Miracle-dz/UniFAR-FTUs huggingface dataset:
The Nuclear Pore Complex and mRNA Export in Cancer

Simple Summary There are multiple processes that can go awry to drive cancer. One of these arises from a dysregulation of trafficking of cellular materials between the two major compartments of the cell—the nucleus and the cytoplasm. These compartments are separated by a membrane or “wall”, but in this wall reside a series of tunnels, or pores, that permit specific materials to transit. One of these materials, known as RNA, carries the information from the nucleus to the cytoplasm to make proteins that can act in certain cellular processes such as growth or survival. If these RNAs transit between compartments inappropriately, they can cause dysregulation of a wide array of cellular processes, which in turn can contribute to cancer. This review describes the relevant pathways and presents strategies to target this process in cancer. Abstract Export of mRNAs from the nucleus to the cytoplasm is a key regulatory step in the expression of proteins. mRNAs are transported through the nuclear pore complex (NPC). Export of mRNAs responds to a variety of cellular stimuli and stresses. Revelations of the specific effects elicited by NPC components and associated co-factors provides a molecular basis for the export of selected RNAs, independent of bulk mRNA export. Aberrant RNA export has been observed in primary human cancer specimens. These cargo RNAs encode factors involved in nearly all facets of malignancy. Indeed, the NPC components involved in RNA export as well as the RNA export machinery can be found to be dysregulated, mutated, or impacted by chromosomal translocations in cancer. The basic mechanisms associated with RNA export with relation to export machinery and relevant NPC components are described. Therapeutic strategies targeting this machinery in clinical trials is also discussed. These findings firmly position RNA export as a targetable feature of cancer along with transcription and translation.
Nano-Fertilization as an Emerging Fertilization Technique: Why Can Modern Agriculture Benefit from Its Use?

There is a need for a more innovative fertilizer approach that can increase the productivity of agricultural systems and be more environmentally friendly than synthetic fertilizers. In this article, we reviewed the recent development and potential benefits derived from the use of nanofertilizers (NFs) in modern agriculture. NFs have the potential to promote sustainable agriculture and increase overall crop productivity, mainly by increasing the nutrient use efficiency (NUE) of field and greenhouse crops. NFs can release their nutrients at a slow and steady pace, either when applied alone or in combination with synthetic or organic fertilizers. They can release their nutrients in 40–50 days, while synthetic fertilizers do the same in 4–10 days. Moreover, NFs can increase the tolerance of plants against biotic and abiotic stresses. Here, the advantages of NFs over synthetic fertilizers, as well as the different types of macro and micro NFs, are discussed in detail. Furthermore, the application of NFs in smart sustainable agriculture and the role of NFs in the mitigation of biotic and abiotic stress on plants is presented. Though NF applications may have many benefits for sustainable agriculture, there are some concerns related to the release of nanoparticles (NPs) from NFs into the environment, with the subsequent detrimental effects that this could have on both human and animal health. Future research should explore green synthesized and biosynthesized NFs, their safe use, bioavailability, and toxicity concerns.
Plant Sources Responsible for the Chemical Composition and Main Bioactive Properties of Poplar-Type Propolis

Propolis is a resinous mixture, made by the honeybees from substances collected from tree or other plant buds, plant exudates, or resins found in the stem, branches, or leaves of different plants. The geographical origin of propolis is given by plant sources from respective areas. Different studies have classified this bee product according to the vegetal material from the same areas. Poplar-type propolis has the widest spread in the world, in the temperate zones from Europe, Asia, or North America. The name is given by the main plant source from where the bees are collecting the resins, although other vegetal sources are present in the mentioned areas. Different Pinus spp. , Prunus spp. , Acacia spp. and also Betula pendula, Aesculus hippocastanum, and Salix alba are important sources of resins for “poplar-type” propolis. The aim of this review is to identify the vegetal material’s chemical composition and activities of plant resins and balms used by the bees to produce poplar-type propolis and to compare it with the final product from similar geographical regions. The relevance of this review is to find the similarities between the chemical composition and properties of plant sources and propolis. The latest determination methods of bioactive compounds from plants and propolis are also reviewed.
Origin of ferromagnetism of (Co,Al)-codoped ZnO from first-principles calculations

