Elucidating the clinical and immunological value of m6A regulatormediated methylation modification patterns in adrenocortical carcinoma

N6-methyladenosine methylation(m6A)is a common type of epigenetic alteration that prominently affects the prognosis of tumor patients.However,it is unknown how the m6A regulator affects the tumor microenvironment(TME)cell infiltration in adrenocortical carcinoma(ACC)and how it affects the prognosis of ACC patients yet.The m6A alteration patterns of 112 ACC patients were evaluated,furthermore,the association with immune infiltration cell features was investigated.The unsupervised clustering method was applied to typify the m6A alteration patterns of ACC patients.The principal component analysis(PCA)technique was taken to create the m6A score to assess the alteration pattern in specific malignancies.We found two independent patterns of m6A alteration in ACC patients.The TME cell infiltration features were significantly in accordance with phenotypes of tumor immune-inflamed and immune desert in both patterns.The m6Ascore also served as an independent predictive factor in ACC patients.The somatic copy number variation(CNV)and patients prognosis can be predicted by m6A alteration patterns.Moreover,the ACC patients with high m6A scores had better overall survival(OS)and higher efficiency in immune checkpoint blockade therapy.Our work demonstrated the significance of m6A alteration to the ACC patients immunotherapy.The individual m6A alteration patterns analysis might contribute to ACC patients prognosis prediction and immunotherapy choice.

ERp44 C160S/C212S mutants regulate IP_(3)R_(1) channel activity

Previous studies have indicated that ERp44 inhibits inositol 1,4,5-trisphosphate(IP3)-induced Ca2+release(IICR)via IP3R1,but the mechanism remains largely unexplored.Using extracellular ATP to induce intracellular calcium transient as an IICR model,Ca2+image,pull down assay,and Western blotting experiments were carried out in the present study.We found that extracellular ATP induced calcium transient via IP3Rs(IICR)and the IICR were markedly decreased in ERp44 overexpressed Hela cells.The inhibitory effect of C160S/C212S but not C29S/T396A/ΔT(331–377)mutants of ERp44 on IICR were significantly decreased compared with ERp44.However,the binding capacity of ERp44 to L3V domain of IP3R1(1L3V)was enhanced by ERp44 C160S/C212S mutation.Taken together,these results suggest that the mutants of ERp44,C160/C212,can more tightly bind to IP3R1 but exhibit a weak inhibition of IP3R1 channel activity in Hela cells.

Regulating the microenvironment with nanomaterials:Potential strategies to ameliorate COVID-19

COVID-19,caused by SARS-CoV-2,has resulted in serious economic and health burdens.Current treatments remain inadequate to extinguish the epidemic,and efficient therapeutic approaches for COVID-19 are urgently being sought.Interestingly,accumulating evidence suggests that microenvironmental disorder plays an important role in the progression of COVID-19 in patients.In addition,recent advances in nanomaterial technologies provide promising opportunities for alleviating the altered homeostasis induced by a viral infection,providing new insight into COVID-19 treatment.Most literature reviews focus only on certain aspects of microenvironment alterations and fail to provide a comprehensive overview of the changes in homeostasis in COVID-19 patients.To fill this gap,this review systematically discusses alterations of homeostasis in COVID-19 patients and potential mechanisms.Next,advances in nanotechnology-based strategies for promoting homeostasis restoration are summarized.Finally,we discuss the challenges and prospects of using nanomaterials for COVID-19 management.This review provides a new strategy and insights into treating COVID-19 and other diseases associated with microenvironment disorders.