Drug Repurposing-Based Brain-Targeting Self-Assembly Nanoplatform Using Enhanced Ferroptosis against Glioblastoma.

Glioblastoma (GBM), the most aggressive and lethal form of malignant brain tumor, is a therapeutic challenge due to the drug filtration capabilities of the blood-brain barrier (BBB). Interestingly, glioblastoma tends to resist apoptosis during chemotherapy, but is susceptible to ferroptosis. Developing therapies that can effectively target glioblastoma by crossing the BBB and evoke ferroptosis are, therefore, crucial for improving treatment outcomes. Herein, a versatile biomimetic nanoplatform, L-D-I/NPs, is designed that self-assembled by loading the antimalarial drug dihydroartemisinin (DHA) and the photosensitizer indocyanine green (ICG) onto lactoferrin (LF). This nanoplatform can selectively target glioblastoma by binding to low-density lipoprotein receptor-related protein-1 (LRP1) and crossing the BBB, thus inducing glioblastoma cell ferroptosis by boosting intracellular reactive oxygen species (ROS) accumulation and iron overload. In addition, L-D-I/NPs have demonstrated the ability to effectively suppress the progression of orthotopic glioblastoma and significantly prolong survival in a mouse glioblastoma model. This nanoplatform has facilitated the application of non-chemotherapeutic drugs in tumor treatment with minimal adverse effects, paving the way for highly efficient ferroptosis-based therapies for glioblastoma.

3BDO Alleviates Seizures and Improves Cognitive Function by Regulating Autophagy in Pentylenetetrazol (PTZ)-Kindled Epileptic Mice Model.

3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3 H)-one (3BDO) is a mTOR agonist that inhibits autophagy. The main purpose of this study is to investigate the effects of 3BDO on seizure and cognitive function by autophagy regulation in pentylenetetrazol (PTZ)-kindled epileptic mice model. The PTZ-kindled epileptic mice model was used in study. The behavioral changes and electroencephalogram (EEG) of the mice in each group were observed. The cognitive functions were tested by Morris water maze test. The loss of hippocampal neurons was detected by hematoxylin-eosin (HE) staining and immunofluorescence analysis. Immunohistochemistry, western blot and q-PCR were employed to detect the expression of autophagy-related proteins and mTOR in the hippocampus and cortex. Less seizures, increased hippocampal neurons and reduced astrocytes of hippocampus were observed in the 3BDO-treated epileptic mice than in the PTZ-kindled epileptic mice. Morris water maze test results showed that 3BDO significantly improved the cognitive function of the PTZ-kindled epileptic mice. Western blot analyses and q-PCR revealed that 3BDO inhibited the expression of LC3, Beclin-1, Atg5, Atg7 and p-ULK1/ULK1, but increased that of p-mTOR/mTOR, p-P70S6K/P70S6K in the hippocampus and temporal lobe cortex of epileptic mice. Immunohistochemistry and immunofluorescence also showed 3BDO inhibited the LC3 expression and increased the mTOR expression in the hippocampus of epileptic mice. In addition, the autophagy activator EN6 reversed the decrease in the 3BDO-induced autophagy and aggravated the seizures and cognitive dysfunction in the epileptic mice. 3BDO regulates autophagy by activating the mTOR signaling pathway in PTZ-kindled epileptic mice model, thereby alleviating hippocampus neuronal loss and astrocytes proliferation, reducing seizures and effectively improving cognitive function. Therefore, 3BDO may have potential value in the treatment of epilepsy.

The impact of perceived risk of online takeout packaging and the moderating role of educational level.

With the rapid development of e-commerce and the impact of COVID-19, online takeout has become the first choice of more and more consumers. Previous research has indicated that food packaging is of great significance to marketing performance, yet very little is known about the mechanisms through which food packaging pollution risk affects online takeout consumption. This study proposes an expanded model of the Theory of Planned Behavior (TPB) by incorporating the Concept of Perceived Risk (CPR) to analyze the mechanism of consumers' packaging pollution risk perception (PPRP) on their purchasing intention toward online takeout. Online survey was performed to collect data from 336 valid respondents in China, which was analyzed using structural equation modeling. The research findings verify the effectiveness of the TPB in the context of Chinese online takeout. Notably, the PPRP of online takeout was found to have a significant negative impact on consumers' attitudes, subjective norms, and perceived behavioral control (PBC). It was also confirmed that consumers' attitudes, subjective norms, and PBC regarding online takeout partially mediate the negative relationship between PPRP and purchase intention. In addition, the findings corroborate the granular nuances among three groups concerning consumers' education level. The results do not only provide suggestions to the online takeout industry but also contribute theoretical value and practical significance for the improvement of sustainable food consumption.

