bluuebunny/crossref_metadata_2025 huggingface dataset:
MiR-200b in heme oxygenase-1-modified bone marrow mesenchymal stem cell-derived exosomes alleviates inflammatory injury of intestinal epithelial cells by targeting high mobility group box 3
Authors: Sun Dong , Cao Huan , Yang Liu , Lin Ling , Hou Bin , Zheng Weiping , Shen Zhongyang , Song Hongli
Published: June 2020

Heme Oxygen-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) are effective to protect and repair transplanted small bowel and intestinal epithelial cells (IECs); however, the mechanism and the role of HO-1/BMMSCs-derived exosomes is unclear. In the present study, we aimed to verify that exosomes from a HO-1/BMMSCs and IEC-6 cells (IEC-6s) co-culture system could reduce the apoptosis of IEC-6s and decrease the expression of the tight junction protein, zona occludens 1, in the inflammatory environment. Using mass spectrometry, we revealed that high mobility group box 3 (HMGB3) and phosphorylated c-Jun NH2-terminal kinase (JNK), under the influence of differentially abundant proteins identified through proteomic analysis, play critical roles in the mechanism. Further studies indicated that microRNA miR-200b, which was upregulated in exosomes derived from the co-culture of HO-1/BMMSCs and IEC-6s, exerted its role by targeting the 3′ untranslated region of Hmgb3 in this biological process. Functional experiments confirmed that miR-200b overexpression could reduce the inflammatory injury of IEC-6s, while intracellular miR-200b knockdown could significantly block the protective effect of HO-1/BMMSCs exosomes on the inflammatory injury of IEC-6s. In addition, the level of miR-200b in cells and exosomes derived from HO-1/BMMSCs stimulated by tumor necrosis factor alpha was significantly upregulated. In a rat small bowel transplantation model of allograft rejection treated with HO-1/BMMSCs, we confirmed that the level of miR-200b in the transplanted small bowel tissue was increased significantly, while the level of HMGB3/JNK was downregulated significantly. In conclusion, we identified that exosomes derived from HO-1/BMMSCs play an important role in alleviating the inflammatory injury of IECs. The mechanism is related to miR-200b targeting the abnormally increased expression of the Hmgb3 gene in IECs induced by inflammatory injury. The reduced level of HMGB3 then decreases the inflammatory injury.
The RBP1–CKAP4 axis activates oncogenic autophagy and promotes cancer progression in oral squamous cell carcinoma
Authors: Gao Ling , Wang Qibo , Ren Wenhao , Zheng Jingjing , Li Shaoming , Dou Zhichao , Kong Xinjuan , Liang Xiao , Zhi Keqian
Published: June 2020

Retinol-binding protein 1 (RBP1) is involved in several physiological functions, including the regulation of the metabolism and retinol transport. Studies have shown that it plays an important role in the pathogenesis of several types of cancer. However, the role of RBP1 and its correlation with autophagy in oral squamous cell carcinoma (OSCC) pathogenesis remain unknown. In this study, RBP1 was identified as the most significantly upregulated DEPs with a >2-fold change in OSCC samples when compared to normal tissues through iTRAQ-based proteomics analysis coupled with 2D LC–MS/MS. RBP1 overexpression was significantly associated with malignant phenotypes (differentiation, TNM stage, and lymphatic metastasis) of OSCC. In vitro experiments demonstrated that RBP1 was significantly increased in OSCC tissues and cell lines compared with control group. RBP1 overexpression promoted cell growth, migration, and invasion of OSCC cells. Silencing of RBP1 suppressed tumor formation in xenografted mice. We further demonstrated that the RBP1–CKAP4 axis was a critical regulator of the autophagic machinery in OSCC, inactivation of autophagy rescued the RBP1–CKAP4-mediated malignant biological behaviors of OSCC cells. Overall, a mechanistic link was provided by RBP1–CKAP4 between primary oncogenic features and the induction of autophagy, which may provide a potential therapeutic target that warrants further investigation for treatment of OSCC.
The lncRNA lincNMR regulates nucleotide metabolism via a YBX1 - RRM2 axis in cancer
Authors: Gandhi Minakshi , Groß Matthias , Holler Jessica M. , Coggins Si’Ana A. , Patil Nitin , Leupold Joerg H. , Munschauer Mathias , Schenone Monica , Hartigan Christina R. , Allgayer Heike , Kim Baek , Diederichs Sven
Published: June 2020

Long intergenic non-coding RNA-Nucleotide Metabolism Regulator (lincNMR) is a long non-coding RNA (lncRNA) which is induced in hepatocellular carcinoma. Its depletion invokes a proliferation defect, triggers senescence and inhibits colony formation in liver, but also breast and lung cancer cells. Triple-label SILAC proteomics profiles reveal a deregulation of key cell cycle regulators in lincNMR-depleted cells like the key dNTP synthesizing enzymes RRM2, TYMS and TK1, implicating lincNMR in regulating nucleotide metabolism. LincNMR silencing decreases dNTP levels, while exogenous dNTPs rescues the proliferation defect induced by lincNMR depletion. In vivo RNA Antisense Purification (RAP-MS) identifies YBX1 as a direct interaction partner of lincNMR which regulates RRM2, TYMS and TK1 expression and binds to their promoter regions. In a Chick Chorioallantoic Membrane (CAM) in vivo model, lincNMR-depleted tumors are significantly smaller. In summary, we discover a lincRNA, lincNMR, which regulates tumor cell proliferation through a YBX1-RRM2-TYMS-TK1 axis governing nucleotide metabolism.
A flexible and physically transient electrochemical sensor for real-time wireless nitric oxide monitoring
Authors: Li Rongfeng , Qi Hui , Ma Yuan , Deng Yuping , Liu Shengnan , Jie Yongsheng , Jing Jinzhu , He Jinlong , Zhang Xu , Wheatley Laura , Huang Congxi , Sheng Xing , Zhang Milin , Yin Lan
Published: June 2020

