Roxadustat for the treatment of anemia in patients with lower-risk myelodysplastic syndrome: Open-label, dose-selection, lead-in stage of a phase 3 study.

Anemia is the predominant cytopenia in myelodysplastic syndromes (MDS) and treatment options are limited. Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor approved for the treatment of anemia of chronic kidney disease in the UK, EU, China, Japan, South Korea, and Chile. MATTERHORN is a phase 3, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of roxadustat in anemia of lower risk-MDS. Eligible patients had baseline serum erythropoietin ≤ 400 mIU/mL, and a low packed RBC transfusion burden. In this open-label (OL), dose-selection, lead-in phase, enrolled patients were assigned to 1 of 3 roxadustat starting doses (n = 8 each): 1.5, 2.0, and 2.5 mg/kg. The primary efficacy endpoint of the OL phase was the proportion of patients with transfusion independence (TI) for ≥ 8 consecutive weeks in the first 28 treatment weeks. A secondary efficacy endpoint was the proportion of patients with a ≥ 50% reduction in RBC transfusions over an 8-week period compared with baseline. Adverse events were monitored. Patients were followed for 52 weeks. Of the 24 treated patients, TI was achieved in 9 patients (37.5%) at 28 and 52 weeks; 7 of these patients were receiving 2.5 mg/kg dose when TI was achieved. A ≥ 50% reduction in RBC transfusions was achieved in 54.2% and 58.3% of patients at 28 and 52 weeks, respectively. Oral roxadustat dosed thrice weekly was well tolerated. There were no fatalities or progression to acute myeloid leukemia. Based on these outcomes, 2.5 mg/kg was the chosen starting roxadustat dose for the ongoing double-blind study phase.

Roxadustat for anemia in patients with end-stage renal disease incident to dialysis.

BACKGROUND: We evaluated the efficacy and safety of roxadustat versus epoetin alfa for the treatment of chronic kidney disease-related anemia in patients new to dialysis. METHODS: HIMALAYAS was a Phase 3, open-label, epoetin alfa-controlled trial. Eligible adults were incident to hemodialysis/peritoneal dialysis for 2 weeks to ≤4 months prior to randomization and had mean hemoglobin (Hb) ≤10.0 g/dL. Primary endpoints were mean Hb (g/dL) change from baseline averaged over Weeks 28-52 regardless of rescue therapy [non-inferiority criterion: lower limit of 95% confidence interval (CI) for treatment difference >-0.75] and percentage of patients achieving an Hb response between Weeks 1 and 24 censored for rescue therapy (non-inferiority margin for between-group difference -15%). Adverse events were monitored. RESULTS: The intent-to-treat population included patients randomized to roxadustat (n = 522) or epoetin alfa (n = 521). Mean (standard deviation) Hb changes from baseline averaged over Weeks 28-52 were 2.57 (1.27) and 2.36 (1.21) in the roxadustat and epoetin alfa groups. Roxadustat was non-inferior [least squares mean difference: 0.18 (95% CI 0.08, 0.29)] to epoetin alfa. Percentages of patients with an Hb response were 88.2% and 84.4% in the roxadustat and epoetin alfa groups, respectively. Roxadustat was non-inferior to epoetin alfa [treatment-group difference 3.5% (95% CI -0.7%, 7.7%)]. Adverse event rates were comparable between treatment groups. CONCLUSIONS: Roxadustat was efficacious for correcting and maintaining Hb levels compared with epoetin alfa. Roxadustat had an acceptable safety profile.

Expression and Role of Biosynthetic, Transporter, Receptor, and Responsive Genes for Auxin Signaling during Clubroot Disease Development.

