bluuebunny/crossref_metadata_2025 huggingface dataset:
Coordinated Control Strategy of Electricity-Heat-Gas Integrated Energy System Considering Renewable Energy Uncertainty and Multi-Agent Mixed Game
Authors: Jing Yan , Zhiqiang Duan , Jiemai Gao , Siyuan Chen , Bing Zhou , Yajie Wang
Published: June 2022

The Integrated Energy System (IES) can promote social energy transformation and low-carbon development, which is also an effective means to make contributions to energy structure optimization, energy consumption reduction, and new energy consumption. However, the IES has the characteristics of complex energy flow, and strong uncertainty with multi-agents. Therefore, traditional mathematical optimization models are difficult to comprehensively and accurately reflect the interest needs of different entities in the integrated energy microgrid. Aiming at this problem, a two-level collaborative control strategy model of “electricity-heat-gas” IES based on multi-agent deep reinforcement learning is proposed in this paper. The upper layer of this model is a multi-agent hybrid game decision-making model based on the Multi-Agent Deep Deterministic Policy Gradient algorithm (MADDPG), and the lower layer contains the power and gas flow calculation model. The lower model provides the upper model with the energy flow data of the IES and the upper layer rewards the decision-making behavior of the agent based on the energy flow data provided by the lower layer. Effectively solving the high-dimensional nonlinear optimization problem existing in the complex coupling network, this method can improve the convergence and training speed of the model. In this paper, the IEEE 33-node distribution network and 20-node gas network coupling system are provided to verify the model. The simulation results show that the proposed collaborative control strategy method can provide effective decision-making for electric-agent and gas-agent and realize the efficient and economic operation of the integrated energy system.
Strain Specific Variations in Acinetobacter baumannii Complement Sensitivity
Authors: Kamuyu Gathoni , Ercoli Giuseppe , Ramos-Sevillano Elisa , Willcocks Sam , Kewcharoenwong Chidchamai , Kiratisin Pattarachai , Taylor Peter W. , Wren Brendan W. , Lertmemongkolchai Ganjana , Stabler Richard A. , Brown Jeremy S.
Published: June 2022

The complement system is required for innate immunity against Acinetobacter baumannii, an important cause of antibiotic resistant systemic infections. A. baumannii strains differ in their susceptibility to the membrane attack complex (MAC) formed from terminal complement pathway proteins, but the reasons for this variation remain poorly understood. We have characterized in detail the complement sensitivity phenotypes of nine A. baumannii clinical strains and some of the factors that might influence differences between strains. Using A. baumannii laboratory strains and flow cytometry assays, we first reconfirmed that both opsonization with the complement proteins C3b/iC3b and MAC formation were inhibited by the capsule. There were marked differences in C3b/iC3b and MAC binding between the nine clinical A. baumannii strains, but this variation was partially independent of capsule composition or size. Opsonization with C3b/iC3b improved neutrophil phagocytosis of most strains. Importantly, although C3b/iC3b binding and MAC formation on the bacterial surface correlated closely, MAC formation did not correlate with variations between A. baumannii strains in their levels of serum resistance. Genomic analysis identified only limited differences between strains in the distribution of genes required for serum resistance, but RNAseq data identified three complement-resistance genes that were differentially regulated between a MAC resistant and two MAC intermediate resistant strains when cultured in serum. These data demonstrate that clinical A. baumannii strains vary in their sensitivity to different aspects of the complement system, and that the serum resistance phenotype was influenced by factors in addition to the amount of MAC forming on the bacterial surface.
TFR Cells Express Functional CCR6 But It Is Dispensable for Their Development and Localization During Splenic Humoral Immune Responses
Authors: Bastow Cameron R. , Kara Ervin E. , Tyllis Timona S. , Vinuesa Carola G. , McColl Shaun R. , Comerford Iain
Published: June 2022

Follicular T cells including T follicular helper (TFH) and T follicular regulatory (TFR) cells are essential in supporting and regulating the quality of antibody responses that develop in the germinal centre (GC). Follicular T cell migration during the propagation of antibody responses is largely attributed to the chemokine receptor CXCR5, however CXCR5 is reportedly redundant in migratory events prior to formation of the GC, and CXCR5-deficient TFH and TFR cells are still capable of localizing to GCs. Here we comprehensively assess chemokine receptor expression by follicular T cells during a model humoral immune response in the spleen. In addition to the known follicular T cell chemokine receptors Cxcr5 and Cxcr4, we show that follicular T cells express high levels of Ccr6, Ccr2 and Cxcr3 transcripts and we identify functional expression of CCR6 protein by both TFH and TFR cells. Notably, a greater proportion of TFR cells expressed CCR6 compared to TFH cells and gating on CCR6+CXCR5hiPD-1hi T cells strongly enriched for TFR cells. Examination of Ccr6-/- mice revealed that CCR6 is not essential for development of the GC response in the spleen, and mixed bone marrow chimera experiments found no evidence for an intrinsic requirement for CCR6 in TFR cell development or localisation during splenic humoral responses. These findings point towards multiple functionally redundant chemotactic signals regulating T cell localisation in the GC.
Characterization of the Intra-tumoral B Cell Immunoglobulin Repertoire Is of Prognostic Value for Esophageal Squamous Cell Carcinoma
Authors: Wang Zhizhong , Cheng Zhenguo , Lu Shuangshuang , Chard Dunmall Louisa S. , Wang Jun , Guo Yongjun , Wang Yaohe
Published: June 2022

