bluuebunny/crossref_metadata_2025 huggingface dataset:
IL-21 Receptor Blockade Shifts the Follicular T Cell Balance and Reduces De Novo Donor-Specific Antibody Generation
Authors: Nian Yeqi , Xiong Zhilei , Zhan Panpan , Wang Zhen , Xu Yang , Wei Jianghao , Zhao Jie , Fu Yingxin
Published: April 2021

Donor-specific antibodies (DSAs) play a key role in chronic kidney allograft injury. Follicular T helper (Tfh) cells trigger the humoral alloimmune response and promote DSA generation, while T-follicular regulatory (Tfr) cells inhibit antibody production by suppressing Tfh and B cells. Interleukin (IL)-21 exerts a distinct effect on Tfh and Tfr. Here, we studied whether blocking IL-21R with anti-IL-21R monoclonal antibody (αIL-21R) changes the Tfh/Tfr balance and inhibits DSA generation. First, we investigated the impact of αIL-21R on CD4+ T cell proliferation and apoptosis. The results showed that αIL-21R did not have cytotoxic effects on CD4+ T cells. Next, we examined Tfh and regulatory T cells (Tregs) in an in vitro conditioned culture model. Naïve CD4+ T cells were isolated from 3-month-old C57BL/6 mice and cultured in Tfh differentiation inducing conditions in presence of αIL-21R or isotype IgG and differentiation was evaluated by CXCR5 expression, a key Tfh marker. αIL-21R significantly inhibited Tfh differentiation. In contrast, under Treg differentiation conditions, FOXP3 expression was inhibited by IL-21. Notably, αIL-21R rescued IL-21-inhibited Treg differentiation. For in vivo investigation, a fully mismatched skin transplantation model was utilized to trigger the humoral alloimmune response. Consistently, flow cytometry revealed a reduced Tfh/Tfr ratio in recipients treated with αIL-21R. Germinal center response was evaluated by flow cytometry and lectin histochemistry. We observed that αIL-21R significantly inhibited germinal center reaction. Most importantly, DSA levels after transplantation were significantly inhibited by αIL-21R at different time points. In summary, our results demonstrate that αIL-21R shifts the Tfh/Tfr balance toward DSA inhibition. Therefore, αIL-21R may be a useful therapeutic agent to prevent chronic antibody mediated rejection after organ transplantation.
Immunomodulatory Effects of Dopamine in Inflammatory Diseases
Authors: Feng Yifei , Lu Yan
Published: April 2021

Dopamine (DA) receptor, a significant G protein-coupled receptor, is classified into two families: D1-like (D1 and D5) and D2-like (D2, D3, and D4) receptor families, with further formation of homodimers, heteromers, and receptor mosaic. Increasing evidence suggests that the immune system can be affected by the nervous system and neurotransmitters, such as dopamine. Recently, the role of the DA receptor in inflammation has been widely studied, mainly focusing on NLRP3 inflammasome, NF-κB pathway, and immune cells. This article provides a brief review of the structures, functions, and signaling pathways of DA receptors and their relationships with inflammation. With detailed descriptions of their roles in Parkinson disease, inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis, this article provides a theoretical basis for drug development targeting DA receptors in inflammatory diseases.
Seasonal Changes in Dissolved Organic Matter Composition in a Patagonian Fjord Affected by Glacier Melt Inputs
Authors: Marshall Matthew G. , Kellerman Anne M. , Wadham Jemma L. , Hawkings Jon R. , Daneri Giovanni , Torres Rodrigo , Pryer Helena V. , Beaton Alexander , Ng Hong Chin , Urra Alejandra , Robinson Laura F. , Spencer Robert G. M.
Published: April 2021

Biogeochemical processes in fjords are likely affected by changes in surrounding glacier cover but very little is known about how meltwater directly influences dissolved organic matter (DOM) in fjords. Moreover, the data available are restricted to a handful of northern hemisphere sites. Here we analyze seasonal and spatial variation in dissolved organic carbon (DOC) concentration and DOM composition (spectrofluorescence, ultrahigh resolution mass spectrometry) in Baker-Martinez Fjord, Chilean Patagonia (48°S), to infer the impacts of rapid regional deglaciation on fjord DOM. We show that surface layer DOC concentrations do not vary significantly between seasons, but DOM composition is sensitive to differences in riverine inputs. In summer, higher protein-like fluorescence reflects increased glacial meltwater inputs, whilst molecular level data show weaker influence from marine DOM due to more intense stratification. We postulate that the shifting seasonal balance of riverine and marine waters affects the supply of biolabile peptides and organic nitrogen cycling in the surface layer. Trends in DOM composition with increasing salinity are consistent with patterns in estuaries (i.e. preferential removal of aromatic compounds and increasing relative contribution of unsaturated and heteroatom-rich DOM from marine sources). Preliminary estimates also suggest that at least 10% of the annual organic carbon stock in this fjord is supplied by the four largest, glacially fed rivers and that these inputs are dominated by dissolved (84%) over particulate organic carbon. Riverine DOC may therefore be an important carbon subsidy to bacterial communities in the inner fjord. The overall findings highlight the biogeochemical sensitivity of a Patagonian fjord to changes in glacier melt input, which likely has relevance for other glaciated fjords in a warming climate.
HABreports: Online Early Warning of Harmful Algal and Biotoxin Risk for the Scottish Shellfish and Finfish Aquaculture Industries
Authors: Davidson Keith , Whyte Callum , Aleynik Dmitry , Dale Andrew , Gontarek Steven , Kurekin Andrey A. , McNeill Sharon , Miller Peter I. , Porter Marie , Saxon Rachel , Swan Sarah
Published: April 2021

