Death Process Research Articles

Leukotoxin A Production and Release by JP2 and Non-JP2 Genotype Aggregatibacter actinomycetemcomitans in Relation to Culture Conditions.

Aggressive forms of periodontitis, especially in young patients, are often associated with an increased proportion of the Gram-negative bacterium Aggregatibacter actinomycetemcomitans of the microbiota of the affected periodontal sites. One of the virulence factors of A. actinomycetemcomitans is a leukotoxin (LtxA) that induces a pro-inflammatory cell death process in leukocytes. A. actinomycetemcomitans exhibits a large genetic diversity and different genotypes vary in LtxA production capacity. The genotype JP2 is a heavy LtxA producer due to a 530-base pair deletion in the promoter for the toxin genes, and this trait has been associated with an increased pathogenic potential. The present study focused on the production and release of LtxA by different A. actinomycetemcomitans genotypes and serotypes under various growth conditions. Four different strains of this bacterium were cultured in two different culture broths, and the amount of LtxA bound to the bacterial surface or released into the broths was determined. The cultures were examined during the logarithmic and the early stationary phases of growth. The JP2 genotype exhibited the highest LtxA production among the strains tested, and production was not affected by the growth phase. The opposite was observed with the other strains. The composition of the culture broth had no effect on the growth pattern of the tested strains. However, the abundant release of LtxA from the bacterial surface into the culture broth was found in the presence of horse serum. Besides confirming the enhanced leucotoxicity of the JP2 genotype, the study provides new data on LtxA production in the logarithmic and stationary phases of growth and the effect of media composition on the release of the toxin from the bacterial membrane.

On integrals of birth–death processes at random time

In this paper, we consider a time-changed path integral of the homogeneous birth–death process. Here, the time changes according to an inverse stable subordinator. It is shown that its joint distribution with the time-changed birth–death process is governed by a fractional partial differential equation. In a linear case, the explicit expressions for the Laplace transform of their joint generating function, means, variances and covariance are obtained. The limiting behavior of this integral process has been studied. Later, we consider the fractional integrals of linear birth–death processes and their time-changed versions. The mean values of these fractional integrals are obtained and analyzed. In a particular case, it is observed that the time-changed path integral of the linear birth–death process and the fractional integral of time-changed linear birth–death process have equal mean growth.

Application of Separation Surgery Combined with Radiofrequency Ablation and Bone Cement Strengthening in Thoracolumbar Metastasis.

The spine is a common site for metastatic tumors, with 5%-10% of patients developing epidural spinal cord compression (ESCC), which significantly reduces their quality of life and accelerates the process of death. When total en-bloc spondylectomy (TES) radical surgery does not achieve the desired tumor control, palliative care remains the primary treatment option. Traditional laminar decompression or partial tumor resection can only relieve local compression. Although the surgical trauma and complications are less, these methods cannot effectively address tumor recurrence and secondary compression. Therefore, separation surgery combined with radiofrequency ablation and bone cement strengthening was used to treat thoracolumbar metastatic tumors, aiming to achieve good clinical results. In this protocol, the steps and key points of separation surgery combined with radiofrequency ablation and bone cement reinforcement for thoracolumbar metastatic tumors are introduced in detail. Meanwhile, the clinical data of 67 cases of thoracolumbar metastatic tumors in our hospital meeting the inclusion criteria were retrospectively analyzed. Different treatment methods divided the patients into two groups: separation surgery combined with radiofrequency ablation and bone cement strengthening (group A, 33 cases) and the radiotherapy group (group B, 34 cases). All patients were evaluated using improved Tokuhashi, Tomita, SINS, and ESCC scores before treatment. VAS score, Frankel grading, and Karnofsky scores during different periods of the two treatments were compared to assess the clinical outcomes. Studies have shown that separation surgery combined with radiofrequency ablation and bone cement strengthening can significantly reduce pain, promote neurological function recovery, enhance mobility, and improve quality of life in treating thoracolumbar metastatic tumors.

Establishment of diagnostic model and identification of diagnostic markers between liver cancer and cirrhosis based on multi-chip and machine learning.

