Dual chemical bonding construction of electrochemical peptide sensor based on GDY/MOFs(Fe) composite for ultra-low determination of prostate-specific antigen.

A novel "double chemical bonding" electrochemical peptide biosensor 2FcP-GA-GDY(Fe)@NMIL-B was developed for highly selective, ultrasensitive, and ultrastable identification of prostate-specific antigen (PSA). The C-Fe-O chemical bond linking Fe-Graphdiyne (Fe-GDY) with NH2-MIL88B(Fe) (NMIL88B) as the first chemical bonding of electrode carrier Fe-GDY@NH2-MIL88B(Fe) (GDY(Fe)@NMIL) significantly accelerates electron transport. With glutaraldehyde (GA) as a crosslinking agent, the Schiff-base -NC- formed by GDY(Fe)@NMIL nanocomposites links the two Fc molecules labeled peptides (2FcP) as the second chemical bonding, facilitating high-density attachment of peptides to the electrode carrier in a firm manner. When the PSA analyte is introduced to identify and cleave the specific peptide, the release of ferrocene from its head leads to a decrease in the electrical signal, enabling sensitive detection. The prepared sensing platform exhibits exceptional analytical performance for PSA with an extended linear response range from 10 fg mL-1 to 50 ng mL-1. Additionally, the detection limit has been significantly reduced to an ultra-low level of only 0.94 fg mL-1, surpassing those reported in most literature by several orders of magnitude. Moreover, the 2FcP-GA-GDY(Fe)@NMIL-B sensor has excellent selectivity and stability while also showcasing great potential for practical application of PSA detection in human serum using the standard addition method.

Label-free MXene-assisted field effect transistor for the determination of IL-6 in patients with kidney transplantation infection.

A spiral interdigitated MXene-assisted field effect transistor (SiMFETs) was proposed for determination of IL-6 in patients with kidney transplantation infection. Our SiMFETs demonstrated enhanced IL-6 detection range of 10 fg/mL-100 ng/mL due to the combination of optimized transistor's structure and semiconducting nanocomposites. Specifically, on one hand, MXene-based field effect transistor drastically amplified the amperometric signal for determination of IL-6; on the other hand, the multiple spiral structure of interdigitated drain-source architecture improved the transconductance of FET biosensor. The developed SiMFETs biosensor demonstrated satisfactory stability for 2 months, and favorable reproducibility and selectivity against other biochemical interferences. The SiMFETs biosensor exhibited acceptable correlation coefficient (R2=0.955) in quantification of clinical biosamples. The sensor successfully distinguished the infected patients from the health control with enhanced AUC of 0.939 (sensitivity of 91.7%, specificity of 86.7%). Those merits introduced here may pave an alternative strategy for transistor-based biosensor in point-of-care clinic applications.

Hypoxia-Inducible Factor 2α Attenuates Renal Ischemia-Reperfusion Injury by Suppressing CD36-Mediated Lipid Accumulation in Dendritic Cells in a Mouse Model.

BACKGROUND: Hypoxia and hypoxia-inducible factors (HIFs) play essential and multiple roles in renal ischemia-reperfusion injury (IRI). Dendritic cells (DCs) comprise a major subpopulation of the immunocytes in the kidney and are key initiators and effectors of the innate immune responses after IRI. The role of HIF-2α in DCs remains unclear in the context of renal IRI. METHODS: To investigate the importance of HIF-2α in DCs upon renal IRI, we examined the effects of DC-specific HIF-2α ablation in a murine model. Bone marrow-derived DCs (BMDCs) from DC-specific HIF-2α-ablated mice and wild-type mice were used for functional studies and transcriptional profiling. RESULTS: DC-specific ablation of HIF-2α led to hyperactivation of natural killer T (NKT) cells, ultimately exacerbating murine renal IRI. HIF-2α deficiency in DCs triggered IFN-γ and IL-4 production in NKT cells, along with upregulation of type I IFN and chemokine responses that were critical for NKT cell activation. Mechanistically, loss of HIF-2α in DCs promoted their expression of CD36, a scavenger receptor for lipid uptake, increasing cellular lipid accumulation. Furthermore, HIF-2α bound directly to a reverse hypoxia-responsive element (rHRE) in the CD36 promoter. Importantly, CD36 blockade by sulfo-N-succinimidyl oleate (SSO) reduced NKT cell activation and abolished the exacerbation of renal IRI elicited by HIF-2α knockout. CONCLUSIONS: Our study reveals a previously unrecognized role of the HIF-2α/CD36 regulatory axis in rewiring DC lipid metabolism under IRI-associated hypoxia. These findings suggest a potential therapeutic target to resolve long-standing obstacles in treatment of this severe complication.