Decoding the spermatogonial stem cell niche under physiological and recovery conditions in adult mice and humans

The intricate interaction between spermatogonial stem cell (SSC) and testicular niche is essential for maintaining SSC homeostasis; however, this interaction remains largely uncharacterized. In this study, to characterize the underlying signaling pathways and related paracrine factors, we delineated the intercellular interactions between SSC and niche cell in both adult mice and humans under physiological conditions and dissected the niche-derived regulation of SSC maintenance under recovery conditions, thus uncovering the essential role of C-C motif chemokine ligand 24 and insulin-like growth factor binding protein 7 in SSC maintenance. We also established the clinical relevance of specific paracrine factors in human fertility. Collectively, our work on decoding the adult SSC niche serves as a valuable reference for future studies on the aetiology, diagnosis, and treatment of male infertility.</p

Patterns and environmental controls of soil organic carbon density in Chinese shrublands

The soils of shrublands are important for organic carbon storage in terrestrial ecosystems, but geographical patterns and environmental controls of soil organic carbon (SOC) remain largely understudied compared to other terrestrial ecosystems, leaving a significant gap in our understanding of terrestrial ecosystem carbon budgets. Here, we quantified SOC density (SOCD) and its potential determinants based on a comprehensive dataset with a consistent stratified random sampling of extensive soil profiles down to the parent material or to one meter depth across 1211 sites across China. Our up-to-date estimate of SOCD in Chinese shrublands is an average of 8.36 kg m(-2), and ca. 43% of SOC is stored in the upper 20 cm relative to the one meter top soil, which is higher than estimates for shrublands globally. We also observed that SOCD was positively related to shrubland biomass and more so with belowground biomass. Furthermore, SOCD was positively related to mean annual precipitation (MAP), soil total nitrogen (N), phosphorus (P), clay and silt percent, but decreased with increasing mean annual temperature (MAT). Dark felty soils stored the highest SOCD and frigid desert soils stored the lowest. Soil total nitrogen (N), MAP, soil type, MAT, and belowground biomass, soil clay, and pH were the best predictors of total SOCD in Chinese shrublands. We concluded that Chinese shrubland soils store the lowest density of organic carbon so far recorded compared to forests and grasslands, and that the vertical distribution of SOC in Chinese shrublands was much shallower. While both climate (in particular MAP) and soil total N exerted dominant control over geographical patterns of SOCD across Chinese shrublands, soil type also played a significant role. Our study also emphasizes this key role of edaphic variables in determining the SOCD of shrublands and that they should be better incorporated into large-scale assessments of SOC dynamics. Our study extends existing work conducted in forest and grasslands and provides the most up-to-date knowledge on benchmark values for SOCD in Chinese shrublands, with important implications for predicting the fate of C stored in shrubland soils in response to climate change

Effect of Pabpc6 knockout on spermatogenesis of male mice

Objective To investigate the role of cytoplasmic poly (A) binding protein-6 (PABPC6) in spermatogenesis of male mice. Methods The Pabpc6 in C57BL/6J mice was knocked out by CRISPR/Cas9 targeting, and the Pabpc6 was identified by PCR. Three types of mice with different genotypes of Pabpc6+/+, Pabpc6+/- and Pabpc6-/- were obtained by mating and breeding. Testis was weighed;Morphological observation and sperm counting were carried out. The mRNA and protein expression levels of Pabpc6 in different tissues were detected by real-time quantitative PCR and Western blot. Immunofluorescence and hematoxylin-eosin staining were used to observe the location of the gene and the morphological changes in the convoluted spermatic tubule of testis. Results The Pabpc6 knockout mice were successfully identified. Pabpc6 was highly expressed in testicular tissue(P＜0.001). Immunofluorescence showed that Pabpc6 was mainly expressed in spermatocyte at early sperm stage. Compared with wild-type mice, knockout mice showed no significant differences in testicular shape, sperm morphology, sperm count and the morphology of convoluted spermatic ducts. Conclusions Pabpc6 is found to be highly expressed in the testis tissue of mice. Pabpc6 has no obvious effect on spermatogenesis of male mice after knockout of Pabpc6. The results indicate that the protein encoded by Pabpc6 is not necessary for spermatogenesis of mice

PEPTIDE NANOFILAMENTS USED FOR REPLICA-MOLDING: A COMBINATION OF "BOTTOM-UP" AND "TOP-DOWN"