Most cases of hepatocellular carcinoma (HCC) arise as a consequence of cirrhosis. In this study, our objective is to construct a comprehensive diagnostic model that investigates the diagnostic markers distinguishing between cirrhosis and HCC. Based on multiple GEO datasets containing cirrhosis and HCC samples, we used lasso regression, random forest (RF)-recursive feature elimination (RFE) and receiver operator characteristic analysis to screen for characteristic genes. Subsequently, we integrated these genes into a multivariable logistic regression model and validated the linear prediction scores in both training and validation cohorts. The ssGSEA algorithm was used to estimate the fraction of infiltrating immune cells in the samples. Finally, molecular typing for patients with cirrhosis was performed using the CCP algorithm. The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model. In both the training and validation cohorts, the model exhibited an area under the curve (AUC) greater than 0.9 and a kappa value of approximately 0.9. Additionally, the calibration curve demonstrated excellent concordance between observed and predicted incidence rates. Comparatively, HCC displayed overall downregulation of infiltrating immune cells compared to cirrhosis. Notably, CCBE1 showed strong correlations with the tumour immune microenvironment as well as genes associated with cell death and cellular ageing processes. Furthermore, cirrhosis subtypes with high linear predictive scores were enriched in multiple cancer-related pathways. In conclusion, we successfully identified diagnostic markers distinguishing between cirrhosis and hepatocellular carcinoma and developed a novel diagnostic model for discriminating the two conditions. CCBE1 might exert a pivotal role in regulating the tumour microenvironment, cell death and senescence.

Challenges in estimating species' age from phylogenetic trees

AbstractAimSpecies age, the elapsed time since origination, can give insight into how species longevity might influence eco‐evolutionary dynamics, which has been hypothesized to influence extinction risk. Traditionally, species' ages have been estimated from fossil records. However, numerous studies have recently used the branch lengths of time‐calibrated phylogenies as estimates of the ages of extant species. This approach poses problems because phylogenetic trees only contain direct information about species identity at the tips and not along the branches. Here, we show that incomplete taxon sampling, extinction and different assumptions about speciation modes can significantly alter the relationship between true species age and phylogenetic branch lengths, leading to high error rates. We found that these biases can lead to erroneous interpretations of eco‐evolutionary patterns derived from comparing phylogenetic age and other traits, such as extinction risk.InnovationFor bifurcating speciation, the default assumption in most analyses of species age, we propose a probabilistic approach based on the properties of a birth–death process to improve the estimation of species ages. Our approach can reduce the error by one order of magnitude under cases of high extinction and a high percentage of unsampled extant species.Main conclusionOur results call for caution in interpreting the relationship between phylogenetic ages and eco‐evolutionary traits, as this can lead to biased and erroneous conclusions. We show that, under the assumption of bifurcating speciation, we can obtain unbiased approximations of species age by combining information from branch lengths with the expectations of a birth–death process.

Dose-Dependent Alterations of Lysosomal Activity and Alpha-Synuclein in Peripheral Blood Monocyte-Derived Macrophages and SH-SY5Y Neuroblastoma Cell Line by upon Inhibition of MTOR Protein Kinase – Assessment of the Prospects of Parkinson’s Disease Therapy

To date, the molecular mechanisms of the common neurodegenerative disorder Parkinson’s disease (PD) are unknown and, as a result, there is no neuroprotective therapy that may stop or slow down the process of neuronal cell death. The aim of the current study was to evaluate the prospects of using the mTOR molecule as a potential target for PD therapy due to the dose-dependent effect of mTOR kinase activity inhibition on cellular parameters associated with, PD pathogenesis. The study used peripheral blood monocyte-derived macrophages and SH-SY5Y neuroblastoma cell line. As a result, we have for the first time showed that inhibition of mTOR by Torin1 only at a concentration of 100 nM affects the level of the lysosomal enzyme glucocerebrosidase (GCase), encoded by the GBA1 gene. Mutations in GBA1 are considered a high-risk factor for PD development. This concentration led a decrease in pathological phosphorylated alpha-synuclein (Ser129), an increase in its stable tetrameric form with no changes in the lysosomal enzyme activities and concentrations of lysosphingolipids. Our findings suggest that inhibition of the mTOR protein kinase could be a promising approach for developing therapies for PD, particularly for GBA1-associated PD.

