bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Storms on Legionella pneumophila in Cooling Tower Water, Implications for Human Health
Authors: Brigmon Robin L. , Turick Charles E. , Knox Anna S. , Burckhalter Courtney E.
Published: December 2020

At the U.S. Department of Energy’s Savannah River Site (SRS) in Aiken, SC, cooling tower water is routinely monitored for Legionella pneumophila concentrations using a direct fluorescent antibody (DFA) technique. Historically, 25–30 operating SRS cooling towers have varying concentrations of Legionella in all seasons of the year, with patterns that are unpredictable. Legionellosis, or Legionnaires’ disease (LD), is a pneumonia caused by Legionella bacteria that thrive both in man-made water distribution systems and natural surface waters including lakes, streams, and wet soil. Legionnaires’ disease is typically contracted by inhaling L. pneumophila, most often in aerosolized mists that contain the bacteria. At the SRS, L. pneumophila is typically found in cooling towers ranging from non-detectable up to 108 cells/L in cooling tower water systems. Extreme weather conditions contributed to elevations in L. pneumophila to 107–108 cells/L in SRS cooling tower water systems in July–August 2017. L. pneumophila concentrations in Cooling Tower 785-A/2A located in SRS A-Area, stayed in the 108 cells/L range despite biocide addition. During this time, other SRS cooling towers did not demonstrate this L. pneumophila increase. No significant difference was observed in the mean L. pneumophila mean concentrations for the towers (p < 0.05). There was a significant variance observed in the 285-2A/A Tower L. pneumophila results (p < 0.05). Looking to see if we could find “effects” led to model development by analyzing 13 months of water chemistry and microbial data for the main factors influencing the L. pneumophila concentrations in five cooling towers for this year. It indicated chlorine and dissolved oxygen had a significant impact (p < 0.0002) on cooling tower 785A/2A. Thus, while the variation in the log count data for the A-area tower is statistically greater than that of the other four towers, the average of the log count data for the A-Area tower was in line with that of the other towers. It was also observed that the location of 785A/2A and basin resulted in more debris entering the system during storm events. Our results suggest that future analyses should evaluate the impact of environmental conditions and cooling tower design on L. pneumophila water concentrations and human health.
Study on the Function of the Inositol Polyphosphate Kinases Kcs1 and Vip1 of Candida albicans in Energy Metabolism
Authors: Peng Xueling , Yu Qilin , Liu Yingzheng , Ma Tianyu , Li Mingchun
Published: December 2020

In Saccharomyces cerevisiae, inositol polyphosphate kinase KCS1 but not VIP1 knockout is of great significance for maintaining cell viability, promoting glycolysis metabolism, and inducing mitochondrial damage. The functions of Candida albicans inositol polyphosphate kinases Kcs1 and Vip1 have not yet been studied. In this study, we found that the growth rate of C. albicans vip1Δ/Δ strain in glucose medium was reduced and the upregulation of glycolysis was accompanied by a decrease in mitochondrial activity, resulting in a large accumulation of lipid droplets, along with an increase in cell wall chitin and cell membrane permeability, eventually leading to cell death. Relieving intracellular glycolysis rate or increasing mitochondrial metabolism can reduce lipid droplet accumulation, causing a reduction in chitin content and cell membrane permeability. The growth activity and energy metabolism of the vip1Δ/Δ strains in a non-fermentable carbon source glycerol medium were not different from those of the wild-type strains, indicating that knocking out VIP1 did not cause mitochondria damage. Moreover, C. albicans KCS1 knockout did not affect cell activity and energy metabolism. Thus, in C. albicans, Vip1 is more important than Kcs1 in regulating cell viability and energy metabolism.
Thiamine-Mediated Cooperation Between Auxotrophic Rhodococcus ruber ZM07 and Escherichia coli K12 Drives Efficient Tetrahydrofuran Degradation
Authors: Huang Hui , Qi Minbo , Liu Yiming , Wang Haixia , Wang Xuejun , Qiu Yiyang , Lu Zhenmei
Published: December 2020

Tetrahydrofuran (THF) is a universal solvent widely used in the synthesis of chemicals and pharmaceuticals. As a refractory organic contaminant, it can only be degraded by a small group of microbes. In this study, a thiamine auxotrophic THF-degrading bacterium, Rhodococcus ruber ZM07, was isolated from an enrichment culture H-1. It was cocultured with Escherichia coli K12 (which cannot degrade THF but can produce thiamine) and/or Escherichia coli K12ΔthiE (which can neither degrade THF nor produce thiamine) with or without exogenous thiamine. This study aims to understand the interaction mechanisms between ZM07 and K12. We found that K12 accounted for 30% of the total when cocultured and transferred with ZM07 in thiamine-free systems; in addition, in the three-strain (ZM07, K12, and K12ΔthiE) cocultured system without thiamine, K12ΔthiE disappeared in the 8th transfer, while K12 could still stably exist (the relative abundance remained at approximately 30%). The growth of K12 was significantly inhibited in the thiamine-rich system. Its proportion was almost below 4% after the fourth transfer in both the two-strain (ZM07 and K12) and three-strain (ZM07, K12, and K12ΔthiE) systems; K12ΔthiE’s percentage was higher than K12’s in the three-strain (ZM07, K12, and K12ΔthiE) cocultured system with exogenous thiamine, and both represented only a small proportion (less than 1% by the fourth transfer). The results of the coculture of K12 and K12ΔthiE in thiamine-free medium indicated that intraspecific competition between them may be one of the main reasons for the extinction of K12ΔthiE in the three-strain (ZM07, K12, and K12ΔthiE) system without exogenous thiamine. Furthermore, we found that ZM07 could cooperate with K12 through extracellular metabolites exchanges without physical contact. This study provides novel insight into how microbes cooperate and compete with one another during THF degradation.
Cardinium Localization During Its Parasitoid Wasp Host’s Development Provides Insights Into Cytoplasmic Incompatibility
Authors: Doremus Matthew R. , Stouthamer Corinne M. , Kelly Suzanne E. , Schmitz-Esser Stephan , Hunter Martha S.
Published: December 2020

