Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Mechanism and Kinetics of Tetramethrin Degradation Using an Indigenous Gordonia cholesterolivorans A16

Tetramethrin is a pyrethroid insecticide that is commonly used worldwide. The toxicity of this insecticide into the living system is an important concern. In this study, a novel tetramethrin-degrading bacterial strain named A16 was isolated from the activated sludge and identified as Gordonia cholesterolivorans. Strain A16 exhibited superior tetramethrin degradation activity, and utilized tetramethrin as the sole carbon source for growth in a mineral salt medium (MSM). High-performance liquid chromatography (HPLC) analysis revealed that the A16 strain was able to completely degrade 25 mg·L−1 of tetramethrin after 9 days of incubation. Strain A16 effectively degraded tetramethrin at temperature 20–40 °C, pH 5–9, and initial tetramethrin 25–800 mg·L−1. The maximum specific degradation rate (qmax), half-saturation constant (Ks), and inhibition constant (Ki) were determined to be 0.4561 day−1, 7.3 mg·L−1, and 75.2 mg·L−1, respectively. The Box–Behnken design was used to optimize degradation conditions, and maximum degradation was observed at pH 8.5 and a temperature of 38 °C. Five intermediate metabolites were identified after analyzing the degradation products through gas chromatography–mass spectrometry (GC-MS), which suggested that tetramethrin could be degraded first by cleavage of its carboxylester bond, followed by degradation of the five-carbon ring and its subsequent metabolism. This is the first report of a metabolic pathway of tetramethrin in a microorganism. Furthermore, bioaugmentation of tetramethrin-contaminated soils (50 mg·kg−1) with strain A16 (1.0 × 107 cells g−1 of soil) significantly accelerated the degradation rate of tetramethrin, and 74.1% and 82.9% of tetramethrin was removed from sterile and non-sterile soils within 11 days, respectively. The strain A16 was also capable of efficiently degrading a broad spectrum of synthetic pyrethroids including D-cyphenothrin, chlorempenthrin, prallethrin, and allethrin, with a degradation efficiency of 68.3%, 60.7%, 91.6%, and 94.7%, respectively, after being cultured under the same conditions for 11 days. The results of the present study confirmed the bioremediation potential of strain A16 from a contaminated environment.
The Zebrafish Model to Understand Epigenetics in Renal Diseases

Epigenetic modifications are able to alter gene expression and include DNA methylation, different histone variants, and post-transcriptional modifications (PTMs), such as acetylation or phosphorylation, and through short/long RNAs, respectively. In this review, we focus on current knowledge concerning epigenetic modifications in gene regulation. We describe different forms of epigenetic modifications and explain how epigenetic changes can be detected. The relevance of epigenetics in renal diseases is highlighted with multiple examples and the use of the zebrafish model to study glomerular diseases in general and epigenetics in renal diseases in particular is discussed. We end with an outlook on how to use epigenetic modifications as a therapeutic target for different diseases. Here, the zebrafish model can be employed as a high-throughput screening tool not only to discover epigenetic alterations contributing to disease, but also to test novel substances that change epigenetic signatures in vivo. Therefore, the zebrafish model harbors the opportunity to find novel pathogenic pathways allowing a pre-selection of potential targets and compounds to be tested for renal diseases.
Plastic Crushing Failure of Bio-Inspired Cellular Hierarchical Topological Sandwich Core

