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This work presents the results of lessons learned from a home-grown AI-enhanced educational technology that combines interactive learning, social features, and Large Language Models to promote environmental sustainability awareness and waste management learning. The system employs an Environmental Legislative-guided Large Language Model (EL-LLM) to transform complex environmental regulations into accessible educational content and provide personalized feedback. Through both static posts and interactive quizzes, the platform facilitates formal instruction and informal social learning. Multiple evaluative user studies conducted between 2023-2024 evaluated the system's effectiveness in promoting sustainability awareness and understanding. Our analysis reveals complementary strengths between user-generated and AI-generated educational content, while demonstrating strong alignment with United Nations Sustainable Development Goals (SDGs), particularly those related to responsible consumption (SDG 12), water and marine life (SDG 6, SDG 14), and life on land (SDG 15). This research contributes to a new understanding of how AI-enhanced educational technologies can effectively promote environmental sustainability while supporting global sustainability goals through an engaging learning experience.

There is increasing evidence that inducing neuronal mitophagy can be used as a therapeutic intervention for Alzheimer’s disease. Here, we screen a library of 2024 FDA-approved drugs or drug candidates, revealing UMI-77 as an unexpected mitophagy activator. UMI-77 is an established BH3-mimetic for MCL-1 and was developed to induce apoptosis in cancer cells. We found that at sub-lethal doses, UMI-77 potently induces mitophagy, independent of apoptosis. Our mechanistic studies discovered that MCL-1 is a mitophagy receptor and directly binds to LC3A. Finally, we found that UMI-77 can induce mitophagy in vivo and that it effectively reverses molecular and behavioral phenotypes in the APP/PS1 mouse model of Alzheimer’s disease. Our findings shed light on the mechanisms of mitophagy, reveal that MCL-1 is a mitophagy receptor that can be targeted to induce mitophagy, and identify MCL-1 as a drug target for therapeutic intervention in Alzheimer’s disease. Previous work suggests that mitophagy in neurons is could be therapeutic in Alzheimer’s disease (AD). Here, the authors screen a library of drugs and identify UMI-77, a mitophagy inducer with beneficial effects in an AD mouse model, by binding MCL-1, which they identify as a mitophagy receptor.

With the aim of mitigating the impact of wind power integration and source-load-side uncertainties on an integrated energy system, we initially employed the Monte Carlo simulation in this study to randomly generate multiple wind power output/load scenarios in accordance with probability distribution functions. Additionally, we proposed a two-stage optimization method. In the first stage of our study, an enhanced African vulture optimization algorithm was applied to perform multi-objective optimization targeting fuel cost and carbon emissions across various scenarios, thereby solving the Pareto frontier to obtain multiple candidate solutions. In the study’s second stage, comprehensively considering fuel cost, carbon emission, and wind power penetration rate, evidential reasoning was utilized to determine the optimal operation strategy among the candidates. Finally, a combined heat and power system composed of the IEEE 30-bus system and a 32-node heating network was simulated. The results demonstrate that this decision-making approach can effectively reflect the merits of candidate solutions, thus validating the feasibility of the designed research methodology.

Chaperone-mediated autophagy (CMA) is a lysosomedependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases. However, the mechanisms that regulate CMA are not fully understood. Here, using unbiased drug screening approaches, we discover Metformin, a drug that is commonly the first medication prescribed for type 2 diabetes, can induce CMA. We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation. Notably, we find that amyloid-beta precursor protein (APP) is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent manner. The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity. Importantly, we find that in the APP/ PS1 mouse model of Alzheimer's disease (AD), activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβ plaque levels and reverses the molecular and behavioral AD phenotypes. Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.

Sorafenib is the first-line chemotherapeutic therapy for advanced hepatocellular carcinoma (HCC). However, sorafenib resistance significantly limits its therapeutic efficacy, and the mechanisms underlying resistance have not been fully clarified. Here we report that a circular RNA, circRNA-SORE (a circular RNA upregulated in sorafenib-resistant HCC cells), plays a significant role in sorafenib resistance in HCC. We found that circRNA-SORE is upregulated in sorafenib-resistant HCC cells and depletion of circRNA-SORE substantially increases the cell-killing ability of sorafenib. Further studies revealed that circRNA-SORE binds the master oncogenic protein YBX1 in the cytoplasm, which prevents YBX1 nuclear interaction with the E3 ubiquitin ligase PRP19 and thus blocks PRP19-mediated YBX1 degradation. Moreover, our in vitro and in vivo results suggest that circRNA-SORE is transported by exosomes to spread sorafenib resistance among HCC cells. Using different HCC mouse models, we demonstrated that silencing circRNA-SORE by injection of siRNA could substantially overcome sorafenib resistance. Our study provides a proof-of-concept demonstration for a potential strategy to overcome sorafenib resistance in HCC patients by targeting circRNA-SORE or YBX1.

