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Lycodine alkaloids are important natural products with diverse biological effects. In this manuscript, we set out the first structural optimization of the 2-pyridone moiety of Lycodine alkaloid via selective O-arylation under metal-free conditions and obtained a series of potent bioactive molecules against monosodium urate (MSU)-induced IL-1β production. Further investigations demonstrated that these natural product derivatives could activate the neuro-immunomodulatory cholinergic anti-inflammatory pathway (CAP) to block the initial phase of NLRP3 inflammasome activation. Compared with the clinical drugs hydrocortisone and indomethacin, as well as commercially available CAP agonists GTS-21 and pnu282987, 3k and 3q possessed greater potency against MSU-induced IL-1β production. Meanwhile, these molecules possessed less cytotoxicity against promonocytic THP-1 macrophages when compared with colchicine. This work reports a concise strategy for direct modification of 2-pyridone moiety from natural Lycodine alkaloids, and provides novel frameworks for discovering CAP activators and drugs for gout arthritis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Jun-Cheng Su and Ji-Hong Gu reports financial support was provided by National Natural Science Foundation of China. Jun-Cheng Su reports financial support was provided by Guangxi Natural Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sulfur dioxide (SO 2 ) is a significant gas signaling molecule in organisms, and viscosity is a crucial parameter of the cellular microenvironment. They are both involved in regulating many physiological processes in the human body. However, abnormalities in SO 2 and viscosity levels are associated with various diseases, such as cardiovascular disease, lung cancer, respiratory diseases, neurological disorders, diabetes and Alzheimer's disease. Hence, it is essential to explore novel and efficient fluorescent probes for simultaneously monitoring SO 2 and viscosity in organisms., Results: We selected quinolinium salt with good stability, high fluorescence intensity, good solubility and low cytotoxicity as the fluorophore and developed a highly sensitive ratiometric probe QQD to identify SO 2 and viscosity changes based on Förster resonance energy transfer/twisted intramolecular charge transfer (FRET/TICT) mechanism. Excitingly, compared with other probes for SO 2 detection, QQD not only identified HSO 3 - /SO 3 2- with a large Stokes shift (218 nm), low detection limit (1.87 μM), good selectivity, high energy transfer efficiency (92 %) and wide recognition range (1.87-200 μM), but also identified viscosity with a 26-fold fluorescence enhancement and good linearity. Crucially, QQD was applied to detect HSO 3 - /SO 3 2- and viscosity in actual water and food samples. In addition, QQD had low toxicity and good photostability for imaging HSO 3 - /SO 3 2- and viscosity in cells. These results confirmed the feasibility and reliability of QQD for HSO 3 - /SO 3 2- and viscosity imaging and environmental detection., Significance: We reported a unique ratiometric probe QQD for detecting HSO 3 - /SO 3 2- and viscosity based on the quinolinium skeleton. In addition to detecting HSO 3 - /SO 3 2- and viscosity change in actual water and food samples, QQD could also monitor the variations of HSO 3 - /SO 3 2- and viscosity in cells, which provided an experimental basis for further exploration of the role of SO 2 derivatives and viscosity in biological systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pseudo-natural products (PNPs) design strategy provides a great valuable entrance to effectively identify of novel bioactive scaffolds. In this report, novel pseudo-rutaecarpines were designed via the combination of several privileged structure units and 46 target compounds were synthesized. Most of them display moderate to potent inhibitory effect on LPS-induced NO production and low cytotoxicity in RAW264.7 macrophage. The results of the anti-inflammatory efficacy and action mechanism of compounds 7l and 8c indicated that they significantly reduced the release of IL-6, IL-1β and TNF-α. Further studies revealed that they can strongly inhibit the activation of NF-κB and MAPK signal pathways. The LPS-induced acute liver injury mice model studies not only confirmed their anti-inflammatory efficacy in vivo but also could effectively relieve the liver injury in mice. The results suggest that compounds 