Telomere Length and Male Fertility

Over the past decade, telomeres have attracted increasing attention due to the role they play in human fertility. However, conflicting results have been reported on the possible association between sperm telomere length (STL) and leukocyte telomere length (LTL) and the quality of the sperm parameters. The aim of this study was to run a comprehensive study to investigate the role of STL and LTL in male spermatogenesis and infertility. Moreover, the association between the sperm parameters and 11 candidate single nucleotide polymorphisms (SNPs), identified in the literature for their association with telomere length (TL), was investigated. We observed no associations between sperm parameters and STL nor LTL. For the individual SNPs, we observed five statistically significant associations with sperm parameters: considering a p < 0.05. Namely, ACYP2˗rs11125529 and decreased sperm motility (p = 0.03); PXK˗rs6772228 with a lower sperm count (p = 0.02); NAF1˗rs7675998 with increased probability of having abnormal acrosomes (p = 0.03) and abnormal flagellum (p = 0.04); ZNF208˗rs8105767 and reduction of sperms with normal heads (p = 0.009). This study suggests a moderate involvement of telomere length in male fertility; however, in our analyses four SNPs were weakly associated with sperm variables, suggesting the SNPs to be pleiotropic and involved in other regulatory mechanisms independent of telomere homeostasis, but involved in the spermatogenic process.     

Targeted editing of intronic-splicing silencer enhancement of SMN2 Exon 7 inclusion by CRISPR/Case 9

Spinal muscular atrophy (SMA) is an autosomal recessive hereditary neuromuscular disease. Exon 7 and 8 of survival of motor neuron 1 (SMN1) gene or only exon 7 homology deletion leads to the failure to produce a full-length SMN gene. The copy number of SMN2 gene with high homology of SMN1 affects the degree of disease and was the target gene for targeting therapy, in which splicing silencer in intron 7 was the key to suppress the inclusion of exon 7. In this study, we projected to use CRISPR/Case 9 for the targeted editing of intronic-splicing silencer (ISS) sequence to promote the inclusion of SMN2 exon 7 and increase the production of SMN2 full-length (FL) gene expression. It happens that there was a protospacer adjacent motif (PAM) at one end of the ISS sequence according to the design of sgRNA. The recombinant vector of sgRNA HSMN2 CRISPR/Case 9 was constructed and transfected into HEK293 cells. Sequencing results showed that the ISS sequence could be edited accurately and targeting in the predicted direction, in which deleting small fragments, inserting small amounts and mutation. Quantitative analysis of RT-PCR products by restriction enzyme of DdeI digestion showed that the FL of SMN2 increased by 8% (P < 0.05). In the primary cultured chondrocytes of SMA mice, in which sgRNA HSMN2 CRISPR/Case9 recombinant vector transfection could increase the SMN2 FL gene by 23% (P < 0.05) and significantly improve SMN protein levels (P < 0.05). CRISPR/Case 9 is an effective tool for gene editing and therapy of hereditary diseases, but it is rarely reported in the treatment of SMA diseases. This study shows that CRISPR/Case 9 was first used for the precision target of ISS sequence editing, which can effectively promote the production of SMN2 FL gene expressions, in which there was an important clinical reference value.     

Decoding the Roles of Long Noncoding RNAs in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. HCC is associated with several etiological factors, including HBV/HCV infections, cirrhosis, and fatty liver diseases. However, the molecular mechanism underlying HCC development remains largely elusive. The advent of high-throughput sequencing has unveiled an unprecedented discovery of a plethora of long noncoding RNAs (lncRNAs). Despite the lack of coding capacity, lncRNAs have key roles in gene regulation through interacting with various biomolecules. It is increasingly evident that the dysregulation of lncRNAs is inextricably linked to HCC cancer phenotypes, suggesting that lncRNAs are potential prognostic markers and therapeutic targets. In light of the emerging research in the study of the regulatory roles of lncRNAs in HCC, we discuss the association of lncRNAs with HCC. We link the biological processes influenced by lncRNAs to cancer hallmarks in HCC and describe the associated functional mechanisms. This review sheds light on future research directions, including the potential therapeutic applications of lncRNAs.     

