Bone defects/fractures are common in older people suffering from osteoporosis. Traditional hydroxyapatite (HA) materials for osteoporotic bone repair face many challenges, including limited bone formation and aseptic loosening of orthopedic implants. In this study, a new multifunctional HA is synthesized by spontaneous assembly of alendronate (AL) and FeO onto HA nanocrystals for osteoporotic bone regeneration. The chemical coordination of AL and FeO with HA does not induce lattice deformation, resulting in a functionalized HA (Func-HA) with proper magnetic property and controlled release manner. The Func-HA nanocrystals have been encapsulated in polymer substrates to further investigate their osteogenic capability. In vitro and in vivo evaluations reveal that both AL and FeO, especially the combination of two functional groups on HA, can inhibit osteoclastic activity and promote osteoblast proliferation and differentiation, as well as enhance implant osseointegration and accelerate bone remodeling under osteoporotic condition. The as-developed Func-HA with coordinating antiresorptive ability, magnetic property, and osteoconductivity might be a desirable biomaterial for osteoporotic bone defect/fracture treatment.

Spermatogenesis is a complex and dynamic processwhich is precisely controlledby genetic and epigenetic factors. With the development of new technologies (e.g., single-cell RNA sequencing), increasingly more regulatory genes related to spermatogenesis have been identified. In this review, we address the roles and mechanisms of novel genes in regulatingthenormal and abnormal spermatogenesis. Specifically, we discussed the functions and signaling pathways of key new genes in mediating the proliferation, differentiation, and apoptosis of rodent and human spermatogonial stem cells (SSCs), as well as in controlling the meiosis of spermatocytes and other germ cells. Additionally, we summarized the gene regulation in the abnormal testicular microenvironment or the niche by Sertoli cells, peritubularmyoid cells, and Leydig cells. Finally, we pointed out the future directions for investigating the molecular mechanisms underlying human spermatogenesis. This review could offer novel insights into genetic regulation in the normal and abnormal spermatogenesis, and it provides new molecular targets for gene therapy of male infertility.

We investigated the mRNA expression of V-ATPase CA II, NFAT2, and RANK as well as bone mineral density (BMD) in bilaterally ovariectomized (OVX) rats treated with pulsed electromagnetic fields (PEMF), to explore the mechanism by which PEMF alter bone at the molecular level in vivo. 24 Sprague-Dawley female rats were randomly divided into three different groups: SHAM, OVX, ovariectomy with PEMF stimulation (PEMF+OVX). The PEMF frequency was 3.8 mT, 8 Hz, for 40 min per day. Eight rats in each group were treated for 28 days. At the end of the intervention, the body weight and BMD were measured. The mRNA expression of V-ATPase, CA II, NFAT2 and RANK were analyzed by real-time fluorescent-nested quantitative polymerase chain reaction (RT-PCR). The V-ATPase, CAII, NFAT2 and RANK genes show strong expression in the OVX group as compared with the SHAM group (P<0.001, respectively). The mRNAs expression of V-ATPase, CAII, NFAT2 and RANK in PEMF treatment group were significantly lower than that in OVX group, respectively (p=0.001, p=0.000, p=0.013, P=0.04, respectively). The V-ATPase, CAII and RANK mRNA expression in the PEMF+OVX group were higher than SHAM group (p=0.04, p=0.001, p=0.000, respectively). However, the NFAT2 mRNA expression did not show a statistically significant difference between the SHAM and the PEMF+OVX group (P=0.08). This study indicated that exposure to PEMF restrained bone resorption in order to elevate BMD, and this outcome occurred in part through RANK-signaling by the CN/NFAT pathway to regulate bone metabolism. Alternatively, PEMF may promote the BMD through regulating the expression of NFAT2 genes. It may have certain significance in the treatment target of osteoporosis.

BackgroundThe pathological mechanism of Barrett’s esophagus (BE) is still unclear. In the present study, pathway cross-talks were analyzed to identify hub pathways for BE, with the purpose of finding an efficient and cost-effective detection method to discover BE at its early stage and take steps to prevent its progression.Material/MethodsWe collected and preprocessed gene expression profile data, original pathway data, and protein-protein interaction (PPI) data. Then, we constructed a background pathway cross-talk network (BPCN) based on the original pathway data and PPI data, and a disease pathway cross-talk network (DPCN) based on the differential pathways between the PPI data and the BE and normal control. Finally, a comprehensive analysis was conducted on these 2 networks to identify hub pathway cross-talks for BE, so as to better understand the pathological mechanism of BE from the pathway level.ResultsA total of 12 411 genes, 300 pathways (6919 genes), and 787 896 PPI interactions (16 730 genes) were separately obtained from their own databases. Then, we constructed a BPCN with 300 nodes (42 293 interactions) and a DPCN with 296 nodes (15 073 interactions). We identified 4 hub pathways: AMP signaling pathway, cGMP-PKG signaling pathway, natural killer cell-mediated cytotoxicity, and osteoclast differentiation. We found that these pathways might play important roles during the occurrence and development of BE.ConclusionsWe predicted that these pathways (such as AMP signaling pathway and cAMP signaling pathway) could be used as potential biomarkers for early diagnosis and therapy of BE.