bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a Goat Intersexuality-Associated Novel Variant Through Genome-Wide Resequencing and Hi-C
Authors: E Guang-Xin , Zhou Dong-Ke , Zheng Zhu-Qing , Yang Bai-Gao , Li Xiang-Long , Li Lan-Hui , Zhou Rong-Yan , Nai Wen-Hui , Jiang Xun-Ping , Zhang Jia-Hua , Hong Qiong-Hua , Ma Yue-Hui , Chu Ming-Xing , Gao Hui-Jiang , Zhao Yong-Ju , Duan Xing-Hai , He Yong-Meng , Na Ri-Su , Han Yan-Guo , Zeng Yan , Jiang Yu , Huang Yong-Fu
Published: February 2021

Background:Polled intersex syndrome (PIS) leads to reproductive disorders in goats and exerts a heavy influence on goat breeding. Since 2001, the core variant of an 11.7 kb deletion at ~129 Mb on chromosome 1 (CHI1) has been widely used as a genetic diagnostic criterion. In 2020, a ~0.48 Mb insertion within the PIS deletion was identified by sequencing in XX intersex goats. However, the suitability of this variation for the diagnosis of intersex goats worldwide and its further molecular genetic mechanism need to be clarified.

Results:The whole-genome selective sweep of intersex goats from China was performed with whole-genome next-generation sequencing technology for large sample populations and a case–control study on interbreeds. A series of candidate genes related to the goat intersexuality phenotype were found. We further confirmed that a ~0.48 Mb duplicated fragment (includingERGandKCNJ15) downstream of the ~20 Mb PIS region was reversely inserted into the PIS locus in intersex Chinese goats and was consistent with that in European Saanen and Valais black-necked goats. High-throughput chromosome conformation capture (Hi-C) technology was then used to compare the 3D structures of the PIS variant neighborhood in CHI1 between intersex and non-intersex goats. A newly found structure was validated as an intrachromosomal rearrangement. This inserted duplication changed the original spatial structure of goat CHI1 and caused the appearance of several specific loop structures in the adjacent ~20 kb downstream region ofFOXL2.

Conclusions:Results suggested that the novel complex PIS variant genome was sufficient as a broad-spectrum clinical diagnostic marker of XX intersexuality in goats from Europe and China. A series of private dense loop structures caused by segment insertion into the PIS deletion might affect the expression ofFOXL2or other neighboring novel candidate genes. However, these structures require further in-depth molecular biological experimental verification. In general, this study provided new insights for future research on the molecular genetic mechanism underlying female-to-male sex reversal in goats.
Algorithmic Annotation of Functional Roles for Components of 3,044 Human Molecular Pathways
Authors: Sorokin Maxim , Borisov Nicolas , Kuzmin Denis , Gudkov Alexander , Zolotovskaia Marianna , Garazha Andrew , Buzdin Anton
Published: February 2021

Current methods of high-throughput molecular and genomic analyses enabled to reconstruct thousands of human molecular pathways. Knowledge of molecular pathways structure and architecture taken along with the gene expression data can help interrogating the pathway activation levels (PALs) using different bioinformatic algorithms. In turn, the pathway activation profiles can characterize molecular processes, which are differentially regulated and give numeric characteristics of the extent of their activation or inhibition. However, different pathway nodes may have different functions toward overall pathway regulation, and calculation of PAL requires knowledge of molecular function of every node in the pathway in terms of its activator or inhibitory role. Thus, high-throughput annotation of functional roles of pathway nodes is required for the comprehensive analysis of the pathway activation profiles. We proposed an algorithm that identifies functional roles of the pathway components and applied it to annotate 3,044 human molecular pathways extracted from the Biocarta, Reactome, KEGG, Qiagen Pathway Central, NCI, and HumanCYC databases and including 9,022 gene products. The resulting knowledgebase can be applied for the direct calculation of the PALs and establishing large scale profiles of the signaling, metabolic, and DNA repair pathway regulation using high throughput gene expression data. We also provide a bioinformatic tool for PAL data calculations using the current pathway knowledgebase.
SARS-CoV-2 Early Screening at the Point of Entry: Travelers From Bangladesh to Italy–July 2020
Authors: Rueca Martina , Di Caro Antonino , Gruber Cesare Ernesto Maria , Messina Francesco , Giombini Emanuela , Valli Maria Beatrice , Lalle Eleonora , Lanini Simone , Vairo Francesco , Capobianchi Maria Rosaria , Bartolini Barbara
Published: February 2021

We report phylogenetic and mutational analysis by NGS of six SARS-CoV-2 strains from patients flying from Bangladesh to Italy (July 2020). Data suggest that no further circulation of such imported strains occurred in Italy, stating the efficacy of early screening at the point of entry and supporting the importance of molecular epidemiology in monitoring the efficacy of control measures.
Case Report: Preimplantation Genetic Testing and Pregnancy Outcomes in Women With Alport Syndrome
Authors: Shi Wei-Hui , Ye Mu-Jin , Chen Song-Chang , Zhang Jun-Yu , Chen Yi-Yao , Zhou Zhi-Yang , Qin Ning-Xin , Zhou Xuan-You , Xu Nai-Xin , Jiang Zi-Ru , Lin Jing , Huang He-Feng , Xu Chen-Ming
Published: February 2021

Background

Alport syndrome, a monogenic kidney disease, is characterized by progressive hemorrhagic nephritis, sensorineural hearing loss, and ocular abnormalities. Mutations in COL4A5 at Xq22 accounts for 80–85% of X-linked Alport syndrome patients. Three couples were referred to our reproductive genetics clinic for prenatal or preconception counseling.

