bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of SN38-Resistant T47D Breast Cancer Cell Sublines Overexpressing BCRP, MRP1, MRP2, MRP3, and MRP4
Authors: Lee Hee-Jeong , Choi Cheol-Hee
Published: January 2021

BackgroundAlthough several novel resistant breast cancer cell lines have been established, only a few resistant breast cancer cell lines overexpress breast cancer resistance proteins (BCRP). The aim of this study was to establish new resistant breast cancer cell lines overexpressing BCRP using SN38 (7-ethyl-10-hydroxycamptothecin), an active metabolite of irinotecan and was to discover genes and mechanisms associated with multidrug resistance.MethodsSN38-resistant T47D breast cancer cell sublines were selected from the wild-type T47D cells by gradually increasing SN38 concentration. The sensitivity of the cells to anti-cancer drugs was assessed by 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Expression profiles of the resistance-related transporters were examined using the resistance diagnostic kit (Drugsporter®), real time RT-PCR, and western blot analysis. Intracellular drug accumulation in the resistant cells was determined using flow cytometry.ResultsThe SN38-resistant T47D breast cancer cell sublines T47D/SN120 and T47D/SN150 were established after long-term exposure (more than 16 months) of wild-type T47D cells to 120 nM and 150 nM SN38, respectively. T47D/SN120 and T47D/SN150 cells were more resistant to SN38 (14.5 and 59.1 times, respectively), irinotecan (1.5 and 3.7 times, respectively), and topotecan (4.9 and 12 times, respectively), than the wild-type parental cells. Both T47D/SN120 and T47D/SN150 sublines were cross-resistant to various anti-cancer drugs. These resistant sublines overexpressed mRNAs of MRP1, MRP2, MRP3, MRP4, and BCRP. The DNA methylase inhibitor 5-aza-2'-deoxycytidine and the histone deacetylase inhibitor trichostatin A increased the expression levels of BCRP, MRP1, MRP2, MRP3, and MRP4 transcripts in T47D/WT cells. Drug accumulation was found to be lower in T47D/SN120 and T47D/SN150 cells, compared to that in T47D/WT cells. However, treatment with known chemosensitizers increased the intracellular drug accumulation and sensitivity of anti-tumor agents.ConclusionT47D/SN120 and T47D/SN150 cells overexpressed MRP1, MRP2, MRP3, MRP4, and BCRP due to the suppression of epigenetic gene silencing via DNA hypermethylation and histone deacetylation. Although these resistant cells present a higher resistance to various anti-cancer drugs than their parental wild-type cells, multidrug resistance was overcome by treatment with chemosensitizers. These SN38 resistant T47D breast cancer cell sublines expressing resistance proteins can be useful for the development of new chemosensitizers.
The Association of the BRAF V600E Mutation with Clinicopathologic Characteristics in Chinese Population with Conventional Papillary Thyroid Carcinoma
Authors: Zhou Sheng Li , Guo Yan Ping , Zhang Lei , Deng Tao , Xu Zi Guang , Ding Chao , Sun Wen Cong , Zhao Yue Wu , Kong Ling Fei
Published: January 2021

Objective:The aim of the study is to evaluate the association of the BRAFV600E mutation with the clinicopathologic characteristics in Chinese population with papillary thyroid carcinoma (PTC).MethodsA total of 943 PTC patients who underwent thyroidectomy from 2014 to 2016 at Henan Provincial People’s Hospital were included in the present study. The BRAFV600E mutation was examined in each resected specimen by quantitative Real-time PCR (qRT-PCR) technique. Results The PTC patients were subclassified into the overall, PTC>10mm and papillary thyroid microcarcinoma(PTMC) groups. The positive rate of BRAFV600E mutation was 85.4% in Chinese patients with PTC. In both overall PTC and PTC> 10mm groups, the BRAFV600E mutation was much more frequently detected in elderly patients and patients at T1 stage (P< 0.05). In addition, the positive rate of BRAFV600E mutation was significantly higher in PTC patients without concomitant Hashimoto’s thyroiditis in overall PTC and PTMC groups (P< 0.05). Furthermore, logistic regression analysis suggested that the risk of having a larger tumor diameter was increased by 6-fold when BRAFV600E mutation in the PTMC group. No association between the BRAFV600E mutation and other clinicopathologic factors was observed. ConclusionThe BRAFV600E mutation was significantly associated with patients age and T stage. Furthermore, the risk of having a larger tumor size was significantly increased when BRAFV600E mutation in the PTMC group. which suggests that BRAFV600E mutation might play an important role in the activation of early thyroid carcinogenesis, the effect might weaken in the progression of PTC.
Ultrasound-targeted Simvastatin-loaded Microbubble Destruction Promotes OA Cartilage Repair by Modulating Cholesterol Efflux Pathway Mediated by PPARγ in Rabbits.
Authors: Wang Xinwei , Wang Danbi , Cheng Kai , Wang Qi , Wang Xiaoju , Lin Qiang , Song Jiulong , Xia Peng , Li Xueping
Published: January 2021

