bluuebunny/crossref_metadata_2025 huggingface dataset:
BMP-2 Promotes Bone Formation in Bone Defects in Which Bone Remodeling Is Suppressed by Long-Term and High-Dose Zoledronic Acid
Authors: Moon Young Jae , Jeong Seongyup , Lee Kwang-Bok
Published: September 2021

Background: The use of long-term and high-dose bisphosphate is associated with severely suppressed bone turnover and the delayed union of fractures. However, therapeutic methods to overcome the negative effects of bisphosphonate use are lacking. Bone morphogenetic proteins (BMPs) are powerful osteoinductive proteins. We hypothesized that BMPs had similar effects as autografts in patients with decreased bone healing potential due to long-term bisphosphonate treatment. The purpose of this study was to compare BMPs with demineralized freeze-dried bone grafts and autografts in a rat femoral bone defect model with long-term and high-dose bisphosphonate treatment. Methods: Forty rats were divided into the following four groups depending upon the materials implanted into the femoral defect after ten weeks of bisphosphonate (zoledronic acid) injections: Group I: absorbable collagen sponge (control); group II: demineralized freeze-dried bone graft; group III: autogenous bone graft; and group IV: rhBMP-2 with an absorbable collagen sponge. Radiographic union, micro computed tomography (CT) analysis, manual palpation, and histologic analysis were evaluated. Results: The radiographic union rate, manual union rate, and micro-CT bone volume in groups III and IV were significantly higher than those in groups I and II. Groups III and IV showed similar results to each other. Although the amount of immature bone in the BMP-treated group was large, the effect was similar to that of autografts in the bone defect model in which bone turnover was severely reduced by bisphosphonate treatment. Conclusion: BMP might be a good substitute for autografts in patients with decreased bone healing potential due to long-term bisphosphonate treatment.
KnotAli: Informed Energy Minimization Through the Use of Evolutionary Information
Authors: Gray Mateo , Chester Sean , Jabbari Hosna
Published: September 2021

BackgroundImproving the prediction of structures, especially those containing pseudoknots (structures with crossing base pairs) is an ongoing challenge. Homology-based methods utilize structural similarities within a family to predict the structure. However, their prediction is limited to the consensus structure, and the quality of the alignment. Minimum free energy (MFE) based methods, on the other hand, do not rely on familial information and can predict structures of novel RNA molecules. Their prediction normally suffers from inaccuracies due to their underlying energy parameters. ResultsWe present a new method for prediction of RNA pseudoknotted secondary structures that combines the strengths of MFE prediction and alignment-based methods. KnotAli takes a multiple RNA sequence alignment and uses covariation and thermodynamic energy minimization to predict secondary structures for each individual sequence in the alignment. We compared KnotAli’s performance to that of three other alignment-based programs, on a large data set of 10 families with pseudoknotted and pseudoknot-free reference structures. We produced sequence alignments for each family using two well-known sequence aligners (MUSCLE and MAFFT). We found KnotAli to be superior in 6 of the 10 families for MUSCLE and 7 of the 10 for MAFFT. ConclusionsWe find KnotAli’s predictions to be less dependent on alignment quality. In particular, KnotAli is shown to have more accurate predictions compared to other leading methods as alignment quality deteriorates. KnotAli can be found online on github at https://github.com/mateog4712/KnotAli
Enhanced Cellulase Production by Talaromyces Amestolkiae CMIAT055 using Banana Pseudostem
Authors: Faheina Genilton S , Sousa Kally A , Zilli Jerri E , Vergara Carlos , Pinto Gustavo A. Saavedra , de Santiago-Aguiar Rilvia Saraiva
Published: September 2021

Cellulases are a complex of enzymes necessary for the complete solubilization of cellulose in sugars, thus playing a key role in the natural carbon cycle through the hydrolysis of lignocellulosic structures. The aim of this study was to evaluate the increase in the capacity of Talaromyces amestolkiae CMIAT 055 to produce cellulases by optimizing the components of the culture medium containing banana pseudostem as an inducer, as well as in different agitation configurations in a bioreactor. Optimization was performed through statistical experimental design (Plackett-Burman and DCCR), a study of pH control in bioreactors, and a study of the agitation system by comparing impellers with different flow profiles in the liquid medium. For this purpose, a wild strain of Talaromyces amestolkiae CMIAT 055 was used. In the Plackett-Burman and DCCR statistical design, four components of the culture medium were significant and optimized for greater synthesis of FPase: banana pseudostem, CaCl2, KH2PO4, and urea. In bioreactors tests, these parameters were beneficial for greater enzyme activities: maintenance of pH at 5.0, use of Pitched blade impeller, and rotation speed at 300 rpm. Comparing the first test using banana pseudostem in an Erlenmeyer flask to the last fermentation process in bioreactors, it was observed that the total cellulase activity increased from 424.7 FPU/L to 2172.8 FPU/L. This fact showed that the strategies adopted in this study are a pertinent way to reduce the cost of enzyme production through the use of lignocellulosic materials.
Do the prices of a preventive animal health product affect dairy farmers’ willingness to pay and product use? Evidence from an experimental study
Authors: Cariappa A G , Chandel Balwant , Sendhil R , Dixit Anil , Sankhala Gopal , Mani Veena , Meena Brajendra
Published: September 2021