Numerical simulation and mathematical modeling of biomechanical stress distribution in poroelastic tumor tissue via magnetic field and bio-ferro-fluid

Based on scientific evidence, it seems that bio-magnetic systems can change the process of cancer cell death by affecting the distribution of pressure and mechanical stress in the tumor tissue. Already most of the research has been done experimentally and few mathematical modeling and numerical simulations have been done to investigate the relationship between the magnetic parameters and the mechanical stress of the tumor tissue. This is despite the fact that in order to be able to make new equipment with the help of medical engineering methods, it is definitely necessary that the mathematics governing the problem and changes in the effective magnetic parameters (such as the shape of the magnetic source, magnetic flux density, magnetic source distance and ferro-fluid volume fraction) should be studied as much as possible. In this research, using numerical simulation and mathematical modeling, four common geometrical shapes (rectangular and circular) of the static magnetic field source were used to investigate the relationship between the change of the effective magnetic parameters and the mechanical stress created in the tumor tissue. The results of this research showed that when the magnetic flux density and ferro-fluid volume fraction and also the distance between the magnet and the tissue are kept constant, as well as without spending any extra energy, for a rectangular magnet, just by changing the way the source is placed on the tissue, the average biomechanical stress inside the tumor tissue causes a 25 % change. Also, for a circular magnet, just by doubling the radius of the magnet, the average biomechanical stress inside the tumor tissue causes a 73 % change.

Cuproptosis-Related Genes as Prognostic Biomarkers for Sepsis: Insights into Immune Function and Personalized Immunotherapy.

This study aimed to discover diagnostic and prognostic biomarkers for sepsis immunotherapy through analyzing the novel cellular death process, cuproptosis. We used transcriptome data from sepsis patients to identify key cuproptosis-related genes (CuRGs). We created a predictive model and used the CIBERSORT algorithm to observe the link between these genes and the septic immune microenvironment. We segregated sepsis patients into three subgroups, comparing immune function, immune cell infiltration, and differential analysis. Single-cell sequencing and real-time quantitative PCR were used to view the regulatory effect of CuRGs on the immune microenvironment and compare the mRNA levels of these genes in sepsis patients and healthy controls. We established a sepsis forecast model adapted to heart rate, body temperature, white blood cell count, and cuproptosis key genes. This was followed by a drug sensitivity analysis of cuproptosis key genes. Our results filtered three key genes (LIAS, PDHB, PDHA1) that impact sepsis prognosis. We noticed that the high-risk group had poorer immune cell function and lesser immune cell infiltration. We also discovered a significant connection between CuRGs and immune cell infiltration in sepsis. Through consensus clustering, sepsis patients were classified into three subgroups. The best immune functionality and prognosis was observed in subgroup B. Single-cell sequencing exposed that the key genes manage the immune microenvironment by affecting T cell activation. The qPCR results highlighted substantial mRNA level reduction of the three key genes in the SP compared to the HC. The prediction model, which combines CuRGs and traditional diagnostic indicators, performed better in accuracy than the other markers. The drug sensitivity analysis listed bisphenol A as highly sensitive to all the key genes. Our study suggests these CuRGs may offer substantial potential for sepsis prognosis prediction and personalized immunotherapy.

Pentylenetetrazole-Induced Seizures in Wistar Male Albino Rats with Reference to Glutamate Metabolism.

