bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of the Delta Change Approach on the Severity of Ice-jam Flooding Under Future Climate Scenarios
Authors: Das Apurba , Rokaya Prabin , Lindenschmidt Karl-Erich
Published: August 2021

Projection of the impact of future climate on ice-jam flood intensity is an essential component of a flood mitigation strategy for many northern communities. General Circulation Model (GCM) outputs are used to derive hydrological conditions under future climate scenarios. Although GCMs are often downscaled to a point of interest, there can still be significant differences between modelled climate scenarios and historically observed climate scenarios. Therefore, the model-indicated changes between baseline and future values of climatic scenarios are applied to observed baseline values to estimate projected future values. This can be carried out by using the delta change method which is an approach for adjusting GCM output. This study evaluates the impact of the delta change method on the frequency and severity of ice-jam flooding under a future climate scenario. The Athabasca River at Fort McMurray is presented as the test site. Streamflow conditions were derived from a physically-based hydrological model, Modélisation Environnementale communautaire-Surface Hydrology (MESH), by forcing the Canadian Regional Climate Model (CRCM) driven by the Third Generation Coupled Climate Model (CGCM3) for both baseline (1971–2000) and future (2041–2070) periods. Streamflow under future climatic conditions was developed based on the delta change method for both absolute and relative changes. The adjusting streamflow was then used in a fully dynamic river ice hydraulic model, RIVICE, to project future ice-jam scenarios using a stochastic modelling framework. Finally, the impact of the delta changes on the frequency and severity of simulated ice-jam flooding was assessed by producing ice-jam stage-frequency distributions (SFDs) under future climatic conditions. The results indicate that there is a notable difference in the projected frequency and severity of ice-jam flooding between absolute and relative change approaches.
Historical Variability And Future Changes In Seasonal Extreme Temperature Over Iran
Authors: Zarrin Azar , Dadashi-Roudbari Abbasali , Hassani Samira
Published: August 2021

The extreme temperature indices (ETI) are an important indicator of climate change, the detection of their changes over the next years can play an important role in the Climate Action Plan (CAP). In this study, four temperature indices (Mean of daily minimum temperature (TN), Mean of daily maximum temperature (TX), Cold-spell duration index (CSDI), and Warm-spell duration index (WSDI)) were defined by ETCCDI and two new indices of the Maximum number of consecutive frost days (CFD) and the Maximum number of consecutive summer days (CSU) were calculated to examine ETIs in Iran under climate change conditions. We used minimum and maximum daily temperature of five General circulation models (GCMs) including HadGEM2-ES, IPSL-CM5A-LR, GFDL-ESM2M, MIROC-ESM-CHEM, and NorESM1-M from the set of CMIP5 Bias-Correction models. We investigated Two Representative Concentration Pathway (RCP) scenarios of RCP4.5 and RCP8.5 – during the historical (1965-2005) and future (2021-2060 and 2061-2100) periods. The performance of each model was evaluated using the Taylor diagram on a seasonal scale. Among models, GFDL-ESM2M and HadGEM2-ES models showed the highest, and NorESM1-M and IPSL-CM5A-LR models showed the lowest performance in Iran. Then an ensemble model was generated using Independence Weighted Mean (IWM) method. The results of multi-model ensembles (MME) showed a higher performance compared to individual CMIP5 models in all seasons. Also, the uncertainty value was significantly reduced, and the correlation value of the MME model reached 0.95 in all seasons. Additionally, it is found that WSDI and CSU indices showed positive anomalies in future periods and CSDI and CFD showed negative anomalies throughout Iran. Also, at the end of the 21st century, no cold spells are projected in almost every part of Iran. The CSU index showed that Iran's summer days are increasing sharply, according to the results of the RCP8.5 scenario in spring (MAM) and autumn (SON), the CSU will increase by 18.79 and 20.51 days, respectively at the end of the 21st century. It is projected that in the future, the spring and autumn seasons will be shorter and, summers, will be much longer than before.
Global methane and nitrous oxide emissions from non-marine waters
Authors: Zheng Yajing , Wu Shuang , Xiao Shuqi , Yu Kai , Fang Xiantao , Freeman Christopher , Liu Shuwei , Zou Jianwen
Published: August 2021

Non-marine waters (i.e., rivers, reservoirs, lakes, ponds, streams and estuaries) are globally significant emitters of methane (CH4) and nitrous oxide (N2O) to the atmosphere, while global estimates of these emissions have been hampered due to the lack of a worldwide comprehensive database with the collection of complete CH4 and N2O flux components. Here we synthesize 2997 in-situ flux or concentration measurements of CH4 and N2O from 277 peer-reviewed publications to examine the role of non-marine waters in shaping climate change. Here we estimate that inland waters including rivers, reservoirs, lakes and streams together release 94.49 Tg CH4 yr− 1 (ebullition plus diffusion) and 1.52 Tg N2O yr− 1 (diffusion) to the atmosphere, yielding an overall CO2-equivalent emission total of 3.05 Pg CO2 yr− 1, representing roughly 59% of CO2 emissions (5.13 Pg CO2 yr− 1) from these four aquatic ecosystems, with lakes acting as the largest emitter for both trace gases. Ebullition is noticed as a dominant flux component, contributing up to 62–84% of total CH4 fluxes across all inland waters. Chamber-derived CH4 flux rates are significantly greater than those determined by diffusion model-based methods for commonly capturing of both diffusive and ebullitive fluxes. The synthesis of global N2O measurements projected that rivers exhibit the highest indirect N2O emission factor (EF5, 0.028%), while streams have the lowest EF5 value (0.015%). Our study reveals a major oversight in regional and global CH4 budgets from inland waters, caused by neglect of the dominant role of ebullition pathways in those emissions. The indirect EF5 values established in this study generally suggest an order of magnitude downward revision is required in current IPCC default EF5 values for inland waters and estuaries. Our findings further indicate that a comprehensive understanding of the magnitude and patterns of CH4 and N2O emissions from non-marine waters is essential in defining the way that these natural ecosystems shape our climate.
A prominent role for precision composting in sustainable agriculture
Authors: Zhao Shuaixiang , Schmidt Susanne , Gao Hongjian , Li Tingyu , Chen Xinping , Hou Yong , Chadwick David , Tian Jing , Dou Zhengxia , Zhang Weifeng , Zhang Fusuo
Published: August 2021

