Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibiotic Resistance Genes and Associated Phenotypes in Escherichia coli and Enterococcus from Cattle at Different Production Stages on a Dairy Farm in Central California

The objectives of this study were to characterize overall genomic antibiotic resistance profiles of fecal Escherichia coli and Enterococcus spp. from dairy cattle at different production stages using whole-genome sequencing and to determine the association between antimicrobial resistance (AMR) phenotypes and their corresponding genotypes. The Comprehensive Antibiotic Resistance Database (CARD) and ResFinder, two publicly available databases of antimicrobial resistance genes, were used to annotate isolates. Based on the ResFinder database, 27.5% and 20.0% of tested E. coli isolates (n = 40) harbored single and ≥3 antimicrobial resistance genes, respectively; for Enterococcus spp. , we observed 87.8% and 8.2%, respectively. The highest prevalence of AMR genes in E. coli was for resistance to tetracycline (27.5%), followed by sulphonamide (22.5%) and aminoglycoside (20.0%); the predominant antimicrobial resistance genes in Enterococcus spp. targeted macrolide drugs (77.6%). Based on the CARD database, resistance to ≥3 antimicrobial classes was observed in all E. coli and 77.6% in Enterococcus spp. isolates. A high degree of agreement existed between the resistance phenotype and the presence of resistance genes for various antimicrobial classes for E. coli but much less so for isolates of Enterococcus. Consistent with prior work, fecal E. coli and Enterococcus spp. isolates from calves harbored a wide spectrum of resistance genes, compared to those from cattle at other production stages, based on the cross-sectional samples from the studied farm.
Simple Fabrication of Solid-State Nanopores on a Carbon Film

Solid-state nanopores are widely used as a platform for stochastic nanopore sensing because they can provide better robustness, controllable pore size, and higher integrability than biological nanopores. However, the fabrication procedures, including thin film preparation and nanopore formation, require advanced micro-and nano-fabrication techniques. Here, we describe the simple fabrication of solid-state nanopores in a commercially available material: a flat thin carbon film-coated micro-grid for a transmission electron microscope (TEM). We attempted two general methods for nanopore fabrication in the carbon film. The first method was a scanning TEM (STEM) electron beam method. Nanopores were fabricated by irradiating a focused electron beam on the carbon membrane on micro-grids, resulting in the production of nanopores with pore diameters ranging from 2 to 135 nm. The second attempt was a dielectric breakdown method. In this method, nanopores were fabricated by applying a transmembrane voltage of 10 or 30 V through the carbon film on micro-grids. As a result, nanopores with pore diameters ranging from 3.7 to 1345 nm were obtained. Since these nanopores were successfully fabricated in the commercially available carbon thin film using readily available devices, we believe that these solid-state nanopores offer great utility in the field of nanopore research.
Co-Delivery of Curcumin and Bioperine via PLGA Nanoparticles to Prevent Atherosclerotic Foam Cell Formation

Cholesterol-rich arterial plaques characterize atherosclerosis, a significant cause of heart disease. Nutraceuticals have received attention over the years, demonstrating potential benefits towards treating and preventing cardiovascular diseases (CVD), including atherosclerosis. Curcumin, a potent polyphenol present in Curcuma longa, has shown remarkable anti-atherosclerotic activity via anti-inflammatory and anti-oxidative properties. The bioavailability and low water solubility of curcumin limit its clinical translational purposes. These issues can be circumvented effectively by nano-drug delivery systems that can target atherosclerotic plaque sites. In this work, we chose to use curcumin and a natural bioenhancer called Bioperine (derived from Piper nigrum) inside a polymeric nano-drug delivery system for targeting atherosclerotic plaque sites. We selected two different ratios of curcumin:Bioperine to study its comparative effect on the inhibition of oxidized low-density lipoprotein (Ox-LDL)-induced foam cell formation. Our studies demonstrated that Cur-Bio PLGA NPs (both ratios) maintained the cell viability in THP-1 monocyte-derived macrophages above 80% at all periods. The 1:0.2:10 ratio of Cur-Bio PLGA NPs at a concentration of 250 μg/mL illustrated an enhanced reduction in the relative cholesterol content in the THP-1-derived foam cells compared to the 1:1:10 ratio. Confocal microscopy analysis also revealed a reduction in macrophage-mediated foam cell formation when administered with both the ratios of Cur-Bio PLGA NPs. Relative fold change in the mRNA expression of the genes involved in the inflammatory pathways in the atherosclerotic process downregulated NF-κB, CCL2/MCP-1, CD-36, and STAT-3 activity while upregulating the SCAR-B1 expression when treated with the Cur-Bio PLGA NPs. This study thus highlights the importance of natural-based compounds towards the therapeutic intervention against atherosclerotic activity when administered as preventive medicine.
Standardized Edible Bird’s Nest Extract Prevents UVB Irradiation-Mediated Oxidative Stress and Photoaging in the Skin