Should we distribute preventive animal health products for free or charge a positive price? The decision depends on the price sensitivity of the product and the effect prices have on product use. We explore this idea through a field experiment in which we randomize the price a farmer faces for an animal health product. We find that the demand for the product is highly sensitive to prices; willingness to pay (WTP) decreased from 44% at ₹ 100 to 18% at ₹ 500. Further, among farmers who were willing to pay, the product usage rate was 71% and usage did not increase in prices (lack of screening effect). Furthermore, we find that farmers whose animals were sick in the baseline had a higher WTP. These findings support the human capital model relating to demand for human health products. We argue that individuals behave in a similar way when the decisions concern their own health or the health of an animal they rear for commercial purposes. A highly subsidized distribution of the product is recommended due to high price sensitivity, lack of screening effect, equitable distribution among poor and lesser implementation costs found in this study.
Sustainability Analysis of Improvement of Contaminated Clayey Soil Using Lime Piles Technique
Authors: Karkush Mahdi O. , Kareem Mahmoud S. Abdul , Babu Sivakumar
Published: September 2021

This study aims to use the concept of sustainability and provide guidance to geotechnical engineers to contribute towards greater sustainability in geotechnical design and construction. The methodology of the sustainability framework aims to support indicators and tools used in the sustainability concept in geotechnical engineering. In addition, available indicators will be used to analyze the role of natural resources, social impacts, environmental and economic aspects. In order to demonstrate the sustainability assessment approach, a case study is evaluated using the methodology of sustainability framework by using Multi-Criteria Analysis (MCA). The assessment is studied for raft footing and deep foundations (driven and bored piles A foundation treatment of 15×15 m and 0.45 m thickness to carry a high static load or to carry cyclic loading is analyzed. The results indicate the calculations of sustainability indices from the multicriteria analysis show that the option of raft footing than deep foundation if raft provides adequate allowable load by improving the soil using lime piles technique is sustainable.
Do Adsorbent Pore Size and Specific Surface Area Affect The Kinetics of Methyl Orange Aqueous Phase Adsorption?
Authors: IWUOZOR KINGSLEY OGEMDI , Ighalo Joshua O. , Emenike Ebuka Chizitere , Igwegbe Chinenye Adaobi , Adeniyi Adewale George
Published: September 2021

The kinetics of any adsorption reaction gives more information on the rate at which the adsorbate is taken up by the adsorbent, which is responsible for the residence time of an adsorbate uptake at the adsorbent-aqueous phase interface. This study was aimed at determining the effect of pore size as well as specific surface area (SSA) on the kinetics of the uptake of methyl orange (MO). The basis of the analysis was from data on kinetic models sourced from recent literature. ANOVA of the data revealed that statistical significance was achieved for SSA but not for pore size (at a significance level of 0.05). This called for a more theoretical perspective on the research data. The kinetics constant for micropores is far higher than for the two selected regimes of the mesopore. For the SSA, 100–10 m2/g adsorbents had a higher mean k2 value. This suggested that adsorbents in the SSA range had pore sizes that favour rapid uptake. However, further studies will be needed to gain a better understanding of how SSA affects adsorption kinetics. The study also discussed the technical limitations that could arise due to the use of kinetic model linearisation.
Attitudes Toward End-Of-Life Decisions Other Than Assisted Death Amongst Doctors in Northern Portugal
Authors: Gonçalves José António Ferraz
Published: September 2021

Background

Doctors often deal with end-of-life issues other than assisted death, such as incompetent patients and treatment withdrawal, including food and fluids.
Methods

A link to a questionnaire was sent by email three times, at intervals of one week, to the doctors registered in the Northern Section of the Portuguese Medical Association.
Results

The questionnaire was returned by 1148 (9%) physicians. This study shows that only a minority of Portuguese doctors were willing to give one or more drugs in lethal doses to cognitively incompetent patients with an incurable, advanced, and progressive disease at the request of a family member or other close person, and even less would do it on their own initiative. Concerning the withdrawal of support of life measures in advanced and progressive diseases at the patient’s request, most doctors were in favor, but much fewer doctors agreed with the suspension of supportive life measures at the request of a family member, another close person, or by their own unilateral decision. However, concerning the suspension of food and fluids, fewer agreed with that action. Portuguese doctors favor the administration of drugs for suffering control, even foreseeing they could shorten life,
Conclusion

Most doctors in this study respect patients’ autonomy, but do not agree with measures decided by others that have an impact on patients’ survival. They also agree with the administration of drugs for suffering control, even considering the possibility of shortening life.
Obesity is Not Associated with Perioperative Adverse Events in Patients Undergoing Complex Revision Surgery for the Thoracolumbar Spine
Authors: Hirase Takashi , Ling Jeremiah F. , Haghshenas Varan ,   Richard Fuld 3rd, Dong David , Hanson Darrell S. , Meyer B. Christoph , Marco Rex A.W.
Published: September 2021

Study Design: Retrospective cohort studyObjective: This study sought to determine the relationship between obesity and perioperative adverse events (AEs) with patients undergoing complex revision thoracolumbar spine surgery while controlling for psoas muscle index (PMI) as a confounding variable.Methods: Between May 2016 and February 2020, a retrospective analysis of individuals undergoing complex revision surgery of the thoracolumbar spine was performed at a single institution. Obesity was defined as BMI ≥ 30.0 kg/m2. PMI < 500 mm2/m2 for males and < 412 mm2/m2 for females were used to define sarcopenia. A Spine Surgical Invasiveness Index (SSII) > 10 was used to define complex revision surgery. A multivariable logistic regression model was used to ascertain the effects of sarcopenia, obesity, age, and gender on the likelihood of the occurrence of any AE.Results: The study included 114 patients. 54 patients were in the obese cohort and 60 patients in the non-obese cohort. There was not a significant difference in perioperative outcomes of both the obese and non-obese patients. Multivariable analysis demonstrated that sarcopenic individuals had a significantly higher likelihood for an AE than non-sarcopenic individuals (OR: 7.53, 95% CI: 3.05-18.60). Obesity did not have a significant effect in predicting AEs.Conclusions: Obesity is not associated with perioperative AEs, 30-day readmission rates, 30-day re-operation rates, rate of discharge to a facility, or post-operative length of stay (LOS) among patients undergoing complex revision thoracolumbar spine surgery.Level of Evidence: III
Current Tobacco Use and Susceptibility To Using Tobacco Among Non-Users of Tobacco: A Cross-Sectional Study Among School-Going Adolescents in Sierra Leone
Authors: James Peter Bai , Kabba John Alimamy , Bah Abdulai Jawo , Idriss Ayesha , Kitchen Chenai , Conteh Eugene B , Lahai Michael , Dalinjong Philip Ayizem
Published: September 2021

