bluuebunny/crossref_metadata_2025 huggingface dataset:
Erythrocyte sphingosine kinase regulates intraerythrocytic development of Plasmodium falciparum
Authors: Sah Raj Kumar , Pati Soumya , Saini Monika , Singh Shailja
Published: January 2021

The sphingolipid pool is key regulator of vital cellular functions in Plasmodium falciparum a causative agent for deadly malaria. Erythrocytes, the host for asexual stage of Plasmodium, are major reservoir for Sphingosine-1-phosphate (S1P). Erythrocyte possesses Sphingosine kinase (SphK) that catalyzed its biosynthesis from sphingosine (Sph). Since, Plasmodium lacks SphK homologous protein it can be envisaged that it co-opts sphingolipids from both intraerythrocytic as well as extracellular pools for its growth and development. Herein, by sphingosine-NBD probing, we report that infected erythrocytes imports Sph from extracellular pool, which is converted to S1P and thereby taken by P. falciparum. Next, by targeting of the SphK through specific inhibitor N,N-Dimethylsphingosine DMS, we show a reduction in erythrocyte endogenous S1P pool and SphK-phosphorylation that led to inhibition in growth and development of ring stage P. falciparum. Owing to the role of S1P in erythrocyte glycolysis we analyzed uptake of NBD-Glucose and production of lactate in DMS treated and untreated plasmodium. DMS treatment led to decreased glycolysis in Plasmodium. Interestingly the host free Plasmodium did not show any effect on glycolysis with DMS treatment indicating its host-mediated effect. Further to understand the in-vivo anti-plasmodial effects of exogenous and endogenous erythrocyte S1P level, Sphingosine-1-phosphate lyase (S1PL) inhibitor (THI), S1P and SphK-1 inhibitor (DMS), were used in Plasmodium berghei ANKA (PbA) mice model. DMS treatment led to reduction of endogenous S1P conferred significant decrease in parasite load, whereas the plasma level S1P modulated by (THI) and exogenous S1P have no effect on growth of Plasmodium. This suggested erythrocyte endogenous S1P pool is important for Plasmodium growth whereas the plasma level S1P has no effect. Altogether, this study provides insight on cellular processes regulated by S1P in P. falciparum and highlights the novel mechanistically distinct molecular target i.e. SphK-1.
Competing-risk analysis of coronavirus disease 2019 in-hospital mortality in a Northern Italian centre from SMAtteo COvid19 REgistry (SMACORE)
Authors: Zuccaro Valentina , Celsa Ciro , Sambo Margherita , Battaglia Salvatore , Sacchi Paolo , Biscarini Simona , Valsecchi Pietro , Pieri Teresa Chiara , Gallazzi Ilaria , Colaneri Marta , Sachs Michele , Roda Silvia , Asperges Erika , Lupi Matteo , Di Filippo Alessandro , Seminari Elena , Di Matteo Angela , Novati Stefano , Maiocchi Laura , Enea Marco , Attanasio Massimo , Cammà Calogero , Bruno Raffaele
Published: January 2021

An accurate prediction of the clinical outcomes of European patients requiring hospitalisation for Coronavirus Disease 2019 (COVID-19) is lacking. The aim of the study is to identify predictors of in-hospital mortality and discharge in a cohort of Lombardy patients with COVID-19. All consecutive hospitalised patients from February 21st to March 30th, 2020, with confirmed COVID-19 from the IRCCS Policlinico San Matteo, Pavia, Lombardy, Italy, were included. In-hospital mortality and discharge were evaluated by competing risk analysis. The Fine and Gray model was fitted in order to estimate the effect of covariates on the cumulative incidence functions (CIFs) for in-hospital mortality and discharge. 426 adult patients [median age 68 (IQR 56 to 77 years)] were admitted with confirmed COVID-19 over a 5-week period; 292 (69%) were male. By 21 April 2020, 141 (33%) of these patients had died, 239 (56%) patients had been discharged and 46 (11%) were still hospitalised. Among these 46 patients, updated as of 30 May, 2020, 5 (10.9%) had died, 8 (17.4%) were still in ICU, 12 (26.1%) were transferred to lower intensity care units and 21 (45.7%) were discharged. Regression on the CIFs for in-hospital mortality showed that older age, male sex, number of comorbidities and hospital admission after March 4th were independent risk factors associated with in-hospital mortality. Older age, male sex and number of comorbidities definitively predicted in-hospital mortality in hospitalised patients with COVID-19.
Potential role of M2 TAMs around lymphatic vessels during lymphatic invasion in papillary thyroid carcinoma
Authors: Kabasawa Takanobu , Ohe Rintaro , Aung Naing Ye , Urano Yuka , Kitaoka Takumi , Tamazawa Nobuyuki , Utsunomiya Aya , Yamakawa Mitsunori
Published: January 2021

The aim of this study was to examine whether lymphatic invasion in papillary thyroid carcinoma (PTC) occurs when tumour-associated macrophages (TAMs) injure lymphatic vessels together with cancer cells. While there was no difference in the lymphatic vessel density in PTC and follicular thyroid carcinoma (FTC), the number of TAMs around the lymphatic vessels was increased in PTC compared to that in FTC. In particular, TAMs were observed together with cancer cells in lymphatic invasive lesions, and the number of M2 cells inside and outside the lymphatic vessels showed a significant correlation. MMP-2 mRNA was expressed in nonneoplastic stromal cells as well as cancer cells, and double immunofluorescence staining confirmed M2 positivity. Consequently, this study reveals that M2 TAMs around lymphatic vessels within the tumour border of PTC may be associated with the lymphatic invasion of cancer cells. This study represents a step forward in elucidating the mechanism of lymphatic invasion.
Silicon alleviates salinity stress in licorice (Glycyrrhiza uralensis) by regulating carbon and nitrogen metabolism
Authors: Cui Jiajia , Zhang Enhe , Zhang Xinhui , Wang Qi
Published: January 2021

