bluuebunny/crossref_metadata_2025 huggingface dataset:
Sialidase and Sialyltransferase Inhibitors: Targeting Pathogenicity and Disease
Authors: Bowles William H. D. , Gloster Tracey M.
Published: July 2021

Sialidases (SAs) and sialyltransferases (STs), the enzymes responsible for removing and adding sialic acid to other glycans, play essential roles in viruses, bacteria, parasites, and humans. Sialic acid is often the terminal sugar on glycans protruding from the cell surface in humans and is an important component for recognition and cell function. Pathogens have evolved to exploit this and use sialic acid to either “cloak” themselves, ensuring they remain undetected, or as a mechanism to enable release of virus progeny. The development of inhibitors against SAs and STs therefore provides the opportunity to target a range of diseases. Inhibitors targeting viral, bacterial, or parasitic enzymes can directly target their pathogenicity in humans. Excellent examples of this can be found with the anti-influenza drugs Zanamivir (Relenza™, GlaxoSmithKline) and Oseltamivir (Tamiflu™, Roche and Gilead), which have been used in the clinic for over two decades. However, the development of resistance against these drugs means there is an ongoing need for novel potent and specific inhibitors. Humans possess 20 STs and four SAs that play essential roles in cellular function, but have also been implicated in cancer progression, as glycans on many cancer cells are found to be hyper-sialylated. Whilst much remains unknown about how STs function in relation to disease, it is clear that specific inhibitors of them can serve both as tools to gain a better understanding of their activity and form the basis for development of anti-cancer drugs. Here we review the recent developments in the design of SA and ST inhibitors against pathogens and humans.
The Interplay Between Prenatal Adversity, Offspring Dopaminergic Genes, and Early Parenting on Toddler Attentional Function
Authors: Szekely Eszter , Jolicoeur-Martineau Alexia , Atkinson Leslie , Levitan Robert D. , Steiner Meir , Lydon John E. , Fleming Alison S. , Kennedy James L. , Wazana Ashley
Published: July 2021

Background: Few studies have explored the complex gene-by-prenatal environment-by-early postnatal environment interactions that underlie the development of attentional competence. Here, we examined if variation in dopamine-related genes interacts with prenatal adversity to influence toddler attentional competence and whether this influence is buffered by early positive maternal behavior.

Methods: From the Maternal Adversity, Vulnerability and Neurodevelopment cohort, 134 participants (197 when imputing missing data) had information on prenatal adversity (prenatal stressful life events, prenatal maternal depressive symptoms, and birth weight), five dopamine-related genes (DAT1, DRD4, DRD2, COMT, BDNF), observed maternal parenting behavior at 6 months and parent-rated toddler attentional competence at 18 and 24 months. The Latent Environmental and Genetic Interaction (LEGIT) approach was used to examine genes-by-prenatal environment-by-postnatal environment interactions while controlling for sociodemographic factors and postnatal depression.

Results: Our hypothesis of a three-way interaction between prenatal adversity, dopamine-related genes, and early maternal parenting behavior was not confirmed. However, consistent two-way interactions emerged between prenatal adversity and dopamine-related genes; prenatal adversity and maternal parenting behavior, and dopamine-related genes and maternal parenting behavior in relation to toddler attentional competence. Significant interaction effects were driven by theDAT1, COMT, andBDNFgenotypes; prenatal stressful life events; maternal sensitivity, tactile stimulation, vocalization, and infant-related activities.

Conclusions: Multiple dopamine-related genes affected toddler attentional competence and they did so in interaction with prenatal adversity and the early rearing environment, separately. Effects were already visible in young children. Several aspects of early maternal parenting have been identified as potential targets for intervention.
Neuroendocrine Mechanisms Underlying Non-breeding Aggression: Common Strategies Between Birds and Fish
Authors: Quintana Laura , Jalabert Cecilia , Fokidis H. Bobby , Soma Kiran K. , Zubizarreta Lucia
Published: July 2021

Aggression is an adaptive behavior that plays an important role in gaining access to limited resources. Aggression may occur uncoupled from reproduction, thus offering a valuable context to further understand its neural and hormonal regulation. This review focuses on the contributions from song sparrows (Melospiza melodia) and the weakly electric banded knifefish (Gymnotus omarorum). Together, these models offer clues about the underlying mechanisms of non-breeding aggression, especially the potential roles of neuropeptide Y (NPY) and brain-derived estrogens. The orexigenic NPY is well-conserved between birds and teleost fish, increases in response to low food intake, and influences sex steroid synthesis. In non-breeding M. melodia, NPY increases in the social behavior network, and NPY-Y1 receptor expression is upregulated in response to a territorial challenge. In G. omarorum, NPY is upregulated in the preoptic area of dominant, but not subordinate, individuals. We hypothesize that NPY may signal a seasonal decrease in food availability and promote non-breeding aggression. In both animal models, non-breeding aggression is estrogen-dependent but gonad-independent. In non-breeding M. melodia, neurosteroid synthesis rapidly increases in response to a territorial challenge. In G. omarorum, brain aromatase is upregulated in dominant but not subordinate fish. In both species, the dramatic decrease in food availability in the non-breeding season may promote non-breeding aggression, via changes in NPY and/or neurosteroid signaling.
Mechanical Thrombectomy in Isolated Occlusion of the Proximal Posterior Cerebral Artery
Authors: Herweh Christian , Abdalkader Mohamad , Nguyen Thanh N. , Puetz Volker , Schöne Daniela , Kaiser Daniel , Chen Chih-Hao , Jeng Jiann-Shing , Möhlenbruch Markus A. , Ringleb Peter A. , Nagel Simon
Published: July 2021

Introduction: Endovascular therapy (EVT) is established as first-line treatment for acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. For basilar artery occlusion, recent randomized clinical trials demonstrated not only equipoise but also advantages for EVT under particular circumstances. It remains unclear whether EVT offers an advantage over best medical management (BMM) including thrombolysis (IVT) in isolated occlusion of the proximal posterior cerebral artery (PCAO).