Compost use in agriculture has the potential to increase the productivity and sustainability of food systems and to mitigate climate change. But the use of diverse compost types in unsuitable biophysical conditions cause uncertain outcomes for crop yields, soil organic carbon (SOC) and nitrous oxide (N2O) emissions. Here, we performed a global meta-analysis with over 2000 observations to determine whether a Precision Composting Strategy (PCS) that aligns suitable composts and application methods with target crop and environment can advance sustainable food production. Eleven key predictors of compost (carbon-to-nutrient ratios, pH, salt content), management (nitrogen supply) and biophysical settings (crop type, soil texture, SOC, pH, temperature, rainfall) determined 80% of the effect on crop yield, SOC, and N2O emissions. We estimate that a PCS could increase global cereal production by 354.5 Tg annually, approximately 1.7-times Africa’s current cereal yield. We further estimate that annual Carbon sequestration could increase by 170.4 Tg Carbon, approximately 20% of the global potential of croplands. This points to a central role of PCS in current and emerging agriculture consistent with the United Nations’ Sustainable Development Goals.
Causal Effects of Life Course Adiposity on Chronic Kidney Disease: A Mendelian Randomization Study
Authors: Yang Wanchun , Chen Hongchun , Yuan Qiuyun , Zou Yang
Published: August 2021

Background Obesity is reported to be tightly correlated the development of chronic kidney disease (CKD). However, whether there exists causation is unknown, and it remains controversial about the role of obesity in CKD is protective or destructive. In this study, we try to infer the causal relationship between life course adiposity and CKD, to provide a rationale for obesity management in CKD patients.Methods A two-sample Mendelian randomization (MR) analysis was conducted to explore the causal relationship of life course adiposity traits including including body mass index (BMI), childhood BMI, body fat percentage (BF), birth weight (BW), waist circumference, hip circumference and waist-to-hip ratio (WHR) to CKD. Significant single nucleotide polymorphisms from genome-wide association study on human adiposity traits were utilized as exposure instruments, and summary statistics of CKD as outcome. The causal relationship was evaluated by inverse variance weighted, MR Egger regression and weighted median methods, and further verified by extensive sensitivity analyses.Results Genetically determined one standard deviation increase in adult BMI was associated with higher risk of CKD in all four MR methods. And other indexes including childhood BMI, body fat percentage, and waist/hip circumference also have a causal effect on the risk of CKD. The results were robust under all sensitivity analyses.Conclusions There exist causal effect of life course adiposity on the risk of CKD. A genetic predisposition to higher adult BMI may increase the risk of CKD.
Berberine Exhibits Neuroprotective Effects Through Reduced Autophagy and Mediated Microglial Polarization in a Rat Model of Intracerebral Hemorrhage
Authors: Lei Qiang , Hu Zhiping , Yang Binbin , Zhou Fangfang
Published: August 2021

Introduction: Intracerebral haemorrhage (ICH) induces autophagy excessive activation and microglia mainly switched into proinflammatory M1 type, which can cause severe secondary injury. Current evidence has implied that berberine has a protective effect against ischaemic stroke through mediated autophagy and microglial polarization. However, the neuroprotective effect of berberine in intracerebral haemorrhage (ICH) remains unclear. Methods: In this study the effect of berberine on a rat model of intracerebral haemorrhage was investigated through Immunofluorescence, qPCR, ELISA, and western blot.Results: Berberine administration significantly reduces cellular apoptosis, brain edema and neurological deficits via inhibited autophagy, promoted M1 type microglia to M2 type, and subsequently exerts anti-inflammation effects in a rat model of ICH. Conclusions: These results suggest that berberine reduced secondary injury and improved neurological outcomes in ICH model.
The Effect of SNPs in lncRNA As ceRNA on the Risk and Prognosis of Hepatocellular Carcinoma
Authors: Mo Han , Wang Xi , Ji Guohua , Liang Xiao , Yang Yi , Sun Wenjing , Jia Xueyuan , Xu Lidan , Qiao Yuandong , Zhou Henan , Zhao Wenhui , Fu Songbin , Zhang Xuelong
Published: August 2021

