bluuebunny/crossref_metadata_2025 huggingface dataset:
Glutathione Peroxidase 1 Protects Against Peroxynitrite-Induced Spiral Ganglion Neuron Damage Through Attenuating NF-κB Pathway Activation
Authors: Wang Xue , Han Yuechen , Chen Fang , Wang Man , Xiao Yun , Wang Haibo , Xu Lei , Liu Wenwen
Published: March 2022

Glutathione peroxidase 1 (GPX1) is a crucial antioxidant enzyme that prevented the harmful accumulation of intra-cellular hydrogen peroxide. GPX1 might contribute in limiting cochlear damages associated with aging or acoustic overexposure, but the function of GPX1 in the inner ear remains unclear. The present study was designed to investigate the effect of GPX1 on cochlear spiral ganglion neurons (SGNs) against oxidative stress induced by peroxynitrite, a versatile oxidant generated by the reaction of superoxide anion and nitric oxide. Here, we first found that the expression of GPX1 in cultured SGNs was downregulated after peroxynitrite exposure. Then, the GPX1 mimic ebselen and the gpx1 knockout (gpx1–/–) mice were used to investigate the role of GPX1 in SGNs treated with peroxynitrite. The pretreatment with ebselen significantly increased the survived SGN numbers, inhibited the apoptosis, and enhanced the expression of 4-HNE in the cultured SGNs of peroxynitrite + ebselen group compared with the peroxynitrite-only group. On the contrary, remarkably less survived SGNs, more apoptotic SGNs, and the higher expression level of 4-HNE were detected in the peroxynitrite + gpx1–/– group compared with the peroxynitrite-only group. Furthermore, rescue experiments with antioxidant N-acetylcysteine (NAC) showed that the expression of 4-HNE and the apoptosis in SGNs were significantly decreased, while the number of surviving SGNs was increased in peroxynitrite + NAC group compared the peroxynitrite-only group and in peroxynitrite + gpx1–/– + NAC group vs. peroxynitrite + gpx1–/– group. Finally, mechanistic studies showed that the activation of nuclear factor-kappa B (NF-κB) was involved in the SGNs damage caused by peroxynitrite and that GPX1 protected SGNs against peroxynitrite-induced damage, at least in part, via blocking the NF-κB pathway activation. Collectively, our findings suggest that GPX1 might serve as a new target for the prevention of nitrogen radical-induced SGNs damage and hearing loss.
Improving Localization Accuracy of Neural Sources by Pre-processing: Demonstration With Infant MEG Data
Authors: Clarke Maggie D. , Larson Eric , Peterson Erica R. , McCloy Daniel R. , Bosseler Alexis N. , Taulu Samu
Published: March 2022

We discuss specific challenges and solutions in infant MEG, which is one of the most technically challenging areas of MEG studies. Our results can be generalized to a variety of challenging scenarios for MEG data acquisition, including clinical settings. We cover a wide range of steps in pre-processing, including movement compensation, suppression of magnetic interference from sources inside and outside the magnetically shielded room, suppression of specific physiological artifact components such as cardiac artifacts. In the assessment of the outcome of the pre-processing algorithms, we focus on comparing signal representation before and after pre-processing and discuss the importance of the different components of the main processing steps. We discuss the importance of taking the noise covariance structure into account in inverse modeling and present the proper treatment of the noise covariance matrix to accurately reflect the processing that was applied to the data. Using example cases, we investigate the level of source localization error before and after processing. One of our main findings is that statistical metrics of source reconstruction may erroneously indicate that the results are reliable even in cases where the data are severely distorted by head movements. As a consequence, we stress the importance of proper signal processing in infant MEG.
Amyloid-Related Imaging Abnormalities With Anti-amyloid Antibodies for the Treatment of Dementia Due to Alzheimer's Disease
Authors: Withington Charles G. , Turner R. Scott
Published: March 2022

Second-generation anti-amyloid monoclonal antibodies are emerging as a viable therapeutic option for individuals with prodromal and mild dementia due to Alzheimer's disease (AD). Passive immunotherapy with aducanumab (Aduhelm), lecanemab, donanemab, and gantenerumab all lower CNS amyloid (Aβ) burden but come with a significant risk of amyloid-related imaging abnormality (ARIA)—the most common side effect of this class of drugs. While usually asymptomatic and detected only on brain MRI, ARIA may lead to new signs and symptoms including headache, worsening confusion, dizziness, visual disturbances, nausea, and seizures. In addition, one fatality related to ARIA-E (edema) with aducanumab and one fatality due to ARIA-H (hemorrhage) with donanemab are reported to date. ARIA-E may be associated with excessive neuroinflammation and saturation of perivascular clearance pathways, while ARIA-H may be related to vascular amyloid clearance with weakening and rupture of small blood vessels. The risk of ARIA-E is higher at treatment initiation, in ApoE4 carriers, with higher dosage, and with >4 of microhemorrhages on a baseline MRI. The risk of ARIA-H increases with age and cerebrovascular disease. Dose titration mitigates the risk of ARIA, and contraindications include individuals with >4 microhemorrhages and those prescribed anti-platelet or anti-coagulant drugs. A brain MRI is required before aducanumab is initiated, before each scheduled dose escalation, and with any new neurologic sign or symptom. Management of ARIA ranges from continued antibody treatment with monthly MRI monitoring for asymptomatic individuals to temporary or permanent suspension for symptomatic individuals or those with moderate to severe ARIA on MRI. Controlled studies regarding prevention and treatment of ARIA are lacking, but anecdotal evidence suggests that a pulse of intravenous corticosteroids may be of benefit, as well as a course of anticonvulsant for seizures.
Diffusion Tensor Based White Matter Tract Atlases for Pediatric Populations
Authors: Short Sarah J. , Jang Dae Kun , Steiner Rachel J. , Stephens Rebecca L. , Girault Jessica B. , Styner Martin , Gilmore John H.
Published: March 2022

