bluuebunny/crossref_metadata_2025 huggingface dataset:
LEDGF/p75 is Required for an Efficient DNA Damage Response
Authors: Liedtke Victoria , Schröder Christian , Roggenbuck Dirk , Weiss Romano , Stohwasser Ralf , Schierack Peter , Rödiger Stefan , Schenk Lysann
Published: November 2020

BackgroundLens epithelium derived growth factor splice variant of 75 kDa (LEDGF/p75), is overexpressed in different solid cancers and cancer cell lines and various autoinflammatory diseases. Due to its ability to bind chromatin, it acts as a transcriptional co-activator and promotes anti-apoptotic signalling pathways that lead to increased tumour aggressiveness and resistance to chemotherapy. The role of LEDGF/p75 in DNA-damage repair (DDR) is still not completely elucidated particularly regarding the ubiquitin-dependent regulation and degradation of DDR signalling molecules.MethodsDifferent LEDGF model cell lines were generated, a complete knock-out of LEDGF (KO) as well as the re-expression of LEDGF/p75 or LEDGF/p52 using CRISPR/Cas9 technology. Then, various assays were performed to determine their proliferation and migration capacity as well as their chemosensitivity. Moreover, DDR signalling pathways were investigated by western blot and immunofluorescence.ResultsLEDGF-deficient cells exhibited a decreased proliferation (dt (WT) = 21 h, dt (KO) = 26 h) , 60 % decreased migration, as well as an 30-50 % increased sensitivity towards the topoisomerase II inhibitor etoposide. Moreover, LEDGF depleted cells showed a significant reduction by 65 % in the recruitment of downstream DDR-related proteins like replication protein A 32 kDa subunit (RPA32) after exposure to etoposide. Re-expression of LEDGF/p75 rescued all knock-out effects, while re-expression of LEDGF/p52 had no effect.Surprisingly, untreated LEDGF KO cells showed an increased amount of DNA fragmentation combined with an increased formation of γH2AX and Breast cancer type 1 susceptibility protein (BRCA1). In contrast, the protein levels of ubiquitin-conjugating enzyme UBC13 and nuclear proteasome activator PA28γ were substantially reduced upon LEDGF KO. ConclusionsThis study provides evidence that LEDGF is not only an important player in the DDR after chemotherapeutic treatments but is also involved in the maintenance of the general genome integrity. Moreover, this study provides for the first time an insight into the possible role of LEDGF in the ubiquitin-dependent regulation of DDR signalling molecules and highlights the involvement of LEDGF/p75 in homology-directed DNA repair.
Selenium Biofortified Alfalfa Hay Supplemented to Dairy Heifers During the Peripartum Affects the Antioxidant Function of Albumin but Has Little Impact on Metabolic and Immune Function
Authors: Jaaf Shana , Mezzetti Matteo , Trevisi Erminio , Cherian Gita , Bionaz Massimo
Published: November 2020

Background: the peripartum is the most critical period in dairy cows with high incidence of diseases due to immune dysfunctions, often paired with systemic inflammation and oxidative stress. Selenium is a trace mineral that plays an important role in anti-oxidative function and immune response. We hypothesize that supplementing dairy cows with a relatively small amount of Se-biofortified hay during the last 40 days of pregnancy and early lactation improves performance, metabolism, oxidative status, and immune response.Methods: ten Jersey and 8 Holstein pregnant dairy heifers were divided into two groups and supplemented with 1 kg/100 kg BW of Se-biofortified (Sel; n=9; 3.2 ppm Se) or non-biofortified (Ctr; n=9; 0.4 ppm Se) alfalfa hay from 40 days prior- to 2 weeks post-partum. Heifers were monitored daily for feed intake, activity, and milk yield, and weekly for BW and BCS. Milk samples were assessed for components and fatty acid profile. Blood samples were collected regularly to assess metabolic, oxidative, and inflammatory biomarkers, and to evaluate leukocytes phagocytosis and differential through flow cytometry.Results: supplementation of Se biofortified hay did not affect feed intake, milk yield, BW, BCS, milk components, and any of the parameters measured on leukocytes but increased the hematocrit. Animal receiving Se biofortified hay had larger concentration of plasma albumin and a tendency for larger blood urea, indicating a possible better liver status, especially post-partum. None of the parameters measured in plasma related to the oxidative status were affected, except the concentration of advanced oxidation protein products that was greater in Sel vs. Ctr. The concentration of advanced oxidation protein products was negatively correlated with parameters related to inflammation but positively associated to plasma albumin suggesting a possible improved anti-oxidative function of circulating albumin by Se-biofortified hay supplementation.Conclusions: feeding Se-biofortified hay during pregnancy in dairy heifers had little effect on metabolic, inflammatory, and oxidative status parameters with no effect on performance or immune response. Supplementation with Se-biofortified hay increased plasma level of albumin, possibly as consequence of improved liver function, promoting the antioxidant role of albumin as indicated by increased AOPP.
No changes in adolescent's sedentary behaviour across Europe between 2002 and 2017
Authors: López-Fernández Jorge , López-Valenciano Alejandro , Mayo Xián , Liguori Gary , Lamb Martin , Copeland Robert , Jiménez Alfonso
Published: November 2020