Salt stress is one of the key factors that limits the cultivation of Glycyrrhiza uralensis Fisch. (G. uralensis) in the northern part of China. In this study, three salt treatments (including 21, 42 and 63 ds/m NaCl/kg dry soil) and four Si (silicon) concentrations (including 0, 1.4, 2.8 and 4.2 ds/m SiO2/kg K2SiO3 in dry soil) were tested using G. uralensis as the plant material in a pot experiment with three replications. The results showed that the application of various concentrations of Si increased sucrose synthetase (SS), sucrose phosphate synthetase (SPS) and glutamine synthetase (GS), as well as nitrate reductase (NR) activities, and promoted carbon and nitrogen metabolism. Si application also increased the root dry weight of G. uralensis. Multilevel comparative analysis showed that the application of 2.8 ds/m SiO2 was the optimum rate for improved growth and yield of G. uralensis under different salt levels. This study provides important information that can form the basis for the cultivation of high-yielding and high-quality G. uralensis in saline soils.
Preliminary clinical experience applying donor-derived cell-free DNA to discern rejection in pediatric liver transplant recipients
Authors: Zhao Dong , Zhou Tao , Luo Yi , Wu Cheng , Xu Dongwei , Zhong Chengpeng , Cong Wenming , Liu Qiang , Zhang Jianjun , Xia Qiang
Published: January 2021

Donor-derived cell-free DNA (dd-cfDNA) has been of major interest recently as a non-invasive marker of graft injury, but has not yet been extensively tested in children. From May to September in 2019, a total of 76 pediatric patients receiving a liver graft were enrolled and there were 27 patients excluded. Ultimately plasma samples and matched liver specimens from 49 patients were successfully collected whenever rejection was suspected clinically. Dd-cfDNA were analyzed and then compared to biopsy. Of these, 11 (22.4%) patients were found to have rejection by biopsy. Dd-cfDNA levels were higher among patients with rejection compared to those with no rejection. In subgroup analysis, dd-cfDNA% among patients with rejection differed from those with EBV/CMV infection and DILI patients. Similarly, observations were available concerning dd-cfDNA (cp/mL). The AUC for dd-cfDNA% and dd-cfDNA (cp/mL) were 0.878, 0.841, respectively, both of which were higher than conventional LFTs. For rejection, dd-cfDNA% ≥ 28.7% yielded a sensitivity of 72.7%, specificity 94.7% and dd-cfDNA (cp/mL) ≥ 2076 cp/mL, yielded a sensitivity of 81.8%, specificity 81.9%. Of note, the dd-cfDNA distribution was significantly different between whole liver and LLS transplantation. In the setting of pediatric LTx, dd-cfDNA appears to be a sensitive biomarker indicating the presence of rejection.

International Clinical Trails Registry Platform: ChiCTR1900022406.
Transcriptome-wide high-throughput mapping of protein–RNA occupancy profiles using POP-seq
Authors: Srivastava Mansi , Srivastava Rajneesh , Janga Sarath Chandra
Published: January 2021

Interaction between proteins and RNA is critical for post-transcriptional regulatory processes. Existing high throughput methods based on crosslinking of the protein–RNA complexes and poly-A pull down are reported to contribute to biases and are not readily amenable for identifying interaction sites on non poly-A RNAs. We present Protein Occupancy Profile-Sequencing (POP-seq), a phase separation based method in three versions, one of which does not require crosslinking, thus providing unbiased protein occupancy profiles on whole cell transcriptome without the requirement of poly-A pulldown. Our study demonstrates that ~ 68% of the total POP-seq peaks exhibited an overlap with publicly available protein–RNA interaction profiles of 97 RNA binding proteins (RBPs) in K562 cells. We show that POP-seq variants consistently capture protein–RNA interaction sites across a broad range of genes including on transcripts encoding for transcription factors (TFs), RNA-Binding Proteins (RBPs) and long non-coding RNAs (lncRNAs). POP-seq identified peaks exhibited a significant enrichment (p value < 2.2e−16) for GWAS SNPs, phenotypic, clinically relevant germline as well as somatic variants reported in cancer genomes, suggesting the prevalence of uncharacterized genomic variation in protein occupied sites on RNA. We demonstrate that the abundance of POP-seq peaks increases with an increase in expression of lncRNAs, suggesting that highly expressed lncRNA are likely to act as sponges for RBPs, contributing to the rewiring of protein–RNA interaction network in cancer cells. Overall, our data supports POP-seq as a robust and cost-effective method that could be applied to primary tissues for mapping global protein occupancies.
CRISPR-based transcriptional activation tool for silent genes in filamentous fungi
Authors: Mózsik László , Hoekzema Mirthe , de Kok Niels A. W. , Bovenberg Roel A. L. , Nygård Yvonne , Driessen Arnold J. M.
Published: January 2021

Filamentous fungi are historically known to be a rich reservoir of bioactive compounds that are applied in a myriad of fields ranging from crop protection to medicine. The surge of genomic data available shows that fungi remain an excellent source for new pharmaceuticals. However, most of the responsible biosynthetic gene clusters are transcriptionally silent under laboratory growth conditions. Therefore, generic strategies for activation of these clusters are required. Here, we present a genome-editing-free, transcriptional regulation tool for filamentous fungi, based on the CRISPR activation (CRISPRa) methodology. Herein, a nuclease-defective mutant of Cas9 (dCas9) was fused to a highly active tripartite activator VP64-p65-Rta (VPR) to allow for sgRNA directed targeted gene regulation. dCas9-VPR was introduced, together with an easy to use sgRNA “plug-and-play” module, into a non-integrative AMA1-vector, which is compatible with several filamentous fungal species. To demonstrate its potential, this vector was used to transcriptionally activate a fluorescent reporter gene under the control of the penDE core promoter in Penicillium rubens. Subsequently, we activated the transcriptionally silent, native P. rubens macrophorin biosynthetic gene cluster by targeting dCas9-VPR to the promoter region of the transcription factor macR. This resulted in the production of antimicrobial macrophorins. This CRISPRa technology can be used for the rapid and convenient activation of silent fungal biosynthetic gene clusters, and thereby aid in the identification of novel compounds such as antimicrobials.
Visual fixations rather than saccades dominate the developmental eye movement test
Authors: Tanke Nouk , Barsingerhorn Annemiek D. , Boonstra F. Nienke , Goossens Jeroen
Published: January 2021