Real-time sensing of nitric oxide (NO) in physiological environments is critically important in monitoring neurotransmission, inflammatory responses, cardiovascular systems, etc. Conventional approaches for NO detection relying on indirect colorimetric measurement or built with rigid and permanent materials cannot provide continuous monitoring and/or require additional surgical retrieval of the implants, which comes with increased risks and hospital cost. Herein, we report a flexible, biologically degradable and wirelessly operated electrochemical sensor for real-time NO detection with a low detection limit (3.97 nmol), a wide sensing range (0.01–100 μM), and desirable anti-interference characteristics. The device successfully captures NO evolution in cultured cells and organs, with results comparable to those obtained from the standard Griess assay. Incorporated with a wireless circuit, the sensor platform achieves continuous sensing of NO levels in living mammals for several days. The work may provide essential diagnostic and therapeutic information for health assessment, treatment optimization and postsurgical monitoring.
Extreme rainfall events alter the trophic structure in bromeliad tanks across the Neotropics
Authors: Romero Gustavo Q. , Marino Nicholas A. C. , MacDonald A. Andrew M. , Céréghino Régis , Trzcinski M. Kurtis , Mercado Dimaris Acosta , Leroy Céline , Corbara Bruno , Farjalla Vinicius F. , Barberis Ignacio M. , Dézerald Olivier , Hammill Edd , Atwood Trisha B. , Piccoli Gustavo C. O. , Bautista Fabiola Ospina , Carrias Jean-François , Leal Juliana S. , Montero Guillermo , Antiqueira Pablo A. P. , Freire Rodrigo , Realpe Emilio , Amundrud Sarah L. , de Omena Paula M. , Campos Alice B. A. , Kratina Pavel , O’Gorman Eoin J. , Srivastava Diane S.
Published: June 2020

Changes in global and regional precipitation regimes are among the most pervasive components of climate change. Intensification of rainfall cycles, ranging from frequent downpours to severe droughts, could cause widespread, but largely unknown, alterations to trophic structure and ecosystem function. We conducted multi-site coordinated experiments to show how variation in the quantity and evenness of rainfall modulates trophic structure in 210 natural freshwater microcosms (tank bromeliads) across Central and South America (18°N to 29°S). The biomass of smaller organisms (detritivores) was higher under more stable hydrological conditions. Conversely, the biomass of predators was highest when rainfall was uneven, resulting in top-heavy biomass pyramids. These results illustrate how extremes of precipitation, resulting in localized droughts or flooding, can erode the base of freshwater food webs, with negative implications for the stability of trophic dynamics.
Enhancing oxidation resistance of Cu(I) by tailoring microenvironment in zeolites for efficient adsorptive desulfurization
Authors: Li Yu-Xia , Shen Jia-Xin , Peng Song-Song , Zhang Jun-Kai , Wu Jie , Liu Xiao-Qin , Sun Lin-Bing
Published: June 2020

The zeolite Cu(I)Y is promising for adsorptive removal of thiophenic sulfur compounds from transportation fuels. However, its application is seriously hindered by the instability of Cu(I), which is easily oxidized to Cu(II) even under atmospheric environment due to the coexistence of moisture and oxygen. Here, we report the adjustment of zeolite microenvironment from hydrophilic to superhydrophobic status by coating polydimethylsiloxane (yielding Cu(I)Y@P), which isolates moisture entering the pores and subsequently stabilizes Cu(I) despite the presence of oxygen. Cu(I) in Cu(I)Y@P is stable upon exposure to humid atmosphere for 6 months, while almost all Cu(I) is oxidized to Cu(II) in Cu(I)Y for only 2 weeks. The optimized Cu(I)Y@P material after moisture exposure can remove 532 μmol g−1 of thiophene and is much superior to Cu(I)Y (116 μmol g−1), regardless of similar uptakes for unexposed adsorbents. Remarkably, Cu(I)Y@P shows excellent adsorption capacity of desulfurization for water-containing model fuel.
Pores for thought: generative adversarial networks for stochastic reconstruction of 3D multi-phase electrode microstructures with periodic boundaries
Authors: Gayon-Lombardo Andrea , Mosser Lukas , Brandon Nigel P. , Cooper Samuel J.
Published: June 2020

The generation of multiphase porous electrode microstructures is a critical step in the optimisation of electrochemical energy storage devices. This work implements a deep convolutional generative adversarial network (DC-GAN) for generating realistic n-phase microstructural data. The same network architecture is successfully applied to two very different three-phase microstructures: A lithium-ion battery cathode and a solid oxide fuel cell anode. A comparison between the real and synthetic data is performed in terms of the morphological properties (volume fraction, specific surface area, triple-phase boundary) and transport properties (relative diffusivity), as well as the two-point correlation function. The results show excellent agreement between datasets and they are also visually indistinguishable. By modifying the input to the generator, we show that it is possible to generate microstructure with periodic boundaries in all three directions. This has the potential to significantly reduce the simulated volume required to be considered “representative” and therefore massively reduce the computational cost of the electrochemical simulations necessary to predict the performance of a particular microstructure during optimisation.
Effect of Ion Irradiation Introduced by Focused Ion-Beam Milling on the Mechanical Behaviour of Sub-Micron-Sized Samples
Authors: Liu Jinqiao , Niu Ranming , Gu Ji , Cabral Matthew , Song Min , Liao Xiaozhou
Published: June 2020