Diffusion Tensor Imaging (DTI) is a non-invasive neuroimaging method that has become the most widely employed MRI modality for investigations of white matter fiber pathways. DTI has proven especially valuable for improving our understanding of normative white matter maturation across the life span and has also been used to index clinical pathology and cognitive function. Despite its increasing popularity, especially in pediatric research, the majority of existing studies examining infant white matter maturation depend on regional or white matter skeleton-based approaches. These methods generally lack the sensitivity and spatial specificity of more advanced functional analysis options that provide information about microstructural properties of white matter along fiber bundles. DTI studies of early postnatal brain development show that profound microstructural and maturational changes take place during the first two years of life. The pattern and rate of these changes vary greatly throughout the brain during this time compared to the rest of the life span. For this reason, appropriate image processing of infant MR imaging requires the use of age-specific reference atlases. This article provides an overview of the pre-processing, atlas building, and the fiber tractography procedures used to generate two atlas resources, one for neonates and one for 1- to 2-year-old populations. Via the UNC-NAMIC DTI Fiber Analysis Framework, our pediatric atlases provide the computational templates necessary for the fully automatic analysis of infant DTI data. To the best of our knowledge, these atlases are the first comprehensive population diffusion fiber atlases in early pediatric ages that are publicly available.
Circular RNA in Acute Central Nervous System Injuries: A New Target for Therapeutic Intervention
Authors: Zhang Li , Li Zhenxing , Mao Lei , Wang Handong
Published: March 2022

Acute central nervous system (CNS) injuries, including ischemic stroke, traumatic brain injury (TBI), spinal cord injury (SCI) and subarachnoid hemorrhage (SAH), are the most common cause of death and disability around the world. As a kind of non-coding ribonucleic acids (RNAs) with endogenous and conserve, circular RNAs (circRNAs) have recently attracted great attentions due to their functions in diagnosis and treatment of many diseases. A large number of studies have suggested that circRNAs played an important role in brain development and involved in many neurological disorders, particularly in acute CNS injuries. It has been proposed that regulation of circRNAs could improve cognition function, promote angiogenesis, inhibit apoptosis, suppress inflammation, regulate autophagy and protect blood brain barrier (BBB) in acute CNS injuries via different molecules and pathways including microRNA (miRNA), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), ph1osphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT), Notch1 and ten-eleven translocation (TET). Therefore, circRNAs showed great promise as potential targets in acute CNS injuries. In this article, we present a review highlighting the roles of circRNAs in acute CNS injuries. Hence, on the basis of these properties and effects, circRNAs may be developed as therapeutic agents for acute CNS injury patients.
Resistant Potato Starch Alters the Cecal Microbiome and Gene Expression in Mice Fed a Western Diet Based on NHANES Data
Authors: Smith Allen D. , Chen Celine , Cheung Lumei , Ward Robert , Hintze Korry J. , Dawson Harry D.
Published: March 2022

Several studies indicate that the four major types of resistant starch (RS1-4) are fermented in the cecum and colon to produce short-chain fatty acids (SCFAs) and can alter the microbiome and host physiology. However, nearly all these studies were conducted in rodents fed with a diet that does not approximate what is typically consumed by humans. To address this, mice were fed a Total Western Diet (TWD) based on National Health and Nutrition Examination Survey (NHANES) data that mimics the macro and micronutrient composition of a typical American diet for 6 weeks and then supplemented with 0, 2, 5, or 10% of the RS2, resistant potato starch (RPS), for an additional 3 weeks. The cecal microbiome was analyzed by 16S sequencing. The alpha-diversity of the microbiome decreased with increasing consumption of RPS while a beta-diversity plot showed four discreet groupings based on the RPS level in the diet. The relative abundance of various genera was altered by feeding increasing levels of RPS. In particular, the genus Lachnospiraceae NK4A136 group was markedly increased. Cecal, proximal, and distal colon tissue mRNA abundance was analyzed by RNASeq. The cecal mRNA abundance principal component analysis showed clear segregation of the four dietary groups whose separation decreased in the proximal and distal colon. Differential expression of the genes was highest in the cecum, but substantially decreased in the proximal colon (PC) and distal colon (DC). Most differentially expressed genes were unique to each tissue with little overlap in between. The pattern of the observed gene expression suggests that RPS, likely through metabolic changes secondary to differences in microbial composition, appears to prime the host to respond to a range of pathogens, including viruses, bacteria, and parasites. In summary, consumption of dietary RPS led to significant changes to the microbiome and gene expression in the cecum and to a lesser extent in the proximal and distal colon.
Early Dinner Time and Caloric Restriction Lapse Contribute to the Longevity of Nonagenarians and Centenarians of the Italian Abruzzo Region: A Cross-Sectional Study
Authors: Angelino Donato , Pietrangeli Francesca , Serafini Mauro
Published: March 2022