Magnetic mechanisms for the (Co,Al)-codoped ZnO, based on the first-principles calculations, are evaluated. Additional electrons induced by Al doping can stabilize the ferromagnetic state in Co-doped ZnO. The Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction may be the dominant mechanism when the distance between Co and Al is far away, while the double-exchange interaction may gain an advantage over the RKKY when the distance is near. The multiple mechanisms can explain the relationship between the magnetic performance and the relative substitutional site of Al. The study yields insight into the origin of the ferromagnetism of ZnO-based materials.
Burden of diabetic macular oedema in patients receiving antivascular endothelial growth factor therapy in South Korea: a healthcare resource use and cost analysis

Objective To examine healthcare resource utilisation (HRU) and direct medical costs for patients with diabetic macular oedema (DME) treated with antivascular endothelial growth factor (anti-VEGF) in Korea by comparing with those for (1) patients with diabetes mellitus (DM) without retinopathy and (2) patients with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF. Design Retrospective cohort study. Setting The Korean National Health Insurance (NHI) database from 1 January 2014 to 31 December 2016. Participants We identified 1398 patients older than 30 years of age who received anti-VEGF treatment for DME in 2015 after excluding patients who had a diagnosis of nAMD in 2015 and any cancer in the preceding year. Main outcome measures One-year healthcare resource use and direct medical costs of patients with DME treated with anti-VEGF. Results In total, 1398 patients with DME receiving anti-VEGF, 12 813 patients with DM without retinopathy and 12 222 patients with nAMD receiving anti-VEGF were identified. Hospital admissions and outpatient visits were highest in patients with DME, while the number of licensed anti-VEGF injections in those with DME was about half that of those with nAMD (2.1 vs 3.9 per patient per year). Mean 1-year medical costs were also higher in patients with DME (US$6723) than in those with DM without retinopathy (US$2687) and nAMD (US$4980). In a multivariable analysis with matched cohorts, DME was associated with 66% higher medical costs for comorbid diseases (adjusted OR (aOR), 1.66; 95% CI 1.45 to 1.90) and 50% lower anti-VEGF injections (aOR, 0.50; 95% CI 0.46 to 0.54) compared with nAMD. Conclusions The overall HRU and economic burden for DME treated with anti-VEGF were higher than for DM without retinopathy or for nAMD treated with anti-VEGF. Meanwhile, the lower number of licensed anti-VEGF injections compared with nAMD may reflect a potential lack of ophthalmological treatment for DME supported by the NHI in Korea.
Encoding and control of orientation to airflow by a set of Drosophila fan-shaped body neurons

The insect central complex (CX) is thought to underlie goal-oriented navigation but its functional organization is not fully understood. We recorded from genetically-identified CX cell types in Drosophila and presented directional visual, olfactory, and airflow cues known to elicit orienting behavior. We found that a group of neurons targeting the ventral fan-shaped body (ventral P-FNs) are robustly tuned for airflow direction. Ventral P-FNs did not generate a ‘map’ of airflow direction. Instead, cells in each hemisphere were tuned to 45° ipsilateral, forming a pair of orthogonal bases. Imaging experiments suggest that ventral P-FNs inherit their airflow tuning from neurons that provide input from the lateral accessory lobe (LAL) to the noduli (NO). Silencing ventral P-FNs prevented flies from selecting appropriate corrective turns following changes in airflow direction. Our results identify a group of CX neurons that robustly encode airflow direction and are required for proper orientation to this stimulus.
Effect of Excessive or Restrictive Energy on Growth Performance, Meat Quality, and Intramuscular Fat Deposition in Finishing Ningxiang Pigs

