Research Progress on Biomimetic Nanomaterials for Electrochemical Glucose Sensors.

Diabetes has become a chronic disease that necessitates timely and accurate detection. Among various detection methods, electrochemical glucose sensors have attracted much attention because of low cost, real-time detection, and simple and easy operation. Nonenzymatic biomimetic nanomaterials are the vital part in electrochemical glucose sensors. This review article summarizes the methods to enhance the glucose sensing performance of noble metal, transition metal oxides, and carbon-based materials and introduces biomimetic nanomaterials used in noninvasive glucose detection in sweat, tear, urine, and saliva. Based on these, this review provides the foundation for noninvasive determination of trace glucose for diabetic patients in the future.

Ube2s stabilizes ß-Catenin through K11-linked polyubiquitination to promote mesendoderm specification and colorectal cancer development.

The canonical Wnt/ß-Catenin signaling pathway is widely involved in regulating diverse biological processes. Dysregulation of the pathway results in severe consequences, such as developmental defects and malignant cancers. Here, we identified Ube2s as a novel activator of the Wnt/ß-Catenin signaling pathway. It modified ß-Catenin at K19 via K11-linked polyubiquitin chain. This modification resulted in an antagonistic effect against the destruction complex/ß-TrCP cascade-orchestrated ß-Catenin degradation. As a result, the stability of ß-Catenin was enhanced, thus promoting its cellular accumulation. Importantly, Ube2s-promoted ß-Catenin accumulation partially released the dependence on exogenous molecules for the process of embryonic stem (ES) cell differentiation into mesoendoderm lineages. Moreover, we demonstrated that UBE2S plays a critical role in determining the malignancy properties of human colorectal cancer (CRC) cells in vitro and in vivo. The findings in this study extend our mechanistic understanding of the mesoendodermal cell fate commitment, and provide UBE2S as a putative target for human CRC therapy.

Uev1A-Ubc13 catalyzes K63-linked ubiquitination of RHBDF2 to promote TACE maturation.

The TNFα-induced NF-κB signaling pathway plays critical roles in multiple biological processes. Extensive studies have explored the mechanisms regulating this signaling cascade, and identified an E2 complex, Uev1A-Ubc13, that mediates K63-linked poly-Ub chain formation and thus recruits NEMO to activate the signaling transduction. In this study, we demonstrate that the Uev1A-Ubc13 complex simultaneously serves as a repressor of the NF-κB pathway. It was found that cells overexpressing UEV1A silence the signal cascade earlier than control cells. Importantly, UEV1A overexpression enhances TACE maturation to shed the TNFα receptor. The Uev1A-Ubc13 complex interacts with RHBDF2, a key factor promoting TACE maturation, and inhibition of the Uev1A-Ubc13 activity interferes with RHBDF2-promoted TACE maturation. Furthermore, upon TNFα stimulation, the Uev1A-Ubc13 complex cooperates with CHIP to promote K63-linked ubiquitination of RHBDF2, enhancing its activity toward TACE maturation and subsequently blocking TNFα-induced NF-κB signaling.