Recent findings showed the role of late-night eating in metabolic disorders, highlighting the importance of meal timing for health. No evidence is available on the role of meal timing for longevity. The aim of this study was to survey, in a cross-sectional study, meal timing and dietary habits of 68 nonagenarians and centenarians of the Abruzzo region, Italy. Results showed an early dinner (7:13 p.m.) and a calorie restriction lapse of 17.5 h between dinner and the following lunch. The frequency of consumption was high for cereals, vegetables, fruits, and legumes; low for meat, processed meat, and eggs; and negligible for sweets. Subjects were physically active throughout life. Our results support the importance of a daily caloric restriction lapse, hampering nocturnal postprandial stress and optimizing metabolic response, associated with high consumption of plant-based foods and physical activity for the longevity of centenarians from Abruzzo.
Special Chimeric Antigen Receptor (CAR) Modifications of T Cells: A Review
Authors: Miao Lele , Zhang Juan , Huang Binjie , Zhang Zhengchao , Wang Song , Tang Futian , Teng Muzhou , Li Yumin
Published: March 2022

Chimeric antigen receptor (CAR) -T cell therapy has become one of the hot topics in tumor immunity research in recent years. Although CAR-T cell therapy is highly effective in treating hematological malignancies, there are numerous obstacles that prevent CAR-T cells from having anti-tumor effects. Traditional CARs, from the first to the fourth generation, are incapable of completely overcoming these challenges. Therefore, identifying ways to boost the efficacy of CAR-T cells by utilizing the limited tumor surface antigens has become an urgent area of research. Certain special CARs that have special structures, special systems, or are greatly improved on the basis of traditional CARs, such as tandem CAR, dual-signaling CARs, AND-gate CARs, inhibitory CAR, AND-NOT CARs, CARs with three scFvs, ON/OFF-switch CARs, and universal CARs have been introduced. This study aims to use these special CARs to improve the anti-tumor ability, accuracy, and safety of CAR-T cells. In addition to summarizing various special CARs of T cells, this paper also expounds some of our own conjectures, aiming to provide reference and inspiration for CARs researchers.
Glycerophosphoinositol Promotes Apoptosis of Chronic Lymphocytic Leukemia Cells by Enhancing Bax Expression and Activation
Authors: Boncompagni Gioia , Varone Alessia , Tatangelo Vanessa , Capitani Nagaja , Frezzato Federica , Visentin Andrea , Trentin Livio , Corda Daniela , Baldari Cosima T. , Patrussi Laura
Published: March 2022

An imbalance in the expression of pro- and anti-apoptotic members of the Bcl-2 family of apoptosis-regulating proteins is one of the main biological features of CLL, highlighting these proteins as therapeutic targets for treatment of this malignancy. Indeed, the Bcl-2 inhibitor Venetoclax is currently used for both first-line treatment and treatment of relapsed or refractory CLL. An alternative avenue is the transcriptional modulation of Bcl-2 family members to tilt their balance towards apoptosis. Glycerophosphoinositol (GroPIns) is a biomolecule generated from membrane phosphoinositides by the enzymes phospholipase A2 and lysolipase that pleiotropically affects key cellular functions. Mass-spectrometry analysis of GroPIns interactors recently highlighted the ability of GroPIns to bind to the non-receptor tyrosine phosphatase SHP-1, a known promoter of Bax expression, suggesting that GroPIns might correct the Bax expression defect in CLL cells, thereby promoting their apoptotic demise. To test this hypothesis, we cultured CLL cells in the presence of GroPIns, alone or in combination with drugs commonly used for treatment of CLL. We found that GroPIns alone increases Bax expression and apoptosis in CLL cells and enhances the pro-apoptotic activity of drugs used for CLL treatment in a SHP-1 dependent manner. Interestingly, among GroPIns interactors we found Bax itself. Short-term treatments of CLL cells with GroPIns induce Bax activation and translocation to the mitochondria. Moreover, GroPIns enhances the pro-apoptotic activity of Venetoclax and Fludarabine in CLL cells. These data provide evidence that GroPIns exploits two different pathways converging on Bax to promote apoptosis of leukemic cells and pave the way to new studies aimed at testing GroPIns in combination therapies for the treatment of CLL.
The Long Non-Coding RNA HOXC-AS3 Promotes Glioma Progression by Sponging miR-216 to Regulate F11R Expression
Authors: Li Yongshuai , Peng Lu , Cao Xianwen , Yang Kun , Wang Zhen , Xiao Yong , Xiao Hong , Qian Chunfa , Liu Hongyi
Published: March 2022

HOXC cluster antisense RNA 3 (HOXC-AS3) is a long noncoding RNA (lncRNA) that plays a crucial role in various tumors; nevertheless, its role in glioma and its mechanism have not been completely elucidated. In this research, we discovered that HOXC-AS3 was over-expression in glioma cells and tissues and was associated with prognosis. Next, we determined that HOXC-AS3 targeted miR-216 as a sponge and that the F11 receptor (F11R) was the target of miR-216 by online databases analysis, qRT–PCR, and luciferase reporter assay. In addition, the rescue experiments confirmed that HOXC-AS3 regulated the expression of F11R by competitively binding miR-216 and functioning as a competing endogenous RNA (ceRNA). The intracranial glioblastoma mouse model suggested that HOXC-AS3 could promote glioma malignant progression in vivo. In summary, our study shows that the HOXC-AS3/miR-216/F11R axis plays an important role in the malignant progression of glioma, and may provide new ideas for the treatment of glioma.
The CXCR1/CXCR2 Inhibitor Reparixin Alters the Development of Myelofibrosis in the Gata1low Mice
Authors: Verachi Paola , Gobbo Francesca , Martelli Fabrizio , Martinelli Andrea , Sarli Giuseppe , Dunbar Andrew , Levine Ross L. , Hoffman Ronald , Massucci Maria Teresa , Brandolini Laura , Giorgio Cristina , Allegretti Marcello , Migliaccio Anna Rita
Published: March 2022