Esophageal Squamous Cell carcinomas (ESCC) is a highly heterogeneous malignancy that is among the leading cause of cancer-related death worldwide. B cells play pivotal roles in the immune defense system and cancer progression and regression, yet the repertoire of tumor infiltrating B cells (TIBs) and its association with clinical outcome remains unexplored in ESCC. Here we collected bulk RNA-seq sequencing data from 119 ESCC tumors and matched adjacent normal samples to delineate the B cell repertoire. We found that ESCC is more heavily infiltrated by B cells and plasma cells compared to activated T cells. The immunoglobulin heavy chain variable region (IGHV) gene usage was remarkably biased and IGHV3-74 was under-represented in ESCC tumors. The TIBs showed a more oligoclonal profile along with widespread clonal expansion and IgG subclass switch events (CSRs). Survival analysis revealed several unexpected associations between tumor infiltrating B cells and prognosis. Higher levels of immunoglobulin expression (IGH), CD138 expression, IGH to MS4A1 ratio, CSR events and clone diversity are all associated with better survival. Notably, we found that the abundance of CD20-negative IgG2-producing plasma cells has a strong positive effect on overall survival with a hazard ratio (HR) of 0.40 (log-rank p: 0.002). Combing molecular subtyping, the IgG2-producing plasma cells could stratify high-risk patients more accurately with a HR of 0.253 (log-rank p: 0.0006). The direct link between protective B cell populations and ESCC prognosis provides biomarkers for high-risk patient selection and holds great promise for developing strategies for immunotherapy targeting B cells in ESCC patients.
Impaired Kallikrein-Kinin System in COVID-19 Patients' Severity
Authors: Alfaro Enrique , Díaz-García Elena , García-Tovar Sara , Zamarrón Ester , Mangas Alberto , Galera Raúl , Nanwani-Nanwani Kapil , Pérez-de-Diego Rebeca , López-Collazo Eduardo , García-Río Francisco , Cubillos-Zapata Carolina
Published: June 2022

COVID-19 has emerged as a devastating disease in the last 2 years. Many authors appointed to the importance of kallikrein-kinin system (KKS) in COVID-19 pathophysiology as it is involved in inflammation, vascular homeostasis, and coagulation. We aim to study the bradykinin cascade and its involvement in severity of patients with COVID-19. This is an observational cohort study involving 63 consecutive patients with severe COVID-19 pneumonia and 27 healthy subjects as control group. Clinical laboratory findings and plasma protein concentration of KKS peptides [bradykinin (BK), BK1-8], KKS proteins [high–molecular weight kininogen (HK)], and KKS enzymes [carboxypeptidase N subunit 1 (CPN1), kallikrein B1 (KLKB1), angiotensin converting enzyme 2 (ACE2), and C1 esterase inhibitor (C1INH)] were analyzed. We detected dysregulated KKS in patients with COVID-19, characterized by an accumulation of BK1-8 in combination with decreased levels of BK. Accumulated BK1-8 was related to severity of patients with COVID-19. A multivariate logistic regression model retained BK1-8, BK, and D-dimer as independent predictor factors to intensive care unit (ICU) admission. A Youden’s optimal cutoff value of −0.352 was found for the multivariate model score with an accuracy of 92.9%. Multivariate model score-high group presented an odds ratio for ICU admission of 260.0. BK1-8 was related to inflammation, coagulation, and lymphopenia. Our data suggest that BK1-8/BK plasma concentration in combination with D-dimer levels might be retained as independent predictors for ICU admission in patients with COVID-19. Moreover, we reported KKS dysregulation in patients with COVID-19, which was related to disease severity by means of inflammation, hypercoagulation, and lymphopenia.
Aerobic Exercise Training With Optimal Intensity Increases Cardiac Thermal Tolerance in Juvenile Rainbow Trout
Authors: Pettinau Luca , Seppänen Eila , Sikanen Asko , Anttila Katja
Published: June 2022

Domestication and selective breeding for rapid-growth have impaired the cardiorespiratory system of salmonids, which might compromise their capacity to tolerate environmental stressors, such as heat waves. Exercise training by swimming has been proposed as a potential tool to enhance growth, cardiac function and disease resilience in farmed fish and thereby improves aquaculture production. However, whether exercise training could also improve cardiac robustness against heat waves, which are becoming more common and cause severe challenges to aquaculture, remains unknown. Here, we trained juvenile rainbow trout at three different training velocities: 0.06 m*s-1 (or 0.9 body lengths per second [bl*s-1]; control group), 0.11 m*s-1 (or 1.7 bl*s-1; medium speed group) and 0.17 m*s-1 (or 2.7 bl*s-1; high speed group) for 5 weeks, 6h per day, 5 days per week. Measuring maximal heart rate (fHmax) during acute warming, we demonstrated that training at 1.7 bl*s-1 was optimal in order to increase the temperature at which fHmax reached its peak (Tpeak) as well as the upper thermal tolerance of the cardiovascular function (arrhythmia temperature, TARR), up to 3.6°C as compared to the control fish. However, more intensive training did not provide similar improvement on thermal tolerance. Both training regimes enhanced the ventricular citrate synthase activity which may provide higher aerobic energy production capacity for ventricles. Further mechanistic studies are needed to understand the complex interactions between training intensities and changes in thermal tolerance. Although not conclusive on that point, our findings present a valid training programme for hatchery salmonids to increase their cardiac thermal tolerance and consequently probably also their capacity to tolerate heat waves, which has a direct application for aquaculture.
Cellulose Derivative-Based Bioadhesive Blend Patch for Transdermal Drug Delivery
Authors: Manna Sreejan , Dhanalakshmi Dadala , Bhowmik Manas , Jana Sougata , Jana Subrata
Published: June 2022

