Miracle-dz/UniFAR-FTUs huggingface dataset:
Cancer Alters the Metabolic Fingerprint of Extracellular Vesicles

Simple Summary Cancer changes cell metabolism. In this study, we explored if the metabolic rewiring also alters the metabolite content of cancer-derived extracellular vesicles (EVs). For this, metabolomes of EVs from different cancers (prostate, cutaneous T-cell lymphoma, and colon cancer cell lines) were compared with the metabolomes of control EVs derived from matched non-cancerous cell lines. The metabolomes of EVs from all three cancer types significantly differed from their respective control EVs by elevated levels of proline and succinate. Additionally, prostate and cutaneous T-cell lymphoma cell line –derived EVs contained elevated levels of creatinine and folate when compared to controls. In conclusion, this study presents the first evidence that a shared panel of metabolites in EVs reflects the altered metabolic state of multiple cancer cell types in vitro. These results warrant further studies of the significance and usability of a metabolic fingerprint in cancer studies and for biomarker discovery. Abstract Cancer alters cell metabolism. How these changes are manifested in the metabolite cargo of cancer-derived extracellular vesicles (EVs) remains poorly understood. To explore these changes, EVs from prostate, cutaneous T-cell lymphoma (CTCL), colon cancer cell lines, and control EVs from their noncancerous counterparts were isolated by differential ultracentrifugation and analyzed by nanoparticle tracking analysis (NTA), electron microscopy (EM), Western blotting, and liquid chromatography-mass spectrometry (LC-MS). Although minor differences between the cancerous and non-cancerous cell-derived EVs were observed by NTA and Western blotting, the largest differences were detected in their metabolite cargo. Compared to EVs from noncancerous cells, cancer EVs contained elevated levels of soluble metabolites, e.g., amino acids and B vitamins. Two metabolites, proline and succinate, were elevated in the EV samples of all three cancer types. In addition, folate and creatinine were elevated in the EVs from prostate and CTCL cancer cell lines. In conclusion, we present the first evidence in vitro that the altered metabolism of different cancer cells is reflected in common metabolite changes in their EVs. These results warrant further studies on the significance and usability of this metabolic fingerprint in cancer.
Dangerous Pathogens as a Potential Problem for Public Health

Pathogens are various organisms, such as viruses, bacteria, fungi, and protozoa, which can cause severe illnesses to their hosts. Throughout history, pathogens have accompanied human populations and caused various epidemics. One of the most significant outbreaks was the Black Death, which occurred in the 14th century and caused the death of one-third of Europe’s population. Pathogens have also been studied for their use as biological warfare agents by the former Soviet Union, Japan, and the USA. Among bacteria and viruses, there are high priority agents that have a significant impact on public health. Bacillus anthracis, Francisella tularensis, Yersinia pestis, Variola virus, Filoviruses (Ebola, Marburg), Arenoviruses (Lassa), and influenza viruses are included in this group of agents. Outbreaks and infections caused by them might result in social disruption and panic, which is why special operations are needed for public health preparedness. Antibiotic-resistant bacteria that significantly impede treatment and recovery of patients are also valid threats. Furthermore, recent events related to the massive spread of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an example of how virus-induced diseases cannot be ignored. The impact of outbreaks, such as SARS-CoV-2, have had far-reaching consequences beyond public health. The economic losses due to lockdowns are difficult to estimate, but it would take years to restore countries to pre-outbreak status. For countries affected by the 2019 coronavirus disease (COVID-19), their health systems have been overwhelmed, resulting in an increase in the mortality rate caused by diseases or injuries. Furthermore, outbreaks, such as SARS-CoV-2, will induce serious, wide-ranging (and possibly long-lasting) psychological problems among, not only health workers, but ordinary citizens (this is due to isolation, quarantine, etc.). The aim of this paper is to present the most dangerous pathogens, as well as general characterizations, mechanisms of action, and treatments.
Translesion synthesis of the major nitrogen mustard-induced DNA lesion by human DNA polymerase η.