Birth traits of Holstein calves compared with Holstein,Jersey, Montbéliarde,Normande, and Viking Red-sired crossbred calves

Holstein (HO) calves, 3-breed crossbred calves of Montbéliarde, Viking Red, and HO (MVH), and 3-breed crossbred calves of Normande, Jersey, and Viking Red (NJV) were compared for gestation length (GL), calf weight at birth (CW), calving difficulty (CD), and stillbirth (SB) in 2 research herds at the University of Minnesota. Calves were born from January 2009 to December 2019. For the St. Paul and Morris herds, HO calves (n = 1,121) were compared with MVH calves (n = 1,393) from primiparous and multiparous cows. For the single herd analysis at Morris, HO calves (n = 476), MVH calves (n = 922), and NJV calves (n = 405) were compared from primiparous and multiparous cows. Primiparous and multiparous births were analyzed separately because multiparous cows had multiple births, and CD and SB are likely different traits for primiparous and multiparous cows. Statistical analysis of GL, CW, CD, and SB included fixed effects of sex of calf, herd, breed group of calf, and year-season of calving. For the St. Paul and Morris herds, HO calves from primiparous (278 d) and multiparous (279 d) HO cows had shorter GL compared with MVH calves from primiparous (280 d) and multiparous (282 d) crossbred cows. The HO calves (39.4 and 43.2 kg, respectively) from primiparous and multiparous HO cows had lower CW compared with MVH calves (40.3 and 44.3 kg, respectively) from primiparous and multiparous crossbred cows. Calving difficulty and SB were not different for HO and MVH calves from primiparous and multiparous cows. For the single herd analysis at Morris, HO calves (278 and 279 d, respectively) from primiparous and multiparous HO cows had shorter GL compared with MVH calves (281 and 282 d, respectively) and NJV calves (282 and 282 d, respectively) from primiparous and multiparous crossbred cows. The CW of HO calves (38.6 and 42.0 kg, respectively) from primiparous and multiparous HO cows was lower compared with MVH calves (39.7 and 42.9 kg, respectively), but higher compared with NJV calves (35.1 and 38.0 kg, respectively) from primiparous and multiparous crossbred cows. Calving difficulty and SB did not differ for HO, MVH, and NJV calves from primiparous and multiparous cows. The longer GL for crossbred calves and higher CW for MVH calves did not increase CD and SB for primiparous and multiparous cows. Dairy producers may implement 3-breed rotational crossbreeding systems that include the HO, Jersey, Normande, Montbéliarde, and Viking Red breeds, and some breeds may increase GL and CW without an increase in CD and SB.     

Deterministic and probabilistic ship pitch prediction using a multi-predictor integration model based on hybrid data preprocessing,reinforcement learning and improved QRNN

The deterministic and probabilistic prediction of ship motion is important for safe navigation and stable real-time operational control of ships at sea. However, the volatility and randomness of ship motion, the non-adaptive nature of single predictors and the poor coverage of quantile regression pose serious challenges to uncertainty prediction, making research in this field limited. In this paper, a multi-predictor integration model based on hybrid data preprocessing, reinforcement learning and improved quantile regression neural network (QRNN) is proposed to explore the deterministic and probabilistic prediction of ship pitch motion. To validate the performance of the proposed multi-predictor integrated prediction model, an experimental study is conducted with three sets of actual ship longitudinal motions during sea trials in the South China Sea. The experimental results indicate that the root mean square errors (RMSEs) of the proposed model of deterministic prediction are 0.0254°, 0.0359°, and 0.0188°, respectively. Taking series #2 as an example, the prediction interval coverage probabilities (PICPs) of the proposed model of probability predictions at 90%, 95%, and 99% confidence levels (CLs) are 0.9400, 0.9800, and 1.0000, respectively. This study signifies that the proposed model can provide trusted deterministic predictions and can effectively quantify the uncertainty of ship pitch motion, which has the potential to provide practical support for ship early warning systems.     