Background: Most the HCC susceptible loci identified by GWAS are located in non-coding regions, and the mechanism of action remains unclear. The objective of this study was to explore the relationship among SNPs on lncRNA that affects ceRNA mechanism and the risk and prognosis of HCC.Methods: Combined with multiple databases, eight lncRNA genes that affect HCC were systematically screened through the mechanism of lncRNA-mediated ceRNA, and 15 SNPs that affect miRNA binding in the eight lncRNA genes were annotated. Genotyping was conducted in 800 HCC cases and 801 healthy controls from a Han population in Northeast China to examine the genetic risk associated with HCC.Results: The GG, GC and GG + GC genotypes of HOTAIR rs7958904 were found to be associated with a 0.65, 0.59 and 0.63-fold decreased HCC risk, respectively. Moreover, in the stratified analysis of clinical characteristics and biochemical indexes, HCC patients with PVT1 rs3931282 AA + GA genotypes were less prone to develop late-stage tumors; rs1134492 and rs10589312 in PVT1 and rs84557 in EGFR-AS1 showed significant associations with AST, ALT or AST/ALT ratio. Conclusions: The results provide new insights of how non-coding loci confer the interindividual differences to susceptibility and progression of HCC.
Alpha-Lipoic Acid and Ginkgo Biloba Ameliorate Testicular Dysfunctions Induced by Silver Nanoparticles in Rats
Authors: TOHAMY Hossam G. , lebda mohamed , sadek kadry , elfeky mohamed , elsayed yasser , samak dalia , hamed heba , abouzed tarek
Published: August 2021

Silver nanoparticles (AgNPs) are more commonly utilised in medicine, however they have negative effects on the majority of organs, including the reproductive system. AgNPs were reported to be able to reach the testes due to their small size, which allows them to pass through blood testicular barriers. The goal of this study was to see if LA (alpha lipoic acid) or GB (ginkgo biloba) might protect adult rat testes after intraperitoneal injection of AgNPs. Forty male healthy adult Wister albino rats were randomly assigned to four groups (10 rats each); control, AgNPs-intoxicated group intraperitoneally injected AgNPs 50 mg/kg b.w, 3 times a week, LA + AgNPs group intoxicated with AgNPs and orally gavaged with 100 mg LA/kg b.w, and GB + AgNPs group injected with AgNPs and orally given GB extract 120 mg/kg b.w were continued for 30 consecutive days. Biochemical changes in testicular tissue (testosterone, ACP, and Prostatic acid phosphatase), oxidative indices in testicles tissues, mRNA expression of pro-apoptotic (BAX) and anti-apoptotic (BCL-2) biomarkers, histological, and immunohistochemical changes were studied. Significant decrease in serum testosterone level and elevation in ACP and PACP enzyme activity in AgNPs treated group than in the control. In addition, lowering in tGSH, GSH GR, GPx and elevation MDA and GSSG were observed in AgNPs treated group than control. Decreasing in mRNA expression thirodexin-1 (Txn-1), transforming growth factor-1β (TGF-1β), anti-apoptic (BCL-2) and elevation the expression of proapoptic biomarkers (BAX) in the testis homogenates of rats exposed to silver nanoparticles. Strong positive action to BAX and lowering the action of Ki-67antibody were observed. Because of their antioxidant, anti-inflammatory, and anti-apoptotic properties, co-treatment with LA or GB may be beneficial in reducing the harmful effects of AgNPs on the testicles.
Development of live vaccine based on the Enterococcus faecium L3 vector for prevention influenza infections
Authors: Desheva Yulia , Leontieva Galina , Kramskaya Tatiana , Gupalova Tatiana , Kopteva Olga , Losev Igor , Bormotova Elena , Suvorov Alexander
Published: August 2021

Probiotic microorganisms are currently considered as a promising platform for the development of recombinant vaccines expressing foreign antigens. In this study we generated and evaluated the live mucosal recombinant vaccine by integrating genes encoding influenza virus neuraminidase (NA) of N2 subtype into the DNA of the probiotic strain Enterococcus faecium L3 (L3). We confirmed NA expression in the pili of L3 using immune electron microscopy. Mice were fed with a probiotic vaccine containing the NA gene (L3-NA) or pure L3. Oral administration of L3-NA caused detectable increase of virus-specific serum IgG and local IgA after the third feeding. A the same time, single spleen cell suspensions were stimulated with whole A(H1N1)pdm09 virus followed by flow cytometry. In mice received L3-NA, the content of cytotoxic T-lymphocytes was more pronounced compared to mice receiving pure L3. Immunization with L3-NA increased the survival rate by 34% when the mice were infected using A(H1N1)pdm09 influenza virus after the third feeding. After S. pneumonia post-influenza infection, the L3-NA immunized mice were 50% more protected from lethality in comparison with L3 fed mice. Thus, a live probiotic vaccine candidate based on L3 induced the formation of systemic and local immunity and provide protection against complicated influenza. The approach based on a probiotic vaccine expressing viral epitopes can allow repeated immunization during epidemic season.
Haplotype-based phylogenetic analysis uncovers the tetraploid progenitor of sweet potato
Authors: Yan Mengxiao , Li Ming , Moeinzadeh M-Hossein , Quispe-Huamanquispe Dora G. , Fan Weijuan , Nie Haozhen , Wang Zhangying , Heider Bettina , Jarret Robert , Kreuze Jan , Gheysen Godelieve , Wang Hongxia , Bock Ralph , Vingron Martin , Yang Jun
Published: August 2021

