bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological Evaluation of [18F]AlF-NOTA-NSC-GLU as a Positron Emission Tomography Tracer for Hepatocellular Carcinoma
Authors: Lin Liping , Xiang Xianhong , Su Shu , Liu Shaoyu , Xiong Ying , Ma Hui , Yuan Gongjun , Nie Dahong , Tang Ganghua
Published: April 2021

Purpose: N-(2-[18F]fluoropropionyl)-L-glutamate ([18F]FPGLU) for hepatocellular carcinoma (HCC) imaging has been performed in our previous studies, but its radiosynthesis method and stability in vivo need to be improved. Hence, we evaluated the synthesis and biological properties of a simple [18F]-labeled glutamate analog, [18F]AlF-1,4,7-triazacyclononane-1,4,7-triacetic-acid-2-S-(4-isothiocyanatobenzyl)-l-glutamate ([18F]AlF-NOTA-NSC-GLU), for HCC imaging.

Procedures: [18F]AlF-NOTA-NSC-GLU was synthesized via a one-step reaction sequence from NOTA-NSC-GLU. In order to investigate the imaging value of [18F]AlF-NOTA-NSC-GLU in HCC, we conducted positron emission tomography/computed tomography (PET/CT) imaging and competitive binding of [18F]AlF-NOTA-NSC-GLU in human Hep3B tumor-bearing mice. The transport mechanism of [18F]AlF-NOTA-NSC-GLU was determined by competitive inhibition and protein incorporation experiments in vitro.

Results: [18F]AlF-NOTA-NSC-GLU was prepared with an overall radiochemical yield of 29.3 ± 5.6% (n = 10) without decay correction within 20 min. In vitro competitive inhibition experiments demonstrated that the Na+-dependent systems XAG-, B0+, ASC, and minor XC- were involved in the uptake of [18F]AlF-NOTA-NSC-GLU, with the Na+-dependent system XAG- possibly playing a more dominant role. Protein incorporation studies of the Hep3B human hepatoma cell line showed almost no protein incorporation. Micro-PET/CT imaging with [18F]AlF-NOTA-NSC-GLU showed good tumor-to-background contrast in Hep3B human hepatoma-bearing mouse models. After [18F]AlF-NOTA-NSC-GLU injection, the tumor-to-liver uptake ratio of [18F]AlF-NOTA-NSC-GLU was 2.06 ± 0.17 at 30 min post-injection. In vivo competitive binding experiments showed that the tumor-to-liver uptake ratio decreased with the addition of inhibitors to block the XAG system.

Conclusions: We have successfully synthesized [18F]AlF-NOTA-NSC-GLU as a novel PET tracer with good radiochemical yield and high radiochemical purity. Our findings indicate that [18F]AlF-NOTA-NSC-GLU may be a potential candidate for HCC imaging. Also, a further biological evaluation is underway.
Recent Advances in TiO2-Based Heterojunctions for Photocatalytic CO2 Reduction With Water Oxidation: A Review
Authors: Li Kai , Teng Chao , Wang Shuang , Min Qianhao
Published: April 2021

Photocatalytic conversion of CO2 into solar fuels has gained increasing attention due to its great potential for alleviating the energy and environmental crisis at the same time. The low-cost TiO2 with suitable band structure and high resistibility to light corrosion has proven to be very promising for photoreduction of CO2 using water as the source of electrons and protons. However, the narrow spectral response range (ultraviolet region only) as well as the rapid recombination of photo-induced electron-hole pairs within pristine TiO2 results in the low utilization of solar energy and limited photocatalytic efficiency. Besides, its low selectivity toward photoreduction products of CO2 should also be improved. Combination of TiO2 with other photoelectric active materials, such as metal oxide/sulfide semiconductors, metal nanoparticles and carbon-based nanostructures, for the construction of well-defined heterostructures can enhance the quantum efficiency significantly by promoting visible light adsorption, facilitating charge transfer and suppressing the recombination of charge carriers, resulting in the enhanced photocatalytic performance of the composite photocatalytic system. In addition, the adsorption and activation of CO2 on these heterojunctions are also promoted, therefore enhancing the turnover frequency (TOF) of CO2 molecules, so as to the improved selectivity of photoreduction products. This review focus on the recent advances of photocatalytic CO2 reduction via TiO2-based heterojunctions with water oxidation. The rational design, fabrication, photocatalytic performance and CO2 photoreduction mechanisms of typical TiO2-based heterojunctions, including semiconductor-semiconductor (S-S), semiconductor-metal (S-M), semiconductor-carbon group (S-C) and multicomponent heterojunction are reviewed and discussed. Moreover, the TiO2-based phase heterojunction and facet heterojunction are also summarized and analyzed. In the end, the current challenges and future prospects of the TiO2-based heterostructures for photoreduction of CO2 with high efficiency, even for practical application are discussed.
Macroscale Superlubricity Accomplished by Sb2O3-MSH/C Under High Temperature
Authors: Gao Kai , Wang Bin , Shirani Asghar , Chang Qiuying , Berman Diana
Published: April 2021