Methods: Patients with AIS due to PCAO proven by CT or MR angiography were retrospectively identified from local databases at four comprehensive stroke centers in Germany, USA, and Taiwan between 2012 and 2020. Demographic and clinical data were collected, and imaging characteristics including pretherapeutic, interventional, and follow-up imaging were reviewed locally at each center. Patients were grouped according to therapy, i.e., BMM including IVT alone vs. BMM and EVT. Efficacy endpoints were early neurological improvement (ENI) after 24 h or at discharge, good outcome (modified Rankin scale 0–2) after 3 months, as well as hemorrhagic complications and in-house deaths as safety endpoints.

Results: We included 130 patients of whom 23 (17.7%) received EVT. EVT patients had more proximal occlusions (69.9 vs. 43%, p = 0.023) and had a better premorbid function [premorbid mRS, 0 (0–4) vs. 1 (0–3), p < 0.01] when compared to BMM patients. IVT showed a trend toward being less performed in the EVT group (21.7 vs. 41.1%, p = 0.1), while other baseline parameters were balanced. Successful reperfusion was achieved in 52% of EVT patients. ENI was more frequent in the EVT group (61 vs. 35.5%, p = 0.034). Good outcome at 90 days and safety endpoints did not differ. In a bivariate analysis, ENI was independently predicted by the use of EVT (OR, 2.76; CI, 1.055–7.04) and the baseline National Institutes of Health Stroke Scale (NIHSS) (OR, 1.082; CI, 1.027–1.141 per point increase).

Discussion: EVT in isolated PCAO appears safe and feasible. Positive effects on clinical outcome are primarily on ENI but also depend on the initial stroke severity. Further prospective or randomized studies are needed to better describe the potential long-term clinical benefits of EVT for PCAO as compared with best medical management.
Monoamine Levels and Parkinson’s Disease Progression: Evidence From a High-Performance Liquid Chromatography Study
Authors: Wichit Patsorn , Thanprasertsuk Sekh , Phokaewvarangkul Onanong , Bhidayasiri Roongroj , Bongsebandhu-phubhakdi Saknan
Published: July 2021

Parkinson’s disease (PD) is associated with dysfunction of monoamine neurotransmitter systems. We investigated changes in the levels of monoamine and their metabolites in PD patients, together with their association to clinical profiles. PD patients and age-matched control subjects (n = 40 per group) were enrolled. Using high-performance liquid chromatography (HPLC) with an electrochemical detector, levels of monoamines (dopamine, DA; norepinephrine, NE; epinephrine, EPI; and serotonin, 5-HT) were measured in plasma, while the metabolites (homovanillic acid, HVA; vanillylmandelic acid, VMA; and 5-hydroxyindoleacetic acid, 5-HIAA) were measured in urine. Plasma DA level was not significantly different between PD and control groups. PD patients had significantly higher plasma NE but lower EPI and 5-HT levels. PD patients had a significantly higher HVA/DA ratio and lower VMA/NE ratio than control subjects, while the 5-HIAA/5-HT ratio was not different between the groups. Regarding the association between monoamine levels and clinical profiles, the DA level had a negative relationship with disease duration and the 5-HT level had a negative relationship with severity of motor impairment. These findings emphasized the involvements of several neurotransmission systems and their association with clinical profiles in PD patients, demonstrated by quantification of monoamine levels in peripheral body fluids. This could benefit appropriate pharmacological treatment planning in respect of monoamine changes and might also help predict subsequent clinical symptoms.
Effects of Multisession Anodal Electrical Stimulation of the Auditory Cortex on Temporary Noise-Induced Hearing Loss in the Rat
Authors: Díaz Iván , Colmenárez-Raga Ana Cecilia , Pérez-González David , Carmona Venezia G. , Plaza Lopez Ignacio , Merchán Miguel A.
Published: July 2021