Background
Tobacco use is a global health threat associated with a high disease burden and deaths. Studies concerning current tobacco use and susceptibility to using tobacco products among adolescents who are potential adult tobacco users in Sierra Leone have not been explored. We aimed to estimate the prevalence and correlates of current tobacco use and tobacco non-users susceptibility to using tobacco amongst Sierra Leonean high-school students.
Method
We used data obtained from the 2017 Sierra Leone Global Youth Tobacco Survey (GYTS), which presented information collected from 6680 students aged 11-17years nationwide. Gender-based correlates of current use and susceptibility to using tobacco among non-tobacco users were determined by complex sample logistic regression analyses. Adjusted odds ratios (AOR) and respective 95% confidence intervals (CIs) were reported. p-values less than 0.005 were considered significant.
Results
The prevalence of current tobacco use among high school adolescents in Sierra Leone was 10.7% and was higher in males (12.2%) than in females (7.4%). Male [AOR = 1.32 (95%CI:1.01–1.72)], exposure to household secondhand smoke [AOR = 2.68(95%CI:1.71–4.20)], having peers who smoke [AOR = 3.07(1.53–6.16)] were more likely to be currently using tobacco. On the other hand, adolescents exposed to antismoking media messages were less likely to be current tobacco users [AOR = 0.45(95%CI: 0.24–0.83)]. The overall tobacco non-users susceptibility to using tobacco among adolescents in Sierra Leone was 18.2% [male (18.0%), female (18.5%)]. Exposure to tobacco promotion [AOR = 1.50(95%CI:1.07–2.11)] and non-exposure to antismoking education [AOR = 1.39(95%CI:1.04–1.85)] were significantly associated with tobacco non-users’ susceptibility to using tobacco.
Conclusion
Our study suggests that one-in-ten school-going adolescents currently use tobacco, with nearly one in five non-users susceptible to using tobacco. Given the high prevalence of tobacco product use among Sierra Leonean adults, our findings highlight the need for policies and interventions to prevent tobacco use behaviour among adolescents aimed at averting tobacco use in adulthood.
Valorization of Fig (Ficus carica Linn.) Waste Leaves: HPLC-QTOF-MS/MS-DPPH System For Online Screening And Identification of Antioxidant Compounds
Authors: Li Chunying , Yu Meiting , Li Shen , Yang Xue , Qiao Bin , Shi Sen , Zhao Chunjian , Fu Yujie
Published: September 2021

Fig (Ficus carica Linn.) leaves are produced each year and often thrown away as wastes, resulting in a waste of resources. Fig waste leaves are rich in flavonoids, which have strong antioxidant activity, however, the antioxidant components are not clear. So as to take full advantage of fig waste leaves, antioxidant capacity of different extracts (petroleum ether, ethyl acetate and water) was evaluated by 1, 1-diphenyl-2-picrylhydrazyl (DPPH), 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS) and ferric-ion reducing antioxidant power (FRAP) methods. The results showed that flavonoids in ethyl acetate extraction had the highest content, 83.92 ± 0.01 mg/g, and maximum DPPH scavenging activity (IC50 0.54 mg/mL), highest ABTS scavenging rate (80.28%), FRAP (3.46 mmol/g). Furthermore, HPLC-QTOF-MS/MS-DPPH method was developed for the first time to identify 11 flavonoids in fig waste leaves. This rapid and efficient method can not only be used for screening the antioxidant components in fig waste leaves, but also can be combined with mass spectrometry to identify the compounds with antioxidant capacity. There are three flavonoids with significant antioxidant capacity, which are 3-O-(rhamnopyranosyl-glucopyranosyl)-7-O-(glucopyranosyl)-quercetin, isoschaftoside and rutin. The results confirmed that fig waste leaves contain a variety of antioxidant components, which contributed to increase the value of fig waste leaves as antioxidants.
Study on the Mechanism of Lactobacillus Rhamnosus Probio-M9 Combined With Antibiotics on Staphylococcus Aureus Mastitis in Rat
Authors: Bo Xu Rui , Zhang Heping
Published: September 2021

This study aims to investigate the potential anti-inflammatory mechanism of Lactobacillus rhamnosus Probio-M9 (Probio-M9) combined with antibiotics. Probio-M9, a probiotic strain previously isolated from the milk of healthy women. The Illumina Hiseq platform performs metagenomic sequencing on faeces samples at various time points; UPLC-Q-TOF/MS is used to detect a large number of endogenous metabolites in the serum of rats with mastitis induced by Staphylococcus aureus. The results show that the Probio-M9 combined with antibiotics increases beneficial intestinal bacteria (Lactobacillus murinus, Lactobacillus reuteri) and positively regulates metabolites (linoleic acid, glycerophospholipids, arachidonic acid, Sphingolipids. etc.), reduce inflammation in the body to play a protective role against mastitis. This research provides a new research method to relieve mastitis, and also provides a theoretical basis for the development and utilization of Probio-M9.
Screening and Purification of NanB Sialidase from Pasteurella Multocida with Activity in Hydrolyzing Sialic Acid Neu5Acα(2-6)Gal
Authors: Nugroho Christian Marco Hadi , Kurnia Ryan Septa , Tarigan Simson , Silaen Otto Sahat Martua , Widyaningtyas Silvia Tri , Wibawan I Wayan Teguh , Natalia Lily , Soebandrio Amin
Published: September 2021