Epilepsy is a common and heterogenous neurological disorder characterized by recurrent spontaneous seizures. Animal models like rats play a crucial role in finding of mechanism of epilepsy in different brain regions. i.e., cerebral cortex, cerebellum, hippocampus, and pons medulla. Glutamate is an important excitatory neurotransmitter in the central nervous system and also glutamate plays a vital role in neuronal development and memory. The process of neuronal death evolved by glutamate receptor activation, has been hypothesized in both acute and chronic degenerative disorders including epilepsy. Considering the multifactorial neurochemical and neurophysiological malfunctions consequent to epileptic seizures, a few antiepileptic drugs are designed, to mitigate the debilitating aspects of epilepsy. Rat model, pentylenetetrazole (PTZ), an anticonvulsant drug, was selected for the present study. Induction of epilepsy/convulsions was induced by an intraperitoneal injection of PTZ (60 mg/kg body weight) in saline. Biochemical assays performed through spectrophotometer. Glutamine and Glutamine synthetase levels were decreased in the epileptic rats brain regions i.e., hippocampus, cerebellum, cerebral cortex, and pons medulla; glutamate dehydrogenase and glutaminase levels were increased in all the regions of epilepsy induced rats. Highest values are recorded in hippocampus when compared to other brain regions. PTZ suppresses the function of Glutamine and Glutamine synthetase activities in selected brain regions of rat and enhances the activities of the glutaminase and glutamate dehydrogenase when compared to control rats.

A Review of Research on the Role of Different Types of Religiosity in Terror Management

This review paper aims to reveal the role of different types of religiosity based on research addressing religiosity in terms of in-group and out-group distinction within the scope of Terror Management Theory (TMT). Studies point out two important results of the phenomenon: the first is the fact that general religiosity focusing on only one aspect of religiosity (religious belongingness, afterlife belief, etc.) to measure religiosity increases worldview defense, supporting the hypothesis of mortality salience. The second is the fact that different religious orientations (intrinsic, fundamentalist, etc.) cause various reactions, depending on their unique characteristics when mortality is salient. In the current study, possible reasons for the differences between research findings are discussed. In order to clarify the roles that different types of religiosity play in terror management, a classification based on the strong-flexible and exclusive-inclusive poles of the “belief” and “belonging” dimensions suggested by Sarouglu has been proposed. It has been argued that religiosity types would function in terror management in different ways, depending on the classification in which they are placed. For example, when the religious worldview is threatened, the strong-exclusive pattern (e.g., religious fundamentalism) can lead to more negative reactions, while the strong-inclusive pattern (e.g., intrinsic religiosity) can be associated with positive processes in inter-group relationships. Future research on this classification and types of religiosity can provide unique contributions to developing TMT. On the other hand, knowing the roles of different forms of religiosity in managing existential concerns may be of therapeutic benefit in coping with death, bereavement, grief and related processes.

Redox-Regulated Iron Metabolism and Ferroptosis in Ovarian Cancer: Molecular Insights and Therapeutic Opportunities.

Ovarian cancer (OC), known for its lethality and resistance to chemotherapy, is closely associated with iron metabolism and ferroptosis-an iron-dependent cell death process, distinct from both autophagy and apoptosis. Emerging evidence suggests that dysregulation of iron metabolism could play a crucial role in OC by inducing an imbalance in the redox system, which leads to ferroptosis, offering a novel therapeutic approach. This review examines how disruptions in iron metabolism, which affect redox balance, impact OC progression, focusing on its essential cellular functions and potential as a therapeutic target. It highlights the molecular interplay, including the role of non-coding RNAs (ncRNAs), between iron metabolism and ferroptosis, and explores their interactions with key immune cells such as macrophages and T cells, as well as inflammation within the tumor microenvironment. The review also discusses how glycolysis-related iron metabolism influences ferroptosis via reactive oxygen species. Targeting these pathways, especially through agents that modulate iron metabolism and ferroptosis, presents promising therapeutic prospects. The review emphasizes the need for deeper insights into iron metabolism and ferroptosis within the redox-regulated system to enhance OC therapy and advocates for continued research into these mechanisms as potential strategies to combat OC.

Comparative analysis and evolution of civilian versus combatant mortality ratios in Israel-Gaza conflicts, 2008-2023.

