Cyanobacterial Ampholyte Hydrogels Developed by the Cationization of Sulfated Polysaccharides and Their Cell-Compatibility.

Sacran is a cyanobacterial supergiant polysaccharide with carboxylate and sulfate groups that exhibits antiallergic and antiinflammatory properties. However, its high anionic functions restrict cell compatibility. Quaternary ammonium groups were substituted to form sacran ampholytes, and the cell compatibility of the cationized sacran hydrogels was evaluated. The cationization process involved the reaction of N-(3-chloro-2-hydroxypropyl)trimethylammonium chloride with the primary amine or hydroxyl groups of sacran. The degree of cationization ranged from 32 to 87% for sugar residues. Hydrogels of sacran ampholytes were prepared by annealing their dried sheets by thermal cross-linking; these hydrogels exhibited anisotropic expansion properties. The water contact angle on the hydrogels decreased from 26.5 to 15.3° with an increase in the degree of cationization, thereby enhancing hydrophilicity. The IC50 values of sacran ampholytes decreased with an increased degree of cationization, resulting in a reduction in cytotoxicity toward the L-929 mouse fibroblast cell line. This reduction was associated with an increase in the cell proliferation density after 3 days of incubation. Scanning electron microscopy images showed fibroblast intercellular connections. Therefore, the sacran ampholyte hydrogel exhibited increased hydrophilicity and cell compatibility, which is beneficial for various biomedical applications.

Eco-friendly synthesis of an α-Fe2O3/rGO nanocomposite and its application in high-performance asymmetric supercapacitors.

This work presents an innovative and environmentally friendly biological synthesis approach for producing α-Fe2O3 nanoparticles (NPs) and the successful synthesis of α-Fe2O3/reduced graphene oxide (rGO) nanocomposites (NCs). This novel synthesis route utilizes freshly extracted albumin, serving as both a reducing agent and a stabilizing agent, rendering it eco-friendly, cost-effective, and sustainable. A combination of characterization techniques including X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, and field emission scanning electron microscopy (FE-SEM) was employed to predict and confirm the formation of the as-synthesized α-Fe2O3 NPs and α-Fe2O3/rGO NCs. Transmission electron microscopy (TEM) verified the anisotropic nature of the synthesized nanoparticles. To gain insight into the enhanced capacitance of the α-Fe2O3/rGO NCs, a series of electrochemical tests, namely cyclic voltammetry (CV), galvanostatic charge-discharge (GCD), electrochemical impedance spectroscopy (EIS), and stability assessments, were conducted in a conventional three-electrode configuration. Furthermore, a two-electrode asymmetric supercapacitor (ASC) device was fabricated to assess the practical viability of this material. The α-Fe2O3/rGO NCs exhibited a remarkable potential window of 2 V in an aqueous electrolyte, coupled with exceptional cycling stability. Even after undergoing 10 000 cycles, the capacitive retention exceeded 100%, underlining the promising potential of this material for advanced energy storage applications.

Comparing knowledge, attitudes, and practices in cardiovascular disease prevention and health promotion between community and hospital pharmacists in Saudi Arabia: A cross-sectional study.

Purpose: Saudi Arabia is one of the leading nations in the world in terms of the high frequency of chronic diseases and their associated risk factors. Knowledge and awareness are crucial for pharmacists to play an active role in the prevention of cardiovascular diseases (CVD). The current study assessed the pharmacists' knowledge, attitude, and practice to determine the potential differences with respect to their respective practice settings toward CVD prevention and related health promotions. Methods: It is a cross-sectional study targeted the registered pharmacists in the Kingdom of Saudi Arabia. An online questionnaire was prepared, and the link was circulated through various social media platforms. Descriptive statistics, multivariate linear regression analysis and chi square test were used to analyze the data accordingly. Results: A total of 324 pharmacists were included in the study. Among these, 157 (48.4 %) were community pharmacists, and the remaining were hospital pharmacists (51.6 %). No significant differences in knowledge scores were observed between community and hospital pharmacists. The mean attitude score among community and hospital pharmacists was found to be 26.40 ± 5.125 and 25.09 ± 5.393 respectively, which was statistically significant (p = 0.026). Similarly, the total practice scores across the settings were statistically significant (p = 0.02). Gender plays a significant role in terms of knowledge scores among both community and hospital pharmacists (p = 0.016 & 0.029). Gender, professional practice experience, and number of prescriptions handled and prescriptions with CVD medications showed significant differences in the distribution of positive attitudes and good practice frequency between community and hospital pharmacists. Conclusion: It is evident that there is a deficiency in knowledge among hospital pharmacists compared to community pharmacists. Which indicates that there is a need for a rigorous continuous pharmacy education covering the fundamental aspects of CVD primary prevention and health promotion among pharmacists, given more focus on hospital pharmacists.

