bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Antibacterial Activity of Indocyanine Green-Loaded Graphene Oxide via Synergistic Contact Killing, Photothermal and Photodynamic Therapy
Authors: Chen Yuan , Huang Wenlong , Dong Yuanhao , Yu Xiaotong , Mo Anchun , Peng Qiang
Published: February 2022

Methicillin-resistant Staphylococcus aureus (MRSA) has become a serious threat to human’s health. Recently, photodynamic/photothermal therapy (PDT/PTT) has emerged as promising strategies against antibiotics-resistant pathogens due to their broad antibacterial spectrum
and negligible resistance. In this work, the photosensitizer indocyanine green (ICG) was loaded on graphene oxide (GO) nanosheets with good encapsulation efficiency high to 92.31%. Under near-infrared (NIR) irradiation, the anti-MRSA efficiency of GO (20 μg/ml), ICG (5 μg/ml)
and ICG-GO (5 μg/ml–20 μg/ml) was 33.76%, 40.15% and 99.86%, respectively. We further showed that NIR irradiation mildly increased the temperature to 43.1 °C for ICG-GO, and lead to the highest reactive oxygen species (ROS) generation (316.51% and 157.11% compared
to ICG alone and GO alone). In conclusion, ICG-GO has a great potential for antibacterial treatment due to its synergistic contact killing, photothermal and photodynamic activity.
Biodegradable Biomaterial Arterial Stent in the Treatment of Coronary Heart Disease
Authors: Li Ya , Cui Chun-Bian , Li Ya-Zhuo , Tan Da-Wei , Jia Xin-Wei , Liu Sheng-Hui , Feng Hui-Ping , Feng Cui-Na
Published: February 2022

This study aims to evaluate the clinical application value of two materials, drug-eluting stent, and biodegradable stent, in the treatment of coronary heart disease. The results show that the therapeutic effects of drug-eluting stents and biodegradable stents are similar. Both treatment
methods have high safety and effectiveness. The ideal coronary artery stent should have good biocompatibility, safety, and possibility.
Treatment of Traumatic Cartilage Defects of Rabbit Knee Joint by Adipose Derived Stem Cells Combined with Kartogenin Hydroxyapatite Nano-Microsphere Complex
Authors: Wang Zhan , Han Xingwen , Song Zhengdong , Gao Zhao , Zhao Yuhao , Wang Wenji
Published: February 2022

Kartogenin (KGN) can effectively promote the differentiation of adipose derived stem cells (ADSCs) into chondrocytes. With the help of three-dimensional slow-release technology, nano-microspheres are generated and used for cartilage repair. First, KGN solution was prepared, which was
dissolved in distilled water, and NaOH solution, HEPES buffer, sodium chloride particles, and hydroxyapatite (HA) solution were added to prepare KGN-HA gel solution containing KGN. ADSCs were isolated from the posterior iliac of four-week-old New Zealand rabbits. After 0.5 mL of rabbit second-generation
ADSCs suspension was taken, 2 mL KGN-HA gel solution was added, and they were mixed well to obtain ADSCs/KGN-HA gel. After drying treatment, ADSCs/KGN-HA nanospheres were precipitated. In the experiment, the minimum inhibitory concentration (MIC) of Staphylococcus aureus (MIC) >
2 μg/mL in each group of KGN-HA gel solution was reached within 30 days. Group K3 had the highest KGN encapsulation rate and the largest cumulative release. The biological activity of ADSCs was good in the ADSCs/KGN-HA nanoparticle solution. After two weeks of incubation, the nanospheres
were positive for type II collagen staining/toluidine blue staining, that was, chondrocyte phenotype. The rabbit knee articular cartilage defect model was established. The defect part was filled with ADSCs/KGN-HA gel, which was similar in color to the surrounding tissues. The two sides of
the tissue section and the surrounding cartilage tissue healed well, and no carrier material remained. Moreover, the cells were round, with cartilage lacuna formed around them, and after the simple periosteum was covered and repaired, the surface was sunken. The cell structure changed, and
the healing with the surroundings was poor. In summary, under the slow release of KGN, ADSCs/KGN-HA nanospheres made ADSCs maintain a good biological form, which grew and proliferated normally. The ADSCs/KGN-HA nanoparticles cultured in vitro had a good repair effect on the animal model
of articular cartilage defects.
Mesoporous Silica Nanoparticles Carrying MicroRNA-124 to Target P2Y12 Facilitates Cerebral Angiogenesis in Lacunar Cerebral Infarction Through Stem Cell Factor/c-Kit Signaling Pathway
Authors: Wang Jian , Zheng Bo , Yang Shu , Fan Jian , Sun Hao , Wang Jianhong
Published: February 2022