Objective: To evaluate ultrasound-targeted simvastatin-loaded microbubble destruction (UTMDSV) attenuation of osteoarthritis (OA) progression in rabbits through modulation of the peroxisome proliferator-activated receptor (PPARγ)-mediated cholesterol efflux pathway.Methods: In vitro, chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV) and UTMDsv on alternate days for 4 weeks. Chondrocytes were also treated with PPARγ inhibitor, PPARγ inhibitor+UTMDsv and UTMDsv. The cholesterol efflux rate and triglyceride were measured respectively by assay kit and oil red O staining. In vivo, the OA rabbits were treated with a single intra-articular injection of UTMD, SV and UTMDSV every 7 days for 4 weeks. Cartilage histopathology was assessed by safranin-O staining and the Mankin score. Total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) in rabbit knee synovial fluid were detected by enzyme-marker assay. Aggrecan, collagen II and PPARγ expression levels were analyzed western blotting (WB).Results: OA models exhibited primarily by a loss of aggrecan and collagen II, changes to subchondral bone architecture and cartilage degradation. In vitro, UTMDSV significantly increased the cholesterol efflux rate and aggrecan, collagen II and PPARγ levels in OA chondrocytes; these effects were blocked by the PPARγ inhibitor. In vivo, UTMDSV significantly increased aggrecan, collagen II, PPARγ and HDL-C levels, while TC levels and Mankin scores were decreased compared with the UTMD, SV, OA and control groups (95% CI: 0.069 to 6.671).Conclusion: UTMDSV promotes the expression of aggrecan and collagen II and relieve cartilage degradation by modulating the PPARγ-mediated cholesterol efflux pathway in rabbits.
Frequent, Quantitative Bone Planar Scintigraphy for Determination of Bone Anabolism in Growing Mice
Authors: Zaloszyc Ariane , Schmitt Claus Peter , Sayeh Amira , Higel Laetitia , Gros Catherine Isabelle , Bornert Fabien , Aubertin-Kirch Gaelle , Dillenseger Jean-Philippe , Goetz Christian , Constantinesco André , Fischbach Michel , Bahram Siamak , Choquet Philippe
Published: January 2021

BackgroundTo provide insight into bone turnover, quantitative measurements of bone remodeling are required. Radionuclide studies are widely used in clinical care, but have been rarely used in the exploration of the bone in preclinical studies. We describe a bone planar scintigraphy method for frequent assessment of bone activity in mice across the growing period. Since repeated venous radiotracer injections are hardly feasible in mice, we investigated the subcutaneous route.MethodsRepeated phosphonate tracer bone planar scintigraphy studies of the knee region and μCT to measure femur growth rate were performed in eight mice between week 6 and week 27 of life, i.e. during their growth period. Three independent investigators assessed the regions of interest (ROI). An index was calculated based on the counts in knees ROI (normalized by pixels and seconds), corrected for the activity administered, the decay between administration and imaging, and individual weights.ResultsA total of 97 scintigraphy studies and 90 μCT were performed. Repeated subcutaneous tracer injections were well tolerated and allowed for adequate radionuclide studies. Mean scintigraphic indexes in the knees ROI decreased from 87.4 ± 13.0x10-6 counts.s-1.pixel-1.MBq-1.g-1 at week 6 to 13.1 ± 3.9x10-6 counts.s-1.pixel-1.MBq-1.g-1 at week 27. The time constant of the fitted exponential decay was equal to 23.6 days. Mean femur length assessed by μCT increased from 12.2 ± 0.8 mm at week 6 to 15.8 ± 0.2 mm at week 24. The time constant of the fitted Gompertz law was equal to 26.7 days.ConclusionThis study demonstrates the potential of repeated bone planar scintigraphy in growing mice, with subcutaneous route for tracer administration, for quantitative assessment of bone remodeling.
Design and Experimental Investigation of a Novel Spiral Microfluidic Chip to Separate Wide Size Range of Micro-Particles Aimed at Cell Separation
Authors: Tabatabaei Seyed Ali , targhi Mohammad Zabetian
Published: January 2021

BackgroundIsolation of microparticles and biological cells on microfluidic chips has received considerable attention due to their applications in numerous areas such as medical and engineering fields. Microparticles separation are of great importance in bioassays owing to the need for a smaller sample and device size, and lower manufacturing costs. In this study, we first explain the concepts of separation and microfluidic science along with their applications in the medical sciences, and then, a conceptual design of a novel inertial microfluidic system is proposed and analyzed. The PDMS spiral microfluidic device was fabricated, and its effects on the separation of particles with sizes similar to biological particles were experimentally analyzed. This separation technique can be used in the process of separating cancer cells from the normal ones in the blood samples.ResultsThese components required for testing were selected, assembled, and finally, a very affordable microfluidic kit was provided. Different experiments were designed, and the results were analyzed using appropriate software and methods. Separator system tests with polydisperse hollow glass particles (diameter 2-20 µm), and monodisperse Polystyrene particles (diameter 5,15 µm), and the results exhibit an acceptable chip performance with 86 percent of efficiency for both monodisperse particles and polydisperse particles. The microchannel collects particles with an average diameter of 15.8 μm, 9.4 μm, and 5.9 μm at the Proposed reservoirs. ConclusionThis chip can be integrated into a more extensive point-of-care diagnostic system to test blood samples, and it could be said Based on the results of the experiments, this low-cost and user-friendly setting can be used for a variety of microparticle separation programs such as cell separation in biological assays.
Favorable Outcomes with Reduced Steroid Use in Juvenile Dermatomyositis
Authors: Orandi Amir B. , Fotis Lampros , Lai Jamie , Morris Hallie , White Andrew , French Anthony R. , Baszis Kevin
Published: January 2021

