Bis(4-cyano-1-methyl­pyridinium) bis­(1,2-dicyano­ethene-1,2-dithiol­ato-κ2 S,S′)cuprate(II)

The title ion-pair compound, (C7H7N2)2[Cu(C4N2S2)2], was obtained by the direct reaction of CuCl2·2H2O, disodium maleonitrile­dithiol­ate (Na2mnt) and 4-cyano-1-methyl­pyridinium iodide. The anion and one pyridinium cation lie entirely on a mirror plane, whereas for the other cation, a crystallographic mirror plane runs through the N and para-C atoms of the pyridine ring, the methyl C atom, and the cyano group. In the crystal, ions are linked into a three-dimensional network by C—H⋯N hydrogen bonds

What Differs on the Enzymatic Acetylation Mechanisms for Arylamines and Arylhydrazines Substrates? A Theoretical Study

The acetylation mechanisms of several selected typical substrates from experiments, including arylamines and arylhydrazines, are investigated with the density functional theory in this paper. The results indicate that all the transition states are characterized by a four-membered ring structure, and hydralazine (HDZ) is the most potent substrate. The bioactivity for all the compounds is increased in a sequence of PABA ≈ 4-AS < 4-MA < 5-AS ≈ INH < HDZ. The conjunction effect and the delocalization of the lone pairs of N atom play a key role in the reaction. All the results are consistent with the experimental data

Aurora-A contributes to cisplatin resistance and lymphatic metastasis in non-small cell lung cancer and predicts poor prognosis

BACKGROUND: Platinum-based chemotherapy improves survival among patients with non-small cell lung cancer (NSCLC), but the efficiency is limited due to resistance. In this study, we aimed to identify the expression of Aurora-A and its correlation with cisplatin resistance and prognosis in NSCLC. METHODS: We used immunohistochemical analysis to determine the expression of Aurora-A protein in 102 NSCLC patients treated by surgery and adjuvant cisplatin-based chemotherapy. The prognostic significances were assessed by Kaplan-Meier survival estimates and Cox models. The potential role of Aurora-A in the regulation of cisplatin resistance in NSCLC cells was examined by transfections using expression vector and small interfering RNA or using small-molecule inhibitors. RESULTS: Aurora-A expression was significantly associated with clinical stage (p = 0.018), lymph node metastasis (p = 0.038) and recurrence (p = 0.005), and was an independent prognostic parameter in multivariate analysis. High level of Aurora-A expression predicted poorer overall survival (OS) and progression-free survival (PFS). In vitro data showed that Aurora-A expression was elevated in cisplatin-resistant lung cancer cells, and overexpression or knockdown of Aurora-A resulted in increased or decreased cellular resistance to cisplatin. Furthermore, inhibition of Aurora-A reversed the migration ability of cisplatin-resistant cells. CONCLUSIONS: The current findings suggest that high Aurora-A expression is correlated with cisplatin-based chemotherapeutic resistance and predicts poor patient survival in NSCLC. Aurora-A might serve as a predictive biomarker of drug response and therapeutic target to reverse chemotherapy resistance

Feline umbilical cord-derived mesenchymal stem cells: isolation, identification, and antioxidative stress role through NF-κB signaling pathway