MicroRNA (miRNA)-124 inhibitor may enhance cerebral blood vessel formation in lacunar cerebral infarction (LCI) and mesoporous silica nanoparticles are highlighted as a drug carrier which improves patients’ outcome. This study explored the impact of miR-124 and its promising targeted
gene P2Y12 encapsulated by mesoporous silica nanoparticles (MSNs) on progression of LCI, and its interaction between SCF/c-kit signaling pathway. After establishment of animal models, the animals were divided into 6 groups, namely: model group, blank group, empty carrier group,
carrier + miR-124 inhibitor group, SCF/c-kit inhibitor group, and P2Y12 agonist group. Western blot analysis and microscope determined the expression level of miR-124 in the rat brain tissue slices. MVD, SCF and c-kit P2Y12 protein expression levels were detected and
their targeting relationship was verified. miR-124 was poorly expressed in the cells of rats with LCI upon injection of MSNs carrying miR-124-inhibitor. The LCI model group had the highest number of VEGF-positive. Compared with the model group, the number in the carrier + miR-124 inhibitor
group was lowest. Moreover, treatment with SCF/c-kit inhibitor and P2Y12 agonist also obtained reduction in the number of VEGF-positive cells with less prominent effect (P < 0.05). With elevation of MVD in the LCI rats, injection of P2Y12 agonist or SCF/c-kit
inhibitor significantly decreased the amount of MVD, while miR-124 inhibitor-loaded MSNs better reduced the MVD level. Besides, the LCI rats exhibited up-regulated level of P2Y12 protein. Injection of P2Y12 agonist or SCF/c-kit inhibitor dramatically decreased the level
of P2Y12, where the level was still higher than that of carrier + miR-124 inhibitor group. Moreover, administration of miR-124 inhibitor-loaded MSNs resulted in increased SCF and c-kit protein level, and SCF/c-kit inhibitor group and P2Y12 agonist group also had increased
SCF and c-kit protein level, compared to the model group. Mechanistically, the miR-124 was indicated to target P2Y12 with stronger fluorescence intensity in mutant plasmid (P < 0.05). MSN-encapsulated miR-124 inhibitor increased the expression of SCF/c-kit protein by targeting
P2Y12, thereby enhancing regeneration of cerebral blood vessels in LCI.
Recent Advances in Engineered Noble Metal Nanomaterials as a Surface-Enhanced Raman Scattering Active Platform for Cancer Diagnostics
Authors: Chen Yun , Yu Fangfang , Wang Yihan , Liu Weiwei , Ye Jing , Xiao Jiang , Liu Xiaohui , Jiang Hui , Wang Xuemei
Published: February 2022

Recently, noble metal nanomaterials have been extensively studied in the fields of biosensing, environmental catalysis, and cancer diagnosis and treatment, due to their excellent electrical conductivity, high surface area, and individual physical and optical properties. Early research
on the surface-enhanced Raman scattering (SERS) effect was focused on the cognition of the SERS phenomenon and enhancing its sensitivity for single-molecule detection. With the development of nanomaterials and nanotechnology, the advances and applications based on SERS substrates have been
accelerated. Among them, noble metal nanomaterials are mainly used as SERS-active substrates to enhance SERS signals owing to their compelling surface plasmon resonance (SPR) properties. This review provides recent advances, perspectives, and challenges in SERS assays based on engineered noble
metal nanomaterials for early cancer diagnosis.
Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways
Authors: Cheng Ziping , Liu Yangjie , Ma Mengyuan , Sun Shiyu , Ma Zengqing , Wang Yu , Yu Liyuan , Qian Xuping , Sun Luning , Zhang Xuehui , Liu Yun , Wang Yongqing
Published: February 2022

Background

Many clinical studies have shown a correlation between proton pump inhibitors (PPIs) and osteoporosis or fractures. The purpose of this study was to establish a murine model of chronic oral PPI administration to verify whether PPIs caused bone metabolic impairment and investigate the relevant molecular mechanism underlying the effects of PPIs on MC3T3-E1 murine osteoblasts.

Methods

A lansoprazole-induced bone loss model was used to investigate the damaging effects of PPIs. In vivo, immunohistochemistry, Hematoxylin–Eosin (HE) staining, micro-CT analysis, and blood biochemical analyses were used to evaluate the effect of lansoprazole on bone injury in mice. In vitro, the effects of lansoprazole and related signaling pathways in MC3T3-E1 cells were investigated by CCK-8 assays, EdU assays, flow cytometry, laser confocal microscopy, patch clamping, reverse transcription-quantitative polymerase chain reaction and Western blotting.

Results

After 6 months of lansoprazole gavage in ICR mice, the micro-CT results showed that compared with that in the vehicle group, the bone mineral density (BMD) in the high-dose group was significantly decreased (P < 0.05), and the bone microarchitecture gradually degraded. Biochemical analysis of bone serum showed that blood calcium and phosphorus were both decreased (P < 0.01). We found that long-term administration of lansoprazole impaired skeletal function in mice. In vitro, we found that lansoprazole (LPZ) could cause calcium overload in MC3T3-E1 cells leading to apoptosis, and 2-APB, an inhibitor of IP3R calcium release channel and SOCE pathway, effectively blocked increase in calcium caused by LPZ, thus protecting cell viability.

Conclusions

Longterm administration of LPZ induced osteoporotic symptoms in mice, and LPZ triggered calcium increases in osteoblasts in a concentration-dependent manner. Intracellular calcium ([Ca2+]i) persisted at a high concentration, thereby causing endoplasmic reticulum stress (ERS) and inducing osteoblast apoptosis.
Phosphorylation of BCL2 at the Ser70 site mediates RANKL-induced osteoclast precursor autophagy and osteoclastogenesis
Authors: Ke Dianshan , Yu Yunlong , Li Chenglong , Han Junyong , Xu Jie
Published: February 2022

Background

Phosphorylation modification of BCL2 is involved in receptor activator of nuclear factor-κB ligand (RANKL)-induced autophagy of osteoclast precursors (OCPs) and osteoclastogenesis. As an antiapoptotic molecule, the role of BCL2 phosphorylation in osteoclastogenesis is unknown. This study aimed to explore how BCL2 phosphorylation at specific sites regulates osteoclastogenesis.

Methods

We first examined the effects of RANKL on BCL2 phosphorylation at different sites (Ser70 and Ser87) in OCPs. In vivo, transgenic mice overexpressing RANKL (Tg-hRANKL mice) were used to observe the effects of RANKL on phosphorylated BCL2 at different sites in OCPs of trabecular bone. Subsequently, using site-directed mutagenesis, we observed the respective effect of BCL2 mutations at different phosphorylation sites in OCPs on osteoclastogenesis, apoptosis, autophagy and the affinity between BCL2 and Beclin1/BAX under RANKL intervention.

