The branch-thorn occurrence of Lycium ruthenicum is associated with leaf DNA hypermethylation in response to soil water content

Molecular Biology Reports - Lycium ruthenicum is an eco-economic shrub which can exist in two forms, thorny and thornless under varying soil moisture conditions. The aim of this study was to...     

Body Weight-Supported Treadmill Training Ameliorates Motoneuronal Hyperexcitability by Increasing GAD-65/67 and KCC2 Expression via TrkB Signaling in Rats with Incomplete Spinal Cord Injury

Neurochemical Research - Spasticity is a typical consequence after spinal cord injury (SCI). The critical reasons are reducing the synthesis of Gamma-Aminobutyric Acid (GABA), glycine and potassium...     

Design,synthesis, and evaluation of chalcone-Vitamin E-donepezil hybrids as multi-target-directed ligands for the treatment of Alzheimer’s disease

A novel series of chalcone-Vitamin E-donepezil hybrids was designed and developed based on multitarget-directed ligands (MTDLs) strategy for treating Alzheimer’s disease (AD). The biological results revealed that compound 17f showed good AChE inhibitory potency (ratAChE IC₅₀ = 0.41 µM; eeAChE IC₅₀ = 1.88 µM). Both the kinetic analysis and docking study revealed that 17f was a mixed type AChE inhibitor. 17f was also a good antioxidant (ORAC = 3.3 eq), selective metal chelator and huMAO-B inhibitor (IC₅₀ = 8.8 µM). Moreover, it showed remarkable inhibition of self- and Cu²⁺-induced Aβ_1–42 aggregation with a 78.0 and 93.5% percentage rate at 25 µM, respectively, and disassembled self-induced and Cu²⁺-induced aggregation of the accumulated Aβ_1–42 fibrils with 72.3 and 84.5% disaggregation rate, respectively. More importantly, 17f exhibited a good neuroprotective effect on H₂O₂-induced PC12 cell injury and presented good blood-brain barrier permeability in vitro. Thus, 17f was a promising multi-target-directed ligand for treating AD.     

CPEB3 deficiency in mice affect ovarian follicle development and causes premature ovarian insufficiency

Premature ovarian insufficiency (POI) is a heterogeneous and multifactorial disorder. In recent years, there has been an increasing interest in research on the pathogenesis and treatment of POI, owing to the implementation of the second-child policy in China. Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is an RNA-binding protein that can bind to specific RNA sequences. CPEB3 can bind to and affect the expression, cellular location, and stability of target RNAs. Cpeb3 is highly expressed in the ovary; however, its functions remain unknown. In this study, Cpeb3-mutant mice were used to characterize the physiological functions of CPEB3. Cpeb3-mutant female mice manifested signs of gradual loss of ovarian follicles, ovarian follicle development arrest, increased follicle atresia, and subfertility with a phenotype analogous to POI in women. Further analysis showed that granulosa cell proliferation was inhibited and apoptosis was markedly increased in Cpeb3-mutant ovaries. In addition, the expression of Gdf9, a potential target of CPEB3, was decreased in Cpeb3-mutant ovaries and oocytes. Altogether, these results reveal that CPEB3 is essential for ovarian follicle development and female fertility as it regulates the expression of Gdf9 in oocytes, disruption of which leads to impaired ovarian follicle development and POI.Subject terms: RNA-binding proteins, Infertility     

Strigo-D2—a bio-sensor for monitoring spatio-temporal strigolactone signaling patterns in intact plants

Strigolactones (SLs) are a class of plant hormones that mediate biotic interactions and modulate developmental programs in response to endogenous and exogenous stimuli. However, a comprehensive view on the spatio-temporal pattern of SL signaling has not been established, and tools for a systematic in planta analysis do not exist. Here, we present Strigo-D2, a genetically encoded ratiometric SL signaling sensor that enables the examination of SL signaling distribution at cellular resolution and is capable of rapid response to altered SL levels in intact Arabidopsis (Arabidopsis thaliana) plants. By monitoring the abundance of a truncated and fluorescently labeled SUPPRESSOR OF MAX2 1-LIKE 6 (SMXL6) protein, a proteolytic target of the SL signaling machinery, we show that all cell types investigated have the capacity to respond to changes in SL levels but with very different dynamics. In particular, SL signaling is pronounced in vascular cells but low in guard cells and the meristematic region of the root. We also show that other hormones leave Strigo-D2 activity unchanged, indicating that initial SL signaling steps work in isolation from other hormonal signaling pathways. The specificity and spatio-temporal resolution of Strigo-D2 underline the value of the sensor for monitoring SL signaling in a broad range of biological contexts with highly instructive analytical depth.