Here, we report the high-temperature superlubricity phenomenon accomplished in coatings produced by burnishing powders of antimony trioxide (Sb2O3) and magnesium silicate hydroxide coated with carbon (MSH/C) onto the nickel superalloy substrate. The tribological analysis performed in an open-air experimental setup revealed that with the increase of testing temperature, the coefficient of friction (COF) of the coating gradually decreases, finally reaching the superlubricity regime (the COF of 0.008) at 300°C. The analysis of worn surfaces using in-situ Raman spectroscopy suggested the synergistic effect of the inner Sb2O3 adhesion layer and the top MSH/C layer, which do not only isolate the substrate from the direct exposure to sliding but also protect it from oxidation. The cross-sectional transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) results indicated the tribochemically-activated formation of an amorphous carbon layer on the surface of the coating during sliding. Formation of the film enables the high-temperature macroscale superlubricity behavior of the material system.
Preparation of Graphene Oxide-Embedded Hydrogel as a Novel Sensor Platform for Antioxidant Activity Evaluation of Scutellaria baicalensis
Authors: Yan Shuai , Yue Yinzi , Zeng Li , Su Lianlin , Hao Min , Zhang Wei , Wang Xiaopeng
Published: April 2021

Antioxidation is very important in medicine and food. The current evaluation technologies often have many shortcomings. In this work, an improved electrochemical sensing platform for the evaluation of antioxidant activity has been proposed. A hydrogel was prepared based on graphene oxide, zinc ions, and chitosan. Zinc ions play the role of crosslinking agents in hydrogels. The structure of chitosan can be destroyed by injecting hydrogen peroxide into the hydrogel, and the free zinc ions can diffuse to the surface of the electrode to participate in the electrochemical reaction. This electrochemical sensor can evaluate the antioxidant activity by comparing the current difference of zinc reduction before and after adding the antioxidant. With the help of graphene oxide, this hydrogel can greatly enhance the sensing effect. We conducted tests on 10 real samples. This proposed electrochemical platform has been successfully applied for evaluating the antioxidant activity of Scutellaria baicalensis, and the results were compared to those obtained from the 2,2-diphenyl-1-picrylhydrazyl-based traditional analysis technique.
Stool Banking for Fecal Microbiota Transplantation: Methods and Operations at a Large Stool Bank
Authors: Chen Justin , Zaman Amanda , Ramakrishna Bharat , Olesen Scott W.
Published: April 2021

Objectives

Fecal microbiota transplantation (FMT) is a recommended therapy for recurrent Clostridioides difficile infection and is being investigated as a potential therapy for dozens of microbiota-mediated indications. Stool banks centralize FMT donor screening and FMT material preparation with the goal of expanding access to FMT material while simultaneously improving its safety, quality, and convenience. Although there are published consensuses on donor screening guidelines, there are few reports about the implementation of those guidelines in functioning stool banks.

Methods

To help inform consensus standards with data gathered from real-world settings and, in turn, to improve patient care, here we describe the general methodology used in 2018 by OpenBiome, a large stool bank, and its outputs in that year.

Results

In 2018, the stool bank received 7,536 stool donations from 210 donors, a daily average of 20.6 donations, and processed 4,271 of those donations into FMT preparations. The median time a screened and enrolled stool donor actively donated stool was 5.8 months. The median time between the manufacture of an FMT preparation and its shipment to a hospital or physician was 8.9 months. Half of the stool bank’s partner hospitals and physicians ordered an average of 0.75 or fewer FMT preparations per month.

Conclusions

Further knowledge sharing should help inform refinements of stool banking guidelines and best practices.
Citizen Sensing: An Action-Orientated Framework for Citizen Science
Authors: Coulson Saskia , Woods Mel ,   Making Sense EU
Published: April 2021

Citizen Sensing, a correlative of Citizen Science, employs low-cost sensors to evidence local environmental issues and empowers citizens to use the data they collect. Whilst motivations for participation can vary, communities affected by pollution frequently have changemaking as their goal. Social innovation is closely aligned with citizen sensing, however the process of co-creating practices and solutions with citizens who wish to shape their world can be highly complex to design. Therefore, our research articulates an action-orientated framework which emerges from a 2-year pan European project by which follow-on communities may replicate sensing initiatives more easily. The authors examine five studies and explore the cross-cutting principles, phases, stakeholders, methods, and challenges which form this framework. The authors argue that whilst data collection and data awareness are crucial to the citizen sensing process, there are precursory and subsequent stages which are necessary to equip citizens to address complex environmental challenges and take action on them. Therefore, this paper focuses on the stages and methods which are distinctive to citizen sensing. It concludes with recommendations for future practice for citizen sensing and citizen science.
Sortilin as a Biomarker for Cardiovascular Disease Revisited
Authors: Møller Peter Loof , Rohde Palle D. , Winther Simon , Breining Peter , Nissen Louise , Nykjaer Anders , Bøttcher Morten , Nyegaard Mette , Kjolby Mads
Published: April 2021