When children have visual and/or oculomotor deficits, early diagnosis is critical for rehabilitation. The developmental eye movement (DEM) test is a visual-verbal number naming test that aims to measure oculomotor dysfunction in children by comparing scores on a horizontal and vertical subtest. However, empirical comparison of oculomotor behavior during the two subtests is missing. Here, we measured eye movements of healthy children while they performed a digital version of the DEM. In addition, we measured visual processing speed using the Speed Acuity test. We found that parameters of saccade behavior, such as the number, amplitude, and direction of saccades, correlated with performance on the horizontal, but not the vertical subtest. However, the time spent on making saccades was very short compared to the time spent on number fixations and the total time needed for either subtest. Fixation durations correlated positively with performance on both subtests and co-varied tightly with visual processing speed. Accordingly, horizontal and vertical DEM scores showed a strong positive correlation with visual processing speed. We therefore conclude that the DEM is not suitable to measure saccade behavior, but can be a useful indicator of visual-verbal naming skills, visual processing speed, and other cognitive factors of clinical relevance.
Identification of VOCs in essential oils extracted using ultrasound- and microwave-assisted methods from sweet cherry flower
Authors: Zhang Huimin , Yan Hongguang , Li Quan , Lin Hui , Wen Xiaopeng
Published: January 2021

The floral fragrance of plants is an important indicator in their evaluation. The aroma of sweet cherry flowers is mainly derived from their essential oil. In this study, based on the results of a single-factor experiment, a Box–Behnken design was adopted for ultrasound- and microwave-assisted extraction of essential oil from sweet cherry flowers of the Brooks cultivar. With the objective of extracting the maximum essential oil yield (w/w), the optimal extraction process conditions were a liquid–solid ratio of 52 mL g−1, an extraction time of 27 min, and a microwave power of 435 W. The essential oil yield was 1.23%, which was close to the theoretical prediction. The volatile organic compounds (VOCs) of the sweet cherry flowers of four cultivars (Brooks, Black Pearl, Tieton and Summit) were identified via headspace solid phase microextraction (SPME) and gas chromatography–mass spectrometry (GC–MS). The results showed that a total of 155 VOCs were identified and classified in the essential oil from sweet cherry flowers of four cultivars, 65 of which were shared among the cultivars. The highest contents of VOCs were aldehydes, alcohols, ketones and esters. Ethanol, linalool, lilac alcohol, acetaldehyde, (E)-2-hexenal, benzaldehyde and dimethyl sulfide were the major volatiles, which were mainly responsible for the characteristic aroma of sweet cherry flowers. It was concluded that the VOCs of sweet cherry flowers were qualitatively similar; however, relative content differences were observed in the four cultivars. This study provides a theoretical basis for the metabolism and regulation of the VOCs of sweet cherry flowers.
In silico analysis of epitope-based vaccine candidate against tuberculosis using reverse vaccinology
Authors: Bibi Shaheen , Ullah Inayat , Zhu Bingdong , Adnan Muhammad , Liaqat Romana , Kong Wei-Bao , Niu Shiquan
Published: January 2021

Tuberculosis (TB) kills more individuals in the world than any other disease, and a threat made direr by the coverage of drug-resistant strains of Mycobacterium tuberculosis (Mtb). Bacillus Calmette–Guérin (BCG) is the single TB vaccine licensed for use in human beings and effectively protects infants and children against severe military and meningeal TB. We applied advanced computational techniques to develop a universal TB vaccine. In the current study, we select the very conserved, experimentally confirmed Mtb antigens, including Rv2608, Rv2684, Rv3804c (Ag85A), and Rv0125 (Mtb32A) to design a novel multi-epitope subunit vaccine. By using the Immune Epitopes Database (IEDB), we predicted different B-cell and T-cell epitopes. An adjuvant (Griselimycin) was also added to vaccine construct to improve its immunogenicity. Bioinformatics tools were used to predict, refined, and validate the 3D structure and then docked with toll-like-receptor (TLR-3) using different servers. The constructed vaccine was used for further processing based on allergenicity, antigenicity, solubility, different physiochemical properties, and molecular docking scores. The in silico immune simulation results showed significant response for immune cells. For successful expression of the vaccine in E. coli, in-silico cloning and codon optimization were performed. This research also sets out a good signal for the design of a peptide-based tuberculosis vaccine. In conclusion, our findings show that the known multi-epitope vaccine may activate humoral and cellular immune responses and maybe a possible tuberculosis vaccine candidate. Therefore, more experimental validations should be exposed to it.
Quantitative evaluation and comparison of coronary artery characteristics by 3D coronary volume reconstruction
Authors: Kim Yongcheol , Bray Jonathan James Hyett , Waterhouse Benjamin , Gall Alexander , Connolly Georgia May , Sammut Eva , Bruno Vito Domenico , Tulloh Robert , Adlam David , Johnson Thomas W.
Published: January 2021