Nitrogen mustards are among the first modern anticancer chemotherapeutics that are still widely used as non-specific anticancer alkylating agents. While the mechanism of action of mustard drugs involves the generation of DNA interstrand cross-links, the predominant lesions produced by these drugs are nitrogen half-mustard-N7-dG (NHMG) adducts. The bulky major-groove lesion NHMG, if left unrepaired, can be bypassed by translesion synthesis DNA polymerases. However, studies of the translesion synthesis past NHMG have not been reported so far. Here we present the first synthesis of an oligonucleotide containing a site-specific NHMG. We also report kinetic and structural characterization of human DNA polymerase η (polη) bypassing NHMG. The templating NHMG slows dCTP incorporation ~130-fold, while it increases the misincorporation frequency ~10-30-fold, highlighting the promutagenic nature of NHMG. A crystal structure of polη incorporating dCTP opposite NHMG shows a Watson-Crick NHMG:dCTP base pair with a large propeller twist angle. The nitrogen half-mustard moiety fits snugly into an open cleft created by the Arg61-Trp64 loop of polη, suggesting a role of the Arg61-Trp64 loop in accommodating bulky major groove adducts during lesion bypass. Overall, our results presented here provide first insights into translesion synthesis of the major DNA adduct formed by nitrogen mustard drugs.
Biotherapies in Uveitis

Non-infectious uveitis (NIU) represents one of the leading causes of blindness in developed countries. The therapeutic strategy aims to rapidly control intra-ocular inflammation, prevent irremediable ocular damage, allow corticosteroid sparing and save the vision, and has evolved over the last few years. Anterior NIU is mostly managed with topical treatment in adults. However, for intermediate, posterior and pan-uveitis, notably when both eyes are involved, systemic treatment is usually warranted. Biotherapies are recommended in case of inefficacy or non-tolerance of conventional immunosuppressive drugs in non-anterior NIU. Anti-tumor necrosis factor alpha (anti-TNF-α) agents are by far the most widely used, especially adalimumab (ADA) and infliximab (IFX). In case of sight-threatening uveitis in Behçet’s disease or in case of risk of severe recurrences, respectively IFX and ADA may be recommended as first-line therapy. Many questions are left unanswered; how long to treat NIU, how to discontinue anti-TNF-α agents, what biologic to use in case of anti-TNF-α failure? The objective of this review is to present an updated overview of knowledge on the use of biological treatments in NIU.
Effect of Co-contamination by PAHs and Heavy Metals on Bacterial Communities of Diesel Contaminated Soils of South Shetland Islands, Antarctica

Diesel oil is the main source of energy used in Antarctica. Since diesel is composed of toxic compounds such as polycyclic aromatic hydrocarbons (PAHs) and heavy metals, it represents a constant threat to the organisms inhabiting this continent. In the present study, we characterized the chemical and biological parameters of diesel-exposed soils obtained from King George Island in Antarctica. Contaminated soils present PAH concentrations 1000 times higher than non-exposed soils. Some contaminated soil samples also exhibited high concentrations of cadmium and lead. A 16S metagenome analysis revealed the effect of co-contamination on bacterial communities. An increase in the relative abundance of bacteria known as PAH degraders or metal resistant was determined in co-contaminated soils. Accordingly, the soil containing higher amounts of PAHs exhibited increased dehydrogenase activity than control soils, suggesting that the microorganisms present can metabolize diesel. The inhibitory effect on soil metabolism produced by cadmium was lower in diesel-contaminated soils. Moreover, diesel-contaminated soils contain higher amounts of cultivable heterotrophic, cadmium-tolerant, and PAH-degrading bacteria than control soils. Obtained results indicate that diesel contamination at King George island has affected microbial communities, favoring the presence of microorganisms capable of utilizing PAHs as a carbon source, even in the presence of heavy metals.
Combining Magnetization Transfer Ratio MRI and Quantitative Measures of Walking Improves the Identification of Fallers in MS