Background
High-intensity glucocorticoid regimens are commonly used to induce and maintain remission in Juvenile Dermatomyositis (JDM) but are associated with several adverse side-effects. Eminence-based treatment guidelines from CARRA and SHARE both advocate induction of intravenous pulse steroids followed by high dose oral steroids (2 mg/kg) tapered over 12 months. This study compares the time to disease control with reduced glucocorticoid dosing.
Methods
We retrospectively reviewed the records at a single tertiary-care children’s hospital of patients with JDM between 2000 and 2014 who had a minimum of 2 years of follow-up. The primary outcome measure was time to control of muscle and skin disease. Additional outcome measures included glucocorticoid dosing, effect of treatment on height, frequency of calcinosis and complications from treatment.
Results
Of the 69 patients followed during the study period, 31 fulfilled inclusion criteria. Median length of follow-up was 4.58 years, (3–7.5). Myositis control was achieved in a median of 7.1 months (range 0.9–63.4). Cutaneous disease control was achieved in a median of 16.7 months (range 4.3–89.5). The median starting dose of glucocorticoids was 0.85 mg/kg/day, (range 0.5–1.74). The median duration of steroid treatment was 9.1 months, (range 4.7–17.4), while the median duration of any pharmacotherapy was 29.2 months (range 10.4 to 121.3). Sustained disease control off medications was achieved in 21/31 (68%) patients by the end of review. Persistent calcinosis was identified in only one patient (3%).
Conclusion
Current accepted treatment paradigms for JDM include oral glucocorticoids beginning at 2 mg/kg/d reduced over 12 months; however, our results suggest that treatment using reduced doses and durations with early use of steroid-sparing agents are comparably effective in achieving favorable outcomes in JDM.
A pentagonal hydrogen-bond network facilitates an exceptional preference for asparagine in the S2 subsite of Stenotrophomonas maltophilia dipeptidyl peptidase 7
Authors: Nakamura Akihiro , Suzuki Yoshiyuki , Sakamoto Yasumitsu , Roppongi Saori , Kushibiki Chisato , Yonezawa Natsuri , Takahashi Masato , Shida Yosuke , Gouda Hiroaki , Nonaka Takamasa , Tanaka Nobutada , Ogasawara Wataru
Published: January 2021

The emergence of drug-resistant bacteria has become a major problem worldwide. Bacterial dipeptidyl peptidases 7 and 11 (DPP7s and DPP11s), belonging to the family-S46 peptidases, are important enzymes for bacterial growth and are not present in mammals. Therefore, specific inhibitors for these peptidases are promising as potential antibiotics. While the molecular mechanisms underlining strict substrate specificity at the S1 subsite of S46 peptidases have been well studied, those of relatively broad substrate preference at the S2 subsite of these peptidases are unknown. In this study, we performed structural and biochemical analyses on DPP7 from Stenotrophomonas maltophilia (SmDPP7). SmDPP7 showed substrate preference for hydrophobic amino acids at the S2 subsite in general, but as an exception, also for asparagine, a hydrophilic amino acid. Structural analyses of SmDPP7 revealed that this exceptional preference to asparagine is caused by a hydrogen bonding network at the bottom of the S2 subsite. The residues in the S2 subsite are well conserved among S46 peptidases as compared with those in the S1 subsite. We expect that our findings will contribute toward the development of a universal inhibitor of S46 peptidases. (184 words / 200 words)
Network Pharmacology-Based Investigation of Potential Targets of Astragalus-Angelica Compound Acting on Diabetic Nephropathy
Authors: Dong Youzi , Zhao Quanlin
Published: January 2021

Through network pharmacology and molecular docking to explore the mechanism of astragalus-angelica compound in the treatment of diabetic nephropathy (DN). Screen the components and targets of astragalus and angelica compound on the TCMSP and the BATMAN-TCM, and use Cytoscape 3.7.2 to establish a component-target interaction network. Relevant targets of DN were searched through related databases, and the common targets of astragalus-angelica compound prescription and DN were obtained after comparison. The target protein interaction analysis and visualization processing were performed, and gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis were performed through David database, and molecular docking was performed using PyMoL and AutoDock Vina software. Through network pharmacology screening, 142 main targets of astragalus-angelica compound in the treatment of DN have been identified. KEGG pathway enrichment analysis shows that the above key targets are related to apoptosis, oxidative stress, inflammation, insulin resistance and other related pathways. Molecular docking shows that the target protein has a good combination with the main active ingredients of astragalus-angelica compound. Astragalus-angelica compound may act on VEGFA, TP53, IL-6, TNF, mark1 and other targets to treat DN by regulating apoptosis, oxidative stress, inflammation, glucose and lipid metabolism and other pathways. Research methods based on network pharmacology and molecular docking provide new ideas for the pathogenesis and treatment of DN.
Effect of Pelvic Floor Muscle Electrical Stimulation on Lumbopelvic Control in Women With Stress Urinary Incontinence: Randomized Controlled Trial
Authors: Hwang Ui-jae , Lee Min-seok , Jung Sung-hoon , Kwon Oh-yun
Published: January 2021

