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Abstract Background Rheumatoid arthritis, a chronic autoimmune disease, is characterized by synovial hyperplasia and cartilage erosion. Here, we investigated the potential mechanism of action of quercetin, the main component of flavonoids, in treating rheumatoid arthritis. Object To examine the anti-arthritic effects of quercetin and elucidate the specific mechanisms that differentiate its metabolic effects on autoimmune and inflammatory responses at the synovial cell level. Methods We created a collagen-induced arthritis (CIA) model in Wistar rats, which were administered quercetin (50 or 100 mg/kg) continuously for four weeks via stomach perfusion. The arthritis score, histopathological staining, radiological assessment, and serum biochemical parameters were used to study the impact of quercetin on disease improvement. Additionally, immunofluorescence was employed to detect JAK1/STAT3/HIF-1α expression in rat joints. Moreover, the effects of quercetin (20, 40, and 80 µmol/L) on the properties and behavior of synovial fibroblasts were evaluated in an in vitro MH7A cell model using flow cytometry, CCK8, and transwell assays. Further, the mRNA expression levels of inflammatory cytokines IL1β, IL6, IL17, and TNFα were assessed by quantitative real-time PCR. Glucose, lactate, lactate dehydrogenase, pyruvate, pyruvate dehydrogenase, and adenosine triphosphate assay kits were employed to measure the metabolic effects of quercetin on synovial fibroblasts. Finally, immunoblotting was used to examine the impact of quercetin on the JAK1/STAT3/HIF-1α signaling pathway in synovial fibroblasts. Results In vivo experiments confirmed the favorable effects of quercetin in CIA rats, including an improved arthritis score and reduced ankle bone destruction, in addition to a decrease in the pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in serum. Immunofluorescence verified that quercetin may ameliorate joint injury in rats with CIA by inhibiting JAK1/STAT3/HIF-1α signaling. Various in vitro experiments demonstrated that quercetin effectively inhibits IL-6-induced proliferation of MH7A cells and reduces their migratory and invasive behavior, while inducing apoptosis and reducing the expression of the pro-inflammatory cytokines IL1β, IL6, IL17, and TNFα at the mRNA level. Quercetin caused inhibition of glucose, lactate, lactate dehydrogenase, pyruvate, and adenosine triphosphate and increased pyruvate dehydrogenase expression in MH7A cells. It was further confirmed that quercetin may inhibit energy metabolism and inflammatory factor secretion in MH7A cells through JAK1/STAT3/HIF-1α signaling. Conclusions Quercetin’s action on multiple target molecules and pathways makes it a promising treatment for cartilage injury in rheumatoid arthritis. By reducing joint inflammation, improving joint metabolic homeostasis, and decreasing immune system activation energy, quercetin inhibits the JAK1/STAT3/HIF-1α signaling pathway to improve disease status.

Arc fault detection devices are mandatory worldwide for mitigating DC series arc faults in photovoltaic systems. However, they are prone to nuisance tripping. Artificial intelligence-based approaches can be a solution, but they are “black boxes” and challenging to modify. This paper proposes an explainability and attention-based method to investigate the intensive details of such an algorithm. The contributions of an arc feature to the proposed model can be visualized by the proposed interpretable methodology so that insensitive arc features can be removed to reduce the quantity of input data. Additionally, the structure of the proposed model can be optimized by cutting the redundant layers. Thus, an accuracy of 99.63% is achieved with only 48.48% of the parameters compared to the original model. Finally, the optimized model is implemented by a Cortex M7-based microprocessor with a runtime of only 7.8 ms, making it ready for industrial application.

N6‐methyladenosine (m6A) is one of the most abundant internal modifications in eukaryotic messenger RNAs (mRNAs) and non‐coding RNAs (ncRNAs). It is a reversible and dynamic RNA modification that has been observed in both internal coding segments and untranslated regions. Studies indicate that m6A modifications play important roles in translation, RNA splicing, export, degradation and ncRNA processing control. In this review, we focus on the profiles and biological functions of RNA m6A methylation on both mRNAs and ncRNAs. The dynamic modification of m6A and its potential roles in cancer development are discussed. Moreover, we discuss the possibility of m6A modifications serving as potential biomarkers for cancer diagnosis and targets for therapy.

N6-methyladenosine (m6A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m6A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m6A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.

