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Selective modulation of retinaldehyde dehydrogenases (RALDHs)-the main aldehyde dehydrogenase (ALDH) enzymes converting retinal into retinoic acid (RA), is very important not only in the RA signaling pathway but also for the potential regulatory effects on RALDH isozyme-specific processes and RALDH-related cancers. However, very few selective modulators for RALDHs have been identified, partly due to variable overexpression protocols of RALDHs and insensitive activity assay that needs to be addressed. In the present study, deletion of the N-terminal disordered regions is found to enable simple preparation of all RALDHs and their closest paralog ALDH2 using a single protocol. Fluorescence-based activity assay was employed for enzymatic activity investigation and screening for RALDH-specific modulators from extracts of various spices and herbs that are well-known for containing many phyto-derived anti-cancer constituents. Under the established conditions, spice and herb extracts exhibited differential regulatory effects on RALDHs/ALDH2 with several extracts showing potential selective inhibition of the activity of RALDHs. In addition, the presence of magnesium ions was shown to significantly increase the activity for the natural substrate retinal of RALDH3 but not the others, while His-tag cleavage considerably increased the activity of ALDH2 for the non-specific substrate retinal. Altogether we propose a readily reproducible workflow to find selective modulators for RALDHs and suggest potential sources of selective modulators from spices and herbs.

The blood brain barrier (BBB) protects the central nervous system from toxins and pathogens in the blood by regulating permeation of molecules through the barrier interface. In vitro BBB models described to date reproduce some aspects of BBB functionality, but also suffer from incomplete phenotypic expression of brain endothelial traits, difficulty in reproducibility and fabrication, or overall cost. To address these limitations, we describe a three-dimensional (3D) BBB model based on a hybrid paper/nanofiber scaffold. The cell culture platform utilizes lens paper as a framework to accommodate 3D culture of astrocytes. An electrospun nanofiber layer is coated onto one face of the paper to mimic the basement membrane and support growth of an organized two-dimensional layer of endothelial cells (ECs). Human induced pluripotent stem cell-derived ECs and astrocytes are co-cultured to develop a human BBB model. Morphological and spatial organization of model are validated with confocal microscopy. Measurements of transendothelial resistance and permeability demonstrate the BBB model develops a high-quality barrier and responds to hyperosmolar treatments. RNA-sequencing shows introduction of astrocytes both regulates EC tight junction proteins and improves endothelial phenotypes related to vasculogenesis. This model shows promise as a model platform for future in vitro studies of the BBB.

The 2019 outbreak of coronavirus disease (COVID-19) in Wuhan (Hubei province of China) has given rise to a pandemic spread of virus, more than 240 million incidences and a death toll larger than 5 million people. COVID-19 has set off large efforts in research, therapy and patient care, as well as public and private debates in every imaginable form. A number of scientists used the publication platforms provided by the Federation of the European Biochemical Societies (FEBS) to present their research data, reviews, opinions and other contributions relating to COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, I highlight the recent COVID-19 papers which have been published and collected in a Virtual Issue in FEBS Letters, and discuss their implications towards understanding the molecular, biochemical and cellular mechanisms of SARS-CoV-2 infections, vaccine development and antiviral discovery strategies.

Despite improvements in modern cardiovascular therapy, the morbidity and mortality of ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and worldwide. Patients with IHD may benefit from therapies that would accelerate natural processes of postnatal collateral vessel formation and/or muscle regeneration. Here, we discuss the use of cells in the context of heart repair, and the most relevant results and current limitations from clinical trials using cell-based therapies to treat IHD and HF. We identify and discuss promising potential new therapeutic strategies that include ex vivo cell-mediated gene therapy, the use of biomaterials and cell-free therapies aimed at increasing the success rates of therapy for IHD and HF. The overall aim of this Position Paper of the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to improve the therapeutic application of cell-based therapies for cardiac regeneration and repair.

The international financial and political crisis named Panama Papers (2016) provided a rather good material for information studies, particularly for digital diplomatics. First, the comments, in some languages, allow to analyze how media and newspapers use the words information, data, document, file and record, each with its own culture: some papers are directly written with the own words of the journalist, others are translations, showing notably the differences between English and French professional and common vocabulary. Second, it was also an opportunity to check the place of email in those cases of disclosure of sensitive data in the “society of information”. The point is that the fragility of the digital files themselves (format, preservation) is not the worse for information and records management; the risk is more linked to the fragility of the international network and the ability of search engines to reach these records, wherever they may be stored.

