bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular-Scale Dynamics of Long Range Retrograde Brain-Derived Neurotrophic Factor Transport Shaped by Cellular Spatial Context
Authors: Vermehren-Schmaedick Anke , Olah Mark J. , Ramunno-Johnson Damien , Lidke Keith A. , Cohen Michael S. , Vu Tania Q.
Published: March 2022

Retrograde neurotrophin (NT) transport is a specialized form of signal transduction used to conduct information from axons to the cell bodies of central and peripheral nervous system neurons. It is activated upon NT-Trk receptor binding, NT-Trk internalization into signaling endosomes, and their motion along the axon toward the cell body. Brain-derived neurotrophic factor (BDNF) is an abundant NT that modulates key brain and spinal cord functions, and defects in BDNF trafficking are associated with neuronal death, neurodegenerative diseases and in nerve injury. Decades of study have yielded impressive progress in elucidating NT retrograde transport; however, much information remains unclear. For example, while it is known that NT function is dependent on tight control of NT-receptor intracellular trafficking, data describing the precise spatiotemporal molecular dynamics of their axonal to somatic transport are lacking. In past work, we showed the use of discrete, photo-bleaching-resistant quantum dot (QD)-BNDF probes to activate and track BDNF-TrkB receptor internalization; this revealed a rich diversity of molecular motions that intracellular BDNF signaling endosomes undergo within the soma of nodose ganglia sensory neurons. Here, we used combined techniques of discrete QD-BDNF tracking with compartmented microfluidic chambers to characterize retrograde BDNF-TrkB transport over long-ranging distances of primary dorsal root ganglion sensory neuronal axons. Our new findings show that axonal retrograde motion is comprised of heterogeneous mixtures of diffusive behaviors, pauses, and variations in net molecular-motor-dependent transport speeds. Notably, specific molecular dynamic features such as NT speed were dependent on spatial context that could be categorized in distance from distal axons and proximity to the soma and were not entirely dictated by active motor transport speed. The important implication is recognition that NT-receptor retrograde transport is comprised of molecular dynamics, which change over the course of long-range trafficking to shape overall transport and possibly signaling.
The Sheep as a Comprehensive Animal Model to Investigate Interdependent Physiological Pressure Propagation and Multiparameter Influence on Cerebrospinal Fluid Dynamics
Authors: Trimmel Nina Eva , Podgoršak Anthony , Oertel Markus Florian , Jucker Simone , Arras Margarete , Schmid Daners Marianne , Weisskopf Miriam
Published: March 2022

The present study aims to develop a suitable animal model for evaluating the physiological interactions between cerebrospinal fluid (CSF) dynamics, hemodynamics, and abdominal compartment pressures. We seek to contribute to the enhanced recognition of the pathophysiology of CSF-dependent neurological disorders like hydrocephalus and the improvement of available treatment options. To date, no comprehensive animal model of CSF dynamics exists, and establishing an accurate model will advance our understanding of complex CSF physiology. Persisting knowledge gaps surrounding the communication and pressure propagation between the cerebrospinal space and adjacent anatomical compartments exacerbate the development of novel therapies for neurological diseases. Hence, the need for further investigation of the interactions of vascular, craniospinal, and abdominal pressures remains beyond dispute. Moreover, the results of this animal study support the optimization of in vitro test benches for medical device development, e.g., ventriculoperitoneal shunts. Six female white alpine sheep were surgically equipped with pressure sensors to investigate the physiological values of intracranial, intrathecal, arterial, central venous, jugular venous, vesical pressure, and four differently located abdominal pressures. These values were measured simultaneously during the acute animal trial with sheep under general anesthesia. Both carotid and femoral arterial blood pressure indicate a reliable and comparable representation of the systematic blood pressure. However, the jugular venous pressure and the central venous pressure in sheep in dorsal recumbency do not correlate well under general anesthesia. Furthermore, there is a trend for possible comparability of lateral intraventricular and lumbar intrathecal pressure. Nevertheless, animal body position during measurements must be considered since different body constitutions can alter the horizontal line between the cerebral ventricles and the lumbar subarachnoid space. While intra-abdominal pressure measurement in the four different abdominal quadrants yielded greater inter-individual variability, intra-vesical pressure measurements in our setting delivered comparable values for all sheep. We established a novel and comprehensive ovine animal model to investigate interdependent physiologic pressure propagation and multiparameter influences on CSF dynamics. The results of this study will contribute to further in vitro bench testing, the derivation of novel quantitative models, and the development of a pathologic ovine hydrocephalus model.
Generating Ensembles of Dynamic Misfolding Proteins
Authors: Karamanos Theodoros K. , Kalverda Arnout P. , Radford Sheena E.
Published: March 2022

The early stages of protein misfolding and aggregation involve disordered and partially folded protein conformers that contain a high degree of dynamic disorder. These dynamic species may undergo large-scale intra-molecular motions of intrinsically disordered protein (IDP) precursors, or flexible, low affinity inter-molecular binding in oligomeric assemblies. In both cases, generating atomic level visualization of the interconverting species that captures the conformations explored and their physico-chemical properties remains hugely challenging. How specific sub-ensembles of conformers that are on-pathway to aggregation into amyloid can be identified from their aggregation-resilient counterparts within these large heterogenous pools of rapidly moving molecules represents an additional level of complexity. Here, we describe current experimental and computational approaches designed to capture the dynamic nature of the early stages of protein misfolding and aggregation, and discuss potential challenges in describing these species because of the ensemble averaging of experimental restraints that arise from motions on the millisecond timescale. We give a perspective of how machine learning methods can be used to extract aggregation-relevant sub-ensembles and provide two examples of such an approach in which specific interactions of defined species within the dynamic ensembles of α-synuclein (αSyn) and β2-microgloblulin (β2m) can be captured and investigated.
Nexmifa Regulates Axon Morphogenesis in Motor Neurons in Zebrafish
Authors: Zheng Yu-qin , Suo Gui-hai , Liu Dong , Li Hai-ying , Wu You-jia , Ni Hong
Published: March 2022