We investigated whether standardized edible bird’s nest extract (BNE-PK) can prevent ultraviolet B (UVB) irradiation-mediated oxidative stress and photoaging in the skin using in vitro and in vivo models. BNE-PK increased skin hydration by hyaluronic acid synthesis and activation of ceramide synthase in UVB-irradiated hairless mice and HaCaT cells. Furthermore, BNE-PK suppressed melanogenesis by down-regulation of the cAMP/PKA/CREB/MITF/TRP-1/TRP-2/tyrosinase pathway in UVB-irradiated hairless mice and 3-isobutyl-1-methylxanthine (IBMX)-treated B16F10 cells. In UVB-irradiated hairless mice, BNE-PK attenuated the wrinkle formation-related JNK/c-FOS/c-Jun/MMP pathway and activated the TGF-βRI/SMAD3/pro-collagen type I pathway during UVB-mediated oxidative stress. Based on these findings, our data suggest that BNE-PK may potentially be used for the development of effective natural anti-photoaging functional foods for skin health.
The Connection between Czc and Cad Systems Involved in Cadmium Resistance in Pseudomonas putida

Heavy metal pollution is widespread and persistent, and causes serious harm to the environment. Pseudomonas putida, a representative environmental microorganism, has strong resistance to heavy metals due to its multiple efflux systems. Although the functions of many efflux systems have been well-studied, the relationship between them remains unclear. Here, the relationship between the Czc and Cad systems that are predominantly responsible for cadmium efflux in P. putida KT2440 is identified. The results demonstrated that CzcR3, the response regulator of two-component system CzcRS3 in the Czc system, activates the expression of efflux pump genes czcCBA1 and czcCBA2 by directly binding to their promoters, thereby helping the strain resist cadmium stress. CzcR3 can also bind to its own promoter, but it has only a weak regulatory effect. The high-level expression of czcRS3 needs to be induced by Cd2+, and this relies on the regulation of CadR, a key regulator in the Cad system, which showed affinity to czcRS3 promoter. Our study indicates that the Cad system is involved in the regulation of the Czc system, and this relationship is important for maintaining the considerable resistance to cadmium in P. putida.
Cerium(III) Nitrate Containing Electrospun Wound Dressing for Mitigating Burn Severity

