Integrating genome-wide association study with transcriptomic data to predict candidate genes influencing Brassica napus root and biomass-related traits under low phosphorus conditions.

BACKGROUND: Rapeseed (Brassica napus L.) is an essential source of edible oil and livestock feed, as well as a promising source of biofuel. Breeding crops with an ideal root system architecture (RSA) for high phosphorus use efficiency (PUE) is an effective way to reduce the use of phosphate fertilizers. However, the genetic mechanisms that underpin PUE in rapeseed remain elusive. To address this, we conducted a genome-wide association study (GWAS) in 327 rapeseed accessions to elucidate the genetic variability of 13 root and biomass traits under low phosphorus (LP; 0.01 mM P +). Furthermore, RNA-sequencing was performed in root among high/low phosphorus efficient groups (HP1/LP1) and high/low phosphorus stress tolerance groups (HP2/LP2) at two-time points under control and P-stress conditions. RESULTS: Significant variations were observed in all measured traits, with heritabilities ranging from 0.47 to 0.72, and significant correlations were found between most of the traits. There were 39 significant trait-SNP associations and 31 suggestive associations, which integrated into 11 valid quantitative trait loci (QTL) clusters, explaining 4.24-24.43% of the phenotypic variance observed. In total, RNA-seq identified 692, 1076, 648, and 934 differentially expressed genes (DEGs) specific to HP1/LP1 and HP2/LP2 under P-stress and control conditions, respectively, while 761 and 860 DEGs common for HP1/LP1 and HP2/LP2 under both conditions. An integrated approach of GWAS, weighted co-expression network, and differential expression analysis identified 12 genes associated with root growth and development under LP stress. In this study, six genes (BnaA04g23490D, BnaA09g08440D, BnaA09g04320D, BnaA09g04350D, BnaA09g04930D, BnaA09g09290D) that showed differential expression were identified as promising candidate genes for the target traits. CONCLUSION: 11 QTL clusters and 12 candidate genes associated with root and development under LP stress were identified in this study. Our study's phenotypic and genetic information may be exploited for genetic improvement of root traits to increase PUE in rapeseed.

Transcriptome analysis reveals key regulatory genes for root growth related to potassium utilization efficiency in rapeseed (Brassica napus L.).

Root system architecture (RSA) is the primary predictor of nutrient intake and significantly influences potassium utilization efficiency (KUE). Uncertainty persists regarding the genetic factors governing root growth in rapeseed. The root transcriptome analysis reveals the genetic basis driving crop root growth. In this study, RNA-seq was used to profile the overall transcriptome in the root tissue of 20 Brassica napus accessions with high and low KUE. 71,437 genes in the roots displayed variable expression profiles between the two contrasting genotype groups. The 212 genes that had varied expression levels between the high and low KUE lines were found using a pairwise comparison approach. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional classification analysis revealed that the DEGs implicated in hormone and signaling pathways, as well as glucose, lipid, and amino acid metabolism, were all differently regulated in the rapeseed root system. Additionally, we discovered 33 transcription factors (TFs) that control root development were differentially expressed. By combining differential expression analysis, weighted gene co-expression network analysis (WGCNA), and recent genome-wide association study (GWAS) results, four candidate genes were identified as essential hub genes. These potential genes were located fewer than 100 kb from the peak SNPs of QTL clusters, and it was hypothesized that they regulated the formation of the root system. Three of the four hub genes' homologs-BnaC04G0560400ZS, BnaC04G0560400ZS, and BnaA03G0073500ZS-have been shown to control root development in earlier research. The information produced by our transcriptome profiling could be useful in revealing the molecular processes involved in the growth of rapeseed roots in response to KUE.

The impact of maize straw incorporation on arsenic and cadmium availability, transformation and microbial communities in alkaline-contaminated soils.