Results

RANKL promoted BCL2 phosphorylation at the Ser70 (S70) site, but not the Ser87 (S87) site, in OCPs. Moreover, Tg-hRANKL mice had stronger BCL2 phosphorylation capacity at S70, not S87, in the OCPs of trabecular bone than wild-type mice in the same nest. Furthermore, BCL2 mutation at S70, not S87, inhibited RANKL-induced osteoclast differentiation and bone resorption activity. In addition, BCL2 mutation at S70 promoted OCP apoptosis, while BCL2 mutation at S87 showed the opposite effect. Remarkably, the BCL2 mutation at S70, not S87, inhibited OCP autophagic activity. Furthermore, BCL2 mutation at S70 enhanced the coimmunoprecipitation of BCL2 and Beclin1, whereas BCL2 mutation at S87 enhanced the coimmunoprecipitation of BCL2 and BAX in OCPs. More importantly, OCP autophagy, osteoclast differentiation and resorption pits inhibited by BCL2 mutation at S70 could be reversed by Beclin1 upregulation with TAT-Beclin1.

Conclusion

RANKL activates OCP autophagy through BCL2 phosphorylation at S70, thereby promoting osteoclastogenesis, which indicates that the inactivation of BCL2 at S70 in OCPs may be a therapeutic strategy for pathological bone loss.
Post-traumatic headache after mild traumatic brain injury in a one-year follow up study – risk factors and return to work
Authors: Kraemer Yvonn , Mäki Kaisa , Marinkovic Ivan , Nybo Taina , Isokuortti Harri , Huovinen Antti , Korvenoja Antti , Melkas Susanna , Harno Hanna
Published: February 2022

Background

Post-traumatic headache (PTH) is a common symptom following mild traumatic brain injury (mTBI). Patients at risk to develop acute PTH (aPTH) and further persistent PTH (pPTH) need to be recognized.

Methods

This is a one-year follow-up of 127 patients with mTBI, aged 18 to 68, referred to outpatient clinic in the Helsinki University Hospital. Symptoms were assessed at the emergency department (ED), with structured interview at outpatient clinic visit and with Rivermead post-concussion symptom questionnaire at one, three, and 12 months after injury. Psychiatric disorders were assessed with Structured Clinical Interview for DSM-IV Axis I disorders at 3-4 months and return to work (RTW) from patient records.

Results

At one month, 77/127 patients (61%) had aPTH. According to multiple logistic regression analysis, risk factors for aPTH were headache at the emergency department (ED) (OR 5.43), other pain (OR 3.19), insomnia (OR 3.23), and vertigo (OR 5.98). At three months, 17 patients (22% of aPTH patients) had developed pPTH, and at one year, 4 patients (24% of pPTH patients) still presented with pPTH. Risk factors for pPTH at three months were older age (OR 1.06) and current insomnia (OR 12.3). The frequency of psychiatric disorders did not differ between the groups. pPTH patients performed worse on their RTW.

Conclusions

Risk factors for aPTH were insomnia, headache at ED, other pain, and vertigo and for pPTH, insomnia and older age. RTW rate was lower among pPTH patients.
Exploring neuronal mechanisms involved in the scratching behavior of a mouse model of allergic contact dermatitis by transcriptomics
Authors: Liu Boyu , Chen Ruixiang , Wang Jie , Li Yuanyuan , Yin Chengyu , Tai Yan , Nie Huimin , Zeng Danyi , Fang Junfan , Du Junying , Liang Yi , Shao Xiaomei , Fang Jianqiao , Liu Boyi
Published: February 2022

Background

Allergic contact dermatitis (ACD) is a common skin condition characterized by contact hypersensitivity to allergens, accompanied with skin inflammation and a mixed itch and pain sensation. The itch and pain dramatically affects patients’ quality of life. However, still little is known about the mechanisms triggering pain and itch sensations in ACD.

Methods

We established a mouse model of ACD by sensitization and repetitive challenge with the hapten oxazolone. Skin pathological analysis, transcriptome RNA sequencing (RNA-seq), qPCR, Ca2+ imaging, immunostaining, and behavioral assay were used for identifying gene expression changes in dorsal root ganglion innervating the inflamed skin of ACD model mice and for further functional validations.

Results

The model mice developed typical ACD symptoms, including skin dryness, erythema, excoriation, edema, epidermal hyperplasia, inflammatory cell infiltration, and scratching behavior, accompanied with development of eczematous lesions. Transcriptome RNA-seq revealed a number of differentially expressed genes (DEGs), including 1436-DEG mRNAs and 374-DEG-long noncoding RNAs (lncRNAs). We identified a number of DEGs specifically related to sensory neuron signal transduction, pain, itch, and neuroinflammation. Comparison of our dataset with another published dataset of atopic dermatitis mouse model identified a core set of genes in peripheral sensory neurons that are exclusively affected by local skin inflammation. We further found that the expression of the pain and itch receptor MrgprD was functionally upregulated in dorsal root ganglia (DRG) neurons innervating the inflamed skin of ACD model mice. MrgprD activation induced by its agonist β-alanine resulted in exaggerated scratching responses in ACD model mice compared with naïve mice.