Nexmif is mainly expressed in the central nervous system (CNS) and plays important roles in cell migration, cell to cell and cell-matrix adhesion, and maintains normal synaptic formation and function. Nevertheless, it is unclear how nexmif is linked to motor neuron morphogenesis. Here, we provided in situ hybridization evidence that nexmifa (zebrafish paralog) was localized to the brain and spinal cord and acted as a vital regulator of motor neuron morphogenesis. Nexmifa deficiency in zebrafish larvae generated abnormal primary motor neuron (PMN) development, including truncated Cap axons and decreased branches in Cap axons. Importantly, RNA-sequencing showed that nexmifa-depleted zebrafish embryos caused considerable CNS related gene expression alterations. Differentially expressed genes (DEGs) were mainly involved in axon guidance and several synaptic pathways, including glutamatergic, GABAergic, dopaminergic, cholinergic, and serotonergic synapse pathways, according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. In particular, when compared with other pathways, DEGs were highest (84) in the axon guidance pathway, according to Organismal Systems. Efna5b, bmpr2b, and sema6ba were decreased markedly in nexmifa-depleted zebrafish embryos. Moreover, both overexpression of efna5b mRNA and sema6ba mRNA could partially rescued motor neurons morphogenesis. These observations supported nexmifa as regulating axon morphogenesis of motor neurons in zebrafish. Taken together, nexmifa elicited crucial roles during motor neuron development by regulating the morphology of neuronal axons.
Vitamin D and Calcium Supplementation Reverses Tenofovir-Caused Bone Mineral Density Loss in People Taking ART or PrEP: A Systematic Review and Meta-Analysis
Authors: Bi Xiaoyan , Liu Fan , Zhang Xiangjun , Wang Hongyi , Ye Zehao , Yun Ke , Huang Xiaojie , Ding Haibo , Geng Wenqing , Xu Junjie
Published: March 2022

Background

The decrease of bone mineral density (BMD) after the intake of Tenofovir disoproxil fumarate (TDF)-based drugs in people living with HIV/AIDS (PLWHA) and HIV-negative key populations under pre-exposure prophylaxis (PrEP) regimen raised concerns. Previous findings on the effects of vitamin D (VD) and calcium supplements and the recovery of BMD loss were inconclusive. The optimal doses of VD and calcium and its supplementary duration remained unknown. Therefore, we conducted a systematic review and meta-analysis to synthesize current evidence on VD and calcium supplements to inform clinical practice.

Methods

We searched PubMed, Web of Science, Cochrane library, and EMBASE databases for all placebo-controlled trials and prospective cohort studies published before March 5, 2021 that investigated VD and calcium supplements in participants taking TDF-based drugs. The keywords calcium, vitamin D, Tenofovir, and BMD were used for the searches. The primary outcome was changes of spine and hip BMD. A subgroup analysis was performed to determine the factors that were related to the effects of VD supplements on BMD. Locally weighted regression (loess) was used to determine the relationships of VD supplements, supplementary duration, and changes of BMD. This study was registered at PROSPERO (No. 42021231000).

Findings

Seven eligible studies including 703 participants were included in the analyses. The meta-analysis found that VD and calcium supplementation was related to a significant increase of BMD in the spine and hip [standardized mean difference (SMD) 0.43; 95% CI, 0.25 to 0.61, p = 0.009]. Moreover, positive dose-response relationships were demonstrated between doses of VD and calcium supplements, supplementary duration, and BMD recovery. Patients who took VD with the dose level of 4,000 IU/D obtained the highest BMD improvement (SMD 0.59, 95% CI, 0.43 to 0.74). No side effects were reported on VD and calcium supplementation.

Interpretation

We found the VD and calcium supplementation was associated with increases of BMD in participants taking TDF-based drugs. An optimal supplementary dose of 4,000 IU/D for VD was suggested for clinicians. The findings could be used in clinical practice to improve the BMD outcomes in people who were taking TDF-based drugs.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/.
Association Between Endometriosis and Prognosis of Ovarian Cancer: An Updated Meta-Analysis
Authors: Chen Peng , Zhang Chi-Yuan
Published: March 2022

Objective

Increased risk of ovarian cancer (OC) among endometriosis patients has been proposed. However, the association between endometriosis and prognosis of OC remains controversial. This study evaluated whether endometriosis had influence on the survival outcomes of OC through a meta-analysis.

Methods

Relevant studies were retrieved from PubMed, Embase, and Web of Science databases and were evaluated using the Newcastle-Ottawa Quality Assessment Scale. Effect size was presented as hazard ratio (HR) and 95% confidence interval (CI). Heterogeneity test evaluation was performed using Cochran’s Q test and I2 statistics. Publication bias was determined using Egger’s test. Statistical analysis was performed using Stata 12.0 software.

