Genotypes, epidemiological variables and fungicides application associated with wheat leaf rust development and grain yield.

The present study was carried out at the Plant Pathology Hafizabad Research Station, the University of Layyah, during the crop seasons 2021-2022 and 2022-2023 to evaluate the response of various wheat genotypes against leaf rust severity (%), environmental conditions favourable for disease development and grain yield. Except for minimum temperature and minimum relative humidity, which had a negative association with disease development, there was a significant correlation between leaf rust severity (%) and all environmental conditions such as maximum temperature, maximum relative humidity, rainfall, and wind speed. All epidemiological variables such as maximum temperature, minimum temperature, minimum relative humidity, rainfall and wind speed significantly affect the disease progression. The disease predictive model accounted for 48-69 % variability in leaf rust severity. The model performance was evaluated using the coefficient of determination (R2 = 0.69) and RMSE, both demonstrated acceptable predictive results for leaf rust severity (%) management. Leaf rust severity (%) increased with an increase in maximum temperature (17.8-30 °C), maximum relative humidity (76.3-85 %), rainfall (2.2-10.85 mm) and wind speed 1.1-2.7 km/h and decreased with the increase of minimum temperature (7.91-16.71 °C) minimum relative humidity (47.15-56.45 %) during both rating seasons 2021-2022 and 2022-2023. The single and two applications of fungicides at the Zadok's scale 3, ZS 4.3, and ZS 5.4 stages led to a significant reduction in grain yield losses caused by leaf rust severity (%) in both the 2021-2022 and 2022-2023 crop seasons. Single and two sprays of prothioconazole, were found to be the first choice among all treatments to reduce the disease severity and increase grain production and maximum gross revenue (513.1-777.8$/ha), as compared to followed by single and two sprays of propiconazole (Progress), tebuconazole + trifloxystrobin, tebuconazole, bixafen + tebuconazole, and propiconazole (Tilt), respectively. These findings recommend the involvement of genotype resistance and weather predictors in wheat leaf rust development, along with fungicide application studies, to improve the predictability of host resistance to disease, future models, and the sustainability of disease control methods.

Rising Mortality among Non-Hispanics due to Pancreatic Cancer in the United States. A CDC Database analysis.

PURPOSE: To examine mortality trends among non-Hispanic (NH) adults with pancreatic cancer. METHOD: CDC-WONDER database was used to extract death certificate data on pancreatic cancer-related mortality in NH adults aged ≥ 45 from 1999 to 2020. Age-adjusted mortality rates (AAMRs) per 100,000 persons and annual percent changes (APCs) were calculated and stratified by year, age, sex, race, and region. RESULTS: From 1999 to 2020, 783,772 deaths occurred among middle-aged (45-64) and older (65-85 +) NH adults. Overall AAMR increased from 31.7 in 1999 to 33.8 in 2020 (APC: 0.35; 95% CI:0.28-0.41). NH older adults had higher AAMRs (67.9) than NH middle-aged adults (12.5). Men consistently had higher AAMRs (37.7) than women (28.4). NH African Americans had the highest AAMRs (40.8) compared to NH Whites (32.1), NH American Indians (23.9), and NH Asians (22.4). Metropolitan areas had a higher AAMR (32.7) than non-metropolitan areas (32.2). The Northeast region had the highest AAMR (34.0) followed by Midwest (33.2), South (32.2), and West (30.1). Delaware, District of Columbia, Louisiana, Michigan, and Mississippi had the highest AAMRs among states. CONCLUSIONS: Pancreatic cancer-related mortality among NH adults has increased from 1999 to 2020. Highest AAMRs were reported in older men, NH African Americans, the Northeastern and metropolitan areas.

Influence of maize genotypes and harvest stages on in-silo fermentation quality and nutritional value of corn silage during hot summer condition of the tropics.

