Complete genome analysis of Bacillus velezensis TS5 and its potential as a probiotic strain in mice

IntroductionIn recent years, a large number of studies have shown that Bacillus velezensis has the potential as an animal feed additive, and its potential probiotic properties have been gradually explored.MethodsIn this study, Illumina NovaSeq PE150 and Oxford Nanopore ONT sequencing platforms were used to sequence the genome of Bacillus velezensis TS5, a fiber-degrading strain isolated from Tibetan sheep. To further investigate the potential of B. velezensis TS5 as a probiotic strain, in vivo experiments were conducted using 40 five-week-old male specific pathogen-free C57BL/6J mice. The mice were randomly divided into four groups: high fiber diet control group (H group), high fiber diet probiotics group (HT group), low fiber diet control group (L group), and low fiber diet probiotics group (LT group). The H and HT groups were fed high-fiber diet (30%), while the L and LT groups were fed low-fiber diet (5%). The total bacteria amount in the vegetative forms of B. velezensis TS5 per mouse in the HT and LT groups was 1 × 109 CFU per day, mice in the H and L groups were given the same volume of sterile physiological saline daily by gavage, and the experiment period lasted for 8 weeks.ResultsThe complete genome sequencing results of B. velezensis TS5 showed that it contained 3,929,788 nucleotides with a GC content of 46.50%. The strain encoded 3,873 genes that partially related to stress resistance, adhesion, and antioxidants, as well as the production of secondary metabolites, digestive enzymes, and other beneficial nutrients. The genes of this bacterium were mainly involved in carbohydrate metabolism, amino acid metabolism, vitamin and cofactor metabolism, biological process, and molecular function, as revealed by KEGG and GO databases. The results of mouse tests showed that B. velezensis TS5 could improve intestinal digestive enzyme activity, liver antioxidant capacity, small intestine morphology, and cecum microbiota structure in mice.ConclusionThese findings confirmed the probiotic effects of B. velezensis TS5 isolated from Tibetan sheep feces and provided the theoretical basis for the clinical application and development of new feed additives

Honokiol Crosses BBB and BCSFB, and Inhibits Brain Tumor Growth in Rat 9L Intracerebral Gliosarcoma Model and Human U251 Xenograft Glioma Model

BACKGROUND: Gliosarcoma is one of the most common malignant brain tumors, and anti-angiogenesis is a promising approach for the treatment of gliosarcoma. However, chemotherapy is obstructed by the physical obstacle formed by the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). Honokiol has been known to possess potent activities in the central nervous system diseases, and anti-angiogenic and anti-tumor properties. Here, we hypothesized that honokiol could cross the BBB and BCSFB for the treatment of gliosarcoma. METHODOLOGIES: We first evaluated the abilities of honokiol to cross the BBB and BCSFB by measuring the penetration of honokiol into brain and blood-cerebrospinal fluid, and compared the honokiol amount taken up by brain with that by other tissues. Then we investigated the effect of honokiol on the growth inhibition of rat 9L gliosarcoma cells and human U251 glioma cells in vitro. Finally we established rat 9L intracerebral gliosarcoma model in Fisher 344 rats and human U251 xenograft glioma model in nude mice to investigate the anti-tumor activity. PRINCIPAL FINDINGS: We showed for the first time that honokiol could effectively cross BBB and BCSFB. The ratios of brain/plasma concentration were respectively 1.29, 2.54, 2.56 and 2.72 at 5, 30, 60 and 120 min. And about 10% of honokiol in plasma crossed BCSFB into cerebrospinal fluid (CSF). In vitro, honokiol produced dose-dependent inhibition of the growth of rat 9L gliosarcoma cells and human U251 glioma cells with IC(50) of 15.61 µg/mL and 16.38 µg/mL, respectively. In vivo, treatment with 20 mg/kg body weight of honokiol (honokiol was given twice per week for 3 weeks by intravenous injection) resulted in significant reduction of tumor volume (112.70±10.16 mm(3)) compared with vehicle group (238.63±19.69 mm(3), P = 0.000), with 52.77% inhibiting rate in rat 9L intracerebral gliosarcoma model, and (1450.83±348.36 mm(3)) compared with vehicle group (2914.17±780.52 mm(3), P = 0.002), with 50.21% inhibiting rate in human U251 xenograft glioma model. Honokiol also significantly improved the survival over vehicle group in the two models (P<0.05). CONCLUSIONS/SIGNIFICANCE: This study provided the first evidence that honokiol could effectively cross BBB and BCSFB and inhibit brain tumor growth in rat 9L intracerebral gliosarcoma model and human U251 xenograft glioma model. It suggested a significant strategy for offering a potential new therapy for the treatment of gliosarcoma

