bluuebunny/crossref_metadata_2025 huggingface dataset:
The Promising Role of Microbiome Therapy on Biomarkers of Inflammation and Oxidative Stress in Type 2 Diabetes: A Systematic and Narrative Review
Authors: Paul Pradipta , Kaul Ridhima , Abdellatif Basma , Arabi Maryam , Upadhyay Rohit , Saliba Reya , Sebah Majda , Chaari Ali
Published: May 2022

Background

One in 10 adults suffer from type 2 diabetes (T2D). The role of the gut microbiome, its homeostasis, and dysbiosis has been investigated with success in the pathogenesis as well as treatment of T2D. There is an increasing volume of literature reporting interventions of pro-, pre-, and synbiotics on T2D patients.

Methods

Studies investigating the effect of pro-, pre-, and synbiotics on biomarkers of inflammation and oxidative stress in T2D populations were extracted from databases such as PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to January 2022.

Results

From an initial screening of 5,984 hits, 47 clinical studies were included. Both statistically significant and non-significant results have been compiled, analyzed, and discussed. We have found various promising pro-, pre-, and synbiotic formulations. Of these, multistrain/multispecies probiotics are found to be more effective than monostrain interventions. Additionally, our findings show resistant dextrin to be the most promising prebiotic, followed closely by inulin and oligosaccharides. Finally, we report that synbiotics have shown excellent effect on markers of oxidative stress and antioxidant enzymes. We further discuss the role of metabolites in the resulting effects in biomarkers and ultimately pathogenesis of T2D, bring attention toward the ability of such nutraceuticals to have significant role in COVID-19 therapy, and finally discuss few ongoing clinical trials and prospects.

Conclusion

Current literature of pro-, pre- and synbiotic administration for T2D therapy is promising and shows many significant results with respect to most markers of inflammation and oxidative stress.
“Sandwich Therapy”—Immunotherapy Plus Concurrent Chemoradiotherapy for Advanced Esophagogastric Junction Carcinoma: Report of Two Cases and Literature Review
Authors: Wu Lei , Liu Juan , Liang Long , Mao Mian , Li Xiangpan , Li Tao , Lang Jinyi , Wang Qifeng
Published: May 2022

Introduction

Esophagogastric junction (EGJ) carcinomas develop in the transition zone between the esophagus and stomach. The incidence of EGJ carcinoma has steadily increased over the past few decades. Most patients are first diagnosed at an advanced stage, which renders them ineligible for surgery. Current methods for the treatment of advanced EGJ carcinoma include surgery, chemotherapy, local palliative therapy, and supportive care; however, none of these treatment methods has provided satisfactory therapeutic effects when used alone.

Case Report

We report two cases of patients with EGJ carcinoma who were sequentially treated with immunotherapy plus induction chemotherapy, followed by immunotherapy plus concurrent chemoradiotherapy and maintenance immunotherapy. Both patients achieved extended overall survival times with good quality of life with this new therapeutic approach.

Conclusion

Immunotherapy plus chemoradiotherapy may therefore be a reasonable option for treatment of selected EGJ carcinoma patients. However, well-designed trials for the acquisition of additional evidence are required to validate the findings in this study.
MSLN Correlates With Immune Infiltration and Chemoresistance as a Prognostic Biomarker in Ovarian Cancer
Authors: Li Yike , Tian Wanjia , Zhang Hong , Zhang Zhijian , Zhao Qinghe , Chang Lei , Lei Ningjing , Zhang Weiwei
Published: May 2022

Mesothelin (MSLN) is a glycoprotein with various expression degrees in different tumors including mesothelioma, ovarian cancer, pancreatic cancer, etc. MSLN is considered to play an important role in cell survival, proliferation, and tumor progression. Although the expression of MSLN in tumors makes it a potential therapeutic target, its mechanism of action is still unclear, especially its correlation with immune cells infiltration in the tumor microenvironment has not been investigated. In this study, we detected the overexpression of MSLN in ovarian cancer using database analysis and tissue-array staining. We further evaluated the diagnostic value of MSLN and found it was associated with poor overall survival in ovarian cancer. In addition, the high expression of MSLN was significantly related to the immune-related genes and chemoresistant genes. We confirmed the overexpression of MSLN in the chemoresistant ovarian cancer cell lines. Our research suggests that MSLN participates in a variety of pathways related to the suppression of immune activation and promotion of chemoresistance, leading to a poor prognosis in ovarian cancer.
Factors Affecting the Exercise Capacity in Pediatric Primary Hypertension
Authors: Zhang Hui , Chen Yeshi , Zheng Tong , Zhang Mingming , Li Xiaohui , Shi Lin
Published: May 2022

Purpose

Exercise training is crucial to the early intervention of pediatric primary hypertension (PHT). However, much less is known about exercise capacity in this disease. This work investigated the exercise capacity in pediatric PHT and analyzed the factors affecting exercise capacity.

Methods

The study enrolled children with PHT at the Children's Hospital Capital Institute of Pediatrics between July 2017 and July 2020. The Bruce protocol of the treadmill exercise test (TET) was used to assess exercise capacity. Multivariate ordinal logistic regression and generalized linear models were used to analyze factors affecting exercise capacity.