Thermal injuries pose a risk for service members in prolonged field care (PFC) situations or to civilians in levels of lower care. Without access to prompt surgical intervention and treatment, potentially salvageable tissues are compromised, resulting in increases in both wound size and depth. Immediate debridement of necrotic tissue enhances survivability and mitigates the risks of burn shock, multiple organ failure, and infection. However, due to the difficulty of surgical removal of the burn eschar in PFC situations and lower levels of care, it is of utmost importance to develop alternative methods for burn stabilization. Studies have indicated that cerium(III) nitrate may be used to prolong the time before surgical intervention is required. The objective of this study was to incorporate cerium(III) nitrate into an electrospun dressing that could provide burst release. Select dosages of cerium(III) nitrate were dissolved with either pure solvent or polyethylene oxide (PEO) for coaxial or traditional electrospinning set-ups, respectively. The solutions were coaxially electrospun onto a rotating mandrel, resulting in a combined nonwoven mesh, and then compared to traditionally spun solutions. Dressings were evaluated for topography, morphology, and porosity using scanning electron microscopy and helium pycnometry. Additionally, cerium(III) loading efficiency, release rates, and cytocompatibility were evaluated in both static and dynamic environments. Imaging showed randomly aligned polymer nanofibers with fiber diameters of 1161 ± 210 nm and 1090 ± 250 nm for traditionally and coaxially spun PEO/cerium(III) nitrate dressings, respectively. Assay results indicated that the electrospun dressings contained cerium(III) nitrate properties, with the coaxially spun dressings containing 33% more cerium(III) nitrate than their traditionally spun counterparts. Finally, release studies revealed that PEO-based dressings released the entirety of their contents within the first hour with no detrimental cytocompatibility effects for coaxially-spun dressings. The study herein shows the successful incorporation of cerium(III) nitrate into an electrospun dressing.
Burn Injury Induces Proinflammatory Plasma Extracellular Vesicles That Associate with Length of Hospital Stay in Women: CRP and SAA1 as Potential Prognostic Indicators

Severe burn injury is a devastating form of trauma that results in persistent immune dysfunction with associated morbidity and mortality. The underlying drivers of this immune dysfunction remain elusive, and there are no prognostic markers to identify at-risk patients. Extracellular vesicles (EVs) are emerging as drivers of immune dysfunction as well as biomarkers. We investigated if EVs after burn injury promote macrophage activation and assessed if EV contents can predict length of hospital stay. EVs isolated early from mice that received a 20% total body surface area (TBSA) burn promoted proinflammatory responses in cultured splenic macrophages. Unbiased LC-MS/MS proteomic analysis of early EVs (<72 h post-injury) from mice and humans showed some similarities including enrichment of acute phase response proteins such as CRP and SAA1. Semi-unbiased assessment of early human burn patient EVs found alterations consistent with increased proinflammatory signaling and loss of inhibition of CRP expression. In a sample of 50 patients with large burn injury, EV SAA1 and CRP were correlated with TBSA injury in both sexes and were correlated with length of hospital stay in women. These findings suggest that EVs are drivers of immune responses after burn injury and their content may predict hospital course.
Controlling Alternaria cerealis MT808477 Tomato Phytopathogen by Trichoderma harzianum and Tracking the Plant Physiological Changes

Plant responses during the pathogen infection and the pathogen control reflect its strategies to protect its cells. This work represents the Alternaria cerealis MT808477 as a phytopathogen causing leaf spot disease in tomatoes. A. cerealis was identified morphologically and genetically by 18SrRNA, and its pathogenicity was confirmed by light and scanning electron microscopy. Trichoderma harzianum has the ability to control A. cerealis MT808477 by stimulating various cell responses during the controlling process. The cell behavior during the biological control process was observed by analyses of total phenol, flavonoids, terpenoids, antioxidant, malondialdehyde and antioxidant enzymes (catalase and peroxidase). The extracts of infected tomato leaves were tested against plant and human pathogenic microorganisms. Results showed that the biological control process activates the defense cell strategies by increasing the plant tolerance, and activation of plant defense systems. The total phenol, flavonoids, terpenoids, antioxidant and malondialdehyde were increased after 48 h. Catalase and peroxidase were increased in infected tomato plants and decreased during the biological control process, reflecting the decrease of cell stress. Leaves extract inhibited the growth of nine plant and human pathogenic microorganisms. Biological control represents a safe and effective solution to phytopathogens that decreases plant cell stress by stimulating various defensive agents.
Effect of Rhizobium Inoculation with Phosphorus and Nitrogen Fertilizer on Physico - Chemical Properties of the Groundnut Soil

