bluuebunny/crossref_metadata_2025 huggingface dataset:
Decelerated epigenetic aging associated with mood stabilizers in the blood of patients with bipolar disorder
Authors: Okazaki Satoshi , Numata Shusuke , Otsuka Ikuo , Horai Tadasu , Kinoshita Makoto , Sora Ichiro , Ohmori Tetsuro , Hishimoto Akitoyo
Published: May 2020

There is high mortality among patients with bipolar disorder (BD). Studies have reported accelerated biological aging in patients with BD. Recently, Horvath and Hannum et al. independently developed DNA methylation (DNAm) profiles as “epigenetic clocks,” which are the most accurate biological age estimate. This led to the development of two accomplished measures of epigenetic age acceleration (EAA) using blood samples, namely, intrinsic and extrinsic EAA (IEAA and EEAA, respectively). IEAA, which is based on Horvath’s clock, is independent of blood cell counts and indicates cell-intrinsic aging. On the other hand, EEAA, which is based on Hannum’s clock, is associated with age-dependent changes in blood cell counts and indicates immune system aging. Further, Lu et al. developed the “GrimAge” clock, which can strongly predict the mortality risk, and DNAm-based telomere length (DNAmTL). We used a DNAm dataset from whole blood samples obtained from 30 patients with BD and 30 healthy controls. We investigated Horvath EAA, IEAA, Hannum EAA, EEAA, Grim EAA, DNAmTL, and DNAm-based blood cell composition. Compared with controls, there was a decrease in Horvath EAA and IEAA in patients with BD. Further, there was a significant decrease in Horvath EAA and IEAA in patients with BD taking medication combinations of mood stabilizers (including lithium carbonate, sodium valproate, and carbamazepine) than in those taking no medication/monotherapy. This study provides novel evidence indicating decelerated epigenetic aging associated with mood stabilizers in patients with BD.
Survival benefit of tamoxifen in male breast cancer: prospective cohort analysis
Authors: Eggemann Holm , Brucker Cosima , Schrauder Michael , Thill Marc , Flock Felix , Reinisch Mattea , Costa Serban-Dan , Ignatov Atanas
Published: May 2020

Background

Due to the lack of prospective data, current treatment of male breast cancer (MBC) is based on information obtained from retrospective analysis or by extrapolation from studies on female patients. In this prospectively enrolled cohort study, we retrospectively examined the survival effect of tamoxifen in MBC patients.

Methods

In this prospectively enrolled cohort study, 448 patients with MBC were treated between May 2009 and June 2018. The primary endpoint was disease-free survival (DFS).

Results

Between May 2009 and June 2018, 448 men with breast cancer were identified, with a median age at diagnosis of 69 years (range 27–96 years). The median follow-up was 39 months (range 3–89 months). Most tumours were larger than 20 mm; invasive ductal carcinoma was of no special histological type and with an intermediate grade of differentiation. Almost half of the men were diagnosed with positive axillary lymph nodes (43.5%). Hormone receptor (HR) positivity was observed in 98.4% of the patients. Notably, DFS among men who did not receive tamoxifen was significantly reduced as compared with those who underwent tamoxifen therapy (P = 0.002). The recurrence rate and mortality in the group of patients without and with tamoxifen treatment were 18.2% and 11.2%, respectively. The most common localisation of metastases was the bone. After adjustment for prognostic factors, we found that tamoxifen was found to reduce the recurrence rate by 68% (hazard ratio HR = 0.32; 95% confidence interval, CI: 0.14–0.74).

Conclusions

Tamoxifen treatment was associated with improved DFS for MBC patients.

Clinical trial registration

DRKS00009536.
LncRNA CANT1 suppresses retinoblastoma progression by repellinghistone methyltransferase in PI3Kγ promoter
Authors: Ni Hongyan , Chai Peiwei , Yu Jie , Xing Yue , Wang Shaoyun , Fan Jiayan , Ge Shengfang , Wang Yefei , Jia Renbing , Fan Xianqun
Published: May 2020

Retinoblastoma (RB) is the most common malignant intraocular tumor of childhood. Recent studies have shown that long noncoding RNAs (lncRNAs), which are longer than 200 bp and without protein-coding ability, are key regulators of tumorigenesis. However, the role of lncRNAs in retinoblastoma remains to be elucidated. In this study, we found that the expression of lncRNA CASC15-New-Transcript 1 (CANT1) was significantly downregulated in RB. Notably, overexpression of CANT1 significantly inhibited RB growth both in vitro and in vivo. Furthermore, lncRNA CANT1, which was mainly located in the nucleus, occupied the promoter of phosphoinositide 3-kinase gamma (PI3Kγ) and blocked histone methyltransferase hSET1 from binding to the PI3Kγ promoter, thus abolishing hSET1-mediated histone H3K4 trimethylation of the PI3Kγ promoter and inhibiting PI3Kγ expression. Furthermore, we found that silencing PI3Kγ either by lncRNA CANT1 overexpression or by PI3Kγ siRNA, reduced the activity of PI3K/Akt signaling and suppressed RB tumorigenesis. In summary, lncRNA CANT1 acts as a suppressor of RB progression by blocking gene-specific histone methyltransferase recruitment. These findings outline a new CANT1 modulation mechanism and provide an alternative option for the RB treatment.
The circular RNA FAM169A functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR-583 and BTRC
Authors: Guo Wei , Mu Kun , Zhang Bin , Sun Chao , Zhao Ling , Dong Zhan-Yin , Cui Qing
Published: May 2020