Results

Of 190 patients, 146 (76.8%) were male, and the median age was 13 (11, 14). Most children accomplished TET and achieved the submaximal heart rates (189 [99.5%]). Children with lower resting diastolic blood pressure (DBP) and 24 h average diastolic blood pressure (ADBP) could achieve a TET stage of 6 or more, whereas children with higher DBP and ADBP could only achieve a TET stage of 3 (P all < 0.05). Children with lower DBP and 24 h ADBP were also associated with greater metabolic equivalents (METs; r = −0.237, r = −0.179, P all < 0.05). The completion of TET stages was negatively associated with female (OR = 0.163), younger age (OR = 1.198), greater body mass index (BMI, OR = 0.921), and higher 24 h ADBP (OR = 0.952, P all < 0.05). In addition, METs were negatively associated with female (β = −1.909), younger age (β = 0.282), greater BMI (β = −0.134), and higher 24 h ADBP (β = −0.063, P all < 0.05).

Conclusions

Exercise capacity was impaired among pediatric PHT patients. Female gender, younger age, greater BMI, and higher 24 h ADBP are independently associated with the exercise capacity in pediatric PHT. These findings may help developing scientific exercise prescriptions for pediatric PHT.
Mechanism-Based Pharmacokinetic Model for the Deglycosylation Kinetics of 20(S)-Ginsenosides Rh2
Authors: Ren Hong-can , Sun Jian-guo , A Ji-ye , Gu Sheng-hua , Shi Jian , Shao Feng , Ai Hua , Zhang Jing-wei , Peng Ying , Yan Bei , Huang Qing , Liu Lin-sheng , Sai Yang , Wang Guang-ji , Yang Cheng-guang
Published: May 2022

Aim: The 20(S)-ginsenoside Rh2 (Rh2) is being developed as a new antitumor drug. However, to date, little is known about the kinetics of its deglycosylation metabolite (protopanoxadiol) (PPD) following Rh2 administration. The aim of this work was to 1) simultaneously characterise the pharmacokinetics of Rh2 and PPD following intravenous and oral Rh2 administration, 2) develop and validate a mechanism-based pharmacokinetic model to describe the deglycosylation kinetics and 3) predict the percentage of Rh2 entering the systemic circulation in PPD form.

Methods: Plasma samples were collected from rats after the I.V. or P.O. administration of Rh2. The plasma Rh2 and PPD concentrations were determined using HPLC-MS. The transformation from Rh2 to PPD, its absorption, and elimination were integrated into the mechanism based pharmacokinetic model to describe the pharmacokinetics of Rh2 and PPD simultaneously at 10 mg/kg. The concentration data collected following a 20 mg/kg dose of Rh2 was used for model validation.

Results: Following Rh2 administration, PPD exhibited high exposure and atypical double peaks. The model described the abnormal kinetics well and was further validated using external data. A total of 11% of the administered Rh2 was predicted to be transformed into PPD and enter the systemic circulation after I.V. administration, and a total of 20% of Rh2 was predicted to be absorbed into the systemic circulation in PPD form after P.O. administration of Rh2.

Conclusion: The developed model provides a useful tool to quantitatively study the deglycosylation kinetics of Rh2 and thus, provides a valuable resource for future pharmacokinetic studies of glycosides with similar deglycosylation metabolism.
Epigenetic Reader Bromodomain Containing Protein 2 Facilitates Pathological Cardiac Hypertrophy via Regulating the Expression of Citrate Cycle Genes
Authors: Lin Zhirong , Li Zhenzhen , Guo Zhen , Cao Yanjun , Li Jingyan , Liu Peiqing , Li Zhuoming
Published: May 2022

The bromodomain and extra-terminal domain proteins (BETs) family serve as epigenetic “readers”, which recognize the acetylated histones and recruit transcriptional regulator complexes to chromatin, eventually regulating gene transcription. Accumulating evidences demonstrate that pan BET inhibitors (BETi) confer protection against pathological cardiac hypertrophy, a precursor progress for developing heart failure. However, the roles of BET family members, except BRD4, remain unknown in pathological cardiac hypertrophy. The present study identified BRD2 as a novel regulator in cardiac hypertrophy, with a distinct mechanism from BRD4. BRD2 expression was elevated in cardiac hypertrophy induced by β-adrenergic agonist isoprenaline (ISO) in vivo and in vitro. Overexpression of BRD2 upregulated the expression of hypertrophic biomarkers and increased cell surface area, whereas BRD2 knockdown restrained ISO-induced cardiomyocyte hypertrophy. In vivo, rats received intramyocardial injection of adeno-associated virus (AAV) encoding siBRD2 significantly reversed ISO-induced pathological cardiac hypertrophy, cardiac fibrosis, and cardiac function dysregulation. The bioinformatic analysis of whole-genome sequence data demonstrated that a majority of metabolic genes, in particular those involved in TCA cycle, were under regulation by BRD2. Real-time PCR results confirmed that the expressions of TCA cycle genes were upregulated by BRD2, but were downregulated by BRD2 silencing in ISO-treated cardiomyocytes. Results of mitochondrial oxygen consumption rate (OCR) and ATP production measurement demonstrated that BRD2 augmented cardiac metabolism during cardiac hypertrophy. In conclusion, the present study revealed that BRD2 could facilitate cardiac hypertrophy through upregulating TCA cycle genes. Strategies targeting inhibition of BRD2 might suggest therapeutic potential for pathological cardiac hypertrophy and heart failure.
Cannabis for Medical Use: Analysis of Recent Clinical Trials in View of Current Legislation
Authors: Baratta F. , Pignata I. , Ravetto Enri L. , Brusa P.
Published: May 2022