Multiple sclerosis (MS) impacts balance and walking function, resulting in accidental falls. History of falls and clinical assessment are commonly used for fall prediction, yet these measures have limited predictive validity. Falls are multifactorial; consideration of disease-specific pathology may be critical for improving fall prediction in MS. The objective of this study was to examine the predictive value of clinical measures (i.e., walking, strength, sensation) and corticospinal tract (CST) MRI measures, both discretely and combined, to fall status in MS. Twenty-nine individuals with relapsing-remitting MS (mean ± SD age: 48.7 ± 11.5 years; 17 females; Expanded Disability Status Scale (EDSS): 4.0 (range 1–6.5); symptom duration: 11.9 ± 8.7 years; 14 fallers) participated in a 3T brain MRI including diffusion tensor imaging and magnetization transfer ratio (MTR) and clinical tests of walking, strength, sensation and falls history. Clinical measures of walking were significantly associated with CST fractional anisotropy and MTR. A model including CST MTR, walk velocity and vibration sensation explained >31% of the variance in fall status (R2 = 0.3181) and accurately distinguished 73.8% fallers, which was superior to stand-alone models that included only MRI or clinical measures. This study advances the field by combining clinical and MRI measures to improve fall prediction accuracy in MS.
Non-Invasive Electrochemical Biosensors Operating in Human Physiological Fluids

Non-invasive healthcare technologies are an important part of research and development nowadays due to the low cost and convenience offered to both healthcare receivers and providers. This work overviews the recent advances in the field of non-invasive electrochemical biosensors operating in secreted human physiological fluids, viz. tears, sweat, saliva, and urine. Described electrochemical devices are based on different electrochemical techniques, viz. amperometry, coulometry, cyclic voltammetry, and impedance spectroscopy. Challenges that confront researchers in this exciting area and key requirements for biodevices are discussed. It is concluded that the field of non-invasive sensing of biomarkers in bodily fluid is highly convoluted. Nonetheless, if the drawbacks are appropriately addressed, and the pitfalls are adroitly circumvented, the approach will most certainly disrupt current clinical and self-monitoring practices.
Mass Spectrometry-Based Solid Phase Peptide Reaction Assay for Detecting Allergenicity Using an Immobilized Peptide-Conjugating Photo-Cleavable Linker

The biological process of skin sensitization depends on the ability of a sensitizer to modify endogenous proteins. A direct peptide reactivity assay (DPRA), based on the biological process of skin sensitization, was developed as an alternative to controversial animal experiments. Although DPRA has been endorsed by industries and is internationally accepted as promising, it has several drawbacks, such as incompatibility with hydrophobic chemicals, inability to perform detailed reaction analysis, and ability to evaluate only single components. Here, we demonstrated that sensitizers and peptide adducts can be easily identified using a mass spectrometry-based solid-phase peptide reaction assay (M-SPRA). We synthesized peptides with a photo-cleavable linker immobilized on resins. We showed the potential of M-SPRA in predicting skin sensitization by measuring the peptide adducts that were selectively eluted from the resin after cleaving the linker post-reaction. M-SPRA provides more detailed information regarding chemical reactivity and accurate assessment of test samples, including mixtures. M-SPRA may be helpful for understanding the binding mechanism of sensitizers (toxicology), which may assist in further refining reactivity assays and aiding in the interpretation of reactivity data.
Piceatannol protects against cerebral ischemia/reperfusion-induced apoptosis and oxidative stress via the Sirt1/FoxO1 signaling pathway

