Based on the construction objectives of the enterprise financial sharing management platform, this paper focuses on the design concept and implementation process of each system module based on the ...overall system design under the framework of the financial sharing platform. The BP neural network algorithm is used to evaluate the financial information risk, the particle swarm optimization algorithm is used to optimize the database, the big data visualization technology is used for digitizing the financial information, and the metadata sharing technology is used to transfer the financial sharing data, to complete the financial information sharing. Through testing the platform, it is concluded that the real-time packet loss rate of financial sharing data is kept below 20%, and the average response time of multi-user clicks is within 2S. Therefore, the sharing function, the function of each module, and the performance of the platform in this paper can meet the needs of enterprises.
Senile osteoporosis has become a worldwide bone disease with the aging of the world population. It increases the risk of bone fracture and seriously affects human health. Unlike postmenopausal ...osteoporosis which is linked to menopause in women, senile osteoporosis is due to aging, hence, affecting both men and women. It is commonly found in people with more than their 70s. Evidence has shown that with age increase, bone marrow stromal cells (BMSCs) differentiate into more adipocytes rather than osteoblasts and undergo senescence, which leads to decreased bone formation and contributes to senile osteoporosis. Therefore, it is necessary to uncover the molecular mechanisms underlying the functional changes of BMSCs. It will benefit not only for understanding the senile osteoporosis development, but also for finding new therapies to treat senile osteoporosis. Here, we review the recent advances of the functional alterations of BMSCs and the related mechanisms during senile osteoporosis development. Moreover, the treatment of senile osteoporosis by aiming at BMSCs is introduced.
Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies. Herein, gold ...nanostars-based PEGylated multifunctional nanoprobes were prepared with conjugated CD44v6 monoclonal antibodies (CD44v6-GNS) as the targeting ligands. It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon near-infrared (NIR) laser treatment (790 nm, 1.5 W/cm(2), 5 min) in vitro experiment. Orthotopic and subcutaneous xenografted nude mice models of human gastric cancer were established. Subsequently, biodistribution and photothermal therapeutic effects after being intravenously injected with the prepared nanoprobes were assessed. Photoacoustic imaging revealed that CD44v6-GNS nanoprobes could target the gastric cancer vascular system actively at 4 h post-injection, while the probes inhibited tumor growth remarkably upon NIR laser irradiation, and even extended survivability of the gastric cancer-bearing mice. The CD44v6-GNS nanoprobes exhibited great potential for applications of gastric cancer targeted imaging and photothermal therapy in the near future.
Piezo channels are mechanosensitive ion channels located in the cell membrane and function as key cellular mechanotransducers for converting mechanical stimuli into electrochemical signals. Emerged ...as key molecular detectors of mechanical forces, Piezo channels’ functions in bone have attracted more and more attention. Here, we summarize the current knowledge of Piezo channels and review the research advances of Piezo channels’ function in bone by highlighting Piezo1′s role in bone cells, including osteocyte, bone marrow mesenchymal stem cell (BM-MSC), osteoblast, osteoclast, and chondrocyte. Moreover, the role of Piezo channels in bone diseases is summarized.
Osteoblast differentiation leading to bone formation requires a coordinated transcriptional program. Osteoblastic cells with low level of microtubule actin crosslinking factor 1 (MACF1) show reduced ...osteoblast differentiation ability, however, the comprehensive mechanism of MACF1's action remains unexplored. In the current study, we found that MACF1 knockdown suppressed osteoblast differentiation by altering the transcriptome dynamics. We further identified two MACF1-interacted proteins, cyclin-dependent kinase 12 (CDK12) and MYST/Esa1-associated factor 6 (MEAF6), and two MACF1-interacted transcription factors (TFs), transcription factor 12 (TCF12) and E2F transcription factor 6 (E2F6), which repress osteoblast differentiation by altering the expression of osteogenic TFs and genes. Moreover, we found that MACF1 regulated cytoplasmic-nuclear localization of itself, TCF12 and E2F6 in a concentration-dependent manner. MACF1 oppositely regulates the expression of TCF12 and transcription factor 7 (TCF7), two TFs that drive osteoblast differentiation to opposite directions. This study reveals that MACF1, a cytoskeletal protein, acts as a sponge for repressors of osteoblast differentiation to promote osteoblast differentiation and contributes to a novel mechanistic insight of osteoblast differentiation and transcription dynamics.
Immunotherapy begins to be widely used due to the increasing exploration and gratifying effects in multiple cancers. Chordoma, as a rare bone malignant tumor, often recurs and metastasizes after ...undergoing surgery and radiotherapy. Therefore, immunotherapy can be explored as an emerging, potentially effective treatment to improve the survival rate and clinical benefit of patients. However, a variety of immune-related adverse events (irAEs) cannot be avoided completely. And the immunotherapy-induced myocarditis, as a rare but fatal irAE, has been increasingly reported. Understanding the mechanism involved in irAEs can inform best practices for side effects management. Here, we firstly reported a case of immune myocarditis and subsequent myasthenia gravis (MG) following anti-PD-1 treatment for chordoma.