Cannabis has long been regarded as a recreational substance in the Western world. The recent marketing authorization of some medicinal products of industrial origin and the introduction onto the market of inflorescences for medical use mean that medical doctors can now prescribe Cannabis-based medicines in those countries which allow it. Nevertheless, there is still considerable controversy on this topic in the scientific community. In particular, this controversy concerns: the plant species to be used; the pathologies that can be treated and consequently the efficacy and safety of use; the routes of administration; the methods of preparation; the type and dosage of cannabinoids to be used; and, the active molecules of interest. As such, although medical Cannabis has been historically used, the results of currently completed and internationally published studies are inconclusive and often discordant. In light of these considerations, the aim of this work is to analyse the current legislation in countries that allow the use of medical Cannabis, in relation to the impact that this legislation has had on clinical trials. First of all, a literature search has been performed (PubMed and SciFinder) on clinical trials which involved the administration of Cannabis for medical use over the last 3 years. Of the numerous studies extrapolated from the literature, only about 43 reported data on clinical trials on medical Cannabis, with these mainly being performed in Australia, Brazil, Canada, Denmark, Germany, Israel, Netherlands, Switzerland, the United Kingdom and the United States of America. Once the reference countries were identified, an evaluation of the legislation in relation to Cannabis for medical use in each was carried out via the consultation of the pertinent scientific literature, but also of official government documentation and that of local regulatory authorities. This analysis provided us with an overview of the different legislation in these countries and, consequently, allowed us to analyse, with greater awareness, the results of the clinical trials published in the last 3 years in order to obtain general interest indications in the prosecution of scientific research in this area.
Tizoxanide Promotes Apoptosis in Glioblastoma by Inhibiting CDK1 Activity
Authors: Huang Si , Xiao Jingxian , Wu Junyong , Liu Jiayi , Feng Xueping , Yang Chengdong , Xiang Daxiong , Luo Shilin
Published: May 2022

The antiparasitic drug nitazoxanide (NTZ) has received considerable attention for its potential in cancer therapy. In this study, we demonstrate that tizoxanide (TIZ), an active metabolite of NTZ, exhibits antiglioma activity in vitro and in vivo by inducing G2/M cell cycle arrest and apoptosis. In vitro, TIZ dose-dependently inhibited the proliferation of U87, U118, and A172 human glioblastoma (GBM) cells at 48 h with IC50 values of 1.10, 2.31, and 0.73 µM, respectively. Treatment with TIZ (1 and 10 µM) also dose-dependently inhibited the colony formation of these GBM cells and accumulated ROS damage in the nucleus. In silico target fishing combined with network pharmacological disease spectrum analyses of GBM revealed that cycle-dependent kinase 1 (CDK1) is the most compatible target for TIZ and molecular docking by Molecule Operating Environment (MOE) software confirmed it. Mechanistically, TIZ inhibited the phosphorylation of CDK1 at Thr161 and decreased the activity of the CDK1/cyclin B1 complex, arresting the cell cycle at the G2/M phase. TIZ may induce apoptosis via the ROS-mediated apoptotic pathway. In vivo, TIZ suppressed the growth of established subcutaneous and intracranial orthotopic xenograft models of GBM without causing obvious side effects and prolonged the survival of nude mice bearing glioma. Taken together, our results demonstrated that TIZ might be a promising chemotherapy drug in the treatment of GBM.
Integrating Network Pharmacology and Metabolomics to Elucidate the Mechanism of Action of Huang Qin Decoction for Treament of Diabetic Liver Injury
Authors: Xu Xiaomin , Fang Cheng , Wang Yu , Lu Fang , Liu Shumin
Published: May 2022

Huang Qin Decoction (HQD), is used for the treatment of diabetic liver injury (DLI) and in this study, its mechanisms were evaluated by metabonomics and system pharmacology. To study the anti-DLI effects of HQD. The 48 male db/db mice were fed adaptively for one week, and a random blood glucose test was performed twice. The db/db mice with a blood glucose level of more than 11.1mol/l were separated into four groups: the model group, the active control group, the high-dose HQD group the low-dose HQD group, the control group consisted of db/m mice. Using the UHPLC/Q-TOF-MS metabolomics approach, 18 metabolites were found to be profoundly altered in the model group, and the levels of these biomarkers were significantly recovered after treatment with HQD. 8 signaling pathways related to HQD, including the Sphingolipid metabolism, Taurine and hypotaurine metabolism, Phenylalanine metabolism, Glutathione metabolism and Glycerophospholipid metabolism, etc. were explored. In addition, the system pharmacology paradigm revealed that HQD contains 141 active ingredients and is related to 265 genes, and 1404 disease genes are related to DLI. The construction of the HQD composition-target-DLI network identified a total of 161 intersection genes. We identified 10 key genes, which is partially compatible with the results of metabolomics. The integrated approach metabolomics and network pharmacology revealed that additional detailed investigation focused on five major targets, including CAT, PTGS2, MAPK3, AKT1, and MAPK8, and their essential metabolites (sphinganine, sphingosine, Glutahione, Oxidized gutahione, Dihydrolipoamide) and pathway (glycerol phospholipid metabolism and tryptophan metabolism). The significant affinity of the primary target for the HQD was confirmed by molecular docking. The results demonstrate that the combination of metabolomics and network pharmacology could be used to reflect the effects of HQD on the biological network and metabolic state of DLI and to evaluate the drug efficacy of HQD and its related mechanisms.
The Effect of Whole-Body Traditional and Functional Resistance Training on CAVI and Its Association With Muscular Fitness in Untrained Young Men
Authors: Zuo Chongwen , Bo Shumin , Li Qing , Zhang Li
Published: May 2022