Methods

Prenatal diagnoses were performed by amplifying targeted regions of COL4A5. Targeted next-generation sequencing (NGS)-based haplotype analysis or karyomapping was performed in two patients. Pregnancy outcomes in the three patients were collected and analyzed. Published Alport syndrome cases were searched in Pubmed and Embase.

Results

Prenatal diagnoses in two cases showed one fetus harbored the same pathogenic mutation as the proband and the other was healthy. The couple with an affected fetus and the patient with a family history of Alport syndrome chose to take the preimplantation genetic testing (PGT) procedure. One unaffected embryo was transferred to the uterus, and a singleton pregnancy was achieved, respectively. Two patients presented non-nephrotic range proteinuria (<3 g/24 h) during pregnancy and the three cases all delivered at full-term. However, published Alport cases with chronic kidney disease or proteinuria during pregnancy were came with a high rate (75%) of adverse maternal and fetal outcomes.

Conclusion

The PGT procedure performed in this study was proven to be practicable and might be expanded to be applied in other monogenic diseases. Moderate or severe renal impairments in Alport syndrome were strongly associated with adverse maternal and fetal outcomes, and baseline proteinuria was a potential predictor for pregnancy outcomes of Alport syndrome as other kidney diseases.
Immunoregulatory Effects of Mitochondria Transferred by Extracellular Vesicles
Authors: She Zhou , Xie Min , Hun Marady , Abdirahman Amin Sheikh , Li Cuifang , Wu Feifeng , Luo Senlin , Wan Wuqing , Wen Chuan , Tian Jidong
Published: February 2021

Mitochondria participate in immune regulation through various mechanisms, such as changes in the mitochondrial dynamics, as metabolic mediators of the tricarboxylic acid cycle, by the production of reactive oxygen species, and mitochondrial DNA damage, among others. In recent years, studies have shown that extracellular vesicles are widely involved in intercellular communication and exert important effects on immune regulation. Recently, the immunoregulatory effects of mitochondria from extracellular vesicles have gained increasing attention. In this article, we review the mechanisms by which mitochondria participate in immune regulation and exert immunoregulatory effects upon delivery by extracellular vesicles. We also focus on the influence of the immunoregulatory effects of mitochondria from extracellular vesicles to further shed light on the underlying mechanisms.
Advances in the Arms Race Between Silkworm and Baculovirus
Authors: Jiang Liang , Goldsmith Marian R. , Xia Qingyou
Published: February 2021

Insects are the largest group of animals. Nearly all organisms, including insects, have viral pathogens. An important domesticated economic insect is the silkworm moth Bombyx mori. B. mori nucleopolyhedrovirus (BmNPV) is a typical baculovirus and a primary silkworm pathogen. It causes major economic losses in sericulture. Baculoviruses are used in biological pest control and as a bioreactor. Silkworm and baculovirus comprise a well-established model of insect–virus interactions. Several recent studies have focused on this model and provided novel insights into viral infections and host defense. Here, we focus on baculovirus invasion, silkworm immune response, baculovirus evasion of host immunity, and enhancement of antiviral efficacy. We also discuss major issues remaining and future directions of research on silkworm antiviral immunity. Elucidation of the interaction between silkworm and baculovirus furnishes a theoretical basis for targeted pest control, enhanced pathogen resistance in economically important insects, and bioreactor improvement.
Histopathological Findings Predict Renal Recovery in Severe ANCA-Associated Vasculitis Requiring Intensive Care Treatment
Authors: Hakroush Samy , Tampe Desiree , Korsten Peter , Ströbel Philipp , Zeisberg Michael , Tampe Björn
Published: February 2021

Renal involvement is a common and severe complication of AAV as it can cause ESRD. Histopathological subgrouping and ARRS are helpful to predict long-term ESRD in patients with AAV. Because a subgroup of critically ill patients with severe AAV present with deterioration of kidney function requiring RRT at admission, we here aimed to evaluate histopathological findings and predictive value of Berden's histopathological subgrouping and ARRS for severity of AKI and requirement of RRT during the short-term clinical course in critically ill patients requiring intensive care treatment and predictors for short-term renal recovery in patients requiring RRT. A subgroup of 15/46 (32. 6%) AAV patients with biopsy-proven AAV required RRT during the short-term course of disease, associated with requirement of critical care treatment. While histopathological subgrouping and ARRS were associated with requirement of acute RRT, presence of global glomerular scarring was the strongest predictor of failure to recover from RRT after initiation of remission induction therapy. This new aspect requires further investigation in a prospective controlled setting for therapeutic decision making especially in this subgroup.
A Comparative Clinical Study of a Novel Pre-colonoscopy Bowel Capsule Preparation Against Two Commercially Available Liquid Preparations
Authors: Kingston-Smith Harriet , Gunaratne Anoja W. , Saxon John , Ramrakha Sanjay , Dawson Marie Vic M. , Clancy Annabel , Wettstein Antony , Borody Thomas J.
Published: February 2021

Background and Aims: Colonoscopy surveillance depends on effective bowel preparation. Inadequate bowel preparation can lead to inaccurate clinical diagnosis, insufficient visualization of the colon and increased risk of missed diagnosis. This study aimed to compare the efficacy and safety of a novel Capsule Bowel Preparation (RitePrep), high-volume (2L) polyethylene glycol electrolyte solution (MoviPrep®) and low-volume (1L) polyethylene glycol electrolyte solution (Plenvu™).

