CO2驱油-埋存一体化评价方法

CO2驱油-埋存一体化工程项目缺乏能够同时评价CO2的驱油和埋存效果及综合评价项目的方法。为此,本文提出了CO2驱油-埋存一体化评价方法,构建了驱油-埋存综合效应因子,引入粒子群优化（PSO）算法来优化驱油-埋存过程前、中、后期的注入速度、生产流压和阶段时长。研究结果表明:在不考虑生产成本的情况下,注采时间越长,驱油-埋存效果越好。无论是以驱油还是以埋存为主,项目初期均要维持高压低速驱替。若注重埋存效果,项目中期需要降低注入速度,项目的后期则需要重新提高注入速度;若注重驱油效果,项目中、后期需要大幅降低注入速度,同时要酌情降低生产流压,提高产油量。     

中国煤电生命周期二氧化碳和大气污染物排放相互影响建模分析

煤电在中国电力供应结构中占据主导地位,其环境影响是研究热点之一。建立中国煤电生命周期二氧化碳和大气污染物排放分析模型,基于文献调研构建参数数据库,测算中国煤电的单位发电量排放。结果表明,近年来中国煤电生命周期单位发电量的CO₂、SO₂、NO_x和PM_2.5排放分别为838.6 g/（kW·h）、0.34 g/（kW·h）、0.32 g/（kW·h）和0.08 g/（kW·h）。其中煤电单位发电量大气污染物排放,比实施超低排放改造前,下降幅度超过90%。研究发现,增大单机机组规模和进行超低排放改造能够有效降低煤电发电过程的大气污染物排放,采用煤电燃烧后碳捕集和存储(carbon capture and storage, CCS)处理技术能够使煤电CO₂排放下降到144 g/（kW·h）,助力碳中和目标实现。如果不采用更加严格的大气污染物排放标准和处理方式,CCS技术可能会使煤电大气污染物排放强度上升30%~40%,这与碳捕集过程使用的技术有关。     

The Antithrombotic Agent Pterostilbene Interferes with Integrin αIIbβ3-Mediated Inside-Out and Outside-In Signals in Human Platelets

Platelets play a crucial role in the physiology of primary hemostasis and pathological processes such as arterial thrombosis; thus, developing a therapeutic target that prevents platelet activation can reduce arterial thrombosis. Pterostilbene (PTE) has remarkable pharmacological activities, including anticancer and neuroprotection. Few studies have reported the effects of pterostilbene on platelet activation. Thus, we examined the inhibitory mechanisms of pterostilbene in human platelets and its role in vascular thrombosis prevention in mice. At low concentrations (2–8 μM), pterostilbene strongly inhibited collagen-induced platelet aggregation. Furthermore, pterostilbene markedly diminished Lyn, Fyn, and Syk phosphorylation and hydroxyl radical formation stimulated by collagen. Moreover, PTE directly hindered integrin α_IIbβ₃ activation through interfering with PAC-1 binding stimulated by collagen. In addition, pterostilbene affected integrin α_IIbβ₃-mediated outside-in signaling, such as integrin β₃, Src, and FAK phosphorylation, and reduced the number of adherent platelets and the single platelet spreading area on immobilized fibrinogen as well as thrombin-stimulated fibrin clot retraction. Furthermore, pterostilbene substantially prolonged the occlusion time of thrombotic platelet plug formation in mice. This study demonstrated that pterostilbene exhibits a strong activity against platelet activation through the inhibition of integrin α_IIbβ₃-mediated inside-out and outside-in signaling, suggesting that pterostilbene can serve as a therapeutic agent for thromboembolic disorders.     

Differential Cytotoxicity Mechanisms of Copper Complexed with Disulfiram in Oral Cancer Cells

Disulfiram (DSF), an irreversible aldehyde dehydrogenase inhibitor, is being used in anticancer therapy, as its effects in humans are known and less adverse than conventional chemotherapy. We explored the potential mechanism behind the cytotoxicity of DSF-Cu⁺/Cu²⁺ complexes in oral epidermoid carcinoma meng-1 (OECM-1) and human gingival epithelial Smulow-Glickman (SG) cells. Exposure to CuCl₂ or CuCl slightly but concentration-dependently decreased cell viability, while DSF-Cu⁺/Cu²⁺ induced cell death in OECM-1 cells, but not SG cells. DSF-Cu⁺/Cu²⁺ also increased the subG1 population and decreased the G1, S, and G2/M populations in OECM-1 cells, but not SG cells, and suppressed cell proliferation in both OECM-1 and SG cells. ALDH enzyme activity was inhibited by CuCl and DSF-Cu⁺/Cu²⁺ in SG cells, but not OECM-1 cells. ROS levels and cellular senescence were increased in DSF-Cu⁺/Cu²⁺-treated OECM-1 cells, whereas they were suppressed in SG cells. DSF-Cu⁺/Cu²⁺ induced mitochondrial fission in OECM-1 cells and reduced mitochondrial membrane potential. CuCl₂ increased but DSF- Cu²⁺ impaired oxygen consumption rates and extracellular acidification rates in OECM-1 cells. CuCl₂ stabilized HIF-1α expression under normoxia in OECM-1 cells, and complex with DSF enhanced that effect. Levels of c-Myc protein and its phosphorylation at Tyr58 and Ser62 were increased, while levels of the N-terminal truncated form (Myc-nick) were decreased in DSF-Cu⁺/Cu²-treated OECM-1 cells. These effects were all suppressed by pretreatment with the ROS scavenger NAC. Overexpression of c-Myc failed to induce HIF-1α expression. These findings provide novel insight into the potential application of DSF-CuCl₂ complex as a repurposed agent for OSCC cancer therapy.     