We present an on-line early warning system that is operational in Scottish coastal waters to minimize the risk to humans and aquaculture businesses in terms of the human health and economic impacts of harmful algal blooms (HABs) and their associated biotoxins. The system includes both map and time-series based visualization tools. A “traffic light” index approach is used to highlight locations at elevated HAB/biotoxin risk. High resolution mathematical modelling of cell advection, in combination with satellite remote sensing, provides early warning of HABs that advect from offshore waters to the coast. Expert interpretation of HAB, biotoxin and environmental data in light of recent and historical trends is used to provide, on a weekly basis, a forecast of the risk from HABs and their biotoxins to allow mitigation measures to be put in place by aquaculture businesses, should a HAB event be imminent.
lncRNA SNHG9 Promotes Cell Proliferation, Migration, and Invasion in Human Hepatocellular Carcinoma Cells by Increasing GSTP1 Methylation, as Revealed by CRISPR-dCas9
Authors: Ye Shanting , Ni Yong
Published: April 2021

Hepatocellular carcinoma (HCC) is among the major causes of cancer-related mortalities globally. Long non-coding RNAs (LncRNAs), as epigenetic molecules, contribute to malignant tumor incidences and development, including HCC. Although LncRNA SNHG9 is considered an oncogene in many cancers, the biological function and molecular mechanism of SNHG9 in HCC are still unclear. We investigated the effects of lncRNA SNHG9 on the methylation of glutathione S-transferase P1 (GSTP1) and the progression of HCC. Histological data analysis, CRISPR-dCas9, and cytological function experiment were used to study the expression level and biological function of SNHG9 in HCC. There was an upregulated expression of SNHG9 in HCC, which was associated with shorter disease-free survival. Knockdown of SNHG9 can inhibit cell proliferation, block cell cycle progression, and inhibit cell migration and invasion by upregulating GSTP1. LncRNA SNHG9 recruits methylated enzymes (DNMT1, DNMT3A, and DNMT3B) to increase GSTP1 promoter methylation, a common event in the development of HCC. Inhibition of lncRNA SNHG9 demethylates GSTP1, which prevents HCC progression, presents a promising therapeutic approach for HCC patients.
Neuregulins in Neurodegenerative Diseases
Authors: Ou Guan-yong , Lin Wen-wen , Zhao Wei-jiang
Published: April 2021

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), are typically characterized by progressive neuronal loss and neurological dysfunctions in the nervous system, affecting both memory and motor functions. Neuregulins (NRGs) belong to the epidermal growth factor (EGF)-like family of extracellular ligands and they play an important role in the development, maintenance, and repair of both the central nervous system (CNS) and peripheral nervous system (PNS) through the ErbB signaling pathway. They also regulate multiple intercellular signal transduction and participate in a wide range of biological processes, such as differentiation, migration, and myelination. In this review article, we summarized research on the changes and roles of NRGs in neurodegenerative diseases, especially in AD. We elaborated on the structural features of each NRG subtype and roles of NRG/ErbB signaling networks in neurodegenerative diseases. We also discussed the therapeutic potential of NRGs in the symptom remission of neurodegenerative diseases, which may offer hope for advancing related treatment.
Working Memory Alterations After a Romantic Relationship Breakup
Authors: Verhallen Anne M. , Renken Remco J. , Marsman Jan-Bernard C. , ter Horst Gert J.
Published: April 2021

Experiencing stress can have a disadvantageous effect on mental well-being. Additional to the relation between suffering from chronic stress and depression, both stress (acute and chronic) and depression are associated with cognitive alterations, including working memory. The breakup of a relationship is considered to be a stressful event that can lead to symptoms of depression in otherwise healthy people. Additional to elevated depression scores, stress-related cognitive alterations may occur in this population as well. Therefore, in the present fMRI study we investigated whether experiencing a relationship breakup is associated with working memory alterations and whether this is related to depressive symptom severity. A three workload version of the n-back task (0-back, 1-back, 2-back) was used to measure working memory in subjects who experienced a breakup in the preceding 6 months (“heartbreak group”, n = 70) and subjects in a romantic relationship (“relationship group”, n = 46). Behavioral task performance was compared between the two groups. Functional MRI scans were analyzed using General Linear Model (GLM) activation analyses. Workload conditions were contrasted to each other and to baseline and group differences were assessed. To investigate whether brain networks are associated with depressive symptom severity within the heartbreak group specifically, a post hoc feature-based Independent Component Analysis was performed on the 2-back > 0-back contrast images to identify brain regions that covaried across subjects. Behaviorally, the heartbreak group performed similar at high workload (i.e., 2-back) and better at moderate workload (i.e., 1-back) than the relationship group. GLM analysis revealed an interaction between group and 2-back > 0-back, 2-back > 1-back and 2-back > baseline; the heartbreak group showed less precuneus activation compared to the relationship group. Furthermore, within the heartbreak group, we found a negative association between depressive symptom severity and a brain network representing mostly the precuneus, anterior cingulate gyrus and supplementary motor cortex. Our findings suggest that the effect of a breakup is accompanied by workload-dependent working memory alterations. Therefore, we propose that this population can potentially be used to investigate the interplay between stress, cognitive functioning and depression.
Functions and Mechanisms of the Voltage-Gated Proton Channel Hv1 in Brain and Spinal Cord Injury
Authors: He Junyun , Ritzel Rodney M. , Wu Junfang
Published: April 2021