There is a need for statistical methodologies that scrutinize civilian casualties in conflicts, evaluating the degree to which the conduct of war affects civilians and breaches the laws of war. Employing an epidemiological method, this study introduced, developed, and applied a novel approach for investigating mortality of civilians versus combatants in conflicts. A deterministic mathematical model, structured by age and sex, was developed to describe the process of conflict-related deaths among both combatants and civilians. The model was calibrated using demographic and conflict-related data from different Israel-Gaza conflicts. To quantify the extent of the impact on civilians and determine whether they are the primary focus of a conflict, a statistical metric, the index of killing civilians, along with associated criteria, was devised. The model-estimated proportion of deaths in Gaza categorized as combatants was 62.1% (95% uncertainty interval (UI): 57.6-66.2%), 51.1% (95% UI: 47.1-54.9%), and 12.7% (95% UI: 9.7-15.4%) in the 2008-2009, 2014, and 2023 Israel-Gaza conflicts, respectively. The index of killing civilians was 0.61 (95% UI: 0.51-0.74), 0.96 (95% UI: 0.82-1.12), and 7.01 (95% UI: 5.50-9.29) in the 2008-2009, 2014, and 2023 conflicts, respectively. These index values indicate strong evidence for civilians being an object of war in the 2008-2009 and 2014 conflicts, but combatants were still identified as the primary focus of the conflict. In the 2023 conflict, there is robust evidence for civilians being an object of war, with civilians identified as the primary focus of the conflict. Findings imply a progressive shift in Israel's rules of engagement over time, with a trend towards higher acceptance of casualties among civilians. The 2023 conflict stands apart from preceding Israel-Gaza conflicts, with civilians identified as the primary focus of the conflict.

Bimetallic phosphidethe nanoparticles as photo-enhanced nanozymes for synergistic cancer immunotherapy

<p class="MsoNormal" style="margin-top: 12pt; text-align: justify;"><span lang="EN-US" style="font-family: 'times new roman', times, serif; font-size: 14pt;">Nanozyme with biomimetic enzyme activity has the advantages of good catalytic performance, high stability, and is not easily affected by temperature. However, the application of tumor microenvironment (TME) in the tumor is limited due to its low catalytic activity. Herein, a multifunctional nanozyme based on CuCoP with multivalent metal ions (Cu+/Cu2+ and Co2+/ Co3+) provides an innovative strategy for constructing acid-responsive cancer therapy. CuCoP has excellent photothermal properties (photothermal conversion efficiency of 66.9%) as well as glutathione (GSH) peroxidase activity and high photo-enhanced peroxidase-like (POD) enzyme activity in weak acid TME. CuCoP can consume the overexpressed GSH, thus alleviating the antioxidant capacity of the tumor, and reduces Cu2+/ Co3+ to Cu+/ Co 2+. Subsequently, the generated Cu+/Co2+ will react with endogenous H2O2 to generate cytotoxic hydroxyl radical (•OH), which have high catalytic efficiency in weakly acidic TME. Crucially, the synergistic effect of PTT and the cascade reaction of bimetallic atoms with GSH and H2O2 can effectively reduce antioxidant capacity, inhibit tumors and trigger effective immune cell death (ICD) process, which caused a strong immune response and inhibit tumor recurrence and metastasis. As a novel bimetallic sulfide nanoenzyme triggered by TME, CuCoP has great research value in cancer therapy.</span></p>