The protective effect of the efferent system against acoustic trauma (AT) has been shown by several experimental approaches, including damage to one ear, sectioning of the olivocochlear bundle (OCB) in the floor of the IV ventricle, and knock-in mice overexpressing outer hair cell (OHC) cholinergic receptors, among others. Such effects have been related to changes in the regulation of the cholinergic efferent system and in cochlear amplification, which ultimately reverse upon protective hearing suppression. In addition to well-known circuits of the brainstem, the descending corticofugal pathway also regulates efferent neurons of the olivary complex. In this study, we applied our recently developed experimental paradigm of multiple sessions of electrical stimulation (ES) to activate the efferent system in combination with noise overstimulation. ABR thresholds increased 1 and 2 days after AT (8–16 kHz bandpass noise at 107 dB for 90 min) recovering at AT + 14 days. However, after multiple sessions of epidural anodal stimulation, no changes in thresholds were observed following AT. Although an inflammatory response was also observed 1 day after AT in both groups, the counts of reactive macrophages in both experimental conditions suggest decreased inflammation in the epidural stimulation group. Quantitative immunocytochemistry for choline acetyltransferase (ChAT) showed a significant decrease in the size and optical density of the efferent terminals 1 day after AT and a rebound at 14 days, suggesting depletion of the terminals followed by a long-term compensatory response. Such a synthesis recovery was significantly higher upon cortical stimulation. No significant correlation was found between ChAT optical density and size of the buttons in sham controls (SC) and ES/AT + 1day animals; however, significant negative correlations were shown in all other experimental conditions. Therefore, our comparative analysis suggests that cochleotopic cholinergic neurotransmission is also better preserved after multisession epidural stimulation.
A Biomimetic, SoC-Based Neural Stimulator for Novel Arbitrary-Waveform Stimulation Protocols
Authors: Culaclii Stanislav , Wang Po-Min , Taccola Giuliano , Yang William , Bailey Brett , Chen Yan-Peng , Lo Yi-Kai , Liu Wentai
Published: July 2021

Novel neural stimulation protocols mimicking biological signals and patterns have demonstrated significant advantages as compared to traditional protocols based on uniform periodic square pulses. At the same time, the treatments for neural disorders which employ such protocols require the stimulator to be integrated into miniaturized wearable devices or implantable neural prostheses. Unfortunately, most miniaturized stimulator designs show none or very limited ability to deliver biomimetic protocols due to the architecture of their control logic, which generates the waveform. Most such designs are integrated into a single System-on-Chip (SoC) for the size reduction and the option to implement them as neural implants. But their on-chip stimulation controllers are fixed and limited in memory and computing power, preventing them from accommodating the amplitude and timing variances, and the waveform data parameters necessary to output biomimetic stimulation. To that end, a new stimulator architecture is proposed, which distributes the control logic over three component tiers – software, microcontroller firmware and digital circuits of the SoC, which is compatible with existing and future biomimetic protocols and with integration into implantable neural prosthetics. A portable prototype with the proposed architecture is designed and demonstrated in a bench-top test with various known biomimetic output waveforms. The prototype is also tested in vivo to deliver a complex, continuous biomimetic stimulation to a rat model of a spinal-cord injury. By delivering this unique biomimetic stimulation, the device is shown to successfully reestablish the connectivity of the spinal cord post-injury and thus restore motor outputs in the rat model.
EvAn: Neuromorphic Event-Based Sparse Anomaly Detection
Authors: Annamalai Lakshmi , Chakraborty Anirban , Thakur Chetan Singh
Published: July 2021

Event-basedcameras are bio-inspired novel sensors that asynchronously record changes in illumination in the form of events. This principle results in significant advantages over conventional cameras, such as low power utilization, high dynamic range, and no motion blur. Moreover, by design, such cameras encode only the relative motion between the scene and the sensor and not the static background to yield a very sparse data structure. In this paper, we leverage these advantages of an event camera toward a critical vision application—video anomaly detection. We propose an anomaly detection solution in the event domain with a conditional Generative Adversarial Network (cGAN) made up of sparse submanifold convolution layers. Video analytics tasks such as anomaly detection depend on the motion history at each pixel. To enable this, we also put forward a generic unsupervised deep learning solution to learn a novel memory surface known as Deep Learning (DL) memory surface. DL memory surface encodes the temporal information readily available from these sensors while retaining the sparsity of event data. Since there is no existing dataset for anomaly detection in the event domain, we also provide an anomaly detection event dataset with a set of anomalies. We empirically validate our anomaly detection architecture, composed of sparse convolutional layers, on this proposed and online dataset. Careful analysis of the anomaly detection network reveals that the presented method results in a massive reduction in computational complexity with good performance compared to previous state-of-the-art conventional frame-based anomaly detection networks.
Effects of Daytime Dry Fasting on Hydration, Glucose Metabolism and Circadian Phase: A Prospective Exploratory Cohort Study in Bahá'í Volunteers
Authors: Koppold-Liebscher Daniela A. , Klatte Caroline , Demmrich Sarah , Schwarz Julia , Kandil Farid I. , Steckhan Nico , Ring Raphaela , Kessler Christian S. , Jeitler Michael , Koller Barbara , Ananthasubramaniam Bharath , Eisenmann Clemens , Mähler Anja , Boschmann Michael , Kramer Achim , Michalsen Andreas
Published: July 2021

Background: Religiously motivated Bahá'í fasting (BF) is a form of intermittent dry fasting celebrated by abstaining from food and drinks during daylight hours every year in March for 19 consecutive days.

Aim: To test the safety and effects of BF on hydration, metabolism, and the circadian clock.

Methods: Thirty-four healthy Bahá'í volunteers (15 women) participated in this prospective, exploratory cohort study. Laboratory examinations were carried out in four study visits: before fasting (V0), in the third week of fasting (V1) as well as 3 weeks (V3) and 3 months (V4) after fasting. Data collection included blood and urine samples, anthropometric measurements and bioelectrical impedance analysis. At V0 and V1, 24- and 12-hour urine and serum osmolality were measured. At V0–V2, alterations in the circadian clock phase were monitored in 16 participants. Our study was augmented by an additional survey with 144 healthy Bahá'í volunteers filling out questionnaires and with subgroups attending metabolic measurements (n = 11) and qualitative interviews (n = 13), the results of which will be published separately.