Auxins play a pivotal role in clubroot development caused by the obligate biotroph Plasmodiophora brassicae. In this study, we investigated the pattern of expression of 23 genes related to auxin biosynthesis, reception, and transport in Chinese cabbage (Brassica rapa) after inoculation with P. brassicae. The predicted proteins identified, based on the 23 selected auxin-related genes, were from protein kinase, receptor kinase, auxin responsive, auxin efflux carrier, transcriptional regulator, and the auxin-repressed protein family. These proteins differed in amino acids residue, molecular weights, isoelectric points, chromosomal location, and subcellular localization. Leaf and root tissues showed dynamic and organ-specific variation in expression of auxin-related genes. The BrGH3.3 gene, involved in auxin signaling, exhibited 84.4-fold increase in expression in root tissues compared to leaf tissues as an average of all samples. This gene accounted for 4.8-, 2.6-, and 5.1-fold higher expression at 3, 14, and 28 days post inoculation (dpi) in the inoculated root tissues compared to mock-treated roots. BrNIT1, an auxin signaling gene, and BrPIN1, an auxin transporter, were remarkably induced during both cortex infection at 14 dpi and gall formation at 28 dpi. BrDCK1, an auxin receptor, was upregulated during cortex infection at 14 dpi. The BrLAX1 gene, associated with root hair development, was induced at 1 dpi in infected roots, indicating its importance in primary infection. More interestingly, a significantly higher expression of BrARP1, an auxin-repressed gene, at both the primary and secondary phases of infection indicated a dynamic response of the host plant towards its resistance against P. brassicae. The results of this study improve our current understanding of the role of auxin-related genes in clubroot disease development.

Expression and Role of Response Regulating, Biosynthetic and Degrading Genes for Cytokinin Signaling during Clubroot Disease Development.

The obligate biotroph Plasmodiophora brassicae causes clubroot disease in oilseeds and vegetables of the Brassicaceae family, and cytokinins play a vital role in clubroot formation. In this study, we examined the expression patterns of 17 cytokinin-related genes involved in the biosynthesis, signaling, and degradation in Chinese cabbage inoculated with the Korean pathotype group 4 isolate of P. brassicae, Seosan. This isolate produced the most severe clubroot symptoms in Chinese cabbage cultivar "Bullam-3-ho" compared to three other Korean geographical isolates investigated. BrIPT1, a cytokinin biosynthesis gene, was induced on Day 1 and Day 28 in infected root tissues and the upregulation of this biosynthetic gene coincided with the higher expression of the response regulators BrRR1, on both Days and BrRR6 on Day 1 and 3. BrRR3 and 4 genes were also induced during gall enlargement on Day 35 in leaf tissues. The BrRR4 gene, which positively interact with phytochrome B, was consistently induced in leaf tissues on Day 1, 3, and 14 in the inoculated plants. The cytokinin degrading gene BrCKX3-6 were induced on Day 14, before gall initiation. BrCKX2,3,6 were induced until Day 28 and their expression was downregulated on Day 35. This insight improves our current understanding of the role of cytokinin signaling genes in clubroot disease development.

Genome-wide characterization and expression profiling of PDI family gene reveals function as abiotic and biotic stress tolerance in Chinese cabbage (Brassica rapa ssp. pekinensis).

BACKGROUND: Protein disulfide isomerase (PDI) and PDI-like proteins contain thioredoxin domains that catalyze protein disulfide bond, inhibit aggregation of misfolded proteins, and function in isomerization during protein folding in endoplasmic reticulum and responses during abiotic stresses.Chinese cabbage is widely recognized as an economically important, nutritious vegetable, but its yield is severely hampered by various biotic and abiotic stresses. Because of, it is prime need to identify those genes whose are responsible for biotic and abiotic stress tolerance. PDI family genes are among of them. RESULTS: We have identified 32 PDI genes from the Br135K microarray dataset, NCBI and BRAD database, and in silico characterized their sequences. Expression profiling of those genes was performed using cDNA of plant samples imposed to abiotic stresses; cold, salt, drought and ABA (Abscisic Acid) and biotic stress; Fusarium oxysporum f. sp. conglutinans infection. The Chinese cabbage PDI genes were clustered in eleven groups in phylogeny. Among them, 15 PDI genes were ubiquitously expressed in various organs, while 24 PDI genes were up-regulated under salt and drought stress. By contrast, cold and ABA stress responsive gene number were ten and nine, respectively. In case of F. oxysporum f. sp. conglutinans infection 14 BrPDI genes were highly up-regulated. Interestingly, BrPDI1-1 gene was identified as putative candidate against abiotic (salt and drought) and biotic stresses, BrPDI5-2 gene for ABA stress, and BrPDI1-4, 6-1 and 9-2 were putative candidate genes for both cold and chilling injury stresses. CONCLUSIONS: Our findings help to elucidate the involvement of PDI genes in stress responses, and they lay the foundation for functional genomics in future studies and molecular breeding of Brassica rapa crops. The stress-responsive PDI genes could be potential resources for molecular breeding of Brassica crops resistant to biotic and abiotic stresses.

Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study.

BACKGROUND: Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin. STUDY DESIGN: Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study. SETTING & PARTICIPANTS: Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa. INTERVENTION: Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous epoetin alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of epoetin alfa responsiveness. Intravenous iron was prohibited. OUTCOMES: Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of -0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2). MEASUREMENTS: Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset). RESULTS: Baseline epoetin alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and epoetin alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the epoetin alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus epoetin alfa (P<0.05). In part 2, the average roxadustat dose requirement for Hb level maintenance was ∼1.7mg/kg. The least-squares-mean ΔHb in roxadustat-treated individuals was comparable to that in epoetin alfa-treated individuals (about -0.5g/dL) and the least-squares-mean difference in ΔHb between both treatment arms was -0.03 (95% CI, -0.39 to 0.33) g/dL (mixed effect model-repeated measure). Roxadustat significantly reduced mean total cholesterol levels, not observed with epoetin alfa. No safety concerns were raised. LIMITATIONS: Short treatment duration and small sample size. CONCLUSIONS: In this phase 2 study of anemia therapy in patients with end-stage renal disease on maintenance hemodialysis therapy, roxadustat was well tolerated and effectively maintained Hb levels.

Genome-wide identification and characterization of MADS-box family genes related to organ development and stress resistance in Brassica rapa.

BACKGROUND: MADS-box transcription factors (TFs) are important in floral organ specification as well as several other aspects of plant growth and development. Studies on stress resistance-related functions of MADS-box genes are very limited and no such functional studies in Brassica rapa have been reported. To gain insight into this gene family and to elucidate their roles in organ development and stress resistance, we performed genome-wide identification, characterization and expression analysis of MADS-box genes in B. rapa. RESULTS: Whole-genome survey of B. rapa revealed 167 MADS-box genes, which were categorized into type I (Mα, Mß and Mγ) and type II (MIKC(c) and MIKC*) based on phylogeny, protein motif structure and exon-intron organization. Expression analysis of 89 MIKC(c) and 11 MIKC* genes was then carried out. In addition to those with floral and vegetative tissue expression, we identified MADS-box genes with constitutive expression patterns at different stages of flower development. More importantly, from a low temperature-treated whole-genome microarray data set, 19 BrMADS genes were found to show variable transcript abundance in two contrasting inbred lines of B. rapa. Among these, 13 BrMADS genes were further validated and their differential expression was monitored in response to cold stress in the same two lines via qPCR expression analysis. Additionally, the set of 19 BrMADS genes was analyzed under drought and salt stress, and 8 and 6 genes were found to be induced by drought and salt, respectively. CONCLUSION: The extensive annotation and transcriptome profiling reported in this study will be useful for understanding the involvement of MADS-box genes in stress resistance in addition to their growth and developmental functions, which ultimately provides the basis for functional characterization and exploitation of the candidate genes for genetic engineering of B. rapa.

Identification and expression analysis of WRKY family genes under biotic and abiotic stresses in Brassica rapa.

WRKY proteins constitute one of the largest transcription factor families in higher plants, and they are involved in multiple biological processes such as plant development, metabolism, and responses to biotic and abiotic stresses. Genes of this family have been well documented in response to many abiotic and biotic stresses in many plant species, but not yet against Pectobacterium carotovorum subsp. carotovorum and Fusarium oxysporum f.sp. conglutinans in any of the plants. Moreover, potentiality of a specific gene may vary depending on stress conditions and genotypes. To identify stress resistance-related potential WRKY genes of Brassica rapa, we analyzed their expressions against above-mentioned pathogens and cold, salt, and drought stresses in B. rapa. Stress resistance-related functions of all Brassica rapa WRKY (BrWRKY) genes were firstly analyzed through homology study with existing biotic and abiotic stress resistance-related WRKY genes of other plant species and found a high degree of homology. We then identified all BrWRKY genes in a Br135K microarray dataset, which was created by applying low-temperature stresses to two contrasting Chinese cabbage doubled haploid (DH) lines, Chiifu and Kenshin, and selected 41 BrWRKY genes with high and differential transcript abundance levels. These selected genes were further investigated under cold, salt, and drought stresses as well as after infection with P. carotovorum subsp. carotovorum and F. oxysporum f.sp. conglutinans in B. rapa. The selected genes showed an organ-specific expression, and 22 BrWRKY genes were differentially expressed in Chiifu compared to Kenshin under cold and drought stresses. Six BrWRKY genes were more responsive in Kenshin compared to Chiffu under salt stress. In addition, eight BrWRKY genes showed differential expression after P. carotovorum subsp. carotovorum infection and five genes after F. oxysporum f.sp. conglutinans infection in B. rapa. Thus, the differentially expressed BrWRKY genes might be potential resources for molecular breeding of Brassica crops against abiotic and biotic stresses and several genes, which showed differential expressions commonly in response to several stresses, might be useful for multiple stress resistance. These findings would also be helpful in resolving the complex regulatory mechanism of WRKY genes in stress resistance and for this further functional genomics study of these potential genes in different Brassica crops is essential.

