storage properties with a specific capacity of 88 mA hg−1 at an ultrahigh rate of 100 C. The redox reaction mechanism of the MoO3 electrode in the hydrogen‐ion cell was investigated in detail. The results reveal a conversion reaction of the MoO3 electrode into H0.88MoO3 during the first hydrogen‐ion insertion process and reversible intercalation/deintercalation of hydrogen ions between H0.88MoO3 and H0.12MoO3 during the following cycles. This study reveals new opportunities for the development of high‐power energy storage devices with lightweight elements.
NH4Be2BO3F2 and γ‐Be2BO3F: Overcoming the Layering Habit in KBe2BO3F2 for the Next‐Generation Deep‐Ultraviolet Nonlinear Optical Materials
Authors: Peng Guang , Ye Ning , Lin Zheshuai , Kang Lei , Pan Shilie , Zhang Min , Lin Chensheng , Long Xifa , Luo Min , Chen Yu , Tang Yu‐Huan , Xu Feng , Yan Tao
Published: May 2018

KBe2BO3F2 (KBBF) is still the only practically usable crystal that can generate deep‐ultraviolet (DUV) coherent light by direct second harmonic generation (SHG). However, applications are hindered by layering, leading to difficulty in the growth of thick crystals and compromised mechanical integrity. Despite efforts, it is still a great challenge to discover new nonlinear optical (NLO) materials that overcome the layering while keeping the DUV SHG available. Now, two new DUV NLO beryllium borates have been successfully designed and synthesized, NH4Be2BO3F2 (ABBF) and γ‐Be2BO3F (γ‐BBF), which not only overcome the layering but also can be used as next‐generation DUV NLO materials with the shortest type I phase‐matching second‐harmonic wavelength down to 173.9 nm and 146 nm, respectively. Significantly, γ‐BBF is superior to KBBF in all metrics and would be the most outstanding DUV NLO crystal.
Cofactor Biogenesis in Cysteamine Dioxygenase: C−F Bond Cleavage with Genetically Incorporated Unnatural Tyrosine
Authors: Wang Yifan , Griffith Wendell P. , Li Jiasong , Koto Teruaki , Wherritt Daniel J. , Fritz Elizabeth , Liu Aimin
Published: May 2018

Cysteamine dioxygenase (ADO) is a thiol dioxygenase whose study has been stagnated by the ambiguity as to whether or not it possesses an anticipated protein‐derived cofactor. Reported herein is the discovery and elucidation of a Cys‐Tyr cofactor in human ADO, crosslinked between Cys220 and Tyr222 through a thioether (C−S) bond. By genetically incorporating an unnatural amino acid, 3,5‐difluoro‐tyrosine (F2‐Tyr), specifically into Tyr222 of human ADO, an autocatalytic oxidative carbon–fluorine bond activation and fluoride release were identified by mass spectrometry and 19F NMR spectroscopy. These results suggest that the cofactor biogenesis is executed by a powerful oxidant during an autocatalytic process. Unlike that of cysteine dioxygenase, the crosslinking results in a minimal structural change of the protein and it is not detectable by routine low‐resolution techniques. Finally, a new sequence motif, C‐X‐Y‐Y(F), is proposed for identifying the Cys‐Tyr crosslink.
Photoinduced Miyaura Borylation by a Rare‐Earth‐Metal Photoreductant: The Hexachlorocerate(III) Anion
Authors: Qiao Yusen , Yang Qiaomu , Schelter Eric J.
Published: May 2018

The first photoinduced carbon(sp2)–heteroatom bond forming reaction by a rare‐earth‐metal photoreductant, a Miyaura borylation, has been achieved. This simple, scalable, and novel borylation method that makes use of the hexachlorocerate(III) anion ([CeIIICl6]3−, derived from CeCl3) has a broad substrate scope and functional‐group tolerance and can be conducted at room temperature. Combined with Suzuki–Miyaura cross‐coupling, the method is applicable to the synthesis of various biaryl products, including through the use of aryl chloride substrates.
Functional Neuroimaging of Nociceptive and Pain‐Related Activity in the Spinal Cord and Brain: Insights From Neurovascular Coupling Studies
Authors: Paquette Thierry , Jeffrey‐Gauthier Renaud , Leblond Hugues , PichÉ Mathieu
Published: May 2018