Background: This study was performed to determine the effectiveness of 8 weeks of pelvic floor muscle (PFM) training by electrical stimulation (ES) on PFM function, lumbopelvic control, abdominal muscle thickness, and the contraction ratio in women with stress urinary incontinence (SUI). Methods: Women with SUI were randomized into an ES group (n = 18) or control group (n = 18). The ES group underwent a PFM ES training during 8-week, and the control group underwent only a general exercise without PFM training. PFM functions was measured using a perineometer. Lumbopelvic control was measured by one- and double-leg lowering tests. Abdominal muscle thickness and the contraction ratio during the active straight leg raise maneuver were measured by sonography. Results: The ES group showed significantly higher PFM strength and power than controls (p < 0.05) at after 8 weeks of training. PFM strength and power were significantly increased after 8 weeks of training in the ES group (p < 0.05). The ES group showed significantly higher values than the controls in both the one- and double-leg lowering tests (p < 0.05) at after 8 weeks of training. There were no significant between- or within-group differences, at rest or during contraction, in transverse abdominis (TrA), internal oblique abdominis (IO), or external oblique abdominis (EO) muscle thickness. Conclusion: Improvements in PFM functions by PFM ES could enhance lumbopelvic control in women with SUI.Trial registration: Clinical Research information Service, KCT0003357. Registered 11th November 2018 - Retrospectively registered, https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=12678<ype=&rtype=
Soil Nitrogen Treatment Alters Microbiome Networks Across Farm Niches
Authors: Wang XinYue , Reilly Kerri , Biswas Ambarish , Johnson Linda , Teasdale Suliana , Grelet Gwen , Podolyan Ana , Gregorini Pablo , Morales Sergio , Attwood Graeme
Published: January 2021

BackgroundAgriculture is fundamental for food production, and microbiomes support agricultural through multiple essential ecosystem services. Despite the importance of individual (i.e. niche specific) agricultural microbiomes, microbiome interactions across niches are not well-understood. To observe the linkages between nearby agricultural microbiomes, multiple approaches (16S, 18S, and ITS) were used to inspect a broad coverage of niche microbiomes. Here we examined agricultural microbiome responses to 3 different nitrogen treatments (0 kg/ha/yr, 150kg/ha/yr and 300kg/ha/yr) in soil and tracked linked responses in other neighbouring farm niches (rumen, faecal, white clover leaf, white clover root, rye grass leaf, rye grass root)ResultsNitrogen treatment had little impact on microbiome structure or composition across niches, but drastically reduced the microbiome network connectivity in soil. Networks of 16S microbiomes were the most sensitive to nitrogen treatment across amplicons, where ITS microbiome networks were the least responsive.ConclusionsNitrogen enrichment in soil altered soil and the neighbouring microbiome networks, supporting our hypotheses that nitrogen treatment in soil altered microbiomes in soil and in nearby niches. This suggested that agricultural microbiomes across farm niches are ecologically interactive. Therefore, knock-on effects on neighbouring niches should to be considered when management is applied to a single agricultural niche.
Decreased neutrophil phagocytosis and killing of bacteria in COVID-19 patients
Authors: Nomani Masoumeh , Varahram Mohammad , Tabarsi Payam , Hashemian Seyed MohamadReza , Jamaati Hamidreza , Malekmohammad Majid , Ghazi Mona , Adcock Ian M. , Mortaz Esmaeil
Published: January 2021

A new coronavirus disease was described in December 2019 (COVID-19) in Wuhan City, Hubei Province, China and has reached pandemic status. According to the World Health Organization, the incubation time from being infected to symptom emergence averages 5-6 days for COVID-19 but can be up to 14 days. The mortality rate varies in different countries but is greater in elderly people and in patients with cardiovascular disease, diabetes and chronic respiratory diseases. Patients with chronic respiratory diseases often have reduced neutrophil function. We sought to measure neutrophil phagocytosis and bacterial killing in COVID-19 patients. 30 COVID-19 patients and 9 healthy individuals were recruited from the Masih Daneshvari Hospital (Tehran, Iran) from March-May 2020. Polymorphonuclear (PMN) cells were isolated from whole fresh blood and incubated with green fluorescent protein (GFP) labelled methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Phagocytosis was determined by measuring the florescence of co-cultures of bacteria and neutrophils and reported as the lag time before exponential growth. The number of viable bacteria was determined after 70 h by the Colony-Forming Unit (CFU). Bacterial phagocytosis of SA (22±0.9 versus 9.2±0.5h, p<0.01) and PA (12.4±0.6 versus 4.5±0.22, p<0.01) was significantly reduced in COVID-19 patients compared with healthy control subjects. After 70h there was a significant increase in CFU in COVID-19 subjects compared with healthy control subjects for both SA (2.6±0.09 x 108 versus 0.8±0.04 x 108 CFU/ml, p<0.001) and PA (2.2±0.09 x 109 versus 1.0±0.06 x 109 CFU/ml, p<0.001).These results suggests a defect in bacterial clearance by neutrophils in COVID-19 patients.
EEG Patterns in Patients with Prader-Willi Syndrome
Authors: Elia Maurizio , Rutigliano Irene , Sacco Michele , Madeo Simona , Wasniewska Malgorzata , Pomi Alessandra Li , Trifirò Giuliana , Bella Paolo Di , De Lucia Silvana , Vetri Luigi , Iughetti Lorenzo , Delvecchio Maurizio
Published: January 2021

