Combined Liver Stiffness and Α-fetoprotein Further beyond the Sustained Virologic Response Visit as Predictors of Long-Term Liver-Related Events in Patients with Chronic Hepatitis C.

Aims: Long-term risk stratification using combined liver stiffness (LS) and clinically relevant blood tests acquired at the baseline further beyond the sustained virologic response (SVR) visit for chronic hepatitis C (CHC) has not been thoroughly investigated. This study retrospectively investigated the prognostics of liver-related events (LREs) further beyond the SVR visit. Methods: Cox regression and random forest models identified the key factors, including longitudinal LS and noninvasive test results, that could predict LREs, including hepatocellular carcinoma, during prespecified follow-ups from 2010 to 2021. Kaplan-Meier survival analysis estimated the significance of between-group risk stratification. Results: Of the entire eligible cohort (n = 520) of CHC patients with SVR to antiviral therapy, 28 (5.4%) patients developed post-SVR LREs over a median follow-up period of 6.1 years (interquartile range = 3.5-8.7). The multivariate Cox regression analysis identified two significant predictors of LREs after the year 3 post-SVR (Y3PSVR) baseline (LRE, n = 15 of 28, 53.6%, median follow-up = 4.1 [1.6-6.4] years after Y3PSVR): LS at Y3PSVR (adjusted hazard ratio [aHR] = 3.980, 95% confidence interval [CI] = 2.085-7.597, P < 0.001), and α-fetoprotein (AFP) at Y3PSVR (aHR = 1.017, 95% CI = 1.001-1.034, P=0.034). LS ≥1.45 m/s and AFP ≥3.00 ng/mL for Y3PSVR yielded positive likelihood ratios of 4.24 and 2.62, respectively. Kaplan-Meier analysis revealed that among the stratified subgroups, the subgroup with concurrent LS ≥1.45 m/s and AFP ≥3.00 ng/mL at Y3PSVR exhibited the highest risk of LREs after Y3PSVR (log-rank P < 0.001). Conclusion: We recommend the combined use of concurrent LS and AFP in future prediction models for LREs in CHC. Patients with concurrently high LS and AFP values further beyond the SVR visit may require a recall policy involving intense surveillance.

Marangoni spreading time evolution and synergism in binary surfactant mixtures.

HYPOTHESIS: Marangoni spreading driven by localized surfactant solution deposition previously has been studied only for single surfactant systems. For binary surfactant mixtures, interactions that generate surface tension synergism, a thermodynamic effect, may also synergistically enhance Marangoni spreading dynamics, introducing the concept of Marangoni synergism. Spreading dynamics and possible Marangoni synergism should depend not only on thermodynamic properties but also kinetic properties of the binary system. EXPERIMENTS AND MODELING: Tracer experiments that capture post-deposition surfactant front motion were performed in parallel with computational modeling, using binary surfactant pairs with varying interaction strengths. The model coupled the Navier-Stokes and advective diffusion equations with a Frumkin-type binary adsorption model. FINDINGS: We confirm the existence of Marangoni synergism. Stronger binary surfactant attraction favors synergism in both surface tension reduction and Marangoni spreading. Binary composition ranges over which surface tension synergism occurs differ from those for Marangoni synergism, indicating that the origins of the two synergistic effects are not identical. Analysis of model spreading velocities show that the thermodynamic spreading parameter is the controlling factor at early times for both single and binary surfactant systems, while the intrinsic adsorption and desorption kinetics influence spreading velocities and thus the occurrence of Marangoni synergism at later times.

Fabrication and Photocatalytic Properties of Zinc Tin Oxide Nanowires Decorated with Silver Nanoparticles.