Results: Exploratory data analysis revealed that serum osmolality (n = 34, p < 0.001) and 24-hour urine osmolality (n = 34, p = 0.003) decreased during daytime fasting but remained largely within the physiological range and returned to pre-fasting levels during night hours. BMI (body mass index), total body fat mass, and resting metabolic rate decreased during fasting (n = 34, p < 0.001), while body cell mass and body water appeared unchanged. The circadian phase estimated by transcript biomarkers of blood monocytes advanced by 1.1 h (n = 16, p < 0.005) during fasting and returned to pre-fasting values 3 weeks after fasting. Most observed changes were not detectable anymore 3 months after fasting.

Conclusions: Results indicate that BF (Bahá'í fasting) is safe, has no negative effects on hydration, can improve fat metabolism and can cause transient phase shifts of circadian rhythms.

Trial Registration:https://www.clinicaltrials.gov/, identifier: NCT03443739.
Fermented and Germinated Processing Improved the Protective Effects of Foxtail Millet Whole Grain Against Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis and Gut Microbiota Dysbiosis in C57BL/6 Mice
Authors: Zhang Yuhan , Liu Wei , Zhang Di , Yang Yanbing , Wang Xianshu , Li Lingfei
Published: July 2021

This study investigated the effects of foxtail millet whole grain flours obtained through different processing methods on alleviating symptoms and gut microbiota dysbiosis in a dextran sulfate sodium (DSS)-induced murine colitis model. Sixty C57BL/6 mice were divided into six groups (n = 10 in each group), including one control group (CTRL) without DSS treatment and five DSS-treated groups receiving one of the following diets: AIN-93M standard diet (93MD), whole grain foxtail millet flour (FM), fermented (F-FM), germinated (G-FM), and fermented-germinated foxtail millet flour (FG-FM). A comparison of the disease activity index (DAI) demonstrated that foxtail millet whole grain-based diets could alleviate the symptoms of enteritis to varying degrees. In addition, 16S rRNA gene sequencing revealed that FG-FM almost completely alleviated DSS-induced dysbiosis. Mice on the FG-FM diet also had the lowest plasma IL-6 levels and claudin2 expression levels in the colon, indicating reduced systemic inflammation and improved gut barrier function. This study suggested that foxtail millet whole grain is an attractive choice for the intervention of IBD and gut microbiota dysbiosis, and its prebiotic properties are highly affected by the processing methods.
A CT-Based Radiomics Nomogram for Preoperative Prediction of Lymph Node Metastasis in Periampullary Carcinomas
Authors: Bi Lei , Liu Yubo , Xu Jingxu , Wang Ximing , Zhang Tong , Li Kaiguo , Duan Mingguang , Huang Chencui , Meng Xiangjiao , Huang Zhaoqin
Published: July 2021

Purpose

To establish and validate a radiomics nomogram for preoperatively predicting lymph node (LN) metastasis in periampullary carcinomas.

Materials and Methods

A total of 122 patients with periampullary carcinoma were assigned into a training set (n = 85) and a validation set (n = 37). The preoperative CT radiomics of all patients were retrospectively assessed and the radiomic features were extracted from portal venous-phase images. The one-way analysis of variance test and the least absolute shrinkage and selection operator regression were used for feature selection. A radiomics signature was constructed with logistic regression algorithm, and the radiomics score was calculated. Multivariate logistic regression model integrating independent risk factors was adopted to develop a radiomics nomogram. The performance of the radiomics nomogram was assessed by its calibration, discrimination, and clinical utility with independent validation.

Results

The radiomics signature, constructed by seven selected features, was closely related to LN metastasis in the training set (p < 0.001) and validation set (p = 0.017). The radiomics nomogram that incorporated radiomics signature and CT-reported LN status demonstrated favorable calibration and discrimination in the training set [area under the curve (AUC), 0.853] and validation set (AUC, 0.853). The decision curve indicated the clinical utility of our nomogram.

Conclusion

Our CT-based radiomics nomogram, incorporating radiomics signature and CT-reported LN status, could be an individualized and non-invasive tool for preoperative prediction of LN metastasis in periampullary carcinomas, which might assist clinical decision making.
Long-Term Surgical Outcomes of Liver Resection for Hepatocellular Carcinoma in Patients With HBV and HCV Co-Infection: A Multicenter Observational Study
Authors: Jia Hang-Dong , Liang Lei , Li Chao , Wu Han , Wang Hong , Liang Ying-Jian , Zhou Ya-Hao , Gu Wei-Min , Fan Xin-Ping , Zhang Wan-Guang , Chen Ting-Hao , Chen Zhi-Yu , Zhong Jian-Hong , Lau Wan Yee , Pawlik Timothy M. , Diao Yong-Kang , Xu Qiu-Ran , Shen Feng , Zhang Cheng-Wu , Huang Dong-Sheng , Yang Tian
Published: July 2021

Background

Hepatocellular carcinoma (HCC) is one of the most serious consequences of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study sought to investigate long-term outcomes after liver resection for HCC among patients with HBV/HCV co-infection (HBV/HCV-HCC) compared with patients with HBV infection (HBV-HCC).

