A ZBP1 isoform blocks ZBP1-mediated cell death.

ZBP1 is an interferon (IFN)-induced nucleic acid (NA) sensor that senses unusual Z-form NA (Z-NA) to promote cell death and inflammation. However, the mechanisms that dampen ZBP1 activation to fine-tune inflammatory responses are unclear. Here, we characterize a short isoform of ZBP1 (referred to as ZBP1-S) as an intrinsic suppressor of the inflammatory signaling mediated by full-length ZBP1. Mechanistically, ZBP1-S depresses ZBP1-mediated cell death by competitive binding with Z-NA for Zα domains of ZBP1. Cells from mice (Ripk1D325A/D325A) with cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome are alive but sensitive to IFN-induced and ZBP1-dependent cell death. Intriguingly, Ripk1D325A/D325A cells die spontaneously when ZBP1-S is deleted, indicating that cell death driven by ZBP1 is under the control of ZBP1-S. Thus, our findings reveal that alternative splicing of Zbp1 represents autogenic inhibition for regulating ZBP1 signaling and indicate that uncoupling of Z-NA with ZBP1 could be an effective strategy against autoinflammations.

Photoacoustic Imaging Probes for Theranostic Applications.

Photoacoustic imaging (PAI), an emerging biomedical imaging technology, capitalizes on a wide range of endogenous chromophores and exogenous contrast agents to offer detailed information related to the functional and molecular content of diseased biological tissues. Compared with traditional imaging technologies, PAI offers outstanding advantages, such as a higher spatial resolution, deeper penetrability in biological tissues, and improved imaging contrast. Based on nanomaterials and small molecular organic dyes, a huge number of contrast agents have recently been developed as PAI probes for disease diagnosis and treatment. Herein, we report the recent advances in the development of nanomaterials and organic dye-based PAI probes. The current challenges in the field and future research directions for the designing and fabrication of PAI probes are proposed.

Microelectrode-Based Electrochemical Sensing Technology for in Vivo Detection of Dopamine: Recent Developments and Future Prospects.

Dopamine (DA) is an essential type of neurotransmitter in the central nervous system. DA neurons usually exist as nuclei which are mainly found in the ventral tegmental area (VTN) and substantia nigra pars compacta (SNc). Parkinson's disease, epilepsy, schizophrenia and other diseases are all related to the abnormal metabolism of DA. Compared with traditional DA detection methods such as spectrophotometry and electrophoresis, electrochemical sensing technology has high detection efficiency, high sensitivity, fast and convenient real-time detection, which is recognized as the most effective method for measuring neurotransmitters in vivo. The working electrode of an electrochemical sensor can be generally divided into the conventional electrode and the microelectrode according to its size. The microelectrode shows excellent properties such as high sensitivity, high temporal resolution, and high spatial resolution while detecting DA, which makes it possible to detect neurotransmitters in vivo. In order to further investigate the role of DA in regulating action, emotion, and cognition, and to further clarify the relationship between DA abnormalities or lack and neurological diseases such as Parkinson, more and more researchers apply microelectrode-based electrochemistry sensing technology to detect DA in vivo. This article reviews recent applications of microelectrodes and the latest researches in DA detection in vivo, focusing on the following three types of microelectrodes: (1) non-nanomaterial-modified carbon fiber microelectrodes (CFE); (2) nanomaterial-modified microelectrodes; (3) microelectrode arrays (MEA).

Disrupting the Cdk9/Cyclin T1 heterodimer of 7SK snRNP for the Brd4 and AFF1/4 guided reconstitution of active P-TEFb.

