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Complex operating conditions, such as low temperature, can affect the degradation and safety stability of lithium-ion batteries (LIBs). This paper conducts research on the aging evolution and safety characteristics of LIBs under low-temperature conditions (−20 °C), to reveal the change laws of battery degradation and the trends of thermal parameters of aging LIBs. Cycling and charging/discharging experiments under low temperatures were conducted to collect realistic battery data. Various factors such as temperature, cycle number, charging/discharging rate, and depth of discharge/charge (DOD/DOC) are taken into consideration to test the battery cycling and thermal performance. With collected experimental results, basic electrical states of LIBs such as open-circuit voltage (OCV), internal resistance, and capacity are presented. Then, the capacity loss and internal resistance growth are also described and analyzed under various charge/discharge rates and DODs/DOCs. The experimental results show that low temperatures cause an almost 30% increase in polarization resistance, with nonlinear changes in total internal resistance. Moreover, the battery capacity and internal resistance also have extreme points with different charge/discharge rates under −20 °C, which may demonstrate that the charge/discharge rates of LIBs can be optimized under low temperature. Thermal runaway (TR) experiments were also conducted, and the self-heating rate and other indices are presented to show that an aging battery under low temperature still holds large energy to develop TR. The aging trends of LIBs under low temperatures are summarized, and battery safety is clarified to provide a reference for battery lifetime and safety management under low-temperature conditions.

Cannabigerol (CBG), a non-psychoactive cannabinoid found in cannabis, has emerged as a promising therapeutic agent with a diverse range of potential applications. Unlike its well-known counterpart tetrahydrocannabinol (THC), CBG does not induce intoxication, making it an attractive option in the clinic. Recent research has shed light on CBG’s intriguing molecular mechanisms, highlighting its potential to modulate multiple physiological processes. This review delves into the current understanding of CBG’s molecular interactions and explores its therapeutic power to alleviate various conditions, including cancer, metabolic, pain, and inflammatory disorders, amongst others. We discuss how CBG interacts with the endocannabinoid system and other key signaling pathways, such as CB1, CB2, TPR channels, and α2-adrenoceptor, potentially influencing inflammation, pain, neurodegeneration, and other ailments. Additionally, we highlight the ongoing research efforts aimed at elucidating the full spectrum of CBG’s therapeutic potential and its safety profile in clinical settings. Through this comprehensive analysis, we aim to provide a deeper understanding of CBG’s role in promoting human health and pave the way for future research endeavors.

The ability of cancer cells to evade immune destruction is governed by various intrinsic factors including their metabolic state. Here we demonstrate that inactivation of dihydroorotate dehydrogenase (DHODH), a pyrimidine synthesis enzyme, increases cancer cell sensitivity to T cell cytotoxicity through induction of ferroptosis. Lipidomic and metabolomic analyses reveal that DHODH inhibition reduces CDP-choline level and attenuates the synthesis of phosphatidylcholine (PC) via the CDP-choline-dependent Kennedy pathway. To compensate this loss, there is increased synthesis from phosphatidylethanolamine via the phospholipid methylation pathway resulting in increased generation of very long chain polyunsaturated fatty acid-containing PCs. Importantly, inactivation of Dhodh in cancer cells promotes the infiltration of interferon γ-secreting CD8 + T cells and enhances the anti-tumor activity of PD-1 blockade in female mouse models. Our findings reveal the importance of DHODH in regulating immune evasion through a CDP-choline dependent mechanism and implicate DHODH as a promising target to improve the efficacy of cancer immunotherapies. Various intrinsic factors, including the metabolic state of cancer cells, govern their ability to evade immune destruction. Here the authors show that inactivation of dihydroorotate dehydrogenase (DHODH), an enzyme in the pyrimidine synthesis pathway, increases the sensitivity of cancer cells to T cell cytotoxicity through CDP-Choline dependent induction of ferroptosis.

Palmitoylation is a reversible post-translational lipid modification of proteins, catalyzed by the Zinc finger DHHC domain-containing (ZDHHC) family of palmitoyltransferases. Palmitoylation plays a pivotal role in regulating localization, stability, trafficking, and interactions, thereby contributing to a wide range of cellular processes. Dysregulation of palmitoylation has been implicated in numerous pathological conditions, including metabolic disorders, muscular diseases, mitochondrial disorders, cancer, and neurodegeneration. In this review, we summarize recent advances in understanding S-palmitoylation, emphasizing its critical roles in protein regulation, cellular and physiological processes, and its implications in both health and disease. Additionally, we highlight emerging therapeutic opportunities and novel strategies in therapeutic applications targeting this lipid modification.