The development of xenon plasma focused ion-beam (Xe+ PFIB) milling technique enables site-specific sample preparation with milling rates several times larger than the conventional gallium focused ion-beam (Ga+ FIB) technique. As such, the effect of higher beam currents and the heavier ions utilized in the Xe+ PFIB system is of particular importance when investigating material properties. To investigate potential artifacts resulting from these new parameters, a comparative study is performed on transmission electron microscopy (TEM) samples prepared via Xe+ PFIB and Ga+ FIB systems. Utilizing samples prepared with each system, the mechanical properties of CrMnFeCoNi high-entropy alloy (HEA) samples are evaluated with in situ tensile straining TEM studies. The results show that HEA samples prepared by Xe+ PFIB present better ductility but lower strength than those prepared by Ga+ FIB. This is due to the small ion-irradiated volumes and the insignificant alloying effect brought by Xe irradiation. Overall, these results demonstrate that Xe+ PFIB systems allow for a more efficient material removal rate while imparting less damage to HEAs than conventional Ga+ FIB systems.
Parallel validation of a green-solvent extraction method and quantitative estimation of multi-mycotoxins in staple cereals using LC-MS/MS
Authors: Gbashi Sefater , Njobeh Patrick Berka , Madala Ntakadzeni Edwin , De Boevre Marthe , Kagot Victor , De Saeger Sarah
Published: June 2020

In this study, 15 different mycotoxins were estimated in three staple cereals from selected agro-ecological regions in Nigeria using a ‘novel’ green extraction method, pressurized hot water extraction (PHWE) in comparison to a conventional solvent extraction method. Discrimination of the results of PHWE and solvent extraction using principal component analysis (PCA) and orthogonal projection to latent structures discriminate analysis (OPLS-DA) did not yield any differential clustering patterns. All maize samples (n = 16), 32% (n = 38) of sorghum and 35% (n = 37) of millet samples were positive for at least one of the 15 tested mycotoxins. Contamination levels for the cereals were higher in the warm humid rain forest region and gradually decreased towards the hot and arid region in the north of the country. The results demonstrate the applicability of PHWE as a possible alternative extraction method to conventional methods of extraction, which are solvent based.
Predictability modulates neurocognitive semantic processing of non-verbal narratives
Authors: Coderre Emily L. , O’Donnell Elizabeth , O’Rourke Emme , Cohn Neil
Published: June 2020

Predictability is known to modulate semantic processing in language, but it is unclear to what extent this applies for other modalities. Here we ask whether similar cognitive processes are at play in predicting upcoming events in a non-verbal visual narrative. Typically developing adults viewed comics sequences in which a target panel was highly predictable (“high cloze”), less predictable (“low cloze”), or incongruent with the preceding narrative context (“anomalous”) during EEG recording. High and low predictable sequences were determined by a pretest where participants assessed “what happened next?”, resulting in cloze probability scores for sequence outcomes comparable to those used to measure predictability in sentence processing. Through both factorial and correlational analyses, we show a significant modulation of neural responses by cloze such that N400 effects are diminished as a target panel in a comic sequence becomes more predictable. Predictability thus appears to play a similar role in non-verbal comprehension of sequential images as in language comprehension, providing further evidence for the domain generality of semantic processing in the brain.
Fixed-Point Fluid structure interaction analysis BASED ON geometrically exact approach
Authors: Yu Mingliang , Nie Xueyuan , Yang Guowei , Zhong Peinan
Published: June 2020

The fluid structure interaction analysis for structures exhibiting large deformations is carried out by using a strong coupling method, in which a fixed point method with Aitken’s dynamic relaxation is employed to accelerate convergence of the coupling iteration, and geometrically exact beam approach initiated by Simo is adopted to simulate the nonlinear flexible beam models. An improved implicit time integration algorithm is given to improve the computation accuracy of structural dynamics. To verify the validity of the fixed-point method in the compressible flows which is usually used in incompressible fluid, it is applied for flutter analysis of AGARD 445.6 wing in the transonic regime. The case of flow-induced vibration of a flexible beam demonstrates that the approach based on geometrically exact beam theory is suitable for the fluid structure interaction analysis and the fixed-point method with Aitken’s relaxation is of great efficiency and robustness in the FSI computation.
Neuroprotective effects of low-dose G-CSF plus meloxicam in a rat model of anterior ischemic optic neuropathy
Authors: Liu Pei-Kang , Wen Yao-Tseng , Lin Wei , Kapupara Kishan , Tai Minghong , Tsai Rong-Kung
Published: June 2020

Non-arteritic anterior ischemic optic neuropathy (NAION) causes a sudden loss of vision and lacks effective treatment. Granulocyte colony-stimulating factor (G-CSF) provides neuroprotection against the experimental optic nerve injuries but also induce leukocytosis upon typical administration. We found synergetic neuroprotective effects of meloxicam and low dose G-CSF without leukocytosis in a rat model of anterior ischemic optic neuropathy (rAION). The WBC counts in the low-dose G-CSF-plus meloxicam-treated group were similar to the sham-operated group. Combination treatment of low-dose G-CSF plus meloxicam preserved RGCs survival and visual function, reduced RGC apoptosis and the macrophages infiltration, and promote more M2 phenotype of macrophage/microglial transition than the low-dose GCSF treatment or the meloxicam treatment. Moreover, the combination treatment induced higher serine/threonine kinase 1 (Akt1) expression. The combination treatment of low-dose G-CSF plus meloxicam lessened the leukocytotic side effect and provided neuroprotective effects via Akt1 activation in the rAION model. This approach provides crucial preclinical information for the development of alternative therapy in AION.
Plant virus particles with various shapes as potential adjuvants
Authors: Evtushenko Ekaterina A. , Ryabchevskaya Ekaterina M. , Nikitin Nikolai A. , Atabekov Joseph G. , Karpova Olga V.
Published: June 2020