Prader-Willi syndrome (PWS) is a rare disease determined by the loss of the paternal copy of the 15q11-q13 region, characterized by hypotonia, hyperphagia and obesity, short stature, hypogonadism, craniofacial dysmorphisms, cognitive and behavioral disturbances. The aims of this retrospective study were to analyze interictal EEG findings in a group of PWS patients and to correlate them with genetic, clinical and neuroimaging data. Demographic, clinical, genetic, EEG, and neuroimaging data about seventy-four patients were collected. Associations between the presence of EEG paroxysmal abnormalities, genotype, clinical and neuroimaging features were investigated. Four patients (5.4%) presented a drug-sensitive epilepsy. Interictal EEG paroxysmal abnormalities, focal or multifocal, were present in 25.7% of the cases, and normalization of EEG occurred in about 25% of the cases. In 63.2% of the cases paroxysmal abnormalities were localized over the middle-posterior regions bilaterally. Brain magnetic resonance imaging (MRI) was performed in 39 patients (abnormal in 59%). No relevant associations were found between EEG paroxysmal abnormalities and all the other variables considered. Interictal EEG paroxysmal abnormalities, in particular with a bilateral middle-posterior localization, could represent an important neurological feature of PWS not associated with genotype, cognitive or behavior endophenotypes, MRI anomalies, or prognosis.
Sigma-1 Receptor Activation Suppresses Microglia M1 Polarization via Regulating Endoplasmic Reticulum–Mitochondria Contact and Mitochondrial Functions in Stress-induced Hypertension Rats
Authors: Ooi Kokwin , Hu Li , Feng Yi , Han Chengzhi , Ren Xiaorong , Qian Xinyi , Huang Haofeng , Chen Sijia , Shi Qi , Lin Hong , Wang Jijiang , Zhu Danian , Wang Rui , Xia Chunmei
Published: January 2021

Background Exposure to stress plays a detrimental role in the pathogenesis of hypertension via noninflammatory pathways. Microglial neuroinflammation in the rostral ventrolateral medulla (RVLM) exacerbates stress-induced hypertension (SIH) by increasing sympathetic hyperactivity. Mitochondria of microglia are the regulators of innate immune response. Sigma-1R (σ-1R) localizes to the mitochondria-associated membranes (MAMs) and regulates endoplasmic reticulum (ER) and mitochondria communication, in part through its chaperone activity. The present study aims to investigate the protective role of σ-1R on microglial-mediated neuroinflammation. Methods Stress-induced hypertension (SIH) was induced in rats using electric foot shocks and intermittent noise. Arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured to evaluate the sympathetic nervous system (SNS) activities. SKF10047 (100µM), an agonist of σ-1R, was administrated to rats, then σ-1R localization and MAMs alterations were detected by immuno-electron microscopy. Mitochondrial calcium homeostasis was examined in primary microglia and/or BV-2 cells. The effect of SKF10047 treatment on the mitochondrial respiratory function of cultured microglia was measured using a Seahorse Extracellular Flux Analyzer. Confocal microscopic images were performed to indicate mitochondrial dynamics. Results Stress reduced σ-1R in the MAMs localization, leading to decreased ER-mitochondria contact and IP3R-GRP75-VDAC calcium transport complexes expression in the RVLM of rats. SKF10047 promotes the length and coverage of MAMs in the prorenin treated microglia. Prorenin treatment increases mitoROS levels, and inhibits Ca2+ signaling between the two organelles, therefore negatively affects ATP production in BV2 cells, and these effects are reversed by SKF10047 treatment. We find that mitochondrial hyperfusion and M1 polarization in prorenin-treated microglia. SKF10047 suppresses microglial M1 phenotype and RVLM neuroinflammation, subsequently ameliorates sympathetic hyperactivity in stress-induced hypertensive rats.Conclusion Sigma-1 receptor activation suppresses microglia M1 polarization and neuroinflammation via regulating endoplasmic reticulum–mitochondria contact and mitochondrial functions in stress-induced hypertension rats.
Evaluating the Influence of Music at Different Sound Pressure Levels on Medical Students’ Performance of Standardized Laparoscopic Box Training Exercises
Authors: Platzer Lisa Katharina , Grozinger Philipp , Orthmann Natalie , Deutsch Thomas Maximilian , Hennigs André , Domschke Christoph , Wallwiener Markus , Rom Joachim , Riedel Fabian
Published: January 2021

BackgroundThe influence of music on the performance of surgical procedures such as laparoscopy is controversial and methodologically difficult to quantify. Here, outcome measurements using laparoscopic box training tools under standardized conditions might offer a feasible approach. To date, the effect of music exposure at different sound pressure levels (SPL) on outcome has not been evaluated systematically for laparoscopic novices. MethodsBetween May 2017 and October 2018, n=87 students (49 males, 38 females) from Heidelberg University Medical School performed three different laparoscopy exercises using the “Luebecker Toolbox” that were repeated twice under standardized conditions. Time was recorded for each run. All students were randomly assigned to four groups exposed to the same music compilation but at different SPLs (50-80 dB), an acoustically shielded (earplug) group, or a control group (no intervention). ResultsBest absolute performance was shown under exposure to 70 dB in all three exercises (a, b, c) with mean performance time of 121, 142, and 115 s (p<0.05 for a and c). For the control group mean performance times were 157, 144, and 150 s, respectively. In the earplug group, no significant difference in performance was found compared to the control group (p>0.05) except for exercise (a) (p=0.011).ConclusionMusic exposure seems to have beneficial effects on training performance. In comparison to the control group, significantly better results were reached at 70 dB SPL, while exposure to lower (50 or 60 dB) or higher (80 dB) SPL as well as under acoustic shielding did not influence performance.
Effect of Three Different Needle Holders on Gastrointestinal Anastomosis Construction Time and Bursting Pressure in Equine Jejunal Segments
Authors: Averay Kate , Galen Gaby van , Ward Michael , Verwilghen Denis
Published: January 2021