Increasing evidence of the uncertainty of crop straw returning in heavy metal-contaminated soil is a significant concern. The present study investigated the influence of 1 and 2% maize straws (MS) amendment on As and Cd bioavailability in two different alkaline soils (A-industrial and B-irrigation) after 56 days of ageing. Adding MS to the two soils decreased the pH by 1.28 (A soil) and 1.13 (B soil) and increased the concentration of dissolved organic carbon (DOC) by 54.40 mg/kg (A soil) and 100.00 mg/kg (B soil) during the study period. After 56 days of ageing, the overall NaHCO3-As and DTPA-Cd increased by 40% and 33% (A) and 39% and 41% (B) soils, respectively. The MS additions increased the alteration of As and Cd exchangeable and residual fractions, whereas advanced solid-state 13C nuclear magnetic resonance (NMR) revealed that alkyl C and alkyl O-C-O in A soil and alkyl C, Methoxy C/N-alkyl, and alkyl O-C-O in B soil significantly contributed to the As and Cd mobilisation. Collectively, 16 S rRNA analyses revealed Acidobacteria, Firmicutes, Chloroflexi, Actinobacteria and Bacillus promoted the As and Cd mobilisation following the MS addition, while principle component analysis (PCA) demonstrated that bacterial proliferation significantly influenced MS decomposition, resulting in As and Cd mobilisation in the two soils. Overall, the study highlights the implications of applying MS to As- and Cd-contaminated alkaline soil and offers the framework for conditions to be considered during As- and Cd-remediation efforts, especially when MS is the sole remediation component.

The sequential effect of absorptive capacity, strategic agility, and sustainable competitive advantage on sustainable business performance of SMEs.

A company's environmental sensitivity primarily depends on its sustainability. Hence, investigating the factors that affect sustainable business performance contributes to the literature on the environment. Based on a resource-based view, dynamic capabilities, and contingency theory, this study examines the sequential relationships between the absorptive capacity, strategic agility, sustainable competitive advantage, and sustainable business performance of small- and medium-sized enterprises (SMEs), as well as the mediating role of sustainable competitive advantage in the relationship between strategic agility and sustainable business performance. The data for the study was collected from 421 SMEs operating as family businesses and analyzed using SEM. Research findings show that the sub-dimensions of absorptive capacity, acquisition, and exploitation affect strategic agility; strategic agility affects sustainable competitive advantage, and sustainable competitive advantage affects sustainable business performance. In addition to these sequential relationships, sustainable competitive advantage was found to play a full mediating role in the relationship between strategic agility and sustainable business performance. The findings of the study highlight the process to achieve sustainable performance for SMEs, which are the backbone of developing economies in today's highly turbulent economic conditions.

Transcriptomic profiling and genomic rearrangement landscape of Nigerian prostate cancer.

BACKGROUND: Men of African ancestry have disproportionately high incidence rates of prostate cancer (PCa) and have high mortality rates. While there is evidence for a higher genetic predisposition for incidence of PCa in men of African ancestry compared to men of European ancestry, there have been few transcriptomic studies on PCa in men of African ancestry in the African continent. OBJECTIVE: We performed transcriptomic profiling and fusion analysis on bulk RNA sequencing (RNA-seq) samples from 24 Nigerian PCa patients to investigate the transcriptomic and genomic rearrangement landscape of PCa in Nigerian men. DESIGN: Bulk RNA-seq was performed on 24 formalin-fixed paraffin-embeded (FFPE) prostatectomy specimens of Nigerian men. Transcriptomic analysis was performed on 11 high-quality samples. Arriba Fusion and STAR Fusion were used for fusion detection. RESULTS: 4/11 (36%) of the samples harbored an erythroblast transformation-specific (ETS) fusion event; 1/11 (9%) had a TMPRSS2-ERG fusion; 2/11 had a TMPRSS2-ETV5 fusion, and 1/11 had a SLC45A3-SKIL fusion. Hierarchical clustering of normalized and mean-centered gene expression showed clustering of fusion positive samples. Furthermore, we developed gene set signatures for Nigerian PCa based on fusion events. By projecting the cancer genome atlas prostate adenocarcinoma (TCGA-PRAD) bulk RNA-seq data set onto the transcriptional space defined by these signatures derived from Nigerian PCa patients, we identified a positive correlation between the Nigerian fusion signature and fusion positive samples in the TCGA-PRAD data set. CONCLUSIONS: Less frequent ETS fusion events other than TMPRSS2-ERG such as TMPRSS2-ETV5 and non-ETS fusion events such as SLC45A3-SKIL may be more common in PCa in Nigerian men. This study provides useful working transcriptomic signatures that characterize oncogenic states representative of specific gene fusion events in PCa from Nigerian men.