Background One of the most important part of tissue engineering (TE) is a matrix called scaffold. A good scaffold integrates with the host tissue and support the growth and differentiation of the cells. Collagen is the most abundant protein in the ECM and has been considered to be a group of proteins with a characteristic molecular structure—fibrillar structure, which contributes to the extracellular scaffolding. Objective In this research we study the biocompatibility and attachment of collagen scaffold by measuring the level of availability of mesenchymal stem cell (MSC) cluster from stromal vascular fraction (SVF). Method This study was experimental invitro on MSC culture derived from SVF, with post-test control group design. Biocompatibility was measured by viability of MSC from SVF with marker Propidium Iodine through flowcytometry and electron microscope was used to assess the population density of MSC from SVF by measuring the number of cluster cells seen. Result Oxidize cellulose has the greatest value of MSC cluster with average number of 2003 cell cluster. This result was significant with p, Highlights • Biocompatibility and attachment of collagen scaffold. • Measuring the level of availability of mesenchymal stem cell (MSC) cluster from stromal vascular fraction (SVF). • Experimental in vitro study on MSC culture derived from SVF. • Biocompatibility was measured by viability of MSC from SVF with marker Propidium Iodine through flowcytometry. • Electron microscope was used to assess the population density of MSC from SVF.

The glutathione (GSH) level in human serum is closely associated with several life-threatening diseases, and tracing the aberrant GSH level can monitor the subhealth conditions at an early stage fo...

For this Special Issue “2020 Feature Papers by JDB’ Editorial Board Members,” we present a collection of studies, including original research papers, and review articles by our distinguished editorial board members that focus on advances in understanding multicellular organisms’ growth, differentiation, and remodeling [...]

The medical autopsy (also called hospital or clinical autopsy) is a highly specialised medical procedure, which requires professional expertise and suitably equipped facilities. To ensure high standards of performance, the Working Group of Autopsy Pathology of the European Society of Pathology (ESP) suggests a code of practice as a minimum standard for centres performing medical autopsies. The proposed standards exclusively address autopsies in adults, and not forensic autopsies, perinatal/or paediatric examinations. Minimum standards for organisation, standard of premises, and staffing conditions, as well as minimum requirements for level of expertise of the postmortem performing specialists, documentation, and turnaround times of the medical procedure, are presented. Medical autopsies should be performed by specialists in pathology, or by trainees under the supervision of such specialists. To maintain the required level of expertise, autopsies should be performed regularly and in a number that ensures the maintenance of good practice of all participating physicians. A minimum number of autopsies per dedicated pathologist in a centre should be at least 50, or as an average, at least one autopsy per working week. Forensic autopsies, but not paediatric/perinatal autopsies may be included in this number. Turnaround time for final reports should not exceed 3 weeks (14 working days) for autopsies without fixation of brain/spinal cord or other time-consuming additional examinations, and 6 weeks (30 working days) for those with fixation of brain/spinal cord or additional examinations.

High-sensitivity C-reactive protein (hs-CRP) has been regarded as a risk predictor of cardiovascular disease (CVD). Despite there are many methods to detect hs-CRP, quantitative, rapid, convenient, multiplex and highly sensitive measurement of it is still a challenge for point-of-care applications. In this study, we developed a paper-based ELISA to detect hs-CRP and the sensitive chemiluminescence was applied as detection signal. In this developed assay method, CRP concentration and chemiluminescence intensity were linearly correlated (r = 0.999) with a limit of detection (LOD) as low as 0.49 ng mL−1, which was comparable to that of conventional ELISA and superior to most of the current reported POCT methods for detection of hs-CRP. The precision of the assay was confirmed for low coefficient of variations, less than 7% for intra-assay and less than 10% for inter-assay. In clinical sample analysis, the results of hs-CRP detected by this assay were in good accordance with which obtained by commercial high sensitivity ELISA kit for in vitro diagnosis (r = 0.975). This assay required only 4 μL of sample and could be finished in less than 30 min. It may therefore be employed as a rapid pre-screening tool to identify patients with elevated risk of CVD.