The present study was conducted to validate the Chinese version of the Adult Decision-Making Competence scale. 364 college students were recruited from four universities in China. The results ...indicate the Chinese Adult Decision-Making Competence subscales have good internal consistency and the two-factor structure in the study of Bruine de Bruin et al. (2007) was conformed. Gender differences were found in Resistance to Sunk Cost. Differences of Applying Decision Rules and Consistency in Risk Perception were found between participants with different education background. Overall, the Chinese Adult Decision-Making Competence scale is validated in China.
: Irisin, a novel exercise-induced myokine, was shown to mediate beneficial effects of exercise in osteoporosis. Microgravity is a major threat to bone homeostasis of astronauts during long-term ...spaceflight, which results in decreased bone formation.
: The hind-limb unloading mice model and a random position machine are respectively used to simulate microgravity in vivo and in vitro.
: We demonstrate that not only are bone formation and osteoblast differentiation decreased, but the expression of fibronectin type III domain-containing 5 (Fdnc5; irisin precursor) is also downregulated under simulated microgravity. Moreover, a lower dose of recombinant irisin (r-irisin) (1 nM) promotes osteogenic marker gene (alkaline phosphatase (
), collagen type 1 alpha-1(
)) expressions, ALP activity, and calcium deposition in primary osteoblasts, with no significant effect on osteoblast proliferation. Furthermore, r-irisin could recover the decrease in osteoblast differentiation induced by simulated microgravity. We also find that r-irisin increases β-catenin expression and partly neutralizes the decrease in β-catenin expression induced by simulated microgravity. In addition, β-catenin overexpression could also in part attenuate osteoblast differentiation reduction induced by simulated microgravity.
: The present study is the first to show that r-irisin positively regulates osteoblast differentiation under simulated microgravity through increasing β-catenin expression, which may reveal a novel mechanism, and it provides a prevention strategy for bone loss and muscle atrophy induced by microgravity.
Studies suggest that resource scarcity leads to risky behaviors. From a cognitive perspective, a scarcity mindset affects the decision-making process. Does perceived scarcity therefore affect risk ...taking when making decisions? This study (N = 213) was conducted in western China to examine the effect of perceived scarcity on risky choices. Our results revealed that participants in the scarcity condition tended to be more risk averse than participants in the control condition when making a risky decision. Perceived scarcity increased the probability of choosing the safe option that offered a sure gain. The effect of psychological variables (emotion, risk attitude, personality, impulsivity, self-control and ego depletion) on risky choices was also tested. Risk attitude, urgency in impulsivity, and deliberate action in self-control also influence risky choices.
Non-redundant properties such as hypoxia and acidosis promote tumor metabolic adaptation and limit anti-cancer therapies. The key to the adaptation of tumor cells to hypoxia is the transcriptional ...and stable expression of hypoxia-inducible factor-1 alpha (HIF-1α). The phosphorylation-activated tumorigenic signal PI3K/AKT/mTOR advances the production of downstream HIF-1α to adapt to tumor hypoxia. Studies have elucidated that acid favors inhibition of mTOR signal. Nonetheless, carbonic anhydrase IX (CAIX), overexpressed on membranes of hypoxia tumor cells with pH-regulatory effects, attenuates intracellular acidity, which is unfavorable for mTOR inhibition. Herein, a drug delivery nanoplatform equipped with dual PI3K/mTOR inhibitor Dactolisib (NVP-BEZ235, BEZ235) and CAIX inhibitor 4-(2-aminoethyl) benzene sulfonamide (ABS) was designed to mitigate hypoxic adaptation and improve breast cancer treatment.
ABS and PEG-NH
were successfully modified on the surface of hollow polydopamine (HPDA), while BEZ235 and Chlorin e6 (Ce6) were effectively loaded with the interior of HPDA to form HPDA-ABS/PEG-BEZ235/Ce6 (H-APBC) nanoparticles. The release of BEZ235 from H-APBC in acid microenvironment could mitigate PI3K/mTOR signal and resist HIF-1α-dependent tumor hypoxia adaptation. More importantly, ABS modified on the surface of H-APBC could augment intracellular acids and enhances the mTOR inhibition. The nanoplatform combined with phototherapy inhibited orthotopic breast cancer growth while reducing spontaneous lung metastasis, angiogenesis, based on altering the microenvironment adapted to hypoxia and extracellular acidosis.
Taken together, compared with free BEZ235 and ABS, the nanoplatform exhibited remarkable anti-tumor efficiency, reduced hypoxia adaptation, mitigated off-tumor toxicity of BEZ235 and solved the limited bioavailability of BEZ235 caused by weak solubility.
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