Characterization and stress-induced expression analysis of Alfin-like transcription factors in Brassica rapa.

The Alfin-like (AL) transcription factors (TFs) family is involved in many developmental processes, including the growth and development of roots, root hair elongation, meristem development, etc. However, stress resistance-related function and the regulatory mechanism of these TFs have yet to be elucidated. This study identified 15 Brassica rapa AL (BrAL) TFs from BRAD database, analyzed the sequences and profiled their expression first time in response to Fusarium oxysporum f. sp. conglutinans and Pectobacterium carotovorum subsp. carotovorum in fection, cold, salt and drought stresses in B. rapa. Structural and phylogenetic analyses of 15 BrAL TFs revealed four distinct groups (groups I-IV) with AL TFs of Arabidopsis thaliana. In the expression analyses, ten BrAL TFs showed responsive expression after F. oxysporum f. sp. conglutinans infection, while all BrAL TFs showed responses under cold, salt and drought stresses in B. rapa. Interestingly, ten BrAL TFs showed responses to both biotic and abiotic stress factors tested here. The differentially expressed BrAL TFs thus represent potential resources for molecular breeding of Brassica crops resistant against abiotic and biotic stresses. Our findings will also help to elucidate the complex regulatory mechanism of AL TFs in stress resistance and provide a foundation for further functional genomics studies and applications.

Unraveling the genetic enigma of rice submergence tolerance: Shedding light on the role of ethylene response factor-encoding gene SUB1A-1.

The world's low-lying rice (Oryza sativa) cultivation areas are under threat of submergence or flash flooding due to global warming. Rice plants manifest a variety of physiological and morphological changes to cope with submergence and hypoxia, including lowering carbohydrate consumption, inhibiting shoot elongation, and forming a thicker leaf gas film during submergence. Functional studies have revealed that submergence tolerance in rice is mainly determined by an ethylene response factor (ERF) transcription factor-encoding gene, namely SUBMERGENCE 1A-1 (SUB1A-1) located in the SUB1 quantitative trait locus. The SUB1A-1-dependent submergence tolerance is manifested through hormonal signaling involving ethylene, gibberellic acid, brassinosteroid, auxin and jasmonic acid. Considerable progress has been made toward the introduction of SUB1A-1 into rice varieties through a conventional marker-assisted backcrossing approach. Here, we review the recent advances in the physiological, biochemical and molecular dynamics of rice submergence tolerance mediated by the 'quiescence strategy'. Thus, the present review aims to provide researchers with insights into the genetics of rice submergence tolerance and future perspectives for designing submergence-resilient plants for sustainable agriculture under the uncertainties of climate change.

Exploring relationship among nitrogen fertilizer, yield and nitrogen use efficiency in modern wheat varieties under subtropical condition.

Due to variations in the length of crop growth and the dynamics of soil nitrogen, the nitrogen (N) requirements of different wheat varieties may change. In this relation, during two successive wheat-growing seasons in 2018 and 2019, pot experiments were conducted to assess relationship among N fertilizer, yield and efficiency of N use in contemporary wheat varieties. Ten varieties of wheat viz. BARI Gom -24, BARI Gom -25, BARI Gom -26, BARI Gom -27, BARI Gom -28, BARI Gom -29, BARI Gom-30, BARI Gom-31, BARI Gom-32, and BARI Gom-33 and four N levels e.g. N 0, N 45 kg ha-1, N 90 kg ha-1 and N 135 kg ha-1 were used in the study. Completely randomized design (CRD) was followed with three replications. Wheat yield and yield-contributing elements like spike length, 1000- grain weight, and grain yield enhanced at N levels up to N 90 kg ha-1. The principal component analysis illustrated that the range BARI -32 had the most grain manufacturing and N use efficiency with N 90 kg ha-1 application. Correlation depicted that there is a robust relation amongst N use, yield and N use efficiency. Dendrogram organized primarily based totally at the resemblance via way of means of Euclidean distance among wheat varieties and it was confirmed that varieties allocated in clusters II had been greater diverse. The end consequence found out big hereditary difference in wheat which could doubtlessly be used for the wide range cultivation and breeding plan.

