bluuebunny/crossref_metadata_2025 huggingface dataset:
Coupling effects among elementary polarization properties
Authors: Gao Wanrong
Published: January 2021

In this work, we propose that there exist coupling effects among birefringence, dichroism and off-diagonal depolarization parameters of differential Mueller matrix of random anisotropic media. An anisotropic spatial correlation function of anisotropic random medium is proposed to explain this phenomenon. The consequences of these effects are then pointed out. The idea in this work is very helpful for accurate interpretation of the measured Mueller matrices of optically anisotropic depolarizing medium. In addition, the concept of the anisotropic spatial correlation function of anisotropic random medium will open a new door and will play a central role for analyzing polarized light scattering by anisotropic random media.
Characteristics and electrochemical performances of silicon/carbon nanofiber/graphene composite films as anode materials for binder-free lithium-ion batteries
Authors: Cong Ruye , Choi Jin-Yeong , Song Ju-Beom , Jo Minsang , Lee Hochun , Lee Chang-Seop
Published: January 2021

We report the interfacial study of a silicon/carbon nanofiber/graphene composite as a potentially high-performance anode for rechargeable lithium-ion batteries (LIBs). Silicon nanoparticle (Si)/carbon nanofiber (CNF)/reduced graphene oxide (rGO) composite films were prepared by simple physical filtration and an environmentally-friendly thermal reduction treatment. The films were used as high-performance anode materials for self-supporting, binder-free LIBs. Reducing graphene oxide improves the electron conductivity and adjusts to the volume change during repeated charge/discharge processes. CNFs can help maintain the structural stability and prevent the peeling off of silicon nanoparticles from the electrodes. When the fabricated Si/CNF/rGO composites were used as anodes of LIBs, the initial specific capacity was measured to be 1894.54 mAh/g at a current density of 0.1 A/g. After 100 cycles, the reversible specific capacity was maintained at 964.68 mAh/g, and the coulombic efficiency could reach 93.8% at the same current density. The Si/CNF/rGO composite electrode exhibited a higher specific capacity and cycle stability than an Si/rGO composite electrode. The Si/CNF/rGO composite films can effectively accommodate and buffer changes in the volume of silicon nanoparticles, form a stable solid–electrolyte interface, improve the conductivity of the electrode, and provide a fast and efficient channel for electron and ion transport.
Electric dipole induced bulk ferromagnetism in dimer Mott molecular compounds
Authors: Yoshimoto Ryo , Yamashita Satoshi , Akutsu Hiroki , Nakazawa Yasuhiro , Kusamoto Tetsuro , Oshima Yugo , Nakano Takehito , Yamamoto Hiroshi M. , Kato Reizo
Published: January 2021

Magnetic properties of Mott–Hubbard systems are generally dominated by strong antiferromagnetic interactions produced by the Coulomb repulsion of electrons. Although theoretical possibility of a ferromagnetic ground state has been suggested by Nagaoka and Penn as single-hole doping in a Mott insulator, experimental realization has not been reported more than half century. We report the first experimental possibility of such ferromagnetism in a molecular Mott insulator with an extremely light and homogeneous hole-doping in π-electron layers induced by net polarization of counterions. A series of Ni(dmit)2 anion radical salts with organic cations, where dmit is 1,3-dithiole-2-thione-4,5-dithiolate can form bi-layer structure with polarized cation layers. Heat capacity, magnetization, and ESR measurements substantiated the formation of a bulk ferromagnetic state around 1.0 K with quite soft magnetization versus magnetic field (M–H) characteristics in (Et-4BrT)[Ni(dmit)2]2 where Et-4BrT is ethyl-4-bromothiazolium. The variation of the magnitude of net polarizations by using the difference of counter cations revealed the systematic change of the ground state from antiferromagnetic one to ferromagnetic one. We also report emergence of metallic states through further doping and applying external pressures for this doping induced ferromagnetic state. The realization of ferromagnetic state in Nagaoka–Penn mechanism can paves a way for designing new molecules-based ferromagnets in future.
A simple and effective approach to quantitatively characterize structural complexity
Authors: Zhang Gongqiao , Hui Gangying , Yang Aiming , Zhao Zhonghua
Published: January 2021

This study brings insight into interpreting forest structural diversity and explore the classification of individuals according to the distribution of the neighbours in natural forests. Natural forest communities with different latitudes and distribution patterns in China were used. Each tree and its nearest neighbours form a structural unit. Random structural units (or random trees) in natural forests were divided into different sub-types based on the uniform angle index (W). The proportions of different random structural units were analysed. (1) There are only two types of random structural units: type R1 looks similar to a dumbbell, and type R2 looks similar to a torch. These two random structural units coexist in natural forests simultaneously. (2) The proportion of type R1 is far less than that of R2, is only approximately 1/3 of all random structural units or random trees; R2 accounts for approximately 2/3. Furthermore, the proportion of basal area presents the same trend for both random structural units and random trees. R2 has approximately twice the basal area of R1. Random trees (structural units) occupy the largest part of natural forest communities in terms of quantity and basal area. Meanwhile, type R2 is the largest part of random trees (structural units). This study finds that the spatial formation mechanism of natural forest communities which is of great significance to the cultivation of planted forests.
Spatial memory deficiency early in 6xTg Alzheimer’s disease mouse model
Authors: Kang Shinwoo , Kim Jinho , Chang Keun-A
Published: January 2021