In this study, matrix-type transdermal patches of glibenclamide were developed using a combination of hydrophilic and hydrophobic polymers for investigating the efficacy of transdermal carriers. A cellulose derivative, HPMC E50, was used as a hydrophilic matrix-forming polymer, and Eudragit RS 100 was used as a hydrophobic polymer. The solvent casting technique was employed to develop a transdermal blend patch formulation using chloroform and methanol as the casting solvent. No drug–polymer interaction was observed by the FTIR study. The membrane permeation study exhibited a sustained release of glibenclamide up to 12 h within a range of 76.15 ± 2.80% to 101.01 ± 0.33% depending on the polymeric ratio. The increased concentration of Eudragit RS 100 in different formulations has gradually decreased the amount of drug penetration through the membrane. The kinetic analysis showed the release is best explained by zero-order kinetics, followed by Higuchi and first order. The release exponent suggested shifting of non-Fickian diffusion to the super case II transport drug release mechanism when Eudragit RS 100 concentration was increased. It is concluded that the developed formulations may be a better alternative to the conventional oral delivery of glibenclamide.
Associations of Abdominal Visceral Fat Content and Plasma Adiponectin Level With Intracranial Atherosclerotic Stenosis: A Cross-Sectional Study
Authors: Wang Fei-Hong , Meng Long-Yan , Yu Tong-Ya , Tan Yan , Quan Hui , Hu Jia-Yu , Bai Qing-Ke , Xie Jun-Chao , Zhao Yan-Xin
Published: June 2022

Background

Abdominal obesity and adipocytokines are closely related to atherosclerosis, and adiponectin level is considered one of the important clinical indicators. This study aimed to analyze the associations of abdominal visceral fat content and adiponectin level with intracranial atherosclerotic stenosis (ICAS).

Methods

A total of 186 patients were enrolled in this study. Patients were distributed into ICAS and non-ICAS by the degree of artery stenosis. Plasma adiponectin levels and the ratio of visceral adipose tissue (VAT) to subcutaneous adipose tissue (SAT) were measured. The related factors of intracranial atherosclerotic stenosis were determined using multivariable logistic regression analysis.

Results

The VAT/SAT ratio (OR, 26.08; 95% CI, 5.92–114.83; p < 0.001) and adiponectin (OR, 0.61; 95% CI, 0.44–0.84; p = 0.002) were found to be the independent predictors of ICAS in a multivariable logistic regression analysis. The prevalence of ICAS increased (T1: 27.4%; T2: 50.0%; T3: 75.8%) as the VAT/SAT ratio tertile increased (p < 0.001). The prevalence of ICAS decreased (T1: 72.6%; T2: 54.8%; T3: 25.8%) as the adiponectin tertile increased (p < 0.001). In ROC curves analysis, VAT/SAT ratio had a sensible accuracy for the prediction of ICAS. The optimal cut-off value of VAT/SAT ratio to predict ICAS in this study was 1.04 (AUC: 0.747; p < 0.001; sensitivity: 67.4%; specificity: 74.7%). The optimal adiponectin cutoff was 3.03 ug/ml (AUC: 0.716; p < 0.001; sensitivity:75.8%; specificity: 61.5%).

Conclusion

Higher VAT/SAT ratio and lower plasma adiponectin levels were closely related to the increased risk of intracranial atherosclerotic stenosis.
Transient Response and Firing Behaviors of Memristive Neuron Circuit
Authors: Fang Xiaoyan , Tan Yao , Zhang Fengqing , Duan Shukai , Wang Lidan
Published: June 2022

The signal transmission mechanism of the Resistor-Capacitor (RC) circuit is similar to the intracellular and extracellular signal propagating mechanism of the neuron. Thus, the RC circuit can be utilized as the circuit model of the neuron cell membrane. However, resistors are electronic components with the fixed-resistance and have no memory properties. A memristor is a promising neuro-morphological electronic device with nonvolatile, switching, and nonlinear characteristics. First of all, we consider replacing the resistor in the RC neuron circuit with a memristor, which is named the Memristor-Capacitor (MC) circuit, then the MC neuron model is constructed. We compare the charging and discharging processes between the RC and MC neuron circuits. Secondly, two models are compared under the different external stimuli. Finally, the synchronous and asynchronous activities of the RC and MC neuron circuits are performed. Extensive experimental results suggest that the charging and discharging speed of the MC neuron circuit is faster than that of the RC neuron circuit. Given sufficient time and proper external stimuli, the RC and MC neuron circuits can produce the action potentials. The synchronous and asynchronous phenomena in the two neuron circuits reproduce nonlinear dynamic behaviors of the biological neurons.
Predictive Value of Geriatric Nutritional Risk Index in Patients With Lower Extremity Peripheral Artery Disease: A Meta-Analysis
Authors: Liu Guodong , Zou Chen , Jie Yu , Wang Pei , Wang Xiaoyan , Fan Yu
Published: June 2022

Background

Conflicting results have been reported on the value of the Geriatric Nutritional Risk Index (GNRI) in predicting adverse outcomes in patients with peripheral artery disease (PAD). The objective of this meta-analysis was to evaluate the association of GNRI with adverse outcomes in patients with lower extremity PAD.