Non-atherosclerotic abnormalities of vessel calibre, aneurysm and ectasia, are challenging to quantify and are often overlooked in qualitative reporting. Utilising a novel 3-dimensional (3D) quantitative coronary angiography (QCA) application, we have evaluated the characteristics of normal, diabetic and aneurysmal or ectatic coronary arteries. We selected 131 individuals under 50 years-of-age, who had undergone coronary angiography for suspected myocardial ischaemia between 1st January 2011 and 31st December 2015, at the Bristol Heart Institute, Bristol, UK. This included 42 patients with angiographically normal coronary arteries, 36 diabetic patients with unobstructed coronaries, and 53 patients with abnormal coronary dilatation (aneurysm and ectasia). A total of 1105 coronary segments were analysed using QAngio XA 3D (Research Edition, Medis medical imaging systems, Leiden, The Netherlands). The combined volume of the major coronary arteries was significantly different between each group (1240 ± 476 mm3 diabetic group, 1646 ± 391 mm3 normal group, and 2072 ± 687 mm3 abnormal group). Moreover, the combined coronary artery volumes correlated with patient body surface area (r = 0.483, p < 0.01). Inter-observer variability was assessed and intraclass correlation coefficient of the total coronary artery volume demonstrated a low variability of 3D QCA (r = 0.996, p < 0.001). Dedicated 3D QCA facilitates reproducible coronary artery volume estimation and allows discrimination of normal and diseased vessels.
Increased infiltration of regulatory T cells in hepatocellular carcinoma of patients with hepatitis B virus pre-S2 mutant
Authors: Teng Chiao-Fang , Li Tsai-Chung , Wang Ting , Liao Da-Ching , Wen Yi-Hsuan , Wu Tzu-Hua , Wang John , Wu Han-Chieh , Shyu Woei-Cherng , Su Ih-Jen , Jeng Long-Bin
Published: January 2021

Hepatocellular carcinoma (HCC) is a frequent and deadly human cancer worldwide that is intimately associated with chronic hepatitis B virus (HBV) infection. Pre-S2 mutant is a HBV oncoprotein that plays important roles in HCC development and is linked to poor prognosis in HCC patients. However, the profiles of tumor-infiltrating lymphocytes in HCC tissues of pre-S2 mutant-positive patients remain unknown. In this study, we performed fluorescent immunohistochemistry staining to detect the infiltration of ‘anti-tumor’ cytotoxic T lymphocytes (CTLs) and ‘pro-tumor’ regulatory T cells (Tregs) in pre-S2 mutant-positive and -negative HCC patients. We showed that pre-S2 mutant-positive patients had a significantly higher infiltration of CD4+CD25+ cells and forkhead box P3 (Foxp3)-expressing cells but similar CTLs and lower granzyme B-expressing cells in HCC tissues compared with pre-S2 mutant-negative patients. Moreover, the percentage of pre-S2 plus pre-S1 + pre-S2 deletion (pre-S2 mutant) was positively correlated with the density of CD4+CD25+ cells and Foxp3-expressing cells but negatively with granzyme B-expressing cells in HCC tissues. Considering that increased intratumoral Tregs have been shown to promote tumor immune evasion, our data may provide new insights into the pathogenesis of HBV pre-S2 mutant-induced HCC and suggest that therapeutics targeting Tregs may be a promising strategy for treating pre-S2 mutant-positive high-risk patient population.
Aberrant serum parathyroid hormone, calcium, and phosphorus as risk factors for peritonitis in peritoneal dialysis patients
Authors: Liao Chia-Te , Zheng Cai-Mei , Lin Yen-Chung , Wu Mei-Yi , Lin Yuh-Feng , Hsu Yung-Ho , Hsu Chih-Cheng , Wu Mai-Szu
Published: January 2021

Identifying modifiable risk factors of peritoneal dialysis (PD)-related peritonitis is of clinical importance in patient care. Mineral bone disease (MBD) has been associated with mortality and morbidity in end-stage kidney disease (ESKD) patients. However, its influence on PD related peritonitis due to altered host immunity remains elusive. This study investigated whether abnormal biomarkers of MBD are associated with the development of peritonitis in patients undergoing maintenance PD. We conducted a retrospective observational cohort study, analysing data derived from a nationwide dialysis registry database in Taiwan, from 2005 to 2012. A total of 5750 ESKD patients commencing PD therapy during this period were enrolled and followed up to 60 months or by the end of the study period. The patients were stratified based on their baseline serum parathyroid hormone (PTH) levels, calcium (Ca) levels or phosphorus (P) levels, respectively or in combinations. The primary outcome was the occurrence of first episode of peritonitis, and patient outcomes such as deaths, transfer to haemodialysis or receiving renal transplantation were censored. Peritonitis-free survival and the influence of PTH, Ca, P (individual or in combination) on the peritonitis occurrence were analysed. A total of 5750 PD patients was enrolled. Of them, 1611 patients experienced their first episode of peritonitis during the study period. Patients with low PTH, high Ca or low P levels, respectively or in combination, had the lowest peritonitis-free survival. After adjusting for age, sex and serum albumin levels, we found that the combinations of low PTH levels with either high Ca levels or low/normal P levels were significant risk factors of developing peritonitis. Abnormal mineral bone metabolism in maintenance PD patients with low serum PTH levels, in combination with either high Ca levels or low/normal P levels, could be novel risk factors of PD-related peritonitis.
Hyperpolarized 13C pyruvate magnetic resonance spectroscopy for in vivo metabolic phenotyping of rat HCC
Authors: Bliemsrieder Elisabeth , Kaissis Georgios , Grashei Martin , Topping Geoffrey , Altomonte Jennifer , Hundshammer Christian , Lohöfer Fabian , Heid Irina , Keim Dominik , Gebrekidan Selamawit , Trajkovic-Arsic Marija , Winkelkotte AM , Steiger Katja , Nawroth Roman , Siveke Jens , Schwaiger Markus , Makowski Marcus , Schilling Franz , Braren Rickmer
Published: January 2021

