Ginkgetin aglycone exerts anti-osteoporotic effect via regulation of NOX4/Akt/PI3K pathway

Purpose: To investigate the protective effect of Ginkgetin aglycone (GA) on ovariectomy-induced osteoporosis in rats, as well as the mechanism of action involved. Methods: Adult female Wistar rats (n = 40) were separated into four group: normal control, ovariectomy (OVR), 100 mg GA/kg dose, and 200 mg GA/kg dose. The rats were ovariectomized using standard procedures, except for those in normal control group. Rats in the two treatment groups received 100 or 200 mg GA/kg orally for a period of 12 weeks. Biochemical assays were performed on the urine and blood. Markers of bone formation and mediators of inflammation were assessed. Bone microarchitectural changes were examined using micro-CT scanner, while Western blotting was used to determine the expressions of NOX4, NF-κB p65, PI3K, Akt and JNK proteins in rat femurs. Results: Phosphorus and calcium levels in the serum varied among different groups. Levels of calcium, phosphorus and creatinine decreased (p < 0.01) significantly to a greater extent in the urine of GA group than in that of OVR group (p < 0.05). Interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α) and osteocalcin (OC) levels and the activity of alkaline phosphatase (ALP) decreased more in GA group than in OVR group. In GA-treated group, bone mineral density (BMD) was enhanced in a dose dependent manner than OVR group (p < 0.05). Treatment with GA ameliorated altered bone microarchitecture in OVR rats. Treatment of osteoporotic rats with GA led to significant and dosedependent decrease in the expressions of JNK, NOX4, NF-κB p65 and PI3K, and (p < 0.05) increase in the expression of Akt in femur tissue. Conclusion: In conclusion, result of study proves the anti-osteoporotic activity of GA is exerted via regulation of NOX4/PI3K/Akt pathway

Halide-Assisted Atmospheric Pressure Growth of Large WSe2 and WS2 Monolayer Crystals

Chemical vapor deposition (CVD) of two-dimensional (2D) tungsten dichalcogenide crystals requires steady flow of tungsten source in the vapor phase. This often requires high temperature and low pressure due to the high sublimation point of tungsten oxide precursors. We demonstrate atmospheric pressure CVD of WSe2 and WS2 monolayers at moderate temperatures (700 ~ 850 oC) using alkali metal halides (MX where M= Na or K and X=Cl, Br or I) as the growth promoters. We attribute the facilitated growth to the formation of volatile tungsten oxyhalide species during growth, which leads to efficient delivery of the precursor to the growth substrates. The monolayer crystals were found to be free of unintentional doping with alkali metal and halogen atoms. Good field-effect transistor (FET) performances with high current on/off ratio ~10 7, hole and electron mobilities up to 102 and 26 cm2 V 1 s-1 for WSe2 and electron mobility of ~14 cm2 V-1 s-1 for WS2 devices were achieved.Comment: 21 pages, 4 figures in manuscript & 10 pages, 6 figures in supplementary materia

Ghost in the Minecraft: Generally Capable Agents for Open-World Enviroments via Large Language Models with Text-based Knowledge and Memory

The captivating realm of Minecraft has attracted substantial research interest in recent years, serving as a rich platform for developing intelligent agents capable of functioning in open-world environments. However, the current research landscape predominantly focuses on specific objectives, such as the popular "ObtainDiamond" task, and has not yet shown effective generalization to a broader spectrum of tasks. Furthermore, the current leading success rate for the "ObtainDiamond" task stands at around 20%, highlighting the limitations of Reinforcement Learning (RL) based controllers used in existing methods. To tackle these challenges, we introduce Ghost in the Minecraft (GITM), a novel framework integrates Large Language Models (LLMs) with text-based knowledge and memory, aiming to create Generally Capable Agents (GCAs) in Minecraft. These agents, equipped with the logic and common sense capabilities of LLMs, can skillfully navigate complex, sparse-reward environments with text-based interactions. We develop a set of structured actions and leverage LLMs to generate action plans for the agents to execute. The resulting LLM-based agent markedly surpasses previous methods, achieving a remarkable improvement of +47.5% in success rate on the "ObtainDiamond" task, demonstrating superior robustness compared to traditional RL-based controllers. Notably, our agent is the first to procure all items in the Minecraft Overworld technology tree, demonstrating its extensive capabilities. GITM does not need any GPU for training, but a single CPU node with 32 CPU cores is enough. This research shows the potential of LLMs in developing capable agents for handling long-horizon, complex tasks and adapting to uncertainties in open-world environments. See the project website at https://github.com/OpenGVLab/GITM

