VEGFR2 blockade inhibits glioblastoma cell proliferation by enhancing mitochondrial biogenesis.

BACKGROUND: Glioblastoma is an aggressive brain tumor linked to significant angiogenesis and poor prognosis. Anti-angiogenic therapies with vascular endothelial growth factor receptor 2 (VEGFR2) inhibition have been investigated as an alternative glioblastoma treatment. However, little is known about the effect of VEGFR2 blockade on glioblastoma cells per se. METHODS: VEGFR2 expression data in glioma patients were retrieved from the public database TCGA. VEGFR2 intervention was implemented by using its selective inhibitor Ki8751 or shRNA. Mitochondrial biogenesis of glioblastoma cells was assessed by immunofluorescence imaging, mass spectrometry, and western blot analysis. RESULTS: VEGFR2 expression was higher in glioma patients with higher malignancy (grade III and IV). VEGFR2 inhibition hampered glioblastoma cell proliferation and induced cell apoptosis. Mass spectrometry and immunofluorescence imaging showed that the anti-glioblastoma effects of VEGFR2 blockade involved mitochondrial biogenesis, as evidenced by the increases of mitochondrial protein expression, mitochondria mass, mitochondrial oxidative phosphorylation (OXPHOS), and reactive oxygen species (ROS) production, all of which play important roles in tumor cell apoptosis, growth inhibition, cell cycle arrest and cell senescence. Furthermore, VEGFR2 inhibition exaggerated mitochondrial biogenesis by decreased phosphorylation of AKT and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), which mobilized PGC1α into the nucleus, increased mitochondrial transcription factor A (TFAM) expression, and subsequently enhanced mitochondrial biogenesis. CONCLUSIONS: VEGFR2 blockade inhibits glioblastoma progression via AKT-PGC1α-TFAM-mitochondria biogenesis signaling cascade, suggesting that VEGFR2 intervention might bring additive therapeutic values to anti-glioblastoma therapy.

Podiatrist intervention could reduce the incidence of foot ulcers in patients with diabetes: a hospital survey in China.

OBJECTIVE: This study aimed to evaluate the effectiveness of podiatrists in preventing diabetic foot ulcers (DFUs) in China. METHOD: The study was a prospective investigation. A total of 300 patients were enrolled from May 2016 to May 2018 in Handan Central Hospital, China. All patients who participated in this study had been diagnosed with type 2 diabetes, according to the International Classification of Diseases (ICD-10). All participants underwent our survey, which included basic patient data and information about DFUs. The patients were followed for one year, during which time they received appropriate intervention from podiatrists, including lifestyle guidance, callus resection, tinea grinding and ingrown nail correction. At the end of the year all the patients were surveyed again. The data before and after the year were statistically compared. RESULTS: The results showed that the incidence of DFUs in patients with diabetes was significantly decreased after one year of intervention from podiatrists (20.7% versus 6.7%, p<0.001). Additionally, there was a negative correlation between the number of intervention visits and the number of DFU occurrences (Spearman correlation coefficient: -0.496, p<0.001). Furthermore, we found that 68 patients with a history of DFUs or amputation had an obviously reduced incidence of DFUs after intervention by a podiatrist (89.7% versus 27.9%, p<0.001). We also investigated other foot risk factors in all participants, such as limb neuropathy (76.3%), lower extremity vascular disease (65.7%) and foot paralysis (43.7%). CONCLUSION: The results of this study help in understanding the situation of patients with diabetes in China and to prove that standardised podiatrist intervention has an important role in inhibiting the occurrence and development of DFUs.

P-type Polymers in Semitransparent Organic Photovoltaics.

P-type polymers are polymeric semiconducting materials that conduct holes and have extensive applications in optoelectronics such as organic photovoltaics. Taking the advantage of intrinsic discontinuous light absorption of organic semiconductors, semitransparent organic photovoltaics (STOPVs) present compelling opportunities in various potential applications such as building-integrated photovoltaics, agrivoltaics, automobiles, and wearable electronics. The characteristics of p-type polymers, including optical, electronic, and morphological properties, determine the performance of STOPVs, and the requirements for p-type polymers differ between opaque organic photovoltaics and STOPVs. Hence, in this Minireview, recent advances of p-type polymers used in STOPVs are systematically summarized, with emphasis on the effects of chemical structures, conformation structures, and aggregation structures of p-type polymers on the performance of STOPVs. Furthermore, new design concepts and guidelines are also proposed for p-type polymers to facilitate the future development of high-performance STOPVs.

The analysis of pedestrian flow in the smart city by improved DWA with robot assistance.

With the acceleration of urbanization in China, the urban population continues to grow, leading to frequent occurrences of crowded public spaces, which in turn trigger traffic congestion and even safety accidents. In order to more effectively control pedestrian flow, enhance the efficiency and safety of public spaces, this experiment conducts in-depth research and improvement on the traditional Dynamic Window Approach (DWA), and applies it to the fine control of pedestrian flow. Specifically, this study comprehensively reviews and analyzes the characteristics of pedestrian traffic flow and the working principles of traditional DWA. Based on this, the shortcomings of traditional DWA in dealing with complex pedestrian flow scenarios are identified, and targeted improvement solutions are proposed. The core of this improvement scheme lies in the introduction of a new evaluation function, enabling DWA to more accurately balance various factors in the decision-making process, including pedestrian movement speed, direction, and spatial distribution. Subsequently, the improved DWA is validated through simulation experiments. The experimental scenario is set in an area of 18 m*18 m, and compared with traditional DWA, the improved DWA shows significant advantages in trajectory length and travel time. Specifically, the trajectory length of the traditional DWA robot is 19.4 m, with a required time of 34.8 s, while the trajectory length of the improved DWA robot is shortened to 18.7 m, and the time is reduced to 18.6 s. This result fully demonstrates the effectiveness of the improved DWA in optimizing pedestrian flow control. The improved DWA proposed in this study not only has strong scientific validity but also demonstrates high efficiency in practical applications. This study has important reference value for improving the safety of urban public spaces and improving pedestrian traffic flow conditions, and provides new ideas for the further development of pedestrian flow control technology in the future.

Toward high-performance organic photovoltaics: the new cooperation of sequential solution-processing and promising non-fullerene acceptors.

Organic photovoltaics (OPVs) have long been a hot topic due to their light weight, low cost, and flexibility. Simple blend-based OPVs have sufficient donor/acceptor (D/A) interfaces and high exciton dissociation efficiency, which result in certified high power conversion efficiency (PCE) exceeding 18%. However, the difficult morphology control and poor device stability limit further progress toward higher PCE and future application. Sequential solution-processing with tunable vertical phase distribution, D/A interfaces, and charge transportation pathways not only benefit device stability but can also overcome the up-scaling challenge. In recent years, the development of non-fullerene acceptors (NFAs) has been very rapid, which is attributed to their tunable energy levels, bandgaps, planarity, and crystallinity. In this minireview, the opportunities for the cooperation of sequential solution-processing and NFAs are revealed based on their characteristics, such as diverse molecular shapes, abundant functional groups and heteroatoms, and various aggregation states for NFAs; independent active layer processing, controllable D/A interfaces, and excellent device stability for sequential solution-processing. Few but important existing examples are discussed to display the prospects of sequential solution-processed fullerene-free OPVs toward high PCE, good device stability, high semitransparency, and large-area industrial manufacture. Finally, some possible research directions are predicted and the main issues that need to be overcome are proposed for sequential solution-processed fullerene-free OPVs toward higher performance.