Rapid multiple protein sequence search by parallel and heterogeneous computation.

MOTIVATION: Protein sequence database search and multiple sequence alignment generation is a fundamental task in many bioinformatics analyses. As the data volume of sequences continues to grow rapidly, there is an increasing need for efficient and scalable multiple sequence query algorithms for super-large databases without expensive time and computational costs. RESULTS: We introduce Chorus, a novel protein sequence query system that leverages parallel model and heterogeneous computation architecture to enable users to query thousands of protein sequences concurrently against large protein databases on a desktop workstation. Chorus achieves over 100× speedup over BLASTP without sacrificing sensitivity. We demonstrate the utility of Chorus through a case study of analyzing a ∼1.5-TB large-scale metagenomic datasets for novel CRISPR-Cas protein discovery within 30 min. AVAILABILITY AND IMPLEMENTATION: Chorus is open-source and its code repository is available at https://github.com/Bio-Acc/Chorus.

Testicular volume is a noninvasive predictor of sperm retrieval failure in idiopathic nonobstructive azoospermia.

We investigated the prognostic importance of noninvasive factors in predicting sperm retrieval failure in idiopathic nonobstructive azoospermia (iNOA). We studied 193 patients with nonobstructive azoospermia who underwent microsurgical testicular sperm extraction. The Chi-square test and Mann-Whitney U tests for clinical parameters and seminiferous tubule distribution were used for between-group comparisons. A logistic regression analysis was conducted to identify predictors of retrieval failure. Area under the receiver operating characteristic curve for each variable was evaluated, and the net clinical benefit was calculated using a clinical decision curve. Patients with iNOA had a lower sperm retrieval rate than those with known causes. Moreover, testicular volume was an independent factor affecting sperm extraction outcomes (odds ratio = 0.79, P < 0.05). The testicular volume cut-off value was 6.5 ml (area under the curve: 0.694). The patients with iNOA were categorized into two groups on the basis of the distribution of seminiferous tubules observed. The sperm retrieval rate and testicular volume were significantly different between the groups with a uniform or heterogeneous tubule distribution. There was also a significant association between a uniform tubule distribution and testicular volume. In conclusion, a testicular volume of more than 6.5 ml effectively predicts microsurgical testicular sperm extraction failure due to a uniform tubule distribution in patients with iNOA.

Efficacy of various surgical approaches in treating hematospermia using transurethral seminal vesiculoscopy.

PURPOSE: To explore the efficacy of different approaches of seminal vesiculoscopy surgery and the predictive factors of good treatment outcome. MATERIALS AND METHODS: A retrospective analysis of 68 patients who underwent seminal vesiculoscopy for hematospermia in our hospital from January 2015 to January 2021. According to different surgical approaches, they were divided into three groups: natural ejaculatory ducts (method A, 45 cases), assisted transurethral resection/incision of ejaculatory ducts (method B, 14 cases), fenestration in prostatic utricle (method C, 9 cases). We analyzed the recurrence rate of the three surgical approaches and the predictive factors of treatment efficacy. RESULTS: The total recurrence rate after the seminal vesiculoscopy for hematospermia in this group was 32.35%. The postoperative recurrence rates of the three methods were 24.44% for method A, 50.00% for method B and 44.44% for method C, and there was no significant difference among the three methods (P > 0.05). The data of five predictors of 45 cases in method A group were included in the Univariate Logistic analysis, the results suggest that whether complicated with seminal tract stones/cysts was an effective predictor (OR 0.250, P = 0.022), which was still an effective predictor in the Multivariate Logistic analysis model (OR 0.244, P = 0.010). CONCLUSIONS: The Transurethral seminal vesiculoscopy technique demonstrates a low postoperative recurrence rate in treating hematospermia. Among the various approaches, the intraoperative use of natural orifices through the ejaculatory duct exhibits the lowest recurrence rate. Additionally, seminal tract stones/cysts effectively predict favorable postoperative outcomes.

In Situ Nano-SiO2 Electrospun Polyethylene-Oxide-Based Nano-Fiber Composite Solid Polymer Electrolyte for High-Performance Lithium-Ion Batteries.

Polyethylene oxide (PEO)-based composite polymer electrolytes (CPEs) containing in situ SiO2 fillers are prepared using an electrostatic spinning method at room temperature. Through the in situ hydrolysis of tetraethyl silicate (TEOS), the generated SiO2 nanospheres are uniformly dispersed in the PEO matrix to form a 3D ceramic network, which enhances the mechanical properties of the electrolyte as a reinforcing phase. The interaction between SiO2 nanospheres and PEO chains results in chemical bonding with a decrease in the crystallinity of the PEO matrix, as well as the complexation strength of PEO chains with lithium ions during the hydrolysis process. Meanwhile, the addition of SiO2 nanospheres can disturb the orderliness of PEO chain segments and further suppress the crystallization of the PEO matrix. Therefore, improved mechanical/electrochemical properties can be obtained in the as-spun electrolyte with the unique one-dimensional high-speed ion channels. The electrospun CPE with in situ SiO2 (10 wt%, ca. 45 nm) has a higher ionic conductivity of 1.03 × 10-3 S cm-1 than that of the mechanical blending one. Meanwhile, the upper limit of the electrochemical stability window is up to 5.5 V versus Li+/Li, and a lithium-ion migration number can be of up to 0.282 at room temperature. In addition, in situ SiO2 electrospun CPE achieves a tensile strength of 1.12 MPa, elongation at the break of 488.1%, and it has an excellent plasticity. All in all, it is expected that the electrospun CPE prepared in this study is a promising one for application in an all-solid-state lithium-ion battery (LIB) with a high energy density, long life cycle, and high safety.