Alzheimer’s disease (AD) is mainly characterized by the deposition of extracellular amyloid plaques and intracellular accumulation of neurofibrillary tangles (NFTs). While the recent 5xFAD AD mouse model exhibits many AD-related phenotypes and a relatively early and aggressive amyloid β production, it does not show NFTs. Here, we developed and evaluated a novel AD mouse model (6xTg-AD, 6xTg) by crossbreeding 5xFAD mice with mice expressing mutant (P301L) tau protein (MAPT). Through behavioral and histopathological tests, we analyzed cognitive changes and neuropathology in 6xTg mice compared to their respective parental strains according to age. Spatial memory deficits occurred in 6xTg mice at 2 months of age, earlier than they occurred in 5xFAD mice. Histopathological data revealed aggressive Aβ42 and p-tau accumulation in 6xTg mice. Microglial activation occurred in the cortex and hippocampus of 6xTg mice beginning at 2 months. In 6xTg model mice, the synaptic loss was observed in the cortex from 4 months of age and in the hippocampus from 6 months of age, and neuronal loss appeared in the cortex from 4 months of age and in the hippocampus 6 months of age, earlier than it is observed in the 5xFAD and JNPL3 models. These results showed that each pathological symptom appeared much faster than in their parental animal models. In conclusion, these novel 6xTg-AD mice might be an advanced animal model for studying AD, representing a promising approach to developing effective therapy.
Trends in the kidney cancer mortality-to-incidence ratios according to health care expenditures of 56 countries
Authors: Sung Wen-Wei , Ko Po-Yun , Chen Wen-Jung , Wang Shao-Chuan , Chen Sung-Lang
Published: January 2021

The incidence and mortality rates in kidney cancer (KC) are increasing. However, the trends for mortality have varied among regions over the past decade, which may be due to the disparities in medical settings, such as the availability of frequent imaging examinations and effective systemic therapies. The availability of these two medical options has been proven to be positively correlated with a favorable prognosis in KC and may be more common in countries with better health care systems and greater expenditures. The delicate association between the trends in clinical outcomes in KC and health care disparities warrant detailed observation. We applied a delta-mortality-to-incidence ratio (δMIR) for KC to compare two years as an index for the improvement in clinical outcomes and the mortality-to-incidence ratio (MIR) of a single year to evaluate their association with the Human Development Index (HDI), current health expenditure (CHE) per capita, and CHE as a percentage of gross domestic product (CHE/GDP) by using linear regression analyses. A total of 56 countries were included based on data quality reports and missing data. We discovered that the HDI, CHE per capita, and CHE/GDP were negatively correlated with the MIRs for KC (p < 0.001, p < 0.001, and p < 0.001, respectively). No significant association was observed between the δMIRs and the HDI, CHE per capita, and CHE/GDP among the included countries, and only the CHE/GDP shows a trend toward significance. Interestingly, the δMIRs related with an increase in relative health care investment include δCHE per capita and δCHE/GDP.
Improving sewage sludge compost process and quality by carbon sources addition
Authors: Meng Liqiang , Li Weiguang , Zhang Shumei , Zhang Xiancheng , Zhao Yi , Chen Li
Published: January 2021

In present study, the effects of carbon sources on compost process and quality were evaluated in the lab-scale sewage sludge (SS) composting. The composting experiments were performed for 32 days in 5 L reactors. The results showed that carbon sources could change the nitrogen conversion and improve the compost quality. Especially, the readily degradable carbon source could promote organic matter degradation, improve nitrogen conversion process and accelerate compost maturation. The addition of glucose and sucrose could increase dissolved organic carbon, CO2 emission, dehydrogenase activity, nitrification and germination index during the SS composting. That's because glucose and sucrose could be quickly used by microbes as energy and carbon source substance to increase activity of microbes and ammonia assimilation. What's more, the NH3 emission was reduced by 26.9% and 32.1% in glucose and sucrose treatments, respectively. Therefore, the addition of readily degradable carbon source could reduce NH3 emission and improve compost maturity in the SS composting.
Percutaneous ultrasound guided PEG-coated gold nanoparticles enhanced radiofrequency ablation in liver
Authors: Mocan Tudor , Stiufiuc Rares , Popa Calin , Nenu Iuliana , Pestean Cosmin , Nagy Andras Laszlo , Mocan Lavinia Patricia , Leucuta Daniel Corneliu , Hajjar Nadim Al , Sparchez Zeno
Published: January 2021

To investigate the effects of PEG-coated gold nanoparticles on ablation zone volumes following in vivo radiofrequency ablation of porcine liver. This prospective study was performed following institutional animal care and committee approval was used. Radiofrequency ablations were performed in the livers of ten Sus scrofa domesticus swines. During each ablation, 10 mL (mL) of Peg-coated gold nanoparticles at two different concentrations (0.5 mg/mL and 0.01 mg/mL) were injected through the electrode channel into the target zone. For the control group, 10 mL of physiological saline was used. Five to ten minutes after each ablation, contrast enhanced ultrasound (CEUS) was performed to evaluate the volume of the coagulation zone. On day five we performed another CEUS and the animals were sacrificed. Treated tissues were explanted for quantification of the ablation zones’ volumes. Hematoxylin and eosin (H&E) staining was also performed for histologic analysis. A total of 30 ablations were performed in the livers. The mean coagulation zone volume as measured by CEUS on day 5 after RFA was: 21.69 ± 3.39 cm3, 19.22 ± 5.77 cm3, and 8.80 ± 3.33 cm3 for N1, N2 and PS respectively. The coagulation zone volume after N1 and N2 treatments was significantly higher compared to PS treatment (p < 0.001 and p = 0.025 respectively). There was no difference between N1 and N2 treatment (p = 0.60). In our proof-of concept, pilot study we have shown for the first time that when injected directly into the target tissue during RFA, gold nanoparticles can substantially increase the coagulation zone.
Adverse effects of iron deficiency anemia on pregnancy outcome and offspring development and intervention of three iron supplements
Authors: Zhang Qi , Lu Xiao-Min , Zhang Min , Yang Chen-Ying , Lv Si-Yuan , Li Shi-Fen , Zhong Cai-Yun , Geng Shan-Shan
Published: January 2021