Genetic variants in the genomic region containing SORT1 (encoding the protein sortilin) are strongly associated with cholesterol levels and the risk of coronary artery disease (CAD). Circulating sortilin has therefore been proposed as a potential biomarker for cardiovascular disease. Multiple studies have reported association between plasma sortilin levels and cardiovascular outcomes. However, the findings are not consistent across studies, and most studies have small sample sizes. The aim of this study was to evaluate sortilin as a biomarker for CAD in a well-characterized cohort with symptoms suggestive of CAD. In total, we enrolled 1,173 patients with suspected stable CAD referred to coronary computed tomography angiography. Sortilin was measured in plasma using two different technologies for quantifying circulating sortilin: a custom-made enzyme-linked immunosorbent assay (ELISA) and OLINK Cardiovascular Panel II. We found a relative poor correlation between the two methods (correlation coefficient = 0.21). In addition, genotyping and whole-genome sequencing were performed on all patients. By whole-genome regression analysis of sortilin levels measured with ELISA and OLINK, two independent cis protein quantitative trait loci (pQTL) on chromosome 1p13.3 were identified, with one of them being a well-established risk locus for CAD. Incorporating rare genetic variants from whole-genome sequence data did not identify any additional pQTLs for plasma sortilin. None of the traditional CAD risk factors, such as sex, age, smoking, and statin use, were associated with plasma sortilin levels. Furthermore, there was no association between circulating sortilin levels and coronary artery calcium score (CACS) or disease severity. Sortilin did not improve discrimination of obstructive CAD, when added to a clinical pretest probability (PTP) model for CAD. Overall, our results indicate that studies using different methodologies for measuring circulating sortilin should be compared with caution. In conclusion, the well-known SORT1 risk locus for CAD is linked to lower sortilin levels in circulation, measured with ELISA; however, the effect sizes are too small for sortilin to be a useful biomarker for CAD in a clinical setting of low- to intermediate-risk chest-pain patients.
A New Extreme Detection Method for Remote Compound Extremes in Southeast China
Authors: Wang Luqing , Zhao Qinglin , Gao Si , Zhang Wei , Feng Li
Published: April 2021

The compound heat wave and extreme precipitation events are responsible for severe damages to the environment and human societies. Although major advances have been made in understanding the compound extremes (e.g., drought and heat wave), little is known about two types of extremes synchronized/connected in different regions in China. Here we identify a new type of compound extreme termed as “remote compound extreme” with the aid of a new extreme value detection method that combines isolated forest and quantile statistics. The new compound extremes are reflected by a statistically significant correlation (i.e., 0.52) between heat wave in the Pearl River Delta and extreme precipitation in the Yangtze River Delta. The remote compound extreme may be tied to the western Pacific subtropical high that modulates typhoons, surface temperature in the Pearl River Delta and extreme precipitation in the middle and lower reaches of the Yangtze River.
Multi-Proxy Records of Late Holocene Flood Events From the Lower Reaches of the Narmada River, Western India
Authors: Sukumaran Prabhin , Sant Dhananjay A. , Krishnan K. , Rangarajan Govindan , Basavaiah Nathani , Schwenninger Jean-Luc
Published: April 2021

Analyses of a fluvial sedimentary sequence from the lower reaches of the Narmada River establish a record of rhythmic cycles of sediment facies that represent floods during the late Holocene. The south-west Indian monsoon strongly influences the study area, and heavy rainfall or cyclones which originate from either the Bay of Bengal or the Arabian Sea, also affect the region. Optically stimulated luminescence dating places the 8 m thick sediment sequence in the climate transition phase which ranges from the Medieval Warm Period to the Little Ice Age. Multi-proxy analyses including high-resolution granulometry, magnetic susceptibility, ferromagnetic mineral concentration, facies major oxide geochemistry, and micro-fossil records (from two sedimentary units) are used to study these late Holocene flood events. The latter are characterised by multiple sediment facies, depositional events, changes in channel morphology, and distinctive flood signatures. Integration of these records enables to identify two distinct aggradations viz. phase I and phase II, as well as a relative change in channel morphology. The study describes 11 flooding events and their imprints over multi-proxy records. Historic documents and instrumental records from the town of Bharuch referring to floods, movement of channel sand, channel shallowing, and the dysfunction of the ancient port of Bharuch further validate the inferences drawn from the sedimentary sequence. The study exemplifies the need to use high resolution and multi-proxy studies to interpret paleoflood records and climate signatures in order to build archives of monsoonal rivers.
Evaluation of Precipitation in the Chinese Regional Reanalysis Using Satellite Estimates, Gauge-Based Observations and Global Reanalysis
Authors: Lu Yutong , Shao Min , Fang Juan , Pan Yinong , Tang Jianping
Published: April 2021

Two high-resolution Chinese regional reanalysis (CNRR) datasets at a resolution of 18 km during the period of 1998–2009 are generated by Gridpoint Statistical Interpolation (GSI) data assimilation system and spectral nudging (SN) method. The precipitation from CNRR is comprehensively evaluated against the observational datasets and global reanalysis ERA5 over East-Asia. The climatology mean, seasonal variability, extreme events, and summer diurnal cycle of precipitation are analyzed. Results show that CNRR reasonably reproduces the observed characteristics of rainfall, although some biases exist. The spatial distribution of climatology mean precipitation is well simulated by CNRR, while overestimation exists especially on the west side of Tibetan-Plateau (TP). CNRR reproduces the unimodal feature of the annual cycle with overestimations of summer precipitation, and well produces the probability of light and moderate rainfall but tend to overestimate heavy and extreme precipitation over most regions in China. The overall spatial distribution of extreme precipitation indices can be captured by CNRR. The diurnal cycle of summer precipitation, as well as the amplitude of diurnal cycle, are better reproduced by CNRR-GSI, capturing eastward propagation of diurnal phase from TP along the Yangtze River. CNRR-GSI generally outperforms CNRR-SN over most regions of China except in reproducing heavy and extreme rainfall in the Yangtze River Basin (YRB) and South China (SC) regions. CNRR-GSI shows comparable results with the latest ERA5 and outperforms it in simulating the diurnal cycle of precipitation. This dataset can be considered as a reliable source for precipitation related applications.
Decentralized Fast Delayed Signal Cancelation Secondary Control for Low Voltage Ride-Through Application in Grid Supporting Grid Feeding Microgrid
Authors: Buraimoh Elutunji , Davidson Innocent E. , Martinez-Rodrigo Fernando
Published: April 2021