P-TEFb modulates RNA polymerase II elongation through alternative interaction with negative and positive regulation factors. While inactive P-TEFbs are mainly sequestered in the 7SK snRNP complex in a chromatin-free state, most of its active forms are in complex with its recruitment factors, Brd4 and SEC, in a chromatin-associated state. Thus, switching from inactive 7SK snRNP to active P-TEFb (Brd4/P-TEFb or SEC/P-TEFb) is essential for global gene expression. Although it has been shown that cellular signaling stimulates the disruption of 7SK snRNP, releasing dephosphorylated and catalytically inactive P-TEFb, little is known about how the inactive released P-TEFb is reactivated. Here, we show that the Cdk9/CycT1 heterodimer released from 7SK snRNP is completely dissociated into monomers in response to stress. Brd4 or SEC then recruits monomerized Cdk9 and CycT1 to reassemble the core P-TEFb. Meanwhile, the binding of monomeric dephosphorylated Cdk9 to either Brd4 or SEC induces the autophosphorylation of T186 of Cdk9. Finally, the same mechanism is employed during nocodazole released entry into early G1 phase of cell cycle. Therefore, our studies demonstrate a novel mechanism by which Cdk9 and CycT1 monomers are reassembled on chromatin to form active P-TEFb by its interaction with Brd4 or SEC to regulate transcription.

Research on Evaluating the Filtering Method for Broiler Sound Signal from Multiple Perspectives.

Broiler sounds can provide feedback on their own body condition, to a certain extent. Aiming at the noise in the sound signals collected in broiler farms, research on evaluating the filtering methods for broiler sound signals from multiple perspectives is proposed, and the best performer can be obtained for broiler sound signal filtering. Multiple perspectives include the signal angle and the recognition angle, which are embodied in three indicators: signal-to-noise ratio (SNR), root mean square error (RMSE), and prediction accuracy. The signal filtering methods used in this study include Basic Spectral Subtraction, Improved Spectral Subtraction based on multi-taper spectrum estimation, Wiener filtering and Sparse Decomposition using both thirty atoms and fifty atoms. In analysis of the signal angle, Improved Spectral Subtraction based on multi-taper spectrum estimation achieved the highest average SNR of 5.5145 and achieved the smallest average RMSE of 0.0508. In analysis of the recognition angle, the kNN classifier and Random Forest classifier achieved the highest average prediction accuracy on the data set established from the sound signals filtered by Wiener filtering, which were 88.83% and 88.69%, respectively. These are significantly higher than those obtained by classifiers on data sets established from sound signals filtered by other methods. Further research shows that after removing the starting noise in the sound signal, Wiener filtering achieved the highest average SNR of 5.6108 and a new RMSE of 0.0551. Finally, in comprehensive analysis of both the signal angle and the recognition angle, this research determined that Wiener filtering is the best broiler sound signal filtering method. This research lays the foundation for follow-up research on extracting classification features from high-quality broiler sound signals to realize broiler health monitoring. At the same time, the research results can be popularized and applied to studies on the detection and processing of livestock and poultry sound signals, which has extremely important reference and practical value.

DACH1, a novel target of miR-218, participates in the regulation of cell viability, apoptosis, inflammatory response, and epithelial-mesenchymal transition process in renal tubule cells treated by high-glucose.

Objective: This report was designed to assess the functional role of miR-218/dachshund family transcription factor 1 (DACH1) in diabetic kidney disease (DKD) and investigate its possible molecular mechanism.Materials and Methods: From the GEO database, we downloaded different datasets for analyzing the expression of miR-218 and DACH1 in DKD. TargetScan was adopted to predict the binding sites between miR-218 and DACH1, which was further verified by dual-luciferase reporter assays. The renal proximal tubule cells (HK-2) treated with high glucose (HG) were used as an in vitro model. QRT-PCR and western blot were used to determine the expression of DACH1 and other relative factors. Cell counting kit-8 and flow cytometer were applied to detect cell viability and apoptosis. The levels of inflammatory cytokines were determined by an ELISA assay.Results: A prominent raise of miR-218 was observed in DKD through bioinformatics analysis, which was further confirmed in the HG-induced model. DACH1 is a target of miR-218. miR-218 reduced cell viability and induced apoptosis by negatively regulating DACH1. Moreover, upregulating miR-218 in HG models increased the concentrations of pro-inflammatory cytokines TNF-α and IL-1ß, reduced the level of anti-inflammatory cytokine IL-10, and promoted the epithelial-mesenchymal transition (EMT) process, which is possibly achieved by targeting DACH1. While downregulating miR-218 showed the opposite results.Conclusion: These data demonstrated that, under an in vitro HG environment, miR-218 suppressed the HK-2 cells proliferation, promoted apoptosis, caused an inflammatory response, and facilitated the EMT process largely by targeting DACH1, providing an insight into the therapeutic intervention of DKD.