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Mechanisms coordinating pancreatic β cell metabolism with insulin secretion are essential for glucose homeostasis. One key mechanism of β cell nutrient sensing uses the mitochondrial GTP (mtGTP) cycle. In this cycle, mtGTP synthesized by succinyl-CoA synthetase (SCS) is hydrolyzed via mitochondrial PEPCK (PEPCK-M) to make phosphoenolpyruvate, a high-energy metabolite that integrates TCA cycling and anaplerosis with glucose-stimulated insulin secretion (GSIS). Several strategies, including xenotopic overexpression of yeast mitochondrial GTP/GDP exchanger (GGC1) and human ATP and GTP-specific SCS isoforms, demonstrated the importance of the mtGTP cycle. These studies confirmed that mtGTP triggers and amplifies normal GSIS and rescues defects in GSIS both in vitro and in vivo. Increased mtGTP synthesis enhanced calcium oscillations during GSIS. mtGTP also augmented mitochondrial mass, increased insulin granule number, and membrane proximity without triggering de-differentiation or metabolic fragility. These data highlight the importance of the mtGTP signal in nutrient sensing, insulin secretion, mitochondrial maintenance, and β cell health.

The widespread occurrence of Carboniferous Wuluate Formation volcanic rocks in the West Kunlun is closely related to the evolution of the Paleo-Tethys but has received little attention. In this study, we conducted detailed fieldwork on the Wuluate Formation in West Kunlun and performed zircon U‒Pb dating, whole-rock major and trace element analysis, whole-rock Sr-Nd isotope analysis, and in situ zircon Hf isotope analyses. The Wuluate Formation is characterized by a bimodal volcanic suite. Zircon U‒Pb dating indicates that the rhyolites erupted at ca. 348–353 Ma, which is coeval with the zircon U‒Pb dating result of 354 Ma for the basalt. The basalts show a tholeiitic magmatic evolution trend with flattened REE patterns and depleted whole-rock Sr-Nd and zircon Hf isotopes, indicating geochemical affinity to back-arc basin basalt (BABB). Trace element modelling results indicate that the primitive basaltic compositions fit well with the products of the DMM + sediments + H2O source under melting conditions of asthenospheric temperature and thin lithosphere thickness, and the REE modelling results show that the basalts underwent 40% to 95% crystallographic differentiation of olivine, monazite, hornblende, plagioclase, and magnetite. The silicic rocks are calcic to calcic-alkaline and meta/peraluminous. They exhibit flattened REE patterns and slightly enriched zircon Hf isotopes, which could originate from Precambrian metaigneous sources of West Kunlun. The Kungai bimodal suite is likely to have formed in a back-arc setting corresponding to the northward subduction of Paleo-Tethys. The subduction of Paleo-Tethys had already occurred, and a back-arc basin had developed before the Early Carboniferous. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is a common cancer with high mortality worldwide. PANoptosis is a novel inflammatory programmed cell death modality with the characteristics of pyroptosis, apoptosis and necroptosis. It is necessary to explore PANoptosis‐related genes in LUAD patients and offer evidence for prognosis prediction and therapeutic strategies. Single‐cell RNA sequencing data and RNA expression profiles of LUAD patients from The Cancer Genome Atlas and Gene Expression Omnibus databases are used to screen PANoptosis‐related differential genes for the construction of a risk model. Fifteen PANoptosis‐related markers with prognostic value were identified by Least Absolute Shrinkage and Selection Operator (LASSO)–Cox regression analysis. Kaplan–Meier analysis and receiver operating characteristic curve analysis further demonstrated the significant predictive capability. Immune infiltration, Single Nucleotide Variants (SNV) mutations, and clinical drug susceptibility were analyzed. In conclusion, a risk model of 15 PANoptosis‐related genes has significant value in prognostic prediction for LUAD and has potential to direct clinical therapeutic strategies during the treatment. [ABSTRACT FROM AUTHOR]