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.     

Inhibition of RANKL-Induced Osteoclastogenesis by Novel Mutant RANKL

Background: Recently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK–RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.; Methods: The effects of point-mutated RANKL (mRANKL-MT) on osteoclastogenesis were assessed by tartrate-resistant acid phosphatase (TRAP), resorption pit formation, quantitative real-time polymerase chain reaction (qPCR), western blot, NFATc1 nuclear translocation, micro-CT and histomorphological assay in wild type RANKL (mRANKL-WT)-induced in vitro and in vivo experimental mice model. Results: As a proof of concept, treatment with the mutant RANKL led to the stimulation of GSK-3β phosphorylation, as well as the inhibition of NFATc1 translocation, mRNA expression of TRAP and OSCAR, TRAP activity, and bone resorption, in RANKL-induced mouse models; and Conclusions: The results of our study demonstrate that the mutant RANKL can be used as a therapeutic agent for osteoporosis by inhibiting RANKL-induced osteoclastogenesis via comparative inhibition of RANKL. Moreover, the mutant RANKL was found to lack the toxic side effects of most osteoporosis treatments.     

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.     

Nacre-Inspired,Liquid Metal-Based Ultrasensitive Electronic Skin by Spatially Regulated Cracking Strategy

The realization of liquid metal-based wearable systems will be a milestone toward high-performance, integrated electronic skin. However, despite the revolutionary progress achieved in many other components of electronic skin, liquid metal-based flexible sensors still suffer from poor sensitivity due to the insufficient resistance change of liquid metal to deformation. Herein, a nacre-inspired architecture composed of a biphasic pattern (liquid metal with Cr/Cu underlayer) as “bricks” and strain-sensitive Ag film as “mortar” is developed, which breaks the long-standing sensitivity bottleneck of liquid metal-based electronic skin. With 2 orders of magnitude of sensitivity amplification while maintaining wide (>85%) working range, for the first time, liquid metal-based strain sensors rival the state-of-art counterparts. This liquid metal composite features spatially regulated cracking behavior. On the one hand, hard Cr cells locally modulate the strain distribution, which avoids premature cut-through cracks and prolongs the defect propagation in the adjacent Ag film. On the other hand, the separated liquid metal cells prevent unfavorable continuous liquid-metal paths and create crack-free regions during strain. Demonstrated in diverse scenarios, the proposed design concept may spark more applications of ultrasensitive liquid metal-based electronic skins, and reveals a pathway for sensor development via crack engineering.     

Single image dehazing using a new color channel

Images with hazy scene suffer from low-contrast, which reduces the visible quality of the scene, thus making object detection a more challenging task. Low-contrast can result from foggy weather conditions during image acquisition. Dehazing is a process of removal of haze from the photography of a hazy scene. Single-image dehazing based on dark channel priors are well-known techniques in this field. However, the performance of such techniques is limited to priors or constraints. Moreover, this type of method fails when images have sky-region. So, a method is proposed, which can restore the visibility of hazy images. First, a hazy image is divided into blocks of size 32 × 32, then the score of each block is calculated to select a block having the highest score. Atmospheric light is calculated from the selected block. A new color channel is considered to remove atmospheric scattering, obtained channel value and atmospheric light are then used to calculate the transmission map in the second step. Third, radiance is computed using a transmission map and atmospheric light. The illumination scaling factor is adopted to enhance the quality of a dehazed image in the final step. Experiments are performed on six datasets namely, I-HAZE, O-HAZE, BSDS500, FRIDA, RESIDE dataset and natural images from Google. The proposed method is compared against 11 state-of-the-art methods. The performance is analyzed using fourteen quantitative evaluation metrics. All the results demonstrate that the proposed method outperforms 11 state-of-the-art methods in most of the cases.     

自重湿陷性黄土地基预钻孔浸水处理的可靠度设计方法

为解决传统预浸水法存在的浸水时间长、浸水处理范围难以确定等不足,基于土体中水分运移规律,依据可靠度理论、极限状态设计方法及复合 Poisson 过程原理,提出一种消除黄土湿陷性的处理浸水方法——预钻孔浸水法。给出了利用预钻孔浸水法对自重湿陷性黄土地基进行浸水时,水平向及竖直向浸水影响范围的确定模型;在此基础上结合达西定律给出了浸水孔设计参数如孔深、孔间距及浸水孔个数的确定方法。结合铜川某工程,设计进行了现场预钻孔浸水试验,对该方法的合理性进行了验证,并通过现场钻探、现场勘探、室内湿陷性试验等方法对该方法的处理效果进行了评价。该浸水方法具有浸水时间短、浸水影响范围可根据浸水孔布设进行控制等优点,且浸水处理效果良好,完全符合施工要求。     

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.     

剪切解络-超滤分离金属关键指标预测与验证

根据剪切解络-超滤过程中金属离子的动态浓度关系和质量守恒定律,采用CodeBlocks17.12软件编写程序,建立了剪切解络-超滤工艺关键指标预测模型,实现了金属离子浓度、回收率、体积稀释倍数等指标的预测,并用实验加以验证。依次在转速800 r/min、1 400 r/min、3 000 r/min下回收模拟废水中43 μg/L的Co²⁺、995 μg/L的Ni²⁺和88 μg/L的La³⁺,3种金属的回收率均达99.8%以上时,超滤过程体积稀释倍数的预测值分别为7.0、7.5、5.75,实验值分别为7.5、7.25、6.25,可见预测值与实验值基本一致。本模型对研究方案制定和调整有实际指导意义。