Methods

Relevant studies were comprehensively searched in PubMed and Embase databases until December 31, 2021. Eligible studies should evaluate the value of GNRI in predicting major adverse cardiovascular and leg events (MACLEs), all-cause mortality, and amputation in patients with lower extremity PAD.

Results

Eight studies reporting on 9 articles involving 5,541 patients were included. A fixed-effect model meta-analysis showed that patients with PAD with low GNRI had an increased risk of MACLEs [adjusted risk ratio (RR) 2.26; 95% confidence interval (CI) 1.54–3.31] and all-cause mortality (RR 2.38; 95% CI 1.71–3.31) compared with those with high GNRI. When analysis of GNRI is by continuous data, 10 units of GNRI decrease was associated with 36% and 44% higher risk of MACLEs and all-cause mortality, respectively. However, per 10 units GNRI score decrease was not significantly associated with a higher risk of amputation (p = 0.051).

Conclusion

Low GNRI may be an independent predictor of adverse outcomes in patients with lower extremity PAD. Routine screening of nutritional status using the GNRI may provide important prognostic information in patients with PAD.
Diet Containing Soy Protein Concentrate With Low and High Isoflavones for 9 Weeks Protects Against Non-alcoholic Fatty Liver Steatosis Using Obese Zucker Rats
Authors: Hakkak Reza , Spray Beverly , Børsheim Elisabet , Korourian Soheila
Published: June 2022

Non-alcoholic fatty liver disease (NAFLD), is one of the main liver diseases in the US and the world which often is related to obesity. Previously, we reported short- and long-term consumption of soy protein isolate diet with high isoflavones can reduce liver steatosis in the male and female obese Zucker rat model. However, the effects of high vs. low soy isoflavones on NAFLD is less known. The objectives of the present study were to examine the role of isoflavones levels in soy protein concentrate diets on protection against NAFLD in an obese rat model. Forty-two 6-week old lean (L, n = 21) and obese (O, n = 21) Zucker rats were randomly assigned to 1 of 3 dietary groups: casein diet (C = control), soy protein concentrate with low isoflavones (LIF), or soy protein concentrate with high isoflavones (HIF) for 9 weeks. Rats were weighed twice weekly. After 9 weeks, rats were sacrificed and samples of livers were taken for histopathological analysis. Serums were collected to measure ALT and AST levels. Results indicate that obese rats gained significantly more weight than lean rats for all three diet groups (P < 0.001). No significant difference in body weight between LC, LLIF and LHIF was noted. However, the OLIF and OHIF rats gained significantly more weight than OC rats (P < 0.001). Liver steatosis scores were significantly greater in obese rats compared to lean rats (P < 0.001). The OLIF and OHIF-fed rats had significantly reduced steatosis scores than OC rats (P = 0.013 and P < 0.001, respectively). The serum ALT levels were significantly greater in OC, OLIF and OHIF compared to LC, LLIF and LHIF, respectively (P < 0.001, P < 0.001, and P = 0.011). AST serum levels were greater in OC and OLIF compared to LC and LLIF, respectively (P = 0.001 and P = 0.022). In summary, we found that soy protein concentrate with isoflavones protects against liver steatosis and the protection is greater with a higher concentration of isoflavones.
A Molecularly Characterized Preclinical Platform of Subcutaneous Renal Cell Carcinoma (RCC) Patient-Derived Xenograft Models to Evaluate Novel Treatment Strategies
Authors: Gürgen Dennis , Becker Michael , Dahlmann Mathias , Flechsig Susanne , Schaeffeler Elke , Büttner Florian A. , Schmees Christian , Bohnert Regina , Bedke Jens , Schwab Matthias , Wendler Johann J. , Schostak Martin , Jandrig Burkhard , Walther Wolfgang , Hoffmann Jens
Published: June 2022

Renal cell carcinoma (RCC) is a kidney cancer with an onset mainly during the sixth or seventh decade of the patient’s life. Patients with advanced, metastasized RCC have a poor prognosis. The majority of patients develop treatment resistance towards Standard of Care (SoC) drugs within months. Tyrosine kinase inhibitors (TKIs) are the backbone of first-line therapy and have been partnered with an immune checkpoint inhibitor (ICI) recently. Despite the most recent progress, the development of novel therapies targeting acquired TKI resistance mechanisms in advanced and metastatic RCC remains a high medical need. Preclinical models with high translational relevance can significantly support the development of novel personalized therapies. It has been demonstrated that patient-derived xenograft (PDX) models represent an essential tool for the preclinical evaluation of novel targeted therapies and their combinations. In the present project, we established and molecularly characterized a comprehensive panel of subcutaneous RCC PDX models with well-conserved molecular and pathological features over multiple passages. Drug screening towards four SoC drugs targeting the vascular endothelial growth factor (VEGF) and PI3K/mTOR pathway revealed individual and heterogeneous response profiles in those models, very similar to observations in patients. As unique features, our cohort includes PDX models from metastatic disease and multi-tumor regions from one patient, allowing extended studies on intra-tumor heterogeneity (ITH). The PDX models are further used as basis for developing corresponding in vitro cell culture models enabling advanced high-throughput drug screening in a personalized context. PDX models were subjected to next-generation sequencing (NGS). Characterization of cancer-relevant features including driver mutations or cellular processes was performed using mutational and gene expression data in order to identify potential biomarker or treatment targets in RCC. In summary, we report a newly established and molecularly characterized panel of RCC PDX models with high relevance for translational preclinical research.
Clinical Characteristics, Co-Mutations, and Treatment Outcomes in Advanced Non-Small-Cell Lung Cancer Patients With the BRAF-V600E Mutation
Authors: Qu Jingjing , Shen Qian , Li Yuping , Kalyani Farhin Shaheed , Liu Li , Zhou Jianya , Zhou Jianying
Published: June 2022

Background

Limited treatment outcome data is available for advanced non-small cell lung cancer (NSCLC) patients with BRAF V600E mutations. In this multicenter study, we describe therapeutic options and survival outcomes for patients with mutated BRAF V600E.

