The Impacts of Bone Marrow Mesenchymal Stem Cells (BMSCs)-Derived Periostin on Epithelial-Mesenchymal Transition (EMT) of Cervical Cancer Cells

Epithelial-mesenchymal transition (EMT) is closely related to the migrating and invading behaviors of cells. Periostin is one of the essential components in the extracellular matrix and can induce EMT of cells and their sequential metastasis. But its underlying mechanism is unclear. The Hela and BMSC cell lines were assigned into Periostin-mimic group, Periostin-Inhibitor group and Periostin-NC group followed by analysis of cell migration and invasion, expression of E-Cadherin, Vimentin, β-Catenin, Snail, MMP-2, MMP-9, PTEN, and p-PTEN. Cells in Periostin-mimic group exhibited lowest migration, least number of invaded cells, as well as lowest levels of Vimentin, β-Catenin, Snail, MMP-2, MMP-9, p-PTEN, Akt, p-Akt, p-GSK-3β, p-PDK1 and p-cRcf, along with highest levels of E-cadherin and PTEN. Moreover, cells in Periostin-NC group had intermediate levels of these above indicators, while, the Periostin-Inhibitor group exhibited the highest migration rate, the most number of invaded cells, and the highest levels of these proteins (P < 0.05). In conclusion, BMSCs-derived Periostin can influence the EMT of cervical cancer cells possibly through restraining the activity of the PI3K/AKT signal transduction pathway, indicating that Periostin might be a target of chemotherapy in clinics for the treatment of cervical cancer.

Prevalence and Clinical Characteristics of Patients with Pause-Dependent Atrioventricular Block

Background: In patients with complete atrioventricular block (AVB), the prevalence and clinical characteristics of patients with pause-dependent AVB (PD-AVB) is not known. Our objective was to assess the prevalence of PD-AVB in a population of patients with complete (or high-grade) AVB. Methods: Twelve-lead electrocardiogram (ECG) and/or telemonitoring from patients admitted (from September 2020 to November 2021) for complete (or high-degree) AVB were prospectively collected at the University Hospital of Nice. The ECG tracings were analyzed by an electrophysiologist to determine the underlying mechanism of PD-AVB. Results: 100 patients were admitted for complete (or high-grade) AVB (men 55%; 82 ± 12 years). Arterial hypertension was present in 68% of the patients. Baseline QRS width was 117 ± 32 ms, and mean left ventricular ejection fraction was 56 ± 7%. Fourteen patients (14%) with PD-AVB were identified, and presented similar clinical characteristics in comparison with patients without PD-AVB, except for syncope (which was present in 86% versus 51% in the non-PD-AVB patients, p = 0.01). PD-AVB sequence was induced by: Premature atrial contraction (8/14), premature ventricular contraction (5/14), His extrasystole (1/14), conduction block in a branch (1/14), and atrial tachycardia termination (1/14). All patients with PD-AVB received a dual-chamber pacemaker during hospitalization. Conclusion: The prevalence of PD-AVB was 14%, and may be underestimated. PD-AVB episodes were more likely associated with syncope in comparison with patients without PD-AVB.

Influence of Defect Number, Distribution Continuity and Orientation on Tensile Strengths of the CNT-Based Networks: A Molecular Dynamics Study

Networks based on carbon nanotube (CNT) have been widely utilized to fabricate flexible electronic devices, but defects inevitably exist in these structures. In this study, we investigate the influence of the CNT-unit defects on the mechanical properties of a honeycomb CNT-based network, super carbon nanotube (SCNT), through molecular dynamics simulations. Results show that tensile strengths of the defective SCNTs are affected by the defect number, distribution continuity and orientation. Single-defect brings 0 ~ 25% reduction of the tensile strength with the dependency on defect position and the reduction is over 50% when the defect number increases to three. The distribution continuity induces up to 20% differences of tensile strengths for SCNTs with the same defect number. A smaller arranging angle of defects to the tensile direction leads to a higher tensile strength. Defective SCNTs possess various modes of stress concentration with different concentration degrees under the combined effect of defect number, arranging direction and continuity, for which the underlying mechanism can be explained by the effective crack length of the fracture mechanics. Fundamentally, the force transmission mode of the SCNT controls the influence of defects and the cases that breaking more force transmission paths cause larger decreases of tensile strengths. Defects are non-negligible factors of the mechanical properties of CNT-based networks and understanding the influence of defects on CNT-based networks is valuable to achieve the proper design of CNT-based electronic devices with better performances. Graphical Abstract

