bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Role of Macrophage Phenotypes and CCL2 in the Pathogenesis of Takayasu Arteritis
Authors: Kong Xiufang , Xu Ming , Cui Xiaomeng , Ma Lingying , Cheng Huiyong , Hou Jun , Sun Xiaoning , Ma Lili , Jiang Lindi
Published: May 2021

Objectives

To investigate vascular macrophage phenotype as well as vascular and peripheral chemokine (C-C motif) ligand 2 (CCL2) expression during different stages of disease progression in patients with Takayasu Arteritis (TA).

Methods

In this study, 74 patients with TA and 50 controls were recruited. TA disease activity was evaluated with Kerr scores. Macrophage phenotype and CCL2 expression were examined by immunohistochemistry in vascular specimens from 8 untreated and 7 treated TA patients, along with 4 healthy controls. Serum CCL2 were quantified by enzyme-linked immune-absorbent assay from TA patients at baseline (n=59), at 6-months (n=38), and from 46 healthy volunteers. Vascular macrophage phenotype, vascular CCL2 expression and serum CCL2 levels during different stages, as well as the relationship between serum CCL2 and disease activity or other inflammatory parameters (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin 6 (IL-6)) were investigated.

Results

In untreated patients, vascular M1 macrophages and CCL2 showed increased expression, mainly in the adventitia. In contrast, in treated patients, vascular adventitial M1 and CCL2 expression were decreased, while vascular medial M2 macrophages and CCL2 levels were increased. Distribution of macrophages and CCL2 was consistent within the TA vascular lesions regardless of the disease stage. Furthermore, peripheral CCL2 was elevated in patients with TA (TA: 160.30 ± 120.05 vs. Control: 65.58 ± 54.56 pg/ml, P < 0.001). CCL2 levels were found to correlate with ESR, CRP, and IL-6 (all R values between 0.55 and 0.6, all P < 0.001). Receiver operating curve analysis demonstrated that CCL2 (at the cut-off value of 100.36 pg/ml) was able to predict disease activity (area under the curve = 0.74, P = 0.03). Decrease in CCL2 level was observed in patients with clinical remission (CR), but not in patients without CR, after 6 months of treatment (CR patients: baseline 220.18 ± 222.69 vs. post-treatment 88.71 ± 55.89 pg/ml, P = 0.04; non-CR patients: baseline 142.45 ± 104.76 vs. post-treatment 279.49 ± 229.46 pg/ml, P = 0.02).

Conclusions

Macrophages contribute to vascular pathological changes in TA by undergoing phenotype transformation. CCL2 is an important factor for recruiting macrophages and a potential biomarker for disease activity.
Early Embryonic Loss Following Intravaginal Zika Virus Challenge in Rhesus Macaques
Authors: Newman Christina M. , Tarantal Alice F. , Martinez Michele L. , Simmons Heather A. , Morgan Terry K. , Zeng Xiankun , Rosinski Jenna R. , Bliss Mason I. , Bohm Ellie K. , Dudley Dawn M. , Aliota Matthew T. , Friedrich Thomas C. , Miller Christopher J. , O’Connor David H.
Published: May 2021

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) and is primarily transmitted byAedesspecies mosquitoes; however, ZIKV can also be sexually transmitted. During the initial epidemic and in places where ZIKV is now considered endemic, it is difficult to disentangle the risks and contributions of sexual versus vector-borne transmission to adverse pregnancy outcomes. To examine the potential impact of sexual transmission of ZIKV on pregnancy outcome, we challenged three rhesus macaques (Macaca mulatta) three times intravaginally with 1 x 107PFU of a low passage, African lineage ZIKV isolate (ZIKV-DAK) in the first trimester (~30 days gestational age). Samples were collected from all animals initially on days 3 through 10 post challenge, followed by twice, and then once weekly sample collection; ultrasound examinations were performed every 3-4 days then weekly as pregnancies progressed. All three dams had ZIKV RNA detectable in plasma on day 3 post-ZIKV challenge. At approximately 45 days gestation (17-18 days post-challenge), two of the three dams were found with nonviable embryos by ultrasound. Viral RNA was detected in recovered tissues and at the maternal-fetal interface (MFI) in both cases. The remaining viable pregnancy proceeded to near term (~155 days gestational age) and ZIKV RNA was detected at the MFI but not in fetal tissues. These results suggest that sexual transmission of ZIKV may represent an underappreciated risk of pregnancy loss during early gestation.
Seasonal and Interannual Variability of the CO2 System in the Eastern Mediterranean Sea: A Case Study in the North Western Levantine Basin
Authors: Wimart-Rousseau Cathy , Wagener Thibaut , Álvarez Marta , Moutin Thierry , Fourrier Marine , Coppola Laurent , Niclas-Chirurgien Laure , Raimbault Patrick , D’Ortenzio Fabrizio , Durrieu de Madron Xavier , Taillandier Vincent , Dumas Franck , Conan Pascal , Pujo-Pay Mireille , Lefèvre Dominique
Published: May 2021