Method

This was a retrospective study in which BRAF V600E-mutated advanced NSCLC patients were retrospectively recruited between January 2015 and December 2021 and had their clinical characteristics, co-mutations, and treatment efficacy assessed.

Results

Fifty-three patients with BRAF V600E-mutant advanced NSCLC were included in the study, of which 64.2% were non-smokers, and the BRAF V600E mutation was more prevalent in men (52.8%). In addition, 96.2% of the patients had adenocarcinoma, and most (96.2%) received first-line therapy (23.5% anti-BRAF), with a progression-free survival (PFS) and overall survival (OS) of 10.0 [95% confidence interval (CI): 1.5–36.0 months] and 24.0 months [95% CI: 3.0–53.0 months], respectively. Twenty-three patients (43.4%) received second-line treatment (39.1% anti-BRAF), and PFS and OS were 5.0 [95% CI: 1.0–21.0 months] and 13.0 months [95% CI: 1.5–26.0 months], respectively. BRAF and MEK-targeted therapy (dabrafenib plus trametinib) produced longer PFS compared with that of chemotherapy with or without bevacizumab as a first-line (NA vs. 4.0 months, P = 0.025) or second-line therapy (6.0 vs. 4.6 months, P = 0.017). NSCLC patients harboring driver oncogene mutations such as BRAF V600E, EGFR, or ALK should be treated using targeted therapies. Concurrent TP53 mutations were the most common, affecting 11.3% (n = 6) of the patients, followed by EGFR 19 Del (n = 5). Patients with concurrent mutations had shorter PFS (9.0 vs. 10.0 months, P = 0.875) and OS (14.0 vs. 15.0 months, P = 0.555) than those without these mutations.

Conclusion

These results suggest that combined BRAF- and MEK-targeted therapy is effective in BRAF V600E-mutated advanced NSCLC patients. Dabrafenib and trametinib re-challenge is also an option for patients with BRAF V600E-mutated NSCLC.
EV-Mediated Chemoresistance in the Tumor Microenvironment: Is NF-κB a Player?
Authors: Di Vito Nolfi Mauro , Vecchiotti Davide , Flati Irene , Verzella Daniela , Di Padova Monica , Alesse Edoardo , Capece Daria , Zazzeroni Francesca
Published: June 2022

Drug resistance is a major impediment to patient survival and remains the primary cause of unsuccessful cancer therapy. Drug resistance occurs in many tumors and is frequently induced by chemotherapy which triggers a defensive response both in cancerous and cancer-associated cells that constitute the tumor microenvironment (TME). Cell to cell communication within the TME is often mediated by extracellular vesicles (EVs) which carry specific tumor-promoting factors able to activate survival pathways and immune escape mechanisms, thus sustaining tumor progression and therapy resistance. NF-κB has been recognized as a crucial player in this context. NF-κB activation is involved in EVs release and EVs, in turn, can trigger NF-κB pathway activation in specific contexts, based on secreting cytotype and their specific delivered cargo. In this review, we discuss the role of NF-κB/EVs interplay that sustain chemoresistance in the TME by focusing on the molecular mechanisms that underlie inflammation, EVs release, and acquired drug resistance.
Mechanism of Neural Regeneration Induced by Natural Product LY01 in the 5×FAD Mouse Model of Alzheimer’s Disease
Authors: Li Xiao-Wan , Lu Yang-Yang , Zhang Shu-Yao , Sai Ning-Ning , Fan Yu-Yan , Cheng Yong , Liu Qing-Shan
Published: June 2022

Background: A sharp decline in neural regeneration in patients with Alzheimer’s disease (AD) exacerbates the decline of cognition and memory. It is of great significance to screen for innovative drugs that promote endogenous neural regeneration. Cytisine N-methylene-(5,7,4′-trihydroxy)-isoflavone (LY01) is a new compound isolated from the Chinese herbal medicine Sophora alopecuroides with both isoflavone and alkaloid characteristic structures. Its pharmacological effects are worth studying.

Objective: This study was designed to determine whether LY01 delays the cognitive and memory decline in the early stage of AD and whether this effect of LY01 is related to promoting neural regeneration.

Methods: Eight-week-old 5×Familial Alzheimer’s Disease (5×FAD) mice were used as disease models of early AD. Three doses of LY01 administered in two courses (2 and 5 weeks) of treatment were tested. Cognition, memory, and anxiety-like behaviors in mice were evaluated by the Morris water maze, fear conditioning, and open field experiments. Regeneration of neurons in the mouse hippocampus was observed using immunofluorescence staining. The effect of LY01 on cell regeneration was also demonstrated using a series of tests on primary cultured neurons, astrocytes, and neural stem cells (NSCs). In addition, flow cytometry and transcriptome sequencing were carried out to preliminarily explored the mechanisms.