Arthropods harbor heritable intracellular symbionts that may manipulate host reproduction to favor symbiont transmission. In cytoplasmic incompatibility (CI), the symbiont sabotages the reproduction of infected males such that high levels of offspring mortality result when they mate with uninfected females. In crosses with infected males and infected females, however (the “rescue” cross), normal numbers of offspring are produced. A common CI-inducing symbiont,Cardinium hertigii, causes variable levels of CI mortality in the parasitoid wasp,Encarsia suzannae.Previous work correlated CI-induced mortality with male development time in this system, although the timing ofCardiniumCI-induction and the relationship between development time and CI mortality was not well understood. Here, using a combination of crosses, manipulation of development time, and fluorescence microscopy, we identify the localization and the timing of the CI-induction step in theCardinium-E. suzannaesystem. Antibiotic treatment of adultCardinium-infected males did not reduce the mortality associated with the CI phenotype, suggesting that CI-alteration occurs prior to adulthood. Our results suggest that the alteration step occurs during the pupal period, and is limited by the duration of pupal development: 1)Encarsiaproduces most sperm prior to adulthood, 2) FISH localization ofCardiniumin testes showed an association with sperm nuclei throughout spermatogenesis but not with mature sperm, and 3) two methods of prolonging the pupal period (cool temperatures and the juvenile hormone analog methoprene) both caused greater CI mortality, suggesting the degree of alteration is limited by the duration of the pupal stage. Based on these results, we compare two models for potential mechanisms ofCardiniumsperm modification in the context of what is known about analogous mechanisms ofWolbachia, a more extensively studied CI-inducing symbiont.
Which Current and Novel Diagnostic Avenues for Bacterial Respiratory Diseases?
Authors: Rytter Héloïse , Jamet Anne , Coureuil Mathieu , Charbit Alain , Ramond Elodie
Published: December 2020

Bacterial acute pneumonia is responsible for an extremely large burden of death worldwide and diagnosis is paramount in the management of patients. While multidrug-resistant bacteria is one of the biggest health threats in the coming decades, clinicians urgently need access to novel diagnostic technologies. In this review, we will first present the already existing and largely used techniques that allow identifying pathogen-associated pneumonia. Then, we will discuss the latest and most promising technological advances that are based on connected technologies (artificial intelligence-based and Omics-based) or rapid tests, to improve the management of lung infections caused by pathogenic bacteria. We also aim to highlight the mutual benefits of fundamental and clinical studies for a better understanding of lung infections and their more efficient diagnostic management.
Side of Lesions Predicts Surgical Outcomes in Patients With Drug-Resistant Temporal Lobe Epilepsy Secondary to Focal Cortical Dysplasia Type IIIa
Authors: He Xinghui , Liu Dingyang , Yang Zhuanyi , Zhang Junmei , Li Sushan , Yang Zhiquan
Published: December 2020

Objective: This study aims to evaluate the surgical outcomes and analyze the predictors of surgical outcomes in patients undergoing anterior temporal lobectomy (ATL) for drug-resistant temporal lobe epilepsy (TLE) secondary to focal cortical dysplasia (FCD) type IIIa.

Methods: Data on patients with drug-resistant TLE secondary to FCD type IIIa who had undergone ATL at Xiangya Hospital, Central South University from January 2014 to April 2018, were collected retrospectively. International League Against Epilepsy (ILAE) classification was used to evaluate postoperative seizure outcomes. Predictors of surgical outcomes were identified by using univariate and multivariate analyses.

Results: A total of 43 patients with drug-resistant TLE secondary to FCD type IIIa who had undergone ATL were included in this study. Twenty patients had right ATL, and 23 patients had left ATL. With a follow-up of 2–6 years, 76.7% (33 of 43) of patients were seizure-free. Univariate and multivariate analysis results indicated that lesions on the right side independently predict postoperative seizure freedom (OR, 0.08; 95% CI, 0.01–0.72; P = 0.024).

Conclusion: ATL is an effective therapy for patients with drug-resistant TLE secondary to FCD type IIIa. Patients with lesions on the right side are more likely to achieve postoperative seizure freedom.
Case Report: Parasomnia Overlap Disorder Induced by Obstructive Sleep Hypopnea Apnea Syndrome: A Case Report and Literature Review
Authors: Sun Yun , Li Jie , Zhang Xinjun , Jiao Qingyan , Yang Shutong , Ji Lijie
Published: December 2020