Intervertebral disc degeneration (IDD) is an important factor leading to low back pain, although the underlying mechanisms remain poorly understood. In this study we examined the role of circular RNA FAM169A (circ-FAM169A) in degenerative nucleus pulposus (NP) tissues, and validated its function in cultured human NP cells. Overexpression of circ-FAM169A in NP cells markedly enhanced extracellular matrix (ECM) catabolism and suppressed ECM anabolism in NP cells. Furthermore, circ-FAM169A sequestered miR-583, which could potentially upregulate BTRC, an inducer of the NF-κB signaling pathway. In conclusion, the present study revealed that circ-FAM169A promotes IDD development via miR-583/BTRC signaling. These findings provide a potential therapeutic option for the treatment of IDD.
IL-33-induced neutrophil extracellular traps degrade fibronectin in a murine model of bronchopulmonary dysplasia
Authors: Jin Rui , Xu Junjie , Gao Qianqian , Mao Xiaonan , Yin Jiao , Lu Keyu , Guo Yan , Zhang Mingshun , Cheng Rui
Published: May 2020

Bronchopulmonary dysplasia (BPD) is the leading cause of chronic lung disease in preterm neonates. Extracellular matrix (ECM) abnormalities reshape lung development, contributing to BPD progression. In the present study, we first discovered that the ECM component fibronectin was reduced in the pulmonary tissues of model mice with BPD induced by lipopolysaccharide (LPS) and hyper-oxygen. Meanwhile, interleukin-33 (IL-33) and other inflammatory cytokines were elevated in BPD lung tissues. LPS stimulated the production of IL-33 in alveolar epithelial cells via myeloid differentiation factor 88 (MyD88), protein 38 (p38), and nuclear factor-kappa B (NF-κB) protein 65 (p65). Following the knockout of either IL-33 or its receptor suppression of tumorigenicity 2 (ST2) in mice, BPD disease severity was improved, accompanied by elevated fibronectin. ST2 neutralization antibody also relieved BPD progression and restored the expression of fibronectin. IL-33 induced the formation of neutrophil extracellular traps (NETs), which degraded fibronectin in alveolar epithelial cells. Moreover, DNase-mediated degradation of NETs was protective against BPD. Finally, a fibronectin inhibitor directly decreased fibronectin and caused BPD-like disease in the mouse model. Our findings may shed light on the roles of IL-33-induced NETs and reduced fibronectin in the pathogenesis of BPD.
Deubiquitinase USP47-stabilized splicing factor IK regulates the splicing of ATM pre-mRNA
Authors: Ka Hye In , Lee Sunyi , Han Sora , Jeong Ae Lee , Park Ji Young , Joo Hyun Jeong , Soh Su Jung , Park Doyeon , Yang Young
Published: May 2020

IK depletion leads to an aberrant mitotic entry because of chromosomal misalignment through the enhancement of Aurora B activity at the interphase. Here, we demonstrate that IK, a spliceosomal component, plays a crucial role in the proper splicing of the ATM pre-mRNA among other genes related with the DNA Damage Response (DDR). Intron 1 in the ATM pre-mRNA, having lengths <200 bp, was not spliced in the IK-depleted cells and led to a deficiency of the ATM protein. Subsequently, the IK depletion-induced ATM protein deficiency impaired the ability to repair the damaged DNA. Because the absence of SMU1 results in IK degradation, the mechanism underlying IK degradation was exploited. IK was ubiquitinated in the absence of SMU1 and then subjected to proteolysis through the 26S proteasome. To prevent the proteolytic degradation of IK, a deubiquitinating enzyme, USP47, directly interacted with IK and stabilized it through deubiquitination. Collectively, our results suggest that IK is required for proper splicing of the ATM pre-mRNA and USP47 contributes toward the stabilization of IK.
Immune cell profiling of COVID-19 patients in the recovery stage
by single-cell sequencing
Authors: Wen Wen , Su Wenru , Tang Hao , Le Wenqing , Zhang Xiaopeng , Zheng Yingfeng , Liu Xiuxing , Xie Lihui , Li Jianmin , Ye Jinguo , Dong Liwei , Cui Xiuliang , Miao Yushan , Wang Depeng , Dong Jiantao , Xiao Chuanle , Chen Wei , Wang Hongyang
Published: May 2020

COVID-19, caused by SARS-CoV-2, has recently affected over 1,200,000
people and killed more than 60,000. The key immune cell subsets change and their
states during the course of COVID-19 remain unclear. We sought to comprehensively
characterize the transcriptional changes in peripheral blood mononuclear cells
during the recovery stage of COVID-19 by single-cell RNA sequencing technique. It
was found that T cells decreased remarkably, whereas monocytes increased in patients
in the early recovery stage (ERS) of COVID-19. There was an increased ratio of
classical CD14++ monocytes with high inflammatory gene
expression as well as a greater abundance of
CD14++IL1β+ monocytes in
the ERS. CD4+ T cells and CD8+
T cells decreased significantly and expressed high levels of inflammatory genes in
the ERS. Among the B cells, the plasma cells increased remarkably, whereas the naïve
B cells decreased. Several novel B cell-receptor (BCR) changes were identified, such
as IGHV3-23 and IGHV3-7, and isotypes (IGHV3-15, IGHV3-30, and IGKV3-11) previously
used for virus vaccine development were confirmed. The strongest pairing
frequencies, IGHV3-23-IGHJ4, indicated a monoclonal state associated with SARS-CoV-2
specificity, which had not been reported yet. Furthermore, integrated analysis
predicted that IL-1β and M-CSF may be novel candidate target genes for inflammatory
storm and that TNFSF13, IL-18, IL-2, and IL-4 may be beneficial for the recovery of
COVID-19 patients. Our study provides the first evidence of an inflammatory immune
signature in the ERS, suggesting COVID-19 patients are still vulnerable after
hospital discharge. Identification of novel BCR signaling may lead to the
development of vaccines and antibodies for the treatment of COVID-19.
Transcriptional and epigenetic basis of Treg cell development and function: its genetic anomalies or variations in autoimmune diseases
Authors: Ohkura Naganari , Sakaguchi Shimon
Published: May 2020