Effect of Reproductive Stage-Waterlogging on the Growth and Yield of Upland Cotton (Gossypium hirsutum).

The reproductive stage of cotton (Gossypium sp.) is highly sensitive to waterlogging. The identification of potential elite upland cotton (Gossypium hirsutum) cultivar(s) having higher waterlogging tolerance is crucial to expanding cotton cultivation in the low-lying areas. The present study was designed to investigate the effect of waterlogging on the reproductive development of four elite upland cotton cultivars, namely, Rupali-1, CB-12, CB-13, and DM-3, against four waterlogging durations (e.g., 0, 3, 6, and 9-day). Waterlogging stress significantly impacted morpho-physiological, biochemical, and yield attributes of cotton. Two cotton cultivars, e.g., CB-12 and Rupali-1, showed the lowest reduction in plant height (6 and 9%, respectively) and boll weight (8 and 5%, respectively) at the highest waterlogging duration of 9 days. Physiological and biochemical data revealed that higher leaf chlorophyll, proline, and relative water contents, and lower malondialdehyde contents, particularly in CB-12 and Rupali-1, were positively correlated with yield. Notably, CB-12 and Rupali-1 had higher seed cotton weight (90.34 and 83.10 g, respectively), lint weight (40.12 and 39.32 g, respectively), and seed weight (49.47 and 43.78 g, respectively) per plant than CB-13 and DM-3 in response to the highest duration of waterlogging of 9 days. Moreover, extensive multivariate analyses like Spearman correlation and the principle component analysis revealed that CB-12 and Rupali-1 had greater coefficients in yield and physiological attributes at 9-day waterlogging, whereas CB-13 and DM-3 were sensitive cultivars in response to the same levels of waterlogging. Thus, CB-12 and Rupali-1 might be well adapted to the low-lying waterlogging-prone areas for high and sustained yield.

Assessing Silicon-Mediated Growth Performances in Contrasting Rice Cultivars under Salt Stress.

Silicon (Si) application has great potential to improve salt tolerance in a variety of crop plants. However, it is unclear how Si influences the responses of contrasting rice cultivars when exposed to excessive salt. Here, we investigated the functions of Si in alleviating the negative effects of salt stress on two contrasting rice cultivars, namely BRRI dhan48 (salt-sensitive) and Binadhan-10 (salt-tolerant). Rice seedlings was pre-treated with three doses of Si (as silicic acid; 0, 1 and 2 mM) for 14 days at one-day interval before being exposed to salt stress (10 dSm-1) in a sustained water bath system. The results demonstrated that the seedlings of BRRI dhan48 and Binadhan-10, respectively exhibited substantial reductions in shoot height (16 and 9%), shoot fresh weight (64 and 43%) and shoot dry weight (50 and 39%) under salinity. Intriguingly, BRRI dhan48 pre-treated with 1 and 2 mM Si, respectively, showed a higher increase in shoot height (SH) (by 25.90 and 26.08%) as compared with Binadhan-10 (by 3 and 8%) under salt stress compared with their respective controls. Data revealed that a comparatively higher improvement in the growth performances of the salt-induced Si pre-treated BRRI dhan48 than that of Binadhan-10. For example, 1 and 2 mM of Si treatments significantly attributed to elevated leaf relative water content (RWC) (13 and 22%), proline (138 and 165%), chlorophyll a (42 and 44%), chlorophyll b (91 and 72%), total chlorophyll (58 and 53%) and carotenoids (33 and 29%), and recovery in the reductions of electrolyte leakage (13 and 21%), malondialdehyde content (23 and 30%) and shoot Na+/K+ ratio (22 and 52%) in BRRI dhan48 compared with Si-untreated control plants under salt stress. In addition, we found salt-tolerant Binadhan-10 also had enhanced RWC (9 and 19%), proline (12 and 26%) with pre-treatment with 1 and 2 mM of Si, respectively, under salt stress, while no significant differences were noticed in the case of photosynthetic pigments and Na+/K+ ratio. Our results showed that Si supplementation potentiated higher salt-tolerance ability in the salt-sensitive BRRI dhan48 as compared with salt-tolerant Binadhan-10. Thus, Si application could be highly beneficial in the growth recovery of the salinity-affected salt-sensitive high yielding rice cultivars in the saline-prone areas.