At present, the differentiation potential and antioxidant activity of feline umbilical cord-derived mesenchymal stem cells (UC-MSCs) have not been clearly studied. In this study, feline UC-MSCs were isolated by tissue adhesion method, identified by flow cytometry detection of cell surface markers (CD44, CD90, CD34, and CD45), and induced differentiation toward osteogenesis and adipogenesis in vitro. Furthermore, the oxidative stress model was established with hydrogen peroxide (H2O2) (100 μM, 300 μM, 500 μM, 700 μM, and 900 μM). The antioxidant properties of feline UC-MSCs and feline fibroblasts were compared by morphological observation, ROS detection, cell viability via CCK-8 assay, as well as oxidative and antioxidative parameters via ELISA. The mRNA expression of genes related to NF-κB pathway was detected via quantitative real-time polymerase chain reaction, while the levels of NF-κB signaling cascade-related proteins were determined via Western Blot. The results showed that feline UC-MSCs highly expressed CD44 and CD90, while negative for CD34 and CD45 expression. Feline UC-MSCs cultured under osteogenic and adipogenic conditions showed good differentiation capacity. After being exposed to different concentrations of H2O2 for eight hours, feline UC-MSCs exhibited the significantly higher survival rate than feline fibroblasts. A certain concentration of H2O2 could up-regulate the activities of SOD2 and GSH-Px in feline UC-MSCs. The expression levels of p50, MnSOD, and FHC mRNA in feline UC-MSCs stimulated by 300 μM and 500 μM H2O2 significantly increased compared with the control group. Furthermore, it was observed that 500 μM H2O2 significantly enhanced the protein levels of p-IκB, IκB, p-p50, p50, MnSOD, and FHC, which could be reversed by BAY 11-7,082, a NF-κB signaling pathway inhibitor. In conclusion, it was confirmed that feline UC-MSCs, with good osteogenesis and adipogenesis abilities, had better antioxidant property which might be related to NF-κB signaling pathway. This study lays a foundation for the further application of feline UC-MSCs in treating the various inflammatory and oxidative injury diseases of pets

Patrilineal Perspective on the Austronesian Diffusion in Mainland Southeast Asia

The Cham people are the major Austronesian speakers of Mainland Southeast Asia (MSEA) and the reconstruction of the Cham population history can provide insights into their diffusion. In this study, we analyzed non-recombining region of the Y chromosome markers of 177 unrelated males from four populations in MSEA, including 59 Cham, 76 Kinh, 25 Lao, and 17 Thai individuals. Incorporating published data from mitochondrial DNA (mtDNA), our results indicated that, in general, the Chams are an indigenous Southeast Asian population. The origin of the Cham people involves the genetic admixture of the Austronesian immigrants from Island Southeast Asia (ISEA) with the local populations in MSEA. Discordance between the overall patterns of Y chromosome and mtDNA in the Chams is evidenced by the presence of some Y chromosome lineages that prevail in South Asians. Our results suggest that male-mediated dispersals via the spread of religions and business trade might play an important role in shaping the patrilineal gene pool of the Cham people

A novel method for precise implantation of tracheal Y-shaped stent

The tracheal Y-shaped stent is mainly used for the treatment of critical patients with airway stenosis or esophagotracheal fistula near carina. A novel method for precise implantation of Y-shaped tracheal stents was developed using double-lumen endotracheal intubation and flexible bronchoscopy. This approach aims to address the limitations associated with X-ray or rigid bronchoscopy guidance, such as operational difficulties and the risk of inaccurate stent placement leading to implantation failure or suffocation. With this new technique, 13 tracheal Y-shaped stents were successfully implanted. This method shows promise in reducing the complexity of stent implantation and facilitating timely treatment for patients in need. Additionally, it has the potential to update current operating standards and guidelines for this procedure

Effects of acidification on nitrification and associated nitrous oxide emission in estuarine and coastal waters

In the context of an increasing atmospheric carbon dioxide (CO2) level, acidification of estuarine and coastal waters is greatly exacerbated by land-derived nutrient inputs, coastal upwelling, and complex biogeochemical processes. A deeper understanding of how nitrifiers respond to intensifying acidification is thus crucial to predict the response of estuarine and coastal ecosystems and their contribution to global climate change. Here, we show that acidification can significantly decrease nitrification rate but stimulate generation of byproduct nitrous oxide (N2O) in estuarine and coastal waters. By varying CO2 concentration and pH independently, an expected beneficial effect of elevated CO2 on activity of nitrifiers (“CO2-fertilization” effect) is excluded under acidification. Metatranscriptome data further demonstrate that nitrifiers could significantly up-regulate gene expressions associated with intracellular pH homeostasis to cope with acidification stress. This study highlights the molecular underpinnings of acidification effects on nitrification and associated greenhouse gas N2O emission, and helps predict the response and evolution of estuarine and coastal ecosystems under climate change and human activities.publishedVersio