Methods: Patients (n = 120) were divided into three groups and were administered either RitePrep, MoviPrep® or Plenvu™ as a pre-colonoscopy bowel preparation followed by a colonoscopy at a single center. Validated Boston Bowel Preparation Score (BBPS) and bubble score were used to evaluate bowel cleanliness. Blood tests were also evaluated. The scores and the blood results were analyzed using Kruskal-Wallis and Chi-squared tests.

Results: A total of 120 patients (median age of 55; 57 males) [RitePrep (n = 40), MoviPrep® (n = 40) and Plenvu™ (n = 40)] were included in the study. RitePrep was the most effective method for cleansing the bowel, with a significantly higher median BBPS compared to MoviPrep® and Plenvu™ (p = 0.006 and 0.024, respectively). Nearly 50% of the patients in Plenvu™ group showed increased serum osmolality disturbance. Nausea and vomiting were higher in Plenvu™ and MoviPrep® groups than RitePrep group.

Conclusions: RitePrep was demonstrated to be a more effective and safe preparation than the other two preparations. RitePrep was not only well-tolerated by all patients; the preparation sufficiently cleared the ascending, transverse, and descending colon, enabling optimal visualization for the clinician. RitePrep was also much safer than the comparators, with no alteration in electrolytes measured. For both the clinician and the patient, RitePrep was the preferred preparation.
A Metagenomic Analysis of Mosquito Virome Collected From Different Animal Farms at Yunnan–Myanmar Border of China
Authors: Hameed Muddassar , Wahaab Abdul , Shan Tongling , Wang Xin , Khan Sawar , Di Di , Xiqian Liu , Zhang Jun-Jie , Anwar Muhammad Naveed , Nawaz Mohsin , Li Beibei , Liu Ke , Shao Donghua , Qiu Yafeng , Wei Jianchao , Ma Zhiyong
Published: February 2021

Metagenomic analysis of mosquito-borne and mosquito-specific viruses is useful to understand the viral diversity and for the surveillance of pathogens of medical and veterinary importance. Yunnan province is located at the southwest of China and has rich abundance of mosquitoes. Arbovirus surveillance is not conducted regularly in this province particularly at animal farms, which have public health as well as veterinary importance. Here, we have analyzed 10 pools of mosquitoes belonging toCulex tritaeniorhyncus,Aedes aegypti,Anopheles sinensis, andArmigeres subalbatusspecies, collected from different animal farms located at Yunnan province of China by using metagenomic next-generation sequencing technique. The generated viral metagenomic data reveal that the viral community matched by the reads was highly diverse and varied in abundance among animal farms, which contained more than 19 viral taxonomic families, specific to vertebrates, invertebrates, fungi, plants, protozoa, and bacteria. Additionally, a large number of viral reads were related to viruses that are non-classified. The viral reads related to animal viruses included parvoviruses, anelloviruses, circoviruses, flaviviruses, rhabdoviruses, and seadornaviruses, which might be taken by mosquitoes from viremic animal hosts during blood feeding. Notably, the presence of viral reads matched with Japanese encephalitis virus, Getah virus, and porcine parvoviruses in mosquitoes collected from different geographic sites suggested a potential circulation of these viruses in their vertebrate hosts. Overall, this study provides a comprehensive knowledge of diverse viral populations present at animal farms of Yunnan province of China, which might be a potential source of diseases for humans and domestic animals.
A Novel Aza-Derivative Inhibits agr Quorum Sensing Signaling and Synergizes Methicillin-Resistant Staphylococcus aureus to Clindamycin
Authors: Bernabè Giulia , Dal Pra Matteo , Ronca Vittoria , Pauletto Anthony , Marzaro Giovanni , Saluzzo Francesca , Stefani Annalisa , Artusi Ilaria , De Filippis Vincenzo , Ferlin Maria Grazia , Brun Paola , Castagliuolo Ignazio
Published: February 2021

Increasing antibiotic resistance and diminishing pharmaceutical industry investments have increased the need for molecules that can treat infections caused by dangerous pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). Quorum Sensing (QS) is a signaling mechanism that regulates bacterial virulence in pathogens. A report demonstrating that the anti-inflammatory drug Diflunisal reduces MRSA virulence factors’ expression prompted us to design, synthesize and test 16 aza-analogs as inhibitors of S. aureus virulence factors controlled by the accessory gene regulator (agr) QS system. At first, we evaluated by qRT-PCR the activity of compounds on rnaIII expression, a QS related gene. Azan-7 was the most active molecule tested and it did not show cytotoxic activity in human cell lines. Moreover, we demonstrated that it did not affect bacterial proliferation. Regulation of MRSA virulence genes by Azan-7 was investigated using qRT-PCR and RNAseq. Azan-7 significantly reduced hla, psmα, hysA, agrA, cap1A, and cap1C gene expression. In silico docking demonstrated that Azan-7 binds the response regulator AgrA. This data was confirmed by electrophoretic mobility shift assay (EMSA) reporting that Azan-7 binding to AgrA protein strongly reduced the AgrA-DNA complex formation at the P3 promoter region involved in the regulation of rnaIII transcription. Azan-7 inhibited MRSA-mediated haemolysis, reduced survival of the pathogen at low pH levels, and increased macrophage killing. In addition, Azan-7 enhanced MRSA susceptibility to clindamycin both in planktonic growth and biofilm. Azan-7 did not induce resistance over 10 days in culture. It was equally active against all the AgrA MRSA subtypes encountered among clinical isolates, but it was not active against Staphylococcus epidermidis, although the AgrA proteins show an approximate 80% homology. These results demonstrate that Azan-7 inhibits the expression of MRSA virulence factors by interfering in the QS and synergizes MRSA biofilm with clindamycin, indicating the compound as a promising candidate for the treatment of MRSA infections.
Population Genomic Analysis of Listeria monocytogenes From Food Reveals Substrate-Specific Genome Variation
Authors: Bechtel Tyler D. , Gibbons John G.
Published: February 2021