The seasonal variability of the carbonate system in the eastern Mediterranean Sea (EMed) was investigated based on discrete total alkalinity (AT), total dissolved inorganic carbon (CT), and pH measurements collected during three cruises around Crete between June 2018 and March 2019. This study presents a detailed description of this new carbonate chemistry dataset in the eastern Mediterranean Sea. We show that the North Western Levantine Basin (NWLB) is unique in terms of range of AT variation vs. CT variation in the upper water column over an annual cycle. The reasons for this singularity of the NWLB can be explained by the interplay between strong evaporation and the concomitant consumption of CT by autotrophic processes. The high range of AT variations, combined to temperature changes, has a strong impact on the variability of the seawater pCO2 (pCO2SW). Based on Argo float data, an entire annual cycle for pCO2SW in the NWLB has been reconstructed in order to estimate the temporal sequence of the potential “source” and “sink” of atmospheric CO2. By combining this dataset with previous observations in the NWLB, this study shows a significant ocean acidification and a decrease in the oceanic surface pHT25 of −0.0024 ± 0.0004 pHT25 units.a–1. The changes in the carbonate system are driven by the increase of atmospheric CO2 but also by unexplained temporal changes in the surface AT content. If we consider that the EMed will, in the future, encounter longer, more intense and warmer summer seasons, this study proposes some perspectives on the carbonate system functioning of the “future” EMed.
DNA Barcoding Mushroom Spawn Using EF-1α Barcodes: A Case Study in Oyster Mushrooms (Pleurotus)
Authors: Zhao Peng , Ji Sen-Peng , Cheng Xian-Hao , Bau Tolgor , Dong Hong-Xin , Gao Xing-Xi
Published: May 2021

Oyster mushrooms (genus Pleurotus) are widespread and comprise the most commonly cultivated edible mushrooms in the world. Species identification of oyster mushroom spawn based on cultural, morphological, and cultivated characteristics is time consuming and can be extraordinarily difficult, which has impeded mushroom breeding and caused economic loss for mushroom growers. To explore a precise and concise approach for species identification, the nuclear ribosomal internal transcribed spacer (ITS), 28S rDNA, and the widely used protein-coding marker translation elongation factor 1α (EF-1α) gene were evaluated as candidate DNA barcode markers to investigate their feasibility in identifying 13 oyster mushroom species. A total of 160 sequences of the candidate loci were analyzed. Intra- and interspecific divergences and the ease of nucleotide sequence acquisition were the criteria used to evaluate the candidate genes. EF-1α showed the best intra- and interspecific variation among the candidate markers and discriminated 84.6% of the species tested, only being unable to distinguish two closely related species Pleurotus citrinopileatus and Pleurotus cornucopiae. Furthermore, EF-1α was more likely to be acquired than ITS or 28S rDNA, with an 84% success rate of PCR amplification and sequencing. For ITS and 28S rDNA, the intraspecific differences of several species were distinctly larger than the interspecific differences, and the species identification efficiency of the two candidate markers was worse (61.5 and 46.2%, respectively). In addition, these markers had some sequencing problems, with 55 and 76% success rates of sequencing, respectively. Hence, we propose EF-1α as a possible DNA barcode marker for oyster mushroom spawn.
A Comparison of Blood Pathogen Detection Among Droplet Digital PCR, Metagenomic Next-Generation Sequencing, and Blood Culture in Critically Ill Patients With Suspected Bloodstream Infections
Authors: Hu Bangchuan , Tao Yue , Shao Ziqiang , Zheng Yang , Zhang Run , Yang Xuejing , Liu Jingquan , Li Xi , Sun Renhua
Published: May 2021

Metagenomic next-generation sequencing (mNGS) and droplet digital PCR (ddPCR) have recently demonstrated a great potential for pathogen detection. However, few studies have been undertaken to compare these two nucleic acid detection methods for identifying pathogens in patients with bloodstream infections (BSIs). This prospective study was thus conducted to compare these two methods for diagnostic applications in a clinical setting for critically ill patients with suspected BSIs. Upon suspicion of BSIs, whole blood samples were simultaneously drawn for ddPCR covering 20 common isolated pathogens and four antimicrobial resistance (AMR) genes, mNGS, and blood culture. Then, a head-to-head comparison was performed between ddPCR and mNGS. A total of 60 episodes of suspected BSIs were investigated in 45 critically ill patients, and ddPCR was positive in 50 (83.3%), mNGS in 41 (68.3%, not including viruses), and blood culture in 10 (16.7%) episodes. Of the 10 positive blood cultures, nine were concordantly identified by both mNGS and ddPCR methods. The head-to-head comparison showed that ddPCR was more rapid (~4 h vs. ~2 days) and sensitive (88 vs. 53 detectable pathogens) than mNGS within the detection range of ddPCR, while mNGS detected a broader range of pathogens (126 vs. 88 detectable pathogens, including viruses) than ddPCR. In addition, a total of 17 AMR genes, including 14 blaKPC and 3 mecA genes, were exclusively identified by ddPCR. Based on their respective limitations and strengths, the ddPCR method is more useful for rapid detection of common isolated pathogens as well as AMR genes in critically ill patients with suspected BSI, whereas mNGS testing is more appropriate for the diagnosis of BSI where classic microbiological or molecular diagnostic approaches fail to identify causative pathogens.
Effects of Gallic Acid on Fermentation Parameters, Protein Fraction, and Bacterial Community of Whole Plant Soybean Silage
Authors: Wang Cheng , Zheng Mingyang , Wu Shuo , Zou Xuan , Chen Xiaoyang , Ge Liangfa , Zhang Qing
Published: May 2021