The aim of the experiment was to evaluate the potential of promising summer maize genotypes and optimal stage of harvesting these genotypes for ensiling in terms of dry matter (DM), starch, and crude protein (CP) yields, silage fermentation quality, nutrients profile, total digestible nutrients, metabolizable energy (ME) content, Cornell Net Carbohydrate and Protein System (CNCPS) carbohydrate (CHO) subfractions composition, in vitro DM digestibility (DMD) and in situ starch degradation characteristics. Six maize genotypes were chosen for the study: DK9108 from Monsanto, P30Y87, P3939 from Pioneer, QPM-300 (quality protein maize) and W94 from the International Maize and Wheat Improvement Center (CIMMYT), and a local cultivar, Afgoii, from the Cereal Research Institute (Persabaq, KP). A total of 72 plots (8 m × 10 m) were blocked in three replicate fields, and within each field, each genotype was sown in four replicate plots according to a randomized complete block design. For the data analysis, the Proc-Mixed procedure of Statistical Analysis System with repeated measure analysis of variance was used. The DM yield was strongly influenced (P < 0.001) by maize genotypes, varying from 12.6 to 17.0 tons/ha. Except for total CHO and ammonia nitrogen (NH3-N), the contents of all measured chemical components varied (P < 0.001) among the genotypes. Further comparison revealed that, genotype P3939 had a higher (P < 0.05) content of CP (7.27 vs. 6.92%), starch (36.7 vs. 27.9%), DMD (65.4 vs. 60.0%), ME (2.51 vs. 2.30 Mcal/kg) and lactic acid (5.32 vs. 4.83%) and lowest content of NDF (37.3 vs. 43.1%), pH (3.7 vs. 4.10) compared to the local cultivar (Afgoii). Advancement of post-flowering maturity from 25 to 35% DM (23 to 41 days after flowering (DAF)) increased (P < 0.05) the DM yield (10.4 to 17.8 tons/ha), starch content (29.1 to 35.0%), DMD (65.3 to 67.3%) and ME (2.34 to 2.47 Mcal/kg), and decreased (P < 0.001) the contents of CP (7.42-6.73%), NDF (48.8-38.5%), pH (4.10 to 3.60), NH3-N (8.93-7.80%N) and effective degradability of starch (95.4 to 89.4). Results showed that for higher yields and silage nutritional and fermentation quality, maize crops should be harvested at whole crop DM content of 30-35% (34 to 41 DAF). It was further concluded that genotype P3939 is the most suitable summer maize genotype for silage production in terms of yields and silage nutritional and fermentation quality under the hot environmental conditions of the tropics.

Spectral Efficiency Maximization for Mixed-Structure Cognitive Radio Hybrid Wideband Millimeter-Wave Transceivers in Relay-Assisted Multi-User Multiple-Input Multiple-Output Systems.

This paper proposes a cognitive radio network (CRN)-based hybrid wideband precoding for maximizing spectral efficiency in millimeter-wave relay-assisted multi-user (MU) multiple-input multiple-output (MIMO) systems. The underlying problem is NP-hard and non-convex due to the joint optimization of hybrid processing components and the constant amplitude constraint imposed by the analog beamformer in the radio frequency (RF) domain. Furthermore, the analog beamforming solution common to all sub-carriers adds another layer of design complexity. Two hybrid beamforming architectures, i.e., mixed and fully connected ones, are taken into account to tackle this problem, considering the decode-and-forward (DF) relay node. To reduce the complexity of the original optimization problem, an attempt is made to decompose it into sub-problems. Leveraging this, each sub-problem is addressed by following a decoupled design methodology. The phase-only beamforming solution is derived to maximize the sum of spectral efficiency, while digital baseband processing components are designed to keep interference within a predefined limit. Computer simulations are conducted by changing system parameters under different accuracy levels of channel-state information (CSI), and the obtained results demonstrate the effectiveness of the proposed technique. Additionally, the mixed structure shows better energy efficiency performance compared to its counterparts and outperforms benchmarks.