Spinal cord and brain processes underlie pain perception, which produces systemic cardiovascular changes. In turn, the autonomic nervous system regulates vascular function in the spinal cord and brain in order to adapt to these systemic changes, while neuronal activity induces local vascular changes. Thus, autonomic regulation and pain processes in the brain and spinal cord are tightly linked and interrelated. The objective of this topical review is to discuss work on neurovascular coupling during nociceptive processing in order to highlight supporting evidence and limitations for the use of cerebral and spinal fMRI to investigate pain mechanisms and spinal nociceptive processes. Work on functional neuroimaging of pain is presented and discussed in relation to available neurovascular coupling studies and related issues. Perspectives on future work are also discussed with an emphasis on differences between the brain and the spinal cord and on different approaches that may be useful to improve current methods, data analyses and interpretation. In summary, this review highlights the lack of data on neurovascular coupling during nociceptive stimulation and indicates that hemodynamic and BOLD responses measured with fMRI may be biased by nonspecific vascular changes. Future neuroimaging studies on nociceptive and pain‐related processes would gain further understanding of neurovascular coupling in the brain and spinal cord and should take into account the effects of systemic vascular changes that may affect hemodynamic responses. Anat Rec, 301:1585–1595, 2018. © 2018 Wiley Periodicals, Inc.
Morphological and Cellular Characterization of the Fetal Canine (Canis lupus familiaris) Subventricular Zone, Rostral Migratory Stream, and Olfactory Bulb
Authors: Orechio Dailiany , Andrade Aguiar Bruna , Baroni Diniz Giovanne , Cioni Bittencourt Jackson , Haemmerle Carlos A. S. , Watanabe Ii‐Sei , Miglino Maria Angelica , Castelucci Patricia
Published: May 2018

The existence of neurogenesis in the adult brain is a widely recognized phenomenon, occurring in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the dentate gyrus in several vertebrate species. Neural precursors originated in the SVZ migrate to the main olfactory bulb (MOB), originating the rostral migratory stream (RMS) in the process. To better understand the formation of the adult neurogenic niches in dogs, we investigated the cellular composition and morphological organization of these areas in 57 days‐old dog fetuses. Using multiple immunohistochemical markers, we demonstrated that the SVZ in the canine fetus is remarkably similar to the adult SVZ, with glial GFAP‐immunoreactive (‐ir) cells, DCX‐ir neuroblasts and SOX2‐ir neuronal progenitors tangentially organized along the dorsal lateral ventricle. The fetal RMS has all the features of its adult counterpart and closely resembles the RMS of other mammalian species. The late‐development canine MOB has most of the neurochemical features of the adult MOB, including an early‐developed TH‐ir population and maturing CALR‐ir interneurons, but CALB‐ir neurons in the granule cell layer will only appear in the post‐partum period. Taken together, our results suggest that the canine fetal development of adult neurogenic niches closely resembles those of primates, and dogs may be suitable models of human adult neurogenesis. Anat Rec, 301:1570–1584, 2018. © 2018 Wiley Periodicals, Inc.
3DMRIModeling of Thin and Spatially Complex Soft Tissue Structures without Shrinkage: Lamprey Myosepta as an Example
Authors: Wood Bradley M. , Jia Guang , Carmichael Owen , Mcklveen Kevin , Homberger Dominique G.
Published: May 2018

3D imaging techniques enable the nondestructive analysis and modeling of complex structures. Among these, MRI exhibits good soft tissue contrast, but is currently less commonly used for nonclinical research than X‐ray CT, even though the latter requires contrast‐staining that shrinks and distorts soft tissues. When the objective is the creation of a realistic and complete 3D model of soft tissue structures, MRI data are more demanding to acquire and visualize and require extensive post‐processing because they comprise noncubic voxels with dimensions that represent a trade‐off between tissue contrast and image resolution. Therefore, thin soft tissue structures with complex spatial configurations are not always visible in a single MRI dataset, so that standard segmentation techniques are not sufficient for their complete visualization. By using the example of the thin and spatially complex connective tissue myosepta in lampreys, we developed a workflow protocol for the selection of the appropriate parameters for the acquisition of MRI data and for the visualization and 3D modeling of soft tissue structures. This protocol includes a novel recursive segmentation technique for supplementing missing data in one dataset with data from another dataset to produce realistic and complete 3D models. Such 3D models are needed for the modeling of dynamic processes, such as the biomechanics of fish locomotion. However, our methodology is applicable to the visualization of any thin soft tissue structures with complex spatial configurations, such as fasciae, aponeuroses, and small blood vessels and nerves, for clinical research and the further exploration of tensegrity. Anat Rec, 301:1745–1763, 2018. © 2018 Wiley Periodicals, Inc.
Metabolomic comparison between wild Ophiocordyceps sinensis and artificial cultured Cordyceps militaris
Authors: Chen Lin , Liu Yuetao , Guo Qingfeng , Zheng Qingxia , Zhang Wancun
Published: May 2018