The in vivo assessment of tissue metabolism represents a novel strategy for the evaluation of oncologic disease. Hepatocellular carcinoma (HCC) is a high-prevalence, high-mortality tumor entity often discovered at a late stage. Recent evidence indicates that survival differences depend on metabolic alterations in tumor tissue, with particular focus on glucose metabolism and lactate production. Here, we present an in vivo imaging technique for metabolic tumor phenotyping in rat models of HCC. Endogenous HCC was induced in Wistar rats by oral diethyl-nitrosamine administration. Peak lactate-to-alanine signal ratios (L/A) were assessed with hyperpolarized magnetic resonance spectroscopic imaging (HPMRSI) after [1-13C]pyruvate injection. Cell lines were derived from a subset of primary tumors, re-implanted in nude rats, and assessed in vivo with dynamic hyperpolarized magnetic resonance spectroscopy (HPMRS) after [1-13C]pyruvate injection and kinetic modelling of pyruvate metabolism, taking into account systemic lactate production and recirculation. For ex vivo validation, enzyme activity and metabolite concentrations were spectroscopically quantified in cell and tumor tissue extracts. Mean peak L/A was higher in endogenous HCC compared to non-tumorous tissue. Dynamic HPMRS revealed higher pyruvate-to-lactate conversion rates (kpl) and lactate signal in subcutaneous tumors derived from high L/A tumor cells, consistent with ex vivo measurements of higher lactate dehydrogenase (LDH) levels in these cells. In conclusion, HPMRS and HPMRSI reveal distinct tumor phenotypes corresponding to differences in glycolytic metabolism in HCC tumor tissue.
Age affects procedural paired-associates learning in the grey mouse lemur (Microcebus murinus)
Authors: Schmidtke Daniel
Published: January 2021

The ability to associate memorized objects with their location in space gradually declines during normal aging and can drastically be affected by neurodegenerative diseases. This study investigates object-location paired-associates learning (PAL) in the grey mouse lemur (Microcebus murinus), a nonhuman primate model of brain aging. Touchscreen-based testing of 6 young adults (1–5 years) and 6 old adults (> 7 years) in the procedural rodent dPAL-task revealed significant age-related performance decline, evident in group differences in the percentage of correct decision during learning and the number of sessions needed to reach a predefined criterion. Response pattern analyses suggest decreased susceptibility to relative stimulus-position biases in young animals, facilitating PAL. Additional data from a subset of “overtrained” individuals (n = 7) and challenge sessions using a modified protocol (sPAL) further suggest that learning criteria routinely used in animal studies on PAL can underestimate the endpoint at which a stable performance is reached and that more conservative criteria are needed to improve construct validity of the task. To conclude, this is the first report of an age effect on dPAL and corroborates the role of mouse lemurs as valuable natural nonhuman primate models in aging research.
Fenofibrate attenuates doxorubicin-induced cardiac dysfunction in mice via activating the eNOS/EPC pathway
Authors: Huang Wen-Pin , Yin Wei-Hsian , Chen Jia-Shiong , Huang Po-Hsun , Chen Jaw-Wen , Lin Shing-Jong
Published: January 2021

Endothelial progenitor cells (EPCs) improve endothelial impairment, which in turn restores endothelial function in patients with heart failure (HF). In the present study, we tested whether fenofibrate, with its anti-inflammatory and vasoprotective effects, could improve myocardial function by activating EPCs through the eNOS pathway in a doxorubicin (DOX)-induced cardiomyopathy mouse model. Wild-type mice were divided into 4 groups and treated with vehicle, DOX + saline, DOX + fenofibrate, and DOX + fenofibrate + L-NAME (N(ω)-nitro-L-arginine methyl ester). DOX-induced cardiac atrophy, myocardial dysfunction, the number of circulating EPCs and tissue inflammation were analyzed. Mice in the DOX + fenofibrate group had more circulating EPCs than those in the DOX + saline group (2% versus 0.5% of total events, respectively) after 4 weeks of treatment with fenofibrate. In addition, the inhibition of eNOS by L-NAME in vivo further abolished the fenofibrate-induced suppression of DOX-induced cardiotoxic effects. Protein assays revealed that, after DOX treatment, the differential expression of MMP-2 (matrix metalloproteinase-2), MMP-9 (matrix metalloproteinase-9), TNF-α (tumor necrosis factor-α), and NT-pro-BNP (N-terminal pro-B-type natriuretic peptide) between saline- and DOX-treated mice was involved in the progression of HF. Mechanistically, fenofibrate promotes Akt/eNOS and VEGF (vascular endothelial growth factor), which results in the activation of EPC pathways, thereby ameliorating DOX-induced cardiac toxicity.
Disturbance type determines how connectivity shapes ecosystem resilience
Authors: Pearson Ryan M. , Schlacher Thomas A. , Jinks Kristin I. , Olds Andrew D. , Brown Christopher J. , Connolly Rod M.
Published: January 2021

Connectivity is fundamentally important for shaping the resilience of complex human and natural networks when systems are disturbed. Ecosystem resilience is, in part, shaped by the spatial arrangement of habitats, the permeability and fluxes between them, the stabilising functions performed by organisms, their dispersal traits, and the interactions between functions and stressor types. Controlled investigations of the relationships between these phenomena under multiple stressors are sparse, possibly due to logistic and ethical difficulties associated with applying and controlling stressors at landscape scales. Here we show that grazing performance, a key ecosystem function, is linked to connectivity by manipulating the spatial configuration of habitats in microcosms impacted by multiple stressors. Greater connectivity enhanced ecosystem function and reduced variability in grazing performance in unperturbed systems. Improved functional performance was observed in better connected systems stressed by harvesting pressure and temperature rise, but this effect was notably reversed by the spread of disease. Connectivity has complex effects on ecological functions and resilience, and the nuances should be recognised more fully in ecosystem conservation.
Nrf2 regulates cell motility through RhoA–ROCK1 signalling in non-small-cell lung cancer cells
Authors: Ko Eunsun , Kim Dasom , Min Dong Wha , Kwon Seung-Hae , Lee Ji-Yun
Published: January 2021

Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of several antioxidant and anti-inflammatory enzymes. It binds to its endogenous inhibitor Kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm under normal conditions. Various endogenous or environmental oxidative stresses can disrupt the Nrf2/Keap1 complex, allowing Nrf2 to translocate into the nucleus, where it induces the transcription of various cytoprotective enzymes by binding to antioxidant responsive elements. These enzymes have been reported to play a role in regulating tumour growth, angiogenesis, and chemoprevention. Invasion and migration are the most harmful aspects of cancer; they directly impacts the patients’ survival. Although the roles of Keap1/Nrf2 and their downstream genes in various cancers have been widely documented, their role in regulating cell motility still remains unclear, particularly in cancer cells. We observed that Nrf2 suppression following treatment with brusatol in non-small-cell lung cancer (NSCLC) cells with either exogenously introduced Keap1 or siNrf2 resulted in the inhibition of cell migration and invasion, with shrinking cell morphology due to decreased focal adhesions via inhibition of the RhoA–ROCK1 pathway. Nrf2 overexpression showed opposite results. Thus, the Nrf2/Keap1 pathway may affect cell motility by dysregulating the RhoA–ROCK1 signalling pathway in NSCLC.
Self-monitoring of blood glucose in association with glycemic control in newly diagnosed non-insulin-treated diabetes patients: a retrospective cohort study
Authors: Sia Hon-Ke , Kor Chew-Teng , Tu Shih-Te , Liao Pei-Yung , Wang Jiun-Yi
Published: January 2021

The benefits of self-monitoring of blood glucose (SMBG) on glycemic control among type 2 diabetes (T2DM) patients not receiving insulin remains controversial. This study aimed to examine the association between SMBG and glycemic control in these patients. This retrospective longitudinal study enrolled 4987 eligible patients from a medical center in Taiwan. Data were collected from electronic medical records at 0 (baseline), 3, 6, 9, and 12 (end-point) months after enrollment. Patients were assigned to the early SMBG group or to the non-user group depending on whether they performed SMBG at baseline. Differences in glycated hemoglobin (HbA1c) reduction between groups at each time-point were assessed using SMBG group-by-time interaction in generalized estimating equations models, which were established using backward elimination method for multivariate regression analysis. Subgroup analyses for patients using non-insulin and insulin secretagogues were performed additionally. The estimated maximal difference in HbA1c reduction between groups (early SMBG users vs. non-users) was 0.55% at 3 months. Subgroup analyses showed maximal differences of 0.61% and 0.52% at 3 months in the non-insulin and insulin secretagogues groups, respectively. SMBG group-by-time interaction was statistically significant at 3 months and lasted for 12 months. The finding suggests that performing SMBG at disease onset was positively associated with better glycemic control in newly diagnosed non-insulin-treated T2DM patients, regardless whether non-insulin secretagogues or insulin secretagogues were used.
Single molecule turnover of fluorescent ATP by myosin and actomyosin unveil elusive enzymatic mechanisms
Authors: Ušaj Marko , Moretto Luisa , Vemula Venukumar , Salhotra Aseem , Månsson Alf
Published: January 2021

Benefits of single molecule studies of biomolecules include the need for minimal amounts of material and the potential to reveal phenomena hidden in ensembles. However, results from recent single molecule studies of fluorescent ATP turnover by myosin are difficult to reconcile with ensemble studies. We found that key reasons are complexities due to dye photophysics and fluorescent contaminants. After eliminating these, through surface cleaning and use of triple state quenchers and redox agents, the distributions of ATP binding dwell times on myosin are best described by 2 to 3 exponential processes, with and without actin, and with and without the inhibitor para-aminoblebbistatin. Two processes are attributable to ATP turnover by myosin and actomyosin respectively, whereas the remaining process (rate constant 0.2–0.5 s−1) is consistent with non-specific ATP binding to myosin, possibly accelerating ATP transport to the active site. Finally, our study of actin-activated myosin ATP turnover without sliding between actin and myosin reveals heterogeneity in the ATP turnover kinetics consistent with models of isometric contraction.
An acylhydrazone-based AIE organogel for the selective sensing of submicromolar level Al3+ and Al(iii)-based metallogel formation to detect oxalic acid
Authors: Wang Bin , Li Juan , Shui Shipeng , Xu Jie
Published: January 2021

The compound L can be fluorescence-tunable depending on the water volume fraction and optically sense Al3+ without interference.
Electroanalytical profiling of cocaine samples by means of an electropolymerized molecularly imprinted polymer using benzocaine as the template molecule
Authors: Grothe Renata A. , Lobato Alnilan , Mounssef Bassim , Tasić Nikola , Braga Ataualpa A. C. , Maldaner Adriano O. , Aldous Leigh , Paixão Thiago R. L. C. , Gonçalves Luís Moreira
Published: January 2021

Cocaine samples were ‘finger-printed’ using e-MIPs, constructed on the surface of portable SPCEs. The SWV data with suitable chemometric analysis provides valuable information about the drugs’ provenience which is crucial to tackle drug traffic.
Applications of DNA-nanozyme-based sensors
Authors: Yu Renzhong , Wang Rui , Wang Zhaoyin , Zhu Qinshu , Dai Zhihui
Published: January 2021

In this review, the research progress of the sensors based on the DNA-nanozymes were summarized.
Mechanistic aspects of functional layer formation in hybrid one-step designed GOx/Nafion/Pd-NPs nanobiosensors
Authors: Butyrskaya E. V. , Korkmaz N. , Zolotukhina E. V. , Krasiukova V. , Silina Y. E.
Published: January 2021

Although excellent analytical performance of nanobiosensors is undoubtful, their exact molecular structure often remains unclear.
A 3D printed in vitro bone model for the assessment of molecular and cellular cues in metastatic neuroblastoma
Authors: Aveic Sanja , Janßen Simon , Nasehi Ramin , Seidelmann Max , Vogt Michael , Pantile Marcella , Rütten Stephan , Fischer Horst
Published: January 2021

From PSc to CSc: modeling heterogeneous tumor microenvironments of the neuroblastoma bone metastatic niche.
Pentapeptide IKVAV-engineered hydrogels for neural stem cell attachment
Authors: Yin Yixia , Wang Wenwu , Shao Qi , Li Binbin , Yu Dan , Zhou Xin , Parajuli Jayanti , Xu Haixing , Qiu Tong , Yetisen Ali Kemal , Jiang Nan
Published: January 2021