The application of cosmetics is indispensable in our current society. In recent years, with an increasing awareness of the long-term health benefits of naturally sourced ingredients, plant-based cosmetic products have gained increasing attention. Lilium belongs to the Liliaceae family, which is one of the main plant families used in cosmetics for skin care treatment. A large number of studies have shown that Lilium plants are rich in components such as phenolic acids, flavonoids, and polysaccharides, with high potential for cosmetic applications. However, the application of lilies in cosmetics has not been systematically reported. This knowledge gap can easily lead to the neglect of its application in cosmetics because lilies are most familiar as ornamental plants. Integrating academic papers and patent publications, we analyzed the potential cosmetic application ingredients in lily, as well as their applications in cosmetics and related efficacy. Patent analysis showed that applications for lily-related cosmetic patents are mainly concentrated in East Asia, including China, Korea, and Japan. The application of lilies involves all aspects of cosmetics, such as sunscreens, facial cleansers, facial masks, conditioners, and so on. Its functions are also rich and diverse, including antiaging, radiation protective, whitening, moisturizing, freckle removal, acne treatment, and hair regeneration promotion. In addition, lilies are compatible with the application of other herbs. Moreover, with a change in people’s consumption concepts and the consideration of long-term health benefits, lily-based food and medicine innovation with health care and beautification effects may be a promising direction.

There is a growing interest in using paper as a biomaterial scaffold for cell-based applications. In this study, we made the first attempt to fabricate a paper-based array for the culture, proliferation, and direct differentiation of human induced pluripotent stem cells (hiPSCs) into functional beating cardiac tissues and create "a beating heart on paper." This array was simply constructed by binding a cured multi-well polydimethylsiloxane (PDMS) mold with common, commercially available paper substrates. Three types of paper material (print paper, chromatography paper and nitrocellulose membrane) were tested for adhesion, proliferation and differentiation of human-derived iPSCs. We found that hiPSCs grew well on these paper substrates, presenting a three-dimensional (3D)-like morphology with a pluripotent property. The direct differentiation of human iPSCs into functional cardiac tissues on paper was also achieved using our modified differentiation approach. The cardiac tissue retained its functional activities on the coated print paper and chromatography paper with a beating frequency of 40-70 beats per min for up to three months. Interestingly, human iPSCs could be differentiated into retinal pigment epithelium on nitrocellulose membrane under the conditions of cardiac-specific induction, indicating the potential roles of material properties and mechanical cues that are involved in regulating stem cell differentiation. Taken together, these results suggest that different grades of paper could offer great opportunities as bioactive, low-cost, and 3D in vitro platforms for stem cell-based high-throughput drug testing at the tissue/organ level and for tissue engineering applications.

History has been kind to Christian Bohr (1855–1911). His name is attached eponymously to three different areas of respiratory physiology. The first is the Bohr dead space, which refers to the portion of the tidal volume that does not undergo gas exchange. The second is the increase in oxygen affinity of hemoglobin caused by the addition of carbon dioxide to the blood. This is known as the Bohr effect and is a very important feature of gas exchange, both in the lung and in peripheral tissues. Both of these contributions by Bohr are familiar to most students. Bohr’s third contribution refers to the calculation of the changes in the Po2 of blood as oxygen is loaded in the pulmonary capillary, the so-called Bohr integration. This contribution is less well known now, partly because of the advent of digital computing, but it was important in its day. The analysis is challenging because the very nonlinear shape of the oxygen dissociation curve means that the Po2 difference between the alveolar gas and the capillary blood, which is the driving pressure for diffusion, changes in a complicated way. All three papers are in German, and two of them are long and tedious to read. English translations are available, but few people read the papers, despite the fact that the first two articles are very frequently cited. In the present article, Bohr’s contributions are reviewed, and some parts of the articles that are particularly difficult to understand are clarified.

A microfluidic paper-based analytical device (μPADs) immunoassay for detection of the blood native biomarker D-dimer is reported. The μPAD is created by wax printing on a single piece of chromatographic paper and combined with an anti-D-dimer capture antibody and conjugates of anti-D-dimer antibody with 40 nm gold nanoparticles. The presence of D-dimer in buffer/simulated plasma samples is successfully reported for concentrations as low as 15 ng D-dimer/mL. Linearity between signal intensity and D-dimer concentration is observed up to 100 ng/mL. Using an appropriate dilution, the test could be used to yield positive results only for those samples with a D-dimer concentration above the clinically relevant threshold range of 250–500 ng/mL. Finally, the merits and pitfalls of using μPADs as compared to lateral flow devices in immunoassays are discussed.

