Aromatic Alcohol-Based pH-Sensitive Chromophore with a Unique Near-Infrared Dual-Band Solvatochromic Property and Its Application as a Ratiometric Fluorescent Sensor for G-Quadruplexes.

Solvatochromes have gained great attention because of their unique roles in monitoring biomolecular location, interaction, and dynamics. Particularly, solvatochromes presenting both red-shifting excitation and dual-band switchable emission are in great demand yet significantly difficult to come true. In this article, we disclose an aromatic alcohol-based pH-sensitive chromophore NIR-HBT that not only presents red-shifting excitation and solvent-dependent dual-band emission but also shows high photostability and excellent brightness. To the best of our knowledge, this is the first solvatochrome to simultaneously display these optical properties. Especially, in contrast to the reported dual-band solvatochromes whose solvatochromism is achieved by affecting their excited state behaviors, the solvatochromism of NIR-HBT is realized by modulating its ground state proton dissociation, which is a new solvatochromic mechanism that has not been reported. Furthermore, based on the dual-band solvatochromism of NIR-HBT and its intrinsic binding ability to GQs, near-infrared ratiometric detection of GQs is achieved. These results indicate that NIR-HBT is an attractive solvatochrome that can be used to develop near-infrared ratiometric biosensors for biological research. More broadly, the discovered solvatochromic mechanism can also open new horizons for exploring the solvatochrome.

Coronary sodium [18F]fluoride activity predicts outcomes post-CABG: a comparative evaluation with conventional metrics.

PURPOSE: The value of preoperative multidisciplinary approach remains inadequately delineated in forecasting postoperative outcomes of patients undergoing coronary artery bypass grafting (CABG). Herein, we aimed to ascertain the efficacy of multi-modality cardiac imaging in predicting post-CABG cardiovascular outcomes. METHODS: Patients with triple coronary artery disease underwent cardiac sodium [18F]fluoride ([18F]NaF) positron emission tomography/computed tomography (PET/CT), coronary angiography, and CT-based coronary artery calcium scoring before CABG. The maximum coronary [18F]NaF activity (target-to-blood ratio [TBR]max) and the global coronary [18F]NaF activity (TBRglobal) was determined. The primary endpoint was perioperative myocardial infarction (PMI) within 7-day post-CABG. Secondary endpoint included major adverse cardiac and cerebrovascular events (MACCEs) and recurrent angina. RESULTS: This prospective observational study examined 101 patients for a median of 40 months (interquartile range: 19-47 months). Both TBRmax (odds ratio [OR] = 1.445; p = 0.011) and TBRglobal (OR = 1.797; P = 0.018) were significant predictors of PMI. TBRmax>3.0 (area under the curve [AUC], 0.65; sensitivity, 75.0%; specificity, 56.8%; p = 0.036) increased PMI risk by 3.661-fold, independent of external confounders. Kaplan-Meier test revealed a decrease in MACCE survival rate concomitant with an escalating TBRmax. TBRmax>3.6 (AUC, 0.70; sensitivity, 76.9%; specificity, 73.9%; p = 0.017) increased MACCEs risk by 5.520-fold. Both TBRmax (hazard ratio [HR], 1.298; p = 0.004) and TBRglobal (HR = 1.335; p = 0.011) were significantly correlated with recurrent angina. No significant associations were found between CAC and SYNTAX scores and between PMI occurrence and long-term MACCEs. CONCLUSION: Quantification of coronary microcalcification activity via [18F]NaF PET displayed a strong ability to predict early and long-term post-CABG cardiovascular outcomes, thereby outperforming conventional metrics of coronary macrocalcification burden and stenosis severity. TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Committee (number: ChiCTR1900022527; URL: www.chictr.org.cn/showproj.html?proj=37933 ).

A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle.

Glutamine metabolism plays a pivotal role in cancer progression, immune cell function, and the modulation of the tumor microenvironment. Dysregulated glutamine metabolism has been implicated in cancer development and immune responses, supported by mounting evidence. Cancer cells heavily rely on glutamine as a critical nutrient for survival and proliferation, while immune cells require glutamine for activation and proliferation during immune reactions. This metabolic competition creates a dynamic tug-of-war between cancer and immune cells. Targeting glutamine transporters and downstream enzymes involved in glutamine metabolism holds significant promise in enhancing anti-tumor immunity. A comprehensive understanding of the intricate molecular mechanisms underlying this interplay is crucial for developing innovative therapeutic approaches that improve anti-tumor immunity and patient outcomes. In this review, we provide a comprehensive overview of recent advances in unraveling the tug-of-war of glutamine metabolism between cancer and immune cells and explore potential applications of basic science discoveries in the clinical setting. Further investigations into the regulation of glutamine metabolism in cancer and immune cells are expected to yield valuable insights, paving the way for future therapeutic interventions.

