bluuebunny/crossref_metadata_2025 huggingface dataset:
A hierarchy of selection pressures determines the organization of the T cell receptor repertoire
Authors: Mark Michal , Reich-Zeliger Shlomit , Greenstein Erez , Reshef Dan , Madi Asaf , Chain Benny , Friedman Nir
Published: July 2022

We systematically examine the receptor repertoire in T cell subsets in young, adult, and LCMV-infected mice. Somatic recombination generates diversity, resulting in the limited overlap between nucleotide sequences of different repertoires even within the same individual. However, statistical features of the repertoire, quantified by the V gene and CDR3 k-mer frequency distributions, are highly conserved. A hierarchy of immunological processes drives the evolution of this structure. Intra-thymic divergence of CD4+ and CD8+ lineages imposes subtle but dominant differences observed across repertoires of all subpopulations in both young and adult mice. Differentiation from naive through memory to effector phenotype imposes an additional gradient of repertoire diversification, which is further influenced by age in a complex and lineage-dependent manner. The distinct repertoire of CD4+ regulatory T cells is more similar to naive cells in young mice and to effectors in adults. Finally, we describe divergent (naive and memory) and convergent (CD8+ effector) evolution of the repertoire following acute infection with LCMV. This study presents a quantitative framework that captures the structure of the repertoire in terms of its fundamental statistical properties and describes how this structure evolves as individual T cells differentiate, migrate and mature in response to antigen exposure.
The TAM receptor tyrosine kinases Axl and Mer drive the maintenance of highly phagocytic macrophages
Authors: Jiménez-García Lidia , Mayer Christopher , Burrola Patrick G. , Huang Youtong , Shokhirev Maxim N. , Lemke Greg
Published: July 2022

Many apoptotic thymocytes are generated during the course of T cell selection in the thymus, yet the machinery through which these dead cells are recognized and phagocytically cleared is incompletely understood. We found that the TAM receptor tyrosine kinases Axl and Mer, which are co-expressed by a specialized set of phagocytic thymic macrophages, are essential components of this machinery. Mutant mice lacking Axl and Mer exhibited a marked accumulation of apoptotic cells during the time that autoreactive and nonreactive thymocytes normally die. Unexpectedly, these double mutants also displayed a profound deficit in the total number of highly phagocytic macrophages in the thymus, and concomitantly exhibited diminished expression of TIM-4, CD163, and other non-TAM phagocytic engulfment systems in the macrophages that remained. Importantly, these previously unrecognized deficits were not confined to the thymus, as they were also evident in the spleen and bone marrow. They had pleiotropic consequences for the double mutants, also previously unrecognized, which included dysregulation of hemoglobin turnover and iron metabolism leading to anemia.
The molecular diversity of transcriptional factor TfoX is a determinant in natural transformation in Glaesserella parasuis
Authors: Tang Xiaoyu , Yang Zhen , Dai Ke , Liu Geyan , Chang Yung-Fu , Tang Xinwei , Wang Kang , Zhang Yiwen , Hu Bangdi , Cao Sanjie , Huang Xiaobo , Yan Qigui , Wu Rui , Zhao Qin , Du Senyan , Lang Yifei , Han Xinfeng , Huang Yong , Wen Xintian , Wen Yiping
Published: July 2022

Natural transformation is a mechanism by which a particular bacterial species takes up foreign DNA and integrates it into its genome. The swine pathogen Glaesserella parasuis (G. parasuis) is a naturally transformable bacterium. The regulation of competence, however, is not fully understood. In this study, the natural transformability of 99 strains was investigated. Only 44% of the strains were transformable under laboratory conditions. Through a high-resolution melting curve and phylogenetic analysis, we found that genetic differences in the core regulator of natural transformation, the tfoX gene, leads to two distinct natural transformation phenotypes. In the absence of the tfoX gene, the highly transformable strain SC1401 lost its natural transformability. In addition, when the SC1401 tfoX gene was replaced by the tfoX of SH0165, which has no natural transformability, competence was also lost. These results suggest that TfoX is a core regulator of natural transformation in G. parasuis, and that differences in tfoX can be used as a molecular indicator of natural transformability. Transcriptomic and proteomic analyses of the SC1401 wildtype strain, and a tfoX gene deletion strain showed that differential gene expression and protein synthesis is mainly centered on pathways related to glucose metabolism. The results suggest that tfoX may mediate natural transformation by regulating the metabolism of carbon sources. Our study provides evidence that tfoX plays an important role in the natural transformation of G. parasuis.
Screening of Spirulina strains for high copper adsorption capacity through Fourier transform infrared spectroscopy
Authors: Liu Jinghua , Zhu Changwei , Li Zhengpeng , Zhou Haoyuan
Published: July 2022