In this study, a distributed secondary control is proposed alongside the conventional primary control to form a hierarchical control scheme for the Low Voltage Ride-Through (LVRT) control and applications in the inverter-based microgrid. The secondary control utilizes a fast Delayed Signal Cancelation (DSC) algorithm for the secondary control loop to control the reactive and active power reference by controlling the sequences generated. The microgrid consists of four Distributed Energy Resources (DER) sources interfaced to the grid through interfacing inverters coordinated by droop for effective power-sharing according to capacities. The droop also allows for grid supporting application for microgrid’s participation in frequency and voltage regulation in the main grid. The proposed decentralized fast DSC performance is evaluated with centralized secondary and traditional primary control using OPAL-RT Lab computation and MATLAB/SIMULINK graphical user interface for offline simulations and real-time digital simulator verification. This study presents and discusses the results.
Mining Subsidence-Induced Microtopographic Effects Alter the Interaction of Soil Bacteria in the Sandy Pasture, China
Authors: Zhang Qi , Ma Jing , Yang Yongjun , Luo Zhanbin , Wang Yifei , Chen Fu
Published: April 2021

The microtopographic changes induced by coal mining subsidence caused a series of environmental problems such as soil erosion, and vegetation degradation in the mining area. However, the corresponding influence on surface vegetation and soil characteristic in different parts of the slope was completely different. To understand soil and vegetation degradation in coal mines and their future ecological restoration, it was crucial to investigate the origin. The relationship between soil microbial community diversity, structure, and taxa in the slope of subsidence area of different topographic locations in Daliuta coal mine, Shannxi, China, was determined by high throughput sequencing and molecular ecological network analysis. The relationship between the bacterial communities, environmental factors, and soil physicochemical properties was also investigated. We found a new topographic trait formed by surface subsidence to deteriorate the living environment of vegetation and the bacterial community. The vegetation coverage, soil water content, organic matter, and urease and dehydrogenase activities decreased significantly (p < 0.05). Although soil bacterial community diversity in the subsidence area did not differ significantly, the dominant taxa in different topographic locations varied. The molecular ecological networks representing bacterial community structure and function were also totally different. The networks in the middle and the top of the slope tend to be more complicated, and the interaction between species is obviously stronger than that of the bottom. However, the network in the bottom slope approached simplicity, and weak interaction, predominantly cooperative, was observed within and between modules. Meanwhile, the double stress of aridity and the lack of carbon source induced by subsidence also enhanced the capacity of the soil bacterial community to metabolize complex carbon sources at the bottom of the slope.
Analysis of mRNA Expression and DNA Methylation Datasets According to the Genomic Distribution of CpG Sites in Osteoarthritis
Authors: Yi Peng , Xu Xiongfeng , Yao Jiawei , Qiu Bo
Published: April 2021

Abstract Objectives Transcriptional changes in cartilage can impact function by causing degradation such as that which occurs during the development of osteoarthritis (OA). Epigenetic regulation may be a key factor leading to transcriptional changes in OA. In this study, we performed a combined analysis of DNA methylation and gene expression microarray datasets and identified key transcription factors (TFs) central to the regulation of gene expression in OA. Methods A DNA methylation profile dataset (GSE63106) and a gene expression profiling dataset (GSE114007) were extracted from the Gene Expression Omnibus (GEO). We used ChAMP methylation analysis and the Limma package to identify differentially methylation genes (DMGs) and differentially expressed genes (DEGs) from normal and human knee cartilage samples in OA. Function enrichment analysis of DMGs was conducted using the DAVID database. A combined analysis of DEGs and DMGs was conducted to identify key TFs in OA. We then validated the mRNA expression of selected TFs in normal and OA cartilage by RT-qPCR. Primary chondrocytes were cultured and treated with the DNA methylation inhibitor 5-Aza-2-deoxycytidine (5-Aza) for functional validation. Results We identified 2,170 differential methylation sites (DMS) containing 1005 genes and 1986 DEGs between normal human and OA cartilage. Functional analysis of DMGs revealed that focal adhesion, extracellular matrix (ECM)-receptor interactions, the PI3K-Akt signaling pathway, and the FoxO signaling pathway were involved in OA. Integrated analysis showed a subset of 17 TFs. Four TFs (ELF3, SOX11, RARA, and FOXD2) were validated. RT-qPCR results showed the mRNA expression of SOX11, RARA, and FOXD2 were consistent with the results from the mRNA expression data. However, the expression of ELF3 could not be validated. Upon 5-Aza-2′-deoxycytidine (5-Aza) treatment, the mRNA levels of ELF3 and SOX11 were down-regulated, whilst RARA was up-regulated, and FOXD2 showed no significant change in expression level. Conclusions the effect of DNA methylation on the transcriptional regulation is related to the distribution of methylated sites across the genome. Epigenetic studies on the positions of DMS in transcriptional units can inform a better understanding of the function of DNA methylation and its transcription regulation.
Autophagy-Related Long Non-coding RNA Signature as Indicators for the Prognosis of Uveal Melanoma
Authors: Cui Yi , Zheng Mi , Chen Jing , Xu Nuo
Published: April 2021