Whole plant soybean (WPS) is a kind of legume resource with characteristics of high nutrition, large biomass, and wide distribution. In the present study, we have investigated the feasibility and effects of gallic acid (GA) on WPS silage quality, nitrogen distribution, tannin content, and bacterial community. The 0.5 and 1% (fresh matter basis) GA were added into WPS for dynamic ensiling (days 3, 7, 14, and 30, respectively). The results showed that the WPS silage with GA addition significantly decreased pH value (6.16–5.38 at ensiling day 30), coliform bacteria count and butyric acid (65.3–62.0 g/kg dry matter at ensiling day 30), and amino nitrogen contents (259–88.2 g/kg total nitrogen at ensiling day 30) and promoted lactic acid (9.62–31.5 g/kg dry matter at ensiling day 30), acetic acid (24.1–85.6 g/kg dry matter at ensiling day 30), and tannin (total phenol and hydrolyzable tannin) contents. Additionally, the GA addition also contributed to the change of bacterial community, where Firmicutes and Lactobacillus were most abundant on phylum and genus levels, respectively. The above results suggested that GA additive applied in WPS silage was an effective strategy to protect nutrition and improve fermentation quality, and the 1% GA addition showed a better effect.
Substrate Specificities and Inhibition Pattern of the Solute Carrier Family 10 Members NTCP, ASBT and SOAT
Authors: Grosser Gary , Müller Simon Franz , Kirstgen Michael , Döring Barbara , Geyer Joachim
Published: May 2021

Three carriers of the solute carrier family SLC10 have been functionally characterized so far. Na+/taurocholate cotransporting polypeptide NTCP is a hepatic bile acid transporter and the cellular entry receptor for the hepatitis B and D viruses. Its intestinal counterpart, apical sodium-dependent bile acid transporter ASBT, is responsible for the reabsorption of bile acids from the intestinal lumen. In addition, sodium-dependent organic anion transporter SOAT specifically transports sulfated steroid hormones, but not bile acids. All three carriers show high sequence homology, but significant differences in substrate recognition that makes a systematic structure-activity comparison attractive in order to define the protein domains involved in substrate binding and transport. By using stably transfected NTCP-, ASBT-, and SOAT-HEK293 cells, systematic comparative transport and inhibition experiments were performed with more than 20 bile acid and steroid substrates as well as different inhibitors. Taurolithocholic acid (TLC) was identified as the first common substrate of NTCP, ASBT and SOAT with Km values of 18.4, 5.9, and 19.3 µM, respectively. In contrast, lithocholic acid was the only bile acid that was not transported by any of these carriers. Troglitazone, BSP and erythrosine B were identified as pan-SLC10 inhibitors, whereas cyclosporine A, irbesartan, ginkgolic acid 17:1, and betulinic acid only inhibited NTCP and SOAT, but not ASBT. The HBV/HDV-derived myr-preS1 peptide showed equipotent inhibition of the NTCP-mediated substrate transport of taurocholic acid (TC), dehydroepiandrosterone sulfate (DHEAS), and TLC with IC50 values of 182 nM, 167 nM, and 316 nM, respectively. In contrast, TLC was more potent to inhibit myr-preS1 peptide binding to NTCP with IC50 of 4.3 µM compared to TC (IC50 = 70.4 µM) and DHEAS (IC50 = 52.0 µM). Based on the data of the present study, we propose several overlapping, but differently active binding sites for substrates and inhibitors in the carriers NTCP, ASBT, SOAT.
Indirect Vibration of the Upper Limbs Alters Transmission Along Spinal but Not Corticospinal Pathways
Authors: Barss Trevor S. , Collins David F. , Miller Dylan , Pujari Amit N.
Published: May 2021

The use of upper limb vibration (ULV) during exercise and rehabilitation continues to gain popularity as a modality to improve function and performance. Currently, a lack of knowledge of the pathways being altered during ULV limits its effective implementation. Therefore, the aim of this study was to investigate whether indirect ULV modulates transmission along spinal and corticospinal pathways that control the human forearm. All measures were assessed under CONTROL (no vibration) and ULV (30 Hz; 0.4 mm displacement) conditions while participants maintained a small contraction of the right flexor carpi radialis (FCR) muscle. To assess spinal pathways, Hoffmann reflexes (H-reflexes) elicited by stimulation of the median nerve were recorded from FCR with motor response (M-wave) amplitudes matched between conditions. An H-reflex conditioning paradigm was also used to assess changes in presynaptic inhibition by stimulating the superficial radial (SR) nerve (5 pulses at 300Hz) 37 ms prior to median nerve stimulation. Cutaneous reflexes in FCR elicited by stimulation of the SR nerve at the wrist were also recorded. To assess corticospinal pathways, motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation of the contralateral motor cortex were recorded from the right FCR and biceps brachii (BB). ULV significantly reduced H-reflex amplitude by 15.7% for both conditioned and unconditioned reflexes (24.0 ± 15.7 vs. 18.4 ± 11.2% Mmax; p < 0.05). Middle latency cutaneous reflexes were also significantly reduced by 20.0% from CONTROL (−1.50 ± 2.1% Mmax) to ULV (−1.73 ± 2.2% Mmax; p < 0.05). There was no significant effect of ULV on MEP amplitude (p > 0.05). Therefore, ULV inhibits cutaneous and H-reflex transmission without influencing corticospinal excitability of the forearm flexors suggesting increased presynaptic inhibition of afferent transmission as a likely mechanism. A general increase in inhibition of spinal pathways with ULV may have important implications for improving rehabilitation for individuals with spasticity (SCI, stroke, MS, etc.).
Cannabinoid Signaling in Auditory Function and Development
Authors: Ghosh Sumana , Stansak Kendra , Walters Bradley J.
Published: May 2021