Methods

Patients who underwent curative-intent liver resection for HCC were identified from a multicenter Chinese database. Using propensity score matching (PSM), patients with HBV/HCV-HCC were matched one-to-one to patients with HBV-HCC. Overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups before and after PSM.

Results

Among 2,467 patients identified, 93 (3.8%) and 2,374 (96.2%) patients had HBV/HCV-HCC and HBV-HCC, respectively. Compared with patients with HBV-HCC, patients with HBV/HCV-HCC were older, have poorer liver-related characteristics but better tumor-related characteristics. PSM created 88 pairs of patients with comparable liver- and tumor-related characteristics (all P > 0.2). In the PSM cohort, the 3- and 5-year RFS rates in patients with HBV/HCV-HCC were 48.3% and 38.9%, which were significantly poorer than patients with HBV-HCC (61.8% and 49.2%, P = 0.037). Meanwhile, the 3- and 5-year OS rates in patients with HBV/HCV-HCC were also poorer than patients with HBV-HCC (65.4% and 51.1% vs. 73.7% and 63.0%), with a difference close to be significant between them (P = 0.081).

Conclusion

Comparing to patients with HBV-HCC, liver resection resulted in relatively poorer long-term surgical outcomes in patients with HBV/HCV-HCC.
Meta-Analysis of the Efficacy of Laparoscopic Pyeloplasty for Ureteropelvic Junction Obstruction via Retroperitoneal and Transperitoneal Approaches
Authors: Ji Fengming , Chen Li , Wu Chengchuang , Li Jinrong , Hang Yu , Yan Bing
Published: July 2021

Objective: This study aimed to evaluate the clinical efficacy of laparoscopic pyeloplasty (LP) for ureteropelvic junction obstruction (UPJO) via retroperitoneal and transperitoneal approaches.

Method: A systematic literature search on keywords was undertaken using PubMed, Cochrane Library, Embase, China Nation Knowledge (CNKI), and Wanfang. The eligible literature was screened according to inclusion and exclusion criteria. Meta-analysis was performed by using RevMan 5.0 software.

Results: According to the inclusion and exclusion criteria, 12 studies were identified with a total of 777 patients. Four hundred eight patients were treated with retroperitoneal laparoscopic pyeloplasty (RLP), and 368 patients were treated with transperitoneal laparoscopic pyeloplasty (TLP). The meta-analysis results showed that the two approaches were similar in terms of presence of postoperative hospital stay, postoperative complication, the rate of conversion, and recurrence (p > 0.05). The operative time in the TLP group was significantly shorter than the RLP group (MD = 16.6; 95% CI, 3.40–29.80; p = 0.01). The duration of drainage was significantly shorter (MD = −1.06; 95% CI, −1.92 to −0.19; p = 0.02), and the score of postoperative visual analog score (VAS) was significantly lower in the RLP group than in the TLP group (MD = −0.52; 95% CI, −0.96 to −0.08; p = 0.02).

Conclusion: Both approaches have good success rates and low postoperative complication rates. RLP provides a shorter duration of drainage and lower VAS score, but it takes more operative time than TLP.
Glomerular Damage in Trichloroethylene-Sensitized Mice: Targeting Cathepsin L-Induced Hyperactive mTOR Signaling
Authors: Wang Feng , Dai Yuying , Huang Meng , Zhang Chenchen , Huang Liping , Wang Hui , Ye Liangping , Wu Qifeng , Zhang Xuejun , Zhu Qixing
Published: July 2021

Trichloroethylene (TCE) is a serious health hazard for workers with daily exposure, causing occupational medicamentosa-like dermatitis due to TCE (OMDT) and glomerular damage. Recent studies suggest that mTORC1 signaling is activated in various glomerular disorders; however, the role of mTORC1 signaling in TCE-induced glomerular damage remains to be explored. In the present study, 6 OMDT patients were enrolled and a TCE-sensitized mouse model was established to investigate molecular mechanisms underlying the glomerular damage associated with OMDT. Glomerular damage was assessed by levels of urine nephrin, H&E staining, and renal function test. Ultrastructural change of podocyte was investigated by transmission electron microscopy. The podocyte-related molecules including nephrin, α-actinin-4, and integrin β1 were visualized by immunofluorescence. The activation of mTORC1 signaling was confirmed by Western blot. Glomerular apoptosis was examined by the TUNEL test and Western blotting. Expression and location of cathepsin L (CTSL) were assessed by RT-PCR and immunofluorescence. Our results showed that TCE sensitization caused damage to glomerular structural integrity and also increased the activation of mTORC1 signaling, which was accompanied by podocyte loss, hypertrophy, and glomerular apoptosis. Importantly, we also found that over-expressed CTSL was mainly located in podocyte and CTSL inhibition could partially block the activation of mTORC1 signaling. Thus, our findings suggested a novel mechanism whereby hyperactive mTOR signaling contributes to TCE sensitization–induced and immune-mediated glomerular damage via CTSL activation.
Phenethyl Isothiocyanate Induces Apoptosis Through ROS Generation and Caspase-3 Activation in Cervical Cancer Cells
Authors: Shoaib Shoaib , Tufail Saba , Sherwani Mohammad Asif , Yusuf Nabiha , Islam Najmul
Published: July 2021