Iron deficiency anemia (IDA) is a common micronutrient deficiency among pregnant women with severe consequences including impaired immuno-inflammatory system, premature birth, fetal death etc. The present study aimed to investigate the effects of three iron supplements on IDA female rats and their offspring. The IDA female rat model was established with low iron diet and the rats were then mated. After pregnancy, rats were fed diets containing different iron supplements (iron polysaccharide complex, iron protein succinylate and ferrous sulfate) until their offspring were 42 days old. Pregnancy outcomes, haematological, iron metabolism, physical and neurological development indexes were determined. The results showed that all three iron supplements improved the levels of hematological parameters of both mother and offspring rats. After iron supplementation, serum iron, transferrin saturation and serum ferritin levels were increased compared with the IDA group. The level of ferritin light chain in the liver and spleen of both mother and offspring rats in iron supplemented groups was significantly higher than that of the IDA group. The average number of born alive per litter in the iron treatment groups was significantly higher than that in the IDA group. Iron supplements also improved the physical growth and neurobehavioral development of offspring rats. It was also found that iron supplementation improved the expression of ferritin light chain and the synaptic growth associated proteins in the brain and hippocampus. No significant difference was found in the efficacy of three iron supplements. These results suggest that pregnant and postpartum IDA affects pregnancy outcomes, offspring physical development and causes neural impairment. Sufficient iron supplementation can significantly improve IDA and its adverse effects on both mother and offspring.
Innovative analytical model for temperature prediction of front-end accessory drive
Authors: Liu Xingchen , Behdinan Kamran
Published: January 2021

The front-end accessory drive belt drive system is a critical component in the vehicle engine. To avoid thermal deterioration under static state operating conditions, the thermal distribution for the belt drive system at each condition must be determined in an efficient manner. Due to the numerical approach is not feasible to address this concern because of its high computational cost, this paper proposes a reliable and efficient novel analytical thermal model to achieve this goal. This work develops the state-of-the-art heat transfer ordinary differential equations (ODEs) describing the thermal flow and heat dissipations on the complex structures of pulleys. Then it integrates these ODEs with heat transfer governing equations of the belt and heat exchanges to establish an innovative system of equations that can be solved within a few seconds to provide temperature plots. Moreover, experiments were conducted on a dynamometer to verify the accuracy of the proposed model under a wide range of conditions. The results indicate that the measured temperatures are in good agreement with the corresponding analytical results. Owing to its efficiency, the proposed model can be integrated with other mechanical characterizations of the belt drive system in terms of design, optimization, and thermal fatigue analyses.
Fracture detection from Azimuth-dependent seismic inversion in joint time–frequency domain
Authors: Pan Xinpeng , Zhang Dazhou , Zhang Pengfei
Published: January 2021

Detection of fracture properties can be implemented using azimuth-dependent seismic inversion for optimal model parameters in time or frequency domain. Considering the respective potentials for sensitivities of inversion resolution and anti-noise performance in time and frequency domain, we propose a more robust azimuth-dependent seismic inversion method to achieve fracture detection by combining the Bayesian inference and joint time–frequency-domain inversion theory. Both Cauchy Sparse and low-frequency constraint regularizations are introduced to reduce multi-solvability of model space and improve inversion reliability of model parameters. Synthetic data examples demonstrate that the frequency bandwidth of inversion result is almost the same for time, frequency and joint time–frequency domain inversion in seismic dominant frequency band using the noise-free data, but the frequency bandwidth in joint time–frequency domain is larger than that in time and frequency domains using low- signal-to-noise-ratio (SNR) data. The results of cross-correlation coefficients validate that the joint time–frequency-domain inversion retains both the excellent characteristics of high resolution in frequency-domain inversion and the advantage of strong anti-noise ability in time-domain inversion. A field data example further demonstrates that our proposed inversion approach in joint time–frequency domain may provide a more stable technique for fracture detection in fractured reservoirs.
Development of a predictive model utilizing the neutrophil to lymphocyte ratio to predict neoadjuvant chemotherapy efficacy in early breast cancer patients
Authors: Zhu Jiujun , Jiao Dechuang , Zhao Yajie , Guo Xuhui , Yang Yue , Xiao Hui , Liu Zhenzhen
Published: January 2021