Plants of the genus Cannabis have been used by humans for millennia for a variety of purposes. Perhaps most notable is the use of certain Cannabis strains for their psychoactive effects. More recently, several biologically active molecules within the plants of these Cannabis strains, called phytocannabinoids or simply cannabinoids, have been identified. Furthermore, within human cells, endogenous cannabinoids, or endocannabinoids, as well as the receptors and secondary messengers that give rise to their neuromodulatory effects, have also been characterized. This endocannabinoid system (ECS) is composed of two primary ligands—anandamide and 2-arachidonyl glycerol; two primary receptors—cannabinoid receptors 1 and 2; and several enzymes involved in biosynthesis and degradation of endocannabinoid ligands including diacylglycerol lipase (DAGL) and monoacylglycerol lipase (MAGL). Here we briefly summarize cannabinoid signaling and review what has been discerned to date with regard to cannabinoid signaling in the auditory system and its roles in normal physiological function as well as pathological conditions. While much has been uncovered regarding cannabinoid signaling in the central nervous system, less attention has been paid to the auditory system specifically. Still, evidence is emerging to suggest that cannabinoid signaling is critical for the development, maturation, function, and survival of cochlear hair cells (HCs) and spiral ganglion neurons (SGNs). Furthermore, cannabinoid signaling can have profound effects on synaptic connectivity in CNS structures related to auditory processing. While clinical cases demonstrate that endogenous and exogenous cannabinoids impact auditory function, this review highlights several areas, such as SGN development, where more research is warranted.
Value of Pyruvate Carboxylase in Thyroid Fine-Needle Aspiration Wash-Out Fluid for Predicting Papillary Thyroid Cancer Lymph Node Metastasis
Authors: Liu Chang , Zhang Lu , Liu Yang , Zhao Qingqing , Pan Yu , Zhang Yifan
Published: May 2021

The incidence of papillary thyroid carcinoma (PTC) is increasing. Lymph node metastatic status of PTC is a major factor for decision marking of surgery and surgical extend, however, no reliable tool exists for prediction of PTC nodal metastasis, for example, ultrasound cannot qualitatively diagnose and effectively detect central lymph node metastasis (CLNM). Therefore, the development of a new diagnostic biomarker is crucial for CLNM. Metabolic dysregulation is an important factor associated with malignancy and metastasis of tumors. Pyruvate carboxylase (PC) is a major anaplerotic enzyme that catalyzes the carboxylation of pyruvate to form oxaloacetate, which has been suggested to be involved in the tumorigenesis of several cancers, including PTC. This study aimed to explore the role of PC expression in thyroid fine-needle aspiration (FNA) wash-out fluid for predicting CLNM in PTC, and to explore how PC is involved in PTC development. The expression levels of PC in PTC tissues and normal thyroid tissues were first compared based on bioinformatics analysis of public databases, including the Gene Expression Profiling (GEPIA), Oncomine and Gene Expression Omnibus (GEO) databases. Then, the PC mRNA and protein expression levels were measured by RT-PCR and Immunohistochemistry (IHC) in surgical tissues from a total of 42 patients with surgically confirmed PTC, and compared in patients with and without CLNM. Further, to assess PC expression in diagnostic biopsies, a total of 71 thyroid nodule patients with ultrasound-guided FNA wash-out fluid samples and cytological diagnosis were prospectively enrolled in the study. Then, we analyzed the mechanism of PC-mediated PTC progression in vitro. This study showed that PC expression was higher in PTC tissues and thyroid FNA wash-out fluid samples from patients with CLNM than those from patients without CLNM, and that PC-induced PTC metastasis may occur through the TGF-β/Smad-regulated epithelial–mesenchymal transition (EMT) pathway.
Decitabine Sensitizes the Radioresistant Lung Adenocarcinoma to Pemetrexed Through Upregulation of Folate Receptor Alpha
Authors: Wang Yuqing , Huang Jie , Wu Qiong , Zhang Jingjing , Ma Zhiyuan , Zhu Lucheng , Xia Bin , Ma Shenglin , Zhang Shirong
Published: May 2021

Chemotherapy is the backbone of subsequent treatment for patients with lung adenocarcinoma (LUAD) exhibiting radiation resistance, and pemetrexed plays a critical role in this chemotherapy. However, few studies have assessed changes in the sensitivity of LUAD cells to pemetrexed under radioresistant circumstances. Therefore, the objectives of this study were to delineate changes in the sensitivity of radioresistant LUAD cells to pemetrexed and to elucidate the related mechanisms and then develop an optimal strategy to improve the cytotoxicity of pemetrexed in radioresistant LUAD cells. Our study showed a much lower efficacy of pemetrexed in radioresistant cells than in parental cells, and the mechanism of action was the significant downregulation of folate receptor alpha (FRα) by long-term fractionated radiotherapy, which resulted in less cellular pemetrexed accumulation. Interestingly, decitabine effectively reversed the decrease in FRα expression in radioresistant cells through an indirect regulatory approach. Thereafter, we designed a combination therapy of pemetrexed and decitabine and showed that the activation of FRα by decitabine sensitizes radioresistant LUAD cells to pemetrexed both in vitro and in xenografts. Our findings raised a question regarding the administration of pemetrexed to patients with LUAD exhibiting acquired radioresistance and accordingly suggested that a combination of pemetrexed and decitabine would be a promising treatment strategy.
Transvesical Retzius-Sparing Versus Standard Robot-Assisted Radical Prostatectomy: A Retrospective Propensity Score-Adjusted Analysis
Authors: Deng Wen , Jiang Hao , Liu Xiaoqiang , Chen Luyao , Liu Weipeng , Zhang Cheng , Zhou Xiaochen , Fu Bin , Wang Gongxian
Published: May 2021

Objectives

To estimate the safety and efficiency of transvesical Retzius-sparing robot-assisted radical prostatectomy (T-RARP) compared with standard robot-assisted radical prostatectomy (S-RARP) for localized prostate cancer (PCa).