Listeria monocytogenes is the major causative agent of the foodborne illness listeriosis. Listeriosis presents as flu-like symptoms in healthy individuals, and can be fatal for children, elderly, pregnant women, and immunocompromised individuals. Estimates suggest that L. monocytogenes results in ∼1,600 illnesses and ∼260 deaths annually in the United States. L. monocytogenes can survive and persist in a variety of harsh environments, including conditions encountered in production of fermented dairy products such as cheese. For instance, microbial growth is often limited in soft cheese fermentation because of harsh pH, water content, and salt concentrations. However, L. monocytogenes has caused a number of deadly listeriosis outbreaks through the contamination of cheese. The purpose of this study was to understand if genetically distinct populations of L. monocytogenes are associated with particular foods, including cheese and dairy. To address this goal, we analyzed the population genetic structure of 504 L. monocytogenes strains isolated from food with publicly available genome assemblies. We identified 10 genetically distinct populations spanning L. monocytogenes lineages 1, II, and III and serotypes 1/2a, 1/2b, 1/2c, 4b, and 4c. We observed an overrepresentation of isolates from specific populations with cheese (population 2), fruit/vegetable (population 2), seafood (populations 5, 8 and 9) and meat (population 10). We used the Large Scale Blast Score Ratio pipeline and Roary to identify genes unique to population 1 and population 2 in comparison with all other populations, and screened for the presence of antimicrobial resistance genes and virulence genes across all isolates. We identified > 40 genes that were present at high frequency in population 1 and population 2 and absent in most other isolates. Many of these genes encoded for transcription factors, and cell surface anchored proteins. Additionally, we found that the virulence genes aut and ami were entirely or partially deleted in population 2. These results indicate that some L. monocytogenes populations may exhibit associations with particular foods, including cheese, and that gene content may contribute to this pattern.
Characterization and Function of a Novel Welan Gum Lyase From Marine Sphingomonas sp. WG
Authors: Chang Ai-Ping , Qian Jin , Li Hui , Wang Ying-Lu , Lin Jie-Ying , He Qiao-Mei , Shen Ya-Ling , Zhu Hu
Published: February 2021

Welan gum, a kind of microbial exopolysaccharides, produced by the genus Sphingomonas, have great potential for application in many fields, such as the food industry, cement production, and enhanced oil recovery. But there are still challenges to reduce the cost, enhance the production and the quality. Herein, the bioinformatics analysis of WelR gene was preformed, and the characterization and function of WelR, welan gum lyase, from Sphingomonas sp. WG were investigated for the first time. The results indicated that 382nd (Asn), 383rd (Met), 494th (Asn), and 568th (Glu) were the key amino acid residues, and C-terminal amino acids were essential to keeping the stability of WelR. The optimal temperature and pH of the enzymatic activity were found to be 25°C and 7.4, respectively. And WelR was good low temperature resistance and alkali resistant. K+, Mg2+, Ca2+, Mn2+, and EDTA increased WelR activities, in contrast to Zn2+. Coupled with the change in glucose concentration and growth profile, the qRT-PCR results indicated that WelR may degrade welan gum existing in the culture to maintain bacterial metabolism when glucose was depleted. This work will lay a theoretical foundation to establish new strategies for the regulation of welan gum biosynthesis.
Networks Are Associated With Depression in Patients With Parkinson’s Disease: A Resting-State Imaging Study
Authors: Liao Haiyan , Cai Sainan , Shen Qin , Fan Jie , Wang Tianyu , Zi Yuheng , Mao Zhenni , Situ Weijun , Liu Jun , Zou Ting , Yi Jinyao , Zhu Xiongzhao , Tan Changlian
Published: February 2021

Background

Disturbance of networks was recently proposed to be associated with the occurrence of depression in Parkinson’s disease (PD). However, the neurobiological mechanism of depression underlying PD remains unclear.

Objective

This study was conducted to investigate whether intra-network and inter-network brain connectivity is differently changed in PD patients with and without depression (PDD and PDND patients, respectively).

Methods

Forty-one PDD patients, 64 PDND patients, and 55 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (fMRI). The default mode network (DMN), executive control network (ECN), salience network (SN), precuneus network (PCUN), and sensorimotor network (SMN) were extracted using independent component analysis (ICA), and then the functional connectivity (FC) values within and between these networks were measured.

Results

PDD patients exhibited abnormal FC values within the DMN, ECN, SN, PCUN, and SMN. In addition, PDD patients demonstrated decreased connectivity between anterior SN (aSN) and bilateral ECN, between posterior SN (pSN) and dorsal DMN (dDMN), and between PCUN and dDMN/SMN/bilateral ECN. Connectivity within the left hippocampus of dDMN and the right medial superior frontal gyrus of aSN was a significant predictor of depression level in PD patients.

