Global Characterization of Metabolic Genes Regulating Survival and Immune Infiltration in Osteosarcoma

Background: The alterations in metabolic profile of tumors have been identified as one of the prognostic hallmarks of cancers, including osteosarcoma. These alterations are majorly controlled by groups of metabolically active genes. However, the regulation of metabolic gene signatures in tumor microenvironment of osteosarcoma has not been well explained.Objectives: Thus, we investigated the sets of previously published metabolic genes in osteosarcoma patients and normal samples.Methods: We applied computational techniques to identify metabolic genes involved in the immune function of tumor microenvironment (TME) and survival and prognosis of the osteosarcoma patients. Potential candidate gene PAICS (phosphoribosyl aminoimidazole carboxylase, phosphoribosyl aminoimidazole succino carboxamide synthetase) was chosen for further studies in osteosarcoma cell lines for its role in cell proliferation, migration and apoptosis.Results: Our analyses identified a list of metabolic genes differentially expressed in osteosarcoma tissues. Next, we scrutinized the list of genes correlated with survival and immune cells, followed by clustering osteosarcoma patients into three categories: C1, C2, and C3. These analyses led us to choose PAICS as potential candidate gene as its expression showed association with poor survival and negative correlation with the immune cells. Furthermore, we established that loss of PAICS induced apoptosis and inhibited proliferation, migration, and wound healing in HOS and MG-63 cell lines. Finally, the results were supported by constructing and validating a prediction model for prognosis of the osteosarcoma patients.Conclusion: Here, we conclude that metabolic genes specifically PAICS play an integral role in the immune cell infiltration in osteosarcoma TME, as well as cancer development and metastasis.

Osteogenic Differentiation of Human Mesenchymal Stem Cells Modulated by Surface Manganese Chemistry in SLA Titanium Implants

The manganese (Mn) ion has recently been probed as a potential candidate element for the surface chemistry modification of titanium (Ti) implants in order to develop a more osteogenic surface with the expectation of taking advantage of its strong binding affinity to the integrins on bone-forming cells. However, the exact mechanism of how Mn enhances osteogenesis when introduced into the surface of Ti implants is not clearly understood. This study investigated the corrosion resistance and potential osteogenic capacity of a Mn-incorporated Ti surface as determined by electrochemical measurement and examining the behaviors of human mesenchymal stem cells (MSCs) in a clinically available sandblasted/acid-etched (SLA) oral implant surface intended for future biomedical applications. The surface that resulted from wet chemical treatment exhibited the formation of a Mn-containing nanostructured TiO2 anatase thin film in the SLA implant and improved corrosion resistance. The Mn-incorporated SLA surface displayed sustained Mn ion release and enhanced osteogenesis-related MSC function, which enhanced early cellular events such as spreading, focal adhesion, and mRNA expression of critical adhesion-related genes and promoted full human MSC differentiation into mature osteoblasts. Our findings indicate that surface Mn modification by wet chemical treatment is an effective approach to produce a Ti implant surface with increased osteogenic capacity through the promotion of the osteogenic differentiation of MSCs. The improved corrosion resistance of the resultant surface is yet another important benefit of being able to provide favorable osseointegration interface stability with an increased barrier effect.

The effect of Kappaphycus alvarezii active fraction on oxidative stress and inflammation in streptozotocin and nicotinamide-induced diabetic rats

Background High glucose concentration increases the glycation process which leads to oxidative stress and inflammation, that can cause complications in diabetes. Several medicinal plants have been used in the treatment of diabetes and its complications. One of them is Kappaphycus alvarezii, an algae that has known antidiabetic abilities. This study aimed to examine the effect of K. alvarezii active fraction on plasma hydrogen peroxide (H2O2) and Tumor Necrosis Factor α (TNFα) levels, renal NADPH oxidase 4 (NOX4) and Nuclear Factor κ B (NFκB) gene expressions. Methods Active fraction was obtained from bioassay-guided fractionation with antiglycation ability. In vivo study was performed on twenty Wistar male rats. The level of H2O2 was measured using H2O2 Assay Kit, the Optical Density value measured using spectrophotometer at a wavelength of 405 nm. Plasma TNFα level was measured using ELISA. Renal NOX4 and NFκB gene expression was analyzed using qPCR. Results Active fraction significantly reduced plasma H2O2 but not TNFα levels. Furthermore, renal NOX4 gene expression was lower in the diabetic rat group treated with active fraction compared to the untreated group but not NFκB gene expression. Conclusions K. alvarezii active fraction has an activity to reduce plasma H2O2 as well as renal NOX4 gene expression. Therefore, this fraction could be developed as a potential candidate for diabetes treatment through oxidative stress mechanisms.