The hexaploid sweet potato is one of the most important root crops worldwide. However, its genetic origins, especially that of its tetraploid progenitor, are unclear. In this study, we conceived a pipeline consisting of a genome-wide variation-based phylogeny and a novel haplotype-based phylogenetic analysis (HPA) to determine that the tetraploid accession CIP695141 of Ipomoea batatas 4x from Peru is the tetraploid progenitor of sweet potato. We detected biased gene exchanges between subgenomes. The B1 to B2 subgenome conversions were almost 3-fold higher than the B2 to B1 subgenome conversions. Our analyses revealed that the genes involved in storage root formation, sugar transport, stress resistance, and maintenance of genome stability have been selected during the speciation and domestication of sweet potato. This study sheds lights on the evolution of sweet potato and paves a way for the improvement of sweet potato.
Microbial diversity in an early earth analogue: From ancient novelty to modern commonality
Authors: Hahn C. Ryan , Farag Ibrahim , Murphy Chelsea , Podar Mircea , Elshahed Mostafa , Youssef Noha
Published: August 2021

Life emerged and diversified in the absence of molecular oxygen 1. The prevailing anoxia and unique sulfur chemistry in the Paleo-, Meso- and Neoarchean, and early Proterozoic eons may have supported microbial communities that are drastically different than those currently thriving on the earth’s surface 2–4. Zodletone spring in southwestern Oklahoma represents a unique habitat where spatial sampling could substitute for geological eons: from the anoxic, surficial light-exposed sediments simulating a preoxygenated earth, to overlaid water column where air exposure simulates the relentless oxygen intrusion during the Neo-Proterozoic 5. We discovered a remarkably diverse microbial community in the spring sediments, with two thirds (340/516) of the metagenomic assembled genomes belonging to 200 bacterial and archaeal families that were either previously undescribed or are extremely rare elsewhere on earth. Such diversity is underpinned by the widespread occurrence of sulfite-, thiosulfate-, tetrathionate-, and sulfur-reduction, in contrast with a paucity of sulfate-reduction metabolism in those taxa. This greatly expands the diversity of lineages mediating reductive sulfur cycling processes in the tree of life. In the overlaying water community oxygen intrusion leads to the establishment of a significantly less diverse community dominated by well-characterized lineages and the prevalence of oxidative sulfur cycling processes. Such transition from ancient novelty to modern commonality underscores the profound impact of the great oxygenation event on the earth’s surficial anoxic community.. It also suggests that novel and rare lineages encountered in current anaerobic habitats could represent taxa once thriving on the anoxic earth that have failed to adapt to the progressive oxygenation.
Molecular Insights into Ultra-Humanisation of mAbs: Crystal Structure of Ultra-Humanised anti-pTau Fab Reveals Unmodified Binding Interactions
Authors: Brinth Alette R. , Svenson Kristine , Mosyak Lidia , Cunningham Orla , Hickling Timothy , Lambert Matthew
Published: August 2021

Administration of therapeutic antibodies can elicit adverse immune responses in patients through the generation of anti-drug antibodies that, in turn, affect the efficacy of the therapeutic. Removal of foreign amino acid content by humanization can lower the immunogenic risk of the therapeutic mAb. We previously developed the ultra-humanization technology “Augmented Binary Substitution” which enables single-step CDR germ-lining of antibodies. The application of ABS to a chicken anti-pTau antibody generated an ultra-humanised variant, anti-pTau C21-ABS, with increased human amino acid content in the CDRs and minimized in-silico predicted immunogenicity risk. Here, we report the high-resolution crystal structure of anti-pTau C21-ABS Fab in complex with the pTau peptide to further examine how ultra-humanisation via CDR germlining is facilitated without altering antigen affinity. This co-complex structure reveals an unaltered epitope and minimal changes in the paratope structure. These findings confirm that ABS enables the germlining of amino acids within CDRs by exploiting CDR plasticity, to minimize redundant foreign amino acid CDR content, without altering the mechanism of binding.
Structural And Functional Changes In Soil Microbes By Foliar Drift Spray of Seaweed Extract As Revealed By Metagenomics
Authors: Trivedi Khanjan , Kumar Ranjeet , Vijayanand K. G. , Bhojani Gopal , Kubavat Denish , ghosh Arup
Published: August 2021

Kappaphycus alvarezii seaweed extract (KSWE) is known to enhance crop productivity and impart stress tolerance and our preliminary studies showed their biostimulatory effect on soil bacteria also. Close to one quarter of the foliar spray carried out on maize falls on soil either as drift or from leaf as drip. Hence it was hypothesized, it would profoundly influence soil microbes under stress. An experiment was conducted with five treatments, with or without KSWE application at critical stages of maize under soil moisture stress and compared with an irrigated control. Illumina platform was employed for analysis of V3-V4 region of 16S rRNA gene from the soil metagenome. Total of 345,552 operational taxonomic units were generated which were classified into 55 phyla, 152 classes, 240 orders, 305 families and 593 genera. Shannon’s index and Shannon’s equitability indicated increased soil bacterial diversity by multiple KSWE applications under duress. The abundance of Steroidobacter, Balneimonas, Rubrobacter, Bacillus, Alicyclobacillus, Anaerolinea and Nitrospira genera decreased (49-79%) in drought imposed at V5,10, and 15 stages of maize over the irrigated control, while it significantly improved when followed by KSWE application under drought. Nitrosomonas, Nitrosovibrio, Rubrobacter, Flavobacterium genera and several other taxa which are important for plant growth promotion and nutrient cycling were found to be enriched by KSWE application under drought. Treatments having enriched microbial abundance due to KSWE application under stress recorded higher soil enzymatic activities and cob yield, suggesting the contribution of altered soil ecology mediated by KSWE as one of the reasons for yield improvement.
Modified Adaptive Mechanism For Optimising IEEE 802.15.4 WPANs For Wireless Sensor Networks
Authors: Bamber Sukhvinder Singh , Dogra Naveen , Angurala Mohit
Published: August 2021