Neutrophils and lymphocytes are key regulators of breast cancer (BC) development and progression. Neutrophil to lymphocyte ratio (NLR) values have been found to offer clear prognostic utility when evaluating BC patients. In this study, we sought to determine whether BC patient baseline NLR values are correlated with pathological complete response (pCR) following neoadjuvant chemotherapy (NCT) treatment. In total, 346 BC patients underwent NCT at our hospital from January 1, 2014 to October 31, 2019, and data pertaining to these patients were retrospectively analyzed. Correlations between clinicopathological characteristics and pCR rates were assessed via multivariate logistic regression analyses. A predictive scoring model was used to gauge the likelihood of pCR based upon regression coefficient (β) values for each significant variable identified through these analyses. NLR cut-off values suitable for identifying patients likely to achieve pCR following NCT treatment were calculated using receiver operating characteristic (ROC) curves. All patients in the present study were females with a median age of 48 years old (range 22–77). An optimal NLR cut-off value of 1.695 was identified and was associated with respective sensitivity and specificity values of 63.6% and 45.5%. We found that higher NLR values were significantly associated with younger age, premenopausal status, and non-pCR status. Logistic regression analyses indicated that NLR, tumor size, hormone receptor (HR) status, and Ki-67 expression were all independent predictors of pCR. The area under the curve (AUC) for the resultant predictive scoring model was 0.705, and this model was assessed via K-fold cross-validation (k = 10) and bootstrapping validation, yielding respective AUC values of 0.68 and 0.694. Moreover, the incorporation of NLR into this predictive model incrementally improved its overall prognostic value relative to that of a model not incorporating NLR (AUC = 0.674). BC patients with a lower baseline NLR are more likely to exhibit pCR following NCT treatment, indicating that NLR may be a valuable biomarker for BC patient prognostic evaluation and treatment planning. Overall, our results demonstrate that this NLR-based predictive model can efficiently predict NCT efficacy in early BC patients with a high degree of accuracy.
THz guided-mode resonance notch filter with variable filtering strength
Authors: Bark Hyeon Sang , Jang Kyu-Ha , Lee Kitae , Jeong Young Uk , Jeon Tae-In
Published: January 2021

In this paper, we propose a terahertz (THz) guided-mode resonance (GMR) notch filter made of a monolithic polyethylene terephthalate (PET) film, which has a monolayer grating structure. The proposed configuration shows both polarization-dependent and polarization-independent notch filter characteristics for the incident THz wave depending on the rotation angle of the second grating film. When the rotation angle is 0°, the filtering strength (transmittance) at resonance frequency changes from 0.4 (0.996) to 99.0% (0.010) according to the incident polarization. The transmittance continuously decreases with increasing rotation angle until 90°. When the rotation angle is 90°, the transmittance converges to 0.065 (± 0.015) independent of the incident wave polarization. When the incident polarization angle ranges from 90° to 180°, paradoxically, the transmittance through the two GMR grating films is greater than the transmittance through only the first GMR grating film due to the enhancement of the vertical component of the THz wave. These results agree well with a calculation using a polar coordinate system.
Deuterium-labeled Raman tracking of glucose accumulation and protein metabolic dynamics in Aspergillus nidulans hyphal tips
Authors: Yasuda Mitsuru , Takeshita Norio , Shigeto Shinsuke
Published: January 2021

Filamentous fungi grow exclusively at their tips, where many growth-related fungal processes, such as enzyme secretion and invasion into host cells, take place. Hyphal tips are also a site of active metabolism. Understanding metabolic dynamics within the tip region is therefore important for biotechnology and medicine as well as for microbiology and ecology. However, methods that can track metabolic dynamics with sufficient spatial resolution and in a nondestructive manner are highly limited. Here we present time-lapse Raman imaging using a deuterium (D) tracer to study spatiotemporally varying metabolic activity within the hyphal tip of Aspergillus nidulans. By analyzing the carbon–deuterium (C–D) stretching Raman band with spectral deconvolution, we visualize glucose accumulation along the inner edge of the hyphal tip and synthesis of new proteins from the taken-up D-labeled glucose specifically at the central part of the apical region. Our results show that deuterium-labeled Raman imaging offers a broadly applicable platform for the study of metabolic dynamics in filamentous fungi and other relevant microorganisms in vivo.
Preference, performance, and chemical defense in an endangered butterfly using novel and ancestral host plants
Authors: Haan Nathan L. , Bowers M. Deane , Bakker Jonathan D.
Published: January 2021

Adoption of novel host plants by herbivorous insects can require new adaptations and may entail loss of adaptation to ancestral hosts. We examined relationships between an endangered subspecies of the butterflyEuphydryas editha(Taylor’s checkerspot) and three host plant species. Two of the hosts (Castilleja hispida, Castilleja levisecta) were used ancestrally while the other,Plantago lanceolata, is exotic and was adopted more recently. We measured oviposition preference, neonate preference, larval growth, and secondary chemical uptake on all three hosts. Adult females readily laid eggs on all hosts but favoredPlantagoand tended to avoidC. levisecta.Oviposition preference changed over time. Neonates had no preference among host species, but consistently chose bracts over leaves within bothCastillejaspecies. Larvae developed successfully on all species and grew to similar size on all of them unless they ate onlyCastillejaleaves (rather than bracts) which limited their growth. Diet strongly influenced secondary chemical uptake by larvae. Larvae that atePlantagoorC. hispidaleaves contained the highest concentrations of iridoid glycosides, and iridoid glycoside composition varied with host species and tissue type. Despite having largely switched to a novel exotic host and generally performing better on it, this population has retained breadth in preference and ability to use other hosts.
Distribution of cortactin in cerebellar Purkinje cell spines
Authors: Szabó Lilla E. , Marcello G. Mark , Süth Miklós , Sótonyi Péter , Rácz Bence
Published: January 2021