Simple Summary The present study indicated that excessive energy enhanced fat deposition by upregulating expression of lipogenic genes in the longissimus thoracis of a Chinese fat-type pig. In addition, impairment in meat quality resulted in reduced meat tenderness and increased cross-sectional area of muscle fiber aroused by promoting glycolytic muscle fibers differentiation in muscles. These results provided a new perspective on the energy needs of Ningxiang pigs. Abstract This study investigated the effects of excessive or restrictive energy on growth performance, meat quality, intramuscular fat (IMF) deposition, and related gene expression in finishing Ningxiang pigs. A total of 36 Ningxiang pigs (43.26 ± 3.21 kg) were randomly assigned to three treatments (6 pens of 2 piglets per treatment) and fed by one of three dietary treatments until the pigs of each treatment weighed approximately 75 kg equally. The three treatments were control diet (digestible energy, DE:13.02 MJ/kg, CON), excessive energy diet (DE 15.22 MJ/kg, EE), and restrictive energy diet (DE 10.84 MJ/kg, RE). Results showed that EE improved average daily gain (ADG) and feed conversion ratio (FCR) (p < 0.01), while nothing significantly changed by RE except FCR increasing (p < 0.01). EE increased the content of IMF and triglycerides (TG) (p < 0.05), L*24h and b*45min (p < 0.01), while decreasing cooking loss and meat tenderness in longissimus thoracis (LT) (p < 0.05). b*24h was significantly increased with the increase of energy level (p < 0.01). Meanwhile, EE increased the cross-sectional area (CSA) of muscle fiber and the mRNA expression of myosin heavy chain (MyHC) IIb, acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), and adipocyte fatty-acid binding protein (FABP4) (p < 0.05). In addition, throughout: A diet supplemented with excessive energy promoted IMF deposition by positively changing lipogenic potential while decreasing tenderness by increasing glycolytic muscle fibers, which together affected meat quality. In terms of growth performance and meat quality, the present study suggests that the low-energy diet is suitable for finishing Ningxiang pigs.
The Interplay between Mitochondrial Morphology and Myomitokines in Aging Sarcopenia

Sarcopenia is a chronic disease characterized by the progressive loss of skeletal muscle mass, force, and function during aging. It is an emerging public problem associated with poor quality of life, disability, frailty, and high mortality. A decline in mitochondria quality control pathways constitutes a major mechanism driving aging sarcopenia, causing abnormal organelle accumulation over a lifetime. The resulting mitochondrial dysfunction in sarcopenic muscles feedbacks systemically by releasing the myomitokines fibroblast growth factor 21 (FGF21) and growth and differentiation factor 15 (GDF15), influencing the whole-body homeostasis and dictating healthy or unhealthy aging. This review describes the principal pathways controlling mitochondrial quality, many of which are potential therapeutic targets against muscle aging, and the connection between mitochondrial dysfunction and the myomitokines FGF21 and GDF15 in the pathogenesis of aging sarcopenia.
Modeling and Simulation of Process Technology for Nanoparticulate Drug Formulations—A Particle Technology Perspective

Crystalline organic nanoparticles and their amorphous equivalents (ONP) have the potential to become a next-generation formulation technology for dissolution-rate limited biopharmaceutical classification system (BCS) class IIa molecules if the following requisites are met: (i) a quantitative understanding of the bioavailability enhancement benefit versus established formulation technologies and a reliable track record of successful case studies are available; (ii) efficient experimentation workflows with a minimum amount of active ingredient and a high degree of digitalization via, e.g., automation and computer-based experimentation planning are implemented; (iii) the scalability of the nanoparticle-based oral delivery formulation technology from the lab to manufacturing is ensured. Modeling and simulation approaches informed by the pharmaceutical material science paradigm can help to meet these requisites, especially if the entire value chain from formulation to oral delivery is covered. Any comprehensive digitalization of drug formulation requires combining pharmaceutical materials science with the adequate formulation and process technologies on the one hand and quantitative pharmacokinetics and drug administration dynamics in the human body on the other hand. Models for the technical realization of the drug production and the distribution of the pharmaceutical compound in the human body are coupled via the central objective, namely bioavailability. The underlying challenges can only be addressed by hierarchical approaches for property and process design. The tools for multiscale modeling of the here-considered particle processes (e.g., by coupled computational fluid dynamics, population balance models, Noyes–Whitney dissolution kinetics) and physiologically based absorption modeling are available. Significant advances are being made in enhancing the bioavailability of hydrophobic compounds by applying innovative solutions. As examples, the predictive modeling of anti-solvent precipitation is presented, and options for the model development of comminution processes are discussed.
Control of the Texture of Titania−Silica Mixed Oxides Prepared by Nonhydrolytic Sol−Gel