Controlled Transport of Individual Microparticles Using Dielectrophoresis.

A dielectrophoretic device employing a planar array of microelectrodes is designed for controlled transport of individual microparticles. By exciting the electrodes in sequence, a moving dielectrophoretic force is created that can drag a particle across the electrodes in a straight line. The electrode shapes are designed to counter any lateral drift of the trapped particle during transport. This facilitates single particle transport by creating a narrow two-dimensional corridor for the moving dielectrophoretic force to operate on. The design and analysis processes are discussed in detail. Numerical simulations are performed to calculate the electromagnetic field distribution and the generated dielectrophoretic force near the electrodes. The Langevin equation is used for analyzing the trajectory of a microparticle under the influence of the external forces. The simulations show how the designed electrode geometry produces the necessary lateral confinement required for successful particle transport. Finally, experimental results are presented showing controlled bidirectional linear transport of single polystyrene beads of radius 10 and 5 µm for a distances 840 and 1100 µm, respectively. The capabilities of the proposed platform make it suitable for micro total analysis systems (µTAS) and lab-on-a-chip (LOC) applications.

Virtual Screening for Identification of Dual Inhibitors against CDK4/6 and Aromatase Enzyme.

CDK4/6 and aromatase are prominent targets for breast cancer drug discovery and are involved in abnormal cell proliferation and growth. Although aromatase inhibitors have proven to be effective (for example exemestane, anastrozole, letrozole), resistance to treatment eventually occurs through the activation of alternative signaling pathways, thus evading the antiproliferative effects of aromatase inhibitors. One of the evasion pathways is Cylin D-CDK4/6-Rb signaling that promotes tumor proliferation and resistance to aromatase inhibitors. There is significant evidence that the sequential inhibition of both proteins provides therapeutic benefits over the inhibition of one target. The basis of this study objective is the identification of molecules that are likely to inhibit both CDK4/6 and aromatase by computational chemistry techniques, which need further biochemical studies to confirm. Initially, a structure-based pharmacophore model was constructed for each target to screen the sc-PDB database. Consequently, pharmacophore screening and molecular docking were performed to evaluate the potential lead candidates that effectively mapped both of the target pharmacophore models. Considering abemaciclib (CDK4/6 inhibitor) and exemestane (aromatase inhibitor) as reference drugs, four potential virtual hit candidates (1, 2, 3, and 4) were selected based on their fit values and binding interaction after screening a sc-PDB database. Further, molecular dynamics simulation studies solidify the stability of the lead candidate complexes. In addition, ADMET and DFT calculations bolster the lead candidates. Hence, these combined computational approaches will provide a better therapeutic potential for developing CDK4/6-aromatase dual inhibitors for HR+ breast cancer therapy.

Spatial variation in livelihood security among livestock-based agricultural farming systems in climatically vulnerable Indian Sundarbans.

Farm households in the UNESCO World Heritage site Sundarbans face serious problems, including increased soil salinity, frequent extreme weather events, seawater intrusion and flood damage, all of which cause distress to the livelihoods of the farm families. Policymakers commonly acknowledge livestock as a crucial resource for mitigating economic losses caused by crop failures due to extreme weather events. Despite Sundarbans' vulnerability to extreme weather events, smallholder farmers' livelihoods vary across the region. Identifying spatial livelihood variations aids in targeted strategies to address climate extremes. We chose the highest cow- and buffalo-populated blocks among the 19 blocks in the Sundarbans to assess variations in livelihood dimensions, including nutritional, economic, social and infrastructural security. We used dummy variable regression models to examine the differences in livelihood security dimensions among households living in different locations. The study found that Namkhana had the highest livelihood security score among the blocks studied, while Gosaba had the lowest score because it's in a remote area with limited infrastructure. The study found a significant difference in the overall livelihood security score among the blocks we examined, indicating the need for a location-specific, cluster-based approach for the overall development of the Sundarbans. The study can shape a policy framework for socio-economic development in the Indian Sundarbans through its findings on location-specific livelihood security. For securing smallholder farmers' livelihoods in the vulnerable Sundarbans region, policymakers must give priority to improving infrastructure, viz., roads, marketing facilities and animal healthcare centers.