This study aimed to develop an autophagy-associated long non-coding RNA (lncRNA) signature to predict the prognostic outcomes of uveal melanoma (UM). The data of UM from The Cancer Genome Atlas (TCGA) were enrolled to obtain differentially expressed genes (DEGs) between metastasizing and non-metastasizing UM patients. A total of 13 differentially expressed autophagy genes were identified and validated in Gene Expression Omnibus, and 11 autophagy-related lncRNAs were found to be associated with overall survival. Through performing least absolute shrinkage and selection operator regression analyses, a six-autophagy-related lncRNA signature was built, and its efficacy was confirmed by receiver-operating characteristic, Kaplan–Meier analysis, and univariate and multivariate Cox regression analyses. A comprehensive nomogram was established and its clinical net benefit was validated by decision curve analysis. GSEA revealed that several biological processes and signaling pathways including Toll-like receptor signaling pathway, natural killer cell-mediated cytotoxicity, and B- and T-cell receptor signaling pathway were enriched in the high-risk group. CIBERSORT results showed that the signature was related to the immune response especially HLA expression. This signature could be deployed to assist clinicians to identify high-risk UM patients and help scientists to explore the molecular mechanism of autophagy-related lncRNAs in UM pathogenesis.
Identification of miRNA in Sheep Intramuscular Fat and the Role of miR-193a-5p in Proliferation and Differentiation of 3T3-L1
Authors: Han Fuhui , Zhou Lisheng , Zhao Le , Wang Lei , Liu Lirong , Li Haijuan , Qiu Jixian , He Jianning , Liu Nan
Published: April 2021

Intramuscular fat (IMF) is one of the most critical parameters affecting meat quality and mainly affected by genetic factors. MicroRNA as an important regulatory factor, which is still a lack of research in the development of sheep IMF deposition. We used RNA sequencing (RNA-seq) and cell-level validation to explore the role of miRNA in IMF deposition. As for this purpose, longissimus thoracis et lumborum (LTL) samples of 2 month-old (Mth-2) and 12 months-old (Mth-12) Aohan fine-wool sheep (AFWS) were used to identified miRNAs expression. We found 59 differentially expressed miRNAs (DE-miRNA) between these age groups and predicted their 1,796 target genes. KEGG functional enrichment analysis revealed eight pathways involved in lipid metabolism-related processes, including fatty acid elongation and the AMPK signaling pathway. A highly expressed DE-miRNA, miR-193a-5p, was found to serve a function in 3T3-L1 preadipocyte differentiation. Luciferase assay demonstrated that miR-193a-5p directly binds to the 3′-UTR region of ACAA2. By constructing mimics and inhibitor vector transfecting into 3T3-L1 cells to explore the effect of miR-193a-5p on cell proliferation and differentiation, we demonstrated that overexpression of miR-193a-5p inhibited 3T3-L1 preadipocyte proliferation, as evidenced by decreased mRNA and protein expression of CDK4 and CyclinB. CCK-8 assay showed that miR-193a-5p significantly inhibited cell proliferation. Similarly, the overexpression of miR-193a-5p inhibited 3T3-L1 preadipocyte differentiation and adipocyte-specific molecular markers’ expression, leading to a decrease in PPARγ and C/EBPα and ACAA2. Inhibition of miR-193a-5p had the opposite effects. Our study lists the miRNAs associated with intramuscular lipid deposition in sheep and their potential targets, striving to improve sheep meat quality.
Airway Telomere Length in Lung Transplant Recipients
Authors: Mackintosh John A. , Yerkovich Stephanie T. , Tan Maxine E. , Samson Luke , Hopkins Peter MA , Chambers Daniel C.
Published: April 2021

Introduction

Chronic lung allograft dysfunction (CLAD) represents the major impediment to long term survival following lung transplantation. Donor and recipient telomere length have been shown to associate with lung transplant outcomes, including CLAD. In this study we aimed to measure the telomere lengths of bronchial and bronchiolar airway cells in lung allografts early after transplantation and to investigate associations with CLAD and all-cause mortality.

Methods

This prospective, longitudinal study was performed at The Prince Charles Hospital, Australia. Airway cells were collected via bronchial and bronchiolar airway brushings at post-transplant bronchoscopies. The relative telomere length in airway cells was determined by quantitative PCR based on the T/S ratio. All patients were censored for CLAD and all-cause mortality in August 2020.

Results

In total 231 bronchoscopies incorporating transbronchial brush and bronchial brush were performed in 120 patients. At the time of censoring, 43% and 35% of patients, respectively, had developed CLAD and had died. Airway bronchiolar and bronchial telomere lengths were strongly correlated (r=0.78, p<0.001), confirming conservation of telomere length with airway branch generation. Both the bronchiolar (r = -0.34, p<0.001) and bronchial (r = -0.31, p<0.001) telomere length decreased with age. Shorter airway telomere length was associated with older donor age and higher donor pack-year smoking history. Neither the bronchiolar nor the bronchial airway telomere length were associated with the development of CLAD (HR 0.39 (0.06-2.3), p=0.30; HR 0.66 (0.2-1.7), p=0.39, respectively) or all-cause mortality (HR 0.92 (0.2-4.5), p=0.92; HR 0.47 (0.1-1.9), p=0.28, respectively).