Reperfusion is a critical therapeutic intervention used following acute ischemic stroke; however, it may cause cerebral ischemia/reperfusion injury (CIRI) and aggravate brain damage. Piceatannol (Pic), a hydroxylated analog of resveratrol, has been reported to exhibit anti-inflammatory effects. However, the detailed molecular mechanisms and its effects on CIRI have not been sufficiently assessed, and, to the best of our knowledge, current methods of prevention of CIRI are limited. The aim of the present study was to investigate the effects of Pic on improving neurological function in a mouse model of CIRI. For the animal experiments, 8-week-old C57BL/6 mice were raised and randomly grouped, and an in vivo model of CIRI was established. Mice were administered a low (10 mg/kg/day) or high-dose (20 mg/kg/d) of Pic 1 h after CIRI orally and once daily for the next 6 days. Neurological dysfunction was assessed using a modified neurological severity score and a rotarod test 1 week after CIRI establishment, and the cognitive status of the mice was assessed using a Morris water maze. Hematoxylin and eosin staining was used to evaluate the histopathological changes. The expression levels of sirtuin 1 (Sirt1), FoxO1, cleaved caspase-3 (CC-3), Bax and Bcl-2 were measured using western blotting. Intracellular reactive oxygen species (ROS) generation, antioxidant enzymes [superoxide dismutase, glutathione (GSH) peroxidase and catalase] and non-enzymatic antioxidants (GSH) were also detected using spectrophotometry. After inhibition of the Sirt1/FoxO1 pathway, a TUNEL assay was used for the detection of apoptotic cells in vitro and in vivo. The co-localization of neuron-specific nuclear protein and CC-3 was assessing using immunofluorescent staining. Pic improved neurological functions and ameliorated hippocampal neuronal pathology following CIRI. In addition, the expression levels of CC-3 and Bax and intracellular ROS levels were increased, while levels of antioxidant and non-enzymatic enzymes were decreased in the mouse model of CIRI. Low and high doses of Pic significantly decreased ROS production and the expression levels of apoptosis-related proteins, but increased antioxidant enzyme levels. However, a high-dose of Pic did not result in increased levels of non-enzymatic enzymes. Furthermore, low and high doses of Pic treatment significantly activated the Sirt1/FoxO1 pathway. Following inhibition of the Sirt1/FoxO1 pathway, the percentage of TUNEL-positive cells and expression of CC-3 were increased, and CC-3 was enriched in neurons. The antioxidant effects of Pic were blocked by inhibition of Sirt1 in vitro and in vivo. In conclusion, these results suggested that Pic may exert a neuroprotective effect against in hippocampal neurons via the Sirt1/FoxO1 pathway.
Detection of Alzheimer's Disease using cortical diffusion tensor imaging

The aim of this research was to test a novel in‐vivo brain MRI analysis method that could be used in clinical cohorts to investigate cortical architecture changes in patients with Alzheimer's Disease (AD). Three cohorts of patients with probable AD and healthy volunteers were used to assess the results of the method. The first group was used as the “Discovery” cohort, the second as the “Test” cohort and the last “ATN” (Amyloid, Tau, Neurodegeneration) cohort was used to test the method in an ADNI 3 cohort, comparing to amyloid and Tau PET. The method can detect altered quality of cortical grey matter in AD patients, providing an additional tool to assess AD, distinguishing between these and healthy controls with an accuracy range between good and excellent. These new measurements could be used within the “ATN” framework as an index of cortical microstructure quality and a marker of Neurodegeneration. Further development may aid diagnosis, patient selection, and quantification of the “Neurodegeneration” component in response to therapies in clinical trials.
An insight into the evolutionary history of Indonesian cattle assessed by whole genome data analysis

The domestication of Indonesian cattle was investigated through a study of their genetic diversity, up to the genome level. Little documentation exists regarding the history of domestication of Indonesian cattle and questions remain despite a growing body of molecular evidence. In this study, we genotyped seven Indonesian cattle breeds using an Illumina BovineSNP50 Bead Chip to provide insight into their domestication and demographic history in a worldwide population context. Our analyses indicated the presence of hybrid cattle, with Bos javanicus and Bos indicus ancestries being most prevalent, as well as purebred cattle. We revealed that all the breeds were interconnected through several migration events. However, their demographic status varied widely. Although almost all the Indonesian cattle had an effective population size higher than the minimum level required to ensure breed fitness, efforts are still needed to maintain their genetic variability and purity.
Dose-dependent Photodynamic Effects of 9-A ceto xy-2,7,12,17-tet ra ki s-(p- m et h o xyet hy I)- porphycene In Vitro