Conclusions

We identified the molecular changes and cellular pathways in peripheral sensory ganglia during ACD that might participate in neurogenic inflammation, pain, and itch. We further revealed that the pain and itch receptor MrgprD is functionally upregulated in DRG neurons, which might contribute to peripheral pain and itch sensitization during ACD. Thus, targeting MrgprD may be an effective method for alleviating itch and pain in ACD.
An efficient and pragmatic approach for regulatory aquatic mixture risk assessment of pesticides
Authors: Dietrich Christian , Wang Magnus , Ebeling Markus , Gladbach Anja
Published: February 2022

The current regulatory approach to address aquatic mixture toxicity for pesticides in the EU (EFSA J 11:3290, 2013) is rather complex: in typical cases it requires conducting the entire mixture risk assessment scheme for every exposure scenario separately (e.g. 6–8 ecotoxicological endpoints, for each of the nine exposure scenarios for the European Central Zone with 24 common mitigation measure combinations result in over 1700 sub-scenarios to be assessed). This article discusses the available concepts for a mixture toxicity assessment, the key questions raised and the implementation of these questions in existing risk assessment approaches. Based on this, an alternative, more efficient assessment scheme for aquatic mixture risk assessment (AMiRA) is proposed with the aim of facilitating the practical conduct and interpretation of the assessment while addressing the key questions and preserving the level of protection. The scheme assesses product risk (including a check for non-additive effects), the presence of a risk driver and gains efficiency by the straightforward use of risk quotients (RQ) to calculate mixture risk quotients (RQmix) that are equivalent to the calculation of exposure toxicity ratios for a mixture (ETRmix,CA = Exposure-Toxicity-Ratio for mixtures based on concentration addition) proposed by EFSA (EFSA J 11:3290, 2013). A case study is provided underlining the equivalence of the proposed approach to the EFSA (EFSA J 11:3290, 2013) decision tree.
Coronavirus disease (COVID-19) and conjunctival sac swab findings
Authors: Vesely Pavol , Novakova Elena , Stubna Michal , Trnka Michal , Jurenova Denisa , Lyskova Darina , Furda Robert , Plesnikova Paulina , Himic Vratko , Furdova Alena
Published: February 2022

Background

The purpose of this article is to evaluate the positivity of conjunctival sac swab by PCR (Polymerase chain reaction) test in COronaVIrus Disease 19 (COVID-19) patients.

Methods

Inclusion criteria of our study were COVID-19 patients hospitalized during March 2021 in inpatient wards at University Hospitals in towns Bratislava and Zilina, Slovakia. The conjunctival sac swabs collected by four ophthalmologists were stored for 24 h, then analyzed in the laboratory of the Department of Microbiology and Immunology, Jessenius Faculty of Medicine in Martin, Comenius University, Slovakia. The sampling apparatus, used for conjunctival sac swab, was the Dacron polyester swab.

Results

We examined one group of 302 COVID-19 patients, 168 Male (56%) and 134 Female (44%). The patients’ mean age was 66.3 ± 13.66 years, ranging from 25 to 96 years, and the mean length of hospital stay in our patients with a nasopharyngeal positive PCR test was 7.33 ± 4.76, from 2 to 24 days.

The PCR tests from the conjunctival sac swabs were positive in 33 patients (11%), negative in 259 patients (86%), and ten patients (3%) were with the unclear result. In the group of 33 positive patients were 17 males with a mean age of 74.6 ± 13.59 years and 16 females with a mean age of 70.63 ± 14.17 years.

The cycle threshold (CT) values differed significantly between conjunctival sac swabs from the nasopharynx and the conjunctiva. Medians of the values were 25.1 (14.1, 32.1) and 31.5 (22.6, 36.6) (P <  0.001), respectively.

Conclusion

This study affirmed that in COVID-19 patients the SARS-CoV-2 was detectable with PCR test in conjunctival sac swab, but the positivity rate was only about one to ten cases (11%).
Comparison of the choice of animals for re-sequencing in two maternal pig lines
Authors: Dauben Christina M. , Große-Brinkhaus Christine , Heuß Esther M. , Henne Hubert , Tholen Ernst
Published: February 2022

Next-generation sequencing is a promising approach for the detection of causal variants within previously identified quantitative trait loci. Because of the costs of re-sequencing experiments, this application is currently mainly restricted to subsets of animals from already genotyped populations. Imputation from a lower to a higher marker density could represent a useful complementary approach. An analysis of the literature shows that several strategies are available to select animals for re-sequencing. This study demonstrates an animal selection workflow under practical conditions. Our approach considers different data sources and limited resources such as budget and availability of sampling material. The workflow combines previously described approaches and makes use of genotype and pedigree information from a Landrace and Large White population. Genotypes were phased and haplotypes were accurately estimated with AlphaPhase. Then, AlphaSeqOpt was used to optimize selection of animals for re-sequencing, reflecting the existing diversity of haplotypes. AlphaSeqOpt and ENDOG were used to select individuals based on pedigree information and by taking into account key animals that represent the genetic diversity of the populations. After the best selection criteria were determined, a subset of 57 animals was selected for subsequent re-sequencing. In order to evaluate and assess the advantage of this procedure, imputation accuracy was assessed by setting a set of single nucleotide polymorphism (SNP) chip genotypes to missing. Accuracy values were compared to those of alternative selection scenarios and the results showed the clear benefits of a targeted selection within this practical-driven approach. Especially imputation of low-frequency markers benefits from the combined approach described here. Accuracy was increased by up to 12% compared to a randomized or exclusively haplotype-based selection of sequencing candidates.
GWAS and genomic prediction of milk urea nitrogen in Australian and New Zealand dairy cattle
Authors: van den Berg Irene , Ho Phuong N. , Nguyen Tuan V. , Haile-Mariam Mekonnen , MacLeod Iona M. , Beatson Phil R. , O’Connor Erin , Pryce Jennie E.
Published: February 2022