Naturally arising regulatory CD4+T (Treg) cells, which specifically express the transcription factor FoxP3 in the nucleus and CD25 and CTLA-4 on the cell surface, are a T-cell subpopulation specialized for immune suppression, playing a key role in maintaining immunological self-tolerance and homeostasis. FoxP3 is required for Treg function, especially for its suppressive activity. However, FoxP3 expression per se is not necessary for Treg cell lineage commitment in the thymus and insufficient for full Treg-type gene expression in mature Treg cells. It is Treg-specific epigenetic changes such as CpG demethylation and histone modification that can confer a stable and heritable pattern of Treg type gene expression on developing Treg cells in a FoxP3-independent manner. Anomalies in the formation of Treg-specific epigenome, in particular, Treg-specific super-enhancers, which largely include Treg-specific DNA demethylated regions, are indeed able to cause autoimmune diseases in rodents. Furthermore, in humans, single nucleotide polymorphisms in Treg-specific DNA demethylated regions associated with Treg signature genes, such asIL2RA (CD25)andCTLA4, can affect the development and function of naïve Treg cells rather than effector T cells. Such genetic variations are therefore causative of polygenic common autoimmune diseases including type 1 diabetes and rheumatoid arthritis via affecting endogenous natural Treg cells. These findings on the transcription factor network with FoxP3 at a key position as well as Treg-specific epigenetic landscape facilitate our understanding of Treg cell development and function, and can be exploited to prepare functionally stable FoxP3-expressing Treg cells from antigen-specific conventional T cells to treat autoimmune diseases.
TRAF3IP3 negatively regulates cytosolic RNA induced anti-viral signaling by promoting TBK1 K48 ubiquitination
Authors: Deng Meng , Tam Jason W. , Wang Lufei , Liang Kaixin , Li Sirui , Zhang Lu , Guo Haitao , Luo Xiaobo , Zhang Yang , Petrucelli Alex , Davis Beckley K. , Conti Brian J. , June Brickey W. , Ko Ching-Chang , Lei Yu L. , Sun Shaocong , Ting Jenny P. -Y.
Published: May 2020

Innate immunity to nucleic acids forms the backbone for anti-viral immunity and several inflammatory diseases. Upon sensing cytosolic viral RNA, retinoic acid-inducible gene-I-like receptors (RLRs) interact with the mitochondrial antiviral signaling protein (MAVS) and activate TANK-binding kinase 1 (TBK1) to induce type I interferon (IFN-I). TRAF3-interacting protein 3 (TRAF3IP3, T3JAM) is essential for T and B cell development. It is also well-expressed by myeloid cells, where its role is unknown. Here we report that TRAF3IP3 suppresses cytosolic poly(I:C), 5’ppp-dsRNA, and vesicular stomatitis virus (VSV) triggers IFN-I expression in overexpression systems and Traf3ip3−/− primary myeloid cells. The mechanism of action is through the interaction of TRAF3IP3 with endogenous TRAF3 and TBK1. This leads to the degradative K48 ubiquitination of TBK1 via its K372 residue in a DTX4-dependent fashion. Mice with myeloid-specific gene deletion of Traf3ip3 have increased RNA virus-triggered IFN-I production and reduced susceptibility to virus. These results identify a function of TRAF3IP3 in the regulation of the host response to cytosolic viral RNA in myeloid cells.
A microsporidian impairs Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes
Authors: Herren Jeremy K. , Mbaisi Lilian , Mararo Enock , Makhulu Edward E. , Mobegi Victor A. , Butungi Hellen , Mancini Maria Vittoria , Oundo Joseph W. , Teal Evan T. , Pinaud Silvain , Lawniczak Mara K. N. , Jabara Jordan , Nattoh Godfrey , Sinkins Steven P.
Published: May 2020

A possible malaria control approach involves the dissemination in mosquitoes of inherited symbiotic microbes to block Plasmodium transmission. However, in the Anopheles gambiae complex, the primary African vectors of malaria, there are limited reports of inherited symbionts that impair transmission. We show that a vertically transmitted microsporidian symbiont (Microsporidia MB) in the An. gambiae complex can impair Plasmodium transmission. Microsporidia MB is present at moderate prevalence in geographically dispersed populations of An. arabiensis in Kenya, localized to the mosquito midgut and ovaries, and is not associated with significant reductions in adult host fecundity or survival. Field-collected Microsporidia MB infected An. arabiensis tested negative for P. falciparum gametocytes and, on experimental infection with P. falciparum, sporozoites aren’t detected in Microsporidia MB infected mosquitoes. As a microbe that impairs Plasmodium transmission that is non-virulent and vertically transmitted, Microsporidia MB could be investigated as a strategy to limit malaria transmission.
Non-vector-borne transmission of lumpy skin disease virus
Authors: Aleksandr Kononov , Olga Byadovskaya , David Wallace B. , Pavel Prutnikov , Yana Pestova , Svetlana Kononova , Alexander Nesterov , Vladimir Rusaleev , Dmitriy Lozovoy , Alexander Sprygin
Published: May 2020