A major role for human (h)CXCL8 (interleukin-8) in the pathobiology of myelofibrosis (MF) has been suggested by observations indicating that MF megakaryocytes express increased levels of hCXCL8 and that plasma levels of this cytokine in MF patients are predictive of poor patient outcomes. Here, we demonstrate that, in addition to high levels of TGF-β, the megakaryocytes from the bone marrow of theGata1lowmouse model of myelofibrosis express high levels of murine (m)CXCL1, the murine equivalent of hCXCL8, and its receptors CXCR1 and CXCR2. Treatment with the CXCR1/R2 inhibitor, Reparixin in aged-matchedGata1lowmice demonstrated reductions in bone marrow and splenic fibrosis. Of note, the levels of fibrosis detected using two independent methods (Gomori and reticulin staining) were inversely correlated with plasma levels of Reparixin. Immunostaining of marrow sections indicated that the bone marrow from the Reparixin-treated group expressed lower levels of TGF-β1 than those expressed by the bone marrow from vehicle-treated mice while the levels of mCXCL1, and expression of CXCR1 and CXCR2, were similar to that of vehicle-treated mice. Moreover, immunofluorescence analyses performed on bone marrow sections fromGata1lowmice indicated that treatment with Reparixin induced expression of GATA1 while reducing expression of collagen III in megakaryocytes. These data suggest that inGata1lowmice, Reparixin reduces fibrosis by reducing TGF-β1 and collagen III expression while increasing GATA1 in megakaryocytes. Our results provide a preclinical rationale for further evaluation of this drug alone and in combination with current JAK inhibitor therapy for the treatment of patients with myelofibrosis.
Preoperative Prediction of Malignant Transformation of Sinonasal Inverted Papilloma Using MR Radiomics
Authors: Yan Yang , Liu Yujia , Tao Jianhua , Li Zheng , Qu Xiaoxia , Guo Jian , Xian Junfang
Published: March 2022

Purpose

Accurate preoperative prediction of the malignant transformation of sinonasal inverted papilloma (IP) is essential for guiding biopsy, planning appropriate surgery and prognosis of patients. We aimed to investigate the value of MRI-based radiomics in discriminating IP from IP-transformed squamous cell carcinomas (IP-SCC).

Methods

A total of 236 patients with IP-SCC (n=92) or IP (n=144) were enrolled and divided into a training cohort and a testing cohort. Preoperative MR images including T1-weighted, T2-weighted, and contrast enhanced T1-weighted images were collected. Radiomic features were extracted from MR images and key features were merged into a radiomic model. A morphological features model was developed based on MR morphological features assessed by radiologists. A combined model combining radiomic features and morphological features was generated using multivariable logistic regression. For comparison, two head and neck radiologists were independently invited to distinguish IP-SCC from IP. The area under the receiver operating characteristics curve (AUC) was used to assess the performance of all models.

Results

A total of 3948 radiomic features were extracted from three MR sequences. After feature selection, we saved 15 key features for modeling. The AUC, sensitivity, specificity, and accuracy on the testing cohort of the combined model based on radiomic and morphological features were respectively 0.962, 0.828, 0.94, and 0.899. The diagnostic ability of the combined model outperformed the morphological features model and also outperformed the two head and neck radiologists.

Conclusions

A combined model based on MR radiomic and morphological features could serve as a potential tool to accurately predict IP-SCC, which might improve patient counseling and make more precise treatment planning.
The Protective Effect of Pilose Antler Peptide on CUMS-Induced Depression Through AMPK/Sirt1/NF-κB/NLRP3-Mediated Pyroptosis
Authors: Hu Yue , Zhao Min , Zhao Tong , Qi Mingming , Yao Guangda , Dong Yu
Published: March 2022

Background: Pilose antler peptide (PAP), prepared from the pilose antler of Cervus nippon Temminck, is widely used in traditional Chinese medicine (TCM) against various inflammatory disorders. TCM prescriptions containing pilose antler are often prescribed clinically to treat depression. However, the pharmacological mechanisms of how PAP, against inflammation, prevents and treats depression remain poorly understood.

Methods: PAP was identified by de novo sequencing and database searching. Then, behavioral tests were conducted to investigate the effect of PAP on CUMS-exposed mice. In parallel, Nissl staining and Golgi-Cox staining were used for exploring the effect of PAP on neural cells and dendritic spine density. Additionally, the expression of key proteins of the AMPK/Sirt1/NF-κB/NLRP3 pathway was analyzed by Western blot. Finally, the CUMS procedure was conducted for 6 weeks. At the 5th week, PAP and fluoxetine (Flu) were intragastrically treated for 2 weeks. The silencing information regulator-related enzyme 1 (Sirt1) inhibitor EX-527 and the AMP-activated protein kinase (AMPK) inhibitor dorsomorphin were employed to investigate the effects of Sirt1 and AMPK on PAP-mediated depression.

