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Abstract mRNA vaccines are regarded as a highly promising avenue for next‐generation cancer therapy. Nevertheless, the intricacy of production, inherent instability, and low expression persistence of linear mRNA significantly restrict their extensive utilization. Circular RNAs (circRNAs) offer a novel solution to these limitations due to their efficient protein expression ability, which can be rapidly generated in vitro without the need for extra modifications. Here, we present a novel neoantigen vaccine based on circRNA that induces a potent anti‐tumor immune response by expressing hepatocellular carcinoma‐specific tumor neoantigens. By cyclizing linearRNA molecules, we were able to enhance the stability of RNA vaccines and form highly stable circRNA molecules with the capacity for sustained protein expression. We confirmed that neoantigen‐encoded circRNA can promote dendritic cell (DC) activation and enhance DC‐induced T‐cell activation in vitro, thereby enhancing T‐cell killing of tumor cells. Encapsulating neoantigen‐encoded circRNA within lipid nanoparticles for in vivo expression has enabled the creation of a novel circRNA vaccine platform. This platform demonstrates superior tumor treatment and prevention in various murine tumor models, eliciting a robust T‐cell immune response. Our circRNA neoantigen vaccine offers new options and application prospects for neoantigen immunotherapy in solid tumors.

The ability to clone large DNA fragments from genomes is valuable for both basic and applied research, such as the construction of synthetic genomes, and the expression of biosynthetic gene clusters (BGCs) for natural product discovery. Here, we report a fast and efficient platform for the direct capture of genome DNAs, by combining CRISPR and Gibson assembly. We demonstrate this method with the ability of cloning large DNA fragments ranging from 30 to 77 kb from various host genomes, achieving a near 100% cloning fidelity for DNA fragments below 50 kb. We next demonstrate this method by the cloning of a 40 kb fragment from Streptomyces ceruleus A3(2), which is rich in BGCs for natural products; and used this method cloning the 40 kb fengycin synthetic gene cluster from B. subtilis 168, encoding for a class of peptides with bioactivity. This method provides efficient and simple opportunities for assembling large DNA constructs from distant sources.

This study aims to evaluate the effect of rhythm training in the early coordination development and to find out its role in the transfer of specific performance in young swimmers. Eighty young swimmers aged eight to twelve were divided randomly into a control group (CON, n = 40, M/F=17/23) or an experimental group (EXP, n = 40, M/F=19/21). A total of 72 swimmers completed all the training programs and tests included in this study (CON, n = 35, M/F=15/20; EXP, n = 37, M/F=16/21). The training programme lasted 12 weeks. During the study period, all groups participated in the same swimming training program with the control group participating six times a week, and the experimental group participating four times a week with an additional two rhythm trainings each week. The height, weight, walking backwards ability, jumping sideways ability, and 25 m freestyle were measured for each participant and an index of coordination was analyzed from recordings of the participant’s 25 m freestyle. The results indicated that participation in rhythm training resulted in improved general motor and swimming-specific coordination among the swimmers, but the results varied by number of years of sport-specific training experience. The swimmers with more training experience improved more in swimming-specific coordination but less in general motor coordination. This study strengthens the evidence for the effectiveness of early rhythm training in swimmers, indicating that it is feasible to design programs to address general and sport-specific coordination in young athletes.

Background Anthropometric characteristics are important factors that affect swimming performance. The aim of this study is to build a discriminant model using anthropometric factors to identify elite short-to-medium-distance freestyle swimmers through an adaptive Lasso approach. Methods The study recruited 254 swimmers (145 males and 109 females) who were divided them into elite (aged 17.9 ± 2.2 years, FINA points 793.8 ± 73.8) and non-elite (aged 17.1 ± 1.3 years, FINA points 560.6 ± 78.7) groups. Data for 73 variables were obtained, including basic information, anthropometric and derivative indicators. After filtering out highly correlated variables, 24 candidate variables were retained to be used in adaptive Lasso to select variables for prediction of elite swimmers. Deviance and area under the curve (AUC) were applied to assess the goodness of fit and prediction accuracy of the model, respectively. Results The adaptive Lasso selected 12 variables using the whole sample, with an AUC being 0.926 (95% CI [0.895–0.956]; P = 2.42 × 10−29). In stratified analysis by gender, nine variables were selected for male swimmers with an AUC of 0.921 (95% CI [0.880–0.963]; P = 8.82 × 10−17), and eight variables were for female swimmers with an AUC of 0.941 (95% CI [0.898–0.984]; P = 7.67 × 10−15). Conclusion The adaptive Lasso showed satisfactory performance in selecting anthropometric characteristics to identify elite swimmers. Additional studies with longitudinal data or data from other ethnicities are needed to validate our findings.