Development of chitosan-based edible film incorporated with purified flavonoids from Moringa oleifera: Structural, thermal, antibacterial activity and application.

Purified flavonoids (PF) from Moringa oleifera leaves were incorporated in chitosan (CS) polymer at different concentrations (0.5-4%) to produce a novel edible film. The physical, structure, mechanical, and bio-functional characterizations of the film were evaluated. The incorporation of PF significantly (p < 0.05) improved the thickness, solubility, swelling, and color of CS-films. Incorporating 4% of Moringa oleifera purified flavonoids (MOPF) improved the water vapor permeability from 8.85 to 2.47 g-1 s-1 Pa-1, and increased the film surface heterogeneity observed by SEM. Results also indicated that PF enhanced the mechanical properties and thermal stability of CS-films. The FTIR results indicated alterations in the CS-MOPF composite films' characteristics. Additionally, the incorporation of MOPF increased the antioxidation capacity. Furthermore, 4% of MOPF inhibited the activity of pathogenic bacteria in packed beef burgers. These results suggest that CS-MOPF composite films with enhanced technological and bio-functional properties could be industrially applied to increase the shelf-life of packaged foods.

MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review.

Neurodegenerative diseases (NDs) are characterized by abnormalities within neurons of the brain or spinal cord that gradually lose function, eventually leading to cell death. Upon examination of affected tissue, pathological changes reveal a loss of synapses, misfolded proteins, and activation of immune cells-all indicative of disease progression-before severe clinical symptoms become apparent. Early detection of NDs is crucial for potentially administering targeted medications that may delay disease advancement. Given their complex pathophysiological features and diverse clinical symptoms, there is a pressing need for sensitive and effective diagnostic methods for NDs. Biomarkers such as microRNAs (miRNAs) have been identified as potential tools for detecting these diseases. We explore the pivotal role of miRNAs in the context of NDs, focusing on Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Huntington's disease, and Amyotrophic Lateral Sclerosis. The review delves into the intricate relationship between aging and NDs, highlighting structural and functional alterations in the aging brain and their implications for disease development. It elucidates how miRNAs and RNA-binding proteins are implicated in the pathogenesis of NDs and underscores the importance of investigating their expression and function in aging. Significantly, miRNAs exert substantial influence on post-translational modifications (PTMs), impacting not just the nervous system but a wide array of tissues and cell types as well. Specific miRNAs have been found to target proteins involved in ubiquitination or de-ubiquitination processes, which play a significant role in regulating protein function and stability. We discuss the link between miRNA, PTM, and NDs. Additionally, the review discusses the significance of miRNAs as biomarkers for early disease detection, offering insights into diagnostic strategies.

Synergistic reductive catalytic effects of an organic and inorganic hybrid covalent organic framework for hydrogen fuel production.

Electrocatalytic hydrogen generation in alkaline medium has become widely used in a variety of sectors. However, the possibility for additional performance improvement is hampered by slow kinetics. Because of this restriction, careful control over processes such as water dissociation, hydroxyl desorption and hydrogen recombination is required. Covalent organic frameworks (COFs) based on porphyrin and polyoxometalates (POMs) show encouraging electrocatalytic performance, offering a viable route for effective and sustainable hydrogen generation. Their specific architectures lead to increased electrocatalytic activity, which makes them excellent choices for developing water electrolysis as a clean energy conversion method in the alkaline medium. In this regard, TTris@ZnPor and Lindqvist POM were coordinated to create a new eco-friendly and highly active covalent organic framework (TP@VL-COF). In order to describe TP@VL-COF, extensive structural and morphological investigations were carried out through FTIR, 1H NMR, elemental analysis, SEM, fluorescence, UV-visible, PXRD, CV, N2-adsorption isotherm, TGA and DSC analyses. In an alkaline medium, the electrocatalytic capability of 20%C/Pt, TTris@ZnPor, Lindqvist POM and TP@VL-COF was explored and compared for the hydrogen evolution reaction (HER). The TP@VL-COF showed the best catalytic efficiency for HER in an alkaline electrolyte, requiring just a 75 mV overpotential to drive 10 mA cm-2 and outperforming 20%C/Pt, TTris@ZnPor, Lindqvist POM and other reported catalysts. The Tafel slope value also indicates faster kinetics for TP@VL-COF (114 mV dec-1) than for 20%C/Pt (182 mV dec-1) TTris@ZnPor (116 mV dec-1) and Lindqvist POM (125 mV dec-1).