Results: We found that LY01 reduced the decline of cognition and memory in the early stage of 5×FAD mice. This effect was related to the proliferation of astrocytes, the proliferation and migration of NSCs, and increases in the number of new cells and neural precursor cells in the dentate gyrus area of 5×FAD mice. This phenomenon could be observed both in 2-week-old female and 5-week-old male LY01-treated 5×FAD mice. The neuronal regeneration induced by LY01 was related to the regulation of the extracellular matrix and associated receptors, and effects on the S phase of the cell cycle.

Conclusion: LY01 increases the proliferation of NSCs and astrocytes and the number of neural precursor cells in the hippocampus, resulting in neural regeneration in 5×FAD mice by acting on the extracellular matrix and associated receptors and regulating the S phase of the cell cycle. This provides a new idea for the early intervention and treatment of AD.
Correlation Optics, Coherence and Optical Singularities: Basic Concepts and Practical Applications
Authors: Angelsky O. V. , Bekshaev A. Ya. , Zenkova C. Yu. , Ivansky D. I. , Zheng Jun
Published: June 2022

The main idea of this review is to trace the interrelations and inter-transitions between the basic concepts and approaches of the correlation optics (including the light coherence) and the singular optics dealing with networks of “exceptional” points of light fields. The principles and examples are described of formation of light fields with required structures (amplitude, phase and polarization distributions, spectral properties as well as the internal energy flows and energy gradients responsible for optical forces) via superpositions of model optical fields of simple standard configurations and under controllable correlation conditions. The theoretical and experimental results, obtained by the authors and other researchers, demonstrate possibilities of the general approach to the complex fields formation with spatial and polarization inhomogeneities. A special topic, considered in more detail, is the interaction of structured optical fields with the media containing suspended micro- and nanoparticles, their inhomogeneous heating by the laser radiation and the accompanying self-diffraction and self-focusing phenomena. Possible light-induced phase transitions and controllable generation of the gas-vapor microbubbles in the medium are discussed. Specific optical singularities in polychromatic light fields are analyzed in connection to the field coherence. Some experimental solutions for revealing the fine structure of optical fields by means of the interference schemes are presented. Practical applications for the micromanipulation techniques, optical diagnostics of remote and random objects, optical treatment and laboratory practice in biology and medicine are described and discussed.
A Novel Quantitative Arousal-Associated EEG-Metric to Predict Severity of Respiratory Distress in Obstructive Sleep Apnea Patients
Authors: S Malatantis-Ewert , K Bahr , H Ding , Ludwig Katharina , N Koirala , T Huppertz , H Gouveris , M Muthuraman
Published: June 2022

Respiratory arousals (RA) on polysomnography (PSG) are an important predictor of obstructive sleep apnea (OSA) disease severity. Additionally, recent reports suggest that more global indices of desaturation such as the hypoxic burden, namely the area under the curve (AUC) of the oxygen saturation (SaO2) PSG trace may better depict the desaturation burden in OSA. Here we investigated possible associations between a new metric, namely the AUC of the respiratory arousal electroencephalographic (EEG) recording, and already established parameters as the apnea/hypopnea index (AHI), arousal index and hypoxic burden in patients with OSA. In this data-driven study, polysomnographic data from 102 patients with OSAS were assessed (32 female; 70 male; mean value of age: 52 years; mean value of Body-Mass-Index-BMI: 31 kg/m2). The marked arousals from the pooled EEG signal (C3 and C4) were smoothed and the AUC was estimated. We used a support vector regressor (SVR) analysis to predict AHI, arousal index and hypoxic burden as captured by the PSG. The SVR with the arousal-AUC metric could quite reliably predict the AHI with a high correlation coefficient (0,58 in the training set, 0,65 in the testing set and 0,64 overall), as well as the hypoxic burden (0,62 in the training set, 0,58 in the testing set and 0,59 overall) and the arousal index (0,58 in the training set, 0,67 in the testing set and 0,66 overall). This novel arousal-AUC metric may predict AHI, hypoxic burden and arousal index with a quite high correlation coefficient and therefore could be used as an additional quantitative surrogate marker in the description of obstructive sleep apnea disease severity.
Not all Forms of Muscle Hypertonia Worsen With Fatigue: A Pilot Study in Para Swimmers
Authors: Puce Luca , Bragazzi Nicola Luigi , Currà Antonio , Marinelli Lucio , Mori Laura , Cotellessa Filippo , Chamari Karim , Ponzano Marta , Samanipour Mohammad Hossein , Nikolaidis Pantelis T. , Biz Carlo , Ruggieri Pietro , Trompetto Carlo
Published: June 2022

In hypertonic muscles of patients with upper motor neuron syndrome (UMNS), investigation with surface electromyography (EMG) with the muscle in a shortened position and during passive muscle stretch allows to identify two patterns underlying hypertonia: spasticity and spastic dystonia. We recently observed in Para swimmers that the effect of fatigue on hypertonia can be different from subject to subject. Our goal was, therefore, to understand whether this divergent behavior may depend on the specific EMG pattern underlying hypertonia. We investigated eight UMNS Para swimmers (five men, mean age 23.25 ± 3.28 years), affected by cerebral palsy, who presented muscle hypertonia of knee flexors and extensors. Muscle tone was rated using the Modified Ashworth Scale (MAS). EMG patterns were investigated in rectus femoris (RF) and biceps femoris (BF) before and after two fatiguing motor tasks of increasing intensity. Before the fatiguing tasks, two subjects (#2 and 7) had spasticity and one subject (#5) had spastic dystonia in both RF and BF. Two subjects (#3 and 4) showed spasticity in RF and spastic dystonia in BF, whereas one subject (#1) had spasticity in RF and no EMG activity in BF. The remaining two subjects (#6 and 8) had spastic dystonia in RF and no EMG activity in BF. In all the 16 examined muscles, these EMG patterns persisted after the fatiguing tasks. Spastic dystonia increased (p < 0.05), while spasticity did not change (p > 0.05). MAS scores increased only in the muscles affected by spastic dystonia. Among the phenomena possibly underlying hypertonia, only spastic dystonia is fatigue-dependent. Technical staff and medical classifiers should be aware of this specificity, because, in athletes with spastic dystonia, intense and prolonged motor activity could negatively affect competitive performance, creating a situation of unfairness among Para athletes belonging to the same sports class.
NAC Transcription Factor TwNAC01 Positively Regulates Drought Stress Responses in Arabidopsis and Triticale
Authors: Wang Meng , Ren Li-Tong , Wei Xiao-Yong , Ling Yue-Ming , Gu Hai-Tao , Wang Shan-Shan , Ma Xue-Feng , Kong Guang-Chao
Published: June 2022