The voltage-gated proton channel Hv1 is a newly discovered ion channel that is highly conserved among species. It is known that Hv1 is not only expressed in peripheral immune cells but also one of the major ion channels expressed in tissue-resident microglia of the central nervous systems (CNS). One key role for Hv1 is its interaction with NADPH oxidase 2 (NOX2) to regulate reactive oxygen species (ROS) and cytosolic pH. Emerging data suggest that excessive ROS production increases and requires proton currents through Hv1 in the injured CNS, and manipulations that ablate Hv1 expression or induce loss of function may provide neuroprotection in CNS injury models including stroke, traumatic brain injury, and spinal cord injury. Recent data demonstrating microglial Hv1-mediated signaling in the pathophysiology of the CNS injury further supports the idea that Hv1 channel may function as a key mechanism in posttraumatic neuroinflammation and neurodegeneration. In this review, we summarize the main findings of Hv1, including its expression pattern, cellular mechanism, role in aging, and animal models of CNS injury and disease pathology. We also discuss the potential of Hv1 as a therapeutic target for CNS injury.
Factors Influencing Recanalization After Mechanical Thrombectomy With First-Pass Effect for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis
Authors: Bai Xuesong , Zhang Xiao , Wang Jie , Zhang Yinhang , Dmytriw Adam A. , Wang Tao , Xu Ran , Ma Yan , Li Long , Feng Yao , Mena Carolina Severiche , Yang Kun , Wang Xue , Song Haiqing , Ma Qingfeng , Jiao Liqun
Published: April 2021

Background: First-pass effect (FPE) is increasingly recognized as a predictor of good outcome in large vessel occlusion (LVO). This systematic review and meta-analysis aimed to elucidate the factors influencing recanalization after mechanical thrombectomy (MT) with FPE in treating acute ischemic stroke (AIS).

Methods: Main databases were searched for relevant randomized controlled trials (RCTs) and observational studies reporting influencing factors of MT with FPE in AIS. Recanalization was assessed by the modified thrombolysis in cerebral ischemia (mTICI) score. Both successful (mTICI 2b-3) and complete recanalization (mTICI 2c-3) were observed. Risk of bias was assessed through different scales according to study design. The I2 statistic was used to evaluate the heterogeneity, while subgroup analysis, meta-regression, and sensitivity analysis were performed to investigate the source of heterogeneity. Visual measurement of funnel plots was used to evaluate publication bias.

Results: A total of 17 studies and 6,186 patients were included. Among them, 2,068 patients achieved recanalization with FPE. The results of meta-analyses showed that age [mean deviation (MD):1.21,95% confidence interval (CI): 0.26–2.16; p = 0.012], female gender [odds ratio (OR):1.12,95% CI: 1.00–1.26; p = 0.046], diabetes mellitus (DM) (OR:1.17,95% CI: 1.01–1.35; p = 0.032), occlusion of internal carotid artery (ICA) (OR:0.71,95% CI: 0.52–0.97; p = 0.033), occlusion of M2 segment of middle cerebral artery (OR:1.36,95% CI: 1.05–1.77; p = 0.019), duration of intervention (MD: −27.85, 95% CI: −42.11–13.58; p < 0.001), time of onset to recanalization (MD: −34.63, 95% CI: −58.45–10.81; p = 0.004), general anesthesia (OR: 0.63,95% CI: 0.52–0.77; p < 0.001), and use of balloon guide catheter (BGC) (OR:1.60,95% CI: 1.17–2.18; p = 0.003) were significantly associated with successful recanalization with FPE. At the same time, age, female gender, duration of intervention, general anesthesia, use of BGC, and occlusion of ICA were associated with complete reperfusion with FPE, but M2 occlusion and DM were not.

Conclusion: Age, gender, occlusion site, anesthesia type, and use of BGC were influencing factors for both successful and complete recanalization after first-pass thrombectomy. Further studies with more comprehensive observations indexes are need in the future.
Electroencephalography as a Biomarker for Functional Recovery in Spinal Cord Injury Patients
Authors: Simis Marcel , Doruk Camsari Deniz , Imamura Marta , Filippo Thais Raquel Martins , Rubio De Souza Daniel , Battistella Linamara Rizzo , Fregni Felipe
Published: April 2021

Background

Functional changes after spinal cord injury (SCI) are related to changes in cortical plasticity. These changes can be measured with electroencephalography (EEG) and has potential to be used as a clinical biomarker.

Method

In this longitudinal study participants underwent a total of 30 sessions of robotic-assisted gait training (RAGT) over a course of 6 weeks. The duration of each session was 30 min. Resting state EEG was recorded before and after 30-session rehabilitation therapy. To measure gait, we used the Walking Index for Spinal Cord Injury Scale, 10-Meter- Walking Test, Timed-Up-and-Go, and 6-Min-Walking Test. Balance was measured using Berg Balance Scale.

Results

Fifteen participants with incomplete SCI who had AIS C or D injuries based on American Spinal Cord Injury Association Impairment Scale classification were included in this study. Mean age was 35.7 years (range 17–51) and the mean time since injury was 17.08 (range 4–37) months. All participants showed clinical improvement with the rehabilitation program. EEG data revealed that high beta EEG activity in the central area had a negative correlation with gait (p = 0.049; β coefficient: −0.351; and adj-R2: 0.23) and balance (p = 0.043; β coefficient: −0.158; and adj-R2:0.24) measured at baseline, in a way that greater high beta EEG power was related to worse clinical function at baseline. Moreover, improvement in gait and balance had negative correlations with the change in alpha/theta ratio in the parietal area (Gait: p = 0.049; β coefficient: −0.351; adj-R2: 0.23; Balance: p = 0.043; β coefficient: −0.158; and adj-R2: 0.24).