Optimum Nitrogen Application Acclimatizes Root Morpho-Physiological Traits and Yield Potential in Rice under Subtropical Conditions.

Nitrogen (N) is a highly essential macronutrient for plant root growth and grain yield (GY). To assess the relationship among N, root traits, and the yield of boro (dry season irrigated) rice, a pot experiment was performed in the Department of Agronomy, Bangladesh Agricultural University, Mymensingh, Bangladesh, during the boro rice season of 2020-2021. Three boro rice varieties, namely BRRI dhan29, Hira-2, and Binadhan-10, were planted at four N doses: 0 kg ha-1 (N0), 70 kg ha-1 (N70), 140 kg ha-1 (N140), and 210 kg ha-1 (N210). The experiment was conducted following a completely randomized design with three replicates. The varieties were evaluated for root number (RN), root length (RL), root volume (RV), root porosity (RP), leaf area index (LAI), total dry matter (TDM), and yield. The results indicated that the Binadhan-10, Hira-2, and BRRI dhan29 varieties produced better root characteristics under at the N140 and N210 levels. A substantial positive association was noticed between the grain yield and the root traits, except for root porosity. Based on the root traits and growth dynamics, Binadhan-10 performed the best at the N140 level and produced the highest grain yield (26.96 g pot-1), followed by Hira-2 (26.35 g pot-1) and BRRI dhan29 (25.90 g pot-1).

Dissecting the Relationship between Root Morphological Traits and Yield Attributes in Diverse Rice Cultivars under Subtropical Condition.

Understanding the link between root morphological traits and yields is crucial for improving crop management. To evaluate this link, a pot experiment was conducted in the net house of the Department of Agronomy, Bangladesh Agricultural University, Mymensingh, Bangladesh during the boro(dry season irrigated) rice growing season of 2019-20. Thirteen cultivars, named BRRI dhan29, BRRI dhan58, BRRI dhan67, BRRI dhan74, BRRI dhan81, Binadhan-8, Binadhan-10, Hira-2, Tej gold, SL8H, Jagliboro, Rata boro, and Lakhai, were used following a completely randomized design (CRD) with three replications. The cultivars were screened for root number (RN), root length (RL), root volume (RV), root porosity (RP), leaf area index (LAI), total dry matter (TDM), and grain yield (GY). A considerable variation in root traits, LAI, and TDM were found among the studied cultivars, and the highest GY (26.26 g pot-1)was found for Binahan-10. Thirteen cultivars were grouped into three clusters using hierarchical cluster analysis, where clusters 1, 2, and 3 assembled with 3, 5, and 5 cultivars, respectively. Considering all of the studied traits, Cluster 3 (Binadhan-10, Hira-2, BRRI dhan29, BRRI dhan58, and Tejgold) showed promise, followed by Cluster 2 (BRRI dhan81, BRRI dhan67, SL8H, BRRI dhan74, and Binadhan-8). Principal component analysis (PCA) revealed that the RV, RDW, RFW, TDM, and GY are effective traits for rice cultivation.

Silicon-mediated heat tolerance in higher plants: A mechanistic outlook.

Heat stress, resulting from global warming, is considered one of the major challenges to be addressed for increasing plant survival and productivity worldwide. Although plants have a built-in defense mechanism against heat stress, such strategy seems to be insufficient to counteract heat adversities under extreme temperature regimes. Hence, increasing heat tolerance in plants for sustainable yields is one of the biggest challenges for researchers in the coming decades. Conventional plant breeding approach to enhance heat tolerance has gained some successes; however, more efforts are needed to make plants resilient to heat stress for increasing crop production during ongoing climate change. Thus, exploring 'heat stress mitigation strategies' using cost-effective and eco-friendly approaches may be quick and sustainable alternatives. The use of silicon (Si) and Si-nanoparticles (Si-NPs) in enhancing heat tolerance in plants has recently gained much attention. Application of Si and Si-NPs can assist plants to overcome heat-induced oxidative stress through the acceleration of reactive oxygen species detoxification by modulating the antioxidant systems and regulating transcription of key genes associated with heat stress responses. In fact, molecular rationale behind Si-mediated heat tolerance in plants is largely unknown. In this minireview, we made efforts to understand the mechanistic aspects of heat-induced responses and damages in plants, and possible molecular dynamics of Si-induced heat tolerance in plants. We also highlighted recent advances on how Si induces heat tolerance potential in plants and future perspectives on how Si can contribute to sustainable crop production under the increasing threat of global climate change.