A series of titania−silica xerogels was prepared using nonhydrolytic sol−gel routes. The parameters explored were the nature of the oxygen donors (alkoxides or diisopropyl ether), the amount of liquid phase in the gel, the titanium content, the reaction time, and the reaction temperature. The samples were characterized using FT-Raman, FTIR, and DRUV−Vis spectroscopy, XRD, TGA, and N2 physisorption. Spectroscopic data indicated a molecular scale dispersion of the Ti atoms. The titania−silica nonhydrolytic xerogels were mesoporous with specific surface areas up to 1040 m2 g-1 and pore volumes up to 1.53 cm3 g-1. The mesoporous texture of the xerogels is ascribed to the high degree of condensation of nonhydrolytic gels, which prevents complete pore collapse during the evaporation of solvent. The average pore diameter could be adjusted in the 2−6 nm range by changing the volume fraction of liquid phase, reaction time, or reaction temperature.
Shifting the Immune-Suppressive to Predominant Immune-Stimulatory Radiation Effects by SBRT-PArtial Tumor Irradiation Targeting HYpoxic Segment (SBRT-PATHY)

Simple Summary This review presents and summarizes the key components and outcomes of a novel, unconventional radiation approach aimed to exploit immune-stimulatory radiation effects which, being added to direct radiation tumor cell killing, may improve the therapeutic ratio of radiotherapy. This technique, as a product of translational oncology research, was intentionally developed for the induction of immune-mediated bystander and abscopal effects in the treatment of unresectable bulky tumors which have much fewer therapeutic options and show poor prognoses after conventional treatments. This review offers insights into a unique unconventional radiotherapy technique which, due to its higher immunogenic potential, may improve the prognosis of patients affected by highly complex malignancies, providing additional opportunities for future research in terms of combining novel immuno-modulating agents with more modern radiotherapy approaches. Abstract Radiation-induced immune-mediated abscopal effects (AE) of conventional radiotherapy are very rare. Whole-tumor irradiation leads to lymphopenia due to killing of immune cells in the tumor microenvironment, resulting in immunosuppression and weak abscopal potential. This limitation may be overcome by partial tumor irradiation sparing the peritumoral immune-environment, and consequent shifting of immune-suppressive to immune-stimulatory effect. This would improve the radiation-directed tumor cell killing, adding to it a component of immune-mediated killing. Our preclinical findings showed that the high-single-dose irradiation of hypoxic tumor cells generates a stronger bystander effect (BE) and AE than the normoxic cells, suggesting their higher “immunogenic potential”. This led to the development of a novel Stereotactic Body RadioTherapy (SBRT)-based PArtial Tumor irradiation targeting HYpoxic segment (SBRT-PATHY) for induction of the immune-mediated BE and AE. Encouraging SBRT-PATHY-clinical outcomes, together with immunohistochemical and gene-expression analyses of surgically removed abscopal-tumor sites, suggested that delivery of the high-dose radiation to the partial (hypoxic) tumor volume, with optimal timing based on the homeostatic fluctuation of the immune response and sparing the peritumoral immune-environment, would significantly enhance the immune-mediated anti-tumor effects. This review discusses the current evidence on the safety and efficacy of SBRT-PATHY in the treatment of unresectable hypoxic bulky tumors and its bystander and abscopal immunomodulatory potential.
Precision EDM of Micron-Scale Diameter Hole Array Using in-Process Wire Electro-Discharge Grinding High-Aspect-Ratio Microelectrodes