Different applications of Wireless Sensor Networks (WSNs) have different expectations from the working of Medium Access Control (MAC) protocols. Some value reliability more than delay incurred while some demand a fair trade-off for the factors like: Throughput, Bit Error Rate (BER) etc. This paper evaluates the performance of Wireless Personal Area Networks (WPANs) from 802.15.4 group for WSNs with modified algorithm which helps in reducing the Medium Access Delay and Delay in reaching of the packet from one end to another end. In this paper certain modifications to existing algorithm have been proposed for reducing the Medium Access Delay and to reduce the number of packets dropped. The result comparisons on the performance parameters like: network output load, generated acknowledged traffic, media access delay, battery consumed and delay in packet transmission from one end to another end that the back-off number & exponent values used for transmission play vital role for improving the performance of WSNs as they directly affect the number of packets dropped, successfully acknowledged and Medium Access Delay.
Association Between Acute Colonic Pseudo-Obstruction (Ogilvie Syndrome) And Nimodipine Use. Case Series And Comprehensive Review
Authors: De Jesus Orlando , Jiménez José Sánchez , Vicenty Juan C.
Published: August 2021

Background:Nimodipine is a calcium channel blocker indicated for the management of patients with aneurysmal subarachnoid hemorrhage (SAH). Oral nimodipine has rarely been implicated in the development of acute colonic pseudo-obstruction in patients treated for SAH. Nimodipine acts by inhibiting the transmembrane influx of calcium ions essential for the excitation-contraction coupling process of smooth muscle cells. We thought that its mechanism of action could predispose patients to develop acute colonic pseudo-obstruction (Ogilvie syndrome). The purpose of this study was to revise the existing literature concerning the association between acute colonic pseudo-obstruction and nimodipine use in patients with SAH.Methods:Two patients with aneurysmal SAH who received oral nimodipine and developed Ogilvie syndrome were discussed. All previously published cases of aneurysmal SAH associated with acute colonic pseudo-obstruction were reviewed. Conclusion:This report linking the oral use of nimodipine with Ogilvie syndrome may further support the association of this disease with nimodipine use during the treatment of patients with aneurysmal SAH.
Mechanistic Insights on Cytotoxicity of KOLR by targeting Signaling Complexes of phosphodiesterase 3B and Rap guanine nucleotide exchange factor 3
Authors: Li Mingqian , Li Fei , Chen Jiabin , Chen Guanping , Cao Jili , Li Jiacheng , Dong Liyao , Yu Zhihong , Wang Yifan , Li Jing , Lu Yingyan , Zhou Chun , Zhu Yongqiang , Li Qun , Chai Kequn
Published: August 2021

Background

Protein signaling complexes play important roles in prevention of several cancer types and can be used for development of targeted therapy. The roles of signaling complexes of phosphodiesterase 3B (PDE3B) and Rap guanine nucleotide exchange factor 3 (RAPGEF3), which are two important enzymes of cyclic adenosine monophosphate (cAMP) metabolism, in cancer have not been fully explored.
Methods

The natural product Kaempferol-3-O-(3′′,4′′-di-E-p-coumaroyl)-α-L-rhamnopyranoside designated as KOLR was extracted from Cinnamomum pauciflorum Nees leaves using reverse phase chromatography, high-resolution mass spectrometry, and nuclear magnetic resonance spectroscopy. The antitumor effect of KOLR was analyzed by multiple cell proliferation and metastasis experiments. The PDE3B/RAPGEF3 complex was found to be the target of KOLR through mRNA sequencing, Co-Immunoprecipitation assay, gene knock-down, gene mutation of drug-resistance cell line, and molecular docking. In vivo studies have shown that KOLR has the same antitumor mechanism.
Results

KOLR exhibited cytotoxic effects against selected cancer cells, except for AsPC-1 pancreatic cancer cell line. KOLR stabilized PDE3B/RAPGEF3 signaling complex thus inhibiting AKT phosphorylation and Rap-1 activation. Notably, mutation of RAPGEF3 G557A inhibited effect of KOLR on stabilizing PDE3B/RAPGEF3 complex in AsPC-1 cells. Furthermore, downregulation of PDE3B expression inhibited cytotoxic effect of KOLR on tumor cells. Downregulation of RAPGEF3 and Rap-1 expression promoted apoptosis of tumor cells and inhibited tumor metastasis. PDE3B inhibits activity of RAPGEF3 and activation of downstream signaling pathway.
Conclusion

The findings of this study show that KOLR could stabilize PDE3B/RAPGEF3 signaling complex to play an anti-tumor role and the PDE3B/RAPGEF3 complex is a potential therapeutic cancer target.
Characteristics of COVID-19-related Clinical Studies and Factors Affecting the Recruitment and Completeness: a Large Cross-sectional Study
Authors: Lei Mingxing , Li Jinglan , Lv Houchen , Lin Feng , Zhang Licheng
Published: August 2021

