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ABSTRACTBackgroundConsidering the rise of new SARS-CoV-2 variants that have reduced the efficacy of COVID-19 vaccines, the development of new antiviral medications for the disease has become increasingly necessary. In this study, ASC10, a novel antiviral prodrug, was studied in a phase 1 trial in healthy Chinese participants.Research design and methodsPart 1 involved 60 participants, receiving 50–800 mg ASC10 or placebo twice daily for 5.5 days. Part 2, with 12 participants, explored ASC10 dosing in the fed/fasting states.ResultsASC10-A, the main pharmacologically active metabolite, rapidly appeared in plasma (Tmax: 1.00–2.00 h) and decreased (t1/2: 1.10–3.04 h) without accumulation. The Cmaxand area under the plasma concentration – time curve (AUC) of ASC10-A increased dose-dependently (50–800 mg BID) over 5.5 days, with no accumulation. The Tmaxwas slightly delayed in the fed state; however, the Cmaxand AUC were similar between the fed and fasting states. Adverse events (AEs) were comparable (ASC10/placebo, 66.7%) and mostly mild (95%).ConclusionASC10 was demonstrated to be safe and well tolerated and exhibited dose-proportional exposure and minimal food effects.Clinical trial registrationwww.clinicaltrials.govidentifier is NCT05523141.

Patients with IDH-wild-type glioblastomas have a poor five-year survival rate along with limited treatment efficacy due to immune cell (glioma-associated microglia and macrophages) infiltration promoting tumour growth and resistance. To enhance therapeutic options, our study investigated the unique RNA–RNA-binding protein complex LOC–DHX15. This complex plays a crucial role in driving immune cell infiltration and tumour growth by establishing a feedback loop between cancer and immune cells, intensifying cancer aggressiveness. Targeting this complex with blood–brain barrier-permeable small molecules improved treatment efficacy, disrupting cell communication and impeding cancer cell survival and stem-like properties. Focusing on RNA–RNA-binding protein interactions emerges as a promising approach not only for glioblastomas without the IDH mutation but also for potential applications beyond cancer, offering new avenues for developing therapies that address intricate cellular relationships in the body.

ABSTRACTBackground: To determine the safety and immunogenicity of a novel recombinant adenovirus type 5 vector based Ebola virus disease vaccine (Ad5-EBOV) in Africans in China.Methods: A phase 1, dose-escalation, open-label trial was conducted. 61 healthy Africans were sequentially enrolled, with 31 participants receiving one shot intramuscular injection and 30 participants receiving a double-shot regimen. Primary and secondary end points related to safety and immunogenicity were assessed within 28 d after vaccination. This study was registered with ClinicalTrials.gov (NCT02401373).Results: Ad5-EBOV is well tolerated and no adverse reaction of grade 3 or above was observed. 53 (86.89%) participants reported at least one adverse reaction within 28 d of vaccination. The most common reaction was fever and the mild pain at injection site, and there were no significant difference between these 2 groups. Ebola glycoprotein-specific antibodies appeared in all 61 participants and antibodies titers peaked after 28 d of vaccination. The geometric mean titres (GMTs) were similar between these 2 groups (1919.01 vs1684.70 P = 0.5562). The glycoprotein-specific T-cell responses rapidly peaked after 14 d of vaccination and then decreased, however, the percentage of subjects with responses were much higher in the high-dose group (60.00% vs9.68%, P = 0.0014). Pre-existing Ad5 neutralizing antibodies could significantly dampen the specific humoral immune response and cellular response to the vaccine.Conclusion: The application of Ad5-EBOV demonstrated safe in Africans in China and a specific GP antibody and T-cell response could occur 14 d after the first immunization. This acceptable safety profile provides a reliable basis to proceed with trials in Africa.