Microalgae have emerged as promising biosorbents for the removal of toxic metals from industrial effluents due to the presence of various free functional groups. While the constitutes are distinct among different algal strains, it needs to screen the algae with high adsorption capacities for heavy metal ions by analyzing the algal components. In this study, a rapid and nondestructive Fourier transform infrared (FTIR) method combined PCA algorithm was used to discriminate algal strains according to their cellular components. With FTIR spectroscopy, we have found that the algal strains for high copper adsorption capacity (RH44, XS58, AH53, and RZ22) can be well differentiated from other strains via assessing the components involved in the biosorption of copper ions at the spectral window range of 1,200–900 cm−1 mainly attributed to polysaccharides. Correspondingly, the copper removal efficiency by different Spirulina strains was also measured by biochemical assay and scanning electron microscopy (SEM) in order to confirm the screening result. Compared with the chemical measurement, the assessment based on spectral features appears fairly good in the evaluation and differentiation of copper adsorption capacity in various Spirulina strains. This study illustrates that FTIR spectroscopy may serve as a fast and effective tool to investigate the functional groups for copper ions binding in the Spirulina cell and it even offers a useful and accurate new approach to rapidly assess potential adsorbents for the high capacity of copper adsorption.
Circulating exo-miR-154-5p regulates vascular dementia through endothelial progenitor cell-mediated angiogenesis
Authors: Han Xue , Zhou Li , Tu Yu , Wei Jiajia , Zhang Jiajia , Jiang Guojun , Shi Qiaojuan , Ying Huazhong
Published: July 2022

Background

Vascular dementia (VaD) mainly results from cerebral vascular lesions and tissue changes, which contribute to neurodegenerative processes. Effective therapeutic approaches to targeting angiogenesis may reduce mortality of VaD. Endothelial progenitor cells (EPCs) play a key role in postnatal angiogenesis. Many exosomal microRNAs (exo-miRNAs) have been reported to involve in the development of dementia. The present study was designed to investigate whether the expression profile of the exo-miRNAs is significantly altered in patients with VaD and to reveal the function of differentially expressed miRNAs and the relevant mechanisms in EPC-mediated angiogenesis in VaD rat model.

Results

Exosomes isolated from serum of patients with VaD (n = 7) and age-matched control subjects (n = 7), and miRNA sequencing and bioinformatics analysis found that circulating exosome miRNA-155-5p, miRNA-154-5p, miR-132-5p, and miR-1294 were upregulated in patients with VaD. The expression of miRNA-154-5p was further verified to be upregulated in clinical samples (n = 23) and 2-vessel occlusion-induced VaD rat model by reverse transcription quantitative PCR (RT-qPCR). Notably, miRNA-154-5p inhibition in bone marrow-EPCs (BM-EPCs) from VaD rats improved EPC functions, including tube formation, migration, and adhesion, and elevated concentrations of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α). The mRNA levels of ICAM-1, VCAM-1, and MCP-1 were reduced in miRNA-154-5p-inhibited EPCs. In addition, miRNA-154-5p inhibition increased the level of superoxide dismutase (SOD), and decreased reactive oxygen species (ROS) in EPCs. PRKAA2 was chosen as a promising target gene of miR-154-5p, and miRNA-154-5p inhibition upregulated the protein expression of AMPKα2. Furthermore, upregulation of miR-154-5p markedly diminished EPC functions and inhibited angiogenesis following EPC transplantation in VaD rats.

Conclusion

Circulating exo-miR-154-5p was upregulated in patients with VaD, and miR-154-5p upregulation was associated with impaired EPC functions and angiogenesis in VaD rat model. Therefore, miR-154-5p is a promising biomarker and therapeutic strategy for VaD.
Effect of atrial fibrillation on outcomes after mechanical thrombectomy and long-term ischemic recurrence in patients with acute basilar artery occlusion
Authors: Zhao Chenhao , Luo Weidong , Liu Xing , Luo Jun , Song Jiaxing , Yuan Junjie , Liu Shuai , Huang Jiacheng , Kong Weilin , Hu Jinrong , Yang Jie , Sun Ruidi , Yue Chengsong , Xie Dongjing , Li Linyu , Sang Hongfei , Qiu Zhongming , Li Fengli , Wu Deping , Zi Wenjie , Yang Qingwu
Published: July 2022

Introduction

According to the literature on anterior circulation, comorbid atrial fibrillation (AF) is not associated with a worse functional outcome, lower reperfusion rates, or higher rates of intracranial hemorrhage after mechanical thrombectomy (MT) compared to intravenous thrombolysis (IVT) or treatment with supportive care. However, data are limited for the effect of comorbid AF on procedural and clinical outcomes of acute basilar artery occlusion (ABAO) after MT. This study aimed to investigate the effect of atrial fibrillation on outcomes after MT and long-term ischemic recurrence in patients with ABAO.

Methods

We performed a registered study of the Endovascular Treatment for Acute Basilar Artery Occlusion Study (BASILAR, which is registered in the Chinese Clinical Trial Registry, http://www.chictr.org.cn; ChiCTR1800014759) from January 2014 to May 2019, which included 647 patients who underwent MT for ABAO, 136 of whom had comorbid AF. Prospectively defined baseline characteristics, procedural outcomes, and clinical outcomes were reported and compared.

