Nasal Administration of bFGF-Loaded Nanoliposomes Attenuates Neuronal Injury and Cognitive Deficits in Mice with Vascular Dementia Induced by Repeated Cerebral Ischemia‒Reperfusion.

Introduction: Basic fibroblast growth factor (bFGF) shows great potential for preventing vascular dementia (VD). However, the blood‒brain barrier (BBB) and low bioavailability of bFGF in vivo limit its application. The present study investigated how nasal administration of bFGF-loaded nanoliposomes (bFGF-lips) affects the impaired learning and cognitive function of VD mice and the underlying mechanism involved. Methods: A mouse model of VD was established through repeated cerebral ischemia‒reperfusion. A Morris water maze (MWM) and novel object recognition (NOR) tests were performed to assess the learning and cognitive function of the mice. Hematoxylin and eosin (HE) staining, Nissl staining and TUNEL staining were used to evaluate histopathological changes in mice in each group. ELISA and Western blot analysis were used to investigate the molecular mechanism by which bFGF-lips improve VD incidence. Results: Behavioral and histopathological analyses showed that cognitive function was significantly improved in the bFGF-lips group compared to the VD and bFGF groups; in addition, abnormalities and the apoptosis indices of hippocampal neurons were significantly decreased. ELISA and Western blot analysis revealed that bFGF-lips nasal administration significantly increased the concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), bFGF, B-cell lymphoma 2 (Bcl-2), phosphorylated protein kinase B (PAKT), nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1) and haem oxygenase-1 (HO-1) in the hippocampus of bFGF-lips mice compared with the VD and bFGF groups. Furthermore, the concentrations of malondialdehyde (MDA), caspase-3 and B-cell lymphoma 2-associated X (Bax) were clearly lower in the bFGF-lips group than in the VD and bFGF groups. Conclusion: This study confirmed that the nasal administration of bFGF-lips significantly increased bFGF concentrations in the hippocampi of VD mice. bFGF-lips treatment reduced repeated I/R-induced neuronal apoptosis by regulating apoptosis-related protein concentrations and activating the phosphatidylinositol-3-kinase (PI3K)/(AKT)/Nrf2 signaling pathway to inhibit oxidative stress.

Surgical Continuum Manipulator Control Using Multiagent Team Deep Q Learning.

Continuum manipulator has shown great potential in surgical applications. The flexibility of the continuum manipulator helps it achieve many complicated surgeries, such as neurosurgery, vascular surgery, abdominal surgery, etc. In this paper, we propose a Team Deep Q learning framework (TDQN) to control a 2-DoF surgical continuum manipulator with four cables, where two cables in a pair form one agent. During the learning process, each agent shares state and reward information with the other one, which namely is centralized learning. Using the shared information, TDQN shows better targeting accuracy than multiagent deep Q learning (MADQN) by verifying on a 2-DoF cable-driven surgical continuum manipulator. The root mean square error during tracking with and without disturbance are 0.82mm and 0.16mm respectively using TDQN, whereas 1.52mm and 0.98mm using MADQN respectively.Clinical Relevance-The proposed TDQN shows a promising future in improving control accuracy under disturbance and maneuverability in robotic-assisted endoscopic surgery.

Solamargine induces apoptosis of human renal carcinoma cells via downregulating phosphorylated STAT3 expression.

Solamargine (SM), an active compound derived from Solanum nigrum, triggers apoptosis and inhibits the metastatic and oxidative activities of various types of tumor cells. However, the effect of SM on human renal carcinoma cells remains unknown. In the present study, the molecular mechanisms underlying the antitumor effects of SM on ACHN and 786-O cells were elucidated. Specifically, MTT and colony formation assays were conducted to evaluate the impact of SM treatment on the proliferation of ACHN and 786-O cells, and flow cytometry was conducted to determine the influence of SM on the apoptosis rates of these cells. In addition, the expression of target proteins was determined by western blotting. The results revealed that SM not only inhibited cell viability but also promoted the apoptosis of ACHN and 786-O cells in a time- and dose-dependent manner. Moreover, treatment of ACHN and 786-O cells with SM significantly enhanced the caspase-3, caspase-8 and caspase-9 activities. Furthermore, SM downregulated the expression of phosphorylated signal transducer and activator of transcription-3 (p-STAT3) and Bcl-2 but increased the expression of cleaved caspase-3, -8, -9 and Bax. BAY2353, a p-STAT3 inhibitor, inhibited the viability of ACHN and 786-O cells, increased the expression of cleaved caspase-9 and Bax and decreased the expression of p-STAT3 and Bcl-2. Further experiments demonstrated that SM inhibited tumor growth in xenograft nude mice without causing specific toxicity to the major organs. Collectively, these findings indicated that SM not only inhibited the viability but also promoted the apoptosis of ACHN and 786-O cells, through a mechanism involving downregulation of p-STAT3 expression.