Background: Resistance training-induced changes in the muscle function is essential for the health promotion of the young and older, but the discrepancies of the effect of resistance training on arterial stiffness leads to the divergence regarding to the effect of resistance training on cardiovascular health. What confuses our understanding in this field may be the following factors: external load (higher intensity vs. lighter intensity), participants’ cardiovascular health, and arterial stiffness assessment measurement. The purpose of the present study was to investigate the effects of the whole-body traditional high-intensity vs. functional low-intensity resistance training protocol on systemic arterial stiffness, and their association with muscular fitness components in untrained young men.

Methods: In this randomized controlled trial, twenty-nine untrained young men (mean age about 22.5 years old) were randomized into a 6-weeks (three sessions per week) supervised whole-body traditional high-intensity resistance group (TRT, n = 15) consisting of 4–5 sets of 12 repetitions (70%1RM, lower-repetitions) or a whole-body functional low-intensity resistance group (FRT, n = 14) with 4–5 sets of 20 repetitions (40%1RM, higher-repetitions) to volitional failure. The systemic arterial stiffness (cardio-ankle vascular index, CAVI) and muscular fitness components were assessed before and after the 6-weeks training program.

Results: There was a significant decrease (pre-post) for CAVI only in FRT group (p < 0.05), but no significant difference was observed between two groups. In addition, the TRT and FRT groups showed equally significantly increased in maximal strength, muscular endurance and power (within group: both p < 0.01); however, the independent t test exhibited that the difference between two groups in terms of change in maximal strength, muscular endurance and power were no significant (p > 0.05). Furthermore, the reduction in CAVI was negatively correlated with the increase in 1RM of bench press for all participants (r = −0.490, p < 0.01).

Conclusion:Using present criterion-standard assessments measurements demonstrates that CAVI was significantly reduced after 6-weeks functional resistance training with beneficial effect on muscular fitness. Negative and significant association between CAVI and 1RM bench press indicated the cardiovascular health may be involved in the regulation of resistance training.
Comprehensive Transcriptome Sequencing Analysis of Hirudinaria manillensis in Different Growth Periods
Authors: Shan Huiquan , Ren Ke , Liu Jiasheng , Rehman Saif ur , Yan Xiuying , Ma Xiaocong , Zheng Yalin , Feng Tong , Wang Xiaobo , Li Zhipeng , Zhou Weiguan , Chuang Chen , Liang Mingkun , Zheng Jinghui , Liu Qingyou
Published: May 2022

Medical leeches are widely been used in biochemical and clinical medical studies, helping to restore blood circulation to grafted or severely injured tissue. Mostly, adult leeches are being used in the traditional pharmacopeia, but the gene expression profiling of leeches in different growth periods is not well-reported. So, in this study, we used transcriptome analysis to analyze the comparative gene expression patterns of Hirudinaria manillensis (H. manillensis) in different growth periods, including larval, young, and adult stages. We constructed 24 cDNA libraries from H. manillensis larval, young, and adult stages, and about 54,639,118 sequences were generated, 18,106 mRNA transcripts of which 958 novel mRNAs and 491 lncRNAs were also assembled as well. Furthermore, the results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the differentially upregulated genes from the larval to adult stages were enriched in pathways such as cilium, myofibril, contractile fiber, cytoskeleton proteins, dilated cardiomyopathy, adrenergic signaling in cardiomyocytes, etc. Moreover, in the adult stages, a significant increase in the expression of the Hirudin-HM (HIRM2) genes was detected. In addition, our comparative transcriptome profiling data from different growth stages of H. manillensis also identified a large number of DEGs and DElncRNAs which were tentatively found to be associated with the growth of H. manillensis; as it grew, the muscle-related gene expression increased, while the lipid metabolism and need for stimulation and nutrition-related genes decreased. Similarly, the higher expression of HIRM2 might attribute to the high expression of protein disulfide isomerase gene family (PDI) family genes in adulthood, which provides an important clue that why adult leeches rather than young leeches are widely used in clinical therapeutics and traditional Chinese medicine.
A Cys2His2 Zinc Finger Transcription Factor BpSZA1 Positively Modulates Salt Stress in Betula platyphylla
Authors: Zhang Xi , Guo Qing , Qin Linlin , Li Li
Published: May 2022