Plant viruses are biologically safe for mammals and can be successfully used as a carrier/platform to present foreign epitopes in the course of creating novel putative vaccines. However, there is mounting evidence that plant viruses, their virus-like and structurally modified particles may also have an immunopotentiating effect on antigens not bound with their surface covalently. Here, we present data on the adjuvant properties of plant viruses with various shapes (Tobacco mosaic virus, TMV; Potato virus X, PVX; Cauliflower mosaic virus, CaMV; Bean mild mosaic virus, BMMV) and structurally modified TMV spherical particles (SPs). We have analysed the effectiveness of immune response to individual model antigens (ovalbumin, OVA/hen egg lysozyme, HEL) and to OVA/HEL in compositions with plant viruses/SPs, and have shown that CaMV, TMV and SPs can effectively induce total IgG titers to model antigen. Some intriguing data were obtained when analysing the immune response to the plant viruses/SPs themselves. Strong immunity was induced to CaMV, BMMV and PVX, whereas TMV and SPs stimulated considerably lower self-IgG titers. Our results provide new insights into the immunopotentiating properties of plant viruses and can be useful in devising adjuvants based on plant viruses.
Iron stored in ferritin is chemically reduced in the presence of aggregating Aβ(1-42)
Authors: Everett James , Brooks Jake , Lermyte Frederik , O’Connor Peter B. , Sadler Peter J. , Dobson Jon , Collingwood Joanna F. , Telling Neil D.
Published: June 2020

Atypical low-oxidation-state iron phases in Alzheimer’s disease (AD) pathology are implicated in disease pathogenesis, as they may promote elevated redox activity and convey toxicity. However, the origin of low-oxidation-state iron and the pathways responsible for its formation and evolution remain unresolved. Here we investigate the interaction of the AD peptide β-amyloid (Aβ) with the iron storage protein ferritin, to establish whether interactions between these two species are a potential source of low-oxidation-state iron in AD. Using X-ray spectromicroscopy and electron microscopy we found that the co-aggregation of Aβ and ferritin resulted in the conversion of ferritin’s inert ferric core into more reactive low-oxidation-states. Such findings strongly implicate Aβ in the altered iron handling and increased oxidative stress observed in AD pathogenesis. These amyloid-associated iron phases have biomarker potential to assist with disease diagnosis and staging, and may act as targets for therapies designed to lower oxidative stress in AD tissue.
Enhanced Pitch Discrimination for Cochlear Implant Users with a New Haptic Neuroprosthetic
Authors: Fletcher Mark D. , Thini Nour , Perry Samuel W.
Published: June 2020

The cochlear implant (CI) is the most widely used neuroprosthesis, recovering hearing for more than half a million severely-to-profoundly hearing-impaired people. However, CIs still have significant limitations, with users having severely impaired pitch perception. Pitch is critical to speech understanding (particularly in noise), to separating different sounds in complex acoustic environments, and to music enjoyment. In recent decades, researchers have attempted to overcome shortcomings in CIs by improving implant technology and surgical techniques, but with limited success. In the current study, we take a new approach of providing missing pitch information through haptic stimulation on the forearm, using our new mosaicOne_B device. The mosaicOne_B extracts pitch information in real-time and presents it via 12 motors that are arranged in ascending pitch along the forearm, with each motor representing a different pitch. In normal-hearing subjects listening to CI simulated audio, we showed that participants were able to discriminate pitch differences at a similar performance level to that achieved by normal-hearing listeners. Furthermore, the device was shown to be highly robust to background noise. This enhanced pitch discrimination has the potential to significantly improve music perception, speech recognition, and speech prosody perception in CI users.
Activation of SIRT6 by DNA hypomethylating agents and clinical consequences on combination therapy in leukemia
Authors: Carraway Hetty E. , Malkaram Sridhar A. , Cen Yana , Shatnawi Aymen , Fan Jun , Ali Hamdy E. A. , Abd Elmageed Zakaria Y. , Buttolph Thomm , Denvir James , Primerano Donald A. , Fandy Tamer E.
Published: June 2020

The FDA-approved DNA hypomethylating agents (DHAs) like 5-azacytidine (5AC) and decitabine (DAC) demonstrate efficacy in the treatment of hematologic malignancies. Despite previous reports that showed histone acetylation changes upon using these agents, the exact mechanism underpinning these changes is unknown. In this study, we investigated the relative potency of the nucleoside analogs and non-nucleoside analogs DHAs on DNA methylation reversal using DNA pyrosequencing. Additionally, we screened their effect on the enzymatic activity of the histone deacetylase sirtuin family (SIRT1, SIRT2, SIRT3, SIRT5 and SIRT6) using both recombinant enzymes and nuclear lysates from leukemia cells. The nucleoside analogs (DAC, 5AC and zebularine) were the most potent DHAs and increased the enzymatic activity of SIRT6 without showing any significant increase in other sirtuin isoforms. ChIP-Seq analysis of bone marrow cells derived from six acute myeloid leukemia (AML) patients and treated with the nucleoside analog DAC induced genome-wide acetylation changes in H3K9, the physiological substrate for SIRT6. Data pooling from the six patients showed significant acetylation changes in 187 gene loci at different chromosomal regions including promoters, coding exons, introns and distal intergenic regions. Signaling pathway analysis showed that H3K9 acetylation changes are linked to AML-relevant signaling pathways like EGF/EGFR and Wnt/Hedgehog/Notch. To our knowledge, this is the first report to identify the nucleoside analogs DHAs as activators of SIRT6. Our findings provide a rationale against the combination of the nucleoside analogs DHAs with SIRT6 inhibitors or chemotherapeutic agents in AML due to the role of SIRT6 in maintaining genome integrity and DNA repair.
A machine learning-based prognostic predictor for stage III colon cancer
Authors: Jiang Dan , Liao Junhua , Duan Haihan , Wu Qingbin , Owen Gemma , Shu Chang , Chen Liangyin , He Yanjun , Wu Ziqian , He Du , Zhang Wenyan , Wang Ziqiang
Published: June 2020