Low soil fertility status, nutritional imbalance and inappropriate agronomic practices are the major problems limiting the current production and yield of groundnut, therefore a study was conducted during 2015/2016 at the green house of the Universiti Kebangsaan Malaysia (UKM), Bangi, Malaysia, to evaluate the effect of Rhizobium inoculation, in combination with P and N fertilization on the growth and yield of groundnut. The experiment included plots with and without Rhizobium-inoculated treatments, two rates of P fertilizer (0, 82 kg ha-1) and two rates of N fertilizer (0, 27 kg ha-1). The treatments were laid out in a split-split plot design with two main plots (plots with and without rhizobium), two sub plots (for two Nitrogen levels) and two sub sub-plots (for two phosphorus levels), and the experiment replicated thrice. The results showed that the treatment of R+N1P1 increased significantly effect on soil pH by 5.89 units, the R+N1P1 significantly effect on Organic Matter, Soil organic C, soil total N, soil CEC, and available P by (4.87%, 2.13%, 0.34%, 7.0 meq/100g, and 94.36 μg/g, respectively). Based on the results of the present study, it was concluded that the soil properties can be increased with the use of P and N fertilizers along with rhizobium inoculants.
Selective Breeding for Disease-Resistant PRNP Variants to Manage Chronic Wasting Disease in Farmed Whitetail Deer

Chronic wasting disease (CWD) is a fatal transmissible spongiform encephalopathy (TSE) of cervids caused by a misfolded variant of the normal cellular prion protein, and it is closely related to sheep scrapie. Variations in a host’s prion gene, PRNP, and its primary protein structure dramatically affect susceptibility to specific prion disorders, and breeding for PRNP variants that prevent scrapie infection has led to steep declines in the disease in North American and European sheep. While resistant alleles have been identified in cervids, a PRNP variant that completely prevents CWD has not yet been identified. Thus, control of the disease in farmed herds traditionally relies on quarantine and depopulation. In CWD-endemic areas, depopulation of private herds becomes challenging to justify, leading to opportunities to manage the disease in situ. We developed a selective breeding program for farmed white-tailed deer in a high-prevalence CWD-endemic area which focused on reducing frequencies of highly susceptible PRNP variants and introducing animals with less susceptible variants. With the use of newly developed primers, we found that breeding followed predictable Mendelian inheritance, and early data support our project’s utility in reducing CWD prevalence. This project represents a novel approach to CWD management, with future efforts building on these findings.
Prediction of Epitaxial Grain Growth in Single-Track Laser Melting of IN718 Using Integrated Finite Element and Cellular Automaton Approach

The mechanical properties of selective laser melting (SLM) components are fundamentally dependent on their microstructure. Accordingly, the present study proposes an integrated simulation framework consisting of a three-dimensional (3D) finite element model and a cellular automaton model for predicting the epitaxial grain growth mode in the single-track SLM processing of IN718. The laser beam scattering effect, melt surface evolution, powder volume shrinkage, bulk heterogeneous nucleation, epitaxial growth, and initial microstructure of the substrate are considered. The simulation results show that during single-track SLM processing, coarse epitaxial grains are formed at the melt–substrate interface, while fine grains grow at the melt–powder interface with a density determined by the intensity of the heat input. During the solidification stage, the epitaxial grains and bulk nucleated grains grow toward the top surface of the melt pool along the temperature gradient vectors. The rate of the epitaxial grain growth varies as a function of the orientation and size of the partially melted grains at the melt–substrate boundary, the melt pool size, and the temperature gradient. This is observed that by increasing heat input from 250 J/m to 500 J/m, the average grain size increases by ~20%. In addition, the average grain size reduces by 17% when the initial substrate grain size decreases by 50%. In general, the results show that the microstructure of the processed IN718 alloy can be controlled by adjusting the heat input, preheating conditions, and initial substrate grain size.
An Attenuated Targeted-TNF Localizes to Tumors In Vivo and Regains Activity at the Site of Disease

Antibody-cytokine fusion proteins (immunocytokines) are gaining importance for cancer therapy, but those products are often limited by systemic toxicity related to the activity of the cytokine payload in circulation and in secondary lymphoid organs. Tumor necrosis factor (TNF) is used as a pro-inflammatory payload to trigger haemorrhagic necrosis and boost anti-cancer immunity at the tumor site. Here we describe a depotentiated version of TNF (carrying the single point mutation I97A), which displayed reduced binding affinity to its cognate receptor tumor necrosis factor receptor 1 (TNFR-1) and lower biocidal activity. The fusion of the TNF(I97A) mutant to the L19 antibody promoted restoration of anti-tumor activity upon accumulation on the cognate antigen, the alternatively spliced EDB domain of fibronectin. In vivo administration of high doses (375 μg/Kg) of the fusion protein showed a potent anti-tumor effect without apparent toxicity compared with the wild type protein. L19-TNFI97A holds promise for the targeted delivery of TNF activity to neoplastic lesions, helping spare normal tissues.
Artificial Intelligence, Machine Learning and Deep Learning in Ion Channel Bioinformatics