Results

Twenty-one studies involving 38641 patients were included. For the total OC, there were significant differences in overall survival (OS) [HR (95% CI)=0.67 (0.55, 0.80), P<0.001] and progression-free survival (PFS) [HR (95% CI)=0.58 (0.42, 0.81), P=0.001] between endometriosis-associated ovarian cancer (EAOC) and non-EAOC patients in the random-effects models (P<0.05). For ovarian clear cell cancer, there were significant differences in terms of OS [HR (95% CI)=0.63 (0.48, 0.83), P=0.001] and PFS [HR (95% CI)=0.67 (0.52, 0.87), P=0.002] between EAOC and non-EAOC patients in the fixed-effects models (P>0.05). Subgroup analysis suggested no significant differences between EAOC and non-EAOC in OS and PFS in the univariate analysis per subgroup, and PFS in the American subgroup (P>0.05).

Conclusion

EAOC patients tended to have better OS and PFS than non-EAOC patients. Conducting higher quality prospective cohort studies with large sample sizes is recommended to confirm the authenticity of the current study’s results.

Systematic Review Registration

https://inplasy.com/inplasy-2022-3-0109/.
Evaluation Exploration of Atlas-Based and Deep Learning-Based Automatic Contouring for Nasopharyngeal Carcinoma
Authors: Wang Jinyuan , Chen Zhaocai , Yang Cungeng , Qu Baolin , Ma Lin , Fan Wenjun , Zhou Qichao , Zheng Qingzeng , Xu Shouping
Published: March 2022

Purpose

The purpose of this study was to evaluate and explore the difference between an atlas-based and deep learning (DL)-based auto-segmentation scheme for organs at risk (OARs) of nasopharyngeal carcinoma cases to provide valuable help for clinical practice.

Methods

120 nasopharyngeal carcinoma cases were established in the MIM Maestro (atlas) database and trained by a DL-based model (AccuContour®), and another 20 nasopharyngeal carcinoma cases were randomly selected outside the atlas database. The experienced physicians contoured 14 OARs from 20 patients based on the published consensus guidelines, and these were defined as the reference volumes (Vref). Meanwhile, these OARs were auto-contoured using an atlas-based model, a pre-built DL-based model, and an on-site trained DL-based model. These volumes were named Vatlas, VDL-pre-built, and VDL-trained, respectively. The similarities between Vatlas, VDL-pre-built, VDL-trained, and Vref were assessed using the Dice similarity coefficient (DSC), Jaccard coefficient (JAC), maximum Hausdorff distance (HDmax), and deviation of centroid (DC) methods. A one-way ANOVA test was carried out to show the differences (between each two of them).

Results

The results of the three methods were almost similar for the brainstem and eyes. For inner ears and temporomandibular joints, the results of the pre-built DL-based model are the worst, as well as the results of atlas-based auto-segmentation for the lens. For the segmentation of optic nerves, the trained DL-based model shows the best performance (p < 0.05). For the contouring of the oral cavity, the DSC value of VDL-pre-built is the smallest, and VDL-trained is the most significant (p < 0.05). For the parotid glands, the DSC of Vatlas is the minimum (about 0.80 or so), and VDL-pre-built and VDL-trained are slightly larger (about 0.82 or so). In addition to the oral cavity, parotid glands, and the brainstem, the maximum Hausdorff distances of the other organs are below 0.5 cm using the trained DL-based segmentation model. The trained DL-based segmentation method behaves well in the contouring of all the organs that the maximum average deviation of the centroid is no more than 0.3 cm.

Conclusion

The trained DL-based segmentation performs significantly better than atlas-based segmentation for nasopharyngeal carcinoma, especially for the OARs with small volumes. Although some delineation results still need further modification, auto-segmentation methods improve the work efficiency and provide a level of help for clinical work.
Preoperative Clinical Characteristics Predict Recurrent Laryngeal Nerve Lymph Node Metastasis and Overall Survival in Esophageal Squamous Cell Carcinoma: A Retrospective Study With External Validation
Authors: Yan Hao-Ji , Mao Wen-Jun , Yu Rui-Xuan , Jiang Kai-Yuan , Huang Heng , Zong Zheng-Dong , Qian Qin-Chun , Guo Xiao-Guang , Wen Hong-Ying , Tian Dong
Published: March 2022

Background

Recurrent laryngeal nerve (RLN) lymph node metastasis (LNM) is not rare in patients with esophageal squamous cell carcinoma (ESCC). We aimed to develop and externally validate a preoperative nomogram using clinical characteristics to predict RLN LNM in patients with ESCC and evaluate its prognostic value.

Methods

A total of 430 patients with ESCC who underwent esophagectomy with lymphadenectomy of RLN LNs at two centers between May 2015 and June 2019 were reviewed and divided into training (center 1, n = 283) and external validation cohorts (center 2, n = 147). Independent risk factors for RLN LNM were determined by multivariate logistic regression, and a nomogram was developed. The performance of the nomogram was assessed in terms of discrimination, calibration, clinical usefulness, and prognostic value. The nomogram was internally validated by the bootstrap method and externally validated by the external validation cohort.

Results

Multivariate analysis indicated that clinical T stage (P <0.001), endoscopic tumor length (P = 0.003), bioptic tumor differentiation (P = 0.004), and preoperative carcinoembryonic antigen level (P = 0.001) were significantly associated with RLN LNM. The nomogram had good discrimination with the area under the curve of 0.770 and 0.832 after internal and external validations. The calibration curves and decision curve analysis confirmed the good calibration and clinical usefulness of this model. High-risk of RLN LNM predicted by the nomogram was associated with worse overall survival in the external validation cohort (P <0.001).