The latest research shows that current chemotherapeutics are ineffective because of the development of resistance in cervical cancer cells, and hence, their scope of use is limited. The main concern of researchers at the moment is the discovery of safe and effective antiproliferative plant chemicals that can aid in the battle against cervical cancer. Previous studies have shown the possible anticancer potential of phenethyl isothiocyanate obtained from cruciferous plants for many cancers, which targets various signaling pathways to exercise chemopreventive and therapeutic effects. This provides the basis for studying phenethyl isothiocyanate's therapeutic potential against cervical cancer. In the present study, cervical cancer cells were treated with various doses of phenethyl isothiocyanate, alone and in combination with cisplatin. Phenethyl isothiocyanate alone was sufficient to cause nucleus condensation and fragmentation and induce apoptosis in cervical cancer cells, but evident synergistic effects were observed in combination with cisplatin. In addition, phenethyl isothiocyanate treatment increased the production of intracellular ROS in a dose-dependent manner in cervical cancer cells. Furthermore, investigation of phenethyl isothiocyanate induced mitochondrial reactive oxygen species production, and activation of caspases showed that phenethyl isothiocyanate significantly activated caspase-3.
Robust Optical Frequency Comb Generation by Using a Three-Stage Optical Nonlinear Dynamic
Authors: Zhang Yali , Liao Shuxu , Wang Guan , Yang Ke , Zhang Zhiyao , Zhang Shangjian , Liu Yong
Published: July 2021

In this article, we propose and investigate a novel scheme to generate optical frequency combs (OFCs) by using a three-stage generator, which is based on optical injection–induced dynamics cascaded by subharmonic electro-optic modulation and the four-wave mixing (FWM) effect. A primary seed OFC is rooted from the nonlinear dynamics in the optically injected semiconductor laser, and its performance is improved using a two-stage booster based on subharmonic electro-optic modulation and the FWM effect. The comb spacing can be easily tuned by adjusting that of the primary seed OFC or through electro-optic modulation by the use of subharmonics with different orders. Moreover, it becomes stabilized because the phase relationship between the comb teeth can be fixed in the process of subharmonic electro-optic modulation. Its optical spectrum continues to be broadened in the following FWM process. Finally, robust OFCs with a comb spacing of 4 GHz and a comb teeth number of 23 and a comb spacing of 5 GHz and a comb teeth number of 21 are experimentally demonstrated.
Beam Splitters Fabricated by Nonlinear Focusing of Femtosecond Laser Writing in Pure YAG Crystal
Authors: Wu Pengfei , Yang Senchi , Ren Yingying , Liu Hongliang
Published: July 2021

We report on the fabrication of waveguides and beam splitters in pure YAG crystals by femtosecond laser direct writing (FLDW). During the femtosecond laser writing process, a positive refractive index is induced through the nonlinear focusing above the focus position, resulting in an unusual guiding cross-sectional configuration. The supported guiding modes at 632.8 nm are measured and analyzed using the end–face coupling system. The propagation loss can be as low as 1.9 dB/cm for the single-line waveguide. Different from the geometry of the traditional fs-laser modified area, this novel structure might offer a new approach in the quest toward integrated photonics.
Bile Acids, Liver Cirrhosis, and Extrahepatic Vascular Dysfunction
Authors: Sauerbruch Tilman , Hennenberg Martin , Trebicka Jonel , Beuers Ulrich
Published: July 2021

The bile acid pool with its individual bile acids (BA) is modulated in the enterohepatic circulation by the liver as the primary site of synthesis, the motility of the gallbladder and of the intestinal tract, as well as by bacterial enzymes in the intestine. The nuclear receptor farnesoid X receptor (FXR) and Gpbar1 (TGR5) are important set screws in this process. Bile acids have a vasodilatory effect, at least according to in vitro studies. The present review examines the question of the extent to which the increase in bile acids in plasma could be responsible for the hyperdynamic circulatory disturbance of liver cirrhosis and whether modulation of the bile acid pool, for example, via administration of ursodeoxycholic acid (UDCA) or via modulation of the dysbiosis present in liver cirrhosis could influence the hemodynamic disorder of liver cirrhosis. According to our analysis, the evidence for this is limited. Long-term studies on this question are lacking.
Trait Expression and Environmental Responses of Pea (Pisum sativum L.) Genetic Resources Targeting Cultivation in the Arctic
Authors: Carlson-Nilsson Ulrika , Aloisi Karolina , Vågen Ingunn M. , Rajala Ari , Mølmann Jørgen B. , Rasmussen Søren K. , Niemi Mari , Wojciechowska Ewelina , Pärssinen Pertti , Poulsen Gert , Leino Matti W.
Published: July 2021

