Miracle-dz/UniFAR-FTUs huggingface dataset:
Susceptibility of South Texas Aedes aegypti to Pyriproxyfen

Simple Summary We evaluated the susceptibility of an Ae. aegypti strain from the Lower Rio Grande Valley (LRGV) of South Texas to the insect growth regulator pyriproxyfen. We observed a difference in the inhibition of emergence to the lowest doses of pyriproxyfen tested between our field strain and a susceptible strain. However, the doses used are 10 times lower from the recommended application of <50 ppb for vector control programs. Our results suggest that pyriproxyfen should be an effective active ingredient in the LRGV to help reduce Ae. aegypti populations in the LRGV. Abstract An integral part to integrated mosquito management is to ensure chemical products used for area-wide control are effective against a susceptible population of mosquitoes. Prior to conducting an intervention trial using an insect growth regulator, pyriproxyfen, in South Texas to control Aedes aegypti, we conducted a larval bioassay to evaluate baseline levels of susceptibility. We used seven serially-diluted doses ranging from 2.5 ppb to 6.3 × 10−4 ppb. We observed 100% inhibition emergence (IE) at even the lowest dose of 6.3 × 10−4 ppb in our susceptible reference colony of Ae. aegypti Liverpool. In our field strain of Ae. aegypti (F5 colonized from South Texas) we observed 79.8% IE at 6.3 × 10−4 ppb, 17.7% IE at 1.25 × 10−3 ppb, 98.7% IE at 1.25 × 10−2 ppb, and 100% emergence inhibition for the remainder of the doses. Given that commercial pyriproxyfen products are labeled for doses ranging to 50 ppb, we conclude that the field population sampled by this study are susceptible to this insect growth regulator.
Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

Cardiac tissue engineering aims at creating contractile structures that can optimally reproduce the features of human cardiac tissue. These constructs are becoming valuable tools to model some of the cardiac functions, to set preclinical platforms for drug testing, or to alternatively be used as therapies for cardiac repair approaches. Most of the recent developments in cardiac tissue engineering have been made possible by important advances regarding the efficient generation of cardiac cells from pluripotent stem cells and the use of novel biomaterials and microfabrication methods. Different combinations of cells, biomaterials, scaffolds, and geometries are however possible, which results in different types of structures with gradual complexities and abilities to mimic the native cardiac tissue. Here, we intend to cover key aspects of tissue engineering applied to cardiology and the consequent development of cardiac organoids. This review presents various facets of the construction of human cardiac 3D constructs, from the choice of the components to their patterning, the final geometry of generated tissues, and the subsequent readouts and applications to model and treat cardiac diseases.
Impact of Extraction Method on the Detection of Quality Biomarkers in Normal vs. DFD Meat

The objective of this work was to demonstrate how the extraction method affects the reliability of biomarker detection and how this detection depends on the biomarker location within the cell compartment. Different extraction methods were used to study the sarcoplasmic and myofibrillar fractions of the Longissimus thoracis et lumborum muscle of young bulls of the Asturiana de los Valles breed in two quality grades, standard (Control) or dark, firm, and dry (DFD) meat. Protein extractability and the expression of some of the main meat quality biomarkers—oxidative status (lipoperoxidation (LPO) and catalase activity (CAT)), proteome (SDS-PAGE electrophoretic pattern), and cell stress protein (Hsp70)—were analyzed. In the sarcoplasmic fraction, buffers containing Triton X-100 showed significantly higher protein extractability, LPO, and higher intensity of high-molecular-weight protein bands, whereas the TES buffer was more sensitive to distinguishing differences in the protein pattern between the Control and DFD meat. In the myofibrillar fraction, samples extracted with the lysis buffer showed significantly higher protein extractability, whereas samples extracted with the non-denaturing buffer showed higher results for LPO, CAT, and Hsp70, and higher-intensity bands in the electrophoretic pattern. These findings highlight the need for the careful selection of the extraction method used to analyze the different biomarkers considering their cellular location to adapt the extractive process.
Substance P Serves as a Balanced Agonist for MRGPRX2 and a Single Tyrosine Residue Is Required for β-Arrestin Recruitment and Receptor Internalization