The transmission of “lumpy skin disease virus” (LSDV) has prompted intensive research efforts due to the rapid spread and high impact of the disease in recent years, especially in Eastern Europe and Balkan countries. In this study, we experimentally evaluate the vaccine-derived virulent recombinant LSDV strain (Saratov/2017) and provide solid evidence on the capacity of the virus for transmission in a vector-proof environment. In the 60-day long experiment, we used inoculated bulls (IN group) and two groups of in-contact animals (C1 and C2), with the former (C1) being in contact with the inoculated animals at the onset of the trial and the latter (C2) being introduced at day 33 of the experiment. The infection in both groups of contact animals was confirmed clinically, serologically and virologically, and viremia was demonstrated in blood, nasal and ocular excretions, using molecular tools. Further studies into LSDV biology are a priority to gain insights into whether the hypothesized indirect contact mode evidenced in this study is a de novo-created feature, absent from both parental stains of the novel (recombinant) LSDV isolate used, or whether it was dormant, but then unlocked by the process of genetic recombination. Author summary: In global terms, LSD has been termed a “neglected disease” due to its historic natural occurrence of being restricted to Africa and, occasionally, Israel. However, after its slow spread throughout the Middle East, the disease is now experiencing a resurgence of research interest following a recent and rapid spread into more northern latitudes. Given the dearth of solid findings on potential transmission mechanisms, no efficient or reliable control program currently exists, which does not involve the use of live attenuated vaccines or stamping out policies – both of which are controversial for implementation in non-endemic regions or countries. The vector-borne mode is the only working concept currently available, but with scarce evidence to support the aggressive spread northwards – except for human-assisted spread, including legal or illegal animal transportation. The emergence of outbreaks is not consistently linked to weather conditions, with the potential for new outbreaks to occur and spread rapidly. Here, for the first time, we provide evidence for indirect contact-mode transmission for a naturally-occurring recombinant LSDV isolated from the field. In an insect-proof facility, we obtained solid evidence that the novel LSDV strain can pass to in-contact animals. Given the recombinant nature of the virus utilised, its genetic background relating to the observed transmission pattern within the study needs to be delineated.
Transcriptomic profiles reveal differences in zinc metabolism, inflammation, and tight junction proteins in duodenum from cholesterol gallstone subjects
Authors: Riveras Eleodoro , Azocar Lorena , Moyano Tomas C. , Ocares Marcia , Molina Hector , Romero Diego , Roa Juan C. , Valbuena Jose R. , Gutiérrez Rodrigo A. , Miquel Juan F.
Published: May 2020

Cholesterol Gallstone Disease (GSD) is a common multifactorial disorder characterized by crystallization and aggregation of biliary cholesterol in the gallbladder. The global prevalence of GSD is ~10–20% in the adult population but rises to 28% in Chile (17% among men and 30% among women). The small intestine may play a role in GSD pathogenesis, but the molecular mechanisms have not been clarified. Our aim was to identify the role of the small intestine in GSD pathogenesis. Duodenal biopsy samples were obtained from patients with GSD and healthy volunteers. GSD status was defined by abdominal ultrasonography. We performed a transcriptome study in a discovery cohort using Illumina HiSeq. 2500, and qPCR, immunohistochemistry and immunofluorescence were used to validate differentially expressed genes among additional case-control cohorts. 548 differentially expressed genes between GSD and control subjects were identified. Enriched biological processes related to cellular response to zinc, and immune and antimicrobial responses were observed in GSD patients. We validated lower transcript levels of metallothionein, NPC1L1 and tight junction genes and higher transcript levels of genes involved in immune and antimicrobial pathways in GSD patients. Interestingly, serum zinc and phytosterol to cholesterol precursor ratios were lower in GSD patients. A significant association was observed between serum zinc and phytosterol levels. Our results support a model where proximal small intestine plays a key role in GSD pathogenesis. Zinc supplementation, modulation of proximal microbiota and/or intestinal barrier may be novel targets for strategies to prevent GSD.
Clinical Performance of Flash Glucose Monitoring System in Patients with Liver Cirrhosis and Diabetes Mellitus
Authors: Costa Dalila , Lourenço Joana , Monteiro Ana Margarida , Castro Beatriz , Oliveira Patricia , Tinoco Maria Carmo , Fernandes Vera , Marques Olinda , Gonçalves Raquel , Rolanda Carla
Published: May 2020

Flash glucose monitoring system (FGMS) is an improved subset of continuous glucose monitoring with a recognized effectiveness on glycemic control, though validation in patients with Liver Cirrhosis (LC) is lacking. To evaluate the accuracy of FGMS in patients with Type 2 Diabetes Mellitus (DM) and LC, a prospective, case-control study was performed in 61 ambulatory patients with LC and DM (LC group, n = 31) or DM (Control group, n = 30). During 14 days, patients performed 4 assessments per day of self-monitoring of blood glucose (SMBG, reference value) followed by FGMS scanning. There were 2567 paired SMBG and FGMS values used in the accuracy analysis, with an overall mean absolute relative difference (MARD) of 12.68% in the LC group and 10.55% in the control group (p < 0,001). In patients with LC, the percentage of readings within Consensus Consensus Error Grid analysis Zone A and A + B were 80.36% and 99,26%, respectively. Sensor clinical accuracy was not affected by factors such as body mass index, age, gender, Child-Pugh score or edematoascitic decompensation. This is the first study to approach FGMS clinical accuracy in LC, revealing a potential usability of this system to monitor glycemic control in this population.
A promising and cost-effective biochar adsorbent derived from jujube pit for the removal of Pb(II) from aqueous solution
Authors: Gao Junkai , Liu Yu , Li Xuebin , Yang Mouyuan , Wang Jinbao , Chen Yan
Published: May 2020

This study evaluated the Pb(II) sorption capacity of jujube pit biochar (JPB) in aqueous solution, which was derived from jujube pit by pyrolysis and used as a promising and economical adsorbent. More importantly, the utilization of JPB could realize the recycling of agricultural residues. The JPB was characterized using conventional science technologies, including SEM, BET and FT-IR, and the sorption capacity of JPB for lead ions was investigated according to different adsorption parameters, such as the kinetics data, solution pH, isotherms data, coexisting ions of Na+ and K+, desorption and reusability, and solution temperature. The results of kinetics data suggested that the lead ion adsorption process by JPB could be fast to reach equilibrium within 30 min. Additionally, the adsorption capacity of JPB for Pb(II) was calculated to be maximum for 137.1 mg/g at pH 6.0. More importantly, after five cycles of desorption and reuse, the JPB still reached 70% of its original adsorption capacity. All the results suggested that JPB had a broad application prospect for the purification of lead ions in practical.
Cell viscoelasticity is linked to fluctuations in cell biomass distributions
Authors: Nguyen Thang L. , Polanco Edward R. , Patananan Alexander N. , Zangle Thomas A. , Teitell Michael A.
Published: May 2020