Background: Health organizations have been alerted to the high levels of sedentary behaviour (SB) among adolescents as well as to the health and social consequences of excess sedentary time. However, SB changes of European Union (EU) adolescents over time are yet to be reported. This study aimed to identify SB changes the EU adolescents (15-17 years) between 2002 and 2017, and to analyse the prevalence of SB according to the gender.Methods: SB of 2542 adolescents (1335 boys and 1207 girls) as a whole sample and country-by-country was analysed in 2002, 2005, 2013, and 2017 using the Sport and Physical Activity EU Special Eurobarometers' data. SB was measured using the sitting time question from the short version of the International Physical Activity Questionnaire (IPAQ), such that 4h30min of daily sitting time was the delineating point to determine excess SB behaviour (≥4h30min of sitting time) or not (≤4h30min of sitting time). A χ2 test was used to compare the prevalence of SB between survey years. Furthermore, SB prevalence between genders was analysed using a Z-Score test for two population proportions. Results: The prevalence of SB among EU adolescents across each of the four survey years ranged from 74.2% and 76.8%, rates that are considered high. High levels of SB were also displayed by both genders (girls: 76.8% to 81.2%; boys: 71.7% to 76.7%). No significant differences in the prevalence of SB among years (p>0.05) were found for the whole sample, girls, or boys. Also, no significant differences in the prevalence of SB between girls and boys were found. Conclusion: The SB prevalence in adolescents is extremely high (76.8% in 2017) but remained steady from 2002-2017, and European girls and boys reported similar prevalence of SB across the same time frame.
Identification of the active compounds and pharmacological mechanisms of Xiaoqinglong decoction for asthma based on network pharmacology and molecular docking technology
Authors: Li Haili , Zhou Jianpeng , Wei Zuyou , Chen Feng , Deng Jingmin
Published: November 2020

Background and purposeAsthma has become the most common chronic respiratory disease in the world. Xiaoqinglong decoction (XQLD) is described as a commonly used drug for treatment and prevention of asthma for thousands of years, however, its underlying molecular mechanisms have not been clarified completely. Therefore, a network pharmacology and molecular docking technology were used to uncover the active compounds and pharmacological mechanism of XQLD on asthma.MethodsBioactive ingredients and targets of XQLD, asthma-related targets were obtained from public databases. Cytoscape software was used to construct biological networks. DAVID database was used to perform Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking was performed to further verify the internal relationship between the active ingredients and key targets.ResultsA total of 169 bioactive ingredients and 127 gene targets of XQLD were identified. The network analysis indicated that quercetin, kaempferol, stigmasterol, β-sitosterol, and luteolin may be candidate agents. The IL6, VEGFA, NFKBIA, ICAM1, VCAM1, PPARG, IRF1, CYP3A4, CYP1B1 and CYP1A1 could become potential drug targets. The KEGG suggested that PI3K-AKT, Estrogen, FoxO, MAPK, HIF-1 signaling pathway may play a significant role in treating asthma. Molecular docking showed that quercetin, kaempferol, stigmasterol, β-sitosterol, and luteolin combined well with IL6, VEGFA, PPARG, CYP3A4.ConclusionThis study predicted the main ingredients, potential drug targets and pharmacological mechanism of XQLD on asthma from a new sight, as well as provided a promising approach for the research of chemical basis and pharmacology in Traditional Chinese medicine (TCM).
Effectiveness of Integrated Aedes albopictus Management in Southern Switzerland
Authors: Ravasi Damiana , Monton Diego Parrondo , Tanadini Matteo , Flacio Eleonora
Published: November 2020

BackgroundThe exotic invasive tiger mosquito, Aedes albopictus, appeared in southern Switzerland in 2003. The spread of the mosquito has been surveyed constantly since then and an integrated vector management (IVM) has been implemented to control its numbers. The control measures focus on the aquatic phase of the mosquito with removal of breeding sites and larvicide applications in public areas. Private areas are reached through extensive information campaigns to citizens. Here, we evaluated the efficacy of the IVM.MethodsSince all the municipalities with Ae. albopictus in southern Switzerland are currently implementing the IVM, Italian municipalities just across the Swiss-Italian border, where Ae. albopictus is present but no coordinated intervention programme is in place, served as control. Ovitraps and adult female traps were used to measure mosquito abundance in 2019. Generalised Mixed-Effects Models were used to model the numbers of Ae. albopictus eggs and adult females collected. The numbers of Ae. albopictus eggs were then compared to the numbers of eggs collected in 2012-2013 in a previous assessment of the IVM, using a hurdle model.ResultsMean Ae. albopictus egg and adult female numbers in 2019 were consistently higher in the municipalities not following an IVM programme. In these municipalities, there were about four times (3.8) more eggs than in the municipalities implementing an IVM programme. Also, the numbers of eggs and adult females increased steadily from the beginning of the Ae. albopictus reproductive season, reaching a peak in August. In contrast, the increase in numbers of Ae. albopictus was much more contained in the municipalities implementing an IVM programme, without reaching an evident peak. Comparison with data from 2012 and 2013 showed that the gap between intervention and non-intervention areas has almost doubled in the past six years.ConclusionsThe results of the survey demonstrate the efficacy of the IVM programme implemented in southern Switzerland, compared to municipalities not implementing defined control measures. With the constant implementation of an IVM, it is possible to contain the numbers of Ae. albopictus at a manageable level, reducing the nuisance for the human population and the risk of arbovirus epidemics.
Mitochondrial Analysis of Oribatid Mites Provides Insights into Their Atypical tRNAs Annotation, Genome Rearrangement and Evolution
Authors: Zhan Xuebing , Chen Bing , Fang Yu , Dong Fangyuan , Fang Weixi , Luo Qian , Chu Lingmiao , Feng Rui , Wang Yan , Su Xuan , Fang Ying , Xu Jiaoyang , Zuo Zetao , Xia Xingquan , Yu Jiegen , Sun Entao
Published: November 2020