Background

Urinary nitrogen leakage is an environmental concern in dairy cattle. Selection for reduced urinary nitrogen leakage may be done using indicator traits such as milk urea nitrogen (MUN). The result of a previous study indicated that the genetic correlation between MUN in Australia (AUS) and MUN in New Zealand (NZL) was only low to moderate (between 0.14 and 0.58). In this context, an alternative is to select sequence variants based on genome-wide association studies (GWAS) with a view to improve genomic prediction accuracies. A GWAS can also be used to detect quantitative trait loci (QTL) associated with MUN. Therefore, our objectives were to perform within-country GWAS and a meta-GWAS for MUN using records from up to 33,873 dairy cows and imputed whole-genome sequence data, to compare QTL detected in the GWAS for MUN in AUS and NZL, and to use sequence variants selected from the meta-GWAS to improve the prediction accuracy for MUN based on a joint AUS-NZL reference set.

Results

Using the meta-GWAS, we detected 14 QTL for MUN, located on chromosomes 1, 6, 11, 14, 19, 22, 26 and the X chromosome. The three most significant QTL encompassed the casein genes on chromosome 6, PAEP on chromosome 11 and DGAT1 on chromosome 14. We selected 50,000 sequence variants that had the same direction of effect for MUN in AUS and MUN in NZL and that were most significant in the meta-analysis for the GWAS. The selected sequence variants yielded a genetic correlation between MUN in AUS and MUN in NZL of 0.95 and substantially increased prediction accuracy in both countries.

Conclusions

Our results demonstrate how the sharing of data between two countries can increase the power of a GWAS and increase the accuracy of genomic prediction using a multi-country reference population and sequence variants selected based on a meta-GWAS.
Functionally prioritised whole-genome sequence variants improve the accuracy of genomic prediction for heat tolerance
Authors: Cheruiyot Evans K. , Haile-Mariam Mekonnen , Cocks Benjamin G. , MacLeod Iona M. , Mrode Raphael , Pryce Jennie E.
Published: February 2022

Background

Heat tolerance is a trait of economic importance in the context of warm climates and the effects of global warming on livestock production, reproduction, health, and well-being. This study investigated the improvement in prediction accuracy for heat tolerance when selected sets of sequence variants from a large genome-wide association study (GWAS) were combined with a standard 50k single nucleotide polymorphism (SNP) panel used by the dairy industry.

Methods

Over 40,000 dairy cattle with genotype and phenotype data were analysed. The phenotypes used to measure an individual’s heat tolerance were defined as the rate of decline in milk production traits with rising temperature and humidity. We used Holstein and Jersey cows to select sequence variants linked to heat tolerance. The prioritised sequence variants were the most significant SNPs passing a GWAS p-value threshold selected based on sliding 100-kb windows along each chromosome. We used a bull reference set to develop the genomic prediction equations, which were then validated in an independent set of Holstein, Jersey, and crossbred cows. Prediction analyses were performed using the BayesR, BayesRC, and GBLUP methods.

Results

The accuracy of genomic prediction for heat tolerance improved by up to 0.07, 0.05, and 0.10 units in Holstein, Jersey, and crossbred cows, respectively, when sets of selected sequence markers from Holstein cows were added to the 50k SNP panel. However, in some scenarios, the prediction accuracy decreased unexpectedly with the largest drop of − 0.10 units for the heat tolerance fat yield trait observed in Jersey cows when 50k plus pre-selected SNPs from Holstein cows were used. Using pre-selected SNPs discovered on a combined set of Holstein and Jersey cows generally improved the accuracy, especially in the Jersey validation. In addition, combining Holstein and Jersey bulls in the reference set generally improved prediction accuracy in most scenarios compared to using only Holstein bulls as the reference set.

Conclusions

Informative sequence markers can be prioritised to improve the genomic prediction of heat tolerance in different breeds. In addition to providing biological insight, these variants could also have a direct application for developing customized SNP arrays or can be used via imputation in current industry SNP panels.
DrugShot: querying biomedical search terms to retrieve prioritized lists of small molecules
Authors: Kropiwnicki Eryk , Lachmann Alexander , Clarke Daniel J. B. , Xie Zhuorui , Jagodnik Kathleen M. , Ma’ayan Avi
Published: February 2022

Background

PubMed contains millions of abstracts that co-mention terms that describe drugs with other biomedical terms such as genes or diseases. Unique opportunities exist for leveraging these co-mentions by integrating them with other drug-drug similarity resources such as the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 signatures to develop novel hypotheses.

Results

DrugShot is a web-based server application and an Appyter that enables users to enter any biomedical search term into a simple input form to receive ranked lists of drugs and other small molecules based on their relevance to the search term. To produce ranked lists of small molecules, DrugShot cross-references returned PubMed identifiers (PMIDs) with DrugRIF or AutoRIF, which are curated resources of drug-PMID associations, to produce an associated small molecule list where each small molecule is ranked according to total co-mentions with the search term from shared PubMed IDs. Additionally, using two types of drug-drug similarity matrices, lists of small molecules are predicted to be associated with the search term. Such predictions are based on literature co-mentions and signature similarity from LINCS L1000 drug-induced gene expression profiles.