Obstructive sleep apnea hypopnea syndrome (OSAHS) and parasomnia overlap disorder (POD) are types of sleep disorders. When the symptoms of both conditions coexist, the POD symptoms are most likely caused by OSAHS. In these cases, the symptoms of POD will be relieved when OSAHS is effectively treated. We refer to these cases as symptomatic POD (related to OSAHS), which differs in pathophysiology, complications, and treatment from idiopathic POD. It is important to note that the treatment for idiopathic POD may aggravate the symptoms of OSAHS. In this case, we used video polysomnography (v-PSG) on a POD patient with suspected OSAHS to distinguish idiopathic POD from symptomatic POD, to inform the appropriate treatment course. The video results and clinical features lead us to diagnose symptomatic POD, and we treated the patient with auto-set continuous positive airway pressure to address their OSAHS. This course of treatment resolved all POD-related symptoms. Here, we discuss this case and review the relevant literature. This report highlights the importance of the use of v-PSG in the clinical diagnosis, differential diagnosis, and subsequent treatment of POD.
Identification of Novel MeCP2 Cancer-Associated Target Genes and Post-Translational Modifications
Authors: Castro-Piedras Isabel , Vartak David , Sharma Monica , Pandey Somnath , Casas Laura , Molehin Deborah , Rasha Fahmida , Fokar Mohamed , Nichols Jacob , Almodovar Sharilyn , Rahman Rakhshanda Layeequr , Pruitt Kevin
Published: December 2020

Abnormal regulation of DNA methylation and its readers has been associated with a wide range of cellular dysfunction. Disruption of the normal function of DNA methylation readers contributes to cancer progression, neurodevelopmental disorders, autoimmune disease and other pathologies. One reader of DNA methylation known to be especially important is MeCP2. It acts a bridge and connects DNA methylation with histone modifications and regulates many gene targets contributing to various diseases; however, much remains unknown about how it contributes to cancer malignancy. We and others previously described novel MeCP2 post-translational regulation. We set out to test the hypothesis that MeCP2 would regulate novel genes linked with tumorigenesis and that MeCP2 is subject to additional post-translational regulation not previously identified. Herein we report novel genes bound and regulated by MeCP2 through MeCP2 ChIP-seq and RNA-seq analyses in two breast cancer cell lines representing different breast cancer subtypes. Through genomics analyses, we localize MeCP2 to novel gene targets and further define the full range of gene targets within breast cancer cell lines. We also further examine the scope of clinical and pre-clinical lysine deacetylase inhibitors (KDACi) that regulate MeCP2 post-translationally. Through proteomics analyses, we identify many additional novel acetylation sites, nine of which are mutated in Rett Syndrome. Our study provides important new insight into downstream targets of MeCP2 and provide the first comprehensive map of novel sites of acetylation associated with both pre-clinical and FDA-approved KDACi used in the clinic. This report examines a critical reader of DNA methylation and has important implications for understanding MeCP2 regulation in cancer models and identifying novel molecular targets associated with epigenetic therapies.
Exploratory Analysis of Qualitative MR Imaging Features for the Differentiation of Glioblastoma and Brain Metastases
Authors: Meier Raphael , Pahud de Mortanges Aurélie , Wiest Roland , Knecht Urspeter
Published: December 2020

Objectives

To identify qualitative VASARI (Visually AcceSIble Rembrandt Images) Magnetic Resonance (MR) Imaging features for differentiation of glioblastoma (GBM) and brain metastasis (BM) of different primary tumors.

Materials and Methods

T1-weighted pre- and post-contrast, T2-weighted, and T2-weighted, fluid attenuated inversion recovery (FLAIR) MR images of a total of 239 lesions from 109 patients with either GBM or BM (breast cancer, non-small cell (NSCLC) adenocarcinoma, NSCLC squamous cell carcinoma, small-cell lung cancer (SCLC)) were included. A set of adapted, qualitative VASARI MR features describing tumor appearance and location was scored (binary; 1 = presence of feature, 0 = absence of feature). Exploratory data analysis was performed on binary scores using a combination of descriptive statistics (proportions with 95% binomial confidence intervals), unsupervised methods and supervised methods including multivariate feature ranking using either repeated fitting or recursive feature elimination with Support Vector Machines (SVMs).

Results

GBMs were found to involve all lobes of the cerebrum with a fronto-occipital gradient, often affected the corpus callosum (32.4%, 95% CI 19.1–49.2), and showed a strong preference for the right hemisphere (79.4%, 95% CI 63.2–89.7). BMs occurred most frequently in the frontal lobe (35.1%, 95% CI 28.9–41.9) and cerebellum (28.3%, 95% CI 22.6–34.8). The appearance of GBMs was characterized by preference for well-defined non-enhancing tumor margin (100%, 89.8–100), ependymal extension (52.9%, 36.7–68.5) and substantially less enhancing foci than BMs (44.1%, 28.9–60.6 vs. 75.1%, 68.8–80.5). Unsupervised and supervised analyses showed that GBMs are distinctively different from BMs and that this difference is driven by definition of non-enhancing tumor margin, ependymal extension and features describing laterality. Differentiation of histological subtypes of BMs was driven by the presence of well-defined enhancing and non-enhancing tumor margins and localization in the vision center. SVM models with optimal hyperparameters led to weighted F1-score of 0.865 for differentiation of GBMs from BMs and weighted F1-score of 0.326 for differentiation of BM subtypes.

Conclusion

VASARI MR imaging features related to definition of non-enhancing margin, ependymal extension, and tumor localization may serve as potential imaging biomarkers to differentiate GBMs from BMs.
Neutrophils as Orchestrators in Tumor Development and Metastasis Formation
Authors: Kalafati Lydia , Mitroulis Ioannis , Verginis Panayotis , Chavakis Triantafyllos , Kourtzelis Ioannis
Published: December 2020