Conclusions

Aberrant intra- and inter-network FC is involved in several important hubs in the large-scale networks, which can be a biomarker for distinguishing PDD from PDND.
Visual Noise Effect on Contour Integration and Gaze Allocation in Autism Spectrum Disorder
Authors: Mihaylova Milena Slavcheva , Bocheva Nadejda Bogdanova , Totev Tsvetalin Totev , Staykova Svetla Nikolaeva
Published: February 2021

Contradictory results have been obtained in the studies that compare contour integration abilities in Autism Spectrum Disorders (ASDs) and typically developing individuals. The present study aimed to explore the limiting factors of contour integration ability in ASD and verify the role of the external visual noise by a combination of psychophysical and eye-tracking approaches. To this aim, 24 children and adolescents with ASD and 32 age-matched participants with typical development had to detect the presence of contour embedded among similar Gabor elements in a Yes/No procedure. The results obtained showed that the responses in the group with ASD were not only less accurate but also were significantly slower compared to the control group at all noise levels. The detection performance depended on the group differences in addition to the effect of the intellectual functioning of the participants from both groups. The comparison of the agreement and accuracy of the responses in the double-pass experiment showed that the results of the participants with ASD are more affected by the increase of the external noise. It turned out that the internal noise depends on the level of the added external noise: the difference between the two groups was non-significant at the low external noise and significant at the high external noise. In accordance with the psychophysical results, the eye-tracking data indicated a larger gaze allocation area in the group with autism. These findings may imply higher positional uncertainty in ASD due to the inability to maintain the information of the contour location from previous presentations and interference from noise elements in the contour vicinity. Psychophysical and eye-tracking data suggest lower efficiency in using stimulus information in the ASD group that could be caused by fixation instability and noisy and unstable perceptual template that affects noise filtering.
A Compact Model of Ovonic Threshold Switch Combining Thermal Dissipation Effect
Authors: Zhang Shiqing , Xu Hui , Li Zhiwei , Liu Sen , Song Bing , Li Qingjiang
Published: February 2021

Ovonic threshold switch (OTS) has received great attention in neuromorphic computing due to its support for high-density synapse array as a selector and leaky-integration-firing functions Hodgkin-Huxley neurons. However, there is no simple and complete model for device simulation and integrated circuit design, which hindered application until now. In this work, we developed a compact physical model of OTS based on the Poole-Frenkel effect accompanied by the thermal dissipation effect for the first time. The thermal dissipation effect describes the energy flow between the device and the environment so that the model is more practical. Compared with previous experiments, the numerical results fairly fitted the electrical characteristics, demonstrating the model validity. In addition, the relation of the device performance with material and structure was deduced, which can facilitate optimizing the OTS device. The model will be useful for device design and implemented with high speed for simplicity.
Construction and Validation of Nomograms Predicting Survival in Triple-Negative Breast Cancer Patients of Childbearing Age
Authors: Cui Xiang , Song Deba , Li Xiaoxu
Published: February 2021

Background

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer with poorest clinical outcomes. Patients of childbearing age have a higher probability of TNBC diagnosis, with more demands on maintenance and restoration of physical and psychosocial function. This study aimed to design effective and comprehensive nomograms to predict survival in these patients.

Methods

We used the SEER database to identify patients with TNBC aged between 18 and 45 and randomly classified these patients into a training (n=2,296) and a validation (n=2,297) cohort. Nomograms for estimating overall survival (OS) and breast cancer-specific survival (BCSS) were generated based on multivariate Cox proportional hazards models and competing-risk models in the training cohort. The performances of the nomograms were quantified in the validation cohort using calibration curves, time-dependent receiver operating characteristic (ROC) curves and Harrell’s concordance index (C-index).

Results

A total of 4,593 TNBC patients of childbearing age were enrolled. Four prognostic factors for OS and six for BCSS were identified and incorporated to construct nomograms. In the validation cohort, calibration curves showed excellent agreement between nomogram-predicted and actual survival data. The nomograms also achieved relatively high Harrell’s C-indexes and areas under the time-dependent ROC curves for estimating OS and BCSS in both training and validation cohorts.

Conclusions

Independent prognostic factors were identified, and used to develop nomograms to predict OS and BCSS in childbearing-age patients with TNBC. These models could enable individualized risk estimation and risk-adapted treatment for these patients.
Dichondra repens J.R.Forst. and G.Forst.: A Review of Its Traditional Uses, Chemistry, Pharmacology, Toxicology and Applications
Authors: Yao Qi , Wang Ying , Dong Zhiyu , Lai Chencen , Chang Botao , Gong Qiuju , Ren Shuaijun , Sun Dongxue , Lu Jie , Gao Ying
Published: February 2021

Ethnopharmacology relevance:Dichondra repens J.R.Forst. and G.Forst (DRF; Convolvulaceae, called Matijin in Chinese), has been traditionally used to treat jaundice, bacillary dysentery, urinary tract infection, edema, contusions, and strains and sprains based on traditional Chinese medicine (TCM) concepts.

Aim of study: This paper intends to provide a comprehensive and critical analysis of research on DRF focusing on a relationship between traditional uses and pharmacological effects, evaluating the therapeutic potential of this plant.

Methods: Relevant data on DRF were retrieved from available databases.

Results: The heat-clearing and detoxifying, and removing the phlegm and turbid urine effects of DRF are linked to its anti-hepatitis B virus (HBV), anti-inflammatory, and hepatoprotective activities. Especially, the hepatoprotective effects of DRF are mainly based on anti-HBV activities of phenylalanine dipeptides Matijin-Su (MTS) and its derivatives derived from this plant. Further, a phase I anti-HBV clinical trial of a candidate compound named bentysrepinine (Y101, Chinese name Tifentai) has been completed. Also, anti-tumor, analgesic, and antibacterial properties have been reported in the extracts and compounds from DRF. Although pharmacy, pharmacodynamics, toxicology, and pharmacokinetics of bentysrepinine have been systemically reported, no studies have reported chemistry, safety, pharmacology of other compounds or extracts systemically.