Conclusions

In this cohort, airway telomere length was associated with donor age and smoking history but was not associated with the future development of CLAD or all-cause mortality.
Endoplasmic Reticulum-Mitochondria Crosstalk and Beta-Cell Destruction in Type 1 Diabetes
Authors: Vig Saurabh , Lambooij Joost M. , Zaldumbide Arnaud , Guigas Bruno
Published: April 2021

Beta-cell destruction in type 1 diabetes (T1D) results from the combined effect of inflammation and recurrent autoimmunity. In response to inflammatory signals, beta-cells engage adaptive mechanisms where the endoplasmic reticulum (ER) and mitochondria act in concert to restore cellular homeostasis. In the recent years it has become clear that this adaptive phase may trigger the development of autoimmunity by the generation of autoantigens recognized by autoreactive CD8 T cells. The participation of the ER stress and the unfolded protein response to the increased visibility of beta-cells to the immune system has been largely described. However, the role of the other cellular organelles, and in particular the mitochondria that are central mediator for beta-cell survival and function, remains poorly investigated. In this review we will dissect the crosstalk between the ER and mitochondria in the context of T1D, highlighting the key role played by this interaction in beta-cell dysfunctions and immune activation, especially through regulation of calcium homeostasis, oxidative stress and generation of mitochondrial-derived factors.
Modeling of Virus Survival Time in Respiratory Droplets on Surfaces: A New Rational Approach for Antivirus Strategies
Authors: Di Novo N. G. , Carotenuto A. R. , Mensitieri G. , Fraldi M. , Pugno N. M.
Published: April 2021

The modeling of the viability decay of viruses in sessile droplets is addressed considering a droplet sitting on a smooth surface characterized by a specific contact angle. To investigate, at prescribed temperature, how surface energy of the material and ambient humidity cooperate to determine the virus viability, we propose a model which involves the minimum number of thermodynamically relevant parameters. In particular, by considering a saline water droplet (one salt) as the simplest approximation of real solutions (medium and natural/artificial saliva), the evaporation is described by a first-order time-dependent nonlinear differential equation properly rearranged to obtain the contact angle evolution as the sole unknown function. The analyses were performed for several contact angles and two typical droplet sizes of interest in real situations by assuming constant ambient temperature and relative humidity in the range 0–100%. The results of the simulations, given in terms of time evolution of salt concentration, vapor pressure, and droplet volume, elucidate some previously not yet well-understood dynamics, demonstrating how three main regimes—directly implicated in nontrivial trends of virus viability and to date only highlighted experimentally—can be recognized as the function of relative humidity. By recalling the concept of cumulative dose of salts (CD), to account for the effect of the exposition of viruses to salt concentration on virus viability, we show how the proposed approach could suggest a chart of a virus fate by predicting its survival time at a given temperature as a function of the relative humidity and contact angle. We found a good agreement with experimental data for various enveloped viruses and predicted in particular for the Phi6 virus, a surrogate of coronavirus, the characteristic U-shaped dependence of viability on relative humidity. Given the generality of the model and once experimental data are available that link the vulnerability of a certain virus, such as SARS-CoV-2, to the concentrations of salts or other substances in terms of CD, it is felt that this approach could be employed for antivirus strategies and protocols for the prediction/reduction of human health risks associated with SARS-CoV-2 and other viruses.
Bond Behavior of Steel-Recycled Aggregate Concrete Interface After High Temperatures and Spraying Water Cooling
Authors: Zhou Chunheng , Cao Jiazhang , Chen Zongping
Published: April 2021

Using recycled aggregate concrete (RAC) in steel-reinforced concrete structure is an effective way to eliminate the adverse effects of recycled aggregate, which has an excellent application prospect. Fire has a great destructiveness to steel-reinforced recycled aggregate concrete (SRRAC) structure; hence, the bond performance of SRRAC after high temperature, as the prerequisite for the composite between steel and RAC, is the key problem for structural safety and the corresponding safety assessment after fire. In this article, the residual bond behaviors of steel-recycled aggregate concrete interface after different high temperatures and spraying water cooling were studied through the push-out test. The failure modes and load–slip curves were examined. The ultimate bond strength, residual bond strength, and elastic bond shear stiffness of specimens after high temperature and cooling for the regime of spraying water were evaluated and compared to that of natural air. A parametric analysis of temperature, replacement percentage, and studs was conducted. A calculation approach for the ultimate bond strength and residual bond strength of SRRAC after high temperature was developed based on the sensitive analysis of gray system theory and regression analysis. Results showed that the bond properties of SRRAC specimens after high temperature were decreased as exposure temperature increased. The cooling regime of spraying water has a more significant influence on the ultimate strength and residual strength than that of natural air. The specimens with studs on both flange and web have the highest bond properties after high temperature. In all the factors, the number of studs showed the largest gray relational degree to the bond strength of SRRAC. The developed approach provided a reliable prediction of bond strength for SRRAC after high temperature.
Uremic Toxins in Organ Crosstalk
Authors: Lowenstein Jerome , Nigam Sanjay K.
Published: April 2021