The effect of deformation on the oriented crystal structure of polypropylene, specializing in capacitor film during stretching at high temperature, was verified. Two kinds of polypropylene with different isotacticity were stretched to different deformation ratios at the same temperature, and the microstructures of the oriented crystals were analyzed by synchrotron 2d wide‐angle/small‐angle X‐ray scattering technique. Results showed that during partial melting stretching, the thickness of lamellar stacks remained constant at a fixed temperature, and the thicknesses of the lamellae crystals, and the amorphous region were invariable over a wide range of stretching deformation. However, the increased deformation led to a decrease in the lateral dimensions of the lamellar stack, indicating that the oriented crystals slipped and broke up along the stretch direction, resulting in the formation of microfibrillar structures. This increase was accompanied by an increase in crystal orientation induced by external forces. Additionally, higher isotacticity facilitated the acquisition of a high degree of orientation and crystallinity, but it had less effect on the lamellar stack thickness. This paper elucidated the relationship between the oriented crystal structure and the deformation behavior of polypropylene, thereby providing a fundamental theoretical basis for optimizing the properties of films based on the hot‐stretching process.

Under stress, the endomembrane system undergoes reorganization to support autophagosome biogenesis, which is a central step in autophagy. How the endomembrane system remodels has been poorly understood. Here we identify a new type of membrane contact formed between the ER–Golgi intermediate compartment (ERGIC) and the ER-exit site (ERES) in the ER–Golgi system, which is essential for promoting autophagosome biogenesis induced by different stress stimuli. The ERGIC–ERES contact is established by the interaction between TMED9 and SEC12 which generates a short distance opposition (as close as 2–5 nm) between the two compartments. The tight membrane contact allows the ERES-located SEC12 to transactivate COPII assembly on the ERGIC. In addition, a portion of SEC12 also relocates to the ERGIC. Through both mechanisms, the ERGIC–ERES contact promotes formation of the ERGIC-derived COPII vesicle, a membrane precursor of the autophagosome. The ERGIC–ERES contact is physically and functionally different from the TFG-mediated ERGIC–ERES adjunction involved in secretory protein transport, and therefore defines a unique endomembrane structure generated upon stress conditions for autophagic membrane formation.

Autophagy mediates the cellular response to nutrient deprivation, protein aggregation, and pathogen invasion in human. Dysfunction of autophagy has been implicated in multiple human diseases including cancer. The identification of novel autophagy factors in mammalian cells will provide critical mechanistic insights into how this complicated cellular pathway responds to a broad range of challenges. Here, we report the cloning of an autophagy-specific protein that we called Barkor (Beclin 1-associated autophagy-related key regulator) through direct interaction with Beclin 1 in the human phosphatidylinositol 3-kinase class III complex. Barkor shares 18% sequence identity and 32% sequence similarity with yeast Atg14. Elimination of Barkor expression by RNA interference compromises starvation- and rapamycin-induced LC3 lipidation and autophagosome formation. Overexpression of Barkor leads to autophagy activation and increased number and enlarged volume of autophagosomes. Tellingly, Barkor is also required for suppression of the autophagy-mediated intracellular survival of Salmonella typhimurium in mammalian cells. Mechanistically, Barkor competes with UV radiation resistance associated gene product (UVRAG) for interaction with Beclin 1, and the complex formation of Barkor and Beclin1 is required for their localizations to autophagosomes. Therefore, we define a regulatory signaling pathway mediated by Barkor that positively controls autophagy through Beclin 1 and represents a potential target for drug development in the treatment of human diseases implicated in autophagic dysfunction.

The nucleotide oligomerization domain (NOD)–like receptors 1 and 2 (NOD1/2) are intracellular pattern-recognition proteins that activate immune signaling pathways in response to peptidoglycans associated with microorganisms. Recruitment to bacteria-containing endosomes and other intracellular membranes is required for NOD1/2 signaling, and NOD1/2 mutations that disrupt membrane localization are associated with inflammatory bowel disease and other inflammatory conditions. However, little is known about this recruitment process. We found that NOD1/2 S-palmitoylation is required for membrane recruitment and immune signaling. ZDHHC5 was identified as the palmitoyltransferase responsible for this critical posttranslational modification, and several disease-associated mutations in NOD2 were found to be associated with defective S-palmitoylation. Thus, ZDHHC5-mediated S-palmitoylation of NOD1/2 is critical for their ability to respond to peptidoglycans and to mount an effective immune response.

Fan power generation, a form of new energy, has gained significant attention. However, as fan capacities grow, the challenges in the development process also increase. A wind maneuver model experiment system must be constructed to simulate the actual fan operation dynamics. The wind turbine simulator is essential for conducting experiments on wind turbines and advancing the research of wind power production technology. However, due to the insufficient moment of inertia in wind turbine simulators under laboratory conditions, physical compensation methods are challenging to implement. Therefore, most scholars rely on software compensation algorithms to realize the stability simulation of wind turbine simulators with small moments of inertia and actual wind turbines with large moments of inertia. Under this research background, this paper presents the existing moment of inertia compensation strategies based on current research hotspots. The theoretical foundation covers the mechanical dynamic models of both actual wind turbines and simulators along with an analysis of inertia compensation strategies, including high-order filters and feedforward bias suppression. Finally, the Simulink simulation platform is used to compare and validate the effectiveness of these strategies.