Limited biomarkers have been identified as prognostic predictors for stage III colon cancer. To combat this shortfall, we developed a computer-aided approach which combing convolutional neural network with machine classifier to predict the prognosis of stage III colon cancer from routinely haematoxylin and eosin (H&E) stained tissue slides. We trained the model by using 101 cancers from West China Hospital (WCH). The predictive effectivity of the model was validated by using 67 cancers from WCH and 47 cancers from The Cancer Genome Atlas Colon Adenocarcinoma database. The selected model (Gradient Boosting-Colon) provided a hazard ratio (HR) for high- vs. low-risk recurrence of 8.976 (95% confidence interval (CI), 2.824–28.528; P, 0.000), and 10.273 (95% CI, 2.177–48.472; P, 0.003) in the two test groups, from the multivariate Cox proportional hazards analysis. It gave a HR value of 10.687(95% CI, 2.908–39.272; P, 0.001) and 5.033 (95% CI,1.792–14.132; P, 0.002) for the poor vs. good prognosis groups. Gradient Boosting-Colon is an independent machine prognostic predictor which allows stratification of stage III colon cancer into high- and low-risk recurrence groups, and poor and good prognosis groups directly from the H&E tissue slides. Our findings could provide crucial information to aid treatment planning during stage III colon cancer.
Growth Factor Midkine Aggravates Pulmonary Arterial Hypertension via Surface Nucleolin
Authors: Kinoshita Daisuke , Shishido Tetsuro , Takahashi Tetsuya , Yokoyama Miyuki , Sugai Takayuki , Watanabe Ken , Tamura Harutoshi , Nishiyama Satoshi , Takahashi Hiroki , Arimoto Takanori , Miyamoto Takuya , Watanabe Tetsu , Kishida Satoshi , Kadomatsu Kenji , Abe Jun-ichi , Takeishi Yasuchika , Konta Tsuneo , Kubota Isao , Watanabe Masafumi
Published: June 2020

Pulmonary arterial hypertension (PAH) is a progressive fatal disease caused by pulmonary arterial remodeling. Midkine regulates cell proliferation and migration, and it is induced by hypoxia, but its roles in pulmonary arterial remodeling remain unclear. Serum midkine levels were significantly increased in PAH patients compared with control patients. Midkine expression was increased in lungs and sera of hypoxia-induced PAH mice. Hypoxia-induced pulmonary arterial remodeling and right ventricular hypertrophy were attenuated in midkine-knockout mice. Midkine-induced proliferation and migration of pulmonary arterial smooth muscle cells (PASMC) and epidermal growth factor receptor (EGFR) signaling were significantly increased under hypoxia, which also induced cell-surface translocation of nucleolin. Nucleolin siRNA treatment suppressed midkine-induced EGFR activation in vitro, and nucleolin inhibitor AS1411 suppressed proliferation and migration of PASMC induced by midkine. Furthermore, AS1411 significantly prevented the development of PAH in Sugen hypoxia rat model. Midkine plays a crucial role in PAH development through interaction with surface nucleolin. These data define a role for midkine in PAH development and suggest midkine-nucleolin-EGFR axis as a novel therapeutic target for PAH.
Enhanced spinal neuronal responses as a mechanism for increased number and size of active acupoints in visceral hyperalgesia
Authors: Fan Yu , Ryu Yeonhee , Zhao Rongjie , Bills Kyle B. , Steffensen Scott C. , Yang Chae Ha , Kim Hee Young
Published: June 2020

Acupuncture has been used to treat a variety of illness and involves the insertion and manipulation of needles into specific points on the body (termed “acupoints”). It has been suggested that acupoints are not merely discrete, static points, but can be dynamically changed according to the pathological state of internal organs. We investigated in a rat model of mustard oil (MO)-induced visceral hyperalgesia whether the number and size of acupoints were modified according to the severity of the colonic pain, and whether the changes were associated with enhanced activity of the spinal dorsal horn. In MO-treated rats, acupoints showing neurogenic inflammation (termed “neurogenic spots” or Neuro-Sps) were found both bilaterally and unilaterally on the leg. The number and size of these acupoints increased along with increasing doses of MO. Electroacupuncture of the acupoints generated analgesic effects on MO-induced visceral hypersensitivity. The MO-treated rats showed an increase in c-Fos expression in spinal dorsal horn neurons and displayed increased evoked activity and a prolonged after-discharge in spinal wide dynamic response (WDR) neurons in response to colorectal distension. Increased number and size of neurogenic inflammatory acupoints following MO treatment were reduced by inhibiting AMPA and NMDA receptors in the spinal cord. Our findings suggest that acupoints demonstrate increased number and size along with severity of visceral pain, which may be associated with enhanced neuronal responses in spinal dorsal horn neurons.
Retinal Oxygen Delivery, Metabolism, and Extraction Fraction during Long-Term Bilateral Common Carotid Artery Occlusion in Rats
Authors: Leahy Sophie , Farzad Shayan , Blair Norman P. , Shahidi Mahnaz
Published: June 2020