Molecular cloning, characterization and expression analysis of three key starch synthesis-related genes from the bulb of a rare lily germplasm, Lilium brownii var. giganteum.

Starch is the predominant compound in bulb scales, and previous studies have shown that bulblet development is closely associated with starch enrichment. However, how starch synthesis affects bulbification at the molecular level is unclear. In this study, we demonstrate that Lilium brownii var. giganteum, a wild lily with a giant bulb in nature, and L. brownii, the native species, have different starch levels and characteristics according to cytological and ultra-structural observations. We cloned the complete sequence of three key gene-encoding enzymes (LbgAGPS, LbgGBSS, andLbgSSIII) during starch synthesis by rapid amplification of 5' and 3' complementary DNA (cDNA) ends (RACE) technology. Bioinformatics analysis revealed that the proteins deduced by these genes contain the canonical conserved domains. Constructed phylogenetic trees confirmed the evolutionary relationships with proteins from other species, including monocotyledons and dicotyledons. The transcript levels of various tissues and time course samples obtained during bulblet development uncovered relatively high expression levels in bulblets and gradual increase expression accompanying bulblet growth. Moreover, a set of single nucleotide polymorphisms (SNPs) was discovered in the AGPS genes of four lily genotypes, and a purifying selection fashion was predicted according to the non-synonymous/synonymous (Ka/Ks) values. Taken together, our results suggested that key starch-synthesizing genes might play important roles in bulblet development and lead to distinctive phenotypes in bulblet size.

Change in Sucrose Cleavage Pattern and Rapid Starch Accumulation Govern Lily Shoot-to-Bulblet Transition in vitro.

In bulb crops, bulbing is a key progress in micropropagation and is the feature that most distinguishes bulbous crops from other plants. Generally, bulbing involves a shoot-to-bulblet transition; however, the underlying mechanism remains elusive. We explored this process by tracking the shoot-to-bulblet transition under different culture conditions. Rapid starch accumulation occurred at 15 days after transplanting (DAT) in the bulblet-inducing treatments as confirmed via histological observations and the significant elevation of starch synthesis related-gene transcription, including LohAGPS, LohAGPL, LohGBSS, LohSS, and LohSBE. However, for shoots that did not transition to bulblets and maintained the shoot status, much higher soluble sugars were detected. Interestingly, we observed a clear shift from invertase-catalyzed to sucrose synthase-catalyzed sucrose cleavage pattern based on the differential expression of LohCWIN and LohSuSy during the key transition stage (prior to and after bulbing at 0-15 DAT). Shoots that transitioned into bulblets showed significantly higher LohSuSy expression, especially LohSuSy4 expression, than shoots that did not transition. A symplastic phloem unloading pathway at the bulblet emergence stage (15 DAT) was verified via the 6(5)-carboxyfluorescein diacetate fluorescent tracer. We propose that starch is the fundamental compound in the shoot-to-bulblet transition and that starch synthesis is likely triggered by the switch from apoplastic to symplastic sucrose unloading, which may be related to sucrose depletion. Furthermore, this study is the first to provide a complete inventory of the genes involved in starch metabolism based on our transcriptome data. Two of these genes, LohAGPS1.2b and LohSSIIId, were verified by rapid amplification of cDNA ends cloning, and these data will provide additional support for Lilium research since whole genome is currently lacking.