Results

On multivariate analysis, AF predicted a shorter puncture-to-recanalization time, higher first-pass effect rate, and lower incidence of angioplasty and/or stenting (p < 0.01). AF had no effect on intracranial hemorrhage incidence [adjusted odds ratio (aOR), 1.093; 95% confidence interval (CI), 0.451–2.652], 90-day functional outcomes (adjusted common odds ratio, 0.915; 95% CI, 0.588–1.424), or mortality (aOR, 0.851; 95% CI, 0.491–1.475) after MT. The main findings were robust in the subgroup and 1-year follow-up analyses. Comorbid AF was the remaining predictor of ischemic recurrence (aOR, 4.076; 95% CI, 1.137–14.612).

Conclusions

The study revealed no significant difference in the safety and efficacy of MT for ABAO regardless of whether patients had comorbid AF. However, a higher proportion of patients with AF experienced ischemic recurrence within 1 year after MT.
A new perspective of hypothalamic disease: Shapiro's syndrome
Authors: Ren Linan , Gang Xiaokun , Yang Shuo , Sun Meixin , Wang Guixia
Published: July 2022

Shapiro's syndrome (SS) is characterized by spontaneous periodic hypothermia. It occurs to patients regardless of age or sex. To date, <60 cases have been reported worldwide. Current knowledge of the disease is limited to clinical feature since the pathogenesis and etiology are still controversial. In this review, the clinical characteristics, pathological mechanism, and possible etiology of the syndrome were reviewed to improve the clinical understanding of the disease.
Psychological well-being and cognitive aging in Black, Native American, and White Alzheimer’s Disease Research Center participants
Authors: Wyman Mary F. , Van Hulle Carol A. , Umucu Emre , Livingston Sydnee , Lambrou Nickolas H. , Carter Fabu P. , Johnson Sterling C. , Asthana Sanjay , Gleason Carey E. , Zuelsdorff Megan
Published: July 2022

Psychological well-being is associated with cognition in later life but has not been examined across diverse populations—including minoritized communities at disproportionately high risk of dementia. Further, most previous work has not been able to examine links between specific facets of psychological well-being and performance within distinct cognitive domains that can capture subclinical impairment. Using a well-characterized sample followed through enrollment in an NIH-funded Alzheimer’s Disease Center, we sought to test these associations within three racial groups at baseline. Participants were N = 529 cognitively unimpaired Black, American Indian/Alaska Native (AI/AN), and white middle-aged and older adults (mean age = 63.6, SD = 8.1, range = 45–88 years) enrolled in the Wisconsin Alzheimer’s Disease Research Center’s Clinical Core. Predictors included validated NIH Toolbox Emotion Battery scales assessing positive affect, general life satisfaction, and meaning and purpose. Outcomes included performance on widely used tests of executive functioning and episodic memory. We conducted race-stratified regression models to assess within-group relationships. Black and AI/AN participants reported lower life satisfaction than white participants. Racial disparities were not observed for positive affect or meaning and purpose scores. Across groups, life satisfaction predicted better executive functioning. Similar associations were observed for positive affect in Black and AI/AN samples but not among whites. In general, well-being measures were not related to performance on tests of episodic memory. Our results highlight well-being as a potentially important determinant of late-life cognitive health, particularly executive functioning, that is modifiable if older adults are connected with appropriate resources and supports. Further, psychological well-being may represent a potent target for brain health interventions tailored for Black and Native communities.
Asking questions that matter – Question prompt lists as tools for improving the consent process for neurotechnology clinical trials
Authors: Schönau Andreas , Goering Sara , Versalovic Erika , Montes Natalia , Brown Tim , Dasgupta Ishan , Klein Eran
Published: July 2022

Implantable neurotechnology devices such as Brain Computer Interfaces (BCIs) and Deep Brain Stimulators (DBS) are an increasing part of treating or exploring potential treatments for neurological and psychiatric disorders. While only a few devices are approved, many promising prospects for future devices are under investigation. The decision to participate in a clinical trial can be challenging, given a variety of risks to be taken into consideration. During the consent process, prospective participants might lack the language to consider those risks, feel unprepared, or simply not know what questions to ask. One tool to help empower participants to play a more active role during the consent process is a Question Prompt List (QPL). QPLs are communication tools that can prompt participants and patients to articulate potential concerns. They offer a structured list of disease, treatment, or research intervention-specific questions that research participants can use as support for question asking. While QPLs have been studied as tools for improving the consent process during cancer treatment, in this paper, we suggest they would be helpful in neurotechnology research, and offer an example of a QPL as a template for an informed consent tool in neurotechnology device trials.
Stress Affects Central Compensation of Neural Responses to Cochlear Synaptopathy in a cGMP-Dependent Way
Authors: Savitska Daria , Hess Morgan , Calis Dila , Marchetta Philine , Harasztosi Csaba , Fink Stefan , Eckert Philipp , Ruth Peter , Rüttiger Lukas , Knipper Marlies , Singer Wibke
Published: July 2022