Strigo-D2 is a genetically encoded sensor visualizing spatio-temporal patterns of strigolactone signaling levels in intact plants based on the activity ratio of two fluorescent marker proteins.     

Suppression of lysosomal-associated protein transmembrane 5 ameliorates cardiac function and inflammatory response by inhibiting the nuclear factor-kappa B (NF-κB) pathway after myocardial infarction in mice

Myocardial infarction (MI) as the remarkable presentation of coronary artery disease is still a reason for morbidity and mortality in worldwide. Lysosomal-associated protein transmembrane 5 (LAPTM5) is a lysosomal-related protein found in hematopoietic tissues and has been confirmed as a positive regulator of pro-inflammatory pathways in macrophages. However, the role of LAPTM5 in MI remains unknown. In this study, we found that both mRNA and protein expression levels of LAPTM5 were significantly elevated in MI mice. Suppression of LAPTM5 in myocardial tissues decreased cardiac fibrosis and improved cardiac function after MI. At the molecular level, downregulated LAPTM5 dramatically suppressed the macrophage activation and inflammatory response via inhibiting the activation of the nuclear factor-kappa B (NF-κB) pathway. Collectively, suppression of LAPTM5 in myocardial tissues inhibits the pro-inflammatory response and the cardiac dysfunction caused by MI. This study indicated that LAPTM5 as a pro-inflammatory factor plays a crucial role in MI disease.     

关帝山云杉次生林树木径向生长的空间关联及其影响因子

以关帝山4 hm²云杉次生林样地为研究对象,按照CTFS(Center for Tropical Forest Science)技术规范对样地树木进行连续定位监测。利用2010至2015年间样地主要树种生长量观测数据,结合地形、土壤等环境因子调查及采样测定数据,分析了树木种群径向生长的空间关联性及其随生境的变化,并探讨了树木种群径向生长的影响因素。结果表明,青杄、华北落叶松、红桦、白桦和辽东栎为云杉次生林主要树种,在样地4个生境型(山脊生境、低海拔缓坡生境、高海拔缓坡生境、低洼地陡坡生境)中均有分布且呈现不同的径级结构。标记相关函数分析显示,同一生境型中,5树种径向生长的空间关联性各异;对于同一树种,径向生长的空间自相关性不仅具有尺度依赖性,同时生境型的不同导致树木径向生长的空间关联性发生变化。线性混合效应模型分析显示,初始胸径对树木径向生长的显著正效应在样地各类生境型的所有种群中普遍存在;生物因子对树木径向生长的显著影响只在特定生境型的青杄种群中被检测到,表明树木径向生长受同种邻体影响,但其影响显著性因树种而异;环境因子中,海拔和凹凸度对树木径向生长呈显著负效应...     

Furo[2,3-d]pyrimidines as Mackinazolinone/Isaindigotone Analogs: Synthesis,Modification, Antitumor Activity,and Molecular Docking Study

The chemical transformation of the tricyclic furo[2,3-d]pyrimidines was performed under isosteric and scaffold-hopping strategies focusing on the synthesis of its arylidene and imine-containing derivatives. Naturally-occurring alkaloids mackinazolinone and isaindigotone were as templates of target heterocycles. Synthesized compounds evaluated for their antitumor activity on human cancer cervical HeLa, breast MCF-7, and colon HT-29 cell lines. Four compounds: 8c , 8e , 10b , and 10c demonstrated potency against HeLa and HT-29 cell lines, and IC₅₀ values were between 7.37–13.72 μM, respectively. The molecular docking results showed that compounds 8c and 10b had good binding and high matching with the target EGFR protein.