Background: Equine small intestinal resection and anastomosis is a procedure where optimizing speed, without compromising integrity, is advantageous. There is a range of different needle holders available, but little is published on their impact on surgical technique in veterinary medicine. The objectives of this study were to investigate if the needle holder type influences the anastomosis construction time, and the anastomosis quality (estimated by bursting pressure), and whether the bursting pressure is influenced by the anastomosis construction time. Single layer end-to-end jejunojejunal anastomoses were performed on jejunal segments harvested from equine cadavers. These segments were randomly allocated to four groups. Three groups based on the needle holder type that was used: 16.5 cm Frimand (Group 1), 16 cm Mayo-Hegar (Group 2) or 20.5 cm Mayo-Hegar (Group 3) needle holders. One (Group 4) as control without anastomoses. Anastomosis construction time was recorded. Bursting pressure was determined by pumping green coloured fluid progressively into the lumen whilst recording intraluminal pressures. Maximum pressure reached prior to failure was recorded as bursting pressure. Construction times and bursting pressures were compared between needle holder, and the correlation between bursting pressure and construction time was estimated.Results: Construction times were not statistically different between groups. Yet, the mean construction time was shortest in Group 2 followed by Group 3, with Group 1 having the longest mean construction time but showing most consistency. Segments from Group 2 and Group 3 burst at a statistically significantly lower pressure than those from Group 4. Group 4 and Group 1 were not different. The mean bursting pressure was highest in Group 4, followed by Group 1 and Group 2, with Group 3 having the lowest mean bursting pressure. Anastomosis construction time and bursting pressure were not correlated.Conclusions: The tested needle holders had a significant effect on bursting pressure, but not on anastomosis construction time. The Frimand needle holder shows promise to be superior for anastomoses in a clinical setting. However, future studies need to confirm these findings.
Propagation of desert moss Syntrichia caninervis in peat pellet: a method for rapidly obtaining large numbers of cloned gametophytes
Authors: Liu Xiujin , Zhou Ping , Li Xiaoshuang , Zhang Daoyuan
Published: January 2021

Background
Syntrichia caninervis is a typical desiccation tolerance moss, which is a dominant species forming biological soil crust in the Gurbantunggut Desert. This study investigated the effect of different explants on regeneration potential by propagating on peat pellet.
Result
Juvenile and green leaves can regenerate secondary protonema within one week and shoot in half a month in peat pellet. Rhizoid has strong ability to regenerate, like leaf regeneration, the secondary protonema is the dominant type of regenerant. The process of stem regeneration is similar with whole gametophyte. Stem is the most important integral body part when propagation. The whole gametophyte is the most optimal materials for rapidly propagating.
Conclusion
This article improves the state of our current knowledge in desiccation tolerance moss cultivation, highlighting efforts to effectively obtain large number of gametophytes through different parts of explant. This work provides a useful resource for the research of S. caninervis as well as biocrust restoration.
The Capacity and Organization of Gustatory Working Memory
Authors: Lim Xue Li , Höchenberger Richard , Ruda Iryna , Fink Gereon , Viswanathan Shivakumar , Ohla Kathrin
Published: January 2021

Remembering a particular taste is crucial in food intake and associative learning. We investigated whether taste can be dynamically encoded, maintained, and retrieved on short time-scales consistent with working memory (WM). We used novel single and multi-item taste recognition tasks to investigate the organization and capacity of gustatory WM. In Experiment 1, we show that a single taste can be reliably recognized despite multiple oro-sensory interferences suggesting active and resilient maintenance. When multiple tastes were presented, the resolution with which these could be maintained, depended on their serial position implying a role of attention. Participants reliably recognized up to three tastes, compatible with a limited capacity of gustatory WM. Lastly, recognition was better for match than foil trials likely due to increased stimulus similarity in foil trials. Together, the results advocate a hybrid model of gustatory WM with a limited number of slots where items are stored with varying precision.
The Global Body Size Biomass Spectrum is Multimodal
Authors: Tekwa Edward , Catalano Katrina , Bazzicalupo Anna , Pinsky Malin
Published: January 2021

Recent research provides an unprecedented account of the diversity and biomass of life, but the data also suggest unexplained patterns such as the co-dominance of very different life forms. We compile the planetary body size biomass spectrum across all taxa and investigate possible underlying forces. We find that small (10-14 g) and large (106 g) organisms vastly outweigh other sizes. The global spectrum reveals an allometric power exponent close to zero, with the marine spectrum in particular showing multiple closely packed modes that are compatible with metabolic food webs. All habitat realms share two distinct size modes that correspond well to the evolutionary innovations of unicellular and complex multicellular life forms, plus a smaller third mode representing unicellular endosymbiotic life. Each mode contains both producers and consumers. These findings show both differences and similarities across habitat realms and point to a size-based synthesis of microevolution, macroevolution, and macroecology.
Evolution of the Yangtze River reconstructed by the largest molecular phylogeny of Cyprinidae
Authors: Chen Feng , Xue Ge , Wang Yeke , Zhang Hucai , He Jun , Chen Jun , Xie Ping
Published: January 2021