Materials and Methods

174 patients bearing localized PCa and undergoing T-RARP or S-RARP between October 2017 and January 2020 were retrospectively enrolled in our analysis. All potential baseline confounders were strictly restrained with propensity-score matching (PM) method (1: 1). Within the matched setting, the perioperative and functional outcomes were compared between the T-RARP and S-RARP groups, while the oncological results and functional recovery of the two arms were presented with Kaplan-Meier curves.

Results

Finally, 114 and 60 eligible patients harbouring localized PCa were identified in the S-RARP and T-RARP group, respectively. No significant differences between the two groups were found in all baseline characteristics after PM. Within the matched cohort, no case was converted to open surgery in either group. The T-RARP group was significantly related to a higher mean operative time (p = 0.001) and shorter median hospital stay length (p < 0.001). There were not significant differences in the median estimated blood loss and specimen Gleason score between the two arms. The proportions of transfusion, pT3a disease, postoperative complication, and positive surgical margin in the T-RARP group were also comparable to that in the S-RARP group. The mean prostate-specific antigen and median erectile functional scores did not differ significantly between the two groups at postoperative 3 months and last follow-up. T-RARP vs. S-RARP had significantly improved urinary continence (UC) rates at the removal of catheter (p < 0.001) and postoperative 3 months (p < 0.001), but the significant difference between the two groups in UC recovery disappeared at last follow-up (p = 0.119). No significant difference in biochemical recurrence-free survival was observed following the two surgeries (p = 0.727).

Conclusions

T-RARP by experienced hands was feasible for selected patients with clinically localized PCa, yielding significantly improved early return to UC and similar erectile functional preservation without compromising oncological control when compared with the standard approach.
Polyphenolic-Rich Compounds From Dillenia pentagyna (Roxb.) Attenuates the Doxorubicin-Induced Cardiotoxicity: A High-Frequency Ultrasonography Assisted Approach
Authors: Tene Kalyani , Kalyan Kumar M. , Basveshwar G. , Eswara Rao P. , Jagadeesh Kumar G. , kumar Pramod , Pemmaraju Deepak B. , Murty U. S. N. , Gogoi Ranadeep , Naidu V. G. M.
Published: May 2021

Cardiovascular complications are the foremost concern in patients undergoing anticancer therapy. There is an unmet need to address the problems arising from the drug-induced toxicity for the long-term benefit of the patients undergoing chemotherapy. Alternative medicines are gaining their prosperity in addressing the various drug-induced organ toxicity. Dillenia pentagyna Roxb (DP) is an ethnomedicinal plant rich in flavonoids and phenolic contents. In India & Nepal, DP is a common ingredient of traditional medicines used to treat multiple ailments like inflammation, cancer, and diabetes. However, its protective role against doxorubicin (Dox) induced cardiotoxicity remains unexplored. Herein, we investigated the potential effects of various extracts/fractions obtained from the DP’s bark against Dox-induced cardiotoxicity, both in-vitro and in-vivo. The anti-oxidant content of the extracts/fractions was evaluated by using DPPH, ABTS and FRAP chemical assays. The results indicated that the hydroalcoholic (HA) extract of DP has intense anti-oxidant potential. Further fractionation of DP revealed that the phenolic-rich fraction (F1) has a high anti-oxidant potential. The protective effect of extract/fraction was also investigated in the H9c2 cell line following the Dox-induced cardiotoxicity model. We observed that the pre-treatment of extract/fraction in cardiomyocytes had exhibited increased cell viability. Fluorescence-based chemical assays indicated a decreased ROS levels in the treated groups in comparison to the Dox control group. The effect of DP was evaluated further in balb/c mice by the Dox-induced cardiotoxicity model. Non-invasive techniques like high-frequency ultrasonography and electrocardiogram revealed that the mice pre-treated with DP had improved cardiac functionality (left ventricular ejection fraction and stroke volume) and normalized the electrocardiograms compared to the Dox control group. Further, biochemical analysis with the cardiac tissues revealed that the cytoprotective proteins like HO-1, SOD-2, and Nrf-2 were elevated in the DP treated groups compared to the Dox control group. Overall, our results suggested that the bioactive extract/fractions of DP helped alleviate the Dox-induced cardiotoxicity. LC-QTOF-ESI-MS analysis of DP and F1 indicated that polyphenolic anti-oxidant compounds like gallic acid, syringic acid, and sinapic acid could be responsible for the potent -cardioprotective effect. Future understanding of the pharmacokinetics and pharmacodynamic parameters can help translate from the bench to the bedside.
A 112 Gb/s Radiation-Hardened Mid-Board Optical Transceiver in 130-nm SiGe BiCMOS for Intra-Satellite Links
Authors: Giannakopoulos Stavros , Sourikopoulos Ilias , Stampoulidis Leontios , Ostrovskyy Pylyp , Teply Florian , Tittelbach-Helmrich K. , Panic Goran , Fischer Gunter , Grabowski Alexander , Zirath Herbert , Ayzac Philippe , Venet Norbert , Maho Anaëlle , Sotom Michel , Jones Shaun , Wood Grahame , Oxtoby Ian
Published: May 2021

