Design and implementation of SRIO multiple channel control system based on FPGA

In board and chip interconnection, SRIO(Serail RapidIO) has higher bandwidth and reliability than other protocol. In this paper, the HELLO format of the MSG (message) interface is used to multi-interface design method at the sending end, and the Round-Robin processing mechanism is used internally to realize the competition processing of the multi-channel interface sharing one SRIO interface when sending data at the same time. It supports the arbitrary expansion of the number of interfaces and the clock domain. After testing and verification, the system can realize the data sending and receiving of 64 channels under different clocks at most, and the delay between the single channel and the packet can be as low as 4μs. It has good application value in the direction of SRIO transmission application

TCF12 regulates the TGF-β/Smad2/3 signaling pathway to accelerate the progression of osteoarthritis by targeting CXCR4

Objective: Osteoarthritis (OA), which involves total joint damage and dysfunction, is a leading cause of disability worldwide. However, its exact pathogenesis remains unclear. Here, we identified TCF12 as an important regulator of the progression of OA. Methods: qRT-PCR, immunoblotting and immunohistochemistry (IHC) were used to detect the expression level of TCF12. The interaction of TCF12 with its downstream factor CXCR4 was assessed by Western blotting, immunofluorescence, qRT-PCR and luciferase assays. A mouse model was generated to examine the functions and mechanism of TCF12 in vivo. Result: TCF12 expression was upregulated in chondrocytes stimulated with IL-1β and osteoarthritic chondrocytes. TCF12 upregulates the expression of CXCR4 and leads to dysfunction of the TGF-β signaling pathway. Furthermore, knockdown of TCF12 alleviated cartilage damage in a mouse model generated by destabilization of the medial meniscus (DMM). Conclusion: TCF12 aggravates the progression of OA by targeting CXCR4 and then activating the TGF-β signaling pathway, suggesting that TCF12 may be a new target for the treatment of OA. The translational potential of this article: Transcription Factor 12(TCF12), is known to regulate cell development and differentiation, It has been widely studied in various organs and diseases, but its role in OA remains unclear. Here, we identified Transcription Factor 12(TCF12) as an important regulator mediating chondrocyte senescence and cartilage extracellular matrix degradation indicating its role in OA. We found that TCF12 expression was upregulated both locally and systemically as OA advanced in patients with OA, and in mice after DMM surgery to induce OA. TCF12 expression caused striking progressive articular cartilage damage, synovial hyperplasia in OA mice, and remarkably, it was relieved by intra-articular administration of mutant mouse TCF12 lentiviral vector (shTCF12). Furthermore, TCF12 upregulated the expression of CXCR4, leading to exacerbation of experimental OA partially through activation of TGF-β signaling in chondrocytes. TCF12 expression was upregulated in chondrocytes treated with IL-1β and osteoarthritic chondrocytes. Our findings established an essential role of TCF12 in chondrocyte senescence and cartilage extracellular matrix degradation during OA, and identified intra-articular injection of TCF12 as a potential therapeutic strategy for OA prevention and treatment

Giant electric field-induced second harmonic generation in polar skyrmions

Abstract Electric field-induced second harmonic generation allows electrically controlling nonlinear light-matter interactions crucial for emerging integrated photonics applications. Despite its wide presence in materials, the figures-of-merit of electric field-induced second harmonic generation are yet to be elevated to enable novel device functionalities. Here, we show that the polar skyrmions, a topological phase spontaneously formed in PbTiO3/SrTiO3 ferroelectric superlattices, exhibit a high comprehensive electric field-induced second harmonic generation performance. The second-order nonlinear susceptibility and modulation depth, measured under non-resonant 800 nm excitation, reach ~54.2 pm V−1 and ~664% V−1, respectively, and high response bandwidth (higher than 10 MHz), wide operating temperature range (up to ~400 K) and good fatigue resistance (>1010 cycles) are also demonstrated. Through combined in-situ experiments and phase-field simulations, we establish the microscopic links between the exotic polarization configuration and field-induced transition paths of the skyrmions and their electric field-induced second harmonic generation response. Our study not only presents a highly competitive thin-film material ready for constructing on-chip devices, but opens up new avenues of utilizing topological polar structures in the fields of photonics and optoelectronics

A Cullin 5-based complex serves as an essential modulator of ORF9b stability in SARS-CoV-2 replication

Abstract The ORF9b protein, derived from the nucleocapsid’s open-reading frame in both SARS-CoV and SARS-CoV-2, serves as an accessory protein crucial for viral immune evasion by inhibiting the innate immune response. Despite its significance, the precise regulatory mechanisms underlying its function remain elusive. In the present study, we unveil that the ORF9b protein of SARS-CoV-2, including emerging mutant strains like Delta and Omicron, can undergo ubiquitination at the K67 site and subsequent degradation via the proteasome pathway, despite certain mutations present among these strains. Moreover, our investigation further uncovers the pivotal role of the translocase of the outer mitochondrial membrane 70 (TOM70) as a substrate receptor, bridging ORF9b with heat shock protein 90 alpha (HSP90α) and Cullin 5 (CUL5) to form a complex. Within this complex, CUL5 triggers the ubiquitination and degradation of ORF9b, acting as a host antiviral factor, while HSP90α functions to stabilize it. Notably, treatment with HSP90 inhibitors such as GA or 17-AAG accelerates the degradation of ORF9b, leading to a pronounced inhibition of SARS-CoV-2 replication. Single-cell sequencing data revealed an up-regulation of HSP90α in lung epithelial cells from COVID-19 patients, suggesting a potential mechanism by which SARS-CoV-2 may exploit HSP90α to evade the host immunity. Our study identifies the CUL5-TOM70-HSP90α complex as a critical regulator of ORF9b protein stability, shedding light on the intricate host–virus immune response dynamics and offering promising avenues for drug development against SARS-CoV-2 in clinical settings