The impact of facemask on patients with COPD: A systematic review and meta-analysis.

Background: Since the emergence of COVID-19, mandatory facemask wearing has been implemented around the world to prevent viral transmission, however, the impact of wearing facemasks on patients with COPD was unclear. Methods: The current study undertakes a systematic review and meta-analysis of a comprehensive literature retrieval from six databases, based on the pre-determined eligibility criteria, irrespective of language. The risk of bias was assessed using an established instrument. We primarily focused on analyzing ETCO2, SpO2, and heart and respiratory rates, and also considered the impacts on physiological and exercise performance. A descriptive summary of the data and possible meta-analysis was performed. Forest plots were generated to pool estimates based on each of the study outcomes. Results: Of the 3,751 publications considered, six publications were selected for a systematic review and two publications were included for meta-analysis, however, the quality of these six studies was relatively low overall. In the case of inactivity, the facemask wearing COPD cohort had higher respiratory rates than that of the non-facemask wearing cohort (MD = 1.00 and 95% CI 0.47-1.53, P < 0.05). There was no significant difference in ETCO2 (MD = 0.10 and 95% CI -1.57-1.78, P > 0.05) and heart rate (MD = 0.40 and 95% CI -3.59-4.39, P > 0.05) nor SpO2 (MD = -0.40 and 95% CI -0.84-0.04, P > 0.05) between the COPD patients with and without facemasks. Furthermore, it was observed that the only significant differences between the COPD patients with and without facemasks undertaking different activities were FEV1 (%) (MD = 3.84 and 95% CI 0.14-7.54, P < 0.05), FEV1/FVC (%) (MD = 3.25 and 95% CI 0.71-5.79, P < 0.05), and blood lactate (MD = -0.90 and 95% CI -1.73 to -0.07, P < 0.05). Conclusion: Wearing facemasks decreased the exercise performance of patients with COPD, however, it had minimal impact on physiological indexes. Further investigations will be performed on the high-quality data from randomized control studies. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=326265, identifier: CRD42022326265.

Tableting Performance of Maize and Potato Starches Used in Combination as Binder/Disintegrant in Metronidazole Tablet Formulation.

Objectives: This study aimed to characterize the tableting performance of maize and potato starches, when used in combination either as a disintegrant or binder in solid dosage form development. Materials and Methods: Wet granulation was used to process metronidazole granules incorporating either maize starch, potato starch, or a combination of the two starches as binders or disintegrant at 10% w/w. Granule analysis was carried out on the various formulations and subsequently compressed into tablets weighing approximately 500 mg following the addition of extragranular excipients. Tablet properties were assessed after 24 h of storage. Results: Analysis of granule properties did not reveal a wide variation across the formulations irrespective of the type and combination of starches used in the formulation either as binder or disintegrant. It was observed, however, that there were slight differences in particle size, bulk and tapped densities of granule formulations containing the combined starch as excipients compared to granule formulations containing individual starch as the excipient. Tablets prepared using the combined starches as binder had lower tensile strength and disintegration time compared to other formulations incorporating the individual starches as binders. However, when evaluated as disintegrant, the tablet formulation containing the combined starches produced tablets with relatively lower disintegration time compared to formulations containing the individual starches as disintegrant. Conclusion: The study concludes that the combination of maize and potato starches as excipients in tablet formulation influenced the outcome of granule and tablet properties.

Quantitative trait loci mapping reveals important genomic regions controlling root architecture and shoot biomass under nitrogen, phosphorus, and potassium stress in rapeseed (Brassica napus L.).