The neuropeptide substance P (SP) mediates neurogenic inflammation and pain and contributes to atopic dermatitis in mice through the activation of mast cells (MCs) via Mas-related G protein-coupled receptor (GPCR)-B2 (MrgprB2, human ortholog MRGPRX2). In addition to G proteins, certain MRGPRX2 agonists activate an additional signaling pathway that involves the recruitment of β-arrestins, which contributes to receptor internalization and desensitization (balanced agonists). We found that SP caused β-arrestin recruitment, MRGPRX2 internalization, and desensitization. These responses were independent of G proteins, indicating that SP serves as a balanced agonist for MRGPRX2. A tyrosine residue in the highly conserved NPxxY motif contributes to the activation and internalization of many GPCRs. We have previously shown that Tyr279 of MRGPRX2 is essential for G protein-mediated signaling and degranulation. To assess its role in β-arrestin-mediated MRGPRX2 regulation, we replaced Tyr279 in the NPxxY motif of MRGPRX2 with Ala (Y279A). Surprisingly, we found that, unlike the wild-type receptor, Y279A mutant of MRGPRX2 was resistant to SP-induced β-arrestin recruitment and internalization. This study reveals the novel findings that activation of MRGPRX2 by SP is regulated by β-arrestins and that a highly conserved tyrosine residue within MRGPRX2’s NPxxY motif contributes to both G protein- and β-arrestin-mediated responses.
Reference Values for DXA-Derived Visceral Adipose Tissue in Adults 40 Years and Older from a European Population: The Tromsø Study 2015–2016

Background Reference values for visceral adipose tissue (VAT) are needed and it has been advocated that body composition measures depend on both the technique and methods applied, as well as the population of interest. We aimed to develop reference values for VAT in absolute grams (VATg), percent (VAT%), and as a kilogram-per-meters-squared index (VATindex) for women and men, and investigate potential differences between these measures and their associations with cardiometabolic risk factors (including metabolic syndrome (MetS)). Methods In the seventh survey of the population-based Tromsø Study, 3675 participants (aged 40–84, 59% women) attended whole-body DXA scans (Lunar Prodigy GE) from where VAT was derived. We used descriptive analysis, correlations, receiver operating characteristics (ROC), and logistic regression to propose reference values for VAT and investigated VAT's association with cardiometabolic risk factors, MetS and single MetS components. Further, Youden's index was used to suggest threshold values for VAT. Results VATg and VATindex increased until age 70 and then decreased, while VAT% increased with age across all age groups. VAT (all measurement units) was moderate to highly correlated and significantly associated with all cardiometabolic risk factors, except for total cholesterol. Associations between MetS, single MetS components, and VATg and VATindex were similar, and VAT% did not contribute any further to this association. Conclusion These VAT reference values and thresholds, developed in a sample of adults of Norwegian origin, could be applied to other studies with similar populations using the same DXA device and protocols. The associations between VAT and cardiometabolic risk factors were similar across different measurement units of VAT.
Boosting the Photoaged Skin: The Potential Role of Dietary Components

Skin photoaging is mainly induced by ultraviolet (UV) irradiation and its manifestations include dry skin, coarse wrinkle, irregular pigmentation, and loss of skin elasticity. Dietary supplementation of nutraceuticals with therapeutic and preventive effects against skin photoaging has recently received increasing attention. This article aims to review the research progress in the cellular and molecular mechanisms of UV-induced skin photoaging. Subsequently, the beneficial effects of dietary components on skin photoaging are discussed. The photoaging process and the underlying mechanisms are complex. Matrix metalloproteinases, transforming growth factors, skin adipose tissue, inflammation, oxidative stress, nuclear and mitochondrial DNA, telomeres, microRNA, advanced glycation end products, the hypothalamic–pituitary–adrenal axis, and transient receptor potential cation channel V are key regulators that drive the photoaging-associated changes in skin. Meanwhile, mounting evidence from animal models and clinical trials suggests that various food-derived components attenuate the development and symptoms of skin photoaging. The major mechanisms of these dietary components to alleviate skin photoaging include the maintenance of skin moisture and extracellular matrix content, regulation of specific signaling pathways involved in the synthesis and degradation of the extracellular matrix, and antioxidant capacity. Taken together, the ingestion of food-derived functional components could be an attractive strategy to prevent skin photoaging damage.
From Antisense RNA to RNA Modification: Therapeutic Potential of RNA-Based Technologies