7l and 8c might serve as lead compounds to develop therapeutic drugs for treatment of inflammation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cheng-xue Pan reports financial support was provided by National Natural Science Foundation of China. Jun-Cheng Su reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Local cryoablation guided by CT or ultrasound has been widely applied in the treatment of hepatocellular carcinoma. However, it is still difficult to apply this technique in certain regions such as the diaphragm dome, the first hepatic hilum, and regions adjacent to the gallbladder. This study aimed to evaluate the safety and efficacy of using magnetic resonance imaging (MRI)-guided percutaneous cryoablation as well as the effect of using an open MRI system in guiding and monitoring the treatment of hepatocellular carcinoma in these regions., Methods: Cryoablation, guided by an open 0.35T MRI scanner and with the assistance of an MRI-compatible optical navigation system, was performed on 32 patients with hepatocellular carcinoma at the diaphragm dome, the first hepatic hilum, and regions adjacent to the gallbladder. Each patient had one or two tumors. The total number of tumors treated was 36. The tumor diameters ranged from 2.5 to 10.0 cm (mean 4.7+/-1.8 cm). The cryosurgical system was MRI-compatible and equipped with cryoprobes 1.47 mm in outside diameter. Under the guidance of MRI in combination with the optical navigation system, the cryoprobes were introduced percutaneously into a tumor at the planned targeting points while critical organs or tissues were avoided. Each cryoablation procedure included two freezing-thawing cycles, and MRI images were acquired dynamically to monitor the ablation of the tumor from time to time during the operation. In order to investigate the therapeutic effects of a cryoablation procedure, AFP measurements and liver-enhanced MRI or CT-enhanced scans were performed at regular times., Results: MRI and optical navigation system-guided cryoablation procedures were successfully performed on all 32 patients (36 tumor sites) and no serious complications occurred. The follow-up period ranged from 5 to 12 months. The 6- and 12-month overall survival rates were 96.8% and 90.6%, respectively. According to the diagnosis of liver-enhanced MRI scans, 10 patients (31.3%) had complete ablation, 18 (56.3%) partial ablation (>80%), 3 (9.4%) stable disease (>50% ablation), and 1 (3.1%) progressive disease (a new tumor site in the liver). The overall efficacy was 87.5%., Conclusions: MR-guided percutaneous cryoablation using optical navigation is a safe and effective minimally invasive procedure for the treatment of hepatocellular carcinoma at certain special regions, which is difficult to treat with other imaging guidance approaches. With its unique and superb imaging functions, MRI plays an important role in the display, guidance, and monitoring of the cryoablation procedure in treating hepatocellular carcinoma at these special regions. Equipped with an MRI-compatible optical navigation system, MRI-guided therapy makes the cryoablation procedure more precise and safe.

Background: As the major target of Angiotensin II (Ang II) in the vessel wall, vascular smooth muscle cells (VSMCs) are a tentative source to produce C-reactive protein (CRP). However, it is largely unknown if Ang II is capable of inducing CRP production in VSMCs., Methods and Results: Ang II induced a concentration-dependent release of CRP in cultured rat VSMCs as measured by sandwich ELISA. Real-time PCR revealed that Ang II significantly upregulated CRP mRNA level in vitro. Ang II-induced CRP generation in aortic VSMCs was also investigated using double-labeled fluorescent immunohistochemistry and in situ hybridization in subchronic Ang II administration in rats. Losartan but not PD123319 markedly blocked the Ang II-induced CRP production in cultured VSMCs, suggesting that such effect was mediated via Ang II type 1 receptor. Further, Western blotting analysis showed that mitogen-activated protein kinase (MAPK) activation was obligatory in Ang II-induced CRP production, since specific MAPK inhibitor PD098059 almost abolished the action., Conclusions: We identified that Ang II is capable of inducing CRP generation in VSMCs, in which Ang II type 1 receptor followed by MAPK signal pathway is involved. It strengthened the role of Ang II-induced CRP production by VSMCs in the inflammatory process in atherosclerosis.