Several lines of clinical and experimental evidence suggest that immune cell plasticity is a central player in tumorigenesis, tumor progression, and metastasis formation. Neutrophils are able to promote or inhibit tumor growth. Through their interaction with tumor cells or their crosstalk with other immune cell subsets in the tumor microenvironment, they modulate tumor cell survival. Here, we summarize current knowledge with regards to the mechanisms that underlie neutrophil–mediated effects on tumor establishment and metastasis development. We also discuss the tumor-mediated effects on granulopoiesis and neutrophil precursors in the bone marrow and the involvement of neutrophils in anti-tumor therapeutic modalities.
Molecular Alterations in Metastatic Ovarian Cancer From Gastrointestinal Cancer
Authors: Chen Chao , Ge Xiaoxu , Zhao Yamei , Wang Da , Ling Limian , Zheng Shu , Ding Kefeng , Wang Jian , Sun Lifeng
Published: December 2020

Reports indicate that most metastatic ovarian cancer (MOC) originates from gastrointestinal cancer (GIC). Notably, GICs metastasize to the ovary frequently via 3 main routes including hematogenous spread, lymphogenous spread, and transcoelomic spread. Nonetheless, the mechanism of the progression remains unknown, and only a handful of literature exists on the molecular alteration implicated in MOC from GIC. This work collected existing evidence and literature on the vital molecules of the metastatic pathway and systematically analyzed them geared toward exploring the mechanism of the metastatic pathway of MOC. Further, this review described dominating molecular alteration in the metastatic process from cancer cells detaching away from lesions to arrive at the ovary, including factors for regulating signaling pathways in epithelial-interstitial transformation, invading, and surviving in the circulatory system or abdominal cavity. We interrogated the basis of the ovary as a distant metastatic site. This article provides new insights into the metastatic pathway and generates novel therapeutic targets for effective treatment and satisfactory outcomes in GIC patients.
Quercetin Induces Apoptosis via Downregulation of Vascular Endothelial Growth Factor/Akt Signaling Pathway in Acute Myeloid Leukemia Cells
Authors: Shi Huan , Li Xin-Yu , Chen Yao , Zhang Xing , Wu Yong , Wang Zi-Xuan , Chen Pan-Hong , Dai Hui-Qi , Feng Ji , Chatterjee Sayantan , Li Zhong-Jie , Huang Xiao-Wei , Wei Hong-Qiao , Wang Jigang , Lu Guo-Dong , Zhou Jing
Published: December 2020

Acute myeloid leukemia (AML) is an aggressive haematological malignancy characterized by highly proliferative accumulation of immature and dysfunctional myeloid cells. Quercetin (Qu), one kind of flavonoid, exhibits anti-cancer property in multiple types of solid tumor, but its effect on acute myeloid leukemia is less studied, and the underlying mechanisms still largely unknown. This study aimed to explore the specific target and potential mechanism of quercetin-induced cell death in AML. First, we found that quercetin induces cell death in the form of apoptosis, which was caspase dependent. Second, we found that quercetin-induced apoptosis depends on the decrease of mitochondria membrane potential (MMP) and Bcl-2 proteins. With quantitative chemical proteomics, we observed the downregulation of VEGFR2 and PI3K/Akt signaling in quercetin-treated cells. Consistently, cell studies also identified that VEGFR2 and PI3K/Akt signaling pathways are involved in the action of quercetin on mitochondria and Bcl-2 proteins. The decrease of MMP and cell death could be rescued when PI3K/Akt signaling is activated, suggesting that VEGFR2 and PI3K/Akt exert as upstream regulators for quercetin effect on apoptosis induction in AML cells. In conclusion, our findings from this study provide convincing evidence that quercetin induces cell death via downregulation of VEGF/Akt signaling pathways and mitochondria-mediated apoptosis in AML cells.
Antidepressant Use and the Risk of Major Adverse Cardiovascular Events in Patients Without Known Cardiovascular Disease: A Retrospective Cohort Study
Authors: Jang Ha Young , Kim Jae Hyun , Song Yun-Kyoung , Shin Ju-Young , Lee Hae-Young , Ahn Yong Min , Oh Jung Mi , Kim In-Wha
Published: December 2020

Aims: Conflicting data exist on whether an association exists between antidepressants and the risk of major adverse cardiovascular events (MACEs) in patients with depression. This may be due to the use of various study designs and residual or unmeasured confounding. We aimed to assess the association between antidepressant use and the risk of MACEs while considering various covariates, including severity of depression and the cardiovascular disease (CVD) risk score.

Methods: Patients newly diagnosed with depression with no history of ischemic heart disease and stroke were followed-up from 2009 to 2015. We conducted Cox proportional hazard regression analysis to estimate hazard ratios (HRs) for each antidepressant for MACE risk.

Result: We followed-up (median, 4.4 years) 31,830 matched patients with depression (15,915 antidepressant users and 15,915 non-users). In most patients (98.7%), low-dose tricyclic antidepressants (TCAs) were related with a significantly increased risk of MACEs [adjusted HR = 1.20, 95% confidence interval (CI) = 1.03–1.40]. Duration response relationship showed a gradually increasing HR from 1.15 (95% CI = 0.98–1.33; <30 days of use) to 1.84 (95% CI = 1.35–2.51; ≥365 days of use) (p for trend <0.01). High Korean atherosclerotic CVD risk score (≥7.5%) or unfavorable lifestyle factors (smoking, alcohol intake, and exercise) were significantly associated with MACEs.