The Yangtze River is the largest river in Asia, but its evolutionary history has long been debated. Diverse groups of endemic freshwater fishes have evolved in this river. Here we represent the historical spatiotemporal pattern of the endemic East Asian cyprinid clade based on the largest molecular phylogeny of Cyprinidae, including 1420 species and fossil records. Based on the evolution of egg types adapting to different hydrological conditions, we show that the ancestors of this endemic clade (laying adhesive eggs) were distributed in southern East Asia before ~24 Ma and subsequently dispersed to the Yangtze River basin to spawn semi-buoyant eggs at ~19 Ma. These results indicate that the Yangtze River reversed its flow direction from southward to eastward to form the present river system within the Oligocene-Miocene boundary (~24-19 Ma). Some East Asian cyprinids evolved into fishes producing adhesive eggs again at ~13 Ma, together with an increased net diversification rate, indicating that the river began to form a potamo-lacustrine system during the Mid-Miocene. The new sketch of the formation history of the Yangtze River system through Cyprinidae phylogeny, together with the evolution of egg types in endemic East Asia cyprinids, has better spatiotemporal integrity than traditional geological studies.
Characterization of the Mechanism of Action of Lanraplenib, a Novel Spleen Tyrosine Kinase Inhibitor, in Models of Lupus Nephritis
Authors: Pohlmeyer Christopher W. , Shang Ching , Han Pei , Cui Zhi-Hua , Jones Randall M. , Clarke Astrid S. , Murray Bernard P. , Lopez David A. , Newstrom David W. , Inzunza M. David , Matzkies Franziska G. , Currie Kevin S. , Paolo Julie A. Di
Published: January 2021

Background B cells are critical mediators of systemic lupus erythematosus (SLE) and lupus nephritis (LN), and antinuclear antibodies can be found in the serum of approximately 98% of patients with SLE. Spleen tyrosine kinase (SYK) is a nonreceptor tyrosine kinase that mediates signaling from immunoreceptors, including the B cell receptor. Active, phosphorylated SYK has been observed in tissues from patients with SLE or cutaneous lupus erythematosus, and its inhibition is hypothesized to ameliorate disease pathogenesis. We sought to evaluate the efficacy and characterize the mechanism of action of lanraplenib, a selective oral SYK inhibitor, in the New Zealand black/white (NZB/W) murine model of SLE and LN.Methods Lanraplenib was evaluated for inhibition of primary human B cell functions in vitro. Furthermore, the effect of SYK inhibition on ameliorating LN-like disease in vivo was determined by treating NZB/W mice with lanraplenib, cyclophosphamide, or a vehicle control. Glomerulopathy and immunoglobulin G (IgG) deposition were quantified in kidneys. The concentration of proinflammatory cytokines was measured in serum. Splenocytes were analyzed by flow cytometry for B cell maturation and T cell memory maturation, and the presence of T follicular helper and dendritic cells. Results In human B cells in vitro, lanraplenib inhibited B cell activating factor-mediated survival as well as activation, maturation, and immunoglobulin M production. Treatment of NZB/W mice with lanraplenib improved overall survival, prevented the development of proteinuria, and reduced blood urea nitrogen concentrations. Kidney morphology was significantly preserved by treatment with lanraplenib as measured by glomerular diameter, protein cast severity, interstitial inflammation, vasculitis, and frequency of glomerular crescents; treatment with lanraplenib reduced glomerular IgG deposition. Mice treated with lanraplenib had reduced concentrations of serum proinflammatory cytokines. Lanraplenib blocked disease-driven B cell maturation and T cell memory maturation in the spleen.Conclusions Lanraplenib blocked the progression of LN-like disease in NZB/W mice. Human in vitro and murine in vivo data suggest that lanraplenib may be efficacious in preventing disease progression in patients with LN at least in part by inhibiting B cell maturation. These data provide additional rationale for the use of lanraplenib in the treatment of SLE and LN.
Synergism between nonane and emanations from soil as cues in oviposition-site selection of natural populations of Anopheles gambiae and Culex quinquefasciatus
Authors: Mwingira Victor Saturnus , Mboera Leonard E.G. , Takken Willem
Published: January 2021