Background: Coronavirus disease 2019 (COVID-19) has generated an unprecedented clinical research response, but the data about the characteristics of COVID-19-related clinical studies were scarce. The study aimed to describe the characteristics of COVID-19-related clinical studies registered at ClinicalTrials.gov and further identify factors affecting the recruitment and completeness of these studies.Methods: The study extracted 5,672 studies and included 5,430 studies relating to COVID-19 registered at ClinicalTrials.gov. We presented the characteristics of all included clinical studies. Identification of risk factors for recruitment status was achieved using the multiple logistic regression models, and identification of risk factors for completion time was obtained using the multiple Cox proportional hazards regression models. Subgroup analyses were also performed in the interventional studies. Results: Of the included studies, only 19.59% (1064/5430) had completed recruitment, and 55.93% (3037/5430) were interventional studies. The peak of the number of clinical studies relating to COVID-19 was seven months earlier than the first peak of the number of COVID-19 cases globally. In all included studies, participants only including male (P=0.02), Participants including child (P=0.01), smaller enrollment (P<0.01), and studies not being funded by industry (P=0.01) and the National Institutes of Health (NIH) (P<0.01), and observational studies (P<0.01) tended to be associated to higher completed recruitment rates. Regarding the interventional studies, Participants including child (P=0.04), smaller enrollment (P<0.01), a crossover intervention model (P<0.01), and primary purpose involving in device feasibility (P<0.01) and treatment (P=0.03) were associated with shorter completion time, while being funded by industry (P=0.01) and NIH (P<0.01), primary purpose involving in basic science (P<0.01), and biological interventions (P<0.01) were associated with longer completion time.Conclusion: A multitude of clinical studies relating to COVID-19 are registered in responding to the pandemic and the response is rapid and timely, but these clinical studies are frequently not completed. Increased focus on establishing global initiatives and networks to coordinate recruitment efforts may be needed. Several independent risk factors are identified to guide the design of COVID-19-related clinical studies. This may be significant to avoid waste and ensure that the participation of all participants in clinical researches contributes to the treatment or prevention of COVID-19.
Novel Therapeutic Mechanism of Action of Metformin and Its Nanoformulation in Alzheimer's Disease and Role of AKT/ERK/GSK Pathway.
Authors: Kumar Harish , Chakrabarti Amitava , Sarma Phulen , Modi Manish , Banerjee Dibyajyoti , Radotra B.D. , Bhatia Alka , Medhi Bikash
Published: August 2021

Background: Insulin resistance in brain plays a critical role in the pathogenesis of Alzheimer's disease (AD). Metformin is a blood brain barrier crossing anti-diabetic insulin-sensitizer drug. Current study has evaluated the therapeutic and mechanistic role of conventional as well as solid lipid nanoformulation (SLN) of metformin in intracerebro ventricular (ICV) Aβ (1-42) rat-model of AD. Methods: SLN-metformin was prepared by the micro-emulsification method and further evaluated by zetasizer and scanning electron-microscopy. In the animal experimental phase, AD was induced by bilateral ICV injection of Aβ using stereotaxic technique, whereas control group (sham) received ICV-NS. 14 days post-model induction, ICV- Aβ treated rats were further divided into 5 groups: disease control (no treatment), Metformin dose of (50mg/kg, 100mg/kg and 150 mg/kg), SLN of metformin 50mg/kg and memantine 1.8mg/kg (positive-control). Animals were tested for cognitive performance (in EPM, MWM) after 21 days of therapy, and then sacrificed. Brain homogenate was evaluated using ELISA for (Aβ (1-42), hyperphosphorylated tau, pAKTser473, GSK-3β, p-ERK,) and HPLC (metformin level). Brain histopathology was used to evaluate neuronal injury score (H&E) and Bcl2 and BAX (IHC). Results: The average size of SLN-metformin was <200 nm and was of spherical in shape with 94.08% entrapment efficiency. Compared to sham, the disease-control group showed significantly higher (p≤0.05) memory impairment (in MWM and EPM), higher hyperphosphorylated tau, Aβ (1-42), and Bax and lower Bcl-2 expression. Metformin was detectable in brain. Treatment with metformin and its SLN form significantly decreased the memory impairment as well as decreased the expression of hyperphosphorylated tau, Aβ(1-42), Bax expression and increased expression of Bcl-2 in brain. AKT-ERK-GSK3β-Hyperphosphorylated tau pathway can be implicated in the protective efficacy of metformin. Conclusion: Both metformin and SLN metformin is found to be effective as therapeutic agent in ICV-AB rat model of AD. AKT-ERK-GSK3β-Hyperphosphorylated tau pathway is found to be involved in the protective efficacy of metformin.
Landscape configuration affects probability of apex predator presence and community structure in experimental metacommunities
Authors: Wolfe Ellie , Hammill Edd , Memmott Jane , Clements Christopher F.
Published: August 2021