Gas chromatographic-mass spectrometric analysis, antioxidant, antiproliferative and antibacterial activities of the essential oil of Prangospabularia.

The essential oil composition of the shoot parts of Prangos pabularia, growing in Drass area of Ladakh, India, along with its antioxidant, antibacterial and anticancer activity, is reported for the first time. Gas chromatography coupled with mass spectrometry (GC-MS) revealed the presence of 31 constituents, representing 97.342% of the total essential oil. The major constituents of essential oil were Durylaldehyde (62.161%), Bicyclo [3.1.1] hept-2-en-4-ol (8.846%), Chrysanthenyl acetate (5.120%) followed by unknown (3.420%), (-)-Spathulenol (3.028%), Mesityl aldehyde (2.402%) and Hexahydro farnesyl acetone (1.683%. Cytotoxic activity of the essential oil by MTT assay against human breast adenocarcinoma (MCF7), human breast (HBL-100), human cervical cancer (HELA) and human lung adenocarcinoma epithelial (A549) cells, at four different concentrations (20, 30, 50 & 100 µg/mL) revealed that the activity of 56.12% against A549 (human lung) cell line at 20 µg/mL concentration was the highest. The Essential oil displayed a significant free radical scavenging activity with DPPH. Antibacterial activity was carried out against 3 g positive and 2-g negative bacteria at four different concentrations using Agar Well Diffusion Method taking streptomycin sulphate as reference. The essential oil displayed significant and broad-spectrum antibacterial activity against different bacteria used. The MIC of the oil ranged from 2.06 to 5.00 µg/mL. The zones of inhibition were lesser for Micrococcus and Escherichia coli compared to other strains of bacteria.

Type I Interferons Enhance the Repair of Ultraviolet Radiation-Induced DNA Damage and Regulate Cutaneous Immune Suppression.

Type I interferons (IFNs) are important enhancers of immune responses which are downregulated in human cancers, including skin cancer. Solar ultraviolet (UV) B radiation is a proven environmental carcinogen, and its exposure contributes to the high prevalence of skin cancer. The carcinogenic effects of UV light can be attributed to the formation of cyclobutane pyrimidine dimers (CPD) and errors in the repair and replication of DNA. Treatment with a single dose of UVB (100 mJ/cm2) upregulated IFNα and IFNß in the skin of C57BL/6 mice. IFNα and IFNß were predominantly produced by CD11b+ cells. In mice lacking the type I IFN receptor 1 (IFNAR1), the repair of CPD following cutaneous exposure to a single dose of UVB (100 mJ/cm2) was decreased. UVB induced the expression of the DNA repair gene xeroderma pigmentosum A (XPA) in wild-type (WT) mice. In contrast, such treatment in IFNAR1 (IFNAR1-/-) mice downregulated XPA. A local UVB regimen consisting of UVB radiation (150 mJ/cm2) for 4 days followed by sensitization with hapten 2,4, dinitrofluorobenzene (DNFB) resulted in significant suppression of immune responses in both WT and IFNAR1-/- mice. However, there were significantly higher CD4+CD25+Foxp3+ regulatory T-cells in the draining lymph nodes of IFNAR1-/- mice in comparison to WT mice. Overall, our studies reveal a previously unknown action of type I IFNs in the repair of photodamage and the prevention of UVB-induced immune suppression.

Effect of supplementation of phytogenic feed additives on intake, in vitro fermentation, growth performance and carcass traits in weaned Barbari kids reared under intensive feeding.