基于多通道的ICU脑血管疾病死亡风险预测模型

死亡风险预测指根据病人临床体征监测数据来预测未来一段时间的死亡风险。对于ICU病患，通过死亡风险预测可以有针对性地对病人做出临床诊断，以及合理安排有限的医疗资源。基于临床使用的MEWS和Glasgow昏迷评分量表，针对ICU病人临床监测的17项生理参数，提出一种基于多通道的ICU脑血管疾病死亡风险预测模型。引入多通道概念应用于BiLSTM模型，用于突出每个生理参数对死亡风险预测的作用。采用Attention机制用于提高模型预测精度。实验数据来自MIMIC [Ⅲ]数据库，从中提取3?080位脑血管疾病患者的16?260条记录用于此次研究，除了六组超参数实验之外，将所提模型与LSTM、Multichannel-BiLSTM、逻辑回归（logistic regression）和支持向量机（support vector machine, SVM）四种模型进行了对比分析，准确率Accuracy、灵敏度Sensitive、特异性Specificity、AUC-ROC和AUC-PRC作为评价指标，实验结果表明，所提模型性能优于其他模型，AUC值达到94.3%。     

Functional Dysregulations in CA1 Hippocampal Networks of a 3-Hit Mouse Model of Schizophrenia

For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility—partial deletion of the MAP6 gene, early-life stress—maternal separation, and pharmacological treatment—chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABA_A receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis.     

Influence of thermal runaway in styrene–acrylonitrile bulk copolymerization revealed by computational fluid dynamics modeling

The computational fluid dynamics (CFD) and kinetic-based moment methods coupled approach is adopted to simulate the bulk copolymerization of styrene–acrylonitrile (SAN) in a stirred tank reactor. Numerical simulations are carried out to investigate the impacts of impeller speed, monomer ratio, initiator ratio, and initial reaction temperature on the copolymerization process and product properties. Particularly, the Chaos theory is selected as a criterion for evaluating the occurrence of the thermal runaway. The Flory's and Stockmayer's distributions are employed to calculate chain length distribution and copolymer composition distribution of copolymer. The simulation results highlight that the appearance of thermal runaway can be postponed by properly increasing the rotation speed, decreasing the initiator loadings, initial acrylonitrile contents and initial reactor temperature. Furthermore, significant differences exist in the product properties that predicted by the ideal and non-ideal models, which demonstrates that the temperature heterogeneity plays a crucial role in SAN copolymerization. This study could offer references for the safe operation and design of polymerization processes.     

基于深度学习的彩色以及近红外图像去马赛克

单传感器捕获的彩色-近红外（RGB-NIR）图像存在光谱干扰，从而导致重建出的标准彩色图像（RGB）图像与近红外（NIR）图像存在色彩失真以及细节信息模糊。针对这个问题提出一种基于深度学习的去马赛克方法，通过引入跳远连接与稠密连接解决了梯度消失和梯度弥散问题，使得网络更容易训练，并且提升了网络的拟合能力。首先，用浅层特征提取层提取了马赛克图像的像素相关性以及通道相关性等低级特征；然后，将得到的浅层特征图输入到连续多个的残差稠密块以提取专门针对去马赛克的高级语义特征；其次，为充分利用低级特征与高级特征，将多个残差稠密块提取到的特征进行组合；最后，通过全局跳远连接恢复最终的RGB-NIR图像。在深度学习框架Tensorflow上使用公共的图像与视觉表示组（IVRG）数据集、有植被的户外多光谱图像（OMSIV）数据集和森林（Forest）三个公开数据集进行实验。实验结果表明，所提方法优于基于多级自适应残差插值、基于卷积卷积和神经神经网络以及基于深度残差U型网络的主流的RGB-NIR图像去马赛克方法。     

热处理对挤压态Mg-6Gd-5Y-1Zn合金组织与性能的影响

通过对Mg-6Gd-5Y-1Zn(质量分数,%)合金在固溶和时效处理状态下显微组织和力学性能的研究发现,α-Mg基体、沿挤压方向分布的条状18R-LPSO相、少量的Mg₂₄(GdYZn)₅ 相以及细层片状的14H-LPSO相构成了挤压态合金的组成相。挤压态合金经固溶(T4)处理后,一部分18R-LPSO相溶入基体,并且基体中的14H-LPSO相伸长同时粗化。挤压态合金经过固溶加时效(T6)处理后,大量β′相从α-Mg基体中析出。T6态合金的室温力学性能最好,其屈服强度、抗拉强度及伸长率分别为272 MPa、406 MPa和6.1%。β′相沉淀也发生在挤压态合金的直接人工时效(T5)处理过程,但相比于T6处理,14H-LPSO相和β′相在基体中的体积分数均偏低。