Study on sialidases as antiviral agents has been widely performed, but many types of sialidase had not been tested for their antiviral activity. One of such sialidase is the NanB sialidase of Pasteurella multocida, which has never been isolated for further study. In this study, the activity of NanB sialidase was investigated in silico by docking the NanB sialidase of Pasteurella multocida to the Neu5Acα(2-6)Gal ligand. Additionally, some local isolates of Pasteurella multocida, which had the NanB gene were screened, and the proteins were isolated for further testing regarding their activity in hydrolyzing Neu5Acα(2-6)Gal. In silico studies showed that the NanB sialidase possesses an exceptional affinity towards forming a protein-ligand complex with Neu5Acα(2-6)Gal. This was further confirmed by showing that a dose of 0.258 U/ml (100%) NanB sialidase of Pasteurella multocida B018 can hydrolyze up to 44.28% of Neu5Acα(2-6)Gal in chicken red blood cells and 81.95% in rabbit red blood cells. This study suggested that the NanB sialidase of Pasteurella multocida B018 has a potent antiviral activity that can inhibit avian influenza virus infection.
Estimating the Two Graph Dextran-Stearic Acid-Spermine Polymers Based on Iron Oxide Nanoparticles as Carrier for Gene Delivery
Authors: Ashtiyani Mehrnoosh Kazemi , Hajipour-Verdom Behnam , Satari Mohammad , Abdolmaleki Parviz , Hosseinkhani Saman , Shaki Hossein
Published: September 2021

BackgroundNon-viral gene carriers because of their limited side effects, biocompatibility, simplicity and taking the advantages of electrostatic interactions have shown noticeable potential in gene delivery. The low transfection rate of non-viral vectors under physiological conditions is a significant issue. MethodsWe investigated the efficacy of hydrophilic and hydrophobic groups on gene carriers such as two synthesized amphiphilic polymer of dextran-stearic acid-spermine (DSASP) with verified lipid and amine conjugations that associated with Fe3O4 superparamagnetic nanoparticles to promote the target delivery and decrease the transfection time using static magnetic field.ResultsOur findings illustrate that magnetic nanoparticles are spherical with positive surface charges and superparamagnetic behaviors. The DSASP–pDNA/MNPs offered a strong pDNA condensation, protection against DNase degradation, significant cell viability in HEK 293T cells. Although conjugations of spermine play a critical role in transfection efficiency, amphiphilic polymer with more derivatives of stearic acid showed better transfection yields. ConclusionDSASP amphiphilic magnetic carriers offer new insights for gene delivery due to the amine contents and ameliorate the uptake of complexes via cell membrane based on its hydrophilic surface.
hsa-miR-124-3p: A New Potential Prognostic Target For Multiple Myeloma
Authors: Gong Hui , Kang Chunxiang , Du Fang , Zhou Shengtang
Published: September 2021

The relationship of Exosomal RNAs released within the bone marrow microenvironment and Prognosis of patients with multiple myeloma has not been thoroughly studied. This study aims to evaluate which exosomal RNAs can prompt the prognosis of patients with multiple myeloma. Exosomes were isolated from the bone marrow fluid of patients with good treatment effect or not. Then they were characterized by dynamic light scattering, transmission electron microscopy, and Western blot analysis. The isolated exosomes stimulate PRMI8226 cells, observe the migration ability and proliferation ability of PRMI8226 cells. Then we performed exosome miRNA sequencing, performed bioinformatics analysis of differential miRNAs, and evaluated several miRNAs that may affect the treatment effect. To determine the actual value of these miRNAs in clinical applications, we collected a collection of clinical samples for verification. We found that bone marrow-derived exosomes from patients with different therapeutic effects have different effects on PRMI8226 cells. Exosomes with a poor prognosis can promote the proliferation and migration of PRMI8226 cells, while exosomes with a good prognosis have no impact on PRMI8226 cells. The miRNA sequencing results showed differentially expressed miRNAs in exosomes from different sources. These differential miRNAs can be enriched in pathways related to cancer development. Validation in clinical specimens found that exosomal mir-124-3p are highly expressed in patients with poor therapeutic effects. This study suggested exosomal miRNA plays a vital role in the development and treatment of multiple myeloma. Some miRNAs that can promote tumor progression are highly expressed in bone marrow exosomes of patients with poor therapeutic effects, such as hsa-miR-124-3p, hsa-miR-451b, hsa-miR-509-3p. Among them, hsa-miR-124-3 is promising as a predictor of therapeutic effect.
Immunogenomic Analyses of the Prognostic Predictive Model for Patients with Renal Cancer
Authors: Feng Tao , Zhao Jiahui , Wei Dechao , Guo Pengju , Yang Xiaobing , Li Qiankun , Fang Zhou , Wei Ziheng , Li Mingchuan , Jiang Yongguang , Luo Yong
Published: September 2021

