血管生成素样蛋白4和Ⅱ型肺泡细胞表面抗原-6与急性呼吸窘迫综合征严重程度的关系及对预后的评估效能研究

摘要 目的：分析血管生成素样蛋白4(ANGPTL4)和Ⅱ型肺泡细胞表面抗原-6(KL-6)与急性呼吸窘迫综合征严重程度的关系及对预后的评估效能。方法：选择我院自2020年1月至2022年12月收治的120例急性呼吸窘迫综合征患者作为研究对象（观察组）,根据氧合指数（PaO₂/FiO₂）分为轻度组、中度组和重度组;另选120例非急性呼吸窘迫综合征患者作为对照组。检测所有患者血清ANGPTL4和KL-6的表达水平,分析血清ANGPTL4和KL-6与APACHE Ⅱ评分、PaO₂/FiO₂的关系,使用受试者工作特征曲线（ROC）下面积（AUC）评价血清ANGPTL4联合KL-6对急性呼吸窘迫综合征预后的评估效能。结果：对比对照组,观察组血清ANGPTL4、KL-6的表达水平均明显升高（P＜0.05）;血清ANGPTL4、KL-6的表达水平在轻度组、中度组和重度组中差异有统计学意义,且急性呼吸窘迫综合征越严重,升高越明显（P＜0.05）;经Pearson相关性分析,急性呼吸窘迫综合征患者血清ANGPTL4、KL-6的表达水平与PaO₂/FiO₂呈负相关,与APACHE Ⅱ评分呈正相关（P＜0.05）;经ROC曲线分析,血清ANGPTL4联合KL-6预测急性呼吸窘迫综合征患者入院28d内死亡的敏感度为90.14%、特异度为65.74%,AUC为0.900。结论：血清ANGPTL4、KL-6表达水平升高与急性呼吸窘迫综合征严重程度增大密切相关,两者联合在患者预后评估中具有一定价值,可作为判断病情及预后的辅助指标。     

Directed movements of ciliary and flagellar membrane components: a review.

The ability to rapidly translocate polystyrene microspheres attached to the surface of a plasma membrane domain reflects a unique form of cellular force transduction occurring in association with the plasma membrane of microtubule based cell extensions. This unusual form of cell motility can be utilized by protistan organisms for whole cell locomotion, the early events in mating, and transport of food organisms along the cell surface, and possibly intracellular transport of certain organelles. Since surface motility is observed in association with cilia and flagella of algae, sea urchin embryos and cultured mammalian cells, it is likely that it serves an additional role beyond those already cited; this is likely to be the transport of precursors for the assembly and turnover of ciliary and flagellar membranes and axonemes. In the case of the Chlamydomonas flagellum, where surface motility has been most extensively studied, it appears that cross-linking of flagellar surface exposed proteins induces a transmembrane signaling pathway that activates machinery for moving flagellar membrane proteins in the plane of the flagellar membrane. This signaling pathway in vegetative Chlamydomonas reinhardtii appears to involve an influx of calcium, a rise in intraflagellar free calcium concentration and a change in the level of phosphorylation of specific membrane-matrix proteins. It is hypothesized that flagellar surface contact with a solid substrate (during gliding), a polystyrene microsphere or another flagellum (during mating) will all activate a signaling pathway similar to the one artificially activated by the use of monoclonal antibodies to flagellar membrane glycoproteins. A somewhat different signaling pathway, involving a transient rise in intracellular cAMP level, may be associated with the mating of Chlamydomonas gametes, which is initiated by flagellum-flagellum contact. The hypothesis that the widespread observation of microsphere movements on various ciliary and flagellar surfaces may reflect a mechanism normally utilized to transport axonemal and membrane subunits along the internal surface of the organelle membrane presents a paradox in that one would expect this to be a constitutive mechanism, not one necessarily activated by a signaling pathway.     