Retinal functional, biochemical, and anatomical changes have been previously reported in long-term experimental permanent bilateral common carotid artery occlusion (BCCAO). The purpose of the current study was to investigate progressive reductions in retinal oxygen metabolism (MO2) due to inadequate compensation by oxygen delivery (DO2) and extraction fraction (OEF) after BCCAO. Twenty-nine rats were subjected to BCCAO and were imaged after 3 hours, 3 days, 7 days, or 14 days. Six rats underwent a sham procedure. Phosphorescence lifetime and blood flow imaging were performed in both eyes to measure retinal oxygen contents and total retinal blood flow, respectively. DO2, MO2, and OEF were calculated from these measurements. Compared to the sham group, DO2 and MO2 were reduced after all BCCAO durations. OEF was increased after 3 hours and 3 days of BCCAO, but was not different from the sham group after 7 and 14 days. Between 3 and 7 days of BCCAO, DO2 increased, OEF decreased, and there was no significant difference in MO2. These findings may be useful to understand the pathophysiology of retinal ischemia.
Impact of chronic HCV treatment on quality of life of patients with metabolic disorders in context of immunological disturbances
Authors: Kierepa Agata , Witkowska Aleksandra , Kaczmarek Mariusz , Książek Krzysztof , Mikuła-Pietrasik Justyna , Żeromski Jan , Kowala-Piaskowska Arleta , Mozer-Lisewska Iwona
Published: June 2020

Chronic viral hepatitis C (CHC) and its complications have a negative effect on patient’s quality of life. We evaluated the impact of a successful interferon-free treatment on the quality of life of patients with obesity and metabolic disorders in the context of immunological disturbances. Twenty overweight or obese (BMI > 25) patients with CHC were tested before the therapy and after a successful treatment regimen. After the therapy, patient’s emotional well-being improved (p = 0.02), while physical well-being remained unchanged. There was a decrease of patient’s liver fibrosis and an increase of steatosis along with body mass. Among HCV-infected individuals, the expression of toll-like receptor 3 (TLR3) on lymphocytes was higher than in the control group (p = 0.03), but it decreased (p = 0.001) after the treatment. There was also a decrease of the intensity of immunofluorescence of FoxP3+ after the treatment (p = 0.04). Our study showed an improvement in mental aspects of patient’s quality of life after the treatment. Unfortunately, probably due to rapid immunological changes, patient’s BMI, serum cholesterol levels and hepatic steatosis have a tendency to increase and may lead to cardiovascular and other complications, like hepatocellular carcinoma.
A theoretical investigation on reciprocity-inspired wide-angle spectrally-selective THz absorbers augmented by anisotropic metamaterials
Authors: Mohammadi Mansoureh , Rajabalipanah Hamid , Abdolali Ali
Published: June 2020

In this paper, a theoretical framework relying on the reciprocity theorem is proposed to accurately design a spectrally-selective THz superstrate-loaded metamaterial absorber (SLMA) exhibiting wide-angle feature. By leveraging high-order Floquet harmonics in a generalized transmission line model characterizing the conventional metamaterial absorbers (MAs), it is demonstrated that MAs suffer from impedance mismatch, especially at near grazing angles. From an impedance matching viewpoint, this major challenge is tackled in this paper via two different designs, exploiting a magneto-electric anisotropic Huygens' metamaterial and a multilayer dielectric structure at a certain distance over the MA plane. The numerical results corroborate well the theoretical predictions, elucidating that the proposed SLMA significantly broadens the angular performance of the MA up to near grazing angles (about 80°), where high absorptivity is still achieved in both principal planes. The deteriorating effect of diffraction modes has been comprehensively analyzed. In comparison to the previous wide-angle MA reports based on intricate particle geometries and brute-force optimizations, the proposed design features a straightforward semi-analytical algorithm, which can also be re-developed for microwave, mid-infrared, and optical frequency bands and for any type of MA element. The proposed SLMA would be very promising for various wavelength-selective applications such as sensors and imaging.
Increased both PD–L1 and PD–L2 expressions on monocytes of patients with hepatocellular carcinoma was associated with a poor prognosis
Authors: Yasuoka Hidetaka , Asai Akira , Ohama Hideko , Tsuchimoto Yusuke , Fukunishi Shinya , Higuchi Kazuhide
Published: June 2020

Anti-programmed cell death-1 (PD-1) antibodies has been approved to treat HCC. Some PD-1 ligands (PD–L1 and PD–L2) negative tumors respond to treatment of anti-PD-1 antibodies, and this fact may be caused by the expression of PD-1 ligands on non-tumor cells. PD–L1 was recently found to be expressed on CD14+ cells from cancer patients. We investigate PD-1 ligands expression on CD14+ cells of patients with HCC and the role of CD14+ cells in an antitumor response. In this study, 87 patients diagnosed with HCC were enrolled. CD14+ cells from patients with HCC expressed PD–L1 (4.5–95.5%) and PD–L2 (0.2–95.0%). According to cut-off values, we classified patients as those either with PD–L1+PD–L2+CD14+ cells or other types of CD14+ cells. The overall survival of patients with PD–L1+PD–L2+CD14+ cells was shorter than that of patients with other types of CD14+ cells (p = 0.0023). PD–L1+PD–L2+CD14+ cells produced IL-10 and CCL1, and showed little tumoricidal activity against HepG2 cells. The tumoricidal activity of CD8+ cells from patients with PD–L1+PD–L2+CD14+ cells were suppressed by co-cultivation with CD14+ cells from the syngeneic patient. Furthermore, anti-PD-1 antibody restored their tumoricidal activity of CD8+ cells. In conclusion, some patients with HCC have PD–L1+PD–L2+CD14+ cells that suppress their antitumor response. These inhibitory functions of CD14+ cells may be associated with a poor prognosis in these patients.
Author Correction: The potential of neurofilaments analysis using dry-blood and plasma spots
Authors: Lombardi Vittoria , Carassiti Daniele , Giovannoni Gavin , Lu Ching-Hua , Adiutori Rocco , Malaspina Andrea
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Mechanical cell disruption of mustard bran suspensions for improved dispersion properties and protein release
Authors: Donsì Francesco , Velikov Krassimir P.
Published: June 2020