Background: Mitochondrial (mt) genomes of Sarcoptiformes mites typically contain 37 genes. Loss of genes is rare in Sarcoptiformes mite mt genomes, but two of the six previously reported oribatid mites (Acariform Order Sarcoptiformes) are reported to have lost part of their tRNA genes. To determine whether these tRNA genes were indeed lost and whether the loss of tRNAs is universal, we re-annotated all of the available oribatid mites and sequenced the mt genome of Oribatula sakamorii. Methods: The mitogenome of O. sakamorii was sequenced with Illumina Hiseq sequencer. The mt tRNA gene annotated using multi-software combined with manual annotation approach. Phylogenetic analyses of maximum likelihood (ML) and Bayesian inference (BI) were performed with both concatenated nucleotide and amino acid sequences.Results: Mt genomes of O. sakamorii contain 37 genes including 22 tRNA genes. We were able to identify all of the mt tRNA genes that were reported as lost in Steganacarus magnus and Paraleius leontonychus, and revealed some atypical tRNAs annotation errors in oribatid mites. Oribatid mite mt genomes are characterized by low rates of gene rearrangement, with six or seven gene blocks conserved between all of the oribatid mite species and the mt genome of ancestral arthropod. Considering only the relative order of the major genes (PCGs, rRNAs), only one gene or two genes were rearranged relative to the ancestral genome. Both CREx analysis and phylogenetic results supported the origin of the Astigmata within the Oribatida. We also explored the phylogenetic relationships among all of the available oribatid mites and the results also confirm the systematic position of Hermannia in the Crotonioidea superfamily. This is also supported by synapomorphic gene derived boundary.Conclusions: The tRNA "lost" phenomenon is not universal in oribatid mites. Instead of loss, we found that the highly atypical secondary structure of inferred mt tRNA genes makes them unidentifiable by a single type of tRNA search program. Multi-software combined with manual annotation approach can improve the accuracy of tRNA gene annotation. Besides, we determined the correct systematic position of Hermannia and supported the origin of astigmatid mites was from oribatid mites.
Development and Validation of a Simple Equation to Evaluate Dietary Protein Intake Using the Blood Urea Nitrogen/Serum Creatinine Ratio in Patients With Stage 3 Chronic Kidney Disease
Authors: Wang Yanhui , Chen Zujiao , Li Jing , Li Zhen , Xie Jianteng , Wang Duan , Li Sheng , Zhang Yifan , Liang Tiantian , Qiu Xueqian , Qi Chunfang , Li Qiuling , Lin Shaochun , Zhang Shaogui , Wang Wenjian
Published: November 2020

Background: A simple, effective and convenient method to assess dietary protein intake (DPI) for chronic kidney disease (CKD) patients is urgently needed in clinical practice. We developed a simple equation to evaluate DPI in patients with stage 3 CKD with the blood urea nitrogen (BUN)/serum creatinine (SCr) ratio (BUN/SCr).Methods: In a prospective cohort of 136 inpatients with stage 3 CKD from 2 centres, we developed estimation equations based on BUN/SCr and the spot urinary urea nitrogen (UUN)/urinary creatinine (UCr) ratio (UUN/UCr) in combination with sex and body mass index (BMI). These equations were then internally and externally validated.Results: The following candidate parameters were derived from univariate regression analysis for 5 established models: sex, BMI, BUN/SCr, UUN and UUN/UCr. Sex and BMI were included in all models after variable evaluation using multiple regression analysis. UUN, UUN/UCr and BUN/SCr were included in model 3, model 4 and model 5, respectively. Both internal validation and external validation indicated that model 5 resulted in the lowest values of bias and root mean square error and the highest P30 compared with model 3 and model 4. Therefore, the model 5 equation, DPI= -5.18 (-14.49 if the patient is female) +1.89×BMI+1.38×BUN/SCr, was selected because of the higher correlation [r = 0.498 (95% confidence interval 0.163,0.719)] and the smaller distribution of the difference between the predicted and measured protein intakes than those of the other models.Conclusion: The DPI equation developed using BUN/SCr, sex and BMI may be used to estimate protein intake for patients with stage 3 CKD.Trial registrationChinese Clinical Trial Registry Center (ChiCTR-ROC-17011363). Registered in 11 May 2017, Retrospectively registered, http://www.chictr.org.cn/index.aspx
Comparison of Minimally Invasive Reduction Combined With Medial and External Fixation in the Treatment of Intra-articular Calcaneal Fractures
Authors: jianchuan wang , jibin Liu , zongpu wang
Published: November 2020