On the Generalized Birth–Death Process and Its Linear Versions

On the Generalized Birth–Death Process and Its Linear Versions

Effect of ginger, chamomile, and green tea extracts on prostate cancer cells

Prostate cancer (PCa) is a prevalent form of malignancy in males and is a significant contributor to cancer-related mortality worldwide. Because of this, studying the molecular processes of PCa cell growth and death is crucial. Hence, it is imperative to conduct further research on the regulatory mechanism underlying the progression of PCa to enhance our comprehension and identify innovative therapeutic targets. The present study investigates an experimental approach that utilizes cost-effective and environmentally sustainable plant extracts sourced from Egypt, namely ginger, chamomile, and green tea, which have been solubilized in dimethyl sulfoxide (DMSO), then characterized by using different analytical means and techniques, such as HPLC and GC–MS. The present study employed MTT assay, ELISA, and qRT-PCR techniques to assess the possible impact of the investigated extracts on PCa in PC-3 cells. The findings indicate that ginger exhibited a noteworthy cytotoxic impact on PC-3. Remarkably, the treatment of PCa cells with ginger significantly increased relative lactate dehydrogenase (LDH) production compared to those treated with chamomile and green tea extracts. Autophagy may play a crucial role in the context of chemotherapy. Modifying autophagy through its induction or inhibition is a promising and innovative approach to controlcancer progression. Accordingly, it was found that ginger extract affects protein expression levels of autophagy markers LC3B, ATg12, and pro‐apoptotic signaling, including the Caspase-3 signaling pathway. The ELISA findings revealed a significant rise in the average levels of IL-1β and IL-8 after a 12-hour interval. To conclude, it can be inferred that ginger extract possesses the capability to control the production of inflammatory cytokines. Alternatively, utilizing herbal remedies containing ginger as a viable and secure means of treating PCa as an anticancer agent is possible.

Genome-wide expression analysis of vegetative organs during developmental and herbicide-induced whole plant senescence in Arabidopsis thaliana

BackgroundWhole plant senescence represents the final stage in the life cycle of annual plants, characterized by the decomposition of aging organs and transfer of nutrients to seeds, thereby ensuring the survival of next generation. However, the transcriptomic profile of vegetative organs during this death process remains to be fully elucidated, especially regarding the distinctions between natural programmed death and artificial sudden death induced by herbicide.ResultsDifferential genes expression analysis using RNA-seq in leaves and roots of Arabidopsis thaliana revealed that natural senescence commenced in leaves at 45–52 days after planting, followed by roots initiated at 52–60 days. Additionally, both organs exhibited similarities with artificially induced senescence by glyphosate. Transcription factors Rap2.6L and WKRY75 appeared to serve as central mediators of regulatory changes during natural senescence, as indicated by co-expression networks. Furthermore, the upregulation of RRTF1, exclusively observed during natural death, suggested its role as a regulator of jasmonic acid and reactive oxygen species (ROS) responses, potentially triggering nitrogen recycling in leaves, such as the glutamate dehydrogenase (GDH) shunt. Root senescence was characterized by the activation of AMT2;1 and GLN1;3, facilitating ammonium availability for root-to-shoot translocation, likely under the regulation of PDF2.1.ConclusionsOur study offers valuable insights into the transcriptomic interplay between phytohormones and ROS during whole plant senescence. We observed distinct regulatory networks governing nitrogen utilization in leaf and root senescence processes. Furthermore, the efficient allocation of energy from vegetative organs to seeds emerges as a critical determinant of population sustainability of annual Arabidopsis.

Beyond Death: Unmasking the Intricacies of Apoptosis Escape.

Apoptosis, or programmed cell death, maintains tissue homeostasis by eliminating damaged or unnecessary cells. However, cells can evade this process, contributing to conditions such as cancer. Escape mechanisms include anoikis, mitochondrial DNA depletion, cellular FLICE inhibitory protein (c-FLIP), endosomal sorting complexes required for transport (ESCRT), mitotic slippage, anastasis, and blebbishield formation. Anoikis, triggered by cell detachment from the extracellular matrix, is pivotal in cancer research due to its role in cellular survival and metastasis. Mitochondrial DNA depletion, associated with cellular dysfunction and diseases such as breast and prostate cancer, links to apoptosis resistance. The c-FLIP protein family, notably CFLAR, regulates cell death processes as a truncated caspase-8 form. The ESCRT complex aids apoptosis evasion by repairing intracellular damage through increased Ca2+ levels. Antimitotic agents induce mitotic arrest in cancer treatment but can lead to mitotic slippage and tetraploid cell formation. Anastasis allows cells to resist apoptosis induced by various triggers. Blebbishield formation suppresses apoptosis indirectly in cancer stem cells by transforming apoptotic cells into blebbishields. In conclusion, the future of apoptosis research offers exciting possibilities for innovative therapeutic approaches, enhanced diagnostic tools, and a deeper understanding of the complex biological processes that govern cell fate. Collaborative efforts across disciplines, including molecular biology, genetics, immunology, and bioinformatics, will be essential to realize these prospects and improve patient outcomes in diverse disease contexts.