We report the design of a 112 Gb/s radiation-hardened (RH) optical transceiver applicable to intra-satellite optical interconnects. The transceiver chipset comprises a vertical-cavity surface-emitting laser (VCSEL) driver and transimpedance amplifier (TIA) integrated circuits (ICs) with four channels per die, which are adapted for a flip-chip assembly into a mid-board optics (MBO) optical transceiver module. The ICs are designed in the IHP 130 nm SiGe BiCMOS process (SG13RH) leveraging proven robustness in radiation environments and high-speed performance featuring bipolar transistors (HBTs) with fT/fMAX values of up to 250/340 GHz. Besides hardening by technology, radiation-hardened-by-design (RHBD) components are used, including enclosed layout transistors (ELTs) and digital logic cells. We report design features of the ICs and the module, and provide performance data from post-layout simulations. We present radiation evaluation data on analog devices and digital cells, which indicate that the transceiver ICs will reliably operate at typical total ionizing dose (TID) levels and single event latch-up thresholds found in geostationary satellites.
Thioredoxin-1 Is a Target to Attenuate Alzheimer-Like Pathology in Diabetic Encephalopathy by Alleviating Endoplasmic Reticulum Stress and Oxidative Stress
Authors: Guo Yu , Zhang Chenghong , Wang Chunyang , Huang Yufei , Liu Jingyun , Chu Haiying , Ren Xiang , Kong Li , Ma Haiying
Published: May 2021

Varying degrees of central nervous system neuropathy induced by diabetes mellitus (DM) contribute to a cognitive disorder known as diabetic encephalopathy (DE), which is also one of the independent risk factors for Alzheimer’s disease (AD). Endoplasmic reticulum stress (ERS) plays a critical role in the occurrence and development of DE and AD. However, its molecular mechanism remains largely unknown. This study aims to investigate whether thioredoxin-1 (Trx-1) could alleviate DE and AD through ERS, oxidative stress (OS) and apoptosis signaling pathways. Mice were randomly divided into a wild-type group (WT-NC), a streptozotocin (STZ)-treated DM group (WT-DM), a Trx-1-TG group (TG-NC) and a Trx-1-TG DM group (TG-DM). Diabetic animals showed an increase in the time spent in the target quadrant and the number of platform crossings as well as AD-like behavior in the water maze experiment. The immunocontent of the AD-related protein Tau and the levels of cell apoptosis, β-amyloid (Aβ) plaque formation and neuronal degeneration in the hippocampus of the diabetic group were increased. Some key factors associated with ERS, such as protein disulfide isomerase (PDI), glucose-regulated protein 78 (GRP78), inositol-requiring enzyme 1α (IRE1α), tumor necrosis factor receptor-associated factor 2 (TRAF2), apoptosis signal-regulating kinase-1 (ASK1), c-Jun N-terminal kinase (JNK), protein kinase RNA (PKR)-like ER kinase (PERK), and C/EBP homologous protein (CHOP), were upregulated, and other factors related to anti-oxidant stress, such as nuclear factor erythroid 2-related factor (Nrf2), were downregulated in the DM group. Moreover, DM caused an increase in the immunocontents of caspase-3 and caspase-12. However, these changes were reversed in the Trx-1-tg DM group. Therefore, we conclude that Trx-1 might be a key factor in alleviating DE and AD by regulating ERS and oxidative stress response, thus preventing apoptosis.
Evolutionary Rescue as a Mechanism Allowing a Clonal Grass to Adapt to Novel Climates
Authors: Münzbergová Zuzana , Vandvik Vigdis , Hadincová Věroslava
Published: May 2021

Filing gaps in our understanding of species' abilities to adapt to novel climates is a key challenge for predicting future range shifts and biodiversity loss. Key knowledge gaps are related to the potential for evolutionary rescue in response to climate, especially in long-lived clonally reproducing species. We illustrate a novel approach to assess the potential for evolutionary rescue using a combination of reciprocal transplant experiment in the field to assess performance under a changing climate and independent growth chamber assays to assess growth- and physiology-related plant trait maxima and plasticities of the same clones. We use a clonal grass, Festuca rubra, as a model species. We propagated individual clones and used them in a transplant experiment across broad-scale temperature and precipitation gradients, simulating the projected direction of climate change in the region. Independent information on trait maxima and plasticities of the same clones was obtained by cultivating them in four growth chambers representing climate extremes. Plant survival was affected by interaction between plant traits and climate change, with both trait plasticities and maxima being important for adaptation to novel climates. Key traits include plasticity in extravaginal ramets, aboveground biomass, and osmotic potential. The direction of selection in response to a given climatic change detected in this study mostly contradicted the natural trait clines indicating that short-term selection pressure as identified here does not match long-term selection outcomes. Long-lived clonal species exposed to different climatic changes are subjected to consistent selection pressures on key traits, a necessary condition for adaptation to novel conditions. This points to evolutionary rescue as an important mechanism for dealing with climate change in these species. Our experimental approach may be applied also in other model systems broadening our understanding of evolutionary rescue. Such knowledge cannot be easily deduced from observing the existing field clines.
A Systematic Review of Momentary Assessment Designs for Mood and Anxiety Symptoms
Authors: Hall Mila , Scherner Paloma V. , Kreidel Yannic , Rubel Julian A.
Published: May 2021

Background:Altering components of ecological momentary assessment (EMA) measures to better suit the purposes of individual studies is a common and oftentimes necessary step. Though the inherent flexibility in EMA has its benefits, no resource exists to provide an overview of the variability in how convergent constructs and symptoms have been assessed in the past. The present study fills that gap by examining EMA measurement design for mood and anxiety symptomatology.

Methods:Various search engines were used to identify 234 relevant studies. Items administered, data collection schedules (i.e., beeps per day), response scales (i.e., Likert), data collection platforms (i.e., apps), and psychometric properties (i.e., reliability) were extracted.