The NAC transcription factors play important roles in regulating plant growth, development, and senescence, and responding to biotic and abiotic stressors in plants. A novel coding sequence (1,059 bp) was cloned from hexaploid triticale in this study. The putative protein (352 amino acids) encoded by this sequence was over 95% similar to the amino acid sequence of a NAC protein from Aegilops tauschii (XP020161331), and it formed a clade with Ae. tauschii, durum wheat, and barley. The putative protein contained a conserved nature actomyosin (NAM) domain (129 consecutive amino acids) between the 20th and 148th amino acids at the N-terminus and three transcription activation regions at the C-terminus. The novel gene was identified as a triticale NAC gene localized in the nucleus and designated as TwNAC01 (GenBank accession MG736919). The expression levels of TwNAC01 were the highest in roots, followed by leaves and stems when triticale lines were exposed to drought, polyethylene glycol 6,000 (PEG6000), NaCl, cold, methyl jasmonate (MeJA), and abscisic acid (ABA). Transgenic Arabidopsis thaliana overexpressing TwNAC01 had significantly lower leaf water loss rates and longer roots than wild-type (WT) A. thaliana. Virus-induced silencing of the TwNAC01 gene in triticale delayed root development and decreased length of primary root. Under drought stress, leaves of TwNAC01-silenced triticale had higher levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2), but lower relative water content (RWC), net photosynthetic rate, stomatal conductance, intercellular CO2 concentration, and transpiration rate than the leaves of the WT. Gene overexpression and silencing experiments suggested that TwNAC01 improves plant stress tolerance by increasing root length, regulating the water content of plant leaves by reducing MDA and H2O2 content, and adjusting respiration rate. The results suggest that TwNAC01 is a novel NAC transcription factor gene that can be exploited for triticale and cereal improvement.
Synergistic Effect of Melatonin and Selenium Improves Resistance to Postharvest Gray Mold Disease of Tomato Fruit
Authors: Zang Huawei , Ma Jiaojiao , Wu Zhilin , Yuan Linxi , Lin Zhi-Qing , Zhu Renbin , Bañuelos Gary S. , Reiter Russel J. , Li Miao , Yin Xuebin
Published: June 2022

Melatonin (MT) is a ubiquitous hormone molecule that is commonly distributed in nature. MT not only plays an important role in animals and humans but also has extensive functions in plants. Selenium (Se) is an essential micronutrient for animals and humans, and is a beneficial element in higher plants at low concentrations. Postharvest diseases caused by fungal pathogens lead to huge economic losses worldwide. In this study, tomato fruits were treated with an optimal sodium selenite (20 mg/L) and melatonin (10 μmol/L) 2 h and were stored for 7 days at room temperature simulating shelf life, and the synergistic effects of Se and MT collectively called Se-Mel on gray mold decay in tomato fruits by Botrytis cinerea was investigated. MT did not have antifungal activity against B. cinerea in vitro, while Se significantly inhibited gray mold development caused by B. cinerea in tomatoes. However, the interaction of MT and Se showed significant inhibition of the spread and growth of the disease, showing the highest control effect of 74.05%. The combination of MT with Se treatment enhanced the disease resistance of fruits by improving the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), as well as increasing the gene expression level of pathogenesis-related (PR) proteins. Altogether, our results indicate that the combination of MT and Se would induce the activation of antioxidant enzymes and increase the expression of PR proteins genes that might directly enhance the resistance in tomato fruit against postharvest pathogenic fungus B. cinerea.
VaAPL1 Promotes Starch Synthesis to Constantly Contribute to Soluble Sugar Accumulation, Improving Low Temperature Tolerance in Arabidopsis and Tomato
Authors: Liang Guoping , Li Yanmei , Wang Ping , Jiao Shuzhen , Wang Han , Mao Juan , Chen Baihong
Published: June 2022