Environmentally Friendly Synthesis of Highly Substituted Phenols Using Enallenoates and Grignard Reagents.

We developed an efficient and environmentally friendly methodology for selectively synthesizing highly substituted phenols using readily available enallenoates and Grignard reagents. This method consistently yields good to excellent results across over 60 examples, demonstrating the substrate scope and the exploration of phenol product derivatization, further extending the method's utility.

Research on optimization method of railway construction scheme based on multidimensional combination weighting and improved grey theory.

The optimization of railway construction schemes is a complexity system engineering task with multiple dimensions, diverse conditional constraints, and multifaceted objective assessments. The decision-making and scheme evaluation entail subjectivity, randomness, and fuzziness. To address the comprehensive optimization challenge in construction schemes effectively and efficiently, we investigate an optimization method for railway construction schemes. This method is based on multi-dimensional combination weighting and improved grey theory. After analyzing the primary influencing factors, we established a railway construction plan optimization index system comprising 4 dimensions and 18 factors. The weight combination coefficient is determined using the pros and cons solution distance method, and the optimal weight set for the index is determined through the multi-dimensional combination weighting approach. Utilizing the method of superior and inferior solution distance coupled with grey theory, we ascertain the order of advantages and disadvantages for each construction scheme, subsequently achieving construction scheme optimization. To illustrate this, we employ the optimization process for a high-speed railway section in Guangxi as an exemplar. The verification results indicate that the gray relative closeness values for schemes A, B, and C are 0.7089, 0.4813, and 0.4463, respectively. Scheme A has the highest gray relative closeness value, thus making it the optimal route scheme. The optimal results obtained through this method align with the outcomes of expert validation and existing research, thereby validating the effectiveness and practicality of the model. By employing a multidimensional combination weighting method, the deficiencies of traditional indicator weight calculations are mitigated, resulting in indicator weights that are more reflective of the actual circumstances. At the same time, the application of improvements in the grey theory comprehensive evaluation method enables the integration and computation of indicator data for each construction plan. Through the intuitive representation of grey relative closeness, the advantages and disadvantages of each plan are effectively characterized. This enhances the scientific rigor and applicability of the railway construction plan optimization process. The research findings can serve as a reference for similar railway construction scheme selection problems in the future.

Palladium-Catalyzed Dehydrogenative Carbonylative Esterification of Allenoic Acids for the Synthesis of γ-Butyrolactone Derivatives.

A highly efficient dehydrogenative carbonylative esterification of allenoic acids using Pd-catalysis was developed, providing a novel approach to synthesizing esterified γ-butyrolactone derivatives with consistently good to excellent results demonstrated across over 50 examples. Additionally, we used a heterogeneous catalyst known as Pd-AmP-MCF and harnessed biomimetic-aerobic-oxidation conditions to facilitate the practical execution of this reaction. Furthermore, our detailed study of γ-butyrolactone products highlighted their potential in synthesizing bioactive compounds.

Assessment of bidirectional relationships between hypothyroidism and endometrial cancer: a two-sample Mendelian randomization study.

Objective: Hypothyroidism, characterized by reduced thyroid hormone levels, and endometrial cancer, a prevalent gynecological malignancy, have been suggested to have a potential association in previous observational studies. However, the causal relationship between them remains uncertain. This study aimed to investigate the causal relationship between hypothyroidism and endometrial cancer using a bilateral Mendelian randomization approach. Methods: A bidirectional two-sample Mendelian randomization study was conducted using summary statistics from genome-wide association studies to identify genetic variants associated with hypothyroidism and endometrial cancer. The inverse variance weighting method was used as the main analysis, and sensitivity analyses were conducted to validate the MR results. Results: The results of our analysis did not support a causal effect of hypothyroidism (OR: 0.93, p=0.08) or autoimmune hypothyroidism (OR: 0.98, p=0.39) on endometrial cancer risk. In the reverse MR analysis, we did not find a significant causal effect of endometrial cancer on hypothyroidism (OR: 0.96, p=0.75) or autoimmune hypothyroidism (OR: 0.92, p=0.50). Based on subgroup analysis by pathological subtypes of endometrial cancer, the above findings were further substantiated (all p-value >0.05). Conclusions: Our Mendelian randomization analysis suggests a lack of causal association between hypothyroidism and endometrial cancer. To gain a deeper understanding of this association, it is essential to conduct large-scale randomized controlled trials in the future to validate our findings.