Background: Renal cell carcinoma (RCC) is associated with poor prognostic outcomes. The current stratifying system does not predict prognostic outcomes and therapeutic benefits precisely for RCC patients.Methods: Herein, an immune prognostic signature was developed, and its predictive ability was confirmed in the cohorts based on TCGA-KIRC dataset. Several immunogenomic analyses were conducted to investigate the correlations between immune risk scores and immune cell infiltrations, immune checkpoints, cancer genotypes, tumor mutational burden, and responses to chemotherapy and immunotherapy.Results: The immune prognostic signature contained 14 immune-associated genes and was found to be an independent prognostic factor for KIRC. Furthermore, the immune risk score was established as a novel marker for predicting the overall survival outcomes for RCC. The risk score was correlated with some significant immunophenotypic factors, including T cell infiltration, antitumor immunity, antitumor response, oncogenic pathways, and immunotherapeutic and chemotherapeutic response.Conclusions: The immune prognostic, predictive model can be effectively and efficiently used in the prediction of survival outcomes and immunotherapeutic responses of RCC patients.
The Use of Postoperative CRP Levels in Patients With Crohn’s Disease
Authors: Slavin Moran , Goldstein Avygial , Raguan Barak , Rudnicki Yaron , Avital Shmuel , White Ian
Published: September 2021

Background: In colorectal cancer, CRP levels on postoperative days 3-4 have a strong negative predictive value for an anastomotic leak, with threshold values of ~15 on POD 3 and ~13 on POD 4. In Crohn’s disease, CRP levels are perceived as unreliable in the postoperative period because of the underlying inflammatory process. The aim of this study was to investigate the use of postoperative CRP levels in patients with Crohn’s Disease and set threshold values for this population. Methods: This is a retrospective study of the medical records of adult patients with Crohn’s Disease who underwent bowel anastomoses, at a single, high volume center. The operations were performed by a single colorectal consultant who is an inflammatory bowel disease specialist, between 1/2012 and 12/2017. Results: 92 operations were performed. Mean CRP levels and CRP threshold values were higher in the study’s population compared with studies on colorectal cancer patients. A CRP level of 19.56 mg\dL on postoperative day 3 had an area under the curve of 0.865 (sensitivity 88%, specificity 73%) and a NPV of 98% for an anastomotic leak. Patients with an anastomotic leak showed a trend towards decreased postoperative albumin levels (p=0.06). Conclusions: Postoperative CRP values are higher in Crohn’s Disease compared with colorectal cancer. Postoperative CRP levels may rule out anastomotic leaks in patients with Crohn’s Disease with threshold values of 20.3 mg/dL in POD 3, 19.5 mg/dL in POD 4 and 16.7 mg\dL in POD 5.
In-Vivo Comparative Virulence of Different White Spot Syndrome Virus Isolates In Penaeus Vannamei And Whole Genome Comparison Analysis
Authors: Hernández-Montiel Álvaro Hernán , Weidmann Manfred , Bekaert Michael , Ulrich Kristina , Benkaroun Jessica , Giffard-Mena Ivone
Published: September 2021

White Spot Syndrome Virus (WSSV) infects several economically important aquacultural species, causing significant losses to the industry. This virus belongs to the Nimaviridae family, and has a dsDNA genome ranging from 257 to 309 kb (more than 20 isolate genomes fully sequenced and published to date). Multiple routes of infection could be the cause of the high virulence and mortality rates detected in shrimp species. In particular, Penaeus vannamei, differences in isolate virulence have been observed, along with controversy over whether deletions or insertions are associated with gain or loss of virulence.The pathogenicity of three isolates from three locations in Mexico (two from Sinaloa: 'CIAD', and 'Angostura', and one from Sonora: 'Sonora') was evaluated in vivo in white shrimp (P. vannamei) infection assays. Differences were observed in the mortality rate of shrimp among the three isolates, with the Sonora isolate being the most virulent. Subsequently, the complete WSSV genomes were sequenced in depth from the tissues of infected shrimp, and assembled in reference to the genome of isolate CN01 (KT995472), identifying genome sizes for Angostura and Sonora of 289,350 bp and 288,995 bp, respectively. Where three deletion zones were identified compared to CN01 comprising 15 genes, including three envelope proteins VP41A, VP52A and VP41B, one non-structural protein ICP35 and 11 others encoding proteins whose function is currently unknown. In addition, five genes (wsv129, wsv178, wsv204, wsv249 and wsv497) show a modified number of repeat motifs. The main implications and possible effects on viral infection of these modifications are discussed.
The Apoptosis-inducing Antiproliferative Activity and Quantitative Phytochemical Profiling of Polyphenol-rich Part of Leea Aequata L. Leaves
Authors: Mostofa Md. Golam , Reza A. S.M. Ali , Khan Zidan , Tsukahara Toshifumi , Alam AHM Khurshid , Sadik Md Golam
Published: September 2021