Conclusion: Even at low doses, TCA use was associated with MACEs during primary prevention. Longer duration of TCA use correlated with higher HR. Careful monitoring is needed with TCA use in patients with no known CVD history.
A Class I Histone Deacetylase Inhibitor Attenuates Insulin Resistance and Inflammation in Palmitate-Treated C2C12 Myotubes and Muscle of HF/HFr Diet Mice
Authors: Lee Soo Jin , Choi Sung-E , Lee Han Byeol , Song Min-Woo , Kim Young Ha , Jeong Jae Yeop , Kang Yup , Kim Hae Jin , Kim Tae Ho , Jeon Ja Young , Lee Kwan Woo
Published: December 2020

Histone deacetylase (HDAC) inhibitors, which regulate gene expression by inhibiting the deacetylation of histones and nonhistone proteins, have been shown to exert a wide array of biological effects; these include anti-cancer, anti-obesity, and anti-diabetes effects, as well as cardiovascular-protective activity. However, the effects of class I HDAC inhibition on lipotoxicity in C2C12 myotubes and skeletal muscle tissue remain poorly understood. In this study, we investigated the molecular mechanism underlying the protective effect of class I HDAC inhibition under lipotoxic conditions, i.e., in palmitate (PA)-treated C2C12 myotubes and skeletal muscle tissue in high fat (HF)/high fructose (HFr) diet mice. PA treatment of C2C12 myotubes increased HDAC3 protein expression and impaired mitochondrial oxidation, resulting in increased mitochondrial ROS generation and an accumulation of intracellular triglycerides (TG). Prolonged exposure led to increased inflammatory cytokine expression and insulin resistance. In contrast, MS-275, a class I HDAC inhibitor, dramatically attenuated lipotoxicity, preventing PA-induced insulin resistance and inflammatory cytokine expression. Similar beneficial effects were also seen following HDAC3 knockdown. In addition, MS-275 increased the mRNA expression of peroxisome proliferator activator receptor γ-coactivator 1α (PGC1α) and mitochondrial transcription factor A (TFAM), which serve as transcriptional coactivators in the context of mitochondrial metabolism and biogenesis, and restored expression of peroxisome proliferator-activated receptor alpha (PPARα), medium-chain acyl-coenzyme A dehydrogenase (MCAD), enoyl-CoA hydratase, and 3-hydroxyacyl CoA dehydrogenase (EHHADH). In vivo, treatment of HF/HFr-fed mice with MS-275 ameliorated hyperglycemia, insulin resistance, stress signals, and TNF-α expression in skeletal muscle. Taken together, these results suggest that HDAC3 inhibition rather than HDAC1/2 inhibition by MS-275 protects against lipotoxicity in C2C12 myotubes and skeletal muscle, and may be effective for the treatment of obesity and insulin resistance.
Evaluation of Serum/Urine Genomic and Metabolomic Profiles to Improve the Adherence to Sildenafil Therapy in Patients with Erectile Dysfunction
Authors: Rocca Maria Santa , Vignoli Alessia , Tenori Leonardo , Ghezzi Marco , De Rocco Ponce Maurizio , Vatsellas Giannis , Thanos Dimitris , Padrini Roberto , Foresta Carlo , De Toni Luca
Published: December 2020

Type V-phosphodiesterase-inhibitors (PDE5i) are the first choice drugs in the treatment of erectile dysfunction (ED), being effective in 60–70% of patients. However, approximately 50% of patients per year discontinue the treatment with PDE5i after reporting poor drug efficacy or major adverse drug reactions (ADR). To identify early markers of efficacy/safety for the treatment of ED with PDE5i, the basal clinical characteristics of patients, integrated with metabolomics analysis of serum and urine and genomic data, were here correlated with the PDE5i efficacy and the occurrence of ADR upon administration. Thirty-six males with new diagnosis of ED were consecutively recruited and characterized at baseline for anthropometrics, blood pressure, blood glucose, lipid profile, serum levels of thyroid/sex hormones and erectile function evaluated by IIEF-15 questionnaire. Targeted Next Generation Sequencing (NGS) was applied to genes involved in PDE5i pharmacodynamics and pharmacokinetics. Fasting metabolic profiles of serum and urine were assessed by nuclear magnetic resonance (NMR)-based metabolomics analysis. Patients were prescribed on-demand therapy with Sildenafil oro-dispersible film and followed-up after 3 months from recruitment. Baseline data were compared with IIEF-15 score at follow-up and with the occurrence of ADR recorded by a dedicated questionnaire. Twenty-eight patients were finally included in the analysis. Serum LDL-cholesterol levels were increased in those reporting ADR (143.3 ± 13.2 mg/dl ADR vs. 133.1 ± 12.4 mg/dl No ADR; p = 0.046). NGS data showed that specific variants of PDE11A and CYP2D7 genes were more represented in drug responders (both relative risk = 2.7 [0.9–5.1]; p = 0.04). NMR-based metabolomics showed the highest association between serum LDL-cholesterol metabolites and the occurrence of ADR (Hazard ratio = 17.5; p = 0.019). The association between lipid profile and the ADR pattern suggests major cues in the tailoring of ED therapy with PDE5i.
Efficacy and Safety of Sophora flavescens (Kushen) Based Traditional Chinese Medicine in the Treatment of Ulcerative Colitis: Clinical Evidence and Potential Mechanisms
Authors: Chen Mingjun , Ding Yuxuan , Tong Zhanqi
Published: December 2020

Background: Radix Sophorae flavescentis (Kushen), a Chinese herb, is widely used in the treatment of ulcerative colitis (UC) with damp-heat accumulation syndrome (DHAS) according to traditional Chinese medicine (TCM) theory.

Objective: The aim of this study was to illuminate the clinical efficacy and potential mechanisms of Kushen-based TCM formulations in the treatment of UC with DHAS.

Materials and Methods: A systematic literature search was performed in the PubMed, EMBASE, Chinese Biomedical Literature database, China National Knowledge Infrastructure database, Chongqing VIP Information database, and Wanfang database for articles published between January 2000 and July 2020 on randomized controlled trials (RCTs) that used Kushen-based TCM formulations in the treatment of UC with DHAS. A network pharmacology approach was conducted to detect the potential pathways of Kushen against UC with DHAS.