The breakthrough potentials of research papers can be explained by their boundary-spanning qualities. Here, for the first time, we apply the structural variation analysis (SVA) model and its affiliated metrics to investigate the extent to which such qualities characterize a group of Nobel Prize winning papers. We find that these papers share remarkable boundary-spanning traits, marked by exceptional abilities to connect disparate and topically-diverse clusters of research papers. Further, their publications exert structural variations on the scale that significantly alters the betweenness centrality distributions of existing intellectual space. Overall, SVA not only provides a set of leading indicators for describing future Nobel Prize winning papers, but also broadens our understanding of the similar prize-winning properties that may have been overlooked among other regular publications., 27 pages, 8 figures, 9 tables. Submitted to Frontiers in Research Metrics and Analytics

Rocky desertification is a bottleneck that reduces ecological and environmental security in karst areas. Paper mulberry, a unique deciduous tree, shows good performance in rocky desertification areas. Its resistance mechanisms are therefore of high interest. In this study, a lysine acetylation proteomics analysis of paper mulberry seedling leaves was conducted in combination with the purification of acetylated protein by high-precision nano LC-MS/MS. We identified a total of 7130 acetylation sites in 3179 proteins. Analysis of the modified sites showed a predominance of nine motifs. Six positively charged residues: lysine (K), arginine (R), and histidine (H), serine (S), threonine (T), and tyrosine (Y) occurred most frequently at the +1 position, phenylalanine (F) was both detected both upstream and downstream of the acetylated lysines; and the sequence logos showed a strong preference for lysine and arginine around acetylated lysines. Functional annotation revealed that the identified enzymes were mainly involved in translation, transcription, ribosomal structure and biological processes, showing that lysine acetylation can regulate various aspects of primary carbon and nitrogen metabolism and secondary metabolism. Acetylated proteins were enriched in the chloroplast, cytoplasm, and nucleus, and many stress response-related proteins were also discovered to be acetylated, including PAL, HSP70, and ERF. HSP70, an important protein involved in plant abiotic and disease stress responses, was identified in paper mulberry, although it is rarely found in woody plants. This may be further examined in research in other plants and could explain the good adaptation of paper mulberry to the karst environment. However, these hypotheses require further verification. Our data can provide a new starting point for the further analysis of the acetylation function in paper mulberry and other plants.

Clinicians, working in the health-care diagnostic systems of developing countries, currently face the challenges of rising costs, increased number of patient visits, and limited resources. A significant trend is using low-cost substrates to develop microfluidic devices for diagnostic purposes. Various fabrication techniques, materials, and detection methods have been explored to develop these devices. Microfluidic paper-based analytical devices (μPADs) have gained attention for sensing multiplex analytes, confirming diagnostic test results, rapid sample analysis, and reducing the volume of samples and analytical reagents. μPADs, which can provide accurate and reliable direct measurement without sample pretreatment, can reduce patient medical burden and yield rapid test results, aiding physicians in choosing appropriate treatment. The objectives of this review are to provide an overview of the strategies used for developing paper-based sensors with enhanced analytical performances and to discuss the current challenges, limitations, advantages, disadvantages, and future prospects of paper-based microfluidic platforms in clinical diagnostics. μPADs, with validated and justified analytical performances, can potentially improve the quality of life by providing inexpensive, rapid, portable, biodegradable, and reliable diagnostics.

International audience; Plasma Science and Technology offer their valuable contribution to human health since more than 50 years, after decades of experiences in the field of biomaterials; and more than a decade in using plasmas for therapeutic uses in medicine. Current knowledge as well as key challenges and opportunities for the human health have been intensely discussed during the Future in Plasma Science II (FIPS II) workshop in February 2016 in Greifswald, Germany. This contribution summarizes the major outcomes of the meeting and the current literature and consensus with an emphasis on major challenges in the fields of Plasma Science and Technology for improving human health.