Conclusion

In SCI, functional impairment and subsequent improvement following rehabilitation therapy with RAGT correlated with the change in cortical activity measured by EEG. Our results suggest that EEG alpha/theta ratio may be a potential surrogate marker of functional improvement during rehabilitation. Future studies are necessary to improve and validate these findings as a neurophysiological biomarker for SCI rehabilitation.
A Randomized Clinical Trial Comparing Eyetronix Flicker Glass and Patching for Treatment of Amblyopia in Children Reveals Similar Improvements in Vision
Authors: Min Seung Hyun , Chen Shijia , Xu Jinling , Chen Bingzhen , Chen Hui , Wang Yuwen , Zhou Jiawei , Yu Xudong
Published: April 2021

Purpose

Recently, Eyetronix Flicker Glass (EFG) has been introduced as a novel treatment for amblyopia. It alternatively deprives the visual input of each eye rapidly (e.g., 7 Hz). However, whether it is comparable with standard patching therapy is unclear. In this randomized clinical trial, we evaluate the efficacy of an EFG therapy as treatment for amblyopia in children and compare it to the patching therapy.

Methods

We tested 31 children (aged 4–13 years) with amblyopia. They were assigned into one of the two treatment groups and were treated for 12 weeks. The first group was treated with EFG for 1 h/day (Flicker Group) and the latter with a standard patch (Patching Group) for 2 h/day. We designated changes from baseline in best-corrected visual acuity (BCVA) of the amblyopic eye as our primary outcome. Changes from baseline in other visual outcomes, such as contrast sensitivity, stereopsis, and fusional vergence range were measured as secondary outcome.

Results

BCVA improved significantly at 12 weeks relative to baseline in both the Flicker (0.13 ± 0.11 logMAR; mean ± SD) and Patching Groups (0.21 ± 0.14 logMAR). However, the improvements were not significantly different between groups (p = 0.13). Contrast sensitivity also significantly improved at 3 and 12 cycles/degree between baseline and 12 weeks in both groups (p’s < 0.05). However, stereopsis and fusion range did not improve significantly in both groups.

Conclusion

An EFG therapy and patching improved BCVA similarly for children with amblyopia at 12 weeks. Both therapies improved the contrast sensitivity at 3 and 12 cycles per degree (cpd); however, only patching improved the contrast sensitivity at 6 cpd. Both therapies did not benefit binocular visual functions (stereopsis and fusional vergence range). We believe that EFG can be an additional choice for therapy.

Clinical Trial Registration

chictr.org number: ChiCTR2000034436.
Reduced Expression of Hippocampal GluN2A-NMDAR Increases Seizure Susceptibility and Causes Deficits in Contextual Memory
Authors: Acutain Maria Florencia , Griebler Luft Jordana , Vazquez Cecila Alejandra , Popik Bruno , Cercato Magalí C. , Epstein Alberto , Salvetti Anna , Jerusalinsky Diana A. , de Oliveira Alvares Lucas , Baez Maria Verónica
Published: April 2021

N-methyl-D-aspartate receptors are heterotetramers composed of two GluN1 obligatory subunits and two regulatory subunits. In cognitive-related brain structures, GluN2A and GluN2B are the most abundant regulatory subunits, and their expression is subjected to tight regulation. During development, GluN2B expression is characteristic of immature synapses, whereas GluN2A is present in mature ones. This change in expression induces a shift in GluN2A/GluN2B ratio known as developmental switch. Moreover, modifications in this relationship have been associated with learning and memory, as well as different pathologies. In this work, we used a specific shRNA to induce a reduction in GluN2A expression after the developmental switch, bothin vitroin primary cultured hippocampal neurons andin vivoin adult male Wistar rats. Afterin vitrocharacterization, we performed a cognitive profile and evaluated seizure susceptibilityin vivo. Ourin vitroresults showed that the decrease in the expression of GluN2A changes GluN2A/GluN2B ratio without altering the expression of other regulatory subunits. Moreover, rats expressing the anti-GluN2A shRNAin vivodisplayed an impaired contextual fear-conditioning memory. In addition, these animals showed increased seizure susceptibility, in terms of both time and intensity, which led us to conclude that deregulation in GluN2A expression at the hippocampus is associated with seizure susceptibility and learning–memory mechanisms.
Potential Applications of Endo-β-N-Acetylglucosaminidases From Bifidobacterium longum Subspecies infantis in Designing Value-Added, Next-Generation Infant Formulas
Authors: Duman Hatice , Kaplan Merve , Arslan Ayşenur , Sahutoglu Arif Sercan , Kayili Haci Mehmet , Frese Steven A. , Karav Sercan
Published: April 2021