This paper studied the experimental procedures,, test equipment and test methodology of the melt spraying method. Meanwhile, according to performance index of lithium orthosilicate (Li4SiO4) ceramic pebbles to optimize the melt spraying method. Test analysis of the diameter of orthosilicate pebbles, degree of spheroid of orthosilicate pebbles, surface topography of orthosilicate pebbles, metallographic structure of orthosilicate pebbles, section morphology, crushing strength and phase composition. Results in this work indicate that the lithium orthosilicate (Li4SiO4) ceramic pebbles with a flat or even surface，porous internals, diameter of orthosilicate pebbles between 0.9~1.1mm,density of orthosilicate pebbles more than 90%T.D., the mean crushing strength is 25N, the degree of roundness is 1.027 can be obtained by the optimized melt spraying method. The optimization process provides a basis for obtaining the low cost and high performance of the lithium orthosilicate (Li4SiO4) ceramic pebbles.

In order to improve the robustness performance of SURF descriptor applied to stereo image matching, a new matching method is proposed. By using the ratio of minimum to second min Euclidean distance of corresponding features, we can get the coarse matching points aggregation. Then, the epipolar line is computed from calibration parameters. Correspondences are taken as correct correspondences, only if they fall into a small neighborhood of their epipolar line. Taken errors into account, the neighborhood is set (-3, 3). Using this restriction, we can get the correct matching points aggregation. The experimental results show that the correct matches and matching efficiency are better than RANSAC.

The mechanical behavior of rock interior creep fracture evolution and the state are difficult to observe. Combined with the laboratory rock compressive-creep test, the uniaxial creep numerical test based on FLAC3D was carried out. The different positions of the model displacement, stress, strain and damage zone were analyzed under different loading. The mechanical behavior of evolution process and characteristics of rock creep fracture were revealed under the different loading. The results show that: the data of numerical simulation and laboratory test are identical by comparing with laboratory test, and numerical test on simulated rock creep mechanical behavior evolution and methods is feasible and effective. It is a new method that can improve laboratory test of the microscopic creep, provide basis for evaluation of engineering rock mass stability too.

In order to improve the robustness and real time performance of SIFT based image registration algorithms, a new descriptor is proposed. We compute the new descriptor for a log-polar location grid with 3 bins in radial direction (the radius set to 3, 6 and 8) and 12 in angular direction, which results 36 location bins. Firstly, the 3×12 log-polar location grid is rotated to align its dominant orientation to a canonical direction in a different way with SIFT with less computational complexity. The keypoint dominant orientation and its orthogonal orientation is defined as the x and y directions of the descriptor's local coordinate system. After that a 3×3 grid is rotated to align the dominant orientation, and then the rotated 3×3 grid is translated to each pixel within the local 3×12 log-polar location grid. Therefore the local 3×12 log-polar location grid is rotated to align the dominant orientation and the rotation invariance is achieved. Secondly, compute the gradients in x and y directions using the rotated 3×3 grid for each pixel within the keypoint local neighborhood, so each pixel constitutes a gradient vector with 2 dimensions. Thirdly, use the distance from each pixel to the corresponding keypoint and a Gaussian function to assign a weight to the gradients, and then compute the gradients location histogram for the 36 location bins in the 3×12 log-polar grid. Finally, a descriptor with 72 dimensions is constituted and the descriptor is normalized to achieve illumination invariance. The experimental results show that the computational complexity of the new descriptor is reduced about 30% compared with the standard SIFT descriptor while the performance is favorably compared to the standard SIFT descriptor .

The effects of multiple-dose administration of tenofovir disoproxil fumarate (TDF) on the pharmacokinetics of morinidazole (MOR) were compared in healthy subjects. MOR exposure was similar, with an area under the curve from 0 h to infinity (AUC0-∞) treatment ratio for MOR+TDF/MOR of 1.01 (90% confidence interval, 0.97 to 1.06). No relevant differences were observed regarding plasma exposure of metabolites. Renal clearances of MOR and its metabolites were not affected by TDF.