In order to achieve high predictive value of cell chemosensitivity test for clinical efficacy, cancer cells were suggested to be encapsulated and cultured in hydrogel to mimic the natural microenvironment of tumors. However, handling 3D cells/hydrogel culture construct is tedious and cellular response is difficult to be quantitatively analyzed. In the current study, a novel platform for conducting 3D cell culture and analyzing cell viability has been developed towards a high throughput drug screening. Cells encapsulated in the hydrogel were cultured in the microwells of a paper substrate. The substrate was then immersed in the culture medium containing drug for 2 days. At 24 and 48h during the culture course, the paper substrate was placed on the measurement electrodes for conducting the impedance measurement in order to quantify the cell viability in the hydrogel. Cell viability of two human hepatoma cell lines (Huh7 and Hep-G2) was quantitatively investigated under the treatment of two drugs (doxorubicin and etoposide). The results represented by IC50 values revealed that Huh7 cells had a higher drug resistance than Hep-G2 cells and doxorubicin had a higher efficacy than etoposide for treating hepatocellular carcinoma. The current work has demonstrated a high throughput, convenient, and quantitative platform for the investigation of chemosensitivity of cells cultured in the 3D environment.

International audience; Ischaemic heart disease and the heart failure that often results, remain the leading causes of death and disability in Europe and worldwide. As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury (IRI). During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments have been tested in the clinic-however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing. Therefore, in this Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart, we critically analyse the current state of ischaemic conditioning in both the experimental and clinical settings, provide recommendations for improving its translation into the clinical setting, and highlight novel therapeutic targets and new treatment strategies for reducing acute myocardial IRI.

SUMMARY The inner perivitelline layer (IPL) sperm hole assay provides an objective assessment of the number of sperm penetrating the hen’s ovum at the germinal disc. That number will provide insight into numerous parameters concerning fertility, including, but not limited to, the probability of the ovum being fertilized (true fertility), the duration of fertility, an assessment of mating activity, the effect of inseminating in vitro-stored semen, and the influence of spiking a breeder flock. In the current paper, we discuss the use of a filter paper ring to isolate and process the IPL overlying the germinal disc (PL disc) in 5 species of domestic birds. The morphology of the PL disc is also described to assist those using the sperm hole assay during sperm hole counting. The filter ring approach was successfully used with chicken, turkey, duck, goose, and Japanese quail eggs; the PL discs remained intact and stretched across the filter ring and sperm holes, when present, were clearly discernible. Morphologically, the PL disc appeared to be a silhouette of the germinal disc, including the germinal vesicle observed in follicular oocytes. The fibers forming the IPL had a honeycomb-like arrangement that could be mistaken for actual sperm holes in faintly stained slides. Given its diversity of applications and relative simplicity using the filter ring, it is recommended that the sperm hole assay be part of a quality control program at the hatchery. Already used in the scientific community, this filter ring method has the additional advantage that the blastoderm may be collected before the staining process.

A moving-bed bioreactor (MBB) could intensify growth of adherent mammalian cells for viral vaccines. A continuously fed sterile paper passing through a thin liquid layer as a flexible cell substrate is a new concept for bioprocess intensification (BPI). Paper could enable cell expansion with reduced footprint and reduced media consumption as the first stage of a 2-stage growth + infection continuous process. This study focused only on cell growth (stage 1). We report a simple 32 mm paper disc method to evaluate growth of adherent Madin Darby canine kidney cells (MDCK CCL-34) adapted to 5% FBS to confluence on unmodified papers to screen substrates. Bibulous paper was found to be the best substrate for proliferation of MDCK. An MBB process was simulated using paper discs to test growth to confluence (stage 1). Growth was characterized using staining, image analysis; confocal microscopy. Cells grew on the surface of bibulous paper to a confluence of >90% in 192 h. Extending this concept by stabilizing MDCK on paper (end of stage 1) by engineering cells to survive freezing or lyoprotection would enable live cells to be shipped as modules to multiple manufacturing sites for infection resulting in rapid, reproducible viral vaccine manufacture.