Ion channels are linked to important cellular processes. For more than half a century, we have been learning various structural and functional aspects of ion channels using biological, physiological, biochemical, and biophysical principles and techniques. In recent days, bioinformaticians and biophysicists having the necessary expertise and interests in computer science techniques including versatile algorithms have started covering a multitude of physiological aspects including especially evolution, mutations, and genomics of functional channels and channel subunits. In these focused research areas, the use of artificial intelligence (AI), machine learning (ML), and deep learning (DL) algorithms and associated models have been found very popular. With the help of available articles and information, this review provide an introduction to this novel research trend. Ion channel understanding is usually made considering the structural and functional perspectives, gating mechanisms, transport properties, channel protein mutations, etc. Focused research on ion channels and related findings over many decades accumulated huge data which may be utilized in a specialized scientific manner to fast conclude pinpointed aspects of channels. AI, ML, and DL techniques and models may appear as helping tools. This review aims at explaining the ways we may use the bioinformatics techniques and thus draw a few lines across the avenue to let the ion channel features appear clearer.
Diatoms in Volcanic Soils of Mutnovsky and Gorely Volcanoes (Kamchatka Peninsula, Russia)

Volcanic activity has a great impact on terrestrial ecosystems, including soil algae in general and diatoms in particular. To understand the influence of volcanoes on the biodiversity of diatoms, it is necessary to explore the flora of these microorganisms in regions with high volcanic activity, which includes the Kamchatka peninsula. During the study on diatoms in the soils of Mutnovsky and Gorely volcanoes of Kamchatka, 38 taxa were found. The Mutnovsky volcano diatom flora was more diverse and accounted for 35 taxa. Eunotia curtagrunowii, Humidophila contenta, and Pinnularia borealis were the dominant species. In the Gorely volcano, only 9 species were identified, with Caloneis bacillum and Pinnularia borealis prevailing in the samples. Overall, the genera Pinnularia and Eunotia were the most diverse in the studied area. The diatom flora of the studied volcanoes comprises mostly cosmopolitan small-sized taxa with a wide range of ecological plasticity. Our data confirm the high adaptive potential of diatom algae and add new knowledge about the ecology and biogeography of this group of microorganisms.
Induced Pluripotent Stem Cells to Model Juvenile Myelomonocytic Leukemia: New Perspectives for Preclinical Research

Juvenile myelomonocytic leukemia (JMML) is a malignant myeloproliferative disorder arising in infants and young children. The origin of this neoplasm is attributed to an early deregulation of the Ras signaling pathway in multipotent hematopoietic stem/progenitor cells. Since JMML is notoriously refractory to conventional cytostatic therapy, allogeneic hematopoietic stem cell transplantation remains the mainstay of curative therapy for most cases. However, alternative therapeutic approaches with small epigenetic molecules have recently entered the stage and show surprising efficacy at least in specific subsets of patients. Hence, the establishment of preclinical models to test novel agents is a priority. Induced pluripotent stem cells (IPSCs) offer an opportunity to imitate JMML ex vivo, after attempts to generate immortalized cell lines from primary JMML material have largely failed in the past. Several research groups have previously generated patient-derived JMML IPSCs and successfully differentiated these into myeloid cells with extensive phenotypic similarities to primary JMML cells. With infinite self-renewal and the capability to differentiate into multiple cell types, JMML IPSCs are a promising resource to advance the development of treatment modalities targeting specific vulnerabilities. This review discusses current reprogramming techniques for JMML stem/progenitor cells, related clinical applications, and the challenges involved.