Micro-electrical discharge machining (micro-EDM) is a good candidate for processing micro-hole arrays, which are critical features of micro-electro-mechanical systems (MEMS), diesel injector nozzles, inkjet printheads and turbine blades, etc. In this study, the wire vibration of the wire electro-discharge grinding (WEDG) system has been analyzed theoretically, and, accordingly, an improved WEDG method was developed to fabricate micron-scale diameter and high-aspect-ratio microelectrodes for the in-process micro-EDM of hole array with hole diameter smaller than 20 μm. The improved method has a new feature of a positioning device to address the wire vibration problem, and thus to enhance microelectrodes fabrication precision. Using this method, 14 μm diameter microelectrodes with less than 0.4 μm deviation and an aspect ratio of 142, which is the largest aspect ratio ever reported in the literature, were successfully fabricated. These microelectrodes were then used to in-process micro-EDM of hole array in stainless steel. The effects of applied voltage, current and pulse frequency on hole dimensional accuracy and microelectrode wear were investigated. The optimal processing parameters were selected using response–surface experiments. To improve machining accuracy, an in-process touch-measurement compensation strategy was applied to reduce the cumulative compensation error of the micro-EDM process. Using such a system, micro-hole array (2 × 80) with average entrance diameter 18.91 μm and average exit diameter 17.65 μm were produced in 50 μm thickness stainless steel sheets, and standard deviations of hole entrance and exit sides of 0.44 and 0.38 μm, respectively, were achieved.
Volatility Rate of Isopar® L, Benzene, Salt Solution, Potassium Tetraphenyl Borate (KTPB), and their Mixtures by ASTM Method E 2008-04

Abstract Data are provided for the relative rate of volatility of Isopar® L, CSSX solvent, and salt solution in relation to benzene. The results also include rates for mixtures of the various species and the impact of tetraphenylborate on the volatility. The results are consistent with the expected behavior in that the component with a lower boiling point volatizes faster than a component with a higher boiling point. Fick's diffusion law explained the data well and it predicted the diffusivity of Isopar® L (a mixture of hydrocarbons) intermediate temperatures between 35 and 70°C. Inspection of the data shows the volatility of Isopar® L is approximately 1/10th that of the salt solution and approximately 1/100th that of benzene under comparable conditions at the temperatures studied. The results can be used to rank the relative volatility rate of these substances.
Focused Ultrasound and Microbubbles-Mediated Drug Delivery to Brain Tumor

The presence of blood–brain barrier (BBB) and/or blood–brain–tumor barriers (BBTB) is one of the main obstacles to effectively deliver therapeutics to our central nervous system (CNS); hence, the outcomes following treatment of malignant brain tumors remain unsatisfactory. Although some approaches regarding BBB disruption or drug modifications have been explored, none of them reach the criteria of success. Convention-enhanced delivery (CED) directly infuses drugs to the brain tumor and surrounding tumor infiltrating area over a long period of time using special catheters. Focused ultrasound (FUS) now provides a non-invasive method to achieve this goal via combining with systemically circulating microbubbles to locally enhance the vascular permeability. In this review, different approaches of delivering therapeutic agents to the brain tumors will be discussed as well as the characterization of BBB and BBTB. We also highlight the mechanism of FUS-induced BBB modulation and the current progress of this technology in both pre-clinical and clinical studies.
Optimization of the Effects of Different Temperatures and Compositions of Filmogenic Solution on Lactobacillus salivarius Using Predictive Mathematical Models

It is well known that intake of probiotic brings health benefits. Lactic bacteria with probiotic potential have aroused the interest of the industry in developing food products that incorporate such benefits. However, incorporating probiotic bacteria into food is a challenge for the industry, given the sensitivity of probiotic cultures to process conditions. Therefore, the objective of this study is to evaluate gelatin- and inulin-based filmogenic solutions as a potential vehicle for incorporating probiotics into food products and to model the fermentation kinetics. L. salivarius (Lactobacillus salivarius) growth in filmogenic solutions was analyzed under the influence of a variety gelatin concentrations (1.0–3.0%) and inulin concentrations (4.0–6.0%) and fermented under the effect of different temperatures (25–45 °C). A full 23 factorial plan with three replicates at the central point was used to optimize the process. The impacts of process conditions on cell development are fundamental to optimize the process and make it applicable by the industry. The present study showed that the optimal conditions for the development of probiotic cells in filmogenic solutions are a combination of 1.0% gelatin with 4.0% inulin and fermentation temperature of 45 °C. It was observed that the maximum cell growth occurred in an estimated time of about 4 h of fermentation. L. salivarius cell production and substrate consumption during the fermentation of the filmogenic solution were well simulated by a model proposed in this article, with coefficients of determination of 0.981 (cell growth) and 0.991 (substrate consumption).