BackgroundComparison of percutaneous minimally invasive replacement joint inside external fixation technique and tarsal sinus approach to treat Sanders Ⅱ and Ⅲ clinical effect of intra-articular calcaneal fractures.MethodsThe clinical data of 64 cases of calcaneal fracture admitted to our hospital from January 2010 to January 2016 were retrospectively analyzed.According to different surgical methods,they were divided into the percutaneous minimally invasive reduction and internal and external fixation group (30 cases) and the tarsal sinus approach (34 cases).Comparison of two groups of patients with operation time,intraoperative blood loss,hospital stay, postoperative complications and radiographic evaluation including heel bone length,width,height,Bohler Angle,Angle of Gissane,calcaneal varus Angle,clinical efficacy evaluation including the American Orthopaedic Foot and Ankle Society (AOFAS),the visual analogue score for pain(VAS) score,health survey profiles (SF - 36) score and score Maryland ankle function.ResultsPatients in both groups were followed up for 12 to 50 months,an average of 24.8 months.All fractures obtained bone union.The waiting time,hospital stay,intraoperative blood loss and incision complications in the percutaneous minimally invasive medial and external fixation group were lower than those in the tarsal sinus group,and the differences were statistically significant (P<0.01).At the last follow-up,the length,width,height,Angle of Bohler,Angle of Gissane,and Angle of calcaneal varus were significantly increased in both groups (P<0.01),the calcaneal width was significantly lower than that before surgery (P<0.01),and the difference between the two groups was not statistically significant (P > 0.05).Clinical efficacy evaluation The AOFAS,VAS,SF-36 and Maryland scores were (85.28±8.21),(0.84±1.21),(82.95±3.25) and (83.56±3.32) at the last follow-up in the percutaneous minimally invasive medial and external fixation group.The AOFAS, VAS, SF-36 and Maryland scores of the tarsal sinus group were (83.32 ± 7.69),(1.85 ± 1.32),(80.71 ± 5.42),(81.85 ± 2.41) points,and there was no significant difference between the two groups (P > 0.05).ConclusionUnder the condition of having a good command of surgical indications and surgical skills,the use of calcaneoplastic forceps for percutaneous minimally invasive reduction combined with medial and external fixation for treatment of intra-articular calcaneoplasty fractures can achieve similar clinical effects as the tarsal sinus approach.However,the use of calcaneoplastic forceps for percutaneous minimally invasive reduction combined with internal and external fixation has advantages such as fewer complications, less blood loss,and shorter operation time,etc,which is of good safety and worthy of clinical promotion.
β-Ecdysterone Prevents LPS-Induced Osteoclastogenesis by Regulating NF-κB Pathway in Vitro
Authors: Li Yuling , Zhang Jing , Yan Caiping , Chen Qian , Xiang Chao , Zhang Qingyan , Wang Xingkuan , jiang ke
Published: November 2020

BackgroundLipopolysaccharide (LPS), a bacteria product, plays an important role in orthopedic diseases. Drugs that inhibit LPS-induced osteoclastogenesis are urgently needed for the prevention of bone destruction.MethodsIn this study, we evaluated the effect of β-ecdysterone (β-Ecd), a major component of Chinese herbal medicines derived from the root of Achyranthes bidentata BI on LPS-induced osteoclastogenesis in vitro and explored the mechanism underlying the effects of β-Ecd on this.ResultsWe showed that β-Ecd inhibited LPS-induced osteoclast formation from osteoclast precursor RAW264.7 cells. The inhibition occurred through suppressing the production of osteoclast activating TNF-α, IL-1β, PGE2 and COX-2, which led to down-regulating expression of osteoclast-related genes including RANK, TRAF6, MMP-9, CK and CAⅡ. Besides, β-Ecd treatment can inhibit LPS-induced activation of NF-κB signaling pathway in RAW264.7 cells. Meanwhile, inhibition of NF-κB signaling pathway decreased the formation of osteoclasts and expression of pro-inflammatory cytokines which LPS-induced. Collectively, β-Ecd can prevent LPS-induced osteoclast formation in vitro by regulating NF-κB signaling pathway.Conclusions﻿These findings provide evidences that β-Ecd might be beneficial as a valuable choice for the prevention and treatment of bacteria-induced bone destruction disease, and give new insights for understanding its possible mechanism.
Total Hip Arthroplasty Through the Direct Anterior Approach With and Without the Use of a Traction Table; a Matched-control, Retrospective, Single Surgeon Study
Authors: WERNLY DIANE , Wegrzyn Julien , Lallemand Geoffroi , Mahlouly Jaad , Tissot Christophe , Antoniadis Alexander
Published: November 2020

BackgroundHip surgeons performing total hip arthroplasty (THA) through the direct anterior approach (DAA) commonly use a traction table to facilitate exposure. Even though performing THA through DAA without traction table could be technically more demanding, this technique offers the advantage of intraoperative leg length comparison. Therefore, this study aimed to compare clinical outcomes, complication rates, component positioning and leg length discrepancy (LLD) after THA through the DAA performed with or without a traction table.MethodsA single-surgeon continuous series of 75 patients who underwent DAA THA performed with a traction table were matched for gender, age and BMI with 75 patients who underwent DAA THA performed without a traction table (male:62, female:88, with an average age of 68 y.o). Clinical and radiological outcomes, intra- and post-operative complications and LLD were retrospectively assessed.ResultsNo statistically significant difference was detected in surgical time, hospital stay, Harris Hip Score (HHS), complication rates, and implant positioning between the two groups. Leg length restoration was significantly more accurate in the group performed without a traction table (2.4 ± 2 mm vs. 3.7 ± 3.1 mm, respectively; p value ≤ 0.05). No LLD > 10 mm was reported in the group performed without traction table, whereas two cases (2.7 %) were reported in those performed with traction table.ConclusionPerforming THA through DAA without a traction table was associated with a significantly more accurate leg length restoration without significantly increase in the rates of intra- and post-operative complications.
Coronary Artery Spasm is Associated With an Increased Risk of Incident Diabetes: A Nationwide Population-Based Cohort Study
Authors: Hung Ming-Jui , Chang Nen-Chung , Hu Patrick , Chen Tien-Hsing , Mao Chun-Tai , Yeh Chi-Tai , Hung Ming-Yow
Published: November 2020