Conclusion

A nomogram developed by preoperative clinical characteristics demonstrated a good performance to predict RLN LNM and prognosis for patients with ESCC.
Toll-Like Receptor Signalling Pathways and the Pathogenesis of Retinal Diseases
Authors: Titi-Lartey Owuraku , Mohammed Imran , Amoaku Winfried M.
Published: March 2022

There is growing evidence that the pathogenesis of retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD) have a significant chronic inflammatory component. A vital part of the inflammatory cascade is through the activation of pattern recognition receptors (PRR) such as toll-like receptors (TLR). Here, we reviewed the past and current literature to ascertain the cumulative knowledge regarding the effect of TLRs on the development and progression of retinal diseases. There is burgeoning research demonstrating the relationship between TLRs and risk of developing retinal diseases, utilising a range of relevant disease models and a few large clinical investigations. The literature confirms that TLRs are involved in the development and progression of retinal diseases such as DR, AMD, and ischaemic retinopathy. Genetic polymorphisms in TLRs appear to contribute to the risk of developing AMD and DR. However, there are some inconsistencies in the published reports which require further elucidation. The evidence regarding TLR associations in retinal dystrophies including retinitis pigmentosa is limited. Based on the current evidence relating to the role of TLRs, combining anti-VEGF therapies with TLR inhibition may provide a longer-lasting treatment in some retinal vascular diseases.
Chinmedomics Strategy for Elucidating the Pharmacological Effects and Discovering Bioactive Compounds From Keluoxin Against Diabetic Retinopathy
Authors: Kong Ling , Sun Ye , Sun Hui , Zhang Ai-hua , Zhang Bo , Ge Nan , Wang Xi-jun
Published: March 2022

Keluoxin (KLX) is an active agent in the treatment of diabetic retinopathy (DR). However, its mechanism, targets, and effective constituents against DR are still unclear, which seriously restricts its clinical application. Chinmedomics has the promise of explaining the pharmacological effects of herbal medicines and investigating the effective mechanisms. The research results from electroretinography and electron microscope showed that KLX could reduce retinal dysfunction and pathological changes by the DR mouse model. Based on effectiveness, we discovered 64 blood biomarkers of DR by nontargeted metabolomics analysis, 51 of which returned to average levels after KLX treatment including leukotriene D4 and A4, l-tryptophan, 6-hydroxymelatonin, l-phenylalanine, l-tyrosine, and gamma-linolenic acid (GLA). The metabolic pathways involved were phenylalanine metabolism, steroid hormone biosynthesis, sphingolipid metabolism, etc. Adenosine monophosphate-activated protein kinase (AMPK), extracellular signal-regulated protein kinase1/2 (ERK1/2), phosphatidylinositol-3-kinase (PI3K), and protein 70 S6 kinase (p70 S6K) might be potential targets of KLX against DR. This was related to the mammalian target of rapamycin (mTOR) signaling and AMPK signaling pathways. We applied the chinmedomics strategy, integrating serum pharm-chemistry of traditional Chinese medicine (TCM) with metabolomics, to discover astragaloside IV (AS-IV), emodin, rhein, chrysophanol, and other compounds, which were the core effective constituents of KLX when against DR. Our study was the first to apply the chinmedomics strategy to discover the effective constituents of KLX in the treatment of DR, which fills the gap of unclear effective constituents of KLX. In the next step, the research of effective constituents can be used to optimize prescription preparation, improve the quality standard, and develop an innovative drug.
Conditioned Medium From the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Neuropathic Pain in a Partial Sciatic Nerve Ligation Model
Authors: Liu Yao , Kano Fumiya , Hashimoto Noboru , Xia Linze , Zhou Qiao , Feng Xingmei , Hibi Hideharu , Miyazaki Aya , Iwamoto Tsutomu , Matsuka Yoshizo , Zhang Zhijun , Tanaka Eiji , Yamamoto Akihito
Published: March 2022

In neuropathic pain (NP), injury or diseases of the somatosensory system often result in highly debilitating chronic pain. Currently, there is no effective drug for the complete and definitive treatment of NP. We investigated the therapeutic potential of conditioned medium (CM) derived from stem cells from human exfoliated deciduous teeth (SHED-CM) against NP using a mouse partial sciatic nerve ligation (PSL) model. Abnormal pain sensation, such as tactile allodynia and hyperalgesia, can be caused by PSL. In the behavioral test, intravenous administration of SHED-CM greatly improved the PSL-induced hypersensitivity. We found that treatment with SHED-CM resulted in the recruitment of M2 macrophages in the injured sciatic nerve and ipsilateral L4/L5 dorsal root ganglion and suppressed microglial activation in the spinal cord. Notably, specific depletion of the anti-inflammatory M2 macrophages by mannosylated-Clodrosome markedly reduced the antinociceptive effect of SHED-CM. Intravenous administration of CM from M2 induced by SHED-CM (M2-CM) ameliorated the PSL-induced hypersensitivity. We found that M2-CM directly suppressed the expression of nociceptive receptors as well as proinflammatory mediators in Schwann cells. Taken together, our data suggest that SHED-CM ameliorates NP through the induction of the analgesic anti-inflammatory M2 macrophages. Thus, SHED-CM may be a novel therapeutic candidate for NP.
Anti-Epileptic Effect of Crocin on Experimental Temporal Lobe Epilepsy in Mice
Authors: Zhong Kai , Qian Chengyu , Lyu Rui , Wang Xinyi , Hu Zhe , Yu Jie , Ma Jing , Ye Yilu
Published: March 2022