Results: PAP attenuated the behavior alteration caused by CUMS stimulation, decreased the number of neurons, and restored the dendritic spine density. PAP treatment effectively upregulated the expressions of p-AMPK and Sirt1 and suppressed the expressions of Ac-NF-κB, NLRP3, Ac-Caspase-1, GSDMD-N, Cleaved-IL-1β, and Cleaved-IL-18. Moreover, selectively inhibited Sirt1 and AMPK were able to compromise the therapeutic effect of PAP on depression.

Conclusion: The present work indicated that PAP has a protective effect on CUMS-induced depression. In addition, AMPK and Sirt1 played critical roles in the PAP-relieved depression. PAP might be a potential therapeutic option for treating depression.
Study on the SHP2-Mediated Mechanism of Promoting Spermatogenesis Induced by Active Compounds of Eucommiae Folium in Mice
Authors: Mu Hailong , Liu Shuangshi , Tian Shiyang , Chen Beibei , Liu Zengyuan , Fan Yunpeng , Liu Yingqiu , Ma Wuren , Zhang Weimin , Fu Mingzhe , Song Xiaoping
Published: March 2022

Spermatogenesis directly determines the reproductive capacity of male animals. With the development of society, the increasing pressure on people’s lives and changes in the living environment, male fertility is declining. The leaf of Eucommia ulmoides Oliv. (Eucommiae Folium, EF) was recorded in the 2020 Chinese Pharmacopoeia and was used in traditional Chinese medicine as a tonic. In recent years, EF has been reported to improve spermatogenesis, but the mechanisms of EF remain was poorly characterized. In this study, the effect of EF ethanol extract (EFEE) on spermatogenesis was tested in mice. Chemical components related to spermatogenesis in EF were predicted by network pharmacology. The biological activity of the predicted chemical components was measured by the proliferation of C18-4 spermatogonial stem cells (SSCs) and the testosterone secretion of TM3 leydig cells. The biological activity of chlorogenic acid (CGA), the active compound in EF, was tested in vivo. The cell cycle was analysed by flow cytometry. Testosterone secretion was detected by ELISA. RNA interference (RNAi) was used to detect the effect of key genes on cell biological activity. Western blotting, qRT–PCR and immunofluorescence staining were used to analyse the molecular mechanism of related biological activities. The results showed that EFEE and CGA could improve spermatogenesis in mice. Furthermore, the main mechanism was that CGA promoted SSC proliferation, self-renewal and Leydig cell testosterone secretion by promoting the expression of SHP2 and activating the downstream signaling pathways involved in these biological processes. This study provided strong evidence for elucidating the mechanism by which EF promotes the spermatogenesis in mice and a new theoretical basis for dealing with the decrease in male reproductive capacity.
Agonists for Bitter Taste Receptors T2R10 and T2R38 Attenuate LPS-Induced Permeability of the Pulmonary Endothelium in vitro
Authors: Kertesz Zsuzsanna , Harrington Elizabeth O. , Braza Julie , Guarino Brianna D. , Chichger Havovi
Published: March 2022

One of the hallmarks of acute respiratory distress syndrome (ARDS) is an excessive increase in pulmonary vascular permeability. In settings of ARDS, the loss of barrier integrity is mediated by cell–cell contact disassembly and actin remodelling. Studies into molecular mechanisms responsible for improving microvascular barrier function are therefore vital in the development of therapeutic targets for reducing vascular permeability seen in ARDS. Bitter taste receptors (T2Rs) belong to the superfamily of G-protein-coupled receptors found in several extraoral systems, including lung epithelial and smooth muscle cells. In the present study, we show for the first time that several T2Rs are expressed in human pulmonary arterial endothelial cells (HPAECs). Our results focus on those which are highly expressed as: T2R10, T2R14 and T2R38. Agonists for T2R10 (denatonium) and T2R38 (phenylthiourea), but not T2R14 (noscapine), significantly attenuated lipopolysaccharide (LPS)-induced permeability and VE-cadherin internalisation in HPAECs. In T2R10- or T2R38-siRNA knockdown cells, these endothelial-protective effects were abolished, indicating a direct effect of agonists in regulating barrier integrity. Our further findings indicate that T2R10 and T2R38 exert their barrier-protective function through cAMP but via Rac1-dependent and independent pathways, respectively. However, using an in vivo model of ARDS, the T2R38 agonist, phenylthiourea, was not able to protect against pulmonary edema formation. Taken together, these studies identify bitter taste sensing in the pulmonary endothelium to regulate barrier integrity in vitro through cAMP-Rac1 signalling.
Reliability, Validity, and Sensitivity of a Specific Agility Test and Its Relationship With Physical Fitness in Karate Athletes
Authors: Ben Hassen Said , Negra Yassine , Uthoff Aaron , Chtara Moktar , Jarraya Mohamed
Published: March 2022