Conclusion: Phenylalanine dipeptide compounds are main components and MTS is a characteristic substance of DRF. The main pharmacological effect of DRF is anti-HBV activity, which is coherent with the traditional use of this plant in China. Except bentysrepinine, few studies have been conducted on toxicities of the extracts or compounds from DRF. Thus, it is still necessary to evaluate safety, chemistry, pharmacology of the extracts or compounds from DRF regarding the link between traditional uses and modern applications before the future clinical trials. Bacterial sepsis, cholecystitis and tumors may be prior therapeutic targets of this plant in the future.
Low Dose Rivaroxaban for Atherosclerotic Cardiovascular Diseases: A Systematic Review and Meta-analysis
Authors: Chen Can , Kan Yuanqing , Shi Zhenyu , Guo Daqiao , Fu Weiguo , Li Yanli , Lv Qianzhou , Li Xiaoyu , Si Yi
Published: February 2021

Background: This study aims to explore the role of low-dose rivaroxaban (≤10 mg daily) for the treatment of atherosclerotic cardiovascular disease (ASCVD).

Methods: PubMed, Embase and the Cochrane Library were searched for randomized controlled trials (RCTs) of low-dose rivaroxaban in patients with ASCVD including coronary artery disease (CAD) and peripheral artery disease (PAD). Literature screening, data extraction, and risk of bias assessment were carried out independently by two researchers. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using random-effect models to determine risks of outcomes in ASCVD patients treated with rivaroxaban and comparators, and meta-analysis was conducted via Review Manager 5.3.5 software.

Results: 3,768 records were obtained through literature search, and 9 articles representing 6 RCTs ultimately qualified for this study. The meta-analysis indicated that for patients with CAD, the addition of rivaroxaban (5 mg daily) to aspirin could significantly reduce the risk of major adverse cardiovascular events (MACEs) compared with aspirin alone (HR 0.81, 95% CI, 0.72 to 0.91, p = 0.0004, I2 = 60%, 4 studies). For PAD patients receiving rivaroxaban (5 mg daily) plus aspirin, there was no significant reduction in the risk of MACEs (HR 0.84, 95% CI, 0.63 to 1.13, p = 0.25, I2 = 74%, 2 studies); however, there was significant reduction in major adverse limb events (MALEs) (HR 0.54, 95% CI, 0.35 to 0.83, p = 0.005, one studies) and in the composite of MACEs or MALEs (HR 0.78, 95% CI, 0.64 to 0.95, p = 0.02, I2 = 66%, 2 studies) when compared with patients receiving aspirin alone. Meanwhile, rivaroxaban combined with aspirin significantly increased the risk of International Society on Thrombosis and Haemostasis (ISTH) major bleeding compared with aspirin alone in patients with CAD (HR 1.74, 95% CI, 1.43 to 2.13, p < 0.00001, I2 = 0%, 2 studies) and PAD (HR 1.47, 95% CI, 1.19 to 1.83, p = 0.0004, I2 = 0%, 2 studies).

Conclusions: Compared with standard antiplatelet therapy, the addition of a 5 mg daily dose of rivaroxaban to standard antiplatelet therapy may improve cardiovascular or limb outcomes of patients with ASCVD, with an increase in major bleeding. Patients who would benefit from the addition of low-dose rivaroxaban to antiplatelet agents and appropriate dual-pathway antithrombotic strategies should be identified in clinical practice to individualize antithrombotic therapy.
Sinapine Thiocyanate Ameliorates Vascular Endothelial Dysfunction in Hypertension by Inhibiting Activation of the NLRP3 Inflammasome
Authors: Liu Yang , Yin Hong-lin , Li Chao , Jiang Feng , Zhang Shi-jun , Zhang Xin-rong , Li Yun-lun
Published: February 2021

The increase of blood pressure is accompanied by the changes in the morphology and function of vascular endothelial cells. Vascular endothelial injury and hypertension actually interact as both cause and effect. A large number of studies have proved that inflammation plays a significant role in the occurrence and development of hypertension, but the potential mechanism between inflammation and hypertensive endothelial injury is still ambiguous. The purpose of this study was to explore the association between the activation of NLRP3 inflammasome and hypertensive endothelial damage, and to demonstrate the protective effect of sinapine thiocyanate (ST) on endothelia in hypertension. The expression of NLRP3 gene was silenced by tail vein injection of adeno-associated virus (AAVs) in spontaneously hypertensive rats (SHRs), indicating that activation of NLRP3 inflammasome accelerated hypertensive endothelial injury. ST not only protected vascular endothelial function in SHRs by inhibiting the activation of NLRP3 inflammasome and the expression of related inflammatory mediators, but also improved AngII-induced huvec injury. In summary, our results show that alleviative NLRP3 inflammasome activation attenuates hypertensive endothelial damage and ST ameliorates vascular endothelial dysfunction in hypertension via inhibiting activation of the NLRP3 inflammasome.
Serum Metabolomic Profiling to Reveal Potential Biomarkers for the Diagnosis of Fatty Liver Hemorrhagic Syndrome in Laying Hens
Authors: Guo Lianying , Kuang Jun , Zhuang Yu , Jiang Jialin , Shi Yan , Huang Cheng , Zhou Changming , Xu Puzhi , Liu Ping , Wu Cong , Hu Guoliang , Guo Xiaoquan
Published: February 2021