Reducing Red Tape’s Negative Consequences for Leaders: The Buffering Role of Autonomous Motivation

In a context where the amount of red tape in healthcare organizations continues to rise, head nurses’ job satisfaction is constantly under pressure. By building on the Job Demands-Resources model, we developed a theoretical model investigating the relationship between red tape and job satisfaction. By investigating the mediating role of discretionary room and the moderating role of autonomous motivation in this relationship, this study does not only aim to provide additional knowledge regarding the underlying mechanisms in this relationship, but also to increase our understanding of how this suffering at work can be mitigated. Our conditional process analyses (N = 277 head nurses) indicate that red tape undermines head nurses’ job satisfaction and that discretionary room acts as an underlying mechanism in this process. By revealing the mediating role of discretionary room, this study advances our understanding of the risks originating from red tape for leaders. Furthermore, our findings also indicate that autonomous motivation mitigates the negative relation between red tape and discretionary room and between red tape and job satisfaction. As autonomous motivation turns out to be an important protection mechanism against the negative consequences of red tape, organizations should put extra effort into stimulating the autonomous motivation of their leaders. When organizations make sure that their leaders’ job designs and work environments meet the need for autonomy, competence, and relatedness, leaders will become more autonomously motivated, which will buffer the negative impact of red tape.

ACE2 Shedding and the Role in COVID-19

Angiotensin converting enzyme 2 (ACE2), a transmembrane glycoprotein, is an important part of the renin-angiotensin system (RAS). In the COVID-19 epidemic, it was found to be the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). ACE2 maintains homeostasis by inhibiting the Ang II-AT1R axis and activating the Ang I (1-7)-MasR axis, protecting against lung, heart and kidney injury. In addition, ACE2 helps transport amino acids across the membrane. ACE2 sheds from the membrane, producing soluble ACE2 (sACE2). Previous studies have pointed out that sACE2 plays a role in the pathology of the disease, but the underlying mechanism is not yet clear. Recent studies have confirmed that sACE2 can also act as the receptor of SARS-COV-2, mediating viral entry into the cell and then spreading to the infective area. Elevated concentrations of sACE2 are more related to disease. Recombinant human ACE2, an exogenous soluble ACE2, can be used to supplement endogenous ACE2. It may represent a potent COVID-19 treatment in the future. However, the specific administration concentration needs to be further investigated.

Mitochondrial Dysfunction Associates With Acute T Lymphocytopenia and Impaired Functionality in COVID-19 Patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in rapid T lymphocytopenia and functional impairment of T cells. The underlying mechanism, however, remains incompletely understood. In this study, we focused on characterizing the phenotype and kinetics of T-cell subsets with mitochondrial dysfunction (MD) by multicolor flow cytometry and investigating the association between MD and T-cell functionality. While 73.9% of study subjects displayed clinical lymphocytopenia upon hospital admission, a significant reduction of CD4 or CD8 T-cell frequency was found in all asymptomatic, symptomatic, and convalescent cases. CD4 and CD8 T cells with increased MD were found in both asymptomatic and symptomatic patients within the first week of symptom onset. Lower proportion of memory CD8 T cell with MD was found in severe patients than in mild ones at the stage of disease progression. Critically, the frequency of T cells with MD in symptomatic patients was preferentially associated with CD4 T-cell loss and CD8 T-cell hyperactivation, respectively. Patients bearing effector memory CD4 and CD8 T cells with the phenotype of high MD exhibited poorer T-cell responses upon either phorbol 12-myristate-13-acetate (PMA)/ionomycin or SARS-CoV-2 peptide stimulation than those with low MD. Our findings demonstrated an MD-associated mechanism underlying SARS-CoV-2-induced T lymphocytopenia and functional impairment during the acute phase of infection.