Aqueous Allium sativum (garlic) extract ameliorated CdCl2- induced alterations in blood formation and spermatogenesis in albino rats

Purpose: To investigate the ameliorative effect of aqueous garlic extract (AGEx) on cadmium chloride (CdCl2-induced) alterations in the blood and testicles of rats. Methods: A total of 24 male rats (160 - 200 g), randomly assigned into 4 groups (A - D; n = 6), were used to investigate the claimed protective effect of AGEx on blood and spermatogenic tissues following CdCl2-intoxication in albino rats. The rats in Group A served as controls and were given 5 mg/mL of deionized water. Group B rats were given 300 mg/kg of AGEx. Group C rats were given 2 mg/kg of CdCl2. Rats in Group D first received 2 mg/kg of CdCl2, and 300 mg/kg of AGEx 2 h later. All treatments were done every 48 h for a period of six weeks. Results: CdCl2 administration to group C rats reduced (p < 0.05) haematocrit value (PCV), concentration of haemoglobin (Hb), red cells count (RBC), total leucocytes count (tWBC), eosinophil, neutrophil, testicular weights and sperm reserves; but elevated (p < 0.05) lymphocytes count compared with the controls. AGEx 300 mg/kg in group D rats significantly reversed (p < 0.05) the altered parameters compared with the controls. Conclusion: The results demonstrate that administration of aqueous Allium sativum (garlic) extract to male rats enhances spermatogenesis, and ameliorates testicular and haematological alterations induced by cadmium poisoning. Therefore, the spermatogenic principle in AGEx is a potential candidate for the clinical management of male infertility.

Terahertz Channel Propagation Phenomena, Measurement Techniques and Modeling for 6G Wireless Communication Applications: a Survey, Open Challenges and Future Research Directions

The Terahertz (THz) band (0.1-3.0 THz) spans a great portion of the Radio Frequency (RF) spectrum that is mostly unoccupied and unregulated. It is a potential candidate for application in Sixth-Generation (6G) wireless networks as it has the capabilities of satisfying the high data rate and capacity requirements of future wireless communication systems. Profound knowledge of the propagation channel is crucial in communication systems design which nonetheless, is still at its infancy as channel modeling at THz frequencies has been mostly limited to characterizing fixed Point-to-Point (P2P) scenarios up to 300 GHz. Provided the technology matures enough and models adapt to the distinctive characteristics of the THz wave, future wireless communications systems will enable a plethora of new use cases and applications to be realized in addition to delivering higher spectral efficiencies that would ultimately enhance the Quality-of-Service (QoS) to the end user. In this paper, we provide an insight into THz channel propagation characteristics, measurement capabilities and modeling methods along with recommendations that will aid in the development of future models in the THz band. We survey the most recent and important measurement campaigns and modeling efforts found in literature based on the use cases and system requirements identified. Finally, we discuss the challenges and limitations of measurements and modeling at such high frequencies and contemplate the future research outlook toward realizing the 6G vision.

Phloroglucinol as a Potential Candidate against Trypanosoma congolense Infection: Insights from In Vivo, In Vitro, Molecular Docking and Molecular Dynamic Simulation Analyses

Sub-Saharan Africa is profoundly challenged with African Animal Trypanosomiasis and the available trypanocides are faced with drawbacks, necessitating the search for novel agents. Herein, the chemotherapeutic potential of phloroglucinol on T. congolense infection and its inhibitory effects on the partially purified T. congolense sialidase and phospholipase A2 (PLA2) were investigated. Treatment with phloroglucinol for 14 days significantly (p < 0.05) suppressed T. congolense proliferation, increased animal survival and ameliorated anemia induced by the parasite. Using biochemical and histopathological analyses, phloroglucinol was found to prevent renal damages and splenomegaly, besides its protection against T. congolense-associated increase in free serum sialic acids in infected animals. Moreover, the compound inhibited bloodstream T. congolense sialidase via mixed inhibition pattern with inhibition binding constant (Ki) of 0.181 µM, but a very low uncompetitive inhibitory effects against PLA2 (Ki > 9000 µM) was recorded. Molecular docking studies revealed binding energies of −4.9 and −5.3 kcal/mol between phloroglucinol with modeled sialidase and PLA2 respectively, while a 50 ns molecular dynamics simulation using GROMACS revealed the sialidase-phloroglucinol complex to be more compact and stable with higher free binding energy (−67.84 ± 0.50 kJ/mol) than PLA2-phloroglucinol complex (−77.17 ± 0.52 kJ/mol), based on MM-PBSA analysis. The sialidase-phloroglucinol complex had a single hydrogen bond interaction with Ser453 while none was observed for the PLA2-phloroglucinol complex. In conclusion, phloroglucinol showed moderate trypanostatic activity with great potential in ameliorating some of the parasite-induced pathologies and its anti-anemic effects might be linked to inhibition of sialidase rather than PLA2.