Mechanical cell disruption via high-pressure homogenization enables enhanced proteins recovery from yellow mustard bran aqueous suspensions, and contributes to improving their appearance and texture.
Single-chain nanoparticles: opportunities provided by internal and external confinement
Authors: Verde-Sesto Ester , Arbe Arantxa , Moreno Angel J. , Cangialosi Daniele , Alegría Angel , Colmenero Juan , Pomposo José A.
Published: June 2020

This review summarizes the opportunities offered by internal and external confinement of single-chain nanoparticles (SCNPs) in catalysts, drug delivery, sensing, and other emerging potential applications.
Why synthetic virus-like nanoparticles can achieve higher cellular uptake efficiency?
Authors: Li Jiawei , Wang Junfeng , Yao Qiang , Li Tao , Yan Youguo , Li Zhen , Zhang Jun
Published: June 2020

The disruption effect of spikes leads to the superior penetrability of virus-like nanoparticles during the translocation process.
Studies on surface modification of polypropylene composite bipolar plates using an electroless deposition technique
Authors: Yeetsorn Rungsima , Ouajai Walaiporn Prissanaroon , Onyu Kannika
Published: June 2020

The DMFC is predominantly noticeable because it can convert chemical energy directly into electrical energy with higher energy conversion efficiency (∼65%) compared to the efficiency of traditional combustion engines (40%) and with lower emissions.
Transport of nano zerovalent iron (nZVI) coupling with Alcaligenes sp. strain in porous media
Authors: Xia Qing , Huo Mingzhu , Hao Peitong , Zheng Junhao , An Yi
Published: June 2020

Coupling nano zerovalent iron (nZVI) particles with anaerobic bacteria experienced significantly higher transport and lower sedimentation rates than stand-alone nZVI.
Direct hybridization gap from intersite and onsite electronic interactions in CeAg2Ge2
Authors: Banik Soma , Arya A. , Sinha A. K.
Published: June 2020

Electronic and crystal structure studies are presented to describe the role of intersite and onsite interactions for the itinerant electron magnetism in CeAg2Ge2.Magnetovolume effect and hybridization gap opening have been observed at low temperature.
Disulfide based prodrugs for cancer therapy
Authors: Wang Qiang , Guan Jiankun , Wan Jiangling , Li Zifu
Published: June 2020

This review summarizes the progress in disulfide linker technology to balance extracellular stability and intracellular cleavage for optimized disulfide-containing prodrugs.
Retracted Article: Metal-free [2+2+1] cycloaddition polymerization of alkynes, nitriles, and oxygen atoms to functional polyoxazoles
Authors: Dong Lichao , Lan Tian , Liang Yin , Guo Shifeng , Zhang Hao
Published: June 2020

The metal-free [2+2+1] cycloaddition polymerization of alkynes, nitriles, and O-atoms for the regioselective assembly of highly substituted oxazole compounds has been achieved by the use of iodosobenzene (PhIO) with trifluoromethanesulfonic acid (TfOH).
Luminescent chitosan/carbon dots as an effective nano-drug carrier for neurodegenerative diseases
Authors: Mathew Sheril Ann , Praveena P. , Dhanavel S. , Manikandan R. , Senthilkumar S. , Stephen A.
Published: June 2020

Facile preparation of carbon dots and a chitosan nanocomposite embedded with carbon dots to encapsulate dopamine and ensure biocompatibility and bioavailability.
Optimizing the optical and biological properties of 6-(1H-benzimidazole)-2-naphthalenol as a fluorescent probe for the detection of thiophenols: a theoretical study
Authors: Krawczyk Przemysław
Published: June 2020

The study presents the influence of structure modulation by introduction of selected donor and acceptor substituents on the properties of 6-(1H-bezimidazole)-2(2,4-dinitrobenzenesulfonate)naphthalene used in thiophenol identification.
Squirmer rods as elongated microswimmers: flow fields and confinement
Authors: Zantop Arne W. , Stark Holger
Published: June 2020

We characterize simulated flow fields of active squirmer rods in bulk and Hele-Shaw geometry using hydrodynamic multipole expansions.
Bi-functional peptide-based 3D hydrogel-scaffolds
Authors: Diaferia Carlo , Netti Francesca , Ghosh Moumita , Sibillano Teresa , Giannini Cinzia , Morelli Giancarlo , Adler-Abramovich Lihi , Accardo Antonella
Published: June 2020

Over the last few years, hydrogels have been proposed for many biomedical applications, including drug delivery systems and scaffolds for tissue engineering.
Substitutional doping of hybrid organic–inorganic perovskite crystals for thermoelectrics
Authors: Tang Weidong , Zhang Jinshuai , Ratnasingham Sinclair , Liscio Fabiola , Chen Kan , Liu Tianjun , Wan Kening , Galindez Eugenio Suena , Bilotti Emiliano , Reece Mike , Baxendale Mark , Milita Silvia , McLachlan Martyn A. , Su Lei , Fenwick Oliver
Published: June 2020

This work highlights routes towards controlled substitutional doping of halide perovskites on the B-site to optimise their thermoelectric properties.
An intermeshing electron transporting layer for efficient and stable CsPbI2Br perovskite solar cells with open circuit voltage over 1.3 V
Authors: Liu Shuo , Chen Weijie , Shen Yunxiu , Wang Shuhui , Zhang Moyao , Li Yaowen , Li Yongfang
Published: June 2020