Temporal lobe epilepsy (TLE) is a common kind of refractory epilepsy. More than 30% TLE patients were multi-drug resistant. Some patients may even develop into status epilepticus (SE) because of failing to control seizures. Thus, one of the avid goals for anti-epileptic drug development is to discover novel potential compounds to treat TLE or even SE. Crocin, an effective component of Crocus sativus L., has been applied in several epileptogenic models to test its anti-epileptic effect. However, it is still controversial and its effect on TLE remains unclear. Therefore, we investigated the effects of crocin on epileptogenesis, generalized seizures (GS) in hippocampal rapid electrical kindling model as well as SE and spotaneous recurrent seizure (SRS) in pilocarpine-induced TLE model in ICR mice in this study. The results showed that seizure stages and cumulative afterdischarge duration were significantly depressed by crocin (20 and 50 mg/kg) during hippocampal rapid kindling acquisition. And crocin (100 mg/kg) significantly reduced the incidence of GS and average seizure stages in fully kindled animals. In pilocarpine-induced TLE model, the latency of SE was significantly prolonged and the mortality of SE was significantly decreased by crocin (100 mg/kg), which can also significantly suppress the number of SRS. The underlying mechanism of crocin may be involved in the protection of neurons, the decrease of tumor necrosis factor-α in the hippocampus and the increase of brain derived neurotrophic factor in the cortex. In conclusion, crocin may be a potential and promising anti-epileptic compound for treatment of TLE.
Protocatechualdehyde Rescues Oxygen-Glucose Deprivation/Reoxygenation-Induced Endothelial Cells Injury by Inducing Autophagy and Inhibiting Apoptosis via Regulation of SIRT1
Authors: Cao Shidong , Chen Senmiao , Qiao Xilin , Guo Yan , Liu Fang , Ding Zhishan , Jin Bo
Published: March 2022

Background: Oxidative stress-induced endothelial cell death, such as apoptosis and autophagy, plays a critical role in ischemia-reperfusion injury. Protocatechualdehyde (PCA) is a major bioactive component of the traditional Chinese medicine Salvia miltiorrhiza Bunge (Lamiaceae), and it has been proved to be effective in the prevention and treatment of ischemic cardiovascular and cerebrovascular diseases. However, its role in oxidative stress-induced endothelial cell death and its underlying mechanisms remains unclear. This study aims to investigate the effects and mechanisms of PCA on endothelial cell apoptosis and autophagy induced by oxygen-glucose deprivation/reoxygenation (OGD/R) injury.

Methods: After OGD/R induction, human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of PCA. Cell viability, apoptosis, and autophagy were detected by Cell Counting Kit-8 assay, flow cytometry, and monodansylcadaverine assay, respectively. Western blot was applied to explore the effects of PCA on the expression levels of relevant protein factors.

Results: The results show that PCA significantly promoted cell survival rate and cell proliferation and enhanced the antioxidant activity in OGD/R-induced HUVECs. PCA inhibited HUVECs apoptosis, as evidenced by decreased expression of cleaved-caspase-3, Bcl2-associated X (BAX), and increased expression of Bcl-2. PCA induced autophagy by reducing the expression of P62 while increasing the expression of Beclin-1 and LC3 II/I. Meanwhile, PCA enhanced the expression of Sirtuin 1 (SIRT1) and suppressed the expression of P53. When SIRT1 was inhibited by selisistat or SIRT1 small-interfering RNA, the anti-apoptotic and pro-autophagy abilities of PCA were attenuated.

Conclusion: These results demonstrated that PCA rescued HUVECs from OGD/R-induced injury by promoting autophagy and inhibiting apoptosis through SIRT1 and could be developed as a potential therapeutic agent against ischemic diseases.
Galanin Regulates Myocardial Mitochondrial ROS Homeostasis and Hypertrophic Remodeling Through GalR2
Authors: Boal Frederic , Cinato Mathieu , Timotin Andrei , Münzberg Heike , Qualls-Creekmore Emily , Kramar Solomiia , Loi Halyna , Roncalli Jerome , Keita Sokhna , Tronchere Helene , Kunduzova Oksana
Published: March 2022

The regulatory peptide galanin is broadly distributed in the central nervous systems and peripheral tissues where it modulates numerous physiological and pathological processes through binding to its three G-protein-coupled receptors, GalR1-3. However, the function and identity of the galaninergic system in the heart remain unclear. Therefore, we investigated the expression of the galanin receptors in cardiac cells and tissues and found that GalR2 is the dominant receptor subtype in adult mouse hearts, cardiomyocytes and H9C2 cardiomyoblasts. In vivo, genetic suppression of GalR2 promotes cardiac hypertrophy, fibrosis and mitochondrial oxidative stress in the heart. In vitro, GalR2 silencing by siRNA abolished the beneficial effects of galanin on cell hypertrophy and mitochondrial reactive oxygen species (ROS) production. These findings unravel new insights into the role of galaninergic system in the heart and suggest novel therapeutic strategies in heart disease.
Multi-Angle Polarization Index System for Pollen Type Bioaerosol Recognition
Authors: Xu Qizhi , Zeng Nan , Guo Wei , Guo Jun , He Yonghong , Ma Hui
Published: March 2022