The viscoelastic properties of mammalian cells can vary with biological state, such as during the epithelial-to-mesenchymal (EMT) transition in cancer, and therefore may serve as a useful physical biomarker. To characterize stiffness, conventional techniques use cell contact or invasive probes and as a result are low throughput, labor intensive, and limited by probe placement. Here, we show that measurements of biomass fluctuations in cells using quantitative phase imaging (QPI) provides a probe-free, contact-free method for quantifying changes in cell viscoelasticity. In particular, QPI measurements reveal a characteristic underdamped response of changes in cell biomass distributions versus time. The effective stiffness and viscosity values extracted from these oscillations in cell biomass distributions correlate with effective cell stiffness and viscosity measured by atomic force microscopy (AFM). This result is consistent for multiple cell lines with varying degrees of cytoskeleton disruption and during the EMT. Overall, our study demonstrates that QPI can reproducibly quantify cell viscoelasticity.
Al-, Ga-, Mg-, or Li-doped zinc oxide nanoparticles as electron transport layers for quantum dot light-emitting diodes
Authors: Alexandrov Alexei , Zvaigzne Mariya , Lypenko Dmitri , Nabiev Igor , Samokhvalov Pavel
Published: May 2020

Colloidal quantum dots and other semiconductor nanocrystals are essential components of next-generation lighting and display devices. Due to their easily tunable and narrow emission band and near-unity fluorescence quantum yield, they allow cost-efficient fabrication of bright, pure-color and wide-gamut light emitting diodes (LEDs) and displays. A critical improvement in the quantum dot LED (QLED) technology was achieved when zinc oxide nanoparticles (NPs) were first introduced as an electron transport layer (ETL) material, which tremendously enhanced the device brightness and current efficiency due to the high mobility of electrons in ZnO and favorable alignment of its energy bands. During the next decade, the strategy of ZnO NP doping allowed the fabrication of QLEDs with a brightness of about 200 000 cd/m2and current efficiency over 60 cd/A. On the other hand, the known ZnO doping approaches rely on a very fine tuning of the energy levels of the ZnO NP conduction band minimum; hence, selection of the appropriate dopant that would ensure the best device characteristics is often ambiguous. Here we address this problem via detailed comparison of QLEDs whose ETLs are formed by a set of ZnO NPs doped with Al, Ga, Mg, or Li. Although magnesium-doped ZnO NPs are the most common ETL material used in recently designed QLEDs, our experiments have shown that their aluminum-doped counterparts ensure better device performance in terms of brightness, current efficiency and turn-on voltage. These findings allow us to suggest ZnO NPs doped with Al as the best ETL material to be used in future QLEDs.
MicroRNA Profiling of Highly Enriched Human Corneal Epithelial Stem Cells by Small RNA Sequencing
Authors: Kalaimani Lavanya , Devarajan Bharanidharan , Subramanian Umadevi , Ayyasamy Vanniarajan , Namperumalsamy Venkatesh Prajna , Veerappan Muthukkaruppan , Chidambaranathan Gowri Priya
Published: May 2020

The objective of the study was to elucidate the microRNA (miRNA) profile of an enriched human corneal epithelial stem cell (CESC) population in comparison to differentiated central corneal epithelial cells (CCECs) by small RNA sequencing. The CESCs were enriched by differential enzymatic treatment to isolate the basal limbal epithelial cells followed by laser capture microdissection of cells with nucleus to cytoplasm ratio ≥0.7, from donor tissues. Small RNA sequencing was carried out using Illumina NextSeq. 500 platform and the validation of differentially expressed miRNAs by quantitative real-time PCR (qPCR) and locked nucleic acid miRNA in-situ hybridization (LNA-ISH). The sequencing identified 62 miRNAs in CESCs and 611 in CCECs. Six miRNAs: hsa-miR-21-5p, 3168, 143-3p, 10a-5p, 150-5p and 1910-5p were found to be significantly upregulated in enriched CESCs, which was further confirmed by qPCR and LNA-ISH. The expression of hsa-miR-143-3p was exclusive to clusters of limbal basal epithelial cells. The targets of the upregulated miRNAs were predicted to be associated with signaling pathways -Wnt, PI3K-AKT, MAPK and pathways that regulate pluripotency of stem cells, cell migration, growth and proliferation. Further studies are essential to elucidate their functional role in maintenance of stemness. The findings of the study also hypothesize the inherent potential of hsa-miR-143-3p to serve as a biomarker for identifying CESCs.
Region-specific effects of Scrapper on the abundance of glutamate and gamma-aminobutyric acid in the mouse brain
Authors: Eto Fumihiro , Sato Shumpei , Setou Mitsutoshi , Yao Ikuko
Published: May 2020

The brain consists of various areas with anatomical features. Neurons communicate with one another via excitatory or inhibitory synaptic transmission. Altered abundance of neurotransmitters, including glutamate and gamma-aminobutyric acid (GABA), in specific brain regions is closely involved in severe neurological diseases, such as schizophrenia and obsessive-compulsive disorder. SCRAPPER, a ubiquitin E3 ligase, regulates synaptic transmission. Scrapper gene deficiency results in defective neurotransmission due to excessive secretion of neurotransmitters. The present study employed matrix-assisted laser desorption/ionization imaging mass spectrometry to analyze the abundance of amino acid neurotransmitters in Scrapper knockout (SCR-KO) mice. SCR-KO mice exhibited significantly increased glutamate levels in the isocortex (CTX), corpus callosum (CC), thalamus (TH), midbrain (MB), cerebellar cortex (CBX), and caudoputamen (CP) and increased GABA levels in the CTX, CC, TH, MB, CBX and hypothalamus (HY) compared with wild-type mice. These findings indicate that Scrapper deficiency leads to upregulated glutamate and GABA levels in multiple regions. Our results show a differential, region-specific effect of Scrapper on the abundance of glutamate and GABA.
Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion
Authors: Frausto Ricardo F. , Swamy Vinay S. , Peh Gary S. L. , Boere Payton M. , Hanser E. Maryam , Chung Doug. D. , George Benjamin L. , Morselli Marco , Kao Liyo , Azimov Rustam , Wu Jessica , Pellegrini Matteo , Kurtz Ira , Mehta Jodhbir S. , Aldave Anthony J.
Published: May 2020