Plants rely on root systems for nutrient uptake from soils. Marker-assisted selection helps breeders to select desirable root traits for effective nutrient uptake. Here, 12 root and biomass traits were investigated at the seedling stage under low nitrogen (LN), low phosphorus (LP), and low potassium (LK) conditions, respectively, in a recombinant inbred line (RIL) population, which was generated from Brassica napus L. Zhongshuang11 and 4D122 with significant differences in root traits and nutrient efficiency. Significant differences for all the investigated traits were observed among RILs, with high heritabilities (0.43-0.74) and high correlations between the different treatments. Quantitative trait loci (QTL) mapping identified 57, 27, and 36 loci, explaining 4.1-10.9, 4.6-10.8, and 4.9-17.4% phenotypic variances under LN, LP, and LK, respectively. Through QTL-meta analysis, these loci were integrated into 18 significant QTL clusters. Four major QTL clusters involved 25 QTLs that could be repeatedly detected and explained more than 10% phenotypic variances, including two NPK-common and two specific QTL clusters (K and NK-specific), indicating their critical role in cooperative nutrients uptake of N, P, and K. Moreover, 264 genes within the four major QTL clusters having high expressions in roots and SNP/InDel variations between two parents were identified as potential candidate genes. Thirty-eight of them have been reported to be associated with root growth and development and/or nutrient stress tolerance. These key loci and candidate genes lay the foundation for deeper dissection of the NPK starvation response mechanisms in B. napus.

Deciphering the Genetic Basis of Root and Biomass Traits in Rapeseed (Brassica napus L.) through the Integration of GWAS and RNA-Seq under Nitrogen Stress.

An excellent root system is responsible for crops with high nitrogen-use efficiency (NUE). The current study evaluated the natural variations in 13 root- and biomass-related traits under a low nitrogen (LN) treatment in a rapeseed association panel. The studied traits exhibited significant phenotypic differences with heritabilities ranging from 0.53 to 0.66, and most of the traits showed significant correlations with each other. The genome-wide association study (GWAS) found 51 significant and 30 suggestive trait-SNP associations that integrated into 14 valid quantitative trait loci (QTL) clusters and explained 5.7-21.2% phenotypic variance. In addition, RNA sequencing was performed at two time points to examine the differential expression of genes (DEGs) between high and low NUE lines. In total, 245, 540, and 399 DEGs were identified as LN stress-specific, high nitrogen (HN) condition-specific, and HNLN common DEGs, respectively. An integrated analysis of GWAS, weighted gene co-expression network, and DEGs revealed 16 genes involved in rapeseed root development under LN stress. Previous studies have reported that the homologs of seven out of sixteen potential genes control root growth and NUE. These findings revealed the genetic basis underlying nitrogen stress and provided worthwhile SNPs/genes information for the genetic improvement of NUE in rapeseed.

Genome-Wide Association Studies of Root-Related Traits in Brassica napus L. under Low-Potassium Conditions.

Roots are essential organs for a plant's ability to absorb water and obtain mineral nutrients, hence they are critical to its development. Plants use root architectural alterations to improve their chances of absorbing nutrients when their supply is low. Nine root traits of a Brassica napus association panel were explored in hydroponic-system studies under low potassium (K) stress to unravel the genetic basis of root growth in rapeseed. The quantitative trait loci (QTL) and candidate genes for root development were discovered using a multilocus genome-wide association study (ML-GWAS). For the nine traits, a total of 453 significant associated single-nucleotide polymorphism (SNP) loci were discovered, which were then integrated into 206 QTL clusters. There were 45 pleiotropic clusters, and qRTA04-4 and qRTC04-7 were linked to TRL, TSA, and TRV at the same time, contributing 5.25-11.48% of the phenotypic variance explained (PVE) to the root traits. Additionally, 1360 annotated genes were discovered by examining genomic regions within 100 kb upstream and downstream of lead SNPs within the 45 loci. Thirty-five genes were identified as possibly regulating root-system development. As per protein-protein interaction analyses, homologs of three genes (BnaC08g29120D, BnaA07g10150D, and BnaC04g45700D) have been shown to influence root growth in earlier investigations. The QTL clusters and candidate genes identified in this work will help us better understand the genetics of root growth traits and could be employed in marker-assisted breeding for rapeseed adaptable to various conditions with low K levels.