A Randomized Trial of Roxadustat in Anemia of Kidney Failure: SIERRAS Study.

INTRODUCTION: Erythropoiesis-stimulating agents, standard of care for anemia of end-stage kidney disease, are associated with cardiovascular events. We evaluated the efficacy and safety of roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. METHODS: SIERRAS was a phase 3, randomized, open-label, active-controlled study enrolled adults on dialysis for end-stage kidney disease receiving erythropoiesis-stimulating agents for anemia. Patients were randomized (1:1) to thrice-weekly roxadustat or epoetin alfa. Doses were based on previous epoetin alfa dose and adjusted in the roxadustat arm to maintain hemoglobin at ∼11 g/dl during treatment. Epoetin alfa dosing was adjusted per US package insert. Primary efficacy endpoint was mean hemoglobin (g/dl) change from baseline averaged over weeks 28 to 52. Treatment-emergent adverse events were monitored. RESULTS: Enrolled patients (roxadustat, n = 370 and epoetin alfa, n = 371) had similar mean (SD) baseline hemoglobin levels (10.30 [0.66] g/dl). Mean (SD) hemoglobin changes for weeks 28 to 52 were 0.39 (0.93) and -0.09 (0.84) in roxadustat and epoetin alfa, respectively. Roxadustat was noninferior (least squares mean difference: 0.48 [95% confidence interval: 0.37, 0.59]; P < 0.001) to epoetin alfa. Tolerability was comparable between treatments. CONCLUSION: In end-stage kidney disease, roxadustat was noninferior to epoetin alfa in up to 52 weeks of treatment in this erythropoietin-stimulating agent conversion study. Roxadustat had an acceptable tolerability profile.

A Genome-Wide Analysis Reveals Stress and Hormone Responsive Patterns of TIFY Family Genes in Brassica rapa.

The TIFY family is a plant-specific group of proteins with a diversity of functions and includes four subfamilies, viz. ZML, TIFY, PPD, and JASMONATE ZIM-domain (JAZ) proteins. TIFY family members, particularly JAZ subfamily proteins, play roles in biological processes such as development and stress and hormone responses in Arabidopsis, rice, chickpea, and grape. However, there is no information about this family in any Brassica crop. This study identifies 36 TIFY genes in Brassica rapa, an economically important crop species in the Brassicaceae. An extensive in silico analysis of phylogenetic grouping, protein motif organization and intron-exon distribution confirmed that there are four subfamilies of BrTIFY proteins. Out of 36 BrTIFY genes, we identified 21 in the JAZ subfamily, seven in the TIFY subfamily, six in ZML and two in PPD. Extensive expression profiling of 21 BrTIFY JAZs in various tissues, especially in floral organs and at different flower growth stages revealed constitutive expression patterns, which suggest that BrTIFY JAZ genes are important during growth and development of B. rapa flowers. A protein interaction network analysis also pointed to association of these proteins with fertility and defense processes of B. rapa. Using a low temperature-treated whole-genome microarray data set, most of the JAZ genes were found to have variable transcript abundance between the contrasting inbred lines Chiifu and Kenshin of B. rapa. Subsequently, the expression of all 21 BrTIFY JAZs in response to cold stress was characterized in the same two lines via qPCR, demonstrating that nine genes were up-regulated. Importantly, the BrTIFY JAZs showed strong and differential expression upon JA treatment, pointing to their probable involvement in JA-mediated growth regulatory functions, especially during flower development and stress responses. Additionally, BrTIFY JAZs were induced in response to salt, drought, Fusarium, ABA, and SA treatments, and six genes (BrTIFY3a, 3b, 6a, 9a, 9b, and 9c) were identified to have co-responsive expression patterns. The extensive annotation and transcriptome profiling reported in this study will be useful for understanding the involvement of TIFY genes in stress resistance and different developmental functions, which ultimately provides the basis for functional characterization and exploitation of the candidate TIFY genes for genetic engineering of B. rapa.