The aim of this study was to investigate the validity and reliability of a developed specific karate agility test (SKAT) and to examine its relationship with physical fitness. A total of 36 karateka voluntarily participated in this study. During two separate sessions, international and national ranked athletes completed the SKAT by performing three changes of direction (CoD): two in a preplanned manner and one in response to a stimulus that was provided by a live tester (Light tester). Assessment of CoD, horizontal jumping ability, 5 and 10 m sprint time, and dynamic balance were also applied during these two occasions. To evaluate SKAT’s construct validity, two groups were recruited based on their karate results: High- vs. low-ranked athletes. Reliability, validity, and sensitivity of the SKAT were examined from the intraclass correlation coefficient (ICC), standard error of measurement (SEM), smallest worthwhile change (SWC), and receiving operator characteristic analysis. Regarding relative and absolute reliability, the ICC of SKAT was excellent at >0.95 and the SEM was <5%. According to the sensitivity analysis, the power to detect small performance changes can be rated as “good” in karate athletes (SWC > SEM). The SKAT showed a moderate relationship with the CoD, jumping, sprint, and dynamic balance tests. High-ranked athletes were better than their low-ranked counterparts on SKAT (Cohen’s d = 2.00). The area under the receiving operator characteristic curve was 0.76. To sum up, the SKAT is a reliable and valid tool to assess the agility performance of karatekas and can be used by conditioning trainers to detect “true” performance changes.
New Burst-Oscillation Mode in Paced One-Dimensional Excitable Systems
Authors: Lei Zhao , Liu Jiajing , Zhao Yaru , Liu Fei , Qian Yu , Zheng Zhigang
Published: March 2022

A new type of burst-oscillation mode (BOM) is reported for the first time, by extensively investigating the response dynamics of a one-dimensional (1D) paced excitable system with unidirectional coupling. The BOM state is an alternating transition between two distinct phases, i.e., the phase with multiple short spikes and the phase with a long interval. The realizable region and the unrealizable region for the evolution of BOM are identified, which is determined by the initial pulse number in the system. It is revealed that, in the realizable region, the initial inhomogeneous BOM will eventually evolve to the homogeneously distributed spike-oscillation mode (SOM), while it can maintain in the unrealizable region. Furthermore, several dynamical features of BOM and SOM are theoretically predicted and have been verified in numerical simulations. The mechanisms of the emergence of BOM are discussed in detail. It is revealed that three key factors, i.e., the linking time, the system length, and the local dynamics, can effectively modulate the pattern of BOM. Moreover, the suitable parameter region of the external pacing (A, f) that can produce the new type of BOM, has been explicitly revealed. These results may facilitate a deeper understanding of bursts in nature and will have a useful impact in related fields.
GJA1-20k and Mitochondrial Dynamics
Authors: Shimura Daisuke , Shaw Robin M.
Published: March 2022

Connexin 43 (Cx43) is the primary gap junction protein of mammalian heart ventricles and is encoded by the gene Gja1 which has a single coding exon and therefore cannot be spliced. We previously identified that Gja1 mRNA undergoes endogenous internal translation initiated at one of several internal AUG (M) start codons, generating N-terminal truncated protein isoforms that retain the C-terminus distal to the start site. GJA1-20k, whose translation initiates at mRNA M213, is usually the most abundant isoform in cells and greatly increases after ischemic and metabolic stress. GJA1-20k consists of a small segment of the last transmembrane domain and the complete C-terminus tail of Cx43, with a total size of about 20 kDa. The original role identified for GJA1-20k is as an essential subunit that facilitates the trafficking of full-length Cx43 hexameric hemichannels to cell-cell contacts, generating traditional gap junctions between adjacent cells facilitating, in cardiac muscle, efficient spread of electrical excitation. GJA1-20k deficient mice (generated by a M213L substitution in Gja1) suffer poor electrical coupling between cardiomycytes and arrhythmogenic sudden death two to 4 weeks after their birth. We recently identified that exogenous GJA1-20k expression also mimics the effect of ischemic preconditioning in mouse heart. Furthermore, GJA1-20k localizes to the mitochondrial outer membrane and induces a protective and DRP1 independent form of mitochondrial fission, preserving ATP production and generating less reactive oxygen species (ROS) under metabolic stress, providing powerful protection of myocardium to ischemic insult. In this manuscript, we focus on the detailed roles of GJA1-20k in mitochondria, and its interaction with the actin cytoskeleton.
Modulated Light Dependence of Growth, Flowering, and the Accumulation of Secondary Metabolites in Chilli
Authors: Darko Eva , Hamow Kamirán A. , Marček Tihana , Dernovics Mihály , Ahres Mohamed , Galiba Gábor
Published: March 2022

Chili is widely used as a food additive and a flavouring and colouring agent and also has great importance in health preservation and therapy due to the abundant presence of many bioactive compounds, such as polyphenols, flavonoids, carotenoids, and capsaicinoids. Most of these secondary metabolites are strong antioxidants. In the present study, the effect of light intensity and spectral composition was studied on the growth, flowering, and yield of chilli together with the accumulation of secondary metabolites in the fruit. Two light intensities (300 and 500 μmol m–2 s–1) were applied in different spectral compositions. A broad white LED spectrum with and without FR application and with blue LED supplement was compared to blue and red LED lightings in different (80/20 and 95/5%) blue/red ratios. High light intensity increased the harvest index (fruit yield vs. biomass production) and reduced the flowering time of the plants. The amount of secondary metabolites in the fruit varied both by light intensity and spectral compositions; phenolic content and the radical scavenging activity were stimulated, whereas capsaicin accumulation was suppressed by blue light. The red colour of the fruit (provided by carotenoids) was inversely correlated with the absolute amount of blue, green, and far-red light. Based on the results, a schematic model was created, representing light-dependent metabolic changes in chilli. The results indicated that the accumulation of secondary metabolites could be modified by the adjustment of light intensity and spectral composition; however, different types of metabolites required different light environments.
An Easy and Rapid Transformation Protocol for Transient Expression in Cotton Fiber
Authors: Shang Xiaoguang , Zhu Lijie , Duan Yujia , He Qingfei , Zhao Meiyue , Yu Yujia , Guo Wangzhen
Published: March 2022