Conclusions

DrugShot prioritizes drugs and small molecules associated with biomedical search terms. In addition to listing known associations, DrugShot predicts additional drugs and small molecules related to any search term. Hence, DrugShot can be used to prioritize drugs and preclinical compounds for drug repurposing and suggest indications and adverse events for preclinical compounds. DrugShot is freely and openly available at:https://maayanlab.cloud/drugshotandhttps://appyters.maayanlab.cloud/#/DrugShot.
Using amino acids co-occurrence matrices and explainability model to investigate patterns in dengue virus proteins
Authors: Souza Leonardo R. , Colonna Juan G. , Comodaro Joseana M. , Naveca Felipe G.
Published: February 2022

Background

Dengue is a common vector-borne disease in tropical countries caused by the Dengue virus. This virus may trigger a disease with several symptoms like fever, headache, nausea, vomiting, and muscle pain. Indeed, dengue illness may also present more severe and life-threatening conditions like hemorrhagic fever and dengue shock syndrome. The causes that lead hosts to develop severe infections are multifactorial and not fully understood. However, it is hypothesized that different viral genome signatures may partially contribute to the disease outcome. Therefore, it is plausible to suggest that deeper DENV genetic information analysis may bring new clues about genetic markers linked to severe illness.

Method

Pattern recognition in very long protein sequences is a challenge. To overcome this difficulty, we map protein chains onto matrix data structures that reveal patterns and allow us to classify dengue proteins associated with severe illness outcomes in human hosts. Our analysis uses co-occurrence of amino acids to build the matrices and Random Forests to classify them. We then interpret the classification model using SHAP Values to identify which amino acid co-occurrences increase the likelihood of severe outcomes.

Results

We trained ten binary classifiers, one for each dengue virus protein sequence. We assessed the classifier performance through five metrics: PR-AUC, ROC-AUC, F1-score, Precision and Recall. The highest score on all metrics corresponds to the protein E with a 95% confidence interval. We also compared the means of the classification metrics using the Tukey HSD statistical test. In four of five metrics, protein E was statistically different from proteins M, NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5, showing that E markers has a greater chance to be associated with severe dengue. Furthermore, the amino acid co-occurrence matrix highlight pairs of amino acids within Domain 1 of E protein that may be associated with the classification result.

Conclusion

We show the co-occurrence patterns of amino acids present in the protein sequences that most correlate with severe dengue. This evidence, used by the classification model and verified by statistical tests, mainly associates the E protein with the severe outcome of dengue in human hosts. In addition, we present information suggesting that patterns associated with such severe cases can be found mostly in Domain 1, inside protein E. Altogether, our results may aid in developing new treatments and being the target of debate on new theories regarding the infection caused by dengue in human hosts.
csdR, an R package for differential co-expression analysis
Authors: Pettersen Jakob P. , Almaas Eivind
Published: February 2022

Background

Differential co-expression network analysis has become an important tool to gain understanding of biological phenotypes and diseases. The CSD algorithm is a method to generate differential co-expression networks by comparing gene co-expressions from two different conditions. Each of the gene pairs is assigned conserved (C), specific (S) and differentiated (D) scores based on the co-expression of the gene pair between the two conditions. The result of the procedure is a network where the nodes are genes and the links are the gene pairs with the highest C-, S-, and D-scores. However, the existing CSD-implementations suffer from poor computational performance, difficult user procedures and lack of documentation.

Results

We created the R-package aimed at reaching good performance together with ease of use, sufficient documentation, and with the ability to play well with other tools for data analysis. was benchmarked on a realistic dataset with 20,645 genes. After verifying that the chosen number of iterations gave sufficient robustness, we tested the performance against the two existing CSD implementations. was superior in performance to one of the implementations, whereas the other did not run. Our implementation can utilize multiple processing cores. However, we were unable to achieve more than $$\sim$$
∼
2.7 parallel speedup with saturation reached at about 10 cores.

Conclusion

The results suggest that is a useful tool for differential co-expression analysis and is able to generate robust results within a workday on datasets of realistic sizes when run on a workstation or compute server.
Mitochondria in tumour progression: a network of mtDNA variants in different types of cancer
Authors: Cavalcante Giovanna C. , Ribeiro-dos-Santos Ândrea , de Araújo Gilderlanio S.
Published: February 2022

Background

Mitochondrial participation in tumorigenesis and metastasis has been studied for many years, but several aspects of this mechanism remain unclear, such as the association of mitochondrial DNA (mtDNA) with different cancers. Here, based on two independent datasets, we modelled an mtDNA mutation-cancer network by systematic integrative analysis including 37 cancer types to identify the mitochondrial variants found in common among them.

Results

Our network showed mtDNA associations between gastric cancer and other cancer types, particularly kidney, liver, and prostate cancers, which is suggestive of a potential role of such variants in the metastatic processes among these cancer types. A graph-based interactive web tool was made available at www2.lghm.ufpa.br/mtdna. We also highlighted that most shared variants were in the MT-ND4, MT-ND5 and D-loop, and that some of these variants were nonsynonymous, indicating a special importance of these variants and regions regarding cancer progression, involving genomic and epigenomic alterations.

Conclusions

This study reinforces the importance of studying mtDNA in cancer and offers new perspectives on the potential involvement of different mitochondrial variants in cancer development and metastasis.
Identification of quantitative trait loci (QTLs) and candidate genes of seed Iron and zinc content in soybean [Glycine max (L.) Merr.]
Authors: Wang Huan , Jia Jia , Cai Zhandong , Duan Mingming , Jiang Ze , Xia Qiuju , Ma Qibin , Lian Tengxiang , Nian Hai
Published: February 2022

Background

Deciphering the hereditary mechanism of seed iron (Fe) and zinc (Zn) content in soybean is important and sustainable to address the “hidden hunger” that presently affects approximately 2 billion people worldwide. Therefore, in order to detect genomic regions related to soybean seed Fe and Zn content, a recombinant inbred line (RIL) population with 248 lines was assessed in four environments to detect Quantitative Trait Loci (QTLs) related to soybean seed Fe and Zn content.

