Precise Correction of Lhcgr Mutation in Stem Leydig Cells by Prime Editing Rescues Hereditary Primary Hypogonadism in Mice.

Hereditary primary hypogonadism (HPH), caused by gene mutation related to testosterone synthesis in Leydig cells, usually impairs male sexual development and spermatogenesis. Genetically corrected stem Leydig cells (SLCs) transplantation may provide a new approach for treating HPH. Here, a novel nonsense-point-mutation mouse model (LhcgrW495X ) is first generated based on a gene mutation relative to HPH patients. To verify the efficacy and feasibility of SLCs transplantation in treating HPH, wild-type SLCs are transplanted into LhcgrW495X mice, in which SLCs obviously rescue HPH phenotypes. Through comparing several editing strategies, optimized PE2 protein (PEmax) system is identified as an efficient and precise approach to correct the pathogenic point mutation in Lhcgr. Furthermore, delivering intein-split PEmax system via lentivirus successfully corrects the mutation in SLCs from LhcgrW495X mice ex vivo. Gene-corrected SLCs from LhcgrW495X mice exert ability to differentiate into functional Leydig cells in vitro. Notably, the transplantation of gene-corrected SLCs effectively regenerates Leydig cells, recovers testosterone production, restarts sexual development, rescues spermatogenesis, and produces fertile offspring in LhcgrW495X mice. Altogether, these results suggest that PE-based gene editing in SLCs ex vivo is a promising strategy for HPH therapy and is potentially leveraged to address more hereditary diseases in reproductive system.

Evolution trend of soil fertility in tobacco-planting area of Chenzhou, Hunan Province, China.

In this study, the data of fertility indicators of soil samples (0-20 cm) in 1980s, 2000 and 2015 in Chenzhou city were used, and the soil integrated fertility index (IFI) was calculated. The results showed that the soil pH was decreased, total nitrogen (TN), organic matter (OM), available phosphorus (AP) and potassium (AK), exchangeable calcium (Ca2+), magnesium (Mg2+) and available copper (Cu) contents were increased, total phosphorus (TP), available sulfur (S) and water-soluble chlorine (Cl-) contents were decreased, total potassium (TK), available boron (B), iron (Fe), manganese (Mn) and zinc (Zn) were decreased first and then increased. In 2015, most of the fields were higher in pH, OM, TN, AN, AK, Ca2+, Mg2+, S, Fe, Mn, Cu and Zn, suitable in B, but lower in TP, AP, TK, available molybdenum (Mo) and Cl-. Most of the fields were in the middle grade of IFI in 2000 and 2015, and the mean IFI increased from 0.492 to 0.556 from 2000 to 2015. Thus, for soil improvement, more attention should be paid to adjust soil pH, reduce the application of organic, nitrogen and calcium fertilizers, while increase the fertilizer application of other nutrients.

Dynamic Embedding Projection-Gated Convolutional Neural Networks for Text Classification.

Text classification is a fundamental and important area of natural language processing for assigning a text into at least one predefined tag or category according to its content. Most of the advanced systems are either too simple to get high accuracy or centered on using complex structures to capture the genuinely required category information, which requires long time to converge during their training stage. In order to address such challenging issues, we propose a dynamic embedding projection-gated convolutional neural network (DEP-CNN) for multi-class and multi-label text classification. Its dynamic embedding projection gate (DEPG) transforms and carries word information by using gating units and shortcut connections to control how much context information is incorporated into each specific position of a word-embedding matrix in a text. To our knowledge, we are the first to apply DEPG over a word-embedding matrix. The experimental results on four known benchmark datasets display that DEP-CNN outperforms its recent peers.

Autologous transplantation of thecal stem cells restores ovarian function in nonhuman primates.

Premature ovarian insufficiency (POI) is defined as the loss of ovarian activity under the age of 40. Theca cells (TCs) play a vital role during folliculogenesis and TCs dysfunction participate in the pathogenesis of POI. Therefore, transplantation of thecal stem cells (TSCs), which are capable of self-renewal and differentiation into mature TCs, may provide a new strategy for treating POI. To investigate the feasibility, safety, and efficacy of TSCs transplantation in clinically relevant non-human primate (NHP) models, we isolate TSCs from cynomolgus monkeys, and these cells are confirmed to expand continuously and show potential to differentiate into mature TCs. In addition, engraftment of autologous TSCs into POI monkeys significantly improves hormone levels, rescues the follicle development, promotes the quality of oocytes and boosts oocyte maturation/fertilization rate. Taken together, these results for the first time suggest that autologous TSCs can ameliorate POI symptoms in primate models and shed new light on developing stem cell therapy for POI.

Honokiol post-treatment ameliorates myocardial ischemia/reperfusion injury by enhancing autophagic flux and reducing intracellular ROS production.

Honokiol (HKL) is a natural low-molecular-weight biphenolic compound derived from the bark of magnolia trees. Previous studies indicate that HKL exerts potent cardioprotective effects on ischemia/reperfusion (I/R) injury; however, evidence of the further relationship between HKL posttreatment and myocardial I/R injury has not been clearly found. In our study, we explored the protective effect of HKL post treatment on myocardial I/R injury in C57BL/6 mice. We also demonstrated that HKL significantly reduced cellular reactive oxygen species production and attenuated mitochondrial damage in neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation (H/R). In addition, HKL was found to enhance autophagy during I/R or H/R; these effects could be partially blocked by the autophagic flux inhibitor chloroquine. Moreover, our results suggested that enhanced autophagic flux is associated with the Akt signaling pathway. Collectively, our results indicate that HKL posttreatment alleviates myocardial I/R injury and suggest a critical cardioprotective role of HKL in promoting autophagic flux.