Exploring the alteration of gut microbiota and brain function in gender-specific Parkinson’s disease based on metagenomic sequencing

BackgroundThe role of the microbiota-gut-brain axis in Parkinson’s disease (PD) has received increasing attention. Although gender differences are known to an essential role in the epidemiology and clinical course of PD, there are no studies on the sex specificity of the microbiota-gut-brain axis in the development and progression of PD.MethodsFresh fecal samples from 24 PD patients (13 males, 11 females) were collected for metagenomic sequencing. The composition and function of the gut microbiota were analyzed by resting-state functional magnetic resonance imaging (fMRI). Gender-dependent differences in brain ALFF values and their correlation with microbiota were further analyzed.ResultsThe relative abundance of Propionivibrio, Thermosediminibacter, and Flavobacteriaceae_noname was increased in male PD patients. LEfse analysis showed that Verrucomicrobial, Akkermansiaceae, and Akkermansia were dominant in the males. In female patients, the relative abundance of Propionicicella was decreased and Escherichia, Escherichia_coli, and Lachnospiraceae were predominant. The expression of the sesquiterpenoid and triterpenoid biosynthesis pathways was increased in male PD patients and was statistically different from females. Compared to the Male PD patients, female patients showed decreased ALFF values in the left inferior parietal regions, and the relative abundance of Propionivibrio was positively correlated with the regional ALFF values.ConclusionOur study provides novel clinical evidence of the gender-specific relationship between gut microbiota alterations and brain function in PD patients, highlighting the critical role of the microbiota-gut-brain axis in gender differences in PD

Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co-Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors

Background/Aims: Multidrug resistance (MDR) is the most common cause of chemotherapy failure. Upregulation of P-glycoprotein (P-gp) is one of the main mechanisms underlying MDR. Methods: In this study, we developed a targeted drug and small interfering (si)RNA co-delivery system based on specific aptamer-conjugated grapefruit-derived nanovectors (GNVs) that we tested in MDR LoVo colon cancer cells. The internalization of nanovectors in cancer cells was tested by fluorescence microscopy and flow cytometry. The anti-cancer activity in vitro was determined by colony formation and cell apoptosis assays. The biodistribution of nanovectors was analyzed by live imaging and the anti-cancer activity in vivo was observed. Results: GNVs loaded with aptamer increased doxorubicin (Dox) accumulation in MDR LoVo cells, an effect that was abolished by pretreatment with DNase. The LA1 aptamer effectively promoted nanovector internalization into cells at 4°C and increased the targeted delivery of Dox to tumors. Constructs harboring Dox, LA1, and P-gp siRNA more effectively inhibited proliferation and enhanced apoptosis in cultured MDR LoVo cells while exhibiting more potent anti-tumor activity in vivo than free Dox or GNVs loaded with Dox alone or in conjunction with LA1, an effect that was associated with downregulation of P-gp expression. Conclusion: This GNV-based system may be an effective strategy for overcoming MDR in clinical settings

Template Synthesis of Three-Dimensional Cubic Ordered Mesoporous Carbon With Tunable Pore Sizes

Three-dimensional cubic ordered mesoporous carbons with tunable pore sizes have been synthesized by using cubic Ia3d mesoporous KIT-6 silica as the hard template and boric acid as the pore expanding agent. The prepared ordered mesoporous carbons were characterized by powder X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and nitrogen adsorption–desorption analysis. The results show that the pore sizes of the prepared ordered mesoporous carbons with three-dimensional cubic structure can be regulated in the range of 3.9–9.4 nm. A simplified model was proposed to analyze the tailored pore sizes of the prepared ordered mesoporous carbons on the basis of the structural parameters of the silica template

Structural Characterization of Mesoporous Silica Nanofibers Synthesized Within Porous Alumina Membranes

Mesoporous silica nanofibers were synthesized within the pores of the anodic aluminum oxide template using a simple sol–gel method. Transmission electron microscopy investigation indicated that the concentration of the structure-directing agent (EO20PO70EO20) had a significant impact on the mesostructure of mesoporous silica nanofibers. Samples with alignment of nanochannels along the axis of mesoporous silica nanofibers could be formed under the P123 concentration of 0.15 mg/mL. When the P123 concentration increased to 0.3 mg/mL, samples with a circular lamellar mesostructure could be obtained. The mechanism for the effect of the P123 concentration on the mesostructure of mesoporous silica nanofibres was proposed and discussed