In the Arctic part of the Nordic region, cultivated crops need to specifically adapt to adverse and extreme climate conditions, such as low temperatures, long days, and a short growing season. Under the projected climate change scenarios, higher temperatures and an earlier spring thaw will gradually allow the cultivation of plants that could not be previously cultivated there. For millennia, Pea (Pisum sativum L.) has been a major cultivated protein plant in Nordic countries but is currently limited to the southern parts of the region. However, response and adaptation to the Arctic day length/light spectrum and temperatures are essential for the productivity of the pea germplasm and need to be better understood. This study investigated these factors and identified suitable pea genetic resources for future cultivation and breeding in the Arctic region. Fifty gene bank accessions of peas with a Nordic landrace or cultivar origin were evaluated in 2-year field trials at four Nordic locations in Denmark, Finland, Sweden, and Norway (55° to 69° N). The contrasting environmental conditions of the trial sites revealed differences in expression of phenological, morphological, crop productivity, and quality traits in the accessions. The data showed that light conditions related to a very long photoperiod partly compensated for the lack of accumulated temperature in the far north. A critical factor for cultivation in the Arctic is the use of cultivars with rapid flowering and maturation times combined with early sowing. At the most extreme site (69°N), no accession reached full maturation. Nonetheless several accessions, predominantly landraces of a northern origin, reached a green harvest state. All the cultivars reached full maturation at the sub-Arctic latitude in northern Sweden (63°N) when plants were established early in the season. Seed yield correlated positively with seed number and aboveground biomass, but negatively with flowering time. A high yield potential and protein concentration of dry seed were found in many garden types of pea, confirming their breeding potential for yield. Overall, the results indicated that pea genetic resources are available for breeding or immediate cultivation, thus aiding in the northward expansion of pea cultivation. Predicted climate changes would support this expansion.
Genetic Dissection of Root Angle of Brassica napus in Response to Low Phosphorus
Authors: Duan Xianjie , Wang Xiaohua , Jin Kemo , Wang Wei , Liu Haijiang , Liu Ling , Zhang Ying , Hammond John P. , White Philip J. , Ding Guangda , Xu Fangsen , Shi Lei
Published: July 2021

Plant root angle determines the vertical and horizontal distribution of roots in the soil layer, which further influences the acquisition of phosphorus (P) in topsoil. Large genetic variability for the lateral root angle (root angle) was observed in a linkage mapping population (BnaTNDH population) and an association panel ofBrassica napuswhether at a low P (LP) or at an optimal P (OP). At LP, the average root angle of both populations became smaller. Nine quantitative trait loci (QTLs) at LP and three QTLs at OP for the root angle and five QTLs for the relative root angle (RRA) were identified by the linkage mapping analysis in theBnaTNDH population. Genome-wide association studies (GWASs) revealed 11 single-nucleotide polymorphisms (SNPs) significantly associated with the root angle at LP (LPRA). The interval of a QTL for LPRA on A06 (qLPRA-A06c) overlapped with the confidence region of the leading SNP (Bn-A06-p14439400) significantly associated with LPRA. In addition, a QTL cluster on chromosome C01 associated with the root angle and the primary root length (PRL) in the “pouch and wick” high-throughput phenotyping (HTP) system, the root P concentration in the agar system, and the seed yield in the field was identified in theBnaTNDH population at LP. A total of 87 genes on A06 and 192 genes on C01 were identified within the confidence interval, and 14 genes related to auxin asymmetric redistribution and root developmental process were predicted to be candidate genes. The identification and functional analyses of these genes affecting LPRA are of benefit to the cultivar selection with optimal root system architecture (RSA) under P deficiency inBrassica napus.
Impact of Storage Temperature on Pollen Viability and Germinability of Four Serbian Autochthon Apple Cultivars
Authors: Ćalić Dušica , Milojević Jelena , Belić Maja , Miletić Rade , Zdravković-Korać Snežana
Published: July 2021

Globalization has drastically reduced the number of autochthon apple cultivars in the Serbian market and most of them have nearly disappeared; however, some of these cultivars, such as Petrovača, Budimka, Kolačara Pozna, and Kožara, have extraordinary quality, good pomological characteristics, and pest and disease resistance. The present study was conducted to develop a protocol for the storage of pollen for further use in the conservation and breeding of these cultivars. Viability and germination of the mature pollen were testedin vitro, at four storage temperatures (20, 4, −20, and −80°C), right after harvest or 1, 2, 3, 4, 5, and 6 months after storage. Differences in fresh pollen viability and germination between cultivars were statistically significant and ranged from 60 to 88% and 59 to 98%, respectively. Fresh pollen of cv. Budimka showed the highest viability and germination in comparison with other cultivars, especially cv. Kožara. Pollen viability and germination decreased over the storage period, and it was the lowest after 6 months of storage at room temperature in all tested cultivars. Storage at 4°C prolonged the pollen viability and germinability of 1–5 fold, depending on the cultivar and treatment duration; however, the pollen longevity of all cultivars was significantly extended when stored at −20 or −80°C. After 6 months, pollen of cv. Budimka stored at −20 and −80°C showed 14–15 fold higher germination rates in relation to pollen storage at room temperature for the same period. The results of the present study suggest that the pollen of these apple cultivars could be efficiently maintained at −20°C and could be further used for breeding purposes, e.g., for crossings between cultivars that flower at different times of the year.
Effects of Design Aesthetics on the Perceived Value of a Product
Authors: Shi Aiqin , Huo Faren , Hou Guanhua
Published: July 2021