A IKVAV-functionalized hydrogel is developed. It not only enhances neural stem cell (NSC) attachment, growth, and differentiation, but also maintains the proliferation ability of the NSC spheroids in the hydrogel for spinal cord injury repair.
Biomaterials for protein delivery for complex tissue healing responses
Authors: Dorogin Jonathan , Townsend Jakob M. , Hettiaratchi Marian H.
Published: January 2021

Recent advances in biomaterial delivery vehicles have increased the ability to tailor precise protein delivery to restore normal healing cascades and stimulate robust tissue repair.
Molecular engineering to boost the photothermal effect of conjugated oligomer nanoparticles
Authors: Zhang Hui , Guo Lixia , Wang Yunxia , Feng Liheng
Published: January 2021

A novel molecular engineering strategy to enhance the photothermal performance of conjugated molecules was developed by introducing the ethynyl group into the structure for effective antibacterial therapy.
Intricately structured mesoporous organosilica nanoparticles: synthesis strategies and biomedical applications
Authors: Tao Jun , Su Xiaodan , Li Jing , Shi Wenhui , Teng Zhaogang , Wang Lianhui
Published: January 2021

Overview of the intricately structured MONs and their biomedical applications.
Antibody drug conjugates with hydroxamic acid cargos for histone deacetylase (HDAC) inhibition
Authors: Cianferotti Claudio , Faltoni Valentina , Cini Elena , Ermini Elena , Migliorini Francesca , Petricci Elena , Taddei Maurizio , Salvini Laura , Battistuzzi Gianfranco , Milazzo Ferdinando Maria , Anastasi Anna Maria , Chiapparino Caterina , De Santis Rita , Giannini Giuseppe
Published: January 2021

The bioconjugation of hydroxamic acids to antibodies has been made possible through a non-cleavable linker based on thep-mercaptobenzyl alcohol structure that releases hydroxamates in the cells.
Exploring the homopolar dehydrocoupling of ammonia borane by solid-state multinuclear NMR spectroscopy
Authors: Roy Binayak , Pal Urbi , Bishnoi Ankita , O'Dell Luke A. , Sharma Pratibha
Published: January 2021

Solid-state 1H–14NOT HMQC, 11B MQMAS and 1H–11B HETCOR NMR experiments are used to explore the role of homopolar B–B interaction in the thermal dehydrogenation of pure and supported ammonia borane, for it's potential hydrogen storage applications.
Impact of chemistry on the preparation and post-modification of multilayered hollow microcapsules
Authors: Borbora Angana , Manna Uttam
Published: January 2021

Different chemical interactions/bonding allowed LbL deposition of selected constituents, and further post-chemical modifications of chemically reactive multilayered microcapsules allowed to associate desired chemical functionalities.
Concomitant induction to few-layer and 1T-rich two-dimensional MoS2 by rigid segment-containing polysulfide as a sulfur source and in situ intercalator
Authors: Wang Yijuan , Wang Jianzhi , Liu Jie , Xiao Zhuangwei , Xue Yanan , Yu Faquan
Published: January 2021

A rigid segment-containing polysulfide was used as a sulfur source and in situ intercalator to induce the formation of few-layer and 1T-rich MoS2.
Dysprosium-directed metallosupramolecular network on graphene/Ir(111)
Authors: Moreno Daniel , Cirera Borja , Parreiras Sofia O. , Urgel José I. , Giménez-Agulló Nelson , Lauwaet Koen , Gallego José M. , Galán-Mascarós José R. , Martínez José I. , Ballester Pablo , Miranda Rodolfo , Écija David
Published: January 2021

On-surface design of dysprosium-directed metal-organic network on graphene/Ir(111).
Molecular dopant determines the structure of a physisorbed self-assembled molecular network
Authors: Steeno Roelof , Minoia Andrea , Gimenez-Lopez Maria C. , Blunt Matthew O. , Champness Neil R. , Lazzaroni Roberto , Mali Kunal S. , De Feyter Steven
Published: January 2021

The presence of an opportune impurity can change the on-surface assembly behavior via preferential adsorption and nucleation.
Modulation of charge transport through single-molecule bilactam junctions by tuning hydrogen bonds
Authors: Chen Yaorong , Wang Hua-Chun , Tang Yongxiang , Zhou Yu , Huang Longfeng , Cao Jian , Tang Chun , Zhang Manxi , Shi Jia , Liu Junyang , Ren Xiancheng , Xu Yun-Xiang , Hong Wenjing
Published: January 2021

Intramolecular hydrogen bonds provide a strategy to promote the planarity of the structure without additional transmission channels, which tunes the charge transport through molecular devices.
Helically chiral Pd(ii) complexes containing intramolecular Pd⋯Pd metallophilicity as circularly polarized molecular phosphors
Authors: Lin Jinqiang , Xie Mo , Zhang Xiaobao , Gao Qin , Chang Xiaoyong , Zou Chao , Lu Wei
Published: January 2021

Pallas's shining helixes: single-helical and double-helical oligonuclear pincer-type palladium(ii) arylacetylide complexes exhibit circularly polarized phosphorescence with MMLCT parentages in fluid solutions.
Vapour–liquid–solid-like growth of high-quality and uniform 3C–SiC heteroepitaxial films on α-Al2O3(0001) substrates
Authors: Sannodo Naoki , Osumi Asuka , Kaminaga Kenichi , Maruyama Shingo , Matsumoto Yuji
Published: January 2021

We employ our pulsed laser deposition system with rapid beam deflection to demonstrate the heteroepitaxial growth of 3C–SiC thin films by a vapour–liquid–solid-like mechanism by alternating deposition of SiC and NiSi2 flux in nanoscale.
Rational design of the Z-scheme hollow-structure Co9S8/g-C3N4 as an efficient visible-light photocatalyst for tetracycline degradation
Authors: Wang Xueying , Han Rui , Liu Hao , Wang Ximei , Wei Qin , Luo Chuannan
Published: January 2021