In this work, we propose a high-throughput online identification method of bioaerosols based on multi-angle polarization index system (MAPIS). In the study, four categories and 10 subclasses of aerosol samples from biological and non-biological sources are detected under three incident polarization mode. Then their measured MAPIS shows that bioaerosols like pollen can be easily distinguished from other types of aerosols. Not only that, experimental results also indicate the feasibility of fine identification between different kinds of bioaerosols based on MAPIS in P and R modes. To further extract simple and optimized polarization characterization parameters suitable for bioaerosols, we analyze the multidimensional data of MAPIS by PCA then validate the aerosol recognition accuracy using the first two principal components by multiple groups of randomly mixed aerosol datasets. The comparison with PCA components based on only scattering intensity demonstrate that MAPIS can be not only applied in the specific identification of bioaerosols but also suitable for the distinction between different kinds of bioaerosols.
Regulation of Sexually Dimorphic Expression of Major Urinary Proteins
Authors: Penn Dustin J. , Zala Sarah M. , Luzynski Kenneth C.
Published: March 2022

Male house mice excrete large amounts of protein in their urinary scent marks, mainly composed of Major Urinary Proteins (MUPs), and these lipocalins function as pheromones and pheromone carriers. Here, we review studies on sexually dimorphic MUP expression in house mice, including the proximate mechanisms controlling MUP gene expression and their adaptive functions. Males excrete 2 to 8 times more urinary protein than females, though there is enormous variation in gene expression across loci in both sexes. MUP expression is dynamically regulated depending upon a variety of factors. Males regulate MUP expression according to social status, whereas females do not, and males regulate expression depending upon health and condition. Male-biased MUP expression is regulated by pituitary secretion of growth hormone (GH), which binds receptors in the liver, activating the JAK2-STAT5 signaling pathway, chromatin accessibility, and MUP gene transcription. Pulsatile male GH secretion is feminized by several factors, including caloric restriction, microbiota depletion, and aging, which helps explain condition-dependent MUP expression. If MUP production has sex-specific fitness optima, then this should generate sexual antagonism over allelic expression (intra-locus sexual conflict) selectively favoring sexually dimorphic expression. MUPs influence the sexual attractiveness of male urinary odor and increased urinary protein excretion is correlated with the reproductive success of males but not females. This finding could explain the selective maintenance of sexually dimorphic MUP expression. Producing MUPs entails energetic costs, but increased excretion may reduce the net energetic costs and predation risks from male scent marking as well as prolong the release of chemical signals. MUPs may also provide physiological benefits, including regulating metabolic rate and toxin removal, which may have sex-specific effects on survival. A phylogenetic analysis on the origins of male-biased MUP gene expression inMus musculussuggests that this sexual dimorphism evolved by increasing male MUP expression rather than reducing female expression.
Circumference-Based Predictions of Body Fat Revisited: Preliminary Results From a US Marine Corps Body Composition Survey
Authors: Potter Adam W. , Tharion William J. , Holden Lucas D. , Pazmino Angie , Looney David P. , Friedl Karl E.
Published: March 2022

Purpose: Body composition assessment methods are dependent on their underlying principles, and assumptions of each method may be affected by age and sex. This study compared an abdominal circumference-focused method of percent body fat estimation (AC %BF) to a criterion method of dual-energy x-ray absorptiometry (DXA), and a comparative assessment with bioelectrical impedance (BIA), in younger (≤30 years) and older (>age 30 years) physically fit (meeting/exceeding annual US Marine Corps fitness testing requirements) men and women.

Methods: Fit healthy US Marines (430 men, 179 women; 18–57 years) were assessed for body composition by DXA (iDXA, GE Lunar), anthropometry, and BIA (Quantum IV, RJL Systems).

Results: Compared to DXA %BF, male AC %BF underestimated for both ≤30 and >30 years age groups (bias, -2.6 ± 3.7 and -2.5 ± 3.7%); while female AC %BF overestimated for both ≤30 and >30 years age groups (2.3 ± 4.3 and 1.3 ± 4.8%). On an individual basis, lean men and women were overestimated and higher %BF individuals were underestimated. Predictions from BIA were more accurate and reflected less relationship to adiposity for each age and sex group (males: ≤30, 0.4 ± 3.2, >30 years, -0.5 ± 3.5; women: ≤30, 1.4 ± 3.1, >30 years, 0.0 ± 3.3). Total body water (hydration) and bone mineral content (BMC) as a proportion of fat-free mass (FFM) remained consistent across the age range; however, women had a higher proportion of %BMC/FFM than men. Older men and women (>age 30 years) were larger and carried more fat but had similar FFM compared to younger men and women.

Conclusion: The AC %BF provides a field expedient method for the US Marine Corps to classify individuals for obesity prevention, but does not provide research-grade quantitative body composition data.
Transcriptome Analysis Reveals Differences in Anthocyanin Accumulation in Cotton (Gossypium hirsutum L.) Induced by Red and Blue Light
Authors: Shao Dongnan , Zhu Qian-hao , Liang Qian , Wang Xuefeng , Li Yanjun , Sun Yuqiang , Zhang Xinyu , Liu Feng , Xue Fei , Sun Jie
Published: March 2022