Determinants of Intention to Purchase Bottled Water Based on Business Online Strategy in China: The Role of Perceived Risk in the Theory of Planned Behavior.

With the development of the network economy, especially the promotion and popularization of mobile networks, traditional offline businesses are further integrated with online businesses, promoting the development of business online strategies. However, with the growth of enterprises' business, their negative externalities on the environment have gradually become prominent, further affecting sustainable consumption. The relationships between businesses, the environment, and consumption have become the focus of attention. China's fast-growing bottled water companies face similar challenges. The pollution that occurs due to bottled water packaging poses great threats to consumers. Hence, this study extended the Theory of Planned Behavior (TPB) by integrating three risk aspects, namely, water pollution risk perception (WPRP), non-degradable package pollution risk perception (NPPRP), and false information risk perception (FIRP), to examine the consumers' perceptions toward these risk aspects before purchasing bottled water online. This study employed a cross-sectional approach to collect data from online consumers via a survey method. A total of 401 valid samples were collected and then analyzed via a structural equation model using the AMOS statistical package. The results showed that attitude (AT), subjective norm (SN), and perceived behavior control (PBC) toward online bottled water purchase had significant and positive effects on the consumers' purchase intentions (PIs). However, under the influence of risk perception, the consumers' attitudes, SNs and PBC became suppressed by WPRP, and SN became suppressed due to the impact of FIRP. Furthermore, the negative impacts of NPPRP and FIRP on PI were partially mediated by AT, SN and PBC. Meanwhile, WPRP imposed the most significant direct effect on PI. The study results will help businesses to develop better online strategies to reduce the risk perception of bottled water and provide theoretical value and practical guidance for realizing sustainable consumption.

Iron Metabolism and Ferroptosis in Epilepsy.

Epilepsy is a disease characterized by recurrent, episodic, and transient central nervous system (CNS) dysfunction resulting from an excessive synchronous discharge of brain neurons. It is characterized by diverse etiology, complex pathogenesis, and difficult treatment. In addition, most epileptic patients exhibit social cognitive impairment and psychological impairment. Iron is an essential trace element for human growth and development and is also involved in a variety of redox reactions in organisms. However, abnormal iron metabolism is associated with several neurological disorders, including hemorrhagic post-stroke epilepsy and post-traumatic epilepsy (PTE). Moreover, ferroptosis is also considered a new form of regulation of cell death, which is attributed to severe lipid peroxidation caused by the production of reactive oxygen species (ROS) and iron overload found in various neurological diseases, including epilepsy. Therefore, this review summarizes the study on iron metabolism and ferroptosis in epilepsy, in order to elucidate the correlation between iron and epilepsy. It also provides a novel method for the treatment, prevention, and research of epilepsy, to control epileptic seizures and reduce nerve injury after the epileptic seizure.

Regulation of SPARC family proteins in disorders of the central nervous system.

SPARC (secreted protein acidic and rich in cysteine) family of proteins is a class of protein involved in tissue development and repair by regulating cell adhesion, proliferation, metastasis, and growth factor signaling to affect the extracellular matrix (ECM) and interactions between cells. Although being highly valued in non-nerve tissues, studies in both cell and animal models have been revealed that SPARC family proteins may also continue to play a vital role in central nervous system (CNS) diseases and development. These SPARC family proteins are widely expressed in the CNS of normal people, and significantly increased in brain tissue following disease or injury, such as SPARC, SPARCL-1, FSTL-1 and testican. In our review, we will pay attention to the functions of SPARC family proteins in autophagy, apoptosis, angiogenesis, adipogenesis, inflammatory response, and cerebral tissue development, injury and repair mainly including but not limited to axon regeneration, formation of glial scar, neural plasticity, regulation of nerve conduction related receptors and rewiring of neural circuitry.