Dexmedetomidine attenuates lipopolysaccharide-induced renal cell fibrotic phenotypic changes by inhibiting necroinflammation via activating α2-adrenoceptor: A combined randomised animal and in vitro study.

BACKGROUND: Acute kidney injury (AKI) was reported to be one of the initiators of chronic kidney disease (CKD) development. Necroinflammation may contribute to the progression from AKI to CKD. Dexmedetomidine (Dex), a highly selective α2-adrenoreceptor (AR) agonist, has cytoprotective and "anti-" inflammation effects. This study was designed to investigate the anti-fibrotic properties of Dex in sepsis models. METHODS: C57BL/6 mice were randomly treated with an i.p. injection of lipopolysaccharides (LPS) (10 mg/kg) alone, LPS with Dex (25 µg/kg), or LPS, Dex and Atipamezole (Atip, an α2-adrenoreceptor antagonist) (500 µg/kg) (n=5/group). Human proximal tubular epithelial cells (HK2) were also cultured and then exposed to LPS (1 µg/ml) alone, LPS and Dex (1 µM), transforming growth factor-beta 1 (TGF-ß1) (5 ng/ml) alone, TGF-ß1 and Dex, with or without Atip (100 µM) in culture media. Epithelial-mesenchymal transition (EMT), cell necrosis, necroptosis and pyroptosis, and c-Jun N-terminal kinase (JNK) phosphorylation were then determined. RESULTS: Dex treatment significantly alleviated LPS-induced AKI, myofibroblast activation, NLRP3 inflammasome activation, and necroptosis in mice. Atip counteracted its protective effects. Dex attenuated LPS or TGF-ß1 induced EMT and also prevented necrosis, necroptosis, and pyroptosis in response to LPS stimulation in the HK2 cells. The anti-EMT effects of Dex were associated with JNK phosphorylation. CONCLUSIONS: Dex reduced EMT following LPS stimulation whilst simultaneously inhibiting pyroptosis and necroptosis via α2-AR activation in the renal tubular cells. The "anti-fibrotic" and cytoprotective properties and its clinical use of Dex need to be further studied.

Investigating the evolution of reactive species in the CuO-mediated peroxymonosulfate activation process.

The utilization of copper oxide (CuO) as a catalyst in the peroxymonosulfate (PMS) activation process holds great promise for effectively degrading aqueous organic pollutants, while the relevant mechanism remains inadequately understood. In this study, we delve into the evolution pathways of reactive species in the CuO/PMS system through a comprehensive series of experimental analyses. Our findings indicate that various reactive species are generated in the CuO/PMS system with the specific sequence, where the decomposition of surface Cu(II)-OOSO3- leads to the formation of surface Cu(III) species, which are responsible for the subsequent generation of HO•. The reactivity of these reactive species and the sequence of their generation explain the distinct oxidation behaviors of pollutants with different values of ionization potential (IP). In addition, singlet oxygen (1O2) may be produced during the PMS activation process, while its involvement in the oxidation of substrates is deemed negligible. This investigation presents a novel perspective, enhancing our comprehension of the mechanism underlying transition metal-mediated PMS activation processes. ENVIRONMENTAL IMPLICATION: The removal of refractory organic contaminations in water constitutes a fundamental concern within the realm of environmental pollution management. Peroxymonosulfate activation induced by transition metal oxides has garnered significant recognition as a promising technological approach for the degradation of aqueous organic contaminants, while the underlying mechanism remains enigmatic. In this study, we systematically investigate the evolution pathways of reactive species in the CuO/peroxymonosulfate system to reveal the mystery of the reaction mechanism between CuO and peroxymonosulfate. The outcomes of our study contribute to enhancing the practical applicability of transition metal-triggered PMS activation processes.

Self-carbon-thermal-reduction strategy for boosting the Fenton-like activity of single Fe-N4 sites by carbon-defect engineering.

Carbon-defect engineering in metal single-atom catalysts by simple and robust strategy, boosting their catalytic activity, and revealing the carbon defect-catalytic activity relationship are meaningful but challenging. Herein, we report a facile self-carbon-thermal-reduction strategy for carbon-defect engineering of single Fe-N4 sites in ZnO-Carbon nano-reactor, as efficient catalyst in Fenton-like reaction for degradation of phenol. The carbon vacancies are easily constructed adjacent to single Fe-N4 sites during synthesis, facilitating the formation of C-O bonding and lowering the energy barrier of rate-determining-step during degradation of phenol. Consequently, the catalyst Fe-NCv-900 with carbon vacancies exhibits a much improved activity than the Fe-NC-900 without abundant carbon vacancies, with 13.5 times improvement in the first-order rate constant of phenol degradation. The Fe-NCv-900 shows high activity (97% removal ratio of phenol in only 5 min), good recyclability and the wide-ranging pH universality (pH range 3-9). This work not only provides a rational strategy for improving the Fenton-like activity of metal single-atom catalysts, but also deepens the fundamental understanding on how periphery carbon environment affects the property and performance of metal-N4 sites.

Carbon emission reduction potential assessment in food transportation by urban agriculture: A case study of main urban area of Nanjing, China.