A systematic study on the metabolome differences between wild Ophiocordyceps sinensis and artificial cultured Cordyceps militaris was conducted using liquid chromatography−mass spectrometry. Principal component analysis and orthogonal projection on latent structure‐discriminant analysis results showed that C. militaris grown on solid rice medium (R‐CM) and C. militaris grown on tussah pupa (T‐CM) evidently separated and individually separated from wild O. sinensis, indicating metabolome difference among wild O. sinensis, R‐CM and T‐CM. The metabolome differences between R‐CM and T‐CM indicated that C. militaris could accommodate to culture medium by differential metabolic regulation. Hierarchical clustering analysis was further performed to cluster the differential metabolites and samples based on their metabolic similarity. The higher content of amino acids (pyroglutamic acid, glutamic acid, histidine, phenylalanine and arginine), unsaturated fatty acid (linolenic acid and linoleic acid), peptides, mannitol, adenosine and succinoadenosine in O. sinensis make it as an excellent choice as a traditional Chinese medicine for invigoration or nutritional supplementation. Similar compositions with O. sinensis and easy cultivation make artificially cultured C. militaris a possible alternative to O. sinensis.
Anatomical consideration of the occipital cutaneous nerves and artery for the safe treatment of occipital neuralgia
Authors: Shin Kang‐Jae , Kim Hong‐San , O Jehoon , Kwon Hyun‐Jin , Yang Hun‐Mu
Published: May 2018

There is no standardized approach to the greater occipital nerve (GON) block technique for treating occipital neuralgia. The aim of the present study was to validate the previously‐suggested guidelines for conventional injection techniques and to provide navigational guidelines for safe GON block. The GON, lesser occipital nerve (LON) and occipital artery (OA) were carefully dissected in the occipital region of embalmed cadavers. Using a 3 D digitizer, the GON, LON, and OA were observed on the two reference lines. The distances between the landmarks were recorded and statistically analyzed. On the superior nuchal line, the mean distances between the external occipital protuberance (EOP) and the most medial branch of the GON was 33.5 mm. The mean distance between the EOP and the most medial branch of the OA was 37.4 mm. On the EOP‐mastoid process (MP) line, the GON was on the medial third and the LON the lateral third of the EOP‐MP line. The safe injection points on the EOP‐MP line are about 3 cm from the EOP, 1 cm inferior parallel to the EOP‐MP line, and about 3 cm away from the MP. Clin. Anat. 31:1058–1064, 2018. © 2018 Wiley Periodicals, Inc.
The role of mTOR in ovarian Neoplasms, polycystic ovary syndrome, and ovarian aging
Authors: Liu Jin , Wu Dai‐Chao , Qu Li‐Hua , Liao Hong‐Qing , Li Mei‐Xiang
Published: May 2018