Cotton fiber is the most important natural textile material in the world. Identification and functional characterization of genes regulating fiber development are fundamental for improving fiber quality and yield. However, stable cotton transformation is time-consuming, low in efficiency, and technically complex. Moreover, heterologous systems, such as Arabidopsis and tobacco, did not always work to elucidate the function of cotton fiber specifically expressed genes or their promoters. For these reasons, constructing a rapid transformation system using cotton fibers is necessary to study fiber’s specifically expressed genes. In this study, we developed an easy and rapid Agrobacterium-mediated method for the transient transformation of genes and promoters in cotton fibers. First, we found that exogenous genes could be expressed in cotton fibers via using β-glucuronidase (GUS) and green fluorescence protein (GFP) as reporters. Second, parameters affecting transformation efficiency, including LBA4404 Agrobacterium strain, 3 h infection time, and 2-day incubation time, were determined. Third, four different cotton genes that are specifically expressed in fibers were transiently transformed in cotton fibers, and the transcripts of these genes were detected ten to thousand times increase over the control. Fourth, GUS staining and activity analysis demonstrated that the activity profiles of GhMYB212 and GhFSN1 promoters in transformed fibers are similar to their native activity in developmental fibers. Furthermore, the transient transformation method was confirmed to be suitable for subcellular localization studies. In summary, the presented Agrobacterium-mediated transient transformation method is a fast, simple, and effective system for promoter characterization and protein expression in cotton fibers.
Wood Anatomical Responses of European Beech to Elevation, Land Use Change, and Climate Variability in the Central Apennines, Italy
Authors: Miranda Jose Carlos , Calderaro Chiara , Cocozza Claudia , Lasserre Bruno , Tognetti Roberto , von Arx Georg
Published: March 2022

European beech (Fagus sylvatica L.) is a widespread and economically important temperate tree species in Europe. The warmer temperatures and severe drought events expected in the future, especially in Mediterranean areas, could affect the vitality and productivity of beech stands that have been intensively used in these areas in the past. Here, we aim to assess the wood anatomical responses of beech to environmental variability and silvicultural practices by investigating three beech stands along an elevational gradient (1,200 to 1,950 m a.s.l.) in the Apennines (Italy). Therefore, we quantified several anatomical traits of the xylem vessels related to tree hydraulics from five trees per stand and investigated variability between and within tree rings. Our results suggest generally limited trait plasticity, with higher plasticity of mean vessel lumen area and theoretical hydraulic conductivity, while maximum vessel size and mean hydraulic diameter were less plastic, likely because of the stronger determination by tree height. High-elevation trees were hydraulically more limited than trees at a mid and lower elevation as indicated by the more conservative anatomical configuration, i.e., comparatively smaller vessels and a 50% tighter trait coordination. Cessation of coppicing resulted in a hydraulically safer anatomy with comparatively smaller vessels at the most intensively used site (1,200 m), triggered by increased water demand due to an increase in canopy density, and thus, an increase in stand transpiration. Furthermore, maximum vessel size at the beginning showed different climate sensitivity compared to the rest of the tree ring, while intra-ring anatomical profiles showed little difference between normal and the 5 years with the highest and lowest mean temperature and precipitation. Overall, this study highlights the challenges to separate the externally induced medium- to longer-term responses from ontogenetically determined patterns. We, therefore, call for more comprehensive studies to further explore and verify the plasticity of wood anatomical traits in European beech in response to short- to long-term environmental fluctuations to gain a mechanistic understanding useful for sustainable forest ecosystems.
Can Cognitive Control and Attentional Biases Explain More of the Variance in Depressive Symptoms Than Behavioral Processes? A Path Analysis Approach
Authors: Krings Audrey , Simon Jessica , Carré Arnaud , Blairy Sylvie
Published: March 2022

Background

This study explored the proportion of variance in depressive symptoms explained by processes targeted by BA (activation, behavioral avoidance, anticipatory pleasure, and brooding), and processes targeted by cognitive control training (cognitive control, attentional biases, and brooding).

Methods

Five hundred and twenty adults were recruited. They completed a spatial cueing task as a measure of attentional biases and a cognitive task as a measure of cognitive control and completed self-report measures of activation, behavioral avoidance, anticipatory pleasure, brooding, and depressive symptoms. With path analysis models, we explored the relationships between these predictors and depressive symptoms.

Results

BA processes were significant predictors of depressive symptoms, and activation partially predicted anticipatory pleasure, which in turn predicted depressive symptoms. However, cognitive control and attentional biases predicted neither brooding nor depressive symptoms. A comprehensive model including all processes fit the data but did not explain more of the variance in brooding or depressive symptoms than a model including only BA processes.

Limitations

The spatial cueing task was associated with low reliability and the use of a non-clinical sample limited the generalizability of the conclusions.