An intermeshing SnO2ETL is designed and introduced into CsPbI2Br-based inorganic pero-SCs, leading to improved PCE accompanied by reducedEloss.
Origin of the abnormal reduction of the dielectric response for ReCOB crystals and its mechanism: theoretical and experimental exploration
Authors: Lu Xinyu , Li Lili , Tian Shiwei , Li Yanlu , Yu Fapeng , Cheng Xiufeng , Zhao Xian
Published: June 2020

The significant influence of ionic displacement polarization on distinct reduction in dielectric permittivity for LaCOB has been confirmed.
Perovskite nanogels: synthesis, properties, and applications
Authors: Wang Hui , Luo Qing , Sun Mei-Li , Yin Xiong , Wang Leyu
Published: June 2020

Recent advances and outlook in the synthesis, properties, and applications of perovskite nanogels have been summarized in this article.
Organic materials as a passivation layer for metal oxide semiconductors
Authors: Ho Dongil , Jeong Hyewon , Choi Sunwoo , Kim Choongik
Published: June 2020

This highlight reviews the recent studies on organic passivation for the stability enhancement of oxide thin-film transistors.
The relationship between neutrophil–lymphocyte ratio and in-stent restenosis in superficial femoral artery
Authors: Yang Yaobo , Ge Fangfang , Shen Jing , Song Jianbo , Xie Jiapei , Qu Jiangshuai , Mao Xinzu , Kuang Zhaocheng , Wang Xiang , Wu Yejun , Wang Shenghai , Xiao Liang
Published: June 2020

The present study aimed to investigate the relationship between an increase in the pre- and post-operative neutrophil–lymphocyte ratio (NLR) and superficial femoral artery in-stent restenosis (ISR) rate. We recruited 199 patients that underwent superficial femoral artery stenting for lower extremity arteriosclerosis obliterans at our hospital from March 2015 to July 2018. Patients were divided into two groups according to the occurrence of ISR within 1 year (group 1, ISR and group 2, Non-ISR). The after NLR (NLRafter) and NLR change ratio (NLRratio) (P<0.001) were significantly higher in group 1. A NLRafter > 4.3 was associated with an odds ratio of 1.946 (95% CI [1.51–2.50]; P<0.001) for the presence of ISR. A NLRratio > 37.5% was associated with an odds ratio of 3.6 (95% CI [2.03–6.36]; P<0.001) for occurrence of ISR. A NLRafter level > 4.3 had 75% sensitivity and 76% specificity for the prediction of ISR, as identified by the ROC curve. A NLRratio level > 37.5% predicted ISR with 77% sensitivity and 60% specificity. Multivariate logistic regression analysis demonstrated that NLRratio was the strongest independent predictor of ISR (P<0.001). In conclusions, NLRratio could be used as a prognostic marker in superficial femoral artery stents.
Partner-Specific Communication Deficits in Individuals With Alzheimer's Disease
Authors: Paek Eun Jin , Yoon Si On
Published: June 2020

Purpose

Speakers adjust referential expressions to the listeners' knowledge while communicating, a phenomenon called “audience design.” While individuals with Alzheimer's disease (AD) show difficulties in discourse production, it is unclear whether they exhibit preserved partner-specific audience design. The current study examined if individuals with AD demonstrate partner-specific audience design skills.

Method

Ten adults with mild-to-moderate AD and 12 healthy older adults performed a referential communication task with two experimenters (E1 and E2). At first, E1 and participants completed an image-sorting task, allowing them to establish shared labels. Then, during testing, both experimenters were present in the room, and participants described images to either E1 or E2 (randomly alternating). Analyses focused on the number of words participants used to describe each image and whether they reused shared labels.

Results

During testing, participants in both groups produced shorter descriptions when describing familiar images versus new images, demonstrating their ability to learn novel knowledge. When they described familiar images, healthy older adults modified their expressions depending on the current partner's knowledge, producing shorter expressions and more established labels for the knowledgeable partner (E1) versus the naïve partner (E2), but individuals with AD were less likely to do so.

Conclusions

The current study revealed that both individuals with AD and the control participants were able to acquire novel knowledge, but individuals with AD tended not to flexibly adjust expressions depending on the partner's knowledge state. Conversational inefficiency and difficulties observed in AD may, in part, stem from disrupted audience design skills.
The Efficacy of Collaborative Referencing Intervention in Chronic Aphasia: A Mixed-Methods Study
Authors: Devanga Suma R. , Sherrill Martha , Hengst Julie A.
Published: June 2020

Purpose

The feasibility of a collaborative referencing intervention (CRI) for adults with chronic aphasia has been documented in two descriptive case studies (Devanga, 2014; Hengst et al., 2010, 2008). The current Phase II mixed-methods treatment study replicates the CRI with four additional participants (using interpretive research) and investigates how it impacts a traditional measure, participants' confrontational naming abilities, outside of game play (using multiple-probe single-case experimental design).

Method

Four adults with chronic aphasia participated in the study composed of (a) three preparatory sessions, (b) five baseline sessions, (c) 15 CRI sessions with five treatment probes, and (d) six maintenance sessions. A collaborative confrontation naming (CCN) probe (i.e., dependent variable) was administered in each baseline, treatment probe, and maintenance session. Each CRI session (i.e., independent variable) consisted of a photo-matching game with participant and clinician partner taking alternative turns identifying and matching personally relevant treatment cards. CCN probes were scored using a multidimensional rating scale. Fidelity and social validity were also assessed.

Results

Replication of the CRI showed successful and consistent referential learning in all four participant pairs. The multiple-probe analysis of CCN revealed a positive treatment effect on naming in three participants indicating that the CRI was efficacious. High fidelity was maintained throughout the study. Social validity interviews revealed positive outcomes and significant impacts of treatment on the participants' lives.

Conclusion

The CRI demonstrates strong clinical implications for adults with chronic aphasia. Future research exploring the treatment effectiveness and the implementation to a variety of clinical settings is warranted.