Dendritic spines are the primary sites of excitatory transmission in the mammalian brain. Spines of cerebellar Purkinje Cells (PCs) are plastic, but they differ from forebrain spines in a number of important respects, and the mechanisms of spine plasticity differ between forebrain and cerebellum. Our previous studies indicate that in hippocampal spines cortactin—a protein that stabilizes actin branch points—resides in the spine core, avoiding the spine shell. To see whether the distribution of cortactin differs in PC spines, we examined its subcellular organization using quantitative preembedding immunoelectron microscopy. We found that cortactin was enriched in the spine shell, associated with the non-synaptic membrane, and was also situated within the postsynaptic density (PSD). This previously unrecognized distribution of cortactin within PC spines may underlie structural and functional differences in excitatory spine synapses between forebrain, and cerebellum.
Positive-charge tuned gelatin hydrogel-siSPARC injectable for siRNA anti-scarring therapy in post glaucoma filtration surgery
Authors: Chun Yong Yao , Yap Zhu Li , Seet Li Fong , Chan Hiok Hong , Toh Li Zhen , Chu Stephanie W. L. , Lee Ying Shi , Wong Tina T. , Tan Timothy T. Y.
Published: January 2021

Small interfering RNA (siRNA) therapy is a promising epigenetic silencing strategy. However, its widespread adoption has been severely impeded by its ineffective delivery into the cellular environment. Here, a biocompatible injectable gelatin-based hydrogel with positive-charge tuned surface charge is presented as an effective platform for siRNA protection and delivery. We demonstrate a two-step synthesis of a gelatin-tyramine (Gtn-Tyr) hydrogel with simultaneous charge tunability and crosslinking ability. We discuss how different physiochemical properties of the hydrogel interact with siSPARC (siRNA for secreted protein, acidic and rich in cysteine), and study the positive-charge tuned gelatin hydrogel as an effective delivery platform for siSPARC in anti-fibrotic treatment. Through in vitro studies using mouse tenon fibroblasts, the positive-charge tuned Gtn-Tyr hydrogel shows sustained siSPARC cellular internalization and effective SPARC silencing with excellent biocompatibility. Similarly, the same hydrogel platform delivering siSPARC in an in vivo assessment employing a rabbit model shows an effective reduction in subconjunctival scarring in post glaucoma filtration surgery, and is non-cytotoxic compared to a commonly used anti-scarring agent, mitomycin-C. Overall, the current siRNA delivery strategy involving the positive-charge tuned gelatin hydrogel shows effective delivery of gene silencing siSPARC for anti-fibrotic treatment. The current charge tunable hydrogel delivery system is simple to fabricate and highly scalable. We believe this delivery platform has strong translational potential for effective siRNA delivery and epigenetic silencing therapy.
Potential repurposing of four FDA approved compounds with antiplasmodial activity identified through proteome scale computational drug discovery and in vitro assay
Authors: Diallo Bakary N’tji , Swart Tarryn , Hoppe Heinrich C. , Tastan Bishop Özlem , Lobb Kevin
Published: January 2021

Malaria elimination can benefit from time and cost-efficient approaches for antimalarials such as drug repurposing. In this work, 796 DrugBank compounds were screened against 36Plasmodium falciparumtargets using QuickVina-W. Hits were selected after rescoring using GRaph Interaction Matching (GRIM) and ligand efficiency metrics: surface efficiency index (SEI), binding efficiency index (BEI) and lipophilic efficiency (LipE). They were further evaluated in Molecular dynamics (MD). Twenty-five protein–ligand complexes were finally retained from the 28,656 (36 × 796) dockings. Hit GRIM scores (0.58 to 0.78) showed their molecular interaction similarity to co-crystallized ligands. Minimum LipE (3), SEI (23) and BEI (7) were in at least acceptable thresholds for hits. Binding energies ranged from −6 to −11 kcal/mol. Ligands showed stability in MD simulation with good hydrogen bonding and favorable protein–ligand interactions energy (the poorest being −140.12 kcal/mol). In vitro testing showed 4 active compounds with two having IC50values in the single-digit μM range.
Infant circulating MicroRNAs as biomarkers of effect in fetal alcohol spectrum disorders
Authors: Mahnke Amanda H. , Sideridis Georgios D. , Salem Nihal A. , Tseng Alexander M. , Carter R. Colin , Dodge Neil C. , Rathod Aniruddha B. , Molteno Christopher D. , Meintjes Ernesta M. , Jacobson Sandra W. , Miranda Rajesh C. , Jacobson Joseph L.
Published: January 2021

Prenatal alcohol exposure (PAE) can result in cognitive and behavioral disabilities and growth deficits. Because alcohol-related neurobehavioral deficits may occur in the absence of overt dysmorphic features or growth deficits, there is a need to identify biomarkers of PAE that can predict neurobehavioral impairment. In this study, we assessed infant plasma extracellular, circulating miRNAs (exmiRNAs) obtained from a heavily exposed Cape Town cohort to determine whether these can be used to predict PAE-related growth restriction and cognitive impairment. PAE, controlling for smoking as a covariate, altered 27% of expressed exmiRNAs with clinically-relevant effect sizes (Cohen’s d ≥ 0.4). Moreover, at 2 weeks, PAE increased correlated expression of exmiRNAs across chromosomes, suggesting potential co-regulation. In confirmatory factor analysis, the variance in expression for PAE-altered exmiRNAs at 2 weeks and 6.5 months was best described by three-factor models. Pathway analysis found that factors at 2 weeks were associated with (F1) cell maturation, cell cycle inhibition, and somatic growth, (F2) cell survival, apoptosis, cardiac development, and metabolism, and (F3) cell proliferation, skeletal development, hematopoiesis, and inflammation, and at 6.5 months with (F1) neurodevelopment, neural crest/mesoderm-derivative development and growth, (F2) immune system and inflammation, and (F3) somatic growth and cardiovascular development. Factors F3 at 2 weeks and F2 at 6.5 months partially mediated PAE-induced growth deficits, and factor F3 at 2 weeks partially mediated effects of PAE on infant recognition memory at 6.5 months. These findings indicate that infant exmiRNAs can help identify infants who will exhibit PAE-related deficits in growth and cognition.
In vivo multimodal optical imaging of dermoscopic equivocal melanocytic skin lesions
Authors: Elagin V. , Gubarkova E. , Garanina O. , Davydova D. , Orlinskaya N. , Matveev L. , Klemenova I. , Shlivko I. , Shirmanova M. , Zagaynova E.
Published: January 2021