Potential epigenetic modifications implicated in triple- to quadruple-negative breast cancer transition: a review.

Current research on triple-negative breast cancer (TNBC) has resulted in delineation into the quadruple-negative breast cancer (QNBC) subgroup. Epigenetic modifications such as DNA methylation, histone posttranslational modifications and associated changes in chromatin architecture have been implicated in breast cancer pathogenesis. Herein, the authors highlight genes with observed epigenetic modifications that are associated with more aggressive TNBC/QNBC pathogenesis and possible interventions. Advanced literature searches were done on PubMed/MEDLINE, Scopus and Google Scholar. The results suggest that nine epigenetically altered genes/differentially expressed proteins in addition to the downregulated androgen receptor are associated with TNBC aggressiveness and could be implicated in the TNBC to QNBC transition. Thus, restoring the normal expression of these genes via epigenetic reprogramming could be therapeutically beneficial to TNBC and QNBC patients.

When the androgen hormone receptor becomes inactive in triple-negative breast cancer (TNBC) patients, it results in another subtype of breast cancer called quadruple-negative breast cancer (QNBC). This is because these patients already lack the biological activities of three other important hormone receptors. The functions of these receptors are targeted by some drugs used in the management of breast cancers, so the lack of these receptors in TNBC and QNBC patients is thought to be linked with poor response to treatment. Some epigenetic modifications are involved in a more severe disease that is very difficult to control in TNBC patients and could facilitate its transition to the more aggressive QNBC subtype. Treatment response could be improved by restoring the normal function of the altered genes by reversing the observed epigenetic alterations.

Revisiting oil rents-output growth nexus in Nigeria: evidence from dynamic autoregressive distributive lag model and kernel-based regularized least squares approach.

Given the dominant role of oil in terms of foreign exchange earnings in Nigeria, this study revisits the oil rents and output growth nexus, using the novel dynamic autoregressive distributive lag (DYNARDL) model and kernel-based regularized least squares (KRLS) approach over the period 1973-2020. The major finding from this study is that oil rents are less significant for output and also exhibit decreasing marginal effect on output growth in Nigeria. However, our robustness result shows that oil revenue is positive and significantly affects output growth, while corruption dampens output growth. Result from the oil revenue model with a minimum root square mean error, when compared with the oil rents model, corroborate the finding. We are thus of the opinion that oil revenue is more important for output growth in Nigeria than oil rents. Having established this fact, it is recommended that policymakers and the government should accord utmost attention to boosting oil revenue via transparency and accountability. They should also ensure a lasting solution to the nation's high dependency on refined crude oil products importation for a sustainable economic growth and development. Also, more efforts should be directed at developing the seven identified strategic solid minerals to further enhance the revenue base of the government.

Epigenetic modifications associated with genes implicated in cytokine storm: The potential biotherapeutic effects of vitamins and minerals in COVID-19.

Cytokine storm is a phrase used to refer to an abrupt upsurge in the circulating levels of various pro-inflammatory cytokines, causing increased stimulation and activity of immune cells during disease conditions. The binding of pattern recognition receptors to pathogen-associated molecular patterns during COVID-19 infection recruits response machinery involving the activation of transcription factors and proteins required for a robust immune response by host cells. These immune responses could be influenced by epigenetic modifications as evidenced by significant variations in COVID-19 pathophysiology and response to therapy observed among patients across the globe. Considering that circulating levels of interleukin 1, tumor necrosis factor-α, and interleukin 6 are significantly elevated during cytokine storm in COVID-19 patients, genetic and epigenetic variations in the expression and function of these proteins could enhance our understanding of the disease pathogenesis. Treatment options that repress the transcription of specific cytokine genes during COVID-19 infection could serve as possible targets to counteract cytokine storm in COVID-19. Therefore, the present article reviews the roles of cytokines and associated genes in the COVID-19 cytokine storm, identifies epigenetic modifications associated with the disease progression, and possible ameliorative effects of some vitamins and minerals obtained as epigenetic modifiers for the control of cytokine storm and disease severity in COVID-19 patients. PRACTICAL APPLICATIONS: COVID-19 causes mortality and morbidity that adversely affect global economies. Despite a global vaccination campaign, side effects associated with vaccination, misconceptions, and a number of other factors have affected the expected successes. Cytokine storm in COVID-19 patients contributes to the disease pathogenesis and response to therapy. Epigenetic variations in the expression of various cytokines could be implicated in the different outcomes observed in COVID-19 patients. Certain vitamins and minerals have been shown to interfere with the expression and activity of cytokines implicated in cytokine storm, thereby counteracting observed pathologies. This review examines cytokines implicated in cytokine storm in COVID-19, epigenetic modifications that contribute to increased expression of identified cytokines, specific foods rich in the identified vitamins and minerals, and suggests their possible ameliorative benefits. The article will be beneficial to both scientists and the general public who are interested in the role of vitamins and minerals in ameliorating COVID-19.