Fatty liver hemorrhage syndrome (FLHS), a nutritional and metabolic disease that frequently occurs in laying hens, causes serious losses to the poultry industry. Nowadays, the traditional clinical diagnosis of FLHS still has its limitations. Therefore, searching for some metabolic biomarkers and elucidating the metabolic pathway in vivo are useful for the diagnosis and prevention of FLHS. In the present study, a model of FLHS in laying hens induced by feeding a high-energy, low-protein diet was established. Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) was used to analyze the metabolites in serum at days 40 and 80. The result showed that, in total, 40 differential metabolites closely related to the occurrence and development of FLHS were screened and identified, which were mainly associated with lipid metabolism, amino acid metabolism, and energy metabolism pathway disorders. Further investigation of differential metabolites showed 10 potential biomarkers such as 3-hydroxybutyric acid, oleic acid, palmitoleic acid, and glutamate were possessed of high diagnostic values by analyzing receiver operating characteristic (ROC) curves. In conclusion, this study showed that the metabolomic method based on GC-TOF-MS can be used in the clinical diagnosis of FLHS in laying hens and provide potential biomarkers for early risk evaluation of FLHS and further insights into FLHS development.
Poincaré Plot Area of Gamma-Band EEG as a Measure of Emergence From Inhalational General Anesthesia
Authors: Hayase Kazuma , Kainuma Atsushi , Akiyama Koichi , Kinoshita Mao , Shibasaki Masayuki , Sawa Teiji
Published: February 2021

The Poincaré plot obtained from electroencephalography (EEG) has been used to evaluate the depth of anesthesia. A standalone EEG Analyzer application was developed; raw EEG signals obtained from a bispectral index (BIS) monitor were analyzed using an on-line monitoring system. Correlations between Poincaré plot parameters and other measurements associated with anesthesia depth were evaluated during emergence from inhalational general anesthesia. Of the participants, 20 were adults anesthetized with sevoflurane (adult_SEV), 20 were adults anesthetized with desflurane (adult_DES), and 20 were pediatric patients anesthetized with sevoflurane (ped_SEV). EEG signals were preprocessed through six bandpass digital filters (f0: 0.5–47 Hz, f1: 0.5–8 Hz, f2: 8–13 Hz, f3: 13–20 Hz, f4: 20–30 Hz, and f5: 30–47 Hz). The Poincaré plot-area ratio (PPAR = PPA_fx/PPA_f0, fx = f1∼f5) was analyzed at five frequency ranges. Regardless of the inhalational anesthetic used, there were strong linear correlations between the logarithm of PPAR at f5 and BIS (R2 = 0.67, 0.79, and 0.71, in the adult_SEV, adult_DES, and ped_SEV groups, respectively). As an additional observation, a part of EMG activity at the gamma range of 30–47 Hz probably influenced the calculations of BIS and PPAR_f5 with a non-negligible level. The logarithm of PPAR in the gamma band was most sensitive to state changes during the emergence process and could provide a new non-proprietary parameter that correlates with changes in BIS during measurement of anesthesia depth.
Screening of Onion (Allium cepa L.) Genotypes for Drought Tolerance Using Physiological and Yield Based Indices Through Multivariate Analysis
Authors: Gedam Pranjali A. , Thangasamy A. , Shirsat Dhananjay V. , Ghosh Sourav , Bhagat K. P. , Sogam Onkar A. , Gupta A. J. , Mahajan V. , Soumia P. S. , Salunkhe Vanita N. , Khade Yogesh P. , Gawande Suresh J. , Hanjagi P. S. , Ramakrishnan R. Shiv , Singh Major
Published: February 2021

Drought is a leading abiotic constraints for onion production globally. Breeding by using unique genetic resources for drought tolerance is a vital mitigation strategy. With a total of 100 onion genotypes were screened for drought tolerance using multivariate analysis. The experiment was conducted in a controlled rainout shelter for 2 years 2017–2018 and 2018–2019 in a randomized block design with three replications and two treatments (control and drought stress). The plant was exposed to drought stress during the bulb development stage (i.e., 50–75 days after transplanting). The genotypes were screened on the basis of the drought tolerance efficiency (DTE), percent bulb yield reduction, and results of multivariate analysis viz. hierarchical cluster analysis by Ward’s method, discriminate analysis and principal component analysis. The analysis of variance indicated significant differences among the tested genotypes and treatments for all the parameters studied, viz. phenotypic, physiological, biochemical, and yield attributes. Bulb yield was strongly positively correlated with membrane stability index (MSI), relative water content (RWC), total chlorophyll content, antioxidant enzyme activity, and leaf area under drought stress. The genotypes were categorized into five groups namely, highly tolerant, tolerant, intermediate, sensitive, and highly sensitive based on genetic distance. Under drought conditions, clusters II and IV contained highly tolerant and highly sensitive genotypes, respectively. Tolerant genotypes, viz. Acc. 1656, Acc. 1658, W-009, and W-085, had higher DTE (>90%), fewer yield losses (<20%), and performed superiorly for different traits under drought stress. Acc. 1627 and Acc. 1639 were found to be highly drought-sensitive genotypes, with more than 70% yield loss. In biplot, the tolerant genotypes (Acc. 1656, Acc. 1658, W-085, W-009, W-397, W-396, W-414, and W-448) were positively associated with bulb yield, DTE, RWC, MSI, leaf area, and antioxidant enzyme activity under drought stress. The study thus identified tolerant genotypes with favorable adaptive traits that may be useful in onion breeding program for drought tolerance.
Chloroplast Genomes of Two Species of Cypripedium: Expanded Genome Size and Proliferation of AT-Biased Repeat Sequences
Authors: Guo Yan-Yan , Yang Jia-Xing , Li Hong-Kun , Zhao Hu-Sheng
Published: February 2021

