Constraints on the maintenance of wild Taxus cuspidata populations based on regression conservation.

To clarify the key factors constraining the maintenance of wild Taxus cuspidata populations and to develop conservation strategies and technical links for current populations, we investigated the renewal status and distribution patterns of wild T. cuspidata populations in the main distribution areas of China. We analyzed the effects of stand factors and human disturbance on population renewal and maintenance. The results showed that the overall regeneration of wild T. cuspidata populations was poor. The basal diameter and height class structure of renewed individuals showed an unhealthy state. 19% of the area was well regenerated. There were three types of regeneration, including poor regeneration with few adult trees, poor regeneration with many adult trees, and good regeneration with few adult trees. The communities in which T. cuspidata was found could be classified into Abies nephrolepis + Tilia amurensis forest, spinney forest, and Picea jezoensis var. microsperma + A. nephrolepis forest. The renewal number of A. nephrolepis + T. amurensis forest was significantly higher than that of spinney forest. Increased stand density and moderate human disturbance contributed to the regeneration of T. cuspidata. The regenerating T. cuspidata seedlings increased significantly when stand density increased from low to medium. The number of regenerating populations in moderately disturbed habitats was significantly higher than those in lightly disturbed habitats. Human disturbance and habitat were currently critical constraints to maintaining and regenerating wild T. cuspidata populations. The conservation of T. cuspidata should consider current status of population regeneration in each habitat patch to develop corresponding in situ conservation and regression conservation measures and focus on the influence of critical factors such as disturbances and habitat conditions.

Evaluating Efficacy and Safety of Tacrolimus Treatment in Membranous Nephropathy: Results of a Retrospective Study of 182 Patients.

Purpose: Tacrolimus is recommended by KDIGO Clinical Practice Guidelines as an initial therapy for the treatment of membranous nephropathy (MN). However, little is known about the factors that influence response and recurrence of the disease after tacrolimus therapy, and there are limited data regarding the duration of tacrolimus treatment. Here, we present a real-world retrospective cohort study of 182 MN patients treated with tacrolimus, aiming to assess the efficacy and safety of tacrolimus in the treatment of MN. Patients and Methods: The clinical data of 182 patients with MN treated with tacrolimus and followed up for at least one year were analyzed retrospectively for the efficacy and safety of tacrolimus. Results: The mean follow-up period was 27.3 (19.3-41.6) months. A total of 154 patients (84.6%) achieved complete or partial remission, and 28 patients (15.4%) did not. Multivariate Cox regression analysis showed that male and higher baseline BMI were independently associated with lower, while higher serum albumin was associated with higher probability of remission. Among the responders, 56 patients (36.4%) relapsed. After adjustments for age and sex, Cox regression analysis revealed that the longer period of full-dose tacrolimus was administered, the lower the incidence of relapse. However, high levels of serum creatinine and proteinuria at the onset of tacrolimus discontinuation were risk factors for relapse. During the treatment of tacrolimus, a decline in renal function (≥50% increase in serum creatinine after the onset of tacrolimus treatment) was the most common adverse reaction, observed in 20 (11.0%) patients, followed by elevated blood glucose and infection, but the latter two occurred mostly during treatment with tacrolimus plus corticosteroids. Conclusion: Tacrolimus is effective in the treatment of MN, but the relapse rate is high. Clinical studies with larger sample sizes are needed to further explore the use of tacrolimus in the treatment of membranous nephropathy.

The microstructures and mechanical properties of nanocrystalline Li2SiO3: molecular dynamics simulations.

The microstructures and mechanical properties of nanocrystalline Li2SiO3 have been investigated via molecular dynamics calculations. The results indicate that the mean atomic mass densities of nanostructured Li2SiO3 with different mean grain size are slightly lower than that of ordinary crystal Li2SiO3. Interestingly, a significant anti-Hall-Petch effect between yield stress and average grain size is observed in the tensile deformation simulation of the samples. In fact, the curve changes linearly until the strain reaches approximately 0.016-0.018. Next, when the strain is between 0.27 and 0.38, the stress of the sample has a small peak in the plastic flow region. Then, all the samples will begin to fracture at a strain of about 0.39-0.41. Moreover, due to the influence of grain boundary sliding and grain rotation, there are a few dislocations in the samples with the small average grain sizes, highlighting the strong influence of the mechanical properties on the overall tensile deformation of the samples.

[Chemotherapy resistance induced by interleukin-6 in ovarian cancer cells and its signal transduction pathways].

OBJECTIVE: To study the mechanism of chemotherapy resistance caused by interleukin-6 (IL-6) in ovarian cancer cells and its related signal pathways. METHODS: Ovarian cancer cell lines A2780 (IL-6 receptor positive, while non-IL-6-expressing and cisplatin/paclitaxel-responsive) and SKOV3 cell lines (overexpressing of IL-6 receptor and IL-6 and cisplatin/paclitaxel-resistant) were suitable models for this study. The effect of exogenous (a short period of treatment with recombination IL-6) and endogenous IL-6 (by transfecting with plasmid encoding for sense IL-6) in A2780 cells or deleting of endogenous IL-6 expression in SKOV3 cells (by transfecting with plasmid encoding for antisense IL-6) on the sensitivity to cisplatin and paclitaxel was investigated. Meanwhile, the mechanism of chemotherapy resistance caused by IL-6 in ovarian cancer cells and its related signal pathways were also analyzed. RESULTS: We found that both exogenous and endogenous IL-6 induce cisplatin and paclitaxel resistance in non-IL-6-expressing A2780 cells (the resistance multiple to cisplatin and paclitaxel was: exogenous, 6.25 and 7.31; endogenous, 7.13-8.34 and 7.61-10.70), while deleting of endogenous IL-6 expression in IL-6-overexpressing SKOV3 cells promotes its sensitivity to anticancer drugs (the resistance multiple to cisplatin and paclitaxel was 0.15 and 0.10, 0.10 and 0.08). IL-6 significantly up-regulated the expression levels of mRNA and protein of drug resistance-associated genes, MDR1 and GST-π, and apoptosis-inhibiting genes, bcl-2, bcl-xL and XIAP in a dose-dependent manner in A2780 cells. In accordance with this finding, the mRNA and protein levels of MDR1 and GST-π enhanced in sense IL-6-transfected A2780 cells, and reduced in antisense IL-6-transfected SKOV3 cells compared with the corresponding parental and control vector-transfected cells, which had no difference. It was found that PD98059 [mitogen-activated protein kinase-extracellular signal-regulated kinase (MEK) inhibitor] and wortmannin [phosphatidylinositol 3-kinase (PI3K) inhibitor] significantly antagonized IL-6-induced phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt), respectively, and both of them blocked IL-6-induced cisplatin and paclitaxel resistance and the inhibitory effects of PD98059 and wortmannin were dependent on its concentration. CONCLUSIONS: These data suggest that IL-6-induced chemoresistance may be associated with increase of both drug resistance-associated genes (MDR1 and GST-π) and apoptosis-inhibiting genes (bcl-2, bcl-xL and XIAP), and activation of MEK/ERK and PI3K/Akt. Therefore, modulation of IL-6 expression or its related signaling pathway may be a promising strategy of treatment for drug-resistant ovarian cancer.