Results: Eight RCTs with a total of 983 subjects were included in the meta-analysis. Compared with the control subjects (5-aminosalicylic acid therapy), those who received Kushen-based TCM formulations for the treatment of UC showed a significantly higher clinical remission rate (RR = 1.20, 95% CI: [1.04, 1.38], p = 0.02) and lower incidence of adverse events (RR = 0.63, 95% CI [0.39, 1.01], p = 0.06). A component-target-pathway network was constructed, indicating five main components (quercetin, luteolin, matrine, formononetin, and phaseolin), three major targets (Interleukin-6, Myc proto-oncogene protein, and G1/S-specific cyclin-D1) and one key potential therapeutic pathway (PI3K-Akt signaling) of Kushen against UC with DHAS.

Conclusion: Kushen-based TCM formulations provide good efficacy and possess great potential in the treatment of UC. Large-scale and high-quality clinical trials and experimental verification should be considered for further confirmation of the efficacy of Kushen-based formulations.
IL-6 but Not TNFα Levels Are Associated With Time to Pregnancy in Female Rheumatoid Arthritis Patients With a Wish to Conceive
Authors: Bongenaar Margot , Smeele Hieronymus T. W. , Lubberts Erik , Dolhain Radboud J. E. M.
Published: December 2020

Fertility issues are common amongst women with rheumatoid arthritis (RA). Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα), known key players in RA pathogenesis, have been associated with reproductive disorders. This study investigates the role of these cytokines in decreased fertility in women with active RA. Preconception cytokine measurements of 61 patients from the PARA-cohort, a prospective study on RA and pregnancy, were studied in relation to time to pregnancy as a measure for fertility. IL-6 levels were higher in patients with a time to pregnancy longer than 1 year (p= 0.016). Survival analysis of patients stratified by high or low serum IL-6 levels, shows a prolonged time to pregnancy in the high IL-6 group (p= 0.045). Univariate cox regression analysis of IL-6 in relation to time to pregnancy as well as multivariate cox regression analysis correcting for age, disease activity, nulliparity, NSAID use and prednisone use were performed, with hazards ratios for log transformed IL-6 of 0.68 (95% CI: 0.51–0.93,p= 0.015) and 0.66 (95% CI: 0.43–0.99,p= 0.044), respectively. For TNFα, no association with time to pregnancy was found. This study shows that high IL-6, but not TNFα, is associated with decreased fertility in women with RA. This finding provides a rationale to therapeutically target the IL-6 pathway in the time period before pregnancy. More research in the form of large cohort studies on drug safety and the effect of bDMARDS on fertility is needed for implementation of treatment strategies directed at fertility issues in women with RA.
Effect of Combined Electroacupuncture and Selegiline Treatment in Alzheimer’s Disease: An Animal Model
Authors: Cai Mudan , Yang Eun Jin
Published: December 2020

The complexity of pathological mechanisms in Alzheimer’s disease (AD) poses significant challenges to the development of corresponding drugs. Symptom-specific pharmacological interventions and alternative treatments provide promising treatment possibilities. Therefore, we considered a combination of selegiline (SEL) and electroacupuncture (EA). We used an animal model with AD to investigate the effect of a combination of these treatments on cognitive function. 5XFAD mice received a week of SEL treatment and 2 weeks of EA. Novel object recognition and Y-maze tests were subsequently performed to assess their cognitive functions. To determine the molecular action of the combination treatment, Western blots, Aβ1-42 enzyme-linked immunosorbent assays (ELISA), and micro-positron-emission tomography were also performed to assess pathological markers and processes. The results were assessed based on the difference between untreated transgenic, SEL-treated, and SEL- and EA-treated groups of mice. Mice in the combined treatment group demonstrated significantly better cognitive functions, and lesser neuroinflammation than the comparative groups. In addition, mice treated with a combination of SEL and EA did not demonstrate a direct modulation of insoluble Aβ but demonstrated greater glucose metabolism. Our findings demonstrated that SEL combined with EA treatment was associated with better cognitive functioning due to inhibition of neuroinflammation and increased glucose metabolism relative to the comparative groups in a mouse model with AD.
Ganghuo Kanggan Decoction in Influenza: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation
Authors: Lai Yanni , Zhang Qiong , Long Haishan , Han Tiantian , Li Geng , Zhan Shaofeng , Li Yiwei , Li Zonghui , Jiang Yong , Liu Xiaohong
Published: December 2020

Background:Ganghuo Kanggan decoction (GHKGD) is a clinical experience prescription used for the treatment of viral pneumonia in the Lingnan area of China, and its clinical effect is remarkable. However, the mechanism of GHKGD in influenza is still unclear.

Objective:To predict the active components and signaling pathway of GHKGD and to explore its therapeutic mechanism in influenza and to verified itin vivousing network pharmacology.

Methods:The potential active components and therapeutic targets of GHKGD in the treatment of influenza were hypothesized through a series of network pharmacological strategies, including compound screening, target prediction and pathway enrichment analysis. Based on the target network and enrichment results, a mouse model of influenza A virus (IAV) infection was established to evaluate the therapeutic effect of GHKGD on influenza and to verify the possible molecular mechanism predicted by network pharmacology.