Breast cancer is a condition with the highest incidence of all neoplasms and a frequent cause of death. Due to increased incidence and mortality, this disease motivates healthcare professionals to redirect efforts to develop effective strategies for secondary prophylaxis. Imagistic investigations play an important role both in detecting lesions and in post-therapeutic evolutionary follow-up. The objective of the paper is to study cases of premalignant and malignant tumors, with a view to their imagistic identification confirmed in terms of histopathology, to highlight the accuracy of the imagistic examination as an important factor in the diagnosis and adaptation of an appropriate therapeutic attitude. The study was performed on a batch of 768 patients admitted to the Department of Surgery III, "Prof. Dr. Alexandru Trestioreanu" Institute of Oncology, Bucharest, Romania. The classical examined hypothesis is local examination, mammography, ultrasound, with its variations, and histopathological (HP) confirmation, either by thick-needle biopsy puncture and∕or tumor excision. By correlating with HP examination of the imagistic representation of the lesion, we can show the importance or limitation of each imagistic investigation, but especially its usefulness in the choice of therapeutic behavior. Breast cancer screening using classical techniques currently requires implementation of modern techniques to diagnose this disease.

There is growing recognition of the potential value of human induced pluripotent stem cells (hiPSC) for understanding disease and identifying drugs targets. This has been reflected in the establishment of multiple large-scale hiPSC initiatives worldwide. Representatives of these met recently at a workshop supported by the Welcome Trust in the UK and in a focus session at the 2014 ISSCR annual meeting in Vancouver. The purpose was to discuss strategies for making thousands of hiPSC lines widely available with as few restrictions as possible while retaining financial viability and donor privacy. The outcome of these discussions is described here.

In this study, we described a novel method to detect the kinase-to-kinase phosphorylation cascade reaction using a commercially available inkjet printing machine. It is very difficult to accomplish...

In nonclinical safety studies for new drug development, healthy animals have been commonly used. However, in some cases, the use of animal models of human disease is considered to be more favorable in evaluating risks in patients. To elucidate the current status of the use of animal models for nonclinical safety assessment, an internal questionnaire from the Japan Pharmaceutical Manufacturers Association and surveys (questionnaire period: August 27 to September 30, 2015) of both common technical documents and review reports of approved drugs (approval period: May 1999 to May 2017) disclosed by the Pharmaceutical and Medical Devices Agency were conducted. Although there were some concerns and limitations raised, the survey results revealed that animal models have been used in nonclinical safety assessment on a case-by-case basis and that nonclinical safety studies using animal models were included in the data packages of several approved drugs in Japan. The survey results also revealed that nonclinical safety studies using animal models have become more frequent in the past few years. In almost all cases, useful information, such as signs of toxicity under disease conditions and mechanisms of toxic change, was obtained from the results of nonclinical studies using animal models. Note: This is an opinion article submitted to the Toxicologic Pathology Forum. It represents the views of the author(s). It does not constitute an official position of the Society of Toxicologic Pathology, British Society of Toxicological Pathology, or European Society of Toxicologic Pathology, and the views expressed might not reflect the best practices recommended by these Societies. This article should not be construed to represent the policies, positions, or opinions of their respective organizations, employers, or regulatory agencies.

Our objective was to investigate whether the pulp and paper mill industry effluent could affect the testis and Sertoli cells in a fast exposure period. For this, the present study was carried out in immature rats at 10-day-old. Testis treated in vitro with 4% effluent for 1 h presented changes in energy metabolism in terms of a decrease in lactate content and glucose uptake. Elevation in GSH content, as an antioxidant defense mechanism, was also detected. Sertoli cells treated with 4% effluent for 1 hour showed alterations in the mitochondrial metabolism that favor the decoupling of oxidative phosphorylation and the generation of oxygen reactive species and also a time and concentration-dependent delay secretion of acidic vesicles. Our results showed that pollutants present in the pulp and paper mill effluents, in a short time of exposure, are capable of inducing alterations in important metabolic functions in the testis and in Sertoli cells that are crucial for the correct progression of spermatogenesis and fertility.

African swine fever virus (ASFV) is a dsDNA virus responsible for a severe, highly contagious, and lethal disease affecting both domestic and wild pigs. ASFV has brought enormous economic loss to a number of countries, and effective vaccine and therapy are still lacking. Therefore, a rapid, sensitive, and field-deployable detection of ASFV is important for disease surveillance and control. Herein, we developed a Cas12a-mediated portable paper assay to rapidly and precisely detect ASFV. We identified a robust set of crRNAs that recognized the highly conserved region of essential ASFV genes. The Cas12a-mediated detection assay showed low tolerance for mismatch mutations, and no cross-reactivity against other common swine pathogens. We further developed a paper-based assay to allow instrument-free detection of ASFV. Specifically, we applied gold nanoparticle–antibody conjugate to engineer homemade strips and combined it with Cas12a-mediated ASFV detection. This portable paper, instrument-free diagnostics, faithfully detected ASFV in swine samples, showing comparable sensitivity to the traditionally instrument-dependent qPCR method. Taking together, we developed a highly sensitive, instant, and economic Cas12a-mediated paper diagnostics of ASFV, with a great application potential for monitoring ASFV in the field.