Ferroptosis regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer.

Gastric cancer is one of the most common malignant tumors in the world, and its occurrence and development involve complex biological processes. Iron death, as a new cell death mode, has attracted wide attention in recent years. However, the regulatory mechanism of iron death in gastric cancer and its effect on lipid peroxidation metabolism remain unclear. To explore the role of iron death in the development of gastric cancer, reveal its relationship with lipid peroxidation, and provide a new theoretical basis for revealing the molecular mechanism of the occurrence and development of gastric cancer. The process of iron death in gastric cancer cells was simulated by cell culture model, and the occurrence of iron death was detected by fluorescence microscopy and flow cytometry. The changes of gene expression related to iron death and lipid peroxidation metabolism were analyzed by high-throughput sequencing technology. In addition, a mouse model of gastric cancer was established, and the role of iron death in vivo was studied by histology and immunohistochemistry, and the level of lipid peroxidation was detected. These methods comprehensively and deeply reveal the regulatory mechanism of iron death on lipid peroxidation metabolism in the occurrence and development of gastric cancer. Iron death was significantly activated in gastric cancer cells, and at the same time, associated lipid peroxidation levels increased significantly. Through high-throughput sequencing analysis, it was found that iron death regulated the expression of several genes related to lipid metabolism. In vivo experiments demonstrated that increased iron death in gastric cancer mice was accompanied by a significant increase in lipid peroxidation. This study confirmed the important role of iron death in regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer. The activation of iron death significantly increased lipid peroxidation levels, revealing its regulatory mechanism inside the cell.

Mutual aid insurance with a three-state Markov chain

ABSTRACT Mutual aid insurance is a collective type of insurance where the policyholders share the potential losses or risks that they may face. In this paper, we establish a mathematical structure for mutual aid insurance through a three-state (good, bad and death) process, which is driven by an inhomogeneous Markov chain. The objective of maximizing an individual's lifetime utility is achieved by addressing a stochastic control problem that involves both mutual aid insurance and life insurance. We obtain the explicit expressions for optimal consumption, investment strategies, and life insurance premiums by employing the corresponding Hamilton-Jacobi-Bellman equation. In the end, we carry out a numerical analysis to show the significance of mutual aid insurance and demonstrate the optimal mutual aid insurance premium.

MST1 interactomes profiling across cell death in esophageal squamous cell carcinoma

Abstract Objectives Resistance to apoptosis in esophageal squamous cell carcinoma (ESCC) constitutes a significant impediment to treatment efficacy. Exploring alternative cell death pathways and their regulatory factors beyond apoptosis is crucial for overcoming drug resistance and enhancing therapeutic outcomes in ESCC. Methods Mammalian Ste 20-like kinase 1 (MST1) is implicated in regulating various cell deaths, including apoptosis, autophagy, and pyroptosis. Employing enhanced ascorbate peroxidase 2 (APEX2) proximity labeling coupled with immunoprecipitation-mass spectrometry (IP-MS), we elucidated the interactomes of MST1 across these three cell death paradigms. Results Proteomic profiling unveiled the functional roles and subcellular localization of MST1 and its interacting proteins during normal proliferation and various cell death processes. Notably, MST1 exhibited an expanded interactome during cell death compared to normal proliferation and chromosome remodeling functions consistently. In apoptosis, there was a notable increase of mitosis-associated proteins such as INCENP, ANLN, KIF23, SHCBP1 and SUPT16H, which interacted with MST1, alongside decreased expression of the pre-apoptotic protein STK3. During autophagy, the bindings of DNA repair-related proteins CBX8 and m6A reader YTHDC1 to MST1 were enhanced. In pyroptosis, LRRFIP2 and FLII which can inhibit pyroptosis increasingly binding to MST1. Conclusions Our findings delineate potential mechanisms through which MST1 and its interactomes regulate cell death, paving the way for further investigation to validate and consolidate these observations.