Result

Wide variation was found in seed Fe and Zn content in four environments, and genotype, environment, and genotype × environment interactions had significant influences on both the seed Fe and Zn content. A positive correlation was observed between seed Fe content and seed Zn content, and broad-sense heritability (H2) of seed Fe and Zn content were 0.73 and 0.75, respectively. In this study, five QTLs for seed Fe content were detected with 4.57 - 32.71% of phenotypic variation explained (PVE) and logarithm of odds (LOD) scores ranging from 3.60 to 33.79. Five QTLs controlling the seed Zn content were detected, and they individually explained 3.35 to 26.48% of the phenotypic variation, with LOD scores ranging from 3.64 to 20.4. Meanwhile, 409,541 high-quality single-nucleotide variants (SNVs) and 85,102 InDels (except intergenic regions) between two bi-parental lines were identified by whole genome resequencing. A total of 12 candidate genes were reported in one major QTL for seed Fe content and two major QTLs for seed Zn content, with the help of RNA-Seq analysis, gene ontology (GO) enrichment, gene annotation, and bi-parental whole genome sequencing (WGS) data.

Conclusions

Limited studies were performed about microelement of soybean, so these results may play an important role in the biofortification of Fe and Zn and accelerate the development of marker-assisted selection (MAS) for breeding soybeans fortified with iron and zinc.
Complete mitochondrial genomes of three Mangifera species, their genomic structure and gene transfer from chloroplast genomes
Authors: Niu Yingfeng , Gao Chengwen , Liu Jin
Published: February 2022

Background

Among the Mangifera species, mango (Mangifera indica) is an important commercial fruit crop. However, very few studies have been conducted on the Mangifera mitochondrial genome. This study reports and compares the newly sequenced mitochondrial genomes of three Mangifera species.

Results

Mangifera mitochondrial genomes showed partial similarities in the overall size, genomic structure, and gene content. Specifically, the genomes are circular and contain about 63–69 predicted functional genes, including five ribosomal RNA (rRNA) genes and 24–27 transfer RNA (tRNA) genes. The GC contents of the Mangifera mitochondrial genomes are similar, ranging from 44.42–44.66%. Leucine (Leu) and serine (Ser) are the most frequently used, while tryptophan (Trp) and cysteine (Cys) are the least used amino acids among the protein-coding genes in Mangifera mitochondrial genomes. We also identified 7–10 large chloroplast genomic fragments in the mitochondrial genome, ranging from 1407 to 6142 bp. Additionally, four intact mitochondrial tRNAs genes (tRNA-Cys, tRNA-Trp, tRNA-Pro, and tRNA-Met) and intergenic spacer regions were identified. Phylogenetic analysis based on the common protein-coding genes of most branches provided a high support value.

Conclusions

We sequenced and compared the mitochondrial genomes of three Mangifera species. The results showed that the gene content and the codon usage pattern of Mangifera mitochondrial genomes is similar across various species. Gene transfer from the chloroplast genome to the mitochondrial genome were identified. This study provides valuable information for evolutionary and molecular studies of Mangifera and a basis for further studies on genomic breeding of mango.
The impact of chitosan on the early metabolomic response of wheat to infection by Fusarium graminearum
Authors: Deshaies Myriam , Lamari Nadia , Ng Carl K. Y. , Ward Patrick , Doohan Fiona M.
Published: February 2022

Background

Chitosan has shown potential for the control of Fusarium head blight (FHB) disease caused byFusarium graminearum.The objective of this study was to compare the effect of chitosan hydrochloride applied pre- or post-fungal inoculation on FHB and to better understand its’ mode of action via an untargeted metabolomics study.

Results

Chitosan inhibited fungal growthin vitroand, when sprayed on the susceptible wheat cultivar Remus 24 hours pre-inoculation withF. graminearum,it significantly reduced the number of infected spikelets at 7, 14 and 21 days post-inoculation. Chitosan pre-treatment also increased the average grain weight per head, the number of grains per head and the 1000-grain weight compared to the controls sprayed with water. No significant impact of chitosan on grain yield was observed when the plants were sprayed 24 hours post-inoculation withF. graminearum,even if it did result in a reduced number of infected spikelets at every time point. An untargeted metabolomic study using UHPLC-QTOF-MS on wheat spikes revealed that spraying the spikes with both chitosan andF. graminearumactivated known FHB resistance pathways (e.g. jasmonic acid). Additionally, more metabolites were up- or down-regulated when both chitosan andF. graminearumspores were sprayed on the spikes (117), as compared with chitosan (51) orF. graminearumon their own (32). This included a terpene, a terpenoid and a liminoid previously associated with FHB resistance.

Conclusions

In this study we showed that chitosan hydrochloride inhibited the spore germination and hyphal development ofF. graminearum in vitro, triggered wheat resistance against infection byF. graminearumwhen used as a pre-inoculant, and highlighted metabolites and pathways commonly and differentially affected by chitosan, the pathogen and both agents. This study provides insights into how chitosan might provide protection or stimulate wheat resistance to infection byF. graminearum. It also unveiled new putatively identified metabolites that had not been listed in previous FHB or chitosan-related metabolomic studies.
An insight to rhizosphere bacterial community composition and structure of consecutive winter-initiated sugarcane ratoon crop in Southern China
Authors: Khan Abdullah , Jiang Hongtao , Bu Junyao , Adnan Muhammad , Gillani Syeda Wajeeha , Zhang Muqing
Published: February 2022

Background

Ratooning in sugarcane is a crucial strategy for ensuring the long-term sustainability of the sugarcane industry. Knowledge gap relating to the interaction between rhizosphere microbiome and ratooning crop, particularly the impact of different sugarcane cultivars on the rhizosphere microbiome in consecutive ratooning, requires additional research. The response of two different sugarcane cultivars, viz ZZ-1 and ZZ-13, were evaluated in consecutive ratooning towards the rhizosphere microbial community and cane morphological characters.