Twenty-four weaned male Barbari kids (age 144.67 days; weight 11.99 ± 0.49 kg) were divided equally into three groups (T1, T2, and T3) in order to investigate the effect of supplementation of phytogenic feed additives (herbal mixture) in the complete pelleted feed on growth performance, in vitro rumen fermentation and carcass quality in kids reared under stall-fed condition. Treatment groups were as follows: T1, concentrate mixture (40%) plus arhar (Cajanus cajan) straw (60%) in total mixed ration (TMR) form fed ad libitum; T2, T1 diet in complete feed pellets form fed ad libitum; and T3, T1 diet in complete feed pellets form supplemented with herbal mixture (Tulsi/Haldi/Amla/Arni; ratio 1:1:1:1 on DM basis) at 0.5% in complete feed fed ad libitum. The experimental kids in each group were allowed for feeding for 8 months by following the respective feeding schedule. Rumen fermentation pattern under in vitro system was also studied using the same three diets as substrates. After 240 days of feeding, all goats were slaughtered following standard protocol. Total body weight gain (kg) and average daily gain (ADG, g/day/kid) were 18.57, 22.26, and 23.06 kg, and 79.91, 101.49, and 100.18 g in T1, T2, and T3 treatments, respectively. Pelleting of TMR (T2) and supplementation of herbal mixture in pelleted feed (T3) increased (P < 0.001) average daily weight gain in Barbari kids compared to T1 (TMR). Average dry matter intake (DMI, g/day/kid) during growth trial was greater (P < 0.05) in T3 (1079.17) than T1 (849.76) and T2 (968.76). Feed conversion efficiency was 8.92, 9.48, and 8.68% in T1, T2, and T3, respectively. The difference was statistically non-significant among the treatments. Supplementation of herbal mixture in the complete pelleted substrate had adjunct effect on improvement of TCA-precipitable-N and total VFAs in the incubation medium under in vitro system. Carcass weight (kg) tended to increase in finisher kids under T2 (16.58) and T3 (16.70) than T1 (14.61), but the variation was non-significant. The dressing percentage was similar among three treatments. Similarly, the muscle protein, fat, and cholesterol contents remained unaffected by different dietary treatments. Therefore, it may be concluded that densification of feeds in the form of complete pelleted feed and further supplementation with potential phytogenic feed additives increased total DMI and ADG and tended to enhance meat production potential in finisher Barbari kids without changing the meat chemical composition.

Dynamically controlled dielectrophoresis using resonant tuning.

Electrically polarizable micro- and nanoparticles and droplets can be trapped using the gradient electric field of electrodes. But the spatial profile of the resultant dielectrophoretic force is fixed once the electrode structure is defined. To change the force profile, entire complex lab-on-a-chip systems must be re-fabricated with modified electrode structures. To overcome this problem, we propose an approach for the dynamic control of the spatial profile of the dielectrophoretic force by interfacing the trap electrodes with a resistor and an inductor to form a resonant resistor-inductor-capacitor (RLC) circuit. Using a dielectrophoretically trapped water droplet suspended in silicone oil, we show that the resonator amplitude, detuning, and linewidth can be continuously varied by changing the supply voltage, supply frequency, and the circuit resistance to obtain the desired trap depth, range, and stiffness. We show that by proper tuning of the resonator, the trap range can be extended without increasing the supply voltage, thus preventing sensitive samples from exposure to high electric fields at the stable trapping position. Such unprecedented dynamic control of dielectrophoretic forces opens avenues for the tunable active manipulation of sensitive biological and biochemical specimen in droplet microfluidic devices used for single-cell and biochemical reaction analysis.

Safety of balanced propofol and midazolam in upper gastrointestinal endoscopy for sedation in cirrhotic patients.

OBJECTIVE: Sedation for upper gastrointestinal endoscopy (UGIE) in patients with cirrhosis is theoretically associated with high incidence of adverse events due to low levels of binding proteins and decreased hepatic clearance of drugs. The objective of the study was to assess the safety of combined propofol and midazolam sedation in cirrhotic patients undergoing UGIE. METHOD: A total of 500 patients undergoing UGIE were divided in to two groups in a prospective observational study from Jan 1st 2018 to June 30th 2018. Group (I) consisted of cirrhotic patients who underwent the procedure with sedation and Group (II) consisted of non-cirrhotic patients who opted for sedation. The main outcome measurements included vitals monitoring before, during and after procedure, total sedation dose, time to initial and deep sedation, recovery time and complications. RESULTS: There was no significant difference between sedation safety and rate of complications for the cirrhotic and non-cirrhotic patients except for the recovery period during initial 10 minutes. The Modified Aldrete score for the cirrhotic patients was 9.5±0.5 min as compared to 9.8±0.4 min for non-cirrhotic patients (p<0.001) at 10 minutes. Grade 2 hepatic encephalopathy was seen in 0.8% of the cirrhotic patients who required hospitalization for 24 hours. Also balanced sedation was acceptable by the patients and the endoscopists equally with statistically significant scores on endoscopist's assessment of co-operation and assessment of patient's satisfaction scores. CONCLUSIONS: Balanced propofol and midazolam sedation has a good index of safety for both cirrhotic and non-cirrhotic patients and is acceptable by the patients and endoscopists equally.