As an emerging urban green infrastructure and continuous productive urban landscape, urban agriculture can increase the resilience of urban food systems and reduce carbon emission in food transportation. However, there are few studies in China on the potential of urban agriculture and its role in carbon emission reduction. With semantic segmentation and spatial analysis method to identify urban agricultural potential spaces on the ground and rooftops based on satellite images and Lidar point cloud data in the main urban area of Nanjing, we estimated their potential in vegetable production and the CO2 emission reduction effect in food transportation. The results showed that there were 2904.39 hm2 of ground and 2976.96 hm2 of rooftops in the study area with the potential to be used for urban agriculture. Under a scenario with 80% potential space utilization, it could produce approximately 225000 t of vegetables per year, which equated to 43.6% of annual vegetable consumption in the study area. Meanwhile, it would reduce CO2 emission in long distance food transportation by 63700 t per year.

Fun with Frustration? TikTok Influencers' Emotional Expression Predicts User Engagement with COVID-19 Vaccination Messages.

This study examined what kinds of TikTok video and message features are associated with user engagement in the context of COVID-19 vaccination. Content analysis was applied to study a sample of 223 COVID-19 vaccination-related videos from creators with at least 10,000 followers. The content analysis involved coding themes, video formats, the valence of attitude toward vaccination, and emotional expressions from the influencers. A majority of videos showcased personal vaccination experiences, followed by fictitious dramas and instructional information. More fictitious dramas expressed unclear attitudes, neither explicitly supporting nor opposing the COVID-19 vaccine, compared to personal vaccination stories and instructional videos. Some imaginative and dramatic scenes, such as zombie transformation or dramatic spasms after taking the vaccines, were widely imitated across influencers, perhaps humorously, and raised concerns about diminishing positive images of vaccine uptake. Videos with simultaneous expression of humor and frustration significantly predicted engagement when the video content opposed or was uncertain about taking the vaccine, implying the effectiveness of mixed emotional attributes within a message. This study provides insight into how social context and message choices by creators interact to influence audience engagement.

Nitrogen Electroreduction on Borophene-Supported Atomic and Diatomic Transition Metals: Stability, Activity and Selectivity Improvements via Defect-Engineering.

The present work investigated the binding of atomically dispersed transition metals to the perfect and single/double vacancy (SV/DV)-containing defective ß12 -borophenes and the catalytic performance of those corresponding single-atom catalysts (SACs) and diatomic catalysts (DACs) for nitrogen reduction reaction (NRR) by means of density functional theory calculations. Although previous theoretical studies proposed that the inherent hexagon hole of the defect-free ß12 -borophene is capable of anchoring single metal atom for NRR, calculations suggested that the interaction between borophene and doped metal is not strong enough to avoid metal aggregation. For the defective ß12 -borophene with SV, even though the single metal could be stabilized in an 8-membered ring, it was found that the SAC was still ineffective for NRR because of the competitive hydrogen evolution process. Regarding the DV-containing ß12 -borophene, a defective configuration with an unexpected 11-membered hole was proved as the most stable structure, which possessed a very similar average atomic energy (6.25 eV atom-1 ) compared to that of the pristine ß12 sheet (6.26 eV atom-1 ). Two metal atoms could be encapsulated into the confined space of the B11 ring. Compared to SACs, those corresponding DACs were more active for N2 fixation and hydrogenation, and the hydrogen evolution reaction could be passivated, attributing to the synergistic effect of dual metal centres. Among all candidates, the V2 /ß12 -DV was predicted as the most promising catalyst for NRR, with the limiting potential of as low as -0.15 V.

Dexmedetomidine Activates Akt, STAT6 and IRF4 Modulating Cytoprotection and Macrophage Anti-Inflammatory Phenotype Against Acute Lung Injury in vivo and in vitro.

Purpose: This study aims to investigate the cytoprotective and anti-inflammatory effects of an α2-adrenoreceptor (α2-AR) agonist, dexmedetomidine (Dex), on lipopolysaccharides (LPS)-induced acute lung injury and underlying mechanisms with focus on alveolar macrophage polarization modulation. Methods: C57BL/6 mice were intraperitoneally injected LPS (10 mg/kg) with or without Dex (25 µg/kg) and/or α2-AR antagonist atipamezole (Atip, 500 µg/kg). Lung tissues were then analysed to determine injuries. In vitro, human pulmonary epithelial cells (A549) and mice alveolar macrophages (MH-S) were exposed to LPS (10 ng/mL) with or without different concentrations of Dex (0.1-100 nM). Alveolar macrophage polarization, NLRP3 inflammasome activation and inflammatory responses were determined. PTEN/Akt signaling and its downstream transcriptional factors as targets for macrophage polarization were assessed. Results: Dex treatment significantly reduced pro-inflammatory M1 macrophage polarization and NLRP3 inflammasome activation in the lungs relative to the mice treated with LPS. The similar pattern reduction of NLRP3 inflammasome activation by Dex was also found in A549 cells. Atip partly reversed the anti-inflammatory effects of Dex. In cultured alveolar macrophages, Dex reduced LPS-mediated expression of IL-1, -6 and TNF-α receptors while promoting alveolar macrophages differentiation towards a M2 anti-inflammatory phenotype. Additionally, LPS increased Akt signaling activation in a time-dependent manner, which was further activated by Dex via inhibiting phosphatase and tensin homolog (PTEN). The action of Dex on Akt signaling shifted alveolar macrophages from M1 to M2 phenotype through increasing STAT6 and IRF4 transcriptional factors. Conclusion: Dex protected against LPS-induced lung injury and suppressed LPS-induced pulmonary inflammatory responses by attenuating the NLRP3 inflammasome activation and promoting anti-inflammatory M2 macrophage polarization.