In light of the increasing evidence supporting a link between hearing loss and dementia, it is critical to gain a better understanding of the nature of this relationship. We have previously observed that following cochlear synaptopathy, the temporal auditory processing (e.g., auditory steady state responses, ASSRs), is sustained when reduced auditory input is centrally compensated. This central compensation process was linked to elevated hippocampal long-term potentiation (LTP). We further observed that, independently of age, central responsiveness to cochlear synaptopathy can differ, resulting in either a low or high capacity to compensate for the reduced auditory input. Lower central compensation resulted in poorer temporal auditory processing, reduced hippocampal LTP, and decreased recruitment of activity-dependent brain-derived neurotrophic factor (BDNF) expression in hippocampal regions (low compensators). Higher central compensation capacity resulted in better temporal auditory processing, higher LTP responses, and increased activity-dependent BDNF expression in hippocampal regions. Here, we aimed to identify modifying factors that are potentially responsible for these different central responses. Strikingly, a poorer central compensation capacity was linked to lower corticosterone levels in comparison to those of high compensators. High compensators responded to repeated placebo injections with elevated blood corticosterone levels, reduced auditory brainstem response (ABR) wave I amplitude, reduced inner hair cell (IHC) ribbon number, diminished temporal processing, reduced LTP responses, and decreased activity-dependent hippocampal BDNF expression. In contrast, the same stress exposure through injection did not elevate blood corticosterone levels in low compensators, nor did it reduce IHC ribbons, ABR wave I amplitude, ASSR, LTP, or BDNF expression as seen in high compensators. Interestingly, in high compensators, the stress-induced responses, such as a decline in ABR wave I amplitude, ASSR, LTP, and BDNF could be restored through the “memory-enhancing” drug phosphodiesterase 9A inhibitor (PDE9i). In contrast, the same treatment did not improve these aspects in low compensators. Thus, central compensation of age-dependent cochlear synaptopathy is a glucocorticoid and cyclic guanosine-monophosphate (cGMP)-dependent neuronal mechanism that fails upon a blunted stress response.
Electroretinographic responses to luminance and cone-isolating white noise stimuli in macaques
Authors: Kremers Jan , Aher Avinash J. , Parry Neil R. A. , Patel Nimesh B. , Frishman Laura J.
Published: July 2022

Electroretinograms (ERGs) are mass potentials with a retinal origin that can be measured non-invasively. They can provide information about the physiology of the retina. Often, ERGs are measured to flashes that are highly unnatural stimuli. To obtain more information about the physiology of the retina, we measured ERGs with temporal white noise (TWN) stimuli that are more natural and keep the retina in a normal range of operation. The stimuli can be combined with the silent substitution stimulation technique with which the responses of single photoreceptor types can be isolated. We characterized electroretinogram (ERG) responses driven by luminance activity or by the L- or the M-cones. The ERGs were measured from five anesthetized macaques (two females) to luminance, to L-cone isolating and to M-cone isolating stimuli in which luminance or cone excitation were modulated with a TWN profile. The responses from different recordings were correlated with each other to study reproducibility and inter-individual variability. Impulse response functions (IRFs) were derived by cross-correlating the response with the stimulus. Modulation transfer functions (MTFs) were the IRFs in the frequency domain. The responses to luminance and L-cone isolating stimuli showed the largest reproducibility. The M-cone driven responses showed the smallest inter-individual variability. The IRFs and MTFs showed early (high frequency) components that were dominated by L-cone driven signals. A late component was equally driven by L- and M-cone activity. The IRFs showed characteristic similarities and differences relative to flash ERGs. The responses to TWN stimuli can be used to characterize the involvement of retinal cells and pathways to the ERG response. It can also be used to identify linear and non-linear processes.
A protocol for rapid construction of senescent cells
Authors: Yu Xing , Quan Jing , Chen Shuai , Yang Xinyue , Huang Shuai , Yang Gang , Zhang Yujing
Published: July 2022

Aging may be the largest factor for a variety of chronic diseases that influence survival, independence, and wellbeing. Evidence suggests that aging could be thought of as the modifiable risk factor to delay or alleviate age-related conditions as a group by regulating essential aging mechanisms. One such mechanism is cellular senescence, which is a special form of most cells that are present as permanent cell cycle arrest, apoptosis resistance, expression of anti-proliferative molecules, acquisition of pro-inflammatory, senescence-associated secretory phenotype (SASP), and others. Most cells cultured in vitro or in vivo may undergo cellular senescence after accruing a set number of cell divisions or provoked by excessive endogenous and exogenous stress or damage. Senescent cells occur throughout life and play a vital role in various physiological and pathological processes such as embryogenesis, wound healing, host immunity, and tumor suppression. In contrast to the beneficial senescent processes, the accumulation of senescent also has deleterious effects. These non-proliferating cells lead to the decrease of regenerative potential or functions of tissues, inflammation, and other aging-associated diseases because of the change of tissue microenvironment with the acquisition of SASP. While it is understood that age-related diseases occur at the cellular level from the cellular senescence, the mechanisms of cellular senescence in age-related disease progression remain largely unknown. Simplified and rapid models such as in vitro models of the cellular senescence are critically needed to deconvolute mechanisms of age-related diseases. Here, we obtained replicative senescent L02 hepatocytes by culturing the cells for 20 weeks. Then, the conditioned medium containing supernatant from replicative senescent L02 hepatocytes was used to induce cellular senescence, which could rapidly induce hepatocytes into senescence. In addition, different methods were used to validate senescence, including senescence-associated β-galactosidase (SA-β-gal), the rate of DNA synthesis using 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay, and senescence-related proteins. At last, we provide example results and discuss further applications of the protocol.
The role of brain oscillations in post-stroke motor recovery: An overview
Authors: Leonardi Giulia , Ciurleo Rosella , Cucinotta Francesca , Fonti Bartolo , Borzelli Daniele , Costa Lara , Tisano Adriana , Portaro Simona , Alito Angelo
Published: July 2022