There is a wide range of equivocal melanocytic lesions that can be clinically and dermoscopically indistinguishable from early melanoma. In the present work, we assessed the possibilities of combined using of multiphoton microscopy (MPM) and optical coherence angiography (OCA) for differential diagnosis of the equivocal melanocytic lesions. Clinical and dermoscopic examinations of 60 melanocytic lesions revealed 10 benign lesions and 32 melanomas, while 18 lesions remained difficult to diagnose. Histopathological analysis of these lesions revealed 4 intradermal, 3 compound and 3 junctional nevi in the “benign” group, 7 superficial spreading, 14 lentigo maligna and 11 nodular melanomas in the “melanoma” group and 2 lentigo simplex, 4 dysplastic nevi, 6 melanomas in situ, 4 invasive lentigo melanomas and 2 invasive superficial spreading melanomas in the “equivocal” group. On the basis of MPM, a multiphoton microscopy score (MPMS) has been developed for quantitative assessment of melanoma features at the cellular level, that showed lower score for benign lesions compare with malignant ones. OCA revealed that the invasive melanoma has a higher vessel density and thicker blood vessels than melanoma in situ and benign lesions. Discriminant functions analysis of MPM and OCA data allowed to differentiate correctly between all equivocal melanocytic lesions. Therefore, we demonstrate, for the first time, that a combined use of MPM and OCA has the potential to improve early diagnosis of melanoma.
Gut microbiota modulation induced by Zika virus infection in immunocompetent mice
Authors: Corrêa Rafael , de Oliveira Santos Igor , Braz-de-Melo Heloísa Antoniella , de Sant’Ana Lívia Pimentel , das Neves Almeida Raquel , Pasquarelli-do-Nascimento Gabriel , Prado Paulo Sousa , Kobinger Gary P. , Maurice Corinne F. , Magalhães Kelly Grace
Published: January 2021

Gut microbiota composition can modulate neuroendocrine function, inflammation, and cellular and immunological responses against different pathogens, including viruses. Zika virus (ZIKV) can infect adult immunocompetent individuals and trigger brain damage and antiviral responses. However, it is not known whether ZIKV infection could impact the gut microbiome from adult immunocompetent mice. Here, we investigated modifications induced by ZIKV infection in the gut microbiome of immunocompetent C57BL/6J mice. Adult C57BL/6J mice were infected with ZIKV and the gut microbiota composition was analyzed by next-generation sequencing of the V4 hypervariable region present in the bacterial 16S rDNA gene. Our data showed that ZIKV infection triggered a significant decrease in the bacteria belonging to Actinobacteria and Firmicutes phyla, and increased Deferribacteres and Spirochaetes phyla components compared to uninfected mice. Interestingly, ZIKV infection triggered a significant increase in the abundance of bacteria from the Spirochaetaceae family in the gut microbiota. Lastly, we demonstrated that modulation of microbiota induced by ZIKV infection may lead to intestinal epithelium damage and intense leukocyte recruitment to the intestinal mucosa. Taken together, our data demonstrate that ZIKV infection can impact the gut microbiota composition and colon tissue homeostasis in adult immunocompetent mice.
Non-invasive synchronous monitoring of neutrophil migration using whole body near-infrared fluorescence-based imaging
Authors: Leslie Jack , Robinson Stuart M. , Oakley Fiona , Luli Saimir
Published: January 2021

Advances in fluorescence imaging coupled with the generation of near infrared probes have significantly improved the capabilities of non-invasive, real-time imaging in whole animals. In this study we were able to overcome a limitation of in vivo fluorescence imaging and have established a dual cell tracking method where two different cell types can be monitored according to the spectral signature of the cell labelling fluorophore. Using a mouse model of acute liver injury, we have characterised the in vivo migration patterns of wild type and transgenic neutrophils with impaired chemotaxis. Here, we were able to demonstrate that IVIS provides a sensitive multiplexing technology to differentiate two different cell populations based on the spectral signature of the cell labelling fluorophores. This spectral unmixing methodology has the potential to uncover multidimensional cellular interactions involved in many diseases such as fibrosis and cancer. In vivo spectral un-mixing provides a useful tool for monitoring multiple biological process in real-time in the same animal.
G-computation and machine learning for estimating the causal effects of binary exposure statuses on binary outcomes
Authors: Le Borgne Florent , Chatton Arthur , Léger Maxime , Lenain Rémi , Foucher Yohann
Published: January 2021