Molecular Dynamics Simulations Based on 1-Phenyl-4-Benzoyl-1-Hydro-Triazole ERRα Inverse Agonists

Estrogen-related receptor α (ERRα), which is overexpressed in a variety of cancers has been considered as an effective target for anticancer therapy. ERRα inverse agonists have been proven to effectively inhibit the migration and invasion of cancer cells. As few crystalline complexes have been reported, molecular dynamics (MD) simulations were carried out in this study to deepen the understanding of the interaction mechanism between inverse agonists and ERRα. The binding free energy was analyzed by the MM-GBSA method. The results show that the total binding free energy was positively correlated with the biological activity of an inverse agonist. The interaction of the inverse agonist with the hydrophobic interlayer composed of Phe328 and Phe495 had an important impact on the biological activity of inverse agonists, which was confirmed by the decomposition of energy on residues. As Glu331 flipped and formed a hydrogen bond with Arg372 in the MD simulation process, the formation of hydrogen bond interaction with Glu331 was not a necessary condition for the compound to act as an inverse agonist. These rules provide guidance for the design of new inverse agonists.     

Collagen I Modifies Connexin-43 Hemichannel Activity via Integrin α2β1 Binding in TGFβ1-Evoked Renal Tubular Epithelial Cells

Chronic Kidney Disease (CKD) is associated with sustained inflammation and progressive fibrosis, changes that have been linked to altered connexin hemichannel-mediated release of adenosine triphosphate (ATP). Kidney fibrosis develops in response to increased deposition of extracellular matrix (ECM), and up-regulation of collagen I is an early marker of renal disease. With ECM remodeling known to promote a loss of epithelial stability, in the current study we used a clonal human kidney (HK2) model of proximal tubular epithelial cells to determine if collagen I modulates changes in cell function, via connexin-43 (Cx43) hemichannel ATP release. HK2 cells were cultured on collagen I and treated with the beta 1 isoform of the pro-fibrotic cytokine transforming growth factor (TGFβ1) ± the Cx43 mimetic Peptide 5 and/or an anti-integrin α2β1 neutralizing antibody. Phase microscopy and immunocytochemistry observed changes in cell morphology and cytoskeletal reorganization, whilst immunoblotting and ELISA identified changes in protein expression and secretion. Carboxyfluorescein dye uptake and biosensing measured hemichannel activity and ATP release. A Cytoselect extracellular matrix adhesion assay assessed changes in cell-substrate interactions. Collagen I and TGFβ1 synergistically evoked increased hemichannel activity and ATP release. This was paralleled by changes to markers of tubular injury, partly mediated by integrin α2β1/integrin-like kinase signaling. The co-incubation of the hemichannel blocker Peptide 5, reduced collagen I/TGFβ1 induced alterations and inhibited a positive feedforward loop between Cx43/ATP release/collagen I. This study highlights a role for collagen I in regulating connexin-mediated hemichannel activity through integrin α2β1 signaling, ahead of establishing Peptide 5 as a potential intervention.     

Exogenous Integrin αIIbβ3 Inhibitors Revisited: Past,Present and Future Applications

The integrin αIIbβ3 is the most abundant integrin on platelets. Upon platelet activation, the integrin changes its conformation (inside-out signalling) and outside-in signalling takes place leading to platelet spreading, platelet aggregation and thrombus formation. Bloodsucking parasites such as mosquitoes, leeches and ticks express anticoagulant and antiplatelet proteins, which represent major sources of lead compounds for the development of useful therapeutic agents for the treatment of haemostatic disorders or cardiovascular diseases. In addition to hematophagous parasites, snakes also possess anticoagulant and antiplatelet proteins in their salivary glands. Two snake venom proteins have been developed into two antiplatelet drugs that are currently used in the clinic. The group of proteins discussed in this review are disintegrins, low molecular weight integrin-binding cysteine-rich proteins, found in snakes, ticks, leeches, worms and horseflies. Finally, we highlight various oral antagonists, which have been tested in clinical trials but were discontinued due to an increase in mortality. No new αIIbβ3 inhibitors are developed since the approval of current platelet antagonists, and structure-function analysis of exogenous disintegrins could help find platelet antagonists with fewer adverse side effects.     

Deciphering the Binding Interactions between Acinetobacter baumannii ACP and β-ketoacyl ACP Synthase III to Improve Antibiotic Targeting Using NMR Spectroscopy

Fatty acid synthesis is essential for bacterial viability. Thus, fatty acid synthases (FASs) represent effective targets for antibiotics. Nevertheless, multidrug-resistant bacteria, including the human opportunistic bacteria, Acinetobacter baumannii, are emerging threats. Meanwhile, the FAS pathway of A. baumannii is relatively unexplored. Considering that acyl carrier protein (ACP) has an important role in the delivery of fatty acyl intermediates to other FAS enzymes, we elucidated the solution structure of A. baumannii ACP (AbACP) and, using NMR spectroscopy, investigated its interactions with β-ketoacyl ACP synthase III (AbKAS III), which initiates fatty acid elongation. The results show that AbACP comprises four helices, while Ca²⁺ reduces the electrostatic repulsion between acid residues, and the unconserved F47 plays a key role in thermal stability. Moreover, AbACP exhibits flexibility near the hydrophobic cavity entrance from D59 to T65, as well as in the α₁α₂ loop region. Further, F29 and A69 participate in slow exchanges, which may be related to shuttling of the growing acyl chain. Additionally, electrostatic interactions occur between the α₂ and α₃-helix of ACP and AbKAS III, while the hydrophobic interactions through the ACP α₂-helix are seemingly important. Our study provides insights for development of potent antibiotics capable of inhibiting A. baumannii FAS protein–protein interactions.