Human milk is the optimal source of infant nutrition. Among many other health benefits, human milk can stimulate the development of aBifidobacterium-rich microbiome through human milk oligosaccharides (HMOs). In recent years, the development of novel formulas has placed particular focus on incorporating some of the beneficial functional properties of human milk. These include adding specific glycans aimed to selectively stimulate the growth ofBifidobacterium. However, the bifidogenicity of human milk remains unparalleled. DietaryN-glycans are carbohydrate structures conjugated to a wide variety of glycoproteins. These glycans have a remarkable structural similarity to HMOs and, when released, show a strong bifidogenic effect. This review discusses the biocatalytic potential of the endo-β-N-acetylglucosaminidase enzyme (EndoBI-1) fromBifidobacterium longumsubspeciesinfantis (B. infantis), in releasingN-glycans inherently present in infant formula as means to increase the bifidogenicity of infant formula. Finally, the potential implications for protein deglycosylation with EndoBI-1 in the development of value added, next-generation formulas are discussed from a technical perspective.
Targeting c-Jun in A549 Cancer Cells Exhibits Antiangiogenic Activity In Vitro and In Vivo Through Exosome/miRNA-494-3p/PTEN Signal Pathway
Authors: Shao Chen , Huang Yingying , Fu Bingjie , Pan Shunli , Zhao Xiaoxia , Zhang Ning , Wang Wei , Zhang Zhe , Qiu Yuling , Wang Ran , Jin Meihua , Kong Dexin
Published: April 2021

The oncogene c-Jun is activated by Jun N-terminal kinase (JNK). Exosomes are nanometer-sized membrane vesicles released from a variety of cell types, and are essential for cell-to-cell communication. By using specific JNK inhibitor SP600125 or CRISPR/Cas9 to delete c-Jun, we found that exosomes from SP600125-treated A549 cancer cells (Exo-SP) or from c-Jun-KO-A549 cells (Exo-c-Jun-KO) dramatically inhibited tube formation of HUVECs. And the miR-494 levels in SP600125 treated or c-Jun-KO A549 cells, Exo-SP or Exo-c-Jun-KO, and HUVECs treated with Exo-SP or Exo-c-Jun-KO were significantly decreased. Meanwhile, Exo-SP and Exo-c-Jun-KO enhanced expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN). Addition of miR-494 agomir in Exo-c-Jun-KO treated HUVECs inhibited PTEN expression and promoted tube formation, suggesting the target of miR-494 might be PTEN in HUVECs. Moreover, A549 tumor xenograft model and Matrigel plug assay demonstrated that Exo-c-Jun-KO attenuated tumor growth and angiogenesis through reducing miR-494. Taken together, inhibition of c-Jun in A549 cancer cells exhibited antiangiogenic activity in vitro and in vivo through exosome/miRNA-494-3p/PTEN signal pathway.
Intra-Household and Close-Contact SARS-CoV-2 Transmission Among Children – a Systematic Review
Authors: Spielberger Benedikt D. , Goerne Tessa , Geweniger Anne , Henneke Philipp , Elling Roland
Published: April 2021

Introduction: The outbreak of the novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a range of emergency measures worldwide. Early in the pandemic, children were suspected to act as drivers of the COVID-19 spread in the population, which was based on experiences with influenza virus and other respiratory pathogens. Consequently, closures of schools and kindergartens were implemented in many countries around the world, alongside with other non-pharmaceutical interventions for transmission control. Given the grave and multifaceted consequences of contact restriction measures for children, it is crucial to better understand the effect size of these incisive actions for the COVID-19 pandemic. Therefore, we systematically review the current evidence on transmission of SARS-CoV-2 to and by children.

Data Sources: PubMed and preprints uploaded on medRxiv.

Study Selection: Original research articles, case reports, brief communications, and commentaries were included into the analysis. Each title or abstract was independently reviewed to identify relevant articles. Studies in other languages than English were not included.

Data Extraction: Two reviewers independently reviewed the selected studies. Extracted data included citation of each study, type of healthcare setting, location of the study, characteristics of patient population, and reported outcomes.

Results: Data on transmission of SARS-CoV-2 on or by children is scarce. Several studies show a lower seropositivity of children compared to adults, suggesting a lower susceptibility of especially younger children. Most insight currently comes from household studies suggesting, that children are predominantly infected by their household contacts. The contagiousness however, seems to be comparable between children and adults, based on our meta-analysis of included studies.

Conclusions: Larger and systematic studies are urgently needed to better understand the age dependent patterns of SARS-CoV-2 transmission and thereby design more effective non-pharmaceutical interventions to reduce disease transmission.
Role of Optical Neuromonitoring in Neonatal Encephalopathy—Current State and Recent Advances
Authors: Harvey-Jones Kelly , Lange Frederic , Tachtsidis Ilias , Robertson Nicola J. , Mitra Subhabrata
Published: April 2021

Neonatal encephalopathy (NE) in term and near-term infants is a significant global health problem; the worldwide burden of disease remains high despite the introduction of therapeutic hypothermia. Assessment of injury severity and effective management in the neonatal intensive care unit (NICU) relies on multiple monitoring modalities from systemic to brain-specific. Current neuromonitoring tools provide information utilized for seizure management, injury stratification, and prognostication, whilst systemic monitoring ensures multi-organ dysfunction is recognized early and supported wherever needed. The neuromonitoring technologies currently used in NE however, have limitations in either their availability during the active treatment window or their reliability to prognosticate and stratify injury confidently in the early period following insult. There is therefore a real need for a neuromonitoring tool that provides cot side, early and continuous monitoring of brain health which can reliably stratify injury severity, monitor response to current and emerging treatments, and prognosticate outcome. The clinical use of near-infrared spectroscopy (NIRS) technology has increased in recent years. Research studies within this population have also increased, alongside the development of both instrumentation and signal processing techniques. Increasing use of commercially available cerebral oximeters in the NICU, and the introduction of advanced optical measurements using broadband NIRS (BNIRS), frequency domain NIRS (FDNIRS), and diffuse correlation spectroscopy (DCS) have widened the scope by allowing the direct monitoring of oxygen metabolism and cerebral blood flow, both key to understanding pathophysiological changes and predicting outcome in NE. This review discusses the role of optical neuromonitoring in NE and why this modality may provide the next significant piece of the puzzle toward understanding the real time state of the injured newborn brain.
Lipid Metabolism Profiles in Rheumatic Diseases
Authors: Chen Weilin , Wang Qi , Zhou Bin , Zhang Lihua , Zhu Honglin
Published: April 2021