Reaction-Driven Dynamic and Reversible Transformations of Au Single Atoms and Au-Zr Alloys on Zirconia for Efficient Acetylene Hydrochlorination.

Catalysis involving gold supported on metal oxides has undergone extensive examination. However, the nature of the catalytic site under actual reaction conditions and the role of the support continue to be vigorously debated. This study addresses these issues through experimental investigations and theoretical simulations. We explore a novel catalytic mechanism that employs dynamic single-atom catalysis for the hydrochlorination of acetylene. This catalytic mechanism occurs in defective ZrO2-supported Au-Zr single-atom alloys. Specifically, the dynamic single-atom catalysis is a result of the mobility of the gold cation, which is accelerated by Cl radicals and strongly couples with the abundant unsaturated surface sites of ZrO2 in a synergistic manner. As a result, the Au electronic structure dynamically evolves, leading to a decrease in the addition reaction energy barrier. Notably, the Au cation can detach from the Au-Zr alloy structure to catalyze the hydrochlorination of acetylene near the Zr-Ov-Zr sites and then reintegrate back into the Au-Zr alloy structure upon completion of the reaction. This study underscores the significance of dynamic active sites under reaction conditions and their pivotal role in catalysis.

Monitoring the conformational ensemble and lipid environment of a mechanosensitive channel under cyclodextrin-induced membrane tension.

Membrane forces shift the equilibria of mechanosensitive channels enabling them to convert mechanical cues into electrical signals. Molecular tools to stabilize and methods to capture their highly dynamic states are lacking. Cyclodextrins can mimic tension through the sequestering of lipids from membranes. Here we probe the conformational ensemble of MscS by EPR spectroscopy, the lipid environment with NMR, and function with electrophysiology under cyclodextrin-induced tension. We show the extent of MscS activation depends on the cyclodextrin-to-lipid ratio, and that lipids are depleted slower when MscS is present. This has implications in MscS' activation kinetics when distinct membrane scaffolds such as nanodiscs or liposomes are used. We find MscS transits from closed to sub-conducting state(s) before it desensitizes, due to the lack of lipid availability in its vicinity required for closure. Our approach allows for monitoring tension-sensitive states in membrane proteins and screening molecules capable of inducing molecular tension in bilayers.

Hepatoprotective efficacy and interventional mechanism of the panaxadiol saponin component in high-fat diet-induced NAFLD mice.

Dietary administration is a promising strategy for intervention in non-alcoholic fatty liver disease (NAFLD). Our research team has identified a biologically active component, the panaxadiol saponin component (PDS-C) isolated from total saponins of panax ginseng, which has various pharmacological and therapeutic functions. However, the efficacy and mechanism of PDS-C in NAFLD were unclear. This study aimed to elucidate the hepatoprotective effects and underlying action mechanism of PDS-C in NAFLD. Mice were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD and treated with PDS-C and metformin as the positive control for 12 weeks. PDS-C significantly alleviated liver function, hepatic steatosis and blood lipid levels, reduced oxidative stress and inflammation in NAFLD mice. In vitro, PDS-C has been shown to reduce lipotoxicity and ROS levels while enhancing the antioxidant and anti-inflammatory capabilities in HepG2 cells induced by palmitic acid. PDS-C induced AMPK phosphorylation, leading to upregulation of the Nrf2/HO1 pathway expression and downregulation of the NFκB protein level. Furthermore, our observations indicate that PDS-C supplementation improves insulin resistance and glucose homeostasis in NAFLD mice, although its efficacy is not as pronounced as metformin. In conclusion, these results demonstrate the hepatoprotective efficacy of PDS-C in NAFLD and provide potential opportunities for developing functional products containing PDS-C.

Fabrication of close-contact S-scheme Cr2Bi3O11-Bi2O3/Fe3O4@porous carbon microspheres based on in-situ reaction: Enhanced photo-Fenton wastewater treatment.