Porphycenes are chemically pure photosensitizers for topical and systemic photo- dynamic therapy (PDT). Fast cellular uptake of 9-acetoxy-2,7,12,17-tetrakis-(~-methoxyethyl)- porphycene (ATMPn) has been shown previously. HaCaT human keratinocytes were incubated with ATMPn (1 nmol 1 - 1 to 1 ~mol 1 - 1 in DMSO or DOPC liposomes). After i h, cells were irradiated with different light doses (0, 24, 48 J cm- 2) using an incoherent light source (58(~740 nm, 40 mW cm-2). Cytotoxic effects were determined by assessing the mitochondrial activity using the MTT assay 24 h following irradiation. Cytotoxic effects were dependent on ATMPn concentration and light dose. Using 20 nmol 1 - 1, a 50% decrease of mitochondrial activity (ECho) after irradiation with 24 J cm -2 was achieved. Lowering the ATMPn concentration (10 nmol 1 1) and increasing the light dose (48 J cm -2) yielded the same effect (ECho). Maximal decrease of mitochondrial activity (>90%) was achieved using ATMPn concentrations of 50-100 nmol 1 1 and a light dose of 24 J cm-2 or 25 nmol 1 1 -2 ATMPn and 48 J cm There was no difference regarding the dose-dependent cytotoxic effects using either ATMPn in DMSO or DOPC liposomes. In the control group (incubation with I nmol 1 1 to 1 ~mol 1 - 1 ATMPn, no irradiation), dark toxicity was not observed. Cell photosensitization with ATMPn was very efficient in vitro yielding the maximal cytotoxic effect at very low ATMPn concentrations as compared to other photosensitizers. Since ATMPn in DMSO and DOPC liposomes revealed the same cytotoxic effects without dark toxicity, the DMSO formulation, which is much easier to prepare, will be preferred in future studies.
Integrated Motion Measurement for Flexible Structures

Integrated navigation, as an example of integrated motion measurement systems, is typically based on inertial sensors (accelerometers, gyros) and GPS and is commonly used for vehicle guidance. Traditionally, the vehicle of integrated navigation systems is assumed to be a rigid body. However, extending these integrated systems to elastic structures is possible. The considered continuum, in particular a flexible beam, is an attempt to obtain motion measurements of an aerofoil of a flying aircraft with large structural dimensions. Integrated systems considered here in general are fusing different measuring methods by using their benefits and blinding out their disadvantages. For instance, gyros and accelerometers are used to obtain reliable signals with a good time resolution. On the other hand, aiding sensors like radar units and strain gauges are known to be long-term accurate. The kernel of the integrated systems presented in this article consists, however, of an continuous-discrete extended Kalman filter estimating the motion state of the structure. Besides the sensor signals to be amalgamated, the filter requires a kinematical model of the vehicle motion considered, which has to be developed individually. This kinematical model describes the standardised dynamics of the vehicle by means of specific forces, i.e. accelerations, and of rotational velocities. Thus, there are no dynamometers or mass and stiffness properties needed in this approach. Diverse kinematical models of the beam were developed and evaluated, using model reduction in regard of the natural modes. Based on simulation the paper shows this approach, appropriate sensor sets, and estimated motion results of a flexible beam.
Keyword-based Search on Relational Data

Keyword-based search in relational database is an easy and effective way for ordinary users or Web users to access relational databases. Even though the relational database management systems (RDBMs) have provided full-text search capabilities, they do not support keyword-based search model. The text databases and relational databases are different that is challenging task to apply the keyword search techniques in information retrieval (IR) to DB. Much research on keyword-search in relational databases has been developed. But existing researches are still problem which is a growing dissatisfaction among users searching for information that they are actually desirable. In this paper, we propose a new candidate network generation algorithm (Heuristic_CNGen) based on the Iterative Deepening A*( IDA*) algorithm. We also propose a new ranking method by adapting existing IR scoring techniques based on the virtual document. We present the keyword-based search to retrieve relevant queries in relational databases by free-style keyword query that improves the efficiency and effectiveness.