Rheumatic diseases are a group of chronic autoimmune disorders that involve multiple organs or systems and have high mortality. The mechanisms of these diseases are still ill-defined, and targeted therapeutic strategies are still challenging for physicians. Recent research indicates that cell metabolism plays important roles in the pathogenesis of rheumatic diseases. In this review, we mainly focus on lipid metabolism profiles (dyslipidaemia, fatty acid metabolism) and mechanisms in rheumatic diseases and discuss potential clinical applications based on lipid metabolism profiles.
Improvement of Vascular Function by Knockdown of Salusin-β in Hypertensive Rats via Nitric Oxide and Reactive Oxygen Species Signaling Pathway
Authors: Pan Yan , Sun Shuo , Wang Xingxing , Chen Aidong , Fei Xuejie , Wang Wei , Han Ying
Published: April 2021

Purpose

Salusin-β, a multifunctional vasoactive peptide, has a potentially important function in the pathological development of hypertension. However, the exact functional role of salusin-β and the underlying mechanism in this process are still not fully understood. The current study aimed to investigate the effects of silencing salusin-β on vascular function and vascular remodeling, as well as its signaling pathways in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY).

Methods

Silencing salusin-β was performed by caudal vein injection of adenovirus expressing salusin-β short hairpin RNA (shRNA). Acetylcholine (ACh)-induced endothelium-dependent relaxation was used to evaluate vasodilator function, and high K+ solution-induced constriction was used to evaluate vasoconstriction function.

Results

Salusin-β levels in plasma and its protein expression in mesenteric artery (MA), coronary artery (CA), and pulmonary artery (PA) of SHR were higher than those in WKY. The salusin-β level and expression were decreased effectively by salusin-β shRNA. Knockdown of salusin-β decreased arterial blood pressure (ABP) and high K+ solution-induced vascular constrictions, and improved the endothelium-dependent relaxation and vascular remodeling in SHR. The improved effect of silencing salusin-β on ACh-induced relaxation in SHR was almost blocked by the nitric oxide synthase (NOS) inhibitor L-NAME. Compared to WKY, the endothelial NOS (eNOS) activity and level, and nitric oxide (NO) level were decreased, while NAD(P)H oxidase activity and reactive oxygen species (ROS) levels in MA, CA, and PA of SHR were increased, which were all redressed by salusin-β knockdown.

Conclusion

These results indicate that knockdown of salusin-β improves endothelium-dependent vascular relaxation and vascular remodeling and decreases ABP and vasoconstriction in SHR, which might be accomplished by increasing eNOS activation and NO release while inhibiting NAD(P)H oxidase derived-ROS generation. Scavenging salusin-β improves vascular function and then prevents the development and progression of vasculopathy of hypertension.
Design and Additive Manufacturing of a Biomimetic Customized Cranial Implant Based on Voronoi Diagram
Authors: Sharma Neha , Ostas Daniel , Rotar Horatiu , Brantner Philipp , Thieringer Florian Markus
Published: April 2021

Reconstruction of cranial defects is an arduous task for craniomaxillofacial surgeons. Additive manufacturing (AM) or three-dimensional (3D) printing of titanium patient-specific implants (PSIs) made its way into cranioplasty, improving the clinical outcomes in complex surgical procedures. There has been a significant interest within the medical community in redesigning implants based on natural analogies. This paper proposes a workflow to create a biomimetic patient-specific cranial prosthesis with an interconnected strut macrostructure mimicking bone trabeculae. The method implements an interactive generative design approach based on the Voronoi diagram or tessellations. Furthermore, the quasi-self-supporting fabrication feasibility of the biomimetic, lightweight titanium cranial prosthesis design is assessed using Selective Laser Melting (SLM) technology.
Effects of Time-Dependent Protein Restriction on Growth Performance, Digestibility, and mTOR Signaling Pathways in Juvenile White Shrimp Litopenaeus vannamei
Authors: Zhao Wei , Luo Hongjie , Zhu Wanqing , Yuan Xiaoqin , Shao Jianchun
Published: April 2021

A 6-week feeding strategy experiment was conducted to investigate the effects of time-dependent protein restriction and subsequent recovery on shrimp. Diets with protein levels of 43 and 36% were used as adequate and restricted diets, respectively. Shrimp with an initial body weight of 6.52 ± 0.46 g were given four feeding strategies: feeding on an adequate diet for six weeks (T1, the control), having protein-restricted diet in weeks 1 and 4 (T2), being given a protein-restricted diet in weeks 1, 3, and 5 (T3), and having protein-restricted diet in weeks 1, 2, 4, and 5 (T4). WG, SGR, FE, and PER of shrimp in T1–T3 showed no significant difference (P > 0.05), these indicators of T4 were significantly reduced (P < 0.05). No significant differences were found in digestive enzyme activities of shrimp among all treatments (P > 0.05). Crude protein content of shrimp muscle in T4 was lower than that of T1–T3. The expression level of tor in T4 was lower than that in other treatments, while 4e-bp was higher than that of other treatments. To balance saving on feeding cost and growth performance, giving the shrimp a protein-restricted diet for 1 week with subsequent refeeding (T2 and T3) is suitable for shrimp under high-density conditions.
ZmOrphan94 Transcription Factor Downregulates ZmPEPC1 Gene Expression in Maize Bundle Sheath Cells
Authors: Górska Alicja M. , Gouveia Paulo , Borba Ana Rita , Zimmermann Anna , Serra Tânia S. , Carvalho Pedro , Lourenço Tiago F. , Oliveira M. Margarida , Peterhänsel Christoph , Saibo Nelson J. M.
Published: April 2021