Many factors, including illumination, affect anthocyanin biosynthesis and accumulation in plants. light quality is the key factor affecting the process of photoinduced anthocyanin biosynthesis and accumulation. We observed that the red color of the Upland cotton accession Huiyuan with the R1 mutation turned to normal green color under light-emitting diodes (LEDs), which inspired us to investigate the effect of red and blue lights on the biosynthesis and accumulation of anthocyanins. We found that both red and blue lights elevated accumulation of anthocyanins. Comparative transcriptomic analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and GSEA, revealed that genes differentially expressed under different light conditions were enriched with the pathways of circadian rhythm, phenylpropanoid biosynthesis, anthocyanin biosynthesis, and flavone and flavonol biosynthesis. Not surprisingly, all the major structural genes related to biosynthesis of anthocyanins, including the key regulatory MYB transcription factor (GhPAP1D) and anthocyanin transporter (GhGSTF12), were induced by red or blue light treatment. However, LARs and MATEs related to biosynthesis of proanthocyanidins were more significantly up-regulated by red light radiation than by blue light radiation. Vice versa, the accumulation of anthocyanins under red light was not as high as that under blue light. In addition, we demonstrated a potential role of GhHY5, a key regulator in plant circadian rhythms, in regulation of anthocyanin accumulation, which could be achieved via interaction with GhPAP1D. Together, these results indicate different effect of red and blue lights on biosynthesis and accumulation of anthocyanins and a potential module including GhHY5 and GhPAP1D in regulation of anthocyanin accumulation in cotton. These results also suggest that the substrates responsible the synthesis of anthocyanins under blue light is diverted to biosynthesis of proanthocyanidin under red light.
Arbuscular Mycorrhizal Fungi and Dry Raw Garlic Stalk Amendment Alleviate Continuous Monocropping Growth and Photosynthetic Declines in Eggplant by Bolstering Its Antioxidant System and Accumulation of Osmolytes and Secondary Metabolites
Authors: Ghani Muhammad Imran , Ali Ahmad , Atif Muhammad Jawaad , Ali Muhammad , Amin Bakht , Cheng Zhihui
Published: March 2022

Vegetable production under plastic sheds severely threatens regional eco-sustainabilityviaanthropogenic activities (excessive use of agrochemicals, pesticides) and problems associated with replanting. Long-term successive cropping across growing seasons induces continuous cropping stress, whose effects manifest as diminished plant growth. Therefore, it is imperative that we develop environmentally sustainable approaches, such as replacing agrochemicals with vegetable waste like dry raw garlic stalk (DRGS) or use biofertilizers like arbuscular mycorrhizal fungi (AMF) (e.g.,Diversispora epigaea). In this study, the influence of AMF on the growth, biochemical attributes, antioxidant defense system, phytohormones, accumulation of osmolytes, phenols, and mineral elements in eggplant grown on DRGS-amended soils under continuous monocropping (CMC) was studied. The results showed that inoculation with AMF or the DRGS amendment could improve the pigments’ content, photosynthesis, and antioxidant defense system; augmented phytohormones synthesis (except for ABA), and increased the leaves’ mineral nutrients. These parameters were enhanced most by the combined application of AMF and DRGS, which also increased the concentration of osmolytes, including proline, sugars, and free amino acids in eggplant when compared with the control. Furthermore, either AMF and DRGS alone, or in combination, ameliorated the induced stress from continuous cropping by reducing the incidence ofFusariumwilt and production of ROS (reactive oxygen species); lipid peroxidation underwent maximal reduction in plants grown under the combined treatments. The AMF, DRGS, and AMF + DRGS exhibited a lower disease severity index (33.46, 36.42, and 43.01%), respectively, over control. Hence, inoculation with AMF coupled with DRGS amendment alters the photosynthetic attributes in eggplant through the upregulation of its antioxidant system and greater accumulation of osmolytes, which led to the improved growth and yield of eggplant.
StresSeed: The Unfolded Protein Response During Seed Development
Authors: Vitale Alessandro , Pedrazzini Emanuela
Published: March 2022

During seed development, the endoplasmic reticulum (ER) takes care of the synthesis and structural maturation of very high amounts of storage proteins in a relatively short time. The ER must thus adjust its extension and machinery to optimize this process. The major signaling mechanism to maintain ER homeostasis is the unfolded protein response (UPR). Both storage proteins that assemble into ER-connected protein bodies and those that are delivered to protein storage vacuoles stimulate the UPR, but its extent and features are specific for the different storage protein classes and even for individual members of each class. Furthermore, evidence exists for anticipatory UPR directly connected to the development of storage seed cells and for selective degradation of certain storage proteins soon after their synthesis, whose signaling details are however still largely unknown. All these events are discussed, also in the light of known features of mammalian UPR.
Heritable Variation of Foliar Spectral Reflectance Enhances Genomic Prediction of Hydrogen Cyanide in a Genetically Structured Population of Eucalyptus
Authors: Ballesta Paulina , Ahmar Sunny , Lobos Gustavo A. , Mieres-Castro Daniel , Jiménez-Aspee Felipe , Mora-Poblete Freddy
Published: March 2022