An efficient Z-scheme cage-structured Co9S8/g-C3N4 photocatalyst with hollow structure which accelerates the separation of photogenerated charge carriers was constructed for the degradation of tetracycline antibiotics under visible-light.
Re-examining the electronic structure of fluorescent tetra-silver clusters in zeolites
Authors: Chan Bun
Published: January 2021

Zeolite encapsulated complexes of silver clusters show luminescence properties that are tuneable by varying the ligand.
Site-specific hydrogen-atom elimination in photoexcited alkyl radicals
Authors: Chicharro David V. , Zanchet Alexandre , Bouallagui Aymen , Rubio-Lago Luis , García-Vela Alberto , Bañares Luis , Marggi Poullain Sonia
Published: January 2021

A prompt site-specific hydrogen-atom elimination from the α-carbon atom is reported in the photodissociation of several alkyl radicals at 201 nm and discussed in terms of their chemical structure and the role of vibrational promoting modes.
Molecular insights into MXene destructing the cell membrane as a “nano thermal blade”
Authors: Wu Daxin , Zhao Ruixuan , Chen Yu , Wang Ying , Li Jiebo , Fan Yubo
Published: January 2021

The decreased transparency denotes the approach of MXene, which indicated that the penetration process is unspontaneous. After excitation with a light beam, heat is transported through an efficient thermal conduction pathway.
A vibrational spectroscopic and computational study of the structures of protonated imidacloprid and its fragmentation products in the gas phase
Authors: Menard Kelsey J. , Martens Jonathan , Fridgen Travis D.
Published: January 2021

Vibrational spectroscopy and computational chemistry studies were combined with the aim of elucidating the structures of protonated imidacloprid (pIMI), and its unimolecular decomposition products.
New atomic-scale insights into the I/Ni(100) system: phase transitions and growth of an atomically thin NiI2 film
Authors: Komarov N. S. , Pavlova T. V. , Andryushechkin B. V.
Published: January 2021

We use a traditional surface science approach to create and study an atomically thin NiI2 film (a promising two-dimensional ferromagnetic material) formed on Ni(100) substrate as a result of molecular iodine adsorption.
Transport mechanisms in Co-doped ZnO (ZCO) and H-irradiated ZCO polycrystalline thin films
Authors: Di Trolio A. , Amore Bonapasta A. , Barone C. , Leo A. , Carapella G. , Pagano S. , Polimeni A. , Testa A. M.
Published: January 2021

Co doping increases the ZnO resistivity (ρ) at high T (HT), whereas it has an opposite effect at low T (LT). H balances the Co effects by neutralizing the ρ increase at HT and strengthening its decrease at LT.
Twistable dipolar aryl rings as electric field actuated conformational molecular switches
Authors: Jutglar Lozano Kílian , Santiago Raul , Ribas-Arino Jordi , Bromley Stefan T.
Published: January 2021

The electric field induced conformational response of a range of twistable dipolar aryl ring systems is studied using density functional theory based calculations. We assess which factors are most important for efficient molecular switching.
Metal doping of porous materials via a post-synthetic mechano-chemical approach: a general route to design low-loaded versatile catalytic systems
Authors: Marquez-Medina M. Dolores , Luque Rafael , Balu Alina M. , Ivars-Barceló Francisco , Carrillo-Carrión Carolina
Published: January 2021

Mesoporous silica materials doped with metals (Fe/Zr) presented superior catalytic performance for oxidations. The use of MOFs as metal sources improved the metal distribution, and allowed a fine-tuning of Brønsted–Lewis acidity depending on the MOF.
Photo-driven selective CO2 reduction by H2O into ethanol over Pd/Mn–TiO2: suitable synergistic effect between Pd and Mn sites
Authors: Peng Ting , Wang Ke , He Shihui , Chen Xun , Dai Wenxin , Fu Xianzhi
Published: January 2021

The Mn–Pd interaction of Pd/Mn–TiO2 is a promising catalyst to enhance C2H5OH selectivity since Pd with a strong ability to capture and transport electrons and Mn with multifarious activation of the reactant (CO2 and H2O).
Suzuki–Miyaura cross coupling reaction: recent advancements in catalysis and organic synthesis
Authors: Kadu Brijesh S.
Published: January 2021

Suzuki–Miyaura cross coupling reaction (SMCR) – A milestone in the synthesis of C–C coupled compounds.
Ortho-vanillin derived Al(iii) and Co(iii) catalyst systems for switchable catalysis using ε-decalactone, phthalic anhydride and cyclohexene oxide
Authors: Diment Wilfred T. , Stößer Tim , Kerr Ryan W. F. , Phanopoulos Andreas , Durr Christopher B. , Williams Charlotte K.
Published: January 2021

Switchable catalysis is a useful one-pot method to prepare block polyesters utilising a single catalyst exposed to a mixture of monomers.
Ni and Zn N-confused porphyrin complexes as recyclable catalysts for high efficiency solvent-free CO2 fixation into cyclic carbonates
Authors: dela Cruz Jay-ar B. , Hung Chen-Hsiung
Published: January 2021

ZnII[2-N(CH2)5N+(CH3)3Br−NCTPP] is a bifunctional catalyst that exhibits efficiency for CO2 fixation with epoxides with TOF up to 370 000 h−1 and TON 1.3 × 106. It can also be recycled for the formation of glycerol carbonate from CO2 and glycidol.
Hydrolysis of amides to carboxylic acids catalyzed by Nb2O5
Authors: Siddiki S. M. A. Hakim , Rashed Md. Nurnobi , Touchy Abeda Sultana , Jamil Md. A. R. , Jing Yuan , Toyao Takashi , Maeno Zen , Shimizu Ken-ichi
Published: January 2021

An efficient heterogeneous Nb2O5 catalytic system has been developed for industrially important and challenging amide hydrolysis reaction to carboxylic acid through cleavage of resonance stabilized amidic C–N bond.