The advent of cell culture-based methods for the establishment and expansion of human corneal endothelial cells (CEnC) has provided a source of transplantable corneal endothelium, with a significant potential to challenge the one donor-one recipient paradigm. However, concerns over cell identity remain, and a comprehensive characterization of the cultured CEnC across serial passages has not been performed. To this end, we compared two established CEnC culture methods by assessing the transcriptomic changes that occur during in vitro expansion. In confluent monolayers, low mitogenic culture conditions preserved corneal endothelial cell state identity better than culture in high mitogenic conditions. Expansion by continuous passaging induced replicative cell senescence. Transcriptomic analysis of the senescent phenotype identified a cell senescence signature distinct for CEnC. We identified activation of both classic and new cell signaling pathways that may be targeted to prevent senescence, a significant barrier to realizing the potential clinical utility of in vitro expansion.
Side chain effect in the modulation of αvβ3/α5β1 integrin activity via clickable isoxazoline-RGD-mimetics: development of molecular delivery systems
Authors: Ferrazzano Lucia , Corbisiero Dario , Potenza Eleonora , Baiula Monica , Dattoli Samantha Deianira , Spampinato Santi , Belvisi Laura , Civera Monica , Tolomelli Alessandra
Published: May 2020

Construction of small molecule ligand (SML) based delivery systems has been performed starting from a polyfunctionalized isoxazoline scaffold, whose αvβ3 and α5β1 integrins’ potency has been already established. The synthesis of this novel class of ligands was obtained by conjugation of linkers to the heterocyclic core via Huisgen-click reaction, with the aim to use them as “shuttles” for selective delivery of diagnostic agents to cancer cells, exploring the effects of the side chains in the interaction with the target. Compounds 17b and 24 showed excellent potency towards α5β1 integrin acting as selective antagonist and agonist respectively. Further investigations confirmed their effects on target receptor through the analysis of fibronectin-induced ERK1/2 phosphorylation. In addition, confocal microscopy analysis allowed us to follow the fate of EGFP conjugated α5β1 integrin and 17b FITC-conjugated (compound 31) inside the cells. Moreover, the stability in water solution at different values of pH and in bovine serum confirmed the possible exploitation of these peptidomimetic molecules for pharmaceutical application.
IFN-γ and IgG responses to Mycobacterium tuberculosis latency antigen Rv2626c differentiate remote from recent tuberculosis infection
Authors: Amiano Nicolás O. , Morelli María P. , Pellegrini Joaquín M. , Tateosian Nancy L. , Rolandelli Agustín , Seery Vanesa , Castello Florencia A. , Gallego Claudio , Armitano Rita , Stupka Juan , Erschen María A. , Ciallella Lorena M. , de Casado Graciela C. , Cusmano Liliana , Palmero Domingo J. , Iovanna Juan L. , García Verónica E.
Published: May 2020

Tuberculin skin test (TST) and IFN-γ release assays are currently used to detect Mycobacterium tuberculosis (Mtb) infection but none of them differentiate active from latent infection (LTBI). Since improved tests to diagnose Mtb infection are required, we studied the immune response to Mtb latency antigen Rv2626c in individuals exposed to the bacteria during different periods. Tuberculosis patients (TB), TB close contacts (CC: subjects exposed to Mtb for less than three months) and healthcare workers (HW: individuals exposed to Mtb at least two years) were recruited and QuantiFERON (QFT) assay, TST and IFN-γ secretion to Rv2626c were analyzed. Twenty-two percent of the individuals assessed had discordant results between QFT and TST tests. Furthermore, QFT negative and QFT positive individuals produced differential levels of IFN-γ against Rv2626c, in direct association with their exposure period to Mtb. Actually, 91% of CC QFT negative subjects secreted low levels of IFN-γ to Rv2626c, whereas 43% of HW QFT negative people produced elevated IFN-γ amounts against Rv2626c. Conversely, 69% of CC QFT positive subjects didn´t produce IFN-γ to Rv2626c. Interestingly, a similar pattern of IgG anti-Rv2626c plasma levels was observed. Therefore, determination of IFN-γ and IgG levels against the dormancy antigen Rv2626c allows to identify established LTBI.
pH-Dependent Antibacterial Activity of Glycolic Acid: Implications for Anti-Acne Formulations
Authors: Valle-González Elba R. , Jackman Joshua A. , Yoon Bo Kyeong , Mokrzecka Natalia , Cho Nam-Joon
Published: May 2020

Glycolic acid is the smallest alpha hydroxy acid and widely used for skincare applications, including to treat acne vulgaris. Oftentimes, high concentrations of glycolic acid (~20–50 vol%) are incorporated into chemical peels to reduce acne-related inflammation while there is an outstanding need to determine to what extent glycolic acid can potently inhibit Cutibacterium acnes (formerly known as Propionibacterium acnes), which is a Gram-positive bacterium implicated in acne pathogenesis. Herein, we report that glycolic acid exhibits pH-dependent antibacterial activity against C. acnes and mechanistic studies identified that the nonionic form of glycolic acid is more active than the anionic form. The degree of antibacterial activity, including minimum bactericidal concentration (MBC), of glycolic acid was evaluated in the pH range of 3 to 4.5, and the greatest potency was observed at pH 3. In light of skincare formulation needs, we selected the pH 3.5 condition for further testing and determined that glycolic acid kills C. acnes cells by disrupting bacterial cell membranes. While most conventional treatments involve high concentrations of glycolic acid (>20%), our findings support the potential of developing anti-acne formulations with glycolic acid concentrations as low as 0.2% and with pH conditions that are suitable for over-the-counter applications.
A digital embrace to blunt the curve of COVID19 pandemic
Authors: Schwamm Lee H. , Erskine Alistair , Licurse Adam
Published: May 2020