Effectiveness of cephalosporins in hydrolysis and inhibition of Staphylococcus aureus and Escherichia coli biofilms.

IMPORTANCE: Staphylococcus aureus and Escherichia coli contribute to global health challenges by forming biofilms, a key virulence element implicated in the pathogenesis of several infections. OBJECTIVE: The study examined the efficacy of various generations of cephalosporins against biofilms developed by pathogenic S. aureus and E. coli. METHODS: The development of biofilms by both bacteria was assessed using petri-plate and microplate methods. Biofilm hydrolysis and inhibition were tested using first to fourth generations of cephalosporins, and the effects were analyzed by crystal violet staining and phase contrast microscopy. RESULTS: Both bacterial strains exhibited well-developed biofilms in petri-plate and microplate assays. Cefradine (first generation) showed 76.78% hydrolysis of S. aureus biofilm, while significant hydrolysis (59.86%) of E. coli biofilm was observed by cefipime (fourth generation). Similarly, cefuroxime, cefadroxil, cefepime, and cefradine caused 78.8%, 71.63%, 70.63%, and 70.51% inhibition of the S. aureus biofilms, respectively. In the case of E. coli, maximum biofilm inhibition (66.47%) was again shown by cefepime. All generations of cephalosporins were more effective against S. aureus than E. coli, which was confirmed by phase contrast microscopy. CONCLUSIONS AND RELEVANCE: Cephalosporins exhibit dual capabilities of hydrolyzing and inhibiting S. aureus and E. coli biofilms. First-generation cephalosporins exhibited the highest inhibitory activity against S. aureus, while the third and fourth generations significantly inhibited E. coli biofilms. This study highlights the importance of tailored antibiotic strategies based on the biofilm characteristics of specific bacterial strains.

A graph-theoretic approach to ring analysis: Dominant metric dimensions in zero-divisor graphs.

This article investigates the concept of dominant metric dimensions in zero divisor graphs (ZD-graphs) associated with rings. Consider a finite commutative ring with unity, denoted as R, where nonzero elements x and y are identified as zero divisors if their product results in zero (x.y=0). The set of zero divisors in ring R is referred to as L(R). To analyze various algebraic properties of R, a graph known as the zero-divisor graph is constructed using L(R). This manuscript establishes specific general bounds for the dominant metric dimension (Ddim) concerning the ZD-graph of R. To achieve this objective, we examine the zero divisor graphs for specific rings, such as the ring of Gaussian integers modulo m, denoted as Zm[i], the ring of integers modulo n, denoted as Zn, and some quotient polynomial rings. Our research unveils new insights into the structural similarities and differences among commutative rings sharing identical metric dimensions and dominant metric dimensions. Additionally, we present a general result outlining bounds for the dominant metric dimension expressed in terms of the maximum degree, girth, clique number, and diameter of the associated ZD-graphs. Through this exploration, we aim to provide a comprehensive framework for analyzing commutative rings and their associated zero divisor graphs, thereby advancing both theoretical knowledge and practical applications in diverse domains.

Naringin: Cardioprotective properties and safety profile in diabetes treatment.