Design aesthetics play a crucial role in product design. Stakeholders expect to develop highly valuable premium products by improving the design aesthetics of products. Nevertheless, the question of how to evaluate the value of design aesthetics has not been fully addressed. In this study, the effects of design aesthetics on the evaluation of the value of a product were investigated through a strictly controlled experiment in which the neural responses of the participants were measured. Forty participants completed the design aesthetics experiment in a laboratory setting. Images of products were divided into two categories: those representing high– and low–design-aesthetic stimuli. Both types of images were labeled with the same price. Overall, the images representing high design aesthetics elicited smaller N100 and lower P200 amplitudes than did the images representing low design aesthetics. This finding indicates that low design aesthetics attracted more attention than high design aesthetics did and that high design aesthetics triggered positive emotions. Low–design-aesthetic products elicited a larger N400 amplitude. This finding reveals the inconsistency between labeled and expected prices. The present study indicates that the N400 component can be used as an indicator for measuring the perceived value of a product in a future product design study. Our study provides event-related potential indicators that can be easily applied in decision making for measuring the perceived value of a product’s design.
Changes in Parents’ Home Learning Activities With Their Children During the COVID-19 Lockdown – The Role of Parental Stress, Parents’ Self-Efficacy and Social Support
Authors: Oppermann Elisa , Cohen Franziska , Wolf Katrin , Burghardt Lars , Anders Yvonne
Published: July 2021

As a result of the abrupt closures of daycare centers in Germany due to the COVID-19 pandemic, parents’ ability to provide learning opportunities at home became all the more important. Building on the family stress model, the study investigates how parental stress affected changes in parents’ provision of home learning activities (HLA) during the lockdown, compared to before the lockdown. In addition, the study considers parental self-efficacy and perceived social support as protective factors that may play important roles in disrupting the negative effects of stress. Data stems from a nation-wide survey of 7,837 German parents of children ages 1–6 years, which was conducted in Spring 2020 during the first wave of COVID-19 infections and at a time of strict restrictions in Germany. Results revealed that parental stress was negatively related to changes in the provision of HLA. Parental self-efficacy and an intact social support system were protective of parental stress during the lockdown. Additionally, parental self-efficacy and – to a larger extend – perceived social support interacted with parental stress in the relation to changes in the provision of HLA. Specifically, self-efficacy and perceived social support acted as protective factors that buffered the negative influence of stress on parents’ ability to provide educational activities for their children at home. These results have important implications for supporting families with young children during challenging times, such as the COVID-19 pandemic and the temporary closure of daycare centers.
What Behavioral Abilities Emerged at Key Milestones in Human Brain Evolution? 13 Hypotheses on the 600-Million-Year Phylogenetic History of Human Intelligence
Authors: Bennett Max S.
Published: July 2021

This paper presents 13 hypotheses regarding the specific behavioral abilities that emerged at key milestones during the 600-million-year phylogenetic history from early bilaterians to extant humans. The behavioral, intellectual, and cognitive faculties of humans are complex and varied: we have abilities as diverse as map-based navigation, theory of mind, counterfactual learning, episodic memory, and language. But these faculties, which emerge from the complex human brain, are likely to have evolved from simpler prototypes in the simpler brains of our ancestors. Understanding the order in which behavioral abilities evolved can shed light on how and why our brains evolved. To propose these hypotheses, I review the available data from comparative psychology and evolutionary neuroscience.
Measuring Gaze and Arrow Cuing Effects With a Short Test Adapted to Brain Damaged Patients With Unilateral Spatial Neglect: A Preliminary Study
Authors: Narison Rindra , de Montalembert Marie , Bayliss Andrew , Conty Laurence
Published: July 2021

People with left unilateral spatial neglect (USN) following a right brain lesion show difficulty in orienting their attention toward stimuli presented on the left. However, cuing the stimuli with gaze direction or a pointing arrow can help some of them to compensate for this difficulty. In order to build a tool that helps to identify these patients, we needed a short version of the paradigm classically used to test gaze and arow cuing effects in healthy adults, adapted to the capacities of patients with severe attention deficit. Here, we tested the robustness of the cuing effects measured by such a short version in 48 young adult healthy participants, 46 older healthy participants, 10 patients with left USN following a right brain lesion (USN+), and 10 patients with right brain lesions but no USN (USN–). We observed gaze and arrow cuing effects in all populations, independently of age and presence or absence of a right brain lesion. In the neglect field, the USN+ group showed event greater cuing effect than older healthy participants and the USN– group. We showed that gaze and arrow cuing effects are powerful enough to be detected in a very short test adapted to the capacities of older patients with severe attention deficits, which increases their applicability in rehabilitation settings. We further concluded that our test is a suitable basis to develop a tool that will help neuropsychologists to identify USN patients who respond to gaze and/or arrow cuing in their neglect field.
Structure of Relationships Between the University Organizational Image and Student Loyalty
Authors: Álvarez-García José , del Río-Rama María de la Cruz , Oliveira Cristiana , Durán-Sánchez Amador
Published: July 2021

The aim of this research is to contrast an explanatory model of how the perceived organizational image of a university center (faculty) influences its students' loyalty. The data is obtained from a structured survey of students in Spain, obtaining a sample of 224 valid questionnaires. The methodology used is exploratory and confirmatory factor analysis to validate the measurement scales and the estimation of the model is carried out by applying Structural Equation Modeling (SEM). The results show that organizational image is the key variable to influence students' decision to continue taking new courses at the center, as well as to recommend it to other people. It is observed that the greater students' positive perception of the organizational image is, the greater their satisfaction with the center will be, which results in a higher level of loyalty to the center in which they study. However, their identification levels with the center is not a relevant variable in the process of increasing loyalty.