The mammalian target of rapamycin, mTOR, is a serine‐threonine protein kinase downstream of the phosphatidylinositol 3‐kinase (PI3K)‐AKT axis. The pathway can regulate cell growth, proliferation, and survival by activating ribosomal kinases. Recent studies have implicated the mTOR signaling pathway in ovarian neoplasms, polycystic ovary syndrome (PCOS) and premature ovarian failure (POF). Preclinical investigations have demonstrated that the PI3K/AKT/mTOR pathway is frequently activated in the control of various ovarian functions. mTOR allows cancer cells to escape the normal biochemical system and regulates the balance between apoptosis and survival. Some recent studies have suggested that involvement of the mTOR signaling system is an important pathophysiological basis of PCOS. Overexpression of the mTOR pathway can impair the interaction of cumulus cells, lead to insulin resistance, and affect the growth of follicles directly. The roles of mTOR signaling in follicular development have been extensively studied in recent years; abnormalities in this process lead to a series of pathologies such as POF and infertility. To improve understanding of the role of the mTOR signaling pathway in the pathogenesis and development of ovarian diseases, here we review the roles of mTOR signaling in such diseases and discuss the corresponding therapeutic strategies that target this pathway. Clin. Anat. 31:891–898, 2018. © 2018 Wiley Periodicals, Inc.
Retracted: MicroRNA‐92a promotes tumor growth and suppresses immune function through activation of MAPK/ERK signaling pathway by inhibiting PTEN in mice bearing U14 cervical cancer
Authors: Li Zeng‐Hui , Li Lei , Kang Lin‐Ping , Wang Yan
Published: May 2018

Cervical cancer is known as the possible outcome of genital infection, while the molecular mechanisms of initiation, development, and metastasis of cervical cancer have not yet been fully elucidated. Our study aims to investigate the effects of microRNA‐92a (miR‐92a) on tumor growth and immune function by targeting PTEN via the MAPK/ERK signaling pathway in tumor‐bearing mice. C57BL/6 female mice were used for tumor‐bearing mouse models and their tumor and adjacent normal tissues were collected, and normal cervical tissues were obtained from normal mice. Serum levels of tumor necrosis factor‐α (TNF‐α) and soluble interleukin‐2 receptor (sIL‐2R) were detected by ELISA. The cells were divided into the normal, blank, negative control (NC), miR‐92a mimic, miR‐92a inhibitor, siRNA‐PTEN, and miR‐92a inhibitor + siRNA‐PTEN groups. Dual‐luciferase reporter assay was adopted to determine the relationship between PTEN and miR‐92a. Expressions of miR‐92a, PTEN, TNF‐α, sIL‐2R, ERK1, and ERK2 were tested by RT‐qPCR and Western blotting. Cell proliferation was detected by cell count kit‐8 (CCK‐8); cell cycle and apoptosis were detected by flow cytometry. Compared with the normal cervical tissues and adjacent normal tissues, the cervical cancer tissues exhibited increased expressions of miR‐92a, p‐ERK1/2, and serum levels of TNF‐α and sIL‐2R while decreased PTEN expression. PTEN was confirmed to be the target gene of miR‐92a. As compared with the blank and NC groups, expressions of miR‐92a, ERK1 and ERK2 increased, and expressions of PTEN decreased in the miR‐92a mimic group. The miR‐92a mimic group exhibited increased expression levels of TNF‐α and sIL‐2R, cell proliferation, and cell number in S phase but decreased cell apoptosis, and cell number in G0/G1 phase, while the miR‐92a inhibitor group followed opposite trends. miR‐92a promotes tumor growth and suppresses immune function by inhibiting PTEN via activation of the MAPK/ERK signaling pathway in mice bearing U14 cervical cancer.
Synthesis of β‐Ketoamide Curcumin Analogs for Anti‐Diabetic and AGEs Inhibitory Activities
Authors: Banuppriya Govindharasu , Sribalan Rajendran , Fathima Sulthan Alavudeen Rizwan , Padmini Vediappen
Published: May 2018

Two different series of novel β‐ketoamide curcumin analogs enriched in biological activities have been synthesized. The synthesized compounds were screened for their in vitro anti‐diabetic and AGEs inhibitory activities and exhibited potent to good anti‐diabetic and AGEs inhibitory activities. The molecular docking study was also performed with the α‐amylase enzyme.
H2O2 induces PP2A demethylation to downregulate mTORC1 signaling in HEK293 cells
Authors: Tang Shen , Qin Fu , Wang Xinhang , Liang Ziwei , Cai Haiqing , Mo Laiming , Huang Yue , Liang Boyin , Wei Xuejing , Ao Qingqing , Xu Yilu , Liu Yuyang , Xiao Deqiang , Guo Songchao , Lu Cailing , Li Xiyi
Published: May 2018