With the continuous advancement of high-tech industries, how to properly handle pollutants has become urgent. Photocatalysis is a solution that may effectively degrade pollutants into harmless molecules. In this study, we synthesized single crystalline Zn2SnO4 (ZTO) nanowires through chemical vapor deposition and selective etching. The chemical bath redox method was used to modify the ZTO nanowires with Ag nanoparticles to explore the photocatalytic properties of the nanoheterostructures. The combination of the materials here is rare. Optical measurements by photoluminescence (PL) and UV-Vis show that the PL spectrum of ZTO nanowires was mainly in the visible light region and attributed to oxygen vacancies. The luminescence intensity of the nanowires was significantly reduced after modification, demonstrating that the heterojunction could effectively reduce the electron-hole pair recombination. The reduction increased with the increase in Ag decoration. The conversion from the UV-Vis absorption spectrum to the Tauc Plot shows that the band gap of the nanowire was 4.05 eV. With 10 ppm methylene blue (MB) as the degradation solution, ZTO nanowires exhibit excellent photodegradation efficiency. Reusability and stability in photodegradation of the nanowires were demonstrated. Photocatalytic efficiency increases with the number of Ag nanoparticles. The main reaction mechanism was confirmed by photocatalytic inhibitors. This study enriches our understanding of ZTO-based nanostructures and facilitates their applications in water splitting, sewage treatment and air purification.

Surfactant spreading on a deep subphase: Coupling of Marangoni flow and capillary waves.

HYPOTHESIS: Surfactant-driven Marangoni spreading generates a fluid flow characterized by an outwardly moving "Marangoni ridge". Spreading on thin and/or high viscosity subphases, as most of the prior literature emphasizes, does not allow the formation of capillary waves. On deep, low viscosity subphases, Marangoni stresses may launch capillary waves coupled with the Marangoni ridge, and new dependencies emerge for key spreading characteristics on surfactant thermodynamic and kinetic properties. EXPERIMENTS AND MODELING: Computational and physical experiments were performed using a broad range of surfactants to report the post-deposition motion of the surfactant front and the deformation of the subphase surface. Modeling coupled the Navier-Stokes and advective diffusion equations with an adsorption model. Separate experiments employed tracer particles or an optical density method to track surfactant front motion or surface deformation, respectively. FINDINGS: Marangoni stresses on thick subphases induce capillary waves, the slowest of which is co-mingled with the Marangoni ridge. Changing Marangoni stresses by varying the surfactant system alters the surfactant front velocity and the amplitude - but not the velocity - of the slowest capillary wave. As spreading progresses, the surfactant front and its associated surface deformation separate from the slowest moving capillary wave.

Hurricane annual cycle controlled by both seeds and genesis probability.

Understanding tropical cyclone (TC) climatology is a problem of profound societal significance and deep scientific interest. The annual cycle is the biggest radiatively forced signal in TC variability, presenting a key test of our understanding and modeling of TC activity. TCs over the North Atlantic (NA) basin, which are usually called hurricanes, have a sharp peak in the annual cycle, with more than half concentrated in only 3 mo (August to October), yet existing theories of TC genesis often predict a much smoother cycle. Here we apply a framework originally developed to study TC response to climate change in which TC genesis is determined by both the number of pre-TC synoptic disturbances (TC "seeds") and the probability of TC genesis from the seeds. The combination of seeds and probability predicts a more consistent hurricane annual cycle, reproducing the compact season, as well as the abrupt increase from July to August in the NA across observations and climate models. The seeds-probability TC genesis framework also successfully captures TC annual cycles in different basins. The concise representation of the climate sensitivity of TCs from the annual cycle to climate change indicates that the framework captures the essential elements of the TC climate connection.

pH-Dependent Interfacial Tension and Dilatational Modulus Synergism of Oil-Soluble Fatty Acid and Water-Soluble Cationic Surfactants at the Oil/Water Interface.