Identification of entomopathogenic fungi Metarhizium anisopliae and Purpureocillium lilacinum from oil palm plantation soils in Universiti Putra Malaysia

Aims@#Insect pests are one of the major constraints of oil palm production in Malaysia. However, synthetic chemical insecticides are the most common method for its control, despite their negative effects on non-target organisms and the development of resistance. Therefore, the present study is aimed to identify novel indigenous isolates of entomopathogenic fungi (EPF) in oil palm soil as part of integrated pest management (IPM) of oil palm insect pests.@*Methodology and results@#The potential of EPF were isolated from the soil collected from the oil palm plantation in UPM using a mealworm beetle larva (Tenebrio molitor) as an insect bait. Seven Metarhizium anisopliae and two Purpureocillium lilacinum isolates were identified by morphological characterization (macroscopic and microscopic observation) and molecular identification using internal transcribed spacer (ITS) region (ITS region amplification).@*Conclusion, significance and impact of study@#To our knowledge, this is the first time P. lilacinum has been found in the soil of an oil palm plantation or any other host in Malaysia. Furthermore, both of the isolates M. anisopliae and P. lilacinum may be potentially considered as biological control candidates for major insect pests in oil palm.

The role of coast guard courage in the relationship between personality and organizational commitment.

Courageous behaviors are risky and devoted actions performed primarily for the benefit of others, and they closely relate to many beneficial organizational (e.g., commitment) outcomes. Even courage plays a crucial role in many professions' results; investigating it in military content is a primary issue. This paper examined the relationship between the Big Five personality traits and organizational commitment and the moderator role of courage in this relationship by focusing on coast guards. Cross-sectional survey data (n = 512) were obtained from employees and analyzed using the least square method regression analysis. The results showed that the Conscientiousness trait is a strong antecedent for organizational commitment, and courage emerges as a moderator for the relationship between personality traits and organizational commitment. High courage strengthened the effect of Conscientiousness-Emotional Stability on normative commitment, Extraversion-Agreeableness on affective commitment, Openness on continuance, and normative commitment. Practitioners might recruit high conscientious, agreeable, emotionally stable, and courageous candidates considering correlational and moderating effects.

Genetic Dissection of Mature Root Characteristics by Genome-Wide Association Studies in Rapeseed (Brassica napus L.).

Roots are complicated quantitative characteristics that play an essential role in absorbing water and nutrients. To uncover the genetic variations for root-related traits in rapeseed, twelve mature root traits of a Brassica napus association panel were investigated in the field within three environments. All traits showed significant phenotypic variation among genotypes, with heritabilities ranging from 55.18% to 79.68%. Genome-wide association studies (GWAS) using 20,131 SNPs discovered 172 marker-trait associations, including 103 significant SNPs (-log10 (p) > 4.30) that explained 5.24-20.31% of the phenotypic variance. With the linkage disequilibrium r2 > 0.2, these significant associations were binned into 40 quantitative trait loci (QTL) clusters. Among them, 14 important QTL clusters were discovered in two environments and/or with phenotypic contributions greater than 10%. By analyzing the genomic regions within 100 kb upstream and downstream of the peak SNPs within the 14 loci, 334 annotated genes were found. Among these, 32 genes were potentially associated with root development according to their expression analysis. Furthermore, the protein interaction network using the 334 annotated genes gave nine genes involved in a substantial number of interactions, including a key gene associated with root development, BnaC09g36350D. This research provides the groundwork for deciphering B. napus' genetic variations and improving its root system architecture.