Plants produce a wide diversity of specialized metabolites, which fulfill a wide range of biological functions, helping plants to interact with biotic and abiotic factors. In this study, an integrated approach based on high-throughput plant phenotyping, genome-wide haplotypes, and pedigree information was performed to examine the extent of heritable variation of foliar spectral reflectance and to predict the leaf hydrogen cyanide content in a genetically structured population of a cyanogenic eucalyptus (Eucalyptus cladocalyx F. Muell). In addition, the heritable variation (based on pedigree and genomic data) of more of 100 common spectral reflectance indices was examined. The first profile of heritable variation along the spectral reflectance curve indicated the highest estimate of genomic heritability (hg2=0.41) within the visible region of the spectrum, suggesting that several physiological and biological responses of trees to environmental stimuli (ex., light) are under moderate genetic control. The spectral reflectance index with the highest genomic-based heritability was leaf rust disease severity index 1 (hg2=0.58), followed by the anthocyanin reflectance index and the Browning reflectance index (hg2=0.54). Among the Bayesian prediction models based on spectral reflectance data, Bayes B had a better goodness of fit than the Bayes-C and Bayesian ridge regression models (in terms of the deviance information criterion). All models that included spectral reflectance data outperformed conventional genomic prediction models in their predictive ability and goodness-of-fit measures. Finally, we confirmed the proposed hypothesis that high-throughput phenotyping indirectly capture endophenotypic variants related to specialized metabolites (defense chemistry), and therefore, generally more accurate predictions can be made integrating phenomics and genomics.
The Innovation of Entrepreneurship Education for Intangible Cultural Heritage Inheritance From the Perspective of Entrepreneurial Psychology
Authors: Zhou Jie , Qi Ji , Shi Xuefeng
Published: March 2022

The purpose is to help college students start their own businesses and protect and develop China’s intangible cultural heritage. The entrepreneurship of college students in the field of intangible culture is studied from the perspective of entrepreneurial psychology. First, the related characteristics, main content, and research status of college entrepreneurship education are described in detail. Entrepreneurial psychology is divided into entrepreneurial cognition, entrepreneurial emotion and entrepreneurial will. Then, the concept and development status of intangible cultural heritage are briefly summarized to illustrate the importance of inheriting and developing intangible cultural heritage. A questionnaire is designed based on intangible cultural heritage development mode to interview local college students randomly. Finally, the results are analyzed by descriptive statistics. The results show that massive students do not understand the entrepreneurial policy, and only 16% of them know it very well. More than 30% of the students think that entrepreneurship will improve personal responsibility. Nearly 50% of the students believe that entrepreneurship can increase their life experience. Almost 50% of the students have the psychological quality of persistence and courage in entrepreneurship. The final results show that there are great differences in entrepreneurial cognition among students of different grades. Regarding entrepreneurial emotion, there are obvious differences among students of different genders, disciplines, and grades. Regarding the entrepreneurial will, there are only differences among students with different grades. In entrepreneurship education, different teaching methods should be adopted for different ages to comprehensively improve the effect of entrepreneurship education for students of all grades and help them obtain good entrepreneurship results. This exploration provides technical support for the inheritance of material and cultural inheritance and contributes to the entrepreneurship education of college students.
The Impact of Sleep Quality on Subjective Wellbeing Among Older Adults With Multimorbidity: A Moderated Mediation Model
Authors: Zhang Chichen , Dong Fang , Zheng Xiao , Xue Yaqing , Xiao Shujuan , Shi Lei , Xue Benli , Zhang Jiachi , Ou Weiyan
Published: March 2022

Background

Studies have found that poor sleep quality is negatively associated with subjective wellbeing in older adults, but the mechanisms underlying are unclear. In this study, we aimed to examine the mediating role of negative emotions and the moderating role of perceived social support in the relationship between sleep quality and subjective wellbeing in older adults with multimorbidity.

Methods

A multi-stage random sampling method was used to select a sample of 3,266 older adults aged 60 years and older. The Memorial University of Newfoundland Scale of Happiness (MUNSH), Pittsburgh Sleep Quality Index (PSQI), Depression Anxiety Stress Scales-21 (DASS-21), and Perceived Social Support Scale (PSSS) were used to assess subjective wellbeing, sleep quality, negative emotional states, and perceived social support, respectively. The moderated mediation models were examined using SPSS PROCESS Version 3.3 software.

Results

Sleep quality had a significant direct effect on subjective wellbeing in older adults (β = −0.997, t = −11.783, p < 0.001). Negative emotions partially mediated the effect of sleep quality on subjective wellbeing (ab = −0.608, 95%CI: −0.728, −0.497). The indirect effect was moderated by perceived social support (β = −0.038, 95%CI: −0.062, −0.014, p < 0.001; β = −0.002, 95%CI: −0.004, −0.01, p = 0.008).

Conclusion

Negative emotions increased the negative association between sleep quality and the subjective wellbeing of older adults with multimorbidity, and perceived social support played a moderating role. Psychological and behavioral interventions should be implemented as early as possible to promote mental health and enhance social support level of older adults with multimorbidity, and ultimately improve the subjective wellbeing of older adults.
Assessing Students’ Translation Competence: Integrating China’s Standards of English With Cognitive Diagnostic Assessment Approaches
Authors: Mei Huan , Chen Huilin
Published: March 2022

While translation competence assessment has been playing an increasingly facilitating role in translation teaching and learning, it still failed to offer fine-grained diagnostic feedback based on certain reliable translation competence standards. As such, this study attempted to investigate the feasibility of providing diagnostic information about students’ translation competence by integrating China’s Standards of English (CSE) with cognitive diagnostic assessment (CDA) approaches. Under the descriptive parameter framework of CSE translation scales, an attribute pool was established, from which seven attributes were identified based on students’ and experts’ think-aloud protocols. A checklist comprising 20 descriptors was developed from CSE translation scales, with which 458 students’ translation responses were rated by five experts. In addition, a Q-matrix was established by seven experts. By comparing the diagnostic performance of four widely-used cognitive diagnostic models (CDMs), linear logistic model (LLM) was selected as the optimal model to generate fine-grained information about students’ translation strengths and weaknesses. Furthermore, relationships among translation competence attributes were discovered and diagnostic results were shown to differ across high and low proficiency groups. The findings can provide insights for translation teaching, learning and assessment.