In clinical research, there is a growing interest in the use of propensity score-based methods to estimate causal effects. G-computation is an alternative because of its high statistical power. Machine learning is also increasingly used because of its possible robustness to model misspecification. In this paper, we aimed to propose an approach that combines machine learning and G-computation when both the outcome and the exposure status are binary and is able to deal with small samples. We evaluated the performances of several methods, including penalized logistic regressions, a neural network, a support vector machine, boosted classification and regression trees, and a super learner through simulations. We proposed six different scenarios characterised by various sample sizes, numbers of covariates and relationships between covariates, exposure statuses, and outcomes. We have also illustrated the application of these methods, in which they were used to estimate the efficacy of barbiturates prescribed during the first 24 h of an episode of intracranial hypertension. In the context of GC, for estimating the individual outcome probabilities in two counterfactual worlds, we reported that the super learner tended to outperform the other approaches in terms of both bias and variance, especially for small sample sizes. The support vector machine performed well, but its mean bias was slightly higher than that of the super learner. In the investigated scenarios, G-computation associated with the super learner was a performant method for drawing causal inferences, even from small sample sizes.
SPECC1L-deficient primary mouse embryonic palatal mesenchyme cells show speed and directionality defects
Authors: Goering Jeremy P. , Isai Dona G. , Hall Everett G. , Wilson Nathan R. , Kosa Edina , Wenger Luke W. , Umar Zaid , Yousaf Abdul , Czirok Andras , Saadi Irfan
Published: January 2021

Cleft lip and/or palate (CL/P) are common anomalies occurring in 1/800 live-births. Pathogenic SPECC1L variants have been identified in patients with CL/P, which signifies a primary role for SPECC1L in craniofacial development. Specc1l mutant mouse embryos exhibit delayed palatal shelf elevation accompanied by epithelial defects. We now posit that the process of palate elevation is itself abnormal in Specc1l mutants, due to defective remodeling of palatal mesenchyme. To characterize the underlying cellular defect, we studied the movement of primary mouse embryonic palatal mesenchyme (MEPM) cells using live-imaging of wound-repair assays. SPECC1L-deficient MEPM cells exhibited delayed wound-repair, however, reduced cell speed only partially accounted for this delay. Interestingly, mutant MEPM cells were also defective in coordinated cell movement. Therefore, we used open-field 2D cultures of wildtype MEPM cells to show that they indeed formed cell streams at high density, which is an important attribute of collective movement. Furthermore, activation of the PI3K-AKT pathway rescued both cell speed and guidance defects in Specc1l mutant MEPM cells. Thus, we show that live-imaging of primary MEPM cells can be used to assess mesenchymal remodeling defects during palatal shelf elevation, and identify a novel role for SPECC1L in collective movement through modulation of PI3K-AKT signaling.
CD117/c-kit defines a prostate CSC-like subpopulation driving progression and TKI resistance
Authors: Harris Koran S. , Shi Lihong , Foster Brittni M. , Mobley Mary E. , Elliott Phyllis L. , Song Conner J. , Watabe Kounosuke , Langefeld Carl D. , Kerr Bethany A.
Published: January 2021

Cancer stem-like cells (CSCs) are associated with cancer progression, metastasis, and recurrence, and may also represent a subset of circulating tumor cells (CTCs). In our prior study, CTCs in advanced prostate cancer patients were found to express CD117/c-kit in a liquid biopsy. Whether CD117 expression played an active or passive role in the aggressiveness and migration of these CTCs remained an open question. In this study, we show that CD117 expression in prostate cancer patients is associated with decreased overall and progression-free survival and that activation and phosphorylation of CD117 increases in prostate cancer patients with higher Gleason grades. To determine how CD117 expression and activation by its ligand stem cell factor (SCF, kit ligand, steel factor) alter prostate cancer aggressiveness, we used C4-2 and PC3-mm human prostate cancer cells, which contain a CD117+ subpopulation. We demonstrate that CD117+ cells display increased proliferation and migration. In prostaspheres, CD117 expression enhances sphere formation. In both 2D and 3D cultures, stemness marker gene expression is higher in CD117+ cells. Using xenograft limiting dilution assays and serial tumor initiation assays, we show that CD117+ cells represent a CSC population. Combined, these data indicate that CD117 expression potentially promotes tumor initiation and metastasis. Further, in cell lines, CD117 activation by SCF promotes faster proliferation and invasiveness, while blocking CD117 activation with tyrosine kinase inhibitors (TKIs) decreased progression in a context-dependent manner. We demonstrate that CD117 expression and activation drives prostate cancer aggressiveness through the CSC phenotype and TKI resistance.
Incorrect Asian aerosols affecting the attribution and projection of regional climate change in CMIP6 models
Authors: Wang Zhili , Lin Lei , Xu Yangyang , Che Huizheng , Zhang Xiaoye , Zhang Hua , Dong Wenjie , Wang Chense , Gui Ke , Xie Bing
Published: January 2021

Anthropogenic aerosol (AA) forcing has been shown as a critical driver of climate change over Asia since the mid-20th century. Here we show that almost all Coupled Model Intercomparison Project Phase 6 (CMIP6) models fail to capture the observed dipole pattern of aerosol optical depth (AOD) trends over Asia during 2006–2014, last decade of CMIP6 historical simulation, due to an opposite trend over eastern China compared with observations. The incorrect AOD trend over China is attributed to problematic AA emissions adopted by CMIP6. There are obvious differences in simulated regional aerosol radiative forcing and temperature responses over Asia when using two different emissions inventories (one adopted by CMIP6; the other from Peking university, a more trustworthy inventory) to driving a global aerosol-climate model separately. We further show that some widely adopted CMIP6 pathways (after 2015) also significantly underestimate the more recent decline in AA emissions over China. These flaws may bring about errors to the CMIP6-based regional climate attribution over Asia for the last two decades and projection for the next few decades, previously anticipated to inform a wide range of impact analysis.
Shifts in honeybee foraging reveal historical changes in floral resources
Authors: Jones Laura , Brennan Georgina L. , Lowe Abigail , Creer Simon , Ford Col R. , de Vere Natasha
Published: January 2021