Characterization and expression profiling of MYB transcription factors against stresses and during male organ development in Chinese cabbage (Brassica rapa ssp. pekinensis).

MYB proteins comprise a large family of plant transcription factors that play regulatory roles in different biological processes such as plant development, metabolism, and defense responses. To gain insight into this gene superfamily and to elucidate its roles in stress resistance, we performed a comprehensive genome-wide identification, characterization, and expression analysis of MYB genes in Chinese cabbage (Brassica rapa ssp. pekinensis). We identified 475 Chinese cabbage MYB genes, among which most were from R2R3-MYB (256 genes) and MYB-related (202) subfamilies. Analysis of sequence characteristics, phylogenetic classification, and protein motif structures confirmed the existence of several categories (1R, 2R, 3R, 4R, and 5R) of Chinese cabbage MYB genes, which is comparable with MYB genes of other crops. An extensive in silico functional analysis, based on established functional properties of MYB genes from different crop species, revealed 11 and four functional clades within the Chinese cabbage R2R3-MYB and MYB-related subfamilies, respectively. In this study, we reported a MYB-like group within the MYB-related subfamily contains 77 MYB genes. Expression analysis using low temperature-treated whole-genome microarray data revealed variable transcript abundance of 1R/2R/3R/4R/5R-MYB genes in 11 clusters between two inbred lines of Chinese cabbage, Chiifu and Kenshin, which differ in cold tolerance. In further validation tests, we used qRT-PCR to examine the cold-responsive expression patterns of 27 BrMYB genes; surprisingly, the MYB-related genes were induced more highly than the R2R3-MYB genes. In addition, we identified 10 genes with corresponsive expression patterns from a set of salt-, drought-, ABA-, JA-, and SA-induced R2R3-MYB genes. We identified 11 R2R3-MYBs functioning in resistance against biotic stress, including 10 against Fusarium oxysporum f.sp. conglutinans and one against Pectobacterium carotovoram subsp. caratovorum. Furthermore, based on organ-specific expression data, we identified nine R2R3-MYBs that were constitutively expressed in male reproductive tissue, which may provide an important key for studying male sterility in Chinese cabbage. The extensive annotation and transcriptome profiling reported in this study will be useful for understanding the involvement of MYB genes in stress resistance in addition to their growth regulatory functions, ultimately providing the basis for functional characterization and exploitation of the candidate MYB genes for genetic engineering of Chinese cabbage.

Molecular characterization of BZR transcription factor family and abiotic stress induced expression profiling in Brassica rapa.

BRASSINAZOLE-RESISTANT (BZR) transcription factors (TFs) are primarily well known as positive regulators of Brassinosteroid (BR) signal transduction in different plants. BR is a plant specific steroid hormone, which has multiple stress resistance functions besides various growth regulatory roles. Being an important regulator of the BR synthesis, BZR TFs might have stress resistance related activities. However, no stress resistance related functional study of BZR TFs has been reported in any crop plants so far. Therefore, this study identified 15 BZR TFs of Brassica rapa (BrBZR) from a genome-wide survey and characterized them through sequence analysis and expression profiling against several abiotic stresses. Various systematic in silico analysis of these TFs validated the fundamental properties of BZRs, where a high degree of similarity also observed with recognized BZRs of other plant species from the comparison studies. In the organ specific expression analyses, 6 BrBZR TFs constitutively expressed in flower developmental stages indicating their flower specific functions. Subsequently, from the stress resistance related expression profiles differential transcript abundance levels were observed by 6 and 11 BrBZRs against salt and drought stresses, respectively. All BrBZRs showed several folds up-regulation against exogenous ABA treatment. All BrBZRs also showed differential expression against low temperature stress treatments and these TFs were proposed as transcriptional activators of CBF cold response pathway of B. rapa. Notably, three BrBZRs gave co-responsive expression against all the stresses tested here, suggesting their multiple stress resistance related functions. Thus, the findings would be helpful in resolving the complex regulatory mechanism of BZRs in stress resistance and further functional genomics study of these potential TFs in different Brassica crops.