Bio-inspired self-similar hierarchical honeycombs are multifunctional cellular topologies used for resisting various loadings. However, the crushing behavior under large plastic deformation is still unknown. This paper investigates the in-plane compressive response of selective laser melting (SLM) fabricated hierarchical honeycombs. The effects of hierarchical order, relative density as well as constituent material are evaluated. The results show that at small deformation, the AlSi10Mg alloy hierarchical honeycombs show great advantages over the elastic modulus and compressive strength than 316L steel hierarchical honeycombs. As the relative density and hierarchical order increase, the failure mechanism of AlSi10Mg alloy honeycombs gradually changes from a bending-dominated mode to a fracture-dominated mode; whereas all the 316L steel honeycombs fail due to the distortion of original unit cells. At large deformation, the AlSi10Mg alloy honeycombs behave with brittle responses, while the 316L steel honeycombs exhibit ductile responses, showing a negative Poisson’s ratio behavior and gradient deformation of hierarchical unit cells. The addition of unit cell refinements improves the elastic modulus of AlSi10Mg alloy honeycombs and advances the densification of 316L steel honeycombs. In addition, the effect of constituent material on the compressive response of hierarchical honeycombs has been discussed. This study facilitates the development and future potential application of multifunctional ultra-light sandwich structures.
Chemical Composition and Antioxidant, Anti-Inflammatory, and Enzyme Inhibitory Activities of an Endemic Species from Southern Algeria: Warionia saharae

Warionia saharae Benth. & Coss. (Asteraceae) is an endemic species of North Africa naturally grown in the southwest of the Algerian Sahara. In the present study, this species’ hydromethanolic leaf extract was investigated for its phenolic profile characterized by ultra-high-performance liquid chromatography coupled with a diode array detector and an electrospray mass spectrometer (UHPLC-DAD-ESI/MS). Additionally, the chemical composition of W. saharae was analyzed by gas chromatography–mass spectrometry, and its antioxidant potential was assessed through five in vitro tests: DPPH● scavenging activity, ABTS●+ scavenging assay, galvinoxyl scavenging activity, ferric reducing power (FRP), and cupric reducing antioxidant capacity. The UHPLC-DAD-ESI/MS analysis allowed the detection and quantification of 22 compounds, with taxifolin as the dominant compound. The GC–MS analysis allowed the identification of 37 compounds, and the antioxidant activity data indicate that W. saharae extract has a very high capacity to capture radicals due to its richness in compounds with antioxidant capacity. The extract also showed potent α-glucosidase inhibition as well as a good anti-inflammatory activity. However, weak anti-α-amylase and anticholinesterase activities were recorded. Moreover, an in silico docking study was performed to highlight possible interactions between three significant compounds identified in W. saharae extract and α-glucosidase enzyme.
NOD/scid IL‐2Rγnull mice reconstituted with peripheral blood mononuclear cells from patients with Crohn's disease reflect the human pathological phenotype

Crohn's disease (CD) is characterized by pronounced intestinal fibrosis and severe mucosal damage and conventional animal models are limited to reflect these pathological manifestations. The aim of this study was to examine whether the combination of patient immune‐profiling and preclinical studies in a mouse model based on NOD/scid IL‐2Rγnull (NSG) reconstituted with peripheral blood mononuclear cells (PBMC) from CD patients has the capacity to harmonize ex vivo human and in vivo animal studies.
Impacting the Remedial Potential of Nano Delivery-Based Flavonoids for Breast Cancer Treatment

Breast cancer persists as a diffuse source of cancer despite persistent detection and treatment. Flavonoids, a type of polyphenol, appear to be a productive option in the treatment of breast cancer, because of their capacity to regulate the tumor related functions of class of compounds. Plant polyphenols are flavonoids that appear to exhibit properties which are beneficial for breast cancer therapy. Numerous epidemiologic studies have been performed on the dynamic effect of plant polyphenols in the prevention of breast cancer. There are also subclasses of flavonoids that have antioxidant and anticarcinogenic activity. These can regulate the scavenging activity of reactive oxygen species (ROS) which help in cell cycle arrest and suppress the uncontrolled division of cancer cells. Numerous studies have also been performed at the population level, one of which reported a connection between cancer risk and intake of dietary flavonoids. Breast cancer appears to show intertumoral heterogeneity with estrogen receptor positive and negative cells. This review describes breast cancer, its various factors, and the function of flavonoids in the prevention and treatment of breast cancer, namely, how flavonoids and their subtypes are used in treatment. This review proposes that cancer risk can be reduced, and that cancer can be even cured by improving dietary intake. A large number of studies also suggested that the intake of fruit and vegetables is associated with reduced breast cancer and paper also includes the role and the use of nanodelivery of flavonoids in the healing of breast cancer. In addition, the therapeutic potential of orally administered phyto-bioactive compounds (PBCs) is narrowed because of poor stability and oral bioavailability of compounds in the gastrointestinal tract (GIT), and solubility also affects bioavailability. In recent years, creative nanotechnology-based approaches have been advised to enhance the activity of PBCs. Nanotechnology also offers the potential to become aware of disease at earlier stages, such as the detection of hidden or unconcealed metastasis colonies in patients diagnosed with lung, colon, prostate, ovarian, and breast cancer. However, nanoformulation-related effects and safety must not be overlooked. This review gives a brief discussion of nanoformulations and the effect of nanotechnology on herbal drugs.
Pilot Model for Community Based Oral Cancer Screening Program: Outcome from 4 Northeastern Provinces in Thailand