Decreasing floral resources as a result of habitat loss is one of the key factors in the decline of pollinating insects worldwide. Understanding which plants pollinators use is vital to inform the provision of appropriate floral resources to help prevent pollinator loss. Using a globally important pollinator, the honeybee, we show how changes in agricultural intensification, crop use and the spread of invasive species, have altered the nectar and pollen sources available in the UK. Using DNA metabarcoding, we analysed 441 honey samples from 2017 and compared these to a nationwide survey of honey samples from 1952. We reveal that shifts in major plants foraged by honeybees are driven by changes in the availability of these plants within the landscape. Improved grasslands are the most widespread habitat type in the UK, and management changes within this habitat have the greatest potential to increase floral resource availability.
Room-temperature ppb-level SO2 gas sensors based on RGO/WO3 and MWCNTs/WO3 nanocomposites
Authors: Su Pi-Guey , Zheng Yu-Ling
Published: January 2021

ppb-level SO2 gas sensors that were made of multi-walled carbon nanotubes/WO3 (MWCNTs/WO3) and reduced graphene oxide/WO3 (RGO/WO3) for use at room-temperature.
2D phosphorene nanosheets, quantum dots, nanoribbons: synthesis and biomedical applications
Authors: Liu Xifeng , Gaihre Bipin , George Matthew N. , Li Yong , Tilton Maryam , Yaszemski Michael J. , Lu Lichun
Published: January 2021

This review extensively summarized the properties and synthesis methods for phosphorene nanosheets, quantum dots, nanoribbons and their most-recent biomedical applications in bone, nerve, skin, brain, kidney, biosensor, and cancer related fields.
Mechanism-based inhibitors of SIRT2: structure–activity relationship, X-ray structures, target engagement, regulation of α-tubulin acetylation and inhibition of breast cancer cell migration
Authors: Nielsen Alexander L. , Rajabi Nima , Kudo Norio , Lundø Kathrine , Moreno-Yruela Carlos , Bæk Michael , Fontenas Martin , Lucidi Alessia , Madsen Andreas S. , Yoshida Minoru , Olsen Christian A.
Published: January 2021

Sirtuin 2 (SIRT2) is a protein deacylase enzyme that removes acetyl groups and longer chain acyl groups from post-translationally modified lysine residues. Here, we developed small peptide-based inhibitors of its activity in living cells in culture.
Mitochondria specific highly cytoselective iridium(iii)–Cp* dipyridophenazine (dppz) complexes as cancer cell imaging agents
Authors: Roy Nilmadhab , Sen Utsav , Ray Chaudhuri Shreya , Muthukumar Venkatesan , Moharana Prithvi , Paira Priyankar , Bose Bipasha , Gauthaman Ashna , Moorthy Anbalagan
Published: January 2021

We have developed target specific, highly cytoselective, lipophilic and water soluble iridium(iii)–Cp* dipyridophenazine (dppz) cancer theranostic drugs.
Emerging investigator series: emerging disinfection by-product quantification method for wastewater reuse: trace level assessment using tandem mass spectrometry
Authors: Ortega-Hernandez Alejandro , Acayaba Raphael , Verwold Chad , Montagner Cassiana Carolina , Kimura Susana Y.
Published: January 2021

A sensitive analytical method was developed that simultaneously characterizes 25 unregulated DBPs in wastewater effluents. DBP formation potential with HOCl and NH2Cl was evaluated across a full-scale wastewater reuse facility for the first time.
Chemical modulation of Kv7 potassium channels
Authors: Borgini Matteo , Mondal Pravat , Liu Ruiting , Wipf Peter
Published: January 2021

This review describes the synthetic and medicinal chemistry of small molecule modulators of the voltage-gated Kv7 (KCNQ) potassium channels and the available data of their biological and clinical properties.
N-Heterocyclic carbene (NHC)-catalyzed intramolecular benzoin condensation–oxidation
Authors: Satyam Killari , Ramarao Jakkula , Suresh Surisetti
Published: January 2021

NHC-Catalyzed intramolecular benzoin condensation–oxidation has been disclosed for the expedient synthesis of diverse seven-membered heterocyclic 1,2-diketones in good to excellent yields, under ambient conditions.
Synthesis and characterization of bipyridine cobalt(ii) complex modified graphite screen printed electrode: an electrochemical sensor for simultaneous detection of acetaminophen and naproxen
Authors: Kondori Tahere , Tajik Somayeh , Akbarzadeh-T Niloufar , Beitollahi Hadi , Graiff Cloudia , Jang Ho Won , Shokouhimehr Mohammadreza
Published: January 2021

The new Co(ii) compound [Co(5,5′-dmbpy)2(NCS)2] (a1) was prepared by reacting Co(NO3)2·6H2O, 5,5′-dimethyl-2,2′-bipyridine ligand, and Na(SCN).
Characterizing the structure–activity relationships of natural products, tanshinones, reveals their mode of action in inhibiting spleen tyrosine kinase
Authors: Tung Min-Che , Tsai Keng-Chang , Fung Kit-Man , Don Ming-Jaw , Tseng Tien-Sheng
Published: January 2021

The cytosolic non-receptor protein kinase, spleen tyrosine kinase (SYK), is an attractive drug target in autoimmune, inflammatory disorder, and cancers indications.
Band structure regulation in Fe-doped MgZnO by initial magnetic moments
Authors: Zheng Licheng , Yao Qi , Wang Hao , Zhan Huahan , Cai Wenwei , Zhou Yinghui , Kang Junyong
Published: January 2021

The optoelectronic and magnetic properties of Fe-doped MgZnO are regulated by the Fe dopant and its initial magnetic moments.