Results:A total of 116 candidate active compounds and 17 potential targets were identified. The results of the potential target enrichment analysis suggested GHKGD may involve the RLR signaling pathway to reduce inflammation in the lungs.In vivoexperiments showed that GHKGD had a protective effect on pneumonia caused by IAV-infected mice. Compared with the untreated group, the weight loss in the GHKGD group in the BALB/c mice decreased, and the inflammatory pathological changes in lung tissue were reduced (p< 0.05). The expression of NP protein and the virus titers in lung were significantly decreased (p< 0.05). The protein expression of RIG-I, NF-kB, and STAT1 and the level of MAVS and IRF3/7 mRNA were remarkably inhibited in GHKGD group (p< 0.05). After the treatment with GHKGD, the level of Th1 cytokines (IFN-γ, TNF-α, IL-2) was increased, while the expression of Th2 (IL-5, IL4) cytokines was reduced (p< 0.05).

Conclusion:Through a network pharmacology strategy andin vivoexperiments, the multi-target and multi-component pharmacological characteristics of GHKGD in the treatment of influenza were revealed, and regulation of the RLR signaling pathway during the anti-influenza process was confirmed. This study provides a theoretical basis for the research and development of new drugs from GHKGD.
Stiffness of the Gastrocnemius–Achilles Tendon Complex Between Amateur Basketball Players and the Non-athletic General Population
Authors: Chang Tian-Tian , Li Zhe , Wang Xue-Qiang , Zhang Zhi-Jie
Published: December 2020

Muscle and tendon stiffness are related to sports performance, tendinopathy, and tendon degeneration. However, the effects of habitual loading on muscle and tendon mechanical properties are unclear. Using amateur basketball players as examples, we investigated the effects of mechanical loading on the stiffness of the gastrocnemius–Achilles tendon (AT) complex in non-dominant and dominant lower limbs. Then, we evaluated the correlation between gastrocnemius and AT stiffness. Forty participants (20 amateur basketball players; 20 normal non-athletic persons) were recruited for this study. Stiffness of the gastrocnemius–AT complex was assessed using MyotonPRO at neutral position and 10° dorsiflexion of the ankle joint in participants from amateur basketball players and the non-athletic general population. Our results showed a greater stiffness of the gastrocnemius–AT complex in amateur basketball players than that in healthy non-athletic subjects at neutral position and 10° dorsiflexion of the ankle joint (P < 0.05). No significant difference in stiffness was found between the non-dominant and dominant lower limbs either in amateur basketball players or in generally healthy subjects (P > 0.05). A significant positive correlation was obtained between stiffness of the AT and medial gastrocnemius (MG) in amateur basketball players (neutral position: r = 0.726 and P = 0.001; dorsiflexion 10°: r = 0.687 and P = 0.001). The amateur basketball players exhibit significantly higher stiffness value in Achilles and gastrocnemius. This is possibly caused by repeated training effects. The symmetric stiffness of the AT and gastrocnemius exists both in amateur basketball players and generally healthy subjects. A significant correlation between the AT and the MG was found in amateur basketball players.
Scaling Invariance of Sports Sex Gap
Authors: Tang Lu , Ding Wenzheng , Liu Chengyi
Published: December 2020

The controversy over the evolution of sex gap in sports stems from the reported that women’s performance will 1 day overtake men’s in the journal Nature. After debate, the recent studies suggest that the sports sex gap has been stable for a long time, due to insurmountable physiological differences. To find a mathematical model that accurately describes this stable gap, we analyze the best annual records of men and women in 25 events from 1992 to 2017, and find that power-law relationship could be acted as the best choice, with an R-squares as high as 0.999 (p ≤ 0.001). Then, based on the power law model, we use the records of men in 2018 to predict the performance of women in that year and compare them with real records. The results show that the deviation rate of the predicted value is only about 2.08%. As a conclusion, it could be said that there is a constant sex gap in sports, and the records of men and women evolve in parallel. This finding could serve as another quantitative rule in biology.
In vitro Lipolysis and Leptin Production of Elephant Seal Blubber Using Precision-Cut Adipose Tissue Slices
Authors: Debier Cathy , Pirard Laura , Verhaegen Marie , Rzucidlo Caroline , Tinant Gilles , Dewulf Clément , Larondelle Yvan , Smith Donald R. , Rees Jean-François , Crocker Daniel E.
Published: December 2020

Adipose tissue plays key roles in energy homeostasis. Understanding its metabolism and regulation is essential to predict the impact of environmental changes on wildlife health, especially in fasting-adapted species. However,in vivoexperimental work in wild vertebrates can be challenging. We have developed a novelin vitroapproach of precision-cut adipose tissue slices from northern elephant seal (Mirounga angustirostris) as a complementary approach to whole animal models. Blubber biopsies were collected from 14 pups during early and late post-weaning fast (Año Nuevo, CA, United States), precision-cut into 1 mm thick slices and maintained in culture at 37°C for at least 63 h. The slices exhibited an efficient response to ß-adrenergic stimulation, even after 2 days of culture, revealing goodin vitrotissue function. The response to lipolytic stimulus did not vary between regions of outer and inner blubber, but was higher at early than at late fast for inner blubber slices. At early fast, lipolysis significantly reduced leptin production. At this stage, inner blubber slices were also more efficient at producing leptin than outer blubber slices, especially in the non-lipolytic condition. This model will aid the study of adipose tissue metabolism and its response to environmental stressors in marine mammals.
Effective Defense of Aleppo Pine Against the Giant Scale Marchalina hellenica Through Ecophysiological and Metabolic Changes
Authors: Fotelli Mariangela N. , Lyrou Fani G. , Avtzis Dimitrios N. , Maurer Daniel , Rennenberg Heinz , Spyroglou Gavriil , Polle Andrea , Radoglou Kalliopi
Published: December 2020