Structure and Disorder in an Unfolded State under Nondenaturing Conditions from Ensemble Models Consistent with a Large Number of Experimental Restraints

Obtaining detailed structural models of disordered states of proteins under nondenaturing conditions is important for a better understanding of both functional intrinsically disordered proteins and unfolded states of folded proteins. Extensive experimental characterization of the drk N-terminal SH3 domain unfolded state has shown that, although it appears to be highly disordered, it possesses significant nonrandom secondary and tertiary structure. In our previous attempts to generate structural models of the unfolded state using the program ENSEMBLE, we were limited by insufficient experimental restraints and conformational sampling. In this study, we have vastly expanded our experimental restraint set to include ¹H-¹⁵N residual dipolar couplings, small-angle X-ray scattering measurements, nitroxide paramagnetic relaxation enhancements, O₂-induced ¹³C paramagnetic shifts, hydrogen-exchange protection factors, and ¹⁵N R₂ data, in addition to the previously used nuclear Overhauser effects, amino terminal Cu²⁺-Ni²⁺ binding paramagnetic relaxation enhancements, J-couplings, chemical shifts, hydrodynamic radius, and solvent accessibility restraints. We have also implemented a new ensemble calculation methodology that uses iterative conformational sampling and seeks to calculate the simplest possible ensemble models. As a result, we can now generate ensembles that are consistent with much larger experimental data sets than was previously possible. Although highly heterogeneous and having broad molecular size distributions, the calculated drk N-terminal SH3 domain unfolded-state ensembles have very different properties than expected for random or statistical coils and possess significant nonnative α-helical structure and both native-like and nonnative tertiary structure.     

Molecular dynamics simulations of alpha2 --> 8-linked disialoside: conformational analysis and implications for binding to proteins.

Computational methods have played a key role in elucidating the various three-dimensional structures of oligosaccharides. Such structural information, together with other experimental data, leads to a better understanding of the role of oligosaccharide in various biological processes. The disialoside Neu5Ac-alpha2-->8-Neu5Ac appears as the terminal glycan in glycoproteins and glycolipids, and is known to play an important role in various events of cellular communication. Neurotoxins such as botulinum and tetanus require Neu5Ac-alpha2 --> 8-Neu5Ac for infecting the host. Glycoconjugates containing this disialoside and the enzymes catalyzing their biosynthesis are also regulated during cell growth, development, and differentiation. Unlike other biologically relevant disaccharides that have only two linkage bonds, the alpha2-->8-linked disialoside has four: C2-O, O-C8', C8'-C7', and C7'-C6'. The present report describes the results from nine 1 ns MD simulations of alpha2-->8-linked disialoside (Neu5Ac-alpha2-->8-Neu5Ac); simulations were run using GROMOS96 by explicitly considering the solvent molecules. Conformations around the O-C8' bond are restricted to the +sc/+ap regions due to stereochemical reasons. In contrast, conformations around the C2-O and C8'-C7' bonds were found to be largely unrestricted and all the three staggered regions are accessible. The conformations around the C7'-C6' bond were found to be in either the -sc or the anti region. These results are in excellent agreement with the available NMR and potential energy calculation studies. Overall, the disaccharide is flexible and adopts mainly two ensembles of conformations differing in the conformation around the C7'-C6' bond. The flexibility associated with this disaccharide allows for better optimization of intermolecular contacts while binding to proteins and this may partially compensate for the loss of conformational entropy that may be incurred due to disaccharide's flexibility.     

Differentiation-associated changes in membrane proteins of mouse myeloid leukemia cells

The mouse myeloid leukemia cell line (M1) is known to differentiate in vitro into macrophages and granulocytes upon treatment with various inducer including mouse ascitic fluid. Changes of cell surface proteins during differentiation of M1 cells were analyzed by the lactoperoxidase-catalyzed radioiodination method and SDS-polycrylamide slab gel electrphoresis. Treatment of the cells with ascitic fluid changed the electrophoretic pattern of the iodinated proteins, the prominent change being the appearance of a new protein with a molecular weight of 180 000 (P180). Iodinated P180 was also detected in normal macrophages in granulocytes, which are similar to differentiated M1 cells. This protein was metabolically labeled with l-[¹⁴C]fucose, increasing with the period of the treatment. P180 was not expressed on ascitic fluid-treatment of a resistant clone of M1 cells that could not be induced to differentiate. These results indicate that P180 is a glycoprotein that is exposed on the outer surface of differentiated M1 cells, and that its expression is associated with differentiation of the cells.P180 was solubilized from ¹²⁵I-labeled macrophages with detergents bound to concanavalin A-Sepharose. This suggests that P180 is one of the receptors for concanavalin A. Therefore, P180 may contribute partly to the increases in agglutinability by concanavalin A and in the number of concanavalin A binding sites on the surface of M1 cells, which are known to be associated with differentiation of M1 cells.     