The use of recycled concrete aggregates (RCA) instead of natural aggregates in hot-mix asphalt mixtures is one of the ways to achieve energy savings and reduce carbon emissions in road engineering. However, the cement mortar on the surface of RCA adversely affects the adhesion properties between asphalt and aggregates, leading to a reduction in the performance characteristics of asphalt mixtures. In this study, a silane coupling agent (SCA) was employed to improve the adhesion properties of the RCA/asphalt interface. The enhancement mechanism of SCA on the RCA/asphalt interface was investigated from multiple perspectives, including macroscopic properties, interfacial microstructure, and nanoscale interfacial interactions. Firstly, the adhesion behavior and tensile strength of the interface between RCA and asphalt were determined through a boiling water test and direct tensile test, both before and after SCA modification. Secondly, scanning electron microscopy (SEM) was employed to observe the surface microstructure of RCA and the microstructure of the RCA/asphalt interface. Finally, the main component of mortar, calcium silicate hydrate (C-S-H), was taken as the research subject of investigation to examine the hydrogen bonding, interaction energy, and interface transition zone of the C-S-H/asphalt interface system using the molecular dynamics methodology. The results demonstrate a two-level enhancement in the adhesion performance of the interface at the macroscopic scale following SCA modification. The interface tensile strength increased by 72.2% and 119.7% under dry and wet conditions, respectively. At the microscopic scale, it was observed that the surface pores of RCA were repaired after SCA modification, resulting in a more tightly bonded interface between the RCA and asphalt. At the nanoscale, SCA modification reduces the hydrophilicity of the C-S-H surface, increases the interaction energy and water resistance of the C-S-H/asphalt interface, and enhances the weak interface transition zone between C-S-H and asphalt. This study provides a theoretical basis for using SCA to enhance the bond strength of the RCA/asphalt interface and lays the foundation for the application of RCA asphalt mixtures on highways.

Arc faults pose challenges to electric safety, which can cause serious fire hazards. However, the commonly used arc fault detection method is prone to nuisance tripping. This paper proposed a hybrid arc fault detection method based on the improved Mel-Frequency Ceptral Coefficients (MFCC) for preprocessing and a neural network model for arc identification called ARC_MFCC. As per the IEC 62606, twelve different loads/scenarios are considered for this research. An arc tangent-based core filter is employed to improve the MFCC to enhance the arc features within a bandwidth of 3 kHz to 7 kHz. A lightweight neural network model of fully connected cascaded with the MFCC-based preprocessing, which can distinguish the arc fault with normal operation under different test conditions. As a verification result, the ARC_ MFCC can achieve an accuracy of 99.34%. Moreover, the proposed method is implemented by Raspberry pie 4B. Test results show an average running time of about 4.2 ms per sample, which Ensures that the tripping time can meet IEC 62606.

DC arc faults are dangerous to photovoltaic (PV) systems and can cause serious electric fire hazards and property damage. Because the PV inverter works in a high−frequency pulse width modulation (PWM) control mode, the arc fault detection is prone to nuisance tripping due to PV inverter noises. An arc fault detection method based on the autoregressive (AR) model is proposed. A test platform collects the database of this research according to the UL1699B standard, in which three different types of PV inverters are taken into consideration to make it more generalized. The arc current can be considered a nonstationary random signal while the noise of the PV inverter is not. According to the difference in randomness features between an arc and the noise, a detection method based on the AR model is proposed. The Burg algorithm is used to determine model coefficients, while the Akaike Information Criterion (AIC) is applied to explore the best order of the proposed model. The correlation coefficient difference of the model coefficients plays a role as a criterion to identify if there is an arc fault. Moreover, a prototype circuit based on the TMS320F28033 MCU is built for algorithm verification. Test results show that the proposed algorithm can identify an arc fault without a false positive under different PV inverter conditions. The fault clearing time is between 60 ms to 80 ms, which can meet the requirement of 200 ms specified by the standard.