BackgroundNon-diabetic coronary artery spasm (CAS) without obstructive coronary artery disease increases insulin resistance. We investigated the risk of incident type 2 diabetes (diabetes) associated with CAS.MethodsPatient records were retrospectively collected from the Taiwan National Health Insurance Research Database during the period 2000-2012. The matched cohorts consisted of 12,413 patients with CAS and 94,721 patients in the control group. ResultsDuring the entire follow-up, the incidence of newly-diagnosed diabetes was 22.2 events per 1000 person-years in the CAS group and 13.9 events per 1000 person-years in the control group. The increased risk of CAS-related incident diabetes was observed regardless of sex and length of follow-up. The median time to incident diabetes was 2.9 and 3.5 years in the CAS and the control group (P <0.001), respectively, regardless of sex. Although age did not affect the risk of CAS-related incident diabetes, the risk was less apparent in the subgroups of male, dyslipidemia, chronic obstructive pulmonary disease, stroke, gout and medicated hypertension. However, CAS patients aged <50 years compared with patients ≥50 years had a greater risk of incident diabetes in females but not in males. Older CAS patients developed diabetes in a shorter length of time than younger patients.ConclusionCAS is a risk factor for incident diabetes regardless of sex. However, females aged <50 years have a more apparent risk for CAS-related diabetes than old females, which is not observed in males. The median time of 2.9 years to incident diabetes warrants close follow-up.
Cardiovascular Risk is Elevated in Lean Subjects With Non Alcoholic Fatty Liver Disease
Authors: Kim Yuna , Han Eugene , Lee Jae Seung , Lee Hye Won , Kim Beom Kyung , Kim Mi Kyung , Kim Hye Soon , Park Jun Yong , Kim Do Young , Ahn Sang Hoon , Lee Byung-Wan , Kang Eun Seok , Cha Bong-Soo , Lee Yong-ho , Kim Seung Up
Published: November 2020

BackgroundNon-alcoholic fatty liver disease (NAFLD) and obesity are independently associated with increased risk for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality in patients with NAFLD. Many NAFLD patients are lean, but their ASCVD risk compared to obese subjects with NAFLD is unclear.MethodsData from the 2008–2011 Korean National Health and Nutrition Examination Surveys database were analysed (n = 4,786). NAFLD was defined as a comprehensive NAFLD score of ≥40 or a liver fat score of ≥–0.640. ASCVD risk was evaluated using the American College of Cardiology/American Heart Association guidelines. A high probability of ASCVD was defined as an ASCVD risk of >10%.ResultsThe frequency of subjects without NAFLD, with obese NAFLD, and with lean NAFLD was 62.4% (n = 2,987), 26.6% (n = 1,274), and 11.0% (n = 525), respectively. Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of a high ASCVD risk (mean 15.6 ± 14.0 and 51.6%) than those with obese NAFLD and without NAFLD (mean 11.2 ± 11.4 and 39.8%; 7.9 ± 10.9 and 25.5%, all P < 0.001). Subjects with lean NAFLD and significant liver fibrosis showed a significantly higher odds ratio for a high risk for ASCVD than those with obese NAFLD with or without significant liver fibrosis (odds ratio = 2.60 vs. 1.93; P = 0.023).ConclusionsDespite a more favourable metabolic profile, subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of high ASCVD risk than those with obese NAFLD. Similarly, lean subjects with significant liver fibrosis had a higher probability of ASCVD than obese subjects in the subpopulation with NAFLD.
Effect of Acute Heat Stress on Protein Expression and Histone Modification in The Adrenal Gland of Male Layer-Type Country Chickens
Authors: Zheng Hao-Teng , Zhuang Zi-Xuan , Chen Chao-Jung , Liao Hsin-Yi , Chen Hung-Lin , Hsueh Huang-Chun , Chen Chih-Feng , Chen Shuen-Ei , Huang San-Yuan
Published: November 2020

The adrenal gland responds to heat stress by epinephrine and glucocorticoid release to alleviate the adverse effects. This study investigated the effect of acute heat stress on the protein profile and histone modification in the adrenal gland of layer-type country chickens. A total of 192 30-week-old roosters were subject to acute heat stress. A resistant group and a susceptible group were identified according to body temperature change after heat stress. Adrenal glands were collected for global protein expression and histone modification analysis. The results indicated that fatty acid amide hydrolase and parathymosin were downregulated, whereas somatostatin, steroidogenic acute regulatory protein, hydroxy-δ-5-steroid dehydrogenase, 3 beta- and steroid δ-isomerase 1, and prostaglandin E synthase 3 were upregulated in the resistant group. Histone modification analysis identified 115 histone markers. The tri-methylation state of histone H3 lysine 27 (H3K27me3) was significantly more abundant in the susceptible group and showed positive crosstalk with K36me and K37me in the H3 tails. Roosters in the heat-resistant group exhibited lower hypothalamus–pituitary–adrenal axis activity but higher reactivity to maintain body temperature homeostasis. Alteration of adrenal H3K27me3 level was associated with the endocrine function of adrenal H3K27me3 and may have contributed to the thermotolerance of chickens.
Slow Life History Leaves Endangered Snake Vulnerable to Illegal Poaching
Authors: Jolly Chris , von Takach Brenton , Webb Jonathan
Published: November 2020