Mammalian target of rapamycin (mTOR) is a Ser/Thr protein kinase that functions as an ATP and amino acid sensor to govern cell growth and proliferation by mediating mitogen‐ and nutrient‐dependent signal transduction. Protein phosphatase 2A (PP2A), a ubiquitously expressed serine/threonine phosphatase, negatively regulates mTOR signaling. Methylation of PP2A is catalyzed by leucine carboxyl methyltransferase‐1 (LCMT1) and reversed by protein phosphatase methylesterase 1 (PME‐1), which regulates PP2A activity and substrate specificity. However, whether PP2A methylation is related to mTOR signaling is still unknown. In this study, we examined the effect of PP2A methylation on mTOR signaling in HEK293 cells under oxidative stress. Our results show that oxidative stress induces PP2A demethylation and inhibits the mTORC1 signaling pathway. Next, we examined two strategies to block PP2A demethylation under oxidative stress. One strategy was to prevent PP2A demethylation using a PME‐1 inhibitor; the other strategy was to activate PP2A methylation via overexpression of LCMT1. The results show that both the PME‐1 inhibitor and LCMT1 overexpression prevent the mTORC1 signaling suppression induced by oxidative stress. Additionally, LCMT1 overexpression rescued cell viability and the mitochondrial membrane potential decrease in response to oxidative stress. These results demonstrate that H2O2 induces PP2A demethylation to downregulate mTORC1 signaling. These findings provide a novel mechanism for the regulation of PP2A demethylation and mTORC1 signaling under oxidative stress.
Severe allograft rejection in an intestinal transplant patient following oral immunoglobulin treatment for chronic norovirus infection: a case report
Authors: Åberg Fredrik , Savikko Johanna , Anttila Veli‐Jukka , Mäkisalo Heikki
Published: May 2018

Key Clinical Message

In an intestinal transplant patient under triple immunosuppression therapy with tacrolimus levels >10 ng/L, a 2‐day oral immunoglobulin therapy given as treatment for chronic norovirus infection was temporally closely associated with the development of severe steroid‐resistant acute graft rejection, thus suggesting that oral immunoglobulin might be able to promote a rejection response.
Surfactant‐Assisted Fabrication of Cubic Cobalt Oxide Hybrid Hollow Spheres as Catalysts for the Oxygen Reduction Reaction
Authors: Zhong Haihong , Wang Jing , Wang Tiehong , Zhang Shuwei , Li Dianqing , Tang Pinggui , Alonso‐Vante Nicolas , Feng Yongjun
Published: May 2018

Herein, we designed and synthesized a series of carbon‐supported cubic cobalt oxide (CoOx/C−T) hollow spheres annealed at different temperatures (T) by a simple and low‐cost “surfactant‐templated” route at room temperature. Furthermore, we investigated the effect of high‐temperature pyrolysis on electrocatalytic performance of the prepared cubic oxides towards oxygen reduction reaction (ORR) in alkaline medium. Among the three investigated samples (heat treated at 500 °C, 600 °C, 700 °C), CoOx/C‐600 nanoparticles, with the largest surface area (198 m2/g), showed a promising ORR performance with E1/2=0.78 V (vs. RHE) and Eonset=0.88 V (vs. RHE), akin with the commercial Pt/C catalyst. In comparison, the CoOx/C‐600 electrocatalyst also exhibits higher ORR selectivity and longer durability under the investigated conditions.
La5Ti2Cu0.9Ag0.1S5O7 Modified with a Molecular Ni Catalyst for Photoelectrochemical H2 Generation
Authors: Rosser Timothy E. , Hisatomi Takashi , Sun Song , Antón‐García Daniel , Minegishi Tsutomu , Reisner Erwin , Domen Kazunari
Published: May 2018

The stable and efficient integration of molecular catalysts into p‐type semiconductor materials is a contemporary challenge in photoelectrochemical fuel synthesis. Here, we report the combination of a phosphonated molecular Ni catalyst with a TiO2‐coated La5Ti2Cu0.9Ag0.1S5O7 photocathode for visible light driven H2 production. This hybrid assembly provides a positive onset potential, large photocurrents, and high Faradaic yield for more than three hours. A decisive feature of the hybrid electrode is the TiO2 interlayer, which stabilizes the oxysulfide semiconductor and allows for robust attachment of the phosphonated molecular catalyst. This demonstration of an oxysulfide‐molecular catalyst photocathode provides a novel platform for integrating molecular catalysts into photocathodes and the large photovoltage of the presented system makes it ideal for pairing with photoanodes.
How do reaction conditions affect the enantiopure synthesis of 2‐substituted‐1,4‐benzodioxane derivatives?
Authors: Straniero Valentina , Casiraghi Andrea , Fumagalli Laura , Valoti Ermanno
Published: May 2018

