Triptolide prevents bone loss via suppressing osteoclastogenesis through inhibiting PI3K-AKT-NFATc1 pathway

Bone loss (osteopenia) is a common complication in human solid tumour. In addition, after surgical treatment of gynaecological tumour, osteoporosis often occurs due to the withdrawal of oestrogen. The major characteristic of osteoporosis is the low bone mass with micro-architectural deteriorated bone tissue. And the main cause is the overactivation of osteoclastogenesis, which is one of the most important therapeutic targets. Inflammation could induce the interaction of RANKL/RANK, which is the promoter of osteoclastogenesis. Triptolide is derived from the traditional Chinese herb lei gong teng, presented multiple biological effects, including anti-cancer, anti-inflammation and immunosuppression. We hypothesized that triptolide could inhibits osteoclastogenesis by suppressing inflammation activation. In this study, we confirmed that triptolide could suppress RANKL-induced osteoclastogenesis in bone marrow mononuclear cells (BMMCs) and RAW264.7 cells and inhibited the osteoclast bone resorption functions. PI3K-AKT-NFATc1 pathway is one of the most important downstream pathways of RANKL-induced osteogenesis. The experiments in vitro indicated that triptolide suppresses the activation of PI3K-AKT-NFATc1 pathway and the target point located at the upstream of AKT because both NFATc1 overexpression and AKT phosphorylation could ameliorate the triptolide suppression effects. The expression of MDM2 was elevated, which demonstrated the MDM-p53-induced cell death might contribute to the osteoclastogenesis suppression. Ovariectomy-induced bone loss and inflammation activation were also found to be ameliorated in the experiments in vivo. In summary, the new effect of anti-cancer drug triptolide was demonstrated to be anti-osteoclastogenesis, and we demonstrated triptolide might be a promising therapy for bone loss caused by tumour.     

Bmp2 regulates Serpinb6b expression via cAMP/PKA/Wnt4 pathway during uterine decidualization

Serpinb6b is a novel member of Serpinb family and found in germ and somatic cells of mouse gonads, but its physiological function in uterine decidualization remains unclear. The present study revealed that abundant Serpinb6b was noted in decidual cells, and advanced the proliferation and differentiation of stromal cells, indicating a creative role of Serpinb6b in uterine decidualization. Further analysis found that Serpinb6b modulated the expression of Mmp2 and Mmp9. Meanwhile, Serpinb6b was identified as a target of Bmp2 regulation in stromal differentiation. Treatment with rBmp2 resulted in an accumulation of intracellular cAMP level whose function in this differentiation program was mediated by Serpinb6b. Addition of PKA inhibitor H89 impeded the Bmp2 induction of Serpinb6b, whereas 8‐Br‐cAMP rescued the defect of Serpinb6b expression elicited by Bmp2 knock‐down. Attenuation of Serpinb6b greatly reduced the induction of constitutive Wnt4 activation on stromal cell differentiation. By contrast, overexpression of Serpinb6b prevented this inhibition of differentiation process by Wnt4 siRNA. Moreover, blockage of Wnt4 abrogated the up‐regulation of cAMP on Serpinb6b. Collectively, Serpinb6b mediates uterine decidualization via Mmp2/9 in response to Bmp2/cAMP/PKA/Wnt4 pathway.     

Sirtuin 5 regulates the proliferation,invasion and migration of prostate cancer cells through acetyl‐CoA acetyltransferase 1

Sirtuin 5 (SIRT5) is a NAD⁺‐dependent class III protein deacetylase, and its role in prostate cancer has not yet been reported. Therefore, to explore the diagnosis and treatment of prostate cancer, we investigated the effect of SIRT5 on prostate cancer. Sirtuin 5 was assessed by immunohistochemistry in 57 normal and cancerous prostate tissues. We found that the tissue expression levels of SIRT5 in patients with Gleason scores ≥7 were significantly different from those in patients with Gleason scores <7 (P < .05, R > 0). Further, mass spectrometry and pathway screening experiments showed that SIRT5 regulated the activity of the mitogen‐activated protein kinase (MAPK) pathway, which in turn modulated the expression of MMP9 and cyclin D1. Being a substrate of SIRT5, acetyl‐CoA acetyltransferase 1 (ACAT1) was regulated by SIRT5. SIRT5 also regulated MAPK pathway activity through ACAT1. These results revealed that SIRT5 promoted the activity of the MAPK pathway through ACAT1, increasing the ability of prostate cancer cells to proliferate, migrate and invade. Overall, these results indicate that SIRT5 expression is closely associated with prostate cancer progression. Understanding the underlying mechanism may provide new targets and methods for the diagnosis and treatment of the disease.     