Electroacupuncture Preconditioning Improves Myocardial Infarction Injury via Enhancing AMPK-Dependent Autophagy in Rats.

BACKGROUND: Electroacupuncture (EA) pretreatment plays a protective role in myocardial infarction injury. However, the mechanism of electroacupuncture remains unknown. The aim of this study was to confirm the protective effects of electroacupuncture (EA) on myocardial infarction injury and the possible mechanism. METHODS: Sprague-Dawley (SD) rats, used to serve as acute myocardial infarction (AMI) model, were divided into sham group, model (M) group, M+EA group, AMPK inhibitor Compound C (M+EA+CC), and AMPK inhibitor solvent control (M+EA+DMSO) group, respectively. Rats in EA group were pretreated with EA and those in M+EA+CC group with intravenous AMPK inhibitor Compound C. The myocardial morphological changes and infarct size were observed through HE staining and TTC staining, and the concentrations of CK-MB and LDH were detected using ELISA kits. Transmission electron microscopy was employed to observe the autophagosome formation, and the AMPK-dependent autophagy-related protein expression was detected by immunohistochemistry and western blot. RESULTS: EA could alleviate myocardial infarction injury and decrease the concentrations of CK-MB and LDH. Transmission electron microscopy showed that EA could also regulate the AMPK-dependent autophagosome formation and the AMPK-dependent autophagy-related protein expression. AMPK inhibitor Compound C could impair the effect of EA through regulating the concentrations of CK-MB and LDH, autophagosome formation, and autophagy-related protein expression. CONCLUSION: These results indicated that electroacupuncture could improve myocardial infarction injury and induce autophagy, and AMPK-dependent autophagy might be involved in this process.

Hesperetin post-treatment prevents rat cardiomyocytes from hypoxia/reoxygenation injury in vitro via activating PI3K/Akt signaling pathway.

Hesperidin (HES), a citrus fruit extract, has beneficial effects on various ischemia/reperfusion (I/R) models. Here, we investigated the possible positive effect of hesperetin (HPT), an active metabolite of HES, and identified the potential molecular mechanisms involved in cardiomyocytes H/R-induced injury. To construct the cardiomyocyte model of hypoxia/reoxygenation (H/R) injury, cultured neonatal rat cardiomyocytes were subjected to 3h of hypoxia followed by 3h of reoxygenation. Cell viability and apoptosis were detected. The levels of Apoptosis-related proteins and PI3K/Akt proteins were detected by western blot. Our results showed that HPT post-treatment significantly inhibited apoptosis by elevating the expression of Bcl-2, decreasing the expression of Bax and cleaved caspase-3, and diminished the apoptotic cardiomyocytes ratio. Mechanism studies demonstrated that HPT post-treatment up-regulated the expression levels of p-PI3K, and p-Akt. Co-treatment of the cardiomyocytes with the PI3K/Akt-specific inhibitor LY294002 blocked the HPT-induced cardioprotective effects. Taken together, these data suggested that HPT post-treatment prevented cardiomyocytes from H/R injury in vitro most likely through the activation of PI3K/Akt signaling pathway.

Faithful Completion of Images of Scenic Landmarks Using Internet Images.

Previous works on image completion typically aim to produce visually plausible results rather than factually correct ones. In this paper, we propose an approach to faithfully complete the missing regions of an image. We assume that the input image is taken at a well-known landmark, so similar images taken at the same location can be easily found on the Internet. We first download thousands of images from the Internet using a text label provided by the user. Next, we apply two-step filtering to reduce them to a small set of candidate images for use as source images for completion. For each candidate image, a co-matching algorithm is used to find correspondences of both points and lines between the candidate image and the input image. These are used to find an optimal warp relating the two images. A completion result is obtained by blending the warped candidate image into the missing region of the input image. The completion results are ranked according to combination score, which considers both warping and blending energy, and the highest ranked ones are shown to the user. Experiments and results demonstrate that our method can faithfully complete images.

[Effects of Climatic Factors on Contents of Major Medical Components in Smilax china from Different Regions in Western Hunan].

OBJECTIVE: To study the impact of climatic factors on the major medical component in Smilax china, and to supply a scientific and standard operation protocol on the introduction and cultivation. METHODS: Detect the content of major medical components, such as baicalin and astibin, in Smilax china from eight counties of Xiangxi Autonomous Prefecture. And establish their relationship with annual average temperature, Jan average temp, Jul average temp, valid accumulative temp (≥ 10 degress C), annual maximum temp, annual minimum temp, annual precipitation, annual sunshine amount, non-frost period and relative humidity by using the methods of partial least squares regression analysis (PLS). RESULTS: Relative humidity, annual minimum temp and annual precipitation are the dominant factors. Annual minimum temp, annual average temp and valid accumulative temp were significantly correlated to the content of major medical components, thus, relative humidity, annual precipitation and non-frost period were negatively related to them. CONCLUSION: This study provides a scientific basis for resources protection,introduction and cultivation of Smilax china.