Results

Significant changes in the rhizosphere microbiome were observed in the second ratooning over the years. Several important genera were observed in high abundance during the second ratooning, including Burkholderia, Sphingomonas, Bradyzhizobium, and Acidothermus. Cultivar ZZ-13 caused more alterations in the rhizosphere microbiome than ZZ-1, resulting in a more favorable rhizosphere environment for sugarcane growth. The genotypes also varied in terms of nutrients and enzyme activity over the years. There were significant differences between the genotypes and year for number of stalks and yield was significant for genotypes, years and genotype × year.

Conclusion

This finding will help to understand thorough interactions between rhizosphere microorganisms and ratoon sugarcane and lay the foundation for promoting and maximizing yield as far as possible. In the future, this work can serve as guidance in sugarcane husbandry, mainly in Guangxi, China.
The complete chloroplast genome of Onobrychis gaubae (Fabaceae-Papilionoideae): comparative analysis with related IR-lacking clade species
Authors: Moghaddam Mahtab , Ohta Atsushi , Shimizu Motoki , Terauchi Ryohei , Kazempour-Osaloo Shahrokh
Published: February 2022

Background

Plastome (Plastid genome) sequences provide valuable markers for surveying evolutionary relationships and population genetics of plant species. Papilionoideae (papilionoids) has different nucleotide and structural variations in plastomes, which makes it an ideal model for genome evolution studies. Therefore, by sequencing the complete chloroplast genome of Onobrychis gaubae in this study, the characteristics and evolutionary patterns of plastome variations in IR-loss clade were compared.

Results

In the present study, the complete plastid genome of O. gaubae, endemic to Iran, was sequenced using Illumina paired-end sequencing and was compared with previously known genomes of the IRLC species of legumes. The O. gaubae plastid genome was 122,688 bp in length and included a large single-copy (LSC) region of 81,486 bp, a small single-copy (SSC) region of 13,805 bp and one copy of the inverted repeat (IRb) of 29,100 bp. The genome encoded 110 genes, including 76 protein-coding genes, 30 transfer RNA (tRNA) genes and four ribosome RNA (rRNA) genes and possessed 83 simple sequence repeats (SSRs) and 50 repeated structures with the highest proportion in the LSC. Comparative analysis of the chloroplast genomes across IRLC revealed three hotspot genes (ycf1, ycf2, clpP) which could be used as DNA barcode regions. Moreover, seven hypervariable regions [trnL(UAA)-trnT(UGU), trnT(GGU)-trnE(UUC), ycf1, ycf2, ycf4, accD and clpP] were identified within Onobrychis, which could be used to distinguish the Onobrychis species. Phylogenetic analyses revealed that O. gaubae is closely related to Hedysarum. The complete O. gaubae genome is a valuable resource for investigating evolution of Onobrychis species and can be used to identify related species.

Conclusions

Our results reveal that the plastomes of the IRLC are dynamic molecules and show multiple gene losses and inversions. The identified hypervariable regions could be used as molecular markers for resolving phylogenetic relationships and species identification and also provide new insights into plastome evolution across IRLC.
Comparison between dexmedetomidine and propofol on outcomes after coronary artery bypass graft surgery: a retrospective study
Authors: Hu Jie , Lv Bingfeng , West Raha , Chen Xingpeng , Yan Yali , Pac Soo Chen , Ma Daqing
Published: February 2022

Background

Dexmedetomidine (DEX) has a pharmacological profile that should allow rapid recovery and prevent undesirable outcomes such as pulmonary complications.

Methods

This large retrospective study compared the beneficial effects of perioperative infusion of DEX with propofol on the postoperative outcome after coronary artery bypass graft surgery. We reviewed patients’ medical notes at Luoyang Central Hospital from 1st January 2012 to 31st December 2019. All continuous variables, if normally distributed, were presented as mean ± SD; Otherwise, the non-normally distributed data and categorical data were presented as median (25-75 IQR) or number (percentage). The Mann-Whitney U test and Chi-square test were used to evaluate the difference of variables between the DEX and propofol groups. Multivariate logistic regression analysis was performed on the main related and differential factors in the perioperative period.

Results

A total of 1388 patients were included in the study; of those, 557 patients received propofol infusion, and 831 patients received dexmedetomidine. DEX significantly reduced postoperative pulmonary complications compared with propofol, 7.82% vs 13.29%; P < 0.01, respectively. When compared with propofol, DEX significantly shortened the duration of mechanical lung ventilation, 18 (13,25) hours vs 21 (16,37) hours; P < 0.001, the length of stay in the intensive care unit, 51 (42,90) vs 59 (46,94.5) hours; P = 0.001 and hospital stay, 20 (17,24) vs 22 (17,28) days; P < 0.001, respectively. The incidences of postoperative wound dehiscence and infection were significantly reduced with DEX compared with propofol groups, 2.53% vs 6.64%; P < 0.001, respectively. Interestingly, patients receiving DEX had significantly shorter surgical time compared to propofol; 275 (240,310) vs 280 (250,320) minutes respectively (P = 0.005) and less estimated blood loss (P = 0.001).

Conclusion

Perioperative infusion of dexmedetomidine improved the desirable outcomes in patients who had coronary artery bypass graft surgery compared with propofol.