Global wildlife trade is a multibillion-dollar industry and a significant driver of vertebrate extinction risk. Yet, few studies have quantified the impact of wild harvesting for the illicit pet trade on populations. Long-lived species, by virtue of their slow life history characteristics, may be unable to sustain even low levels of harvesting. Here, we assessed the impact of illegal poaching on a metapopulation of endangered broad-headed snakes (Hoplocephalus bungaroides) at gated (protected) and ungated (unprotected) populations. Because broad-headed snakes are long-lived, grow slowly and reproduce infrequently, populations are likely vulnerable to increases in adult mortality. Long-term data revealed that annual survival rates of snakes were significantly lower in the ungated population than the gated population, consistent with the hypothesis of human removal of snakes for the pet trade. Population viability analysis showed that the ungated population has a strongly negative population growth rate and is only prevented from ultimate extinction by dispersal of small numbers of individuals from the gated population. Sensitivity analyses showed that the removal of a small number of adult females was sufficient to impose negative population growth and suggests that threatened species with slow life histories are likely to be especially vulnerable to illegal poaching.
Relationship between the density of tatami stores and COVID-19 morbidity and mortality in Japan
Authors: Iwasaki Soshi , Kigawa Yoshiyasu , Takahashi Kazunobu , Yamakage Michiaki
Published: November 2020

Although the primary mechanism for the spread of coronavirus disease 2019 (COVID-19) infection is through respiratory droplets (1), the virus that causes COVID-19 can survive on smooth surfaces (e.g., stainless steel, plastic, glass) for days at low temperatures (2). Surface transmission represents a possible route of infection, as unwashed hands that touch a contaminated surface can transfer the virus to mucous membranes (e.g., eyes, nose, mouth) (3). However, it is difficult to observe disease transmission directly. Therefore, the Japanese Cluster Countermeasures team has identified the “Three Cs”—Closed spaces with poor ventilation, Crowded places, and Close-contact settings—as factors to avoid to prevent COVID-19 clusters. Identifying other environmental factors that increase or decrease the number of infections would be useful to prevent the spread of COVID-19. Therefore, this study aimed to develop a shoe-related transmission model and enhance COVID-19 transmission route precautions by investigating the associations between the prevalence of COVID-19 and both population density and the distribution of tatami stores in each prefecture in Japan. As a result, a significant negative relationship was observed between the number of tatami stores per 100,000 population and the number of COVID-19 cases and deaths.
Surgery for Craniovertebral Junction Pathologies: Minimally Invasive Anterior Submandibular Retropharyngeal Key-Hole Approach
Authors: Viola Árpád , Kozma István , Süvegh Dávid
Published: November 2020

BackgroundOur objective was to develop a new, minimally invasive surgical technique for the resolution of craniovertebral junction pathologies, which can eliminate the complications of the previous methods, like liquor-leakage, velopharyngeal insufficiency and wound-dehiscence associated with the transoral or lateral approaches.MethodsDuring the first stage of the operation, three patients underwent occipito-cervical dorsal fusion, while the fourth patient received C1-C2 fusion according to Harms. C1-C2 decompressive laminectomy was performed in all four cases. Ventral C1-C2 decompression with microscope assisted minimally invasive anterior submandibular retropharyngeal key-hole approach (MIS ASR) method was performed in the second stage. The MIS ASR similarly to the traditional anterior retropharyngeal surgery – preserves the hard and soft palates, yet can be performed through a 25 mm wide incision with the use of only one retractor.ResultsThe MIS ASR approach was a success in all four cases, there were no intra- and postoperative complications. This method, compared to the transoral approach, provided on average 23% (4.56 cm2 / 6.05 cm2) smaller dural decompression area; nonetheless, the entire pathology could be removed in all cases. After the surgery, all patients have shown significant neurological improvement.ConclusionBased on the outcome of these four cases we think that the MIS ASR approach is a safe alternative to the traditional methods while improving patient safety by reducing the risks of complications.
The Clinical Application of Novel Mini Transoral Endoscopic Thyroidectomy to Avoid Numbness and Pain in Patients with Thyroidectomy
Authors: Ruan Jian , Ning Xiaojie , He Fan , Yuan Yuan , Li Bin , Zhao Jianguo
Published: November 2020

Background: Transoral endoscopic thyroidectomy has been gaining popularity as it allows patients to avoid a visible scar in the neck. However, there are still exiting disadvantages of traditional transoral endoscopic thyroidectomy，including numbness in the lower jaw or excessive edema. Therefore, we designed and applied a novel Mini transoral endoscopic thyroidectomy on patients requiring for thyroidectomy.Patients and Methods: A total of 55 patients requiring for unilateral thyroidectomy who underwent novel Mini transoral endoscopic thyroidectomy (Mini group) were identified from August 2019 to December 2019. As a comparison, a matched cohort of 55 patients requiring for conventional transoral endoscopic thyroidectomy was also identified. The two groups were analyzed in terms of clinical characteristics, perioperative/operative clinical date and post-operative complications. Results: The hospitalization time of patients in the Mini group was obviously less than that in traditional group. Furthermore, the numbness of the lower jaw, nylon wire examination score, pressure needle puncture examination score, or numbness VAS score indicated that the degree of numbness of the jaw in Mini group is significantly better than the traditional group. Moreover, the pain of the axillary incision using the pain VAS score method also showed that Mini group is significantly better than the traditional group. The results of pain of the axillary incision using the VAS score method also showed that novel Mini group was significantly better than that in the traditional group. Furthermore, dysfunction of mandibular muscles was observed in six of fifty-five patients in the traditional group, whereas no dysfunction of mandibular muscles observed in Mini group. At last, the degree of postoperative mandibular edema in Mini group was markedly slighter than that in traditional group. The post-operation infection rate was markedly lower in Mini group.Conclusion: The new novel Mini transoral endoscopic thyroidectomy is safe and feasible, and reduces the damage to the functional muscles such as the mandibular diaphragm and lower lip muscles, which significantly reduces the numbness and edema of the mandible after surgery. Our novel Mini transoral endoscopic thyroidectomy is a feasible and safe advancement, which can be a viable alternative protecting patients from insufferable numbness and pain.
Integrating Hepatitis B Care and Treatment with Existing HIV Services is Possible: A Cost Minimization Analysis from a Low Resource Setting.
Authors: Ejalu David Livingstone , Mutyoba Joan Nankya , Wandera Claude , Seremba Emmanuel , Kambugu Andrew , Easterbrook Philippa , Amandua Jacinto , Muganzi Alex , Rachel Beyagira , Mugagga Kaggwa , Ocama Ponsiano
Published: November 2020