Zinc finger proteins (ZFPs) are widely involved in plant growth and abiotic stress responses, however, few of these proteins have been functionally characterized in tree species. In this study, we cloned and characterized the BpSZA1 gene encoding a C2H2-type ZFP from Betula platyphylla. BpSZA1 is a transcription factor localized in the nucleus, with a transcription activation domain located at the N-terminus. BpSZA1 was predominantly expressed in stems and was induced by salt. We generated transgenic birch lines displaying overexpression (OE) or RNAi silencing (Ri) of BpSZA1 and exposed these along with wild-type birch seedlings to salinity. Phenotypic and physiological parameters such as superoxide dismutase, peroxisome, H2O2 content, proline content, water loss rate, and malondialdehyde content were examined. Overexpression of BpSZA1 in birch conferred increased salt tolerance. Chromatin immunoprecipitation-qPCR and RNA-seq showed that BpSZA1 binds to the GAGA-motif in the promoter of downstream target genes including BpAPX1, BpAPX2, BpCAT, and Bp6PGDH to activate their transcription. BpSZA1 also participates in abscisic acid (ABA) biosynthesis, proline biosynthesis, and the ABA/jasmonic acid pathway to enhance the salt stress of B. platyphylla.
Time Course of Age-Linked Changes in Photosynthetic Efficiency of Spirodela polyrhiza Exposed to Cadmium
Authors: Peršić Vesna , Antunović Dunić Jasenka , Domjan Lucija , Zellnig Günther , Cesar Vera
Published: May 2022

Short-term assessment of adverse effects is essential for populations exposed to higher risk of environmental pollution. This study presents the time course of physiological and morphological changes attributed to cadmium, emphasizing age-linked differences in the susceptibility of photosynthetic apparatus of Spirodela polyrhiza fronds exposed to different cadmium concentrations. A four-frond colony represented by mother, daughter, and granddaughter plants was exposed to cadmium concentrations for 6, 24, and 72 h to establish its effect on different generations of the great duckweed. The duration of cadmium exposure accounted for the most variation in chlorophyll content as the most influential variable, and after 72 h, frond responsiveness was a function of cadmium concentration. Carotenoid contents behaved slightly differently in fronds of different ages, with the oldest mother frond exhibiting accelerated senescence. Chlorophyll fluorescence measurements showed that cadmium affects different photosynthetic electron transport segments relative to the frond's chloroplast structure level. Photosynthesis of mother fronds exposed to low cadmium and daughter fronds exposed to high cadmium was determined by the functionality of primary electron acceptance at the PSII level. Mother plants exposed to higher cadmium concentrations were characterized by closed and inactive reaction centers, dissipated energy outflux, and inhibited photosynthesis. Young fronds exposed to low and high cadmium concentrations were characterized by increased non-reducing reaction centers and thermal phase reduction, with activated dissipative mechanisms at high cadmium concentrations. Cadmium-induced changes in the ultrastructure of chloroplasts were visible after 6 h of exposure to lowest concentrations, with gradual degradation of the thylakoid system as the fronds aged. Younger fronds responded to cadmium more dynamically through molecular, physiological, and anatomical changes and tolerated a more reduced electron transport chain under given conditions than older fronds.
Activation of NLR-Mediated Autoimmunity in Arabidopsis Early in Short Days 4 Mutant
Authors: Huang Xingchuan , Liu Yanan , Huang Jianhua , Fernando W. G. Dilantha , Li Xin , Xia Shitou
Published: May 2022

From a reverse genetic screen using CRISPR/Cas9 gene editing tool, we unintentionally identified an autoimmune mutant. Map-based cloning and whole-genome sequencing revealed that it contains a deletion in SMALL UBIQUITIN-RELATED MODIFIER (SUMO) protease encoding gene EARLY IN SHORT DAYS 4 (ESD4). Previous studies reported that esd4 mutants accumulate elevated levels of plant defense hormone salicylic acid (SA). However, upregulated PATHOGENESIS-RELATED GENE 1 (PR1) expression in esd4 only partly relies on SA level. In this study, we show that plant metabolite N-hydroxypipecolic acid (NHP) biosynthetic genes are upregulated in esd4, and NHP biosynthesis mutant flavin-dependent-monooxygenase 1 (fmo1) partially suppresses the autoimmune phenotypes of esd4, suggestive of a requirement of NHP signaling for the autoimmunity in esd4. As activation of nucleotide-binding leucine-rich repeat immune receptors (NLRs) are associates with the biosynthesis of SA and NHP and lipase-like protein ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) is a key component downstream of many NLRs, we examined the relationship between EDS1 and ESD4 by analyzing the eds1 esd4 double mutant. We found that eds1 largely suppresses esd4 autoimmunity and blocks the elevated expressions of SA and NHP biosynthesis-related genes in esd4. Overall, our study provides evidence supporting the hypothesis that SUMO protease ESD4 likely targets a yet to be identified guardee of NLR by removing its SUMO modification to avoid recognition by the cognate NLR. Loss of ESD4 results in activation of NLR-mediated autoimmunity.
Gene Co-expression Network and Regression Analysis Identify the Transcriptomic, Physiological, and Biochemical Indicators of the Response of Alpine Woody Plant Rhododendron rex to Drought Stress
Authors: Zhou Xiong-Li , Ma Jin-Yan , Liu Zhen-Dian , Dai Ni-fei , Yang Hui-Qin , Yang Liu , Wang Yue-Hua , Shen Shi-Kang
Published: May 2022