While the concept of interfacial tension synergism in surfactant mixtures is well established, little attention has been paid to the possibility of synergistic effects on the interfacial rheology of mixed surfactant systems. Furthermore, interfacial tension synergism is most often investigated for mixtures of surfactants residing in a single phase. Here, we define dilatational modulus synergism and report a study of interfacial tension isotherms and complex dilatational moduli for a binary surfactant system with the two surfactants accessing the oil/water interface from opposite sides. Using an oil-soluble fatty acid surfactant (palmitic acid, PA) that may be ionized at the oil/water interface and a quaternary ammonium water-soluble cationic surfactant (tetradecyltrimethylammonium bromide, TTAB), the binary interfacial interaction was tuned by the aqueous phase pH. Interfacial tensions and dilatational moduli were measured by the pendant drop method for the binary surfactant system as well as the corresponding single-surfactant systems to identify synergistic effects. The possible occurrence of dilatational modulus synergism was probed from two perspectives: one for a fixed total surfactant concentration and the other for a fixed interfacial tension. The aqueous pH was found to have a controlling effect on both interfacial tension synergism and the dilatational modulus synergism. The conditions for interfacial tension synergism coincided with those for the storage modulus synergism: both tension and storage modulus synergisms were observed under all conditions tested at pH 7 where PA was mostly deprotonated, for both perspectives examined, but not for any conditions tested at pH 3 where PA is mostly protonated. The loss modulus synergism exhibited more complex behaviors, such as frequency and interfacial tension dependences, but again was only observed at pH 7. The tension and modulus synergism at pH 7 were attributed to the increased attraction between ionized PA and cationic TTAB and the formation of catanionic complexes at the oil/water interface.

Interfacial dilatational rheology as a bridge to connect amphiphilic heterografted bottlebrush copolymer architecture to emulsifying efficiency.

HYPOTHESIS: Molecular architecture and composition of amphiphilic bottlebrush copolymers will dictate the dominant interfacial relaxation modes and the corresponding dilatational rheology for adsorbed layers at oil/water interfaces in a way that will correlate with the emulsifying efficiency of different bottlebrush copolymers. EXPERIMENTS: Amphiphilic, xylene-soluble poly(ethylene oxide)-poly(n-butyl acrylate) (PEO-PBA) heterografted bottlebrush copolymers with controlled differences in backbone length, hydrophilicity and arm length were synthesized by atom transfer radical polymerization. Dilatational rheology of adsorbed layers at the xylene/water interface was probed via pendant drop tensiometry by measuring the interfacial stress response to either large-amplitude strain cycling or small-amplitude strain oscillation. The rheological response was recorded as a function of interfacial pressure for adsorbed layers under different compression states. Emulsifying efficiency was determined as the lowest copolymer concentration that yielded water-in-xylene emulsions with at least one-month stability against coalescence. FINDINGS: The more hydrophilic copolymers with longer PEO arms exhibited non-hysteretic stress-strain response curves in large-amplitude strain cycling and a tendency for the modulus to increase with increasing interfacial pressure. These were more efficient emulsifiers than less hydrophilic copolymers that exhibited hysteretic interfacial rheology. Mere existence of significant moduli did not correlate with high emulsifying efficiency, while an increase in modulus with increasing interfacial pressure did so.

Dynamin-2 Regulates Postsynaptic Cytoskeleton Organization and Neuromuscular Junction Development.

Neuromuscular junctions (NMJs) govern efficient neuronal communication with muscle cells, relying on proper architecture of specialized postsynaptic compartments. However, the intrinsic mechanism in muscle cells contributing to NMJ development remains unclear. In this study, we reveal that dynamin-2 (Dyn2) is involved in postsynaptic development of NMJs. Mutations of Dyn2 have been linked to human muscular disorder and centronuclear myopathy (CNM), as well as featured with muscle atrophy and defective NMJs, yet the function of Dyn2 at the postsynaptic membrane is largely unknown. We demonstrate that Dyn2 is enriched at the postsynaptic membrane and regulates NMJ development via actin remodeling. Dyn2 functions as an actin-bundling GTPase to regulate podosome turnover and cytoskeletal organization of the postsynaptic apparatus, and CNM-Dyn2 mutations display abnormal actin remodeling and electrophysiological activity of fly NMJs. Altogether, Dyn2 primarily regulates actin cytoskeleton remodeling and NMJ morphogenesis at the postsynaptic membrane, which is distinct from its endocytosis regulatory role at the presynaptic membrane.

Synthesis of IrO2 decorated core-shell PS@PPyNH2 microspheres for bio-interface application.