Flavonoids derived from plants offer a broad spectrum of therapeutic potential for addressing metabolic syndrome, particularly diabetes mellitus (DM), a prevalent non-communicable disease. Hyperglycemia in DM is a known risk factor for cardiovascular diseases (CVDs), which substantially impact global mortality rates. This review examines the potential effects of naringin, a citrus flavonoid, on both DM and its associated cardiovascular complications, including conditions like diabetic cardiomyopathy. The safety profile of naringin is summarized based on various pre-clinical studies. The data for this review was gathered from diverse electronic databases, including Medline, PubMed, ScienceDirect, SpringerLink, Google Scholar, and Emerald Insight. Multiple pre-clinical studies have demonstrated that naringin exerts hypoglycemic and cardioprotective effects by targeting various vascular mechanisms. Specifically, research indicates that naringin down-regulates the renin-angiotensin and oxidative stress systems while concurrently upregulating ß-cell and immune system functions. Clinical trial outcomes also support the therapeutic potential of naringin in managing hyperglycemic states and associated cardiovascular issues. Moreover, toxicity studies have confirmed the safety of naringin in animal models, suggesting its potential for safe administration in humans. In conclusion, naringin emerges as a promising natural candidate for both antidiabetic and cardioprotective purposes, offering potential improvements in health outcomes. While naringin presents a new avenue for therapies targeting DM and CVDs, additional controlled and long-term clinical trials are necessary to validate its efficacy and safety for human use.

Delayed Presentation of Severe Blunt Liver Trauma Following a 12-Foot Fall: A Case Report of a Grade 4 Hepatic Injury With a Concurrent Grade 1 Renal Injury.

The delayed presentation of a 15-year-old female with a complex Grade 4 liver injury and a concurrent Grade 1 renal injury sustained from a fall exemplifies the heightened vulnerability of adolescents to blunt hepatic trauma. Unlike typical presentations where symptoms like abdominal pain and internal bleeding appear immediately, this case emphasises the potential for delayed manifestation, posing unique challenges for diagnosis and management. This case, managed at a leading trauma centre, underscores the distinct challenges compared to adult cases due to adolescents' larger space available for the organ and immature livers. While presenting more management complexity than typical splenic injuries, prompt intervention with emergency laparotomy and hepatic packing proved crucial for the patient's successful outcome. This case emphasises the critical role of early identification, vigilant monitoring, and strict activity restrictions post-operatively for optimal adolescent liver trauma management and serves as a reminder of the spectrum of potential injuries, including bile duct and vascular damage alongside contusions and haematomas.

The gut-brain-axis: A positive relationship between gut microbial dysbiosis and glioblastoma brain tumour.

The glioblastoma brain tumour (GBM) stands out as the most aggressive and resistant-to-treatment malignancy. Nevertheless, the gut-brain connection plays a pivotal role in influencing the growth and activation of the central nervous system. In this particular investigation, we aimed to assess and characterize the gut microbial ecosystem in GBM patients, both quantitatively and qualitatively. We collected faecal samples from 15 healthy volunteers and 25 GBM patients. To delve into the microbial content, we employed PCR-DGGE, targeting the V3 region of the 16S rRNA gene, and conducted qPCR to measure the levels of crucial intestinal bacteria. For a more in-depth analysis, high-throughput sequencing was performed on a selection of 20 random faecal samples (10 from healthy individuals and 10 from GBM patients), targeting the V3+V4 region of the 16S rRNA gene. Our findings from examining the richness and diversity of the gut microbiota unveiled that GBM patients exhibited significantly higher microbial diversity compared to healthy individuals. At the phylum level, Proteobacteria saw a significant increase, while Firmicutes experienced a noteworthy decrease in the GBM group. Moving down to the family level, we observed significantly elevated levels of Enterobacteriaceae, Bacteroidaceae, and Lachnospiraceae in GBM patients, while levels of Veillonellaceae, Rikenellaceae, and Prevotellaceae were notably lower. Delving into genera statistics, we noted a substantial increase in the abundance of Parasutterella, Escherichia-Shigella, and Bacteroides, alongside significantly lower levels of Ruminococcus 2, Faecalibacterium, and Prevotella_9 in the GBM group compared to the control group. Furthermore, when examining specific species, we found a significant increase in Bacteroides vulgatus and Escherichia coli in the GBM group. These observations collectively indicate a marked dysbiosis in the gut microbial composition of GBM patients. Additionally, the GBM group exhibited notably higher levels of alpha diversity when compared to the control group. This increase in diversity suggests a significant bacterial overgrowth in the gut of GBM patients in contrast to the controls. As a result, this research opens up potential avenues to gain a better understanding of the underlying mechanisms, pathways, and potential treatments for GBM, stemming from the significant implications of gut microbial dysbiosis in these patients.

Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) as a Novel Score in Early Detection of Complicated Dengue Fever.

Introduction: The occurrence of dengue fever presents a considerable burden for public health care in developing countries. This study aims to validate APRI as predictor score for severity of dengue fever so that catastrophic events could be prevented, and early triage can save lives. Methods: The retrospective cross-sectional study was done on dengue positive patients from August to November 2023. APRI score was calculated for every patient at the time of admission. The primary end-point was non-complicated disease (Simple dengue fever) vs complicated disease (dengue hemorrhagic fever and dengue shock syndrome). ROC curve was used to identify the role of APRI in prediction of dengue complication. Youden index was used to find the cut-off value of APRI along with sensitivity, specificity, positive and negative likelihood ratios. To further evaluate the role of APRI score, patients were divided into two groups, patients with APRI score greater and lesser than cut-off value. The qualitative variables among two groups were compared by chi-square testing. The predictors of complicated dengue were first determined by univariate regression analysis and then confirmed by multivariate regression analysis. Results: The mean APRI score of 135 patients was 20.06 ± 6.31. AUC for APRI score was 0.93 (p < 0.0001) indicating that APRI score calculated at the time of admission is an excellent marker in determining the complicated dengue. The cut-off value for APRI score was 9.04 (sensitivity 84.91%, specificity 89.02%, p < 0.0001). The patients with APRI <9.04 mostly developed simple dengue fever (54.1%) vs DHF (4.4%) and DSS (1.5%), while patients with APRI >9.04 had more DHF (20.7%) and DSS (12.6%) vs simple dengue fever (6.7%). None of the patient died with APRI <9.04 while the mortality rate was 3.7% in patients with APRI >9.04. Conclusion: The APRI score, calculated at the time of admission, is an excellent marker in determining the severe dengue.

Association of latent autoimmune diabetes of adults with type 3 polyglandular autoimmune syndrome-a diagnostic challenge.

Autoimmune polyendocrine syndromes (APS) encompass m ultiple e ndocrin e gland ins ufficiencies asso ci ated wit h auto immune disease. This c as e report underscores the importance of recognising the association between latent auto immune di a betes of ad ults (LADA) and type 3 polyglandular syndrome. A 42-year-old man belonging to R awalpi ndi, Pakistan, p resented to th e out patient department (OPD) of Ali Medi cal Centre, Islamab ad, i n Januar y 2023 with the complaints o f e xtreme thirs t and frequent urination. The patient reported consistently raised app etite an d eating four to five meals a day along with abrupt weight loss, dry mouth, fatigue occasional dizziness, an d dyspnoea. He was diagno s ed with type 3 polygla ndular syndrome w ith associat io n of LADA. Daily administration of 10 units of glargine insulin, along with six units of rapid-acting insulin, was prescribed. The patient's H bA1c level reduce d in a few months afte r succe ssive follow-up. Patients who exhi bit uncontrol led diabe tes despite dietar y and oral hypoglycaemic management should be further investigated for multiple au toimmune endocrine disorders.

The interaction between formylphenoxyacetic acid derivatives (chalcone and flavones) and ionic surfactants: Insights into binding constants, solubilisation and physiochemical properties.