Many putative uremic toxins—like indoxyl sulfate, p-cresol sulfate, kynurenic acid, uric acid, and CMPF—are organic anions. Both inter-organ and inter-organismal communication are involved. For example, the gut microbiome is the main source of indole, which, after modification by liver drug metabolizing enzymes (DMEs), becomes indoxyl sulfate. Various organic anion transporters (organic anion transporters, OATs; organic anion-transporting polypeptides, OATPs; multidrug resistance-associated proteins, MRPs, and other ABC transporters like ABCG2)—often termed “drug transporters”—mediate movement of uremic toxins through cells and organs. In the kidney proximal tubule, critical roles for OAT1 and OAT3 in regulating levels of protein-bound uremic toxins have been established using knock-out mice. OATs are important in maintaining residual tubular function in chronic kidney disease (CKD); as CKD progresses, intestinal transporters like ABCG2, which extrude urate and other organic anions into the gut lumen, seem to help restore homeostasis. Uremic toxins like indoxyl sulfate also regulate signaling and metabolism, potentially affecting gene expression in extra-renal tissues as well as the kidney. Focusing on the history and evolving story of indoxyl sulfate, we discuss how uremic toxins appear to be part of an extensive “remote sensing and signaling” network—involving so-called drug transporters and drug metabolizing enzymes which modulate metabolism and signaling. This systems biology view of uremic toxins is leading to a new appreciation of uremia as partly due to disordered remote sensing and signaling mechanisms–resulting from, and causing, aberrant inter-organ (e.g., gut-liver- kidney-CNS) and inter-organismal (e.g., gut microbiome-host) communication.
A Deep Learning Based Framework for Diagnosing Multiple Skin Diseases in a Clinical Environment
Authors: Zhu Chen-Yu , Wang Yu-Kun , Chen Hai-Peng , Gao Kun-Lun , Shu Chang , Wang Jun-Cheng , Yan Li-Feng , Yang Yi-Guang , Xie Feng-Ying , Liu Jie
Published: April 2021

Background: Numerous studies have attempted to apply artificial intelligence (AI) in the dermatological field, mainly on the classification and segmentation of various dermatoses. However, researches under real clinical settings are scarce.

Objectives: This study was aimed to construct a novel framework based on deep learning trained by a dataset that represented the real clinical environment in a tertiary class hospital in China, for better adaptation of the AI application in clinical practice among Asian patients.

Methods: Our dataset was composed of 13,603 dermatologist-labeled dermoscopic images, containing 14 categories of diseases, namely lichen planus (LP), rosacea (Rosa), viral warts (VW), acne vulgaris (AV), keloid and hypertrophic scar (KAHS), eczema and dermatitis (EAD), dermatofibroma (DF), seborrheic dermatitis (SD), seborrheic keratosis (SK), melanocytic nevus (MN), hemangioma (Hem), psoriasis (Pso), port wine stain (PWS), and basal cell carcinoma (BCC). In this study, we applied Google's EfficientNet-b4 with pre-trained weights on ImageNet as the backbone of our CNN architecture. The final fully-connected classification layer was replaced with 14 output neurons. We added seven auxiliary classifiers to each of the intermediate layer groups. The modified model was retrained with our dataset and implemented using Pytorch. We constructed saliency maps to visualize our network's attention area of input images for its prediction. To explore the visual characteristics of different clinical classes, we also examined the internal image features learned by the proposed framework using t-SNE (t-distributed Stochastic Neighbor Embedding).

Results: Test results showed that the proposed framework achieved a high level of classification performance with an overall accuracy of 0.948, a sensitivity of 0.934 and a specificity of 0.950. We also compared the performance of our algorithm with three most widely used CNN models which showed our model outperformed existing models with the highest area under curve (AUC) of 0.985. We further compared this model with 280 board-certificated dermatologists, and results showed a comparable performance level in an 8-class diagnostic task.

Conclusions: The proposed framework retrained by the dataset that represented the real clinical environment in our department could accurately classify most common dermatoses that we encountered during outpatient practice including infectious and inflammatory dermatoses, benign and malignant cutaneous tumors.
Possible Sarcopenia and Impact of Dual-Task Exercise on Gait Speed, Handgrip Strength, Falls, and Perceived Health
Authors: Merchant Reshma Aziz , Chan Yiong Huak , Hui Richard Jor Yeong , Lim Jia Yi , Kwek Sing Cheer , Seetharaman Santhosh K. , Au Lydia Shu Yi , Morley John E.
Published: April 2021

Background: Sarcopenia is defined as a progressive age-related loss in muscle mass and strength affecting physical performance. It is associated with many negative outcomes including falls, disability, cognitive decline, and mortality. Protein enriched diet and resistance training have shown to improve muscle strength and function but there is limited evidence on impact of dual-task exercise in possible sarcopenia.

Objective: To evaluate impact of community-based dual-task exercise on muscle strength and physical function in possible sarcopenia defined by either slow gait (SG) or poor handgrip strength (HGS). The secondary aims include effect on cognition, frailty, falls, social isolation, and perceived health.

Methods: Community-dwelling older adults ≥60 years old were recruited from screening program intended to identify seniors at risk, and invited to participate in dual-task exercise program called HAPPY (Healthy Aging Promotion Program for You). One hundred and eleven participants with possible sarcopenia completed 3 months follow-up. Questionnaire was administered on demographics, frailty, sarcopenia, falls, perceived health, social network, functional, and cognitive status. Physical performance included assessment of HGS, gait speed, and Short Physical Performance Battery test (SPPB).