Aim/Objectives: Oxidative stress (OS) caused by the accumulation of free radicals in the body triggers many life-threatening diseases, including cancer. Plants are the rich source of safe and effective medicinal compounds like antioxidants that can prevent OS by scavenging free radicals. The aim of this study was to explore the chemical compositions of the methanolic extract of Leea aequata L. leaves possessed the highest antioxidant and cytotoxic activities.Methods and Materials: The Leea aequata leaves (LAL) was extracted with 80% methanol and the crude methanolic extract of LAL (CME) was successively fractionated with petroleum ether, chloroform, ethyl acetate and finally with water to get petroleum ether (PEF), chloroform (CHF), ethyl acetate (EAF) and aqueous (AQF) fraction, respectively. The antioxidant activity was evaluated by the in vitro standard spectrophotometric methods. The MTT colorimetric method was used to measure cytotoxic activity. Apoptosis was measured using fluorescein annexin V-FITC/PI staining method. GC-MS was used to investigate phytochemical compositions.Results: Among the fractions, the highest phenolic and flavonoid-rich fraction was EAF, which contained 267.05± 8.53 mg of gallic acid equivalent (GAE) and 152.98±1.96 mg of catechin equivalent (CAE)/gm of dried extract, respectively. The EAF was found to be the highest antioxidant and reducing power activities. Also, EAF had the strongest free radical scavenging activity with IC50 values of 5.11, 36.54 and 38.96 µg/mL for DPPH, hydroxyl and lipid peroxide free radicals, respectively. Moreover, EAF significantly reduced the HeLa cell proliferation and it was due to the induction of apoptosis of HeLa cells. Furthermore, GC-MS data revealed that EAF contained 17 compounds. Methyl esters of long chain fatty acid were the major chemical constituents. Interestingly, hexadecanoic acid, methyl ester; 9-octadecenoic acid (Z)-, methyl ester; 9,12-octadecadienoic acid, methyl ester (Z, Z) and phenol, 2,4-bis(1,1-dimethylethyl) are known to be antioxidant and cytotoxic. Antioxidant and anti-cancer activity were significantly correlated with the total content of phenolics and flavonoids, suggest that the fractions could be the good source of antioxidant and anti-cancer agents.Conclusion: The EAF of Leea aequata has strong polyphenolic content compared to the other fractions. The cytotoxic and antioxidant activity of Leea aequata were due to the presence of different bioactive compounds.
Long Non-coding RNA SNHG25 Promotes the Malignancy of Endometrial Cancer by Sponging microRNA-497-5p and Thereby Increasing FASN Expression
Authors: He Yuhua , Xu Shuifang , Qi Yi , Tian Jinfang , Xu Fengying
Published: September 2021

BackgroundSmall nucleolar RNA host gene 25 (SNHG25), a long-noncoding RNA, has been well studied in epithelial ovarian cancer. Yet, the specific functions of SNHG25 in endometrial cancer (EC) have not been researched. In this study, we proposed to expose the clinic significance of SNHG25 in EC, and then unravel the regulatory activity of SNHG25 on the tumor-associated phenotype of EC. More interestingly, the possible molecular events occurred when SNHG25 executives its function in EC were explored thoroughly. MethodsWe measured genes expression applying quantitative real-time polymerase chain reaction. The detailed functions of SNHG25 in EC were examined employing loss-of-function experiments. What’s more, we unveiled the regulatory mechanisms among SNHG25, microRNA-497-5p and fatty acid synthase (FASN) with the application of luciferase reporter assay and RNA Immunoprecipitation. ResultsWe verified a high level of SNHG25 in EC through TCGA dataset and our own cohort. Patients with a high SNHG25 level featured shorter overall survival in contrast to patients with a low SNHG25 level. SNHG25 deficient caused tumor-repressing actions in EC cells by decreasing cell proliferation, migration and invasion and promoting cell apoptosis. Furthermore, we certified the function of SNHG25 depletion in impairing tumor growth in vivo. With respect to the mechanisms, SNHG25 sequestered miR-497-5p as a competing endogenous RNA in EC and consequently positively regulated FASN expression. Striking, the decrease of miR-497-5p or increase of FASN could neutralize the modulatory actions of SNHG25 knockdown in EC cells. Conclusions﻿Depleted SNHG25 hampered the oncogenicity of EC by targeting miR-497-5p/FASN axis. The newly certified SNHG25/miR-497-5p/FASN pathway may potentially have usefulness as a promising target for molecular targeted management.
Fractional-order LCL filters: principle, frequency characteristics, and their analysis
Authors: Xu Junhua , Li Xiaocong , Luo Xueli , Hou Liliang , Qin Jianbo , Meng Xuanren
Published: September 2021

In this paper, a fractional-order LCL (FOLCL) filter is constructed by introducing fractional-order inductors (FOIs) and fractional-order capacitors (FOCs) to replace the inductors and capacitors in a traditional integer-order LCL (IOLCL) filter, respectively. The principle and frequency characteristics of an FOLCL filter are systematically studied, and five important properties are derived and demonstrated in-depth. One of the most important achievements is that we discover the necessary and sufficient condition for the existence of resonance for an FOLCL filter, that is, the sum of the order of the FOIs and the FOC is equal to 2, which provides a theoretical basis for avoiding the resonance of an FOLCL filter effectively in design. The correctness of the theoretical derivation and analysis are verified by digital simulation. Compared with an IOLCL filter, an FOLCL filter presents more flexible and diverse operating characteristics and has a broader application prospect.
Ethnobotanical Survey of Flora Used in Maasai Food System and Traditional Medicine against Gout-related and Other Human Ailments in Monduli, Arusha, Tanzania
Authors: Clement Richard Paul , Raymond Jofrey , Chacha Musa N
Published: September 2021