Spatial separation of the photosynthetic reactions is a key feature of C4metabolism. In most C4plants, this separation requires compartmentation of photosynthetic enzymes between mesophyll (M) and bundle sheath (BS) cells. The upstream region of the gene encoding the maize PHOSPHOENOLPYRUVATE CARBOXYLASE 1 (ZmPEPC1) has been shown sufficient to drive M-specificZmPEPC1gene expression. Although this region has been well characterized, to date, only fewtrans-factors involved in theZmPEPC1gene regulation were identified. Here, using a yeast one-hybrid approach, we have identified three novel maize transcription factors ZmHB87, ZmCPP8, and ZmOrphan94 as binding to theZmPEPC1upstream region. Bimolecular fluorescence complementation assays in maize M protoplasts unveiled that ZmOrphan94 forms homodimers and interacts with ZmCPP8 and with two otherZmPEPC1regulators previously reported, ZmbHLH80 and ZmbHLH90. Trans-activation assays in maize M protoplasts unveiled that ZmHB87 does not have a clear transcriptional activity, whereas ZmCPP8 and ZmOrphan94 act as activator and repressor, respectively. Moreover, we observed that ZmOrphan94 reduces the trans-activation activity of both activators ZmCPP8 and ZmbHLH90. Using the electromobility shift assay, we showed that ZmOrphan94 binds to severalcis-elements present in theZmPEPC1upstream region and one of thesecis-elements overlaps with the ZmbHLH90 binding site. Gene expression analysis revealed thatZmOrphan94is preferentially expressed in the BS cells, suggesting that ZmOrphan94 is part of a transcriptional regulatory network downregulatingZmPEPC1transcript level in the BS cells. Based on both this and our previous work, we propose a model underpinning the importance of a regulatory mechanism within BS cells that contributes to the M-specificZmPEPC1gene expression.
Boosting Biomass Quantity and Quality by Improved Mixotrophic Culture of the Diatom Phaeodactylum tricornutum
Authors: Villanova Valeria , Singh Dipali , Pagliardini Julien , Fell David , Le Monnier Adeline , Finazzi Giovanni , Poolman Mark
Published: April 2021

Diatoms are photoautotrophic unicellular algae and are among the most abundant, adaptable, and diverse marine phytoplankton. They are extremely interesting not only for their ecological role but also as potential feedstocks for sustainable biofuels and high-value commodities such as omega fatty acids, because of their capacity to accumulate lipids. However, the cultivation of microalgae on an industrial scale requires higher cell densities and lipid accumulation than those found in nature to make the process economically viable. One of the known ways to induce lipid accumulation in Phaeodactylum tricornutum is nitrogen deprivation, which comes at the expense of growth inhibition and lower cell density. Thus, alternative ways need to be explored to enhance the lipid production as well as biomass density to make them sustainable at industrial scale. In this study, we have used experimental and metabolic modeling approaches to optimize the media composition, in terms of elemental composition, organic and inorganic carbon sources, and light intensity, that boost both biomass quality and quantity of P. tricornutum. Eventually, the optimized conditions were scaled-up to 2 L photobioreactors, where a better system control (temperature, pH, light, aeration/mixing) allowed a further improvement of the biomass capacity of P. tricornutum to 12 g/L.
Plant Size Plays an Important Role in Plant Responses to Low Water Availability and Defoliation in Two Woody Leguminosae Species
Authors: Wang Ning , Li Qiang , Liu Xiao , Yi Shijie , Zhao Mingming , Sun Xinke , Song Huijia , Peng Xiqiang , Fan Peixian , Gao Qun , Wang Yongtao , Yu Linqian , Wang Hui , Du Ning , Wang Renqing
Published: April 2021

Plant size influences plant responses to combined environmental factors under climate change. However, their roles in plant ecophysiological responses are not fully understood. Two rapidly growing Leguminosae species (Robinia pseudoacacia and Amorpha fruticosa) were used to examine plant responses to combined drought and defoliation treatments (two levels of both treatments). Both 1.5 month-old seedlings and 3 month-old seedlings were grown in a greenhouse, and seedling growth, leaf gas exchanges, stem hydraulics, and concentrations of non-structural carbohydrates were determined after 60 days of treatment. Our results indicated defoliation had no significant effect on plant height, basal diameter, and total biomass whatever plant sizes and species. Under the low water availability treatment, the defoliated seedlings significantly increased by 24% in stem water potential compared with non-defoliated seedlings in large R. pseudoacacia. Compared with the high water availability in large non-defoliated R. pseudoacacia seedlings, the low water availability significantly reduced by 26% in stem starch concentration to maintain the stem soluble sugar concentration stable, but not in small R. pseudoacacia seedlings. We also found a negative correlation between leaf and root soluble sugar concentration under low water availability in A. fruticosa. The results demonstrate defoliation could relieve the effect of low water availability in large seedlings. Large seedlings had more compensatory mechanisms in response to defoliation and drought treatments than small seedlings, thus species with large carbon reserves are more recommended for vegetation restoration under combined drought and defoliation conditions. Future studies with more species are crucial for obtaining more rigorous conclusions.
Genetic Relationships Among Physiological Processes, Phenology, and Grain Yield Offer an Insight Into the Development of New Cultivars in Soybean (Glycine max L. Merr)
Authors: Lopez Miguel Angel , Freitas Moreira Fabiana , Rainey Katy Martin
Published: April 2021