Increasing severity of drought stress due to global change and extreme weather has been affecting the biodiversity, function, and stability of forest ecosystems. However, despite being an important component in the alpine and subalpine vegetation in forest ecosystems, Rhododendron species have been paid rare attention in the study of molecular mechanism of tolerance or response to drought. Herein, we investigated the correlation of transcriptomic changes with the physiological and biochemical indicators of Rhododendron rex under drought stress by using the co-expression network approach and regression analysis. Compared with the control treatment, the number of significantly differentially expressed unigenes (DEGs) increased with the degree of drought stress. The DEGs were mainly enriched in the cell wall metabolic process, signaling pathways, sugar metabolism, and nitrogen metabolism. Coupled analysis of the transcriptome, physiological, and biochemical parameters indicated that the metabolic pathways were highly correlated with the physiological and biochemical indicators under drought stress, especially the chlorophyll fluorescence parameters, such as the actual photosynthetic efficiency of photosystem II, electron transport rate, photochemical quenching coefficient, and the maximum quantum efficiency of photosystem II photochemistry. The majority of the response genes related to the metabolic pathways, including photosynthesis, sugar metabolism, and phytohormone signal pathway, were highly expressed under drought stress. In addition, genes associated with cell wall, pectin, and galacturonan metabolism also played crucial roles in the response of R. rex to drought stress. The results provided novel insight into the molecular response of the alpine woody species under drought stress and may improve the understanding of the response of forest ecosystems to the global climate change.
Effects of Age-of-Acquisition on Proficiency in Polish Sign Language: Insights to the Critical Period Hypothesis
Authors: Tomaszewski Piotr , Krzysztofiak Piotr , Morford Jill P. , Eźlakowski Wiktor
Published: May 2022

This study focuses on the relationship between the age of acquisition of Polish Sign Language (PJM) by deaf individuals and their receptive language skills at the phonological, morphological and syntactic levels. Sixty Deaf signers of PJM were recruited into three equal groups (n = 20): (1) a group exposed to PJM from birth from their deaf parents; (2) a group of childhood learners of PJM, who reported learning PJM between 4 and 8 years; (3) a group of adolescent learners of PJM, who reported learning PJM between 9 and 13 years. The PJM Perception and Comprehension Test was used to assess three aspects of language processing: phonological, morphological and syntactic. Participants were asked to decide whether a series of signs and sentences were acceptable in PJM. Results show that the age of PJM acquisition has a significant impact on performance on this task. The earlier deaf people acquire PJM, the more likely they were to distinguish signs and sentences considered permissible and impermissible in PJM by native signers. Native signers had significantly greater accuracy on the phonological, morphological, and syntactic items than either the Childhood or the Adolescent signers. Further, the Childhood signers had significantly greater accuracy than the Adolescent signers on all three parts of the test. Comparing performance on specific structures targeted within each part of the test revealed that multi-channel signs and negative suffixes posed the greatest challenge for Adolescent signers relative to the Native signers. The above results provide evidence from a less-commonly studied signed language that the age of onset of first language acquisition affects ultimate outcomes in language acquisition across all levels of grammatical structure. In addition, this research corroborates prior studies demonstrating that the critical period is independent of language modality. Contrary to a common public health assumption that early exposure to language is less vital to signed than to spoken language development, the results of this study demonstrate that early exposure to a signed language promotes sensitivity to phonological, morphological and syntactic patterns in language.
Exploration on the Influencing Factors of Overseas Students' Online Chinese Learning Intention During the Epidemic Period
Authors: Zou Xiaoyu
Published: May 2022

In the information age, online teaching has become an essential field of educational development. The work aims to analyze the factors influencing learning intention of Overseas Students (OSs) during the Coronavirus Disease 2019 (COVID-19). The work adopts the method of Unified Theory of Acceptance and Use of Technology (UTAUT), and implements the influencing factor model of open source software online Chinese learning (OCL). Specifically, the OSs of five colleges and universities in Fuzhou are taken as the research objects. The data is collected through questionnaire survey (QS) and Spss25.0 to analyze the reliability and validity of the data, and Amos23.0 is used to validate the model. The results present that autonomy and self-discipline have become the necessary factors affecting open source software OCL, and personal interests and hobbies are the main factors affecting open source software OCL. Meantime, perceived interest, self-learning management, effort expectation, community influence, performance expectation, and promotion conditions have a significant positive impact on the willingness to promote Chinese learning, and their influence degree increases in turn. The conclusion can provide a novel online teaching and learning strategy for open source software under the COVID-19 situation.
Referral for Intensive Home Treatment or Psychiatric Inpatient Care? A Retrospective, Observational Comparison of Patient and Process Characteristics
Authors: van Asperen G. C. Roselie , Wierdsma André I. , de Winter Remco F. P. , Mulder Cornelis Lambert
Published: May 2022

Introduction

Intensive home treatment (IHT) is intended to prevent the (mostly voluntary) admission of mentally ill patients by providing intensive care in their domestic environment. It requires approaches to referral that ensure the delivery of the best possible acute care. Indications for referral may be improved by greater understanding of the clinical profiles of patients referred for IHT and of those referred for inpatient care. As such understanding may also further the development of IHT and innovations within it, we compared the patient and process characteristics associated with IHT referral for those associated with inpatient care.