In this study, UV-vis spectroscopy was employed to investigate the interaction between formylphenoxyacetic acid (FPAA) and its derivatives (chalcone and flavones) with ionic surfactants (SDS, CTAB, and DTAB) in different physiological environments. Changes in the physiochemical properties of FPAA chalcone and flavones including binding constants, partitioning constants, and Gibbs free energy were observed which were influenced by the presence of ionic surfactants computed using mathematical models. The solubilization of the targeted compounds in the ionic surfactants was determined through the binding constant (Kb). The results of the present study indicated that electrostatic interactions played a significant role in the solubilization of the targeted compounds in SDS, CTAB, and DTAB. At pH 4.1, FPAA chalcone exhibited stronger binding affinity with SDS compared to CTAB and DTAB. However, at pH 7.4, chalcone showed stronger binding with DTAB compared to SDS, while negligible interaction with CTAB was observed at pH 7.4. The flavones demonstrated stronger binding with DTAB at pH 7.4 compared to SDS and CTAB and it exhibited strong bonding with CTAB at pH 4.1. The negative values of the Gibbs free energy for binding (ΔGb˚) and partitioning (ΔGp˚) constants displayed the spontaneity of the process. However, FPAA chalcone with SDS and FPAA flavones with DTAB furnished positive ΔGb˚, indicating a non-spontaneous process.

Timosaponin Aâ ¢ induces drug-metabolizing enzymes by activating constitutive androstane receptor (CAR) via dephosphorylation of EGFR signaling pathway.

This study aims to assess the impact of Timosaponin AⅢ (T-AⅢ) on drug-metabolizing enzymes in anticancer treatment. In vivo experiments were conducted in nude mice and ICR mice. Following 24 days of T-AⅢ administration, nude mice exhibited induction of CYP2B10, MDR1, and CYP3A11 in the liver. In the liver of ICR mice, CYP2B10 and MDR1 were up-regulated after 3 days of T-AⅢ administration. In vitro assessments were conducted using HepG2 cells to ascertain the effects and underlying mechanisms. In HepG2 cells, T-AⅢ induced the expression of CYP2B6, MDR1, and CYP3A4, along with CAR activation. CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4. Furthermore, other CAR target genes displayed significant up-regulation. Up-regulation of mCAR was observed in the livers of nude mice and ICR mice. Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation, partially reversed by the MAPK/MEK activator t-BHQ. Inhibition of the ERK1/2 signaling pathway was also observed in vivo. Lastly, T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845, and it suppressed EGF-induced phosphorylation of EGFR, ERK, and CAR. Additionally, T-AⅢ inhibited EGFR phosphorylation in nude mice. Our results demonstrated that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.

Exploring the extrachromosomal plasmid rDNA of Naegleria fowleri AY27 genotype II: A human brain-eating amoeba via high-throughput sequencing.

Naegleria fowleri, also known as brain-earing amoeba, causes severe and rapidly fatal CNS infection in humans called primary amebic meningoencephalitis (PAM). The DNA from the N. fowleri clinical isolate was sequenced for circular extrachromosomal ribosomal DNA (CERE - rDNA). The CERE contains 18 S, 5.8 S, and 28 S ribosomal subunits separated by internal transcribed spacers, 5 open reading frames (ORFs), and mostly repeat elements comprising 7268 bp out of 15,786 bp (46%). A wide variety of variations and recombination events were observed. Finally, the ORFs that comprised only 4 hypothetical proteins were modeled and screened against Zinc drug-like compounds. Two compounds [ZINC77564275 (ethyl 2-(((4-isopropyl-4 H-1,2,4-triazol-3-yl) methyl) (methyl)amino) oxazole-4-carboxylate) and ZINC15022129 (5-(2-methoxyphenoxy)-[2,2'-bipyrimidine]-4,6(1 H,5 H)-dione)] were finalized as potential druggable compounds based on ADME toxicity analysis. We propose that the compounds showing the least toxicity would be potential drug candidates after laboratory experimental validation is performed.