Proteomic analysis of three medically important Nigerian Naja (Naja haje, Naja katiensis and Naja nigricollis) snake venoms.

Proteomics technologies enable a comprehensive study of complex proteins and their functions. The venom proteomes of three medically important Nigerian Elapidae snakes Naja haje, Naja katiensis and Naja nigricollis was studied using HILIC coupled with LC-MS/MS analysis. Results revealed a total of 57, 55, and 46 proteins in the venoms of N. haje, N. katiensis, and N. nigricollis, respectively, with molecular mass ranging between 5 and 185  kDa. These snakes have 38 common proteins in addition to 3 uncommon proteins: actiflagelin, cathelicidin, and cystatin identified in their venoms. The identified proteins belonged to 14 protein families in N. haje and N. katiensis, and 12 protein families in N. nigricollis. Of the total venom proteins, 3FTx was the most abundant protein family, constituting 52% in N. haje and N. katiensis, and 41% in N. nigricollis, followed by PLA2, constituting 37% in N. nigricollis, 26% in N. haje, and 24% in N. katiensis. Other protein families, including LAAO, CRISPs, VEGF, PLB, CVF, SVMP, SVH, AMP, PI, Globin, Actin, and C-type lectins, were also detected, although, at very low abundances. Quantification of the relative abundance of each protein revealed that alpha and beta fibrinogenase and PLA2, which constituted 18-26% of the total proteome, were the most abundant. The 3 uncommon proteins have no known function in snake venom. However, actiflagelin activates sperm motility; cystatin inhibits angiogenesis, while cathelicidin exerts antimicrobial effects. The three Nigerian Naja genus proteomes displayed 70% similarity in composition, which suggests the possibility of formulating antivenom that may cross-neutralise the venoms of cobra species found in Nigeria. These data provide insights into clinically relevant peptides/proteins present in the venoms of these snakes. Data are available via ProteomeXchange with identifier PXD024627.

Prognostic significance of BIRC7/Livin, Bcl-2, p53, Annexin V, PD-L1, DARC, MSH2 and PMS2 in colorectal cancer treated with FOLFOX chemotherapy with or without aspirin.

Evasion of apoptosis is associated with treatment resistance and metastasis in colorectal cancer (CRC). Various cellular processes are associated with evasion of apoptosis. These include overexpression of pro-apoptotic proteins (including p53 and PD-L1), anti-apoptotic proteins (BIRC7/Livin and Bcl-2), chemokine receptors (including DARC), and dysregulation of DNA mismatch repair proteins (including MSH2 and PMS2). The aim of this study was to determine the effect of folinic acid, 5-FU and oxaliplatin (FOLFOX) as a single agent and aspirin plus FOLFOX in various combinations on the aforementioned proteins in human CRC, SW480 cell line and rat models of N-Methyl-N-Nitrosourea (NMU)-induced CRC. In addition, effects of the NMU-induced CRC and chemotherapeutic regimens on haematological and biochemical parameters in the rat models were studied. Immunohistochemistry, immunofluorescence and immunoblot techniques were used to study the expression pattern of the related proteins in the human CRC cells pre- and post-treatment. Double contrast barium enema, post-mortem examination and histological analyses were used to confirm tumour growth and the effect of the treatment in vivo in rat models. Notably, we found in human mucinous CRC, a significant increase in expression of the BIRC7/Livin post-FOLFOX treatment compared with pre-treatment (p = 0.0001). This increase provides new insights into the prognostic role of BIRC7/Livin in evasion of apoptosis and facilitation of treatment resistance, local recurrence and metastasis particularly among mucinous CRCs post-FOLFOX chemotherapy. These poor prognostic features in the CRC may be further compounded by the significant suppression of DARC, PD-L1, PMS2 and overexpression of MSH2 and anti-apoptotic Bcl-2 and p53 proteins observed in our study (p < 0.05). Importantly, we found a significant reduction in expression of BIRC7/Livin and reactivation of DARC and PD-L1 with a surge in Annexin V expression in rat models of CRC cells post-treatment with a sequential dose of aspirin plus FOLFOX compared with other treatments in vivo (p <0.05). The mechanistic rational of these effects underscores the importance of expanded concept of possible aspirin combination therapy with FOLFOX sequentially in future CRC management. Validation of our findings through randomized clinical trials of aspirin plus FOLFOX sequentially in patients with CRC is therefore warranted.