Results:Study designs varied greatly in all aspects across the identified papers. Over 4,600 extracted items were qualitatively analyzed, resulting in the identification of 12 themes. The most EMA items focused on affect, with categories such as “happiness” and “tension” appearing most frequently. We provide all of our data extraction in the format of an open-source database.

Limitations:Despite our best attempts to include as much of the relevant literature as possible, this review and the accompanying database are not exhaustive, but can easily be built upon to include other, newer studies.

Conclusions:The fact that the affect theme featured both positive and negative emotional constructs highlights the dichotomous focus on valence and affect within the literature surrounding anxious and depressive symptomatology. We hope that our database will act as a helpful design decision-making resource for researchers studying this kind of symptomatology in the future.

Systematic Review Registration:PROSPERO (CRD42019139409).
Testing the Disgust-Based Mechanism of Homonegative Attitudes in the Context of the COVID-19 Pandemic
Authors: Szymkow Aleksandra , Frankowska Natalia , Galasinska Katarzyna
Published: May 2021

Negative attitudes and stigmatization can originate from the perception of a disease-related threat. Following the spread of the COVID-19 pandemic, it is often suggested that incidents of discriminatory behavior are the result of defense mechanisms aimed at avoiding pathogens. According to the behavioral immune system theory, people are motivated to distance themselves from individuals who show signs of infection, or who are only heuristically associated with a disease, primarily because of the disgust they evoke. In this paper we focus on negative attitudes toward gay men and lesbians who are among social groups that have been persistently framed as “unclean.” In our correlational study (N= 500 heterosexual participants; Polish sample data collected during the first COVID-19 lockdown in Poland, in March/April 2020) we tested moderation models derived from the behavioral immune system theory. Specifically, we investigated whether perceived vulnerability to disease and perceived threat of contracting COVID-19 moderate the relation between disgust and homonegativity. We found that sexual disgust (but not pathogen nor moral disgust) predicted homonegative attitudes. This effect was stronger for participants expressing higher levels of perceived vulnerability to disease but was not dependent on the perception of the COVID-19 threat. The results reaffirm previous evidence indicating a pivotal role of disgust in disease-avoidance mechanisms. They also point to functional flexibility of the behavioral immune system by demonstrating the moderating role of perceived vulnerability to disease in shaping homonegative attitudes. Finally, they show that the threat of COVID-19 does not strengthen the relationship between disgust and homonegativity.
Selective Auditory Attention Associated With Language Skills but Not With Executive Functions in Swedish Preschoolers
Authors: Tonér Signe , Kallioinen Petter , Lacerda Francisco
Published: May 2021

Associations between language and executive functions (EFs) are well-established but previous work has often focused more on EFs than on language. To further clarify the language–EF relationship, we assessed several aspects of language and EFs in 431 Swedish children aged 4–6, including selective auditory attention which was measured in an event-related potential paradigm. We also investigated potential associations to age, socioeconomic status (SES), bi-/multilingualism, sex and aspects of preschool attendance and quality. Language and EFs correlated weakly to moderately, indicating that relying on measures of vocabulary alone may overestimate the strength of the language–EF relationship. Contrary to predictions, we found no correlations between selective attention and EFs. There were however correlations between morphosyntactic accuracy and selective auditory attention which is in line with previous work and suggests a specific link between morphosyntax and the ability to suppress irrelevant stimuli. In Sweden, socioeconomic differences are rather small and preschool is universally available, but nevertheless, aspects of parental SES predicted children’s performance on all measures. Bi-/multilingual children performed lower on language also when controlling for SES, highlighting the need for interventions to reduce inequalities in educational outcomes already in preschool. A female advantage was found for both language and EFs, whereas preschool attendance and quality were not significantly related to outcome measures. Future work should include longitudinal studies of language and EF development, include children from diverse SES backgrounds and contribute toward a theoretical framework that further clarifies the language–EF relationship.
Long-Term Outcome of Adolescent Anorexia Nervosa: Family Treatment Apartments Compared With Child Psychiatric Inpatient Treatment
Authors: Wallin Ulf , Holmer Riitta
Published: May 2021

Introduction: The family is rarely involved in treatment when the patient with anorexia nervosa (AN) is hospitalized. Family treatment apartment (FTA) represents an intervention that includes the family in the intensive treatment of AN. This study compares the short- and long-term outcomes of adolescents treated in FTA with those who received inpatient hospital care. In FTA, the parents are responsible for providing meal support, whereas in hospital care, the staff is responsible.

Methods: Sixty-eight previous patients admitted during the period 1990–2009 participated in a follow-up, 43 from the FTA where the whole family is admitted for treatment and 25 from regular psychiatric inpatient care. The follow-up consisted of a personal meeting with structured interviews, measurement of height and weight, and self-rating questionnaires.

Result: Readmissions due to weight loss within 6 months from discharge were less common in the FTA group. At follow-up, 14.2 years after admission, there was no difference in eating disorder pathology between the groups. There were significantly lower scores on general psychiatric pathology and significantly higher scores on quality of life in the FTA group.