An Improved Kernelized Correlation Filter Algorithm for Underwater Target Tracking

To obtain accurate underwater target tracking results, an improved kernelized correlation filter (IKCF) algorithm is proposed to track the target in forward-looking sonar image sequences. Specifically, a base sample with a dynamically continuous scale is first applied to solve the poor performance of fixed-scale filters. Then, in order to prevent the filter from drifting when the target disappears and appears again, an adaptive filter update strategy with the peak to sidelobe ratio (PSR) of the response diagram is developed to solve the following target tracking errors. Finally, the experimental results show that the proposed IKCF can obtain accurate tracking results for the underwater targets. Compared to other algorithms, the proposed IKCF has obvious superiority and effectiveness

Efficient Treatment of Rheumatoid Arthritis by Degradable LPCE Nano-Conjugate-Delivered p65 siRNA

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases worldwide, causing severe cartilage damage and disability. Despite the recent progress made in RA treatment, limitations remain in achieving early and efficient therapeutic intervention. Advanced therapeutic strategies are in high demand, and siRNA-based therapeutic technology with a gene-silencing ability represents a new approach for RA treatment. In this study, we created a cationic delivery micelle consisting of low-molecular-weight (LMW) polyethylenimine (PEI)–cholesterol–polyethylene glycol (PEG) (LPCE) for small interfering RNA (siRNA)-based RA gene therapy. The carrier is based on LMW PEI and modified with cholesterol and PEG. With these two modifications, the LPCE micelle becomes multifunctional, and it efficiently delivered siRNA to macrophages with a high efficiency greater than 70%. The synthesized LPCE exhibits strong siRNA protection ability and high safety. By delivering nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 siRNA, the p65 siRNA/LPCE complex efficiently inhibited macrophage-based cytokine release in vitro. Local administration of the p65 siRNA/LPCE complex exhibited a fast and potent anti-inflammatory effect against RA in a mouse model. According to the results of this study, the functionalized LPCE micelle that we prepared has potential gene therapeutic implications for RA

A Study on a Single-Phase HTS Transformer with a Cylindrical Central Iron Core

During the past decade, a number of high temperature superconducting (HTS) transformer prototypes have been designed, and the majority of them are full-core transformers and air-core transformers. However, in this study, we proposed a new type of HTS transformer, where the iron core is different in that the limbs and connecting yokes are absent. To investigate the performance of this type of HTS transformer, we design and fabricate a single-phase HTS partial core transformer prototype using the secondary generation (2G) HTS GdBCO wires. The iron core is at room temperature, and the windings are immersed in liquid Nitrogen. The structures of primary and secondary windings are three layers connected in series and nine double pancakes connected in parallel, respectively. Fundamental characteristics are obtained by standard short-circuit, no-load and load tests in liquid Nitrogen temperature of 77 K. In addition, an equivalent circuit of the HTS transformer is proposed to analyze the characteristic of the transformer. The calculated values based on the equivalent circuit are consistent with that of experiment. The detailed results about the design of the HTS partial-core transformer, the experiment, and the equivalent circuit are presented and discussed in this study

A Study on a Single-Phase HTS Transformer with a Cylindrical Central Iron Core

During the past decade, a number of high temperature superconducting (HTS) transformer prototypes have been designed, and the majority of them are full-core transformers and air-core transformers. However, in this study, we proposed a new type of HTS transformer, where the iron core is different in that the limbs and connecting yokes are absent. To investigate the performance of this type of HTS transformer, we design and fabricate a single-phase HTS partial core transformer prototype using the secondary generation (2G) HTS GdBCO wires. The iron core is at room temperature, and the windings are immersed in liquid Nitrogen. The structures of primary and secondary windings are three layers connected in series and nine double pancakes connected in parallel, respectively. Fundamental characteristics are obtained by standard short-circuit, no-load and load tests in liquid Nitrogen temperature of 77 K. In addition, an equivalent circuit of the HTS transformer is proposed to analyze the characteristic of the transformer. The calculated values based on the equivalent circuit are consistent with that of experiment. The detailed results about the design of the HTS partial-core transformer, the experiment, and the equivalent circuit are presented and discussed in this study