Background Acute myeloid leukemia (AML) is a highly heterogeneous malignancy, presenting significant challenges in accurately predicting patient prognosis. Dysregulation of endoplasmic reticulum (ER) stress and resistance to programmed cell death (PCD) are hallmarks of AML cells. However, the prognostic significance of the interplay between ER stress and cell death pathways in AML remains largely unexplored. Methods We analyzed RNA sequencing and clinical data from 887 AML patients across 4 cohorts to develop an ER stress-related cell death index (ERCDI) using 10 machine-learning algorithms with 117 unique combinations. Survival and time-dependent Receiver Operating Characteristic Curve (ROC) analyses were performed to assess the model’s efficacy. Clinical characteristics, the tumor immune microenvironment, and drug sensitivity differences between the high- and low-risk groups were also analyzed. The CMap database was used to identify potential therapeutic drugs. In vitro and in vivo experiments, including CCK-8, colony formation, flow cytometry, Transwell assays, and xenograft mouse models, were conducted to evaluate the effects of the target genes and candidate drugs. Results The ERCDI demonstrated strong prognostic and predictive performance for prognosis in AML patients. Furthermore, the ERCDI effectively predicted immunotherapy and chemotherapy outcomes and was associated with the immune features of the different risk groups. DNA damage-inducible transcript 4 protein (DDIT4), a key gene associated with ERCDI, is related to poor prognosis in AML patients with high expression. Additionally, the knockdown of DDIT4 significantly inhibited AML cell proliferation, induced cell apoptosis, and promoted cell cycle arrest. Chaetocin was subsequently identified as a candidate compound for AML treatment. Subsequent experiments suggested that combining chaetocin and venetoclax is a potentially promising therapeutic strategy for AML. Conclusion The ERCDI provides personalized risk assessment and treatment recommendations for individual AML patients. The combined use of chaetocin and venetoclax can potentially be repurposed for AML therapy.

Hepatocellular carcinoma (HCC) represents a formidable challenge in oncology, with high mortality rates and limited therapeutic options, particularly for advanced-stage patients. While immunotherapy has shown promise, its efficacy in advanced HCC remains suboptimal, necessitating the exploration of more potent therapeutic strategies. The HCC cell lines underwent treatment with arsenic sulfide and/or anti-PD1, while HepG2/Hepa1-6 cells were transduced with lentiviruses for THBS1 overexpression or knockdown. The MTT assay, FACS, Western blotting, qRT-PCR, and ChIP were employed to assess proliferation, modulation of proteins and genes. Additionally, C57BL/6J mice were utilized to investigate the ability of arsenic sulfide to enhance the efficacy of anti-PD-1 therapy. Here, we investigated the role of arsenic sulfide in HCC treatment and explored its potential synergistic effects and underlying mechanisms when combined with immunotherapy. First of all, using bioinformatics analysis and validation , we identified thrombospondin-1 (THBS1) as a key prognostic factor for HCC in Asian populations. Then, we demonstrated that arsenic sulfide inhibits HCC cell viability, induces apoptosis, and downregulates THBS1 expression. Furthermore, we observed that arsenic sulfide significantly enhances the anti-HCC effects of anti-PD-1 therapy. Mechanistic insights indicate that arsenic sulfide inhibits STAT3 phosphorylation, reduces THBS1 transcription, thereby disrupting the binding between tumor cell THBS1 and T cell CD47, consequently enhancing anti-PD-1 efficacy. Therefore, arsenic sulfide augments anti-PD-1 efficacy against HCC by inhibiting the STAT3-THBS1/CD47 pathway. Collectively, our findings elucidate the role of arsenic sulfide in conjunction with PD - 1 in HCC eradication and its underlying molecular mechanism, providing a precise scientific rationale and a robust theoretical basis for arsenic sulfide's application in HCC treatment.