Background: Flora used by Maasai practitioners (MSPs) in traditional medicine (TM) and food system (FS) were investigated in Monduli District, Arusha, Tanzania. The objective of this study was to document the knowledge on flora used by MSPs in their FS and TM against gout-related and other ailments.Methods: Ethnobotanical knowledge held by 21 MSPs was investigated following standard approaches. Guided field walk, free listing, rigorous individual-interviews and local market surveys were employed to obtain information. Use value (UV) index, relative frequency of citation (RFC), specific RFC (RFCs), fidelity level (FL) and informant consensus factors (ICF) matrices were involved to determine the knowledge on flora used in Maasai FS and TM against gout-related and other ailments.Results: A total of 101 plant species in 83 genera and 47 families, used in Maasai FS and TM were recorded. Food, food processing or storage, and medicinal plant (MPs) flora accounted 29, 32 and 80 species respectively. MPs treated more than 38 ailments. A high proportion of plants recovered, was trees 45.19%; while 88.79% were retrieved from the wild habitat. Roots were mostly used part (30.73%); preparations were made from fresh or dry material and 44-species involved decoction in meat broth or stock. The frequently route of delivery was oral, 85.19%. About 37.5% of the MPs were used to treat joints’ pain or inflammation (ICF = 0.52) whereas, mostly used was Rapanea melanophloeos (FL = 1.00; RFCs = 0.29) followed by Withania somnifera (FL = 0.5; RFCs = 0.24). Withania somnifera frequently used against other gout-related ailments. Vangueria infausta and Olea europaea subsp. Africana uses in FS ranked the highest.Conclusion: The study area is very rich in flora biodiversity, and the flora is an integral part of the indigenous foods’ and health care systems. The flora is exposed to various destructive anthropogenic activities; thus, integrated conservation measures are required. The rich ethnobotanical knowledge held by MSPs, requires an in-depth study and documentation. Investigations of flora used in the FS, and TM, with high FL, and RFCs could contribute to future nutraceuticals and drug discovery against gout and other ailments.
MiR-154-5p Inhibits Prostate Cancer Bone Metastasis by Inactivating PI3K/AKT Signaling
Authors: Ren Dong , Yuan Xiangwei , Cao Jiazheng , Wang Bin , Li Ruixiao , Zhang Rui , Liu Baoyi , Wu Meimei , Ren Liangliang , Meng Zijie , Wu Wanting , Chai Xingxing , Li Lili , Li Ronggang , Huang Xiufang , Wu Jinhua , Zheng Yan , Zeng Jincheng , Zhang Xin , Huang Junjiu , Xue Zhonglin , Li Yuming
Published: September 2021

Background: Generally, both strands of a single pre-miRNA have been demonstrated to play a similar role in the same tumor type. However, there are no available literatures yet so far clarifying the opposite roles of both strands froma single miRNAin one tumor type. The purpose of this study is to investigate the functional role of both strands of miR-154 in bone metastasis of prostate cancer (PCa). Methods: miR-154-5p expression was examinedin 285 clinicalPCa tissuesby in situ hybridization. The clinical correlation ofmiR-154-5p expression with clinicopathological features,and overall and bone metastasis-free survival inPCa patients was evaluated by Kaplan-Meier survival and statisticalanalysis. The biological roles of miR-154-3p and miR-154-5p in the bone metastasis of PCa were investigated both in vitroand in vivo.Bioinformatics analysis, western blot and luciferase reporter analysis were used to determinethe potential targets of miR-154-5p.Luciferase assay and Western blotting were performed to clarify the underlying pathway implicated in the role of miR-154-5p in bone metastasis of PCa.Results: Contrary to the well established pro-bone metastatic role of miR-154-3p in PCa, we found that miR-154-5p expression was reduced in PCa tissues with bone metastasis andbone metastatic PCa cell lines. Downexpression of miR-154-5p was positively associated with bone metastasis status, and predicted poorer bone metastasis-free survival in PCa patients. Gain of function experiments showed that upregulating miR-154-5p repressed, while silencing miR-154-5p promoted invasion, migration and proliferation capacities of PCa cells in vitro. Conversely, miR-154-3p yielded an opposite effect oninvasion and migration capacities of PCa cells. Importantly, administration of agomir-154-5p effectivelyinhibited bone metastasis of PCa cellsin vivo. Mechanistic dissection further demonstrated miR-154-5p inhibited invasion, migration and proliferation by targeting EGFR and FGFR1, leading to inactivation of PI3K/AKT signaling. However, the autocrine levels of corresponding ligands in the supernantant of PCa cells were not affected by the changed expression of miR-154-5p.Conclusion: Our results for the first time reveal the different role of both strands froma single miRNA in bone metastasis of PCa, which will facilitate the development of anti-bone metastatic therapeutic strategy in PCa.
Fused in Sarcoma (FUS) Expression May Predict Survival Outcomes of Patients With Advanced Squamous Cell Cervical Carcinoma
Authors: Fachini Ana Maria Dias , Sarian Luís Otávio , Talarico Maria Cecília Ramiro , Nunes Rafaella Almeida Lima , Costa Larissa Bastos Eloy , Zuliani Antonio Carlos , Termini Lara , Rabelo-Santos Silvia Helena , Zeferino Luiz Carlos
Published: September 2021

Because of its role in preserving DNA/RNA stability, there is an increasing number of studies addressing the relationship between Fused in Sarcoma (FUS) expression and cancer. However, the disparity in FUS/FUS oncogenic vs. tumor-suppressive roles may be attributed to the complex molecular pathways associated with FUS regulation in different cancer types, and its role in cervical carcinogenesis remains largely unexplored. Methods: We determined FUS protein expression in specimens of 61 patients with advanced cervical cancer. Long-term (> 10 years) clinical follow-up data for these patients were available, and we determined disease-free, cancer-related and overall survival as related to FUS expression. Results: There were no significant associations between FUS expression and patients’ age, tumor grade, and acute/late toxicity events related to treatment (either radiation alone or chemoradiation). However, multivariate Cox regression analysis for disease-free survival (recurrence), overall survival (death) and cancer-related survival showed that patients with high average FUS expression fared significantly better than their counterparts with low average FUS expression, both in terms of disease-free survival (HR = 0.31; 95%CI 0.12 to 0.77; p = 0.01) and cancer-related survival (HR = 0.41; 95%CI 0.17 to 0.98; p = 0.04). Conclusions: Our study shows that high FUS protein expression in advanced cervical cancer specimens is a potent harbinger of better prognosis, and can as such be used in clinical practice to help characterize patients and, possibly, plan treatment and follow-up strategies.
Tumor Microenvironment-responsive Nanodrug for Clear-cell Renal Cell Carcinoma Therapy via Triggering Waterfall-like Cascade Ferroptosis
Authors: Ni Wenjun , Li Yongxiang , Liang Lingxia , Lu Cuixia , Zhan Meixiao , Lu Ligong , Xie Qun , Wen Liewei
Published: September 2021