Background: In recent years there has been growing interest in exploring methods by which the care pathways for people with comorbid physical and health problems may be integrated. The success of such an integration however would depend on several factors including feasibility, acceptability and costs involved. Therefore, this report presents estimated provider costs associated with managing an integrated HBV and HIV clinical pathway for patients on life-long treatment in low resource setting in Uganda.Methods: A cost minimisation analysis from the providers perspective was done by considering financial costs as a measure of the amount of money spent on resources used in the clinical pathways. The annual cost per patient was simulated based on total amount of resources spent for all the patient visits to the facility for HBV or HIV care per year.Results: Findings showed that drugs and laboratory tests were the main drivers of costs in the pathways. A high-volume facility (Arua regional referral hospital- ARRH) had a higher cost per patient in both clinics than did the low volume facility (Koboko District Hospital- KDH). Variations occurred due to differences in the carders of health workers, the infrastructure, the amounts of consumables used in the facilities. Cost per HBV patient was $163.59 in ARRH and $145.76 in K DH while the cost per HIV patient was $176.52 in ARRH and $173.23 in KDH. The integration resulted into total saving of $36.73 per patient per year in Arua RRH and $17.5 in Koboko DH. The cost saving accrued from savings from personnel, fixed costs, consumables and utilities incurred in running the standalone Hepatitis B clinic and the reduction in per HIV patient costs from sharing of resources in the integrated pathway. Conclusion: This analysis showed that the application of the integrated Pathway in HIV and HBV patient management could improve hospital cost efficiency compared to operating stand-alone clinics. This could further improve adherence to treatment by Hepatitis B patients and improve patient outcomes as HBV patients get access to counselling services.
Immune-related genes of the larval Holotrichia parallela in response to entomopathogenic nematodes Heterorhabditis beicherriana LF
Authors: Li Ertao , Qin Jianhui , Feng Honglin , Li Jinqiao , Li Xiaofeng , Nyamwasaa Innocent , Cao Yazhong , Ruan Weibin , Li Kebin , Yin Jiao
Published: November 2020

Background
Entomopathogenic nematodes (EPNs) emerge as compatible alternatives to conventional insecticides in controlling Holotrichia parallela larvae (Coleoptera: Scarabaeidae). However, the immune responses of H. parallela against EPNs infection remain unclear.
Results
In present research, RNA-Seq was firstly performed. A total of 89427 and 85741 unigenes were achieved from the midgut of H. parallela larvae treated with Heterorhabditis beicherriana LF for 24 and 72 h, respectively; 2545 and 3156 unigenes were differentially regulated, respectively. Among those differentially expressed genes (DEGs), 74 were identified potentially related to the immune response. Notably, some immune-related genes, such as peptidoglycan recognition protein SC1 (PGRP-SC1), pro-phenoloxidase activating enzyme-I (PPAE-I) and glutathione s-transferase (GST), were induced at both treatment points. Bioinformatics analysis showed that PGRP-SC1, PPAE-I and GST were all involved in anti-parasitic immune process. Quantitative real-time PCR (qRT-PCR) results showed that the three immune-related genes were expressed in all developmental stages; PGRP-SC1 and PPAE-I had higher expressions in midgut and fat body, respectively, while GST exhibited high expression in both of them. Moreover, in vivo silencing of them resulted in increased susceptibility of H. parallela larvae to H. beicherriana LF.
Conclusion
These results suggest that PGRP-SC1, PPAE-I and GST could be used as target genes to disturb the immune system of H. parallela. This study provides the first comprehensive transcriptome resource of H. parallela exposure to nematode challenge that will help to support further comparative studies on host-EPN interactions.
Comparative Transcriptome Analysis Reveals Molecular Mechanism and Regulatory Network of Rosa Chinensis ‘Old Blush’ Leaves in Response to Drought Stress
Authors: Jia Xin , Feng Hui , Bu Yanhua , Lu Yingmin , Ji Naizhe , Zhao Shiwei
Published: November 2020

Background: Rose is one of the most important ornamental crops, but drought limits its yield and quality seriously. Although serval abiotic stress related genes have been identified, the molecular mechanism during rose’s responding to drought stress is still limited. In this study, the transcriptomes of leaves of two-year-old cutting seedlings of Rosa chinensis ’Old Blush’ from three continuous droughted stages (30, 60, 90 days after full watering) and rewatering were analyzed using RNA sequencing. Meanwhile, weighted gene co-expression network analysis (WGCNA) was used to construct a co-expression network associated with the physiological traits of drought response to discover the hub transcription factors involved in drought response.Results: More than 45 million high-quality clean reads were generated from samples and used for comparison with the rose reference genome. A total of 46433 differentially expressed genes were identified. Gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that drought stress caused significant changes in signal transduction, plant hormones, primary and secondary metabolism, and a certain degree of recovery after rewatering. Gene co-expression analysis identified 18 modules, in which four modules have highly degree of correlation with physiological traits. In addition, twenty-two transcription factors including members of NACs, WRKYs, MYBs, ERFs, ARFs and bHLHs with high connectivity in these four modules were screened. Conclusions: The results of this study provided the first transcriptome sequencing report of the drought stress in R.chinensis, and also provided candidate transcription factors in response to drought stress, providing clues for improving the drought tolerance of the rose through molecular breeding in the future.
TAD Cliques Predict Key Features of Chromatin Organization
Authors: Ali Tharvesh M Liyakat , Brunet Annael , Paulsen Jonas , Collas Philippe
Published: November 2020