Stroke is the second cause of disability and death worldwide, highly impacting patient’s quality of life. Several changes in brain architecture and function led by stroke can be disclosed by neurophysiological techniques. Specifically, electroencephalogram (EEG) can disclose brain oscillatory rhythms, which can be considered as a possible outcome measure for stroke recovery, and potentially shaped by neuromodulation techniques. We performed a review of randomized controlled trials on the role of brain oscillations in patients with post-stroke searching the following databases: Pubmed, Scopus, and the Web of Science, from 2012 to 2022. Thirteen studies involving 346 patients in total were included. Patients in the control groups received various treatments (sham or different stimulation modalities) in different post-stroke phases. This review describes the state of the art in the existing randomized controlled trials evaluating post-stroke motor function recovery after conventional rehabilitation treatment associated with neuromodulation techniques. Moreover, the role of brain pattern rhythms to modulate cortical excitability has been analyzed. To date, neuromodulation approaches could be considered a valid tool to improve stroke rehabilitation outcomes, despite more high-quality, and homogeneous randomized clinical trials are needed to determine to which extent motor functional impairment after stroke can be improved by neuromodulation approaches and which one could provide better functional outcomes. However, the high reproducibility of brain oscillatory rhythms could be considered a promising predictive outcome measure applicable to evaluate patients with stroke recovery after rehabilitation.
Lnc-PKD2-2-3/miR-328/GPAM ceRNA Network Induces Cholangiocarcinoma Proliferation, Invasion and 5-FU Chemoresistance
Authors: Zhang Lei , Ma Donglai , Li Fujun , Qiu Gongcai , Sun Dongsheng , Zeng Zhaolin
Published: July 2022

Purpose

Our previous study observed that long non-coding RNA PKD2-2-3 (lnc-PKD2-2-3) is related to advanced tumor features and worse prognosis in cholangiocarcinoma (CCA). Then, this study aimed to further explore the linkage between lnc-PKD2-2-3, miR-328, and GPAM, as well as their effects on regulating CCA viability, mobility, and chemosensitivity.

Methods

Lnc-PKD2-2-3, miR-328, and GPAM expression in 30 pairs of CCA tumor and adjacent tissues, as well as in CCA cell lines, were determined. Two CCA cell lines (HuCCT1 and TFK1) were transfected by lnc-PKD2-2-3 overexpression plasmid, lnc-PKD2-2-3 siRNA, miR-328 inhibitor, and GPAM siRNA alone or in combination, followed by cell proliferation, apoptosis, invasion, and 5-FU chemosensitivity detection. Besides, xenograft mice were established for validation.

Results

Lnc-PKD2-2-3 and GPAM were higher, whereas miR-328 was lower in CCA tissues versus adjacent tissues and also in CCA cell lines versus control cells; meanwhile, they were correlated with each other (all P <0.05). Lnc-PKD2-2-3 knockdown decreased CCA cell proliferation, invasion, and increased apoptosis (all P <0.05), but lnc-PKD2-2-3 overexpression exhibited the opposite and weaker effect. MiR-328 knockdown induced CCA cell proliferation and invasion and also attenuated the effect of lnc-PKD2-2-3-knockdown in these functions (all P <0.05). Subsequently, GPAM knockdown reduced CCA cell proliferation and invasion and also weakened the effect of miR-328-knockdown in these functions (all P <0.05). Additionally, lnc-PKD2-2-3 positively regulated GPAM while negatively regulating miR-328. MiR-328 negatively modified GPAM in CCA cells. Luciferase gene reporter assays verified that lnc-PKD2-2-3 directly bound miR-328 and miR-328 directly bound GPAM. Finally, the lnc-PKD2-2-3/miR-328/GPAM network also regulated the 5-FU chemosensitivity of CCA cells. In vivo experiments further revealed that lnc-PKD2-2-3 overexpression promoted tumor volume and weight but repressed tumor apoptosis in xenograft mice; meanwhile, it increased GPAM expression but decreased miR-328 expression (all P <0.05). Conversely, lnc-PKD2-2-3 knockdown exhibited the opposite effects (all P <0.05).

Conclusion

Lnc-PKD2-2-3/miR-328/GPAM ceRNA network promotes CCA proliferation, invasion, and 5-FU chemoresistance.
WNT4 overexpression and secretion in thymic epithelial tumors drive an autocrine loop in tumor cells in vitro
Authors: Zhang Xiaonan , Schalke Berthold , Kvell Krisztian , Kriegsmann Katharina , Kriegsmann Mark , Graeter Thomas , Preissler Gerhard , Ott German , Kurz Katrin , Bulut Elena , Ströbel Philipp , Marx Alexander , Belharazem Djeda
Published: July 2022

Background

WNT4-driven non-canonical signaling is crucial for homeostasis and age-related involution of the thymus. Abnormal WNT signaling is important in many cancers, but the role of WNT signaling in thymic tumors is largely unknown.