Several biologically active compounds structurally include the enantiopure 2‐substituted‐1,4‐benzodioxane scaffold. The straightforward racemization that affects reactions involving most of the common chemical reactives is thus a crucial issue. The developing of a completely stereo‐controlled synthetic route that does not affect the enantiomeric excess is consequently mandatory. It is also important to set up a reliable chiral HPLC method, able to follow the reaction, and to improve the synthetic performances. Here, we report the chiral investigation of two different synthons, we specifically evaluated the synthetic pathways that could be run in order to afford them, avoiding the racemization processes, which could normally occur in basic conditions. In addition, we developed peculiar chiral HPLC methods in order to resolve the enantiomers, define the enantiomeric excess, and fully characterize these compounds.
HPLC‐ECD and TDDFT‐ECD study of hexahydropyrrolo[1,2‐a]quinoline derivatives
Authors: Tóth László , Mándi Attila , Váradi Dániel , Kovács Tibor , Szabados Anna , Kiss‐Szikszai Attila , Gong Qi , Zhang Haiyan , Mátyus Péter , Antus Sándor , Kurtán Tibor
Published: May 2018

Synthesis of racemic hexahydropyrrolo[1,2‐a]quinoline derivatives (1‐8) was performed by utilizing the Knoevenagel‐[1,5]‐hydride shift‐cyclization domino reaction. Separation of the enantiomers of the chiral products (1‐8) was carried out by chiral high‐performance liquid chromatography, and online high‐performance liquid chromatography‐electronic circular dichroism (ECD) spectra were recorded to elucidate the absolute configuration by comparing the experimental and time‐dependent density functional theory‐ECD spectra obtained at various theoretical levels. For 1 of the products, the time‐dependent density functional theory‐ECD calculations allowed determining both the relative and the absolute configuration by distinguishing the 4 stereoisomers. One of the compounds with spiro 1,3‐cyclohexanedione moiety (7) possessed moderate acetylcholinesterase inhibitory activity, while 3 showed neuroprotective activity in oxygen‐glucose deprivation‐induced neurotoxicity in human neuroblastoma SH‐SY5Y cells.
Relation between age and carotid artery intima‐medial thickness: a systematic review
Authors: van den Munckhof Inge C.L. , Jones Helen , Hopman Maria T.E. , de Graaf Jacqueline , Nyakayiru Jean , van Dijk Bart , Eijsvogels Thijs M.H. , Thijssen Dick H.J.
Published: May 2018

Carotid artery intima‐medial thickness (cIMT) represents a popular measure of atherosclerosis and is predictive of future cardiovascular and cerebrovascular events. Although older age is associated with a higher cIMT, little is known about whether this increase in cIMT follows a linear relationship with age or it is affected under influence of cardiovascular diseases (CVD) or CVD risk factors. We hypothesize that the relationship between cIMT and age is nonlinear and is affected by CVD or risk factors. A systematic review of studies that examined cIMT in the general population and human populations free from CVD/risk factors was undertaken. The literature search was conducted in PubMed, Scopus, and Web of Science. Seventeen studies with 32 unique study populations, involving 10,124 healthy individuals free from CVD risk factors, were included. Furthermore, 58 studies with 115 unique study populations were included, involving 65,774 individuals from the general population (with and without CVD risk factors). A strong positive association was evident between age and cIMT in the healthy population, demonstrating a gradual, linear increase in cIMT that did not differ between age decades (r = 0.91, P < 0.001). Although populations with individuals with CVD demonstrated a higher cIMT compared to populations free of CVD, a linear relation between age and cIMT was also present in this population. Our data suggest that cIMT is strongly and linearly related to age. This linear relationship was not affected by CVD or risk factors.
A requirement for septins and the autophagy receptor p62 in the proliferation of intracellular Shigella
Authors: Lobato‐Márquez Damián , Krokowski Sina , Sirianni Andrea , Larrouy‐Maumus Gerald , Mostowy Serge
Published: May 2018