Biodiversity is declining at an unprecedented rate, highlighting the urgent requirement for well-designed protected areas. Design tactics previously proposed to promote biodiversity include enhancing the number, connectivity, and heterogeneity of reserve patches. However, how the importance of these features changes depending on what the conservation objective is remains poorly understood. Here we use experimental landscapes containing ciliate protozoa to investigate how the number and heterogeneity in size of habitat patches, rates of dispersal between neighbouring patches, and mortality risk of dispersal across the nonhabitat ‘matrix’ interact to affect a number of diversity measures. We show that increasing the number of patches significantly increases γ diversity and reduces the overall number of extinctions, whilst landscapes with heterogeneous patch sizes have significantly higher γ diversity than those with homogeneous patch sizes. Furthermore, the responses of predators depended on their feeding specialism, with generalist predator presence being highest in a single large patch, whilst specialist predator presence was highest in several-small patches with matrix dispersal. Our evidence emphasises the importance of considering how top-down effects can drive community responses to patch configuration.
Oral Health Status Assessment of an African Population: Rationale, Methods and Population Characteristics
Authors: Hewlett Sandra Ama. , Blankson Paa-Kwesi , Aheto Justice M.K. , Anto Francis , Appiah Tony Danso , Sackeyfio Josephine , Koram Kwadwo , Amoah Albert
Published: August 2021

Objectives: Oral health surveys aid in estimating the oral health of a population and provide a projection for future oral health care needs. We report the procedures and rationale of a survey carried out to assess the oral health status and risk factors for oral disease among adults in the Greater Accra Region (GAR) of Ghana. It’s objective was to provide prevalence estimates on dental diseases, oral health behaviour and risk factors, and to establish baseline epidemiological data on the population’s oral health for further research.Methods: This was a population-based cross-sectional study of adults aged 25 years and above. A random, stratified two-stage sampling method was used to select participants from rural and urban communities in three types of districts (Metropolitan, Municipal, Ordinary). A semi- structured questionnaire was used to collect data on socio-demographic characteristics, oral health behaviours and risk factors for oral disease. Anthropometric data and a full-mouth clinical examination was carried out including: soft tissue assessment, tooth count, prosthodontic status, dental caries assessment and periodontal assessment.Results: A total of 729 participants were included in the study with a mean age of 43.9 (±14.6). Majority 425 (61%) were females. Though the metropolitan districts had more dental clinics and personnel, along with better health insurance coverage, they had a higher prevalence of missing teeth, retained roots, severe periodontitis and poorer oral health coverage. The findings also show some significant differences in disease prevalence, within the different localities and districts.Conclusions: Availability and access to oral health services is not the most important determinant of good oral health outcomes in this region. We recommend exploring socio-behavioral and cultural factors as well. This study provides district level data to inform policy and guide further research.
Establish a Prediction Model for the Recurrence Time of Hormone Receptor Positive /human Epidermal Growth Factor Receptor 2-negative Breast Cancer
Authors: Hu Mengyu , Xing Huajie , Li Huiping , Liu Yaxin , Zhang Jiayang
Published: August 2021

ObjectivesThis study aimed to develop a model to predict recurrence time of hormone receptor-positive (HR+) /human epidermal growth factor receptor 2 negative (HER2-) breast cancer patients. MethodsWe included HR+ HER2- metastatic breast cancer (MBC) female patients who arrived at the Department of Breast Oncology in Peking University Cancer Hospital. Data were collected through consulting medical records. Patients were divided into early recurrence group and late recurrence group according to disease-free survival (DFS). Predictors of recurrence time were identified and a nomogram was developed and validated using concordance index (C-index), AUC (area under the curve), and calibration plots. ResultsA total of 639 patients coming to the hospital between April 2007 and October 2019 were included. Median DFS was 50.0 months. 382 patients (59.8%) were presented with early recurrence (DFS ≤5 years), and 257 patients (40.2%) were presented with late recurrence (DFS >5 years). A nomogram based on potentially associated clinicopathological factors was developed and validation results showed the nomogram was well-calibrated to predict recurrence time (AUC=0.703, C-index=0.697). ConclusionsWe have established a well-calibrated nomogram through 639 patients. HR+/HER2- BC patients with premenopausal status at initial diagnosis, less positive lymph nodes, lower level of Ki-67 were more common in late recurrence. The nomogram can predict the risk of late recurrence. Prospectively designed studies are needed to further validate our model.
First Report on the Diversity and Distribution of Parasitic Monogenoids (Platyhelminthes) From Catfishes (Siluriformes) in Arunachal Pradesh, India
Authors: Tripathi Amit , Wangchuk Leki , Narba Dobium , Matey Chawan
Published: August 2021

Monogenoidea (Platyhelminthes), one of the largest groups of ectoparasitic metazoans worldwide, comprises over 10,000 nominal species distributed globally, many of which may represent a serious threat to their fish hosts in aquaculture conditions. The fish fauna of Arunachal Pradesh, India– a global hotspot of biodiversity– is reasonably well-documented, with at least 213 known species (including 69 Siluriformes). These faunas are an essential resource for this tribal state’s economy. In sharp contrast, information on parasitic monogenoids of fish from the region is extremely limited, with only nine species described to date. In this study, 21 species of catfishes were collected and examined with the aim of expanding the current knowledge of the diversity and distribution of monogenoid species from Arunachal Pradesh. 15 (62.5%) of the 21 catfish species studied were infected with a total of 25 monogenoid species (11 previously described and 14 newly discovered in this study). Ten species of catfish were the first host records for new parasite species, while two species of catfish were new host records for previously known monogenoids. Arunachal Pradesh represents new geographic locality records for all 11 previously described parasite species, thus significantly expanding their distribution area from North and South India to extreme Northeast India. The patterns of parasite species richness in relation to three ecological traits (fish habitat, body size, and elevation) as well as host specificity across the 21 examined species of catfishes, the unique problem of too many parasite species in Wallago attu, and the future of parasitology in Arunachal Pradesh, India are discussed.
Expression of M2 Macrophages and Regulatory T Cells in Colorectal Cancer and Their Correlation with Lymph Node Metastasis
Authors: Chen Yanlei , Yang Chunyu , Wang Yue , Ma Xueqian , Wang Yanping , Liu Jinhao , Sun Yan , Song Xiaoyu , Feng Yang , Qiao Shifeng
Published: August 2021

