Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
Animals ; Caenorhabditis elegans/genetics* ; Endosomes/immunology* ; Caenorhabditis elegans Proteins/immunology* ; Phosphatidylinositol 4,5-Diphosphate/immunology* ; Immunity, Innate ; Pseudomonas aeruginosa/immunology* ; rab GTP-Binding Proteins/genetics* ; Diglycerides/metabolism*

Ferroptosis is an iron-dependent cell death modality triggered by the accumulation of lipid peroxides and is closely linked to tumor pathogenesis. Ferritinophagy refers to the selective autophagic degradation of ferritin, releasing intracellular stored iron to maintain iron metabolic homeostasis. This process is also significantly associated with tumor-targeted interventions. This review systematically elucidates the mechanisms of ferroptosis and ferritinophagy, their roles in tumor progression, and the therapeutic potential of pharmacologically induced ferritinophagy in anticancer strategies.

Granulocytic myeloid-derived suppressor cells(G-MDSCs)are the principal subsets of myeloid-derived suppressor cells(MDSCs),which involved in development and progression of a variety of tumor and non-tumor diseases.G-MDSCs mediated disfunction of immune effector cells(such as T cells and NK cells)through producing Arg-1,ROS,iNOS,etc.is major cause of its immunosuppressive function.To date,a large number of studies have focused on tumor-promoting effects of G-MDSCs.However,their complex immunomodulatory functions,especially their positive effects in diseases such as autoimmune arthritis,are often overlooked.Besides,G-MDSCs share the same origin and phenotype with neutrophils,but their immune functions are heterogeneous.Therefore,precision of G-MDSCs targeted therapy will be largely improved if the two can be accurately distinguished,though this field is still under exploration.At present,there are abundant experimental studies on G-MDSCs at home and abroad,mainly in tumors,but there are no domestic reports on the immunomodulatory function of G-MDSCs in tumors and non-tumor diseases.Therefore,in this review,we summarizes the different roles played by G-MDSCs in tumor and non-tumor diseases,in order to reveal the important and complex functions of G-MDSCs in immune regulation.

Ferroptosis is an iron-dependent cell death modality triggered by the accumulation of lipid peroxides and is closely linked to tumor pathogenesis. Ferritinophagy refers to the selective autophagic degradation of ferritin, releasing intracellular stored iron to maintain iron metabolic homeostasis. This process is also significantly associated with tumor-targeted interventions. This review systematically elucidates the mechanisms of ferroptosis and ferritinophagy, their roles in tumor progression, and the therapeutic potential of pharmacologically induced ferritinophagy in anticancer strategies.

Granulocytic myeloid-derived suppressor cells(G-MDSCs)are the principal subsets of myeloid-derived suppressor cells(MDSCs),which involved in development and progression of a variety of tumor and non-tumor diseases.G-MDSCs mediated disfunction of immune effector cells(such as T cells and NK cells)through producing Arg-1,ROS,iNOS,etc.is major cause of its immunosuppressive function.To date,a large number of studies have focused on tumor-promoting effects of G-MDSCs.However,their complex immunomodulatory functions,especially their positive effects in diseases such as autoimmune arthritis,are often overlooked.Besides,G-MDSCs share the same origin and phenotype with neutrophils,but their immune functions are heterogeneous.Therefore,precision of G-MDSCs targeted therapy will be largely improved if the two can be accurately distinguished,though this field is still under exploration.At present,there are abundant experimental studies on G-MDSCs at home and abroad,mainly in tumors,but there are no domestic reports on the immunomodulatory function of G-MDSCs in tumors and non-tumor diseases.Therefore,in this review,we summarizes the different roles played by G-MDSCs in tumor and non-tumor diseases,in order to reveal the important and complex functions of G-MDSCs in immune regulation.

Objective·To analyze the clinical and genetic characteristics of Chinese pediatric patients with Barth syndrome(BTHS)and provide data to support the prevention and treatment of BTHS.Methods·Eighteen pediatric patients diagnosed with BTHS at Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,from January 2010 to November 2023,were included.Clinical data(age,birth weight,family history,electrocardiogram,echocardiogram,urine tandem mass spectrometry,complete blood count,blood biochemistry,and genetic test results)were collected to analyze the clinical characteristics,genetic findings,and prognoses of the patients.Results·The study included 18 male patients with BTHS(including 2 monozygotic twins),consisting of one Yi ethnic and 17 Han Chinese patients.The median age at diagnosis was 3.0(1.0,5.6)months.Fifteen patients experienced decreased cardiac function at disease onset,with a left ventricular ejection fraction(LVEF)below 50%.Dilated cardiomyopathy(DCM)was observed in 15 patients,left ventricular non-compaction(LVNC)in 12 patients,and myocardial hypertrophy in 9 patients.During the diagnosis and follow-up,QTc interval prolongation occurred in 9 patients,ventricular arrhythmias in 2 patients,neutropenia in 9 patients,and monocytosis in 10 patients.Urine tandem mass spectrometry revealed 3-methylglutaconic aciduria(3-MGCA)in 8 of 13 tested patients.Fifteen types of TAZ gene mutation were identified in the 18 patients,including 5 novel mutations.Genetic testing of the parents of 16 patients indicated maternal inheritance in 15 cases.The median follow-up period was 8.5(2.6,29.3)months,during which 12 patients died.The median age at death was 7.5(6.0,12.8)months.Causes of death included heart failure(7 cases,with 4 concurrent infections),sudden death(3 cases),ventricular fibrillation(1 case),and accidental death(1 case).Conclusion·BTHS is a rare genetic disorder with multisystem involvement.Its primary clinical manifestations include cardiomyopathy and neutropenia.The condition typically presents early in life,with severe progression and poor prognosis.Prompt recognition,accurate diagnosis,and early intervention are essential for managing this disease.