Shigella flexneri, a Gram‐negative enteroinvasive pathogen, causes inflammatory destruction of the human intestinal epithelium. During infection of epithelial cells, Shigella escape from the phagosome to the cytosol, where they reroute host cell glycolysis to obtain nutrients for proliferation. Septins, a poorly understood component of the cytoskeleton, can entrap cytosolic Shigella targeted to autophagy in cage‐like structures to restrict bacterial proliferation. Although bacterial entrapment by septin caging has been the subject of intense investigation, the role of septins and the autophagy machinery in the proliferation of noncaged Shigella is mostly unknown. Here, we found that intracellular Shigella fail to efficiently proliferate in SEPT2‐, SEPT7‐, or p62/SQSTM1‐depleted cells. Consistent with a failure to proliferate, single cell analysis of bacteria not entrapped in septin cages showed that the number of metabolically active Shigella in septin‐ or p62‐depleted cells is reduced. Targeted metabolomic analysis revealed that host cell glycolysis is dysregulated in septin‐depleted cells, suggesting a key role for septins in modulation of glycolysis. Together, these results suggest that septins and the autophagy machinery may regulate metabolic pathways that promote the proliferation of intracellular Shigella not entrapped in septin cages.
Identification of NeuN immunopositive cells in the adult mouse subventricular zone
Authors: Saito Kengo , Koike Taro , Kawashima Fumiaki , Kurata Hirofumi , Shibuya Taku , Satoh Takemasa , Hata Yoshio , Yamada Hisao , Mori Tetsuji
Published: May 2018

In the adult rodent subventricular zone (SVZ), there are neural stem cells (NSCs) and the specialized neurogenic niche is critical to maintain their stemness. To date, many cellular and noncellular factors that compose the neurogenic niche and markers to identify subpopulations of Type A cells have been confirmed. In particular, neurotransmitters regulate adult neurogenesis and mature neurons in the SVZ have been only partially analyzed. Moreover, Type A cells, descendants of NSCs, are highly heterogeneous and more molecular markers are still needed to identify them. In the present study, we systematically classified NeuN, commonly used as a marker of mature and immature post‐mitotic neurons, immunopositive (+) cells within the adult mouse SVZ. These SVZ‐NeuN+ cells (SVZ‐Ns) were mainly classified into two types. One was mature SVZ‐Ns (M‐SVZ‐Ns). Neurochemical properties of M‐SVZ‐Ns were similar to those of striatal neurons, but their birth date and morphology were different. M‐SVZ‐Ns were generated during embryonic and early postnatal stages with bipolar peaks and extended their processes along the wall of the lateral ventricle. The second type was small SVZ‐Ns (S‐SVZ‐Ns) with features of Type A cells. They expressed not only markers of Type A cells, but also proliferated and migrated from the SVZ to the olfactory bulb. Furthermore, S‐SVZ‐Ns could be classified into two types by their spatial locations and glutamic acid decarboxylase 67 expression. Our data indicate that M‐SVZ‐Ns are a new component of the neurogenic niche and S‐SVZ‐Ns are newly identified subpopulations of Type A cells.
Post‐crossing segment of dI1 commissural axons forms collateral branches to motor neurons in the developing spinal cord
Authors: Kaneyama Takeshi , Shirasaki Ryuichi
Published: May 2018

The dI1 commissural axons in the developing spinal cord, upon crossing the midline through the floor plate, make a sharp turn to grow rostrally. These post‐crossing axons initially just extend adjacent to the floor plate without entering nearby motor columns. However, it remains poorly characterized how these post‐crossing dI1 axons behave subsequently to this process. In the present study, to address this issue, we examined in detail the behavior of post‐crossing dI1 axons in mice, using the Atoh1 enhancer‐based conditional expression system that enables selective and sparse labeling of individual dI1 axons, together with Hb9 and ChAT immunohistochemistry for precise identification of spinal motor neurons (MNs). We found unexpectedly that the post‐crossing segment of dI1 axons later gave off collateral branches that extended laterally to invade motor columns. Interestingly, these collateral branches emerged at around the time when their primary growth cones initiated invasion into motor columns. In addition, although the length of the laterally growing collateral branches increased with age, the majority of them remained within motor columns. Strikingly, these collateral branches further gave rise to multiple secondary branches in the region of MNs that innervate muscles close to the body axis. Moreover, these axonal branches formed presynaptic terminals on MNs. These observations demonstrate that dI1 commissural neurons develop axonal projection to spinal MNs via collateral branches arising later from the post‐crossing segment of these axons. Our findings thus reveal a previously unrecognized projection of dI1 commissural axons that may contribute directly to generating proper motor output.
Use the Indirect Energy Conversion of the Phosphor Layer to Improve the Performance of Nuclear Batteries
Authors: Zhang Zhengrong , Tang Xiaobin , Liu Yunpeng , Zhou Dayong , Xu Zhiheng , Wu Min , Cao Zhangyi
Published: May 2018