Therapeutic oligonucleotides interact with a target RNA via Watson-Crick complementarity, affecting RNA-processing reactions such as mRNA degradation, pre-mRNA splicing, or mRNA translation. Since they were proposed decades ago, several have been approved for clinical use to correct genetic mutations. Three types of mechanisms of action (MoA) have emerged: RNase H-dependent degradation of mRNA directed by short chimeric antisense oligonucleotides (gapmers), correction of splicing defects via splice-modulation oligonucleotides, and interference of gene expression via short interfering RNAs (siRNAs). These antisense-based mechanisms can tackle several genetic disorders in a gene-specific manner, primarily by gene downregulation (gapmers and siRNAs) or splicing defects correction (exon-skipping oligos). Still, the challenge remains for the repair at the single-nucleotide level. The emerging field of epitranscriptomics and RNA modifications shows the enormous possibilities for recoding the transcriptome and repairing genetic mutations with high specificity while harnessing endogenously expressed RNA processing machinery. Some of these techniques have been proposed as alternatives to CRISPR-based technologies, where the exogenous gene-editing machinery needs to be delivered and expressed in the human cells to generate permanent (DNA) changes with unknown consequences. Here, we review the current FDA-approved antisense MoA (emphasizing some enabling technologies that contributed to their success) and three novel modalities based on post-transcriptional RNA modifications with therapeutic potential, including ADAR (Adenosine deaminases acting on RNA)-mediated RNA editing, targeted pseudouridylation, and 2′-O-methylation.
Experimental study on the inactivation effects of alternative oxidants on the Chironomid larvae

The inactivation effects of several oxidants, including chlorine, chlorine dioxide and ozone on the Chironomid larvae in source water were investigated. In addition, inactivation effect was also evaluated after pre-oxidation by chlorine dioxide, followed by coagulation and sedimentation for raw water. It was founded that chlorine dioxide possessed better inactivation effect than other two oxidants. And the organic matter concentration, pH value and algae concentration had little influence on the inactivation effect. The coagulation beaker test demonstrated that Chironomid larvae in the raw water could be deposited with floccules followed by coagulation and sedimentation process, and had no influences on sedimentation water. The Chironomid larvae would die within 24? h with the chlorine dioxide dose of 1.0? mg·L~(-1), and within 6? h with the dose of 2.0? mg·L~(-1). The excessive propagation of Chironomid larvae could be controlled effectively in sedimentation tank by chlorine dioxide pre-oxidation.
The Performance of Equations That Estimate Glomerular Filtration Rate against Measured Urinary Creatinine Clearance in Critically Ill Patients

The performance of glomerular filtration rate- (GFR-) estimating equations was studied against creatinine clearance measured by 24-hour urine collection (CrCl24h-urine) in critically ill patients. Methods. In this substudy of the PermiT trial (https://clinicaltrials.gov/ct2/show/ISRCTN68144998), patients from King Abdulaziz Medical City-Riyadh who had CrCl24h-urine were included. We estimated GFR using Cockroft–Gault (CG), modification of diet in renal disease study (MDRD), chronic kidney disease epidemiology collaboration (CKD-EPI), and Jelliffe equations. For the CG equation, we entered the actual weight in one calculation (CGactual-wt), and if BMI ≥30 kg/m2, we entered the ideal body weight (CGideal-wt) and the adjusted body weight (CGadjusted-wt) in two calculations. We calculated the MDRD equation based on 4 (MDRD-4) and 6 variables (MDRD-6). The performance of these equations was assessed by different ways including Spearman correlation, bias (difference between estimated GFR and CrCl24h-urine), precision (standard deviation of bias), and Bland–Altman plot analysis. Results. The cohort consisted of 237 patients (age 45 ± 20 years, males 75%, mechanically ventilated 99% with serum creatinine 101 ± 94 µmol/L and CrCl24h-urine 108 ± 69 ml/min/1.73 m2). The correlations between the different equations and CrCl24h-urine were modest (r: 0.62 to 0.79; p < 0.0001). Bias was statistically significant for CGactual-wt (21 ml/min), CGadjusted-wt (12 ml/min), and MDRD-6 (-10 ml/min) equations. Precision ranged from 46 to 54 ml/min. The sensitivity of equations to correctly classify CrCl24h-urine 30–59.9 ml/min/1.73 m2 was 17.2% for CGactual-wt, 30.0% for CGideal-wt, 31.0% for CGadjusted-wt, 31.0% for MDRD-4, 39.1% for MDRD-6, 13.8% for CKD-EPI, and 34.5% for Jelliffe equation. Conclusions. Commonly used GFR-estimating equations had limited ability to properly estimate CrCl24h-urine and to correctly classify GFR into clinically relevant ranges that usually determine dosing of medications.
Does the Microenvironment Hold the Hidden Key for Functional Precision Medicine in Pancreatic Cancer?