Low photo-induced carrier recombination rate, exceptional light absorption, and advantageous recycling performance are crucial attributes of semiconductor photocatalyst for wastewater purification. Herein, based on in-situ reaction, close-contact S-scheme bismuth chromate/bismuth oxide/ferroferric oxide@porous carbon microspheres (Cr2Bi3O11-Bi2O3/Fe3O4@PCs) (F-CBFP) was fabricated using alginates as precursor. Due to the abundance of functional groups on the porous carbon (PCs), Bi2O3 and Cr2Bi3O11 nanoparticles (NPs) are in situ deposited onto the highly conductive 3D magnetic porous Fe3O4@PCs microsphere surface, which not only form tight interfacial contacts and reduces interfacial potential barriers but also prevent agglomeration or shedding of the NPs during photocatalytic reactions. Moreover, density functional theory (DFT) calculations further confirm that the formation of a robust built-in electric field (BIEF) within F-CBFP prompts photo-induced electrons in the conduction band (CB) of Bi2O3 to combine with holes in the valence band (VB) of Cr2Bi3O11, effectively constructing a S-scheme heterojunction system. Also, Fe3O4 can act as a Fenton catalyst, activating the H2O2 generated by Cr2Bi3O11 under illumination. In wastewater treatment, the obtained F-CBFP shows remarkable photo-Fenton degradation (towards methyl orange (97.8 %, 60 min) and tetracycline hydrochloride (95.3 %, 100 min)) and disinfection performance (100 % E. coli inactivation), and exceptional cyclic stability.

The miR-146b-3p/TNFAIP2 axis regulates cell differentiation in acute myeloid leukaemia.

Our purpose is to verify that miR-146b-3p targets the downstream transcript TNFAIP2 in order to reveal the machinery underlying the miR-146b-3p/TNFAIP2 axis regulating acute myeloid leukaemia (AML) differentiation. Bioinformatics analyses were performed using multiple databases and R packages. The CD11b+ and CD14+ cell frequencies were detected using flow cytometry and immunofluorescence staining. The TNFAIP2 protein expression was evaluated using western blotting, immunocytochemistry and immunofluorescence staining. The qRT-PCR was conducted to detect the expression of TNFAIP2 and miR-146b-3p. TNFAIP2 and its correlated genes were enriched in multiple cell differentiation pathways. TNFAIP2 was upregulated upon leukaemic cell differentiation. miR-146b-3p directly targeted TNFAIP2, resulting in a decrease in TNFAIP2 expression. Forced expression of TNFAIP2 or knockdown of miR-146b-3p significantly induced the differentiation of MOLM-13 cells. In this study, we demonstrated that TNFAIP2 is a critical driver in inducing differentiation and that the miR-146b-3p/TNFAIP2 axis involves in regulating cell differentiation in AML.

Early tirofiban versus heparin for bridging dual antiplatelet therapy in patients undergoing coronary endarterectomy combined with coronary artery bypass grafting: a multicenter randomized controlled trial protocol (the THACE-CABG trial).

BACKGROUND: For complete revascularization, patients with diffuse coronary artery disease should have a coronary endarterectomy and a coronary artery bypass graft (CE-CABG). Sadly, CE can lead to a lack of endothelium, which raises the risk of thrombotic events. Even though daily dual antiplatelet therapies (DAPT) have been shown to reduce thrombotic events, the risk of perioperative thrombotic events is high during the high-risk period after CE-CABG, and there is no consistent protocol to bridge DAPT. This trial aims to compare safety and efficacy between tirofiban and heparin as DAPT bridging strategies after CE-CABG. METHODS: In phase I, 266 patients undergoing CE-CABG will be randomly assigned to tirofiban and heparin treatment groups to compare the two treatments in terms of the primary safety endpoint, chest tube drainage in the first 24 h. If the phase I trial shows tirofiban non-inferiority, phase II will commence, in which an additional 464 patients will be randomly assigned. All 730 patients will be studied to compare major cardiovascular and cerebrovascular events (MACCEs) between the groups in the first 30 days after surgery. DISCUSSION: Given the possible benefits of tirofiban administration after CE-CABG, this trial has the potential to advance the field of adult coronary heart surgery. TRIAL REGISTRATION: chictr.org.cn, ChiCTR2200055697. Registered 6 January 2022. https://www.chictr.org.cn/com/25/showproj.aspx?proj=149451 . Current version: 20,220,620.