Management of advanced-stage oral cancer adds a great burden to individuals and health care systems. Community-based oral cancer screening can be beneficial in early detection and treatment. In this study, a novel oral cancer screening program was conducted utilizing an existing network of health care personnel, facilities, and digital database management for efficient coverage of a large population. The screening program considered 392,396 individuals aged ≥40 from four northeastern provinces in Thailand. Three levels of screening were performed: S1 by village healthcare volunteers to identify risk groups, S2 by dental auxiliaries to visually identify abnormal oral lesions, and S3 by dentists for final diagnosis and management. A total of 349,318 individuals were interviewed for S1, and 192,688 were identified as a risk group. For S2, 88,201 individuals appeared, and 2969 were further referred. Out of 1779 individuals who appeared for S3, oral potentially malignant disorders (OPMDs) were identified in 544, non-OPMDs in 1047, doubtful lesions in 52, and no results in 136 individuals. Final treatment was carried out in 704 individuals that included biopsies of 504 lesions, exhibiting 25 cancerous lesions and 298 OPMDs. This study is so far one of the largest oral cancer screening programs conducted in Thailand and showed effective implementation of community-based oral cancer screening.
Degradation and Characterisation of Electrospun Polycaprolactone (PCL) and Poly(lactic-co-glycolic acid) (PLGA) Scaffolds for Vascular Tissue Engineering

The current study aimed to evaluate the characteristics and the effects of degradation on the structural properties of Poly(lactic-co-glycolic acid) (PLGA)- and polycaprolactone (PCL)-based nanofibrous scaffolds. Six scaffolds were prepared by electrospinning, three with PCL 15% (w/v) and three with PLGA 10% (w/v), with electrospinning processing times of 30, 60 and 90 min. Both types of scaffolds displayed more robust mechanical properties with increased spinning times. The tensile strength of both scaffolds with 90-min electrospun membranes did not show a significant difference in their strengths, as the PCL and PLGA scaffolds measured at 1.492 MPa ± 0.378 SD and 1.764 MPa ± 0.7982 SD, respectively. All membranes were shown to be hydrophobic under a wettability test. A degradation behaviour study was performed by immersing all scaffolds in phosphate-buffered saline (PBS) solution at room temperature for 12 weeks and for 4 weeks at 37 °C. The effects of degradation were monitored by taking each sample out of the PBS solution every week, and the structural changes were investigated under a scanning electron microscope (SEM). The PCL and PLGA scaffolds showed excellent fibre structure with adequate degradation, and the fibre diameter, measured over time, showed slight increase in size. Therefore, as an example of fibre water intake and progressive degradation, the scaffold’s percentage weight loss increased each week, further supporting the porous membrane’s degradability. The pore size and the porosity percentage of all scaffolds decreased substantially over the degradation period. The conclusion drawn from this experiment is that PCL and PLGA hold great promise for tissue engineering and regenerative medicine applications.
Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: A Translational Perspective for the Clinician-Scientist