Anchored atomic tungsten on a B40 cage: a highly active and selective single-atom catalyst for nitrogen reduction.

In comparison with the prevalent 2D material-supported single atom catalysts (SACs), the design and fabrication of SACs with single molecule substrates are still challenging. Here we introduce a new type of SAC in which a recently identified all-boron fullerene B40 is employed as the support and its catalytic performance toward the nitrogen reduction reaction (NRR) process is explored in theory. Taking advantage of the novel heptagonal ring substructure on the sphere and the electron-deficient nature of boron, the atomic metals are facile to reside on B40 to form atomically dispersed η7-B40M exohedral complexes. Among a series of candidates, originating from the proper metal-adsorbate interactions, the atomic tungsten-decorated B40W is screened out as the most feasible catalyst for the NRR with a low over-potential and high selectivity to passivate the competitive hydrogen evolution process.

Sevoflurane Enhances Proliferation, Metastatic Potential of Cervical Cancer Cells via the Histone Deacetylase 6 Modulation In Vitro.

BACKGROUND: Sevoflurane is commonly used for cervical cancer surgery, but its effect on cervical cancer cell biology remains unclear. This mechanistic study explores how sevoflurane affects the proliferation and metastatic potential of immortalized cervical cancer cell lines. METHODS: Cultured cervical cancer Caski and HeLa lines were exposed to 1, 2, or 3% sevoflurane for 2 or 4 h. Cell proliferation was determined through the Kit-8 assay and Ki-67 immunofluorescent staining. Cell migration and invasion were evaluated with the Transwell assay. Immunofluorescent staining and Western blot analysis were used to identify sevoflurane-induced morphological and biochemical changes. RESULTS: Sevoflurane exposure for either 2 or 4 h significantly increased HeLa cell proliferation in a time- and concentration-dependent manner to be 106 ± 2.7% and 107 ± 1.4% relative to the controls (n = 10; P = 0.036; P = 0.022) at 24 h after exposure and to be 106 ± 2.2% and 106 ± 1.7% relative to the controls (n = 10; P = 0.031; P = 0.023) at the highest concentration of 3% sevoflurane studied, respectively, but not Caski cells. Sevoflurane promoted invasion ability (1.63 ± 0.14 and 1.92 ± 0.12 relative to the controls) and increased cell size (1.69 ± 0.21 and 1.76 ± 0.13 relative to the controls) of Caski and HeLa cells (n = 6; all P < 0.001), respectively. Sevoflurane increased histone deacetylase 6 expression in both cells, and histone deacetylase 6 knockdown abolished the prometastatic effects of sevoflurane. Sevoflurane also induced deacetylation of α-tubulin in a histone deacetylase 6-dependent manner. The protein kinase B (AKT) or extracellular regulated protein kinase (ERK1/2) phosphorylation inhibition attenuated sevoflurane-induced histone deacetylase 6 expression. CONCLUSIONS: Sevoflurane enhanced proliferation, migration, and invasion of immortalized cervical cancer cells, which was likely associated with increasing histone deacetylase 6 expression caused by phosphatidylinositide 3-kinase/AKT- and ERK1/2-signaling pathway activation.

Dexmedetomidine inhibits astrocyte pyroptosis and subsequently protects the brain in in vitro and in vivo models of sepsis.

Sepsis is life-threatening and often leads to acute brain damage. Dexmedetomidine, an α2-adrenoceptor agonist, has been reported to possess neuroprotective effects against various brain injury but underlying mechanisms remain elusive. In this study, in vitro and in vivo models of sepsis were used to explore the effects of dexmedetomidine on the inflammasome activity and its associated glia pyroptosis and neuronal death. In vitro, inflammasome activation and pyroptosis were found in astrocytes following lipopolysaccharide (LPS) exposure. Dexmedetomidine significantly alleviated astrocyte pyroptosis and inhibited histone release induced by LPS. In vivo, LPS treatment in rats promoted caspase-1 immunoreactivity in astrocytes and caused an increase in the release of pro-inflammatory cytokines of IL-1ß and IL-18, resulting in neuronal injury, which was attenuated by dexmedetomidine; this neuroprotective effect was abolished by α2-adrenoceptor antagonist atipamezole. Dexmedetomidine significantly reduced the high mortality rate caused by LPS challenge. Our data demonstrated that dexmedetomidine may protect glia cells via reducing pyroptosis and subsequently protect neurons, all of which may preserve brain function and ultimately improve the outcome in sepsis.