Discussion: The treatment in FTA aims to give the family the ability to handle AN when it is most challenging. FTA may thus provide a helpful context for treatment with a basic sense of security along with skills that could contribute to better general mental health at follow-up.
Can Radar Remote Life Sensing Technology Help Combat COVID-19?
Authors: Islam Shekh M. M. , Fioranelli Francesco , Lubecke Victor M.
Published: May 2021

COVID-19, caused by SARS-CoV-2, is now a global pandemic disease. This outbreak has affected every aspect of life including work, leisure, and interaction with technology. Governments around the world have issued orders for travel bans, social distancing, and lockdown to control the spread of the virus and prevent strain on hospitals. This paper explores potential applications for radar-based non-contact remote respiration sensing technology that may help to combat the COVID-19 pandemic, and outlines potential advantages that may also help to reduce the spread of the virus. Applications arising from recent developments in the state of the art for transceiver and signal processing technologies will be discussed along associated technical implications. These applications include remote breathing rate monitoring, continuous identity authentication, occupancy detection, and hand gesture recognition. This paper also highlights future research directions that must be explored further to bring this innovative non-contact sensor technology into real-world implementation.
Post-exercise Body Cooling: Skin Blood Flow, Venous Pooling, and Orthostatic Intolerance
Authors: Seeley Afton D. , Giersch Gabrielle E. W. , Charkoudian Nisha
Published: May 2021

Athletes and certain occupations (e.g., military, firefighters) must navigate unique heat challenges as they perform physical tasks during prolonged heat stress, at times while wearing protective clothing that hinders heat dissipation. Such environments and activities elicit physiological adjustments that prioritize thermoregulatory skin perfusion at the expense of arterial blood pressure and may result in decreases in cerebral blood flow. High levels of skin blood flow combined with an upright body position augment venous pooling and transcapillary fluid shifts in the lower extremities. Combined with sweat-driven reductions in plasma volume, these cardiovascular alterations result in levels of cardiac output that do not meet requirements for brain blood flow, which can lead to orthostatic intolerance and occasionally syncope. Skin surface cooling countermeasures appear to be a promising means of improving orthostatic tolerance via autonomic mechanisms. Increases in transduction of sympathetic activity into vascular resistance, and an increased baroreflex set-point have been shown to be induced by surface cooling implemented after passive heating and other arterial pressure challenges. Considering the further contribution of exercise thermogenesis to orthostatic intolerance risk, our goal in this review is to provide an overview of post-exercise cooling strategies as they are capable of improving autonomic control of the circulation to optimize orthostatic tolerance. We aim to synthesize both basic and applied physiology knowledge available regarding real-world application of cooling strategies to reduce the likelihood of experiencing symptomatic orthostatic intolerance after exercise in the heat.
Preparatory Knee Flexion-Extension Movements Enhance Rapid Sidestepping Performance in Collegiate Basketball Players
Authors: Fujimoto Masahiro , Uchida Eri , Nagano Akinori , Rogers Mark W. , Isaka Tadao
Published: May 2021

Lower-limb weight-bearing load distribution in stationary standing influences the timing of rapid first step initiation of importance for functional movement activities and agility performance in sports. This study investigated the effect of pre-step lower-limb loading and unloading with preparatory knee flexion-extension movements on sidestepping performance in fifteen male collegiate basketball players. Participants performed two-choice (step limb) reaction time sidestepping under two conditions: without preparatory movements before the go cue (no-prep–NP) and with continuous alternating knee extension and flexion movements (prep–P). The reaction signal was provided at the beginning of knee extension and flexion and during these movements which corresponded with the largest and smallest loading instants and the transition states between those instants. Sidestepping performance was assessed with three-dimensional kinematic data and ground reaction forces. Step initiation onset time was significantly faster by 13–15% than the NP condition when initiated in the knee flexion phase (p ≤ 0.028, r ≥ 0.70), whereas step-limb unloading interval from step initiation to step lift-off was significantly faster by 12–15% in the knee extension phase (p ≤ 0.01, r ≥ 0.74). The preparatory movements significantly shortened step lift-off by 10–12% (p ≤ 0.013, r ≥ 0.73) and step duration by 17–21% (p < 0.001, r ≥ 0.85) with 19–22% faster step velocity (p < 0.001, r ≥ 0.84), which resulted in 14–15% shorter overall time to step landing (p < 0.001, r ≥ 0.84), irrespective of the loading phases. These results indicated that lower-limb loading with pre-step knee flexion facilitated faster step initiation, while lower-limb unloading with knee extension facilitated faster step-limb unloading, both resulting in faster step lift-off. Bilateral knee flexion-extension movements as a preparatory action could be utilized by invasion sports players to facilitate reactive stepping performance for more effective movement initiation.
Genome-Wide Identification and Expression of the PIN Auxin Efflux Carrier Gene Family in Watermelon (Citrullus lanatus)
Authors: Shang Huaiguo , Zhang Na , Xie Zhouli , Deng Siyu , Yi Licong , Huang Xing
Published: May 2021

As one of the world’s most popular fruits, watermelon (Citrus lanatus) is cultivated in more than 3 million hectares across the globe, with a yearly yield of more than 100 million tons. According to ‘97103’ genome version 1, a previous study has shown that the watermelon genome consists of 11 PIN genes. However, the higher quality ‘97103’ genome version 2 was recently assembled by using PacBio long reads with the benefit of fast development sequencing technology. Using this new assembly, we conducted a new genome-wide search for PIN genes in watermelon and compared it with cucumber and melon genomes. We identified nine, nine, and eight PINs in watermelon, cucumber, and melon, respectively. Phylogenetic analysis revealed a distinct evolutionary history of PIN proteins in watermelon, which is shown by the orphan PIN6 in watermelon. We further conducted an expression analysis of the watermelon PIN genes in silico and by qRT-PCR. ClaPIN6 might not play an essential role during shoot regeneration, which is closely related to species-specific evolution. However, the up-regulated expression patterns of ClaPIN1-1 and ClaPIN1-3 indicated their important roles during shoot regeneration. The result of this research will benefit future studies to understand the regulating mechanisms of auxin in watermelon shoot regeneration.