Materials & Methods

Expression and function of WNT4 and FZD6 were analyzed using qRT–PCR, Western blot, ELISA, in biopsies of non-neoplastic thymi (NT), thymoma and thymic carcinomas. ShRNA techniques and functional assays were used in primary thymic epithelial cells (pTECs) and TC cell line 1889c. Cells were conventionally (2D) grown and in three-dimensional (3D) spheroids.

Results

In biopsy, WHO classified B3 thymomas and TCs showed increased WNT4 expression compared with NTs. During short-term 2D culture, WNT4 expression and secretion declined in neoplastic pTECs but not in 3D spheroids or medium supplemented with recombinant WNT4 cultures. Under the latter condition, the growth of pTECs was accompanied by increased expression of non-canonical targets RAC1 and JNK. Down-regulation of WNT4 by shRNA induced cell death in pTECs derived from B3 thymomas and led to decreased RAC1, but not JNK protein phosphorylation. Pharmacological inhibition of NF-κB decreased both RAC1 and JNK phosphorylation in neoplastic pTECs.

Conclusions

Lack of the age-related decline of non-canonical WNT4 expression in TETs and restoration of declining WNT4 expression through exogeneous WNT4 or 3D culture of pTECs hints at an oncogenic role of WNT4 in TETs and is compatible with the WNT4 autocrine loop model. Crosstalk between WNT4 and NF-κB signaling may present a promising target for combined interventions in TETs.
Identification and characterization of a novel gene involved in glandular trichome development in Nepeta tenuifolia
Authors: Zhou Peina , Dang Jingjie , Shi Zunrui , Shao Yongfang , Sang Mengru , Dai Shilin , Yue Wei , Liu Chanchan , Wu Qinan
Published: July 2022

Nepeta tenuifoliais a medicinal plant rich in terpenoids and flavonoids with antiviral, immunoregulatory, and anti-inflammatory activities. The peltate glandular trichome (PGT) is a multicellular structure considered to be the primary storage organ for monoterpenes; it may serve as an ideal model for studying cell differentiation and the development of glandular trichomes (GTs). The genes that regulate the development of GTs have not yet been well studied. In this study, we identified NtMIXTA1, a GT development-associated gene from the R2R3 MYB SBG9 family.NtMIXTA1overexpression in tobacco resulted in the production of longer and denser GTs. Virus-induced gene silencing ofNtMIXTA1resulted in lower PGT density, a significant reduction in monoterpene concentration, and the decreased expression of genes related to monoterpene biosynthesis. Comparative transcriptome and widely targeted metabolic analyses revealed that silencingNtMIXTA1significantly influenced the expression of genes, and the production of metabolites involved in the biosynthesis of terpenoids, flavonoids, and lipids. This study provides a solid foundation describing a mechanism underlying the regulation of GT development. In addition, this study further deepens our understanding of the regulatory networks involved in GT development and GT development-associated metabolite flux, as well as provides valuable reference data for studying plants with a high medicinal value without genetic transformation.
Improved physiological and morphological traits of root synergistically enhanced salinity tolerance in rice under appropriate nitrogen application rate
Authors: Chen Yinglong , Liu Yang , Ge Jianfei , Li Rongkai , Zhang Rui , Zhang Yang , Huo Zhongyang , Xu Ke , Wei Huanhe , Dai Qigen
Published: July 2022

Numerous papers studied the relations between nitrogen rate and rice yield in saline soils, whereas the rice root morphological and physiological characteristics mediating nitrogen rates in yield formation under varied salinity levels remain less concerns. Through a field experiment applied with five nitrogen rates (0, 210, 255, 300, 345, and 390 kg ha–1) in saline land, we found that rice yield peaked at 7.7 t ha–1 under 300 kg ha–1 nitrogen, and excessive N was not conductive for increasing yield. To further elucidate its internal physiological mechanism, a pot experiment was designed with three N rates (210 [N1], 300 [N2], 390 [N3] kg ha–1) and three salt concentrations (0 [S0], 1.5 [S1], 3.0 [S2] g kg–1 NaCl). Results showed that the average grain yield was decreased by 19.1 and 51.1% under S1 and S2, respectively, while notably increased by 18.5 and 14.5% under N2 and N3, respectively. Salinity stress significantly inhibited root biomass, root length and surface area, root oxidation capacity (ROC), K+ and K+/Na+ ratio, and nitrogen metabolism-related enzyme activities, whereas root Na+ and antioxidant enzyme activities were notably increased. The mechanism of how insufficient N supply (N1) affected rice yield formation was consistent at different salinity levels, which displayed adverse impacts on root morphological and physiological traits, thereby significantly inhibiting leaf photosynthesis and grain yield of rice. However, the mechanism thorough which excessive N (N3) affected yield formation was quite different under varied salinity levels. Under lower salinity (S0 and S1), no significant differences on root morphological traits and grain yield were observed except the significantly decline in activities of NR and GS between N3 and N2 treatments. Under higher salinity level (S2), the decreased ROC, K+/Na+ ratio due to increased Na+, antioxidant enzyme activities, and NR and GS activities were the main reason leading to undesirable root morphological traits and leaf photosynthesis, which further triggered decreased grain yield under N3 treatment, compared to that under N2 treatment. Overall, our results suggest that improved physiological and morphological traits of root synergistically enhanced salinity tolerance in rice under appropriate nitrogen application rate.
Correlational study on cyberbullying and social abilities in intercultural teenagers
Authors: Tomé-Fernández María , Ortiz-Marcos José Manuel , Fernández-Leyva Christian
Published: July 2022