Digital health, virtual care, telehealth, and telemedicine are all terms often used interchangeably to refer to the practice of care delivered from a distance. Because virtual care collapses the barriers of time and distance, it is ideal for providing care that is patient-centered, lower cost, more convenient and at greater productivity. All these factors make virtual care tools indispensable elements in the COVID19 response. In this perspective, we offer implementation guidance and policy insights relevant to the use of virtual care tools to meet the challenges of the COVID19 pandemic.
Paternal restraint stress affects offspring metabolism via ATF-2 dependent mechanisms in Drosophila melanogaster germ cells
Authors: Seong Ki-Hyeon , Ly Nhung Hong , Katou Yuki , Yokota Naoko , Nakato Ryuichiro , Murakami Shinnosuke , Hirayama Akiyoshi , Fukuda Shinji , Kang Siu , Soga Tomoyoshi , Shirahige Katsuhiko , Ishii Shunsuke
Published: May 2020

Paternal environmental factors can epigenetically influence gene expressions in offspring. We demonstrate that restraint stress, an experimental model for strong psychological stress, to fathers affects the epigenome, transcriptome, and metabolome of offspring in a MEKK1-dATF2 pathway-dependent manner in Drosophila melanogaster. Genes involved in amino acid metabolism are upregulated by paternal restraint stress, while genes involved in glycolysis and the tricarboxylic acid (TCA) cycle are downregulated. The effects of paternal restraint stress are also confirmed by metabolome analysis. dATF-2 is highly expressed in testicular germ cells, and restraint stress also induces p38 activation in the testes. Restraint stress induces Unpaired 3 (Upd3), a Drosophila homolog of Interleukin 6 (IL-6). Moreover, paternal overexpression of upd3 in somatic cells disrupts heterochromatin in offspring but not in offspring from dATF-2 mutant fathers. These results indicate that paternal restraint stress affects metabolism in offspring via inheritance of dATF-2-dependent epigenetic changes.
Coalescence of isotropic droplets in overheated free standing smectic films
Authors: Pikina Elena S. , Ostrovskii Boris I. , Pikin Sergey A.
Published: May 2020

A theoretical study of the interaction and coalescence of isotropic droplets in overheated free-standing smectic films (FSSF) is presented.
Electrochemical determination of paracetamol in a pharmaceutical dose by adsorptive voltammetry with a carbon paste/La2O3microcomposite
Authors: Nagles Edgar , Ceroni Mario , Hurtado-Murillo John J. , Hurtado John J.
Published: May 2020

This paper presents a new application for microcomposites based on carbon paste (CP) and La2O3(LaOX).
Synthesis of Co2−xNixO2 (0 < x < 1.0) hexagonal nanostructures as efficient bifunctional electrocatalysts for overall water splitting
Authors: Li Haoquan , Chen Long , Jin Pengfei , Lv Heng , Fu Haihai , Fan Changchun , Peng Shanglong , Wang Gang , Hou Juan , Yu Feng , Shi Yulin
Published: May 2020

Mesoporous Co1.4Ni0.6O2 hexagonal nanoparticles prepared by a simple coprecipitation method followed by a calcination process under Ar atmosphere have excellent overall water splitting performance at 0.1 mg cm−2 trace loading.
4,4′-Difluorobenzhydryl-modified bis(imino)-pyridyliron(ii) chlorides as thermally stable precatalysts for strictly linear polyethylenes with narrow dispersities
Authors: Zhang Qiuyue , Zhang Randi , Han Mingyang , Yang Wenhong , Liang Tongling , Sun Wen-Hua
Published: May 2020

Extremely highly active and thermal-stable bis(imino)pyridine-iron precatalysts appended with (p-FPh)2CH groups were achieved in ethylene polymerization for highly linear polyethylenes with narrow distributions.
A review: crystal growth for high-performance all-inorganic perovskite solar cells
Authors: Chen Weijie , Li Xinqi , Li Yaowen , Li Yongfang
Published: May 2020

The key factors for high-quality all-inorganic perovskite crystal growth.
Physicochemical and antibacterial properties of fabricated ovalbumin–carvacrol gel nanoparticles
Authors: Rao Sheng-qi , Xu Guang-wei , Zeng Hua-wei , Zheng Xiang-feng , Hu Qin , Wang Qing-yan , Yang Zhen-quan , Jiao Xin-an
Published: May 2020

The applications of carvacrol are limited due to its poor stability, water solubility and high volatility. Herein we fabricated ovalbumin–carvacrol gel nanoparticles and then improved solubility, stability and antibacterial property of carvacrol.
Connecting molecular mechanisms of biofilm formation and functional biomaterials
Authors: Lum Samuel B. , Osgood Robert
Published: May 2020

Biofilms are arguably the root cause of most human infections, imposing a high level of public health concern. Exploring the molecular pathogenesis on material interfaces is essential to improving future medical devices.
A poly(3,4-propylenedioxythiophene)/carbon micro-sphere-bismuth nanoflake composite and multifunctional Co-doped graphene for a benchmark photo-supercapacitor
Authors: Das Aparajita , Ojha Manoranjan , Subramanyam Palyam , Deepa Melepurath
Published: May 2020

Efficient storage of sunlight in the form of charge is accomplished by designing and implementing a photo-supercapacitor (PSC) with a novel, cost-effective architecture.
Small mode volume plasmonic film-coupled nanostar resonators
Authors: Charchi Negar , Li Ying , Huber Margaret , Kwizera Elyahb Allie , Huang Xiaohua , Argyropoulos Christos , Hoang Thang
Published: May 2020

Individual plasmonic film-coupled nanostar resonators exhibit polarized optical modes in ultrasmall volumes, which can be useful for applications in sensing or enhanced light-matter interactions.
Injectable DNA-architected nanoraspberry depot-mediated on-demand programmable refilling and release drug delivery
Authors: Hsu Ru-Siou , Fang Jen-Hung , Shen Wei-Ting , Sheu Yu-Chen , Su Cheng-Kuan , Chiang Wen-Hsuan , Hu Shang-Hsiu
Published: May 2020