PS4DR: a multimodal workflow for identification and prioritization of drugs based on pathway signatures.

BACKGROUND: During the last decade, there has been a surge towards computational drug repositioning owing to constantly increasing -omics data in the biomedical research field. While numerous existing methods focus on the integration of heterogeneous data to propose candidate drugs, it is still challenging to substantiate their results with mechanistic insights of these candidate drugs. Therefore, there is a need for more innovative and efficient methods which can enable better integration of data and knowledge for drug repositioning. RESULTS: Here, we present a customizable workflow (PS4DR) which not only integrates high-throughput data such as genome-wide association study (GWAS) data and gene expression signatures from disease and drug perturbations but also takes pathway knowledge into consideration to predict drug candidates for repositioning. We have collected and integrated publicly available GWAS data and gene expression signatures for several diseases and hundreds of FDA-approved drugs or those under clinical trial in this study. Additionally, different pathway databases were used for mechanistic knowledge integration in the workflow. Using this systematic consolidation of data and knowledge, the workflow computes pathway signatures that assist in the prediction of new indications for approved and investigational drugs. CONCLUSION: We showcase PS4DR with applications demonstrating how this tool can be used for repositioning and identifying new drugs as well as proposing drugs that can simulate disease dysregulations. We were able to validate our workflow by demonstrating its capability to predict FDA-approved drugs for their known indications for several diseases. Further, PS4DR returned many potential drug candidates for repositioning that were backed up by epidemiological evidence extracted from scientific literature. Source code is freely available at https://github.com/ps4dr/ps4dr.

Macroeconomic impacts of cigarette consumption in Pakistan.

BACKGROUND: Pakistan has a large population of tobacco users, with about 24 million adults consuming tobacco products in one form or another. There is a dearth of research on the impact of a reduction in tobacco use on Pakistan's economy which can inform policy-makers on the extent that tobacco control measures would affect macroeconomic indicators such as output and employment. OBJECTIVES: The objective of this study is to quantify the changes in output, income and employment resulting from changes in cigarette consumption and to quantify the impact of such changes on the overall economy. METHODOLOGY: The study uses the input-output table for the fiscal year 2010-2011 for Pakistan's economy, to estimate the output, income and employment multipliers. The Leontief input-output model is used to estimate the sectorwise multiplier effects. It estimates direct, indirect and consumption-induced effects of changes in tobacco use on the economy. RESULTS: The cigarette industry's share in large-scale manufacturing and industrial employment is 1.1% and 0.3%, respectively. The estimates of gross output, income and employment multipliers for the cigarette industry have relatively small magnitudes indicating minimal impact on the economy. A simulation analysis based on the latest estimates of price elasticity of cigarette and input-output multipliers, shows that a 10% increase in price will lead to an 11% reduction in cigarette consumption, which translates into annual savings of Pakistani Rupees (Rs) 16 billion by households. Reduction in cigarette consumption will allow individuals to spend their savings on other commodities. For example, spending this amount on food items will lead to a net increase of Rs 40 billion annual output of the economy. CONCLUSION: Reduction in tobacco consumption will lead to initial losses to the economy but there will be considerable gains in output, employment and income due to redistribution of tobacco expenditures.

In-plane near-field optical barrier on a chip.

Nanoparticles trapped on resonant near-field structures engraved on a metallic substrate experience forces due to the engravings, as well as the image-like interaction with the substrate. In the case of normally incident optical excitation, the force due to the substrate is solely perpendicular to its surface. Numerical simulations are presented to demonstrate that under the combined influence of the aforementioned forces, a plasmonic nanoparticle can be repelled from the engraving along the substrate, while attracting it towards the substrate along its normal. This behavior can be achieved over a range of excitation wavelengths of the short wavelength mode of the coupled particle-substrate-trap system. To the best of our knowledge, this is the first illustration of an in-plane near-field optical barrier on a chip. The barrier is stable against resistive heating of the nanoparticle, as well as the induced non-isothermal flow. The wavelength-dependent switch between the proposed in-plane potential barrier and the stable potential well can pave the way for the gated transport of single nanoparticles, while holding them bound to the chip.