The GaAs X‐ray nuclear battery without and with the phosphor layer was investigated under the irradiation of the X‐ray tube. The output power was significantly improved by introducing ZnS : Cu or (Zn,Cd)S : Cu phosphor layer, but not by ZnS : Ag phosphor layer because of the degree of spectral matching between the phosphor layer and the GaAs device. To analyze the radioluminescence (RL) effects of the phosphor layers under X‐ray excitation, we measured the RL spectra of the different phosphor layers. The RL spectra of the different phosphor layers revealed their fluorescence in the wavelength range of approximately 375–675 nm. Light at the exact wavelength can be used by the GaAs device to produce electricity. Considering irradiation damage of ZnS : Cu phosphor layer induced by X‐rays, an additional experiment was carried out to examine irradiation damage of ZnS : Cu. The results indicate that irradiation effect on the RL performance of ZnS : Cu was not obvious.
Fabrication Sandwich‐Like V2O5 Nanosheets Anchor in Graphene Towards High Energy Lithium Cathode Materials
Authors: Wu Lijun , Zhang Yu , Fan Lishuang , Zhang Qi , Wang Pengxiang , Tian Da , Zhang Naiqing , Sun Kening
Published: May 2018

The conventional cathode cannot meet the constantly increasing demand for high specific capacity in next generation cathode. V2O5 is an attractive cathode material due to its high theoretical specific capacity (294 mAh g−1) and affordable cost. Herein, we report a facile process for the fabrication of 2D sandwich‐like V2O5@Graphene nanosheets. Profiting from a synergic strategy inhibiting stacked layered structure and enhanced ion transport within interlayer, the sandwich‐like V2O5@Graphene composite exhibits exceptional high initial reversible capacity (300 mAh g−1 at the 0.5 C), excellent cyclic stability (203 mAh g−1 after 245 cycles) and high‐rate capability (165 mAh g−1 at the 10 C).
Adaptive template generation for amyloid PET using a deep learning approach
Authors: Kang Seung Kwan , Seo Seongho , Shin Seong A. , Byun Min Soo , Lee Dong Young , Kim Yu Kyeong , Lee Dong Soo , Lee Jae Sung
Published: May 2018

Accurate spatial normalization (SN) of amyloid positron emission tomography (PET) images for Alzheimer's disease assessment without coregistered anatomical magnetic resonance imaging (MRI) of the same individual is technically challenging. In this study, we applied deep neural networks to generate individually adaptive PET templates for robust and accurate SN of amyloid PET without using matched 3D MR images. Using 681 pairs of simultaneously acquired 11C‐PIB PET and T1‐weighted 3D MRI scans of AD, MCI, and cognitively normal subjects, we trained and tested two deep neural networks [convolutional auto‐encoder (CAE) and generative adversarial network (GAN)] that produce adaptive best PET templates. More specifically, the networks were trained using 685,100 pieces of augmented data generated by rotating 527 randomly selected datasets and validated using 154 datasets. The input to the supervised neural networks was the 3D PET volume in native space and the label was the spatially normalized 3D PET image using the transformation parameters obtained from MRI‐based SN. The proposed deep learning approach significantly enhanced the quantitative accuracy of MRI‐less amyloid PET assessment by reducing the SN error observed when an average amyloid PET template is used. Given an input image, the trained deep neural networks rapidly provide individually adaptive 3D PET templates without any discontinuity between the slices (in 0.02 s). As the proposed method does not require 3D MRI for the SN of PET images, it has great potential for use in routine analysis of amyloid PET images in clinical practice and research.