Aleppo pine (Pinus halepensis) is widely distributed in the Mediterranean region and in other areas of the world, where it has been introduced due to its adaptive capacity to xerothermic conditions. The giant pine scale Marchalina hellenica often infests Aleppo pine, as well as other pines, in several southeastern European countries, causing pine declines. When combined with the expected intensified heat and drought events in eastern Mediterranean, the impact of this biotic parameter on the host pines may be exacerbated. The importance of understanding the defense mechanisms of Aleppo pine is emphasized by the recent invasion of the pine scale in new regions, like Australia, lacking the insect’s natural enemies, where more intense negative effects on pine species may occur. To date, Aleppo pine’s physiological responses to the infestation by M. hellenica are largely unknown. This study aimed at assessing the responses of Aleppo pine to the giant pine scale attack, both on an ecophysiological and a metabolic level. For this purpose, gas exchange, needle water status, and carbon and nitrogen content were measured during 1 year on healthy and infested adult trees. M etabolic profiling of Aleppo pine needles was also performed before, during, and after the high feeding activity of the insect. The maintenance of stable relative water content, δ13C signatures, and chlorophyll fluorescence in the needles of infested pines indicated that infestation did not induce drought stress to the host pines. At the peak of infestation, stomatal closure and a pronounced reduction in assimilation were observed and were associated with the accumulation of sugars in the needles, probably due to impaired phloem loading. At the end of the infestation period, tricarboxylic acids were induced and phenolic compounds were enhanced in the needles of infested pines. These metabolic responses, together with the recovery of photosynthesis after the end of M. hellenica intense feeding, indicate that in the studied region and under the current climate, Aleppo pine is resilient to the infestation by the giant pine scale. Future research should assess whether these promising defense mechanisms are also employed by other host pines, particularly in regions of the world recently invaded by the giant pine scale, as well as under more xerothermic regimes.
Nitrogen Uptake by Two Plants in Response to Plant Competition as Regulated by Neighbor Density
Authors: Jia Xuan , Huangfu Chaohe , Hui Dafeng
Published: December 2020

Plant species may acquire different forms of nitrogen (N) to reduce competition for the same resource, but how plants respond to neighbors with different densities in their N uptake is still poorly understood. We investigated the effects of competition regime on the uptake of different N forms by two hygrophytes, Carex thunbergii and Polygonum criopolitanum, by conducting a hydroponic test of excised roots and an in situ experiment in a subtropical wetland ecosystem. The two species were grown either in monocultures or mixtures with various neighbor densities. Root functional traits and N uptake rates of different N forms were measured. Our results showed that N uptake was mainly determined by N form, rather than species identity. Both species were able to use organic N sources, but they took up relatively more N supplied as NO3- than as NH4+ or glycine, irrespective of competition treatments. Both species preferred NO3- when grown in monoculture, but in the presence of competitors, the preference of fast-growing C. thunbergii persisted while P. criopolitanum acquired more NH4+ and glycine, with stronger responses being observed at the highest neighbor density. The hydroponic test suggested that these divergences in N acquisition between two species might be partially explained by different root functional traits. To be specific, N uptake rates were significantly positively correlated with root N concentration and specific root length, but negatively correlated with root dry matter content. Our results implicated that C. thunbergii has a competitive advantage with relatively more stable N acquisition strategy despite a lower N recovery than P. criopolitanum, whereas P. criopolitanum could avoid competition with C. thunbergii via a better access to organic N sources, partly mediated by competition regimes.
Comparing the Flavor Characteristics of 71 Tomato (Solanum lycopersicum) Accessions in Central Shaanxi
Authors: Cheng Guoting , Chang Peipei , Shen Yuanbo , Wu Liting , El-Sappah Ahmed H. , Zhang Fei , Liang Yan
Published: December 2020

Flavor is an important quality of mature tomato fruits. Compared with heirloom tomatoes, modern commercial tomato cultivars are considerably less flavorful. This study aimed to compare the flavor of 71 tomato accessions (8 pink cherry, PC; 11 red cherry, RC; 15 pink large-fruited, PL; and 37 red large-fruited, RL) using hedonism scores and odor activity values. Taste compounds were detected using high-performance liquid chromatography. Volatiles were detected using gas chromatography–olfactometry–mass spectrometry. The flavor of tomato accessions can be evaluated using the DTOPSIS analysis method. According to the results of DTOPSIS analysis, 71 tomato accessions can be divided into 4 classes. Tomato accessions PL11, PC4, PC2, PC8, RL35, RC6, and RC10 had better flavor; accessions PC4, PC8, RC10, RL2, and RL35 had better tomato taste; and accessions PL11, PC2, and RC6 had better tomato odor. The concentrations of total soluble solids, fructose, glucose, and citric acid were shown to positively contribute to tomato taste. Tomato odor was mainly derived from 15 volatiles, namely, 1-hexanol, (Z)-3-hexen-1-ol, hexanal, (E)-2-hexenal, (E)-2-heptenal, (E)-2-octenal, (E,E)-2,4-decadienal, (Z)-3,7-dimethyl-2,6-octadieal, 2,6,6-timethyl-1-cyclohexene-1-carboxaldehyde, (2E)-3-(3-pentyl-2-oxiranyl)acrylaldehyde, 6-methyl-5-hepten-2-one, (E)-6,10-dimetyl-5,9-undecadien-2-one, methyl salicylate, 4-allyl-2-methoxyphenol, and 2-isobutylthiazole. Significant positive correlations (P < 0.05) were detected between the compound concentrations and flavor scores. The above-mentioned compounds can be used as parameters for the evaluation of flavor characteristics and as potential targets to improve the flavor quality of tomato varieties.