Synthesis of Nucleic Acid Bases by Metal Ferrite Nanoparticles from a Single Carbon Atom Precursor Molecule: Formamide.

The synthesis of prebiotic molecules from simple precursors is believed to be a crucial scheme in order to study the origin of life processes. The present study describes the one-pot synthesis of purine and pyrimidine nucleic acid bases in the presence of pre-biologically significant binary metal oxide nanoparticles, metal ferrites, namely NiFe2O4, CoFe2O4, CuFe2O4, ZnFe2O4 and MnFe2O4. The products identified are cytosine, isocytosine, 4(3H)-pyrimidinone, adenine, hypoxanthine and purine. The ability of isocytosine (a constitutional isomer of cytosine) to recognize cytosine and guanine through normal and reversed Watson-Crick pairing respectively, demonstrates an important storyline for the genesis of ancient nucleic acids. The relevance of other synthesized nucleic acid bases with respect to the origin of life is also discussed. The divalent metal ions in iron oxide make it an appropriate catalytic system because it demonstrates excellent catalytic performance for the nucleic acid bases synthesis with significantly high yield, as compared to pure iron oxide and some other minerals like silica, alumina, manganese oxides and double metal cyanide complexes.

Doxorubicin triggers splenic contraction and irreversible dysregulation of COX and LOX that alters the inflammation-resolution program in the myocardium.

Doxorubicin (DOX) is a widely used drug for cancer treatment as a chemotherapeutic agent. However, the cellular and integrative mechanism of DOX-induced immunometabolism is unclear. Two-month-old male C57BL/6J mice were divided into high- and low-dose DOX-treated groups with a maintained saline control group. The first group was injected with a high dose of DOX (H-DOX; 15 mg·kg-1·wk-1), and the second group was injected with 7.5 mg·kg-1·wk-1 as a latent low dose of DOX (LL-DOX). H-DOX treatment led to complete mortality in 2 wk and 70% survival in the LL-DOX group compared with the saline control group. Therefore, an additional group of mice was injected with an acute high dose of DOX (AH-DOX) and euthanized at 24 h to compare with LL-DOX and saline control groups. The LL-DOX and AH-DOX groups showed obvious apoptosis and dysfunctional and structural changes in cardiac tissue. Splenic contraction was evident in AH-DOX- and LL-DOX-treated mice, indicating the systems-wide impact of DOX on integrative organs of the spleen, which is essential for cardiac homeostasis and repair. DOX dysregulated splenic-enriched immune-sensitive lipoxygenase and cyclooxygenase in the spleen and left ventricle compared with the saline control group. As a result, lipoxygenase-dependent D- and E-series resolvin precursors, such as 16HDoHE, 4HDoHE, and 12-HEPE, as well as cyclooxygenase-mediated PG species (PGD2, PGE2, and 6-keto-PG2α) were decreased in the left ventricle, suggestive of defective immunometabolism. Both AH-DOX and LL-DOX induced splenic contraction and expansion of red pulp with decreased CD169+ metallophilic macrophages. AH-DOX intoxicated macrophages in the spleen by depleting CD169+ cells in the acute setting and sustained the splenic macrophage loss in the chronic phase in the LL-DOX group. Thus, DOX triggers a vicious cycle of splenocardiac cachexia to facilitate defective immunometabolism and irreversible macrophage toxicity and thereby impaired the inflammation-resolution program. NEW & NOTEWORTHY Doxorubicin (DOX) triggered splenic mass loss and decreased CD169 with germinal center contraction in acute and chronic exposure. Cardiac toxicity of DOX is marked with dysregulation of immunometabolism and thereby impaired resolution of inflammation. DOX suppressed physiological levels of cytokines and chemokines with signs of splenocardiac cachexia.

Neuro-symbolic representation learning on biological knowledge graphs.