This article analyzes the relationship between cyberbullying profile by racist reasons and social abilities in a group of intercultural teenagers living in Spain (N = 1478). The study includes participants aged between 12 and 16 years old (M = 13.99; SD = 1.352). Of these, 738 were male (49.9%) and 740 were female (50.1%). A correlational study was carried out using online tools with suitable psychometrics parameters (content-construct validity and reliability). The first one was a scale that measured social abilities, and the second one evaluated racist or xenophobic cyberbullying, differentiating the victim and aggressor profiles. The results indicated five main findings: (1) generally, the participants analyzed present all their social abilities; (2) for the most part, these participants do not normally experience cyberbullying; (3) a positive correlation exists between the majority of social abilities analyzed and the cybervictim profile. It was also observed a negative correlation between the social ability associated with the ability of making requests and this profile; (4) there is a positive correlation among the six social abilities analyzed and the cyberaggressor profile; (5) the racist or xenophobic cyberbullying are driven not only by the absence of social abilities, but in some cases, they are also driven by socio-demographic variables (i.e., age and gender). Likewise, this work shows how the absence of some social abilities in some participants involve racist or xenophobic experiences as victims and as aggressors, which may be of interest for the analysis of teenagers’ behavior in intercultural contexts, as well as according to age and gender. More transcultural research need to be carried out to know the global perspective of the link between social abilities and the different profiles of racist and xenophobic cyberbullying, framed in the context of social psychology and studies of mass communication.
The Impact of e-Learning Systems on Motivating Students and Enhancing Their Outcomes During COVID-19: A Mixed-Method Approach
Authors: Yahiaoui Fethia , Aichouche Riad , Chergui Khalil , Brika Said Khalfa Mokhtar , Almezher Mohmmad , Musa Adam Ahmed , Lamari Imane Ahmed
Published: July 2022

e-Learning is a key strategy in the course of higher education to improve the results of the educational process and stimulate student motivation. The COVID-19 pandemic imposed on Algerian universities to adopt e-Learning systems to search for effectiveness and efficiency of academic approaches. This paper seeks to remedy these problems by analyzing the impact of e-Learning systems on student motivation and outcomes. A mixed-method approach was used in the data analysis. We conducted the study as a survey, with data being gathered via questionnaires distributed to 398 students. The questionnaire includes open questions that were qualitatively analyzed using content analysis with Nvivo, besides Likert scale questions were quantitatively analyzed and modeled using Structural equation modeling (SEM) with Amos to accomplish the path analysis of the research model. The results of the study showed that student motivation (Attention, Relevance, Confidence, and Satisfaction) and student outcomes (knowledge, skills, and attitudes) are significantly affected by e-Learning systems (Technical and electronic requirements, personal requirements, perceived value, and credibility of e-Learning). The key findings are discussed, and they provide recommendations for future research.
Toward Sustainable Development: Unleashing the Mechanism Among International Technology Spillover, Institutional Quality, and Green Innovation Capability
Authors: Wang Tao , Ding Yuan , Gao Ke , Sun Ruiqi , Wen Chen , Yan Bingzheng
Published: July 2022

Under the background of sustainable development, China’s economic growth engine becomes innovation-driven, and it is an important way for China to rapidly improve its green innovation capability by opening up to the outside world and utilizing the spillover effect of international technology. In this article, the system quality evaluation system is reconstructed by the method of fully arranged polygonal graphical indicators, and the provincial system quality in China is measured and added into the model as a regulating variable. The dynamic panel method and the dynamic threshold panel method are used to test the direct effects of foreign direct investment (FDI) and foreign trade on green innovation capability, the interaction effect of institutional quality, and the threshold effect. Empirical results show that the three technology spillovers have significantly promoted China’s green innovation capability. System quality will affect the determining coefficient of international technology spillovers on China’s green innovation capability. The positive promoting effects of FDI and foreign trade on China’s green innovation capability, all increase with the improvement of China’s system quality. Therefore, when utilizing FDI and foreign trade to promote green innovation in each region, each region should consider creating a good institutional environment for the emergence of international technological effects.
Design of Blended Teaching Model Based on Emotion Recognition and Language Learning
Authors: He Xuelian , Liu Zhenhuan
Published: July 2022