ADP-glucose pyrophosphorylase (AGPase) is a key rate-limiting enzyme involved in starch synthesis. APL1, an AGPase large subunit, plays an important role in the growth and development of grapes; however, its function in withstanding low temperature (LT) remains elusive. Hence, VaAPL1 was cloned from Vitis amurensis (Zuoshan I), and its function was characterized. The gene was highly expressed in the phloem of V. amurensis during winter dormancy (0, −5, and − 10°C). Phylogenetic relationships demonstrated that VaAPL1 was closely genetic related to SlAPL1 (from Solanum lycopersicum), and clustered into I group. Further, VaAPL1 was ectopically expressed in Arabidopsis thaliana (ecotype Columbia, Col) and tomato (“Micro-Tom” tomato) to characterize its function under LT. Compared with Col, the average survival rate of VaAPL1-overexpressing A. thaliana exceeded 75.47% after freezing treatment. Moreover, reactive oxygen species (ROS) content decreased in VaAPL1-overexpressing A. thaliana and tomato plants under LT stress. The activities of AGPase, and starch contents in VaAPL1-overexpressing A. thaliana were higher than in Col after LT stress. The contents of sucrose and glucose were accumulated in overexpressing plants compared with wild-type at 0 h and 24 h after LT stress. Transcriptome sequencing of overexpressing tomato plants revealed involvement in sugar metabolism and the hormone signal pathway, and Ca2+ signaling pathway-related genes were up-regulated. Hence, these results suggest that overexpression of VaAPL1 not only ensured sufficient starch converting into soluble sugars to maintain cell osmotic potential and provided energy, but also indirectly activated signal pathways involved in LT to enhance plant tolerance.
Structural Priming and Inverse Preference Effects in L2 Grammaticality Judgment and Production of English Relative Clauses
Authors: Wei Ran , Kim Sun-A , Shin Jeong-Ah
Published: June 2022

This study investigated inverse preference effects in L2 structural priming of English relative clauses and their potential influences on subsequent learning of target structures. One hundred fourteen Chinese learners of English at a low-to-intermediate proficiency level participated in a structural priming experiment with a pretest-posttest design. The experimental group underwent a priming task in which they orally produced syntactic structures immediately after viewing English object or passive relative clauses as primes, whereas the control group only read sentences unrelated to English relative clauses. A grammaticality judgment task and a sentence completion task were used to measure the inverse preference effect and its subsequent effects on L2 learning. The results showed the presence of structural priming and inverse preference effects in immediate production, which extended to subsequent learning of L2. In subsequent grammaticality judgments and production, L2 learners performed better with English object relative clauses than with English passive relative clauses in comparison with the pretest. The results are discussed in terms of the structural frequency in both L1 and L2 as well as the implicit learning mechanisms of structural priming.
The Development of Cognitive Reappraisal From Early Childhood Through Adolescence: A Systematic Review and Methodological Recommendations
Authors: Willner Cynthia J. , Hoffmann Jessica D. , Bailey Craig S. , Harrison Alexandra P. , Garcia Beatris , Ng Zi Jia , Cipriano Christina , Brackett Marc A.
Published: June 2022

Cognitive reappraisal is an important emotion regulation strategy that shows considerable developmental change in its use and effectiveness. This paper presents a systematic review of the evidence base regarding the development of cognitive reappraisal from early childhood through adolescence and provides methodological recommendations for future research. We searched Scopus, PsycINFO, and ERIC for empirical papers measuring cognitive reappraisal in normative samples of children and youth between the ages of 3 and 18 years published in peer-reviewed journals through August 9th, 2018. We identified 118 studies that met our inclusion criteria. We first present a quantitative review of the methodologies used to investigate cognitive reappraisal in children and adolescents, with attention to variations in methodologies by the sample age range. We then present a qualitative review of findings with attention to: (1) the age at which children begin to effectively use cognitive reappraisal to regulate their emotions, and (2) developmental changes in cognitive reappraisal from early childhood through adolescence. We consider how methodological differences may contribute to inconsistencies in findings, highlight gaps in the literature that remain to be addressed, and make recommendations for future directions.
Support or Suppress? Research on the Mechanism of Employee’s GNS on Innovation Performance: From the Perspective of Status Competition
Authors: Tang Yuhong , Ding Zhenkuo , Hu Xiwu , Tao Ran
Published: June 2022

The purpose of this paper is to investigate how supervisor’s mental state and behavior choice affect the relationship between employees’ strong growth need (GNS) and their innovation performance. Using 210 sets of supervisor-subordinate dyads data from two-wave survey, this research reveals that GNS has a significant positive effect on innovation performance, and leader–member exchange (LMX) mediates the effect of GNS on innovation performance. Supervisor perceived status threat moderates the relationship between GNS and LMX, such that this relationship gets weaker for supervisors with higher perceived status threat. Furthermore, supervisor perceived status threat moderates the relationship between GNS and innovation performance, such that this relationship becomes weaker for supervisors with higher perceived status threat. The study concludes with theoretical and practical implications, as well as future research avenues.
Effects of Concomitant Benzodiazepines and Antidepressants Long-Term Use on Social Decision-Making: Results From the Ultimatum Game
Authors: Fernandes Carina , Garcez Helena , Balaban Senanur , Barbosa Fernando , Pereira Mariana R. , Silveira Celeste , Marques-Teixeira João , Gonçalves Ana R.
Published: June 2022

Benzodiazepines and antidepressants have been shown to change responses to unfairness; however, the effects of their combined use on unfairness evaluation are unknown. This study examines the effects of concomitant benzodiazepines and antidepressants long-term use on the evaluation of fair and unfair offers. To analyze behavioral changes on responses to unfairness, we compared the performance of medicated participants and healthy controls in the Ultimatum Game (UG), both in the proposer and in the respondent role. The results showed that long-term psychotropic users had the worse economic strategy by accepting less offers than control subjects. However, in the proposer role, the unfair offers made by participants were similar between groups. The present results suggest that long-term use of psychotropic medication, specifically the combination of benzodiazepines and antidepressants, may increase the sensitivity to unfairness, resulting in higher rejection rates in conditions where this strategy is the most disadvantageous.