BackgroundThe most common type of kidney tumor, clear-cell renal cell carcinoma (ccRCC) with relatively insidious development and easily metastatic characteristics is generally insensitive to cytotoxic chemotherapy. Advanced ccRCC lacks effective treatment and has a poor prognosis. Fortunately, ccRCC with the hallmark of abundant polyunsaturated fatty acids (PUFAs) content is regarded as intrinsically vulnerable to ferroptosis-based therapeutic strategies. Nonetheless, the classic ferroptosis agonist (RSL3) with low specificity for tumors, short half-life in the blood, poor water solubility and deficient accumulation at the tumor site prevents its reliable application in vivo. ResultsIn this study, iron-based metal-organic framework nanoparticles (MIL-101(Fe) NPs) delivered RSL3 to ccRCC tumors, and then released the iron ions and RSL3 accompanied by the degradation of MIL-101(Fe) NPs in the acidic tumor microenvironment. The MIL-101(Fe)@RSL3 as a pH-responsive nanodrug causes cellular iron overload and promotes the hydroxyl radical (•OH) generation by Fenton reaction to attack PUFAs, leading to the aberrant accumulation of lipid peroxides (L-OOH). Additionally, RSL3 directly inhibits glutathione peroxidase 4 (GPX4) to detoxify L-OOH, and ferrous ions further catalyze the irreversible conversion of highly reactive lipid alkoxyl radicals (L-O•) from L-OOH to triggering waterfall-like cascade ferroptosis. In contrast to the limited antitumor efficiency of free RSL3, MIL-101(Fe)@RSL3 with high encapsulation efficiency (88.7%) shows a significant ccRCC-specific antitumor effect and negligible side effects.ConclusionMIL-101(Fe)@RSL3 could aggravate ferroptosis and be expected to be a promising nanodrug for ccRCC systemic therapy due to the targeted delivery and responsive release of RSL3 and iron ions.
Down-Regulated MAC30 Suppresses Lung Cancer Invasion and EMT by Inhibiting Wnt/β-Catenin Signaling Pathway
Authors: zhou jingzhu , ji xiuhai , chen ruhua , fen yan , ding Hui
Published: September 2021

Backgrounds：Over-expressed meningioma-associated protein (MAC30) was proved to be a biomarker for worse prognosis in non–small cell lung cancer (NSCLC). However, the regulated mechanism of MAC30 in epithelial–mesenchymal transition (EMT) and lung cancer invasion is unknown. Methods：Transformed growth factor (TGF-β) was used to induce EMT in A549 cells in vitro. MAC30 siRNA was transfected into cells to silence the gene expression. Real-Time PCR was prepared to assess the levels of MAC30 mRNA. Methyl thiazolyl tetrazolium (MTT) and Transwell invasion assays were performed to study the proliferation and invasion of A549 cells. Expression of MAC30, EMT-related proteins, Wnt/β-catenin signal and its downstream factors were explored by ELISA. Results: We found enhanced MAC30 expression in A549 cells. MAC30 Knockdown inhibited TGF-β-induced lung cell proliferation and invasion. Furthermore, elevated levels of mesenchymal markers (N-cadherin, vimentin) and decreased levels of epithelial markers E-cadherin in A549 cells with TGF-β incubation were reversed by MAC30 siRNA. Finally, MAC30 knockdown significantly suppressed TGF-β-upregulated protein levels of Wnt/ β-catenin signaling and its downstream genes (surviving, c-myc and cyclin D1). Conclusions: We firstly confirm that MAC30 knockdown limits lung cancer growth and EMT through inhibiting the activation of Wnt/β-catenin pathway.
Promiscuity Mapping of the S100 Protein Family Using a High-Throughput Local Surface Mimetic Holdup Assay
Authors: Simon Márton A. , Bartus Éva , Mag Beáta , Boros Eszter , Roszjár Lea , Gógl Gergő , Travé Gilles , Martinek Tamás A. , Nyitray László
Published: September 2021

S100 proteins are small, typically homodimeric, vertebrate-specific EF-hand proteins that establish Ca2+-dependent protein-protein interactions in the intra- and extracellular environment and are overexpressed in various pathologies. There are about 20 distinct human S100 proteins with numerous potential partner proteins. Here, we used a quantitative holdup assay to measure affinity profiles of most members of the S100 protein family against a library of chemically synthetized foldamers. The profiles allowed us to quantitatively map the binding promiscuity of each member towards the foldamer library. Since the library was designed to systematically contain most binary natural amino acid side chain combinations, the data also provide insight into the promiscuity of each S100 protein towards all potential naturally occurring S100 partners in the human proteome. Such information will be precious for future drug design to interfere with S100 related pathologies.
Entropic Associative Memory for Manuscript Symbols
Authors: Morales Rafael , Hernández Nóe , Cruz Ricardo , Cruz Victor D. , Pineda Luis A.
Published: September 2021

Manuscript symbols can be stored, recognized and retrieved from an entropic digital memory that is associative and distributed but yet declarative; memory retrieval is a constructive operation; symbols not contained in the memory are rejected directly without search; and memory operations can be performed through parallel computations. Manuscript symbols, both letters and numerals, are stored in Associative Memory Registers that have an associated entropy. The memory recognition operation obeys an entropy trade-off between precision and recall, and the entropy level impacts on the quality of the objects recovered through the memory retrieval operation. We discuss the operational characteristics of the system for retrieving objects with both complete and incomplete information, such as severe occlusions. The experiments reported in this paper add evidence that supports the scalability of the framework and its potential for developing practical applications. We also compare the present entropic associative memories to Hopfield’s paradigm and discuss its potential for the study of natural memory.