Immunogenic cell death (ICD) is capable of activating the anti-tumor immune response of the organism; however, it is concurrently a complex process involving multiple factors. The specific factors that impact the occurrence of ICD remain undefined. Through cluster analysis, patient specimens retrieved from the TARGET, TCGA, and GEO AML databases were categorized into two subtypes based on the expression levels of ICD-related genes: ICD-high and ICD-low. We compared the prognostic survival outcomes, pathway enrichment analysis, and immune cell infiltration between these two subtypes. Additionally, we identified factors related to AML development from multiple databases and verified the role of these factors both in vivo and in vitro in activating the immune response during the occurrence of ICD. In the ICD-high subtype, there was a notable increase in the abundance of immune cell populations, along with the enrichment of pathways pertinent to the activation of various immune cells. Despite these immunological enhancements, this subgroup demonstrated a poorer prognosis. This phenomenon was consistently observed across various additional AML datasets, leading us to hypothesize that elevated expression of ICD genes does not invariably correlate with a favorable prognosis. Notably, STK10 exhibited elevated expression in AML, was associated with a poor prognosis, and showed synchronous expression patterns with ICD genes. Inhibition of STK10 led to the activation of ICD and the induction of an antitumor response. Moreover, when combined with other ICD inducers, it produced a synergistic anti-tumor effect. Our results reveal the impact of STK10 on ICD and underscore its key role in initiating ICD.

Drug resistance is a significant obstacle to effective cancer treatment. Drug resistance develops from initially reversible drug‐tolerant cancer cells, which offer therapeutic opportunities to impede cancer relapse. The mechanisms of resistance to proteasome inhibitor (PI) therapy have been investigated intensively, however the ways by which drug‐tolerant cancer cells orchestrate their adaptive responses to drug challenges remain largely unknown. Here, we demonstrated that cyclin A1 suppression elicited the development of transient PI tolerance in mixed‐lineage leukemia (MLL) cells. This adaptive process involved reversible downregulation of cyclin A1, which promoted PI resistance through cell‐cycle arrest. PI‐tolerant MLL cells acquired cyclin A1 dependency, regulated directly by MLL protein. Loss of cyclin A1 function resulted in the emergence of drug tolerance, which was associated with patient relapse and reduced survival. Combination treatment with PI and deubiquitinating enzyme (DUB) inhibitors overcame this drug resistance by restoring cyclin A1 expression through chromatin crosstalk between histone H2B monoubiquitination and MLL‐mediated histone H3 lysine 4 methylation. These results reveal the importance of cyclin A1‐engaged cell‐cycle regulation in PI resistance in MLL cells, and suggest that cell‐cycle re‐entry by DUB inhibitors may represent a promising epigenetic therapeutic strategy to prevent acquired drug resistance. Cyclin A1 suppression elicits the development of transient proteasome inhibitor (PI) tolerance in mixed‐lineage leukemia cells. Reduction of MLL and cyclin A1 is associated with patient relapse and reduced survival in acute lymphoblastic leukemia. Combined PI with deubiquitinating enzyme (DUB) inhibitors overcomes drug resistance by restoring cyclin A1 expression through chromatin crosstalk. Cell‐cycle re‐entry by DUB inhibitors represents a potential therapeutic strategy to prevent acquired drug resistance.

A hypoxic metabolism environment in the tumors is often associated with poor prognostic events such as tumor progression and treatment resistance. In gastric cancer, the mechanism of how hypoxia metabolism affects the tumor microenvironment and immunotherapy efficacy remains to be elucidated. We used the bulk-mapping method to analyze the signatures correlated with the response of immunotherapy in the single-cell dataset. Cellular, pathway, and gene were systematically analyzed in both single-cell and bulk validation datasets. The most significant cell proportion difference between the response and non-response groups was in endothelial cells, which represent the malignant cells. VWF was specifically overexpressed in endothelial cells and was the hub gene of differential genes. EPAS1 was a VWF trans-regulated gene and highly positively correlated with VWF in expression. Knockdown experiments demonstrated that siVWF reduced the expression of VWF, EPAS1, and HIF1A, as well as the synthesis of lactate and adenosine which are indicators of hypoxic metabolism. These results suggest that the overexpression of core malign endothelial genes such as VWF drives hypoxic metabolism in tumors and creates an immunosuppressive environment that reduces the efficacy of immunotherapy. The adverse prognosis of the hypoxia signature was validated in the bulk cohort and significance was further enhanced after selecting core genes and combined survival weight scoring. In summary, high expression of the malignant endothelial cell driver genes VWF and EPAS1 enhances hypoxic metabolism, and malignant cell-immune cell interactions suppress the immune response. Therefore, the two core genes of hypoxic metabolism might represent potential therapeutic and predicting biomarkers for immunotherapy of gastric cancer in the future.