Conclusion

Activation, behavioral avoidance, brooding, and anticipatory pleasure are relevant processes to target in order to reduce depressive symptoms, while cognitive control and attentional biases are not.
Burnout and Its Association With Competence Among Dental Interns in China
Authors: Liu Yingjun , Song Yi , Jiang Yong , Guo Chuanbin , Zhou Yongsheng , Li Tiejun , Ge Wenshu , An Na
Published: March 2022

Intern physicians are generally more burdened by stress than the general population. This cross-sectional study aimed to evaluate the current situation regarding burnout and explore its association with the self-evaluation of competence among Chinese dental interns. A self-administered anonymous survey was conducted on 91 dental interns in the Peking University School of Stomatology, from August 2019 to June 2020. It consisted of a psychological stress questionnaire, including burnout and self-evaluation of clinical competence. The Wilcoxon signed rank test was used to determine the differences between self-evaluation scores of clinical competence. Results showed average scores for emotional exhaustion, depersonalization, and personal accomplishment of 22.22 ± 9.04, 8.16 ± 5.21, and 36.08 ± 7.76, respectively. Dental clinical technology was considered more useful than other clinical competencies, and there was a correlation between its importance and the stress caused by its deficiency (r = −0.201, p = 0.056). Significant associations were found between stress due to a lack of dental clinical technology and high emotional exhaustion (r = 0.273, p < 0.05). Burnout was common among the dental interns, which may be a valuable finding. Among the six different aspects of clinical competence, “dental clinical technology” represented the most stressful item. Strengthening pre-clinical training and promptly conducting targeted training in the early clinical process may be considered as decompression measures.
Impact of Home-Based Learning Experience During COVID-19 on Future Intentions to Study Online: A Chinese University Perspective
Authors: Zhao Liang , Ao Yibin , Wang Yan , Wang Tong
Published: March 2022

As coronavirus disease 2019 (COVID-19) swept the world in early 2020, all the Chinese universities and colleges adopted online learning to fulfill the directive saying “classes suspended but learning continues.” Understanding the impact of this large-scale online learning experience on the future online learning intention of Chinese university students can help design better blended-learning activities. This study applies flow experience and theory of planned behavior (TPB) to construct a theoretical framework for assumption making and the assumptions made are validated by data gained from questionnaires. A total of 6,933 students from 54 institutions in China participated in the investigation, with 5,456 valid questionnaires returned. This study employs partial least squares (PLS) regression and confirmative factor analysis (CFA) to analyze and estimate the measurement model and the structural model. The results indicate that the experience of home-based learning significantly influenced the attitudes of Chinese university students, which in turn had a positive influence on their intention to continue online learning. The research findings provide a theoretical framework and practical guidelines on building a scientific online learning platform with appropriate online learning environments and tasks for a post-COVID-19 era blended-learning in Chinese universities.
Are Women Really Different? Comparison of Men and Women in a Sample of Forensic Psychiatric Inpatients
Authors: Streb Judith , Lutz Maximilian , Dudeck Manuela , Klein Verena , Maaß Christina , Fritz Michael , Franke Irina
Published: March 2022

Background

Women in detention remain a widely understudied group. Although the number of studies in women in prison has grown in the past decade, research on female forensic psychiatric inpatients has not increased, and women are in the minority in forensic psychiatry not only as patients but also as examinees. Consequently, most treatment manuals and risk assessments were developed in male samples and apply to male offenders. However, the same treatment and risk assessment rationale can be applied in male and female mentally ill offenders only if evidence shows that no relevant sex differences exist.

Aims

The aim of the present study was to examine a sample of male and female forensic psychiatric inpatients with substance use disorders and to compare the socio-demographic, legal, and clinical characteristics between the sexes.

Methods

The sample included 115 male and 61 female patients. All patients were in mandatory inpatient forensic psychiatry treatment according to section 64 of the German penal code.

Results

We found no significant differences between men and women in terms of educational status and vocational training. However, women were more often single and less likely to be employed full time, and they reported adverse childhood experiences more often than men. Regarding clinical variables, women appeared to be less likely to have a substance use disorder due to alcohol use and had more previous psychiatric treatments than men. Male patients were significantly younger on first conviction and detention, had more criminal records and served longer total penalties than female patients. Furthermore, men committed more violent crimes and women, more narcotics-related crimes.

Conclusions

The study identified sex-specific differences in forensic psychiatric patients that should be considered in the context of forensic therapy.
Association of Healthy Diet and Physical Activity With Breast Cancer: Lifestyle Interventions and Oncology Education
Authors: Jia Tiantian , Liu Yufeng , Fan Yuanyuan , Wang Lintao , Jiang Enshe
Published: March 2022

Global cancer statistics suggest that breast cancer (BC) is the most diagnosed cancer in women, with an estimated 2. 3 million new cases reported in 2020. Observational evidence shows a clear link between prevention and development of invasive BC and lifestyle-based interventions such as a healthy diet and physical activity. The recent findings reveal that even minimal amounts of daily exercise and a healthy diet reduced the risk of BC, mitigated the side effects of cancer treatment, and stopped the recurrence of cancer in the survivors. Despite the myriad benefits, the implementation of these lifestyle interventions in at-risk and survivor populations has been limited to date. Given the need to disseminate information about the role of physical activity and nutrition in BC reduction, the review aimed to present the recent scientific outreach and update on associations between the lifestyle interventions and BC outcomes to narrow the gap and strengthen the understanding more clearly. This review covers more direct, detailed, and updated scientific literature to respond to frequently asked questions related to the daily lifestyle-based interventions and their impact on BC risk and survivors. This review also highlights the importance of the oncology provider's job and how oncology education can reduce the BC burden.