Multifunctional Nanotherapeutics with Long-Acting Release against Macular Degeneration by Minimally Invasive Administration.

Neovascular age-related macular degeneration (AMD), a leading cause of blindness, requires frequent intravitreal injection of antivascular endothelial growth factor (anti-VEGF), which could generate a succession of complications with poor patient compliance. The current VEGF-targeting therapies often fail in half of patients due to the complex pathologic microenvironment of excessive reactive oxygen species (ROS) production, and increased levels of inflammation are accompanied by choroidal neovascularization (CNV). We herein reported multifunctional nanotherapeutics featuring superior antioxidant and anti-inflammation properties that aim to reverse the pathological condition, alongside its strong targeted antiangiogenesis to CNV and its ability to provide long-term sustained bioactive delivery via the minimally invasive subconjunctival injection, so as to achieve satisfactory wet AMD treatment effects. Concretely, the nanomedicine was designed by coencapsulation of astaxanthin (AST), a red pigmented carotenoid known for its antioxidative, anti-inflammatory and antiapoptotic properties, and axitinib (AXI), a small molecule tyrosine kinase inhibitor that selectively targets the vascular epidermal growth factor receptor for antiangiogenesis, into the Food and Drug Administration (FDA) approved poly(lactic-co-glycolic acid) (PLGA), which forms the nanodrug of PLGA@AST/AXI. Our results demonstrated that a single-dose subconjunctival administration of PLGA@AST/AXI showed a rational synergistic effect by targeting various prevailing risk factors associated with wet AMD, ensuring persistent drug release profiles, maintaining good ocular biocompatibility, and causing no obvious mechanical damage. Such attributes are vital and hold significant potential in treating ocular posterior segment diseases. Moreover, this nanotherapeutic strategy represents a versatile and broad-spectrum nanoplatform, offering a promising alternative for the complex pathological progression of other neovascular diseases.

Emerging Co-Assembled and Sustained Released Natural Medicinal Nanoparticles for Multitarget Therapy of Choroidal Neovascularization.

Age-related macular degeneration (AMD) disease has become a worldwide senile disease, and frequent intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is the mainstream treatment in the clinic, which is associated with sight-threatening complications. Herein, nintedanib, an inhibitor of angiogenesis, and lutein, a potent antioxidant, can co-assemble into nanoparticles through multiple noncovalent interactions. Interestingly, the co-assembled lutein/nintedanib nanoparticles (L/N NPs) exhibit significantly improved stability and achieve long-term sustained release of two drugs for at least two months in mice. Interestingly, in rabbit eyeball with a more complete barrier system, the L/N NPs still successfully distribute in the retina and choroid for a month. In the laser-induced mouse choroidal neovascularization model, the L/N NPs after a minimally invasive subconjunctival administration can successfully inhibit angiogenesis and achieve comparable and even better therapeutic results to that of standard intravitreal injection of anti-VEGF. Therefore, the subconjunctival injection of L/N NPs with long-term sustained drug release behavior represents a promising and innovative strategy for AMD treatment. Such minimally invasive administration together with the ability to effectively inhibit angiogenesis reduce inflammation and counteract oxidative stress and holds great potential for improving patient outcomes and quality of life in those suffering from this debilitating eye condition.

Does higher education promote sustainable development? Role of green technology and financial performance.

How do digitalizing businesses help them achieve sustainable growth? This research examines the mediating function of green technology innovation in answering this question by defining sustainable development performance in terms of corporations' financial and environmental success. The educational system in China is examined to see how much of an impact it has on eco-innovation, as well as the relationship between green technology and innovation. The IFE test was utilized to determine whether or not the associations between variables such as GDP per capita, urbanization, green technology, higher education, and carbon dioxide emissions will continue to exist between 2004 and 2020 in China. The data for this analysis came from 30 of China's provinces. The findings of both the short-term and long-term CS-ARDL estimations demonstrated a positive link between eco-innovation and GDP per capita, green technology, higher education, and CO2 emissions. On the other hand, a negative correlation was found between urbanization and eco-innovation. The next topic covered in the research was how the effects of green technology might be seen in areas such as GDP per capita, higher education, and carbon dioxide emissions. The findings might provide valuable knowledge that developing economies can use to construct a feasible, sustainable path.

LINC00092 Modulates Oxidative Stress and Glycolysis of Breast Cancer Cells via Pyruvate Carboxylase-Mediated AKT/mTOR Pathway.

Background: The discovery of noncoding RNAs (ncRNAs) offers new options for cancer-targeted therapy. This study is aimed at exploring the regulatory function of LINC00092 on breast cancer (BC) oxidative stress and glycolysis, along with internal mechanism concerning pyruvate carboxylase (PC). Methods: Bioinformatics analysis was used to explore LINC00092 (or friend leukemia virus integration 1 (FLI1)) expression on BC progression, as well as oxidative stress and glycolysis in BC. After LINC00092 overexpression or silence, BC cell viability, proliferation, migration, invasion, oxidative stress, glycolysis, and AKT/mTOR pathway were detected. Following 2-DG, SC79, or MK2206 treatment, effects of LINC00092 on BC cells were measured. Moreover, regulatory activity of LINC00092 in PC expression was analyzed. Whether PC participated in the modulation of LINC00092 on BC cell functions was explored. Results: LINC00092 was lowly expressed in BC and negatively related to BC progression. FLI1 bound to LINC00092 promoter to positively modulate LINC00092. LINC00092 overexpression inhibited BC cell proliferation, migration, invasion, oxidative stress, glycolysis, and AKT/mTOR pathway and likewise suppressed BC growth in vivo. Silence of LINC00092 had opposite influences. 2-DG partially reversed the LINC00092 silence-resulted increase of BC cell proliferation. SC79 alleviated the function of LINC00092 overexpression on BC cell functions. MK2206 had the contrary influence of SC79. Besides, LINC00092 bound to PC to modulate ubiquitination degradation of PC protein. PC took part in the influences of LINC00092 on BC cell functions. Conclusions: LINC0092 modulates oxidative stress and glycolysis of BC cells via the PC-mediated AKT/mTOR pathway, which is possibly a target for BC diagnosis and therapy.

Analysis of Stemness and Prognosis of Subtypes in Breast Cancer Using the Transcriptome Sequencing Data.

The stem characteristics of tumor cells have been proposed in theory very early, and we can use the signature of gene expression to speculate the stemness of tumor cells. However, systematic studies on the stemness of breast cancer as well as breast cancer subtypes, and the relationship between stemness and metastasis and prognosis, are still lacking. In the present research, using the transcriptome data of patients with breast cancer in the TCGA database, a stemness prediction model was utilized to derive the stemness of the patients' tumors. We compared the stemness values among different subtypes and the differences with metastasis. COX regression was employed to evaluate the correlation between stemness value as well as prognosis. Using the Lasso-penalized Cox regression machine learning model, we obtained the gene signature of the basal subtype that is related to stemness and can also predict the prognosis of the patient. Patients can be stratified into two groups of high and low stemness, corresponding to good and poor prognosis. Based on further prediction of tumor infiltration by CIBERSORT and prediction of drug response by a connectivity map, we found that the difference in stemness between these two groups is associated with the activation of tumor-killing immune cells and drug response. Our findings can promote the understanding and research of subtypes of basal breast cancer and provide corresponding molecular markers for clinical detection and therapy.