SciPy is an open source scientific computing library for the Python programming language. SciPy 1.0 was released in late 2017, about 16 years after the original version 0.1 release. SciPy has become a de facto standard for leveraging scientific algorithms in the Python programming language, with more than 600 unique code contributors, thousands of dependent packages, over 100,000 dependent repositories, and millions of downloads per year. This includes usage of SciPy in almost half of all machine learning projects on GitHub, and usage by high profile projects including LIGO gravitational wave analysis and creation of the first-ever image of a black hole (M87). The library includes functionality spanning clustering, Fourier transforms, integration, interpolation, file I/O, linear algebra, image processing, orthogonal distance regression, minimization algorithms, signal processing, sparse matrix handling, computational geometry, and statistics. In this work, we provide an overview of the capabilities and development practices of the SciPy library and highlight some recent technical developments., Comment: Article source data is available here: https://github.com/scipy/scipy-articles

The comments sent by Stehr, Lundstom and Karlsson with reference to our article “Calmangafodipir reduces sensory alterations and prevents intraepidermal nerve fiber loss in a mouse model of oxaliplatin-induced peripheral neurotoxicity“ are very interesting, since they suggest possible mechanisms of action of the compound, which might contribute to its protective action [...]

The antioxidant effects of the ethyl acetate fraction of Dillenia indica bark (DIBEt) and the underlying mechanisms were investigated in tert-butyl hydroperoxide (t-BHP)-stimulated oxidative stress in RAW 264.7 cells. Paper spray ionization-mass spectroscopy with positive-ion mode tentatively revealed 27 secondary metabolites in D. indica bark extract, predominant among them were alkaloids, phenolic acids, and flavonoids. A new triterpenoid (nutriacholic acid) was confirmed in DIBEt for the first time. DIBEt had strong free radical-scavenging capabilities and was also able to reduce t-BHP-induced cellular reactive oxygen species (ROS) generation in RAW 264.7 cells. DIBEt was found to prevent oxidative stress by boosting the levels of heme oxygenase-1 (HO-1) through the up-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) via the regulation of extracellular signal-regulated kinase (ERK) phosphorylation in RAW 264.7 cells. These results support the potential of DIBEt for defense against oxidative stress-stimulated diseases.

The Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathology (STP) appointed a working group to address risk assessment for increases in alveolar macrophages following inhalation of pharmaceutical materials. This position paper provides recommendations for inhalation study–specific terminology and interpretation based on literature and information from marketed inhaled drugs. Based on a weight-of-the-evidence approach, and with appropriate consideration of the physical and pharmacological characteristics of the compound, uncomplicated increases in the size or number of alveolar macrophages in nonclinical species are interpreted as nonadverse.

A water vapor barrier and biodegradable packaging material was processed with paper, sodium caseinate (NaCAS) and paraffin wax. The water vapor barrier and the mechanical properties of coated paper were determined. In the first part of this work, the properties of the NaCAS-paper bilayers were investigated. The influence of the coating weight and the paraffin wax concentration was studied. The water vapor permeability (WVP) was decreased by increasing coating weight. Increasing the amount of wax in the coating led to a decrease in WVP. The tensile strength of the papers coated with NaCAS-paraffin wax emulsion was not affected by the coating weight. However, the elongation at break was increased by increasing coating weight. Tearing resistance was increased by increasing paraffin wax concentration. The second part of this work consisted of the study of the paper-NaCAS-paraffin wax three-layer films. The WVP was lowest for the three-layer material due to the hydrophobic character of the wax layer. PRACTICAL APPLICATIONS Paper, which consists of a porous cellulose network, is often coated to improve its barrier properties to water vapor, oxygen and aromas. Natural polymers can be used as barrier coatings on paper packaging materials. Such coatings have the potential to replace current synthetic paper coatings. This study has shown that sodium caseinate coating improves paper strength and ductility. We also found that the greatest reduction in paper water vapor permeability is achieved by addition of a paraffin wax layer to the paper already coated with sodium caseinate. Both bilayer and emulsified coatings processed in this study have potential advantages for some food applications. They may be used as barriers to moisture transfer in food products. They have potential environmental advantages over conventional synthetic films. The use of these biodegradable coatings for packaging reduces waste disposal problems and reduces use of nonrenewable resources.