Eucheuma cottonii sulfated oligosaccharides decrease food allergic responses in animal models by up-regulating regulatory T (Treg) cells

In the present study, the anti-food allergy activity of Eucheuma cottonii sulfated oligosaccharide (ESO) was investigated. ESO was obtained by enzymatic degradation and purified by column chromatography. RBL-2H3 cells and BALB/c mouse model were used to test the anti-food allergy activity of ESO. The effects of ESO on the regulatory T (Treg) cells and bone marrow-derived mast cells (BMMCs) were investigated by flow cytometry. The results of in vivo assay showed that ESO decreased the levels of mast cell protease-1 and histamine and inhibited the levels of specific IgE by 77.7%. In addition, the production of interleukin (IL)-4 and IL-13 was diminished in the ESO groups compared to the non-ESO-treated group. Furthermore, ESO could up-regulate Treg cells by 22.2−97.1%. In conclusion, ESO decreased the allergy response in mice by reducing basophil degranulation, up-regulating Treg cells via Forkhead box protein 3 (Foxp3), and releasing IL-10. ESO may have preventive and therapeutic potential in allergic disease

Novel IL-4/HB-EGF-Dependent Crosstalk Between Eosinophils and Macrophages Controls Liver Regeneration After Ischaemia and Reperfusion Injury

OBJECTIVE: Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair. DESIGN: Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding epidermal growth factor-like growth factor (hb-egf). RESULT: We observed that eosinophils persisted over a week following hepatic IR injury. Their peak accumulation coincided with that of hepatocyte proliferation. Functional studies showed that eosinophil deficiency was associated with a dramatic delay in liver repair, which was normalised by the adoptive transfer of bmEos. Mechanistic studies demonstrated that eosinophil-derived IL-4, but not IL-13, was critically involved in the reparative function of these cells. The data further revealed a selective role of macrophage-dependent IL-4 signalling in liver regeneration. Eosinophil-derived IL-4 stimulated macrophages to produce HB-EGF. Moreover, macrophage-specific hb-egf deletion impaired hepatocyte regeneration after IR injury. CONCLUSION: Together, these studies uncovered an indispensable role of eosinophils in liver repair after acute injury and identified a novel crosstalk between eosinophils and macrophages through the IL-4/HB-EGF axis

The ideal treatment timing for diabetic retinopathy: the molecular pathological mechanisms underlying early-stage diabetic retinopathy are a matter of concern

Diabetic retinopathy (DR) is a prevalent complication of diabetes, significantly impacting patients’ quality of life due to vision loss. No pharmacological therapies are currently approved for DR, excepted the drugs to treat diabetic macular edema such as the anti-VEGF agents or steroids administered by intraocular route. Advancements in research have highlighted the crucial role of early intervention in DR for halting or delaying disease progression. This holds immense significance in enhancing patients’ quality of life and alleviating the societal burden associated with medical care costs. The non-proliferative stage represents the early phase of DR. In comparison to the proliferative stage, pathological changes primarily manifest as microangiomas and hemorrhages, while at the cellular level, there is a loss of pericytes, neuronal cell death, and disruption of components and functionality within the retinal neuronal vascular unit encompassing pericytes and neurons. Both neurodegenerative and microvascular abnormalities manifest in the early stages of DR. Therefore, our focus lies on the non-proliferative stage of DR and we have initially summarized the mechanisms involved in its development, including pathways such as polyols, that revolve around the pathological changes occurring during this early stage. We also integrate cutting-edge mechanisms, including leukocyte adhesion, neutrophil extracellular traps, multiple RNA regulation, microorganisms, cell death (ferroptosis and pyroptosis), and other related mechanisms. The current status of drug therapy for early-stage DR is also discussed to provide insights for the development of pharmaceutical interventions targeting the early treatment of DR