Lipophilic 9,10‐Dehydrofukinone Action on Pathogenic and Non‐Pathogenic Bacterial Biofilms. Why Is This Main Volatile Metabolite in Senecio?

The effect of a natural sesquiterpene ketone, 9,10‐dehydrofukinone (DHF), on pathogenic Staphylococcus aureus and Pseudomonas aeruginosa strains isolated from chronic infectious processes, was the focus of the present study. Lipophilic DHF produced important antibacterial synergistic effects in association with ciprofloxacin (CPX) against two biofilm‐forming strains of S. aureus HT1 (FIC=0.21) and P. aeruginosa HT5 (FIC=0.05). Hence, this mixture constitutes an excellent strategy to combat these biofilm‐producing bacteria that overexpress drug efflux pumps as a resistance mechanism. Additionally, a substantial rise in beneficial Lactobacillus biofilm biomass was determined as a very significant finding of this association. Particularly, a non‐pathogenic biofilm increment of 119 % was quantified when the mixture was added to a probiotic L. acidophilus ATCC SD‐5212 culture. A surface activity enhanced in 71 % with respect to untreated L. acidophilus culture was also generated by the DHF and CPX association, and therefore, a glycoprotein synthesis induction mediated by the mixture is discussed. The results obtained could help in the development of new selective antibiotics. From an ecological standpoint, the present study strongly suggests that DHF is a polyfunctional organic molecule produced with a high yield in Senecio punae that exerts a positive impact on a non‐pathogenic plant bacterium L. plantarum CE105.     

Microdischarge‐Based Direct Current Triboelectric Nanogenerator via Accumulation of Triboelectric Charge in Atmospheric Condition

Direct conversion of mechanical energy into direct current (DC) by triboelectric nanogenerators (TENGs) is one of the desired features in terms of energy conversion efficiency. Although promising applications have been reported using the triboelectric effect, effective DC generating TENGs must be developed for practical purposes. Here, it is reported that continuous DC generation within a TENG itself, without any circuitry, can be achieved by triggering air breakdown via triboelectrification. It is demonstrated that DC generation occurs in combination with i) charge accumulation to generate air breakdown, ii) incident discharge (microdischarge), and iii) conveyance of charges to make the device sustainable. 10.5 mA m^?2 of output current and 10.6 W m^?2 of output power at 33 MΩ load resistance are achieved. Compared to the best DC generating TENGs ever reported, the TENG in this present study generates about 20 times larger root‐mean square current density.     

Suppressing Voltage Fading of Li‐Rich Oxide Cathode via Building a Well‐Protected and Partially‐Protonated Surface by Polyacrylic Acid Binder for Cycle‐Stable Li‐Ion Batteries

Li‐rich manganese based oxides (LRMOs) are considered an attractive high‐capacity cathode for advanced Li‐ion batteries; however, their poor cyclability and gradual voltage fading have hindered their practical applications. Herein, an efficient and facile strategy is proposed to stabilize the lattice structure of LRMOs by surface modification of polyacrylic acid (PAA). The PAA‐coated LRMO electrode exhibits only 104 mV of the voltage fading after 100 cycles and 88% capacity retention over 500 cycles. The structural stability is attributed to the carboxyl groups in PAA chains reacting with oxygen species on the surface of LRMO to form a uniform and tightly coated film, which significantly suppresses the dissolution of transition metal elements from the cathode materials into the electrolyte. Importantly, a H⁺/Li⁺ exchange reaction takes place between the LRMO and PAA, generating a proton‐doped surface layer. Density functional theory calculations and experimental evidence demonstrates that the H⁺ ions in the surface lattice efficiently inhibit the migration of transition metal ions, leading to a stabilized lattice structure. This surface modification approach may provide a new route to building a stable Li‐rich oxide cathode with high capacity retention and low voltage fading for practical Li‐ion battery applications.