Abstract Many types of human cells self-destruct to maintain biological homeostasis and defend the body against pathogenic substances. This process, called regulated cell death (RCD), is important for various biological activities, including the clearance of aberrant cells. Thus, RCD pathways represented by apoptosis have increased in importance as a target for the development of cancer medications in recent years. However, because tumor cells show avoidance to apoptosis, which causes treatment resistance and recurrence, numerous studies have been devoted to alternative cancer cell mortality processes, namely necroptosis, pyroptosis, ferroptosis, and cuproptosis; these RCD modalities have been extensively studied and shown to be crucial to cancer therapy effectiveness. Furthermore, evidence suggests that tumor cells undergoing regulated death may alter the immunogenicity of the tumor microenvironment (TME) to some extent, rendering it more suitable for inhibiting cancer progression and metastasis. In addition, other types of cells and components in the TME undergo the abovementioned forms of death and induce immune attacks on tumor cells, resulting in enhanced antitumor responses. Hence, this review discusses the molecular processes and features of necroptosis, pyroptosis, ferroptosis, and cuproptosis and the effects of these novel RCD modalities on tumor cell proliferation and cancer metastasis. Importantly, it introduces the complex effects of novel forms of tumor cell death on the TME and the regulated death of other cells in the TME that affect tumor biology. It also summarizes the potential agents and nanoparticles that induce or inhibit novel RCD pathways and their therapeutic effects on cancer based on evidence from in vivo and in vitro studies and reports clinical trials in which RCD inducers have been evaluated as treatments for cancer patients. Lastly, we also summarized the impact of modulating the RCD processes on cancer drug resistance and the advantages of adding RCD modulators to cancer treatment over conventional treatments. 

/pdf/targeting-cell-death-pathways-for-cancer-therapy-recent-1s2ymajs.pdf

Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research

Unraveling tumor microenvironment of small-cell lung cancer: implications for immunotherapy.

Cell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell death modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which can be mediated by multifaceted PANoptosome complexes assembled via integrating components from other cell death modalities. There is growing interest in the process and function of PANoptosis. Accumulating evidence suggests that PANoptosis occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, and cancer. Given the impact of PANoptosis across the disease spectrum, this review briefly describes the relationships between pyroptosis, apoptosis, and necroptosis, highlights the key molecules in PANoptosome formation and PANoptosis activation, and outlines the multifaceted roles of PANoptosis in diseases together with a potential for therapeutic targeting. We also discuss important concepts and pressing issues for future PANoptosis research. Improved understanding of PANoptosis and its mechanisms is crucial for identifying novel therapeutic targets and strategies.

PANoptosis: Mechanisms, biology, and role in disease.

Abstract Ferroptosis is an iron-dependent regulated cell death marked by excessive oxidative phospholipids (PLs). The polyunsaturated fatty acids-containing phospholipids (PUFA-PLs) are highly susceptible to lipid peroxidation under oxidative stress. Numerous pulmonary diseases occurrences and degenerative pathologies are driven by ferroptosis. This review discusses the role of ferroptosis in the pathogenesis of pulmonary diseases including asthma, lung injury, lung cancer, fibrotic lung diseases, and pulmonary infection. Additionally, it is proposed that targeting ferroptosis is a potential treatment for pulmonary diseases, particularly drug-resistant lung cancer or antibiotic-resistant pulmonary infection, and reduces treatment-related adverse events. 

/pdf/targeting-ferroptosis-as-a-vulnerability-in-pulmonary-2etovh6z.pdf

Targeting ferroptosis as a vulnerability in pulmonary diseases

Photosensitizer-based photodynamic therapy (PDT) has been considered as a promising modality for fighting diverse types of cancers. PDT directly inhibits local tumors by a minimally invasive strategy, but it seems to be incapable of achieving complete eradication and fails to prevent metastasis and recurrence. Recently, increasing events proved that PDT was associated with immunotherapy by triggering immunogenic cell death (ICD). Upon a specific wavelength of light irradiation, the photosensitizers will turn the surrounding oxygen molecules into cytotoxic reactive oxygen species (ROS) for killing the cancer cells. Simultaneously, the dying tumor cells release tumor-associated antigens, which could improve immunogenicity to activate immune cells. However, the progressively enhanced immunity is typically limited by the intrinsic immunosuppressive tumor microenvironment (TME). To overcome this obstacle, immuno-photodynamic therapy (IPDT) has come to be one of the most beneficial strategies, which takes advantage of PDT to stimulate the immune response and unite immunotherapy for inducing immune-OFF tumors to immune-ON ones, to achieve systemic immune response and prevent cancer recurrence. In this Perspective, we provide a review of recent advances in organic photosensitizer-based IPDT. The general process of immune responses triggered by photosensitizers (PSs) and how to enhance the antitumor immune pathway by modifying the chemical structure or conjugating with a targeting component was discussed. In addition, future perspectives and challenges associated with IPDT strategies are also discussed. We hope this Perspective could inspire more innovative ideas and provide executable strategies for future developments in the war against cancer.