Bovine spongiform encephalopathy (BSE) created a global European crisis in the 1980s and 90s, with very serious health and economic implications. Classical BSE now appears to be under control, to a great extent as a result of a global research effort that identified the sources of prions in meat and bone meal (MBM) and developed new animal-testing tools that guided policy. Priority (www.prionpriority.eu) was a European Union (EU) Framework Program 7 (FP7)-funded project through which 21 European research institutions and small and medium enterprises (SMEs) joined efforts between 2009 and 2014, to conduct coordinated basic and applied research on prions and prion diseases. At the end of the project, the Priority consortium drafted a position paper (www.prionpriority.eu/Priority position paper) with its main conclusions. In the present opinion paper, we summarize these conclusions. With respect to the issue of re-introducing ruminant protein into the feed-chain, our opinion is that sustaining an absolute ban on feeding ruminant protein to ruminants is essential. In particular, the spread and impact of non-classical forms of scrapie and BSE in ruminants is not fully understood and the risks cannot be estimated. Atypical prion agents will probably continue to represent the dominant form of prion diseases in the near future in Europe. Atypical L-type BSE has clear zoonotic potential, as demonstrated in experimental models. Similarly, there are now data indicating that the atypical scrapie agent can cross various species barriers. More epidemiological data from large cohorts are necessary to reach any conclusion on the impact of its transmissibility on public health. Re-evaluations of safety precautions may become necessary depending on the outcome of these studies. Intensified searching for molecular determinants of the species barrier is recommended, since this barrier is key for important policy areas and risk assessment. Understanding the structural basis for strains and the basis for adaptation of a strain to a new host will require continued fundamental research, also needed to understand mechanisms of prion transmission, replication and how they cause nervous system dysfunction and death. Early detection of prion infection, ideally at a preclinical stage, also remains crucial for development of effective treatment strategies. © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC.

The phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that regulate the cellular signal transduction pathways involved in cell growth, proliferation, survival, apoptosis, and adhesion. Deregulation of these pathways are common in oncogenesis, and they are known to be altered in other metabolic disorders as well. Despite its huge potential as an attractive target in these diseases, there is an unmet need for the development of a successful inhibitor. Unlike protein kinase inhibitors, screening for lipid kinase inhibitors has been challenging. Here we report, for the first time, the development of a radioactive lipid kinase screening platform using a phosphocellulose plate that involves transfer of radiolabeled [γ-(32)P]ATP to phosphatidylinositol 4,5-phosphate forming phosphatidylinositol 3,4,5-phosphate, captured on the phosphocellulose plate. Enzyme kinetics and inhibitory properties were established in the plate format using standard inhibitors, such as LY294002, TGX-221, and wortmannin, having different potencies toward PI3K isoforms. ATP and lipid apparent Km for both were determined and IC50 values generated that matched the historical data. Here we report the use of a phosphocellulose plate for a lipid kinase assay (PI3Kβ as the target) as an excellent platform for the identification of novel chemical entities in PI3K drug discovery.

We have compared the fatty acids of the capillary and venous whole blood samples collected on the commercially developed blood collection paper and standard grade filter paper extracted by either the direct methylation or conventional method (including various blood lipids fractions). Also, reproducibility of fatty acids extracted from dried blood on the filter paper after storing at room temperature up to 2 months and at 4 °C up to 6 months was assessed. In conclusion, the direct methylation of fingertip blood collected on both brand of papers produced fatty acids that reflected venous blood fatty acids extracted by the conventional method. Of the eight fatty acids evaluated, capillary DHA showed the strongest correlation with DHA of the venous whole lipids as well as various lipid fractions of the plasma and red cells. However, a prolonged storage of blood samples at 4 °C had deleterious effect on the qualitative value of fatty acids, especially DHA.

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