The size of the chloroplast genome (plastome) of autotrophic angiosperms is generally conserved. However, the chloroplast genomes of some lineages are greatly expanded, which may render assembling these genomes from short read sequencing data more challenging. Here, we present the sequencing, assembly, and annotation of the chloroplast genomes of Cypripedium tibeticum and Cypripedium subtropicum. We de novo assembled the chloroplast genomes of the two species with a combination of short-read Illumina data and long-read PacBio data. The plastomes of the two species are characterized by expanded genome size, proliferated AT-rich repeat sequences, low GC content and gene density, as well as low substitution rates of the coding genes. The plastomes of C. tibeticum (197,815 bp) and C. subtropicum (212,668 bp) are substantially larger than those of the three species sequenced in previous studies. The plastome of C. subtropicum is the longest one of Orchidaceae to date. Despite the increase in genome size, the gene order and gene number of the plastomes are conserved, with the exception of an ∼75 kb large inversion in the large single copy (LSC) region shared by the two species. The most striking is the record-setting low GC content in C. subtropicum (28.2%). Moreover, the plastome expansion of the two species is strongly correlated with the proliferation of AT-biased non-coding regions: the non-coding content of C. subtropicum is in excess of 57%. The genus provides a typical example of plastome expansion induced by the expansion of non-coding regions. Considering the pros and cons of different sequencing technologies, we recommend hybrid assembly based on long and short reads applied to the sequencing of plastomes with AT-biased base composition.
Functioning of PPR Proteins in Organelle RNA Metabolism and Chloroplast Biogenesis
Authors: Wang Xinwei , An Yaqi , Xu Pan , Xiao Jianwei
Published: February 2021

The pentatricopeptide repeat (PPR) proteins constitute one of the largest nuclear-encoded protein families in higher plants, with over 400 members in most sequenced plant species. The molecular functions of these proteins and their physiological roles during plant growth and development have been widely studied. Generally, there is mounting evidence that PPR proteins are involved in the post-transcriptional regulation of chloroplast and/or mitochondrial genes, including RNA maturation, editing, intron splicing, transcripts’ stabilization, and translation initiation. The cooperative action of RNA metabolism has profound effects on the biogenesis and functioning of both chloroplasts and mitochondria and, consequently, on the photosynthesis, respiration, and development of plants and their environmental responses. In this review, we summarize the latest research on PPR proteins, specifically how they might function in the chloroplast, by documenting their mechanism of molecular function, their corresponding RNA targets, and their specific effects upon chloroplast biogenesis and host organisms.
Iris domestica (iso)flavone 7- and 3′-O-Glycosyltransferases Can Be Induced by CuCl2
Authors: Zhang Xiang , Zhu Yan , Ye Jun , Ye Ziyu , Zhu Ruirui , Xie Guoyong , Zhao Yucheng , Qin Minjian
Published: February 2021

In many plants, isoflavones are the main secondary metabolites that have various pharmacological activities, but the low water solubility of aglycones limits their usage. The O-glycosylation of (iso)flavones is a promising way to overcome this barrier. O-glycosyltransferases (UGTs) are key enzymes in the biosynthesis of (iso)flavonoid O-glycosides in plants. However, limited investigations on isoflavonoid O-UGTs have been reported, and they mainly focused on legumes. Iris domestica (L.) Goldblatt et Mabberley is a non-legume plant rich in various isoflavonoid glycosides. However, there are no reports regarding its glycosylation mechanism, despite the I. domestica transcriptome previously being annotated as having non-active isoflavone 7-O-UGTs. Our previous experiments indicated that isoflavonoid glycosides were induced by CuCl2 in I. domestica calli; therefore, we hypothesized that isoflavone O-UGTs may be induced by Cu2+. Thus, a comparative transcriptome analysis was performed using I. domestica seedlings treated with CuCl2, and eight new active BcUGTs were obtained. Biochemical analyses showed that most of the active BcUGTs had broad substrate spectra; however, substrates lacking 5-OH were rarely catalyzed. Real-time quantitative PCR results further indicated that the transcriptional levels of BcUGTs were remarkably induced by Cu2+. Our study increases the understanding of UGTs and isoflavone biosynthesis in non-legume plants.
Perspectives on the 2 × 2 Matrix: Solving Semantically Distinct Problems Based on a Shared Structure of Binary Contingencies
Authors: Neth Hansjörg , Gradwohl Nico , Streeb Dirk , Keim Daniel A. , Gaissmaier Wolfgang
Published: February 2021

Cognition is both empowered and limited by representations. The matrix lens model explicates tasks that are based on frequency counts, conditional probabilities, and binary contingencies in a general fashion. Based on a structural analysis of such tasks, the model links several problems and semantic domains and provides a new perspective on representational accounts of cognition that recognizes representational isomorphs as opportunities, rather than as problems. The shared structural construct of a 2 × 2 matrix supports a set of generic tasks and semantic mappings that provide a unifying framework for understanding problems and defining scientific measures. Our model's key explanatory mechanism is the adoption of particular perspectives on a 2 × 2 matrix that categorizes the frequency counts of cases by some condition, treatment, risk, or outcome factor. By the selective steps of filtering, framing, and focusing on specific aspects, the measures used in various semantic domains negotiate distinct trade-offs between abstraction and specialization. As a consequence, the transparent communication of such measures must explicate the perspectives encapsulated in their derivation. To demonstrate the explanatory scope of our model, we use it to clarify theoretical debates on biases and facilitation effects in Bayesian reasoning and to integrate the scientific measures from various semantic domains within a unifying framework. A better understanding of problem structures, representational transparency, and the role of perspectives in the scientific process yields both theoretical insights and practical applications.