Methods

This retrospective, observational, explorative study was conducted from 2016 to 2019. Patients aged 18 years and older were assessed by the emergency psychiatric outreach services in the greater Rotterdam area (Netherlands). Anonymized data were used to compare patient and process characteristics between patients referred for IHT and those admitted voluntarily. Patient characteristics included gender, age, cultural background, living situation and main diagnosis. Additional the case mix was measured using the Severity of Psychiatric Illness (SPI) scale. Process characteristics included psychiatric history, the total number of contacts with the emergency psychiatric outreach services, assessments during office hours, place of assessment, referrer, and the reason for referral. Using multiple logistic regression analysis, the patient and process characteristics associated with IHT referral were compared with those associated with voluntary admission.

Results

The emergency psychiatric outreach services undertook 12,470 assessments: 655 were referred for HT and 2,875 for voluntary admission. Patient characteristics: referral for IHT rather than voluntary admission was associated with higher motivation for treatment and better family involvement. Process characteristics: referral for IHT rather than voluntary admission was associated with assessment by the crisis services within office hours, no mental health treatment at the time of referral, and referral by a family doctor.

Discussion

IHT in a specific Dutch setting seems to function as an intensive crisis intervention for a subgroup of patients who are motivated for treatment, have social support, and are not in outpatient treatment. The patient and process characteristics of patients referred for IHT should now be studied in more detail, especially, for having more social support, the role of the family members involved.
Developing Indicators to Evaluate Instructor Management of Sports Centers for the People With Disabilities Based on Universal Design Principles in South Korea
Authors: Yi Eunsurk , Shin Jongseob , Oh Ahra
Published: May 2022

This study was conducted to develop evaluation indicators for instructor-led management of sports centers for the disabled using universal design (UD) principles in South Korea. These indicators have been developed through Delphi technique to identify the effectiveness of an instructor's management skills. There were 11 documents related to UD used in the literature review, and seven were related to the evaluation index. Through reading and analyzing the relevant contents of the collected literature and many rounds of the Delphi technique, we selected the method and criteria for deriving the evaluation index. In this study, we developed a method that constitutes an evaluation index. The index comprises one evaluation criterion and four evaluation indices. First, for the sub-items of the “recruitment” category, four principles of UD and one supplementary principle of product performance program (PPP) were applied to create items for the evaluation index. Second, the sub-items of the “education” category comprise three evaluation criteria and 10 evaluation indicators. These were applied to the fourth principle of UD and the first and second by-supplementary principles of PPP. The third category, “welfare,” comprised two evaluation criteria and six evaluation indices, and the first by-supplementary principle of PPP was applied to the evaluation indices. The index created for evaluating instructors in sports centers using the method elucidated in this study was adequately reliable. Following a similar method, more evaluation indicators should be developed for evaluations of other functions (such as programs, public relations, safety, and finance) based on the principles of UD.
RNAseq of Osteoarthritic Synovial Tissues: Systematic Literary Review
Authors: Moore Logan , Pan Zui , Brotto Marco
Published: May 2022

Osteoarthritis (OA) is one of the most common causes of disability in aged people, and it is defined as a degenerative arthropathy, characterized by the disruption in joint tissue. The synovium plays a vital role in maintaining the health of the joint by supplying the nutrients to the surrounding tissues and the lubrication for joint movement. While it is well known that all the joint tissues are communicating and working together to provide a functioning joint, most studies on OA have been focused on bone and cartilage but much less about synovium have been reported. The purpose of this review was to investigate the current literature focused on RNA sequencing (RNAseq) of osteoarthritic synovial tissues to further understand the dynamic transcriptome changes occurring in this pivotal joint tissue. A total of 3 electronic databases (PubMed, CINHAL Complete, and Academic Complete) were systematically searched following PRISMA guidelines. The following criteria was used for inclusion: English language, free full text, between the period 2011–2022, size of sample (n > 10), study design being either retrospective or prospective, and RNAseq data of synovial tissue from OA subjects. From the initial search, 174 articles, 5 met all of our criteria and were selected for this review. The RNAseq analysis revealed several differentially expressed genes (DEGs) in synovial tissue. These genes are related to the inflammatory pathway and regulation of the extracellular matrix. The MMP family, particularly MMP13 was identified by three of the studies, indicating its important role in OA. IL6, a key contributor in the inflammation pathway, was also identified in 3 studies. There was a total of 8 DEGs, MMP13, MMP1, MMP2, APOD, IL6, TNFAIP6, FCER1G, and IGF1 that overlapped in 4 out of the 5 studies. One study focused on microbial RNA in the synovial tissue found that the microbes were differentially expressed in OA subjects too. These differentially expressed microbes have also been linked to the inflammatory pathway. Further investigation with more clinical gene profiling in synovial tissue of OA subjects is required to reveal the causation and progression, as well as aid in the development of new treatments.
Recurrence Quantification Analysis of Ankle Kinematics During Gait in Individuals With Chronic Ankle Instability
Authors: Yen Sheng-Che , Qian Shaodi , Folmar Eric , Hasson Christopher J. , Chou Chun-An
Published: May 2022

Purpose

An investigation of the ankle dynamics in a motor task may generate insights into the etiology of chronic ankle instability (CAI). This study presents a novel application of recurrence quantification analysis (RQA) to examine the ankle dynamics during walking. We hypothesized that CAI is associated with changes in the ankle dynamics as assessed by measures of determinism and laminarity using RQA.