With the vigorous development of Internet technology, great changes have taken place in all aspects of human society. This change is also having an increasingly significant impact on the education sector. It is even a trend to subvert the tradition. This also makes the student's identity a passive recipient of knowledge. At the same time, the final orientation of China's education model is the result of examinations, and there is little guidance for students' interest. Of course, traditional teaching also has the ability to enable students' subject knowledge to be systematically established, and to communicate with teachers in the teaching process, which can improve students' learning efficiency in the classroom. In the face of the information explosion in today's society and the rapid development of the above-mentioned technologies, the change of students' learning mode of knowledge has also ushered in an opportunity to change. The purpose of this paper is to study the establishment of a blended teaching model that combines traditional classrooms with network applications. With the help of the characteristics of network big data, it transforms students' passive learning identities, and combines offline traditional learning classrooms with online learning. In addition to the advantages mentioned above, the advantage of online learning is that some network science and technology can be used for the online learning platform to serve the entire teaching process. Therefore, this paper proposes a blended teaching model based on the network platform for students' emotion recognition and language learning result analysis. And from the experimental results in this paper, it can be seen that the recognition evaluation rate of HTMC, the feature of emotion recognition, is 71.52% and the recognition frequency of ETMC is 73.89%. The above two recognition parameters can better reflect the emotional changes in the mixed teaching process.
RETRACTED: Mental Health Identification of Children and Young Adults in a Pandemic Using Machine Learning Classifiers
Authors: Luo Xuan , Huang Youlian
Published: July 2022

COVID-19 has altered our lifestyle, communication, employment, and also our emotions. The pandemic and its devastating implications have had a significant impact on higher education, as well as other sectors. Numerous researchers have utilized typical statistical methods to determine the effect of COVID-19 on the psychological wellbeing of young people. Moreover, the primary aspects that have changed in the psychological condition of children and young adults during COVID lockdown is analyzed. These changes are analyzed using machine learning and AI techniques which should be established for the alterations. This research work mainly concentrates on children's and young people's mental health in the first lockdown. There are six processes involved in this work. Initially, it collects the data using questionnaires, and then, the collected data are pre-processed by data cleaning, categorical encoding, and data normalization method. Next, the clustering process is used for grouping the data based on their mood state, and then, the feature selection process is done by chi-square, L1-Norm, and ReliefF. Then, the machine learning classifiers are used for predicting the mood state, and automatic calibration is used for selecting the best model. Finally, it predicts the mood state of the children and young adults. The findings revealed that for a better understanding of the effects of the COVID-19 pandemic on children's and youths' mental states, a combination of heterogeneous data from practically all feature groups is required.
Assisted dying requests from people in detention: Psychiatric, ethical, and legal considerations–A literature review
Authors: Franke Irina , Urwyler Thierry , Prüter-Schwarte Christian
Published: July 2022

The principle of equivalence of care states that prisoners must have access to the same standard of health care as the general population. If, as recent court decisions suggest, assisted dying is not limited to people with a terminal physical illness or irremediable suffering, it might also be requested by people with severe mental illness in detention. Some of the countries with legal regulations on assisted dying also have recommendations on how to handle requests from prisoners. However, detention itself can lead to psychological distress and suicidality, so we must consider whether and how people in such settings can make autonomous decisions. Ethical conflicts arise with regard to an individual's free will, right to life, and physical and personal integrity and to the right of a state to inflict punishment. Furthermore, people in prison often receive insufficient mental health care. In this review, we compare different practices for dealing with requests for assisted dying from people in prison and forensic psychiatric facilities and discuss the current ethical and psychiatric issues concerning assisted dying in such settings.
Association between sleep disturbance and mental health of healthcare workers: A systematic review and meta-analysis
Authors: Liu Ying , Zhang Qin , Jiang Fugui , Zhong Hua , Huang Lei , Zhang Yang , Chen Hong
Published: July 2022

Objectives

Sleep disturbance and mental health are challenges for healthcare workers (HCWs). Especially during the COVID-19 pandemic, they experienced more severe sleep and mental health problems. However, the association between sleep disturbance and the mental health of HCWs is still controversial. This study aimed to systematically review the relationship by conducting a systematic review and meta-analysis.

Method

Two researchers retrieved the literature from Web of Science, PubMed, EMBASE, CINAHL, Psyclnfo, and Cochrane Library from the establishment of the databases until November 20, 2021. We used the New Castle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ) to evaluate the risk of bias in prospective research and cross-sectional research, respectively. The major exposure was HCWs’ sleep disturbance, and the major outcome was mental health. The correlation coefficients (r), regression coefficients (β) and odds ratios (OR) of the included studies were integrated.

Result

Fifty-nine studies were included for qualitative analysis, of which 30 studies could be combined and entered into quantitative analysis. There were 23 studies during the COVID-19 pandemic among the 59 included studies. The results of the meta-analysis showed that the correlation coefficient between sleep disturbance and mental health was 0.43 (95% CI: 0.39–0.47). HCWs with sleep disturbance had a 3.74 (95% CI: 2.76–5.07) times higher risk of mental health problems than those without sleep disturbance. The correlation coefficient during the COVID-19 epidemic was 0.45 (95% CI: 0.37–0.53), while it was 0.40 (95% CI: 0.36–0.44) during the non-epidemic period. Subgroup analysis compared the OR results in epidemic and non-epidemic periods of COVID-19, which were 4.48 (95% CI: 2.75–5.07) and 3.74 (95% CI: 2.74–7.32), respectively.

Conclusion

Sleep disturbance and mental health problems were positively correlated among HCWs. Particularly in the COVID-19 pandemic, more attention should be given to this issue.