Background: Processes underlying genome 3D organization and domain formation in the mammalian nucleus are not completely understood. Multiple processes such as transcriptional compartmentalization, DNA loop extrusion and interactions with the nuclear lamina dynamically act on chromatin at multiple levels. Here, we explore long-range interaction patterns between topologically associated domains (TADs) in several cell types.Results: We find that this is connected to many key features of chromatin organization, including open and closed compartments, compaction and loop extrusion processes. We find that domains that form large TAD cliques tend to be repressive across cell types, when comparing gene expression, LINE/SINE repeat content and chromatin subcompartments. Further, TADs in large cliques are larger in genomic size, less dense and depleted of convergent CTCF motifs, in contrast to smaller and denser TADs formed by a loop extrusion processes.Conclusion: Our results shed light on the organizational principles that govern repressive and active domains in the human genome.
Venom-gland Transcriptomic, Venomic, and Antivenomic Profiles of the Spine-bellied Sea Snake (Hydrophis curtus) from the South China Sea
Authors: Zhao Hong-Yan , Wen Lin , Miao Yu-Feng , Du Yu , Sun Yan , Yin Yin , Lin Chi-Xian , Lin Long-Hui , Ji Xiang , Gao Jian-Fang
Published: November 2020

Background: A comprehensive evaluation of the -omic profiles of venom is important for understanding the potential function and evolution of snake venom. Here, we conducted an integrated multi-omics-analysis to unveil the venom-transcriptomic and venomic profiles in a same group of spine-bellied sea snakes (Hydrophis curtus) from the South China Sea, where the snake is a widespread species and might generate regionally-specific venom potentially harmful to human activities. The capacity of two heterologous antivenoms to immunocapture the H. curtus venom was determined for an in-depth evaluation of their rationality in treatment of H. curtus envenomation. In addition, a phylogenetic analysis by maximum likelihood was used to detect the adaptive molecular evolution of full-length toxin-coding unigenes.Results: A total of 90,909,384 pairs of clean reads were generated via Illumina sequencing from a pooled cDNA library of six specimens, and yielding 148,121 unigenes through de novo assembly. Sequence similarity searching harvested 63,845 valid annotations, including 63,789 non-toxin-coding and 56 toxin-coding unigenes belonging to 22 protein families. Three protein families, three-finger toxins (3-FTx), phospholipase A2 (PLA2), and cysteine-rich secretory protein, were detected in the venom proteome. 3-FTx (27.15% in the transcriptome/41.94% in the proteome) and PLA2 (59.71%/49.36%) were identified as the most abundant families in the venom-gland transcriptome and venom proteome. In addition, 24 unigenes from 11 protein families were shown to have experienced positive selection in their evolutionary history, whereas four were relatively conserved throughout evolution. Commercial Naja atra antivenom exhibited a stronger capacity than Bungarus multicinctus antivenom to immunocapture H. curtus venom components, especially short neurotoxins, with the capacity of both antivenoms to immunocapture short neurotoxins being weaker than that for PLA2s.Conclusions: Our study clarified the venom-gland transcriptomic and venomic profiles along with the within-group divergence of a H. curtus population from the South China Sea. Adaptive evolution of most venom components driven by natural selection appeared to occur rapidly during evolutionary history. Notably, the utility of commercial N. atra and B. multicinctus antivenoms against H. curtus toxins was not comprehensive; thus, the development of species-specific antivenom is urgently needed.
The MEP-pathway genes are polyphyletic origin and evolutionary conserved
Authors: Zeng Liping , Dehesh Katayoon
Published: November 2020

BackgroundIsoprenoids are amongst the most ancient and essential class of metabolites produced in all organisms, either via mevalonate (MVA)-and/or methylerythritol dicyclophosphate (MEP)-pathways. The MEP-pathway is present in all plastid-bearing organisms and most eubacteria. However, no comprehensive study reveals the origination and evolutionary characteristics of MEP-pathway genes in eukaryotes.ResultsHere, detailed bioinformatics analyses of the MEP-pathway provide an in-depth understanding the evolutionary history of this indispensable biochemical route, and offer a basis for the co-existence of the cytosolic MVA- and plastidial MEP-pathway in plants given the established exchange of the end products between the two isoprenoid-biosynthesis pathways. Here, phylogenetic analyses establish the contributions of both cyanobacteria and Chlamydiae sequences to the plant’s MEP-pathway genes. Moreover, Phylogenetic and inter-species syntenic block analyses demonstrate that six of the seven MEP-pathway genes have predominantly remained as single-copy in land plants in spite of multiple whole-genome duplication events (WGDs). Substitution rate and domain studies display the evolutionary conservation of these genes, reinforced by their high expression levels. Distinct phenotypic variation among plants with reduced expression levels of individual MEP-pathway genes confirm the indispensable function of each nuclear-encoded plastid-targeted MEP-pathway enzyme in plant growth and development. ConclusionCollectively, these findings reveal the polyphyletic origin and restrict conservation of MEP-pathway genes, and reinforce the potential function of the individual enzymes beyond production of the isoprenoids intermediates.