Deep-learning with synthetic data enables automated picking of cryo-EM particle images of biological macromolecules.

MOTIVATION: Single-particle cryo-electron microscopy (cryo-EM) has become a powerful technique for determining 3D structures of biological macromolecules at near-atomic resolution. However, this approach requires picking huge numbers of macromolecular particle images from thousands of low-contrast, high-noisy electron micrographs. Although machine-learning methods were developed to get rid of this bottleneck, it still lacks universal methods that could automatically picking the noisy cryo-EM particles of various macromolecules. RESULTS: Here, we present a deep-learning segmentation model that employs fully convolutional networks trained with synthetic data of known 3D structures, called PARSED (PARticle SEgmentation Detector). Without using any experimental information, PARSED could automatically segment the cryo-EM particles in a whole micrograph at a time, enabling faster particle picking than previous template/feature-matching and particle-classification methods. Applications to six large public cryo-EM datasets clearly validated its universal ability to pick macromolecular particles of various sizes. Thus, our deep-learning method could break the particle-picking bottleneck in the single-particle analysis, and thereby accelerates the high-resolution structure determination by cryo-EM. AVAILABILITY AND IMPLEMENTATION: The PARSED package and user manual for noncommercial use are available as Supplementary Material (in the compressed file: parsed_v1.zip). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Structural insights into DNA cleavage activation of CRISPR-Cas9 system.

CRISPR-Cas9 technology has been widely used for genome engineering. Its RNA-guided endonuclease Cas9 binds specifically to target DNA and then cleaves the two DNA strands with HNH and RuvC nuclease domains. However, structural information regarding the DNA cleavage-activating state of two nuclease domains remains sparse. Here, we report a 5.2 Å cryo-EM structure of Cas9 in complex with sgRNA and target DNA. This structure reveals a conformational state of Cas9 in which the HNH domain is closest to the DNA cleavage site. Compared with two known HNH states, our structure shows that the HNH active site moves toward the cleavage site by about 25 and 13 Å, respectively. In combination with EM-based molecular dynamics simulations, we show that residues of the nuclease domains in our structure could form cleavage-compatible conformations with the target DNA. Together, these results strongly suggest that our cryo-EM structure resembles a DNA cleavage-activating architecture of Cas9.

Consecutive ultra-short-term heart rate variability to track dynamic changes in autonomic nervous system during and after exercise.

OBJECTIVE: Quantitative measurement of the dynamic changes in autonomic nervous system (ANS) during and after exercise has great significance in clinical, sports training and other fields. A consecutive ultra-short-term (30 s, UST) heart rate variability (HRV) method was proposed to track the exercise-induced autonomic control of heart rate (HR). APPROACH: Twenty-three healthy young men participated in the study. The first four stages of the Modified Bruce Protocol (S0-S3) were performed. Six HRV indices, i.e. HF (power of high frequency ranged from 0.15 to 0.4 Hz), LF (power of low frequency ranged from 0.04 to 0.15 Hz), LF/HF, SD1 and SD2 of Poincaré plot, and SD2/SD1, over 30 s were calculated every 5 s over 3 min RR time series during, as well as after, exercise. MAIN RESULTS: The results showed that during exercise, SD1, SD2, HF and LF dropped down quickly and tended to stabilize. Particularly, SD1 and HF showed a slight upward trend in the lower three stages while the declining time of SD2 in S3 lasted longer than the other stages. SD2/SD1 increased rapidly first and then decreased slowly. The values of SD2/SD1 in S3 remained higher than those in the other stages. After exercise, SD1, SD2, HF and LF kept increasing first and then declined slowly or fluctuated with decaying amplitudes. SD2/SD1 increased initially, then decreased and fluctuated slightly. SIGNIFICANCE: Compared with the indices in frequency domain, the Poincaré indices were more sensitive and accurate in UST measurement of ANS during exercise. The results demonstrated that the UST method could characterize the dynamic changing tendency of ANS during and after exercise and quantify the differences of changes in ANS induced by exercise with different intensities. In particular, the vagal branch functioned dominantly in controlling HR in S0 but the effect of the sympathetic branch on HR enhanced with the increase of exercise intensity. In addition, the transient changes of ANS related with the sudden onset of exercise could also be reflected, despite perhaps being limited by the computation window width to some extent. Thus, the consecutive UST Poincaré indices could provide a feasible and simple method to measure quantitatively the exercise-induced dynamic changes in ANS.