Results: The mean age of the Exercise group was 75.9 years old and 73.0% were women. The Exercise group had more female (73.0 vs. 47.5%), were older (75.9 vs. 72.5 years old), had higher prevalence of falls (32.4 vs. 15.0%), lower BMI (23.7 vs. 25.8), and education (4.0 vs. 7.2 years). The gait speed of the Exercise group increased significantly with significant reduction in the prevalence of SG and poor HGS. All components of SPPB as well as the total score increased significantly while the prevalence of pre-frailty and falls dropped by half. The risk of social isolation reduced by 25% with significant improvement in perceived health and cognition in the Exercise group. Significant impact on improvement gait speed and SPPB persisted after adjustment for baseline factors.

Conclusion: Dual-task exercise program is effective in improving gait speed, SPPB score, and reducing the prevalence of poor HGS with significant improvement in perceived health, cognition, and reduction in falls and frailty. Future prospective randomized control trials are needed to evaluate the effectiveness of dual-task interventions in reversing sarcopenia.
Detecting Protein Communities in Native Cell Extracts by Machine Learning: A Structural Biologist’s Perspective
Authors: Kyrilis Fotis L. , Belapure Jaydeep , Kastritis Panagiotis L.
Published: April 2021

Native cell extracts hold great promise for understanding the molecular structure of ordered biological systems at high resolution. This is because higher-order biomolecular interactions, dubbed as protein communities, may be retained in their (near-)native state, in contrast to extensively purifying or artificially overexpressing the proteins of interest. The distinct machine-learning approaches are applied to discover protein–protein interactions within cell extracts, reconstruct dedicated biological networks, and report on protein community members from various organisms. Their validation is also important, e.g., by the cross-linking mass spectrometry or cell biology methods. In addition, the cell extracts are amenable to structural analysis by cryo-electron microscopy (cryo-EM), but due to their inherent complexity, sorting structural signatures of protein communities derived by cryo-EM comprises a formidable task. The application of image-processing workflows inspired by machine-learning techniques would provide improvements in distinguishing structural signatures, correlating proteomic and network data to structural signatures and subsequently reconstructed cryo-EM maps, and, ultimately, characterizing unidentified protein communities at high resolution. In this review article, we summarize recent literature in detecting protein communities from native cell extracts and identify the remaining challenges and opportunities. We argue that the progress in, and the integration of, machine learning, cryo-EM, and complementary structural proteomics approaches would provide the basis for a multi-scale molecular description of protein communities within native cell extracts.
Secondary Nucleation and the Conservation of Structural Characteristics of Amyloid Fibril Strains
Authors: Hadi Alijanvand Saeid , Peduzzo Alessia , Buell Alexander K.
Published: April 2021

Amyloid fibrils are ordered protein aggregates and a hallmark of many severe neurodegenerative diseases. Amyloid fibrils form through primary nucleation from monomeric protein, grow through monomer addition and proliferate through fragmentation or through the nucleation of new fibrils on the surface of existing fibrils (secondary nucleation). It is currently still unclear how amyloid fibrils initially form in the brain of affected individuals and how they are amplified. A given amyloid protein can sometimes form fibrils of different structure under different solution conditions in vitro, but often fibrils found in patients are highly homogeneous. These findings suggest that the processes that amplify amyloid fibrils in vivo can in some cases preserve the structural characteristics of the initial seed fibrils. It has been known for many years that fibril growth by monomer addition maintains the structure of the seed fibril, as the latter acts as a template that imposes its fold on the newly added monomer. However, for fibrils that are formed through secondary nucleation it was, until recently, not clear whether the structure of the seed fibril is preserved. Here we review the experimental evidence on this question that has emerged over the last years. The overall picture is that the fibril strain that forms through secondary nucleation is mostly defined by the solution conditions and intrinsic structural preferences, and not by the seed fibril strain.
CRISPR/dCas9-Mediated Parkin Inhibition Impairs Mitophagy and Aggravates Apoptosis of Rat Nucleus Pulposus Cells Under Oxidative Stress
Authors: Lan Tao , Zheng Yu-chen , Li Ning-dao , Chen Xiao-sheng , Shen Zhe , Yan Bin
Published: April 2021

Objective

The aim of this study is to explore the role of Parkin in intervertebral disk degeneration (IDD) and its mitophagy regulation mechanism.

Study design and methods

Rat nucleus pulposus (NP) cells were stimulated with hydrogen peroxide (H2O2) to a mimic pathological condition. Apoptosis and mitophagy were assessed by Western blot, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and immunofluorescence staining. The CRISPR–dCas9–KRAB system was used to silence the expression of Parkin.

Result

In this study, we found that Parkin was downregulated in rat NP cells under oxidative stress. In addition, treatment with H2O2 resulted in mitochondrial dysfunction, autophagy inhibition, and a significant increase in the rate of apoptosis of NP cells. Meanwhile, mitophagy inhibition enhanced H2O2-induced apoptosis. Furthermore, repression of Parkin significantly attenuated mitophagy and exacerbated apoptosis.

Conclusion

These results suggested that Parkin may play a protective role in alleviating the apoptosis of NP cells via mitophagy, and that targeting Parkin may provide a promising therapeutic strategy for the prevention of IDD.