Abstract Background Grain size is one of the major determinants of cereal crop yield. As a class of plant polyhydroxysteroids, brassinosteroids (BRs) play essential roles in the regulation of grain size and plant architecture in rice. In a previous research, we cloned qGL3/OsPPKL1 encoding a protein phosphatase with Kelch-like repeat domains, which negatively regulates BR signaling and grain length in rice. Results Here, we screened qGL3-interacting proteins (GIPs) via yeast two-hybrid assay and analyzed the phenotypes of the T-DNA insertion mutants of GIPs. Among these mutants, mutant osak3 presents shorter grain length and dwarfing phenotype. OsAK3 encodes an adenylate kinase, which regulates grain size by controlling cell expansion of rice spikelet glume. Overexpression of OsAK3 resulted in longer grain length. OsAK3 interacts with qGL3 in vivo and in vitro. Lamina inclination, coleoptile elongation and root inhibition experiments showed that the osak3 mutant was less sensitive to exogenous brassinolide (BL) treatment. The transcriptional level of OsAK3 was up-regulated under BL induction. In addition, RNA-Seq data indicate that OsAK3 is involved in a variety of biological processes that regulate BR signaling and grain development in rice. Conclusions Our study reveals a novel BR signaling component OsAK3 in the regulation of grain length, and provides novel clues for uncovering the potential functions of OsAK3 in rice growth and development.

Dermatophytosis, an infectious disease caused by several fungi, can affect the hair, nails, and/or superficial layers of the skin and is of global significance. The most common dermatophytes in cats and dogs are Microsporum canis and Trichophyton mentagrophytes. Wood’s lamp examination, microscopic identification, and fungal culture are the conventional clinical diagnostic methods, while PCR (Polymerase Chain Reaction) and qPCR (Quantitative PCR) are playing an increasingly important role in the identification of dermatophytes. However, none of these methods could be applied to point-of-care testing (POCT). The recent development of the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) based diagnostic platform promises a rapid, accurate, and portable diagnostic tool. In this paper, we present a Cas12a-fluorescence assay to detect and differentiate the main dermatophytes in clinical samples with high specificity and sensitivity. The Cas12a-based assay was performed with a combination of recombinase polymerase amplification (RPA). The results could be directly visualized by naked eyes under blue light, and all tested samples were consistent with fungal culture and sequencing results. Compared with traditional methods, the RPA-Cas12a-fluorescence assay requires less time (about 30 min) and less complicated equipment, and the visual changes can be clearly observed with naked eyes, which is suitable for on-site clinical diagnosis.

Background: S100β is a biomarker of astroglial damage, the level of which is significantly increased following brain injury. However, the characteristics of S100β and its association with prognosis in patients with acute ischemic stroke following intravenous thrombolysis (IVT) remain unclear. Methods: Patients in this multicenter prospective cohort study were prospectively and consecutively recruited from 16 centers. Serum S100β levels were measured 24 h after IVT. National Institutes of Health Stroke Scale (NIHSS) and hemorrhagic transformation (HT) were measured simultaneously. NIHSS at 7 days after stroke, final infarct volume, and modified Rankin Scale (mRS) scores at 90 days were also collected. An mRS score ≥ 2 at 90 days was defined as an unfavorable outcome. Results: A total of 1072 patients were included in the analysis. The highest S100β levels (> 0.20 ng/mL) correlated independently with HT and higher NIHSS at 24 h, higher NIHSS at 7 days, larger final infarct volume, and unfavorable outcome at 3 months. The patients were divided into two groups based on dominant and non-dominant stroke hemispheres. The highest S100β level was similarly associated with the infarct volume in patients with stroke in either hemisphere (dominant: β 36.853, 95% confidence interval (CI) 22.659–51.048, P < 0.001; non-dominant: β 23.645, 95% CI 10.774–36.516, P = 0.007). However, serum S100β levels at 24 h were more strongly associated with NIHSS scores at 24 h and 3-month unfavorable outcome in patients with dominant hemisphere stroke (NIHSS: β 3.470, 95% CI 2.392–4.548, P < 0.001; 3-month outcome: odds ratio (OR) 5.436, 95% CI 2.936–10.064, P < 0.001) than in those with non-dominant hemisphere stroke (NIHSS: β 0.326, 95% CI − 0.735–1.387, P = 0.547; 3-month outcome: OR 0.882, 95% CI 0.538–1.445, P = 0.619). The association of S100β levels and HT was not significant in either stroke lateralization group. Conclusions: Serum S100β levels 24 h after IVT were independently associated with HT, infarct volume, and prognosis in patients with IVT, which suggests the application value of serum S100β in judging the degree of disease and predicting prognosis. [ABSTRACT FROM AUTHOR]