Simple Summary Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest of all major cancers. We now know that a ‘one-size-fits-all’ approach when treating PDAC patients does not work, so research has focused on developing personalised treatment strategies based on the biology of each patient’s tumour. However, most of these strategies ignore the presence of the characteristic fibrotic PDAC stroma which can act like a fortress to protect the tumour from chemotherapy and drive its aggressive nature. In this review, we summarise the role of this ‘fortress’ in protecting PDAC from chemotherapy and highlight the need for pre-clinical models that are informing precision medicine to reflect this hallmark feature of PDAC. We also propose the power of ex vivo whole-tissue culture models that mimic the tumour and its surrounding fortress to inform personalised treatment for PDAC. Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and no significant improvement in patient survival has been seen in the past three decades. Treatment options are limited and selection of chemotherapy in the clinic is usually based on the performance status of a patient rather than the biology of their disease. In recent years, research has attempted to unlock a personalised treatment strategy by identifying actionable molecular targets in tumour cells or using preclinical models to predict the effectiveness of chemotherapy. However, these approaches rely on the biology of PDAC tumour cells only and ignore the importance of the microenvironment and fibrotic stroma. In this review, we highlight the importance of the microenvironment in driving the chemoresistant nature of PDAC and the need for preclinical models to mimic the complex multi-cellular microenvironment of PDAC in the precision medicine pipeline. We discuss the potential for ex vivo whole-tissue culture models to inform precision medicine and their role in developing novel therapeutic strategies that hit both tumour and stromal compartments in PDAC. Thus, we highlight the critical role of the tumour microenvironment that needs to be addressed before a precision medicine program for PDAC can be implemented.
Acute Myeloid Leukemia: Is It T Time?

Simple Summary Acute myeloid leukemia (AML) is a cancer characterized by impaired differentiation and excessive expansion of blood progenitor cells leading to their accumulation in the bone marrow and circulation. The aim of this review is to describe how these leukemic cells can influence the immune system, particularly T lymphocytes that originate from the thymus and are involved in cancers’ and infections’ eradication. We focus on the elderly population, as this disease mainly affects people over 60 years-old. We discuss how AML cells can modify T lymphocytes’ production and functions. We also highlight newly developed therapeutic strategies to improve the anti-leukemic immune response and the clinical outcome of patients. Abstract Acute myeloid leukemia (AML) is a heterogeneous disease driven by impaired differentiation of hematopoietic primitive cells toward myeloid lineages (monocytes, granulocytes, red blood cells, platelets), leading to expansion and accumulation of “stem” and/or “progenitor”-like or differentiated leukemic cells in the bone marrow and blood. AML progression alters the bone marrow microenvironment and inhibits hematopoiesis’ proper functioning, causing sustained cytopenia and immunodeficiency. This review describes how the AML microenvironment influences lymphoid lineages, particularly T lymphocytes that originate from the thymus and orchestrate adaptive immune response. We focus on the elderly population, which is mainly affected by this pathology. We discuss how a permissive AML microenvironment can alter and even worsen the thymic function, T cells’ peripheral homeostasis, phenotype, and functions. Based on the recent findings on the mechanisms supporting that AML induces quantitative and qualitative changes in T cells, we suggest and summarize current immunotherapeutic strategies and challenges to overcome these anomalies to improve the anti-leukemic immune response and the clinical outcome of patients.
Epigenetic Effects of Benzene in Hematologic Neoplasms: The Altered Gene Expression