In recent years, a surge in studies investigating N6-methyladenosine (m6A) modification in human diseases has occurred. However, the specific roles and mechanisms of m6A in kidney disease remain incompletely understood. This study revealed that m6A plays a positive role in regulating renal fibrosis (RF) by inducing epithelial-to-mesenchymal phenotypic transition (EMT) in renal tubular cells. Through comprehensive analyses, including m6A sequencing, RNA-seq, and functional studies, we confirmed the pivotal involvement of zinc finger E-box binding homeobox 2 (ZEB2) in m6A-mediated RF and EMT. Notably, the m6A-modified coding sequence of ZEB2 mRNA significantly enhances its translational elongation and mRNA stability by interacting with the YTHDF1/eEF-2 complex and IGF2BP3, respectively. Moreover, targeted demethylation of ZEB2 mRNA using the dm6ACRISPR system substantially decreases ZEB2 expression and disrupts the EMT process in renal tubular epithelial cells. In vivo and clinical data further support the positive influence of m6A/ZEB2 on RF progression. Our findings highlight the m6A-mediated regulation of RF through ZEB2, revealing a novel therapeutic target for RF treatment and enhancing our understanding of the impact of mRNA methylation on kidney disease. [ABSTRACT FROM AUTHOR]

PURPOSE OF THE STUDY To examine the clinical impact of screw internal fixation on the process of fracture healing and ankle alignment in individuals diagnosed with posterior malleolar (PM) fracture, specifically those with a fracture involving less than 25% of the articular surface (ASR) area. MATERIAL AND METHODS A total of 120 patients diagnosed and treated for PM fracture, encompassing less than 25% of the distal tibial ASR area, were selected from our hospital’s records spanning from September 2021 to June 2023. These people were subsequently divided into two groups, namely the control group (group A) and the observation group (group B), based on the distinct treatment methods employed, with each group consisting of 60 patients. The people in the group A were treated with posterior malleolus non internal fixation, while the patients in the group B were treated with posterior malleolus screw internal fixation. The visual analog scores, peak plantar pressure and AOFAS scores of the two groups were subjected to comparison. RESULTS The visual analog scores in the observation group at 6 months and 12 months after operation were reduced than the group A. Three months after operation, the peak plantar pressure of the affected foot (full foot, hind foot) in the group B was reduced than that of the healthy foot; There was a lack of statistically significant variation observed in the peak plantar pressure (full foot, hind foot) between the affected foot and the healthy foot 12 months after operation in the group B, and the plantar pressure tended to be balanced. Three months after operation, the peak plantar pressure of the affected foot (full foot, hind foot) in the group A was reduced than that of the healthy foot; After a period of 12 months following the surgical procedure, no notable disparity in the maximum pressure exerted on the sole of the foot was observed between the foot that underwent the operation and the unaffected foot in the group A, but the peak plantar pressure of the whole foot was reduced than that of the healthy foot, and the plantar pressure did not tend to be balanced. At the intervals of 6 months and 12 months following the surgical procedure, AOFAS ankle hind foot score in the group B was increased than the group A. CONCLUSIONS The utilization of screw internal fixation demonstrates favorable clinical outcomes in patients presenting with PM fracture encompassing less than 25% of the articular surface area, which is conducive to promoting fracture healing, maintaining good ankle alignment, and promoting patient rehabilitation. [ABSTRACT FROM AUTHOR]

Studies on biological functions of RNA modifications such as N6-methyladenosine (m6A) in mRNA have sprung up in recent years, while the roles of N¹-methyladenosine (m¹A) in cancer progression remain largely unknown. We find m¹A demethylase ALKBH3 can regulate the glycolysis of cancer cells via a demethylation activity dependent manner. Specifically, sequencing and functional studies confirm that ATP5D, one of the most important subunit of adenosine 5′-triphosphate synthase, is involved in m¹A demethylase ALKBH3-regulated glycolysis of cancer cells. The m¹A modified A71 at the exon 1 of ATP5D negatively regulates its translation elongation via increasing the binding with YTHDF1/eRF1 complex, which facilitates the release of message RNA (mRNA) from ribosome complex. m¹A also regulates mRNA stability of E2F1, which directly binds with ATP5D promoter to initiate its transcription. Targeted specific demethylation of ATP5D m¹A by dm¹ACRISPR system can significantly increase the expression of ATP5D and glycolysis of cancer cells. In vivo data confirm the roles of m¹A/ATP5D in tumor growth and cancer progression. Our study reveals a crosstalk of mRNA m¹A modification and cell metabolism, which expands the understanding of such interplays that are essential for cancer therapeutic application. [ABSTRACT FROM AUTHOR]