Endovascular Treatment of Critical Limb Ischemia in Buerger Disease (Thromboangiitis Obliterans) With Midterm Follow-Up: A Viable Option When Bypass Surgery Is Not Feasible.

OBJECTIVE. Thromboangiitis obliterans (TAO) is an occlusive inflammatory disease affecting small- and medium-sized vessels that causes decrease in life quality and eventually limb loss. The only proven treatment method is smoking cessation, but it may be insufficient for limb salvage in patients with critical limb ischemia. In this single-center retrospective study, the feasibility and efficiency of endovascular treatment in TAO were evaluated. MATERIALS AND METHODS. After approval of the local institutional review board, 41 patients who underwent endovascular treatment of TAO between January 2014 and June 2019 were evaluated retrospectively. Technical success and procedure-related complications were recorded. Decrease in Rutherford classification score, relief of pain, and wound healing were evaluated to determine clinical success. Primary patency, limb salvage rate, and amputation-free survival were also evaluated. RESULTS. A total of 45 limbs were treated during the study period. Technical success was achieved in 82.2% of procedures. Mean follow-up was 29.8 months. Clinical improvement was achieved in 35 limbs. Three patients underwent major amputation and 12 patients underwent minor amputation. Amputation-free survival and limb salvage were both 93.3% at both 1 and 2 years. Reintervention was performed in 14 patients because of occlusion and clinical relapsing of the symptoms. CONCLUSION. Endovascular treatment of TAO is feasible, has a potential to prevent limb amputation in patients with critical limb ischemia, and has acceptable technical success and limb salvage rates. Because there is no consensus in treatment of TAO, prospective comparative studies are needed to determine the effectiveness of an endovascular approach.

Patterns of Early-Onset Colorectal Cancer Among Nigerians and African Americans.

PURPOSE: Colorectal cancer (CRC) incidence rates are increasing among individuals < 50 years of age (early-onset CRC) globally with causes unknown. Racial/ethnic disparities in early-onset CRC have also grown more pronounced, because Black individuals have higher early-onset CRC incidence and poorer survival compared with White individuals. We describe the prevalence and burden of early-onset CRC among Africans in Nigeria and African Americans (AAs) in the United States. PATIENTS AND METHODS: We identified Black individuals diagnosed with a first primary CRC ages 18 to 49 years between 1989 and 2017 at Ahmadu Bello University Teaching Hospital in Zaria, Nigeria (Nigerians), and in the United States (AAs) using the National Institutes of Health/National Cancer Institute's SEER program of cancer registries. Multivariable logistic regression models were used to investigate clinical and demographic differences between Nigerians and AAs with early-onset CRC, adjusted for age, sex, tumor site, and histology. RESULTS: A total of 5,019 Black individuals were diagnosed with early-onset CRC over the study period (379 Nigerians; 4,640 AAs). Overall, approximately one third of young Black patients were diagnosed with rectal tumors (35.8%). Nigerian individuals with early-onset CRC were eight-fold more likely to be diagnosed with rectal tumors (odds ratio [OR], 8.14; 95% CI, 6.23 to 10.62; P < .0001) and more likely to be diagnosed at younger ages (OR, 0.87; 95% CI, 0.86 to 0.89; P < .0001) compared with young African Americans in adjusted models. CONCLUSION: Compared with AA individuals diagnosed with early-onset CRC, Nigerian individuals harbor distinct features of early-onset CRC. Additional investigation of the histopathologic and biologic heterogeneity of early-onset CRCs among Black individuals is critical for understanding racial disparities in susceptibility and outcomes, which may have implications for tailored early-onset CRC prevention, detection, and treatment strategies.