Methods

We recorded and analyzed the ankle position trajectories in the frontal and sagittal planes from 12 participants with CAI and 12 healthy controls during treadmill walking. We used time-delay embedding to reconstruct the position trajectories to a phase space that represents the states of the ankle dynamics. Based on the phase space trajectory, a recurrence plot was constructed and two RQA variables, the percent determinism (%DET) and the percent laminarity (%LAM), were derived from the recurrence plot to quantify the ankle dynamics.

Results

In the frontal plane, the %LAM in the CAI group was significantly lower than that in the control group (p < 0.05. effect size = 0.86). This indicated that the ankle dynamics in individuals with CAI is less likely to remain in the same state. No significant results were found in the %DET or in the sagittal plane.

Conclusion

A lower frontal-plane %LAM may reflect more frequent switching between different patterns of neuromuscular control states due to the instabilities associated with CAI. With further study and development, %LAM may have the potential to become a useful biomarker for CAI.
Novel Single Nucleotide Polymorphisms (SNPs) and Genetic Features of the Prion Protein Gene (PRNP) in Quail (Coturnix japonica)
Authors: Kim Yoonhee , Kim Yong-Chan , Jeong Byung-Hoon
Published: May 2022

Prion diseases are fatal infectious diseases caused by conformational changes of a prion protein (PrPSc) derived from a normal prion protein (PrPC). Prion diseases have been reported in several mammalian hosts but not in any birds, including the most popular poultry species, of which chickens showed some resistance to experimental prion infection. To identify the genetic polymorphisms in the quail prion protein gene (PRNP), polymerase chain reaction and DNA sequencing were performed with gene-specific primers in 164 quails. Four in silico programs, including PROVEAN, PANTHER, SIFT, and AMYCO, were used to investigate the effect of non-synonymous single nucleotide polymorphisms (SNPs) on quail PrP. Furthermore, to investigate the genetic relationship of avian PrPs, phylogenetic analysis and multiple sequence alignments were performed using MEGA X program. Finally, the secondary and tertiary structures of avian PrPs were analyzed by SWISS-MODEL. We identified 33 novel SNPs in the quail PRNP gene, including three non-synonymous SNPs, c.56C>T (T19I), c.60C>T (V21I), and c.61G>A (A22S). Although V21I was predicted to have deleterious effects by SIFT, the substitutions of all three amino acids did not affect the amyloid propensity, 3D structure, or hydrogen bonds of quail PrP. Quail PrP showed a close evolutionary relationship and similar secondary and tertiary structures to chicken PrP compared to duck PrP. To our knowledge, this is the first report on the genetic and structural properties of the quail PRNP gene.
About the Essence of Trust: Tell the Truth and Let Me Choose—I Might Trust You
Authors: Gille Felix
Published: May 2022

Trust is critical to the success of health care. We witness a diversification of trust constructs which is due to the context specificity of trust and the popularity of trust in marketing, public, and political debate. This diverse use of trust leads to confusion. To contribute to the dissolution of this confusion, I propose that the essence of trust follows Tell the truth and let me choose—I might trust you. Inferring from empirical and theoretical work, I argue that the conceptual framework of trust is comprised of: communication, truthful information, autonomy, alternatives, and no guarantee. This oversimplification aims to stimulate a debate about the common denominator of existing conceptual frameworks of trust in health care. By refining and agreeing on the core of trust in health care, we will be able to improve debate, improve comparability among trust studies, and improve understandability of policy recommendations to foster trust in health care.
Multi-Color Channels Based Group Sparse Model for Image Restoration
Authors: Kong Yanfen , Zhou Caiyue , Zhang Chuanyong , Sun Lin , Zhou Chongbo
Published: May 2022

The group sparse representation (GSR) model combines local sparsity and nonlocal similarity in image processing, and achieves excellent results. However, the traditional GSR model and all subsequent improved GSR models convert the RGB space of the image to YCbCr space, and only extract the Y (luminance) channel of YCbCr space to change the color image to a gray image for processing. As a result, the image processing process cannot be loyal to each color channel, so the repair effect is not ideal. A new group sparse representation model based on multi-color channels is proposed in this paper. The model processes R, G and B color channels simultaneously when processing color images rather than processing a single color channel and then combining the results of different channels. The proposed multi-color-channels-based GSR model is compared with state-of-the-art methods. The experimental contrast results show that the proposed model is an effective method and can obtain good results in terms of objective quantitative metrics and subjective visual effects.
Spacecraft Staring Attitude Control for Ground Targets Using an Uncalibrated Camera
Authors: Song Chao , Fan Caizhi , Song Haibo , Wang Mengmeng
Published: May 2022

Previous staring attitude control techniques utilize the geographic location of a ground target to dictate the direction of the camera’s optical axis, while the assembly accuracy and the internal structure of the spaceborne camera are not considered. This paper investigates the image-based staring controller design of a video satellite in the presence of uncertain intrinsic and extrinsic camera parameters. The dynamical projection model of the ground target on the image plane is firstly established, and then we linearly parameterize the defined projection errors. Furthermore, a potential function and a self-updating rule are introduced to estimate the parameters online by minimizing the projection errors. As the parameters are updating constantly, an adaptive control algorithm is developed, so that the errors between the current and the desired projections of the ground target converge to zero. The stability is proved using Barbalat’s lemma. Simulation results show that the designed controller can successfully move the target’s projection to the desired coordinate even though the camera parameters are unknown.