MOTIVATION: Biological data and knowledge bases increasingly rely on Semantic Web technologies and the use of knowledge graphs for data integration, retrieval and federated queries. In the past years, feature learning methods that are applicable to graph-structured data are becoming available, but have not yet widely been applied and evaluated on structured biological knowledge. Results: We develop a novel method for feature learning on biological knowledge graphs. Our method combines symbolic methods, in particular knowledge representation using symbolic logic and automated reasoning, with neural networks to generate embeddings of nodes that encode for related information within knowledge graphs. Through the use of symbolic logic, these embeddings contain both explicit and implicit information. We apply these embeddings to the prediction of edges in the knowledge graph representing problems of function prediction, finding candidate genes of diseases, protein-protein interactions, or drug target relations, and demonstrate performance that matches and sometimes outperforms traditional approaches based on manually crafted features. Our method can be applied to any biological knowledge graph, and will thereby open up the increasing amount of Semantic Web based knowledge bases in biology to use in machine learning and data analytics. AVAILABILITY AND IMPLEMENTATION: https://github.com/bio-ontology-research-group/walking-rdf-and-owl. CONTACT: robert.hoehndorf@kaust.edu.sa. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Multimodal mechanistic signatures for neurodegenerative diseases (NeuroMMSig): a web server for mechanism enrichment.

MOTIVATION: The concept of a 'mechanism-based taxonomy of human disease' is currently replacing the outdated paradigm of diseases classified by clinical appearance. We have tackled the paradigm of mechanism-based patient subgroup identification in the challenging area of research on neurodegenerative diseases. RESULTS: We have developed a knowledge base representing essential pathophysiology mechanisms of neurodegenerative diseases. Together with dedicated algorithms, this knowledge base forms the basis for a 'mechanism-enrichment server' that supports the mechanistic interpretation of multiscale, multimodal clinical data. AVAILABILITY AND IMPLEMENTATION: NeuroMMSig is available at http://neurommsig.scai.fraunhofer.de/. CONTACT: martin.hofmann-apitius@scai.fraunhofer.de. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Peptide-Functionalized Hydrogel Cubes for Active Tumor Cell Targeting.

Conjugation of bioactive targeting molecules to nano- or micrometer-sized drug carriers is a pivotal strategy to improve their therapeutic efficiency. Herein, we developed pH- and redox-sensitive hydrogel particles with a surface-conjugated cancer cell targeting ligand for specific tumor-targeting and controlled release of the anticancer drug doxorubicin. The poly(methacrylic acid) (PMAA) hydrogel cubes of 700 nm and 2 µm with a hepsin-targeting (IPLVVPL) surface peptide are produced through multilayer polymer assembly on sacrificial cubical mesoporous cores. Direct peptide conjugation to the disulfide-stabilized hydrogels through a thiol-amine reaction does not compromise the structural integrity, hydrophilicity, stability in serum, or pH/redox sensitivity but does affect internalization by cancer cells. The cell uptake kinetics and the ultimate extent of internalization are controlled by the cell type and hydrogel size. The peptide modification significantly promotes the uptake of the 700 nm hydrogels by hepsin-positive MCF-7 cells due to ligand-receptor recognition but has a negligible effect on the uptake of 2 µm PMAA hydrogels. The selectivity of 700 nm IPLVVPL-PMAA hydrogel cubes to hepsin-overexpressing tumor cells is further confirmed by a 3-10-fold higher particle internalization by hepsin-positive MCF-7 and SK-OV-3 compared to that of hepsin-negative PC-3 cells. This work provides a facile method to fabricate enhanced tumor-targeting carriers of submicrometer size and improves the general understanding of particle design parameters for targeted drug delivery.

The skin microbiome and immune system: Potential target for chemoprevention?

There has been increasing interest in understanding the role of the human microbiome in skin diseases. Microbiome studies are being utilized in skin cancer research in numerous ways. Commensal bacteria are being studied as a potential tool to judge the biggest environmental risk of skin cancer, ultraviolet (UV) radiation. Owing to the recognized link of skin microbes in the process of inflammation, there have been theories linking commensal bacteria to skin cancer. Viral metagenomics has also provided insight into virus linked forms of skin cancers. Speculations can be drawn for skin microbiome that in a manner similar to gut microbiome, they can be involved in chemoprevention of skin cancer. Nonetheless, there are definitely huge gaps in our knowledge of the relationship of microbiome and skin cancers, especially in relation to chemoprevention. The utilization of microbiome in skin cancer research seems to be a promising field and may help yield novel skin cancer prevention and treatment options. This review focuses on recent utilization of the microbiome in skin cancer research, and it explores the potential of utilizing the microbiome in prevention, earlier diagnosis, and treatment of skin cancers.