An injectable DNA-architected nanoraspberry depot (DNR-depot) served as a Dox sponge-like refilling reservoir and magnetothermal converter for refilling, and the magnetothermal heating was induced by the disassembly of DNA for Dox release.
Pollen-derived porous carbon decorated with cobalt/iron sulfide hybrids as cathode catalysts for flexible all-solid-state rechargeable Zn–air batteries
Authors: Fang Weiguang , Bai Zhiman , Yu Xinxin , Zhang Wen , Wu Mingzai
Published: May 2020

A 2D coplanar flexible Zn–air battery based on the pollen-derived cathode bifunctional catalyst (Co–Fe–S@NSRPC) displays competitive battery performance, bending mechanical property and integrability.
Rhodium-catalyzed ortho-acrylation of aryl ketone O-methyl oximes with cyclopropenones
Authors: Liu Yafeng , Tian Yuan , Su Kexin , Guo Xin , Chen Baohua
Published: May 2020

We have developed a rhodium-catalyzed ortho-C–H acrylation of O-methyl ketoximes with cyclopropenones leading to the formation of chalcone derivatives.
Preparation of cage-shaped hexakis(spiroborate)s
Authors: Danjo Hiroshi , Masuda Yuhki , Kidena Yuki , Kawahata Masatoshi , Ohara Kazuaki , Yamaguchi Kentaro
Published: May 2020

Direct construction of anionic hexakis(spiroborate) prismatic cages was realized by the reaction of hexahydroxytriphenylene, bis(dihydroxynaphthalene)s, and boric acid.
Triblock polyester thermoplastic elastomers with semi-aromatic polymer end blocks by ring-opening copolymerization
Authors: Gregory Georgina L. , Sulley Gregory S. , Carrodeguas Leticia Peña , Chen Thomas T. D. , Santmarti Alba , Terrill Nicholas J. , Lee Koon-Yang , Williams Charlotte K.
Published: May 2020

A new series of block polyester thermoplastic elastomers are prepared by a one-pot procedure; they show properties competitive or better than conventional materials and can be fully degraded after use.
Ring-fused cyclobutanesviacycloisomerization of alkylidenecyclopropane acylsilanes
Authors: Eichenberger Sarah , Hönig Moritz , Richter Matthieu J. R. , Gershoni-Poranne Renana , Carreira Erick M.
Published: May 2020

A novel Lewis acid-catalyzed cycloisomerization of alkylidenecyclopropane acylsilanes is disclosed that involves tandem Prins addition/ring expansion/1,2-silyl shift to grant access to bicyclo[4.2.0]octanes and bicyclo[3.2.0]heptanes.
Color, structure, and rheology of a diblock bottlebrush copolymer solution
Authors: Wade Matthew A. , Walsh Dylan , Lee Johnny Ching-Wei , Kelley Elizabeth , Weigandt Katie , Guironnet Damien , Rogers Simon A.
Published: May 2020

A structure–property–process relation is established for a diblock bottlebrush copolymer solution, through a combination of rheo-neutron scattering, imaging, and rheological measurements.
Rational wave solutions to a generalized (2+1)-dimensional Hirota bilinear equation
Authors: Hosseini K. , Mirzazadeh M. , Aligoli M. , Eslami M. , Liu J.G.
Published: May 2020

A generalized form of (2+1)-dimensional Hirota bilinear (2D-HB) equation is considered herein in order to study nonlinear waves in fluids and oceans. The present goal is carried out through adopting the simplified Hirota’s method as well as ansatz approaches to retrieve a bunch of rational wave structures from multiple soliton solutions to breather, rational, and complexiton solutions. Some figures corresponding to a series of rational wave structures are provided, illustrating the dynamics of the obtained solutions. The results of the present paper help to reveal the existence of rational wave structures of different types for the 2D-HB equation.
Four-Dimensional Introital Ultrasound in Assessing Perioperative Pelvic Floor Muscle Functions of Women with Cystoceles
Authors: Huang Wen-Chen , Yang Jenn-Ming , Chen Hsin-Fu
Published: May 2020

Purpose Research on the use of ultrasound to explore the pelvic floor in women is rarely done with introital ultrasound. This study aimed to investigate the performance of four-dimensional (4D) introital ultrasound in the perioperative assessment of pelvic floor muscle (PFM) function in women with cystocele.

Materials and Methods The reliability and agreement of ultrasound measurements were determined by intraclass correlation coefficients (ICC) with 95 % confidence interval and Bland-Altman analysis in 20 women. The validity of ultrasound parameters was assessed by correlating squeezing ultrasound measurements with the modified Oxford scale (MOS) in 317 women. 4D introital ultrasound data of 241 women with (n = 29) and without (n = 212) postoperative cystocele at the 12-month postoperative assessment were retrospectively analyzed. Levator avulsion was diagnosed using tomographic ultrasound imaging. Involuntary and voluntary PFM functions were explored by dynamic changes in the bladder neck and genital hiatus, respectively, upon coughing and squeezing on 4D introital ultrasound.

Results The ICC for the reliability of all tested ultrasound parameters was good to very good. The changes and change ratios of most ultrasound measurements from resting to squeezing were fairly correlated with MOS. Women with postoperative cystocele demonstrated more rates of complete levator avulsion [41.3 % vs. 4.7 %, P < 0.001, odds ratio (OR) 14.26, 95 % confidence interval (CI) 4.88–42.42] and fewer rates of capable voluntary PFM contraction (65.5 % vs. 92.5 %, P < 0.001, OR 0.16, 95 % CI 0.06–0.43) than those without postoperative cystocele postoperatively.

Conclusion 4D introital ultrasound is feasible to assess perioperative PFM function in women with cystocele.