Interface Engineering of Hierarchical Branched Mo‐Doped Ni3S2/NixPy Hollow Heterostructure Nanorods for Efficient Overall Water Splitting

Rational design and construction of bifunctional electrocatalysts with excellent activity and durability is imperative for water splitting. Herein, a novel top‐down strategy to realize a hierarchical branched Mo‐doped sulfide/phosphide heterostructure (Mo‐Ni₃S₂/Ni_xP_y hollow nanorods), by partially phosphating Mo‐Ni₃S₂/NF flower clusters, is proposed. Benefitting from the optimized electronic structure configuration, hierarchical branched hollow nanorod structure, and abundant heterogeneous interfaces, the as‐obtained multisite Mo‐Ni₃S₂/Ni_xP_y/NF electrode has remarkable stability and bifunctional electrocatalytic activity in the hydrogen evolution reaction (HER)/oxygen evolution reaction (OER) in 1 m KOH solutions. It possesses an extremely low overpotential of 238 mV at the current density of 50 mA cm^?2 for OER. Importantly, when assembled as anode and cathode simultaneously, it merely requires an ultralow cell voltage of 1.46 V to achieve the current density of 10 mA cm^?2, with excellent durability for over 72 h, outperforming most of the reported Ni‐based bifunctional materials. Density functional theory results further confirm that the doped heterostructure can synergistically optimize Gibbs free energies of H and O‐containing intermediates (OH*, O*, and OOH*) during HER and OER processes, thus accelerating the catalytic kinetics of electrochemical water splitting. This work demonstrates the importance of the rational combination of metal doping and interface engineering for advanced catalytic materials.     

Rice stripe virus coat protein induces the accumulation of jasmonic acid,activating plant defence against the virus while also attracting its vector to feed

The jasmonic acid (JA) pathway plays crucial roles in plant defence against pathogens and herbivores. Rice stripe virus (RSV) is the type member of the genus Tenuivirus. It is transmitted by the small brown planthopper (SBPH) and causes damaging epidemics in East Asia. The role(s) that JA may play in the tripartite interaction against RSV, its host, and vector are poorly understood. Here, we found that the JA pathway was induced by RSV infection and played a defence role against RSV. The coat protein (CP) was the major viral component responsible for inducing the JA pathway. Methyl jasmonate treatment attracted SBPHs to feed on rice plants while a JA-deficient mutant was less attractive than wild-type rice. SBPHs showed an obvious preference for feeding on transgenic rice lines expressing RSV CP. Our results demonstrate that CP is an inducer of the JA pathway that activates plant defence against RSV while also attracting SBPHs to feed and benefitting viral transmission. This is the first report of the function of JA in the tripartite interaction between RSV, its host, and its vector.     

Land-cover changes and distribution of wetland species in small valley habitats that developed in a Late Pleistocene middle terrace region

Wetlands Ecology and Management - Small valley topology on terraced uplands is a unique groundwater-dependent ecosystem in East Asia. Traditionally, this characteristic valley topology has been...     

宫颈病变患者阴道微生态与高危型HPV感染及宫颈癌相关增殖基因表达的相关性

目的探讨宫颈病变患者阴道微生态与高危型HPV感染及宫颈癌相关增殖基因表达的相关性。方法选择2018年1月至2019年1月间在我院确诊为原发性宫颈癌的患者50例作为宫颈癌组,在我院诊断为宫颈糜烂的患者78例作为宫颈糜烂组,同期在我院进行体检的健康女性100例作为正常对照组。对比3组研究对象的阴道微生态失调率、高危型HPV感染率以及宫颈癌组、宫颈糜烂组患者宫颈病灶组织中宫颈癌相关增殖基因(Prdx4、Nek2、Fhit、BLCAP)mRNA表达量的差异。采用Pearson检验分析宫颈癌患者阴道微生态失调率与高危型HPV感染及宫颈癌相关增殖基因表达的相关性。结果宫颈癌组、宫颈糜烂组患者的阴道微生态失调率、高危型HPV感染率高于正常对照组,其中宫颈癌组患者这两项指标水平高于宫颈糜烂组(均P0.05)。宫颈癌组患者宫颈病灶组织中Prdx4、Nek2 mRNA表达量高于宫颈糜烂组,Fhit、BLCAP mRNA表达量低于宫颈糜烂组(均P0.05)。相关性分析发现,宫颈癌患者阴道微生态失调率与高危型HPV感染率呈正相关,与癌基因(Prdx4、Nek2)mRNA表达量呈正相关,与抑癌基因(Fhit、BLCAP)mRNA表达量呈负相关(均P0.05)。结论宫颈癌患者阴道微生态失调率较高,可能与高危型HPV感染及癌细胞增殖旺盛密切相关。     

The effect of grazing on winter survival of midday gerbil (Meriones meridianus) of different genders

The objective of this study was to investigate the effects of grazing on midday gerbil (Meriones meridianus) population characteristics and survival of animals of different genders. The experiment used a randomized complete block design and was conducted in Alxa Left Banner, Inner Mongolia, China, in 2002 (The agricultural reclamation plots set up in 1994). From April 2006 to October 2010, midday gerbils were live‐trapped in 3 light grazing plots, 3 overgrazed plots, and 3 grazing exclusion plots. The quantity of vegetation was investigated in the two different grazing intensity areas and grazing exclusion area to determine the relationship between gerbils and plant food availability. The results suggested that there was higher gerbil density, individual body mass, and daily body mass growth rate in the grazing exclusion sites than the other sites across the whole year. Females had higher survival in grazing exclusion areas than in other treatments, but the males’ survival showed the opposite pattern. Our results indicated that grazing negatively influenced the midday gerbil population by reducing food availability. Grazing influenced the survival rates of male midday gerbils positively, but had negative effects on females. The reason for gendered differences in survival rates of midday gerbils requires further investigation.