HuR deficiency abrogated the enhanced NLRP3 signaling in experimental ischemic stroke.

Human antigen R (HuR) is a universally expressed RNA-binding protein that plays an essential role in governing the fate of mRNA transcripts. Accumulating evidence indicated that HuR is involved in the development and functions of several cell types. However, its role in cerebral ischemia/reperfusion injury (CIRI) remains unclear. In this study, we found that HuR was significantly upregulated after CIRI. Moreover, we found that silencing HuR could inhibit the inflammatory response of microglia and reduce the damage to neurons caused by oxygen-glucose deprivation/reperfusion treatment. In vivo, we found that microglial HuR deficiency significantly ameliorated CIRI and reduced NLRP3-mediated inflammasome activation. Mechanistically, we found that HuR could regulate NLRP3 mRNA stability by binding to the AU-rich element (ARE) region within the 3' untranslated region (UTR) of NLRP3 mRNA. In addition, we found that the upregulation of HuR was dependent on the upregulation of NADPH oxidase-mediated ROS accumulation. Collectively, our studies revealed that HuR could regulate NLRP3 expression and that HuR deficiency abrogated the enhanced NLRP3 signaling in experimental ischemic stroke. Targeting HuR may be a novel therapeutic strategy for cerebral ischemic stroke treatment.

One-pot and rapid detection of SARS-CoV-2 viral particles in environment using SERS aptasensor based on a locking amplifier.

With the frequent detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in dwellings and wastewater, the risk of transmission of environmental contaminants is of great concern. Fast, simple and sensitive sensors are essential for timely detecting infection and controlling transmission through environment fomites. Herein, we developed a Surface Enhanced Raman Scattering (SERS) aptasensor, which can realize ultrasensitive and rapid assay of SARS-CoV-2 viral particles. In this strategy, we designed a novel locking amplifier which is activated only in the presence of virus by aptamer recognition. The reaction process was carried out though one-pot method at 37 °C, which can save time and resources. In addition, magnetic beads used in reaction system can simplify operation, as well as provide ideas for developing biosensing robots via magnetic field. This SERS aptasensor can detect SARS-CoV-2 virus with a LOD of 260 TU/µL within 40 min in the linear range of 625-10,000 TU/µL. Therefore, this convenience, speediness, sensitivity, and selectivity of detection has great prospects in analyzing SARS-CoV-2 viral particles or other viruses in environment as well as monitoring of environmental virus sources.

Performance of 3D printing biomimetic conch shell and pearl shell hybrid design composites under quasi-static three-point bending load.

The failure process of biomimetic hybrid design composite composed of layers of conch shell and pearl shell was studied through quasi-static three-point bending experiments and numerical simulations. The biomimetic conch shell structure with inclined angles serves as the upper layer of the hybrid structure, while the biomimetic pearl shell structure with traditional brick and mud structure serves as the lower layer of the hybrid structure, forming a hybrid design structure. Four inclined angles were designed for the structural units of the conch shell, namely 15°, 30°, 45°, and 60°. Twenty-four specimens (six specimens for each inclined angle) were prepared using 3D printing technology using both soft and hard matrix materials. The influence of different inclined angles on the fracture strength, fracture toughness, and energy absorption of hybrid design structures was experimentally studied. The biomimetic hybrid design composite specimen with a notch is placed between two supporting rollers, and a loading indenter acts at mid-span. All twenty-four specimens were notched with a triangular tip and a rectangular bottom. A loading rate of 1 mm/min is used to avoid the viscoelastic effect of the composite materials. Details of the specimens, the experimental set-up and procedure are discussed in this paper. Complementary to the experimental studies, an extensive numerical investigation was carried out to study the influence of the aspect ratio of brick and mud units on the fracture initiation and failure of hybrid design structures. The causes of crack initiation and propagation, and failure modes in biomimetic hybrid design structures were postulated. These numerical findings help in reinforcing the experimental results and provide crucial information to enhance further research in this exciting area.

Raman and fourier transform infrared spectroscopy techniques for detection of coronavirus (COVID-19): a mini review.

Coronavirus pandemic has been a huge jeopardy to human health in various systems since it outbroke, early detection and prevention of further escalation has become a priority. The current popular approach is to collect samples using the nasopharyngeal swab method and then test for RNA using the real-time polymerase chain reaction, which suffers from false-positive results and a longer diagnostic time scale. Alternatively, various optical techniques, namely, optical sensing, spectroscopy, and imaging shows a great promise in virus detection. In this mini review, we briefly summarize the development progress of vibrational spectroscopy techniques and its applications in the detection of SARS-CoV family. Vibrational spectroscopy techniques such as Raman spectroscopy and infrared spectroscopy received increasing appreciation in bio-analysis for their speediness, accuracy and cost-effectiveness in detection of SARS-CoV. Further, an account of emerging photonics technologies of SARS-CoV-2 detection and future possibilities is also explained. The progress in the field of vibrational spectroscopy techniques for virus detection unambiguously show a great promise in the development of rapid photonics-based devices for COVID-19 detection.

Ferroptosis sensitization in glioma: exploring the regulatory mechanism of SOAT1 and its therapeutic implications.

Glioma, the most common primary malignant tumor of the central nervous system, lacks effective targeted therapies. This study investigates the role of SOAT1, a key gene involved in cholesterol esterification, in glioma prognosis and its association with ferroptosis. Although the impact of SOAT1 on glioma prognosis has been recognized, its precise mechanism remains unclear. In this study, we demonstrate that inhibiting SOAT1 increases the sensitivity of glioma cells to ferroptosis, both in vitro and in vivo. Mechanistically, SOAT1 positively modulates the expression of SLC40A1, an iron transporter, resulting in enhanced intracellular iron outflow, reduced intracellular iron levels, and subsequent disruption of ferroptosis. Importantly, we find that SOAT1 regulates ferroptosis independently of SREBPs, which are known to be involved in ferroptosis regulation. Furthermore, we identify the involvement of the PI3K-AKT-mTOR signaling pathway in mediating the regulatory effects of SOAT1 on SLC40A1 expression and ferroptosis sensitivity. These findings highlight the contribution of intracellular signaling cascades in the modulation of ferroptosis by SOAT1. We show that inhibiting SOAT1 enhances the efficacy of radiotherapy in gliomas, both in vitro and in vivo, by promoting sensitivity to ferroptosis. This suggests that targeting SOAT1 could potentially improve therapeutic outcomes for glioma patients. In summary, this study uncovers the pivotal role of SOAT1 as a link between cholesterol esterification and ferroptosis in glioma. Our findings underscore the potential of SOAT1 as a promising clinical therapeutic target, providing new avenues for the development of effective treatments for glioma. Further research is warranted to unravel the complete regulatory mechanisms of SOAT1 and explore its clinical applications.