Soybean grain yield has steadily increased during the last century because of enhanced cultivars and better agronomic practices. Increases in the total biomass, shorter cultivars, late maturity, and extended seed-filling period are frequently reported as main contributors for better soybean performance. However, there are still processes associated with crop physiology to be improved. From the theoretical standpoint, yield is the product of efficiency of light interception (Ei), radiation use efficiency (RUE), and harvest index (HI). The relative contribution of these three parameters on the final grain yield (GY), their interrelation with other phenological–physiological traits, and their environmental stability have not been well established for soybean. In this study, we determined the additive–genetic relationship among 14 physiological and phenological traits including photosynthesis (A) and intrinsic water use efficiency (iWUE) in a panel of 383 soybean recombinant inbred lines (RILs) through direct (path analyses) and indirect learning methods [least absolute shrinkage and selection operator (LASSO) algorithm]. We evaluated the stability of Ei, RUE, and HI through the slope from the Finley and Wilkinson joint regression and the genetic correlation between traits evaluated in different environments. Results indicate that both supervised and unsupervised methods effectively establish the main relationships underlying changes in Ei, RUE, HI, and GY. Variations in the average growth rate of canopy coverage for the first 40 days after planting (AGR40) explain most of the changes in Ei. RUE is primarily influenced by phenological traits of reproductive length (RL) and seed-filling (SFL) as well as iWUE, light extinction coefficient (K), and A. HI showed a strong relationship with A, AGR40, SFL, and RL. According to the path analysis, an increase in one standard unit of HI promotes changes in 0.5 standard units of GY, while changes in the same standard unit of RUE and Ei produce increases on GY of 0.20 and 0.19 standard units, respectively. RUE, Ei, and HI exhibited better environmental stability than GY, although changes associated with year and location showed a moderate effect in Ei and RUE, respectively. This study brings insight into a group of traits involving A, iWUE, and RL to be prioritized during the breeding process for high-yielding cultivars.
Cognitive and Motor Learning in Internally-Guided Motor Skills
Authors: Bera Krishn , Shukla Anuj , Bapi Raju S.
Published: April 2021

Several canonical experimental paradigms (e.g., serial reaction time task, discrete sequence production task,m×ntask) have been proposed to study the typical behavioral phenomenon and the nature of learning in sequential keypress tasks. A characteristic feature of most paradigms is that they are representative ofexternally-specifiedsequencing—motor tasks where the environment or task paradigm extrinsically provides the sequence of stimuli, i.e., the responses are stimulus-driven. Previous studies utilizing such canonical paradigms have largely overlooked the learning behaviors in a more realistic class of motor tasks that involveinternally-guidedsequencing—where the sequence of motor actions is self-generated or internally-specified. In this work, we use the grid-navigation task as an instance of internally-guided sequencing to investigate the nature of learning in such paradigms. The participants performed Grid-Sailing Task (GST), which required navigating (by executing sequential keypresses) a 5 × 5 grid from start to goal (SG) position while using a particular key-mapping (KM) among the three cursor-movement directions and the three keyboard buttons. The participants performed two behavioral experiments—Single-SG and Mixed-SG condition. The Single-SG condition required performing GST on a single SG position repeatedly, whereas the Mixed-SG condition involved performing GST using the same KM on two novel SG positions presented in a random, inter-mixed manner. In the Single-SG condition, we show that motor learning contributes to the sequence-specific learning in GST with the repeated execution of the same trajectories. In the Mixed-SG condition, since the participants utilize the previously learned KM, we anticipate a transfer of learning from the Single-SG condition. The acquisition and transfer of a KM-specific internal model facilitates efficient trajectory planning on novel SG conditions. The acquisition of such a KM-specific internal model amounts to trajectory-independent cognitive learning in GST. We show that cognitive learning contributes to the learning in GST by showing transfer-related performance improvements in the Mixed-SG condition. In sum, we show the role of cognitive and motor learning processes in internally-guided sequencing and further make a case for using GST-like grid-navigation paradigms in investigating internally guided skill learning.
On the Factors Influencing Green Purchase Intention: A Meta-Analysis Approach
Authors: Zhuang Wencan , Luo Xiaoguang , Riaz Muhammad Usman
Published: April 2021

This study systematically analyzes the factors that affect consumers’ green purchase intention. Through a comprehensive literature review, the influencing factors of consumers’ green purchase intention are organized into three categories: cognitive factors, consumer individual characteristics, and social factors. Next, a meta-analysis of 54 empirical papers was conducted using Comprehensive Meta-Analysis 3.0 software to quantitatively assess these relationships. The results revealed that green perceived value, attitude, and green trust have a significant positive influence on green purchase intention. Perceived behavior control, perceived consumer effectiveness, and subjective norm also has a strong positive impact on green purchase intention. Collectivism has a positive effect on green purchase intention. Green perceived risk has a significant negative impact on green purchase intention. The study’s findings provide references for enterprises engaged in green product diffusion and organizations responsible for environmental protection.