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare and potentially lethal inherited arrhythmia disease characterized by exercise or emotion-induced bidirectional or polymorphic ventricular tachyarrhythmias. The median age of disease onset is reported to be approximately 10 years of age. The majority of CPVT patients have pathogenic variants in the gene encoding the cardiac ryanodine receptor, or calsequestrin 2. These lead to mishandling of calcium in cardiomyocytes resulting in after-depolarizations, and ventricular arrhythmias. Disease severity is particularly pronounced in younger individuals who usually present with cardiac arrest and arrhythmic syncope. Risk stratification is imprecise and long-term prognosis on therapy is unknown despite decades of research focused on pediatric CPVT populations. The purpose of this review is to summarize contemporary data on pediatric CPVT, highlight knowledge gaps and present future research directions for the clinician-scientist to address.
AMPK Phosphorylation Is Controlled by Glucose Transport Rate in a PKA-Independent Manner

To achieve growth, microbial organisms must cope with stresses and adapt to the environment, exploiting the available nutrients with the highest efficiency. In Saccharomyces cerevisiae, Ras/PKA and Snf1/AMPK pathways regulate cellular metabolism according to the supply of glucose, alternatively supporting fermentation or mitochondrial respiration. Many reports have highlighted crosstalk between these two pathways, even without providing a comprehensive mechanism of regulation. Here, we show that glucose-dependent inactivation of Snf1/AMPK is independent from the Ras/PKA pathway. Decoupling glucose uptake rate from glucose concentration, we highlight a strong coordination between glycolytic metabolism and Snf1/AMPK, with an inverse correlation between Snf1/AMPK phosphorylation state and glucose uptake rate, regardless of glucose concentration in the medium. Despite fructose-1,6-bisphosphate (F1,6BP) being proposed as a glycolytic flux sensor, we demonstrate that glucose-6-phosphate (G6P), and not F1,6BP, is involved in the control of Snf1/AMPK phosphorylation state. Altogether, this study supports a model by which Snf1/AMPK senses glucose flux independently from PKA activity, and thanks to conversion of glucose into G6P.
Characterization of VU0468554, a New Selective Inhibitor of Cardiac G Protein–Gated Inwardly Rectifying K+ Channels

G protein–gated inwardly rectifying K+ (GIRK) channels are critical mediators of excitability in the heart and brain. Enhanced GIRK-channel activity has been implicated in the pathogenesis of supraventricular arrhythmias, including atrial fibrillation. The lack of selective pharmacological tools has impeded efforts to investigate the therapeutic potential of cardiac GIRK–channel interventions in arrhythmias. Here, we characterize a recently identified GIRK-channel inhibitor, VU0468554. Using whole-cell electrophysiological approaches and primary cultures of sinoatrial nodal cells and hippocampal neurons, we show that VU0468554 more effectively inhibits the cardiac GIRK channel than the neuronal GIRK channel. Concentration-response experiments suggest that VU0468554 inhibits Gβγ-activated GIRK channels in noncompetitive and potentially uncompetitive fashion. In contrast, VU0468554 competitively inhibits GIRK-channel activation by ML297, a GIRK-channel activator containing the same chemical scaffold as VU0468554. In the isolated heart model, VU0468554 partially reversed carbachol-induced bradycardia in hearts from wild-type mice but not Girk4–/– mice. Collectively, these data suggest that VU0468554 represents a promising new pharmacological tool for targeting cardiac GIRK channels with therapeutic implications for relevant cardiac arrhythmias. SIGNIFICANCE STATEMENT Although cardiac GIRK–channel inhibition shows promise for the treatment of supraventricular arrhythmias, the absence of subtype-selective channel inhibitors has hindered exploration into this therapeutic strategy. This study utilizes whole-cell patch-clamp electrophysiology to characterize the new GIRK-channel inhibitor VU0468554 in human embryonic kidney 293T cells and primary cultures. We report that VU0468554 exhibits a favorable pharmacodynamic profile for cardiac over neuronal GIRK channels and partially reverses GIRK-mediated bradycardia in the isolated mouse heart model.
The Influence of Cooking Methods and Some Marinades on Polycyclic Aromatic Hydrocarbon Formation in Beef Meat