Simple Summary Benzene is produced by diverse petroleum transformation processes and it is widely employed in industry despite its oncogenic effects. In fact, occupational exposure to benzene may cause hematopoietic malignancy. The leukemogenic action of benzene is particularly complex. Possible processes of onset of hematological malignancies have been recognized as a genotoxic action and the provocation of immunosuppression. However, benzene can induce modifications that do not involve alterations in the DNA sequence, the so-called epigenetics changes. Acquired epigenetic modification may also induce leukemogenesis, as benzene may alter nuclear receptors, and cause changes at the protein level, thereby modifying the function of regulatory proteins, including oncoproteins and tumor suppressor proteins. Abstract Benzene carcinogenic ability has been reported, and chronic exposure to benzene can be one of the risk elements for solid cancers and hematological neoplasms. Benzene is acknowledged as a myelotoxin, and it is able to augment the risk for the onset of acute myeloid leukemia, myelodysplastic syndromes, aplastic anemia, and lymphomas. Possible mechanisms of benzene initiation of hematological tumors have been identified, as a genotoxic effect, an action on oxidative stress and inflammation and the provocation of immunosuppression. However, it is becoming evident that genetic alterations and the other causes are insufficient to fully justify several phenomena that influence the onset of hematologic malignancies. Acquired epigenetic alterations may participate with benzene leukemogenesis, as benzene may affect nuclear receptors, and provoke post-translational alterations at the protein level, thereby touching the function of regulatory proteins, comprising oncoproteins and tumor suppressor proteins. DNA hypomethylation correlates with stimulation of oncogenes, while the hypermethylation of CpG islands in promoter regions of specific tumor suppressor genes inhibits their transcription and stimulates the onset of tumors. The discovery of the systems of epigenetic induction of benzene-caused hematological tumors has allowed the possibility to operate with pharmacological interventions able of stopping or overturning the negative effects of benzene.
Advances in Atypical FT-IR Milk Screening: Combining Untargeted Spectra Screening and Cluster Algorithms

Fourier-transform mid-infrared spectrometry is an attractive technology for screening adulterated liquid milk products. So far, studies on how infrared spectroscopy can be used to screen spectra for atypical milk composition have either used targeted methods to test for specific adulterants, or have used untargeted screening methods that do not reveal in what way the spectra are atypical. In this study, we evaluate the potential of combining untargeted screening methods with cluster algorithms to indicate in what way a spectrum is atypical and, if possible, why. We found that a combination of untargeted screening methods and cluster algorithms can reveal meaningful and generalizable categories of atypical milk spectra. We demonstrate that spectral information (e.g., the compositional milk profile) and meta-data associated with their acquisition (e.g., at what date and which instrument) can be used to understand in what way the milk is atypical and how it can be used to form hypotheses about the underlying causes. Thereby, it was indicated that atypical milk screening can serve as a valuable complementary quality assurance tool in routine FTIR milk analysis.
Consolidated Bioprocessing: Synthetic Biology Routes to Fuels and Fine Chemicals

The long road from emerging biotechnologies to commercial “green” biosynthetic routes for chemical production relies in part on efficient microbial use of sustainable and renewable waste biomass feedstocks. One solution is to apply the consolidated bioprocessing approach, whereby microorganisms convert lignocellulose waste into advanced fuels and other chemicals. As lignocellulose is a highly complex network of polymers, enzymatic degradation or “saccharification” requires a range of cellulolytic enzymes acting synergistically to release the abundant sugars contained within. Complications arise from the need for extracellular localisation of cellulolytic enzymes, whether they be free or cell-associated. This review highlights the current progress in the consolidated bioprocessing approach, whereby microbial chassis are engineered to grow on lignocellulose as sole carbon sources whilst generating commercially useful chemicals. Future perspectives in the emerging biofoundry approach with bacterial hosts are discussed, where solutions to existing bottlenecks could potentially be overcome though the application of high throughput and iterative Design-Build-Test-Learn methodologies. These rapid automated pathway building infrastructures could be adapted for addressing the challenges of increasing cellulolytic capabilities of microorganisms to commercially viable levels.