A novel nanofabrication method that combines both "bottom-up" (template-assisted peptide self-assembling) and "top-down" (replica molding) techniques is introduced. A designer peptide, GAV-9 (NH2-VGGAVVAGV-CONH2), can epitaxially self-assemble into nanofilaments on the surface of mica, which is further used as the diversified masters for the application of replica molding. With in situ atomic force microscopy monitoring, several typical masters are fabricated by peptide self-assembling on the surface of mica. These masters can be easily molded into hard poly(dimethylsiloxane) surfaces, and then further replica-molded into polyurethane surfaces. The polymeric surfaces with regular 1D and 2D patterns on the nanometer scale are expected to have new applications in nanostructure's fabrication.Peptide, self-assembly, nanofabrication, replica molding, atomic force microscopy

Psychosocial interventions for Alzheimer’s disease cognitive symptoms: a Bayesian network meta-analysis

Abstract Background Alzheimer disease (AD) is the most common type of dementia with cognitive decline as one of the core symptoms in older adults. Numerous studies have suggested the value of psychosocial interventions to improve cognition in this population, but which one should be preferred are still matters of controversy. Consequently, we aim to compare and rank different psychosocial interventions in the management of mild to moderate AD with cognitive symptoms. Methods We did a network meta-analysis to identify both direct and indirect evidence in relevant studies. We searched MEDLINE, EMBASE, PsycINFO through the OVID database, CENTRAL through the Cochrane Library for clinical randomized controlled trials investigating psychosocial interventions of cognitive symptoms in patients with Alzheimer disease, published up to August 31, 2017. We included trials of home-based exercise(HE), group exercise(GE), walking program(WP), reminiscence therapy(RT), art therapy(AT) or the combination of psychosocial interventions and acetylcholinesterase inhibitor (ChEIs). We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool. The outcomes investigated were Mini–Mental State Examination (MMSE) and compliance. We did a pair-wise meta-analysis using the fixed-effects model and then did a random-effects network meta-analysis within a Bayesian framework. Results We deemed 10 trials eligible, including 682 patients and 11 treatments. The quality of included study was rated as low in most comparison with Cochrane tools. Treatment effects from the network meta-analysis showed WP was better than control (SMD 4.89, 95% CI -0.07 to 10.00) while cognitive training and acetylcholinesterase inhibitor (CT + ChEIs) was significantly better than the other treatments, when compared with simple ChEIs treatment, assessed by MMSE. In terms of compliance, the pair-wise meta-analysis indicated that WP and HE are better than GE and AT, while CT + ChEIs, CST + ChEIs are better than other combined interventions. Conclusion Our study confirmed the effectiveness of psychosocial interventions for improving cognition or slowing down the progression of cognitive impairment in AD patients and recommended several interventions for clinical practice

Black phosphorus mediated photoporation : a broad absorption nanoplatform for intracellular delivery of macromolecules

Nanoparticle-sensitized photoporation for intracellular delivery of external compounds usually relies on the use of spherical gold nanoparticles as sensitizing nanoparticles. As they need stimulation with visible laser light, they are less suited for transfection of cells in thick biological tissues. In this work, we have explored black phosphorus quantum dots (BPQDs) as alternative sensitizing nanoparticles for photoporation with a broad and uniform absorption spectrum from the visible to the near infra-red (NIR) range. We demonstrate that BPQD sensitized photoporation allows efficient intracellular delivery of both siRNA (>80%) and mRNA (>40%) in adherent cells as well as in suspension cells. Cell viability remained high (>80%) irrespective of whether irradiation was performed with visible (532 nm) or near infrared (800 nm) pulsed laser light. Finally, as a proof of concept, we used BPQD sensitized photoporation to deliver macromolecules in cells with thick phantom tissue in the optical path. NIR laser irradiation resulted in only 1.3x reduction in delivery efficiency as compared to photoporation without the phantom gel, while with visible laser light the delivery efficiency was reduced 2x

CRISPR/Cas9-mediated F1534S substitution in the voltage-gated sodium channel reveals its necessity and sufficiency for deltamethrin resistance in Aedes albopictus

Insecticide resistance in Aedes mosquitoes presents a major challenge to the control of arboviral diseases. However, resistance mechanisms for many of the insecticides remain unknown. A commonly used insecticide, deltamethrin, was used to select a resistance strain of the vector mosquito, Aedes albopictus, and we identified an F1534S substitution in the voltage-gated sodium channel (VGSC) gene product as the first event in generating resistance. Engineering an F1534S substitution using Cas9/gRNA technologies conferred deltamethrin resistance on a previously susceptible strain. Crosses that removed this mutation restored the susceptible phenotype. Predicted protein structural changes and differences in transcript accumulation levels were correlated with the resistance phenotype. Furthermore, F1534S mutations were detected in all resistant Ae. albopictus populations collected in the field. We conclude that the VGSC F1534S mutation is essential for resistance to deltamethrin in Ae. albopictus, and is a suitable molecular index for pyrethroid resistance detection and monitoring in this species