ABSTRACT This study aimed to determine the effect of various marinades and their concentrations, as well as various cooking procedures, on polycyclic aromatic hydrocarbon (PAH) formation in cooked beef. The PAH levels in meat were determined, based on the saponification of lipids by methanolic/potassium hydroxide solution, followed by liquid–liquid extraction and QuEChERS method. Pan frying caused lower levels of BaP (1.39 versus 1.62 µg/kg) and PAH4 (5.58 versus 5.73 µg/kg) in beef meat than barbecuing. For sage and thyme extracts prepared at 0.5 to 2.0 °Brix, a significant decrease in the PAH levels of barbecued meat samples was achieved compared to the controls. The levels of PAHs in the samples containing the commercial marinating material were found to be higher than those in the non-marinated control. The BaP and PAH4 levels found in the meat samples marinated with sage and thyme extracts, were below the EU maximum levels. However, BaP was the highest for Control 2 (2.26 µg/kg), and exceeded the EU maximum limit of 2 mg/kg for BaP in heat-treated meat and meat products. The results show a reducing effect of sage and thyme extracts that are normally used during marinating of meat, on the formation of PAH compounds. Consequently, the extracts of sage and thyme, could be used in the commercial marinating material to reduce the level of PAH compounds formed in meat during cooking.
The Landscape of Pediatric Precision Oncology: Program Design, Actionable Alterations, and Clinical Trial Development

Simple Summary Precision medicine is a revolutionary new way to deliver cancer treatment by targeting specific genetic changes of the cancer of the individual child with the goal of improving cure rates and reducing toxicity. In this review, we illustrate the evolution of cancer treatment in this groundbreaking new era. We compare characteristics and early results of precision medicine programs in pediatric oncology as well as novel clinical trial initiatives translating these findings into potential clinical benefit for all children and adolescents with cancer. Abstract Over the last years, various precision medicine programs have been developed for pediatric patients with high-risk, relapsed, or refractory malignancies, selecting patients for targeted treatment through comprehensive molecular profiling. In this review, we describe characteristics of these initiatives, demonstrating the feasibility and potential of molecular-driven precision medicine. Actionable events are identified in a significant subset of patients, although comparing results is complicated due to the lack of a standardized definition of actionable alterations and the different molecular profiling strategies used. The first biomarker-driven trials for childhood cancer have been initiated, but until now the effect of precision medicine on clinical outcome has only been reported for a small number of patients, demonstrating clinical benefit in some. Future perspectives include the incorporation of novel approaches such as liquid biopsies and immune monitoring as well as innovative collaborative trial design including combination strategies, and the development of agents specifically targeting aberrations in childhood malignancies.
Insights from IgE Immune Surveillance in Allergy and Cancer for Anti-Tumour IgE Treatments

Simple Summary The growing field of AllergoOncology has illustrated potential for the use of IgE in cancer immunotherapy; however, there is still much to be explored within this field, particularly surrounding the links between IgE, allergy, and cancer. Exploring such links may provide useful insights to guide novel IgE-based strategies targeting cancer. Here, we summarise the existing data on both IgE in cancer epidemiology and tumour immunosurveillance, leading to the proposal of a new hypothesis, the combinatorial hypothesis, which attempts to encapsulate the complexity of the relationship between IgE-associated immune responses with cancer; and we discuss how these insights may shape the next generation of IgE-based therapeutics. Abstract IgE, the predominant antibody class of the allergic response, is known for its roles in protecting against parasites; however, a growing body of evidence indicates a significant role for IgE and its associated effector cells in tumour immunosurveillance, highlighted by the field of AllergoOncology and the successes of the first-in-class IgE cancer therapeutic MOv18. Supporting this concept, substantial epidemiological data ascribe potential roles for IgE, allergy, and atopy in protecting against specific tumour types, with a corresponding increased cancer risk associated with IgE immunodeficiency. Here, we consider how epidemiological data in combination with functional data reveals a complex interplay of IgE and allergy with cancer, which cannot be explained solely by one of the existing conventional hypotheses. We furthermore discuss how, in turn, such data may be used to inform future therapeutic approaches, including the clinical management of different patient groups. With epidemiological findings highlighting several high-risk cancer types protected against by high IgE levels, it is possible that use of IgE-based therapeutics for a range of malignant indications may offer efficacy to complement that of established IgG-class antibodies.