BrPARP1, a Poly (ADP-Ribose) Polymerase Gene, Is Involved in Root Development in Brassica rapa under Drought Stress

PARP proteins are highly conserved homologs among the eukaryotic poly (ADP-ribose) polymerases. After activation, ADP-ribose polymers are synthesized on a series of ribozymes that use NAD+ as a substrate. PARPs participate in the regulation of various important biological processes, such as plant growth, development, and stress response. In this study, we characterized the homologue of PARP1 in B. rapa using RNA interference (RNAi) to reveal the underlying mechanism responding to drought stress. Bioinformatics and expression pattern analyses demonstrated that two copy numbers of PARP1 genes (BrPARP1.A03 and BrPARP1.A05) in B. rapa following a whole-genome triplication (WGT) event were retained compared with Arabidopsis, but only BrPARP1.A03 was predominantly transcribed in plant roots. Silencing of BrPARP1 could markedly promote root growth and development, probably via regulating cell division, and the transgenic Brassica lines showed more tolerance under drought treatment, accompanied with substantial alterations including accumulated proline contents, significantly reduced malondialdehyde, and increased antioxidative enzyme activity. In addition, the findings showed that the expression of stress-responsive genes, as well as reactive oxygen species (ROS)-scavenging related genes, was largely reinforced in the transgenic lines under drought stress. In general, these results indicated that BrPARP1 likely responds to drought stress by regulating root growth and the expression of stress-related genes to cope with adverse conditions in B. rapa.

Computable early Caenorhabditis elegans embryo with a phase field model

Morphogenesis is a precise and robust dynamic process during metazoan embryogenesis, consisting of both cell proliferation and cell migration. Despite the fact that much is known about specific regulations at molecular level, how cell proliferation and migration together drive the morphogenesis at cellular and organismic levels is not well understood. Using Caenorhabditis elegans as the model animal, we present a phase field model to compute early embryonic morphogenesis within a confined eggshell. With physical information about cell division obtained from three-dimensional time-lapse cellular imaging experiments, the model can precisely reproduce the early morphogenesis process as seen in vivo, including time evolution of location and morphology of each cell. Furthermore, the model can be used to reveal key cell-cell attractions critical to the development of C. elegans embryo. Our work demonstrates how genetic programming and physical forces collaborate to drive morphogenesis and provides a predictive model to decipher the underlying mechanism.

Transcriptome and HPLC Analysis Reveal the Regulatory Mechanisms of Aurantio-Obtusin in Space Environment-Induced Senna obtusifolia Lines

Senna obtusifolia is a famous medicinal plant that is widely used in Asian countries. Its seed plays an important role in the treatment of many diseases because it contains various anthraquinones and flavonoids. Our previous studies have indicated that three space environment-induced S. obtusifolia lines (SP-lines) i.e., QC10, QC29, and QC46, have higher seed yield and aurantio-obtusin (AO) content. However, the underlying mechanism of higher AO content in SP-lines is still unknown. Herein, transcriptome sequencing and HPLC were employed to analyze the differences between SP-lines and ground control (GC3) and elucidate the regulatory mechanisms of AO accumulation in SP-lines. The results show that 4002 differentially expressed genes (DEGs) were identified in SP-lines versus (vs.) GC3. DEGs in the QC10 vs. GC3, QC29 vs. GC3, and QC46 vs. GC3 comparisons were classified into 28, 36, and 81 GO terms and involved in 63, 74, and 107 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. KEGG pathway and gene expression analysis revealed that DEGs involved in anthraquinone pathways were significantly elevated in QC10 and QC46. Integrating the results of GO annotation, KEGG enrichment, and gene expression analysis, we propose that the elevated genes such as DAHPS, DHQS, and MenB enhance the metabolic flux in the anthraquinone pathway and promote AO content in QC10 and QC46. Taken together, this study elucidated the mechanism of AO content in SP-lines and provides valuable genetic information for S. obtusifolia. In addition, to the best of our knowledge, this study presents the first transcriptome analysis of environment-induced medicinal plants and paves the way to select elite S. obtusifolia varieties in the future.