In this paper, an effective approach is demonstrated for the fabrication of IrO2-decorated polystyrene@functionalized polypyrrole (core@shell; PS@PPyNH2) microspheres. The synthesis begins with the preparation of monodispersive PS microspheres with a diameter of 490 nm, by a process of emulsifier-free emulsion polymerization, followed by a copolymerization process involving pyrrole and PyNH2 monomers in a PS microsphere aqueous suspension, to produce uniform PS@PPyNH2 microspheres with a diameter of 536 nm. The loading of 2 nm IrO2 nanoparticles onto the PS@PPyNH2 microspheres can be easily adjusted by tuning the pH value of the IrO2 colloidal solution and the PS@PPyNH2 suspension. At pH 4, we successfully obtain IrO2-decorated PS@PPyNH2 microspheres via electrostatic attraction and hydrogen bonding simultaneously between the negatively-charged IrO2 nanoparticles and the positively-charged PS@PPyNH2 microspheres. These IrO2-decorated PS@PPyNH2 microspheres exhibit a characteristic cyclic voltammetric profile, similar to that of an IrO2 thin film. The charge storage capacity is 5.19 mA cm-2, a value almost five times greater than that of PS@PPyNH2 microspheres. In addition, these IrO2-decorated PS@PPyNH2 microspheres exhibit excellent cell viability and biocompatibility.

An acute decrease in plasma membrane tension induces macropinocytosis via PLD2 activation.

Internalization of macromolecules and membrane into cells through endocytosis is critical for cellular growth, signaling and plasma membrane (PM) tension homeostasis. Although endocytosis is responsive to both biochemical and physical stimuli, how physical cues modulate endocytic pathways is less understood. Contrary to the accumulating discoveries on the effects of increased PM tension on endocytosis, less is known about how a decrease of PM tension impacts on membrane trafficking. Here, we reveal that an acute decrease of PM tension results in phosphatidic acid (PA) production, F-actin and phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2]-enriched dorsal membrane ruffling and subsequent macropinocytosis in myoblasts. The PA production induced by decreased PM tension depends on phospholipase D2 (PLD2) activation via PLD2 nanodomain disintegration. Furthermore, the 'decreased PM tension-PLD2-macropinocytosis' pathway is prominent in myotubes, reflecting a potential mechanism of PM tension homeostasis upon intensive muscle stretching and relaxation. Together, we identify a new mechanotransduction pathway that converts an acute decrease in PM tension into PA production and then initiates macropinocytosis via actin and PI(4,5)P2-mediated processes.

Highly Selective Dissociation of a Peptide Bond Following Excitation of Core Electrons.

The controlled breaking of a specific chemical bond with photons in complex molecules remains a major challenge in chemistry. In principle, using the K-edge absorption of a particular atomic element, one might excite selectively a specific atomic entity in a molecule. We report here highly selective dissociation of the peptide bonds in N-methylformamide and N-methylacetamide on tuning the X-ray wavelength to the K-edge absorption of the atoms connected to (or near) the peptide bond. The high selectivity (56-71%) of this cleavage arises from the large energy shift of X-ray absorption, a large overlap of the 1s orbital and the valence π* orbital that is highly localized on a peptide bond with antibonding character, and the relatively low bond energy of the peptide bonds. These characteristics indicate that the high selectivity on bond dissociation following core excitation could be a general feature for molecules containing peptide bonds.

Successful salvage of peritoneal catheter in unresolved methicillin-resistant staphylococcus aureus peritonitis by combination treatment with daptomycin and rifampin.

Peritoneal dialysis patients are at an increased risk of Gram-positive organism infections because of disrupted skin barrier function, presence of a peritoneal catheter, and a deficient immunological system. In particular, the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections is clinically challenging. Herein, we present a case of MRSA peritonitis that showed no response to a 14-day treatment with intraperitoneal vancomycin. To overcome unresponsiveness to vancomycin, we shifted the regimen to intraperitoneal daptomycin (given every 6 h through manual peritoneal dialysate exchanges) and oral rifampin (300 mg twice daily). The peritonitis resolved without sequelae or relapse. We suggest daptomycin and rifampin as an alternative combination therapy for MRSA infections that may otherwise remain unresolved.