BackgroundOlfactory cues have been shown to have an important role in guiding gravid mosquito females to selected sites for egg laying. The objective of this study was to determine the influence of emanations from soil from a breeding site and the putative oviposition pheromone nonane on oviposition-site selection of natural populations of Anopheles gambiae sensu lato (s.l.) and Culex quinquefasciatus.MethodsThis field-based study was conducted in Mvomero District in East-central Tanzania. In a dual-choice experimental set up, clay bowls were dug into the ground and filled with one of the following treatments: (i) distilled water + autoclaved soil (control), (ii) distilled water + soil from a natural mosquito breeding site, (iii) distilled water + nonane and (iv) distilled water + nonane + soil from a natural breeding site. Soil was dried and autoclaved or dried only before use. After five days of incubation, larvae were collected daily for 10 days. The median number of larvae per bowl per day was used as outcome measure.ResultsAutoclaved soil had a significant attractive effect on oviposition behaviour of Cx. quinquefasciatus (median values ± s.e: 8.0±1.1; P<0.005) but no effect on An. gambiae (median value ± s.e: 0.0±0.2; P = 0.18). Nonane and emanations from untreated soil significantly and positively influenced the selection of oviposition sites by both An. gambiae s.l. (median values ± s.e.: 12.0 ± 2.0 and 4.5 ± 1.5, respectively; P< 0.0001) and Cx. quinquefasciatus (median values ± s.e.: 19.0 ± 1.3 and 17.0 ± 2.0, respectively; P<0.0001). A mixture of nonane and untreated soil caused a synergistic effect on oviposition behaviour in An. gambiae s.l. (median value ± s.e.: 23.5 ± 2.5; P<0.0001) compared to either nonane (median values ± s.e.: 12.0 ± 2.0; P<0.0001) or untreated soil alone (median value ± s.e.: 4.5 ± 1.5; P<0.0001). A synergistic effect of nonane mixed with untreated soil was also found in Cx. quinquefasciatus (median value ± s.e.: 41.0 ± 2.1; P<0.0001) compared to either nonane (median value ± s.e. 19.0 ± 1.3; P<0.0001) or untreated soil alone (median value ± s.e.: 17.0 ± 2.0; P<0.0001). The oviposition activity index for An. gambiae was 0.56 (P< 0.001) and for Cx. quinquefasciatus 0.59 (P<0.0001).ConclusionThe larval pheromone nonane and emanations from breeding-site soil both induced oviposition in wild An. gambiae s.l. and Cx. quinquefasciatus, with a synergistic effect when both stimuli were present simultaneously. This is the first study in which nonane is shown to cause oviposition under natural conditions, suggesting that this compound can potentially be exploited for the management of mosquito vectors.
Access to and use of sexual and reproductive health services among street children and young adults in Kampala, Uganda: Does Migration matter?
Authors: Bwambale Mulekya Francis , Bukuluki Paul , Moyer Cheryl A. , Borne Bart H.W Van den
Published: January 2021

Background: While the nexus of migration and health outcomes is well acknowledged, the effect of rural-urban migration on use of sexual and reproductive health (SRH) services has received less attention. We assessed the effect of rural-rural migration on the use of SRH services while controlling for confounding and whether there is a difference in the use of SRH services among migrant and non-migrant street children and young adults.Methods: Data were collected among 513 street children and young adults aged 12 - 24 years using face‐to‐face interviews using venue-based time-space sampling (VBTS). Using STATA 16.00, multivariate logistic regression analysis was performed to identify factors associated with SRH services use, with rural-urban migration status as the main predictor. Participants were further classified as new migrants (≤ 2 years of stay in city), established migrants (> 2 years of stay in city), or non-migrants (lifelong native street children) with no rural-urban migration history.Results: Overall, 18.13% of the street children and young adults had ever used contraception/family planning, 58.67% had ever tested for HIV and knew their status while 34.70% had ever been screened for sexually transmitted infections (STIs). Non-migrant street children and young adults were 2.7 times more likely to use SRH services (HIV testing, STI screening and family planning) compared to the migrants (aOR = 2.7, 95%CI 1.23-5.97). Other factors associated with SRH services use among street children and young adults include age (aOR=4.70; 95%CI 2.87 - 7.68), schooling status (aOR = 0.33, 95%CI 0.15-0.76), knowledge of place of care (aOR = 2.71, 95%CI 1.64 - 4.46) and access to SRH information (aOR = 3.23, 95%CI 2.0 - 5.24). Conclusions: Access to and use of SRH services among migrant street children and young adults is low compared to the non-migrant street children and young adults and is independently associated with migration status, age, schooling status, knowledge of place of SRH care and access to SRH information. Our findings call for the need to design and implement multi-dimensional interventions to increase use of SRH services among street children and young adults while taking into consideration their migration patterns.
Spatiotemporal Characteristics and meteorological determinants of Hand, Foot and Mouth Disease in Shaanxi Province, China: a county-level analysis
Authors: Ding Li , Zhang Ning , Zhu Bin , Liu Jinlin , Wang Xue , Liu Feng , Mao Ying
Published: January 2021

Background: Hand, foot and mouth disease (HFMD) is one of the common intestinal infectious diseases worldwide and has caused huge economic and disease burdens in many countries. The average annual incidence rate of HFMD was 11.66% in Shaanxi during the time span from 2009 to 2018. There are distinct differences within Shaanxi, as it is a special region that crosses three temperature zones. Hence, in this study, a spatiotemporal analysis of Shaanxi was performed to reveal the characteristics of the distribution of HFMD and to explore the meteorological determinants of HFMD.Methods: The county-level and municipal data from Shaanxi Province from 2009 to 2018 were applied to research the spatiotemporal characteristics of HFMD and its meteorological determinants. Time series and spatial autocorrelation analyses were applied to assess the spatiotemporal characteristics of HFMD. This study used spatial econometric panel models to explore the relationship between HFMD and meteorological factors based on the data of 107 counties and 10 municipalities.Results: The incidence rate of HFMD displayed no variable trend throughout the whole research period. A high incidence rate of HFMD was observed from June to September, corresponding to a time when the climate is characterized by heavy rain, high temperature, and high humidity. The high-incidence areas were mainly located in the central region in Shaanxi, whereas the low-incidence spots were mainly found in Northern Shaanxi. Regarding the meteorological factors analysed in this study, in general, the incidence rate of HFMD in specific regions was positively associated with the rainfall, temperature and humidity.Conclusion: These results could be applied by the government and the general public to take effective measures to prevent disease. Region-targeted policies could be enacted and implemented in the future according to specific situations in different areas and the relevant meteorological determinants. Additionally, meteorological conditions normally extend to a wide-ranging region; thus, cooperation among surrounding regions is necessary.