Identification and Characterization of Wall-Associated Kinase (WAK) and WAK-like (WAKL) Gene Family in Juglans regia and Its Wild Related Species Juglans mandshurica

Wall-associated kinase (WAK) and WAK-like kinase (WAKL) are receptor-like kinases (RLKs), which play important roles in signal transduction between the cell wall and the cytoplasm in plants. WAK/WAKLs have been studied in many plants, but were rarely studied in the important economic walnut tree. In this study, 27 and 14 WAK/WAKL genes were identified in Juglans regia and its wild related species Juglans mandshurica, respectively. We found tandem duplication might play a critical role in the expansion of WAK/WAKL gene family in J. regia, and most of the WAK/WAKL homologous pairs underwent purified selection during evolution. All WAK/WAKL proteins have the extracellular WAK domain and the cytoplasmic protein kinase domain, and the latter was more conserved than the former. Cis-acting elements analysis showed that WAK/WAKL might be involved in plant growth and development, plant response to abiotic stress and hormones. Gene expression pattern analysis further indicated that most WAK/WAKL genes in J. regia might play a role in the development of leaves and be involved in plant response to biotic stress. Our study provides a new perspective for the evolutionary analysis of gene families in tree species and also provides potential candidate genes for studying WAK/WAKL gene function in walnuts.

Non-invasive and low-artifact in vivo brain imaging by using a scanning acoustic-photoacoustic dual mode microscopy

Photoacoustic imaging is a potential candidate for in-vivo brain imaging, whereas, its imaging performance could be degraded by inhomogeneous multi-layered media, consisted of scalp and skull. In this work, we propose a low-artifact photoacoustic microscopy (LAPAM) scheme, which combines conventional acoustic-resolution photoacoustic microscopy with scanning acoustic microscopy to suppress the reflection artifacts induced by multi-layers. Based on similar propagation characteristics of photoacoustic signals and ultrasonic echoes, the ultrasonic echoes can be employed as the filters to suppress the reflection artifacts to obtain low-artifact photoacoustic images. Phantom experiment is used to validate the effectiveness of this method. Furthermore, LAPAM is applied for in-vivo imaging mouse brain without removing the scalp and the skull. Experimental results show that the proposed method successfully achieves the low-artifact brain image, which demonstrates the practical applicability of LAPAM. This work might improve the photoacoustic imaging quality in many biomedical applications, which involve tissue with complex acoustic properties, such as brain imaging through scalp and skull.

DC performance and AC loss of sub-size MgB2 CICC conductor for fusion magnet application

Given the low price and relatively high transition temperature (39 K) of MgB2 conductor, MgB2-based superconductors are a potential candidate for the lower field fusion coils, such as Poloidal Field (PF) coils, Correction Coils (CC) and Feeders. However, to date, the application of MgB2 is limited to demonstrators in a low magnetic field of up to 5 T and at temperatures of up to 10 to 20 K, relying on cryogen-free, helium gas or liquid hydrogen cooling, which significantly reduce the cost of cryogenic systems. To demonstrate the feasibility and performance verification of large size MgB2 PF conductors based on ITER and CFETR requirements, a 4th-stage subsize MgB2 Cable-In-Conduit Conductor (CICC) cable sample is made at the Institute of Plasma Physics, Chinese Academy of Sciences (ASIPP). The CICC contains 96 in-situ MgB2 superconducting wires, manufactured by Western Superconducting Technology Ltd. (WST) and 48 copper wires. The critical current of the sub-size cables and MgB2 witness wires are examined with different background magnetic fields at 4.2 K. In addition, the AC loss is measured utilizing magnetization and calorimetric methods. To further clarify the influence of electromagnetic force on the AC loss performance, the cable sample is pressed transversely at room temperature and then inserted into a dipole magnet for AC loss measurement at 4.2 K. The critical current at 4.2 K of the subsize MgB2 CICC cable shows 20% degradation compared to the witness wires at 2 T background magnetic field. However, no further critical current degradation is visible during ramping up and down the magnetic field. The coupling loss time constant for 1 T background magnetic field amounts to 480 ms. No significant effect of the applied transverse stress on the coupling loss is observed between 0 and 10 MPa.

Sesamin inhibits cellular inflammation of microglial cells in the retina and alleviates diabetic retinopathy

Diabetic retinopathy (DR) is the most common micro-vascular complication of diabetes, and the leading cause of vision loss and blindness globally. Due to the unsatisfied outcome of current therapies, a novel strategy needs to be developed. BV2 microglial cells were treated with 25 natural compounds respectively in the stimulation of high glucose (HG), to screen for the potential candidate drug. Streptozotocin (STZ)- induced diabetic mice were injected with different doses of the candidate Sesamin every two days for one month. Then, its protective role and possible mechanism were evaluated. Sesamin was selected as candidate drug due to its inhibition on the secretion of tumor necrosis factor-α (TNFα) in the screen assay. Sesamin also dose-dependently inhibited mRNA levels of HG-induced inflammatory cytokines, including TNFα, interleukin (IL)-1β and IL-6, activated NF-κB signaling pathway, and reduced oxidative stress by decreasing reactive oxygen species levels and increasing antioxidant enzymes in the BV2 and primary retinal microglia. Additionally, Sesamin alleviated brain-retinal barrier breakdown by Evan's blue leakage assay and reduced inflammation in Streptozotocin-induced diabetic mice. In conclusion, Sesamin effectively inhibits HG-induced microglial inflammation in the retina both in vivo and in vitro, suggesting that Sesamin might serve as a candidate drug for DR treatment.