BackgroundColorectal cancer (CRC) is among the most common malignancies worldwide. M2 macrophages and regulatory T cells (Tregs) are immunosuppressive cells that can promote tumor progression via inhibiting anti-tumor immunities. However, the significance and correlation of the two types of cells in colorectal cancer are still inconclusive. The purpose of this study is to detect the number of M2 macrophages and Tregs in colorectal cancer and lymph nodes and to explore the clinical and pathological significance of their existence.MethodsThe pathologic specimens and clinical data of 197 patients with Colorectal cancer after radical resection were collected. Immunohistochemical methods were used to detect the expression of M2 macrophages and Tregs in colorectal cancer tissues, adjacent tissues, and lymph node tissues in each group.ResultsCompared with adjacent tissues and non-metastatic lymph node tissues, M2 macrophages and Tregs not only increased significantly in cancer tissues and metastatic lymph node tissues (P < 0.001), but also M2 macrophages in non-metastatic lymph node tissues adjacent to cancer tissues the number of phages expressed also increased significantly (P < 0.05). In addition, there was a positive correlation between the number of cancer tissues and lymph nodes (P < 0.001).ConclusionM2 macrophages are involved in the formation of lymph node immunosuppressive environment and promote the development of CRC and lymph node metastasis together with Tregs. Upregulation of M2 macrophages and Tregs expression is a prognostic marker for monitoring the condition of colorectal cancer and judging the prognosis.
Comparative Analysis of the Mutational Profile in HBV-Related and Non-HBV-Related Hepatocellular Carcinoma
Authors: Du Bingqing , Wang Haifeng , Yang Jie , Wei Yisheng , Shao Zili
Published: August 2021

BackgroundHepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide.The distinct molecular mechanism that regulates cancer progression associated with HBV-related HCC are still unclear.MethodsThe study population included all HCC patients from TCGA lihc_firehose.Mutational signatures of HBV-related HCC samples were calculated with MuSiCa Online website tools. Overall Survival (OS) and disease-free survival（DFS) were estimated according to the log rank in Cox proportional model.Analysis of differential expressed genes was finished with R (version 3.6.3) package DESeq2.Results AXIN1 and CACNA2D1 were significantly higher tested in patients with HBV-related HCC.Mutational signature 26,6 and 16 were detected in HBV-related HCC.TMB of non-HBV-related HCC was significantly higher than HBV-related . Mutations of TTN, MUC16, RYR2, DNAH7 and ARID2 had significant effects on OS in HBV-related but were not associated with prognosis of non-HBV-related HCC.ConclusionWnt/β-catenin and cell cycle signaling pathway may be potentially targets for treatment of HBV-related HCC.Mutation genes of TTN, MUC16, RYR2, DNAH7 and ARID2 may be used as biomarkers of the clinical prognosis and a useful strategy for management of HBV-related HCC.
LINC00261 Inhibits Esophageal Cancer Radioresistance By Downregulating microRNA-552-3p And Promoting DIRAS1
Authors: Yang Baolong , Ma Hongbing , Bian Yan
Published: August 2021

Background: Esophageal cancer (EC) is a life-threatening tumor with a high increasing incidence rate. Long intergenic non-protein coding RNAs (LINCs) are widely researched in EC. This study set out to investigate the role of LINC00261 in EC radioresistance.Methods: Radioresistant EC cell lines TE-1-R and TE-5-R were established using TE-1 and TE-5 cells. LINC00261, microRNA (miR)-552-3p, and DIRAS1 expression in EC tissues and adjacent normal tissues and EC cells was evaluated. Then, survival fraction (SF), colony formation, apoptosis, and γ-H2AX expression were analyzed. The binding relation between LINC00261 and miR-552-3p and between miR-552-3p and DIRAS1 were detected. Eventually, xenograft transplantation was applied to confirm the effect of LINC00261 on EC radioresistance in vivo.Results: LINC00261 and DIRAS1 were weakly expressed in EC tissues and cells, but miR-552-3p was overexpressed. For EC cells with X-ray radiation, overexpression of LINC00261 reduced SF and cell viability, strengthened γ-H2AX expression, and promoted apoptosis, which were all counteracted by miR-522-3p overexpression or DIRAS1 silencing. Mechanically, the binding relation between LINC00261 and miR-552-3p and between miR-552-3p and DIRAS1 were verified. In addition, LINC00261 overexpression suppressed tumor growth and reduced EC radioresistance in vivo.Conclusion: LINC00261 could suppress EC radioresistance via the competing endogenous RNA network to sponge miR-552-3p and upregulate DIRAS1 transcription.