https://pubs.acs.org/doi/pdf/10.1021/jacsau.2c00591

Immuno-photodynamic Therapy (IPDT): Organic Photosensitizers and Their Application in Cancer Ablation

Ferroptosis, necroptosis, and pyroptosis in the tumor microenvironment: perspectives for immunotherapy of SCLC.

With the large-mount access of renewable energy to the electric power grid, the unique seasonal and day and night output fluctuation of renewable energy power generation has brought new challenges to the stable and safe operation of the power system. These challenges mainly include the impact on power grid voltage stability, frequency stability and power angle stability. Therefore, the impact of renewable energy power generation on the stable and safe operation of power system should be be paid enough attention. Due to the characteristics of long-distance, large-scale and high concentration of grid connected renewable energy, the ability of AC system to connect to power grid is relatively weak, which is a typical weak current network. With the continuous expansion of renewable energy grid connection scale, the dynamic characteristics of weak current power grid become more complex, which brings great challenges to the stability and security of power grid. However, in the calculation of power system security and stability, more conservative renewable energy generation model parameters are often used to fix the power grid operation reliability. For better improve the renewable energy acceptance capacity of the system, the proportion of renewable power generation will be further increased. Therefore, establishing an accurate and reasonable renewable energy model is the basis of large-scale renewable energy grid connection security and stability calculation. Further study on the control strategy and parameter adaptability of renewable energy model could be reduced stability risk of high proportion of renewable energy connected to weak current network.

https://doi.org/10.1088/1742-6596/2166/1/012054

Study on the Impact of Renewable Energy Power Generation Transient Characteristics on System Stability in Weak Grid

With the number of wind farms connected to the power system increasing rapidly, the impact of wind power generation system on power grid system stability is becoming increasingly prominent. Especially when the power grid has transient fault, there will be problems such as reverse power flow, large-area power failure of wind farm and so on. This will directly lead to the power system instability and seriously affect the power grid security and stability. Especially in the stage of voltage recovery after the fault is eliminated, the low-voltage fault of the power grid might lead to a sharp rise in the voltage of power grid and overvoltage on the high-voltage line connected to the power grid with wind farm, resulting in the disconnection of the wind power grid connected system. However, China’s current standards do not specify the high-voltage crossing of wind power grid connected system, especially the high-voltage crossing detection device, detection method and detection procedure. Therefore, it is urgent to study the detection technology of wind power high voltage crossing and put forward the detection method. There are many reasons for high-voltage power grid fault, and the interaction between power grid and inverter is more complex in high-voltage fault. If the type test method is used to simulate various high-voltage fault conditions in power system and carry out the test and study on the HVRT( high voltage ride through) performance of wind turbine, the human and material cost is huge and there are many potential safety hazards. At the same time, the grid connection performance of wind turbines are largely related to the control strategy of the controller. Therefore, the semi physical simulation method can be used to research the HVRT detection technology of wind turbine. This can effectively avoid the safety problem of large current and high voltage in the primary circuit, and realize the physical connection between the real controller and the flexible high voltage fault platform model through hardware in the loop simulation. It can simulate the wind turbine capability of high-voltage ride through under various high-voltage fault conditions. It not only has low test cost, but also can deeply study the interaction between power grid and power grid.

https://iopscience.iop.org/article/10.1088/1742-6596/2166/1/012053/pdf

Requirement Analysis of Wind Turbine High Voltage Ride-through Capability Detection and Simulation

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Papers

Ferroptosis, necroptosis, and pyroptosis in the tumor microenvironment: perspectives for immunotherapy of SCLC.

Study on the Impact of Renewable Energy Power Generation Transient Characteristics on System Stability in Weak Grid

Requirement Analysis of Wind Turbine High Voltage Ride-through Capability Detection and Simulation